Relationship Between Neck Circumference and Epicardial Fat Thickness in a Healthy Male Population.

PubMed

Küçük, Uğur; Küçük, Hilal Olgun; Cüce, Ferhat; Balta, Sevket

2016-09-01

Epicardial fat is an upper body visceral fat depot that may play a significant role in the development of adverse metabolic and cardiovascular risk profiles. There is a significant direct relationship between the amount of epicardial fat and general body adiposity (body mass index, BMI), but data regarding subcutaneous adiposity is limited. We conducted a study to determine the association between neck circumference and epicardial fat thickness in healthy young male individuals, and assess their individual correlations with general body adiposity and cardiometabolic risk factors. One hundred consecutive male patients aged 18 years or older with no known major medical conditions were included in the study. All participants underwent detailed physical examination including measurement of blood pressure, weight, height, waist/hip ratio, and neck circumference. Blood was collected to determine fasting glucose and lipid parameters. A standard echocardiographic examination was performed with additional epicardial fat thickness determination. Among 100 study participants, neck circumference correlated significantly with weight, waist circumference, BMI, blood glucose, serum total cholesterol, low-density (LDL)-cholesterol, and triglycerides levels. No significant correlation was found between neck circumference and high-density lipoprotein (HDL)-cholesterol levels. Neck circumference correlated moderately and positively with echocardiographic epicardial fat thickness. Among patients with low cardiometabolic risk, increased neck circumference was associated with increased epicardial fat thickness. A gordura epicárdica é um depósito de gordura visceral na parte superior do organismo que pode desempenhar um papel importante no desenvolvimento de perfis cardiovasculares e metabólicos adversos. Há uma relação direta significativa entre a quantidade de gordura epicárdica e a adiposidade corporal geral (índice de massa corporal, IMC), mas dados sobre a adiposidade subcutânea são limitados. Realizamos um estudo para determinar a associação entre a circunferência do pescoço e a espessura da gordura epicárdica em jovens saudáveis do sexo masculino, além de avaliar as suas correlações individuais com a adiposidade corporal geral e fatores de risco cardiometabólicos. Cem pacientes consecutivos do sexo masculino com idade igual ou superior a 18 anos e sem nenhuma condição médica importante e conhecida foram incluídos no estudo. Todos os participantes foram submetidos a um exame físico detalhado que incluiu medida da pressão arterial, peso, altura, razão cintura/quadril e circunferência do pescoço. Sangue foi coletado para determinação da glicemia de jejum e parâmetros lipídicos. Um exame ecocardiográfico padrão foi realizado com determinação adicional da espessura da gordura epicárdica. Entre os 100 participantes do estudo, a circunferência do pescoço mostrou correlação significativa com o peso, circunferência de cintura, IMC, glicemia e níveis séricos de colesterol total, lipoproteína de baixa densidade (LDL-colesterol) e triglicerídeos. Não foi observada correlação significativa entre a circunferência do pescoço e níveis de colesterol de alta densidade (HDL-colesterol). A circunferência do pescoço correlacionou moderadamente e positivamente com a espessura da gordura epicárdica à ecocardiografia. Entre pacientes com baixo risco cardiometabólico, o aumento da circunferência do pescoço foi associado a um aumento da espessura da gordura epicárdica.

Piezoresponse force microscopy of ferroelectric relaxors =

NASA Astrophysics Data System (ADS)

Kiselev, Dmitry

Nesta tese, ferroelectricos relaxor (I dont know uf the order is correct) de base Pb das familias (Pb,La)(Zr,Ti)O3 (PLZT), Pb(Mg1/3,Nb2/3)O3-PbTiO3 (PMN-PT), Pb(Zn1/3,Nb2/3)O3-PbTiO3 (PZN-PT) foram investigados e analisados. As propriedades ferroelectricas e dielectricas das amostras foram estudadas por metodos convencionais de macro e localmente por microscopia de forca piezoelectrica (PFM). Nos cerâmicos PLZT 9.75/65/35 o contraste da PFM a escala nanometrica foi investigado em funcao do tamanho e orientacao dos graos. Apurou-se que a intensidade do sinal piezoelectrico das nanoestruturas diminui com o aumento da temperatura e desaparece a 490 K (La mol. 8%) e 420 K (9,5%). Os ciclos de histerese locais foram obtidos em funcao da temperatura. A evolucao dos parâmetros macroscopicos e locais com a temperatura de superficie sugere um forte efeito de superficie nas transicoes de fase ferroelectricas do material investigado. A rugosidade da parede de dominio e determinada por PFM para a estrutura de dominio natural existente neste ferroelectrico policristalino. Alem disso, os dominios ferroelectricos artificiais foram criados pela aplicacao de pulsos electricos a ponta do condutor PFM e o tamanho de dominio in-plane foi medido em funcao da duracao do pulso. Todas estas experiencias levaram a conclusao de que a parede de dominio em relaxors do tipo PZT e quase uma interface unidimensional. O mecanismo de contraste na superficie de relaxors do tipo PLZT e medido por PFMAs estruturas de dominio versus evolucao da profundidade foram estudadas em cristais PZN-4,5%PT, com diferentes orientacoes atraves da PFM. Padroes de dominio irregulares com tamanhos tipicos de 20-100 nm foram observados nas superficies com orientacao das amostras unpoled?. Pelo contrario, os cortes de cristal exibem dominios regulares de tamanho micron normal, com os limites do dominio orientados ao longo dos planos cristalograficos permitidos. A existencia de nanodominios em cristais com orientacao esta provisoriamente (wrong Word) atribuida a natureza relaxor de PZN-PT, onde pequenos grupos polares podem formar-se em coindicoes de zero-field-cooling (ZFC). Estes nanodominios sao considerados como os nucleos do estado de polarizacao oposta e podem ser responsaveis pelo menor campo coercitivo para este corte de cristal em particular. No entanto, a histerese local piezoeletrica realizada pelo PFM a escala nanometrica indica uma mudanca de comportamento de PZN-PT semelhante para ambas as orientacoes cristalograficas investigadas. A evolucao das estruturas de dominio com polimento abaixo da superficie do cristal foi investigada. O dominio de ramificacoes e os efeitos de polarizacao de triagem apos o polimento e as medicoes de temperatura tem sido estudados pela PFM e pela analise SEM. Alem disso, verificou-se que a intensidade do sinal piezoelectrico a partir das estruturas de nanodominio diminui com o aumento da temperatura, acabando por desaparecer aos 430 K (orientacao ) e 470 K (orientacao ). Esta diferenca de temperatura nas transicoes de fase local em cristais de diferentes orientacoes e explicada pelo forte efeito de superficie na transicao da fase ferroeletrica em relaxors. A comutacao da polarizacao em relaxor ergodico e nas fases ferroelectricas do sistema PMN-PT foram realizadas pela combinacao de tres metodos, Microscopia de Forca Piezoelectrica, medicao de um unico ponto de relaxamento eletromecânico e por ultimo mapeamento de espectroscopia de tensao. A dependencia do comportamento do relaxamento na amplitude e tempo da tensao de pulso foi encontrada para seguir um comportamento logaritmico universal com uma inclinacao quase constante. Este comportamento e indicativo da progressiva populacao dos estados de relaxamento lento, ao contrario de uma relaxacao linear na presenca de uma ampla distribuicao do tempo de relaxamento. O papel do comportamento de relaxamento, da nao-linearidade ferroelectrica e da heterogeneidade espacial do campo na ponta da sonda de AFM sobre o comportamento do ciclo de histerese e analisada em detalhe. Os ciclos de histerese para ergodica PMN- 10%PT sao mostrados como cineticamente limitados, enquanto que no PMN, com maior teor de PT, sao observados verdadeiros ciclos de histerese ferroelectrica com vies de baixa nucleacao.

Augmentation mastopexy after bariatric surgery: evaluation of patient satisfaction and surgical results.

PubMed

Junior, Wilson Cintra; Modolin, Miguel Luiz Antonio; Rocha, Rodrigo Itocazo; Gemperli, Rolf

2016-01-01

to evaluate patient satisfaction and surgical results obtained after mastopexy with breast implant inclusion. we conducted a prospective study of 20 consecutive female patients with a mean age of 39.9 years, submitted to augmentation mastopexy. We applied semi-directed psychological interviews pre and postoperatively. The answers to the evaluations were tabulated, categorized, and allowed patient satisfaction analysis. We evaluated surgical results through photographic analysis of three independent plastic surgeons, in the pre and postoperative periods, when scores were attributed to the following items: breasts shape, breasts volume, breasts symmetry, nipple-areolar complex position, and scar quality and extent. nineteen patients (95%) referred satisfaction with the surgical results attained (p<0,001). The mean sum of the scores attributed by the three surgeons to each patient varied between 4.7 and 10, with an overall mean of 7.28. The results were considered good or great for 65% of the sample and poor for 8.4%. there was a 95% satisfaction rate among patients with the results obtained through augmentation mastopexy. The photographic analysis of the results obtained a mean score of 7.28, considered as a good result, albeit the weak correlation among evaluators. avaliar a satisfação das pacientes e os resultados cirúrgicos obtidos após a mastopexia com inclusão de implantes mamários. estudo prospectivo com 20 pacientes consecutivas do sexo feminino, com média etária de 39,9 anos, que foram submetidas à mastopexia de aumento. Foram aplicadas entrevistas psicológicas semidirigidas nos períodos pré e pós-operatórios e cujas respostas foram tabuladas, divididas em categorias, e possibilitaram a avaliação da satisfação das pacientes. Foi realizada avaliação dos resultados cirúrgicos através da análise fotográfica por três cirurgiões plásticos independentes, nos períodos pré e pós-operatórios, que atribuíram notas aos seguintes itens: forma da mama, volume da mama, simetria entre as mamas, posicionamento do complexo aréolo-papilar e qualidade e extensão das cicatrizes. dezenove pacientes (95%) referiram satisfação com o resultado cirúrgico obtido (p<0,001). A média das somatórias das notas atribuídas pelos três cirurgiões, referentes a cada paciente, variou entre 4,7 e 10, sendo a média geral de 7,28. Os resultados foram considerados bons ou ótimos para 65% da amostra e pobres para 8,4%. houve satisfação de 95% das pacientes com os resultados obtidos pela mastopexia de aumento. A análise fotográfica dos resultados obteve nota média de 7,28, caracterizado como bom resultado, apesar da fraca concordância entre os avaliadores.

Perda de massa em ventos empoeirados de estrelas supergigantes

NASA Astrophysics Data System (ADS)

Vidotto, A. A.; Jatenco-Pereira, V.

2003-08-01

Em praticamente todas as regiões do diagrama HR, as estrelas apresentam evidências observacionais de perda de massa. Na literatura, pode-se encontrar trabalhos que tratam tanto do diagnóstico da perda de massa como da construção de modelos que visam explicá-la. O amortecimento de ondas Alfvén tem sido utilizado como mecanismo de aceleração de ventos homogêneos. Entretanto, sabe-se que os envelopes de estrelas frias contêm grãos sólidos e moléculas. Com o intuito de estudar a interação entre as ondas Alfvén e a poeira e a sua conseqüência na aceleração do vento estelar, Falceta-Gonçalves & Jatenco-Pereira (2002) desenvolveram um modelo de perda de massa para estrelas supergigantes. Neste trabalho, apresentamos um estudo do modelo acima proposto para avaliar a dependência da taxa de perda de massa com alguns parâmetros iniciais como, por exemplo, a densidade r0, o campo magnético B0, o comprimento de amortecimento da onda L0, seu fluxo f0, entre outros. Sendo assim, aumentando f0 de 10% a partir de valores de referência, vimos que aumenta consideravelmente, enquanto que um aumento de mesmo valor em r0, B0 e L0 acarreta uma diminuição em .

Telephone interventions for adherence to colpocytological examination.

PubMed

Lima, Thais Marques; Nicolau, Ana Izabel Oliveira; Carvalho, Francisco Herlânio Costa; Vasconcelos, Camila Teixeira Moreira; Aquino, Priscila de Souza; Pinheiro, Ana Karina Bezerra

2017-02-06

to test the effects of behavioral and educational intervention by telephone on adherence of women with inappropriate periodicity to colpocytological examination. quasi-experimental study with a sample of 524 women, selected with the following inclusion criteria: be aged between 25 and 64 years, have initiated sexual activity, have inappropriate periodicity of examination and have mobile or landline phone. The women were divided into two groups for application of behavioral and educational intervention by telephone. It was used an intervention script according to the principles of Motivational Interviewing. on comparing the results before and after the behavioral and educational interventions, it was found that there was a statistically significant change (p = 0.0283) with increase of knowledge of women who participated in the educational intervention. There was no change in the attitude of women of any of the groups and there was an increase of adherence to colpocytological examination in both groups (p < 0.0001), with greater adherence of women participating in the behavioral group (66.8%). the behavioral and educational interventions by phone were effective in the adherence of women to colpocytological examination, representing important strategies for permanent health education and promotion of care for the prevention of cervical cancer. testar os efeitos de intervenção comportamental e educativa por telefone na adesão das mulheres com periodicidade inadequada ao exame colpocitológico. estudo quase-experimental, com amostra constituída por 524 mulheres selecionadas conforme os critérios de inclusão: estar na faixa etária entre 25 e 64 anos, ter iniciado atividade sexual, estar com a periodicidade do exame inadequada e possuir telefone móvel ou fixo. As mulheres foram divididas em dois grupos para aplicação da intervenção comportamental e educativa por telefone. Utilizou-se um roteiro de intervenção segundo os preceitos da Entrevista Motivacional. ao comparar antes e depois das intervenções comportamental e educativa constatou-se que houve uma mudança estatisticamente significativa (p = 0,0283) no aumento do conhecimento das mulheres que participaram da intervenção educativa; não houve mudança comprovada na atitude das mulheres de nenhum dos grupos e houve um aumento da adesão ao exame colpocitológico nos dois grupos (p < 0,0001), com maior adesão das mulheres que participaram do grupo comportamental (66,8%). as intervenções comportamentais e educativas por telefone foram eficazes na adesão das mulheres ao exame colpocitológico, representando estratégias importantes para educação permanente em saúde, promovendo a atenção para a prevenção do câncer cérvico-uterino. comprobar los efectos de intervención comportamental y educativa por teléfono en la adhesión de las mujeres, con periodicidad inadecuada, al examen de citología vaginal. estudio casi experimental, con muestra constituida por 524 mujeres seleccionadas conforme a los siguientes criterios de inclusión: estar en el intervalo etario entre 25 y 64 años, haber iniciado actividad sexual, estar con la periodicidad del examen inadecuada y poseer teléfono móvil o fijo. Las mujeres fueron divididas en dos grupos para aplicación de la intervención comportamental y educativa por teléfono. Se utilizó una guía de intervención según los preceptos de la Entrevista Motivacional. al comparar antes y después de la intervención comportamental y educativa se constató que hubo un cambio estadísticamente significativo (p = 0,0283) en el aumento del conocimiento de las mujeres que participaron de la intervención educativa; no hubo cambio comprobado en la actitud de las mujeres de ninguno de los grupos y hubo un aumento de la adhesión al examen de citología vaginal en los dos grupos (p < 0,0001), con mayor adhesión de las mujeres que participaron del grupo comportamental (66,8%). las intervenciones comportamentales y educativas por teléfono fueron eficaces en obtener la adhesión de las mujeres al examen de citología vaginal, representando estrategias importantes para una educación permanente en salud y promoviendo la atención para la prevención del cáncer del cuello uterino.

Factors associated with chronic back pain in adults in Brazil.

PubMed

Malta, Deborah Carvalho; Oliveira, Max Moura de; Andrade, Silvânia Suely Caribé de Araújo; Caiaffa, Waleska Teixeira; Souza, Maria de Fatima Marinho de; Bernal, Regina Tomie Ivata

2017-06-01

To identify associations of chronic back pain with sociodemographic characteristics, lifestyles, body mass index, self-reported chronic diseases and health assessment, according to sex. We analyzed data from the 2013 National Health Survey, estimated the prevalence and their respective 95% confidence intervals (95%CI) of chronic back pain, according to selected variables and performed adjustment by age and education. 18.5% of the Brazilian population reported chronic back pain, 15.5% (95%CI 14.7-16.4) of them being men and 21.1% (95%CI 20.2-22.0) being women. The characteristics that remained associated and statistically significant (p < 0.05) after adjustment, in men, were: age group, higher in men with 65 years or older (ORa = 6.06); low education level; living in rural area; history of smoking, high salt intake, increase in the time of heavy physical activity at work and at home; being overweight (ORa = 1.18) or obese (ORa = 1.26); diagnostic of hypertension (ORa = 1.42), high cholesterol (ORa = 1.60); and worse health assessment in comparison with very good (good [ORa = 1.48]; regular [ORa = 3.22]; poor [ORa = 5.00], very poor [ORa = 8.60]). Among women, they were: increase with age, higher among women with 55-64 years (ORa = 3.64); low education level; history of smoking, regular candy consumption, high salt intake, heavy physical activity at work and at home and increase in the time of these activities; being overweight (ORa = 1.23) or obese (ORa = 1.32); diagnosis of hypertension (ORa = 1.50), high cholesterol (ORa = 1.84); and worse health assessment than very good (good [ORa = 1.43]; regular [ORa = 3.16]; poor [ORa = 5.44], very poor [ORa = 8.19]). Our findings point out differences by sex and contribute to the knowledge of the panorama of chronic back pain, which, besides affecting individuals, generate negative socioeconomic impacts, by causing work-related disabilities and hindering everyday activities. Identificar associações de dor crônica na coluna com características sociodemográficas, estilos de vida, índice de massa corporal, doenças crônicas autorreferidas e avaliação do estado de saúde, segundo sexo. Foram analisados dados da Pesquisa Nacional de Saúde 2013; estimadas as prevalências e seus respectivos intervalos de 95% de confiança (IC95%) da dor crônica na coluna, segundo variáveis selecionadas; e realizado ajuste por idade e escolaridade. 18,5% da população brasileira referiram dor crônica na coluna, sendo 15,5% (IC95% 14,7-16,4) em homens e 21,1% (IC95% 20,2-22,0) em mulheres. As características que se mantiveram associadas após o ajuste e estatisticamente significativas (p < 0,05) em homens foram: aumento com a faixa etária, sendo maior entre aqueles com 65 anos ou mais (ORa = 6,06); baixa escolaridade; morar em área rural; histórico de tabagismo, consumo elevado de sal, aumento do tempo de prática de atividade física pesada no trabalho e atividade pesada no domicílio; ter sobrepeso (ORa = 1,18) ou obesidade (ORa = 1,26); diagnóstico de hipertensão (ORa= 1,42), colesterol elevado (ORa = 1,60); e pior avaliação do estado de saúde (bom [ORa = 1,48]; regular [ORa = 3,22]; ruim [ORa = 5,00], muito ruim [ORa = 8,60]). Entre mulheres: aumento com a faixa etária, sendo maior entre as mulheres com 55-64 anos (ORa = 3,64); menor escolaridade; histórico de tabagismo, consumo de doces regularmente, consumo elevado de sal, atividade e aumento do tempo de prática de atividade física pesada no trabalho e atividade pesada no domicílio; ter sobrepeso (ORa = 1,23) ou obesidade (ORa = 1,32); diagnóstico de hipertensão (ORa = 1,50), colesterol elevado (ORa = 1,84); e piora da avaliação do estado de saúde (bom [ORa = 1,43]; regular [ORa = 3,16]; ruim [ORa = 5,44], muito ruim [ORa = 8,19]). Os achados apontam diferenças por sexo e contribuem no conhecimento do panorama da dor crônica na coluna, que além de afetar o indivíduo, geram impactos socioeconômicos negativos, por ocasionar incapacidades relacionadas ao trabalho e realização de atividades cotidianas.

Contribution to the scintillation detection optimization in double phase detectors for direct detection of dark matter

NASA Astrophysics Data System (ADS)

Balan, Catalin

Na ultima decada, foram feitos grandes progressos no desenvolvimento dos detetores de detecao direta das particulas que constituem a materia negra. Com estrategias do aumento gradual do volume do alvo e, simultaneamente, de reducao dos niveis de fundo, a experiencia XENON obteve resultados muito bons e perspetivas promissoras para a detecao de materia negra. Tarefas relativas a analise de dados experimentais adquiridos com o detetor de dupla fase em uso, assim como as simulacoes do campo eletrico, desenvolvimento, montagem e testes para o proximo detetor XENON1T, assim como a participacao regular na manutencao geral e monitorizacao do prototipo atual XENON100 no LNGS, constituiram o plano de trabalhos para as atividades de investigacao do presente doutoramento e a minha contribuicao para a otimizacao da detecao de cintilacao nos detetores da experiencia XENON. A necessidade de alcancar niveis elevados de sensibilidade, requer inovacao em todos os aspetos fisicos do detetor, assim como a reducao de todas as fontes de radioatividade que contribuem para o fundo. O modo mais indicado de operacao para os detetores com enchimento a Xe no estado liquido e gasoso envolve a medicao da cintilacao primaria e da secundaria provenientes da interacao das particulas no Xe liquido. A razao entre estes dois sinais permite diferenciar claramente a maior parte dos eventos correspondentes as fundo dos eventos correspondentes a WIMPs. Deste modo, a leitura dos sinais correspondentes a cintilacao e de extrema importancia. A amplitude do sinal de cintilacao antes dos fotossensores e maximizada atraves da otimizacao de varios parametros, tais como a geometria do alvo do detetor, a transparencia das grelhas dos eletrodos, a uniformidade do ganho em cintilacao secundaria e a utilizacao de material reflectivo para cobrir as superficies que nao sao fotossensiveis.

Extracellular adenosine 5'-triphosphate concentrations changes in rat spinal cord associated with the activation of urinary bladder afferents. A microdialysis study.

PubMed

Rocha, Jeová Nina

2016-01-01

To determine adenosine 5'-triphosphate levels in the interstice of spinal cord L6-S1 segment, under basal conditions or during mechanical and chemical activation of urinary bladder afferents. A microdialysis probe was transversally implanted in the dorsal half of spinal cord L6-S1 segment in female rats. Microdialysate was collected at 15 minutes intervals during 135 minutes, in anesthetized animals. Adenosine 5'-triphosphate concentrations were determined with a bioluminescent assay. In one group of animals (n=7) microdialysate samples were obtained with an empty bladder during a 10-minutes bladder distension to 20 or 40cmH2O with either saline, saline with acetic acid or saline with capsaicin. In another group of animals (n=6) bladder distention was performed and the microdialysis solution contained the ectonucleotidase inhibitor ARL 67156. Basal extracellular adenosine triphosphate levels were 110.9±35.34fmol/15 minutes, (mean±SEM, n=13), and bladder distention was associated with a significant increase in adenosine 5'-triphosphate levels which was not observed after bladder distention with saline solution containing capsaicin (10µM). Microdialysis with solution containing ARL 67156 (1mM) was associated with significantly higher extracellular adenosine 5'-triphosphate levels and no further increase in adenosine 5'-triphosphate was observed during bladder distension. Adenosine 5'-triphosphate was present in the interstice of L6-S1 spinal cord segments, was degraded by ectonucleotidase, and its concentration increased following the activation of bladder mechanosensitive but not of the chemosensitive afferents fibers. Adenosine 5'-triphosphate may originate either from the central endings of bladder mechanosensitive primary afferent neurons, or most likely from intrinsic spinal neurons, or glial cells and its release appears to be modulated by capsaicin activated bladder primary afferent or by adenosine 5'-triphosphate itself. Determinar as concentrações extracelulares do 5'-trifosfato de adenosina no interstício dos segmentos medulares L6-S1, em condições basais ou durante a ativação mecânica e química das fibras aferentes vesicais. Um cateter de microdiálise foi implantado no sentido transversal na parte dorsal da medula espinal, entre os segmentos L6-S1 de ratas. O microdialisado foi coletado em intervalos de 15 minutos, durante 135 minutos, com os animais anestesiados. A concentração de 5'-trifosfato de adenosina nas amostras foi determinada mediante ensaio de bioluminescência. Em um grupo de animais (n=7), as amostras de microdialisado foram obtidas com a bexiga vazia, com distensão da bexiga para volume de 20 ou 40cmH2O, com solução salina, solução salina com ácido acético, ou solução salina com capsaicina. Em outro grupo (n=6), foi realizada com a bexiga distendida, e a solução para microdiálise continha o inibidor de ectonucleotidase ARL 67156. Os níveis extracelulares de trifosfato de adenosina no início do estudo foram 110,9±35,36fmol/15 minutos (média±EPM, n=13), e a distensão da bexiga causou um aumento nos níveis de 5'-trifosfato de adenosina, o que não foi observado após a distensão da bexiga com solução salina contendo capsaicina (10µM). A microdiálise com solução contendo ARL 67156 (1mM) foi associada com significante aumento dos níveis de trifosfato de adenosina extracelular, e nenhum aumento do trifosfato de adenosina foi observado durante a distensão da bexiga. O 5'-trifosfato de adenosina está presente no interstício do segmento L6-S1 da medula espinal, é degradado por ectonucleotidases, e sua concentração aumentou com a ativação das fibras aferentes mecanossensíveis da bexiga, mas não das quimiossensíveis. O 5'-trifosfato de adenosina pode ter sido liberado das terminações centrais dos neurônios aferentes primários mecanossensíveis ou, mais provavelmente, de neurônios espinais intrínsecos, ou ainda de células gliais. Sua liberação parece ser modulada por fibras aferentes primárias da bexiga ativadas pela capsaicina ou pelo próprio 5'-trifosfato de adenosina.

Fotometria de grupos compactos de galáxias no infravermelho próximo

NASA Astrophysics Data System (ADS)

Brasileiro, F.; Mendes de Oliveira, C.

2003-08-01

Apresentamos medidas nas bandas J, H e K de cerca de 90 galáxias em 34 grupos compactos. Através da combinação dos novos dados, com dados obtidos na literatura para a banda B, investigamos como as luminosidades, cores, tamanhos e massas das galáxias em grupos compactos foram afetadas por processos dinâmicos, e como essas diferem de galáxias em ambientes menos densos. Uma comparação dos novos valores obtidos com aqueles listados no catálogo 2MASS, mostram que para 50 galáxias estudadas em comum, as diferenças nas magnitudes J, H e K estão dentro dos erros fotométricos. Através da construção dos diagramas de cor (J-H x H-K e B-H x J-K), percebemos que as galáxias em grupos compactos ocupam posições no diagrama diferentes das posições de galáxias em campo ou em aglomerados, sendo mais parecidas com as posições ocupadas por galáxias HII, ou com excesso de poeira, acreditamos que tal deslocamento é derivado do aumento da taxa de formação estelar.

Associative organization of nursing: struggles for the social recognition of the profession (1943-1946).

PubMed

Teixeira, Kyvia Rayssa Bezerra; Queirós, Paulo Joaquim Pina; Pereira, Laís de Araújo; Peres, Maria Angélica de Almeida; Almeida, Antonio José de; Santos, Tânia Cristina Franco

2017-01-01

To describe the circumstances that determine the creation of the Brazilian Association of Graduate Nurses of the Federal District Section and analyze its implications for the reorganization of the field of nursing. Qualitative, socio-historical, documentary study. The analysis generated the following category: Creation of a new group to guarantee unity: Brazilian Association of Graduate Nurses in the Federal District Section. The economic crisis resulting from the Second World War, the creation of the Paulista Association of Graduate Nurses and the increase in the number of Schools of Nursing in the country were decisive for the Brazilian Association of Graduate Nurses to reformulate its statute as to guarantee its unit. The creation of the Federal District Section consisted of one of the strategies of the Association to reorganize the field of nursing, in order to ensure the recognition of the profession by the society. Descrever as circunstâncias que determinam a criação da Associação Brasileira de Enfermeiras Diplomadas Seção do Distrito Federal e analisar as implicações dessa criação para a reorganização do campo da enfermagem. Estudo qualitativo, sócio-histórico, documental. A análise gerou a seguinte categoria: Criação de um novo grupo para garantir a unidade: Associação Brasileira de Enfermeiras Diplomadas Seção do Distrito Federal. A crise econômica, decorrente da Segunda Guerra Mundial, a criação da Associação Paulista de Enfermeiras Diplomadas e o aumento do número de escolas de enfermagem no país foram determinantes para que a Associação Brasileira de Enfermeiras Diplomadas reformulasse seu estatuto, de modo a garantir sua unidade. A criação da Seção do Distrito Federal consistiu em uma das estratégias da associação para reorganizar o campo da enfermagem, de modo a assegurar o reconhecimento da profissão pela sociedade.

Effects of dignity therapy on terminally ill patients: a systematic review.

PubMed

Donato, Suzana Cristina Teixeira; Matuoka, Jéssica Yumi; Yamashita, Camila Cristófero; Salvetti, Marina de Goés

2016-01-01

Analyzing the evidence of the effects of dignity therapy onterminally ill patients. A Systematic review of the literature conducted using the search strategy in six databases. Inclusion criteria were primary studies, excluding literature reviews (systematic or not) and conceptual articles. Ten articles were analyzed regarding method, results and evidence level. Dignity therapy improved the sense of meaning andpurpose, will to live, utility, quality of life, dignity and family appreciationin studies with a higher level of evidence. The effects are not well established in relation to depression, anxiety, spirituality and physical symptoms. Studies with a moderate to high level of evidence have shown increased sense of dignity, will to live and sense of purpose. Further studies should be developed to increase knowledge about dignity therapy. Analisar as evidências sobre os efeitos da terapia da dignidade para pacientes em fase terminal de vida. Revisão sistemática da literatura realizada em seis bases de dados na estratégia de busca. Os critérios de inclusão foram estudos primários, excluindo-se revisões da literatura (sistemáticas ou não) e artigos conceituais. Dez artigos foram analisados quanto ao método, aos resultados e nível de evidência. Nos estudos com maior nível de evidência, a terapia da dignidade melhorou o senso de significado, propósito, vontade de viver, utilidade, qualidade de vida, dignidade e apreciação familiar.Os efeitos não estão bem estabelecidos em relação à depressão, ansiedade, espiritualidade e aos sintomas físicos. Os estudos de nível de evidência de moderado a alto demonstraram aumento do senso de dignidade, vontade de viver e senso de propósito. Mais estudos devem ser desenvolvidos para ampliar o conhecimento sobre a terapia da dignidade.

Educational intervention for collecting sputum for tuberculosis: a quasi-experimental study.

PubMed

Sicsú, Amélia Nunes; Salem, Julia Ignez; Fujimoto, Luciana Botinelly Mendonça; Gonzales, Roxana Isabel Cardozo; Cardoso, Maria do Socorro de Lucena; Palha, Pedro Fredemir

2016-06-07

to evaluate the quality of the sputum sample before and after the Nursing guidance to patients. this is a quasi-experimental research design, single group type, before and after, non-randomized study. The study enrolled patients with suspected pulmonary tuberculosis, respiratory symptomatic patients for over three weeks, aged over 18 years, of both genders and without tuberculosis history in the last two years. The educational intervention consisted of individualized guidance on the collection of sputum sample, which was based on the guidelines of the Ministry of Health of Brazil and on the explanatory folder delivery. in this study participated 138 patients with suspected pulmonary tuberculosis. The results showed significant increase of the samples with purulent particles, volume greater than 5 mL and increased rate of patients diagnosed with tuberculosis, after the educational intervention. it was shown that after the educational intervention, it was observed sputum samples with better quality, with satisfactory aspect and volume for the effectiveness of the bacilloscopic examination. avaliar a qualidade da amostra de escarro antes e após as orientações de Enfermagem ao paciente. estudo com delineamento de pesquisa quase experimental, do tipo grupo único, antes e depois, não randomizado. Participaram do estudo pacientes com suspeita de tuberculose pulmonar, sintomáticos respiratórios por mais de três semanas, maiores de 18 anos, de ambos os sexos e sem antecedente de tuberculose nos últimos dois anos. A intervenção educativa consistiu em orientações individualizadas sobre a coleta da amostra de escarro, fundamentadas nas diretrizes do Ministério da Saúde do Brasil e na entrega de folder explicativo. participaram 138 pacientes com suspeita de tuberculose pulmonar. Os resultados evidenciaram importante acréscimo das amostras com partículas purulentas, volume maior que 5mL e aumento na taxa de pacientes diagnosticados com tuberculose, após a intervenção educativa. comprovou-se que, após a intervenção educativa, obtiveram-se amostras de escarro com maior qualidade, com aspecto e volume satisfatórios para efetividade do exame baciloscópico. evaluar la calidad de la muestra de esputo antes y después de las orientaciones de Enfermería al paciente. de estudio con diseño de investigación casi experimental, del tipo grupo único, antes y después, no aleatorio. Participaron del estudio pacientes con sospecha de tuberculosis pulmonar, sintomáticos respiratorios por más de 3 semanas, mayores de 18 años, de los dos sexos y sin antecedente de tuberculosis en los últimos dos años. La intervención educativa consistió en orientaciones individualizadas sobre la recolección de la muestra de esputo, fundamentadas en las directrices del Ministerio de la Salud de Brasil y en la entrega de folder explicativo. participaron 138 pacientes con sospecha de tuberculosis pulmonar. Los resultados evidenciaron un importante aumento de las muestras con partículas purulentas, volumen mayor que 5mL y aumento en la tasa de pacientes diagnosticados con tuberculosis, después de la intervención educativa. se comprobó que, después de la intervención educativa, se obtuvieron muestras de esputo con mejor calidad, con aspecto y volumen satisfactorios para efectividad del examen de baciloscopía.

Projeto educação em ciências com observatórios virtuais: a participação da Escola Moppe no período 2000-2003

NASA Astrophysics Data System (ADS)

Wuensche, C. A.; Gavioli, E.; Oliveira, A. L. P. R. S.; da Silva, C.; Cardoso, H. P.; Estácio, S.

2003-08-01

O projeto Educação em Ciências com Observatórios Virtuais foi concebido pelo Instituto Astronômico e Geofísico da USP, agregando diversas instituições de ensino e pesquisa no país para desenvolver competências diversas na educação fundamental, média e superior utilizando a astronomia como ferramenta multidisciplinar. Este trabalho descreve a participação da MOPPE, escola-piloto do INPE no projeto, no período de 2000-2003. Serão apresentadas 1) a criação de um clube de ciências (1999 a 2001) cujo tema foi a colonização de Marte e 2) a ementa de astronomia trabalhada com as 7a. e 8a. séries do ensino fundamental. A proposta do projeto Colonizando Marte foi estudar diversos aspectos de uma missão interplanetária e construir experiementos que permitissem quantificar esses aspectos. Os resultados obtidos incluiram apresentações nas SBPC Jovem em 2000 e 2001. Discutiremos também as ementas de astronomia trabalhadas desde 2001 e o envolvimento dos alunos com atividades ligadas a astronomia, fora da aula de ciências. A inclusão de astronomia no currículo das últimas séries motivou a participação de mais alunos culminando com a conquista de duas medalhas para alunos da 7a. série na Olimpiada Brasileira de Astronomia em 2002. Houve também um aumento no número de participantes na OBA 2003 e nos projetos de astronomia mais elaborados nas Feira de Ciências de 2001 e 2002. Destacamos em 2003 a inclusão da MOPPE no projeto TIE - Telescopes in Education - da NASA, que utiliza o telescópio do Observatório de Mount Wilson (EUA) para observações remotas em projetos pedagógicos para o ensino de astronomia.

Sensor de orvalho/chuva aplicado à operação de telescópios

NASA Astrophysics Data System (ADS)

Raffaelli, J. C.; Neres, N. L.; Strauss, C.

2003-08-01

Foi desenvolvida uma estação meteorológica para o telescópio robótico Obelix do Observatório Abrahão de Moraes que inclui sensores de temperatura e umidade, além de um inédito sensor de orvalho e chuva que comanda o fechamento automático da cúpula caso haja perigo de condensação. Este sensor é composto de uma malha de segmentos metálicos próximos e detecta o aumento da condutividade do ar que precede a condensação. Esse método é mais confiável que o critério de 100% de umidade, que pode causar falsos alarmes devido a imprecisão dos sensores de umidade em geral e por não considerar a influência dos ventos que dificultam a condensação. O trabalho apresenta o método de construção desse sensor e os testes de avaliação. Sugere-se portanto a inclusão desse sensor nas estações meteorológicas dos telescópios do país.

EVALUATION OF THE THORACOABDOMINAL MOBILITY OF OBESE SUBJECTS IN PRE-BARIATRIC SURGERY.

PubMed

Veloso, Ana Paula Limongi Richardelli; Cusmanich, Karla Garcez

Obesity can affect the thorax, diaphragm, and alterations in respiratory function even if the lungs are within normality. The respiratory compliance is very reduced by the increase in fat mass. To evaluate the effect of the physical therapeutic respiratory exercises on the thoracoabdominal mobility of obese individuals in pre-bariatric surgery. Cross-sectional and descriptive study, which used the cirtometry (axillary, xiphoid and abdominal) to evaluate the mobility of 74 individuals, 27 men and 47 women, in pre-bariatric surgery, assisted by the team EMAD, after eight weeks of physiotherapy, following a protocol of exercises, reevaluating and compared the measures pre and post intervention. Had positive correlation abdominal mobility in the total volume of all participants (p=0.010) and also for all the measures in the measurement of residual volume in three levels (p=0.000). Comparing genders, in total volume, cirtometry abdominal greater for women (p=0.015) when compared to men and residual volume, significance for either men or women in all measurements (p=0.000). Obese patients that underwent the physiotherapeutic treatment during the preoperative period, had pré respiratory dynamics improved by the increase in the mobility of the chest cavity and by the improvement of respiratory conscience. A obesidade pode afetar o tórax e o diafragma, determinando alterações na função respiratória, mesmo quando os pulmões se apresentam dentro da normalidade. A complacência respiratória é muito reduzida pelo aumento de massa gordurosa. Avaliar o efeito de exercícios fisioterapêuticos respiratórios sobre a mobilidade torácica de indivíduos obesos no pré-operatório de cirurgia bariátrica. Estudo transversal e descritivo, que utilizou a cirtometria (axilar, xifoide e abdominal) para avaliar a mobilidade de 74 indivíduos, 27 homens e 47 mulheres, em pré-operatório de cirurgia bariátrica, assistidos pela equipe EMAD, após oito semanas de fisioterapia, seguindo um protocolo de exercícios, reavaliando e comparado as medidas pré e pós a intervenção. Apresentaram correlação positiva a mobilidade abdominal no volume total de todos os participantes (p=0,010) e também para todas as medidas na mensuração do volume residual nos três níveis (p=0,000). Comparando os sexos, no volume total, a cirtometria abdominal maior das mulheres (p=0,015) quando comparada a dos homens e no volume residual, significância tanto para os homens quanto para as mulheres em todas as mensurações (p=0,000). Obesos que se submeteram ao tratamento fisioterapêutico durante o período pré-operatório, tiveram dinâmica respiratória melhorada pelo aumento da mobilidade da caixa torácica e pela melhora da consciência respiratória.

Thin films for gas sensors

NASA Astrophysics Data System (ADS)

Pires, Jose Miguel Alves Correia

Nos ultimos anos tem-se assistido a um aumento dos investimentos na investigacao de novos materiais para aplicacao em sensores. Apesar de ja existir um bom numero de dispositivos explorados comercialmente, muitas vezes, quer devido aos elevados custos de producao, quer devido a uma crescente exigencia do ponto de vista das caracteristicas de funcionamento, continua a ser necessario procurar novos materiais ou novas formas de producao que permitam baixar os custos e melhorar o desempenho dos dispositivos. No campo dos sensores de gases tem-se verificado continuos avancos nos ultimos anos. Continua todavia a ser necessario conhecer melhor, tanto os processos de producao dos materiais, como os mecanismos que regulam a sensibilidade dos dispositivos aos gases, de modo a orientar adequadamente a investigacao dos novos materiais, nomeadamente no que se refere a optimizacao dos parâmetros que nao satisfazem ainda os requisitos do mercado. Um dos materiais que tem mostrado melhores qualidades para aplicacao em sensores de gases de tipo resistivo e o dioxido de estanho. Este material tem sido produzido sob diversas formas e usando diferentes tecnicas, como sejam: sol-gel [1], pulverizacao catodica (sputtering) por magnetrao [2-4], sinterizacao de pos [5, 6], ablacao laser [7] ou RGTO [8]. Os resultados obtidos revelam que as caracteristicas dos dispositivos sao muito dependentes das tecnicas usadas na sua producao. A deposicao usando sputtering reactivo por magnetrao e uma tecnica que permite obter filmes finos de oxido de estanho com diferentes caracteristicas, quer do ponto de vista da estrutura, quer da composicao, e por isso, tambem, com diferentes sensibilidades aos gases. No âmbito deste trabalho, foram produzidos filmes de SnO2 usando sputtering DC reactivo com diferentes condicoes de deposicao. Os substratos usados foram lâminas de vidro e o alvo foi estanho com 99.9% de pureza. Foi estudada a influencia da atmosfera de deposicao, da pressao parcial do O2, da temperatura do substrato e da potencia da descarga na estrutura do material depositado. Durante a deposicao, alem dos parâmetros ja referidos, foram tambem registados a pressao de base antes da entrada dos gases de sputtering, os fluxos de oxigenio e argon durante a deposicao, a distância alvo-substrato, o tempo de deposicao, a corrente e a tensao aplicadas ao magnetrao. Foram feitas algumas experiencias usando uma fonte RF, para comparacao. (Abstract shortened by ProQuest.).

Applications for a hybrid operating room in thoracic surgery: from multidisciplinary procedures to --image-guided video-assisted thoracoscopic surgery.

PubMed

Terra, Ricardo Mingarini; Andrade, Juliano Ribeiro; Mariani, Alessandro Wasum; Garcia, Rodrigo Gobbo; Succi, Jose Ernesto; Soares, Andrey; Zimmer, Paulo Marcelo

2016-01-01

The concept of a hybrid operating room represents the union of a high-complexity surgical apparatus with state-of-the-art radiological tools (ultrasound, CT, fluoroscopy, or magnetic resonance imaging), in order to perform highly effective, minimally invasive procedures. Although the use of a hybrid operating room is well established in specialties such as neurosurgery and cardiovascular surgery, it has rarely been explored in thoracic surgery. Our objective was to discuss the possible applications of this technology in thoracic surgery, through the reporting of three cases. RESUMO O conceito de sala híbrida traduz a união de um aparato cirúrgico de alta complexidade com recursos radiológicos de última geração (ultrassom, TC, radioscopia e/ou ressonância magnética), visando a realização de procedimentos minimamente invasivos e altamente eficazes. Apesar de bem estabelecido em outras especialidades, como neurocirurgia e cirurgia cardiovascular, o uso da sala hibrida ainda é pouco explorado na cirurgia torácica. Nosso objetivo foi discutir as aplicações e as possibilidades abertas por essa tecnologia na cirurgia torácica através do relato de três casos.

Negative pressure therapy for the treatment of complex wounds.

PubMed

Lima, Renan Victor Kümpel Schmidt; Coltro, Pedro Soler; Farina, Jayme Adriano

2017-01-01

The objective of this study is to evaluate the effectiveness of negative pressure therapy (NPT) in the treatment of complex wounds, with emphasis on its mechanisms of action and main therapeutic indications. We searched the Pubmed / Medline database for articles published from 1997 to 2016, and selected the most relevant ones. The mechanisms of action of NPT involveboth physical effects, such as increased perfusion, control of edema and exudate, reduction of wound dimensions and bacterial clearance, and biological ones, such as the stimulation of granulation tissue formation, microdeformations and reduction of Inflammatory response. The main indications of NPT are complex wounds, such as pressure ulcers, traumatic wounds, operative wound dehiscences, burns, necrotizing wounds, venous ulcers, diabetic wounds, skin grafts, open abdomen, prevention of complications in closed incisions and in the association with instillation of solutions in infected wounds. RESUMO O objetivo desse estudo é avaliar a eficácia da terapia por pressão negativa (TPN) no tratamento de feridas complexas, com ênfase em seus mecanismos de ação e principais indicações terapêuticas. Foi realizada revisão na base de dados Pubmed / Medline, em artigos publicados de 1997 a 2016, e selecionados os mais relevantes. O mecanismo de ação da TPN envolve efeitos físicos, como o aumento da perfusão, controle do edema e do exsudato, redução das dimensões da ferida e depuração bacteriana, e biológicos, como o estímulo à formação de tecido de granulação, microdeformações e redução da resposta inflamatória local. As principais indicações da TPN são as feridas complexas como úlceras por pressão, feridas traumáticas, deiscências de ferida operatória, queimaduras, feridas necrotizantes, úlceras venosas, feridas diabéticas, os enxertos de pele, o abdome aberto, na prevenção de complicações em incisões fechadas e na associação com instilação de soluções em feridas infectadas.

Focus and coverage of Bolsa Família Program in the Pelotas 2004 birth cohort.

PubMed

Schmidt, Kelen H; Labrecque, Jeremy; Santos, Iná S; Matijasevich, Alicia; Barros, Fernando C; Barros, Aluisio J D

2017-03-30

To describe the focalization and coverage of Bolsa Família Program among the families of children who are part of the 2004 Pelotas birth cohort (2004 cohort). The data used derives from the integration of information from the 2004 cohort and the Cadastro Único para Programas Sociais do Governo Federal (CadÚnico - Register for Social Programs of the Federal Government), in the 2004-2010 period. We estimated the program coverage (percentage of eligible people who receive the benefit) and its focus (proportion of eligible people among the beneficiaries). We used two criteria to define eligibility: the per capita household income reported in the cohort follow-ups and belonging to the 20% poorest families according to the National Economic Indicator (IEN), an asset index. Between 2004 and 2010, the proportion of families in the cohort that received the benefit increased from 11% to 34%. We observed an increase in all wealth quintiles. In 2010, by income and wealth quintiles (IEN), 62%-72% of the families were beneficiaries among the 20% poorest people, 2%-5% among the 20% richest people, and about 30% of families of the intermediate quintile. According to household income (minus the benefit) 29% of families were eligible in 2004 and 16% in 2010. By the same criteria, the coverage of the program increased from 43% in 2004 to 71% in 2010. In the same period, by the wealth criterion (IEN), coverage increased from 29% to 63%. The focalization of the program decreased from 78% in 2004 to 32% in 2010 according to income, and remained constant (37%) according to the IEN. Among the families of the 2004 cohort, there was a significant increase in the program coverage, from its inception until 2010, when it was near 70%. The focus of the program was below 40% in 2010, indicating that more than half of the beneficiaries did not belong to the target population. Descrever a focalização e a cobertura do Programa Bolsa Família nas famílias de crianças que fazem parte da coorte de nascimentos de Pelotas, 2004 (coorte de 2004). Os dados utilizados derivam da integração de informações da coorte de 2004 e do Cadastro Único para Programas Sociais do Governo Federal, no período de 2004 a 2010. Estimamos a cobertura do programa (percentual de elegíveis que recebem bolsa) e seu foco (proporção de elegíveis entre os beneficiários). Utilizamos dois critérios para definir elegibilidade: a renda familiar per capita relatada nas avaliações da coorte e pertencer aos 20,0% mais pobres pela classificação do Indicador Econômico Nacional, um índice de bens. Entre 2004 e 2010, a proporção de famílias beneficiárias da coorte passou de 11% para 34%. Houve aumento em todos os quintis de riqueza. Em 2010, por quintis de renda e Indicador Econômico Nacional, 62%-72% das famílias eram beneficiárias entre os 20% mais pobres, 2%-5% entre os 20% mais ricos, e cerca de 30% das famílias do quintil intermediário. Pelo critério de renda familiar, excluindo-se o valor do benefício do programa, 29% das famílias eram elegíveis em 2004 e 16% em 2010. Pelo mesmo critério, a cobertura do programa passou de 43% em 2004 para 71% em 2010. No mesmo período, pelo critério de riqueza (Indicador Econômico Nacional), a cobertura passou de 29% para 63%. A focalização do programa caiu de 78% em 2004 para 32% em 2010 de acordo com a renda e permaneceu constante (37%) de acordo com o Indicador Econômico Nacional. Entre as famílias da coorte de 2004, observa-se aumento importante da cobertura do programa, de seu início até 2010, quando ficou perto de 70%. O foco do programa ficou abaixo de 40% em 2010, indicando que mais da metade dos beneficiários não pertencem à população alvo.

Effects of passive inhalation of cigarette smoke on structural and functional parameters in the respiratory system of guinea pigs.

PubMed

Vasconcelos, Thiago Brasileiro de; Araújo, Fernanda Yvelize Ramos de; Pinho, João Paulo Melo de; Soares, Pedro Marcos Gomes; Bastos, Vasco Pinheiro Diógenes

2016-01-01

To evaluate the effects of passive inhalation of cigarette smoke on the respiratory system of guinea pigs. Male guinea pigs were divided into two groups: control and passive smoking, the latter being exposed to the smoke of ten cigarettes for 20 min in the morning, afternoon and evening (30 cigarettes/day) for five days. After that period, inflammatory parameters were studied by quantifying mesenteric mast cell degranulation, as well as oxidative stress, in BAL fluid. In addition, we determined MIP, MEP, and mucociliary transport (in vivo), as well as tracheal contractility response (in vitro). In comparison with the control group, the passive smoking group showed a significant increase in mast cell degranulation (19.75 ± 3.77% vs. 42.53 ± 0.42%; p < 0.001) and in the levels of reduced glutathione (293.9 ± 19.21 vs. 723.7 ± 67.43 nM/g of tissue; p < 0.05); as well as a significant reduction in mucociliary clearance (p < 0.05), which caused significant changes in pulmonary function (in MIP and MEP; p < 0.05 for both) and airway hyperreactivity. Passive inhalation of cigarette smoke caused significant increases in mast cell degranulation and oxidative stress. This inflammatory process seems to influence the decrease in mucociliary transport and to cause changes in pulmonary function, leading to tracheal hyperreactivity. Avaliar os efeitos da inalação passiva da fumaça de cigarro no sistema respiratório de cobaias. Foram utilizadas cobaias machos, divididas em dois grupos: controle e tabagismo passivo, esse último exposto à fumaça de dez cigarros por 20 min pela manhã, tarde e noite (30 cigarros/dia) por 5 dias. Após esse período, parâmetros inflamatórios foram estudados através da contagem de degranulação de mastócitos no mesentério e de estresse oxidativo a partir do LBA. Adicionalmente, foram verificadas PImáx, PEmáx, transporte mucociliar (in vivo) e contratilidade traqueal (in vitro). Na comparação com o grupo controle, o grupo tabagismo passivo apresentou um aumento significativo na degranulação de mastócitos (19,75 ± 3,77% vs. 42,53 ± 0,42%; p < 0,001), nos níveis de glutationa reduzida (293,9 ± 19,21 vs. 723,7 ± 67,43 nM/g de tecido; p < 0,05) e uma redução significativa no transporte mucociliar (p < 0,05), provocando alterações significativas na função pulmonar, tanto na PImáx como na PEmáx (p < 0,05 para ambas), e hiper-reatividade nas vias aéreas. A inalação passiva da fumaça de cigarro ocasionou aumentos significativos na degranulação de mastócitos e no estresse oxidativo. Esse processo inflamatório parece ter influenciado a diminuição do transporte mucociliar e causado alterações na função pulmonar, proporcionando um quadro de hiper-reatividade traqueal.

HOW TO ACHIEVE AND MAINTAIN NOTE 6: POSTGRADUATE PROGRAM IN TRANSLATIONAL SURGERY - UNIFESP.

PubMed

Sabino-Neto, Miguel; Ferreira, Lydia Masako

2015-01-01

To show the way to reach and stay in note 6 in the evaluation process of Medicine III of CAPES. Capes determinations were reviewed concerning this topic, grades 6 and 7, and also the difficulties and facilities of running a program that amounted to Note 6 after restructuring and being in compliance with regulations. The main points to achieve and maintain Note 6 were: 1) regular production of master's and doctoral theses with appropriate distribution among all teachers; 2) average time of appropriate titration, as well as strict selection of students who resets the withdrawals and cancellations; 3) production of scientific articles in high impact journals and with academic and student participation in most part; 4) progressive and substantial increase in fundraising and patent search; 5) progressive increase in international exchanges with joint production; 6) visibility through new bilingual website and updated weekly; 7) numerous solidarity activities in research, but also in health services for the population and even in basic education; 8) rigorous selection of students (through design analysis, curriculum and teacher training program); 9) maintenance of high levels teachers production; 10) preparing new teachers for guidance through participation as co-supervision and involvement in the program to fit the needs. The Postgraduate Program in Translational Surgery went through difficult times; was submitted to a series of measures, adjustments, cooperation and understanding of the teaching staff, that took the program from note 3 - and almost closing - to a level of excellence keeping note 6 for three consecutive three-year periods of evaluation. Mostrar o caminho para alcançar e se manter na nota 6 no processo de avaliação da Medicina III da Capes. Foram revisadas as determinações da Capes concernentes ao tema, conceitos 6 e 7, e também as dificuldades e facilidades próprias da execução de um programa que ascendeu à nota 6 após reestruturação e adequação às normas vigentes. Os pontos principais para alcançar e manter conceito 6 foram: : 1) produção regular de teses de mestrado e doutorado com distribuição adequada entre todos os orientadores; 2) tempo médio de titulação adequado, assim como rígida seleção do alunado que zera as desistências e cancelamentos; 3) produção de artigos científicos alta em revistas de impacto e com participação docente e discente na sua grande maioria; 4) aumento progressivo e substancial da captação de recursos e busca de patentes; 5) aumento progressivo dos intercâmbios internacionais com produção conjunta; 6) visibilidade através de novo site bilíngue e atualizado semanalmente; 7) inúmeras atividades de solidariedade em pesquisa, mas também em Serviços de Saúde para a população e mesmo no ensino básico; 8) rigorosa seleção dos alunos (através de análise de projeto, currículo e programa de estágio docente); 9) manutenção de índices elevados de produção dos docentes; 10) preparação de novos docentes para orientação através de participação como co-orientação e envolvimento no programa para se adequar às necessidades. O Programa de Pós-Graduação em Cirurgia Translacional passou por momentos difíceis e que através de uma série de medidas, ajustes e a colaboração e compreensão do seu corpo docente pode sair da nota 3 e quase fechamento, para um nível de excelência mantendo nota 6 em três triênios seguidos.

[Assessment of a project for integrated management of care given to patients with type-2 diabetes in the Local Health Authority 21 of Legnago (Veneto Region, Northern Italy) in the period 2010-2012].

PubMed

Marcon, Alessandro; Vaona, Alberto; Rigon, Giulio; Carazzolo, Marco; Del Zotti, Franco; Girotto, Sandro; Marafetti, Claudio

2016-01-01

OBIETTIVI: descrivere, nella ASL 21 di Legnago (VR), l'andamento di alcuni indicatori sanitari tra il 2009, anno precedente all'avvio di un progetto triennale per la gestione integrata dell'assistenza al paziente con diabete mellito di tipo 2, e il 2012, ultimo anno del progetto. DISEGNO: studio longitudinale trasversale ripetuto. SETTING E PARTECIPANTI: tutti i pazienti diabetici di tipo 2 della ASL 21, identificati nei database aziendali (in base a esenzioni per patologia, accessi al servizio diabetologico, consumo di farmaci antidiabetici e strisce per la determinazione della glicemia) e nelle cartelle cliniche dei medici di famiglia. PRINCIPALI MISURE DI OUTCOME: numero di test diagnostici e di follow-up erogati, consumo di farmaci, prestazioni specialistiche, accessi al pronto soccorso, ricoveri e mortalità. RISULTATI: nonostante un calo generalizzato (-3,1%) nei test erogati dalla ASL 21 ai suoi assistititi nel periodo 2009-2012, l'analisi ha documentato un marcato aumento per gli esami previsti nella gestione del diabete, quali curve da carico glicemico (+104,3%), emoglobina glicata (+19,0%) e microalbuminuria (+296,1%). I soggetti identificati come diabetici sono aumentati da 8.084 nel 2009 (5,2%) a 9.221 nel 2012 (5,9%). Sono stati osservati aumenti nella prevalenza di pazienti visitati presso un servizio diabetologico (dal 22,6% al 39,0%), nonché negli utilizzatori di metformina (dal 28,0% al 37,5%), insuline (dal 13,5% al 18,3%) e incretine (dall'1,4% al 9,0%). Il consumo di sulfaniluree è, invece, calato (dal 49,9% al 40,8%), come anche l'erogazione di alcune prestazioni specialistiche, gli accessi al pronto soccorso e i ricoveri, mentre il tasso di mortalità è rimasto stabile (29,6 decessi x1.000/anno). CONCLUSIONE: durante il periodo di implementazione del progetto sembra essersi verificato un aumento della sensibilità diagnostica e una maggiore presa in carico del paziente diabetico. Anche se la natura osservazionale dello studio non consente di dimostrare una relazione causa-effetto, i risultati sembrano supportare l'ipotesi che la gestione integrata della patologia migliori l'appropriatezza dell'assistenza.

Association of the protein tyrosine phosphatase non-receptor 22 polymorphism (PTPN22) with endometriosis: a meta-analysis.

PubMed

Pabalan, Noel; Jarjanazi, Hamdi; Christofolini, Denise Maria; Bianco, Bianca; Barbosa, Caio Parente

2017-01-01

To evaluate PTPN22 C1858T polymorphism and the risk of endometriosis. A meta-analysis of 10 published case-control studies (from four articles), with a total sample of 971 cases and 1,181 controls, was performed. We estimated risk (odds ratio and 95% confidence intervals) of endometriosis associations with the C1858T polymorphism. A significant increased risk in all genetic models of the variant T allele with endometriosis (odds ratio: 3.14-5.55; p<0.00001-0.002) was found. The analysis without the study whose controls deviated from the Hardy-Weinberg equilibrium exacerbated these effects in the homozygous and recessive models (odds ratio: 7.19-9.45; p<0.00001-0.0002). In the Italian subgroup, a significant risk association was found in the homozygous and recessive models (odds ratio: 8.72-11.12; p=0.002). The associations observed between PTPN22 (C1858T) and the risk of endometriosis suggest this polymorphism might be a useful susceptibility marker for this disease. Avaliar o polimorfismo PTPN22 C1858T e o risco de endometriose. Foi realizada uma metanálise de 10 estudos caso-controle publicados (a partir de quatro artigos), com uma amostra total de 971 casos e 1.181 controles. O risco da associação da endometriose com o polimorfismo C1858T foi estimado em razão de chance e intervalo de confiança de 95%. Observou-se um aumento de risco significativo em todos os modelos genéticos com o alelo variante T e a endometriose (razão de chance: 3,14-5,55; p<0,00001-0,002). A análise sem incluir o estudo, em que os controles não estavam em equilíbrio de Hardy-Weinberg, mostrou aumento significativo nos modelos homozigotos e recessivos (razão de chance: 7,19-9,45; p<0,00001-0,0002). No subgrupo italiano, uma associação significativa foi encontrada considerando os modelos homozigoto e recessivo (razão de chance: 8,72-11,12; p=0,002). As associações observadas entre PTPN22 (C1858T) e o risco de endometriose sugerem que este polimorfismo pode ser um marcador de suscetibilidade para a endometriose.

The Douro estuarine plume: Detection, processes and dynamics =

NASA Astrophysics Data System (ADS)

Mendes, Renato Paulo dos Santos

O Douro e um dos maiores rios da Peninsula Iberica, constituindo a maior descarga de agua doce para o Oceano Atlântico na costa noroeste portuguesa. A sua pluma estuarina tem particular relevância na dinâmica costeira e na modulacao de fenomenos biogeoquimicos. Sao objetivos desta dissertacao contribuir para a compreensao dos processos fisicos associados a geracao e propagacao da pluma estuarina do Rio Douro no oceano, assim como para o conhecimento dos seus padroes de dispersao e da forma como estes alteram a hidrologia e a circulacao costeira, considerando os agentes forcadores tipicos deste fenomeno (caudal fluvial, vento e mare) e indices climaticos relevantes. Para concretizacao destes objetivos foram desenvolvidas e aplicadas metodologias inovadoras de processamento de dados de detecao remota, assim como novas implementacoes estuarinas e costeiras de modelos numericos. Atraves de imagens MODIS, otimizadas para o estudo de fenomenos costeiros, efetuou-se uma detecao rigorosa da pluma. Identificou-se uma relacao entre o sinal turbido nLw555 e o caudal, demonstrando-se este produto como um bom proxy para a observacao da pluma no oceano. As escalas temporais e espaciais da pluma foram caraterizadas atraves destas imagens, combinadas com dados de caudal fluvial, mare, vento e precipitacao, e tambem com indices climaticos relevantes. Para compreender a propagacao da pluma e caracterizar a sua dinâmica e impacto na circulacao costeira, foi desenvolvida uma aplicacao 3D de modelos estuarinos e costeiros com malhas aninhadas de resolucao variavel. Definiramse e analisaram-se diferentes cenarios de vento e descarga fluvial. A interacao da pluma do Rio Douro e do Minho foi ainda analisada atraves dos resultados de simulacoes baseadas num evento de inverno. Os compositos turbidos mostraram que a pluma e facilmente detetada quando o caudal e maior que 500 m3 s??1. A descarga fluvial e o vento sao os principais forcadores da sua propagacao, enquanto a mare e apenas importante na regiao proxima a embocadura do estuario. Observaram-se relacoes a uma escala interanual entre a turbidez da pluma e os indices climaticos East Atlantic e NAO, com uma correlacao maxima identificada com 1 e 3 meses de desfasamento, respetivamente. Com base nos resultados das simulacoes efetuadas, a pluma e classificada como de larga escala e de advecao superficial, apresentando caracteristicas de uma pluma prototipica. Em condicoes de caudal moderado a elevado, a descarga estuarina e suficiente para gerar uma corrente costeira para norte sem acao do vento. Em eventos de ventos leste, a propagacao da pluma e similar ao caso sem vento, com um aumento da velocidade da corrente. Uma corrente costeira para sul e unicamente identificada sob condicoes de forte vento de oeste. Ventos de norte tendem a estender a pluma para o largo, com uma inclinacao na direcao sudoeste, enquanto ventos de sul intensificam a corrente para norte, sendo a mistura das plumas do Douro e do Minho uma consequencia possivel. A analise desta interacao apontou a contribuicao do Douro como importante na estabilizacao da WIBP e nas trocas de agua entre o oceano e as Rias Baixas. A interacao da pluma do Douro com estuarios localizados a sul da sua foz e a confirmacao in situ da recirculacao observada nos resultados numericos afiguram-se como temas relevantes para investigacoes futuras. None

Workload and associated factors: a study in maritime port in Brazil.

PubMed

Cezar-Vaz, Marta Regina; Bonow, Clarice Alves; Almeida, Marlise Capa Verde de; Sant'Anna, Cynthia Fontella; Cardoso, Leticia Silveira

2016-11-28

to identify the effect of the mental, physical, temporal, performance, total effort and frustration demands in the overall workload, and in the same way analyze the global burden of port labor and associated factors that contribute most to their decrease or increase. a cross-sectional, quantitative study, developed with 232 dock workers. For data collection, a structured questionnaire with descriptive, occupational, smoking and illicit drug use variables was applied, as well as variables on the load on the tasks undertaken at work, based on the questionnaire NASA Task Load Index. For data analysis, we used the analysis of the Poisson regression model. the demands physical demand and total effort showed greater effect on the overall workload, indicating high overall load on port work (134 employees - 58.8%). The following remained associated statistically with high levels of workload: age (p = 0.044), to be employee of the wharfage (p = 0.006), work only at night (p = 0.025), smoking (p = 0.037) and use of illegal drugs (p = 0.029). the workload in this type of activity was high, and the professional category and work shift the factors that contributed to the increase, while the age proved to be a factor associated with a decrease. identificar o efeito das demandas mental, física, temporal, de desempenho, esforço total e frustração na carga global de trabalho, da mesma maneira que analisar a carga global de trabalho portuário e fatores associados que mais contribuem para sua diminuição ou aumento. estudo transversal, quantitativo, desenvolvido com 232 trabalhadores portuários. Para a coleta de dados, foi aplicado um questionário estruturado com variáveis de caracterização, ocupacional, tabagismo e uso de drogas ilícitas, além de variáveis sobre a carga nas tarefas desenvolvidas no trabalho, com base no questionário NASA Task Load Index. Para análise dos dados, utilizou-se a análise do modelo de regressão de Poisson. as demandas exigência física e esforço total apresentaram maior efeito sobre a carga global de trabalho, indicando elevada carga global no trabalho portuário (134 trabalhadores - 58,8%). Permaneceram associados, estatisticamente, com níveis elevados da carga de trabalho: idade (p = 0,044), ser trabalhador da capatazia (p = 0,006), trabalhar somente no período noturno (p = 0,025), tabagismo (p = 0,037) e uso de drogas ilícitas (p = 0,029). a carga de trabalho, nesse tipo de atividade, foi alta, sendo a categoria profissional e o turno de trabalho os fatores que contribuíram para o aumento, enquanto a idade mostrou-se fator associado à sua diminuição. identificar el efecto de las demandas mentales, físicas de tiempo y de desempeño, el esfuerzo total y la frustración en la carga de trabajo global, al mismo tiempo que se analizan la carga global de trabajo portuario y los factores asociados que contribuyen principalmente a su disminución o aumento. estudio transversal cuantitativo desarrollado con 232 trabajadores portuarios. Para la recolección de datos se aplicó un cuestionario estructurado con variables de caracterización, ocupacionales, tabaquismo y uso de drogas ilícitas así como también variables sobre la carga en las tareas desarrolladas en el trabajo, en base en el cuestionario NASA Task Load Index. Para el análisis de los datos se utilizó análisis de regresión de Poisson. las demandas exigencia física y esfuerzo total presentaron mayor efecto sobre la carga global de trabajo, indicando una elevada carga global en el trabajo portuario (134 trabajadores 58,8%). Estaban asociados estadísticamente con niveles elevados de la carga de trabajo: la edad (p = 0,044); ser trabajador de la capatacía (p = 0,006); trabajar solamente en el periodo nocturno (p = 0,025); tabaquismo (p = 0,037); y uso de drogas ilícitas (p = 0,029). la carga de trabajo en este tipo de actividad fue alta, siendo la categoría profesional y el turno de trabajo los factores que contribuyeron para este aumento, mientras que la edad fue un factor asociado a su disminución.

Propriedades de estruturas temporais rápidas submilimétricas durante uma grande explosão solar

NASA Astrophysics Data System (ADS)

Raulin, J.-P.; Kaufmann, P.; Gimenez de Castro, C. G.; Pacini, A. A.; Makhmutov, V.; Levato, H.; Rovira, M.

2003-08-01

Apresentamos novas propriedades de variações rápidas da emissão submilimétrica durante uma das maiores explosões solares do ciclo solar 23. Os dados analisados neste estudo foram obtidos com o Telescópio Solar Submilimétrico (SST), que observa o Sol em 212 GHz e 405 GHz, e comparados com emissões em Raios-X duros e Raios-gama (fótons de energia > 10 MeV), que foram obtidas pelo experimento GRS do Yohkoh. Aplicamos diferentes metodologias para detectar e caracterizar, ao longo do evento, os pulsos submilimétricos (duração de 50-300 ms) detectados acima de uma componente mais lenta (alguns minutos). Os resultados mostram que durante a fase impulsiva, num instante próximo ao tempo do máximo do evento, houve um aumento da ocorrência de maiores e de mais rápidas estruturas temporais. Também identificamos uma boa correlação com as emissões em raios-X e raios-gama (até a faixa de energia 10-100 MeV), indicando que os pulsos rápidos submilimétricos refletiram injeções primárias de energia durante o evento.O espectro do fluxo desses pulsos é crescente com a freqüência entre 212 and 405 GHz, na maioria dos casos, ao contrário do observado para a componente gradual. As posições calculadas para as estruturas rápidas são discretas, compactas e localizadas em toda a área da região ativa, o que é previsto nos modelos de explosões solares decorrentes de instabilidades múltiplas em diferentes pequenas regiões. Por outro lado, a posição calculada para a componente lenta é estável durante a fase impulsiva. Assim, a comparação entre as características do espectro de fluxo e da localização da emissão, para os pulsos rápidos e para a componente gradual, sugere que as respectivas emissões são de natureza diferente.

Hepcidin: an important iron metabolism regulator in chronic kidney disease.

PubMed

Antunes, Sandra Azevedo; Canziani, Maria Eugênia Fernandes

2016-01-01

Anemia is a common complication and its impact on morbimortality in patients with chronic kidney disease (CKD) is well known. The discovery of hepcidin and its functions has contributed to a better understanding of iron metabolism disorders in CKD anemia. Hepcidin is a peptide mainly produced by hepatocytes and, through a connection with ferroportin, it regulates iron absorption in the duodenum and its release of stock cells. High hepcidin concentrations described in patients with CKD, especially in more advanced stages are attributed to decreased renal excretion and increased production. The elevation of hepcidin has been associated with infection, inflammation, atherosclerosis, insulin resistance and oxidative stress. Some strategies were tested to reduce the effects of hepcidin in patients with CKD, however more studies are necessary to assess the impact of its modulation in the management of anemia in this population. Resumo Anemia é uma complicação frequente e seu impacto na morbimortalidade é bem conhecido em pacientes com doença renal crônica (DRC). A descoberta da hepcidina e de suas funções contribuíram para melhor compreensão dos distúrbios do metabolismo de ferro na anemia da DRC. Hepcidina é um peptídeo produzido principalmente pelos hepatócitos, e através de sua ligação com a ferroportina, regula a absorção de ferro no duodeno e sua liberação das células de estoque. Altas concentrações de hepcidina descritas em pacientes com DRC, principalmente em estádios mais avançados, são atribuídas à diminuição da excreção renal e ao aumento de sua produção. Elevação de hepcidina tem sido associada à ocorrência de infecção, inflamação, aterosclerose, resistência à insulina e estresse oxidativo. Algumas estratégias foram testadas para diminuir os efeitos da hepcidina em pacientes com DRC, entretanto, serão necessários mais estudos para avaliar o impacto de sua modulação no manejo da anemia nessa população.

Influência da termoablação com baixa e alta densidade de energia na junção safeno-femoral, utilizando laser endovenoso 1470 nm

PubMed Central

de Araujo, Walter Junior Boim; Erzinger, Fabiano Luiz; Caron, Filipe Carlos; Nejm, Carlos Seme; Timi, Jorge Rufino Ribas

2017-01-01

Resumo Contexto Faz-se importante o conhecimento técnico dos ajustes de potência e de densidade de energia linear endovenosa (linear endovenous energy density, LEED) adequados para atingir o objetivo final da termoablação endovenosa (endovenous laser ablation, EVLA). Objetivos Avaliar a influência de diferentes LEEDs em termos de patência e presença de refluxo, bem como determinar a evolução clínica. Métodos Foram incluídas 60 veias safenas magnas (VSM). Os pacientes foram randomizados em dois grupos: EVLA com baixa potência (7 W e LEED de 20-40 J/cm) e com alta potência (15 W e LEED de 80-100 J/cm). O acompanhamento com eco-Doppler e escore de severidade clínica venoso (VCSS) foi realizado nos intervalos de 3-5 dias, 30 dias, 180 dias e 1 ano após o procedimento. Resultados Dezoito pacientes (29 membros) tratados com 7W de potência e 13 pacientes (23 membros) com 15 W completaram o estudo. Não houve diferença significativa considerando idade, tempo de cirurgia e o uso de analgésicos, lateralidade, gênero e presença de comorbidades. O LEED médio foi de 33,54 J/cm no grupo de 7 W e de 88,66 J/cm no de 15 W. Ambos apresentaram melhora no VCSS, redução significativa dos diâmetros da JSF e ausência de diferença significativa quanto ao aumento do comprimento do coto da VSM e de refluxo após o tratamento. Conclusões A utilização de maior densidade de energia mostrou-se mais efetiva em relação à estabilização do comprimento do coto da VSM e do refluxo em 6 meses. Fazem-se necessários estudos com um período de acompanhamento maior para fundamentar essa hipótese. PMID:29930650

Violence against children and adolescents: the perspective of Primary Health Care.

PubMed

Carlos, Diene Monique; Pádua, Elisabete Matallo Marchesini de; Ferriani, Maria das Graças Carvalho

2017-01-01

To analyze the care provided by Basic Health Units (BHU) to families involved in domestic intrafamily violence against children and adolescents. Qualitative research, based on the Paradigm of Complexity. Data collection was performed with 41 professionals through focus groups and semi-structured interviews. The following categories emerged from data analysis: 'Everything comes here', which reflects the legitimate place of BHUs for the population and the actions taken to build care for families; and 'We only do what is really necessary', which brings the look to violence still based on the positivist and biomedical paradigm. The model of understanding and construction of work processes in the BHU is structured in the aforementioned paradigm. Nurses have the possibility to become agents of change, both in professionals' training and in the care thought and provided to communities. Analisar o cuidado realizado por Unidades Básicas de Saúde (UBS) junto a famílias envolvidas na violência intrafamiliar contra crianças e adolescentes. Pesquisa qualitativa, fundamentada no Paradigma da Complexidade. A coleta de dados foi realizada com 41 profissionais, por meio de grupos focais e entrevistas semiestruturadas. Da análise dos dados, emergiram as seguintes categorias: "Tudo desemboca aqui", que reflete o lugar legitimado das UBSs para a população e as ações realizadas para construção do cuidado às famílias; e "A gente só faz o que é indispensável mesmo", que traz o olhar para a violência ainda pautado no paradigma positivista e biomédico. O modelo de compreensão e construção dos processos de trabalho na UBS é estruturado no último paradigma citado. O enfermeiro tem a possibilidade de se colocar como um agente de mudanças, tanto na formação dos profissionais quanto no cuidado pensado e executado junto às comunidades.

BSSDATA - um programa otimizado para filtragem de dados em radioastronomia solar

NASA Astrophysics Data System (ADS)

Martinon, A. R. F.; Sawant, H. S.; Fernandes, F. C. R.; Stephany, S.; Preto, A. J.; Dobrowolski, K. M.

2003-08-01

A partir de 1998, entrou em operação regular no INPE, em São José dos Campos, o Brazilian Solar Spectroscope (BSS). O BSS é dedicado às observações de explosões solares decimétricas com alta resolução temporal e espectral, com a principal finalidade de investigar fenômenos associados com a liberação de energia dos "flares" solares. Entre os anos de 1999 e 2002, foram catalogadas, aproximadamente 340 explosões solares classificadas em 8 tipos distintos, de acordo com suas características morfológicas. Na análise detalhada de cada tipo, ou grupo, de explosões solares deve-se considerar a variação do fluxo do sol calmo ("background"), em função da freqüência e a variação temporal, além da complexidade das explosões e estruturas finas registradas superpostas ao fundo variável. Com o intuito de realizar tal análise foi desenvolvido o programa BSSData. Este programa, desenvolvido em linguagem C++, é constituído de várias ferramentas que auxiliam no tratamento e análise dos dados registrados pelo BSS. Neste trabalho iremos abordar as ferramentas referentes à filtragem do ruído de fundo. As rotinas do BSSData para filtragem de ruído foram testadas nos diversos grupos de explosões solares ("dots", "fibra", "lace", "patch", "spikes", "tipo III" e "zebra") alcançando um bom resultado na diminuição do ruído de fundo e obtendo, em conseqüência, dados onde o sinal torna-se mais homogêneo ressaltando as áreas onde existem explosões solares e tornando mais precisas as determinações dos parâmetros observacionais de cada explosão. Estes resultados serão apresentados e discutidos.

Ultrasonic location system =

NASA Astrophysics Data System (ADS)

Albuquerque, Daniel Filipe

Esta tese apresenta um sistema de localizacao baseado exclusivamente em ultrassons, nao necessitando de recorrer a qualquer outra tecnologia. Este sistema de localizacao foi concebido para poder operar em ambientes onde qualquer outra tecnologia nao pode ser utilizada ou o seu uso esta condicionado, como sao exemplo aplicacoes subaquaticas ou ambientes hospitalares. O sistema de localizacao proposto faz uso de uma rede de farois fixos permitindo que estacoes moveis se localizem. Devido a necessidade de transmissao de dados e medicao de distancias foi desenvolvido um pulso de ultrassons robusto a ecos que permite realizar ambas as tarefas com sucesso. O sistema de localizacao permite que as estacoes moveis se localizem escutando apenas a informacao em pulsos de ultrassons enviados pelos farois usando para tal um algoritmo baseado em diferencas de tempo de chegada. Desta forma a privacidade dos utilizadores e garantida e o sistema torna-se completamente independente do numero de utilizadores. Por forma a facilitar a implementacao da rede de farois apenas sera necessario determinar manualmente a posicao de alguns dos farois, designados por farois ancora. Estes irao permitir que os restantes farois, completamente autonomos, se possam localizar atraves de um algoritmo iterativo de localizacao baseado na minimizacao de uma funcao de custo. Para que este sistema possa funcionar como previsto sera necessario que os farois possam sincronizar os seus relogios e medir a distancia entre eles. Para tal, esta tese propoe um protocolo de sincronizacao de relogio que permite tambem obter as medidas de distancia entre os farois trocando somente tres mensagens de ultrassons. Adicionalmente, o sistema de localizacao permite que farois danificados possam ser substituidos sem comprometer a operabilidade da rede reduzindo a complexidade na manutencao. Para alem do mencionado, foi igualmente implementado um simulador de ultrassons para ambientes fechados, o qual provou ser bastante preciso e uma ferramenta de elevado valor para simular o comportamento do sistema de localizacao sobre condicoes controladas.

Civil liability of the ophthalmologist in the São Paulo Court of Appeals.

PubMed

Braga, Isabel de Fátima Alvim; Vieira, Kelly de Oliveira; Martins, Thiago Gonçalves Dos Santos

2017-01-01

To conduct a data survey on the subject of medical claims involving civil liability in ophthalmology at the São Paulo Court of Appeals. A case law research was carried out on the São Paulo Court of Appeals website searching for the keyword "ophthalmologist" for all years until 2016. Of the 65 cases found, 29 were selected. There has been an increase in the number of claims in ophthalmology, especially in surgical procedures on the anterior chamber of the eye. Most lower court judgments were for defendant. The study suggested the need for specialists to exercise the required amount of care when treating the patients, so that they may understand the risks inherent to the procedure. Despite the increase in claims, most decisions were favorable for the physician. Realizar um levantamento de dados sobre a temática dos processos envolvendo responsabilidade civil em sede da Oftalmologia no Tribunal de Justiça do Estado de São Paulo. Foi realizada uma pesquisa jurisprudencial por palavra-chave no site do Tribunal de Justiça do Estado de São Paulo com o seguinte termo de pesquisa "oftalmologista" para todos os anos até 2016. Foram encontrados 65 processos, dos quais 29 foram selecionados. Observou-se tendência ao aumento de processos na área, e predominância de processos em procedimentos oftalmológicos cirúrgicos em câmara anterior do olho. A maioria das sentenças de primeira instância foi improcedente. O estudo aponta para a necessidade de atenção dos especialistas para com o paciente, no sentido de que ele compreenda os riscos inerentes ao procedimento. Apesar do aumento de processos, a maioria permanece favorável ao médico.

Incorporando a variabilidade no processo de identificação do modelo de máximo global no Grade of Membership (GoM): considerações metodológicas

PubMed Central

Guedes, Gilvan Ramalho; Siviero, Pamila Cristina Lima; Caetano, André Junqueira; Machado, Carla Jorge; Brondízio, Eduardo

2012-01-01

A disponibilidade de bases de dados cada vez mais complexas e multidimensionais é um dos principais motivadores para o aumento do número de estudos que utilizam análises multivariadas baseadas em lógica de conjuntos nebulosos. Apesar da disseminação do método Grade of Membership nos trabalhos empíricos brasileiros da área de ciências sociais e saúde, questões relativas à identificabilidade e estabilidade dos parâmetros finais estimados pelo programa GoM 3.4 não foram suficientemente aprofundadas. Dada a relevância de se obterem parâmetros únicos e estáveis, Guedes et al. (2010) propuseram um procedimento empírico para localizar um modelo de máximo global (MG) com parâmetros estáveis. Entretanto, seu localizador de MG não incorpora qualquer medida de variabilidade. Neste artigo, tal limitação é contornada por meio da utilização de uma estatística de ponderação – Máximo Global Ponderado (MGP) – semelhante ao coeficiente de variação. Esse indicador busca não penalizar de forma desproporcional situações nas quais os desvios médios, apesar de diferentes de zero, são muito pequenos. Apresentam-se evidências de que o localizador MGP reduz a distância do modelo identificado à real estrutura latente dos dados em análise, quando comparados ao modelo identificado pelo localizador não ponderado, MG. PMID:23293402

Nurses' knowledge to identify early acute kidney injury.

PubMed

Nascimento, Roseli Aparecida Matheus do; Assunção, Murillo Santucci Cesar; Silva, João Manoel; Amendola, Cristina Prata; Carvalho, Taysa Martindo de; Lima, Emerson Quintino; Lobo, Suzana Margareth Ajeje

2016-01-01

To evaluate the knowledgeof nurses on early identification of acute kidney injury (AKI) in intensive care, emergency and hospitalization units. A prospective multi-center study was conducted with 216 nurses, using a questionnaire with 10 questions related to AKI prevention, diagnosis, and treatment. 57.2% of nurses were unable to identify AKI clinical manifestations, 54.6% did not have knowledge of AKI incidence in patients admitted to the ICU, 87.0% of the nurses did not know how to answer as regards the AKI mortality rate in patients admitted to the ICU, 67.1% answered incorrectly that slight increases in serum creatinine do not have an impact on mortality, 66.8% answered incorrectly to the question on AKI prevention measures, 60.4% answered correctly that loop diuretics for preventing AKI is not recommended, 77.6% answered correctly that AKI does not characterize the need for hemodialysis, and 92.5% said they had no knowledge of the Acute Kidney Injury Networkclassification. Nurses do not have enough knowledge to identify early AKI, demonstrating the importance of qualification programs in this field of knowledge. Avaliar o conhecimento do enfermeiro na identificação precoce da Injúria Renal Aguda (IRA) em Unidade de Terapia Intensiva, Unidade de Internação e Emergência. Estudo multicêntrico, prospectivo.Participaram do estudo 216 enfermeiros,por meio de questionário com 10 questões relacionadas à prevenção, ao diagnóstico e ao tratamento da IRA. 57,2% não souberam identificar as manifestações clínicas da IRA, 54,6% não têm conhecimento da incidência de IRA em pacientes internados na UTI, 87,0% dos enfermeiros não souberam responder ao índice de mortalidade de IRA em pacientes internados na UTI, 67,1% responderam incorretamente que aumentos discretos da creatinina sérica não têm impacto na mortalidade, 66,8% responderam incorretamente à questão sobre as medidas de prevenção da IRA, 60,4% acertaram quando responderam que não é recomendada a utilização de diuréticos de alça na prevenção da IRA, 77,6% acertaram ao responder que IRA não caracteriza necessidade de hemodiálise e 92,5% disseram não conhecer a classificação AKIN. Enfermeiros não têm conhecimento suficiente para a identificação precoce da IRA, mostrando a importância de programas de capacitação nesta área do conhecimento.

Design Structure Matrix (DSM) Methods and Applications for Naval Ship Design

DTIC Science & Technology

2013-05-23

Fax: 817-257-7227 E-mail: t.browninufetcu.edu Web : www. t vsonbrown i ng. com Administrative/Business Contact: Mrs. Teresa Miles Hendrix, MPA...mail: t.browninu(ajtcii.edu Web : www.tvsonbrownina.com Administrative/Business Contact: Mrs. Teresa Miles Hendrix, MPA Assistant Director of...STAKEHOLDER COM ABORDAGEM DE SISTEMAS ADAPTATIVOS A COMPLEXIDADE John Findlay, Ph D. e Abby Straus, M. Div. IMPLEMENTANDO FLEXIBILIDADE

Serotoninergic Modulation of Basal Cardiovascular Responses and Responses Induced by Isotonic Extracellular Volume Expansion in Rats.

PubMed

Semionatto, Isadora Ferraz; Raminelli, Adrieli Oliveira; Alves, Angelica Cristina; Capitelli, Caroline Santos; Chriguer, Rosangela Soares

2017-02-01

Isotonic blood volume expansion (BVE) induced alterations of sympathetic and parasympathetic activity in the heart and blood vessels, which can be modulated by serotonergic pathways. To evaluate the effect of saline or serotonergic agonist (DOI) administration in the hypothalamic paraventricular nucleus (PVN) on cardiovascular responses after BVE. We recorded pulsatile blood pressure through the femoral artery to obtain the mean arterial pressure (MAP), systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR) and the sympathetic-vagal ratio (LF/HF) of Wistar rats before and after they received bilateral microinjections of saline or DOI into the PVN, followed by BVE. No significant differences were observed in the values of the studied variables in the different treatments from the control group. However, when animals are treated with DOI followed by BVE there is a significant increase in relation to the BE control group in all the studied variables: MBP (114.42±7.85 vs 101.34±9.17); SBP (147.23±14.31 vs 129.39±10.70); DBP (98.01 ±4.91 vs 87.31±8.61); HR (421.02±43.32 vs 356.35±41.99); and LF/HF ratio (2.32±0.80 vs 0.27±0.32). The present study showed that the induction of isotonic BVE did not promote alterations in MAP, HR and LF/HF ratio. On the other hand, the injection of DOI into PVN of the hypothalamus followed by isotonic BVE resulted in a significant increase of all variables. These results suggest that serotonin induced a neuromodulation in the PVN level, which promotes an inhibition of the baroreflex response to BVE. Therefore, the present study suggests the involvement of the serotonergic system in the modulation of vagal reflex response at PVN in the normotensive rats. Expansão de volume extracelular (EVEC) promove alterações da atividade simpática e parassimpática no coração e vasos sanguíneos, os quais podem ser moduladas por vias serotoninérgicas. Avaliar o efeito da administração de salina ou agonista serotoninérgico (DOI) nos núcleos paraventriculares hipotalâmico (NPV) sobre respostas cardiovasculares após EVEC. Foram obtidos registros da pressão arterial pulsátil, por meio da artéria femoral, para obtenção dos valores da pressão arterial média (PAM), sistólica (PAS), diastólica (PAD), frequência cardíaca (FC) e razão simpático-vagal (LF/HF) de ratos Wistar antes e após receberem microinjeções bilaterais no NPV de salina ou DOI seguida de EVEC. Não foram observadas diferenças significativas dos valores das variáveis estudadas nos diferentes tratamentos do grupo controle. Entretanto, quando os animais são tratados com DOI seguida de EVEC ocorre aumento significativo em relação ao grupo controle com EVEC em todas as variáveis estudadas: PAM (114,42±7,85 vs 101,34±9,17), PAS (147,23±14,31 vs 129,39±10,70), PAD (98,01 ±4,91 vs 87,31±8,61), FC (421,02±43,32 vs 356,35±41,99) e LF/HF (2,32±0,80 vs 0,27±0,32). O presente estudo mostrou que a indução de EVEC isotônica não promoveu alterações na PAM, PAD, PAS, FC e LF/HF. Por outro lado, os animais que receberam microinjeção de DOI no NPV seguida de EVEC apresentaram aumento significativo de todas as variáveis. Esses resultados sugerem que a serotonina exerce uma neuromodulação em nivel do NPV, e essa promove uma inibição da resposta barorreflexa frente à EVEC. Assim, o presente trabalho sugere o envolvimento serotoninérgico na neuromodulação no nivel do NPV na resposta reflexa vagal em ratos normotensos.

Projeto observatórios virtuais: educação através de telescópios robóticos

NASA Astrophysics Data System (ADS)

Santana, P. H. S.; Shida, R. Y.

2003-08-01

O principal objetivo do projeto Observatórios Virtuais é o ensino na área de ciências através de atividades práticas desenvolvidas em colaboração entre instituições de pesquisa em astronomia e escolas de ensino médio e fundamental. Este ano deverá ser concluída a implantação do programa piloto de estudos, pesquisas e observação astronômica direta, com utilização em tempo real de telescópios robóticos, que assim funcionarão como "observatórios virtuais". O objetivo pedagógico das atividades práticas baseadas nas imagens atronômicas é desenvolver as habilidades e competências dos alunos no uso do método científico. Para isso, serão realizados projetos interdisciplinares, a partir de observações astronômicas, já que a astronomia é uma área interdisciplinar por excelência. Essas atividades terão níveis diferenciados de complexidade, que podem ser adequados aos vários graus do ensino e realidades regionais. Será dada ênfase ao desenvolvimento e aplicação em São Paulo, onde atua a equipe do IAG/USP. Como resultados apresentados no presente trabalho, temos a criação de um software em português para o processamento de imagens obtidas através de CCDs e a elaboração de material para as atividades educacionais relacionadas.

Patients with endometriosis using positive coping strategies have less depression, stress and pelvic pain.

PubMed

Donatti, Lilian; Ramos, Denise Gimenez; Andres, Marina de Paula; Passman, Leigh Jonathan; Podgaec, Sérgio

2017-01-01

To determine the correlations between coping strategies, depression, stress levels and pain perception in patients with endometriosis. This prospective and exploratory study included 171 women undergoing treatment for endometriosis between April and August 2014. The questionnaires used were Brief COPE, Beck Depression Inventory, Lipp's Stress Symptom Inventory for Adults and Visual Analogue Scale. Clinical data were collected from electronic medical records. Patients with endometriosis who used positive coping strategies had better adaptation to stress (p<0.004) and less depression (p<0.004). The presence and intensity of depression, stress and acyclic pelvic pain were directly associated (p<0.05). The intensity of dysmenorrhea was associated with the degree of depression (p<0.001), whereas acyclic pelvic pain was associated with the degree of depression (p<0.001), stress level (p<0.001) and stress type (p<0.001). We found a positive association between coping, depression levels, type and levels of stress and pain intensity in patients with endometriosis. The use of maladaptive coping strategies focused on emotion is correlated with increase in depression and stress. Observar a correlação entre estratégias de enfrentamento, depressão, níveis de estresse e percepção de dor em pacientes com endometriose. Estudo prospectivo e exploratório, que incluiu 171 mulheres em tratamento por endometriose entre abril e agosto de 2014. Foram utilizadas as escalas: COPE Breve, Inventário de Depressão de Beck, Inventário de Sintomas de Stress para Adultos de Lipp e a Escala Visual Analógica. Os dados clínicos foram coletados do prontuário eletrônico. Pacientes com endometriose que utilizaram estratégias positivas de enfrentamento apresentaram melhor adaptação ao estresse (p<0,004) e menos depressão (p<0,004). A presença e a intensidade da depressão, do estresse e da dor pélvica estiveram diretamente associadas (p<0,05). A intensidade da dismenorreia foi associada com o grau de depressão (p<0,001), enquanto a intensidade da dor pélvica acíclica esteve associada com o grau de depressão (p<0,001), nível de estresse (p<0,001) e tipo de estresse (p<0,001). Houve associação positiva entre coping, níveis de depressão, tipo e níveis de estresse e intensidade da dor nas pacientes com endometriose. A utilização de estratégias de coping desadaptativa focada na emoção está correlacionada com o aumento da depressão e do estresse.

Properties of self-assembled diluted magnetic semiconductor nanostructures =

NASA Astrophysics Data System (ADS)

Ankiewicz, Amelia Olga Goncalves

Este trabalho centra-se na investigacao da possibilidade de se conseguir um semicondutor magnetico diluido (SMD) baseado em ZnO. Foi levado a cabo um estudo detalhado das propriedades magneticas e estruturais de estruturas de ZnO, nomeadamente nanofios (NFs), nanocristais (NCs) e filmes finos, dopadas com metais de transicao (MTs). Foram usadas varias tecnicas experimentais para caracterizar estas estruturas, designadamente difraccao de raios-X, microscopia electronica de varrimento, ressonancia magnetica, SQUID, e medidas de transporte. Foram incorporados substitucionalmente nos sitios do Zn ioes de Mn2+ e Co2+ em ambos os NFs e NCs de ZnO. Revelou-se para ambos os ioes dopantes, que a incorporacao e heterogenea, uma vez que parte do sinal de ressonancia paramagnetica electronica (RPE) vem de ioes de MTs em ambientes distorcidos ou enriquecidos com MTs. A partir das intensidades relativas dos espectros de RPE e de modificacoes da superficie, demonstra-se ainda que os NCs exibem uma estrutura core-shell. Os resultados, evidenciam que, com o aumento da concentracao de MTs, a dimensao dos NCs diminui e aumentam as distorcoes da rede. Finalmente, no caso dos NCs dopados com Mn, obteve-se o resultado singular de que a espessura da shell e da ordem de 0.3 nm e de que existe uma acumulacao de Mn na mesma. Com o objectivo de esclarecer o papel dos portadores de carga na medicao das interaccoes ferromagneticas, foram co-dopados filmes de ZnO com Mn e Al ou com Co e Al. Os filmes dopados com Mn, revelaram-se simplesmente paramagneticos, com os ioes de Mn substitucionais nos sitios do Zn. Por outro lado, os filmes dopados com Co exibem ferromagnetismo fraco nao intrinseco, provavelmente devido a decomposicao spinodal. Foram ainda efectuados estudos comparativos com filmes de ligas de Zn1-xFexO. Como era de esperar, detectaram-se segundas fases de espinela e de oxido de ferro nestas ligas; todas as amostras exibiam curvas de histerese a 300 K. Estes resultados suportam a hipotese de que as segundas fases sao responsaveis pelo comportamento magnetico observado em muitos sistemas baseados em ZnO. Nao se observou nenhuma evidencia de ferromagnetismo mediado por portadores de carga. As experiencias mostram que a analise de RPE permite demonstrar directamente se e onde estao incorporados os ioes de MTs e evidenciam a importancia dos efeitos de superficie para dimensoes menores que 15 nm, para as quais se formam estruturas core-shell. As investigacoes realizadas no ambito desta tese demonstram que nenhuma das amostras de ZnO estudadas exibiram propriedades de um SMD intrinseco e que, no futuro, sao necessarios estudos teoricos e experimentais detalhados das interaccoes de troca entre os ioes de MTs e os atomos do ZnO para determinar a origem das propriedades magneticas observadas.

Biaxial seismic behaviour of reinforced concrete columns =

NASA Astrophysics Data System (ADS)

Rodrigues, Hugo Filipe Pinheiro

A analise dos efeitos dos sismos mostra que a investigacao em engenharia sismica deve dar especial atencao a avaliacao da vulnerabilidade das construcoes existentes, frequentemente desprovidas de adequada resistencia sismica tal como acontece em edificios de betao armado (BA) de muitas cidades em paises do sul da Europa, entre os quais Portugal. Sendo os pilares elementos estruturais fundamentais na resistencia sismica dos edificios, deve ser dada especial atencao a sua resposta sob acoes ciclicas. Acresce que o sismo e um tipo de acao cujos efeitos nos edificios exige a consideracao de duas componentes horizontais, o que tem exigencias mais severas nos pilares comparativamente a acao unidirecional. Assim, esta tese centra-se na avaliacao da resposta estrutural de pilares de betao armado sujeitos a acoes ciclicas horizontais biaxiais, em tres linhas principais. Em primeiro lugar desenvolveu-se uma campanha de ensaios para o estudo do comportamento ciclico uniaxial e biaxial de pilares de betao armado com esforco axial constante. Para tal foram construidas quatro series de pilares retangulares de betao armado (24 no total) com diferentes caracteristicas geometricas e quantidades de armadura longitudinal, tendo os pilares sido ensaiados para diferentes historias de carga. Os resultados experimentais obtidos sao analisados e discutidos dando particular atencao a evolucao do dano, a degradacao de rigidez e resistencia com o aumento das exigencias de deformacao, a energia dissipada, ao amortecimento viscoso equivalente; por fim e proposto um indice de dano para pilares solicitados biaxialmente. De seguida foram aplicadas diferentes estrategias de modelacao nao-linear para a representacao do comportamento biaxial dos pilares ensaiados, considerando nao-linearidade distribuida ao longo dos elementos ou concentrada nas extremidades dos mesmos. Os resultados obtidos com as varias estrategias de modelacao demonstraram representar adequadamente a resposta em termos das curvas envolventes forca-deslocamento, mas foram encontradas algumas dificuldades na representacao da degradacao de resistencia e na evolucao da energia dissipada. Por fim, e proposto um modelo global para a representacao do comportamento nao-linear em flexao de elementos de betao armado sujeitos a acoes biaxiais ciclicas. Este modelo tem por base um modelo uniaxial conhecido, combinado com uma funcao de interacao desenvolvida com base no modelo de Bouc- Wen. Esta funcao de interacao foi calibrada com recurso a tecnicas de otimizacao e usando resultados de uma serie de analises numericas com um modelo refinado. E ainda demonstrada a capacidade do modelo simplificado em reproduzir os resultados experimentais de ensaios biaxiais de pilares.

Effects that passive cycling exercise have on muscle strength, duration of mechanical ventilation, and length of hospital stay in critically ill patients: a randomized clinical trial.

PubMed

Machado, Aline Dos Santos; Pires-Neto, Ruy Camargo; Carvalho, Maurício Tatsch Ximenes; Soares, Janice Cristina; Cardoso, Dannuey Machado; Albuquerque, Isabella Martins de

2017-01-01

To evaluate the effects that passive cycling exercise, in combination with conventional physical therapy, have on peripheral muscle strength, duration of mechanical ventilation, and length of hospital stay in critically ill patients admitted to the ICU of a tertiary care university hospital. This was a randomized clinical trial involving 38 patients (≥ 18 years of age) on mechanical ventilation who were randomly divided into two groups: control (n = 16), receiving conventional physical therapy; and intervention (n = 22), receiving conventional physical therapy and engaging in passive cycling exercise five days per week. The mean age of the patients was 46.42 ± 16.25 years, and 23 were male. The outcomes studied were peripheral muscle strength, as measured by the Medical Research Council scale, duration of mechanical ventilation, and length of hospital stay. There was a significant increase in peripheral muscle strength (baseline vs. final) in both groups (control: 40.81 ± 7.68 vs. 45.00 ± 6.89; and intervention: 38.73 ± 11.11 vs. 47.18 ± 8.75; p < 0.001 for both). However, the range of increase in strength was higher in the intervention group than in the control group (8.45 ± 5.20 vs. 4.18 ± 2.63; p = 0.005). There were no significant differences between the groups in terms of duration of mechanical ventilation or length of hospital stay. The results suggest that the performance of continuous passive mobilization on a cyclical basis helps to recover peripheral muscle strength in ICU patients. (ClinicalTrials.gov Identifier: NCT01769846 [http://www.clinicaltrials.gov/]). Avaliar os efeitos da realização de exercícios passivos com um cicloergômetro, associada à fisioterapia convencional, na força muscular periférica, no tempo de ventilação mecânica e no tempo de internação hospitalar em pacientes críticos internados em UTI de um hospital universitário terciário. Ensaio clínico randomizado envolvendo 38 pacientes (idade > 18 anos) em ventilação mecânica e divididos aleatoriamente em grupo controle (n = 16), que realizou fisioterapia convencional, e grupo intervenção (n = 22) submetidos a fisioterapia convencional e exercícios passivos em cicloergômetro cinco vezes por semana. A média de idade dos pacientes foi de 46,42 ± 16,25 anos, e 23 eram homens. Os desfechos analisados foram força muscular periférica, mensurada pela escala Medical Research Council, tempo de ventilação mecânica e tempo de internação hospitalar. Houve um aumento significativo da força muscular periférica (basal vs. final) tanto no grupo controle (40,81 ± 7,68 vs. 45,00 ± 6,89; p < 0,001) quanto no grupo intervenção (38,73 ± 11,11 vs. 47,18 ± 8,75; p < 0,001). Entretanto, a variação do aumento da força foi maior no grupo intervenção que no controle (8,45 ± 5,20 vs. 4,18 ± 2,63; p = 0,005). Não foram observadas diferenças significativas entre os grupos quanto ao tempo de ventilação mecânica e tempo de internação hospitalar. Os resultados sugerem que a realização de mobilização passiva contínua de forma cíclica auxilia na recuperação da força muscular periférica de pacientes internados em UTI. (ClinicalTrials.gov Identifier: NCT01769846 [http://www.clinicaltrials.gov/]).

Evaluation of thermochemical biomass conversion in fluidized bed =

NASA Astrophysics Data System (ADS)

Neves, Daniel dos Santos Felix das

Dado o aumento acelerado dos precos dos combustiveis fosseis e as incertezas quanto a sua disponibilidade futura, tem surgido um novo interesse nas tecnologias da biomassa aplicadas a producao de calor, eletricidade ou combustiveis sinteticos. Nao obstante, para a conversao termoquimica de uma particula de biomassa solida concorrem fenomenos bastante complexos que levam, em primeiro lugar, a secagem do combustivel, depois a pirolise e finalmente a combustao ou gasificacao propriamente ditas. Uma descricao relativamente incompleta de alguns desses estagios de conversao constitui ainda um obstaculo ao desenvolvimento das tecnologias que importa ultrapassar. Em particular, a presenca de elevados conteudos de materia volatil na biomassa poe em evidencia o interesse pratico do estudo da pirolise. A importância da pirolise durante a combustao de biomassa foi evidenciada neste trabalho atraves de ensaios realizados num reator piloto de leito fluidizado borbulhante. Verificou-se que o processo ocorre em grande parte a superficie do leito com chamas de difusao devido a libertacao de volateis, o que dificulta o controlo da temperatura do reator acima do leito. No caso da gasificacao de biomassa a pirolise pode inclusivamente determinar a eficiencia quimica do processo. Isso foi mostrado neste trabalho durante ensaios de gasificacao num reator de leito fluidizado de 2MWth, onde um novo metodo de medicao permitiu fechar o balanco de massa ao gasificador e monitorizar o grau de conversao da biomassa. A partir destes resultados tornou-se clara a necessidade de descrever adequadamente a pirolise de biomassa com vista ao projeto e controlo dos processos. Em aplicacoes de engenharia ha particular interesse na estequiometria e propriedades dos principais produtos piroliticos. Neste trabalho procurou-se responder a esta necessidade, inicialmente atraves da estruturacao de dados bibliograficos sobre rendimentos de carbonizado, liquidos piroliticos e gases, assim como composicoes elementares e poderes calorificos. O resultado traduziu-se num conjunto de parâmetros empiricos de interesse pratico que permitiram elucidar o comportamento geral da pirolise de biomassa numa gama ampla de condicoes operatorias. Para alem disso, propos-se um modelo empirico para a composicao dos volateis que pode ser integrado em modelos compreensivos de reatores desde que os parâmetros usados sejam adequados ao combustivel ensaiado. Esta abordagem despoletou um conjunto de ensaios de pirolise com varias biomassas, lenhina e celulose, e temperaturas entre os 600 e 975ºC. Elevadas taxas de aquecimento do combustivel foram alcancadas em reatores laboratoriais de leito fluidizado borbulhante e leito fixo, ao passo que um sistema termo-gravimetrico permitiu estudar o efeito de taxas de aquecimento mais baixas. Os resultados mostram que, em condicoes tipicas de processos de combustao e gasificacao, a quantidade de volateis libertada da biomassa e pouco influenciada pela temperatura do reator mas varia bastante entre combustiveis. Uma analise mais aprofundada deste assunto permitiu mostrar que o rendimento de carbonizado esta intimamente relacionado com o racio O/C do combustivel original, sendo proposto um modelo simples para descrever esta relacao. Embora a quantidade total de volateis libertada seja estabelecida pela composicao da biomassa, a respetiva composicao quimica depende bastante da temperatura do reator. Rendimentos de especies condensaveis (agua e especies orgânicas), CO2 e hidrocarbonetos leves descrevem um maximo relativamente a temperatura para dar lugar a CO e H2 as temperaturas mais altas. Nao obstante, em certas gamas de temperatura, os rendimentos de algumas das principais especies gasosas (e.g. CO, H2, CH4) estao bem correlacionados entre si, o que permitiu desenvolver modelos empiricos que minimizam o efeito das condicoes operatorias e, ao mesmo tempo, realcam o efeito do combustivel na composicao do gas. Em suma, os ensaios de pirolise realizados neste trabalho permitiram constatar que a estequiometria da pirolise de biomassa se relaciona de varias formas com a composicao elementar do combustivel original o que levanta varias possibilidades para a avaliacao e projeto de processos de combustao e gasificacao de biomassa.

Simulação de ejeções de massa coronal

NASA Astrophysics Data System (ADS)

Corsini, M. A.; Silva, A. V. R.

2003-08-01

Ejeções de massa coronal (EMC) são bolhas gigantes de gás permeadas por campos magnéticos que são ejetadas do Sol durante um período de várias horas. Caso estas ejeções atinjam a Terra, geralmente, causam uma série de distúrbios às comunicações de longa distância e navegação, além de danos a satélites e transformadores. Portanto, é desejável que sejamos capazes de prever quando estas ejeções atingirão a Terra. Para tanto, é necessário um bom entendimento dos mecanismos causadores das ejeções e, principalmente, de como se dá a propagação das EMC e sua interação com o vento solar que permeia o meio interplanetário. Nesse sentido foi desenvolvido um programa computacional para resolver as equações MHD (Magneto-Hidro-Dinâmica) que regem a evolução das EMC. Primeiramente foram estabelecidas as condições necessárias para descrever o vento solar, no estado estacionário, que permeia todo o meio interplanetário. Num primeiro momento, resolveu-se o sistema de equações para o caso do vento isotérmico, conhecida como a solução de Parker, a fim de testarmos o modelo. Então, foi considerado o caso do vento solar com temperatura variável no meio interplanetário. Este resultado foi utilizado como a base de nosso sistema em seu instante inicial. Posteriormente foram feitas as considerações necessárias para descrever a propagação da Ejeção de Massa Coronal. As EMC foram simuladas como um aumento de densidade e temperatura local na coroa solar. A órbita e a posição da Terra foram incluídas no sistema. Os dados gerados possibilitaram uma análise da evolução da EMC pelo meio interplanetário até encontrar-se com a Terra. Os perfis de densidade e temperatura a 1 Unidade Astronômica são comparados com os dados de satélites reportados na literatura.

Effects of the application of therapeutic massage in children with cancer: a systematic review.

PubMed

Rodríguez-Mansilla, Juan; González-Sánchez, Blanca; Torres-Piles, Silvia; Martín, Jorge Guerrero; Jiménez-Palomares, María; Bellino, Macarena Núñez

2017-06-08

to learn about the effects of the use of therapeutic massage in children with cancer. systematic review of controlled clinical trials The search was conducted in November 2014 in the following databases: Pubmed, CSIC, Dialnet, Scopus, Cochrane and PEDro. Inclusion criteria were: clinical trials, published in English or Spanish, analyzing the effects of massage on the different stages and types of childhood cancer (between 1 and 18 years old). of 1007 articles found, 7 met the inclusion criteria. Their authors use different massage techniques (Swedish massage, effleurage, petrissage, frictions, pressures), obtaining benefits in the symptoms present during the illness (decrease of pain, nausea, stress, anxiety and increase of white blood cells and neutrophils). therapeutic massage improves the symptoms of children with cancer, but there is a need for more research that may support the effects attributed to it. conocer los efectos del uso del masaje terapéutico en niños con cáncer. revisión sistemática de ensayos clínicos controlados la búsqueda se llevó a cabo en noviembre de 2014 en las bases de datos científicas: Pubmed, CSIC, Dialnet, Scopus, Cochrane y PEDro. Los criterios de inclusión han sido: ensayos clínicos, publicados en inglés o español, en los que se analizaran los efectos del masaje en las diferentes etapas y tipos de cáncer infantil (entre 1 y 18 años). de 1007 artículos localizados, 7 cumplieron los criterios de inclusión. Sus autores utilizan diferentes técnicas de masaje (masaje sueco, effleurage, petrissage, fricciones, presiones), obteniendo beneficios en los síntomas presentes durante la enfermedad (disminución del dolor, náuseas, estrés, ansiedad y aumento de glóbulos blancos y neutrófilos). el masaje terapéutico mejora los síntomas de los niños con cáncer, que respalden los efectos que se le atribuyen. conhecer os efeitos do uso da massagem terapêutica em crianças com câncer. revisão sistemática de ensaios clínicos controlados. A pesquisa foi realizada em novembro de 2014 em bases de dados científicas: Pubmed, CSIC, Dialnet, Scopus, Cochrane and PEDro. Os critérios de inclusão foram: ensaios clínicos, publicados em inglês ou espanhol, analisando os efeitos da massagem nas diferentes fases e tipos de câncer infantil (entre 1 e 18 anos). de 1007 artigos encontrados, 7 preencheram os critérios de inclusão. Os autores utilizam diferentes técnicas de massagem (massagem sueca, effleurage, petrissage, fricções, pressões), obtendo benefícios nos sintomas presentes durante a doença (diminuição da dor, náusea, estresse, ansiedade e aumento de glóbulos brancos e neutrófilos). a massagem terapêutica melhora os sintomas das crianças com câncer, mas são necessárias mais pesquisas que apoiem os efeitos atribuídos a ela.

Factors associated with poor sleep quality in women with cancer.

PubMed

Mansano-Schlosser, Thalyta Cristina; Ceolim, Maria Filomena

2017-03-02

to analyze the factors associated with poor sleep quality, its characteristics and components in women with breast cancer prior to surgery for removing the tumor and throughout the follow-up. longitudinal study in a teaching hospital, with a sample of 102 women. The following were used: a questionnaire for sociodemographic and clinical characterization, the Pittsburgh Sleep Quality Index; the Beck Depression Inventory; and the Herth Hope Scale. Data collection covered from prior to the surgery for removal of the tumor (T0) to T1, on average 3.2 months; T2, on average 6.1 months; and T3, on average 12.4 months. Descriptive statistics and the Generalized Estimating Equations model were used. depression and pain contributed to the increase in the score of the Pittsburgh Sleep Quality Index, and hope, to the reduction of the score - independently - throughout follow-up. Sleep disturbances were the component with the highest score throughout follow-up. the presence of depression and pain, prior to the surgery, contributed to the increase in the global score of the Pittsburgh Sleep Quality Index, which indicates worse quality of sleep throughout follow-up; greater hope, in its turn, influenced the reduction of the score of the Pittsburgh Sleep Quality Index. analizar los factores asociados a la mala calidad del sueño, sus características y componentes en mujeres con cáncer de mama, antes de la cirugía de retirada del tumor y a lo largo del seguimiento. estudio longitudinal, en hospital universitario con muestra de 102 mujeres. Fueron utilizados: un cuestionario de caracterización sociodemográfica y clínica; el Índice de Calidad del Sueño de Pittsburgh; el Inventario de Depresión de Beck; y la Escala de Esperanza de Herth. La recolección comprendió los momentos: antes de la cirugía de retirada del tumor (T0), en (T1) en promedio 3,2 meses, en (T2) en promedio 6,1 meses y en (T3) en promedio 12,4 meses. Se utilizó estadística descriptiva y el modelo de Ecuaciones de Estimación Generalizada. la depresión y el dolor contribuyeron para el aumento del puntaje del Índice de Calidad del Sueño de Pittsburgh y la esperanza para la reducción del puntaje, de manera independiente, a lo largo del seguimiento. Los trastornos del sueño fueron el componente con puntuación más elevada, a lo largo del seguimiento. la presencia de la depresión y del dolor, previos a la cirugía, contribuyeron para el aumento del puntaje global del Índice de Calidad del Sueño de Pittsburgh, lo que indica peor calidad del sueño, a lo largo del seguimiento y, la mayor esperanza, a su vez, influenció en la reducción del puntaje del Índice de Calidad del Sueño de Pittsburgh. analisar os fatores associados à má qualidade do sono, suas características e componentes em mulheres com câncer de mama antes da cirurgia de retirada do tumor e ao longo do seguimento. estudo longitudinal, em hospital universitário com amostra de 102 mulheres. Foram utilizados: questionário de caracterização sociodemográfica e clínica, Índice de Qualidade do Sono de Pittsburgh; Inventário de Depressão de Beck; Escala de Esperança de Herth. Coleta compreendeu antes da cirurgia de retirada do tumor (T0) em T1, em média 3,2 meses; T2, em média 6,1 meses; T3, em média 12,4 meses. Utilizou-se estatística descritiva e o modelo de Equações de Estimação Generalizada. a depressão e a dor contribuíram para o aumento do escore do Índice de Qualidade de Sono de Pittsburgh, e a esperança, para a redução do escore, de maneira independente, ao longo do seguimento. Os transtornos do sono foram o componente com pontuação mais elevada, ao longo do seguimento. a presença de depressão e de dor, previamente à cirurgia, contribuiu para o aumento do escore global do Índice de Qualidade do Sono de Pittsburgh, o que indica pior qualidade do sono, ao longo do seguimento e, a maior esperança, por sua vez, influenciou na redução do escore do Índice de Qualidade do Sono de Pittsburgh.

GROWTH FACTORS AND COX2 IN WOUND HEALING: AN EXPERIMENTAL STUDY WITH EHRLICH TUMORS.

PubMed

Salgado, Flávio L L; Artigiani-Neto, Ricardo; Lopes-Filho, Gaspar de Jesus

2016-01-01

Healing is an innate biological phenomenon, and carcinogenesis acquired, but with common humoral and cellular elements. Carcinogenesis interferes negatively in healing. To evaluate the histological changes in laparotomy scars of healthy Balb/c mice and with an Ehrlich tumor in its various forms of presentation. Fifty-four mice were divided into three groups of 18 animals. First group was the control; the second had Ehrlich tumor with ascites; and the third had the subcutaneous form of this tumor. Seven days after tumor inoculation, all 54 mice were submitted to laparotomy. All of the animals in the experiment were operated on again on 7th day after surgery, with resection of the scar and subsequent euthanasia of the animal. The scars were sent for histological assessment using immunohistochemical techniques to evaluate Cox-2 (cyclooxygenase 2), VEGF (vascular endothelial growth factor) and FGF (fibroblast growth factor). Semi-quantitatively analysis was done in the laparotomy scars and in the abdominal walls far away from the site of the operation. Assessing the weight of the animals, the correct inoculation of the tumor and weight gain in the group with tumoral ascites was observed. The histological studies showed that groups with the tumor showed a statistically significant higher presence of Cox-2 compared to the control. In the Cox-2 analysis of the abdominal wall, the ascites group showed the most significant difference. VEGF did not present any significant differences between the three groups, regardless of the site. The FGF showed a significant increase in animals with the tumor. Histological findings in both laparotomy scar and the abdominal wall showed that with Ehrlich's neoplasia there was an exacerbated inflammatory response, translated by more intense expression of Cox-2 and greater fibroblast proliferation, translated by more intense expression of FGF, that is, it stimulated both the immediate inflammatory reactions, observed with Cox-2 reactions, and late scarring by fibroblasts and FGF. A cicatrização é fenômeno biológico inato, e a carcinogênese adquirido, mas com elementos humorais e celulares comuns. A carcinogênese interfere de forma negativa na cicatrização. Avaliar as modificações histológicas nas cicatrizes laparotômicas de camundongos Balb/c sadios como controles, e com a neoplasia de Ehrlich, em suas diferentes formas de apresentação. Foram utilizados 54 camundongos, divididos em três grupos de 18 animais cada um. O primeiro era controle; o segundo com a neoplasia de Ehrlich em sua forma ascítica; e o terceiro na forma subcutânea. Sete dias após a inoculação do tumor, todos os 54 camundongos foram submetidos à laparotomia e reoperados no sétimo dia de pós-operatório, com ressecção da cicatriz e posterior eutanásia. As cicatrizes foram encaminhadas para estudo histológico com técnicas imunoistoquímicas para avaliar Cox-2 (ciclo-oxigenase 2), VEGF (fator de crescimento do endotélio vascular) e FGF (fator de crescimento dos fibroblastos) e analisadas de forma semiquantitativana tanto na cicatriz laparotômica como na parede abdominal mais distante do local operado. Avaliando o peso, observou-se a correta inoculação do tumor e o aumento de peso no grupo com a neoplasia na modalidade ascítica. Os estudos histológicos mostraram que os grupos com a neoplasia apresentaram maior presença da Cox-2 em relação ao controle, estatisticamente significante. No estudo da Cox-2 da parede abdominal foi o local em que o grupo ascítico apresentou a diferença mais expressiva. O VEGF não apresentou diferenças significantes entre os três grupos, independentemente do local estudado. O FGF teve aumento significante nos animais com neoplasia. Os achados histológicos encontrados tanto na cicatriz das laparotomias quanto na parede abdominal mostraram que com a neoplasia de Ehrlich houve resposta inflamatória exacerbada, traduzida por expressão mais intensa da Cox-2 e maior proliferação fibroblástica, traduzida por expressão mais intensa do FGF, ou seja, estimulou tanto as reações inflamatórias imediatas, observadas nas reações da Cox-2, como nas cicatriciais tardias com os fibroblastos e o FGF.

DEVELOPMENT OF METRICS FOR PROTOCOLS AND OTHER TECHNICAL PRODUCTS.

PubMed

Veiga, Daniela Francescato; Ferreira, Lydia Masako

2015-01-01

To develop a proposal for metrics for protocols and other technical products to be applied in assessing the Postgraduate Programs of Medicine III - Capes. The 2013 area documents of all the 48 Capes areas were read. From the analysis of the criteria used by the areas at the 2013's Triennal Assessment, a proposal for metrics for protocols and other technical products was developed to be applied in assessing the Postgraduate Programs of Medicine III. This proposal was based on the criteria of Biological Sciences I and Interdisciplinary areas. Only seven areas have described a scoring system for technical products. The products considered and the scoring varied widely. Due to the wide range of different technical products which could be considered relevant, and that would not be punctuated if they were not previously specified, it was developed, for the Medicine III, a proposal for metrics in which five specific criteria to be analyzed: Demand, Relevance/Impact, Scope, Complexity and Adherence to the Program. Based on these criteria, each product can receive 10 to 100 points. This proposal can be applied to the item Intellectual Production of the evaluation form, in subsection "Technical production, patents and other relevant production". The program will be scored as Very Good when it reaches mean ≥150 points/permanent professor/quadrennium; Good, mean between 100 and 149 points; Regular, mean between 60 and 99 points; Weak mean between 30 and 59 points; Insufficient, up to 29 points/permanent professor/quadrennium. Desenvolver proposta de métricas para protocolos e outras produções técnicas a serem aplicadas na avaliação dos Programas de Pós-Graduação da Área Medicina III da Capes. Foram lidos os documentos de área de 2013 de todas as 48 Áreas da Capes. A partir da análise dos critérios utilizados por elas na avaliação trienal 2013, foi desenvolvida uma proposta de métricas para protocolos e outras produções técnicas. Esta proposta foi baseada nos critérios adotados pelas Áreas Ciências Biológicas I e Interdisciplinar. Apenas sete áreas descreveram sistema de pontuação para produtos técnicos, e as produções consideradas e a pontuação variaram amplamente. Dada à imensa gama de produções técnicas diferentes que podem ser consideradas relevantes, e que não seriam contempladas em sistema de pontuação caso fossem especificadas, foi desenvolvida para a Medicina III uma proposta de métricas em que são analisados cinco critérios específicos para cada produção: Demanda, Relevância/Impacto, Abrangência, Complexidade e Aderência ao Programa. Com base nestes critérios, cada produção pode receber de 10 a 100 pontos. Esta proposta poderá ser aplicada ao item Produção Intelectual da Ficha de Avaliação, subitem "Produção técnica, patentes e outras produções consideradas relevantes". Será considerado Muito Bom o Programa que obtiver média ≥150 pontos/docente permanente/quadriênio; Bom, média entre 100 e 149 pontos; Regular, média entre 60 e 99 pontos; Fraco, média entre 30 e 59 pontos; e Deficiente média ≤29 pontos/docente permanente/quadriênio.

Hypertriglyceridemia: Is there a role for prophylactic apheresis? A case report.

PubMed

Francisco, Ana Rita; Gonçalves, Inês; Veiga, Fátima; Pedro, Mónica Mendes; Pinto, Fausto J; Brito, Dulce

2016-01-01

Severe hypertriglyceridemia has been consistently associated with an increased risk of cardiovascular disease and other complications, namely acute pancreatitis. We report a case of a 64 year-old woman with hypertrophic cardiomyopathy and metabolic syndrome with triglyceride level of 3260 mg/dL. Plasma exchange was performed with simultaneous medical treatment to achieve a rapid and effective lowering of triglycerides in order to prevent clinical complications. After three plasmapheresis sessions a marked reduction in triglyceride and total cholesterol levels was observed. Several cases have shown the importance of plasmapheresis in the treatment of acute pancreatitis. We intend to demonstrate the applicability of this technique as primary prophylaxis in the presence of extremely high serum triglyceridemia levels. Resumo A hipertrigliceridemia grave tem sido associada de forma consistente ao aumento do risco cardiovascular e a outras complicações, nomeadamente, pancreatite aguda. Descrevemos um caso de uma mulher de 64 anos, com miocardiopatia hipertrófica e síndrome metabólica com valor sérico de triglicerídeos de 3260 mg/dL. Foi efectuada plasmaferese e optimizado o tratamento médico para alcançar uma redução rápida e efectiva dos níveis dos triglicerídeos, prevenindo complicações clínicas. Após três sessões de plasmaferese, verificou-se uma redução marcada dos triglicerídeos e do colesterol total. Existem alguns casos descritos na literatura demonstrado a importância da plasmaferese no tratamento da pancreatite aguda em contexto de hipertrigliceridemia grave. Os autores pretendem com este caso demonstrar a aplicabilidade desta técnica em contexto de prevenção primária em doentes com níveis de triglicerídeos extremamente aumentados.

ALTERNATIVE TECHNIQUE FOR CHOLECYSTECTOMY COMPARABLE TO SINGLE PORT.

PubMed

Sabbag, Carlos; Blitzckow, Ana

2017-01-01

With the advancement of laparoscopic surgery, new techniques have been proposed and disseminated in order to reduce the surgical aggression and get better cosmetic results. To present alternative technique for videocholecystectomy comparable to single port technique using conventional material for laparoscopic surgery. Introduction of laparoscopic devices using two incisions; gallbladder traction with thread, exposition of Calot triangle, and ligature of cystic pedicle with polymer clips. Nine operations were carried out with this method, without complications and no increase in operative time, being compared to conventional videocholecistectomy, however vastly superior in aesthetic results. The technique is feasible, reproducible, showing benefits to patient´s safety. Com o avanço da cirurgia laparoscópica, novas técnicas têm sido propostas e difundidas com o objetivo de diminuir a agressão cirúrgica e obter melhores resultados estéticos. Apresentar técnica alternativa para videocolecistectomia similar à técnica de single port, contudo utilizando material convencional para cirurgia laparoscópica. Procedimento de videocolecistectomia com uso de duas incisões, exposição do trígono de Calot por tração da vesícula biliar com fio e ligadura dos elementos do hilo cístico com clipes de polímero. Foram realizadas nove operações com esse método, não se observando complicações e nem aumento do tempo operatório em relação à videocolecistectomia convencional, contudo com resultado estético grandemente superior. A técnica é factível, reprodutível e mostra benefícios e segurança ao paciente.

Effects of a Single Bout of Resistance Exercise in Different Volumes on Endothelium Adaptations in Healthy Animals.

PubMed

Mota, Marcelo Mendonça; Silva, Tharciano Luiz Teixeira Braga da; Macedo, Fabricio Nunes; Mesquita, Thássio Ricardo Ribeiro; Quintans, Lucindo José; Santana-Filho, Valter Joviniano de; Lauton-Santos, Sandra; Santos, Márcio Roberto Viana

2017-05-01

Resistance exercise (RE) has been recommended for patients with cardiovascular diseases. Recently, a few studies have demonstrated that the intensity of a single bout of RE has an effect on endothelial adaptations to exercise. However, there is no data about the effects of different volumes of RE on endothelium function. The aim of the study was to evaluate the effects of different volumes of RE in a single bout on endothelium-dependent vasodilatation and nitric oxide (NO) synthesis in the mesenteric artery of healthy animals. Male Wistar rats were divided into three groups: Control (Ct); low-volume RE (LV, 5 sets x 10 repetitions) and high-volume RE (HV, 15 sets x 10 repetitions). The established intensity was 70% of the maximal repetition test. After the exercise protocol, rings of mesenteric artery were used for assessment of vascular reactivity, and other mesenteric arteries were prepared for detection of measure NO production by DAF-FM fluorescence. Insulin responsiveness on NO synthesis was evaluated by stimulating the vascular rings with insulin (10 nM). The maximal relaxation response to insulin increased in the HV group only as compared with the Ct group. Moreover, the inhibition of nitric oxide synthesis (L-NAME) completely abolished the insulin-induced vasorelaxation in exercised rats. NO production showed a volume-dependent increase in the endothelial and smooth muscle layer. In endothelial layer, only Ct and LV groups showed a significant increase in NO synthesis when compared to their respective group under basal condition. On the other hand, in smooth muscle layer, NO fluorescence increased in all groups when compared to their respective group under basal condition. Our results suggest that a single bout of RE promotes vascular endothelium changes in a volume-dependent manner. The 15 sets x 10 repetitions exercise plan induced the greatest levels of NO synthesis. O exercício resistido (ER) tem sido recomendado para pacientes com doenças cardiovasculares. Recentemente, alguns estudos demonstraram que a intensidade de uma sessão de ER exerce um efeito sobre a disfunção endotelial. No entanto, não há dados sobre os efeitos de diferentes volumes de ER sobre a função endotelial. O objetivo deste estudo foi avaliar os efeitos de diferentes volumes de ER, realizados em uma única sessão, sobre a vasodilatação dependente do endotélio e síntese de óxido nítrico (NO) em artéria mesentérica de animais saudáveis. Ratos Wistar machos foram divididos em três grupos: Controle (Ct); baixo volume (BV, 5 séries x 10 repetições) e alto volume de ER (AV, 15 séries x 10 repetições). Foi estabelecida a intensidade de 70% do teste de repetição máxima. Após o protocolo de exercício, anéis de artéria mesentérica foram utilizados na avaliação da reatividade vascular, e outras artérias mesentéricas foram preparadas para a detecção da produção de NO por fluorescência com para do DAF-FM. A resposta à insulina pela síntese de NO foi avaliada estimulando-se os anéis vasculares com insulina (10nM). A resposta máxima do relaxamento induzido por insulina foi aumentada somente no grupo AV em comparação ao grupo Ct. Além disso, a inibição da síntese do NO (L-NAME), aboliu completamente o relaxamento vascular induzido por insulina em ratos exercitados. A produção de NO mostrou um aumento dependente do volume no endotélio e no músculo liso. No endotélio, apenas os grupos Ct e BV mostraram aumento significativo na síntese de NO quando comparado aos seus respectivos grupos sob condição basal. No entanto, no músculo liso, a fluorescência foi aumentada em todos os grupos quando comparados aos seus respectivos grupos sob a condição basal. Nossos resultados sugerem que uma única sessão de ER foi capaz de promover adaptações no endotélio vascular. Além disso, nós observamos que este efeito é volume-dependente e o volume de 15 séries x10 repetições induziu o maior aumento na síntese de NO.

Family violence against children and adolescents in context: How the territories of care are imbricated in the picture.

PubMed

Carlos, Diene Monique; Ferriani, Maria das Graças Carvalho

2016-08-08

to understand the context of care addressed to the families involved in family violence against children and adolescents (IVCA), as produced in the context of the Primary Health Care (PHC), from the vantage point of the practitioners of a municipality in the State of Sao Paulo. qualitative research of the social-strategic type, based on the Complexity Paradigm. The participants were 41 health practitioners in five health units of the municipality under study, pertaining to the five districts of the municipality. Data collection was done through 5 focus groups and 10 semi-structured interviews from April 24th 2013 to December 12th 2013. Data analysis was oriented by the comprehension and contextualization mindset and based on the dialogic, recursive and hologramatic principles. two main issues regarding the care provided by the Health of the Family team were identified: the context of this violence (the domestic space) and the power relations that prevail in the territory where this violence surfaces. The community health workers are the targets of specific attention because they experience the live/work dialogic in this same area. paying attention to the territory, and considering the complexity of contexts and dimensions is inherently linked to the design of care to families involved in IVCA in the PHC environment. compreender o contexto de cuidado direcionado às famílias envolvidas na violência intrafamiliar contra crianças e adolescentes (VICCA), produzido a partir da Atenção Primária à Saúde (APS), sob a ótica de profissionais de um município do interior do estado de São Paulo. pesquisa qualitativa, do tipo social estratégica, fundamentada pelo Paradigma da Complexidade. Participaram do estudo 41 profissionais de saúde de cinco unidades do município estudado, cada qual pertencente a um de seus cinco Distritos Sanitários. A coleta de dados foi realizada por meio de 5 grupos focais e 10 entrevistas semiestruturadas, no período de 24/04/13 a 17/12/13. As noções de compreensão e contextualização, e os princípios dialógicos, recursivo e hologramático direcionaram a análise dos dados. identificou-se duas questões cruciais para o cuidado desenvolvido pela equipe de saúde às famílias: o contexto onde essa violência ocorre (O espaço doméstico), e as relações de poder existentes na emergência desse cuidado no território. Os agentes comunitários merecem especial atenção por viverem a dialógica do morar-trabalhar em uma mesma área. o olhar para o território, considerando a complexidade de contextos e dimensões, se apresenta como inerente para o delineamento do cuidado às famílias envolvidas na VICCA no âmbito da APS. comprender el contexto de cuidado dirigido hacia las familias involucradas en violencia familiar contra niños y adolescentes (VICNA) que resulta de la Atención Primaria de la Salud (PHC) desde la óptica de los profesionales de un municipio del interior de Sao Paulo. investigación cualitativa del tipo social-estratégica, fundamentada en el Paradigma de la Complejidad. Participaron en el estudio 41 profesionales de salud de cinco unidades del municipio en estudio, cada una perteneciente a uno de los cinco Distritos Sanitarios. La recolección de datos se realizó por medio de cinco grupos focales y 10 entrevistas semi-estructuradas en el período entre 24/04/2013 y 17/12/2013. Las nociones de comprensión y contextualización y los principios dialógicos, recursivo y hologramático guiaron el análisis de los datos. se identificaron dos cuestiones cruciales para el cuidado desarrollado por el equipo de salud de las familias: el contexto en ocurre esta violencia (El espacio doméstico) y las relaciones de poder que existen en la emergencia de ese cuidado en el territorio. Los trabajadores comunitarios merecen una atención especial ya que viven la dialógica de trabajar/habitar en la misma área. la mirada sobre el territorio, considerando la complejidad de contextos y dimensiones, se presenta como inherente al diseño del cuidado de las familias involucradas en la VICNA en el ámbito de la APS.

Socioeconomic and regional differences in active transportation in Brazil.

PubMed

Sá, Thiago Hérick de; Pereira, Rafael Henrique Moraes; Duran, Ana Clara; Monteiro, Carlos Augusto

2016-06-27

To present national estimates regarding walking or cycling for commuting in Brazil and in 10 metropolitan regions. By using data from the Health section of 2008's Pesquisa Nacional por Amostra de Domicílio (Brazil's National Household Sample Survey), we estimated how often employed people walk or cycle to work, disaggregating our results by sex, age range, education level, household monthly income per capita, urban or rural address, metropolitan regions, and macro-regions in Brazil. Furthermore, we estimated the distribution of this same frequency according to quintiles of household monthly income per capita in each metropolitan region of the country. A third of the employed men and women walk or cycle from home to work in Brazil. For both sexes, this share decreases as income and education levels rise, and it is higher among younger individuals, especially among those living in rural areas and in the Northeast region of the country. Depending on the metropolitan region, the practice of active transportation is two to five times more frequent among low-income individuals than among high-income individuals. Walking or cycling to work in Brazil is most frequent among low-income individuals and the ones living in less economically developed areas. Active transportation evaluation in Brazil provides important information for public health and urban mobility policy-making. Apresentar estimativas nacionais sobre o deslocamento a pé ou de bicicleta no trajeto casa-trabalho no Brasil e em 10 de suas regiões metropolitanas. Utilizando dados do Suplemento sobre Saúde da Pesquisa Nacional por Amostra de Domicílios de 2008, estimamos a frequência de pessoas empregadas que se deslocam a pé ou de bicicleta no trajeto casa-trabalho estratificada por sexo, e segundo faixa etária, escolaridade, renda domiciliar per capita, residência em área urbana ou rural, regiões metropolitanas e macrorregiões do país. Adicionalmente, estimamos a distribuição da mesma frequência segundo quintos da distribuição da renda domiciliar per capita em cada região metropolitana. Um terço dos homens e mulheres empregados desloca-se a pé ou de bicicleta de casa para o trabalho no Brasil. Em ambos os sexos, esta proporção diminui com o aumento da renda e da escolaridade e é maior entre os mais jovens, entre os que residem em área rural e naqueles residentes na região Nordeste. A depender da região metropolitana, a prática de deslocamento ativo entre os mais pobres é de duas a cinco vezes maior do que entre os mais ricos. O deslocamento a pé ou de bicicleta para o trabalho no Brasil é mais frequente entre os mais pobres e entre pessoas que vivem em áreas e regiões economicamente menos desenvolvidas. A avaliação do deslocamento ativo no País traz informações importantes para a discussão de políticas públicas de mobilidade.

Promoting oral care in the preschool child: effects of a playful learning intervention.

PubMed

Sigaud, Cecília Helena de Siqueira; Santos, Bruna Rodrigues Dos; Costa, Priscila; Toriyama, Aurea Tamami Minagawa

2017-01-01

To compare the number of appropriate behaviors for tooth brushing before and after a playful learning intervention with preschool children. A quasi-experimental, quantitative, before and after study design was conducted in an early childhood educational institution, with children between three and five years of age. The intervention consisted of three meetings with educational activities about tooth brushing, whose outcome was evaluated by means of observation of ten behaviors suitable for tooth brushing. Forty-four children participated in the study. The mean of adequate behaviors was 4.4 before the intervention, and 8.5 after the intervention. A significant increase in the adoption of appropriate behaviors for tooth brushing (p <0.01) was identified. Nurses can enhance oral health promotion actions with preschoolers in preschool institution using playful learning interventions. Comparar o número de comportamentos adequados para a escovação de dentes antes e após uma intervenção educativa lúdica com pré-escolares. Estudo quase-experimental, do tipo antes-depois, com abordagem quantitativa e conduzido em instituição de educação infantil com crianças entre três e cinco anos de idade. A intervenção consistiu em três encontros com atividades educativas lúdicas sobre escovação de dentes, cujo efeito foi avaliado por meio da observação de dez comportamentos adequados para a escovação dos dentes. Participaram do estudo 44 crianças. A média de comportamentos adequados foi de 4,4 antes da intervenção e 8,5 após a mesma. Houve um aumento significativo na adoção de comportamentos adequados para a escovação de dentes (p < 0,01). Por meio de intervenções educativas lúdicas, recomenda-se que os enfermeiros potencializem as ações de promoção da saúde bucal com pré-escolares em instituições de educação infantil.

After 10 years, how do changes in asset ownership affect the Indicador Econômico Nacional?

PubMed

Ewerling, Fernanda; Barros, Aluísio J D

2017-03-02

Our main objective was to analyse how the evolution of household assets ownership affected the Indicador Econômico Nacional (IEN - National Wealth index) and to point out the most stable assets and which lost importance more quickly. We analysed the trend of the ownership of each IEN variable and the distribution of the households' scores. We calculated the correlation coefficients of each variable separately with the IEN score and the household income. We also evaluated how the changes of the score distribution over time affected the validity of the published reference cut-points. We used data from consortium surveys conducted every two years from 2002 to 2014 in the city of Pelotas, Brazil. An increase in the educational level of household heads and in the ownership of all IEN assets, except radio and telephone, was observed in the study period. In general, the correlation of the assets with the IEN scores decreased over time. There was an increase in the score, with a consequent increase in the quintiles cut-points, but the distance between these cut-points had no significant variation. Thus, the reference cut-points for Pelotas, quickly became outdated. Some assets showed greatly reduction on its importance for the indicator, and the reference cut-points became obsolete very quickly. It is essential for a standardized wealth (or asset) index with research purposes to be updated frequently, especially the cut-points of reference distribution. Analisar como a evolução temporal da posse de bens domésticos afetou o Indicador Econômico Nacional e como essas mudanças afetaram o poder discriminatório do indicador. Analisou-se a evolução temporal da posse de cada uma das variáveis do Indicador Econômico Nacional, bem como da distribuição do escore dos domicílios. Utilizamos dados de inquéritos populacionais realizados bienalmente no município de Pelotas, RS, de 2002 a 2014. Foi calculado o coeficiente de correlação de cada variável isoladamente com o escore do Indicador Econômico Nacional e com a renda familiar. Avaliamos também como a variação da distribuição do escore ao longo do tempo afetou a validade da utilização dos pontos de corte de referência publicados. Houve aumento da escolaridade dos chefes das famílias e da posse de todos os bens, exceto rádio e linha telefônica no período. A correlação dos bens com o Indicador Econômico Nacional reduziu com o tempo. O escore aumentou, com consequente incremento nos pontos de corte dos quintis, mas a distância entre os pontos não teve variação importante. Assim, os pontos de corte de referência publicados para Pelotas rapidamente ficaram desatualizados. Alguns bens perderam a capacidade discriminatória e os pontos de corte ficaram obsoletos rapidamente. É essencial um indicador de bens padronizado para uso em pesquisa, que seja atualizado com frequência, em especial os pontos de corte da distribuição de referência.

Trends in corrected lung cancer mortality rates in Brazil and regions.

PubMed

Malta, Deborah Carvalho; Abreu, Daisy Maria Xavier de; Moura, Lenildo de; Lana, Gustavo C; Azevedo, Gulnar; França, Elisabeth

2016-06-27

To describe the trend in cancer mortality rates in Brazil and regions before and after correction for underreporting of deaths and redistribution of ill-defined and nonspecific causes. The study used data of deaths from lung cancer among the population aged from 30 to 69 years, notified to the Mortality Information System between 1996 and 2011, corrected for underreporting of deaths, non-registered sex and age , and causes with ill-defined or garbage codes according to sex, age, and region. Standardized rates were calculated by age for raw and corrected data. An analysis of time trend in lung cancer mortality was carried out using the regression model with autoregressive errors. Lung cancer in Brazil presented higher rates among men compared to women, and the South region showed the highest death risk in 1996 and 2011. Mortality showed a trend of reduction for males and increase for women. Lung cancer in Brazil presented different distribution patterns according to sex, with higher rates among men and a reduction in the mortality trend for men and increase for women. Descrever a tendência da mortalidade por câncer de pulmão no Brasil e regiões, antes e após as correções por sub-registro de óbitos, redistribuição de causas mal definidas e causas inespecíficas. Foram utilizados dados de óbitos por câncer de pulmão da população de 30 a 69 anos, notificados ao Sistema de Informação sobre Mortalidade, entre 1996 e 2011, corrigidos para sub-registro de óbitos, declaração de sexo e idade ignorados e causas com códigos mal definidos e inespecíficos segundo sexo, idade e região. Foram calculadas taxas padronizadas por idade para dados brutos e corrigidos. Realizou-se análise da tendência temporal da mortalidade por câncer de pulmão por meio do modelo de regressão com erros autorregressivos. O câncer de pulmão no Brasil apresentou taxas mais elevadas em homens que em mulheres e a região Sul foi a que apresentou maior risco de morte em 1996 e 2011. A mortalidade tendeu a reduzir para o sexo masculino e a aumentar para o sexo feminino. O câncer de pulmão no Brasil apresenta padrão de distribuição diferente segundo sexo, com taxas mais elevadas em homens e com redução da tendência de mortalidade para o sexo masculino e aumento das taxas para o sexo feminino.

[Ecological study on the mortality of residents in Manfredonia (Apulia Region, Southern Italy) from 1970 to 2013].

PubMed

Gianicolo, Emilio Antonio Luca; Mangia, Cristina; Cervino, Marco; Bruni, Antonella; De Marchi, Bruna; Biggeri, Annibale; Porcu, Rosa; Vigotti, Maria Angela

2016-01-01

OBIETTIVI: valutare lo stato di salute della popolazione residente nel comune di Manfredonia dal 1970 al 2013. DISEGNO: analisi descrittiva dell'andamento temporale della mortalità generale, per gruppi di cause, dal 1970 al 2013. SETTING E PARTECIPANTI: i dati di mortalità e le popolazioni residenti sono di fonte Istat. Sono state esaminate 55 cause di decesso. Le analisi sono disaggregate per sesso e periodo. PRINCIPALI MISURE DI OUTCOME: sono stati elaborati i rapporti standardizzati di mortalità (SMR%), con i rispettivi intervalli di confidenza al 90% (IC90%), e i tassi di mortalità standardizzati col metodo diretto (TSD ). RISULTATI: lo stato di salute misurato dal tasso di mortalità per tutte le cause migliora nel tempo: i TSD passano da 92 x10.000 negli anni 1970-1974 a 52 x10.000 nel biennio 2012-2013 negli uomini, da 70 x10.000 a 39 x10.000 nelle donne. Tuttavia, rispetto alla media regionale Manfredonia perde progressivamente il suo vantaggio, passando da -20% a -10% negli uomini, e da -20% a +1,5% nelle donne. Questo andamento è molto evidente per il complesso delle cause cardiovascolari, mentre i tumori maligni sono in generale nella media regionale. Nell'ultimo periodo disponibile per causa di decesso (2006-2011), la mortalità per infarto miocardico è stata più alta della media regionale (uomini: +35%; donne: +54%). I rapporti standardizzati di mortalità (SMR) mostrano tra gli uomini valori in crescita, in particolar modo rispetto al riferimento provinciale, con un eccesso a cominciare dal periodo 2006-2011 (22 decessi/anno e 19 attesi; SMR%: 117,2; IC90% 101,1-135,2; riferimento: provincia di Foggia). Anche tra le donne gli SMR% superano i riferimenti provinciali negli ultimi periodi esaminati (nel 2012-2013: 7 decessi/ anno e 4,2 attesi; SMR%: 116,4; IC90% 97,0-260,7; riferimento: provincia di Foggia). CONCLUSIONI: la mortalità a Manfredonia è diminuita in misura minore rispetto a quella osservata nei riferimenti provinciali e regionali. Il vantaggio che si osservava negli anni Sessanta si è, infatti, ridotto nel tempo, fino ad annullarsi negli ultimi anni. Dal 1970, Manfredonia ha progressivamente perso il vantaggio che aveva. Dagli anni Duemila, la mortalità per infarto del miocardio è in eccesso sulla media regionale e provinciale. Da casi documentati in letteratura si osserva che le popolazioni che sperimentano catastrofi di origine naturale o antropica possono fronteggiare un aumento di patologie cardiovascolari. La mortalità per tumore polmonare mostra un eccesso sulla media regionale, in particolare provinciale, a cominciare dal 2000, coerentemente con i tempi di latenza legati all'esposizione ad arsenico negli anni Settanta.

Quality of life and treatment adherence in hypertensive patients: systematic review with meta-analysis.

PubMed

Souza, Ana Célia Caetano de; Borges, José Wicto Pereira; Moreira, Thereza Maria Magalhães

2016-12-22

To verify the effects of antihypertensive treatment (pharmacological and non-pharmacological) on the health-related quality of life of individuals with hypertension. We conducted a systematic review with meta-analysis using the following databases: IBECS, LILACS, SciELO, Medline, Cochrane, Science Direct, Scopus and the Brazilian Capes Theses and Dissertations Database. The statistical analysis was performed using Review Manager, version 5.2. The average difference was used for the summarization of meta-analytic effect by the fixed-effect model. Twenty studies were included. The summarization of the effect showed an average increase of 2.45 points (95%CI 1.02-3.87; p < 0.0008) in the quality of life of individuals adhering to non-pharmacological treatment for arterial hypertension. Adherence to pharmacological treatment indicated an average increase of 9.24 points (95%CI 8.16-10.33; p < 0.00001) in the quality of life of individuals with arterial hypertension. Non-pharmacological treatment improves the overall quality of life and physical domain of people with arterial hypertension. Adherence to pharmacological treatment has a positive impact on the mental and physical domains of patients, as it did on the overall quality of life score. Verificar os efeitos do tratamento anti-hipertensivo (farmacológico e não-farmacológico) na qualidade de vida relacionada à saúde de pessoas com hipertensão arterial. Foi conduzida revisão sistemática com metanálise utilizando as bases de dados IBECS, Lilacs, SciELO, Medline, Cochrane, Science Direct, Scopus e o banco de teses da Capes. A análise estatística foi realizada pelo Review Manager versão 5.2. Foi utilizada a diferença da média na sumarização do efeito metanalítico pelo modelo de efeito fixo. Vinte estudos foram incluídos. A sumarização do efeito mostrou incremento de 2,45 pontos na média (IC95% 1,02-3,87; p < 0,0008) da qualidade de vida em pessoas com adesão ao tratamento não farmacológico para hipertensão arterial. A adesão ao tratamento farmacológico indicou aumento de 9,24 pontos na média (IC95% 8,16-10,33; p < 0,00001) da qualidade de vida em pessoas com hipertensão arterial. O tratamento não-farmacológico melhora a qualidade de vida global e o domínio físico de pessoas com hipertensão arterial. A adesão ao tratamento farmacológico impacta positivamente nos domínios mental, físico e escore total da qualidade de vida.

Study and optimization of the macroscopic electrical response of carbon based nanocomposites for advanced applications

NASA Astrophysics Data System (ADS)

Silva, Jaime Pedro Oliveira da

A presente tese centrou-se no estudo da resposta da constante dieletrica e condutividade eletrica em materiais compositos nos quais o reforco tinha uma elevada proporcao entre comprimento e diametro. O objeto de estudo foi o efeito de um reforco com uma elevada razao entre comprimento e diametro, concentracao e orientacao na resposta eletrica e dieletrica de um composito. Estes compositos tem uma grande importancia no desenvolvimento de materiais para sensores e atuadores. Num primeiro momento da dissertacao, explorou-se a resposta da constante dieletrica de um composito constituido por nanotubos de carbono como reforco e uma matriz polimerica. Verificou-se que um aumento da razao entre comprimento e diametro do reforco tem o efeito de aumentar a constante dieletrica do composito para uma igual fracao volumetrica de reforco. Constatou-se tambem que materiais na fase nematica demonstram uma constante dieletrica mais baixa quando comparados com materiais onde o reforco esta distribuido aleatoriamente. Ficou ainda demonstrado nesta dissertacao que materiais na fase nematica com razoes entre o comprimento e diametro diferentes a constante dieletrica segue uma lei de potencia. Numa segunda fase do trabalho, foi explorada a condutividade de nanocompositos polimericos reforcados com nanotubos de carbono, atraves de um modelo baseado em cilindros impenetraveis. Ficou demonstrado que o modelo e apropriado para descrever a condutividade eletrica de um nanocomposito polimerico reforcado com nanotubos. As simulacoes desenvolvidas demonstram que, aumentando a razao entre o comprimento e o diametro dos nanotubos de carbono, aumenta a condutividade eletrica do nanocomposito. No entanto, verifica-se que aumentando a anisotropia diminui a condutividade, sendo este efeito mais evidente para fracoes volumetricas maiores. Nesta dissertacao comprovou-se ainda que uma microestrutura gerada por um algoritmo de empacotamento sequencial pode ser descrita por um grafo aleatorio e que a condutividade num composito reforcado com nanofibras de carbono pode ser descrito por uma rede de Bethe. Atraves do uso da teoria das redes complexas, chegou-se a uma expressao para o limite de percolacao e, do mesmo modo, demonstrou-se que “hopping” entre fibras adjacentes resulta numa expressao que corresponde a um regime de desordem fraca. No trabalho desenvolvido tambem foi calculado os expoentes criticos, atraves da teoria das redes, para um sistema 3D composto por cilindros impenetraveis com uma interacao de curto alcance, demonstrando que os expoentes criticos estao relacionados por uma relacao de hiperescala comum para 3D e nao pertencem a mesma classe de universalidade como a percolacao numa rede. A aplicacao do modelo desenvolvido a compositos de epoxy reforcada, com diferentes metodos de dispersao de nanofibras de carbono, revelou que os metodos de dispersao usados para preparar os compositos tem uma forte influencia nas propriedades eletricas que podem ser capturadas pelo modelo. Neste contexto, ficou ainda demonstrado que a condutividade eletrica pode ser descrita por um regime de desordem fraca, isto ´e, um regime onde todas as conexoes fibra-fibra participam na condutividade do composito. O modelo desenvolvido foi aplicado igualmente a compositos de poly (vinylidene fluoride) reforcado com nanotubos de carbono com diferentes tratamentos de termicos de oxidacao. Verificou-se que os tratamentos de superficie aumentam o limite de percolacao e diminuem a condutividade. Nesta dissertacao provamos ainda que a condutividade do composito pode ser atribuida a um mecanismo de “hopping”, fortemente afetado pelos tratamentos de superficie dos reforcos.

Water fluoridation in Brazilian cities at the first decade of the 21st century.

PubMed

Frazão, Paulo; Narvai, Paulo Capel

2017-05-15

To assess the coverage of the fluoridation of the public water supply in Brazilian municipalities at the first decade of the 21st century, according to population size and municipal human development index (MHDI). We have used data produced by national information agencies and the United Nations Development Programme. Population size was separated into < 10,000, 10,000-50,000, and > 50,000 inhabitants. The MHDI was classified into < 0.600, 0.600-0.699, 0.700-0.799, and > 0.799. Absolute and relative inequalities between categories were evaluated using indicators of effect and total impact. We have obtained information for 5,558 municipalities. The coverage rate of water fluoridation increased from 67.7% to 76.3%. Approximately 884 (15.9%) municipalities and 29,600,000 inhabitants started being benefited by the measure. We have observed a significant expansion in municipalities with < 10,000 inhabitants (increase of 21.0 percentage points) and low or very low MHDI (17.7 percentage points). Population coverage of the public policy has increased 8.6%, and we can also see significant reductions in absolute and relative inequality according to population size and MHDI. Regarding municipal coverage rate, there was also a reduction in inequality in all comparisons except for absolute inequality between the categories of MHDI. The public policy has operated as a factor of health protection in the context of the ongoing social protection policies in the country. Avaliar a cobertura da fluoretação da água de abastecimento público em municípios brasileiros na primeira década do século XXI, segundo porte demográfico e nível de desenvolvimento humano municipal (IDH-M). Foram utilizados dados produzidos por agências nacionais de informação e pelo Programa das Nações Unidas para o Desenvolvimento. O porte demográfico foi separado em < 10 mil; 10-50 mil; > 50 mil habitantes. O IDH-M foi classificado em < 0,600; 0,600-0,699; 0,700-0,799; > 0,799. As desigualdades absoluta e relativa entre as categorias foram avaliadas por meio de indicadores de efeito e de impacto total. Foram obtidas informações para 5.558 municípios. A taxa de cobertura da fluoretação da água aumentou de 67,7% para 76,3%. Passaram a ser beneficiados pela medida 884 (15,9%) municípios, e 29,6 milhões de habitantes. Observou-se ampliação expressiva em municípios com < 10 mil habitantes (aumento de 21,0 pontos percentuais) e com IDH-M baixo ou muito baixo (17,7 pontos percentuais). A cobertura populacional da política pública aumentou 8,6%, sendo expressivas as reduções das desigualdades absoluta e relativa segundo o porte demográfico e o IDH-M. Quanto à taxa de cobertura municipal, houve também redução da desigualdade em todas as comparações com exceção da desigualdade absoluta entre as categorias de IDH-M. A política pública operou como fator de proteção sanitária no contexto das políticas de proteção social em curso no país.

Hiperplasia angiolinfoide com eosinofilia: um caso raro em cavidade oral

PubMed Central

Tenório, Jefferson da Rocha; Gonzaga, Amanda Katarinny Goes; Gonçalves, Patrícia Guerra Peixe; de Oliveira, Denise Hélen Imaculada Pereira; Queiroz, Lélia Maria Guedes

2016-01-01

Resumo A hiperplasia angiolinfoide com eosinofilia (HALE) é considerada uma lesão vascular benigna rara que acomete, principalmente, o tecido cutâneo e subcutâneo da região de cabeça e pescoço, mas incomum na cavidade oral. Sua etiopatogenia permanece indefinida, sendo descrita como proliferação vascular reacional, malformação vascular ou neoplasia. Tem como principal diagnóstico diferencial a doença de Kimura. Este trabalho relata um caso de um paciente do sexo masculino, de 50 anos, que exibia aumento de volume nodular na mucosa do lábio superior, com 3 cm de dimensão e 7 anos de evolução. Após a biópsia excisional, o exame histopatológico mostrou lesão bem encapsulada multilobulada com proliferação de capilares sanguíneos com células endoteliais de aspecto epitelioide, infiltrado inflamatório difuso com linfócitos, plasmócitos, inúmeros eosinófilos e presença de folículos linfoides. A análise imuno-histoquímica revelou positividade para CD34 e Ki-67, o que, juntamente com o exame morfológico, direcionou o diagnóstico para HALE. PMID:29930611

Incidence of colorectal cancer in young patients.

PubMed

Campos, Fábio Guilherme C M DE; Figueiredo, Marleny Novaes; Monteiro, Mariane; Nahas, Sérgio Carlos; Cecconello, Ivan

2017-01-01

Sporadic colorectal cancer (CRC) is traditionally diagnosed after de sixth decade of life, although a small percentage of cases are diagnosed in patients under 40 years of age, and incidence is increasing. There exists a great volume of controversy regarding clinical outcome of young patients diagnosed with colorectal cancer (CRC) when compared to elder counterparts. Our aims were to evaluate the rate of CRC in young patients, to review the pertaining literature and to discuss outcomes and clinical prognosis. A retrospective review involving patients with CRC was undertaken, focusing on age at diagnosis. The information extracted from this literature review showed a trend towards a decreased incidence in older people with an opposite effect among adolescents and young adults. Moreover, biological aggressiveness in young adults diagnosed with CRC has not been fully recognized, although it is usually diagnosed later and in association with adverse histological features. Besides that, these features don't affect outcome. These apparent increase in CRC incidence among young patients during the last decades raises the need for a greater suspicious when evaluating common symptoms in this group. Thus, educational programs should widespread information for both population and physicians to improve prevention and early diagnosis results. RESUMO O câncer colorretal (CCR) esporádico é tradicionalmente diagnosticado após a sexta década de vida, embora uma pequena porcentagem de casos seja diagnosticada em doentes abaixo dos 40 anos de idade, e a incidência está aumentando. Existe uma grande controvérsia a respeito da evolução clínica de doentes jovens portadores de CCR em comparação aos mais idosos. Os objetivos deste estudo foram avaliar a prevalência de CCR em doentes jovens, rever a literatura pertinente e discutir suas características mais importantes nesta faixa etária. Para tanto realizou-se revisão da literatura envolvendo doentes com CCR com foco na idade ao diagnóstico. A informação extraída da revisão de literatura demonstrou uma tendência de redução da incidência em pessoas mais idosas com efeito oposto em adolescentes e adultos jovens. Sua agressividade biológica ainda não foi claramente reconhecida, embora seja usualmente diagnosticado mais tardiamente e em associação com características histológicas adversas. Apesar disso, estas características não afetam a evolução. Este aparente aumento na incidência de CCR entre pacientes jovens durante as últimas décadas levanta a necessidade de uma maior suspeita diagnóstica na avaliação de sintomas comuns neste grupo. Assim, programas educacionais devem disseminar informação tanto para população como para médicos a fim de melhorar a prevenção e o diagnóstico precoce.

TENDINOPATHY AND OBESITY.

PubMed

Castro, Adham do Amaral E; Skare, Thelma Larocca; Nassif, Paulo Afonso Nunes; Sakuma, Alexandre Kaue; Barros, Wagner Haese

Tendinopathies and tendon tears account for over 30% of all musculoskeletal consultations. Obesity, which is becoming one of the world´s most prevalent public health issues, may be associated with this condition. To review the literature about tendinopathies and obesity association. This is a descriptive exploratory study using the portal Medline. Literature in English language from 2006 to 2014 were reviewed. The pathogenesis of tendinopathies includes inflammatory, regenerative and degenerative processes that happen simultaneously from early to late phases of the disease. Mechanical stress upon tendons seems to be one of the most important factors to initiate the inflammatory response, but it´s not the only one that can deflagrate it: there are other extrinsic, genetic and metabolic factors that may be involved. Therefore, tendinopathies in obese patients can be due to tendon overload because of the excess of weight, but also because of increased production of pro-inflammatory mediators related to fat tissue such as adipokines. This pro-inflammatory state that obese people can suffer is known as adiposopathy, or sick fat syndrome. Weight loss is associated with decrease in adipokines and improvement of musculoskeletal symptoms. The relation of obesity and tendinopathies is supported by evidences of recent studies, exemplified in this review of literature. As tendinopatias e as fissuras em tendões respondem por 30% de todas as consultas médicas. A obesidade, que está se tornando um dos problemas de saúde pública mais prevalentes no mundo, pode estar associada com esta condição. Revisar a literatura acerca da associação entre obesidade e tendinopatias. Este é um estudo exploratório e descritivo utilizando artigos em língua inglesa do portal médico Medline, do período de 2006 a 2014. Na patogênese das tendinopatias incluem-se elementos inflamatórios, regenerativos e degenerativos que aparecem de maneira simultânea em todos os estágios da doença. O estresse mecânico sobre os tendões parece ser um dos mais importantes na promoção do processo inflamatório inicial. Todavia não é o único. Existem fatores ambientais, genéticos e metabólicos atuando de maneira ativa. Portanto, as tendinopatias em indivíduos obesos podem se dever à sobrecarga mecânica pelo excesso de peso, mas, também, pelo aumento na produção de mediadores pró-inflamatórios relacionados ao tecido adiposo, como as adipocinas. O estado pró-inflamatório existente no indivíduo obeso é conhecido como adiposopatia ou síndrome da "gordura doente". A perda de peso está associada com decréscimo das adipocinas e diminuição da sintomatologia musculoesquelética. A associação da obesidade com tendinopatias tem sido fundamentada em estudos recentes como os desta revisão de literatura.

Comparison of Two Central Venous Pressure Control Strategies to Prevent Atrial Fibrillation After Coronary Artery Bypass Grafting.

PubMed

Costa, Mario Augusto Cray da; Lirani, Wesley; Wippich, Ana Caroline; Lopes, Luana; Tolentino, Eduardo de Souza; Zampar, Beatriz; Schafranski, Marcelo Derbli

2017-04-01

Atrial fibrillation (AF) takes place in 10-40% of patients undergoing coronary artery bypass grafting (CABG), and increases cardiovascular mortality. Enlargement of atrial chambers is associated with increased AF incidence, so patients with higher central venous pressure (CVP) are expected to have larger atrial distension, which increases AF incidence. To compare post-CABG AF incidence, following two CVP control strategies. Interventional, randomized, controlled clinical study. The sample comprised 140 patients undergoing CABG between 2011 and 2015. They were randomized into two groups, G15 and G20, with CVP maintained ≤ 15 cmH2O and ≤ 20 cmH2O, respectively. 70 patients were included in each group. The AF incidence in G15 was 8.57%, and in G20, 22.86%, with absolute risk reduction of 14.28%, and number needed to treat (NNT) of 7 (p = 0.03). Mortality (G15 = 5.71%; G20 = 11.42%; p = 0.07), hospital length of stay (G15 = 7.14 days; G20 = 8.21 days; p = 0.36), number of grafts (median: G15 = 3, G2 = 2; p = 0.22) and cardiopulmonary bypass use (G15 = 67.10%; G20 = 55.70%; p = 0.22) were statistically similar. Age (p = 0.04) and hospital length of stay (p = 0.001) were significantly higher in patients who developed AF in both groups. Keeping CVP low in the first 72 post-CABG hours reduces the relative risk of AF, and may be useful to prevent AF after CABG. A fibrilação atrial (FA) ocorre em 10-40% dos pacientes submetidos a cirurgia de revascularização miocárdica (RM), e eleva a mortalidade cardiovascular. Como o aumento dos átrios está associado ao aumento da incidência de FA, espera-se que pacientes com pressão venosa central (PVC) mais alta tenham maior distensão atrial, o que eleva a incidência dessa arritmia. Comparar a incidência de FA em pós-operatório de RM, seguindo duas estratégias de controle de PVC. Estudo clínico randomizado controlado intervencionista. A amostra foi composta por 140 pacientes submetidos a RM entre 2011 e 2015. Os pacientes foram randomizados em dois grupos, G15 e G20, mantidos com PVC máxima de 15 cmH2O e 20 cmH2O, respectivamente. Foram incluídos 70 pacientes em cada grupo. A incidência da arritmia em G15 foi de 8,57% e, no G20, de 22,86%, com redução de risco absoluto de 14,28% e número necessário para tratar (NNT) de 7 (p = 0,03). Mortalidade (G15 = 5,71%; G20 = 11,42%; p = 0,07), tempo de internamento (G15 = 7,14 dias; G20 = 8,21 dias; p = 0,36), número de enxertos (medianas: G15 = 3, G2 = 2; p = 0,22) e uso de circulação extracorpórea (G15 = 67,10%; G20 = 55,70%; p = 0,22) mostraram-se estatisticamente semelhantes. A idade (p = 0,04) e o tempo de internamento (p = 0,001) foram significativamente maiores nos pacientes que desenvolveram FA nos dois grupos. Manter a PVC com valores mais baixos nas primeiras 72h após a cirurgia de RM reduz o risco relativo de FA e pode ser uma ferramenta útil na prevenção da FA após RM.

Temporal analysis of reported cases of tuberculosis and of tuberculosis-HIV co-infection in Brazil between 2002 and 2012.

PubMed

Gaspar, Renato Simões; Nunes, Natália; Nunes, Marina; Rodrigues, Vandilson Pinheiro

2016-01-01

To investigate the reported cases of tuberculosis and of tuberculosis-HIV co-infection in Brazil between 2002 and 2012. This was an observational study based on secondary time series data collected from the Brazilian Case Registry Database for the 2002-2012 period. The incidence of tuberculosis was stratified by gender, age group, geographical region, and outcome, as was that of tuberculosis-HIV co-infection. Nationally, the incidence of tuberculosis declined by 18%, whereas that of tuberculosis-HIV co-infection increased by 3.8%. There was an overall decrease in the incidence of tuberculosis, despite a significant increase in that of tuberculosis-HIV co-infection in women. The incidence of tuberculosis decreased only in the 0- to 9-year age bracket, remaining stable or increasing in the other age groups. The incidence of tuberculosis-HIV co-infection increased by 209% in the ≥ 60-year age bracket. The incidence of tuberculosis decreased in all geographical regions except the south, whereas that of tuberculosis-HIV co-infection increased by over 150% in the north and northeast. Regarding the outcomes, patients with tuberculosis-HIV co-infection, in comparison with patients infected with tuberculosis only, had a 48% lower chance of cure, a 50% greater risk of treatment nonadherence, and a 94% greater risk of death from tuberculosis. Our study shows that tuberculosis continues to be a relevant public health issue in Brazil, because the goals for the control and cure of the disease have yet to be achieved. In addition, the sharp increase in the incidence of tuberculosis-HIV co-infection in women, in the elderly, and in the northern/northeastern region reveals that the population of HIV-infected individuals is rapidly becoming more female, older, and more impoverished. Investigar os casos notificados de tuberculose e de sua coinfecção com o HIV na população brasileira no período entre 2002 e 2012. Realizou-se um estudo observacional de série temporal, no qual foram analisados dados secundários coletados do Sistema de Informação de Agravos de Notificação, no período entre 2002 e 2012. As incidências de tuberculose e tuberculose-HIV foram estratificadas por sexo, faixa etária, macrorregião e situação de encerramento. A incidência de tuberculose decaiu 18%, enquanto a de coinfecção tuberculose-HIV aumentou 3,8% no país. Houve uma redução geral da incidência de tuberculose apesar do aumento expressivo de tuberculose-HIV em mulheres. A taxa de incidência de tuberculose diminuiu apenas na faixa etária de 0-9 anos, permanecendo estável ou com variação positiva nas outras faixas etárias. A incidência da coinfecção tuberculose-HIV cresceu 209% na faixa etária ≥ 60 anos. A incidência de tuberculose diminuiu em todas as macrorregiões, exceto no Sul, enquanto a de tuberculose-HIV aumentou mais de 150% no Norte e Nordeste. Quanto à situação de encerramento, revelou-se que pacientes com tuberculose-HIV têm 48% menos chance de cura, 50% mais chance de abandonar o tratamento e 94% mais chance de óbito por tuberculose em relação àqueles sem a coinfecção. O presente estudo evidencia a tuberculose como um importante problema de saúde pública no Brasil, uma vez que as metas estabelecidas de cura e controle da doença ainda não foram alcançadas. Ademais, o aumento vertiginoso na incidência de tuberculose-HIV em mulheres, idosos e nas regiões Norte e Nordeste evidencia a feminização, a transição etária e a pauperização pelo HIV.

EFFECT OF CHRONIC INGESTION OF WINE ON THE GLYCEMIC, LIPID AND BODY WEIGHT HOMEOSTASIS IN MICE.

PubMed

Brito-Filho, Sebastião Barreto de; Moura, Egberto Gaspar de; Santos, Orlando José Dos; Sauaia-Filho, Euler Nicolau; Amorim, Elias; Santana, Ewaldo Eder Carvalho; Barros-Filho, Allan Kardec Dualibe; Santos, Rennan Abud Pinheiro

2016-01-01

The health benefits associated with moderate wine consumption, as with ethanol and phenolic compounds, include different mechanisms still little understandable. Evaluate glycemic and weight variations, and the deposit of triglycerides, cholesterol and liver glycogen with red wine consumption. 60 ApoE knockout mice were divided into three groups of 20: Wine Group (WG), Ethanol Group (EG) and Water Group (WAG). They received daily: WG 50 ml of wine and 50 ml water; EG 6 ml ethanol and WAG 94 ml of water. All groups were followed for four months. The food intake was monitored daily, in the period from eight to ten hours and held every five days. The measurement of water intake was also made every five days. The weighing of the animals took place every ten days. The WG had higher weight increase as compared to the other groups. The concentration of hepatic triglyceride was higher in WG (57%) and the EG group was lower (31.6%, p<0.01) than the control. The concentration of cholesterol was lower in the WG (23.6%), as well as EG (24.5%, p<0.05). The concentration of glycogen was higher in WG (16%) and fasting blood glucose was higher in EG compared to the other groups but not both demonstrated a statistically significant difference. The WG increased triglyceride and WAG decreased cholesterol. The triglyceride may be increased due to the high caloric value of wine or some unknown property that led to significant increase in subcutaneous andretroperitoneal fat in mice. Os benefícios para a saúde associados ao consumo moderado de vinho, como etanol e compostos fenólicos, incluem mecanismos diferentes ainda pouco compreensíveis. Avaliar as variações da glicemia, peso e depósito de triglicrideos, colesterol e glicogênio hepático com o uso de vinho tinto. Sessenta camundongos ApoE knockout foram divididos em três grupos de 20: Grupo do Vinho (WG), grupo do Etanol (EG) Grupo Água (WAG). Cada grupo recebeu diariamente: WG 50 ml de vinho e 50 ml de água; EG 6 ml de etanol e WAG 94 ml de água. O WG teve aumento de peso mais elevado em comparação com os outros grupos. A concentração de triglicerídeos foi maior no WG (57%) e no grupo EG inferior (31,6%) do que no controle (p <0,01). A concentração de colesterol foi inferior no WG (23,6%) e no EG (24,5%, p<0,05). A concentração de glicogênio foi maior no WG (16%); a glicemia capilar foi maior no EG em comparação com os outros grupos, mas não demonstrou diferença estatisticamente significativa. Triglicerídeos ficaram aumentados no WG e o colesterol diminuiu no WAG. Os triglicerídeos podem ter aumentado devido ao alto valor calórico do vinho ou alguma propriedade desconhecida que levou ao aumento significativo da gordura subcutânea e retroperitoneal nos camundongos.

Local probe studies on lattice distortions and electronic correlations in manganites

NASA Astrophysics Data System (ADS)

Lopes, Armandina Maria Lima

Nesta tese apresenta-se um estudo experimental das distorcoes locais e correlacoes electronicas em oxidos magneticos com magnetoresistencia colossal. A tecnica de sonda local - Correlacao Angular Perturbada - e utilizada em amostras caracterizadas quanto as suas propriedades macroscopicas nomeadamente propriedades estruturais, magneticas e electricas, tendo em vista a obtencao de informacao microscopica relevante via gradiente de campo electrico e campo magnetico hiperfino, focando em particular os seguintes aspectos: -Distorcoes de rede e agregados de polaroes no sistema LaMnO3+Delta. E apresentado um estudo dos gradientes de campo electrica e campo magnetico hiperfino em amostras representativas do sistema LaMnO3+Delta, correlacionando estas propriedades locais com a caracterizacao das propriedades macroscopicas, efectuada nas mesmas amostras. Desta forma, foi possivel estudar a natureza microscopica das distorcoes polaronicas. Foi dada especial atencao ao composto com composicao LaMnO3.12 uma vez que este e um sistema padrao de uma manganite ferromagnetica-isoladora que apresenta uma transicao estrutural romboedrica (R)-ortorrombica (O) perto da temperatura ambiente. O estudo revelou que agregados de distorcoes locais sobrevivem ate 776 K, na fase de estrutura media mais simetrica (romboedrica), onde, por simetria, os octaedros MnO6 deveriam ser regulares. Estas distorcoes sao semelhantes as observadas no sistema LaMnO3 onde os octaedros MnO6 apresentam uma distorcao Jahn-Teller colectiva. Com a diminuicao da temperatura observa-se um aumento continuo destes agregados. Abaixo de uma temperatura critica estas distorcoes relaxam acomodando-se numa estrutura com reduzidas distorcoes Jahn-teller. Verificou-se tambem que a transicao estrutural (macroscopica) pode ser entendida como uma transicao de percolacao dos ambientes microscopicos. -Coexistencia das ordens electrica e magnetica no sistema Pr1-xCaxMnO3. E apresentado o primeiro estudo de gradiente de campo electrico no sistema Pr1-xCaxMnO3. Este estudo foi efectuado numa larga gama de temperaturas permitindo estudar localmente as diversas transicoes que este sistema apresenta. Em particular, na regiao do diagrama de fases onde existe ordenamento de carga e orbital (0.32

Avaliação dos efeitos do subgalato de bismuto na proliferação de miofibroblastos

PubMed Central

de Lima, Rubianne Ligório; Sampaio, Cláudia Paraguaçu; Seidel, Karin Caroline; Branco, Melina; Sobreiro, Rafaela Mabile

2016-01-01

Resumo Contexto O subgalato de bismuto é um metal pesado e insolúvel, utilizado por suas propriedades adstringentes e hemostáticas. Objetivo Avaliar os efeitos do subgalato de bismuto na cicatrização mediante observação de miofibroblastos em pele de ratos. Métodos Foram utilizados 60 ratos da linhagem Wistar, que receberam uma ferida no dorso da pele. Os animais foram divididos em dois grupos: controle (aplicação diária de cloreto de sódio a 0,9%) e experimental (aplicação diária de 0,5 mg de subgalato de bismuto). Cada grupo foi subdividido em três subgrupos, que foram reoperados para retirada da ferida em 3, 7 e 14 dias. Foi realizada coloração de hematoxilina eosina, picrosirius e imuno-histoquímica para avaliar contagem de miofibroblastos, resposta inflamatória e síntese de colágeno. Resultados Não foi encontrada diferença entre os grupos controle e experimento com relação ao processo inflamatório – subgrupos 3 dias (p = 1), 7 dias (p = 0,474) e 14 dias (p = 303). A avaliação dos colágenos tipo I e III no grupo-controle não demonstrou benefícios de cicatrização – 3 dias (p = 0,436), 7 dias (p = 0,853) e 14 dias (p = 0,436); já no grupo experimental, houve aumento dos colágenos tipos I e III nos subgrupos 3 e 14 dias (p = 0,005). A imuno-histoquímica confirmou os resultados encontrados na coloração hematoxilina eosina, na qual a área de miofibroblastos entre os subgrupos, nos grupos experimental (p = 0,4) e controle (p = 0,336), foi indiferente. Conclusão A utilização do subgalato de bismuto em ferida de pele de ratos não evidenciou benefícios na cicatrização, ou seja, não houve diferença na fibroplasia quando comparados os grupos experimental e controle. PMID:29930592

Influence of hormonal contraceptives and the occurrence of stroke: integrative review.

PubMed

Lima, Adman Câmara Soares; Martins, Larissa Castelo Guedes; Lopes, Marcos Venícios de Oliveira; Araújo, Thelma Leite de; Lima, Francisca Elisângela Teixeira; Aquino, Priscila de Souza; Moura, Escolástica Rejane Ferreira

2017-01-01

To identify scientific evidence regarding the influence of hormonal contraceptive use and the occurrence of stroke. Integrative review of the literature, through database search using the descriptors "contraceptive agents", "contraceptive devices", "contraceptives, Oral" and "Stroke". Original studies in Portuguese, Spanish and English, published in full and available online were included. Studies that did not answer our guiding questions and duplicated studies were excluded. Women using combined oral contraceptives have higher risk of stroke, even with a lower hormonal dosage and different types of progestogen, regardless of the duration of use. The use of contraceptives associated with smoking, hypertension, migraine, hypercholesterolemia, obesity and sedentary lifestyle increases the chance of stroke. Contraceptive patch and vaginal ring are associated to increased risk. Use of combined hormonal contraceptives, except for the injectable and the transdermal ones, increases the chance of occurrence of the event. Progestogen-only contraceptives were considered safe. Identificar evidências científicas acerca da influência do uso de anticoncepcionais hormonais na ocorrência do acidente vascular cerebral (AVC). Revisão integrativa da literatura, com pesquisa em bases de dados, utilizando os descritores "contraceptive agents", "contraceptive devices", "contraceptives, Oral" e "stroke". Foram incluídos artigos originais nos idiomas português, espanhol e inglês, publicados na íntegra e disponíveis eletronicamente. Foram excluídos artigos que não respondiam às questões norteadoras e repetidos. Usuárias de anticoncepcional oral combinado apresentam risco maior de AVC, mesmo com dosagem hormonal menor e diferentes tipos de progestágeno, independente do tempo de uso. A presença associada de tabagismo, hipertensão arterial, enxaqueca, hipercolesterolemia, obesidade e sedentarismo aumenta a chance desse desfecho. Adesivo anticoncepcional e anel vaginal são relacionados ao aumento desse risco. A exposição aos anticoncepcionais hormonais combinados aumenta a chance de ocorrência do evento, exceto o injetável e o transdérmico. Os exclusivos de progestágeno foram considerados seguros.

Relationship between Cardiometabolic Parameters and Elevated Resting and Effort Heart Rate in Schoolchildren.

PubMed

Silva, Cristiane Fernanda da; Burgos, Miria Suzana; Silva, Priscila Tatiana da; Burgos, Leandro Tibiriçá; Welser, Letícia; Sehn, Ana Paula; Horta, Jorge André; Mello, Elza Daniel de; Reuter, Cézane Priscila

2017-09-01

Little has been studied on heart rate and its relationship with metabolic disorders. To identify possible association between heart rate (HR) and metabolic disorders in children and adolescents. This cross-sectional study evaluated 2.098 subjects, aged between 7 and 17 years. The variables evaluated were: HR, systolic (SBP) and diastolic blood pressure (DBP), pulse pressure (PP), double-product (DP), myocardial oxygen consumption (mVO2), lipids, glucose and uric acid levels, body mass index (BMI) and waist circumference (WC). The values of HR at rest and effort were divided into quartiles. The association between continuous values of HR and cardiometabolic indicators was tested by linear regression. LDL cholesterol presented a significantly higher mean (p = 0.003) in schoolchildren with resting HR greater or equal to 91 bpm, compared to students with less than 75 bpm. Compared with the quartiles of effort HR, SBP, DBP, glucose and uric acid presented high values when HR was greater or equal than 185 bpm. SBP, glucose and HDL cholesterol demonstrated a significant association with resting HR. Uric acid was observed as a predictor of increased effort HR. Schoolchildren with a higher resting HR have higher mean of LDL cholesterol. For effort HR, there was an increase in blood pressure, glucose and uric acid levels. Uric acid has been shown to be a predictor of elevated effort HR. Pouco se tem estudado sobre frequência cardíaca e suas relações com alterações metabólicas. Verificar se existe associação entre frequência cardíaca e disfunções metabólicas em crianças e adolescentes. Estudo transversal com 2.098 escolares, com idade entre 7 e 17 anos. As variáveis avaliadas foram: frequência cardíaca (FC), pressão arterial sistólica (PAS), diastólica (PAD) e de pulso (PP), duplo-produto (DP), consumo de oxigênio pelo miocárdio (mVO2), perfil lipídico e glicêmico, níveis de ácido úrico, índice de massa corporal (IMC) e circunferência da cintura (CC). Os valores de FC de repouso e esforço foram divididos em quartis. A associação entre os valores contínuos de FC com indicadores cardiometabólicos foi testada por meio da regressão linear. O colesterol LDL apresentou média significativamente superior (p = 0,003) nos escolares com FC de repouso maior ou igual a 91 bpm, em comparação aos escolares que apresentaram menos de 75 bpm. Comparados com os quartis da FC de esforço, a PAS, PAD, glicose e ácido úrico apresentaram valores elevados quando a FC foi igual ou superior a 185 bpm. A PAS, a glicose e o colesterol HDL demonstraram associação significativa com a FC de repouso. Observou-se o ácido úrico como um preditor do aumento da FC de esforço. Escolares com FC de repouso mais elevada apresentam médias superiores de colesterol LDL. Para FC de esforço, observou-se elevação na pressão arterial, nos níveis de glicose e de ácido úrico. O ácido úrico demonstrou ser preditor da elevação da FC de esforço.

Effects of emissions from sugar cane burning on the trachea and lungs of Wistar rats.

PubMed

Matos, Verena Sampaio Barbosa; Gomes, Felipe da Silva; Oliveira, Tarcio Macena; Schulz, Renata da Silva; Ribeiro, Lídia Cristina Villela; Gonzales, Astria Dias Ferrão; Lima, Januário Mourão; Guerreiro, Marcos Lázaro da Silva

2017-01-01

To evaluate the effects of exposure to emissions from sugar cane burning on inflammatory mechanisms in tissues of the trachea and lung parenchyma in Wistar rats after different periods of exposure. This was an experimental open randomized study. The animals were divided into four groups: a control group (CG) underwent standard laboratory conditions, and three experimental groups were exposed to emissions from sugar cane burning over different periods of time, in days-1 (EG1), 7 (EG7), and 21 (EG21). After euthanasia with 200 mg/kg of ketamine/xylazine, fragments of trachea and lung were collected and fixed in 10% formalin. Histological analyses were performed with H&E and picrosirius red staining. No inflammatory infiltrates were found in the tissues of CG rats. The histological examination of tissues of the trachea and lung parenchyma revealed that the inflammatory process was significantly more intense in EG7 than in the CG (p < 0.05 and p < 0.01, respectively). In comparison with the CG and EG1, angiogenesis in the lung parenchyma and collagen deposition in tracheal tissues were significantly greater only in EG21 (p < 0.001 and p < 0.01, respectively). In this sample, emissions from sugar cane burning induced acute focal and diffuse inflammation in the lamina propria of tracheal tissues, with no loss of ciliated epithelial tissue. In the lung parenchyma of the animals in the experimental groups, there was interstitial and alveolar edema, together with polymorphonuclear cell infiltrates. Avaliar os efeitos da exposição à fumaça da queima da cana-de-açúcar sobre mecanismos inflamatórios em tecidos de traqueia e de parênquima pulmonar de ratos Wistar após diferentes períodos de exposição. Estudo experimental, randomizado, não cego. Os animais foram divididos em quatro grupos: controle (GC), sob condições padrão de laboratório e os demais expostos à fumaça da queima da cana-de-açúcar por diferentes períodos: em 1 (GE1), 7 (GE7) e 21 (GE21) dias. Após a eutanásia com 200 mg/kg de ketamina/xilazina, foram coletados fragmentos de traqueia e pulmão e fixadas em formol 10%. Análises histológicas foram realizadas com coloração com H&E e picrosírius. Não houve infiltrado inflamatório nos tecidos no GC. O processo inflamatório na análise histológica de tecidos de traqueia e de parênquima pulmonar foi significativamente mais intenso no GE7 quando comparado ao GC (p < 0,05 e p < 0,01, respectivamente). Em comparação com os grupos GC e GE1, apenas no GE21 foi observada angiogênese significativa no parênquima pulmonar e aumento significativo de depósitos de colágeno em tecido de traqueia (p < 0,001 e p < 0,01, respectivamente). Nesta amostra, a fumaça da queima de cana-de-açúcar induziu processo inflamatório focal, difuso e agudo em tecidos de traqueia na lâmina própria, sem perda do tecido epitelial ciliado. Houve presença de edemas intersticiais e alveolares e infiltrados de células polimorfonucleares no parênquima pulmonar nos animais dos grupos experimentais.

SADI-S WITH RIGHT GASTRIC ARTERY LIGATION: TECHNICAL SYSTEMATIZATION AND EARLY RESULTS.

PubMed

Gebelli, Jordi Pujol; Gordejuela, Amador Garcia Ruiz de; Ramos, Almino Cardoso; Nora, Mario; Pereira, Ana Marta; Campos, Josemberg Marins; Ramos, Manoela Galvão; Bastos, Eduardo Lemos de Souza; Marchesini, João Batista

Bariatric surgery is performed all over the world with close to 500.000 procedures per year. The most performed techniques are Roux-en-Y gastric bypass and sleeve gastrectomy. Despite this data, the most effective procedure, biliopancreatic diversion with or without duodenal switch, represents only no more than 1.5% of the procedures. Technical complexity, morbidity, mortality, and severe nutritional adverse effects related to the procedure are the main fears that prevent most universal acceptance. To explain the technical aspects and the benefits of the SADI-S with right gastric artery ligation as an effective simplification from the original duodenal switch. Were included all patients undergoing this procedure from the November 2014 to May 2016, describing and analysing aspects of this technique, the systematization and early complications associated with the procedure. A series of 67 patients were operated; 46 were women (68.7%); mean age of the group was 44 years old (33-56); and an average BMI of 53.5 kg/m2 (50-63.5). Surgical time was 115 min (80-180). A total of five patients (7.5%) had any complication and two (2.9%) had to be reoperated. There were two patients with leak, one at the duodenal stump and other at the esophagogastric angle. There was no mortality. Patients stayed at the hospital a median of 2.5 days (1-25). SADI-S with right gastric artery ligation is a safe procedure with few preliminary complications. The technical variations introduced to the classical duodenal switch are reproducible and may allow this procedure to be more popular. All the complications in this series were not related to the ligation of the right gastric artery. Cerca de 500.000 cirurgias bariátricas são realizadas a cada ano em todo o mundo. As técnicas mais realizadas são o bypass gástrico em Y-de-Roux e a gastrectomia vertical. A derivação biliopancreática, com ou sem duodenal switch, é considerada técnica mais eficaz no tratamento cirúrgico do paciente obeso mórbido; entretanto, representa não mais do que 1,5% dos procedimentos na atualidade, pois sua complexidade técnica, morbimortalidade e graves efeitos adversos nutricionais impedem aceitação mais universal. Descrever os aspectos técnicos e os benefícios do SADI-S com ligadura da artéria gástrica direita como um modo simplificado do duodenal switch original. Foram incluídos todos os pacientes submetidos a este procedimento entre novembro 2014 e maio de 2016. Além da descrição da sistematização da técnica operatória, foram analisadas as complicações precoces associadas ao procedimento. Uma série de 67 pacientes foi operada no período analisado; 46 eram mulheres (68,7%) e a média de idade foi de 44 anos (33-56). O IMC médio foi de 53,5 kg/m2 (50-63,5). O tempo cirúrgico médio foi de 115 min (80-180) e a permanência hospitalar média foi de 2,5 dias (1-25). Complicações foram observadas em cinco pacientes (7,5%) e dois (2,9%) tiveram de ser reoperados. Duas pacientes evoluíram com fístula, uma no coto duodenal e outra na junção esofagogástrica. Não houve mortalidade. SADI-S com ligadura da artéria gástrica direita é procedimento seguro com poucas complicações precoces. A simplificação técnica em relação ao duodenal switch clássico pode permitir que este procedimento se torne mais popular. Todas as complicações observadas nesta série não estavam relacionadas com a ligadura da artéria gástrica direita.

University Students' Conceptions about the Moon Phases. (Spanish Title: Concepciones de Estudiantes Universitários sobre Las Fases de la Luna.) Concepções de Estudantes Universitários sobre as Fases da Lua

NASA Astrophysics Data System (ADS)

de Fátima Oliveira Saraiva, Maria; da Silveira, Fernando Lang; Steffani, Maria Helena

2011-07-01

In this article we describe the development of a multiple choice test about lunar phases and analyze the results of its application to ten groups of Physics students at the UFRGS. During the improvement of the test, we noticed that the percentage of right answers about some concepts increased significantly when associated with the reformulation of the question, emphasizing the importance of being careful to avoid incorrect answers generated by unclear questions, and not by ignorance on the matter. We confirm the results of other studies that show that students have great difficulty to relate the Moon's phase with its position in the sky at given time. On the other hand, our results suggest that, in general, students of Physics understand the phenomenon of lunar phases better than the average of university students. En estese artículo se describe la elaboración de una prueba de opción múltiple sobre las fases de la Luna y se analizan los resultados de su aplicación en diez grupos de estudiantes de Física de UFRGS. Durante el mejoramiento de la prueba observamos que el porcentaje de aciertos creció considerablemente cuando considerada una nueva redacción de la pregunta, destacando el cuidado que se debe tomar a fin de evitar respuestas incorrectas generadas por preguntas poco claras y no a causa de la ignorancia de los estudiantes sobre el tema. Confirmamos los resultados de otros estudios que las mayores dificultades de los alumnos sobre el tema fases de la Luna están en relacionar la fase de la Luna con su posición en el cielo en determinado momento. Por otra parte, nuestros resultados sugieren que, en general, los estudiantes de la Física comprenden mejor el fenómeno de las fases lunares que el promedio de los estudiantes universitarios. Neste artigo descrevemos a elaboração de um teste de múltipla escolha sobre as fases da Lua e analisamos os resultados de sua aplicação em dez grupos de estudantes de Física da UFRGS. Durante o aprimoramento do teste notamos que a porcentagem de acertos a respeito de alguns conceitos teve um aumento significativo associado à reformulação da pergunta, ressaltando a importância de tomar cuidado para evitar respostas erradas geradas por perguntas pouco claras e não por ignorância do respondente sobre o assunto. Confirmamos os resultados de outros estudos de que as maiores dificuldades dos alunos sobre o tema Fases da Lua dizem respeito a relacionar a fase que a Lua apresenta com a sua posição no céu em determinada hora. Por outro lado, nossos resultados sugerem que, em geral, os estudantes de Física entendem melhor o fenômeno das fases lunares do que a média dos estudantes universitários.

Characterisation of gas and particle emissions from wildfires =

NASA Astrophysics Data System (ADS)

Vicente, Ana Margarida Proenca

Os incendios florestais sao uma importante fonte de emissao de compostos gasosos e de aerossois. Em Portugal, onde a maioria dos incendios ocorre no norte e centro do pais, os incendios destroem todos os anos milhares de hectares, com importantes perdas em termos economicos, de vidas humanas e qualidade ambiental. As emissoes podem alterar consideravelmente a quimica da atmosfera, degradar a qualidade do ar e alterar o clima. Contudo, a informacao sobre as carateristicas das emissoes dos incendios florestais nos paises do Mediterrâneo e limitada. Tanto a nivel nacional como internacional, existe um interesse crescente na elaboracao de inventarios de emissoes e de regulamentos sobre as emissoes de carbono para a atmosfera. Do ponto de vista atmosferico da monitorizacao atmosferica, os incendios sao considerados um desafio, dada a sua variabilidade temporal e espacial, sendo de esperar um aumento da sua frequencia, dimensao e severidade, e tambem porque as estimativas de emissoes dependem das carateristicas dos biocombustiveis e da fase de combustao. O objetivo deste estudo foi quantificar e caraterizar as emissoes de gases e aerossois de alguns dos mais representativos incendios florestais que ocorreram no centro de Portugal nos veroes de 2009 e de 2010. Efetuou-se a colheita de amostras de gases e de duas fracoes de particulas (PM2.5 e PM2.5-10) nas plumas de fumo em sacos Tedlar e em filtros de quartzo acoplados a um amostrador de elevado volume, respetivamente. Os hidrocarbonetos totais (THC) e oxidos de carbono (CO e CO2) nas amostras gasosas foram analisados em instrumentos automaticos de ionizacao de chama e detetores nao dispersivos de infravermelhos, respetivamente. Para algumas amostras, foram tambem quantificados alguns compostos de carbonilo apos reamostragem do gas dos sacos Tedlar em cartuchos de silica gel revestidos com 2,4-dinitrofenilhidrazina (DNPH), seguida de analise por cromatografia liquida de alta resolucao. Nas particulas, analisou-se o carbono orgânico e elementar (tecnica termo-optica), ioes soluveis em agua (cromatografia ionica) e elementos (espectrometria de massa com plasma acoplado por inducao ou analise instrumental por ativacao com neutroes). A especiacao orgânica foi obtida por cromatografia gasosa acoplada a espectrometria de massa apos extracao com recurso a varios solventes e separacao dos extratos orgânicos em diversas classes de diferentes polaridades atraves do fracionamento com silica gel. Tendo em conta que a estimativa das emissoes dos incendios florestais requer um conhecimento de fatores de emissao apropriados para cada biocombustivel, a base de dados abrangente obtida neste estudo e potencialmente util para atualizar os inventarios de emissoes. Tem vindo a ser observado que a fase de combustao latente sem chama, a qual pode ocorrer simultaneamente com a fase de chama e durar varias horas ou dias, pode contribuir para uma quantidade consideravel de poluentes atmosfericos, pelo que os fatores de emissao correspondentes devem ser considerados no calculo das emissoes globais de incendios florestais. Devido a falta de informacao detalhada sobre perfis quimicos de emissao, a base de dados obtida neste estudo pode tambem ser util para a aplicacao de modelos no recetor no sul da Europa. (Abstract shortened by ProQuest.).

Effect of the exercise of walkers performed in public squares with spontaneous or prescribed intensity on post-exercise hypotension.

PubMed

Silva, Taís Feitosa da; Souza, Alesandra Araújo de; Lima, Fabiano Ferreira de; Suassuna, Jennifer Ariely Sales; Couto, Henrique Eduardo Paiva Lira do; Tenório, Gustavo Roque; Silva, Maria Irene de Andrade Gomes; Dias, Guilherme Leandebal Bonifácio; Silva, Alexandre Sérgio

2017-07-20

To quantify the intensity adopted by walkers in public squares and check the occurrence and magnitude of post-exercise hypotension in the spontaneously adopted intensity and in a prescribed intensity. In 98 volunteers (38 of them being hypertensive), walkers in public squares of the city of João Pessoa, State of Paraíba, Brazil, we have identified the intensity of a usual training monitored by heart rate and we have investigated the occurrence and magnitude of post-exercise hypotension. Subsequently, participants were instructed to walk with moderate intensity. Blood pressure was measured after rest and during post-exercise recovery. Of the total participants, 41% of the hypertensive and 36% of the normotensive individuals walked with light intensity. With the prescription, intensity increased to 55% and 52%, for the hypertensive and normotensive individuals, respectively. In the usual and prescribed intensity, the hypertensive individuals had post-exercise hypotension of -3.7±11.6 mmHg and -4.72±12.8 mmHg, respectively. There was no correlation between post-exercise hypotension and the initial systolic component of the hypertensive individuals (r2 = 0.2; p < 0.002). Walkers in public squares choose light intensity for walking. When they exercise with the prescribed intensity, they increase the intensity, but the magnitude of the PEH is not increase with this guidance. Quantificar a intensidade adotada por caminhantes em praças públicas e verificar a ocorrência e a magnitude da hipotensão pós-exercício na intensidade espontaneamente adotada e em uma intensidade prescrita. Em 98 voluntários (38 hipertensos), caminhantes em praças públicas da cidade de João Pessoa, PB, identificamos a intensidade de um treino habitual monitorada por meio da frequência cardíaca e averiguamos a ocorrência e magnitude de hipotensão pós-exercício. Posteriormente, os participantes foram instruídos a caminhar com intensidade moderada. A pressão arterial foi aferida após o repouso e durante a recuperação pós-exercício. Do total de participantes, 41% dos hipertensos e 36% dos normotensos caminhavam com intensidade leve. Com a prescrição, a intensidade aumentou para 55% e 52%, para hipertensos e normotensos. Na intensidade habitual e prescrita, os hipertensos obtiveram hipotensão pós-exercício de -3,7±11,6 mmHg e -4,72±12,8 mmHg. Houve correlação entre hipotensão pós-exercício e o componente sistólico inicial dos hipertensos (r2 = 0,2; p < 0,002). Caminhantes em praças públicas selecionam intensidade leve para realização de caminhada. Quando realizam exercício com intensidade prescrita, aumentam discretamente a intensidade, mas não obtêm aumento da magnitude da HPE com esta orientação.

THE ALCOHOL CONSUMPTION IS AMENDED AFTER BARIATRIC SURGERY? AN INTEGRATIVE REVIEW.

PubMed

Gregorio, Valeria Duarte; Lucchese, Roselma; Vera, Ivânia; Silva, Graciele C; Silva, Andrecia; Moraes, Rayrane Clarah Chaveiro

Bariatric surgery has been an alternative when conservative methods of weight loss fail. Patients undergoing bariatric surgery have an increased risk of up to 6.5% of problems related to alcohol. Integrative review out to analyze the change of alcohol consumption in this public. Database was accessed from June of 2015 to January of 2016 by searching "bariatric surgery" AND "alcoholism", and their Portuguese equivalents. ScienceDirect, PubMed, Lilacs and Medline, besides manual search, were searched. To be included, the paper should have been published between 2005-2016 and related to bariatric surgery and alcoholism. Theses, dissertations, unpublished papers, case reports and theoretical studies were excluded, and a database was subsequently composed. In 2005 there was only a review of change in alcohol metabolism in patients undergoing bariatric surgery. There were no publications in 2006. In 2007, only one study was published, and it did not meet the inclusion criteria. In 2010, there was an increase of 13% in publications and of 20% in 2012, reaching 40% in 2013. The prevalence and incidence of alcohol consumption in relation to the postoperative time was six months to three years with higher incidence for follow-up treatment by men. Roux-en-Y gastric bypass showed greater association with increased consumption of alcohol during the postoperative period. Alcohol consumption proved to be essential to be faced in bariatric surgery. A cirurgia bariátrica tem-se mostrado alternativa para o insucesso dos métodos conservadores de emagrecimento. Pacientes submetidos a ela têm 6,5% aumento do risco de terem problemas relacionados ao álcool. Realizar revisão integrativa para verificar alteração do consumo de álcool neste publico. A base de dados Science Direct, PubMed, Lilacs, Medline e busca manual foram acessadas entre os meses de junho de 2015 a janeiro de 2016 com os descritores "cirurgia bariátrica" e "alcoolismo" e equivalentes em inglês Os critérios de inclusão foram publicações entre junho de 2005 a janeiro de 2016 relacionadas à cirurgia bariátrica e ao consumo de álcool. Foram excluídas teses, dissertações, trabalhos não publicados, relatos de casos e estudos teóricos. No ano de 2005 houve somente uma revisão relacionada à alteração do metabolismo do álcool em pacientes submetidos à cirurgia bariátrica. Não houve publicações em 2006. Em 2007, houve uma publicação fora dos critérios desta revisão. Em 2010, observou-se aumento de 13% e 20% em 2012, atingindo 40% em 2013. A prevalência e a incidência do consumo de álcool em relação ao tempo de pós-operatório foi de seis meses a três anos com maior seguimento do tratamento por homens. O bypass gástrico em Y-de-Roux apresentou maior associação com o aumento do consumo de álcool durante o pós-operatório. O consumo de álcool é problema que deve ser enfrentado na realização da cirurgia bariátrica.

Jumping in aquatic environment after sciatic nerve compression: nociceptive evaluation and morphological characteristics of the soleus muscle of Wistar rats.

PubMed

Malanotte, Jéssica Aline; Kakihata, Camila Mayumi Martin; Karvat, Jhenifer; Brancalhão, Rose Meire Costa; Ribeiro, Lucinéia de Fátima Chasko; Bertolini, Gladson Ricardo Flor

2017-01-01

To evaluate the effect of jumping in aquatic environment on nociception and in the soleus muscle of trained and not trained Wistar rats, in the treatment of compressive neuropathy of the sciatic nerve. Twenty-five Wistar rats were distributed into five groups: Control, Lesion, Trained + Lesion, Lesion + Exercise, and Trained + Lesion + Exercise. The training was jumping exercise in water environment for 20 days prior to injury, and treatment after the injury. Nociception was evaluated in two occasions, before injury and seven after injury. On the last day of the experiment, the right soleus muscles were collected, processed and analyzed as to morphology and morphometry. In the assessment of nociception in the injury site, the Control Group had higher average than the rest, and the Lesion Group was larger than the Trained + Lesion and Lesion + Exercise Groups. The Control Group showed higher nociceptive threshold in paw, compared to the others. In the morphometric analysis, in relation to Control Group, all the injured groups showed decreased muscle fiber area, and in the Lesion Group was lower than in the Lesion + Exercise Group and Trained + Lesion Group. Considering the diameter of the muscle fiber, the Control Group had a higher average than the Trained + Lesion Group and the Trained + Lesion + Exercise Group; and the Lesion Group showed an average lower than the Trained + Lesion and Lesion + Exercise Groups. Resistance exercise produced increased nociception. When performed prior or after nerve damage, it proved effective in avoiding hypotrophy. The combination of the two protocols led to decrease in diameter and area of the muscle fiber. Avaliar os efeitos do salto em meio aquático, na nocicepção e no músculo sóleo, em ratos Wistar treinados e não treinados, no tratamento de neuropatia compressiva do nervo isquiático. Foram distribuídos em cinco grupos 25 ratos Wistar: Controle, Lesão, Treinado + Lesão, Lesão + Exercício e Treinado + Lesão + Exercício. O treino foi com exercício de salto em meio aquático durante 20 dias, prévio à lesão, e o tratamento ocorreu após a lesão. Foram realizadas avaliações da nocicepção, sendo uma pré-lesão e sete pós-lesão. No último dia de experimento, os músculos sóleos direitos foram coletados, processados e analisados por meio de morfologia e morfometria. Na avaliação da nocicepção no local da lesão, o Grupo Controle apresentou média maior que os demais, e o Grupo Lesão foi maior que os Grupos Treinado + Lesão e Lesão + Exercício. O Grupo Controle apresentou limiar nociceptivo na pata maior com relação aos demais. Nas análises morfométricas, em relação ao Grupo Controle, todos os grupos lesionados apresentaram diminuição da área da fibra muscular; o Grupo Lesão apresentou-se menor que os Grupos Treinado + Lesão e Lesão + Exercício. No diâmetro da fibra muscular, o Grupo Controle apresentou média maior que os Grupos Treinado + Lesão e Treinado + Lesão + Exercício, e o Grupo Lesão apresentou média menor que os Grupos Treinado + Lesão e Lesão + Exercício. O exercício físico resistido produziu aumento da nocicepção. Quando realizado previamente ou após a lesão nervosa, mostrou-se eficaz em evitar a hipotrofia. A associação dos dois protocolos levou à diminuição do diâmetro e da área da fibra muscular.

[Not Available].

PubMed

Corella Aznar, Elena Guadalupe; Ayerza Casas, Ariadna; Samper Villagrasa, Pilar; Rodríguez Vigil, Carmen; Jiménez Montañés, Lorenzo; Calvo Escribano, Carlota; Labarta Aizpun, José Ignacio

2016-06-30

Introducción: los supervivientes de leucemia aguda (LA) infantil presentan un riesgo incrementado de alteraciones metabólicas y cardiovasculares que aumentan su morbimortalidad a largo plazo.Objetivo: estimar la prevalencia de obesidad, resistencia a la insulina, dislipemia e hipertensión arterial como factores de riesgo cardiometabólico (FRCM) en un grupo de supervivientes de LA infantil, y analizar las posibles causas asociadas a su desarrollo.Material y métodos: estudio observacional retrospectivo en 47 supervivientes de LA tratados en un periodo de 4 años, que recibieron seguimiento durante 10 años.Resultados: el 40% de los participantes presentaron al menos un FRCM durante el seguimiento, siendo la dislipemia (aumento LDL) el más frecuente (38,3%), seguido de obesidad/sobrepeso (31,9%) y HTA sistólica (23,4%). El sexo femenino se estableció como factor de riesgo parael desarrollo de todos ellos (RR 1,6; RR 3,16; RR 1,69; p < 0,05). Ningún superviviente desarrolló diabetes mellitus, pero sí resistencia a la insulina el 19,4%. Los pacientes con leucemias de peor pronóstico presentaron mayor riesgo de desarrollar obesidad, resistencia a la insulina y aumento de LDL (RR 3,56; RR 4,08; RR 2,53; p < 0,05). Los pacientes tratados con trasplante de progenitores hematopoyéticos presentaron mayor riesgo de obesidad, aumento de LDL e HTA sistólica (RR 2,86; RR 2,39; RR 3,12; p<0,05). La radioterapia se asoció de igual modo con un incremento de resistencia a la insulina e hipertensión arterial sistólica (RR 2,47; RR 2,53; p < 0,05).Conclusiones: existe un aumento en la prevalencia de obesidad/sobrepeso, dislipemia, resistencia a la insulina y alteración de la tensión arterial sistólica en supervivientes de leucemia aguda infantil a lo largo del tiempo, especialmente en aquellos con enfermedades y tratamientos más agresivos.

Socioeconomic, hygienic, and sanitation factors in reducing diarrhea in the Amazon.

PubMed

Imada, Katiuscia Shirota; Araújo, Thiago Santos de; Muniz, Pascoal Torres; Pádua, Valter Lúcio de

2016-12-22

To analyze the contributions of the socioeconomic, hygienic, and sanitation improvements in reducing the prevalence of diarrhea in a city of the Amazon. In this population-based cross-sectional study, we analyzed data from surveys conducted in the city of Jordão, Acre. In 2005 and 2012, these surveys evaluated, respectively, 466 and 826 children under five years old. Questionnaires were applied on the socioeconomic conditions, construction of houses, food and hygienic habits, and environmental sanitation. We applied Pearson's Chi-squared test and Poisson regression to verify the relationship between origin of water, construction of homes, age of introduction of cow's milk in the diet, place of birth and the prevalence of diarrhea. The prevalence of diarrhea was reduced from 45.1% to 35.4%. We identified higher probability of diarrhea in children who did not use water from the public network, in those receiving cow's milk in the first month after birth, and in those living in houses made of paxiúba. Children born at home presented lower risk of diarrhea when compared to those who were born in hospital, with this difference reversing for the 2012 survey. Sanitation conditions improved with the increase of bathrooms with toilets, implementation of the Programa de Saúde da Família (PSF - Family Health Program), and water treatment in the city. The multivariate regression model identified a statistically significant association between use of water from the public network, construction of houses, late introduction of cow's milk, and access to health service with occurrence of diarrhea. Analisar as contribuições das melhorias socioeconômicas, higiênicas e de saneamento na redução da prevalência de diarreia em uma cidade na Amazônia. Neste estudo transversal de base populacional, foram analisados dados dos inquéritos realizados no município de Jordão, Acre. Em 2005 e 2012, foram avaliadas, respectivamente, 466 e 826 crianças menores de cinco anos. Foram aplicados questionários sobre as condições socioeconômicas, construção dos domicílios, hábitos higiênicos e alimentares e saneamento ambiental. Foi aplicado o teste Qui-quadrado de Pearson e a Regressão de Poisson para verificar a relação existente entre procedência da água, tipo de construção do domicílio, idade de introdução de leite de vaca na dieta e local de nascimento e a prevalência de diarreia. A prevalência de diarreia foi reduzida de 45,1% para 35,4%. Foi identificada maior probabilidade de desenvolvimento de diarreia em crianças que não utilizaram água da rede pública, as que receberam leite de vaca no primeiro mês após o nascimento e as residentes em domicílios de paxiúba. As crianças que nasceram no domicílio apresentaram menor risco de diarreia quando comparadas às que nasceram em hospital, com essa diferença se invertendo para o inquérito de 2012. Ocorreu melhora nas condições de saneamento com aumento no número de banheiro com vasos sanitários, implantação do Programa de Saúde da Família e tratamento de água na sede do município. O modelo de regressão multivariada identificou associação estatisticamente significativa entre utilização de água da rede pública, construção da moradia, introdução tardia de leite de vaca e acesso a serviço de saúde com ocorrência de diarreia.

Predictors of hope among women with breast cancer during chemotherapy.

PubMed

Balsanelli, Alessandra Cristina Sartore; Grossi, Sonia Aurora Alves

2016-01-01

Identifying the predictors of hope in patients with breast cancer during chemotherapy treatment. A prospective longitudinal study. The sample was composed of 122 women who responded to the instruments of hope, anxiety and depression, coping, fatigue, religiosity and self-esteem in the first and last cycle of chemotherapy. These variables were used in adjusting the logistic regression model that characterized multivariate statistics, allowing identification of predictor variables. The increase of hope at the end of chemotherapy treatment was statistically significant (p = 0.012). The delay in undergoing treatment from the onset of breast cancer symptoms, Karnofsky Performance Status, depression, self-esteem and pain were characterized as factors being associated to hope by univariate analysis. Among the variables analyzed, pain was the only predicting factor of hope. Pain was the predicting factor in this sample. Hope increased during treatment and revealed the following associated factors: Karnofsky Performance Status, delay in starting the treatment, depression, self-esteem and pain. This study brought forth a multidisciplinary contribution, allowing for understanding the factors that can influence hope and presenting support to nursing care. The data evidenced conditions of improvement or worsening of hope, which requires interdisciplinary attention in Oncology. Identificar os fatores preditores da esperança nas pacientes com câncer de mama em tratamento quimioterápico. Estudo prospectivo longitudinal. A amostra foi de 122 mulheres que responderam aos instrumentos de esperança, ansiedade e depressão, coping, fadiga, religiosidade e autoestima no primeiro e no último ciclo de quimioterapia. Essas variáveis foram utilizadas no ajuste do modelo de regressão logística que caracterizou a estatística multivariada permitindo a identificação das variáveis preditoras. O aumento da esperança ao final do tratamento quimioterápico foi estatisticamente significante (p = 0,012). A demora na realização do tratamento desde o início dos sintomas do câncer de mama, o Karnofsky Performance Status, a depressão, a autoestima e a dor foram caracterizadas como fatores associados à esperança pela análise univariada. Dentre as variáveis analisadas, a dor apresentou-se como o único fator preditor da esperança. A dor foi o fator preditor nesta amostra. A esperança aumentou durante o tratamento e revelou os fatores associados: Karnofsky Performance Status, demora no início do tratamento, depressão, autoestima e dor. Este estudo trouxe uma contribuição multidisciplinar, permitiu compreender os fatores que podem influenciar a esperança e apresentou subsídios à assistência de enfermagem. Os dados evidenciaram condições de melhora ou agravamento da esperança, o que requer atenção interdisciplinar em Oncologia.

SLEEVE GASTRECTOMY IN PATIENTS WITH MORBID OBESITY AND HIV.

PubMed

Pinto, José Máximo Costa; Lima, Marianna Gomes Cavalcanti Leite de; Almeida, Ana Luiza Melo Cavalcanti de; Sousa, Marcelo Gonçalves

It is estimated that there are nearly 40 million people with the human immunodeficiency virus (HIV) worldwide. Due to the advent of antiretroviral drugs, it has been observed increasing in obesity and metabolic rates among patients undergoing treatment. Thus, numerous surgical therapies for weight loss are proposed for continuous improvement in health of patients with HIV, being the vertical gastrectomy an option for intact intestinal transit. To evaluate the applicability of the vertical gastrectomy in patients with morbid obesity and HIV. Was conducted a systematic review of the literature, in the electronic databases Scopus, Pubmed, Cinahl, Scielo, Cochrane and Lilacs, from 1998 to 2015. MeSH headings used in data collection were "Gastrectomy" and "Morbid obesity" being combined with the descriptor "HIV". Were found 2148 articles in Scopus, 1234 in PubMed and 784 in Cinahl. The articles were analyzed by the Jadad Quality Scale, being reduced to 40 articles, subsequently reassessed using an elaborated form by the Critical Appraisal Skills Programme (CASP), reaching 12 articles in the end. It was found that vertical gastrectomy constitutes a safe and effective method, with low mortality and low rate of postoperative complications, being recommended as surgical technique in patients with obesity, HIV and comorbidities. Estima-se que haja quase 40 milhões de pessoas com o vírus da imunodeficiência adquirida (HIV) no mundo. Com o advento dos antirretrovirais, observou-se aumento da obesidade e de taxas metabólicas nos pacientes em tratamento. Assim, inúmeras terapias cirúrgicas para a perda de peso estão sendo estudadas para a melhoria contínua da saúde dos pacientes com HIV, sendo a gastrectomia vertical uma opção de trânsito íntegro. Avaliar a aplicabilidade da gastrectomia vertical em pacientes com obesidade mórbida e HIV. Foi realizada revisão sistemática de literatura, de artigos publicados nas bases eletrônicas de dados Scopus, Pubmed, Cinahl, Scielo, Cochrane e Lilacs, no período de 1998 a 2015. Os descritores do MeSH utilizados na coleta dos dados foram "Gastrectomia" e "Obesidade mórbida", sendo combinados com o descritor "HIV". Foram encontrados 2.148 artigos na Scopus, 1.234 no Pubmed e 784 na Cinahl. Os artigos foram analisados pela Escala de Qualidade de Jadad, reduzindo para um total de 40 artigos, os quais foram posteriormente reavaliados, utilizando um formulário elaborado pelo Critical Appraisal Skills Programme (CASP), chegando ao montante de 12 artigos ao final. Verificou-se que a gastrectomia vertical constitui método seguro e eficaz, apresentando baixa morbimortalidade e baixo índice de complicações pós-operatórias, sendo técnica cirúrgica segura para uso em pacientes com obesidade, HIV e comorbidades.

[Cyberstalking among Italian nurses: a large multicentric study].

PubMed

Comparcini, Dania; Simonetti, Valentina; Lupo, Roberto; Galli, Francesco; Bocij, Paul; Cicolini, Giancarlo

2016-01-01

Determinare la prevalenza di cyberstalking tra gli infermieri italiani e valutare il livello di ansia e depressione nelle vittime. Da aprile a settembre 2014 è stato condotto uno studio multicentrico trasversale in un campione di infermieri italiani (n=997) utilizzando il questionario "Cyberstalking" per analizzare il fenomeno del cyberstalking. Ai partecipanti, che si sono autodefinite vittime di cyberstalking, è stato chiesto anche di compilare gli strumenti "Beck Depression Inventory" e "State-Trait Anxiety Inventory" per valutare, rispettivamente, i livelli di depressione ed ansia. La prevalenza di cyberstalking tra gli infermieri italiani è risultata pari al 23.3%. Il 42.7% ha dovuto cambiare il proprio stile di vita e lavorativo. Il cyberstalker era prevalentemente di sesso maschile (52%) e, nel 49% dei casi, era un paziente. Le vittime hanno riferito moderati livelli di ansia (media=28.4, SD=23.2) e depressione (media=92.7, SD=18.3); i risultati hanno mostrato un aumento dei livelli di depressione negli infermieri esperti nell'utilizzo del computer, gestori di siti web o blog, e una correlazione negativa tra il livello di ansia e gli infermieri esperti (r = -0.264). Il cyberstalking è un fenomeno che si riscontra frequentemente tra gli infermieri. Il rapporto infermiere - paziente gioca un ruolo centrale nello sviluppo del fenomeno e le vittime hanno riferito disordini correlati allo stress che influenzano la vita lavorativa. Questi risultati preliminari potrebbero sensibilizzare, i dirigenti ospedalieri, la politica e i centri antiviolenza al fine di sviluppare strategie risolutiv.

Effectiveness of personalized face-to-face and telephone nursing counseling interventions for cardiovascular risk factors: a controlled clinical trial.

PubMed

Vílchez Barboza, Vivian; Klijn, Tatiana Paravic; Salazar Molina, Alide; Sáez Carrillo, Katia Lorena

2016-08-08

to evaluate the effect and gender differences of an innovative intervention involving in-person and telephone nursing counseling to control cardiovascular risk factors (arterial hypertension, dyslipidemia, and overweight), improve health-related quality of life and strengthen self-efficacy and social support in persons using the municipal health centers' cardiovascular health program. a randomized controlled clinical trial involving participants randomized into the intervention group who received traditional consultation plus personalized and telephone nursing counseling for 7 months (n = 53) and the control group (n = 56). The study followed the Consolidated Standards of Reporting Trials Statement. women in the intervention group presented a significant increase in the physical and mental health components compared to the control group, with decreases in weight, abdominal circumference, total cholesterol, low-density lipoprotein cholesterol, and the atherogenic index. The effects attributable to the intervention in the men in the intervention group were increased physical and emotional roles and decreased systolic and diastolic pressure, waist circumference, total cholesterol, low-density lipoprotein cholesterol, atherogenic index, cardiovascular risk factor, and 10-year coronary risk. this intervention is an effective strategy for the control of three cardiovascular risk factors and the improvement of health-related quality of life. evaluar efecto y diferencias por sexo de una intervención innovadora "Consejería de Enfermería Personalizada y Telefónica", dirigida al control de factores de riesgo cardiovascular (hipertensión arterial, dislipidemia y sobrepeso) y al mejoramiento de la calidad de vida relacionada con la salud, fortaleciendo la autoeficacia y el apoyo social en personas usuarias del programa de salud cardiovascular de los Centros de Salud Municipales de Concepción. ensayo clínico controlado aleatoriamente y selección aleatoria de participantes; grupo intervención con consulta tradicional más consejería de enfermería personalizada y telefónica durante 7 meses (n=53); y grupo control (n=56); siguiendo la declaración del Consolidated Standards of Reporting Trials. mujeres del grupo intervención, presentaron aumento significativo con respecto al grupo control, en componentes de salud física y mental; disminución de: peso, circunferencia abdominal, colesterol total, colesterol lipoproteínas de baja densidad e índice de aterogenicidad. En hombres del grupo intervención se reflejó como efectos atribuibles a la intervención: 1) aumento en dimensiones del rol físico y emocional; 2) disminución: presión sistólica y diastólica, circunferencia abdominal, colesterol total, colesterol lipoproteínas de baja densidad, índice de aterogenicidad, factor de riesgo cardiovascular y riesgo coronario a 10 años. esta intervención es una estrategia efectiva para el control de tres factores de riesgo cardiovascular y mejoría de calidad de vida relacionada con la salud. avaliar o efeito e as diferenças por sexo de uma intervenção inovadora: o aconselhamento personalizado e por telefone em enfermagem, visando o controle de fatores de risco cardiovascular (hipertensão arterial, dislipidemia e sobrepeso) e a melhora na qualidade de vida relacionada à saúde, fortalecendo a autoeficácia e o apoio social a pessoas que usam o programa de saúde cardiovascular de Centros Municipais de Saúde. ensaio clínico controlado e randomizado, participantes randomizados, grupo de intervenção: consulta tradicional mais aconselhamento personalizado e por telefone em enfermagem por 7 meses (n = 53); e grupo de controle (n = 56); seguindo a declaração Consolidated Standards of Reporting Trials Statement. mulheres do grupo intervenção apresentaram um aumento significativo, em relação ao grupo controle, nos componentes de saúde mental e física, com diminuição do peso, circunferência abdominal, colesterol total, colesterol de lipoproteínas de baixa densidade e índice aterogênico. Em homens do grupo intervenção, os efeitos atribuíveis à intervenção foram: aumentos nos papeis físicos e emocionais, com diminuições na pressão sistólica e diastólica, circunferência abdominal, colesterol total, colesterol de lipoproteínas de baixa densidade, índice aterogênico, fator de risco cardiovascular e risco coronariano em 10 anos. essa intervenção é uma estratégia eficaz para o controle dos três fatores de risco cardiovascular e a melhora da qualidade de vida relacionada à saúde.

Changes in frailty conditions and phenotype components in elderly after hospitalization.

PubMed

Marchiori, Gianna Fiori; Tavares, Darlene Mara Dos Santos

2017-07-10

describing the changes in frailty conditions over the period of a year after hospital discharge, verifying predictive variables for changes in frailty conditions and frailty phenotype components according to worsening, improving and stable groups. a longitudinal survey carried out with 129 elderly. A structured form for socioeconomic and health data, scales (Geriatric Depression Scale - short form, Katz scale, Lawton and Brody scale) and frailty phenotype according to Fried were used. Descriptive analysis and multinomial logistic regression model (p<0.05) were performed. we found that 56.7% of older adults changed their condition from non-frail to pre-frail, with no changes from non-frail to frail. Deaths were found between frail and pre-frail elderly. In the worsening group, the increase in the number of morbidities was a predictor for exhaustion and/or fatigue, while in the improving group, increased dependence on instrumental activities of daily living was a predictor for weight loss, and reduced scores indicative of depression due to low level of physical activity. a greater percentage of changes from non-frail condition to pre-frail older adults were observed, and health variables were only predictive for frailty phenotype components. descrever as mudanças nas condições de fragilidade ao longo de um ano após a alta hospitalar, e verificar as variáveis preditoras da mudança das condições de fragilidade e dos componentes do fenótipo de fragilidade, segundo grupos de piora, melhora e estabilidade. inquérito longitudinal, realizado com 129 idosos. Utilizou-se formulário estruturado para dados socioeconômicos e saúde, escalas (Depressão Geriátrica Abreviada, Katz, Lawton e Brody) e fenótipo de fragilidade, segundo Fried. Procederam-se às análises descritiva e modelo de regressão logística multinomial (p<0,05). constatou-se que 56,7% dos idosos mudaram sua condição de não frágeis para pré-frágeis, não ocorrendo mudança dos não frágeis para frágeis. Observou-se o óbito entre idosos frágeis e pré-frágeis. No grupo de piora, o aumento do número de morbidades foi preditor para exaustão e/ou fadiga, enquanto que, no grupo de melhora, o aumento na dependência das atividades instrumentais de vida diária foi preditor para a perda de peso, e a diminuição dos escores do indicativo de depressão para o baixo nível de atividade física. houve maior percentual de mudança na condição de idosos não frágeis para pré-frágeis e as variáveis de saúde foram preditoras apenas para os componentes do fenótipo de fragilidade. describir los cambios en las condiciones de fragilidad a lo largo de un año después del alta hospitalaria, y verificar las variables predictoras del cambio de las condiciones de fragilidad y de los componentes del fenotipo de fragilidad, según grupos de empeoramiento, mejoría y estabilidad. encuesta longitudinal, realizada con 129 ancianos. Se utilizó formulario estructurado para recoger datos socioeconómicos y salud; se utilizaron las escalas Depresión Geriátrica Abreviada (GDS-15), Actividades Básicas de Vida Diaria de Katz, Actividades Instrumentales de Vida Diaria de Lawton y Brody, y Fenotipo de Fragilidad, según Fried. Se procedió al análisis descriptivo y modelo de regresión logística multinomial (p<0,05). se constató que 56,7% de los ancianos cambiaron su condición de no-frágiles para prefrágiles, no habiendo ocurriendo cambio de los no-frágiles para frágiles. Se observó muerte entre ancianos frágiles y prefrágiles. En el grupo de empeoramiento, el aumento del número de morbilidades fue predictor para agotamiento y/o fatiga, en cuanto en el grupo de mejoría, el aumento en la dependencia de las actividades instrumentales de vida diaria fue predictor para la pérdida de peso y la disminución de los puntajes del indicativo de depresión para el bajo nivel de actividad física. hubo mayor porcentaje de cambio en la condición de ancianos no-frágiles para prefrágiles y las variables de salud fueron predictoras apenas para los componentes del fenotipo de fragilidad.

Social determinants of leprosy in a hyperendemic State in North Brazil.

PubMed

Monteiro, Lorena Dias; Mota, Rosa Maria Salani; Martins-Melo, Francisco Rogerlândio; Alencar, Carlos Henrique; Heukelbach, Jorg

2017-07-20

To identify the socioeconomic, demographic, operational, and health service-related factors associated with the occurrence of leprosy in a hyperendemic State in North Brazil. This is an ecological study based on secondary data from the Sistema de Informações de Agravos de Notificação in municipalities of the State of Tocantins from 2001 to 2012. Units of analysis were the 139 municipalities of the State. Negative binomial log linear regression models were used to estimate incidence rate ratios. In bivariate analysis, the incidence rate ratios were significantly higher for municipalities with higher income ratio of the poorest 20.0% (1.47; 95%CI 1.19-1.81) and better Municipal Human Development Index (1.53; 95%CI 1.14-2.06). In multivariate analysis, the incidence rate ratios were significantly higher in municipalities with higher proportion of immigrants (1.31; 95%CI 1.11-1.55) and higher proportion of households with waste collection (1.37; 95%CI 1.11-1.69). There was a significant reduction in the incidence rate ratio with increased coverage of the Bolsa Família Program (0.98; 95%CI 0.96-0.99). Control programs need to focus on activities in municipalities of greater social vulnerability with intersectoral investment for the improvement of the living conditions of the population. Identificar fatores socioeconômicos, demográficos, operacionais e de serviços de saúde associados à ocorrência da hanseníase em um estado hiperendêmico do norte do Brasil. Estudo ecológico com dados secundários do Sistema de Informações de Agravos de Notificação em municípios do estado do Tocantins de 2001 a 2012. As unidades de análise foram os 139 municípios do estado. Modelos de regressão log linear binomial negativa foram utilizados para estimar as razões de taxas de incidência. Na análise bivariada, a razão de taxa de incidência foi significativamente maior para os municípios com maior razão de renda dos 20,0% mais pobres (1,47; IC95% 1,19-1,81) e melhor Índice de Desenvolvimento Humano Municipal (1,53; IC95% 1,14-2,06). Na múltipla, a razão de taxa de incidência foi significativamente superior em municípios com maior concentração de imigrantes (1,31; IC95% 1,11-1,55) e proporção de domicílios com coleta de lixo (1,37; IC95% 1,11-1,69). Houve redução significativa da razão de taxa de incidência com o aumento da cobertura do programa bolsa família (0,98; IC95% 0,96-0,99). Os programas de controle precisam focar as atividades em municípios de maior vulnerabilidade social com investimentos intersetoriais para a melhoria das condições de vida da população.

Quality of cervical cancer screening in Brazil: external assessment of the PMAQ.

PubMed

Barcelos, Mara Rejane Barroso; Lima, Rita de Cássia Duarte; Tomasi, Elaine; Nunes, Bruno Pereira; Duro, Suele Manjourany Silva; Facchini, Luiz Augusto

2017-07-20

To examine whether demographic and socioeconomic variables and the variables of the organization of services are associated with the quality of cervical cancer screening. This is a survey carried out in the health services of the five Brazilian regions in 2012. The sample consisted of users of basic health units participating in the Program for Improving Access and Quality of the Primary Care. The independent variables analyzed were: socioeconomic characteristics (municipal context), demographic characteristics (user profile), and two domains related to the organization of basic services (work structure and process). The low quality of the screening was assessed from the lack of access, late examination, and lack of guidance. Crude and adjusted analyses by Poisson regression assessed the association between outcomes and independent variables. The values of lack of access, late examination, and lack of guidance were 6.7%, 11.2%, and 19.2%, respectively. Problems of quality were lower according to the increase in Municipal Human Development Index and per capita household income, increasing with population size and municipal coverage of the Family Health Strategy. The Midwest region of the country presented the highest occurrences of low quality outcomes. Indigenous and yellow women had the highest prevalence of outcomes. Women with partner, who received the Bolsa Família Program, and who had paid work had less chances of having lack of access, late examination, and lack of guidance. The appropriate work process in health services decreased the likelihood of low quality in all indicators. Investments in the work process of health teams, social cash transfer programs, and social conditions of the population are essential to improve the quality of the program of cervical cancer screening in Brazil. Analisar se as variáveis demográficas, socioeconômicas e da organização dos serviços estão associadas à qualidade do rastreamento do câncer de colo uterino. Inquérito realizado em serviços de saúde das cinco regiões brasileiras em 2012. A amostra foi composta por usuárias de unidades básicas de saúde participantes do Programa de Melhoria do Acesso e da Qualidade na Atenção Básica. As variáveis independentes analisadas foram: características socioeconômicas (contexto municipal); características demográficas (perfil de usuárias); e dois domínios relativos à organização dos serviços básicos (estrutura e processo de trabalho). A baixa qualidade do rastreamento foi avaliada por meio da falta de acesso, atraso na realização do exame e falta de recebimento de orientações. Análises bruta e ajustada por meio de regressão de Poisson avaliaram a associação entre os desfechos e as variáveis independentes. A falta de acesso, atraso na realização do exame e falta de recebimento de orientações foram de 6,7%, 11,2% e 19,2%, respectivamente. Os problemas de qualidade foram menores de acordo com o aumento do Índice de Desenvolvimento Humano Municipal e da renda familiar per capita, aumentando com o porte populacional e a cobertura municipal da Estratégia Saúde da Família. A região Centro-Oeste do país apresentou as maiores ocorrências dos desfechos de baixa qualidade. As mulheres de raça indígena e amarela tiveram as maiores prevalências dos desfechos. As mulheres com companheiro, que recebiam o benefício do Programa Bolsa Família e tinham trabalho remunerado tiveram menos falta de acesso, menos atraso na realização do exame e menos falta de recebimento de orientações. O processo de trabalho adequado nos serviços de saúde diminuiu a probabilidade de baixa qualidade em todos os indicadores. Investimentos em processo de trabalho das equipes de saúde, programas sociais de transferência de renda e condições sociais da população são essenciais para melhorar a qualidade do programa de rastreamento de colo de útero no Brasil.

EFFECTS OF LONG-TERM ROUX-EN-Y GASTRIC BYPASS ON BODY WEIGHT AND CLINICAL METABOLIC COMORBIDITIES IN BARIATRIC SURGERY SERVICE OF A UNIVERSITY HOSPITAL.

PubMed

Silva, Cátia Ferreira da; Cohen, Larissa; Sarmento, Luciana d'Abreu; Rosa, Felipe Monnerat Marino; Rosado, Eliane Lopes; Carneiro, João Régis Ivar; Souza, Antônio Augusto Peixoto de; Magno, Fernanda Cristina Carvalho Mattos

Due to the high failure rate observed in the clinical treatment of morbid obesity an increase in bariatric surgery indications, as an alternative for the control of obesity and comorbidities, is noticeable. To evaluate the performance of type 2 diabetes mellitus, high blood pressure and dyslipidemia in patients submitted to Roux-en-Y gastric bypass in late follow-up. Retrospective analysis of 59 patients included in the bariatric surgery program. Anthropometric (height and body weight) and laboratory (LDLc, HDLc, VLDLc, triglyceride -TG - and glucose) data were collected on pre- and postoperative stages, through medical records. Among the patients, 86% were female aged 43±11, of whom 52% had attended high school. The average postoperative time was 7±3 years. During the postoperative period, there were decreases of weight and body mass index, respectively (133±06 kg vs 91±04 kg p<0.05 e 49±74 kg/m2 vs 33±79 kg/m2, p<0.05). In comparison to the preoperative stage, lower concentrations of glucose (101.00±26.99 vs 89,11±15.19, p=0.014), total cholesterol rates (179.00±37,95 vs 167.48±28,50, p=0.016), LDLc (104.30±33.12 vs 91.46±24.58, p=0.016), VLDLc (25.40±11,12 vs 15.68±7.40, p<0.01), and TG (143.35±86.35 vs 82.45±37.39, p<0.01) and higher concentrations of HDLc (43.53±8.23 vs 57.90±15.60, p<0.01) were identified in the postoperative stage. 40% of hypertensive patients were still undergoing high blood pressure treatment during the postoperative stage. There was remission of type 2 diabetes mellitus and dyslipidemia on 81% and 94% of the cases, respectively. Roux-en-Y gastric bypass has proven itself to be an effective long term procedure, promoting weight loss, remission of DM2 and dyslipidemia. Em função do alto grau de falência que se observa no tratamento clínico da obesidade mórbida, observa-se um aumento da procura pela cirurgia bariátrica como alternativa para o controle da obesidade e comorbidades. Avaliar a evolução do diabete melito tipo 2, da hipertensão arterial sistêmica e da dislipidemia em pacientes submetidos à gastroplastia redutora em Y-de-Roux no período de pós-operatório tardio. Análise retrospectiva de 59 pacientes inseridos em programa de cirurgia bariátrica. Foram coletados dados antropométricos (altura e peso corporal) e laboratoriais (LDLc, HDLc, VLDLc, triglicerídeo -TG - e glicose) nos períodos pré e pós-operatório por meio de prontuários médicos. Entre os pacientes, 86% eram mulheres com idade de 43±11 anos e 52% tinham cursado o ensino médio. O tempo médio de pós-operatório foi de 7±3 anos. Houve redução no peso e no índice de massa corporal no pós-operatório, respectivamente (133±06 kg vs 91±04 kg p<0,05 e 49±74 kg/m2 vs 33±79 kg/m2, p<0,05). Observou-se concentrações inferiores no pós-operatório, comparado com o pré-operatório, da glicose (101,00±26,99 vs 89,11±15,19, p=0,014), colesterol total (179,00±37,95 vs 167,48±28,50, p=0,016), LDLc (104,30±33,12 vs 91,46±24,58, p=0,016), VLDLc (25,40±11,12 vs 15,68±7,40, p<0,01), e TG (143,35±86,35 vs 82,45±37,39, p<0,01) e maiores de HDLc (43,53±8,23 vs 57,90±15,60, p<0,01 ). No pós-operatório 40% dos pacientes hipertensos ainda estavam em tratamento para hipertensão arterial sistêmica. Houve remissão do diabete melito tipo 2 e da dislipidemia em 81% e 94% dos casos, respectivamente. A gastroplastia redutora em Y-de-Roux mostrou ser procedimento eficaz em longo prazo, com resultados persistentes na perda de peso, remissão do DM2 e da dislipidemia.

The impact of the use of different types of gloves and bare hands for preparation of clean surgical instruments.

PubMed

Bruna, Camila Quartim de Moraes; Souza, Rafael Queiroz de; Massaia, Irineu Francisco Silva; Cruz, Áurea Silveira; Graziano, Kazuko Uchikawa

2016-10-10

to determine if there are differences on the safety of the preparation of clean surgical instruments using different types of gloves and bare hands and evaluate the microbiological load of these preparations without gloves. laboratory procedure with a pragmatic approach, in which the samples were handled with different types of gloves and bare hands. In addition, cytotoxicity assays were carried out by means of the agar diffusion method. Further samples were subjected to microbiological analysis after being handled without gloves. none of the samples showed cytotoxic effect. All microbiological cultures showed growth of microorganisms, but no microorganism has been recovered after autoclaving. there were no differences in the cytotoxic responses regarding the use of different types of gloves and bare hands in the handling of clean surgical instruments, which could entail iatrogenic risk. It is noteworthy that the use of gloves involves increase in the costs of process and waste generation, and the potential allergenic risk to latex. determinar se existe diferenças na segurança do preparo de instrumentais cirúrgicos relacionada ao uso de distintos tipos de luvas e das mãos nuas no preparo, e avaliar a carga microbiológica destes preparados sem luvas. experimento laboratorial com abordagem pragmática, onde amostras foram manipuladas com diferentes tipos de luvas e com as mãos nuas, elaborado teste de citotoxicidade por meio da difusão em ágar. Outras Amostras sofreram análise microbiológica após serem manipuladas sem luvas. nenhuma das amostras apresentou efeito citotóxico. Todas as culturas microbiológicas apresentaram crescimento de microrganismos, embora nenhum microrganismo tenha sido recuperado após a autoclavação. não houve diferenças nas respostas citotóxicas relacionadas ao uso de diferentes tipos de luvas e das mãos nuas na manipulação do instrumental cirúrgico limpo que sinalizasse risco de iatrogenia. Ressalta-se que o uso de luvas implica em aumento dos custos do processo e da geração de resíduos, além do potencial risco alergênico ao látex. determinar si existen diferencias en la seguridad de la preparación del instrumental quirúrgico relacionadas con el uso de diferentes tipos de guantes y de las manos desnudas y evaluar la carga microbiológica de estos preparados sin guantes. experimento de laboratorio con enfoque pragmático, en el que las muestras fueron manejadas con diferentes tipos de guantes y las manos desnudas. Además, un ensayo de citotoxicidad se llevó a cabo mediante el método de difusión en agar. Otras muestras fueron sometidas a análisis microbiológico después de haber sido manipuladas sin guantes. ninguna de las muestras presentó efecto citotóxico. Todos los cultivos microbiológicos mostraron crecimiento de microorganismos, pero ningún microorganismo ha sido recuperado después de la esterilización en autoclave. no hubo diferencias en las respuestas citotóxicas con respecto al uso de diferentes tipos de guantes y de las manos desnudas en el manejo del instrumental quirúrgico limpio, lo que podría conllevar riesgo de yatrogenia. Es de destacar que el uso de guantes implica un aumento de los costos del proceso y la generación de residuos, además del potencial riesgo alergénico al látex.

Costs of topical treatment of pressure ulcer patients.

PubMed

Andrade, Cynthia Carolina Duarte; Almeida, Cláudia Fernanda Dos Santos Calixto de; Pereira, Walkíria Euzébio; Alemão, Márcia Mascarenhas; Brandão, Cristina Mariano Ruas; Borges, Eline Lima

2016-04-01

To evaluate the costs of a topical treatment of pressure ulcer (PU) patients in a hospital unit for treatment of chronic patients in 2014. This is an activity-based costing study. This method encompasses the identification, measurement and pricing of physical and human resources consumed for dressings. Procedure costs varied between BRL 16.41 and BRL 260.18. For PUs of the same category, of near areas and with the same type of barrier/adjuvant, the cost varied between 3.5% and 614.6%. For most dressings, the cost increased proportionally to the increase of the area and to the development of PU category. The primary barrier accounted for a high percentage of costs among all items required to the application of dressings (human and material resources). Dressings applied in sacral PUs had longer application times. This study allowed us to understand the costs involved in the treatment of PUs, and it may support decision-makers and other cost-effectiveness studies. Realizar uma avaliação do custo do tratamento tópico de pacientes com úlceras por pressão (UP), em uma unidade hospitalar de atendimento a pacientes crônicos no ano de 2014. Trata-se de um estudo de custos baseado no Sistema de custeio Baseado em Atividades. Este método contempla a identificação, mensuração e precificação dos recursos físicos e humanos consumidos para a realização de curativos. Os custos dos procedimentos variaram de R$16,41 a R$260,18. Para UP de mesma categoria, de áreas aproximadas e mesmo tipo de cobertura/adjuvante, a variação entre os custos foi de 3,5% a 614,6%. Para a maioria dos curativos, o custo aumentou proporcionalmente ao aumento da área e à progressão da categoria das UP. A cobertura primária representou elevado percentual nos custos entre todos os itens necessários para realizar os curativos (recursos humanos e materiais). Os curativos realizados nas UP sacrais foram os que apresentaram maiores tempos para execução. Este estudo permitiu conhecer os custos envolvidos no tratamento das UP e pode fornecer subsídios para os tomadores de decisão, assim como para a realização de estudos de custo-efetividade.

Negative pressure of the environmental air in the cleaning area of the materials and sterilization center: a systematic review.

PubMed

Ciofi-Silva, Caroline Lopes; Hansen, Lisbeth Lima; Almeida, Alda Graciele Claudio Dos Santos; Kawagoe, Julia Yaeko; Padoveze, Maria Clara; Graziano, Kazuko Uchikawa

2016-09-01

to analyze the scientific evidence on aerosols generated during cleaning activities of health products in the Central Service Department (CSD) and the impact of the negative pressure of the ambient air in the cleaning area to control the dispersion of aerosols to adjacent areas. for this literature systematic review the following searches were done: search guidelines, manuals or national and international technical standards given by experts; search in the portal and databases PubMed, Scopus, CINAHL and Web of Science; and a manual search of scientific articles. the five technical documents reviewed recommend that the CSD cleaning area should have a negative differential ambient air pressure, but scientific articles on the impact of this intervention were not found. The four articles included talked about aerosols formed after the use of a ultrasonic cleaner (an increased in the contamination especially during use) and pressurized water jet (formation of smaller aerosols 5μm). In a study, the aerosols formed from contaminated the hot tap water with Legionella pneumophila were evaluated. there is evidence of aerosol formation during cleanup activities in CSD. Studies on occupational diseases of respiratory origin of workers who work in CSD should be performed. analisar as evidências científicas sobre aerossóis gerados durante atividades de limpeza dos produtos para saúde no Centro de Material e Esterilização (CME) e o impacto da pressão negativa do ar ambiente na área de limpeza para controle da dispersão de aerossóis para áreas adjacentes. para essa revisão sistemática de literatura foram realizadas: busca de diretrizes, manuais ou normas técnicas nacionais e internacionais indicadas por especialistas; busca no portal e bases de dados PUBMED, SCOPUS, Cinahl e Web of Science; e busca manual de artigos científicos. Os cinco documentos técnicos analisados preconizam que na área de limpeza do CME haja diferencial negativo de pressão do ar ambiente, porém não foram encontrados artigos científicos sobre o impacto dessa intervenção. Os quatro artigos incluídos trataram dos aerossóis formados após uso de lavadora ultrassônica (aumento da contaminação principalmente durante o uso) e do jato de água pressurizado (formação de aerossóis menores que 5µm). Em um estudo foram avaliados aerossóis formados a partir de torneira de água quente contaminada com Legionella pneumophila. há evidências sobre formação de aerossóis durante atividades de limpeza em CME. Estudos sobre doenças ocupacionais de origem respiratória dos trabalhadores que atuam em CME devem ser realizados. examinar la evidencia científica sobre los aerosoles generados durante las actividades de limpieza de productos de salud en el Centro de Materiales y Esterilización (CME) y el impacto de la presión negativa del aire ambiente en la zona de limpieza para controlar la dispersión de aerosoles a las zonas adyacentes. para esta revisión sistemática de literatura se llevaron a cabo: búsqueda de directrices, manuales o normas técnicas nacionales e internacionales impartidas por expertos; búsqueda en las bases de datos PUBMED, SCOPUS, Cinahl y Web of Science; y búsqueda manual de artículos científicos. Los cinco documentos técnicos analizados recomiendan que el área de limpieza del CME tenga un diferencial negativo de presión en el aire ambiente, aunque no se han encontrado artículos científicos sobre el impacto de esta intervención. Los cuatro artículos incluidos fueron sobre los aerosoles formados después del uso de la lavadora ultrasónica (aumento de la contaminación, especialmente durante el uso) y chorro de agua a presión (formación de aerosoles menores a 5µm). De esta forma, en un solo estudio se evaluaron los aerosoles formados a partir de un grifo de agua caliente contaminada con Legionella pneumophila. hay evidencia de formación de aerosoles durante las actividades de limpieza en CME. Sin embargo, es necesario realizar estudios sobre las enfermedades profesionales de origen respiratorio de los trabajadores que trabajan en CME.

Impact of neuromuscular electrical stimulation on functional capacity of patients with chronic kidney disease on hemodialysis.

PubMed

Roxo, Renata Spósito; Xavier, Vivian Bertoni; Miorin, Luiz Antônio; Magalhães, Andrea Olivares; Sens, Yvoty Alves Dos Santos; Alves, Vera Lúcia Dos Santos

2016-01-01

Literature shows that patients undergoing hemodialysis present poor physical conditioning and low tolerance to exercise. They may also suffer from respiratory dysfunctions. The purpose of this study was to evaluate the effects of neuromuscular electrical stimulation on pulmonary function and functional capacity of patients with chronic kidney disease on hemodialysis. Forty adult patients with chronic kidney disease on hemodialysis were prospectively studied and randomized into two groups (control n = 20 and treatment n = 20). The treatment group underwent bilateral femoral quadriceps muscles electrical stimulation for 30 minutes during hemodialysis, three times per week, for two months. The patients were evaluated by pulmonary function test, maximum respiratory pressures, maximum one-repetition test, and six-minute walk test (6MWT), before and after the treatment protocol. The treatment group presented increased maximum inspiratory (MIP) (p = 0.02) and expiratory pressures (MEP) (p < 0.0001), muscular strength in maximum one-repetition test (p < 0.001), and distance covered in the 6MWT (p = 0.03), and decreased systolic blood pressure (p < 0.001) and respiratory frequency (p < 0.001) when compared with the control group. Electrical neuromuscular stimulation had a positive impact on pulmonary function and functional capacity, leading to better physical performance in patients on hemodialysis. Pacientes submetidos à hemodiálise apresentam baixo condicionamento físico além de serem acometidos por disfunções respiratórias. Objetivamos avaliar os efeitos da estimulação elétrica neuromuscular na função pulmonar e capacidade funcional de pacientes com doença renal crônica em hemodiálise. 40 adultos com doença renal crônica em hemodiálise foram estudados prospectivamente e randomizados em dois grupos (controle n = 20 e tratamento n = 20). O grupo tratamento realizou protocolo com estimulação elétrica neuromuscular em quadríceps femoral por 30 minutos durante a hemodiálise, três vezes por semana, durante dois meses. Todos pacientes realizaram espirometria, pressões respiratórias máximas, teste de uma repetição máxima e teste da caminhada dos seis minutos (TC6), antes e após o período de acompanhamento. O grupo tratamento apresentou aumento da pressão inspiratória máxima com p = 0,02 na comparação entre grupos e p < 0,001 para a pressão máxima expiratória. O teste de uma repetição máxima e a distância percorrida no TC6 apresentaram-se maiores após o protocolo no grupo de tratamento com p < 0,001 e 0,03 respectivamente. Houve diminuição da pressão arterial sistólica (p < 0,001) e frequência respiratória (p < 0,001) após a estimulação elétrica quando comparado ao grupo controle. A estimulação elétrica neuromuscular teve impacto positivo sobre a função pulmonar e a capacidade funcional levando ao melhor desempenho físico em pacientes em hemodiálise.

Farmyard Manure and Fertilizer Effects on Seed Potato (Solanum tuberosum L.) Yield in Green House Production

NASA Astrophysics Data System (ADS)

László, M.

2009-04-01

Nowadays is widely well know that the potato is an important vegetable crop at Brazíl. It is grown on about 173.000 ha, with total yield of 2.6 million tons year-1. The average yield is 15 t ha-1. This level is very low because degeneration of crop is rapid under high temperature and high viruses pressure. Therefore seed potato propagation and production is principal on consumption potato production. This is why we found it necessary to develop it. The latossolo vermelho soil-farmyard manure- burnt rice straw-fertilizer 4N:14P:8K greenhouse pot trial was set up at the National Vegetable Crops Research Center, Brasília-DF, Brazíl in 1990. The methods of the experiments were soil x farmyard manure x burnt rice straw, soil x 4N:14P:8K fertilizer and soil x farmyard manure x burnt rice straw x 4N:14P:8K fertilizer on randomized block design in total 29 combination of treatments in 5, 5 and 3 repetitions with in a total parcel of 116. According to chemical analysis of the a., soil, b., farmyard manure and c., burnt rice straw the agrochemistry parameters were as follows (estimated datas): a., latossolo vermelho soil: CaCO3 0.3-0.7%, humo 0.9-1.0%, pH (H2O) 5.3, pH (KCl) 4.5, AL- P2O5 3.2-3.5 mg kg-1, AL- K2O 180 mg kg-1, Mg (KCl) 70 mg kg-1, EDTA-Zn 0.5-0.8 mg kg-1, EDTA-Cu 0.5-0.6 mg kg-1, b., farmyard manure: N 1.8 g kg-1, P2O5 2.0 g kg-1, K2O 4.0 g kg-1, c., burnt rice straw: N 0.8 g kg-1, P2O5 7.0 g kg-1, K2O 4.5 g kg-1. The experimental datas were estimated by analysis of variance, ANOVA and MANOVA. The main conclusions were as follows: 1. Mixture of 80% latossolo vermelho, 10% burnt rice straw and 10% farmyard manure were shown best performance on seed potato productivity. The piece of tubers with a 0-20 mm (consumption seeds) was increased by 77%. 2. Total seed potato number was reached maximum at 10.8 g pot-1 4N:14P:8K fertilizer regarding to average of treatments with a 33%. 3. Dry biomassa production plant-1 was decreased by high dose of 4N:14P:8K fertilizer (18.0 g pot-1) with a hard effect (57%). Our results are shown that it was possible developing of the seed potato production under tropical greenhouse conditions by optimalised soil-organic matter-fertilizer system. This datas should be as indicators to sustainable field potato advisory systems. Keywords: potato (Solanum tuberosum L.), greenhouse, latossolo vermelho soil, farmyard manure, burnt rice straw, 4N:14P:8K fertilizer, sustainability, yield Introducáo: Importância e situação actual em produção da batata no Brazíl A batata é atualmente uma das hortaliças de maior importância no Brasíl (Márton 2000a., 2000b.) com um cultivo annual médio de 173.000 ha e uma produção de 2600000 t. A produtividade médio nacional é de 15 t ha-1, muito baixa se considerar que é possivel a obtenção de rendimentos acima de 40 t ha-1. Observa- se também, que existe variação no produtividade entre regiões e estados. E importante como fonte de alimento pelo seu alto valor nutricional a quantidade produzida muito superior por unidade de área a tempo, se comparada com diversas outras culturas (László 2000b., 2000c.). Os estados que tradicionalmente produzem batata em maior ou menor escala são indicados em seguente: Pernambuco, Ceará, Sergipe, Goiás, Mato Grosso, Mato Grosso do Sul, Rondonia e Acre. Os plantios predominantes são o das águas e das secas, sendo o de inverno bem menos expressivo, pois poucas áreas permitem o seu cultivo, na maioria dos casos necessitando- se de irrigação. Considerando as três épocas de plantio e diferentes condições climaticas brasileiras, podemos definir de um modo geral o plantio de batata no Brasíl da seguinte maneira: Nordeste e Centro- Oeste- plantio de inverno, Sudeste- plantio das águas, secas e inverno, Sul- plantio das aguas, secas e inverno. Sendo este último em áreas muito limitadas. Dentre as hortaliças a batata é uma das culturas mais estudadas actualmente. Os principais problemas que afetam a cultura da batata podem ser de ordem agronómica, economica e comercial. Como exemplos destes podem ser citados: o uso racional de matérias orgânicos, esterco de curral e inorgânico fertilizantes. Efeito de materias orgnicânicos e N, P, K elementos minerais para produção da batata As necessidades em N, P, e K elementos minerais da batata são superidas pela aplicação apropriada de matérias orgânicos, esterco de currals, fertilizantes ao solo, combinada com a ambiente (Márton 2001a., 2001b.), época adequada e posição ideal de aplicá- lo. Efeito da materias orgânicos O suprimento de N á batateira provém principalmente da matéria orgânica do solo e do fertilizante aplicado (László 2000a., Márton et all. 2000.). Embora não seja muito praticado no Brasíl, a incorporação de esterco ao solo é fator de aumento da produção de tuberculos. Este resultado favorável poderia ser atribuído ao melhoramento da estrutura do solo, á maior retenção de água pelo e mesmo favorecendo o melhor desenvolvimento do sistema radicular da planta. A batata pode ser cultivada em todo tipo de solo desde que tenha boa drenagem e seja bem estruturado. Isto é tem que ser bem aerado e permitir o bom desenvolvimento dos órgãos subterráneos da batateira. Sem de matéria orgânicos e esterco de curral a tendencia de determinados solos formar crosta, oferecendo uma alta resisténcia mecánica á emergéncia das plantas, pode ser um determinante de stands desuniformes. A cause primaria da formação de crostas é a destruição dos agregados do solo pela excessiva manipulação mecánica resultando em aeração reduzida e aumento da densidade e coesão das particulas do solo. O encrostamento do solo pode ser reduzido através com matérias orgânicos. De maneira geral, a produção de tuberculos em solo de baixa potencialidade (aqueles em que a penetração das raizes é dificultada pela compactação, textura argilosa ou com camadas no solo) será menor do que nagueles com alta potencialidade (boa textura e adequada retenção de agua). Efeito do nitrogênio No Brazíl em todas regiões onde se cultiva batata é raro encontrar solos com elevado teor de nitrogênio e que não precisam de quantidades desta elemento. É o elemento que governa o padrão de desenvolvimento da planta, estimulando principalmente o crescimento da parte aérea (Kádár et all. 2000., László 2000.). Para se obter rendimento de tubérculos é necessário um rápido e curto periodo de desenvolvimento da parte aérea e uma fase de acúmulo maior possível. Para tanto, devem ser evitadas doses muito altas de nitrogênio e, principalmente, se aplicadas tardiamente, pois haverá demasiado desenvolvimento de folhas que demorarão mais a finalizar seu crescimento e maturação. Isto implicará na redução do periodo de intenso desenvolvimento dos tubérculos e armazenagem do amido, resultando em menor produção. Há risco para a saúde na ingestão de alimentos com altos teores de nitrato e nitrito, havendo preocupação com o efeito de doses mais altas de nitrogênio sobre os teores dos mesmos nos tuberculos. Embora haja diferenças entre cultivares, localidades e períodos de armazenamento, há estudos mostrando que a fertilização com até 150 kg ha-1 de nitrogênio não foi suficiente para propiciar niveis preocupantes de nitrato nos tuberculos colhidos. Efeito do fósforo A grande maioria dos solos brasileiros cultivados com batata apresentam limitações ao bom desenvolvimento e produção da cultura em função dos baixos níveis de fósforo. Isto significa que aumentos de produção quase sempre ocorrem quando o solo recebe adubação fosfatada (László 2001a.). Estes aumentos são mais marcantes em solos nunca antes adubados ou com baixo teor de fósforo. Nestes, dificilmente alcanca- se a produção máxima com níveis reduzidos de fósforo. Não seria exagerado supor níveis de 600 a 800 kg ha-1 de P2O5, como sendo aqueles que iriam proporcionar produção máximas, principalmente em solos mais ácidos e pobres em matéria orgânico. A adubação fosfatada é muito importante no crescimento inicial da planta e, além de aumentar a produção de tuberculos em peso e números, aumenta também a quantidade e qualidade do amido neles contidos e reduz perdas durante o armazenamento dos mesmos. A quantidade de fósforo a aplicar dependerá da análise do solo considerando- se principalmente o nível de P existente e a textura do solo. Solos de textura média e arenosa necessitam maior conteúdo de fósforo do que os de textura argilosa para serem considerandos solos de baixo, médio ou alto teor de fósfato. Efeito da potássica Embora seja o elemento mais absorbido pela batateira, nem sempre há resposta positiva da aduba potássica sobre o rendimento da cultura. Provavelmente isto esteja relacionado com níveis elevados deste elemento no solo (Kurnik et all. 2001.). Entretanto, em solos com médios e baixos teores de potássio, aumentos significativos são conseguidos. Por isto, as recomendações de adubação com potássio, nas diversas regiões do mundo, variam de 50-300 kg ha-1 de K2O. Resultados de trabalhos em brasiléiros têm demonstrado que a aduba potássica pode ser substituída pela aplicação de 150 m3 ha-1 de vinhaça de cana de açúcar. Ao elevar- se a dose de fertilização potássica deverá haver precaução para que a adubação magnesiana seja suficiente. O K além de aumentar a produção, em solos deficientes, aumenta também o tamanho dos tubérculos produzidos, e a proporção de tubérculos grandes. Deficiência no suprimento de potássio á planta pode acarretar produção de tubérculos com elevada susceptibilidade aos danos mecánicos pós-colheita. Os tubérculos injuriados enegrecem facilmente e este enegrecimento é inversamente proporcional á quantidade de potássio nos tuberculos. Ademais, quando fritos dão origem a um produto escuro, de baixa valor comercial. Manejo de adubação Diversos fatores como potencial de produção do solo, modo de aplicação do fertilizante dentre outro fatores afetam a resposta da batateira á aplicação de fertilizantes (Refschneider 1987.). Depreende- se pois que no estabelecimento de um nivel ideal de fertilização as variáveis planta, solo e condições climaticas devem ser visualizadas como um sistema pouco provável de ser homogeneo mesmo em nivel de fazenda. Como tal, generalizações a respeito de doses ou niveis de fertlização são difíceis de serem feitas, recomendações exigem julgamento hábil por parte do fazendeiro ou do tecnico responsavel pela cultura (Márton 2001a., 2001b.). Este julgamento será mais preciso conhecendo- se pontos que serão rápidamente discutidos a seguir. A taxa de absorção de nutrientes é governada pela concentração externa ou suprimento de nutrientes pelo solo e a demanda do nutriente criada pelo desenvolvimento e funcinamento normal dos diversos órgãos das plantas. O nivel de nutrientes na solução do solo deve ser suficiamente alto para que suas taxas de absorção não sejam limitantes ao crescimento. Por outro lado, não deve ser demasiado para causar excessiva absorção de outros nutrientes. Forte associação existe entre a absorção de nutrientes e o desenvolvimento da planta. De maneira geral, a fase de rapido desenvolvimento da cultura é acompanhada por um grande aumento na absorção de nutrientes com a taxa de absorção declinado quando a taxa de crescimento diminuiu. Normalmente todos os fertilizantes potássicos e fosfatados são adicionados ao solo na época do plantio. O nitrogênio normalmente é parcelado. Cerca de 2 por 3 do nível recomendado é colocado no sulco de plantio e o restante adicionado por ocasião da amontoa. É uma prática tradicinal e com pouco suporte experimental no condiõces brasileiras. Espera -se que a aplicação parcelada do nitrogênio e mesmo do potássio possem ser benéficas quando houver chuva excessiva ou irrigações mal executadas principalmente em solos mais arenosos onde poderá ocorrer a lixiviacão dos mesmos (Márton 2001a., 2001b.). O parcelamento poderá também ser benéfico quando elevados níveis de fertilizantes porém recomendandos e a aplicação por feita nos sulcos de plantio, pois evitar-se ia assim, elevada concentração salina em torno dos tubérculos plantados, embora a aplicação á lanco, em toda área, possa ser opção vantajosa. Quantidades corretas de fertilizantes, posição ideal e época certa de aplicação, combinadas adequadamente, definem o programa de adubação da batata. Esse programa é variável de acordo com o solo, a batata e condisões ambientais (Márton 2001a.). A dose de um elemento a ser aplicada em batata, é função da quantidade desse elemento suprida pelo solo e da percentagem de recuperação do elemento adicionado ao solo como fertilizante. Resultados experimentais comparando a aplicação de fertilizante á lanco ou localizado mostram respostas variadas sobre a produção. E possivel encontrar resultados iguais em ambos os métodos, de supremacia da aplicação á lanco ou da aplicação localizada (Kurnik et all. 2001.). Parece que baixas quantidades de fertilizantes são mais eficiemente utilizadas quando aplicação nos sulcos de plantios. Entretanto o potancial de produção pode ser aumentando com alta ou mesmo moderada quantidade de fertilizantes aplicados á lanço. A recomendação geral de colocar o adubo no sulco de plantio da batata merece ser questionada. É uma recomendação válida ao entender- se que a batata responde bastante á aplicação de fósforo, que os solos brasileiros tem alta capacidade de absorção de fósforo e que haverá maior proliferação de raízes na área fertilizada. Uma indagação aparece: um solo com baxa disponibilidade de fósforo fora da zona fertilizada permitiria o desenvolvimento ótimo da planta. Algumas evidéncias mostram, para outras espécies, que grande parte do sistema radicular, deve estar exposta ao fósforo para suprir as necessidades das plantas. Ademais, há um determinado valor de concentração de fósforo, na solução do solo, acima da qual a taxa de absorção não é aumentada. Essas considerações suscitam a possibilidade de questionar se a aplicação de fósforo em sulcos seria a forma mais eficiente de usá-lo quando se pretende alcancar elevadas produções. Deve-se lembrar entretanto, que solos tropicais, ainda com baixos teores fósforo e alta capacidade de adsorção, seria necessária dose muito elevada de P, quando aplicada á lanço, em todo o terreno. Se a aplicação localizada do fósforo pode, em parte, ser explicada, a do nitrogênio e potássio não são facilmente justificadas sob o aspecto de eficiéncia de utilização. Pelo contrário, ela pode ser questionada, principalmente pelas suas caracteristicas de difusão, pelo efeito que altas concentração de amónio e cloreto podem ter sobre a pressão osmotica da solução do solo junto aos tubérculos plantados, pelo efeito negativo do cloreto sobre a absorção de fósforo e também sobre a capacidade produtiva das plantas. Portanto, existe a possibilidade de ocorrer toxidez de amónio e de cloreto ao se aplicar doses altas dos fertilizantes nos sulcos de plantios. Isto pode determinar uma menor eficiéncia no uso dos fertilizantes. Materiais e Metodos: Nos desenvolverémos os três experimentos (i.e.: 1., 2., 3.) para aumentár-se do produção e produtividade da batata (Solanum tuberosum L.) semente pré- básica no casa de vegetação com diferentes doságens do latossolo vermelho novo, do esterco de curral e do adubo fórmula 4N:14P:8K no Empresa Brasileira de Pesquisa Agropecuaria- Centro Nacional de Pesquisas de Hortaliças, da Brazília-DF no 1990. Caracteristicas agroquímicas do solo em faixa arado (dados estimados), e conteudos N, P2O5, K2O do esterco de curral e palha de arroz queimado (dados estimados): a., caracteristicas agroquímicas do solo latossolo vermelho (solo novo: nunca foi usado para produção da batata semente): CaCO3 0.3-0.7%, humo 0.9-1.0%, pH (H2O) 5.3, pH (KCl) 4.5, AL- P2O5 3.2-3.5 mg kg-1, AL- K2O 180 mg kg-1, Mg (KCl) 70 mg kg-1, EDTA-Zn 0.5-0.8 mg kg-1, EDTA-Cu 0.5-0.6 mg kg-1 com abastecer fraco destes elementos, b., conteudos N, P2O5, K2O do esterco de curral (qualidade médio): N 1.8 g kg-1, P2O5 2.0 g kg-1, K2O 4.0 g kg-1, c., conteudos N, P2O5, K2O do palha de arroz queimado (palha de arroz foi queimado em um especial forno): N 0.8 g kg-1, P2O5 7.0 g kg-1, K2O 4.5 g kg-1. Nestas provas usarémos para controle a *mistura padrão. O este tratamento é a composição usual neste programa i.e.: 150 l de solo novo, 50 l de palha de arroz queimado, 50 l de esterco de curral, 350 gramas de cal e 300 gramas de adubo da fórmula 4N:14P:8K. Experimento 1. Efeito de diferentes misturas para produção da batata semente pré- básica em casa de vegetação O experimento foi instalado considerando-se sete misturas de substrato (latossolo vermelho novo, esterco de curral, palha de arroz queimado) em 3000 cm3 volume de capacidade de vasos preto com cinco repetições, no delineamento experimental de blocos ao acaso, na mésas experimentais em caso de vegetação. A cultivar foi a Achat, com plãntulas provenientes de cultura de tecidos. A data de plantio foi 18.04.1990. Plantarémos em cada vaso 3-3 "in vitro" plantulas com raiz embaixo de 4cm de superficie da mistura no vasos. Irrigarémos com 12 mm quantidade da augua 2 vezes por semana. Para produção aplicarémos sistema de proteção de plantas como usados no Brasíl. Ambiente foi controlado com ventilação automatizado. Temperatura médio foi 22 0C e humidade médio foi 68% durante de experimento. A data de colheta foi 04.07.1990. As pesagens foram feitos como peso fresco. Os resultados foram submetidos a analise de variáncia, ANOVA. As misturas do substrato utilizadas foram como a seguir no Tabela 1. Experimento 2. Efeito de adubo 4N:14P:8K para produção da batata semente pré- básica em casa de vegetação O experimento foi instalado considerando-se 9 dosagens de adubo da fórmula 4N:14P:8K com latossolo vermelho novo em 3000 cm3 volume de capacidade de vasos preto com cinco repetições, no delineamento experimental de blocos ao acaso na mésas experimentais em casa de vegetação. O adubo foi posicionando no solo de 4 cm abaixo de superficie do solo. A cultivar foi a Achat, com plãntulas provenientes de cultura de tecidos. A data de plantio foi 18.04.1990. Plantarémos em cada vaso 3-3 "in vitro" plantulas com raiz embaixo de 4cm de superficie da mistura no vasos. Irrigarémos com 12 mm quantidade da augua 2 vezes por semana. Para produção aplicarémos sistema de proteção de plantas como usados no Brasíl. Ambiente foi controlado com ventilação automatizado. Temperatura médio foi 22 0C e humidade médio foi 68% durante de experimento. A data de colheta foi 04.07.1990. As pesagens foram feitos como peso fresco. Os resultados foram submetidos a analise de variáncia, ANOVA. As doságens de adubo foram como a seguir no Tabela 2. Experimento 3. Efeito de latossolo vermelho novo, palha de arroz queimado e adubo 4N:14P:8K para produção da batata semente pré- básica em casa de vegetação Para pesquisar estes efeitos o experimento tipo de (2 x 6) foi instalado considerando-se as combinações entre duas misturas (i.e.: 1., 2.) e seis doságens de adubo complexo 4N:14P:8K, com três repetições, no delineamento experimental de bloco ao acaso, sendo 1 vaso (3000 cm3 volume de capacidade de vasos preto) por parcela na mésas experimentais em casa de vegetação. O adubo foi posicionando no solo de 4 cm abaixo de superficie do solo. A cultivar utilizada foi Baraka e o tamanho de tuberculos foi com 0-20 mm. A data de plantio foi 25.09.1990. Plantarémos em cada vaso 3-3 tuberculos com embaixo de 4cm de superficie da mistura no vasos. Irrigarémos com 12 mm quantidade da augua 2 vezes por semana. Para produção aplicarémos sistema de proteção de plantas como usados no Brasíl. Ambiente foi controlado ventilação automatizado. Temperatura médio foi 21 0C é humidade médio foi 66% durante de experimento. A data de colheta foi 14.12.1990. As pesagens foram feitos como peso fresco e matéria seca. Os resultados foram submetidos a analise de variáncia, MANOVA. Os manejos foram como a seguir no Tabela 3. Resultados e Discuscáo Experimento 1. Efeito de diferentes misturas para produção da batata semente pré- básica em casa de vegetação O tratamento 3. i.e.: mistura de 80% latossolo vermelho novo, 10% palha de arroz queimado e 10% esterco de curral, apresentou os maiores valores para numero de tuberculos com 0-20 mm (tamanho de comercial), peso de tuberculos com 0-20 mm e peso total de tuberculos por vaso. Porém, não houve diferencas significativas para o numero tuberculos comerciais, i.e.: com 0-20 mm, para os tratamentos 2., 3., 4., e 5. Portanto, a mistura poderá ter uma composição entre 60 a 90% de latossolo vermelho novo, 6 a 24% de palha de arroz queimado e de 4 a 16% de esterco de curral. Não houve diferenca significativa entre a mistura padrão utilizada e as misturas incluidas nos extremos indicados anteriormente. Porém, a mistura padrão recebeu adubação quimica de 4N:14P:8K (3.6 grama vaso-1) e calcário na dosagem de 4.2 grama vaso-1, o que não aconteceu com as parcelas das misturas em analise. Experimento 2. Efeito de adubo 4N:14P:8K para produção da batata semente pré- básica em casa de vegetação Há um efeito crescente das dóses de 4N:14P:8K nos caracteres observados. Porém, a maior dóse não chegou a ultrapassar a mistura padrão. Experimento 3. Efeito de latossolo vermelho novo, palha de arroz queimado e adubo 4N:14P:8K para produção da batata semente pré- básica em casa de vegetação Efeitos de misturas As duas misturas (i.e.: 1 e 2) deram resultados significativos mais alto que a mistura padrão, em média 54 %. Entre as misturas 1 e 2, foi melhor a 2. (80% latossolo vermelho novo, 10% palha de arroz queimado, 10% esterco de curral). Examinando-se 15 fatores, entre 11 casos afirmou-se a mistura como para melhor que a mistura 1. (70% latossolo vermelho novo, 20% palha de arroz queimado, 10% esterco de curral). Em caso de número de tuberculos 0-20 mm com a mistura 2. foi possivel aumentar geralmente os números de tuberculos em 77% que a mistura padrão. Efeitos de adubação 1. Área da folhas por planta entre manejo foi melhor de modo significativo a doságem de 3.6 grama vaso-1 adubo complexo (3103 cm2 plantas-1). 2. Peso fresco da folhas e de hastes por plantas as tendencias foram parecidos com o da área de folhas. 3. Peso fresco de raizis por planta até 7.2 grama vaso-1 diminuiu depois aumentou. 4. Peso fresco total de tuberculos por planta as crescentes doságens de um modo forte diminuiram a produção de tuberculos de 0 e 18.0 grama vaso-1 em 160% em os dois caso da mistura. 5. Peso de fitomassa fresco por planta foi melhor a 3.6 g vaso-1 (239 grama planta-1 em médio da dois mistura), depois os dados diminuirám. 6. Produção de biomassa fresco por planta a maxima produção (188 grama planta-1) foi obtida com 3.6 grama vaso-1. Deste ponto de modo forte caiu a produção. 7. Peso da matéria seca de folhas, hastes e raizis por planta somente em caso de mistura padrão o resultado foi significativo em relação aos outros tratamentos. 8. Péso da matéria seca de tuberculos total por planta modo significativo diminuiu a produção (0 e 18.0 grama vaso-1 = 360%) em médio da duas misturas. 9. Biomassa produção de materia seca por planta modo significativo diminuiu para efeito de alta dosagens de adubo complexo (0 e 18.0 grama vaso-1 = 158%) em médio da duas misturas. 10. Peso fresco de tuberculos com 0-20 mm as crescentes dosagens de 0 e 18.0 grama vaso-1 diminuiram a produção em 213% em médio da duas misturas. 11. Peso fresco de tuberculos com 20 mm-1 as crescentes dosagens de 0 e 18.0 grama vaso-1 diminuiram a produção assima de 250% em médio da duas misturas. 12. Numero de tuberculos 0-20 mm e 20 mm- por planta com os manejos de 0 e 18.0 grama vaso-1 foi possível aumentar em media 200% sobre a mistura padrão. Os manejo de 18.0 grama de adubo vaso-1 já causaram importante diminuição em relação caso a absoluto controle. 13. Numero total de tuberculos por planta entre manejos foi melhor a dosagem de 7.2 grama vaso-1 adubo complexo 4N:14P:8K comparando da mistura padrão. Nos verificamos-se que a mistura padrão sempre deu menor rasultados do que as outras misturas (i.e.: 1 e 2). Entre as misturas 1 e 2 a melhor foi a número 2. (80% latossolo vermelho novo, 10% palha de arroz queimado, 10% esterco de curral). Com esta mistura e com relação a mistura padrão, foi possível aumentar o número de tuberculos 0-20 mm com 77%. No caso do adubação, verificamos que grande quantidades de adubo acima de 7.2 grama vaso-1, de modo rigoroso diminuiu a produção de batata-semente pré- básica. Este fato deve ser considerado para a eleição das dosagens de adubos. Deve-se indicar o caso de número de tuberculos acima 20 mm-, onde em relação mistura padrão foi possivel aumentar em média 73% os resultados. Reconhecimento: Esta pesquisa foi apoio da Empresa Brasileira de Pesquisa Agropecuaria- Centro Nacional de Pesquisas de Hortaliças, Brasília-DF e Centro Pesquisa de Solo e Agroquímica do Academia Húngara de Ciências, Budapest References Kádár I-Márton L.-Horváth S. 2000. Mineral fertilisation of potato (Solanum tuberosum L.) on calcareous chernozem soil. Plant Production. 49: 291-306. Kurnik E.-Németh T.-Márton L.-Radimszki L. 2001. Effects of a new environment friendly deep fertilization system on a limy chernozem soil parameters. Agrochemistry and Soil Science. Budapest. In press László M. 2000. Nutrition of potato (Solanum tuberosum L.) on Hungary on a chernozem soil. Acta Agronomica Óváriensis. 42: 81-93. László M. 2001a. Climate change and N, P, K, Mg fertilization effects on potato (Solanum tuberosum L.) yield and quality. EAPR. Hamburg. In press László M. 2001b. Year and fertilization effect analysis in long field term experiments. XLIII. Georgikon Days. University of Veszprém. Keszthely László M.-Imre K.-Jose E.M. 2000a. Effects of Crotalaria juncea L. and Crotalaria spectabilis ROTH. on soil fertility and soil conservation in Hungary. Acta Agronomica Óváriensis. 42: 99-106. László M.-Silva J.C.-Jose A.B. 2000b. Ecological friendly dragée technics on different crops and vegetables seeds. Acta Agronomica Óváriensis. 42: 107-111. László M.-Silva J.B.C.-Jose A.B. 2000c. Ecological friendly dragée technics to sustainable precision agriculture. Fertilization in the Third Millenium. CASISCF. Beijing Márton L. 2000a. Effects of NPK fertilizers on potato (Solanum tuberosum L.) yield. Doctoral Ph.D Dissertation. University of Veszprém, Keszthely Márton L. 2000b. Effects of NPK fertilizers on potato (Solanum tuberosum L.) yield. Doctoral Ph.D Thesis. University of Veszprém, Keszthely Márton L. 2001a. Climete change effets on rye (Secale cereale L.) yield. Agrochemistry and Soil Science. Budapest. In press Márton L. 2001b. Climate change and fertilization effect analysis at the Tisza- river basin on rye yield. SZINET. University of Szent István. Gödöllő Márton L.-Kádár I.-Estáquio M.J. 2000. Effects of Crotalaria juncea L. and Crotalaria spectabilis ROTH on soil fertility and soil conservation. ESSC. Man and Soil at the Third Millennium. Abstract Book. 195. Valencia Reifschneider F.J.B. 1987. Produção de batata. Linha Gráfica e Editora. Brasília. p. 239. Tabela 1. Tratamentos do experimento 1. (Brasília-DF, 1990) ------------------------------------------------------------------ Numero de Composição em % Tratamento Solo novo Palha de arroz queimado Esterco de curral ------------------------------------------------------------------ 1. 100 0 0 2. 90 6 4 3. 80 10 10 4. 70 18 12 5. 60 24 16 6. 50 30 20 7. 40 36 24 ----------------------------------------------------------------- Tabela 2. Tratamentos do experimento 2. (Brasília-DF, 1990) ------------------------------------------------------- Numero de Adubo 4:14:8 N P2O5 K2O Tratamento Grama vaso-1 ------------------------------------------------------- 1. 0.0 0.000 0.000 0.000 2. 1.8 0.072 0.252 0.144 3. 3.6 0.144 0.504 0.288 4. 5.4 0.216 0.756 0.432 5. 7.2 0.288 1.008 0.576 6. 9.0 0.360 1.260 0.720 7. 10.8 0.432 1.512 0.864 8. 12.6 0.504 1.764 1.008 9. 14.4 0.576 2.016 1.152 ------------------------------------------------------- Tabela 3. Tratamentos do experimento 3. (Brasília-DF, 1990) ------------------------------------------------------------------------ Num. de Mistura % Trat. Solo novo Palea de arr. Q Esterco de curral 4N:14P:8K g vaso-1 ------------------------------------------------------------------------ 1. 70 20 10 0.0 2 70 20 10 3.6 3. 70 20 10 7.2 4. 70 20 10 10.8 5. 70 20 10 14.4 6. 70 20 10 18.0 7. 80 10 10 0.0 8. 80 10 10 3.6 9. 80 10 10 7.2 10. 80 10 10 10.8 11. 80 10 10 14.4 12. 80 10 10 18.0 ------------------------------------------------------------------------

Assessment of Carotid Intima-Media Thickness as an Early Marker Of Vascular Damage In Hypertensive Children.

PubMed

Baroncini, Liz Andréa Villela; Sylvestre, Lucimary de Castro; Baroncini, Camila Varotto; Pecoits, Roberto

2017-05-01

The increased carotid intima-media thickness (CIMT) correlates with the presence of atherosclerosis in adults and describes vascular abnormalities in both hypertensive children and adolescents. To assess CIMT as an early marker of atherosclerosis and vascular damage in hypertensive children and adolescents compared with non-hypertensive controls and to evaluate the influence of gender, age, and body mass index (BMI) on CIMT on each group. Observational cohort study. A total of 133 hypertensive subjects (male, n = 69; mean age, 10.5 ± 4 years) underwent carotid ultrasound exam for assessment of CIMT. One hundred and twenty-one non-hypertensive subjects (male, n = 64; mean age, 9.8 ± 4.1 years) were selected as controls for gender, age (± 1 year), and BMI (± 10%). There were no significant difference regarding gender (p = 0.954) and age (p = 0.067) between groups. Hypertensive subjects had higher BMI when compared to control group (p = 0.004), although within the established range of 10%. Subjects in the hypertensive group had higher CIMT values when compared to control group (0.46 ± 0.05 versus 0.42 ± 0.05 mm, respectively, p < 0.001; one-way ANOVA). Carotid IMT values were not significantly influenced by gender, age, and BMI when analyzed in both groups separately (Student's t-test for independent samples). According to the adjusted determination coefficient (R²) only 11.7% of CIMT variations were accounted for by group variations, including age, gender, and BMI. Carotid intima-media thickness was higher in hypertensive children and adolescents when compared to the control group. The presence of hypertension increased CIMT regardless of age, gender, and BMI. O aumento da espessura médio-intimal carotídea (EMIC) correlaciona-se com a presença de aterosclerose em adultos e descreve anormalidades vasculares em crianças e adolescentes hipertensos. Avaliar a EMIC como marcador precoce de aterosclerose e dano vascular em crianças e adolescentes hipertensos em comparação com um grupo controle e avaliar a influência do sexo, idade e índice de massa corporal (IMC) sobre a EMIC em cada grupo. Estudo observacional de coorte. Um total de 133 indivíduos hipertensos (sexo masculino, n = 69; idade média 10.5 ± 4 anos) foi submetido à ultrassonografia das artérias carótidas para avaliação da EMIC. Cento e vinte e um indivíduos saudáveis (sexo masculino, n = 64; idade média, 9.8 ± 4.1 anos) foram selecionados como controles para as seguintes características: sexo, idade (± 1ano) e IMC (±10%). Não houve diferenças significativas entre os grupos com relação ao sexo (p = 0,954) e idade (p = 0,067). Os indivíduos hipertensos apresentaram maior IMC (p = 0,004), porém dentro da faixa estabelecida de até 10%. Os indivíduos hipertensos apresentaram maiores valores de EMIC quando comparados ao grupo-controle (0,46 ± 0,05 versus 0,42 ± 0,05 mm, respectivamente, p < 0.001; ANOVA com um parâmetro). Os valores da EMIC não foram influenciados por sexo, idade e IMC quando analisados em ambos os grupos separadamente (Teste t de Student para amostras independentes). De acordo com o coeficiente de determinação (R²) ajustado, apenas 11.7% das variações da EMIC são devidas às variações em cada grupo, incluindo idade, sexo e IMC. A espessura médio-intimal das carótidas apresentou-se aumentada em crianças e adolescentes hipertensos quando comparados ao grupo controle. A presença de hipertensão aumentou a EMIC independentemente de idade, sexo e IMC.

The destruction complex of beta-catenin in colorectal carcinoma and colonic adenoma.

PubMed

Bourroul, Guilherme Muniz; Fragoso, Hélio José; Gomes, José Walter Feitosa; Bourroul, Vivian Sati Oba; Oshima, Celina Tizuko Fujiyama; Gomes, Thiago Simão; Saba, Gabriela Tognini; Palma, Rogério Tadeu; Waisberg, Jaques

2016-01-01

To evaluate the destruction complex of beta-catenin by the expression of the proteins beta-catetenin, adenomatous polyposis coli, GSK3β, axin and ubiquitin in colorectal carcinoma and colonic adenoma. Tissue samples from 64 patients with colorectal carcinoma and 53 patients with colonic adenoma were analyzed. Tissue microarray blocks and slides were prepared and subjected to immunohistochemistry with polyclonal antibodies in carcinoma, adjacent non-neoplastic mucosa, and adenoma tissues. The immunoreactivity was evaluated by the percentage of positive stained cells and by the intensity assessed through of the stained grade of proteins in the cytoplasm and nucleus of cells. In the statistical analysis, the Spearman correlation coefficient, Student's t, χ2, Mann-Whitney, and McNemar tests, and univariate logistic regression analysis were used. In colorectal carcinoma, the expressions of beta-catenin and adenomatous polyposis coli proteins were significantly higher than in colonic adenomas (p<0.001 and p<0.0001, respectively). The immunoreactivity of GSK3β, axin 1 and ubiquitin proteins was significantly higher (p=0.03, p=0.039 and p=0.03, respectively) in colorectal carcinoma than in the colonic adenoma and adjacent non-neoplastic mucosa. The immunohistochemistry staining of these proteins did not show significant differences with the clinical and pathological characteristics of colorectal cancer and colonic adenoma. These results suggest that, in adenomas, the lower expression of the beta-catenin, axin 1 and GSK3β proteins indicated that the destruction complex of beta-catenin was maintained, while in colorectal carcinoma, the increased expression of beta-catenin, GSK3β, axin 1, and ubiquitin proteins indicated that the destruction complex of beta-catenin was disrupted. Avaliar o complexo de destruição da betacatenina no carcinoma colorretal e no adenoma do colo pela expressão das proteínas betacatenina, adenomatous polyposis coli, GSK3β, axina e ubiquitina. Amostras de tecidos de 64 doentes com carcinoma colorretal e de 53 pacientes com adenoma do colo foram analisadas. Blocos de tecidos foram submetidos ao estudo imuno-histoquímico com anticorpos policlonais nos tecidos do carcinoma, mucosa não neoplásica adjacente e adenoma. A imunorreatividade foi avaliada pela porcentagem de positividade de células coradas e pela intensidade do grau de coloração das proteínas no citoplasma e no núcleo das células. Na análise estatística, foram utilizados o coeficiente de correlação de Spearman, os testes t de Student, χ2, Mann-Whitney e de McNemar, e a análise de regressão logística univariada. No carcinoma colorretal, as expressões da betacatenina e da adenomatous polyposis coli foram significativamente maiores do que em adenomas do colo (p<0,001 e p<0,0001, respectivamente). A imunorreatividade das proteínas GSK3β, axina 1 e ubiquitina foi significativamente maior (p=0,03, p=0,039 e p=0,03, respectivamente) no carcinoma colorretal do que no adenoma e na mucosa não neoplásica adjacente. A coloração imuno-histoquímica dessas proteínas não apresentou diferenças significantes em relação às características clinicopatológicas do câncer colorretal e do adenoma. Em adenomas, as menores expressões de betacatenina, axina 1 e GSK3β indicaram que o complexo de destruição da betacatenina estava conservado, enquanto que, no carcinoma colorretal, o aumento das expressões da betacatenina, GSK3β, 1 axina, e ubiquitina indicaram que o complexo de destruição de betacatenina estava alterado.

[Not Available].

PubMed

San Mauro Martín, Ismael; Garicano Vilar, Elena; León Fernández, Joana; Ciudad Cabañas, María José; Collado Yurrita, Luis

2016-07-19

Introducción: recientemente ha surgido el interés por el posible papel de la microbiota intestinal como agente potenciador del rápido aumento que se está observando en el aumento de la prevalencia de obesidad en todo el mundo.Objetivos: relacionar las modificaciones que puede ocasionar el consumo de antibióticos en la microflora intestinal con la obesidad.Métodos: se extrajeron, de las Encuestas Nacionales de Salud de España, entre los años 2001 y 2011, las cifras de ingesta de antibióticos y la prevalencia (%) de obesidad en el mismo rango de edad, género y año. La media total de encuestados fue de 29.904 participantes.Resultados: se encontraron correlaciones significativas (p=0,09) en la asociación de la prevalencia de obesidad y la ingesta de antibióticos. Además, se objetivó que en el sexo masculino esta influencia es el doble que en el femenino.Conclusiones: los descubrimientos recientes en el campo de la microbiota intestinal y su relación con el huésped abren nuevos caminos en la comprensión de ciertas enfermedades inflamatorias y metabólicas, como la obesidad.

Earth and Heavens: Two Separate Universes? (Spanish Title: Tierra y Cielos: ¿Dos Universos Separados?) Terra e Céus: Dois Universos Separados?

NASA Astrophysics Data System (ADS)

Carrascosa, Jaime; Gil-Pérez, Daniel; Solbes, Jordi; Vilches, Amparo

2005-12-01

The study of gravitation constitutes an exceptional occasion to show the richness and complexity of science and technology, contemplating, among other things: the problematic situations which are at the heart of the scientific knowledge, the difficulties encountered in the construction of knowledge and, especially, the necessity of overcoming "common-sense evidence" that proclaimed the existence of an insurmountable barrier between Earth and Heavens, hindering scientific development during many centuries. In this paper we present a program of activities to orient the study of Gravitation atUpperHigh School, favoring students' participation in the reconstruction of this first scientific revolution and giving them the opportunity to see the importance of Astronomy both in the history of science and today. El estudio de la gravitación constituye una ocasión excepcional para mostrar la ciencia y la tecnología en toda su riqueza y complejidad, considerando, entre otros aspectos:

Long-Term Follow-Up of Patients after Percutaneous Coronary Intervention with Everolimus-Eluting Bioresorbable Vascular Scaffold.

PubMed

Meneguz-Moreno, Rafael Alexandre; Costa, José de Ribamar; Moscoso, Freddy Antônio Britto; Staico, Rodolfo; Tanajura, Luiz Fernando Leite; Centemero, Marinella Patrizia; Chaves, Auréa Jacob; Abizaid, Andrea Claudia Leão de Sousa; Sousa, Amanda Guerra de Moraes Rego E; Abizaid, Alexandre Antonio Cunha

2017-02-01

Bioresorbable vascular scaffolds (BVS) were developed to improve the long-term results of percutaneous coronary intervention, restoring vasomotion. To report very late follow-up of everolimus-eluting Absorb BVS (Abbott Vascular, Santa Clara, USA) in our center. Observational retrospective study, in a single Brazilian center, from August 2011 to October 2013, including 49 patients submitted to Absorb BVS implantation. Safety and efficacy outcomes were analyzed in the in-hospital and very late follow-up phases (> 2 years). All 49 patients underwent a minimum follow-up of 2.5 years and a maximum of 4.6 years. Mean age was 56.8 ± 7.6 years, 71.4% of the patients were men, and 26.5% were diabetic. Regarding clinical presentation, the majority (94%) had stable angina or silent ischemia. Device success was achieved in 100% of cases with 96% overall procedure success rate. Major adverse cardiovascular events rate was 4% at 30 days, 8.2% at 1 year, and 12.2% at 2 years, and there were no more events until 4.6 years. There were 2 cases of thrombosis (1 subacute and 1 late). In this preliminary analysis, Absorb BVS showed to be a safe and effective device in the very late follow-up. Establishing the efficacy and safety profiles of these devices in more complex scenarios is necessary. Os suportes vasculares bioabsorvíveis (SVB) foram desenvolvidos com o intuito de melhorar os resultados da intervenção coronária percutânea a longo prazo, restabelecendo-se a vasomotricidade. Reportar o seguimento muito tardio do implante do SVB eluidor de everolimus Absorb® (Abbot Vascular, Santa Clara, EUA) em nosso centro. Estudo observacional, retrospectivo, em um único centro brasileiro, que incluiu 49 pacientes submetidos ao implante do SVB Absorb® entre agosto/2011 e outubro/2013. Foram analisados os desfechos de segurança e eficácia na fase hospitalar e bastante tardia (> 2 anos). Todos os 49 pacientes completaram um seguimento mínimo de 2,5 anos, sendo o máximo de 4,6 anos. A média de idade foi 56,8 ± 7,6 anos, sendo 71,4% da população estudada do sexo masculino e 26,5% composta por diabéticos. Considerando a apresentação clínica, a grande maioria (94%) tinha angina estável ou isquemia silenciosa. Obteve-se sucesso do dispositivo em 100% dos casos e do procedimento, em 96%. A taxa de eventos cardiovasculares maiores foi de 4% aos 30 dias, de 8,2% em 1 ano, e de 12,2% em 2 anos, sem mais eventos até 4,6 anos. Houve 2 casos de trombose (1 subaguda e 1 tardia) até o último seguimento. Nesta análise preliminar, o uso do SVB Absorb® mostrou-se seguro e eficaz no seguimento bastante tardio. Faz-se necessário estabelecer o perfil de eficácia e segurança destes dispositivos em cenários de maior complexidade.

Ovarian hyperstimulation syndrome in a spontaneous singleton pregnancy.

PubMed

Cabar, Fábio Roberto

2016-05-24

The ovarian hyperstimulation syndrome is the combination of increased ovarian volume, due to the presence of multiple cysts and vascular hyperpermeability, with subsequent hypovolemia and hemoconcentration. We report a case of spontaneous syndrome in a singleton pregnancy. This was a spontaneous pregnancy with 12 weeks of gestational age. The pregnancy was uneventful until 11 weeks of gestational age. After that, the pregnant woman complained of progressive abdominal distention associated with abdominal discomfort. She did not report other symptoms. In the first trimester, a routine ultrasonography showed enlarged ovaries, multiples cysts and ascites. Upon admission, the patient was hemodynamically stable, her serum β-hCG was 24,487mIU/mL, thyroid-stimulating hormone was 2.2µUI/mL and free T4 was 1.8ng/dL. All results were within normal parameters. However, levels of estradiol were high (10,562pg/mL). During hospitalization, she received albumin, furosemide and prophylactic dose of enoxaparin. The patient was discharged on the sixth hospital day. RESUMO A síndrome de hiperestimulação ovariana é a combinação do aumento dos ovários, devido à presença de múltiplos cistos e de hiperpermeabilidade vascular, com subsequente hipovolemia e hemoconcentração. Relata-se um caso de síndrome espontânea em uma gestação única. Trata-se de gravidez espontânea com 12 semanas de idade gestacional. A gravidez ocorreu sem intercorrências até 11 semanas de idade gestacional. Após, a gestante passou a se queixar de distensão abdominal progressiva, associada com desconforto abdominal. A paciente não relatava outros sintomas. A ultrassonografia de rotina no primeiro trimestre mostrou ovários aumentados com múltiplos cistos e ascite. No momento da internação, a paciente apresentava-se hemodinamicamente estável, com β-hCG sérico de 24.487mUI/mL, hormônio estimulante da tireoide de 2,2µUI/m e T4 livre de 1,8ng/dL, ou seja, valores dentro dos parâmetros normais. Porém, os níveis de estradiol estavam elevados (10.562pg/mL). Durante a internação, a paciente recebeu albumina, furosemida e enoxaparina profilática. A alta hospitalar ocorreu no sexto dia de internação.

Revista de Saúde Pública in scientific publications on Violence and Health (1967-2015).

PubMed

Schraiber, Lilia Blima; Barros, Claudia; d'Oliveira, Ana Flávia Pires Lucas; Peres, Maria Fernanda Tourinho

2016-11-10

This article retrieved the publications from the Revista de Saúde Pública journal (from 1967 to 2015) on violence and health, on the SciELO and PubMed bases, by searching for the terms "violence", "suicide", "aggression", "bullying", and "external causes", registered in any part of the text. We found 130 articles (the first one published in 1974). We observed: increase of publications over time, with decrease in the last five years; similar production volume in lethal and non-lethal violence; later publication of the latter; few studies in qualitative research; mostly descriptive production; and visualization of the problem more by the acts than by contexts or motivations and aggressors. Social markers were little approached, appearing, from largest to smallest frequency, social class, gender, race/ethnicity, and generation. Human rights were little used and only recently used as analytical framework, connected more to gender than to social class. Although Revista de Saúde Pública has registered the theme in its publications, consolidating it as scientific production line, there is still great explanatory theoretical rarefaction and little intersectionality between violence, social inequalities, and human rights. RESUMO A produção da Revista de Saúde Pública (de 1967 até 2015) sobre violência e saúde foi recuperada nas bases SciELO e PubMed utilizando-se os termos "violência", "suicídio", "agressões", "bullying" e "causas externas", registrados em qualquer parte do texto. Foram encontrados 130 artigos (o primeiro deles publicado em 1974). Constatou-se: aumento das publicações no tempo, com decréscimo nos últimos cinco anos; volume similar de produção em violência letal e não letal; publicação mais tardia desta última; poucos estudos em pesquisa qualitativa; produção majoritariamente descritiva; e visibilização do problema, mais pelos atos que pelos contextos ou motivações e agressores. Os marcadores sociais foram pouco tematizados, aparecendo da maior para a menor frequência, classe social, gênero, raça/etnia e geração. Direitos humanos foi pouco, e apenas recentemente, usado como referencial analítico, conectado mais ao gênero do que à classe social. Embora a Revista de Saúde Pública tenha inscrito o tema em suas publicações, consolidando-o como linha de produção científica, há, ainda, grande rarefação teórica explicativa e pouca interseccionalidade entre violência, desigualdades sociais e direitos humanos.

[In Process Citation].

PubMed

Gonçalves Schemitt, Elizângela; Raskopf Colares, Josieli; Minuzzo Hartmann, Renata; Morgan-Martins, María Isabel; Marroni, Cláudio Augusto; Tuñón, M Jesús; Possa Marroni, Norma

2016-03-25

Introducción: la insuficiencia hepática fulminante (IHF) es un síndrome clínico poco frecuente, que se caracteriza por una disfunción hepática severa y repentina. La tioacetamida (TAA) es una hepatotoxina cuya administración puede inducir necrosis centrolobulillar en las células hepáticas y aumentar la formación de especies reactivas de oxígeno y la peroxidación lipídica en ratas. La glutamina es un precursor para la síntesis de glutatión. Objetivo: el objetivo del estudio es evaluar los efectos antioxidantes de la glutamina en un modelo de rata de IHF inducida por TAA. Métodos: ratas macho Wistar se dividieron en cuatro grupos de acuerdo con el tratamiento y el tiempo de evaluación: control, glutamina (25 mg/kg), tioacetamida (400 mg/kg) y tioacetamida más glutamina. Los animales se evaluaron después de 24, 36 y 48 horas. Se recogieron muestras de sangre para el análisis de los niveles de aspartato aminotransferasa (AST), alanina aminotransferasa (ALT), fosfatasa alcalina (AP), bilirrubina total (TB) y creatinina (CRE), y muestras de hígado para evaluar la peroxidación lipídica, las sustancias reactivas al ácido tiobarbitúrico (TBARS), la actividad de las enzimas antioxidantes superóxido dismutasa (SOD), glutatión peroxidasa (GPx), catalasa (CAT) y glutatión S-transferasa (GST). Además se midieron mediante inmunohistoquímica el factor nuclear kappa N (NF-κB), el fator de necrosis tumoral (TNF-α) y la óxido nítrico sintasa inducible (iNOS). Resultados: la TAA causó alteraciones en los parámetros bioquímicos e histológicos, y el aumento de los marcadores del proceso inflamatorio. Los niveles de TBARS y la actividad de SOD y GST fueron significativamente inferiores en los grupos de glutamina en comparación con TAA. La actividad de CAT se incrementó en los animales tratados con glutamina en comparación con la TAA. La actividad GPx también fue menor a las 36 y 48 h en los animales tratados com glutamina. El daño tisular y la expresión de NF-κB, TNF-α e iNOS fueron significativamente inferiores en los animales tratados con glutamina. Conclusión: la glutamina ha demostrado tener efectos protectores contra el daño hepático en un modelo de IHF inducida por TAA en la rata.

Profile of skin cancer in Pomeranian communities of the State of Espírito Santo.

PubMed

Frasson, Patrícia Henriques Lyra; Duque, Danilo Schwab; Pinto, Estanrley Barcelos; Dalvi, Giulia Cerutti; Madalon, Sammy Zogheib; Nunes, Tarcizo Afonso; DE-Vargas, Paulo Roberto Merçon

2017-01-01

to evaluate the profile of skin cancer in Pomeranian communities of the State of Espírito Santo, composed of descendants of European immigrants, regarding gender and age at diagnosis, lesion size and histological type. we studied histopathological reports of 3,781 patients operated between 2000 and 2010, with resection of 4,881 lesions. We assessed histological type, lesion size, age and gender of the patients at diagnosis and their correlations in the 11-year period. the histopathological examination revealed basal cell carcinoma in 3,159 patients (83.5%), squamous cell carcinoma in 415 (11%), melanoma in 64 (1.7%), and 143 patients (3.8%) had combined lesions of basal cell carcinoma and squamous cell carcinoma. As to size, 47.1% measured between 5.1 and 10mm. The age group of 61 to 70 years was the one that sustained the largest number of surgical interventions (24.3%). There was a predominance of the female gender (2,027, 53.6%) in relation to the male (1,754, 46.4%). basal cell carcinoma was the most frequent histological type. The prevalences of squamous cell carcinoma and melanoma were below the national estimate of the National Cancer Institute. The diagnosis of tumors occurred at more advanced ages (above 60 years) and there was an increase in the incidence and size of skin tumors in the male population. avaliar o panorama do câncer de pele em comunidades pomeranas do Estado do Espírito Santo, compostas por descendentes de imigrantes europeus, quanto ao sexo e idade ao diagnóstico, tamanho da lesão e tipo histológico. foram avaliados laudos histopatológicos de 3781 pacientes operados entre os anos de 2000 e 2010, com ressecção de 4881 lesões. Foram avaliados tipo histológico, tamanho das lesões, idade e sexo dos pacientes ao diagnóstico e suas correlações no período de 11 anos. o exame histopatológico evidenciou carcinoma basocelular em 3159 pacientes (83,5%), carcinoma espinocelular em 415 (11%), melanoma em 64 (1,7%) e 143 pacientes (3,8%) apresentaram lesões combinadas de carcinoma basocelular e carcinoma espinocelular. Quanto ao tamanho, 47,1% media entre 5,1 e 10 mm. O grupo etário de 61 aos 70 anos foi o que sofreu o maior número de intervenções cirúrgicas (24,3%). Houve predomínio do sexo feminino (53,6%, n=2027) em relação ao masculino (46,4%, n=1754). carcinoma basocelular foi o tipo histológico mais frequente. As prevalências do carcinoma espinocelular e do melanoma se situaram abaixo da estimativa nacional do Instituto Nacional de Câncer. O diagnóstico dos tumores ocorreu em idades mais avançadas (acima de 60 anos) e houve aumento da incidência e dimensões dos tumores de pele na população masculina.

Overweight effect on spirometric parameters in adolescents undergoing exercise.

PubMed

Costa, Rayana de Oliveira; Silva, Juliana Pereira; Lacerda, Eliana Mattos; Dias, Rodrigo; Pezolato, Vitor Alexandre; Silva, Carlos Alberto da; Krinski, Kleverton; Correia, Marco Aurélio de Valois; Cieslak, Fabrício

2016-01-01

To evaluate effects of overweight on spirometric parameters in adolescents who underwent bronchial provocation test for exercise. We included 71 male adolescents. The diagnosis of asthma was done based on participants' clinical history and on the International Study Questionnaire Asthma and Allergies in Childhood, and the diagnosis of obesity was based on body mass index above 95th percentile. The bronchospasm induced by exercise was assessed using the run-walk test on a treadmill for eight minutes. The decrease in forced expiratory volume in one second > or equal to 10% before exercise was considered positive, and to calculate the intensity in exercise-induced bronchospasm we measured the maximum percentage of forced expiratory volume in one second and above the curve area. Data analysis was carried out using the Mann-Whitney U test and Friedman test (ANOVA), followed by Wilcoxon test (p<0.05). In addition, we used Fisher's exact test to analyze the exercise-induced bronchospasm frequency. Significant differences were observed among obese adolescents in exercise-induced bronchospasm frequency (p=0,013) and in relation to time required for recovery after exercise (p=0,007). Overweight can influence the increase in the exercise-induced bronchospasm frequency in non-asthmatic adolescents compared with eutrophic adolescents. Avaliar o efeito do excesso de peso sobre parâmetros espirométricos em adolescentes submetidos ao teste de broncoprovocação por exercício. Participaram do estudo 71 adolescentes do sexo masculino. O diagnóstico de asma foi obtido por meio de histórico clínico e do questionário International Study of Asthma and Allergies in Childhood, e o de obesidade, pelo índice de massa corporal acima do percentil 95. Para avaliar o broncoespasmo induzido pelo exercício, utilizou-se o teste correr/caminhar em esteira ergométrica, com duração de 8 minutos, considerando positivo se diminuição do volume expiratório forçado no primeiro segundo >10% do valor pré-exercício e, para a intensidade do broncoespasmo induzido pelo exercício, foram utilizados o cálculo da queda percentual máxima do volume expiratório forçado no primeiro segundo e a área acima da curva. A análise dos dados foi realizada pelo teste U Mann-Whitney e pela ANOVA de Friedman, seguido do teste de Wilcoxon (p<0,05). O teste de Fisher foi empregado para analisar a frequência de broncoespasmo induzido pelo exercício. Foram encontradas diferenças significativas quanto à frequência de broncoespasmo induzido pelo exercício (p=0,013) e ao tempo de recuperação pós-exercício (p=0,007) nos adolescentes obesos. O excesso de peso pode influenciar no aumento da frequência de broncoespasmo induzido pelo exercício em adolescentes não asmáticos, quando comparados a eutróficos.

A murine model of elastase- and cigarette smoke-induced emphysema.

PubMed

Rodrigues, Rubia; Olivo, Clarice Rosa; Lourenço, Juliana Dias; Riane, Alyne; Cervilha, Daniela Aparecida de Brito; Ito, Juliana Tiyaki; Martins, Milton de Arruda; Lopes, Fernanda Degobbi Tenório Quirino Dos Santos

2017-01-01

To describe a murine model of emphysema induced by a combination of exposure to cigarette smoke (CS) and instillation of porcine pancreatic elastase (PPE). A total of 38 C57BL/6 mice were randomly divided into four groups: control (one intranasal instillation of 0.9% saline solution); PPE (two intranasal instillations of PPE); CS (CS exposure for 60 days); and CS + PPE (two intranasal instillations of PPE + CS exposure for 60 days). At the end of the experimental protocol, all animals were anesthetized and tracheostomized for calculation of respiratory mechanics parameters. Subsequently, all animals were euthanized and their lungs were removed for measurement of the mean linear intercept (Lm) and determination of the numbers of cells that were immunoreactive to macrophage (MAC)-2 antigen, matrix metalloproteinase (MMP)-12, and glycosylated 91-kDa glycoprotein (gp91phox) in the distal lung parenchyma and peribronchial region. Although there were no differences among the four groups regarding the respiratory mechanics parameters assessed, there was an increase in the Lm in the CS + PPE group. The numbers of MAC-2-positive cells in the peribronchial region and distal lung parenchyma were higher in the CS + PPE group than in the other groups, as were the numbers of cells that were positive for MMP-12 and gp91phox, although only in the distal lung parenchyma. Our model of emphysema induced by a combination of PPE instillation and CS exposure results in a significant degree of parenchymal destruction in a shorter time frame than that employed in other models of CS-induced emphysema, reinforcing the importance of protease-antiprotease imbalance and oxidant-antioxidant imbalance in the pathogenesis of emphysema. Descrever um modelo murino de enfisema induzido por exposição a fumaça de cigarro (FC) e instilação de elastase pancreática porcina (EPP). Trinta e oito camundongos C57BL/6 foram aleatoriamente divididos em quatro grupos: controle (uma instilação intranasal de solução salina a 0,9%); EPP (duas instilações intranasais de EPP); FC (exposição a FC durante 60 dias) e FC + EPP (duas instilações intranasais de EPP + exposição a FC durante 60 dias). No fim do protocolo experimental, todos os animais foram anestesiados e traqueostomizados para o cálculo de parâmetros de mecânica respiratória. Em seguida, todos os animais foram sacrificados e seus pulmões foram removidos para a medição da intercepção linear média (Lm) e a determinação do número de células imunorreativas a antígeno macrofágico (MAC)-2, metaloproteinase da matriz (MMP)-12 e glicoproteína glicosilada de 91 kDa (gp91phox) no parênquima pulmonar distal e na região peribrônquica. Embora não tenha havido diferenças entre os quatro grupos quanto aos parâmetros de mecânica respiratória avaliados, houve aumento da Lm no grupo FC + EPP. O número de células positivas para MAC-2 na região peribrônquica e no parênquima pulmonar distal foi maior no grupo FC + EPP do que nos outros grupos, assim como o foi o número de células positivas para MMP-12 e gp91phox, porém somente no parênquima pulmonar distal. Nosso modelo de enfisema induzido por instilação de EPP e exposição a FC resulta em um grau significativo de destruição parenquimatosa em um período de tempo menor que o empregado em outros modelos de enfisema induzido por FC, o que reforça a importância do desequilíbrio entre proteases e antiproteases e entre oxidantes e antioxidantes na patogênese do enfisema.

Nurses in post-operative heart surgery: professional competencies and organization strategies.

PubMed

Santos, Ana Paula Azevedo; Camelo, Silvia Helena Henriques; Santos, Fabiana Cristina Dos; Leal, Laura Andrian; Silva, Beatriz Regina da

2016-01-01

To analyze nurses' competencies with regard to their work in post-operative heart surgery and the strategies implemented to mobilize these competencies. This was an exploratory study with a qualitative approach and a methodological design of collective case study. It was carried out in three post-operative heart surgery units, consisting of 18 nurses. Direct observation and semi-structured interviews were employed to collect data. Data were construed through thematic analysis. nine competencies were found, as follows: theoretical-practical knowledge; high-complexity nursing care; nursing supervision; leadership in nursing; decision making; conflict management; personnel management; material and financial resources management; and on-job continued education. Organizational and individual strategies were employed to develop and improve competencies such as regular offerings of courses and lectures, in addition to the individual pursuit for knowledge and improvement. the study is expected to lead future nurses and training centers to evaluate the need for furthur training required to work in cardiac units, and also the need for implementing programs aimed at developing the competencies of these professionals. Analisar as competências dos enfermeiros para atuarem no pós-operatório de cirurgia cardíaca e estratégias implementadas para a mobilização dessas competências. Estudo exploratório, com abordagem qualitativa e desenho metodológico estudo de caso coletivo. Foi realizado em três unidades pós-operatórias de cirurgias cardíacas, com 18 enfermeiros. Na coleta de dados utilizou-se observação direta e entrevista semiestruturada. Para interpretação dos dados optou-se pela análise temática. Foram identificadas nove competências, sendo: conhecimento teórico-prático, cuidados de enfermagem de alta complexidade, supervisão e liderança em enfermagem, tomada de decisão, gerenciamento de conflitos, de recursos humanos, materiais, financeiros e educação continuada em serviço. Estratégias organizacionais e individuais são realizadas a fim de desenvolver e aprimorar competências, tais como: oferecimento de cursos e palestras periodicamente, além da busca individual por conhecimento e aperfeiçoamento. O estudo deve provocar a reflexão de futuros enfermeiros e dos centros formadores quanto à formação necessária para atuar em unidades cardíacas e sobre a necessidade de implementação de programas que visam desenvolver competências nestes profissionais.

Desgarros del epitelio pigmentario de la retina: factores de riesgo, mecanismo y control terapéutico.

PubMed

Clemens, Christoph R; Eter, Nicole

2017-07-11

Los desgarros del epitelio pigmentario de la retina (EPR) se asocian en la mayoría de los casos con los desprendimientos vascularizados del EPR debido a una degeneración macular asociada a la edad (DMAE), y normalmente implican una pérdida adversa de la agudeza visual. Estudios recientes indican que ha habido un aumento en la incidencia de desgarros del EPR desde la introducción de fármacos anti-factor de crecimiento del endotelio vascular (anti-VEGF) así como una asociación temporal entre el desgarro y la inyección intravítrea. Dado que el número de pacientes con DMAE y el número de inyecciones anti-VEGF va en aumento, tanto la dificultad de prevenir desgarros del EPR como el tratamiento tras la formación de los desgarros han adquirido una mayor relevancia. De forma paralela, la evolución de la imagenología de la retina ha contribuido de manera significativa a comprender mejor el desarrollo de los desgarros del EPR en los últimos años. Esta revisión resume los conocimientos que se poseen actualmente sobre el desarrollo, los factores pronósticos y las estrategias terapéuticas de los desgarros del EPR antes y después de que estos se formen. © 2017 S. Karger AG, Basel.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meats, A.

Both wild and released (sterile) Bactrocera tryoni (Froggatt) (Diptera: Tephritidae) and wild Bactrocera papayae (Drew and Hancock) in Australia had patchy distributions and comparisons with predictions of the negative binomial model indicated that the degree of clumping was sometimes very high, particularly at low densities during eradication. An increase of mean recapture rate of sterile B. tryoni on either of 2 trap arrays was not accompanied by a reduction in its coefficient of variation and when recapture rates were high, the percentage of traps catching zero decreased only slightly with increase in recapture rate, indicating that it is not practicablemore » to decrease the heterogeneity of dispersion of sterile flies by increasing the number released. There was often a mismatch between the dispersion patterns of the wild and sterile flies, and the implications of this for the efficiency of the sterile insect technique (SIT) were investigated with a simulation study with the observed degrees of mismatch obtained from the monitoring data and assuming the overall ratio of sterile to wild flies to be 100:1. The simulation indicated that mismatches could result in the imposed rate of increase of wild flies being up to 3.5 times higher than that intended (i.e., 0.35 instead of 0.1). The effect of a mismatch always reduces the efficiency of SIT. The reason for this asymmetry is discussed and a comparison made with host-parasitoid and other systems. A release strategy to counter this effect is suggested. (author) [Spanish] Las moscas naturales y liberadas (esteriles) de Bactrocera tryoni (Froggatt) (Diptera: Tephritidae) y Bactrocera papayae (Drew and Hancock) en Australia tuvieron distribuciones en parches y sus compariciones con las predicciones de un modelo binomial negativo indicaron un nivel de agregacion a veces fue muy alto, particularmente en las densidades bajas durante de eradicacion. Un aumento en el promedio de la tasa de B. tryoni esteriles recapturadas en las dos formas de trampas no fue acompanado por una reduccion en su coeficiente de variacion y cuando las tasas de moscas recapturadas fue alto, el porcentaje de las trampas que capturaron ninguna mosca bajo solo un poco con un aumento en la tasa de las moscas recapturadas, esto indico que no es practicable bajar la heterogenicidad de dispersion de las moscas esteriles por medio de un aumento el numero de moscas liberadas. Muy a menudo se encontro un desajusto entre los patrones de dispersion de las moscas naturales y esteriles, y las implicaciones de esto para la eficiencia de la tecnica del insecto esteril (TIE) fueron investigadas en un estudio de simulacion con los grados de desajustes observados obtenidos de los datos del monitoreo y se considero que la razon general del numero de moscas esteriles a moscas naturales fueron 100:1. La simulacion indico que los desajustes en los patrones de dispersion pueden resultar en una tasa impuesta sobre el aumento de las moscas naturales de hasta 3.5 veces mas alta que la tasa intentada (i.e., 0.35 en vez de 0.1). El efecto de un desajuste siempre reduce la eficiencia de TIS. Se discute la razon para esta asimetria y una comparicion hecha con el sistema de hospedero-parasitoid y otros sistemas. Se sugiere una estrategia de liberacion para contrarrestar este efecto. (author)« less

Increased ultrasensitive C-reactive protein is not associated with obesity in hospitalized heart failure patients.

PubMed

Schommer, Vânia Ames; Stein, Airton Tetelbom; Marcadenti, Aline; Wittke, Estefania Inez; Galvão, André Luís Câmara; Rosito, Guido Bernardo Aranha

2016-01-01

To evaluate the association between obesity and levels of high-sensitivity C-reactive protein (hs-CRP) in patients with heart failure admitted to a tertiary hospital. Cross-sectional study with a consecutive sampling of hospitalized patients with heart failure. Sociodemographic and clinical data were collected, and the nutritional status was assessed through indicators such as body mass index (in kg/m2), waist circumference (in cm), waist-hip ratio, triceps skinfold (in mm) and subscapularis skinfold (in mm). Neck circumference (in cm) was measured as well as serum levels of hs-CRP, in mg/L. Among 123 patients, the mean age was 61.9±12.3 years and 60.2% were male. The median of hs-CRP was 8.87mg/L (3.34 to 20.01). A tendency to an inverse correlation between neck circumference and hs-CRP was detected (r=-0.167; p=0.069). In the multiple linear regression analysis, after adjustment for age, disease severity (NYHA classification III and IV, low ejection fraction, left ventricular dysfunction during diastole), and infectious conditions there was an inverse association between hs-CRP and neck circumference (ß=-0.196; p=0.03) and subscapularis skinfold (ß=-0.005; p=0.01) in the total sample, which was not maintained after the stratification by sex. Increased levels of hs-CRP in patients hospitalized for heart failure were not associated with obesity. Avaliar a associação entre obesidade e níveis de proteína c-reativa ultrassensível (PCR-us) em pacientes com insuficiência cardiac admitidos em um hospital terciário. Estudo transversal com amostragem consecutiva de pacientes com insuficiência cardíaca hospitalizados. Foram coletados dados sociodemográficos e clínicos, e o estado nutricional foi avaliado por meio de indicadores como índice de massa corporal (em kg/m2), circunferência da cintura (em cm), razão cintura-quadril, dobra cutânea tricipital (em mm) e dobra cutânea subescapular (em mm). Circunferência do pescoço (em cm) foi aferida bem como níveis séricos de PCR-us, em mg/L. Em 123 pacientes, a média da idade foi 61,9±12,3 anos, e 60,2% eram do sexo masculino. A mediana de PCR-us foi de 8,87mg/L (3,34 a 20,01). Detectou-se tendência à correlação inversa entre circunferência do pescoço e PCR-us (r=-0,167; p=0,069). Na análise por regressão linear múltipla, após ajustes para idade, gravidade da doença (classificação NYHA III e IV, fração de ejeção baixa, disfunção ventricular esquerda durante a diástole) e quadros infecciosos, houve associação inversa entre PCR-us e circunferência do pescoço (ß=-0,196; p=0,03) e dobra cutânea subescapular (ß=-0,005; p=0,01) na amostra total, que não se manteve após estratificação para sexo. O aumento dos níveis de PCR-us em pacientes hospitalizados por insuficiência cardíaca não se associou à obesidade.

The Influence of Ridge Geometry at the Ultraslow-Spreading Southwest Indiean Ridge (9 deg - 25 deg E): Basalt Composition Sensitivity to Variations in Source and Process

DTIC Science & Technology

2006-02-01

East Pacific Rise , 5 degrees 30’-14 degrees 30’ N , Natures, 322, 422-429. Langmuir, C. H., E. M. Klein, and T. Plank (1992...Mantle source heterogeneity and melting processes beneath seafloor spreading centers: The East Pacific Rise , 18 degrees -19 degrees S, Journal of... East Pacific Rise , Aumento, F., and H. Loubat, The Mid-Atlantic Ridge Near Proc. Ocean Drill. Program Sci. Results, 147, 103-134,

76 FR 12627 - Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 42, DA 42 NG, and DA 42 M-NG...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-08

... Industries GmbH Models DA 42, DA 42 NG, and DA 42 M-NG Airplanes AGENCY: Federal Aviation Administration (FAA... on Diamond aeroplanes, the majority of which were DA 40. In additional, at least 18 doors have been... conditions) while the aeroplane was parked. All DA 40 and DA 42 aeroplanes have a system installed that...

Molecular modeling and cytotoxicity of diffractaic acid: HP-β-CD inclusion complex encapsulated in microspheres.

PubMed

Silva, Camilla V N S; Barbosa, Jéssica A P; Ferraz, Milena S; Silva, Nicácio H; Honda, Neli K; Rabello, Marcelo M; Hernandes, Marcelo Z; Bezerra, Beatriz P; Cavalcanti, Isabella M F; Ayala, Alejandro P; Santos, Noemia P S; Santos-Magalhães, Nereide S

2016-11-01

In this pioneer study, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was used to improve the solubility of the diffractaic acid (DA) via inclusion complex (DA:HP-β-CD). Subsequently, DA:HP-β-CD was incorporated into poly-ε-caprolactone (PCL) microspheres (DA:HP-β-CD-MS). Microspheres containing DA (DA-MS) or DA:HP-β-CD (DA:HP-β-CD-MS) were prepared using the multiple W/O/W emulsion-solvent evaporation technique. The phase-solubility diagram of DA in HP-β-CD (10-50mM) showed an A L type curve with a stability constant K 1:1 =821M -1 . 1 H NMR, FTIR, X-ray diffraction and thermal analysis showed changes in the molecular environment of DA in DA:HP-β-CD. The molecular modeling approach suggests a guest-host complex formation between the carboxylic moiety of both DA and the host (HP-β-CD). The mean particle size of the microspheres were ∅ DA-MS =5.23±1.65μm and ∅ DA:HP-β-CD-MS =4.11±1.39μm, respectively. The zeta potential values of the microspheres were ζ DA-MS =-7.85±0.32mV and ζ DA:HP-β-CD-MS =-6.93±0.46mV. Moreover, the encapsulation of DA:HP-β-CD into microspheres resulted in a more slower release (k 2 =0.042±0.001; r 2 =0.996) when compared with DA-MS (k 2 =0.183±0.005; r 2 =0.996). The encapsulation of DA or DA:HP-β-CD into microspheres reduced the cytotoxicity of DA (IC 50 =43.29μM) against Vero cells (IC 50 of DA-MS=108.48μM and IC 50 of DA:HP-β-CD-MS=142.63μM). Copyright © 2016 Elsevier B.V. All rights reserved.

Methamphetamine-induced neurotoxicity disrupts pharmacologically evoked dopamine transients in the dorsomedial and dorsolateral striatum.

PubMed

Robinson, John D; Howard, Christopher D; Pastuzyn, Elissa D; Byers, Diane L; Keefe, Kristen A; Garris, Paul A

2014-08-01

Phasic dopamine (DA) signaling, during which burst firing by DA neurons generates short-lived elevations in extracellular DA in terminal fields called DA transients, is implicated in reinforcement learning. Disrupted phasic DA signaling is proposed to link DA depletions and cognitive-behavioral impairment in methamphetamine (METH)-induced neurotoxicity. Here, we further investigated this disruption by assessing effects of METH pretreatment on DA transients elicited by a drug cocktail of raclopride, a D2 DA receptor antagonist, and nomifensine, an inhibitor of the dopamine transporter (DAT). One advantage of this approach is that pharmacological activation provides a large, high-quality data set of transients elicited by endogenous burst firing of DA neurons for analysis of regional differences and neurotoxicity. These pharmacologically evoked DA transients were measured in the dorsomedial (DM) and dorsolateral (DL) striatum of urethane-anesthetized rats by fast-scan cyclic voltammetry. Electrically evoked DA levels were also recorded to quantify DA release and uptake, and DAT binding was determined by means of autoradiography to index DA denervation. Pharmacologically evoked DA transients in intact animals exhibited a greater amplitude and frequency and shorter duration in the DM compared to the DL striatum, despite similar pre- and post-drug assessments of DA release and uptake in both sub-regions as determined from the electrically evoked DA signals. METH pretreatment reduced transient activity. The most prominent effect of METH pretreatment on transients across striatal sub-region was decreased amplitude, which mirrored decreased DAT binding and was accompanied by decreased DA release. Overall, these results identify marked intrastriatal differences in the activity of DA transients that appear independent of presynaptic mechanisms for DA release and uptake and further support disrupted phasic DA signaling mediated by decreased DA release in rats with METH-induced neurotoxicity.

Striatal dopamine neurotransmission: regulation of release and uptake

PubMed Central

Sulzer, David; Cragg, Stephanie J.; Rice, Margaret E.

2016-01-01

Dopamine (DA) transmission is governed by processes that regulate release from axonal boutons in the forebrain and the somatodendritic compartment in midbrain, and by clearance by the DA transporter, diffusion, and extracellular metabolism. We review how axonal DA release is regulated by neuronal activity and by autoreceptors and heteroreceptors, and address how quantal release events are regulated in size and frequency. In brain regions densely innervated by DA axons, DA clearance is due predominantly to uptake by the DA transporter, whereas in cortex, midbrain, and other regions with relatively sparse DA inputs, the norepinephrine transporter and diffusion are involved. We discuss the role of DA uptake in restricting the sphere of influence of DA and in temporal accumulation of extracellular DA levels upon successive action potentials. The tonic discharge activity of DA neurons may be translated into a tonic extracellular DA level, whereas their bursting activity can generate discrete extracellular DA transients. PMID:27141430

75 FR 52292 - Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 40 and DA 40F Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-25

... Industries GmbH Models DA 40 and DA 40F Airplanes AGENCY: Federal Aviation Administration (FAA), Department... new airworthiness directive (AD) for all Diamond Aircraft Industries GmbH Models DA 40 and DA 40F... received information from Diamond Aircraft Industries GmbH that the Models DA 40 and DA 40F airplanes have...

77 FR 54800 - Airworthiness Directives; Diamond Aircraft Industries GmbH Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-06

... airworthiness directive (AD) for certain Diamond Aircraft Industries GmbH Models DA 42, DA 42 NG, and DA 42 M-NG... products. The MCAI states: During conversion of a DA 42 to a DA 42 NG, voids were detected in the adhesive... the following Diamond Aircraft Industries GmbH Models DA 42, DA 42 NG, and DA 42 M-NG airplanes...

METHAMPHETAMINE-INDUCED NEUROTOXICITY DISRUPTS PHARMACOLOGICALLY EVOKED DOPAMINE TRANSIENTS IN THE DORSOMEDIAL AND DORSOLATERAL STRIATUM

PubMed Central

Robinson, John D.; Howard, Christopher D.; Pastuzyn, Elissa D.; Byers, Diane L.; Keefe, Kristen A.; Garris, Paul A.

2014-01-01

Phasic dopamine (DA) signaling, during which burst firing by dopamine neurons generates short-lived elevations in extracellular DA in terminal fields called DA transients, is implicated in reinforcement learning. Disrupted phasic DA signaling is proposed to link DA depletions and cognitive-behavioral impairment in methamphetamine (METH)-induced neurotoxicity. Here we further investigated this disruption by assessing effects of METH pretreatment on DA transients elicited by a drug cocktail of raclopride, a D2 DA receptor antagonist, and nomifensine, an inhibitor of the dopamine transporter (DAT). One advantage of this approach is that pharmacological activation provides a large, high-quality data set of transients elicited by endogenous burst firing of DA neurons for analysis of regional differences and neurotoxicity. These pharmacologically evoked DA transients were measured in the dorsomedial (DM) and dorsolateral (DL) striatum of urethane-anesthetized rats by fast-scan cyclic voltammetry. Electrically evoked DA levels were also recorded to quantify DA release and uptake, and DAT binding was determined by autoradiography to index DA denervation. Pharmacologically evoked DA transients in intact animals exhibited a greater amplitude and frequency and shorter duration in the DM compared to the DL striatum, despite similar pre- and post-drug assessments of DA release and uptake in both sub-regions as determined from the electrically evoked DA signals. METH pretreatment reduced transient activity. The most prominent effect of METH pretreatment on transients across striatal sub-region was decreased amplitude, which mirrored decreased DAT binding and was accompanied by decreased DA release. Overall, these results identify marked intrastriatal differences in the activity of DA transients that appear independent of presynaptic mechanisms for DA release and uptake and further support disrupted phasic DA signaling mediated by decreased DA release in rats with METH-induced neurotoxicity. PMID:24562969

Analysis of protein profiles in diabetic rat blood plasma that induced by alloxan

NASA Astrophysics Data System (ADS)

Hidayati, Dewi; Abdulgani, Nurlita; Setiyawan, Hengki; Trisnawati, Indah; Ashuri, Nova Maulidina; Sa'adah, Noor Nailis

2017-06-01

Proteomics is the study to identify the proteins involved in physiological metabolic pathway. The protein profiles of blood plasma from alloxan-induced diabetic rats has investigated using Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (SDS-PAGE). Data were analyzed descriptively based on variations of the type and intensity of the protein. There were identified the similarity of protein variant between diabetic and control rats included ankyrin (200kDa), IgG (150kDa), nephrin (136 kDa), IDE (112 kDA), albumin (66 kDa), prealbumin (55 kDA), CICP (43 kDa), ApoA-V (39 kDa), GAPDH (35 kDa), C-RP (27,1 kDa), leptin (16 kDa) and apelin (13 kDa). However, the apelin profile at diabetic rats shows the higher intensity than control.

Analysis of the mechanisms by which amphetamine releases dopamine from striatal dopaminergic neurons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parker, E.M.

1987-01-01

The goals of the studies were (1) to determine the intraneuronal transmitter pools that contribute to the efflux of dopamine (DA) elicited by amphetamine (AMPH) and (2) to determine the biochemical mechanism by which AMPH increases DA efflux from dopaminergic neurons. AMPH increased the efflux of endogenous DA and decreased the electrically-evoked overflow of (/sup 3/H) acetylcholine (ACh) from superfused rabbit striatal slices. These effects were most pronounced when both vesicular DA stores and DA synthesis were intact. Therefore, extravesicular, newly synthesized DA and vesicular stores of DA contribute to AMPH-induced DA efflux. Simultaneous inhibition of monoamine oxidase (MAO) andmore » neuronal DA uptake did not increase the efflux of endogenous DA or inhibit the electrically-evoked overflow of (/sup 3/H)ACh to the same extent as AMPH. Hence, inhibition of MAO and neuronal DA uptake are probably not the major mechanisms by which AMPH increases DA efflux. The AMPH-induced efflux of endogenous or (/sup 3/H)DA was blocked by inhibitors of neuronal DA uptake.« less

The major histocompatibility complex genes impact pain response in DA and DA.1U rats.

PubMed

Guo, Yuan; Yao, Fan-Rong; Cao, Dong-Yuan; Li, Li; Wang, Hui-Sheng; Xie, Wen; Zhao, Yan

2015-08-01

Our recent studies have shown that the difference in basal pain sensitivity to mechanical and thermal stimulation between Dark-Agouti (DA) rats and a novel congenic DA.1U rats is major histocompatibility complex (MHC) genes dependent. In the present study, we further used DA and DA.1U rats to investigate the role of MHC genes in formalin-induced pain model by behavioral, electrophysiological and immunohistochemical methods. Behavioral results showed biphasic nociceptive behaviors increased significantly following the intraplantar injection of formalin in the hindpaw of DA and DA.1U rats. The main nociceptive behaviors were lifting and licking, especially in DA rats (P<0.001 and P<0.01). The composite pain scores (CPS) in DA rats were significantly higher than those in DA.1U rats in both phases of the formalin test (P<0.01). Electrophysiological results also showed the biphasic increase in discharge rates of C and Aδ fibers of L5 dorsal root in the two strains, and the net change of the discharge rate of DA rats was significantly higher than that of DA.1U rats (P<0.05). The mechanical thresholds decreased after formalin injection in both strains (P<0.01), and the net change in the mechanical threshold in DA was greater than that in DA.1U rats (P<0.05). The expression of RT1-B, representation of MHC class II molecule, in laminae I-II of L4/5 spinal cord in DA rats was significantly higher than that in DA.1U rats in the respective experimental group (P<0.05). These results suggested that both DA and DA.1U rats exhibited nociceptive responses in formalin-induced pain model and DA rats were more sensitive to noxious chemical stimulus than DA.1U rats, indicating that MHC genes might contribute to the difference in pain sensitivity. Copyright © 2015 Elsevier Inc. All rights reserved.

The local effect of octreotide on mechanical pain sensitivity is more sensitive in DA rats than DA.1U rats.

PubMed

Yao, Fan-Rong; Wang, Hui-Sheng; Guo, Yuan; Zhao, Yan

2016-02-01

A recent study by the authors indicated that major histocompatibility complex (MHC) genes are associated with the differences in basal pain sensitivity and in formalin model between Dark-Agouti (DA) and novel congenic DA.1U rats, which have the same genetic background as DA rats except for the u alleles of MHC. The objective of the present study is to investigate whether there is a difference in the pristane-induced arthritis (PIA) model and local analgesic effect of octreotide (OCT) between DA and DA.1U rats. The hindpaw mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were observed. The C unit firings of the tibial nerve evoked by non-noxious and noxious toe movements were recorded by electrophysiological methods in normal and PIA models in DA and DA.1U rats before and after local OCT administration. The expression of somatostatin receptor 2A (SSTR2A) was observed by immunohistochemistry. The results demonstrate that DA rats have a higher mechanical sensitivity than DA.1U rats after PIA. Local OCT administration significantly elevated MWT in DA rats under normal and PIA sate, but not in DA.1U rats. The electrophysiological experiments showed OCT significantly attenuated the firings of C units evoked by non-noxious and noxious stimulation in DA rats more than those in DA.1U rats both in normal and PIA states. In addition, the expression of SSTR2A in the dorsal horn of the spinal cord was significantly higher in DA than in DA.1U rats. All of the findings suggest a higher local analgesic effect of OCT in DA rats than DA.1U rats, which might be associated with the MHC genes. © 2016 John Wiley & Sons Australia, Ltd.

METHAMPHETAMINE-INDUCED NEUROTOXICITY DISRUPTS NATURALLY OCCURRING PHASIC DOPAMINE SIGNALING

PubMed Central

Howard, Christopher D.; Daberkow, David P.; Ramsson, Eric S.; Keefe, Kristen A.; Garris, Paul A.

2013-01-01

Methamphetamine (METH) is a highly addictive drug that is also neurotoxic to central dopamine (DA) systems. Although striatal DA depletions induced by METH are associated with behavioral and cognitive impairments, the link between these phenomena remains poorly understood. Previous work in both METH-pretreated animals and the 6-hydroxydopamine model of Parkinson’s disease suggests that a disruption of phasic DA signaling, which is important for learning and goal-directed behavior, may be such a link. However, prior studies used electrical stimulation to elicit phasic-like DA responses and were also performed under anesthesia, which alters DA neuron activity and presynaptic function. Here we investigated the consequences of METH-induced DA terminal loss on both electrically evoked phasic-like DA signals and so-called “spontaneous” phasic DA transients measured by voltammetry in awake rats. Not ostensibly attributable to discrete stimuli, these sub-second DA changes may play a role in enhancing reward-cue associations. METH-pretreatment reduced tissue DA content in the dorsomedial striatum and nucleus accumbens by ~55%. Analysis of phasic-like DA responses elicited by reinforcing stimulation revealed that METH pretreatment decreased their amplitude and underlying mechanisms for release and uptake to a similar degree as DA content in both striatal subregions. Most importantly, characteristics of DA transients were altered by METH-induced DA terminal loss, with amplitude and frequency decreased and duration increased. These results demonstrate for the first time that denervation of DA neurons alters naturally occurring DA transients and are consistent with diminished phasic DA signaling as a plausible mechanism linking METH-induced striatal DA depletions and cognitive deficits. PMID:23574406

Value of the Qrs-T Angle in Predicting the Induction of Ventricular Tachyarrhythmias in Patients with Chagas Disease.

PubMed

Zampa, Hugo Bizetto; Moreira, Dalmo Ar; Ferreira Filho, Carlos Alberto Brandão; Souza, Charles Rios; Menezes, Camila Caldas; Hirata, Henrique Seichii; Armaganijan, Luciana Vidal

2014-10-28

Background: The QRS-T angle correlates with prognosis in patients with heart failure and coronary artery disease, reflected by an increase in mortality proportional to an increase in the difference between the axes of the QRS complex and T wave in the frontal plane. The value of this correlation in patients with Chagas heart disease is currently unknown. Objective: Determine the correlation of the QRS-T angle and the risk of induction of ventricular tachycardia / ventricular fibrillation (VT / VF) during electrophysiological study (EPS) in patients with Chagas disease. Methods: Case-control study at a tertiary center. Patients without induction of VT / VF on EPS were used as controls. The QRS-T angle was categorized as normal (0-105º), borderline (105-135º) or abnormal (135-180º). Differences between groups for continuous variables were analyzed with the t test or Mann-Whitney test, and for categorical variables with Fisher's exact test. P values < 0.05 were considered significant. Results: Of 116 patients undergoing EPS, 37.9% were excluded due to incomplete information / inactive records or due to the impossibility to correctly calculate the QRS-T angle (presence of left bundle branch block and atrial fibrillation). Of 72 patients included in the study, 31 induced VT / VF on EPS. Of these, the QRS-T angle was normal in 41.9%, borderline in 12.9% and abnormal in 45.2%. Among patients without induction of VT / VF on EPS, the QRS-T angle was normal in 63.4%, borderline in 14.6% and abnormal in 17.1% (p = 0.04). When compared with patients with normal QRS-T angle, those with abnormal angle had a fourfold higher risk of inducing ventricular tachycardia / ventricular fibrillation on EPS [odds ratio (OR) 4; confidence interval (CI) 1.298-12.325; p = 0.028]. After adjustment for other variables such as age, ejection fraction (EF) and QRS size, there was a trend for the abnormal QRS-T angle to identify patients with increased risk of inducing VT / VF during EPS (OR 3.95; CI 0.99-15.82; p = 0.052). The EF also emerged as a predictor of induction of VT / VF: for each point increase in EF, there was a 4% reduction in the rate of sustained ventricular arrhythmia on EPS. Conclusions: Changes in the QRS-T angle and decreases in EF were associated with an increased risk of induction of VT / VF on EPS.Fundamento: O ângulo QRS-T mostra correlação com prognóstico em pacientes com insuficiência cardíaca e doença coronariana, traduzido por um aumento na mortalidade proporcional ao aumento na diferença entre os eixos do complexo QRS e da onda T no plano frontal. Até hoje, nenhuma informação a este respeito foi obtida em pacientes com cardiopatia chagásica. Objetivo: Correlacionar o ângulo QRS-T com a indução de taquicardia ventricular / fibrilação ventricular (TV / FV) em chagásicos durante estudo eletrofisiológico (EEF). Métodos: Estudo caso-controle em centro terciário. Pacientes sem indução de TV / FV ao EEF foram utilizados como controles. O ângulo QRS-T foi categorizado como normal (0-105º), limítrofe (105-135º) e anormal (135-180º). As diferenças entre os grupos foram analisadas pelo teste t ou teste de Mann-Whitney para variáveis contínuas, e teste exato de Fisher ou qui-quadrado para variáveis categóricas. Valores de p < 0,05 foram considerados significativos. Resultados: De 116 pacientes submetidos ao EEF, 37,9% foram excluídos por estarem com dados incompletos / prontuários inativos ou pela impossibilidade de se calcular corretamente o ângulo QRS-T (presença de bloqueio de ramo esquerdo e fibrilação atrial). De 72 pacientes incluídos, 31 induziram TV / FV ao EEF. Destes, o ângulo QRS-T se encontrava normal em 41,9%, limítrofe em 12,9% e anormal em 45,2%. No grupo de pacientes sem indução de TV / FV, o ângulo QRS-T se encontrava normal em 63,4%, limítrofe em 14,6% e anormal em 17,1% (p = 0,04). Quando comparados aos pacientes com ângulo QRS-T normal, o risco de indução de TV / FV nos pacientes com ângulo anormal foi quatro vezes maior [odds ratio (OR) 4; intervalo de confiança (IC) 1,298-12,325; p = 0,028). Após ajuste para outras variáveis como idade, fração de ejeção (FE) e tamanho do QRS, houve tendência do ângulo QRS-T anormal em identificar pacientes com maior risco de indução de TV / FV (OR 3,95; IC 0,99-15,82; p = 0,052). A FE também se evidenciou como preditora de indução de TV / FV: um ponto de aumento na FE reduziu em 4% a taxa de indução de arritmia ventricular sustentada ao EEF. Conclusões: Alterações no ângulo QRS-T e redução na FE estiveram associadas a um aumento no risco de indução de TV / FV ao EEF.

Somatodendritic dopamine release: recent mechanistic insights

PubMed Central

Rice, Margaret E.; Patel, Jyoti C.

2015-01-01

Dopamine (DA) is a key transmitter in motor, reward and cogitative pathways, with DA dysfunction implicated in disorders including Parkinson's disease and addiction. Located in midbrain, DA neurons of the substantia nigra pars compacta project via the medial forebrain bundle to the dorsal striatum (caudate putamen), and DA neurons in the adjacent ventral tegmental area project to the ventral striatum (nucleus accumbens) and prefrontal cortex. In addition to classical vesicular release from axons, midbrain DA neurons exhibit DA release from their cell bodies and dendrites. Somatodendritic DA release leads to activation of D2 DA autoreceptors on DA neurons that inhibit their firing via G-protein-coupled inwardly rectifying K+ channels. This helps determine patterns of DA signalling at distant axonal release sites. Somatodendritically released DA also acts via volume transmission to extrasynaptic receptors that modulate local transmitter release and neuronal activity in the midbrain. Thus, somatodendritic release is a pivotal intrinsic feature of DA neurons that must be well defined in order to fully understand the physiology and pathophysiology of DA pathways. Here, we review recent mechanistic aspects of somatodendritic DA release, with particular emphasis on the Ca2+ dependence of release and the potential role of exocytotic proteins. PMID:26009764

Nicotine- and methamphetamine-induced dopamine release evaluated with in-vivo binding of radiolabelled raclopride to dopamine D2 receptors: comparison with in-vivo microdialysis data.

PubMed

Kim, Sang Eun; Han, Seung-Moo

2009-07-01

The effect of substances which alter extracellular dopamine (DA) concentration has been studied by measuring changes in the binding of radiolabelled raclopride, a DA D2 receptor ligand that is sensitive to endogenous DA. To better characterize the relationship between extracellular DA concentration and DA D2 receptor binding of raclopride, we compared the changes of extracellular DA concentration (measured using in-vivo microdialysis) and in-vivo [3H]raclopride binding induced by different doses of methamphetamine (Meth) and nicotine, drugs that enhance DA release with and without blocking DA transporters (DATs), respectively, in rat striatum. Nicotine elicited a modest increase of striatal extrasynaptic extracellular DA, while Meth produced a marked increase of striatal extrasynaptic DA in a dose-dependent manner. There was a close correlation between the decrease in [3H]raclopride in-vivo binding and the increase in extrasynaptic DA concentration induced by both nicotine (r2=0.95, p<0.001) and Meth (r2=0.98, p=0.001), supporting the usefulness of the radiolabelled raclopride-binding measurement for the non-invasive assessment of DA release following interventions in the living brain. However, the linear regression analysis revealed that the ratio of percent DA increase to percent [3H]raclopride binding reduction was 25-fold higher for Meth (34.8:1) than for nicotine (1.4:1). The apparent discrepancy in the extrasynaptic DA-[3H]raclopride binding relationship between the DA-enhancing drugs with and without DAT-blocking property indicates that the competition between endogenous DA and radiolabelled raclopride takes place at the intrasynaptic rather than extrasynaptic DA D2 receptors and reflects synaptic concentration of DA.

PubMed

Bellido, Diego; Bellido, Virginia

2016-09-20

El sobrepeso y la obesidad se definen como un depósito anormal o excesivo de grasa corporal. El aumento de su prevalencia en las últimas décadas lo convierte en uno de los principales problemas de salud pública que afecta a 42 millones de niños menores de 5 años en el mundo. Su presencia durante la infancia puede ser causa de enfermedades metabólicas hasta ahora consideradas típicas del adulto y mortalidad prematura, por lo que su correcto diagnóstico y tratamiento son fundamentales.

Age-related changes in dopamine signaling in Nurr1 deficient mice as a model of Parkinson’s disease

PubMed Central

Zhang, Lifen; Le, Weidong; Xie, Wenjie; Dani, John A.

2011-01-01

The nuclear receptor related 1 (Nurr1) transcription factor contributes to the development and maintenance of dopamine (DA) neurons in the brain. We found that heterozygous Nurr1 knock-out (Nurr1 +/−) influenced the age-dependent decline in the number of DA neurons and influenced DA signaling. We examined the DA marker, tyrosine hydroxylase, using immunohistochemistry, and we measured DA signaling using fast-scan cyclic voltammetry in 3 age groups of wild-type (Nurr1 +/+) and mutant (Nurr1 +/−) mice: 3–6, 9–12, and 15–23 months old. Prior to significant loss of DA neurons and to the onset of parkinsonian symptoms, young Nurr1 +/− mice (3–6 months) exhibited a decrease in peak evoked DA release that was partially countered by a decrease in the rate of DA reuptake. As peak evoked DA release declined with age for both the wild-type and Nurr1 +/− mice, both genotypes manifested decreased DA reuptake. As the DA release fell further with age, decreased DA reuptake eventually could not adequately compensate the Nurr1 +/− mice. The results indicated that Nurr1 deficiency led to impaired DA release even before significant DA neuron loss. PMID:21531044

Autocorrelation descriptor improvements for QSAR: 2DA_Sign and 3DA_Sign

NASA Astrophysics Data System (ADS)

Sliwoski, Gregory; Mendenhall, Jeffrey; Meiler, Jens

2016-03-01

Quantitative structure-activity relationship (QSAR) is a branch of computer aided drug discovery that relates chemical structures to biological activity. Two well established and related QSAR descriptors are two- and three-dimensional autocorrelation (2DA and 3DA). These descriptors encode the relative position of atoms or atom properties by calculating the separation between atom pairs in terms of number of bonds (2DA) or Euclidean distance (3DA). The sums of all values computed for a given small molecule are collected in a histogram. Atom properties can be added with a coefficient that is the product of atom properties for each pair. This procedure can lead to information loss when signed atom properties are considered such as partial charge. For example, the product of two positive charges is indistinguishable from the product of two equivalent negative charges. In this paper, we present variations of 2DA and 3DA called 2DA_Sign and 3DA_Sign that avoid information loss by splitting unique sign pairs into individual histograms. We evaluate these variations with models trained on nine datasets spanning a range of drug target classes. Both 2DA_Sign and 3DA_Sign significantly increase model performance across all datasets when compared with traditional 2DA and 3DA. Lastly, we find that limiting 3DA_Sign to maximum atom pair distances of 6 Å instead of 12 Å further increases model performance, suggesting that conformational flexibility may hinder performance with longer 3DA descriptors. Consistent with this finding, limiting the number of bonds in 2DA_Sign from 11 to 5 fails to improve performance.

Data Administration at a Regional University: A Case Study.

ERIC Educational Resources Information Center

Gose, Frank J.

Data administration (DA) is a position that has emerged with the growth of information technologies. A review of DA literature confirms that, although DA is widely associated with database management systems (DBMS), there is no standard DA job description, DA staffing and location within the organization vary, and DA functions range in description…

From sanddabs to blue whales: the pervasiveness of domoic acid.

PubMed

Lefebvre, Kathi A; Bargu, Sibel; Kieckhefer, Tom; Silver, Mary W

2002-07-01

Domoic acid (DA) is a potent food web transferred algal toxin that has caused dramatic mortality events involving sea birds and sea lions. Although no confirmed DA toxicity events have been reported in whales, here we present data demonstrating that humpback and blue whales are exposed to the toxin and consume DA contaminated prey. Whale fecal samples were found to contain DA at levels ranging from 10 to 207microg DA g(-1) feces via HPLC-UV methods. SEM analysis of whale feces containing DA, collected from krill-feeding whales, revealed the presence of diatom frustules identified as Pseudo-nitzschia australis, a known DA producer. Humpback whales were observed feeding on anchovies and sardines that contained DA at levels ranging from 75 to 444microg DA g(-1) viscera. DA contamination of whale feces and fish occurred only during blooms of toxic Pseudo-nitzschia. Additionally, several novel fish species collected during a toxic diatom bloom were tested for DA. Fish as diverse as benthic sanddabs and pelagic albacore were found to contain the neurotoxin, suggesting that DA permeates benthic as well as pelagic communities.

Two forms of Vibrio cholerae O1 El Tor hemolysin derived from identical precursor protein.

PubMed

Ikigai, H; Ono, T; Nakae, T; Otsuru, H; Shimamura, T

1999-01-08

Vibrio cholerae O1 grown in heart infusion broth produces two forms of El Tor hemolysin (ETH) monomers of 65 and 50 kDa. These monomers form several different sizes of mixed oligomers ranging from 180 to 280 kDa in the liposomal membranes. We found that the N-terminal amino acid sequences, NH2-Trp-Pro-Ala-Pro-Ala-Asn-Ser-Glu, of both the 65- and 50-kDa toxins were identical. We assumed, therefore, that the 65- and 50-kDa toxins were derivatives of the identical precursor protein and the 50-kDa protein was a truncated derivative of 65-kDa ETH. To substantiate this assumption, we treated the 260-kDa oligomer with trypsin and obtained a 190-kDa oligomer. This 190-kDa oligomer consisted of only the 50-kDa subunits. Both 260- and 190-kDa oligomers formed ion channels indistinguishable from each other in planar lipid bilayers. These results suggest that the essential part of the ETH in forming the membrane-damaging aggregate is a 50-kDa protein.

Evaluation of the Efficacy and Safety of DA-9601 versus Its New Formulation, DA-5204, in Patients with Gastritis: Phase III, Randomized, Double-Blind, Non-Inferiority Study.

PubMed

Choi, Yoon Jin; Lee, Dong Ho; Choi, Myung Gyu; Lee, Sung Joon; Kim, Sung Kook; Song, Geun Am; Rhee, Poong Lyul; Jung, Hwoon Yong; Kang, Dae Hwan; Lee, Yong Chan; Lee, Si Hyung; Choi, Suck Chei; Shim, Ki Nam; Seol, Sang Yong; Moon, Jeong Seop; Shin, Yong Woon; Kim, Hyun Soo; Lee, Soo Teik; Cho, Jin Woong; Choi, Eun Kwang; Lee, Oh Young; Jang, Jin Seok

2017-11-01

This study compared the efficacy of DA-9601 (Dong-A ST Co., Seoul, Korea) and its new formulation, DA-5204 (Dong-A ST Co.), for treating erosive gastritis. This phase III, randomized, multicenter, double-blind, non-inferiority trial randomly assigned 434 patients with endoscopically proven gastric mucosal erosions into two groups: DA-9601 3 times daily or DA-5,204 twice daily for 2 weeks. The final analysis included 421 patients (DA-5204, 209; DA-9601, 212). The primary endpoint (rate of effective gastric erosion healing) and secondary endpoints (cure rate of endoscopic erosion and gastrointestinal [GI] symptom relief) were assessed using endoscopy after the treatment. Drug-related adverse events (AEs), including GI symptoms, were also compared. At week 2, gastric healing rates with DA-5204 and DA-9601 were 42.1% (88/209) and 42.5% (90/212), respectively. The difference between the groups was -0.4% (95% confidence interval, -9.8% to 9.1%), which was above the non-inferiority margin of -14%. The cure rate of gastric erosion in both groups was 37.3%. The improvement rates of GI symptoms with DA-5204 and DA-9601 were 40.4% and 40.8%, respectively. There were no statistically significant differences between the two groups in both secondary endpoints. AEs were reported in 18 (8.4%) patients in the DA-5204 group and 19 (8.8%) in the DA-9601 group. Rates of AE were not different between the two groups. No serious AE or adverse drug reaction (ADR) occurred. These results demonstrate the non-inferiority of DA-5204 compared to DA-9601. DA-5204 is as effective as DA-9601 in the treatment of erosive gastritis. Registered randomized clinical trial at ClinicalTrials.gov (NCT02282670). © 2017 The Korean Academy of Medical Sciences.

Platelets contribute to postnatal occlusion of the ductus arteriosus.

PubMed

Echtler, Katrin; Stark, Konstantin; Lorenz, Michael; Kerstan, Sandra; Walch, Axel; Jennen, Luise; Rudelius, Martina; Seidl, Stefan; Kremmer, Elisabeth; Emambokus, Nikla R; von Bruehl, Marie-Luise; Frampton, Jon; Isermann, Berend; Genzel-Boroviczény, Orsolya; Schreiber, Christian; Mehilli, Julinda; Kastrati, Adnan; Schwaiger, Markus; Shivdasani, Ramesh A; Massberg, Steffen

2010-01-01

The ductus arteriosus (DA) is a fetal shunt vessel between the pulmonary artery and the aorta that closes promptly after birth. Failure of postnatal DA closure is a major cause of morbidity and mortality particularly in preterm neonates. The events leading to DA closure are incompletely understood. Here we show that platelets have an essential role in DA closure. Using intravital microscopy of neonatal mice, we observed that platelets are recruited to the luminal aspect of the DA during closure. DA closure is impaired in neonates with malfunctioning platelet adhesion or aggregation or with defective platelet biogenesis. Defective DA closure resulted in a left-to-right shunt with increased pulmonary perfusion, pulmonary vascular remodeling and right ventricular hypertrophy. Our findings indicate that platelets are crucial for DA closure by promoting thrombotic sealing of the constricted DA and by supporting luminal remodeling. A retrospective clinical study revealed that thrombocytopenia is an independent predictor for failure of DA closure in preterm human newborns, indicating that platelets are likely to contribute to DA closure in humans.

An integrative theory of the phasic and tonic modes of dopamine modulation in the prefrontal cortex.

PubMed

Dreher, Jean-Claude; Burnod, Yves

2002-01-01

This paper presents a model of both tonic and phasic dopamine (DA) effects on maintenance of working memory representations in the prefrontal cortex (PFC). The central hypothesis is that DA modulates the efficacy of inputs to prefrontal pyramidal neurons to prevent interferences for active maintenance. Phasic DA release, due to DA neurons discharges, acts at a short time-scale (a few seconds), while the tonic mode of DA release, independent of DA neurons firing, acts at a long time-scale (a few minutes). The overall effect of DA modulation is modeled as a threshold restricting incoming inputs arriving on PFC neurons. Phasic DA release temporary increases this threshold while tonic DA release progressively increases the basal level of this threshold. Thus, unlike the previous gating theory of phasic DA release, proposing that it facilitates incoming inputs at the time of their arrival, the effect of phasic DA release is supposed to restrict incoming inputs during a period of time after DA neuron discharges. The model links the cellular and behavioral levels during performance of a working memory task. It allows us to understand why a critical range of DA D1 receptors stimulation is required for optimal working memory performance and how D1 receptor agonists (respectively antagonists) increase perseverations (respectively distractability). Finally, the model leads to several testable predictions, including that the PFC regulates DA neurons firing rate to adapt to the delay of the task and that increase in tonic DA release may either improve or decrease performance, depending on the level of DA receptors stimulation at the beginning of the task.

Neurobiological model of stimulated dopamine neurotransmission to interpret fast-scan cyclic voltammetry data.

PubMed

Harun, Rashed; Grassi, Christine M; Munoz, Miranda J; Torres, Gonzalo E; Wagner, Amy K

2015-03-02

Fast-scan cyclic voltammetry (FSCV) is an electrochemical method that can assess real-time in vivo dopamine (DA) concentration changes to study the kinetics of DA neurotransmission. Electrical stimulation of dopaminergic (DAergic) pathways can elicit FSCV DA responses that largely reflect a balance of DA release and reuptake. Interpretation of these evoked DA responses requires a framework to discern the contribution of DA release and reuptake. The current, widely implemented interpretive framework for doing so is the Michaelis-Menten (M-M) model, which is grounded on two assumptions- (1) DA release rate is constant during stimulation, and (2) DA reuptake occurs through dopamine transporters (DAT) in a manner consistent with M-M enzyme kinetics. Though the M-M model can simulate evoked DA responses that rise convexly, response types that predominate in the ventral striatum, the M-M model cannot simulate dorsal striatal responses that rise concavely. Based on current neurotransmission principles and experimental FSCV data, we developed a novel, quantitative, neurobiological framework to interpret DA responses that assumes DA release decreases exponentially during stimulation and continues post-stimulation at a diminishing rate. Our model also incorporates dynamic M-M kinetics to describe DA reuptake as a process of decreasing reuptake efficiency. We demonstrate that this quantitative, neurobiological model is an extension of the traditional M-M model that can simulate heterogeneous regional DA responses following manipulation of stimulation duration, frequency, and DA pharmacology. The proposed model can advance our interpretive framework for future in vivo FSCV studies examining regional DA kinetics and their alteration by disease and DA pharmacology. Copyright © 2015 Elsevier B.V. All rights reserved.

Optogenetic versus electrical stimulation of dopamine terminals in the nucleus accumbens reveals local modulation of presynaptic release

PubMed Central

Melchior, James R.; Ferris, Mark J.; Stuber, Garret D.; Riddle, David R.; Jones, Sara R.

2015-01-01

The nucleus accumbens is highly heterogeneous, integrating regionally distinct afferent projections and accumbal interneurons, resulting in diverse local microenvironments. Dopamine (DA) neuron terminals similarly express a heterogeneous collection of terminal receptors that modulate DA signaling. Cyclic voltammetry is often used to probe DA terminal dynamics in brain slice preparations; however, this method traditionally requires electrical stimulation to induce DA release. Electrical stimulation excites all of the neuronal processes in the stimulation field, potentially introducing simultaneous, multi-synaptic modulation of DA terminal release. We used optogenetics to selectively stimulate DA terminals and used voltammetry to compare DA responses from electrical and optical stimulation of the same area of tissue around a recording electrode. We found that with multiple pulse stimulation trains, optically stimulated DA release increasingly exceeded that of electrical stimulation. Furthermore, electrical stimulation produced inhibition of DA release across longer duration stimulations. The GABAB antagonist, CGP 55845, increased electrically stimulated DA release significantly more than light stimulated release. The nicotinic acetylcholine receptor antagonist, dihydro-β-erythroidine hydrobromide, inhibited single pulse electrically stimulated DA release while having no effect on optically stimulated DA release. Our results demonstrate that electrical stimulation introduces local multi-synaptic modulation of DA release that is absent with optogenetically targeted stimulation. PMID:26011081

The Ubiquitin Receptor DA1 Interacts with the E3 Ubiquitin Ligase DA2 to Regulate Seed and Organ Size in Arabidopsis[C][W

PubMed Central

Xia, Tian; Li, Na; Dumenil, Jack; Li, Jie; Kamenski, Andrei; Bevan, Michael W.; Gao, Fan; Li, Yunhai

2013-01-01

Seed size in higher plants is determined by the coordinated growth of the embryo, endosperm, and maternal tissue. Several factors that act maternally to regulate seed size have been identified, such as AUXIN RESPONSE FACTOR2, APETALA2, KLUH, and DA1, but the genetic and molecular mechanisms of these factors in seed size control are almost totally unknown. We previously demonstrated that the ubiquitin receptor DA1 acts synergistically with the E3 ubiquitin ligase ENHANCER1 OF DA1 (EOD1)/BIG BROTHER to regulate the final size of seeds in Arabidopsis thaliana. Here, we describe another RING-type protein with E3 ubiquitin ligase activity, encoded by DA2, which regulates seed size by restricting cell proliferation in the maternal integuments of developing seeds. The da2-1 mutant forms large seeds, while overexpression of DA2 decreases seed size of wild-type plants. Overexpression of rice (Oryza sativa) GRAIN WIDTH AND WEIGHT2, a homolog of DA2, restricts seed growth in Arabidopsis. Genetic analyses show that DA2 functions synergistically with DA1 to regulate seed size, but does so independently of EOD1. Further results reveal that DA2 interacts physically with DA1 in vitro and in vivo. Therefore, our findings define the genetic and molecular mechanisms of three ubiquitin-related proteins DA1, DA2, and EOD1 in seed size control and indicate that they are promising targets for crop improvement. PMID:24045020

Effects of omeprazole or cola beverage on the pharmacokinetics of oral DA-8159, a new erectogenic, in rats.

PubMed

Lee, Joo H; Bae, Soo K; Kwon, Jong W; Kim, Won B; Lee, Myung G

2005-12-01

The changes in pharmacokinetics of DA-8159 by omeprazole with respect to inhibition of CYP3A1/2 in rats were evaluated. After oral administration of DA-8159 at dose of 30 mg/kg to rats pretreated with oral omeprazole at 30 mg/kg for 1 week, the total area under the plasma concentration-time curve from time zero to time infinity (AUC) of DA-8159 was significantly greater (37.5% increase) than that in control rats. This could be due to inhibition of metabolism of DA-8159 by inhibition of CYP3A1/2 by omeprazole. The AUC(DA-8164 (a metabolite of DA-8159))/AUC(DA-8159) ratio was also smaller (32.4% decrease) with omeprazole. After oral administration of DA-8159 at a dose of 30 mg/kg to rats without or with cola beverage, the pharmacokinetic parameters of DA-8159 and DA-8164 were not significantly different between two groups of rats. This suggested that cola beverage did not have any considerable effects on CYP3A1/2 in rats.

75 FR 75868 - Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 40 and DA 40F Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-07

... Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 40 and DA 40F Airplanes AGENCY: Federal... of the Thielert Engine Owners Group commented that the Model DA 42 has the same door design and the same unsafe condition. He recommended that the AD also apply to the Model DA 42. The FAA has discussed...

Characterization of low molecular weight fragments from gamma irradiated κ-carrageenan used as plant growth promoter

NASA Astrophysics Data System (ADS)

Abad, Lucille V.; Aurigue, Fernando B.; Relleve, Lorna S.; Montefalcon, Djowel Recto V.; Lopez, Girlie Eunice P.

2016-01-01

Radiation degraded κ-carrageenan (1% solution at absorbed doses of 20 kGy and 30 kGy) were tested for its plant growth promoter (PGP) effect on pechay plants under hydroponics condition. Results revealed that higher PGP effects were found in κ-carrageenan irradiated at an absorbed dose of 30 kGy. Mw of irradiated κ-carrageenan as measured by GPC were determined to be 7362 Da and 6762 Da for 20 kGy and 30 kGy, respectively. Fractionation of the irradiated κ-carrageenan (30 kGy) was done to separate different Mw fractions using Mw cut-off filters of 1 kDa, 3 kDa, and 5 kDa. The PGP effect of the different retentates showed that biological activity in plants followed the order of 5 kDa>3 kDa>1 kDa using hydroponics condition but the reverse was observed in the order of 1 kDa>3 kDa>5 kDa when absorbed in plants by foliar spraying. GPC chromatogram indicated at least three (3) low molecular weight (LMW) fragments from radiation modified κ-carrageenan solution with an Mw<2000 Da. A fragment has also been identified with an Mw of as low as 160 Da which was produced under acidic (un-neutralized) condition. This may be attributed to the formation of 5-hydroxymethylfurfural (5-HMF).

The role of N-methyl-D-aspartate receptors and nitric oxide in cochlear dopamine release.

PubMed

Halmos, G; Horváth, T; Polony, G; Fekete, A; Kittel, A; Vizi, E S; van der Laan, B F A M; Zelles, T; Lendvai, B

2008-06-23

Dopamine (DA) released from lateral olivocochlear (LOC) terminals may have a neuroprotective effect in the cochlea. To explore the role of N-methyl-d-aspartate (NMDA) receptors and nitric oxide (NO) in the modulation of a cochlear DA release, we measured the release of [3H]DA from isolated mouse cochlea in response to the application of NMDA. NMDA at 100 muM significantly increased the electrical-field stimulation-evoked and resting release of DA from the cochlea. The NO donor sodium nitroprusside enhanced the basal outflow of DA but failed to influence the evoked release. The administration of the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) alone was ineffective, but it significantly inhibited the initial phase of the NMDA-induced elevation of DA outflow, which suggested the role of NO in the NMDA-induced DA release. The DA uptake inhibitor nomifensine increased the electrically evoked release of DA. Nomifensine failed to change the effect of NMDA on the resting or electrically-evoked DA release, which suggested that the uptake mechanism does not play a role in NMDA-evoked and NO-mediated DA release. In summary, we provide evidence that NO can modulate the release of DA from the cochlea following NMDA receptor activation, but does not affect the uptake of DA.

Amyloid beta precursor protein and ubiquitin epitopes in human and experimental dystrophic axons. Ultrastructural localization.

PubMed Central

Bacci, B.; Cochran, E.; Nunzi, M. G.; Izeki, E.; Mizutani, T.; Patton, A.; Hite, S.; Sayre, L. M.; Autilio-Gambetti, L.; Gambetti, P.

1994-01-01

Dystrophic axons (DA) represent a major pathological feature of several neurodegenerative disorders, including infantile neuroaxonal dystrophy (INAD) and Alzheimer disease. We have previously presented evidence that amyloid beta precursor protein (BPP) and ubiquitin (Ub) are present in DA of different origin. We have now characterized the immunoreactivity of DA experimentally induced in rat by the administration of parabromophenylacetylurea (BPAU) and examined the subcellular localization of Ub and BPP in BPAU-induced DA and in DA present in subjects affected by INAD. BPAU-induced DA strongly immunoreacted with antisera to Ub and to COOH- and NH2-terminal regions of BPP. Immunoblots of DA-enriched brain regions were consistent with an increase in the amount of Ub and BPP in DA. Moreover, BPAU-induced DA immunoreacted with antibodies to PGP 9.5, a neuronal-specific Ub COOH-terminal hydrolase, and to the inducible heat shock protein 70. Antigenic characterization also indicated that the tubulovesicular membranes within DA derived largely from the smooth endoplasmic reticulum rather than from the Golgi system or the synaptic vesicles. Subcellular immunolocalization of Ub and BPP in both INAD- and BPAU-induced DA revealed that Ub and BPP colocalize in granulovesicular material in both conditions. In INAD DA intense Ub immunoreactivity was also detected in nonmembranous electron dense structures that were present only in these DA, probably because of the chronic course of INAD. Although BPP immunostaining may be related to accumulation of BPP-containing membranes in DA, Ub immunostaining is likely to result from activation of the Ub system by the neuron in the attempt to remove excessive and possibly abnormal proteins. A similar pathogenesis can be postulated for DA of Alzheimer disease. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7512790

Metaproteomics of Microbiota in Naturally Fermented Soybean Paste, Da-jiang.

PubMed

Zhang, Ping; Zhang, Pengfei; Xie, Mengxi; An, Feiyu; Qiu, Boshu; Wu, Rina

2018-05-01

Da-jiang is a typical traditional fermented soybean product in China. At present, the proteins in da-jiang are needed to be explored. The composition and species of microbial proteins in traditional fermented da-jiang were analyzed by metaproteomics based on sodium dodecyl sulfonate-polyacrylamide gel electrophoresis (SDS-PAGE) and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The results showed that the number and variety of microbial proteins in the traditional fermented da-jiang from different regions were different. The production site influences the fermentation in da-jiang. Then we analyzed the functions of the microbial proteins identified in da-jiang, and found that they were mainly involved in the process of protein synthesis, glycometabolism and nucleic acid synthesis. In addtion, we compared the proteins composition in different da-jiang. There are 51 common proteins of naturally fermented da-jiang, and 25 common microbial sources. The main commonly microbial sources of fungal proteins are Saccharomyces cerevisiae and Schizosaccharomyces; the main commonly microbial sources of bacterial proteins are Enterococcus faecalis, Leuconostoc mesenteroides, Acinetobacter baumannii, and Bacillus subtilis. These common microbes play the predominant role in da-jiang fermentation. The present results help us to understand the fermentation of da-jiang and improve the quality and safety of final products in the future. The study illustrated metaproteome of microbiota in traditional fermented soybean paste, da-jiang, by sodium dodecyl sulfonate-polyacrylamide gel electrophoresis (SDS-PAGE) and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). A method of extracting metaproteome from microbiota in da-jiang was attempted. The findings help to understand the fermentation of da-jiang and improve the quality and safety of da-jiang in fermented industry. © 2018 Institute of Food Technologists®.

DETECTION OF OCCULT LYMPH NODE TUMOR CELLS IN NODE-NEGATIVE GASTRIC CANCER PATIENTS.

PubMed

Pereira, Marina Alessandra; Ramos, Marcus Fernando Kodama Pertille; Dias, Andre Roncon; Yagi, Osmar Kenji; Faraj, Sheila Friedrich; Zilberstein, Bruno; Cecconello, Ivan; Mello, Evandro Sobroza de; Ribeiro, Ulysses

2017-01-01

The presence of lymph nodes metastasis is one of the most important prognostic indicators in gastric cancer. The micrometastases have been studied as prognostic factor in gastric cancer, which are related to decrease overall survival and increased risk of recurrence. However, their identification is limited by conventional methodology, since they can be overlooked after routine staining. To investigate the presence of occult tumor cells using cytokeratin (CK) AE1/AE3 immunostaining in gastric cancer patients histologically lymph node negative (pN0) by H&E. Forty patients (T1-T4N0) submitted to a potentially curative gastrectomy with D2 lymphadenectomy were evaluated. The results for metastases, micrometastases and isolated tumor cells were also associated to clinicopathological characteristics and their impact on stage grouping. Tumor deposits within lymph nodes were defined according to the tumor-node-metastases guidelines (7th TNM). A total of 1439 lymph nodes were obtained (~36 per patient). Tumor cells were detected by immunohistochemistry in 24 lymph nodes from 12 patients (30%). Neoplasic cells were detected as a single or cluster tumor cells. Tumor (p=0.002), venous (p=0.016), lymphatic (p=0.006) and perineural invasions (p=0.04), as well as peritumoral lymphocytic response (p=0.012) were correlated to CK-positive immunostaining tumor cells in originally negative lymph nodes by H&E. The histologic stage of two patients was upstaged from stage IB to stage IIA. Four of the 28 CK-negative patients (14.3%) and three among 12 CK-positive patients (25%) had disease recurrence (p=0.65). The CK-immunostaining is an effective method for detecting occult tumor cells in lymph nodes and may be recommended to precisely determine tumor stage. It may be useful as supplement to H&E routine to provide better pathological staging. A presença de metástase em linfonodos é um dos indicadores prognósticos mais importantes no câncer gástrico. As micrometástases têm sido estudadas como fator prognóstico no câncer gástrico, sendo relacionadas à diminuição da sobrevida global e aumento do risco de recidiva da doença. Entretanto, sua identificação é limitada pela metodologia convencional, uma vez que podem não ser identificadas pela rotina histopatológica por meio da coloração de H&E. Investigar a presença de células tumorais ocultas através de imunoistoquimica utilizando as citoqueratinas (CK) AE1/AE3 em pacientes com câncer gástrico com linfonodos histologicamente classificados como negativos por H&E. Quarenta pacientes (T1-T4N0) submetidos à gastrectomia potencialmente curativa com linfadenectomia D2 foram avaliados. A presença de metástases, micrometástases e células tumorais isoladas foram correlacionadas com características clínicopatológicas e impacto no estadiamento. Os depósitos tumorais nos linfonodos foram classificados de acordo com o sistema TNM (7º TNM). Um total de 1439 linfonodos foi obtido (~36 por paciente). Células tumorais foram detectadas por imunoistoquimica em 24 linfonodos de 12 pacientes (30%). As células neoplásicas estavam presentes na forma isolada ou em cluster. Invasão tumoral (p=0,002), venosa (p=0,016), linfática (p=0,006) e perineural (p=0,04), assim como resposta linfocítica peritumoral (p=0,012) foram correlacionadas com linfonodos CK-positivos que originalmente eram negativos à H&E. Dois pacientes tiveram o estadiamento alterado, migrando do estádio IB para IIA. Quatro dos 28 CK-negativos (14,3%) e três dos 12 CK-positivos (25%) tiveram recorrência da doença (p=0,65). A imunoistoquimica é meio eficaz para a detecção de células tumorais ocultas em linfonodos, podendo ser recomendada para melhor determinar o estágio do tumor. Ela pode ser útil como técnica complementar à rotina de H&E, de modo a fornecer melhor estadiamento patológico.

Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons

PubMed Central

Steinkellner, Thomas; Farino, Zachary J.; Sonders, Mark S.; Villeneuve, Michael; Freyberg, Robin J.; Przedborski, Serge; Lu, Wei; Hnasko, Thomas S.

2018-01-01

Parkinson’s disease is characterized by the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). DA neurons in the ventral tegmental area are more resistant to this degeneration than those in the SNc, though the mechanisms for selective resistance or vulnerability remain poorly understood. A key to elucidating these processes may lie within the subset of DA neurons that corelease glutamate and express the vesicular glutamate transporter VGLUT2. Here, we addressed the potential relationship between VGLUT expression and DA neuronal vulnerability by overexpressing VGLUT in DA neurons of flies and mice. In Drosophila, VGLUT overexpression led to loss of select DA neuron populations. Similarly, expression of VGLUT2 specifically in murine SNc DA neurons led to neuronal loss and Parkinsonian behaviors. Other neuronal cell types showed no such sensitivity, suggesting that DA neurons are distinctively vulnerable to VGLUT2 expression. Additionally, most DA neurons expressed VGLUT2 during development, and coexpression of VGLUT2 with DA markers increased following injury in the adult. Finally, conditional deletion of VGLUT2 made DA neurons more susceptible to Parkinsonian neurotoxins. These data suggest that the balance of VGLUT2 expression is a crucial determinant of DA neuron survival. Ultimately, manipulation of this VGLUT2-dependent process may represent an avenue for therapeutic development. PMID:29337309

MK-801 protection against methamphetamine-induced striatal dopamine terminal injury is associated with attenuated dopamine overflow.

PubMed

Weihmuller, F B; O'Dell, S J; Marshall, J F

1992-06-01

Repeated administrations of methamphetamine (m-AMPH) produce high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. Pharmacological blockade of N-methyl-D-aspartate (NMDA) receptors has been shown previously to prevent m-AMPH-induced striatal DA terminal injury, but the mechanism for this protection is unclear. In the present study, in vivo microdialysis was used to determine the effects of blockade of NMDA receptors with the noncompetitive antagonist MK-801 on m-AMPH-induced striatal DA overflow. Four injections of MK-801 (0.5 mg/kg, ip) alone did not significantly change extracellular striatal DA concentrations from pretreatment values. Four treatments with m-AMPH (4.0 mg/kg, sc at 2-hr intervals) increased striatal DA overflow, and the overflow was particularly extensive following the fourth injection. This m-AMPH regimen produced a 40% reduction in striatal DA tissue content 1 week later. Treatment with MK-801 15 min before each of the four m-AMPH injections or prior to only the last two m-AMPH administrations attenuated the m-AMPH-induced increase in striatal DA overflow and protected completely against striatal DA depletions. Other MK-801 treatment regimens less effectively reduced the m-AMPH-induced striatal DA efflux and were ineffective in protecting against striatal DA depletions. Linear regression analysis indicated that cumulative DA overflow was strongly predictive (r = -.68) of striatal DA tissue levels measured one week later. These findings suggest that the extensive DA overflow seen during a neurotoxic regimen of m-AMPH is a crucial component of the subsequent neurotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Heterogeneities in Axonal Structure and Transporter Distribution Lower Dopamine Reuptake Efficiency

PubMed Central

Block, Ethan R.; Bartol, Tom M.; Sorkin, Alexander

2018-01-01

Abstract Efficient clearance of dopamine (DA) from the synapse is key to regulating dopaminergic signaling. This role is fulfilled by DA transporters (DATs). Recent advances in the structural characterization of DAT from Drosophila (dDAT) and in high-resolution imaging of DA neurons and the distribution of DATs in living cells now permit us to gain a mechanistic understanding of DA reuptake events in silico. Using electron microscopy images and immunofluorescence of transgenic knock-in mouse brains that express hemagglutinin-tagged DAT in DA neurons, we reconstructed a realistic environment for MCell simulations of DA reuptake, wherein the identity, population and kinetics of homology-modeled human DAT (hDAT) substates were derived from molecular simulations. The complex morphology of axon terminals near active zones was observed to give rise to large variations in DA reuptake efficiency, and thereby in extracellular DA density. Comparison of the effect of different firing patterns showed that phasic firing would increase the probability of reaching local DA levels sufficiently high to activate low-affinity DA receptors, mainly owing to high DA levels transiently attained during the burst phase. The experimentally observed nonuniform surface distribution of DATs emerged as a major modulator of DA signaling: reuptake was slower, and the peaks/width of transient DA levels were sharper/wider under nonuniform distribution of DATs, compared with uniform. Overall, the study highlights the importance of accurate descriptions of extrasynaptic morphology, DAT distribution, and conformational kinetics for quantitative evaluation of dopaminergic transmission and for providing deeper understanding of the mechanisms that regulate DA transmission. PMID:29430519

Modafinil Activates Phasic Dopamine Signaling in Dorsal and Ventral Striata

PubMed Central

Bobak, Martin J.; Weber, Matthew W.; Doellman, Melissa A.; Schuweiler, Douglas R.; Athens, Jeana M.; Juliano, Steven A.

2016-01-01

Modafinil (MOD) exhibits therapeutic efficacy for treating sleep and psychiatric disorders; however, its mechanism is not completely understood. Compared with other psychostimulants inhibiting dopamine (DA) uptake, MOD weakly interacts with the dopamine transporter (DAT) and modestly elevates striatal dialysate DA, suggesting additional targets besides DAT. However, the ability of MOD to induce wakefulness is abolished with DAT knockout, conversely suggesting that DAT is necessary for MOD action. Another psychostimulant target, but one not established for MOD, is activation of phasic DA signaling. This communication mode during which burst firing of DA neurons generates rapid changes in extracellular DA, the so-called DA transients, is critically implicated in reward learning. Here, we investigate MOD effects on phasic DA signaling in the striatum of urethane-anesthetized rats with fast-scan cyclic voltammetry. We found that MOD (30–300 mg/kg i.p.) robustly increases the amplitude of electrically evoked phasic-like DA signals in a time- and dose-dependent fashion, with greater effects in dorsal versus ventral striata. MOD-induced enhancement of these electrically evoked amplitudes was mediated preferentially by increased DA release compared with decreased DA uptake. Principal component regression of nonelectrically evoked recordings revealed negligible changes in basal DA with high-dose MOD (300 mg/kg i.p.). Finally, in the presence of the D2 DA antagonist, raclopride, low-dose MOD (30 mg/kg i.p.) robustly elicited DA transients in dorsal and ventral striata. Taken together, these results suggest that activation of phasic DA signaling is an important mechanism underlying the clinical efficacy of MOD. PMID:27733628

Genomic position affects the expression of tobacco mosaic virus movement and coat protein genes.

PubMed Central

Culver, J N; Lehto, K; Close, S M; Hilf, M E; Dawson, W O

1993-01-01

Alterations in the genomic position of the tobacco mosaic virus (TMV) genes encoding the 30-kDa cell-to-cell movement protein or the coat protein greatly affected their expression. Higher production of 30-kDa protein was correlated with increased proximity of the gene to the viral 3' terminus. A mutant placing the 30-kDa open reading frame 207 nucleotides nearer the 3' terminus produced at least 4 times the wild-type TMV 30-kDa protein level, while a mutant placing the 30-kDa open reading frame 470 nucleotides closer to the 3' terminus produced at least 8 times the wild-type TMV 30-kDa protein level. Increases in 30-kDa protein production were not correlated with the subgenomic mRNA promoter (SGP) controlling the 30-kDa gene, since mutants with either the native 30-kDa SGP or the coat protein SGP in front of the 30-kDa gene produced similar levels of 30-kDa protein. Lack of coat protein did not affect 30-kDa protein expression, since a mutant with the coat protein start codon removed did not produce increased amounts of 30-kDa protein. Effects of gene positioning on coat protein expression were examined by using a mutant containing two different tandemly positioned tobamovirus (TMV and Odontoglossum ringspot virus) coat protein genes. Only coat protein expressed from the gene positioned nearest the 3' viral terminus was detected. Analysis of 30-kDa and coat protein subgenomic mRNAs revealed no proportional increase in the levels of mRNA relative to the observed levels of 30-kDa and coat proteins. This suggests that a translational mechanism is primarily responsible for the observed effect of genomic position on expression of 30-kDa movement and coat protein genes. Images Fig. 2 Fig. 3 Fig. 4 PMID:8446627

Central dopaminergic neurotransmission plays an important role in thermoregulation and performance during endurance exercise.

PubMed

Zheng, Xinyan; Hasegawa, Hiroshi

2016-10-01

Dopamine (DA) has been widely investigated for its potential role in determining exercise performance. It was originally thought that DA's ergogenic effect was by mediating psychological responses. Recently, some studies have also suggested that DA may regulate physiological responses, such as thermoregulation. Hyperthermia has been demonstrated as an important limiting factor during endurance exercise. DA is prominent in the thermoregulatory centre, and changes in DA concentration have been shown to affect core temperature regulation during exercise. Some studies have proposed that DA or DA/noradrenaline (NA) reuptake inhibitors can improve exercise performance, despite hyperthermia during exercise in the heat. DA/NA reuptake inhibitors also increase catecholamine release in the thermoregulatory centre. Intracerebroventricularly injected DA has been shown to improve exercise performance through inhibiting hyperthermia-induced fatigue, even at normal ambient temperatures. Further, caffeine has been reported to increase DA release in the thermoregulatory centre and improves endurance exercise performance despite increased core body temperature. Taken together, DA has been shown to have ergogenic effects and increase heat storage and hyperthermia tolerance. The mechanisms underlying these effects seem to involve limiting/overriding the inhibitory signals from the central nervous system that result in cessation of exercise due to hyperthermia.

Novel codrugs with GABAergic activity for dopamine delivery in the brain.

PubMed

Denora, Nunzio; Cassano, Tommaso; Laquintana, Valentino; Lopalco, Antonio; Trapani, Adriana; Cimmino, Concetta Stefania; Laconca, Leonardo; Giuffrida, Andrea; Trapani, Giuseppe

2012-11-01

This study investigates the use of codrugs of the GABAergic agent 2-phenyl-imidazo[1,2-a]pyridinacetamide and dopamine (DA) or ethyl ester L-Dopa (LD) as a strategy to deliver DA and simultaneously activate GABA-receptors in the brain. For this purpose, both DA and LD ethyl ester were linked by carbamate bond to imidazo[1,2-a]pyridine acetamide moieties to yield two DA- and two LD-imidazopyridine derivatives. These compounds were evaluated in vitro to assess their stability, binding affinities and cell membrane transport, and in vivo to assess their bio-availability via microdialysis studies. The two DA derivatives were adequately stable in buffered solution, but underwent cleavage in diluted human serum. By contrast, the LD derivatives were unstable in buffered solution. Receptor binding studies showed that the DA-imidazopyridine carbamates had binding affinity for benzodiazepine receptors in the nanomolar range. Brain microdialysis experiments indicated that intraperitoneal administration of the DA derivatives sustained DA levels in rat striatum over a 4-h period. These results suggest that DA-imidazopyridine carbamates are new DA codrugs with potential application for DA replacement therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

An improvement of LLNA:DA to assess the skin sensitization potential of chemicals.

PubMed

Zhang, Hongwei; Shi, Ying; Wang, Chao; Zhao, Kangfeng; Zhang, Shaoping; Wei, Lan; Dong, Li; Gu, Wen; Xu, Yongjun; Ruan, Hongjie; Zhi, Hong; Yang, Xiaoyan

2017-01-01

We developed a modified local lymph node assay based on ATP (LLNA:DA), termed the Two-Stage LLNA:DA, to further reduce the animal numbers in the identification of sensitizers. In the Two-Stage LLNA:DA procedure, 13 chemicals ranging from non-sensitizers to extreme sensitizers were selected. The first stage used reduced LLNA:DA (rLLNA:DA) to screen out sensitive chemicals. The second stage used LLNA:DA based on OECD 442 (A) to classify those potential sensitizers screened out in the first stage. In the first stage, the SIs of the methyl methacrylate, salicylic acid, methyl salicylate, ethyl salicylate, isopropanol and propanediol were below 1.8 and need not to be tested in the second step. Others continued to be tested by LLNA:DA. In the second stage, sodium lauryl sulphate and xylene were classified as weak sensitizers. a-hexyl cinnamic aldehyde and eugenol were moderate sensitizers. Benzalkonium chloride and glyoxal were strong sensitizers, and phthalic anhydride was an extreme sensitizer. The 9/9, 11/12, 10/11, and 8/13 (positive or negative only) categories of the Two-Stage LLNA:DA were consistent with those from the other methods (LLNA, LLNA:DA, GPMT/BT and HMT/HPTA), suggesting that Two-Stage LLNA:DA have a high coincidence rate with reported data. In conclusion, The Two-Stage LLNA:DA is in line with the "3R" rules, and can be a modification of LLNA:DA but needs more study.

Monitoring Domoic Acid production by Solid Phase Adsorption Toxin Tracking off the Santa Cruz Municipal Warf, Santa Cruz, California

NASA Astrophysics Data System (ADS)

Nolan, M.; Ziccarelli, L.; Kudela, R. M.

2013-12-01

Certain species of the diatom genus Pseudo-nitzschia are producers of the neurotoxin, domoic acid (DA). DA is known to cause amnesic shellfish poisoning also known as domoic acid poisoning, which can lead to permanent brain damage in humans and marine mammals. DA accumulates at higher trophic levels, generally due to consumption of toxic cells or through trophic transfer, and can potentially cause death of both humans and marine wildlife. The Santa Cruz Municipal Warf experiences periodic rises in DA concentrations, which can reach toxic levels in shellfish, fish, and other marine organisms. While these increases in toxicity often occur during Pseudo-nitzschia blooms, several periods of elevated DA have occurred when diatom abundance is restricted and/or dominated by non-toxic species, and there is increasing evidence that DA dissolved in seawater may be prevalent. One theory suggests that senescent or dead Pseudo-nitzschia cells sink to the benthos while retaining their toxin and are buried in sediment following the death of a bloom. Therefore, DA may accumulate in the benthos, where it is eventually released during storms or wave and tide conditions that disturb the sediment. We sampled DA in situ using Solid Phase Adsorption Toxin Tracking (SPATT) bags SPATT uses a synthetic resin to capture dissolved DA, allowing for the determination of integrated DA concentrations at known time intervals. The alternative method is mussel biotoxin monitoring, but it is less accurate due to uncertainties in the time of DA accumulation within the mussel, and the lack of uptake of dissolved DA by the mussel. We deployed and collected SPATT off the Santa Cruz Municipal Wharf at multiple depths beginning in February 2013. We expect to see increasing DA following the death of a harmful algal bloom. Under pre-bloom conditions, little to no DA has been detected in mussels or surface SPATT, but DA from SPATT is frequently observed at depth, suggesting that the sediment is exposed to (or acts as a reservoir for) DA, and that benthic organisms are chronically exposed to DA.

Intra-aortic balloon pump in cardiogenic shock: state of the art.

PubMed

Thomaz, Petronio Generoso; Moura, Leonel Adelino; Muramoto, Giovana; Assad, Renato Samy

2017-01-01

The clinical definition of cardiogenic shock is that of a low cardiac output and evidence of tissue hypoxia in the presence of adequate blood volume. Cardiogenic shock is the main cause of death related to acute myocardial infarction (AMI), with a mortality rate of 45-70% in the absence of aggressive and highly specialized technical care. The intra-aortic balloon pump (IABP) is one of the most widely used mechanical assisting devices. During the last two decades, about 42% of patients with AMI who evolved with cardiogenic shock received mechanical circulatory assistance with IABP. Its clinical indication has been based on non-randomized studies and registry data. Recent studies have shown that the use of IABP did not reduce 30-day mortality in patients with AMI and cardiogenic shock treated with the strategy of early myocardial revascularization as the planned primary objective. The guidelines of the American Heart Association and of the European Society of Cardiology have reassessed their recommendations based on the results of meta-analyzes, including the IABP-SCHOCK II Trial study, which did not evidence an increase in survival of patients who received mechanical support with IABP. This review article addresses the clinical impact of IABP use in the cardiogenic shock caused by AMI. RESUMO A definição clínica de choque cardiogênico é a de um quadro de baixo débito cardíaco e evidência de hipóxia tecidual, na presença de volemia adequada. O choque cardiogênico representa a principal causa de óbito relacionada ao infarto agudo do miocárdio (IAM), com índice de mortalidade em torno de 45% a 70%, na ausência de cuidados técnicos agressivos e altamente especializados. O balão intra-aórtico (BIA) é um dos dispositivos de assistência mecânica mais utilizados no mundo. Nas duas últimas décadas, cerca de 42% dos pacientes com IAM, que evoluíram com choque cardiogênico, receberam assistência circulatória mecânica com BIA. Sua indicação clínica tem sido baseada em estudos não randomizados e dados de registro. Estudos recentes têm demonstrado que o uso do BIA não reduziu a mortalidade hospitalar (30 dias) em pacientes com IAM e choque cardiogênico, tratados com a estratégia de revascularização precoce do miocárdio como objetivo primário planejado. As diretrizes da Associação Americana de Cardiologia e da Sociedade Europeia de Cardiologia reavaliaram suas recomendações, baseadas nos resultados de metanálises, incluindo o estudo IABP-SCHOCK II Trial, que não evidenciou aumento na sobrevida de pacientes que receberam suporte mecânico com BIA. Este artigo de revisão aborda o impacto clínico do uso do BIA no choque cardiogênico ocasionado pelo IAM.

Intranasal Dopamine Reduces In Vivo [(123)I]FP-CIT Binding to Striatal Dopamine Transporter: Correlation with Behavioral Changes and Evidence for Pavlovian Conditioned Dopamine Response.

PubMed

de Souza Silva, Maria A; Mattern, Claudia; Decheva, Cvetana; Huston, Joseph P; Sadile, Adolfo G; Beu, Markus; Müller, H-W; Nikolaus, Susanne

2016-01-01

Dopamine (DA), which does not cross the blood-brain barrier, has central and behavioral effects when administered via the nasal route. Neither the mechanisms of central action of intranasal dopamine (IN-DA), nor its mechanisms of diffusion and transport into the brain are well understood. We here examined whether IN-DA application influences dopamine transporter (DAT) binding in the dorsal striatum and assessed the extent of binding in relation to motor and exploratory behaviors. We hypothesized that, based on the finding of increased extracellular DA in the striatum induced by application of IN-DA, binding of [(123)I]FP-CIT to the DAT should be decreased due to competition at the receptor. Rats were administered 3 mg/kg IN-DA and vehicle (VEH), with IN-DA injection either preceding or following VEH. Then motor and exploratory behaviors (traveled distance, velocity, center time, sitting, rearing, head-shoulder motility, grooming) were assessed for 30 min in an open field prior to administration of [(123)I]FP-CIT. DAT binding after IN-DA and VEH was measured with small animal SPECT 2 h following administration of the radioligand. (1) After IN-DA application, striatal DAT binding was significantly lower as compared to VEH, indicating that the nasally delivered DA had central action and increased DA levels comparable to that found previously with L-DOPA administration; and (2) DAT binding in response to intranasal VEH was lower when IN-DA application preceded VEH treatment. This finding is suggestive of Pavlovian conditioning of DA at the level of the DAT, since the DA treatment modified (decreased) the binding in response to the subsequent VEH treatment. VEH treatment also reduced motor and exploratory behaviors more when applied before, as compared to when it followed IN-DA application, also indicative of behavioral Pavlovian conditioning akin to that found upon application of various psychostimulant drugs. (a) demonstrate a direct central action of intranasally applied DA on the DAT in the dorsal striatum, indicating enhanced DA availability; and (b) provide first evidence of a Pavlovian conditioned DA response at the DAT. The latter results have relevance to understanding neurochemical mechanisms that underlie placebo action in the treatment of Parkinsonian patients.

Lesion of medial prefrontal dopamine terminals abolishes habituation of accumbens shell dopamine responsiveness to taste stimuli.

PubMed

Bimpisidis, Zisis; De Luca, Maria Antonietta; Pisanu, Augusta; Di Chiara, Gaetano

2013-02-01

Taste stimuli increase extracellular dopamine (DA) in the nucleus accumbens (NAc) and in the medial prefrontal cortex (mPFC). This effect shows single-trial habituation in NAc shell but not in core or in mPFC. Morphine sensitization abolishes habituation of DA responsiveness in NAc shell but induces it in mPFC. These observations support the hypothesis of an inhibitory influence of mPFC DA on NAc DA. To test this hypothesis, we used in vivo microdialysis to investigate the effect of mPFC 6-hydroxy-dopamine (6-OHDA) lesions on the NAc DA responsiveness to taste stimuli. 6-OHDA was infused bilaterally in the mPFC of rats implanted with guide cannulae. After 1 week, rats were implanted with an intraoral catheter, microdialysis probes were inserted into the guide cannulae, and dialysate DA was monitored in NAc shell/core after intraoral chocolate. 6-OHDA infusion reduced tissue DA in the mPFC by 75%. Tyrosine hydroxylase immunohistochemistry showed that lesions were confined to the mPFC. mPFC 6-OHDA lesion did not affect the NAc shell DA responsiveness to chocolate in naive rats but abolished habituation in rats pre-exposed to the taste. In the NAc core, mPFC lesion potentiated, delayed and prolonged the stimulatory DA response to taste but failed to affect DA in pre-exposed rats. Behavioural taste reactions and motor activity were not affected. The results indicate a top-down control of NAc DA by mPFC and a reciprocal relationship between DA transmission in these two areas. Moreover, habituation of DA responsiveness in the NAc shell is dependent upon an intact DA input to the mPFC. © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Complicated function of dopamine in Aβ-related neurotoxicity: Dual interactions with Tyr10 and SNK(26-28) of Aβ.

PubMed

Liu, Mengmeng; Kou, Lu; Bin, Yannan; Wan, Liping; Xiang, Juan

2016-11-01

With the capability to inhibit the formation of amyloid β peptides (Aβ) fibril, dopamine (DA) and other catechol derivatives have been considered for the potential treatment of Alzheimer's disease (AD). Such treatment, however, remains debatable because of the diverse functions of Aβ and DA in AD pathology. Moreover, the complicated oxidation accompanying DA has caused the majority of the previous research to focus on the binding of DA oxides onto Aβ. The molecular mechanism by which Aβ interacts with the reduction state of DA, which is correlative with the brain function, should be urgently explored. By controlling rigorous anaerobic experimental conditions, this work investigated the molecular mechanism of the Aβ/DA interaction, and two binding sites were revealed. For the binding of DA, Tyrosine (Tyr 10 ) was identified as the strong binding site, and serine-asparagine-lysing (SNK(26-28)) segment was the weak binding segment. Furthermore, the Thioflavin T (THT) fluorescence confirmed DA's positive function of inhibiting Aβ aggregation through its weakly binding with SNK(26-28) segment. Meanwhile, 7-OHCCA fluorescence exhibited DA's negative function of enhancing OH generation through inhibiting the Aβ/Cu 2+ coordination. The viability tests of the neuroblastoma SH-SY5Y cells displayed that the coexistence of DA, Cu 2+ , and Aβ induced lower cell viability than free Cu 2+ , indicating the significant negative effect of excessive DA on AD progression. This research revealed the potential DA-induced damage in AD brain, which is significant for understanding the function of DA in AD neuropathology and for designing a DA-related therapeutic strategy for AD. Copyright © 2016 Elsevier Inc. All rights reserved.

Intranasal administration of dopamine attenuates unconditioned fear in that it reduces restraint-induced ultrasound vocalizations and escape from bright light.

PubMed

Talbot, Teddy; Mattern, Claudia; de Souza Silva, Maria Angelica; Brandão, Marcus Lira

2017-06-01

Although substantial evidence suggests that dopamine (DA) enhances conditioned fear responses, few studies have examined the role of DA in unconditioned fear states. Whereas DA does not cross the blood-brain barrier, intranasally-applied dopamine reaches the brain directly via the nose-brain pathways in rodents, providing an alternative means of targeting DA receptors. Intranasal dopamine (IN-DA) has been demonstrated to bind to DA transporters and to increase extracellular DA in the striatum as well as having memory-promoting effects in rats. The purpose of this study was to examine the influence of IN-DA in three tests of fear/anxiety. The three doses of DA hydrochloride (0.03, 0.3, or 1 mg/kg) were applied in a viscous castor oil gel in a volume of 5 µl to each of both nostrils of adult Wistar rats prior to testing of (a) escape from a bright light, using a two-chamber procedure, (b) restraint-induced 22 kHz ultrasound vocalizations (USVs), and (c) exploratory behavior in the elevated plus-maze (EPM). IN-DA dose-dependently reduced escape from bright light and the number of USV responses to restraint. It had no influence on the exploratory behavior in the EPM. IN-DA application reduced escape behavior in two tests of unconditioned fear (escape from bright light and USV response to immobilization). These findings may be interpreted in light of the known antidepressant action of IN-DA and DA reuptake blockers. The results also confirm the promise of the nasal route as an alternative means for targeting the brain's dopaminergic receptors with DA.

Tuning mechanical performance of poly(ethylene glycol) and agarose interpenetrating network hydrogels for cartilage tissue engineering.

PubMed

Rennerfeldt, Deena A; Renth, Amanda N; Talata, Zsolt; Gehrke, Stevin H; Detamore, Michael S

2013-11-01

Hydrogels are attractive for tissue engineering applications due to their incredible versatility, but they can be limited in cartilage tissue engineering applications due to inadequate mechanical performance. In an effort to address this limitation, our team previously reported the drastic improvement in the mechanical performance of interpenetrating networks (IPNs) of poly(ethylene glycol) diacrylate (PEG-DA) and agarose relative to pure PEG-DA and agarose networks. The goal of the current study was specifically to determine the relative importance of PEG-DA concentration, agarose concentration, and PEG-DA molecular weight in controlling mechanical performance, swelling characteristics, and network parameters. IPNs consistently had compressive and shear moduli greater than the additive sum of either single network when compared to pure PEG-DA gels with a similar PEG-DA content. IPNs withstood a maximum stress of up to 4.0 MPa in unconfined compression, with increased PEG-DA molecular weight being the greatest contributing factor to improved failure properties. However, aside from failure properties, PEG-DA concentration was the most influential factor for the large majority of properties. Increasing the agarose and PEG-DA concentrations as well as the PEG-DA molecular weight of agarose/PEG-DA IPNs and pure PEG-DA gels improved moduli and maximum stresses by as much as an order of magnitude or greater compared to pure PEG-DA gels in our previous studies. Although the viability of encapsulated chondrocytes was not significantly affected by IPN formulation, glycosaminoglycan (GAG) content was significantly influenced, with a 12-fold increase over a three-week period in gels with a lower PEG-DA concentration. These results suggest that mechanical performance of IPNs may be tuned with partial but not complete independence from biological performance of encapsulated cells. © 2013 Elsevier Ltd. All rights reserved.

Ventricular fibrillation cardiac arrest produces a chronic striatal hyperdopaminergic state that is worsened by methylphenidate treatment.

PubMed

Nora, Gerald J; Harun, Rashed; Fine, David F; Hutchison, Daniel; Grobart, Adam C; Stezoski, Jason P; Munoz, Miranda J; Kochanek, Patrick M; Leak, Rehana K; Drabek, Tomas; Wagner, Amy K

2017-07-01

Cardiac arrest survival rates have improved with modern resuscitation techniques, but many survivors experience impairments associated with hypoxic-ischemic brain injury (HIBI). Currently, little is understood about chronic changes in striatal dopamine (DA) systems after HIBI. Given the common empiric clinical use of DA enhancing agents in neurorehabilitation, investigation evaluating dopaminergic alterations after cardiac arrest (CA) is necessary to optimize rehabilitation approaches. We hypothesized that striatal DA neurotransmission would be altered chronically after ventricular fibrillation cardiac arrest (VF-CA). Fast-scan cyclic voltammetry was used with median forebrain bundle (MFB) maximal electrical stimulations (60Hz, 10s) in rats to characterize presynaptic components of DA neurotransmission in the dorsal striatum (D-Str) and nucleus accumbens 14 days after a 5-min VF-CA when compared to Sham or Naïve. VF-CA increased D-Str-evoked overflow [DA], total [DA] released, and initial DA release rate versus controls, despite also increasing maximal velocity of DA reuptake (V max ). Methylphenidate (10 mg/kg), a DA transporter inhibitor, was administered to VF-CA and Shams after establishing a baseline, pre-drug 60 Hz, 5 s stimulation response. Methylphenidate increased initial evoked overflow [DA] more-so in VF-CA versus Sham and reduced D-Str V max in VF-CA but not Shams; these findings are consistent with upregulated striatal DA transporter in VF-CA versus Sham. Our work demonstrates that 5-min VF-CA increases electrically stimulated DA release with concomitant upregulation of DA reuptake 2 weeks after brief VF-CA insult. Future work should elucidate how CA insult duration, time after insult, and insult type influence striatal DA neurotransmission and related cognitive and motor functions. © 2017 International Society for Neurochemistry.

NADH:ubiquinone oxidoreductase from bovine heart mitochondria. cDNA sequences of the import precursors of the nuclear-encoded 39 kDa and 42 kDa subunits.

PubMed Central

Fearnley, I M; Finel, M; Skehel, J M; Walker, J E

1991-01-01

The 39 kDa and 42 kDa subunits of NADH:ubiquinone oxidoreductase from bovine heart mitochondria are nuclear-coded components of the hydrophobic protein fraction of the enzyme. Their amino acid sequences have been deduced from the sequences of overlapping cDNA clones. These clones were amplified from total bovine heart cDNA by means of the polymerase chain reaction, with the use of complex mixtures of oligonucleotide primers based upon fragments of protein sequence determined at the N-terminals of the proteins and at internal sites. The protein sequences of the 39 kDa and 42 kDa subunits are 345 and 320 amino acid residues long respectively, and their calculated molecular masses are 39,115 Da and 36,693 Da. Both proteins are predominantly hydrophilic, but each contains one or two hydrophobic segments that could possibly be folded into transmembrane alpha-helices. The bovine 39 kDa protein sequence is related to that of a 40 kDa subunit from complex I from Neurospora crassa mitochondria; otherwise, it is not related significantly to any known sequence, including redox proteins and two polypeptides involved in import of proteins into mitochondria, known as the mitochondrial processing peptidase and the processing-enhancing protein. Therefore the functions of the 39 kDa and 42 kDa subunits of complex I are unknown. The mitochondrial gene product, ND4, a hydrophobic component of complex I with an apparent molecular mass of about 39 kDa, has been identified in preparations of the enzyme. This subunit stains faintly with Coomassie Blue dye, and in many gel systems it is not resolved from the nuclearcoded 36 kDa subunit. Images Fig. 1. PMID:1832859

Advancing Data Assimilation in Operational Hydrologic Forecasting: Progresses, Challenges, and Emerging Opportunities

NASA Technical Reports Server (NTRS)

Liu, Yuqiong; Weerts, A.; Clark, M.; Hendricks Franssen, H.-J; Kumar, S.; Moradkhani, H.; Seo, D.-J.; Schwanenberg, D.; Smith, P.; van Dijk, A. I. J. M.;

Assessment of SWE data assimilation for ensemble streamflow predictions

NASA Astrophysics Data System (ADS)

Franz, Kristie J.; Hogue, Terri S.; Barik, Muhammad; He, Minxue

2014-11-01

An assessment of data assimilation (DA) for Ensemble Streamflow Prediction (ESP) using seasonal water supply hindcasting in the North Fork of the American River Basin (NFARB) and the National Weather Service (NWS) hydrologic forecast models is undertaken. Two parameter sets, one from the California Nevada River Forecast Center (RFC) and one from the Differential Evolution Adaptive Metropolis (DREAM) algorithm, are tested. For each parameter set, hindcasts are generated using initial conditions derived with and without the inclusion of a DA scheme that integrates snow water equivalent (SWE) observations. The DREAM-DA scenario uses an Integrated Uncertainty and Ensemble-based data Assimilation (ICEA) framework that also considers model and parameter uncertainty. Hindcasts are evaluated using deterministic and probabilistic forecast verification metrics. In general, the impact of DA on the skill of the seasonal water supply predictions is mixed. For deterministic (ensemble mean) predictions, the Percent Bias (PBias) is improved with integration of the DA. DREAM-DA and the RFC-DA have the lowest biases and the RFC-DA has the lowest Root Mean Squared Error (RMSE). However, the RFC and DREAM-DA have similar RMSE scores. For the probabilistic predictions, the RFC and DREAM have the highest Continuous Ranked Probability Skill Scores (CRPSS) and the RFC has the best discrimination for low flows. Reliability results are similar between the non-DA and DA tests and the DREAM and DREAM-DA have better reliability than the RFC and RFC-DA for forecast dates February 1 and later. Despite producing improved streamflow simulations in previous studies, the hindcast analysis suggests that the DA method tested may not result in obvious improvements in streamflow forecasts. We advocate that integration of hindcasting and probabilistic metrics provides more rigorous insight on model performance for forecasting applications, such as in this study.

Wirelessly controlled micro- and nanostructures for bioapplications

NASA Astrophysics Data System (ADS)

Lindo, Andre Machado

Apresentar uma contribuicao para a caracterizacao e compreensao do comportamento hidrodinâmico da laguna Ria de Aveiro, baseada num estudo experimental e num estudo de modelacao numerica, e o objectivo deste trabalho. As caracteristicas hidrologicas da Ria de Aveiro foram investigadas atraves da realizacao de varias campanhas de amostragem, tendo sido efectuadas medicoes de altura de agua, salinidade, temperatura da agua e velocidade da corrente em varias estacoes distribuidas ao longo de quatro canais principais da laguna. None

Ultrasonic irradiation enhanced the ability of Fluorescein-DA-Fe(III) on sonodynamic and sonocatalytic damages of DNA molecules.

PubMed

Wu, Qiong; Chen, Xia; Jia, Lizhen; Wang, Yi; Sun, Ying; Huang, Xingjun; Shen, Yuxiang; Wang, Jun

2017-11-01

The interaction of DNA with Bis [N,N-bis (carboxymethyl) aminomethyl] fluorescein-Ferrous(III) (Fluorescein-DA-Fe(III)) with dual functional (sonodynamic and sonocatalytic) activity was studied by UV-vis spectroscopy, fluorescence spectroscopy, FT-IR spectroscopy, circular dichroism (CD) spectroscopy and viscosity measurements. And then, the damage of DNA caused by Fluorescein-DA-Fe(III) under ultrasonic irradiation (US) was researched by agarose gel electrophoresis and cytotoxicity assay. Meanwhile, some influenced factors such as ultrasonic irradiation time and Fluorescein-DA-Fe(III) concentration on the damage degree of DNA molecules were also examined. As a control, for Bis [N,N-bis (carboxymethyl) aminomethyl] fluorescein (Fluorescein-DA), the same experiments were carried out. The results showed that both Fluorescein-DA-Fe(III) and Fluorescein-DA can interact with DNA molecules. Under ultrasonic irradiation, Fluorescein-DA shows sonodynamic activity, which can damage DNA molecules. While, in the presence of Fe(III) ion, the Fluorescein-DA-Fe(III) displays not only sonodynamic activity but also sonocatalytic activity under ultrasonic irradiation, which injures DNA more serious than Fluorescein-DA. The researches confirmed the dual function (sonodynamic activity and sonocatalytic activity) of Fluorescein-DA-Fe(III) and expanded the usage of Fluorescein-DA-Fe(III) as a sonosensitizer in sonodynamic therapy (SDT). Copyright © 2017 Elsevier B.V. All rights reserved.

Domoic acid toxicokinetics in Dungeness crabs: new insights into mechanisms that regulate bioaccumulation.

PubMed

Schultz, Irvin R; Skillman, Ann; Sloan-Evans, Siobhan; Woodruff, Dana

2013-09-15

Domoic acid (DA) is an excitatory neurotoxic amino acid produced by several marine algal species and is the causative agent of amnesic shellfish poisoning. Profound differences in the toxicokinetics of DA have been identified in a wide variety of shellfish. We characterized the toxicokinetics of DA in Dungeness crabs (Metacarcinus magister) after oral and intravascular dosing (IV) using a variety of doses ranging from 0.1 to 20mg/kg. After a 1mg/kg oral dose, DA disappeared from the foregut within 2h and largely accumulated in the hepatopancreas, with hemolymph and other tissues having 100-1000 times lower concentrations. After IV dosing, hemolymph concentrations of DA were unexpectedly high and toxicokinetic analysis indicated the steady-state volume of distribution (Vss) was 123-197 ml/kg, which is well below the hemolymph volume of 350 ml/kg for crabs. This indicated only limited extravascular distribution of DA was occurring after IV injection, which is surprising considering the capacity of the hepatopancreas to sequester DA after oral dosing. Additional studies measured the partitioning of DA in hepatopancreas cellular and subcellular fractions. The subcellular distribution of DA was primarily associated with the S8 fraction and could be filtered through a 30,000 MW cut-off filter, indicating DA was not appreciably bound to macromolecules. Interestingly, very little (<0.4%) of the total hepatopancreas DA tissue content was associated with the cellular fraction isolated after dissociation and separation from tissue fragments. The in vivo and in vitro results led us to hypothesize that DA uptake and distribution is regulated by crustacean orthologs of ATP-binding cassette (ABC) type transporters. We tested this hypothesis by co-exposing crabs to DA and known inhibitors of ABC transporters (verapamil, cyclosporine A and MK-571) and through in vitro studies using isolated hepatopancreas tissue and mixed cell suspensions prepared from hepatopancreas tissue. The in vivo results were inconclusive in that the toxicokinetics of DA was not consistently altered by co-administration of the inhibitors. Two exceptions were MK-571, which significantly increased the total body clearance of DA and co-administration of verapamil, which significantly increased the hepatopancreas tissue content of DA 24h after IV injection. Isolated pieces of hepatopancreas tissue were able to readily absorb DA from incubation media, but mixed cell suspensions did not. The absorption of DA or lack thereof was largely unaffected by co-incubation with verapamil although cell suspensions appeared to accumulate small quantities of DA in the presence of verapamil. Collectively, the results of this study suggest DA accumulates in the extracellular spaces of the hepatopancreas, such as the tubular lumen. Under natural circumstances, crabs feeding on contaminated shellfish would be expected to readily absorb DA, which is then stored and slowly eliminated in urine. If the DA exposure level exceeds the storage capacity of the tissue (as occurred with the 20mg/kg dose), breakthrough occurs resulting in much higher systemic exposure and potential for DA toxicity. Copyright © 2013 Elsevier B.V. All rights reserved.

Pathomechanisms of Dopamine Dysregulation in DYT1 Dystonia: Targets for Therapeutics

DTIC Science & Technology

2016-10-01

DA release in DYT1(ΔE) knockin mice by assessing VMAT2 function, vesicle utilization, the ultrastructure of DA terminals, and D2 DA...in slice, the ultrastructure of DA terminals, D2 DA autoreceptor function nicotinic AChR (nAChR) heteroreceptors function. 2) To determine the

Phosphorylation of Tat-interactive protein 60 kDa by protein kinase C epsilon is important for its subcellular localisation.

PubMed

Sapountzi, Vasileia; Logan, Ian R; Nelson, Glyn; Cook, Susan; Robson, Craig N

2008-01-01

Tat-interactive protein 60 kDa is a nuclear acetyltransferase that both coactivates and corepresses transcription factors and has a definitive function in the DNA damage response. Here, we provide evidence that Tat-interactive protein 60 kDa is phosphorylated by protein kinase C epsilon. In vitro, protein kinase C epsilon phosphorylates Tat-interactive protein 60 kDa on at least two sites within the acetyltransferase domain. In whole cells, activation of protein kinase C increases the levels of phosphorylated Tat-interactive protein 60 kDa and the interaction of Tat-interactive protein 60 kDa with protein kinase C epsilon. A phosphomimetic mutant Tat-interactive protein 60 kDa has distinct subcellular localisation compared to the wild-type protein in whole cells. Taken together, these findings suggest that the protein kinase C epsilon phosphorylation sites on Tat-interactive protein 60 kDa are important for its subcellular localisation. Regulation of the subcellular localisation of Tat-interactive protein 60 kDa via phosphorylation provides a novel means of controlling Tat-interactive protein 60 kDa function.

Cocaine inhibition of nicotinic acetylcholine receptors influences dopamine release

PubMed Central

Acevedo-Rodriguez, Alexandra; Zhang, Lifen; Zhou, Fuwen; Gong, Suzhen; Gu, Howard; De Biasi, Mariella; Zhou, Fu-Ming; Dani, John A.

2014-01-01

Nicotinic acetylcholine receptors (nAChRs) potently regulate dopamine (DA) release in the striatum and alter cocaine's ability to reinforce behaviors. Since cocaine is a weak nAChR inhibitor, we hypothesized that cocaine may alter DA release by inhibiting the nAChRs in DA terminals in the striatum and thus contribute to cocaine's reinforcing properties primarily associated with the inhibition of DA transporters. We found that biologically relevant concentrations of cocaine can mildly inhibit nAChR-mediated currents in midbrain DA neurons and consequently alter DA release in the dorsal and ventral striatum. At very high concentrations, cocaine also inhibits voltage-gated Na channels in DA neurons. Furthermore, our results show that partial inhibition of nAChRs by cocaine reduces evoked DA release. This diminution of DA release via nAChR inhibition more strongly influences release evoked at low or tonic stimulation frequencies than at higher (phasic) stimulation frequencies, particularly in the dorsolateral striatum. This cocaine-induced shift favoring phasic DA release may contribute to the enhanced saliency and motivational value of cocaine-associated memories and behaviors. PMID:25237305

Determination of Domoic Acid in Plankton Net Samples from Golden Horn Estuary, Turkey, Using HPLC with Fluorescence Detection.

PubMed

Dursun, Fuat; Ünlü, Selma; Yurdun, Türkan

2018-03-01

This study focused on the fluctuations of domoic acid (DA) levels in plankton net samples collected from the Golden Horn Estuary (GHE), Turkey, between August 2011 and July 2012. DA concentrations were determined by high-performance liquid chromatography (HPLC), using a fluorenylmethoxycarbonyl (FMOC) derivatization technique. Monthly and biweekly data were evaluated with environmental variables, and their influence on DA production is discussed. DA levels in plankton net samples varied between 0.36 and 94.34 µg L - 1 . DA levels showed remarkable seasonal variation and they were generally higher in May, 2012, but no DA was detected between February and April, 2012. DA production was mostly controlled by temperature, with nitrate and silicate limitations being secondary factors that influenced DA concentrations.

PubMed

Benítez Brito, Néstor; Oliva García, José Gregorio; Delgado Brito, Irina; Pereyra-García Castro, Francisca; Suárez Llanos, José Pablo; Leyva González, Francisco Gustavo; Palacio Abizanda, José Enrique

2016-11-29

Introducción: la alimentación constituye el pilar fundamental del soporte nutricional de los pacientes hospitalizados. Evaluar el grado de aceptación de la dieta es imprescindible en aras de combatir la desnutrición hospitalaria.Objetivos: a) determinar el grado de satisfacción de los pacientes en relación con las dietas; y b) analizar posibles variables asociadas a un grado de satisfacción mayor (apetito y tipo de dieta).Material y métodos: estudio descriptivo de corte transversal. Se emplea una encuesta de 17 preguntas con datos sociodemográficos, datos cualitativos, así como la valoración general del paciente. Se comparó el grado de satisfacción global en función del apetito y el tipo de dieta (terapéutica vs.basal; con sal vs.sosa) (Test no paramétric o Krustal-Wallis y T-Student para muestras independientes, respectivamente).Resultados: mil cuatrocientos trece pacientes. Edad: 53,9 ± 19 años; 51,3% mujeres. Dieta terapéutica (34,9%). Solo el 39,4% tomó dieta con sal. El 66,8% refirió ingresos previos. La alimentación del hospital para un 43% de pacientes fue ''como esperaba'', mientras que para un 44,1% fue ''mejor de lo que esperaba''. El horario de comidas era adecuado (89,1%) y el tiempo para comer, suficiente (96,4%). En cuanto a las características de la comida servida, consideraron como buenas o muy buenas la misma el porcentaje reflejado: sabor/gusto (56.3%), olor (65,5%), cocinado (69,2%), presentación (80,4%), tamaño de ración (75,9%), calidad (73%), cantidad (77,9%), variedad (67,6%), temperatura (70,4%). La valoración global de la alimentación en una escala de 1 a 10 fue de 6,8 ± 2,3. El apetito se asoció a un aumento significativo de la satisfacción global alimentaria del paciente (p < 0,01). El tipo de dieta o la presencia de sal en la misma no se asociaron a un aumento significativo de la satisfacción con la dieta de los pacientes (p = 0,99 y 0,35, respectivamente).Conclusiones: aunque el grado de satisfacción de la dieta de nuestro hospital es aceptable, es preciso introducir mejoras que aumenten su aceptación. El apetito se asocia a un aumento significativo de la satisfacción global alimentaria. La presencia de sal y el tipo de dieta (basal versusterapéutica) no se relacionan con una mejoría significativa de la valoración global de la dieta.

Packaging of the virion host shutoff (Vhs) protein of herpes simplex virus: two forms of the Vhs polypeptide are associated with intranuclear B and C capsids, but only one is associated with enveloped virions.

PubMed

Read, G Sullivan; Patterson, Mary

2007-02-01

The virion host shutoff (Vhs) protein (UL41) is a minor component of herpes simplex virus virions which, following penetration, accelerates turnover of host and viral mRNAs. Infected cells contain 58-kDa and 59.5-kDa forms of Vhs, which differ in the extent of phosphorylation, yet only a 58-kDa polypeptide is incorporated into virions. In pulse-chase experiments, the primary Vhs translation product comigrated in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with the 58-kDa virion polypeptide, and could be chased to 59.5 kDa. While both 59.5-kDa and 58-kDa forms were found in nuclear and cytoplasmic fractions, the 59.5-kDa form was significantly enriched in the nucleus. Both forms were associated with intranuclear B and C capsids, yet only the 58-kDa polypeptide was found in enveloped cytoplasmic virions. A 58-kDa form, but not the 59.5-kDa form, was found in L particles, noninfectious particles that contain an envelope and tegument but no capsid. The data suggest that virions contain two populations of Vhs that are packaged by different pathways. In the first pathway, the primary translation product is processed to 59.5 kDa, is transported to the nucleus, binds intranuclear capsids, and is converted to 58 kDa at some stage prior to final envelopment. The second pathway does not involve the 59.5-kDa form or interactions between Vhs and capsids. Instead, the primary translation product is phosphorylated to the 58-kDa virion form and packaged through interactions with other tegument proteins in the cytoplasm or viral envelope proteins at the site of final envelopment.

Within-family environmental transmission of drug abuse: a Swedish national study.

PubMed

Kendler, Kenneth S; Ohlsson, Henrik; Sundquist, Kristina; Sundquist, Jan

2013-02-01

CONTEXT Drug abuse (DA) strongly runs in families. Does this result solely from genetic factors or does the family environment contribute? OBJECTIVE To determine the familial environmental contribution to the risk for DA. DESIGN Follow-up in 9 public databases (1961-2009) in siblings and spouses. SETTING Sweden. PARTICIPANTS A total of 137 199 sibling pairs and 7561 spousal pairs containing a proband with DA and matched control probands. MAIN OUTCOME MEASURES Drug abuse recorded in medical, legal, or pharmacy registry records. RESULTS In the best-fit model, which contained significant linear, quadratic, and cubic effects, among full sibling pairs containing a proband with DA, the relative risk for DA in the sibling declined from more than 6.0 for siblings born within 2 years of each other to less than 4.5 when born 10 years apart. Controlling for age differences in full sibling pairs, the hazard rate for DA in a sibling when the affected proband was older vs younger was 1.42 (95% CI, 1.31-1.54). In the best-fit model, which contained significant linear, quadratic, and cubic effects, among spousal pairs containing a proband with DA, the relative risk for DA in the spouse declined from more than 25.0 within 1 year of proband DA registration to 6.0 after 5 years. CONCLUSIONS Controlling for genetic effects by examining only full siblings, sibling resemblance for the risk for DA was significantly greater in pairs closer vs more distant in age. Older siblings more strongly transmitted the risk for DA to their younger siblings than vice versa. After one spouse is registered for DA, the other spouse has a large short-lived increase in DA risk. These results support strong familial environmental influences on DA at various life stages. A complete understanding of the familial transmission of DA will require knowledge of how genetic and familial environmental risk factors act and interact over development.

DA-9801 promotes neurite outgrowth via ERK1/2-CREB pathway in PC12 cells.

PubMed

Won, Jong Hoon; Ahn, Kyong Hoon; Back, Moon Jung; Ha, Hae Chan; Jang, Ji Min; Kim, Ha Hyung; Choi, Sang-Zin; Son, Miwon; Kim, Dae Kyong

2015-01-01

In the present study, we examined the mechanisms underlying the effect of DA-9801 on neurite outgrowth. We found that DA-9801 elicits its effects via the mitogen-activated protein kinase (MEK) extracellular signal-regulated kinase (ERK)1/2-cAMP response element-binding protein (CREB) pathway. DA-9801, an extract from a mixture of Dioscorea japonica and Dioscorea nipponica, was reported to promote neurite outgrowth in PC12 cells. The effects of DA-9801 on cell viability and expression of neuronal markers were evaluated in PC12 cells. To investigate DA-9801 action, specific inhibitors targeting the ERK signaling cascade were used. No cytotoxicity was observed in PC12 cells at DA-9801 concentrations of less than 30 µg/mL. In the presence of nerve growth factor (NGF, 2 ng/mL), DA-9801 promoted neurite outgrowth and increased the relative mRNA levels of neurofilament-L (NF-L), a marker of neuronal differentiation. The Raf-1 inhibitor GW5074 and MEK inhibitor PD98059 significantly attenuated DA-9801-induced neurite outgrowth. Additionally, the MEK1 and MEK2 inhibitor SL327 significantly attenuated the increase in the percentage of neurite-bearing PC12 cells induced by DA-9801 treatment. Conversely, the selective p38 mitogen-activated protein kinase inhibitor SB203580 did not attenuate the DA-9801 treatment-induced increase in the percentage of neurite-bearing PC12 cells. DA-9801 enhanced the phosphorylation of ERK1/2 and CREB in PC12 cells incubated with and without NGF. Pretreatment with PD98059 blocked the DA-9801-induced phosphorylation of ERK1/2 and CREB. In conclusion, DA-9801 induces neurite outgrowth by affecting the ERK1/2-CREB signaling pathway. Insights into the mechanism underlying this effect of DA-9801 may suggest novel potential strategies for the treatment of peripheral neuropathy.

Toward development of an in vitro model of methamphetamine-induced dopamine nerve terminal toxicity.

PubMed

Kim, S; Westphalen, R; Callahan, B; Hatzidimitriou, G; Yuan, J; Ricaurte, G A

2000-05-01

To develop an in vitro model of methamphetamine (METH)-induced dopamine (DA) neurotoxicity, striatal synaptosomes were incubated at 37 degrees C with METH for different periods of time (10-80 min), washed once, then tested for DA transporter function at 37 degrees C. METH produced time- and dose-dependent reductions in the V(max) of DA uptake, without producing any change in K(m). Incubation of synaptosomes with the DA neurotoxins 1-methyl-4-phenyl-pyridinium ion, 6-hydroxydopamine, and amphetamine under similar conditions produced comparable effects. In contrast, incubation with fenfluramine, a serotonin neurotoxin, did not. METH-induced decreases in DA uptake were selective, insofar as striatal glutamate uptake was unaffected. Various DA transporter blockers (cocaine, methylphenidate, and bupropion) afforded complete protection against METH-induced decreases in DA uptake, without producing any effect themselves. METH's effects were also temperature dependent, with greater decreases in DA uptake occurring at higher temperatures. Tests for residual drug revealed small amounts (0.1-0.2 microM) of remaining METH, but kinetic studies indicated that decreases in DA uptake were not likely to be due to METH acting as a competitive inhibitor of DA uptake. Decreases in the V(max) of DA uptake were not accompanied by decreases in B(max) of [(3)H]WIN 35,428 binding, possibly because there is no mechanism for removing damaged DA nerve endings from the in vitro preparation Collectively, these results give good support to the development of a valid in vitro model that may prove helpful for elucidating the mechanisms underlying METH-induced DA neurotoxicity.

Modeling Fast-scan Cyclic Voltammetry Data from Electrically Stimulated Dopamine Neurotransmission Data Using QNsim1.0.

PubMed

Harun, Rashed; Grassi, Christine M; Munoz, Miranda J; Wagner, Amy K

2017-06-05

Central dopaminergic (DAergic) pathways have an important role in a wide range of functions, such as attention, motivation, and movement. Dopamine (DA) is implicated in diseases and disorders including attention deficit hyperactivity disorder, Parkinson's disease, and traumatic brain injury. Thus, DA neurotransmission and the methods to study it are of intense scientific interest. In vivo fast-scan cyclic voltammetry (FSCV) is a method that allows for selectively monitoring DA concentration changes with fine temporal and spatial resolution. This technique is commonly used in conjunction with electrical stimulations of ascending DAergic pathways to control the impulse flow of dopamine neurotransmission. Although the stimulated DA neurotransmission paradigm can produce robust DA responses with clear morphologies, making them amenable for kinetic analysis, there is still much debate on how to interpret the responses in terms of their DA release and clearance components. To address this concern, a quantitative neurobiological (QN) framework of stimulated DA neurotransmission was recently developed to realistically model the dynamics of DA release and reuptake over the course of a stimulated DA response. The foundations of this model are based on experimental data from stimulated DA neurotransmission and on principles of neurotransmission adopted from various lines of research. The QN model implements 12 parameters related to stimulated DA release and reuptake dynamics to model DA responses. This work describes how to simulate DA responses using QNsim1.0 and also details principles that have been implemented to systematically discern alterations in the stimulated dopamine release and reuptake dynamics.

Use of IPA to demonstrate loss of forest interior birds from isolated woodlots

USGS Publications Warehouse

Robbins, C.S.; Boone, D.D.; Purroy, F.J.

1983-01-01

'Empleo de indices puntuales de abundancia (IPA) para demostrar la perdida de aves forestales en bosques aislados'. En Maryland, E.U., se seleccionaron bloques boscosos de diferente superficie, divididos en seis clase de tamano (2,8-6 ha, 7-14, 20-30, 34-80, 105-1300, mayores de 4000 ha). En estas ?islas' forestales fue programado un conjunto de muestreos puntuales con estas caracteristicas: 1) Cada punto se visito tres veces. 2) En cada visita se hicieron cuatro censos consecutivos de 5 minutos de duracion, empleando diferentes simbolos para machos cantores, adultos no cantores, aves en vuelo y aves inmaduras. 3) Los conteos se hicieron en tres epocas: final de Mayo, mitad de Junio y final de Junio. 4) Se dividio el tiempo de censo en tres priodos horarios: 5,15-6,30 ; 6,30-8; 8-9,30 hrs. 5) Los puntos se agruparon en co juntos de 4 a 9, considerando que un conjunto es el nlimero que un observador puede cubrir por manana. 6) La vegetacion fue descrita exhaustivamente en cuanto composicion y fisionomla. El principal objetivo que se busca consiste en conocer los requisitos areales de ciertas especies de bosque muy sensibles a la fragmentacion del habitat. Puede observarse (Figura 1) que una serie de migrantes de largo alcance se asientan en relacion con el aumento de la superficie del rodal arbo1ado, sabre todo en macizos de 4.000 o mas hectareas. Sin embargo, las especies sedentarias (Fig. 2) tienen pauta de presencia irregular en funcion del area, forestal, con tendencia a presentarse menos en los bosques mas extensos, Dryocopus pileatus, por excepcion, reacciona negativamente al pequeno tamano de la parcela arbolado, prefiriendo bosques grandes. Parecida respuesta da tambien Sitta carolinensis. Aunque se sabe poco de las exigencias areales de las aves forestales americanas, el metodo de los IPA resulta muy adecuado para esta clase de investigacion de tanto interes en gestion ambiental, posibilitando colectar gran cantidad de datos comparables en un periodo de tiempo muy corto.

Prognosis of carotid dissecting aneurysms

PubMed Central

Larsson, Susanna C.; King, Alice; Madigan, Jeremy; Levi, Christopher; Norris, John W.

2017-01-01

Objective: To determine the natural history of dissecting aneurysm (DA) and whether DA is associated with an increased recurrent stroke risk and whether type of antithrombotic drugs (antiplatelets vs anticoagulants) modifies the persistence or development of DA. Methods: We included 264 patients with extracranial cervical artery dissection (CAD) from the Cervical Artery Dissection in Stroke Study (CADISS), a multicenter prospective study that compared antiplatelet with anticoagulation therapy. Logistic regression was used to estimate age- and sex-adjusted odds ratios. We conducted a systematic review of published studies assessing the natural history of DA and stroke risk in patients with non-surgically-treated extracranial CAD with DA. Results: In CADISS, DA was present in 24 of 264 patients at baseline. In 36 of 248 patients with follow-up neuroimaging at 3 months, 12 of the 24 baseline DAs persisted, and 24 new DA had developed. There was no association between treatment allocation (antiplatelets vs anticoagulants) and whether DA at baseline persisted at follow-up or whether new DA developed. During 12 months of follow-up, stroke occurred in 1 of 48 patients with DA and in 7 of 216 patients without DA (age- and sex-adjusted odds ratio 0.84; 95% confidence interval 0.10–7.31; p = 0.88). Published studies, mainly retrospective, showed a similarly low risk of stroke and no evidence of an increased stroke rate in patients with DA. Conclusions: The results of CADISS provide evidence suggesting that DAs may have benign prognosis and therefore medical treatment should be considered. PMID:28087823

A Behavioral and Genetic Dissection of Two Forms of Olfactory Plasticity in Caenorhabditis elegans: Adaptation and Habituation

PubMed Central

Bernhard, Nirit; van der Kooy, Derek

2000-01-01

Continuous presentation of an olfactory stimulus causes a decrement of the chemotaxis response in the nematode Caenorhabditis elegans. However, the differences between the learning process of habituation (a readily reversible decrease in behavioral response) and other types of olfactory plasticity such as adaptation (a decrement in response due to sensory fatigue, which cannot be dishabituated) have not been addressed. The volatile odorant diacetyl (DA) was used within a single paradigm to assess the distinct processes of olfactory adaptation and habituation. Preexposing and testing worms to 100% DA vapors caused a chemotaxis decrement that was not reversible despite the presentation of potentially dishabituating stimuli. This DA adaptation was abolished in worms with an odr-10 mutation (encoding a high-affinity DA receptor on the AWA neuron), even though naive chemotaxis remained unaffected. Conversely, DA adaptation remained intact in odr-1 mutants (defective in AWC neuron-mediated olfactory behavior), even though naive chemotaxis to DA decreased. Surprisingly, exposure to vapors of intermediate concentrations of DA (0.01% and 25%) did not cause worms to exhibit any response decrement. In contrast to preexposure to high DA concentrations, preexposure to low DA concentrations (0.001%) produced habituation of the chemotaxis response (a dishabituating stimulus could reverse the response decrement back to baseline levels). The distinct behavioral effects produced by DA preexposure highlight a concentration-dependent dissociation between two decremental olfactory processes: adaptation at high DA concentrations versus habituation at low DA concentrations. PMID:10940320

Identification of an abundant 56 kDa protein implicated in food allergy as granule-bound starch synthase

USDA-ARS?s Scientific Manuscript database

Rice, the staple food of South and East Asian counties, is considered to be hypoallergenic. However, several clinical studies have documented rice-induced allergy in sensitive patients. Rice proteins with molecular weights of 14-16 kDa, 26 kDa, 33 kDa and 56 kDa have been identified as allergens. Re...

DaRT: A CALL System to Help Students Practice and Develop Reasoning Skills in Choosing English Articles.

ERIC Educational Resources Information Center

Yoshii, Rika; Milne, Alastair

1998-01-01

Describes DaRT, a computer assisted language-learning system for helping English-as-a-Second-Language students master English articles. DaRT uses a diagrammatic reasoning tool to present communicative contexts for exercises in choosing appropriate articles. This paper describes the development of DaRT and DaRT's system components and concludes…

No Significant Increase in the Δ4- and Δ7-Dafachronic Acid Concentration in the Long-Lived glp-1 Mutant, nor in the Mutants Defective in Dauer Formation.

PubMed

Li, Tie-Mei; Liu, Weilong; Lu, Shan; Zhang, Yan-Ping; Jia, Le-Mei; Chen, Jie; Li, Xiangke; Lei, Xiaoguang; Dong, Meng-Qiu

2015-05-12

The steroid hormone dafachronic acid (DA) regulates dauer formation and lifespan in Caenorhabditis elegans by binding to the nuclear receptor DAF-12. However, little is known about how DA concentrations change under various physiologic conditions and about how DA/DAF-12 signaling interacts with other signaling pathways that also regulate dauer formation and lifespan. Using a sensitive bioanalytical method, we quantified the endogenous DA concentrations in a long-lived germline-less glp-1 mutant and in the Dauer formation-defective (Daf-d) mutants daf-12, daf-16, daf-5, and daf-3. We found that the DA concentration in the glp-1 mutant was similar to that in the wild type (WT). This result is contrary to the long-held belief that germline loss-induced longevity involves increased DA production and suggests instead that this type of longevity involves an enhanced response to DA. We also found evidence suggesting that increased DA sensitivity underlies lifespan extension triggered by exogenous DA. At the L2/L3 stage, the DA concentration in a daf-12 null mutant decreased to 22% of the WT level. This finding is consistent with the previously proposed positive feedback regulation between DAF-12 and DA production. Surprisingly, the DA concentrations in the daf-16, daf-5, and daf-3 mutants were only 19-34% of the WT level at the L2/L3 stage, slightly greater than those in the Dauer formation-constitutive (Daf-c) mutants at the pre-dauer stage (4-15% of the WT L2 control). Our experimental evidence suggested that the positive feedback between DA and DAF-12 was partially induced in the three Daf-d mutants. Copyright © 2015 Li et al.

Combined Application of UHPLC-QTOF/MS, HPLC-ELSD and 1 H-NMR Spectroscopy for Quality Assessment of DA-9801, A Standardised Dioscorea Extract.

PubMed

Kang, Kyo Bin; Ryu, Jayoung; Cho, Youngwoong; Choi, Sang-Zin; Son, Miwon; Sung, Sang Hyun

2017-05-01

DA-9801, a standardised 50% aqueous ethanolic extract of a mixture of Dioscorea japonica and D. nipponica, is a botanical drug candidate for the treatment of diabetic neuropathy, which finished its US phase II clinical trials recently. An advanced quality control method is needed for further development of DA-9801, considering its high contents of both primary and secondary metabolites. Development of a quality assessment strategy for DA-9801, based on the combination of UHPLC-QTOF/MS, HPLC-ELSD, and 1 H-NMR spectroscopy. The method was developed and tested with 15 batch products of DA-9801. The steroidal saponins of DA-9801 were tentatively identified by UHPLC-QTOF/MS and were quantified with the validated HPLC-ELSD method. Primary metabolites of DA-9801 were identified and profiled using 1 H-NMR spectrometry. The batch-to-batch equivalence of DA-9801 was tested with the 1 H-NMR spectra using spectral binning, correlation analysis, and principal component analysis. Six major saponins of DA-9801 were tentatively identified by UHPLC-QTOF/MS. Among them, protodioscin and dioscin were quantified by the validated HPLC-ELSD method. Twenty-six metabolites were identified in 1 H-NMR spectra. The similarity between DA-9801 batches could be evaluated with the NMR spectra of DA-9801. The 1 H-NMR method also revealed that two Dioscorea species contributed distinct amino acids to the contents of DA-9801. This study validates the effectiveness of UHPLC-QTOF/MS, HPLC-ELSD, and 1 H NMR-combined method for quality control of DA-9801 and its crude materials. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Attenuated response to methamphetamine sensitization and deficits in motor learning and memory after selective deletion of β-catenin in dopamine neurons.

PubMed

Diaz-Ruiz, Oscar; Zhang, Yajun; Shan, Lufei; Malik, Nasir; Hoffman, Alexander F; Ladenheim, Bruce; Cadet, Jean Lud; Lupica, Carl R; Tagliaferro, Adriana; Brusco, Alicia; Bäckman, Cristina M

2012-07-20

In the present study, we analyzed mice with a targeted deletion of β-catenin in DA neurons (DA-βcat KO mice) to address the functional significance of this molecule in the shaping of synaptic responses associated with motor learning and following exposure to drugs of abuse. Relative to controls, DA-βcat KO mice showed significant deficits in their ability to form long-term memories and displayed reduced expression of methamphetamine-induced behavioral sensitization after subsequent challenge doses with this drug, suggesting that motor learning and drug-induced learning plasticity are altered in these mice. Morphological analyses showed no changes in the number or distribution of tyrosine hydroxylase-labeled neurons in the ventral midbrain. While electrochemical measurements in the striatum determined no changes in acute DA release and uptake, a small but significant decrease in DA release was detected in mutant animals after prolonged repetitive stimulation, suggesting a possible deficit in the DA neurotransmitter vesicle reserve pool. However, electron microscopy analyses did not reveal significant differences in the content of synaptic vesicles per terminal, and striatal DA levels were unchanged in DA-βcat KO animals. In contrast, striatal mRNA levels for several markers known to regulate synaptic plasticity and DA neurotransmission were altered in DA-βcat KO mice. This study demonstrates that ablation of β-catenin in DA neurons leads to alterations of motor and reward-associated memories and to adaptations of the DA neurotransmitter system and suggests that β-catenin signaling in DA neurons is required to facilitate the synaptic remodeling underlying the consolidation of long-term memories.

Genetic Dissection of Midbrain Dopamine Neuron Development in vivo

PubMed Central

Ellisor, Debra; Rieser, Caroline; Voelcker, Bettina; Machan, Jason T.; Zervas, Mark

2012-01-01

Midbrain dopamine (MbDA) neurons are partitioned into medial and lateral cohorts that control complex functions. However, the genetic underpinnings of MbDA neuron heterogeneity are unclear. While it is known that Wnt1-expressing progenitors contribute to MbDA neurons, the role of Wnt1 in MbDA neuron development in vivo is unresolved. We show that mice with a spontaneous point mutation in Wnt1 have a unique phenotype characterized by the loss of medial MbDA neurons concomitant with a severe depletion of Wnt1-expressing progenitors and diminished LMX1a-expressing progenitors. Wnt1 mutant embryos also have alterations in a hierarchical gene regulatory loop suggesting multiple gene involvement in the Wnt1 mutant MbDA neuron phenotype. To investigate this possibility, we conditionally deleted Gbx2, Fgf8, and En1/2 after their early role in patterning and asked whether these genetic manipulations phenocopied the depletion of MbDA neurons in Wnt1 mutants. The conditional deletion of Gbx2 did not result in re-positioning or distribution of MbDA neurons. The temporal deletion of Fgf8 did not result in the loss of either LMX1a-expressing progenitors nor the initial population of differentiated MbDA neurons, but did result in a complete loss of MbDA neurons at later stages. The temporal deletion and species specific manipulation of En1/2 demonstrated a continued and species specific role of Engrailed genes in MbDA neuron development. Notably, our conditional deletion experiments revealed phenotypes dissimilar to Wnt1 mutants indicating the unique role of Wnt1 in MbDA neuron development. By placing Wnt1, Fgf8, and En1/2 in the context of their temporal requirement for MbDA neuron development, we further deciphered the developmental program underpinning MbDA neuron progenitors. PMID:23041116

Synergistic electron transfer effect-based signal amplification strategy for the ultrasensitive detection of dopamine.

PubMed

Lu, Qiujun; Chen, Xiaogen; Liu, Dan; Wu, Cuiyan; Liu, Meiling; Li, Haitao; Zhang, Youyu; Yao, Shouzhuo

2018-05-15

The selective and sensitive detection of dopamine (DA) is of great significance for the identification of schizophrenia, Huntington's disease, and Parkinson's disease from the perspective of molecular diagnostics. So far, most of DA fluorescence sensors are based on the electron transfer from the fluorescence nanomaterials to DA-quinone. However, the limited electron transfer ability of the DA-quinone affects the level of detection sensitivity of these sensors. In this work, based on the DA can reduce Ag + into AgNPs followed by oxidized to DA-quinone, we developed a novel silicon nanoparticles-based electron transfer fluorescent sensor for the detection of DA. As electron transfer acceptor, the AgNPs and DA-quinone can quench the fluorescence of silicon nanoparticles effectively through the synergistic electron transfer effect. Compared with traditional fluorescence DA sensors, the proposed synergistic electron transfer-based sensor improves the detection sensitivity to a great extent (at least 10-fold improvement). The proposed sensor shows a low detection limit of DA, which is as low as 0.1 nM under the optimal conditions. This sensor has potential applicability for the detection of DA in practical sample. This work has been demonstrated to contribute to a substantial improvement in the sensitivity of the sensors. It also gives new insight into design electron transfer-based sensors. Copyright © 2018. Published by Elsevier B.V.

D-amphetamine (A)-induced dopamine (DA) release is not strictly dependent on newly-synthesized transmitter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parker, E.; Cubeddu, L.

1986-03-05

A is thought to exert its stimulant effects by releasing DA from a newly synthesized transmitter pool. This hypothesis was evaluated directly by measuring the basal efflux and electrically-evoked release of endogenous DA and dihydroxyphenylacetic acid (DOPAC). In striatal slices from reserpine-treated rabbits A increased DA efflux, reduced DOPAC efflux, and inhibited electrically-evoked /sup 3/H-ACh release in a concentration-dependent manner. These effects could not be mimicked by inhibition of neuronal uptake or MAO, but were blocked by inhibition of DA synthesis or neuronal uptake, and were potentiated by inhibition of MAO. In slices with intact vesicular transmitter stores A inducedmore » DA efflux was 2-fold greater than that seen in slices having no vesicular stores. Inhibition of DA synthesis reduced A-induced DA efflux by 60%, but had little effect on the ability of A to inhibit /sup 3/H-ACh release. A also increased the electrical stimulation-evoked overflow of DA (an effect which was attenuated slightly by synthesis inhibition), and potently inhibited DOPAC overflow. These results suggest that: 1) A facilitates efflux of axoplasmic DA by an accelerated exchange diffusion mechanism. The releasable axoplasmic pool is derived from newly synthesized and vesicular transmitter pools; 2) postsynaptic indices of transmitter release may be misleading; and 3) A increases electrically-evoked DA release possibly by inhibiting neuronal uptake.« less

Dehydroandrographolide, an iNOS inhibitor, extracted from Andrographis paniculata (Burm.f.) Nees, induces autophagy in human oral cancer cells.

PubMed

Hsieh, Ming-Ju; Lin, Chiao-Wen; Chiou, Hui-Ling; Yang, Shun-Fa; Chen, Mu-Kuan

2015-10-13

Autophagy, which is constitutively executed at the basal level in all cells, promotes cellular homeostasis by regulating the turnover of organelles and proteins. Andrographolide and dehydroandrographolide (DA) are the two principle components of Andrographis paniculata (Burm.f.) Nees. and are the main contributors to its therapeutic properties. However, the pharmacological activities of dehydroandrographolide (DA) remain unclear. In this study, DA induces oral cancer cell death by activating autophagy. Treatment with autophagy inhibitors inhibited DA-induced human oral cancer cell death. In addition, DA increased LC3-II expression and reduced p53 expression in a time- and concentration-dependent manner. Furthermore, DA induced autophagy and decreased cell viability through modulation of p53 expression. DA-induced autophagy was triggered by an activation of JNK1/2 and an inhibition of Akt and p38. In conclusion, this study demonstrated that DA induced autophagy in human oral cancer cells by modulating p53 expression, activating JNK1/2, and inhibiting Akt and p38. Finally, an administration of DA effectively suppressed the tumor formation in the oral carcinoma xenograft model in vivo. This is the first study to reveal the novel function of DA in activating autophagy, suggesting that DA could serve as a new and potential chemopreventive agent for treating human oral cancer.

Dehydroandrographolide, an iNOS inhibitor, extracted from from Andrographis paniculata (Burm.f.) Nees, induces autophagy in human oral cancer cells

PubMed Central

Hsieh, Ming-Ju; Lin, Chiao-Wen; Chiou, Hui-Ling; Yang, Shun-Fa; Chen, Mu-Kuan

2015-01-01

Autophagy, which is constitutively executed at the basal level in all cells, promotes cellular homeostasis by regulating the turnover of organelles and proteins. Andrographolide and dehydroandrographolide (DA) are the two principle components of Andrographis paniculata (Burm.f.) Nees. and are the main contributors to its therapeutic properties. However, the pharmacological activities of dehydroandrographolide (DA) remain unclear. In this study, DA induces oral cancer cell death by activating autophagy. Treatment with autophagy inhibitors inhibited DA-induced human oral cancer cell death. In addition, DA increased LC3-II expression and reduced p53 expression in a time- and concentration-dependent manner. Furthermore, DA induced autophagy and decreased cell viability through modulation of p53 expression. DA-induced autophagy was triggered by an activation of JNK1/2 and an inhibition of Akt and p38. In conclusion, this study demonstrated that DA induced autophagy in human oral cancer cells by modulating p53 expression, activating JNK1/2, and inhibiting Akt and p38. Finally, an administration of DA effectively suppressed the tumor formation in the oral carcinoma xenograft model in vivo. This is the first study to reveal the novel function of DA in activating autophagy, suggesting that DA could serve as a new and potential chemopreventive agent for treating human oral cancer. PMID:26356821

Apoptosis of lactotrophs induced by D2 receptor activation is estrogen dependent.

PubMed

Radl, Daniela B; Zárate, Sandra; Jaita, Gabriela; Ferraris, Jimena; Zaldivar, Verónica; Eijo, Guadalupe; Seilicovich, Adriana; Pisera, Daniel

2008-01-01

Dopamine (DA) inhibits prolactin release and reduces lactotroph proliferation by activating D2 receptors. DA and its metabolite, 6-hydroxydopamine (6-OHDA), induce apoptosis in different cell types. DA receptors and DA transporter (DAT) were implicated in this action. Considering that estradiol sensitizes anterior pituitary cells to proapoptotic stimuli, we investigated the effect of estradiol on the apoptotic action of DA and 6-OHDA in anterior pituitary cells, and the involvement of the D2 receptor and DAT in the proapoptotic effect of DA. Viability of cultured anterior pituitary cells from ovariectomized rats was determined by MTS assay. Apoptosis was evaluated by Annexin-V/flow cytometry and TUNEL. Lactotrophs were identified by immunocytochemistry. DA induced apoptosis of lactotrophs in an estrogen-dependent manner. In contrast, estradiol was not required to trigger the apoptotic action of 6-OHDA. Cabergoline, a D2 receptor agonist, induced lactotroph apoptosis, while sulpiride, a D2 receptor antagonist, blocked DA-induced cell death. The blockade of DAT by GBR12909 did not affect the apoptotic action of DA, but inhibited 6-OHDA-induced apoptosis. These data show that DA, through D2 receptor activation, induces apoptosis of estrogen-sensitized anterior pituitary cells, and suggest that DA contributes to the control of lactotroph number not only by inhibiting proliferation but also by inducing apoptosis. 2008 S. Karger AG, Basel.

Enhanced dopamine detection sensitivity by PEDOT/graphene oxide coating on in vivo carbon fiber electrodes.

PubMed

Taylor, I Mitch; Robbins, Elaine M; Catt, Kasey A; Cody, Patrick A; Happe, Cassandra L; Cui, Xinyan Tracy

2017-03-15

Dopamine (DA) is a monoamine neurotransmitter responsible for regulating a variety of vital life functions. In vivo detection of DA poses a challenge due to the low concentration and high speed of physiological signaling. Fast scan cyclic voltammetry at carbon fiber microelectrodes (CFEs) is an effective method to monitor real-time in vivo DA signaling, however the sensitivity is somewhat limited. Electrodeposition of poly(3,4-ethylene dioxythiophene) (PEDOT)/graphene oxide (GO) onto the CFE surface is shown to increase the sensitivity and lower the limit of detection for DA compared to bare CFEs. Thicker PEDOT/GO coatings demonstrate higher sensitivities for DA, but display the negative drawback of slow adsorption and electron transfer kinetics. The moderate thickness resulting from 25 s electrodeposition of PEDOT/GO produces the optimal electrode, exhibiting an 880% increase in sensitivity, a 50% decrease in limit of detection and minimally altered electrode kinetics. PEDOT/GO coated electrodes rapidly and robustly detect DA, both in solution and in the rat dorsal striatum. This increase in DA sensitivity is likely due to increasing the electrode surface area with a PEDOT/GO coating and improved adsorption of DA's oxidation product (DA-o-quinone). Increasing DA sensitivity without compromising electrode kinetics is expected to significantly improve our understanding of the DA function in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

Possibility of the transformation of eEF-2 (100 kDa) to eEF-2 (65 kDa) in the peptide elongation process in vitro.

PubMed

Gajko, A; Sredzińska, K; Galasiński, W; Gindzieński, A

1999-02-16

Two active eEF-2 polypeptides of approximately 100 and 65 kDa were copurified from rat liver cells and separated. The fate of eEF-2 (100 kDa) during its binding to ribosomes and in the translocation step of the peptide elongation process was investigated. It was shown that eEF-2 (100 kDa) did not change its form during the process of binding to the ribosomes. In the postribosomal supernatant, obtained from the postincubation mixture of the elongation process, only eEF-2 (65 kDa) was found. These results suggest that the form of eEF-2 (100 kDa), when bound to the ribosome during the elongation process, is transformed to eEF-2 (65 kDa). Copyright 1999 Academic Press.

Physiological adaptation of maternal plasma volume during pregnancy: a systematic review and meta-analysis.

PubMed

de Haas, S; Ghossein-Doha, C; van Kuijk, S M J; van Drongelen, J; Spaanderman, M E A

2017-02-01

To describe the physiological pattern of gestational plasma volume adjustments in normal singleton pregnancy and compare this with the pattern in pregnancies complicated by pregnancy-induced hypertension, pre-eclampsia or fetal growth restriction. We performed a meta-analysis of the current literature on plasma volume adjustments during physiological and complicated pregnancies. Literature was retrieved from PubMed (NCBI) and EMBASE (Ovid) databases. Included studies reported both reference plasma volume measurements (non-pregnant, prepregnancy or postpartum) and measurements obtained during predetermined gestational ages. Mean differences bet ween the reference and pregnancy plasma volume measurements were calculated for predefined intervals of gestational age using a random-effects model described by DerSimonian and Laird. Thirty studies were included in the meta-analysis with publication dates ranging from 1934 to 2007. Plasma volume increased in the first weeks of pregnancy, with the steepest increase occurring during the second trimester. Plasma volume continued to increase in the third trimester with a pooled maximum increase of 1.13 L (95% CI, 1.07-1.19 L), an increase of 45.6% (95% CI, 43.0-48.1%) in physiological pregnancies compared with the reference value. The plasma volume expansion in gestational hypertensive and growth-restricted pregnancies was 0.80 L (95% CI, 0.59-1.02 L), an increase of 32.3% (95% CI, 23.6-41.1%) in the third trimester, a smaller increase than in physiological pregnancies (P < 0.0001). During physiological pregnancy, plasma volume increases by, on average, more than 1 L as compared with non-pregnant conditions. In pregnancies complicated by pregnancy-induced hypertension, pre-eclampsia or fetal growth restriction, plasma volume increase in the third trimester is 13.3% lower than in normal pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Adaptación fisiológica del volumen del plasma materno durante el embarazo: una revisi\\xF3n sistemática y metaanálisis RESUMEN OBJETIVO: Describir el patrón fisiológico de los cambios en el volumen del plasma gestacional en embarazos normales con feto único y compararlo con el patrón en los embarazos complicados por hipertensión gestacional, preeclampsia o restricción del crecimiento fetal. MÉTODOS: Se realizó un metaanálisis de la literatura actual sobre los cambios en el volumen de plasma durante embarazos complicados y fisiológicos. La literatura se obtuvo de las bases de datos PubMed (NCBI) y EMBASE (Ovid). Los estudios incluidos mencionaban tanto mediciones de referencia del volumen plasmático (no embarazada, antes del embarazo o después del parto) como mediciones tomadas a edades gestacionales predeterminadas. Se calcularon las medias de las diferencias entre las mediciones de referencia y las del embarazo para el volumen plasmático a intervalos predefinidos de la edad gestacional, utilizando un modelo de efectos aleatorios descrito por DerSimonian y Laird. En el metaanálisis se incluyeron treinta estudios con fechas de publicación entre 1934 y 2007. El volumen plasmático aumentó en las primeras semanas de embarazo y el mayor incremento se produjo durante el segundo trimestre. El volumen de plasma continuó aumentando en el tercer trimestre con un aumento combinado máximo de 1,13L (IC 95%, 1,7-1,19 L), lo que supone un aumento del 45,6% (IC 95%, 43,0-48,1%) en embarazos fisiológicas en comparación con el valor de referencia. El aumento del volumen plasmático en los embarazos con hipertensión y con crecimiento intrauterino restringido fue de 0,80L (IC 95%, 0,59-1,02 L), lo que supone un aumento del 32,3% (IC 95%, 23,6-41,1%) en el tercer trimestre, y un incremento menor que en los embarazos fisiológicos (P <0,0001). Durante el embarazo fisiológico el volumen de plasma aumenta, en promedio, más de 1L, en comparación con el de las no embarazadas. En los embarazos complicados por hipertensión gestacional, preeclampsia o restricción del crecimiento fetal, el aumento del volumen plasmático en el tercer trimestre es un 13,3% menor que en el embarazo normal. :meta : ,、。 : meta。PubMed(NCBI)EMBASE(Ovid)。(、)。DerSimonianLaird,。 : Meta30,19342007。,。,1.13 L(95% CI,1.07~1.19 L),,45.6%(95% CI,43.0%~48.1%)。0.80 L(95%CI,0.59~1.02 L),32.3%(95% CI,23.6%~41.1%),(P<0.0001)。 : ,,1 L。、,13.3%。. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Tryptic digestion of human GPIIIa. Isolation and biochemical characterization of the 23 kDa N-terminal glycopeptide carrying the antigenic determinant for a monoclonal antibody (P37) which inhibits platelet aggregation.

PubMed Central

Calvete, J J; Rivas, G; Maruri, M; Alvarez, M V; McGregor, J L; Hew, C L; Gonzalez-Rodriguez, J

1988-01-01

Early digestion of pure human platelet glycoprotein IIIa (GPIIIa) leads to a single cleavage of the molecule at 23 kDa far from one of the terminal amino acids. Automated Edman degradation demonstrates that GPIIIa and the smaller (23 kDa) tryptic fragment share the same N-terminal amino acid sequence. A further cleavage occurs in the larger fragment (80 kDa), reducing its apparent molecular mass by 10 kDa. The 23 kDa fragment remains attached to the larger ones in unreduced samples. Stepwise reduction of early digested GPIIIa with dithioerythritol selectively reduces the single disulphide bond joining the smaller (23 kDa) to the larger (80/70 kDa) fragments. Two fractions were obtained by size-exclusion chromatography of early digested GPIIIa after partial or full reduction and alkylation. The larger-size fraction contains the 80/70 kDa fragments, while the 23 kDa fragment is isolated in the smaller. The amino acid compositions of these fractions do not differ very significantly from the composition of GPIIIa; however the 23 kDa fragment contains only 10.2% by weight of sugars and is richer in neuraminic acid. Disulphide bonds are distributed four in the 23 kDa glycopeptide and 20-21 in the 80/70 kDa glycopeptide. The epitope for P37, a monoclonal antibody which inhibits platelet aggregation [Melero & González-Rodríguez (1984) Eur. J. Biochem. 141, 421-427] is situated within the first 17 kDa of the N-terminal region of GPIIIa, which gives a special functional interest to this extracellular region of GPIIIa. On the other hand, the epitopes for GPIIIa-specific monoclonal antibodies, P6, P35, P40 and P97, which do not interfere with platelet aggregation, are located within the larger tryptic fragment (80/70 kDa). Thus, the antigenic areas available in the extracellular surface of GPIIIa for these five monoclonal antibodies are now more precisely delineated. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:2455507

Design of New Bridge-Ring Energetic Compounds Obtained by Diels-Alder Reactions of Tetranitroethylene Dienophile.

PubMed

He, Piao; Mei, Hao-Zheng; Wu, Le; Yang, Jun-Qing; Zhang, Jian-Guo; Cohen, Adva; Gozin, Michael

2018-03-29

The density functional theory method was employed to calculate three-dimensional structures for a series of novel explosophores. The design of new molecules (DA1-DA12) was based on the bridge-ring structures that could be formed via Diels-Alder (DA) reaction of selected nitrogen-rich dienes and tetranitroethylene dienophile. The feasibility of the proposed DA reactions was predicted on the basis of the molecular orbital theory. The strong interactions between the HOMO of dienes, with electron-donating groups (Diene2, Diene6, and Diene8), and the LUMO of tetranitroethylene dienophile suggested thermodynamically favorable formation of the desired DA reaction products. In addition to molecular structures of the explored DA compounds, their physicochemical and energetic properties were also calculated in detail. Due to compact bridge-ring structures, new energetic molecules have highly positive heats of formation (up to 1124.90 kJ·mol -1 ) and high densities (up to 2.04 g·cm -3 ). Also, as a result of all-right ratios of nitrogen and oxygen, most of the new compounds possess high detonation velocities (8.28-10.02 km·s -1 ) and high detonation pressures (30.87-47.83 GPa). Energetic compounds DA1, DA4, and DA12 exhibit a superior detonation performance over widely used HMX explosive, and DA5, DA7, and DA10 could be comparable to the state-of-the-art CL-20 and ONC explosives. Our proposed designs and synthetic methodology should provide a platform for the development of novel energetic materials with superior performance.

Heterotetrameric composition of aquaporin-4 water channels.

PubMed

Neely, J D; Christensen, B M; Nielsen, S; Agre, P

1999-08-24

Aquaporin (AQP) water channel proteins are tetrameric assemblies of individually active approximately 30 kDa subunits. AQP4 is the predominant water channel protein in brain, but immunoblotting of native tissues has previously yielded multiple poorly resolved bands. AQP4 is known to encode two distinct mRNAs with different translation initiating methionines, M1 or M23. Using SDS-PAGE urea gels and immunoblotting with anti-peptide antibodies, four polypeptides were identified in brain and multiple other rat tissues with the following levels of expression: 32 kDa > 34 kDa > 36 kDa > 38 kDa. The 34 and 38 kDa polypeptides react with an antibody specific for the N-terminus of the M1 isoform, and 32 and 36 kDa correspond to the shorter M23 isoform. Immunogold electron microscopic studies with rat cerebellum cryosections demonstrated that the 34 kDa polypeptide colocalizes in perivascular astrocyte endfeet where the 32 kDa polypeptide is abundantly expressed. Velocity sedimentation, cross-linking, and immunoprecipitation analyses of detergent-solubilized rat brain revealed that the 32 and 34 kDa polypeptides reside within heterotetramers. Immunoprecipitation of AQP4 expressed in Xenopus laevis oocytes demonstrated that heterotetramer formation reflects the relative expression levels of the 32 and 34 kDa polypeptides; however, tetramers containing different compositions of the two polypeptides exhibit similar water permeabilities. These studies demonstrate that AQP4 heterotetramers are formed from two overlapping polypeptides and indicate that the 22-amino acid sequence at the N-terminus of the 34 kDa polypeptide does not influence water permeability but may contribute to membrane trafficking or assembly of arrays.

Oleic Acid in the Ventral Tegmental Area Inhibits Feeding, Food Reward, and Dopamine Tone.

PubMed

Hryhorczuk, Cecile; Sheng, Zhenyu; Décarie-Spain, Léa; Giguère, Nicolas; Ducrot, Charles; Trudeau, Louis-Éric; Routh, Vanessa H; Alquier, Thierry; Fulton, Stephanie

2018-02-01

Long-chain fatty acids (FAs) act centrally to decrease food intake and hepatic glucose production and alter hypothalamic neuronal activity in a manner that depends on FA type and cellular transport proteins. However, it is not known whether FAs are sensed by ventral tegmental area (VTA) dopamine (DA) neurons to control food-motivated behavior and DA neurotransmission. We investigated the impact of the monounsaturated FA oleate in the VTA on feeding, locomotion, food reward, and DA neuronal activity and DA neuron expression of FA-handling proteins and FA uptake. A single intra-VTA injection of oleate, but not of the saturated FA palmitate, decreased food intake and increased locomotor activity. Furthermore, intra-VTA oleate blunted the rewarding effects of high-fat/sugar food in an operant task and inhibited DA neuronal firing. Using sorted DA neuron preparations from TH-eGFP mice we found that DA neurons express FA transporter and binding proteins, and are capable of intracellular transport of long-chain FA. Finally, we demonstrate that a transporter blocker attenuates FA uptake into DA neurons and blocks the effects of intra-VTA oleate to decrease food-seeking and DA neuronal activity. Together, these results suggest that DA neurons detect FA and that oleate has actions in the VTA to suppress DA neuronal activity and food seeking following cellular incorporation. These findings highlight the capacity of DA neurons to act as metabolic sensors by responding not only to hormones but also to FA nutrient signals to modulate food-directed behavior.

Concentration-dependent activation of dopamine receptors differentially modulates GABA release onto orexin neurons

PubMed Central

Linehan, Victoria; Trask, Robert B.; Briggs, Chantalle; Rowe, Todd M.; Hirasawa, Michiru

2017-01-01

Dopamine (DA) and orexin neurons play important roles in reward and food intake. There are anatomical and functional connections between these two cell groups, where orexin peptides stimulate DA neurons in the ventral tegmental area and DA inhibits orexin neurons in the hypothalamus. However, the cellular mechanisms underlying DA action on orexin neurons remain incompletely understood. Therefore, the effect of DA on inhibitory transmission to orexin neurons was investigated in rat brain slices using whole cell patch clamp technique. We found that DA modulated the frequency of spontaneous and miniature IPSCs (mIPSCs) in a concentration dependent, bidirectional manner. Low (1 μM) and high concentrations (100 μM) of DA decreased and increased IPSC frequency, respectively. These effects did not accompany a change in mIPSC amplitude and persisted in the presence of G protein signaling inhibitor GDPβS in the pipette, suggesting that DA acts presynaptically. The decrease in mIPSC frequency was mediated by D2 receptors, whereas the increase required co-activation of D1 and D2 receptors and subsequent activation of phospholipase C. In summary, our results suggest that DA has complex effects on GABAergic transmission to orexin neurons, involving cooperation of multiple receptor subtypes. The direction of dopaminergic influence on orexin neurons is dependent on the level of DA in the hypothalamus. At low levels DA disinhibits orexin neurons whereas at high levels it facilitates GABA release, which may act as negative feedback to curb the excitatory orexinergic output to DA neurons. These mechanisms may have implications for consummatory and motivated behaviours. PMID:26036709

Age, period and cohort trends in drug abuse hospitalizations within the total Swedish population (1975-2010)*

PubMed Central

Giordano, Giuseppe N.; Ohlsson, Henrik; Kendler, Kenneth S.; Winkleby, Marilyn A.; Sundquist, Kristina; Sundquist, Jan

2014-01-01

Background: The societal consequences of drug abuse (DA) are severe and well documented, the World Health Organization recommending tracking of population trends for effective policy responses in treatment of DA and delivery of health care services. However, to correctly identify possible sources of DA change, one must first disentangle three different time-related influences on the need for treatment due to DA: age effects, period effects and cohort effects. Methods: We constructed our main Swedish national DA database (spanning four decades) by linking healthcare data from the Swedish Hospital Discharge Register to individuals, which included hospitalisations in Sweden for 1975-2010. All hospitalized DA cases were identified by ICD codes. Our Swedish national sample consisted of 3,078,129 men and 2,921,816 women. We employed a cross-classified multilevel logistic regression model to disentangle any net age, period and cohort effects on DA hospitalization rates. Results: We found distinct net age, period and cohort effects, each influencing the predicted probability ofhospitalisation for DA in men and women. Peak age for DA in both sexes was 33-35 years; net period effects showed an increase in hospitalisation for DA from 1996 to 2001; and in birth cohorts 1968-74, we saw a considerable reduction (around 75%) in predicted probability of hospitalisation for DA. Conclusions: The use of hospital admissions could be regarded as a proxy of the population's health service use for DA. Our results may thus constitute a basis for effective prevention planning, treatment and other appropriate policy responses. PMID:24300899

Persistent Adaptations in Afferents to Ventral Tegmental Dopamine Neurons after Opiate Withdrawal

PubMed Central

Kaufling, Jennifer

2015-01-01

Protracted opiate withdrawal is accompanied by altered responsiveness of midbrain dopaminergic (DA) neurons, including a loss of DA cell response to morphine, and by behavioral alterations, including affective disorders. GABAergic neurons in the tail of the ventral tegmental area (tVTA), also called the rostromedial tegmental nucleus, are important for behavioral responses to opiates. We investigated the tVTA–VTA circuit in rats after chronic morphine exposure to determine whether tVTA neurons participate in the loss of opiate-induced disinhibition of VTA DA neurons observed during protracted withdrawal. In vivo recording revealed that VTA DA neurons, but not tVTA GABAergic neurons, are tolerant to morphine after 2 weeks of withdrawal. Optogenetic stimulation of tVTA neurons inhibited VTA DA neurons similarly in opiate-naive and long-term withdrawn rats. However, tVTA inactivation increased VTA DA activity in opiate-naive rats, but not in withdrawn rats, resembling the opiate tolerance effect in DA cells. Thus, although inhibitory control of DA neurons by tVTA is maintained during protracted withdrawal, the capacity for disinhibitory control is impaired. In addition, morphine withdrawal reduced both tVTA neural activity and tonic glutamatergic input to VTA DA neurons. We propose that these changes in glutamate and GABA inputs underlie the apparent tolerance of VTA DA neurons to opiates after chronic exposure. These alterations in the tVTA–VTA DA circuit could be an important factor in opiate tolerance and addiction. Moreover, the capacity of the tVTA to inhibit, but not disinhibit, DA cells after chronic opiate exposure may contribute to long-term negative affective states during withdrawal. SIGNIFICANCE STATEMENT Dopaminergic (DA) cells of the ventral tegmental area (VTA) are the origin of a brain reward system and are critically involved in drug abuse. Morphine has long been known to affect VTA DA cells via GABAergic interneurons. Recently, GABAergic neurons caudal to the VTA were discovered and named the tail of VTA (tVTA). Here, we show that tVTA GABA neurons lose their capacity to disinhibit, but not to inhibit, VTA DA cells after chronic opiate exposure. The failure of disinhibition was associated with a loss of glutamatergic input to DA neurons after chronic morphine. These findings reveal mechanisms by which the tVTA may play a key role in long-term negative affective states during opiate withdrawal. PMID:26180204

Effect of gamma irradiation on the expressed proteins in the foodborne pathogen Staphylococcus aureus

NASA Astrophysics Data System (ADS)

Trudeau, Karine; Dang Vu, Khanh; Shareck, François; Lacroix, Monique

2012-08-01

A capillary electrophoresis method with UV detection was developed to analyze protein composition of the foodborne pathogen Staphylococcus aureus. Bacterial samples containing 109 CFU/ml, obtained after two cycles of incubations of 24 h, were gamma irradiated at different doses of 1.2, 3.5 and 2.9 kGy to respectively create damage cells, to kill cells and to provoke viable but non cultivable cells (VBNC). It was observed that an irradiation at a sensitive dose of 1.2 kGy caused a significantly increase in the protein with molecular weight (MW) of 17.7 kDa (from 0.61% to 1.2%). This treatment also caused decreases in the expressed proteins with the MWs of 16.3 kDa (from 6.2% to 5.3%) and of 23.4 kDa (from 4.0% to 2.30%). Irradiation at a VBCN dose of 2.9 kGy caused increases in expressed proteins with the MWs of 17.7 kDa (from 0.61% to 3.43%), 18.7 kDa (from 1.04% to 4.30%), 19.5 kDa (from 0.71% to 2.30%), 21.1 kDa (from 1.20% to 3.80%). Moreover, this treatment (2.9 kGy) also caused significantly decreases (P≤0.05) in the expressed proteins with the MW of 30.7 kDa (from 8.6% to 5.15%), 36.3 kDa (from 3.1% to 2.7%) and 40.5 kDa (from 11.3% to 8.5%). Finally, for the irradiation at a lethal dose of 3.5 kGy, it can be found that the expressed proteins with the MW of 17.7 kDa, 18.7 kDa and 19.5 kDa were increased less than that of expressed proteins at the VCNC dose (2.9 kGy) and these might be the very important proteins which are responsible for the survival of the S. aureus. Further, there were also the decreases in expressed proteins with the MW of 30.7 kDa, 36.3 kDa and 75.1 kDa at this dose of treatment (3.5 kGy) which can be expected that these proteins are seriously affected at high dose of γ-irradiation treatment.

TGF-β Signaling in Dopaminergic Neurons Regulates Dendritic Growth, Excitatory-Inhibitory Synaptic Balance, and Reversal Learning.

PubMed

Luo, Sarah X; Timbang, Leah; Kim, Jae-Ick; Shang, Yulei; Sandoval, Kadellyn; Tang, Amy A; Whistler, Jennifer L; Ding, Jun B; Huang, Eric J

2016-12-20

Neural circuits involving midbrain dopaminergic (DA) neurons regulate reward and goal-directed behaviors. Although local GABAergic input is known to modulate DA circuits, the mechanism that controls excitatory/inhibitory synaptic balance in DA neurons remains unclear. Here, we show that DA neurons use autocrine transforming growth factor β (TGF-β) signaling to promote the growth of axons and dendrites. Surprisingly, removing TGF-β type II receptor in DA neurons also disrupts the balance in TGF-β1 expression in DA neurons and neighboring GABAergic neurons, which increases inhibitory input, reduces excitatory synaptic input, and alters phasic firing patterns in DA neurons. Mice lacking TGF-β signaling in DA neurons are hyperactive and exhibit inflexibility in relinquishing learned behaviors and re-establishing new stimulus-reward associations. These results support a role for TGF-β in regulating the delicate balance of excitatory/inhibitory synaptic input in local microcircuits involving DA and GABAergic neurons and its potential contributions to neuropsychiatric disorders. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Apomorphine and the dopamine hypothesis of schizophrenia: a dilemma?

PubMed Central

Dépatie, L; Lal, S

2001-01-01

The dopamine (DA) hypothesis of schizophrenia implicates an enhancement of DA function in the pathophysiology of the disorder, at least in the genesis of positive symptoms. Accordingly, apomorphine, a directly acting DA receptor agonist, should display psychotomimetic properties. A review of the literature shows little or no evidence that apomorphine, in doses that stimulate postsynaptic DA receptors, induces psychosis in non-schizophrenic subjects or a relapse or exacerbation of psychotic symptoms in patients with schizophrenia. After a detailed review of the literature reporting psychotogenic effects of apomorphine in patients with Parkinson's disease, an interpretation of these data is difficult, in part because of several confounding factors, such as the concomitant use of drugs known to induce psychosis and the advanced state of the progressive neurological disorder. In the context of the DA hypothesis of schizophrenia, the limited ability of apomorphine to induce psychosis, in contrast to indirectly acting DA agonists that increase synaptic DA, may be explained by the relatively weak affinity of apomorphine for the D3 receptor compared with DA. Alternatively, enhancement of DA function, though necessary, may be insufficient by itself to induce psychosis. PMID:11394190

Electrospray ionization mass analysis of normal and genetic variants of human serum albumin.

PubMed

Brennan, S O

1998-11-01

Both normal albumin (Al A) and genetically modified forms were isolated from six heterozygous subjects. Albumins from each individual were analyzed by electrospray ionization mass spectrometry (ESI MS), and the mass was compared with that predicted from the protein sequence. In all cases, the Al A was heterogeneous, with components of mass (+/- SE) 66463+/-4, 66586+/-3, and 66718+/-5 Da. Each genetic variant showed similar heterogeneity. The mass increase in Al Casebrook (2214 Da) was very close to that predicted (2205 Da) from protein and carbohydrate sequence analysis, whereas the increase in Al Redhill (2378 Da) was close to that expected (2392 Da) for an Arg-albumin with a disialylated N-linked biantennary oligosaccharide and an Ala-->Thr mutation. The circulating proalbumins, Christchurch and Blenheim, had mass increases of 748 and 756 Da, respectively, over Al A; in excellent agreement with theoretical values of 744 and 756. Clear shifts in mass were also detected for the point substitutions 177Cys-->Phe (44 Da), 1Asp-->Val (20 Da), and Arg-albumin (160 Da).

Dynamic Assessment for 3- and 4-Year-Old Children Who Use Augmentative and Alternative Communication: Evaluating Expressive Syntax.

PubMed

Binger, Cathy; Kent-Walsh, Jennifer; King, Marika

2017-07-12

The developmental readiness to produce early sentences with an iPad communication application was assessed with ten 3- and 4-year-old children with severe speech disorders using graduated prompting dynamic assessment (DA) techniques. The participants' changes in performance within the DA sessions were evaluated, and DA performance was compared with performance during a subsequent intervention. Descriptive statistics were used to examine patterns of performance at various cueing levels and mean levels of cueing support. The Wilcoxon signed-ranks test was used to measure changes within the DA sessions. Correlational data were calculated to determine how well performance in DA predicted performance during a subsequent intervention. Participants produced targets successfully in DA at various cueing levels, with some targets requiring less cueing than others. Performance improved significantly within the DA sessions-that is, the level of cueing required for accurate productions of the targets decreased during DA sessions. Last, moderate correlations existed between DA scores and performance during the intervention for 3 out of 4 targets, with statistically significant findings for 2 of 4 targets. DA offers promise for examining the developmental readiness of young children who use augmentative and alternative communication to produce early expressive language structures.

Developmental analysis of the dopamine-containing neurons of the Drosophila brain

PubMed Central

Hartenstein, Volker; Cruz, Louie; Lovick, Jennifer K.; Guo, Ming

2016-01-01

The Drosophila dopaminergic (DA) system consists of a relatively small number of neurons clustered throughout the brain and ventral nerve cord. Previous work shows that clusters of DA neurons innervate different brain compartments, which in part accounts for functional diversity of the DA system. In this paper, we analyzed the association between DA neuron clusters and specific brain lineages, developmental and structural units of the Drosophila brain which provide a framework of connections that can be followed throughout development. The hatching larval brain contains six groups of primary DA neurons (born in the embryo), which we assign to six distinct lineages. We can show that all larval DA clusters persist into the adult brain. Some clusters increase in cell number during late larval stages while others do not become DA-positive until early pupa. Ablating neuroblasts with hydroxyurea (HU) prior to onset of larval proliferation (generates secondary neurons) confirms these added DA clusters are primary neurons born in the embryo, rather than secondary neurons. A single cluster that becomes DA-positive in the late pupa, PAM1/lineage DALcm1/2, forms part of a secondary lineage which can be ablated by larval HU application. By supplying lineage information for each DA cluster, our analysis promotes further developmental and functional analyses of this important system of neurons. PMID:27350102

Evolution of the ATLAS PanDA workload management system for exascale computational science

NASA Astrophysics Data System (ADS)

Maeno, T.; De, K.; Klimentov, A.; Nilsson, P.; Oleynik, D.; Panitkin, S.; Petrosyan, A.; Schovancova, J.; Vaniachine, A.; Wenaus, T.; Yu, D.; Atlas Collaboration

2014-06-01

An important foundation underlying the impressive success of data processing and analysis in the ATLAS experiment [1] at the LHC [2] is the Production and Distributed Analysis (PanDA) workload management system [3]. PanDA was designed specifically for ATLAS and proved to be highly successful in meeting all the distributed computing needs of the experiment. However, the core design of PanDA is not experiment specific. The PanDA workload management system is capable of meeting the needs of other data intensive scientific applications. Alpha-Magnetic Spectrometer [4], an astro-particle experiment on the International Space Station, and the Compact Muon Solenoid [5], an LHC experiment, have successfully evaluated PanDA and are pursuing its adoption. In this paper, a description of the new program of work to develop a generic version of PanDA will be given, as well as the progress in extending PanDA's capabilities to support supercomputers and clouds and to leverage intelligent networking. PanDA has demonstrated at a very large scale the value of automated dynamic brokering of diverse workloads across distributed computing resources. The next generation of PanDA will allow other data-intensive sciences and a wider exascale community employing a variety of computing platforms to benefit from ATLAS' experience and proven tools.

Nearest clusters based partial least squares discriminant analysis for the classification of spectral data.

PubMed

Song, Weiran; Wang, Hui; Maguire, Paul; Nibouche, Omar

2018-06-07

Partial Least Squares Discriminant Analysis (PLS-DA) is one of the most effective multivariate analysis methods for spectral data analysis, which extracts latent variables and uses them to predict responses. In particular, it is an effective method for handling high-dimensional and collinear spectral data. However, PLS-DA does not explicitly address data multimodality, i.e., within-class multimodal distribution of data. In this paper, we present a novel method termed nearest clusters based PLS-DA (NCPLS-DA) for addressing the multimodality and nonlinearity issues explicitly and improving the performance of PLS-DA on spectral data classification. The new method applies hierarchical clustering to divide samples into clusters and calculates the corresponding centre of every cluster. For a given query point, only clusters whose centres are nearest to such a query point are used for PLS-DA. Such a method can provide a simple and effective tool for separating multimodal and nonlinear classes into clusters which are locally linear and unimodal. Experimental results on 17 datasets, including 12 UCI and 5 spectral datasets, show that NCPLS-DA can outperform 4 baseline methods, namely, PLS-DA, kernel PLS-DA, local PLS-DA and k-NN, achieving the highest classification accuracy most of the time. Copyright © 2018 Elsevier B.V. All rights reserved.

Retention behavior of isomeric polycyclic aromatic sulfur heterocycles in gas chromatography on stationary phases of different selectivity

PubMed Central

Wilson, Walter B.; Sander, Lane C.; Oña-Ruales, Jorge O.; Mössner, Stephanie G.; Sidisky, Leonard M.; Lee, Milton L.; Wise, Stephen A.

2017-01-01

Retention indices for 48 polycyclic aromatic sulfur heterocycles (PASHs) were determined using gas chromatography with three different stationary phases: a 50% phenyl phase, a 50% liquid crystalline dimethylpolysiloxane (LC-DMPS) phase, and an ionic liquid (IL) phase. Correlations between the retention behavior on the three stationary phases and PASH geometry (L/B and T, i.e., length-to-breadth ratio and thickness, respectively) were investigated for the following four isomer sets: (1) 4 three-ring molecular mass (MM) 184 Da PASHs, (2) 13 four-ring MM 234 Da PASHs, (3) 10 five-ring MM 258 Da PASHs, and (4) 20 five-ring MM 284 Da PASHs. Correlation coefficients for retention on the 50% LC-DMPS vs L/B ranged from r = 0.50 (MM 284 Da) to r = 0.77 (MM 234 Da). Correlation coefficients for retention on the IL phase vs L/B ranged from r = 0.31 (MM 234 Da) to r = 0.54 (MM 284 Da). Correlation coefficients for retention on the 50% phenyl vs L/B ranged from r = 0.14 (MM 258 Da) to r = 0.59 (MM 284 Da). Several correlation trends are discussed in detail for the retention behavior of PASH on the three stationary phases. PMID:28089272

Retention behavior of isomeric polycyclic aromatic sulfur heterocycles in gas chromatography on stationary phases of different selectivity.

PubMed

Wilson, Walter B; Sander, Lane C; Oña-Ruales, Jorge O; Mössner, Stephanie G; Sidisky, Leonard M; Lee, Milton L; Wise, Stephen A

2017-02-17

Retention indices for 48 polycyclic aromatic sulfur heterocycles (PASHs) were determined using gas chromatography with three different stationary phases: a 50% phenyl phase, a 50% liquid crystalline dimethylpolysiloxane (LC-DMPS) phase, and an ionic liquid (IL) phase. Correlations between the retention behavior on the three stationary phases and PASH geometry (L/B and T, i.e., length-to-breadth ratio and thickness, respectively) were investigated for the following four isomer sets: (1) 4 three-ring molecular mass (MM) 184Da PASHs, (2) 13 four-ring MM 234Da PASHs, (3) 10 five-ring MM 258Da PASHs, and (4) 20 five-ring MM 284Da PASHs. Correlation coefficients for retention on the 50% LC-DMPS vs L/B ranged from r=0.50 (MM 284Da) to r=0.77 (MM 234Da). Correlation coefficients for retention on the IL phase vs L/B ranged from r=0.31 (MM 234Da) to r=0.54 (MM 284Da). Correlation coefficients for retention on the 50% phenyl vs L/B ranged from r=0.14 (MM 258Da) to r=0.59 (MM 284Da). Several correlation trends are discussed in detail for the retention behavior of PASH on the three stationary phases. Published by Elsevier B.V.

Dynamic Assessment for 3- and 4-Year-Old Children Who Use Augmentative and Alternative Communication: Evaluating Expressive Syntax

PubMed Central

Kent-Walsh, Jennifer; King, Marika

2017-01-01

Purpose The developmental readiness to produce early sentences with an iPad communication application was assessed with ten 3- and 4-year-old children with severe speech disorders using graduated prompting dynamic assessment (DA) techniques. The participants' changes in performance within the DA sessions were evaluated, and DA performance was compared with performance during a subsequent intervention. Method Descriptive statistics were used to examine patterns of performance at various cueing levels and mean levels of cueing support. The Wilcoxon signed-ranks test was used to measure changes within the DA sessions. Correlational data were calculated to determine how well performance in DA predicted performance during a subsequent intervention. Results Participants produced targets successfully in DA at various cueing levels, with some targets requiring less cueing than others. Performance improved significantly within the DA sessions—that is, the level of cueing required for accurate productions of the targets decreased during DA sessions. Last, moderate correlations existed between DA scores and performance during the intervention for 3 out of 4 targets, with statistically significant findings for 2 of 4 targets. Conclusion DA offers promise for examining the developmental readiness of young children who use augmentative and alternative communication to produce early expressive language structures. PMID:28614580

Sequence and expression variations suggest an adaptive role for the DA1-like gene family in the evolution of soybeans.

PubMed

Zhao, Man; Gu, Yongzhe; He, Lingli; Chen, Qingshan; He, Chaoying

2015-05-15

The DA1 gene family is plant-specific and Arabidopsis DA1 regulates seed and organ size, but the functions in soybeans are unknown. The cultivated soybean (Glycine max) is believed to be domesticated from the annual wild soybeans (Glycine soja). To evaluate whether DA1-like genes were involved in the evolution of soybeans, we compared variation at both sequence and expression levels of DA1-like genes from G. max (GmaDA1) and G. soja (GsoDA1). Sequence identities were extremely high between the orthologous pairs between soybeans, while the paralogous copies in a soybean species showed a relatively high divergence. Moreover, the expression variation of DA1-like paralogous genes in soybean was much greater than the orthologous gene pairs between the wild and cultivated soybeans during development and challenging abiotic stresses such as salinity. We further found that overexpressing GsoDA1 genes did not affect seed size. Nevertheless, overexpressing them reduced transgenic Arabidopsis seed germination sensitivity to salt stress. Moreover, most of these genes could improve salt tolerance of the transgenic Arabidopsis plants, corroborated by a detection of expression variation of several key genes in the salt-tolerance pathways. Our work suggested that expression diversification of DA1-like genes is functionally associated with adaptive radiation of soybeans, reinforcing that the plant-specific DA1 gene family might have contributed to the successful adaption to complex environments and radiation of the plants.

Fibroblast growth factor receptor signaling affects development and function of dopamine neurons - inhibition results in a schizophrenia-like syndrome in transgenic mice.

PubMed

Klejbor, Ilona; Myers, Jason M; Hausknecht, Kathy; Corso, Thomas D; Gambino, Angelo S; Morys, Janusz; Maher, Pamela A; Hard, Robert; Richards, Jerry; Stachowiak, Ewa K; Stachowiak, Michal K

2006-06-01

Developing and mature midbrain dopamine (DA) neurons express fibroblast growth factor (FGF) receptor-1 (FGFR1). To determine the role of FGFR1 signaling in the development of DA neurons, we generated transgenic mice expressing a dominant negative mutant [FGFR1(TK-)] from the catecholaminergic, neuron-specific tyrosine hydroxylase (TH) gene promoter. In homozygous th(tk-)/th(tk-) mice, significant reductions in the size of TH-immunoreactive neurons were found in the substantia nigra compacta (SNc) and the ventral tegmental area (VTA) at postnatal days 0 and 360. Newborn th(tk-)/th(tk-) mice had a reduced density of DA neurons in both SNc and VTA, and the changes in SNc were maintained into adulthood. The reduced density of DA transporter in the striatum further demonstrated an impaired development of the nigro-striatal DA system. Paradoxically, the th(tk-)/th(tk-) mice had increased levels of DA, homovanilic acid and 3-methoxytyramine in the striatum, indicative of excessive DA transmission. These structural and biochemical changes in DA neurons are similar to those reported in human patients with schizophrenia and, furthermore, these th(tk-)/th(tk-) mice displayed an impaired prepulse inhibition that was reversed by a DA receptor antagonist. Thus, this study establishes a new developmental model for a schizophrenia-like disorder in which the inhibition of FGF signaling leads to alterations in DA neurons and DA-mediated behavior.

Effect of DA-8031, a novel oral compound for premature ejaculation, on male rat sexual behavior.

PubMed

Kang, Kyung Koo; Sung, Ji Hyun; Kim, Soon Hoe; Lee, Sukhyang

2014-03-01

DA-8031 is a potent and selective serotonin transporter inhibitor developed for the treatment of premature ejaculation. The aim of the present study was to investigate the effects of DA-8031 on male sexual behavior in a rat model. Sexual behavior was examined after an acute oral administration of 10, 30 or 100 mg/kg of DA-8031 in copulation studies with female rats. Pharmacokinetic parameters were calculated after oral administration of DA-8031 at a dose level of 30 mg/kg. DA-8031 treatment produced a dose-dependent increase in ejaculation latency time and showed statistical significance at 30 and 100 mg/kg dosage levels compared with the vehicle (P < 0.05). In addition, DA-8031 treatment reduced the mean number of ejaculations in a dose-dependent manner. No changes in post-ejaculatory interval, numbers of mounts, intromissions or ejaculations were observed at any dose. In pharmacokinetic study, the blood concentration of DA-8031 peaked at 0.38 ± 0.14 h after oral administration, and then rapidly declined with a half-life of 1.79 ± 0.32 h. Treatment with DA-8031 delays the ejaculation latency time without affecting the initiation of mounting behavior or post-ejaculatory interval in rats. Furthermore, DA-8031 is rapidly absorbed and eliminated after oral administration in rats. These preclinical findings provide a clue for the clinical testing of DA-8031 as an "on-demand" agent for premature ejaculation. © 2013 The Japanese Urological Association.

78 FR 46930 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-02

... Counseling and Information Sheet; DA Form 5434; OMB Control Number 0702-TBD. Needs And Uses: The information.... Frequency: On Occasion. SUPPLEMENTARY INFORMATION: Summary of Information Collection Respondents are DA Civilian employees and Soldiers. Departing Soldiers or DA Civilian employees complete the DA Form 5434...

dK/da effects on the SCC growth rates of nickel base alloys in high-temperature water

NASA Astrophysics Data System (ADS)

Chen, Kai; Wang, Jiamei; Du, Donghai; Andresen, Peter L.; Zhang, Lefu

2018-05-01

The effect of dK/da on crack growth behavior of nickel base alloys has been studied by conducting stress corrosion cracking tests under positive and negative dK/da loading conditions on Alloys 690, 600 and X-750 in high temperature water. Results indicate that positive dK/da accelerates the SCC growth rates, and the accelerating effect increases with dK/da and the initial CGR. The FRI model was found to underestimate the dK/da effect by ∼100X, especially for strain hardening materials, and this underscores the need for improved insight and models for crack tip strain rate. The effect of crack tip strain rate and dK/dt in particular can explain the dK/da accelerating effect.

Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat.

PubMed

Anselmi, L; Toti, L; Bove, C; Travagli, R A

2017-11-01

Dopamine (DA)-containing fibers and neurons are embedded within the brain stem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally dependent modulation of gastric tone and phasic contractions, i.e., motility, by DA, however, has not been characterized. With the use of microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were 1 ) assess the gastric effects of brain stem DA application, 2 ) identify the DA receptor subtype, and, 3 ) identify the postganglionic pathway(s) activated. Dopamine microinjection in the DVC decreased gastric tone and motility in both corpus and antrum in 29 of 34 rats, and the effects were abolished by ipsilateral vagotomy and fourth ventricular treatment with the selective DA2 receptor antagonist L741,626 but not by application of the selective DA1 receptor antagonist SCH 23390. Systemic administration of the cholinergic antagonist atropine attenuated the inhibition of corpus and antrum tone in response to DA microinjection in the DVC. Conversely, systemic administration of the nitric oxide synthase inhibitor nitro-l-arginine methyl ester did not alter the DA-induced decrease in gastric tone and motility. Our data provide evidence of a dopaminergic modulation of a brain stem vagal neurocircuit that controls gastric tone and motility. NEW & NOTEWORTHY Dopamine administration in the brain stem decreases gastric tone and phasic contractions. The gastric effects of dopamine are mediated via dopamine 2 receptors on neurons of the dorsal motor nucleus of the vagus. The inhibitory effects of dopamine are mediated via inhibition of the postganglionic cholinergic pathway. Copyright © 2017 the American Physiological Society.

Dynamic fluctuations in dopamine efflux in the prefrontal cortex and nucleus accumbens during risk-based decision making.

PubMed

St Onge, Jennifer R; Ahn, Soyon; Phillips, Anthony G; Floresco, Stan B

2012-11-21

Mesocorticolimbic dopamine (DA) has been implicated in cost/benefit decision making about risks and rewards. The prefrontal cortex (PFC) and nucleus accumbens (NAc) are two DA terminal regions that contribute to decision making in distinct manners. However, how fluctuations of tonic DA levels may relate to different aspects of decision making remains to be determined. The present study measured DA efflux in the PFC and NAc with microdialysis in well trained rats performing a probabilistic discounting task. Selection of a small/certain option always delivered one pellet, whereas another, large/risky option yielded four pellets, with probabilities that decreased (100-12.5%) or increased (12.5-100%) across four blocks of trials. Yoked-reward groups were also included to control for reward delivery. PFC DA efflux during decision making decreased or increased over a session, corresponding to changes in large/risky reward probabilities. Similar profiles were observed from yoked-rewarded rats, suggesting that fluctuations in PFC DA reflect changes in the relative rate of reward received. NAc DA efflux also showed decreasing/increasing trends over the session during both tasks. However, DA efflux was higher during decision making on free- versus forced-choice trials and during periods of greater reward uncertainty. Moreover, changes in NAc DA closely tracked shifts in choice biases. These data reveal dynamic and dissociable fluctuations in PFC and NAc DA transmission associated with different aspects of risk-based decision making. PFC DA may signal changes in reward availability that facilitates modification of choice biases, whereas NAc DA encodes integrated signals about reward rates, uncertainty, and choice, reflecting implementation of decision policies.

Reciprocal responsiveness of nucleus accumbens shell and core dopamine to food- and drug-conditioned stimuli.

PubMed

Bassareo, Valentina; Musio, Paolo; Di Chiara, Gaetano

2011-04-01

Drugs of abuse and palatable food share the ability to stimulate dopamine (DA) transmission in the nucleus accumbens shell. However, while the stimulation of shell DA by food undergoes habituation, that by drugs of abuse does not. This study aims to directly compare the changes of extracellular DA, by microdialysis, in shell and core and prefrontal cortex (PFCX) in response to food- and drug-conditioned stimuli (CSs). Rats were trace-conditioned by Fonzies box (FB) or vanilla box (VB; CS), followed by food: Fonzies, intraoral chocolate solution (food-unconditioned stimulus (US)) and morphine (1.0 mg/Kg sc; drug US). Control (unconditioned) rats received standard food instead of Fonzies, tap water instead of chocolate, saline instead of morphine. Food-CSs increased core but not shell DA, while drug-CSs did the opposite. Food and drug-CSs both increased PFCX DA. Exposure to food-CSs potentiated core and PFCX DA response to food while shell responsiveness was dependent upon the relative CS and US nature. If the CS was intrinsic to the food US (CS = FB/US = Fonzies) the response of shell DA to the US was abolished. If the CS was extrinsic to the food US (CS = FB/US = chocolate; CS = VB/US = Fonzies), shell DA increased in response to the US. Exposure to the drug-CS potentiated the DA response to the drug-US in the shell and in the PFCX, but not in the core. Drug-CSs differentially activate DA as compared to food-CSs in shell and core and differentially affect DA response to the US in these areas. These differences might be relevant for the role of DA in the mechanism of drug addiction.

Two-step processing for activation of the cytolysin/hemolysin of Vibrio cholerae O1 biotype El Tor: nucleotide sequence of the structural gene (hlyA) and characterization of the processed products.

PubMed

Yamamoto, K; Ichinose, Y; Shinagawa, H; Makino, K; Nakata, A; Iwanaga, M; Honda, T; Miwatani, T

1990-12-01

Vibrio cholerae O1 biotype El Tor produces and secretes a 65-kDa cytolysin/hemolysin into the culture medium. We cloned the structural gene (hlyA) for the cytolysin from the total DNA of a V. cholerae O1 El Tor strain, N86. Nucleotide sequence analysis of hlyA revealed an open reading frame consisting of 2,223 bp which can code for a protein of 741 amino acids with a molecular weight of 81,961. Consistent with this, a 79-kDa protein was identified as the product of hlyA by maxicell analysis in Escherichia coli. N-terminal amino acids of this 79-kDa HlyA protein and those of a 65-kDa El Tor cytolysin purified from V. cholerae were Asn-26 and Asn-158, respectively. The 82- and 79-kDa precursors of the 65-kDa mature cytolysin were found in V. cholerae by pulse-chase labeling and Western blot (immunoblot) analysis of hlyA products. Hemolytic activity of the 79-kDa HlyA protein from E. coli was less than 5% that for the 65-kDa cytolysin from V. cholerae. Our results suggest that in V. cholerae, the 82-kDa preprotoxin synthesized in the cytoplasm is secreted through the membranes into the culture medium as the 79-kDa inactive protoxin after cleavage of the signal peptide and is then further processed into the 65-kDa active cytolysin by release of the N-terminal 15-kDa fragment.

Concentration-dependent activation of dopamine receptors differentially modulates GABA release onto orexin neurons.

PubMed

Linehan, Victoria; Trask, Robert B; Briggs, Chantalle; Rowe, Todd M; Hirasawa, Michiru

2015-08-01

Dopamine (DA) and orexin neurons play important roles in reward and food intake. There are anatomical and functional connections between these two cell groups: orexin peptides stimulate DA neurons in the ventral tegmental area and DA inhibits orexin neurons in the hypothalamus. However, the cellular mechanisms underlying the action of DA on orexin neurons remain incompletely understood. Therefore, the effect of DA on inhibitory transmission to orexin neurons was investigated in rat brain slices using the whole-cell patch-clamp technique. We found that DA modulated the frequency of spontaneous and miniature IPSCs (mIPSCs) in a concentration-dependent bidirectional manner. Low (1 μM) and high (100 μM) concentrations of DA decreased and increased IPSC frequency, respectively. These effects did not accompany a change in mIPSC amplitude and persisted in the presence of G-protein signaling inhibitor GDPβS in the pipette, suggesting that DA acts presynaptically. The decrease in mIPSC frequency was mediated by D2 receptors whereas the increase required co-activation of D1 and D2 receptors and subsequent activation of phospholipase C. In summary, our results suggest that DA has complex effects on GABAergic transmission to orexin neurons, involving cooperation of multiple receptor subtypes. The direction of dopaminergic influence on orexin neurons is dependent on the level of DA in the hypothalamus. At low levels DA disinhibits orexin neurons whereas at high levels it facilitates GABA release, which may act as negative feedback to curb the excitatory orexinergic output to DA neurons. These mechanisms may have implications for consummatory and motivated behaviours. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The causal nature of the association between neighborhood deprivation and drug abuse: a prospective national Swedish co-relative control study

PubMed Central

Kendler, K. S.; Ohlsson, H.; Sundquist, K.; Sundquist, J.

2014-01-01

Background Risk for drug abuse (DA) is strongly associated with neighborhood social deprivation (SD). However, the causal nature of this relationship is unclear. Method Three Swedish population-based cohorts were followed up over 5 years for incident registration of DA in medical, legal or pharmacy records. In each cohort, we examined the SD–DA association, controlling carefully for individual socio-economic status (SES) with multiple measures, in the entire sample and among pairs of first cousins, paternal and maternal half-siblings, full siblings and monozygotic (MZ) twins discordant for SD exposure. The number of informative relative pairs ranged from 6366 to 166208. Results In all cohorts, SD was prospectively related to risk for incident DA. In relative pairs discordant for SD exposure, the SD–DA association was similar to that seen in the entire population in cousins, half-siblings, full siblings and MZ twins. Eliminating subjects who were residentially unstable or had DA in the first two follow-up years did not alter this pattern. When divided by age, in the youngest groups, the SD–DA association was weaker in siblings than in the entire population. Conclusions Across three cohorts, controlling for individual SES and confounding familial factors, SD prospectively predicted risk for incident DA registration. These results support the hypothesis that the SD–DA association is in part causal and unlikely to result entirely from personal attributes, which both increase risk for DA and cause selection into high SD environments. At least part of the SD–DA association arises because exposure to SD causes an increased risk of DA. PMID:25055172

Increased dopamine transporter function as a mechanism for dopamine hypoactivity in the adult infralimbic medial prefrontal cortex following adolescent social stress.

PubMed

Novick, Andrew M; Forster, Gina L; Hassell, James E; Davies, Daniel R; Scholl, Jamie L; Renner, Kenneth J; Watt, Michael J

2015-10-01

Being bullied during adolescence is associated with later mental illnesses characterized by deficits in cognitive tasks mediated by prefrontal cortex (PFC) dopamine (DA). Social defeat of adolescent male rats, as a model of teenage bullying victimization, results in medial PFC (mPFC) dopamine (DA) hypofunction in adulthood that is associated with increased drug seeking and working memory deficits. Increased expression of the DA transporter (DAT) is also seen in the adult infralimbic mPFC following adolescent defeat. We propose the functional consequence of this increased DAT expression is enhanced DA clearance and subsequently decreased infralimbic mPFC DA availability. To test this, in vivo chronoamperometry was used to measure changes in accumulation of the DA signal following DAT blockade, with increased DAT-mediated clearance being reflected by lower DA signal accumulation. Previously defeated rats and controls were pre-treated with the norepinephrine transporter (NET) inhibitor desipramine (20 mg/kg, ip.) to isolate infralimbic mPFC DA clearance to DAT, then administered the selective DAT inhibitor GBR-12909 (20 or 40 mg/kg, sc.). Sole NET inhibition with desipramine produced no differences in DA signal accumulation between defeated rats and controls. However, rats exposed to adolescent social defeat demonstrated decreased DA signal accumulation compared to controls in response to both doses of GBR-12909, indicating greater DAT-mediated clearance of infralimbic mPFC DA. These results suggest that protracted increases in infralimbic mPFC DAT function represent a mechanism by which adolescent social defeat stress produces deficits in adult mPFC DA activity and corresponding behavioral and cognitive dysfunction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chronic lithium treatment rectifies maladaptive dopamine release in the nucleus accumbens.

PubMed

Can, Adem; Frost, Douglas O; Cachope, Roger; Cheer, Joseph F; Gould, Todd D

2016-11-01

Chronic lithium treatment effectively reduces behavioral phenotypes of mania in humans and rodents. The mechanisms by which lithium exerts these actions are poorly understood. Pre-clinical and clinical evidence have implicated increased mesolimbic dopamine (DA) neurotransmission with mania. We used fast-scan cyclic voltammetry to characterize changes in extracellular DA concentrations in the nucleus accumbens (NAc) core evoked by 20 and 60 Hz electrical stimulation of the ventral tegmental area (VTA) in C57BL6/J mice treated either acutely or chronically with lithium. The effects of chronic lithium treatment on the availability of DA for release were assessed by depleting readily releasable DA using short inter-train intervals, or administering d-amphetamine acutely to mobilize readily releasable DA. Chronic, but not acute, lithium treatment decreased the amplitude of DA responses in the NAc following 60 Hz pulse train stimulation. Neither lithium treatment altered the kinetics of DA release or reuptake. Chronic treatment did not impact the progressive reduction in the amplitude of DA responses when, using 20 or 60 Hz pulse trains, the VTA was stimulated every 6 s to deplete DA. Specifically, the amplitude of DA responses to 60 Hz pulse trains was initially reduced compared to control mice, but by the fifth pulse train, there was no longer a treatment effect. However, chronic lithium treatment attenuated d-amphetamine-induced increases in DA responses to 20 Hz pulse trains stimulation. Our data suggest that long-term administration of lithium may ameliorate mania phenotypes by normalizing the readily releasable DA pool in VTA axon terminals in the NAc. Read the Editorial Highlight for this article on Page 520. © 2016 International Society for Neurochemistry.

Insulin stimulates the tyrosine phosphorylation of a 61-kilodalton protein in rat adipocytes.

PubMed

Mooney, R A; Bordwell, K L

1992-03-01

Insulin stimulated the tyrosine phosphorylation of a 61-kilodalton (kDa) protein in rat adipocytes prelabeled for 2 h with [32P]orthophosphate. Tyrosine phosphorylation of this 61-kDa protein displayed very similar insulin concentration dependency to receptor autophosphorylation and tyrosine phosphorylation of a high molecular mass receptor substrate of 160 kDa. Phosphorylation of the 61-kDa protein was very rapid with maximum labeling attained at 30 sec, paralleling that of the other two proteins. Phosphoamino acid analysis revealed that each of the insulin-responsive phosphoproteins contained phosphoserine as well as phosphotyrosine, though the ratio of two phosphoamino acids recovered from each protein differed. The 61-kDa protein yielded relatively equal proportions of phosphoserine and phosphotyrosine. In contrast, the insulin receptor yielded relatively more label on phosphotyrosine than phosphoserine, whereas label incorporated into the 160-kDa protein was recovered primarily on phosphoserine. Cleveland peptide maps using either Staphylococcus aureus V8 proteinase or chymotrypsin revealed no similarities between the 61-kDa protein and the other tyrosine phosphorylated proteins. With subcellular fractionation, the 160-kDa protein was found in equal proportions in the high speed pellet (100,000 g) and supernatant. The 61-kDa protein had a similar distribution to that of the 160-kDa protein but was also detected in the low speed pellet (10,000 g). The insulin receptor was localized to the low speed pellet. In summary, rat adipocytes contain an insulin-dependent phosphotyrosyl protein of 61 kDa which is distinct from the more prominent high molecular mass receptor substrate. This 61-kDa protein has characteristics consistent with it being a substrate for the insulin receptor tyrosine kinase.

Depletion of nucleus accumbens dopamine leads to impaired reward and aversion processing in mice: Relevance to motivation pathologies.

PubMed

Bergamini, Giorgio; Sigrist, Hannes; Ferger, Boris; Singewald, Nicolas; Seifritz, Erich; Pryce, Christopher R

2016-10-01

Dopamine (DA) neurotransmission, particularly the ventral tegmental area-nucleus accumbens (VTA-NAcc) projection, underlies reward and aversion processing, and deficient DA function could underlie motivational impairments in psychiatric disorders. 6-hydroxydopamine (6-OHDA) injection is an established method for chronic DA depletion, principally applied in rat to study NAcc DA regulation of reward motivation. Given the increasing focus on studying environmental and genetic regulation of DA function in mouse models, it is important to establish the effects of 6-OHDA DA depletion in mice, in terms of reward and aversion processing. This mouse study investigated effects of 6-OHDA-induced NAcc DA depletion using the operant behavioural test battery of progressive ratio schedule (PRS), learned non-reward (LNR), learned helplessness (LH), treadmill, and in addition Pavlovian fear conditioning. 6-OHDA NAcc DA depletion, confirmed by ex vivo HPLC-ED, reduced operant responding: for gustatory reward under effortful conditions in the PRS test; to a stimulus recently associated with gustatory non-reward in the LNR test; to escape footshock recently experienced as uncontrollable in the LH test; and to avoid footshock by physical effort in the treadmill test. Evidence for specificity of effects to NAcc DA was provided by lack of effect of medial prefrontal cortex DA depletion in the LNR and LH tests. These findings add significantly to the evidence that NAcc DA is a major regulator of behavioural responding, particularly at the motivational level, to both reward and aversion. They demonstrate the suitability of mouse models for translational study of causation and reversal of pathophysiological DA function underlying motivation psychopathologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Independent mediation of unconditioned motor behavior by striatal D1 and D2 receptors in rats depleted of dopamine as neonates.

PubMed

Bruno, J P; Byrnes, E M; Johnson, B J

1995-11-01

The effects of systemic administration of DA receptor antagonists suggest that unconditioned motor behavior in rats depleted of DA as neonates continues to be dependent upon dopaminergic transmission, yet the specific contribution of D1 and D2 receptors to these behaviors has been altered. The purpose of the present study was to determine whether these depletion-induced receptor changes are occurring at the level of striatal DA terminals and their targets. The ability of bilateral intrastriatal injections (0.5 microliter) of DA receptor antagonists to induce motoric deficits was determined in adult rats treated with vehicle or 6-OHDA (100 micrograms, intraventricular) on postnatal day 3. Administration of the D1-like antagonist SCH 23390 (0.5-2.0 micrograms) or the D2-like antagonist clebopride (1.0-4.0 micrograms) induced dose-dependent akinesia, catalepsy, and somatosensory neglect in vehicle-treated controls. In contrast, neither antagonist produced deficits in rats depleted of forebrain DA as neonates. However, combined administration of SCH 23390 + clebopride induced similar akinesia, catalepsy, and somatosensory neglect in both controls and DA depleted animals. Animals depleted of DA were more sensitive than controls to the low doses of this combined D1 + D2 antagonism. These results demonstrate that activation of striatal DA receptors remains necessary for unconditioned motor behavior in rats depleted of DA as neonates. However, the specific contributions of D1- and D2-like receptors to these behaviors differ between intact animals and those depleted of DA as neonates. The ability of endogenous DA acting at either D1 or D2 receptors to support spontaneous motor behavior in rats depleted of DA as neonates may contribute to their relative sparing from parkinsonian deficits.

Effect of 14-kDa and 47-kDa protein molecules of age garlic extract on peritoneal macrophages.

PubMed

Daneshmandi, Saeed; Hajimoradi, Monire; Ahmadabad, Hasan Namdar; Hassan, Zuhair Mohammad; Roudbary, Maryam; Ghazanfari, Tooba

2011-03-01

Garlic (Allium sativum), traditionally being used as a spice worldwide, has different applications and is claimed to possess beneficial effects in several health ailments such as tumor and atherosclerosis. Garlic is also an immunomodulator and its different components are responsible for different properties. The present work aimed to assess the effect of protein fractions of garlic on peritoneal macrophages. 14-kDa and 47-kDa protein fractions of garlic were purified. Mice peritoneal macrophages were lavaged and cultured in a microtiter plate and exposed to different concentrations of garlic proteins. MTT assay was performed to evaluate the viability of macrophage. The amount of nitric oxide (NO) was detected in culture supernatants of macrophages by Griess reagent and furthermore, the cytotoxicity study of culture supernatants was carried out on WEHI-164 fibrosarcoma cell line as tumor necrosis factor-α bioassay. MTT assay results for both 14-kDa and 47-kDa protein fractions of stimulated macrophages were not significant (P > 0.05). Both 14-kDa and 47-kDa fractions significantly suppressed production of NO from macrophages (P = 0.007 and P = 0.003, respectively). Cytotoxicity of macrophages' supernatant on WEHI-164 fibrosarcoma cells was not affected by garlic protein fractions (P = 0.066 for 14-kDa and P = 0.085 for 47-kDa fractions). according to our finding, 14-kDa and 47-kDa fractions of aged garlic extract are able to suppress NO production from macrophages, which can be used as a biological advantage. These molecules had no cytotoxic effect on macrophages and do not increase tumoricidal property of macrophages.

Development and testing of a decision aid for women considering delayed breast reconstruction.

PubMed

Metcalfe, Kelly; Zhong, Toni; O'Neill, Anne C; McCready, David; Chan, Linda; Butler, Kate; Brennenstuhl, Sarah; Hofer, Stefan O P

2018-03-01

The decision to have post-mastectomy breast reconstruction (PMBR) is highly complex and many women feel ill equipped to make this decision. Decision aids have been advocated to promote patient involvement in decision-making by streamlining and standardizing communication between the patient and the health care professional. In this study, we report on the development and testing of a decision aid (DA) for breast cancer survivors considering delayed PMBR. The DA was developed and evaluated in three phases. The first phase included the development of the DA with input and review by practitioners and key stakeholders. The second phase involved pilot testing of the feasibility and acceptability of the DA with a convenience sample of women with delayed PMBR. The third phase involved a pretest/post-test evaluation of the DA for women who were making decisions about their PMBR options. The DA was developed using the Ottawa Decision Support Framework. In the second phase of the study, 21 women completed the acceptability survey, of whom 100% reported that they would recommend the DA to other women. In the third phase, decisional conflict decreased significantly (p < 0.001) and knowledge increased significantly (p < 0.001) from prior to using the DA to 1-2 weeks after using the DA. The DA is feasible and acceptable to women considering delayed PMBR. Furthermore, the DA is effective at reducing decisional conflict and increasing knowledge about delayed PMBR. The DA is an appropriate tool to be used in addition with standard care in women considering PMBR. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Informed decision making before prostate-specific antigen screening: Initial results using the American Cancer Society (ACS) Decision Aid (DA) among medically underserved men.

PubMed

Gökce, Mehmet I; Wang, Xuemei; Frost, Jacqueline; Roberson, Pamela; Volk, Robert J; Brooks, Durado; Canfield, Steven E; Pettaway, Curtis A

2017-02-15

The American Cancer Society (ACS) recommends men have the opportunity to make an informed decision about screening for prostate cancer (PCa). The ACS developed a unique decision aid (ACS-DA) for this purpose. However, to date, studies evaluating the efficacy of the ACS-DA are lacking. The authors evaluated the ACS-DA among a cohort of medically underserved men (MUM). A multiethnic cohort of MUM (n = 285) was prospectively included between June 2010 and December 2014. The ACS-DA was presented in a group format. Levels of knowledge on PCa were evaluated before and after the presentation. Participants' decisional conflict and thoughts about the presentation also were evaluated. Logistic regression analyses were performed to determine factors associated with having an adequate level of knowledge. Before receiving the ACS-DA, 33.1% of participants had adequate knowledge on PCa, and this increased to 77% after the DA (P < .0001). On multivariate analysis, higher education level (odds ratio, 11.19; P = .001) and history of another cancer (odds ratio, 7.45; P = .03) were associated with having adequate knowledge after receiving the DA. Levels of decisional conflict were low and were correlated with levels of knowledge after receiving the DA. The majority of men also rated the presentation as favorable and would recommend the ACS-DA to others. Use of the ACS-DA was feasible among MUM and led to increased PCa knowledge. This also correlated with low levels of decisional conflict. The ACS-DA presented to groups of men may serve as a feasible tool for informed decision making in a MUM population. Cancer 2017;123:583-591. © 2016 American Cancer Society. © 2016 American Cancer Society.

High Doses of Amphetamine Augment, Rather Than Disrupt, Exocytotic Dopamine Release in the Dorsal and Ventral Striatum of the Anesthetized Rat

PubMed Central

Ramsson, Eric S.; Howard, Christopher D.; Covey, Dan P.; Garris, Paul A.

2011-01-01

High doses of amphetamine (AMPH) are thought to disrupt normal patterns of action potential-dependent dopaminergic neurotransmission by depleting vesicular stores of dopamine (DA) and inducing robust non-exocytotic DA release or efflux via dopamine transporter (DAT) reversal. However, these cardinal AMPH actions have been difficult to establish definitively in vivo. Here, we use fast-scan cyclic voltammetry (FSCV) in the urethane-anesthetized rat to evaluate the effects of 10 and 20 mg/kg AMPH on vesicular DA release and DAT function in dorsal and ventral striata. An equivalent high dose of cocaine (40 mg/kg) was also examined for comparison to psychostimulants acting preferentially by DAT inhibition. Parameters describing exocytotic DA release and neuronal DA uptake were determined from dynamic DA signals evoked by mild electrical stimulation previously established to be reinforcing. High-sensitivity FSCV with nanomolar detection was used to monitor changes in the background voltammetric signal as an index of DA efflux. Both doses of AMPH and cocaine markedly elevated evoked DA levels over the entire 2-h time course in the dorsal and ventral striatum. These increases were mediated by augmented vesicular DA release and diminished DA uptake typically acting concurrently. AMPH, but not cocaine, induced a slow, DA-like rise in some baseline recordings. However, this effect was highly variable in amplitude and duration, modest, and generally not present at all. These data thus describe a mechanistically similar activation of action potential-dependent dopaminergic neurotransmission by AMPH and cocaine in vivo. Moreover, DA efflux appears to be a unique, but secondary, AMPH action. PMID:21806614

Naval Supply Systems Command: Data Administration Planning and Implementation

DTIC Science & Technology

1989-03-01

determined that management’s lack of understanding is an inhibitor of successful DA. Equally important is the DA group’s comprehension of...is the actual staff responsible for DA. Kahn [Ref. 5] found that an insufficient DA staff was another inhibitor of successful DA implementation. Two...Logistic Network ( NLN ) architecture. 7 3. NAVSUP Strategic Directions Three of NAVSUP’s strategic directions pertain to this study. The first is the

Dopamine induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages in rat C6 glioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin, Tian; Wang, Chenlong; Chen, Xuewei

Dopamine (DA), a monoamine catecholamine neurotransmitter with antiangiogenic activity, stabilizes tumor vessels in colon, prostate and ovarian cancers, thus increases chemotherapeutic efficacy. Here, in the rat C6 glioma models, we investigated the vascular normalization effects of DA and its mechanisms of action. DA (25, 50 mg/kg) inhibited tumor growth, while a precursor of DA (levodopa) prolonged the survival time of rats bearing orthotopic C6 glioma. DA improved tumor perfusion, with significant effects from day 3, and a higher level at days 5 to 7. In addition, DA decreased microvessel density and hypoxia-inducible factor-1α expression in tumor tissues, while increasing themore » coverage of pericyte. Conversely, an antagonist of dopamine receptor 2 (DR2) (eticlopride) but not DR1 (butaclamol) abrogated DA-induced tumor regression and vascular normalization. Furthermore, DA improved the delivery and efficacy of temozolomide therapy. Importantly, DA increased representative M1 markers (iNOS, CXCL9, etc.), while decreasing M2 markers (CD206, arginase-1, etc.). Depletion of macrophages by clodronate or zoledronic acid attenuated the effects of DA. Notably, DA treatment induced M2-to-M1 polarization in RAW264.7 cells and mouse peritoneal macrophages, and enhanced the migration of pericyte-like cells (10T1/2), which was reversed by eticlopride or DR2-siRNA. Such changes were accompanied by the downregulation of VEGF/VEGFR2 signaling. In summary, DA induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages. Thus, targeting the tumor microvasculature by DA represents a promising strategy for human glioma therapy. - Highlights: • Dopamine induces tumor growth inhibition and vascular normalization in rat C6 glioma. • Dopamine switches macrophage phenotype from M2 to M1. • Dopamine-induced vascular normalization is mediated by macrophage polarization. • Dopamine is a promising agent targeting the microvasculature in tumor microenvironment.« less

The Protective Effect of Pregnancy on Risk for Drug Abuse: A Population, Co-relative, Co-spouse, and Within-Individual Analysis

PubMed Central

Kendler, Kenneth S.; Ohlsson, Henrik; Svikis, Dace S.; Sundquist, Kristina; Sundquist, Jan

2017-01-01

Objective To determine whether pregnancy is an intrinsic motivator for drug abuse (DA) cessation. Method We conducted, in Swedish females born 1980–1990 who gave birth at ages 20–35 (N=149,512), prospective cohort, co-relative, co-spouse, and within-person analyses of registration for DA during pregnancy. DA was assessed from medical, criminal and pharmacy registries. Results In the population, rates of DA were lower during pregnancy (unadjusted OR=0.67, 95% CIs 0.60–0.74). Compared to population results, the negative association between pregnancy and DA was moderately stronger in cousins (OR=0.49, 0.39–0.62) and substantially stronger in siblings (OR=0.35, 0.24–0.51) discordant for pregnancy. The estimated OR for DA in pregnancy-discordant monozygotic twins was even stronger: 0.17 (0.10–0.31). Within-individuals, the OR for DA while pregnant compared to an equivalent pre-pregnancy interval was similar to that seen in pregnancy-discordant monozygotic twins: 0.22 (0.19–0.26). Compared to cohabiting fathers, mothers had a greater reduction in risk for DA during pregnancy (OR=0.40, 0.34–0.47). Pregnancy was more protective in those with low parental education and without a cohabiting actively drug abusing father. Compared to pre-pregnancy baseline, within-individual analyses indicate risk for DA is also substantially reduced post-partum e.g. day 0–242 OR=0.13 (0.11–0.16). Conclusions Risk for DA in women is substantially reduced during pregnancy. Multiple analyses suggest that this association is largely causal, suggesting that pregnancy is indeed a strong intrinsic motivator for DA cessation. Similar strong protective effects may be present immediately post-partum. Our results have implications for our etiologic models of DA and especially for contingency management programs seeking to reduce DA risk. PMID:28595490

Serotonin System Implication in l-DOPA-Induced Dyskinesia: From Animal Models to Clinical Investigations

PubMed Central

Carta, Manolo; Tronci, Elisabetta

2014-01-01

In the recent years, the serotonin system has emerged as a key player in the induction of l-DOPA-induced dyskinesia (LID) in animal models of Parkinson’s disease. In fact, serotonin neurons possess the enzymatic machinery able to convert exogenous l-DOPA to dopamine (DA), and mediate its vesicular storage and release. However, serotonin neurons lack a feedback control mechanism able to regulate synaptic DA levels. While in a situation of partial DA depletion spared DA terminals can buffer DA released from serotonin neurons, the progression of DA neuron degeneration impairs this protective mechanism, causing swings in synaptic DA levels and pulsatile stimulation of post-synaptic DA receptors. In line with this view, removal of serotonin neurons by selective toxin, or pharmacological silencing of their activity, produced complete suppression of LID in animal models of Parkinson’s disease. In this article, we will revise the experimental evidence pointing to the important role of serotonin neurons in dyskinesia, and we will discuss the clinical implications. PMID:24904522

N-Acetyltransferase 2 Genotypes Are Associated With Diisocyanate-Induced Asthma.

PubMed

Yucesoy, Berran; Kissling, Grace E; Johnson, Victor J; Lummus, Zana L; Gautrin, Denyse; Cartier, André; Boulet, Louis-Philippe; Sastre, Joaquin; Quirce, Santiago; Tarlo, Susan M; Cruz, Maria-Jesus; Munoz, Xavier; Luster, Michael I; Bernstein, David I

2015-12-01

To investigate whether genetic variants of N-acetyltransferase (NAT) genes are associated with diisocyanate asthma (DA). The study population consisted of 354 diisocyanate-exposed workers. Genotyping was performed using a 5'-nuclease polymerase chain reaction assay. The NAT2 rs2410556 and NAT2 rs4271002 variants were significantly associated with DA in the univariate analysis. In the first logistic regression model comparing DA+ and asymptomatic worker groups, the rs2410556 (P = 0.004) and rs4271002 (P < 0.001) single nucleotide polymorphisms and the genotype combination, NAT2 rs4271002*NAT1 rs11777998, showed associations with DA risk (P = 0.014). In the second model comparing DA+ and DA- groups, NAT2 rs4271002 variant and the combined genotype, NAT1 rs8190845*NAT2 rs13277605, were significantly associated with DA risk (P = 0.022, P = 0.036, respectively). These findings suggest that variations in the NAT2 gene and their interactions contribute to DA susceptibility.

Performances on simulator and da Vinci robot on subjects with and without surgical background.

PubMed

Moglia, Andrea; Ferrari, Vincenzo; Melfi, Franca; Ferrari, Mauro; Mosca, Franco; Cuschieri, Alfred; Morelli, Luca

2017-08-17

To assess whether previous training in surgery influences performance on da Vinci Skills Simulator and da Vinci robot. In this prospective study, thirty-seven participants (11 medical students, 17 residents, and 9 attending surgeons) without previous experience in laparoscopy and robotic surgery performed 26 exercises at da Vinci Skills Simulator. Thirty-five then executed a suture using a da Vinci robot. The overall scores on the exercises at the da Vinci Skills Simulator show a similar performance among the groups with no statistically significant pair-wise differences (p < .05). The quality of the suturing based on the unedited videos of the test run was similar for the intermediate (7 (4, 10)) and expert group (6.5 (4.5, 10)), and poor for the untrained groups (5 (3.5, 9)), without statistically significant difference (p < .05). This study showed, for subjects new to laparoscopy and robotic surgery, insignificant differences in the scores at the da Vinci Skills Simulator and at the da Vinci robot on inanimate models.

( sup 3 H)Dopamine uptake by platelet storage granules in schizophrenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabey, J.M.; Graff, E.; Oberman, Z.

1992-01-01

({sup 3}H)Dopamine (DA) uptake by platelet storage granules was determined in 26 schizophrenic male patients, paranoid type (14 acute stage; 12 in remission) and 20 age-matched, normal controls. maximum velocity (Vmax) of DA uptake was significantly higher in acute patients, than patients in remission or controls (p>0.05). The apparent Michaelis constant (kM) of DA uptake in acute patients was also significantly different from chronic patients a substantial diminution of DA uptake, while haloperidol produced a substantial diminution of DA uptake, while haloperidol (10{sup {minus}4}, 10{sup {minus}5} M) did not affect the assay. Considering that a DA disequilibrium in schizophrenia maymore » be expressed not only in the brain, but also in the periphery and that an increased amount of DA accumulated in the vesicles, implies that an increased quantity of catecholamine is available for release, our findings suggest additional evidence for the role of DA overactivity in the pathophysiology of this disorder.« less

Da Vinci robot-assisted system for thymectomy: experience of 55 patients in China.

PubMed

Jun, Yi; Hao, Li; Demin, Li; Guohua, Dong; Hua, Jing; Yi, Shen

2014-09-01

Da Vinci robot-assisted thymectomy has been used in the past several years in China, however, practical experience in performing this approach in China remains limited. Thus, the study aimed to evaluate the experience of da Vinci robot-assisted thymectomy in China. From June 2010 to December 2012, 55 patients with diseases of the thymus underwent thymectomy using the da Vinci surgical HD robotic system. The clinical data of the da Vinci robot-assisted thymectomies were compared with the data of video-assisted thoracoscopic thymectomies in the same period. All da Vinci robot operations were successful. This is a retrospective analysis which demonstrated that compared with video-assisted thoracoscopic thymectomy in the same period, the clinical outcomes of da Vinci robot-assisted thymectomy were not significantly different. The da Vinci robot-assisted thymectomy is a safe, minimally invasive, and convenient operation, and shows promise for general thoracic surgery in China. Copyright © 2014 John Wiley & Sons, Ltd.

Origin of the DA and non-DA white dwarf stars

NASA Technical Reports Server (NTRS)

Shipman, Harry L.

1989-01-01

Various proposals for the bifurcation of the white dwarf cooling sequence are reviewed. 'Primordial' theories, in which the basic bifurcation of the white dwarf sequence is rooted in events predating the white dwarf stage of stellar evolution, are discussed, along with the competing 'mixing' theories in which processes occurring during the white dwarf stage are responsible for the existence of DA or non-DA stars. A new proposal is suggested, representing a two-channel scenario. In the DA channel, some process reduces the hydrogen layer mass to the value of less than 10 to the -7th. The non-DA channel is similar to that in the primordial scenario. These considerations suggest that some mechanism operates in both channels to reduce the thickness of the outermost layer of the white dwarf. It is also noted that accretion from the interstellar medium has little to do with whether a particular white dwarf becomes a DA or a non-DA star.

Selective inhibition of dopamine-beta-hydroxylase enhances dopamine release from noradrenergic terminals in the medial prefrontal cortex.

PubMed

Devoto, Paola; Flore, Giovanna; Saba, Pierluigi; Frau, Roberto; Gessa, Gian L

2015-10-01

Disulfiram has been claimed to be useful in cocaine addiction therapy, its efficacy being attributed to dopamine-beta-hydroxylase (DBH) inhibition. Our previous results indicate that disulfiram and the selective DBH inhibitor nepicastat increase extracellular dopamine (DA) in the rat medial prefrontal cortex (mPFC), and markedly potentiated cocaine-induced increase. Concomitantly, in rats with cocaine self-administration history, cocaine-seeking behavior induced by drug priming was prevented, probably through overstimulation of D1 receptors due to the DA increase. The present research was aimed at studying the neurochemical mechanisms originating the enhanced DA release. Noradrenergic system ablation was attained by intracerebroventricular (i.c.v.) administration of the neurotoxin anti-DBH-saporin (aDBH-sap). DA, noradrenaline (NA), and DOPAC were assessed by HPLC after ex vivo tissue extraction or in vivo microdialysis. Control and denervated rats were subjected to microdialysis in the mPFC and caudate nucleus to evaluate the effect of nepicastat-cocaine combination on extracellular DA levels and their regulation by α2-adrenoceptors. Fifteen days after neurotoxin or its vehicle administration, tissue and extracellular NA were reduced to less than 2% the control value, while extracellular DA was increased by approximately 100%. In control rats, nepicastat given alone and in combination with cocaine increased extracellular DA by about 250% and 1100%, respectively. In denervated rats, nepicastat slightly affected extracellular DA, while in combination with cocaine increased extracellular DA by 250%. No differences were found in the caudate nucleus. Clonidine almost totally reversed the extracellular DA elevation produced by nepicastat-cocaine combination, while it was ineffective in denervated rats. This research shows that the increase of extracellular DA produced by nepicastat alone or in combination with cocaine was prevented by noradrenergic denervation. The results indicate that nepicastat enhances DA release from noradrenergic terminals supposedly by removing NA from α2-autoreceptors. In addition to the inhibition of DA uptake, the latter mechanism may explain the synergistic effect of cocaine on nepicastat-induced DA release.

Cloning and functional characterization of the DA2 receptor gene in Chinese mitten crab (Eriocheir sinensis)

PubMed Central

Xu, Min-jie; Zhang, Cong; Yang, Zhigang

2018-01-01

Dopamine (DA) plays a modulatory role in numerous physiological processes such as light adaptation and food intake, and exerts these functions through DA receptors (DARs). This study presents, for the first time, isolation and characterization of the dopamine receptor 2(DA2 receptor) cDNA from the intestinal tissue of Eriocheir sinensis, an economically important freshwater aquaculture species in China. The DA2 receptor cDNA sequence, which was obtained by rapid amplification of cDNA ends, is 2369bp long, encode peptide of 589 amino acid, and is highly homologous to related sequences in crustaceans. Analysis of the deduced amino acid sequence and the structure of the DA2 indicated that this receptor is a member of the family of G protein-coupled receptors (GPCRs), as it contains seven transmembrane domains and other common signatures of GPCRs. RT-PCR showed that the expression of the DA2 receptor gene was distributed in various tissues, and high expression levels were observed in the cranial ganglia and the thoracic ganglia. Further study of the effect of photoperiod on DA2 expression showed that constant darkness induced a significant increase in DA2 expression in the cranial ganglia. Finally, analysis of DA2 receptor expression under different feeding statuses showed that there was significantly greater expression in the hepatopancreas and intestines after feeding than before feeding, but there were no differences in expression between the before feeding and during feeding periods in either tissue. Our results indicate that the DA2 receptor structurally belongs to the family of G protein-coupled receptors, and that the cranial ganglia are the main tissues in which the DA2 receptor participates in light adaptation during dark hours. In addition, the DA2 receptor in E. sinensis may be involved in the physiological regulation of the hepatopancreas and digestive tract after the ingestion of food. This study provides a foundation for further exploration of the light adaptation and digestive functions of the DA2 receptor in decapods. PMID:29554147

Factors associated with mortality in patients undergoing coronary artery bypass grafting.

PubMed

Koerich, Cintia; Lanzoni, Gabriela Marcellino de Melo; Erdmann, Alacoque Lorenzini

2016-08-08

to investigate the factors associated with mortality in patients undergoing coronary artery bypass grafting in a cardiovascular referral hospital in Santa Catarina. quantitative, exploratory, descriptive and retrospective study. The medical records of 1447 patients, from 2005 to 2013, were analyzed for statistically related variables, these being: profile, hospitalization diagnosis, risk factors for coronary artery disease, complications recorded during the hospitalization, length of hospitalization and cause of death. the mortality rate was 5.3% during the study period. Death was more common in females and those of black skin color, with a mean age of 65 years. Acute myocardial infarction was the most common hospitalization diagnosis. The majority of the complications recorded during hospitalization were characterized by changes in the cardiovascular system, with longer hospitalization periods being directly related to death from septic shock. the data provide subsidies for nursing work with preventive measures and early detection of complications associated with coronary artery bypass grafting. This reinforces the importance of using the data as quality indicators, aiming to guarantee care guided by reliable information to guide managers in planning patient care and high complexity health services. conhecer os fatores associados à mortalidade de pacientes submetidos à cirurgia de revascularização do miocárdio em hospital referência cardiovascular em Santa Catarina. estudo quantitativo, exploratório, descritivo e retrospectivo. Foram analisados os prontuários de 1447 pacientes, entre 2005 e 2013, e as variáveis relacionadas estatisticamente, sendo estas: perfil, diagnóstico da internação, fatores de risco para doença arterial coronariana, intercorrências registradas na internação, tempo de internação e causa do óbito. a taxa de mortalidade foi de 5,3% no período do estudo. Os óbitos foram mais frequentes em negros, do sexo feminino e média de idade de 65 anos. O infarto agudo do miocárdio foi o diagnóstico de internação que apresentou maior representatividade. A maioria das intercorrências registradas durante a internação caracterizou-se por alterações do sistema cardiovascular e o maior tempo de internação teve relação direta com óbito por choque séptico. os dados fornecem subsídios para a enfermagem atuar com medidas preventivas e identificação precoce de intercorrências associadas à cirurgia de revascularização do miocárdio. Reforça-se a importância da utilização dos dados como indicadores de qualidade objetivando garantir um cuidado pautado em informações confiáveis que orientem gestores no planejamento da assistência ao paciente e dos serviços de saúde de alta complexidade. conocer los factores asociados a la mortalidad de pacientes sometidos a cirugía de revascularización del miocardio en un hospital de referencia cardiovascular en el estado de Santa Catarina. estudio cuantitativo, exploratorio, descriptivo y retrospectivo. Fueron analizados las fichas médicas de 1.447 pacientes, entre 2005 y 2013; las variables relacionadas estadísticamente fueron: perfil, diagnóstico de la internación, factores de riesgo para enfermedad arterial coronariana, complicaciones registradas en la internación, tiempo de internación y causa de la muerte. la tasa de mortalidad fue de 5,3%, en el período del estudio. Las muertes fueron más frecuentes en negros, sexo femenino y promedio de edad de 65 años. El infarto agudo del miocardio fue el diagnóstico de internación que presentó mayor representatividad. La mayoría de las complicaciones registradas durante la internación se caracterizó por alteraciones del sistema cardiovascular; el mayor tiempo de internación tuvo relación directa con muerte por choque séptico. los datos suministran informaciones para que la enfermería pueda actuar con medidas preventivas e identificar precozmente complicaciones asociadas a la cirugía de revascularización del miocardio. Se refuerza la importancia de la utilización de datos como indicadores de calidad, objetivando garantizar un cuidado guiado por informaciones confiables que orienten a los administradores en la planificación de la asistencia al paciente y en los servicios de salud de alta complejidad.

Utility of Ultraportable Echocardiography in the Preoperative Evaluation of Noncardiac Surgery.

PubMed

Costa, Jean Allan; Almeida, Maria Lucia Pereira; Estrada, Tereza Cristina Duque; Werneck, Guilherme Lobosco; Rocha, Alexandre Marins; Rosa, Maria Luiza Garcia; Ribeiro, Mario Luiz; Mesquita, Claudio Tinoco

2016-11-01

The ultraportable echocardiogram machine, with relevant portability and easiness in performing diagnoses, when in experienced hands, may contribute to the reliability of preoperative evaluation in noncardiac surgeries. To assess cardiac function parameters in patients aged older than 60 years, candidates of elective noncardiac surgeries, classified as ASA1 or ASA 2 according to surgical risk. A total of 211 patients referred for elective surgeries, without suspicion of previous heart diseases, were included in the study. Assessment of patients was conducted by conventional echocardiogram using the ultraportable V Scan (GE) device right after the pre-anesthetic clinical evaluation. We assessed the clinical impact of echocardiography results by using a questionnaire addressed to the anesthetist. Mean age of patients was 68.9 ± 7.0 years, 154 were women. The most frequent surgeries were: a) facectomy - cataract - 18; b) inguinal hernia surgery - 18; c) Cholecystectomy - 16. We found 58 normal tests (27.5%), 70 (33.2%) with mild valve reflux, and 83 (39.3%) with relevant abnormality, such as increase in heart chamber size, global and/or segmental contractile dysfunction, significant valve dysfunction or other unspecified. Test results caused delay of surgical procedure for a more detailed cardiac evaluation in 20 (9.5%) patients, and change in anesthetic management in 7 (3.3%). There was a considerable clinical impact with the use of the ultraportable echocardiography, since one out of every ten patients evaluated had their clinical management changed due to the detection of previously unsuspected, significant heart diseases, with the potential for severe complications. O ecocardiógrafo ultraportátil, com importante mobilidade e facilidade diagnóstica em mãos experientes pode contribuir para a segurança na avaliação pré-operatória em cirurgias não cardíacas. Avaliar os parâmetros de função cardíaca nos pacientes com mais de 60 anos de idade, candidatos a cirurgias não-cardíacas eletivas, classificados como ASA 1 ou ASA 2 na classificação de risco cirúrgico. Foram incluídos 211 pacientes direcionados para cirurgias eletivas diversas e sem suspeita prévia de cardiopatia. Os pacientes foram avaliados por técnica ecocardiográfica convencional, usando o aparelho ultraportátil V Scan (GE) logo após a avaliação clínica pré-anestésica. Avaliamos o impacto clínico dos resultados da ecocardiografia por um questionário dirigido ao anestesista. A idade média dos pacientes foi 68,9 ± 7,0 anos, 154 do sexo feminino. As cirurgias mais frequentes foram: a) Facectomia-catarata - 18; b) Herniorrafia inguinal - 18; c) Colecistectomia - 16. No total, foram observados 58 exames normais (27,5%), 70 (33,2%) exames que apresentavam leves refluxos valvares e 83 (39,3%) exames com alguma anormalidade relevante, como aumento de câmara cardíaca, disfunção contrátil global e/ou segmentar, disfunção valvar mais significativa ou outra não especificada. Os resultados determinaram que 20 (9,5%) pacientes tivessem seus procedimentos cirúrgicos adiados até avaliação cardiológica mais detalhada e em 7 (3,3%) houve mudança na conduta anestésica. Houve um impacto clínico considerável com o uso da ecocardiografia ultraportátil, pois um em cada dez pacientes avaliados sofreu modificação na conduta clínica, em função da detecção de cardiopatias significativas, não suspeitadas previamente, e com potencial para complicações graves.

Deciding how many embryos to transfer after in vitro fertilisation: development and pilot test of a decision aid.

PubMed

van Peperstraten, Arno M; Hermens, Rosella P M G; Nelen, Willianne L D M; Stalmeier, Peep F M; Wetzels, Alex M M; Maas, Pettie H M; Kremer, Jan A M; Grol, Richard P T M

2010-01-01

When deciding how many embryos to transfer during in vitro fertilisation (IVF), clinicians and patients have to balance optimizing the chance of pregnancy against preventing multiple pregnancies and the associated complications. This paper describes the development and pilot test of a patient decision aid (DA) for this purpose. The development of the DA consisted of a literature search, establishment of the format, and a pilot test among IVF patients. The DA development was supervised by a panel of experts in the fields of subfertility, obstetrics and DA-research and it was based on the criteria of the International Patient Decision Aid Standards. One Cochrane review and 34 articles were selected for the DA content. The DA presents information in text, summaries, tables, figures and through an interactive worksheet. The DA was reviewed positively and as acceptable for use in clinical practice by patients and professionals. The DA was thoroughly developed and is likely to be helpful for the decision-making process for the number of embryos transferred after IVF. Physicians and researchers can use the DA without restriction in clinical practice or research related to decision-making.

Biosynthesis and intracellular transport of the receptor for platelet-derived growth factor.

PubMed Central

Claesson-Welsh, L; Rönnstrand, L; Heldin, C H

1987-01-01

The biosynthesis of the receptor for platelet-derived growth factor (PDGF) was examined in metabolically labeled human foreskin fibroblasts. The receptor was synthesized as a 145-kDa precursor, which, when incubated with endo-beta-N-acetylglucosaminidase H (endo H), underwent a 15-kDa decrease in molecular mass. This indicates that the size of the core protein is about 130 kDa and that the 145-kDa form represents a receptor precursor carrying high-mannose N-linked oligosaccharide groups. Within 15 min after synthesis, the receptor was converted to a 165-kDa form. This form was entirely resistant to endo H treatment and probably represents a receptor molecule that has undergone further posttranslational modification, including O-linked glycosylation. Subsequently, within 30 min, a molecule of 170 kDa--i.e., the size of the mature receptor--appeared. A slightly larger molecule, of 175 kDa, which could be immunoprecipitated from PDGF-stimulated 32P-labeled cells, probably represents a receptor further modified by autophosphorylation. The 170-kDa molecule had an isoelectric point of about 4.5. Addition of PDGF increased the turnover rate of the 170-kDa PDGF receptor. Images PMID:2827155

Persistent Adaptations in Afferents to Ventral Tegmental Dopamine Neurons after Opiate Withdrawal.

PubMed

Kaufling, Jennifer; Aston-Jones, Gary

2015-07-15

Protracted opiate withdrawal is accompanied by altered responsiveness of midbrain dopaminergic (DA) neurons, including a loss of DA cell response to morphine, and by behavioral alterations, including affective disorders. GABAergic neurons in the tail of the ventral tegmental area (tVTA), also called the rostromedial tegmental nucleus, are important for behavioral responses to opiates. We investigated the tVTA-VTA circuit in rats after chronic morphine exposure to determine whether tVTA neurons participate in the loss of opiate-induced disinhibition of VTA DA neurons observed during protracted withdrawal. In vivo recording revealed that VTA DA neurons, but not tVTA GABAergic neurons, are tolerant to morphine after 2 weeks of withdrawal. Optogenetic stimulation of tVTA neurons inhibited VTA DA neurons similarly in opiate-naive and long-term withdrawn rats. However, tVTA inactivation increased VTA DA activity in opiate-naive rats, but not in withdrawn rats, resembling the opiate tolerance effect in DA cells. Thus, although inhibitory control of DA neurons by tVTA is maintained during protracted withdrawal, the capacity for disinhibitory control is impaired. In addition, morphine withdrawal reduced both tVTA neural activity and tonic glutamatergic input to VTA DA neurons. We propose that these changes in glutamate and GABA inputs underlie the apparent tolerance of VTA DA neurons to opiates after chronic exposure. These alterations in the tVTA-VTA DA circuit could be an important factor in opiate tolerance and addiction. Moreover, the capacity of the tVTA to inhibit, but not disinhibit, DA cells after chronic opiate exposure may contribute to long-term negative affective states during withdrawal. Dopaminergic (DA) cells of the ventral tegmental area (VTA) are the origin of a brain reward system and are critically involved in drug abuse. Morphine has long been known to affect VTA DA cells via GABAergic interneurons. Recently, GABAergic neurons caudal to the VTA were discovered and named the tail of VTA (tVTA). Here, we show that tVTA GABA neurons lose their capacity to disinhibit, but not to inhibit, VTA DA cells after chronic opiate exposure. The failure of disinhibition was associated with a loss of glutamatergic input to DA neurons after chronic morphine. These findings reveal mechanisms by which the tVTA may play a key role in long-term negative affective states during opiate withdrawal. Copyright © 2015 the authors 0270-6474/15/3510290-14$15.00/0.

Selective Ablation of GIRK Channels in Dopamine Neurons Alters Behavioral Effects of Cocaine in Mice.

PubMed

McCall, Nora M; Kotecki, Lydia; Dominguez-Lopez, Sergio; Marron Fernandez de Velasco, Ezequiel; Carlblom, Nicholas; Sharpe, Amanda L; Beckstead, Michael J; Wickman, Kevin

2017-02-01

The increase in dopamine (DA) neurotransmission stimulated by in vivo cocaine exposure is tempered by G protein-dependent inhibitory feedback mechanisms in DA neurons of the ventral tegmental area (VTA). G protein-gated inwardly rectifying K + (GIRK/Kir3) channels mediate the direct inhibitory effect of GABA B receptor (GABA B R) and D 2 DA receptor (D 2 R) activation in VTA DA neurons. Here we examined the effect of the DA neuron-specific loss of GIRK channels on D 2 R-dependent regulation of VTA DA neuron excitability and on cocaine-induced, reward-related behaviors. Selective ablation of Girk2 in DA neurons did not alter the baseline excitability of VTA DA neurons but significantly reduced the magnitude of D 2 R-dependent inhibitory somatodendritic currents and blunted the impact of D 2 R activation on spontaneous activity and neuronal excitability. Mice lacking GIRK channels in DA neurons exhibited increased locomotor activation in response to acute cocaine administration and an altered locomotor sensitization profile, as well as increased responding for and intake of cocaine in an intravenous self-administration test. These mice, however, showed unaltered cocaine-induced conditioned place preference. Collectively, our data suggest that feedback inhibition to VTA DA neurons, mediated by GIRK channel activation, tempers the locomotor stimulatory effect of cocaine while also modulating the reinforcing effect of cocaine in an operant-based self-administration task.

Enhanced Dopamine Detection Sensitivity by PEDOT/Graphene Oxide Coating on in vivo Carbon Fiber Electrodes

PubMed Central

Taylor, I. Mitch; Robbins, Elaine M.; Catt, Kasey A.; Cody, Patrick A.; Weaver, Cassandra L.; Cui, Xinyan Tracy

2016-01-01

Dopamine (DA) is a monoamine neurotransmitter responsible for regulating a variety of vital life functions. In vivo detection of DA poses a challenge due to the low concentration and high speed of physiological signaling. Fast scan cyclic voltammetry at carbon fiber microelectrodes (CFEs) is an effective method to monitor real-time in vivo DA signaling, however the sensitivity is somewhat limited. Electrodeposition of poly(3,4-ethylene dioxythiophene) (PEDOT)/graphene oxide (GO) onto the CFE surface is shown to increase the sensitivity and lower the limit of detection for DA compared to bare CFEs. Thicker PEDOT/GO coatings demonstrate higher sensitivities for DA, but display the negative drawback of slow adsorption and electron transfer kinetics. The moderate thickness resulting from 25 s electrodeposition of PEDOT/GO produces the optimal electrode, exhibiting an 880% increase in sensitivity, a 50% decrease in limit of detection and minimally altered electrode kinetics. PEDOT/GO coated electrodes rapidly and robustly detect DA, both in solution and in the rat dorsal striatum. This increase in DA sensitivity is likely due to increasing the electrode surface area with a PEDOT/GO coating and improved adsorption of DA’s oxidation product (DA-o-quinone). Increasing DA sensitivity without compromising electrode kinetics is expected to significantly improve our understanding of the DA function in vivo. PMID:27268013

Evidence for a dopamine intrinsic direct role in the regulation of the ovary reproductive function: in vitro study on rabbit corpora lutea.

PubMed

Parillo, Francesco; Maranesi, Margherita; Mignini, Fiorenzo; Marinelli, Lisa; Di Stefano, Antonio; Boiti, Cristiano; Zerani, Massimo

2014-01-01

Dopamine (DA) receptor (DR) type 1 (D1R) has been found to be expressed in luteal cells of various species, but the intrinsic role of the DA/DRs system on corpora lutea (CL) function is still unclear. Experiments were devised to characterize the expression of DR types and the presence of DA, as well as the in vitro effects of DA on hormone productions by CL in pseudopregnant rabbits. Immunoreactivity and gene expression for D1R decreased while that for D3R increased in luteal and blood vessel cells from early to late pseudopregnant stages. DA immunopositivity was evidenced only in luteal cells. The DA and D1R agonist increased in vitro release of progesterone and prostaglandin E2 (PGE2) by early CL, whereas the DA and D3R agonist decreased progesterone and increased PGF2α in vitro release by mid- and late CL. These results provide evidence that the DA/DR system exerts a dual modulatory function in the lifespan of CL: the DA/D1R is luteotropic while the DA/D3R is luteolytic. The present data shed new light on the physiological mechanisms regulating luteal activity that might improve our ability to optimize reproductive efficiency in mammal species, including humans.

Effectivity of immunostimulant from Zoothamnium penaei protein membrane for decreasing the mortality rate of white shrimp (Litopenaeus vannamei) in traditional plus pond

NASA Astrophysics Data System (ADS)

Mahasri, G.; Kusdarwati, R.; Kismiyati; Rozi; Gustrifandi, H.

2018-04-01

The purpose of this research was to analys immunogenic membrane protein as immunostimulant development material to control the mortality of white shrimp in traditional plus pond. This research was designed to use explorative experiment and experimental laboratory methods which used completed random sampling design. Collected data was analyzed with analysis of variance for examination of survival rate (SR), total haemocyte count (THC) and differensial haemocyte Count (DHC). The research divided into 2 part of riset: (1) Identification, cultivation Zoothamnium penaei, analysed of membrane protein by SDS-PAGE, (2) Field test protein membran on Survival Rate level, immune response (THC and/or DHC level) and infestation of Zoothamnium penaei in traditional plus pond. The result showed that there were seven bands membrane protein of Zoothamnium penaei with molecular weight 38 kDa, 48 kDa, 67 kDa, 71 kDa, 77 kDa, 98 kDa dan 104 kDa by using SDS-PAGE. Immunogenicity tested decrease by using ELISA and western blotting there are only found three bands with molecular weight 38 kDa, 48 kDa dan 67 kDa. The membrane protein could increase the immun respons and decrease the mortality, by subsequenly, it could increase the survival rate from 17% until 68% and pressured the parasite infestation of white shrimp.

The 29-kDa proteins phosphorylated ion thrombin-activated human platelets are forms of the estrogen receptor-related 27-kDa heat shock protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mendelsohn, M.E.; Yan Zhu; O'Neill, S.

Thrombin plays a critical role in platelet activation, hemostasis, and thrombosis. Cellular activation by thrombin leads to the phosphorylation of multiple proteins, most of which are unidentified. The authors have characterized several 29-kDa proteins that are rapidly phosphorylated following exposure of intact human platelets to thrombin. A murine monoclonal antibody raised to an unidentified estrogen receptor-related 29-kDa protein selectively recognized these proteins as well as a more basic, unphosphorylated 27-kDa protein. Cellular activation by thrombin led to a marked shift in the proportion of protein from the 27-kDa unphosphorylated form to the 29-kDa phosphoprotein species. Using this antibody, they isolatedmore » and sequenced a human cDNA clone encoding a protein that was identical to the mammalian 27-kDa heat shock protein (HSP27), a protein of uncertain function that is known to be phosphorylated to several forms and to be transcriptionally induced by estrogen. The 29-kDa proteins were confirmed to be phosphorylated forms of HSP27 by immunoprecipitation studies. Thus, the estrogen receptor-related protein is HSP27, and the three major 20-kDa proteins phosphorylated in thrombin-activated platelets are forms of HSP27. These data suggest a role for HSP27 in the signal transduction events of platelet activation.« less

The rare DAT coding variant Val559 perturbs DA neuron function, changes behavior, and alters in vivo responses to psychostimulants.

PubMed

Mergy, Marc A; Gowrishankar, Raajaram; Gresch, Paul J; Gantz, Stephanie C; Williams, John; Davis, Gwynne L; Wheeler, C Austin; Stanwood, Gregg D; Hahn, Maureen K; Blakely, Randy D

2014-11-04

Despite the critical role of the presynaptic dopamine (DA) transporter (DAT, SLC6A3) in DA clearance and psychostimulant responses, evidence that DAT dysfunction supports risk for mental illness is indirect. Recently, we identified a rare, nonsynonymous Slc6a3 variant that produces the DAT substitution Ala559Val in two male siblings who share a diagnosis of attention-deficit hyperactivity disorder (ADHD), with other studies identifying the variant in subjects with bipolar disorder (BPD) and autism spectrum disorder (ASD). Previously, using transfected cell studies, we observed that although DAT Val559 displays normal total and surface DAT protein levels, and normal DA recognition and uptake, the variant transporter exhibits anomalous DA efflux (ADE) and lacks capacity for amphetamine (AMPH)-stimulated DA release. To pursue the significance of these findings in vivo, we engineered DAT Val559 knock-in mice, and here we demonstrate in this model the presence of elevated extracellular DA levels, altered somatodendritic and presynaptic D2 DA receptor (D2R) function, a blunted ability of DA terminals to support depolarization and AMPH-evoked DA release, and disruptions in basal and psychostimulant-evoked locomotor behavior. Together, our studies demonstrate an in vivo functional impact of the DAT Val559 variant, providing support for the ability of DAT dysfunction to impact risk for mental illness.

Preclinical and Clinical Studies Demonstrate That the Proprietary Herbal Extract DA-5512 Effectively Stimulates Hair Growth and Promotes Hair Health.

PubMed

Yu, Jae Young; Gupta, Biki; Park, Hyoung Geun; Son, Miwon; Jun, Joon-Ho; Yong, Chul Soon; Kim, Jeong Ah; Kim, Jong Oh

2017-01-01

The proprietary DA-5512 formulation comprises six herbal extracts from traditional oriental plants historically associated with therapeutic and other applications related to hair. Here, we investigated the effects of DA-5512 on the proliferation of human dermal papilla cells (hDPCs) in vitro and on hair growth in C57BL/6 mice and conducted a clinical study to evaluate the efficacy and safety of DA-5512. DA-5512 significantly enhanced the viability of hDPCs in a dose-dependent manner ( p < 0.05), and 100 ppm of DA-5512 and 1  μ M minoxidil (MXD) significantly increased the number of Ki-67-positive cells, compared with the control group ( p < 0.05). MXD (3%) and DA-5512 (1%, 5%) significantly stimulated hair growth and increased the number and length of hair follicles (HFs) versus the controls (each p < 0.05). The groups treated with DA-5512 exhibited hair growth comparable to that induced by MXD. In clinical study, we detected a statistically significant increase in the efficacy of DA-5512 after 16 weeks compared with the groups treated with placebo or 3% MXD ( p < 0.05). In conclusion, DA-5512 might promote hair growth and enhance hair health and can therefore be considered an effective option for treating hair loss.

The rare DAT coding variant Val559 perturbs DA neuron function, changes behavior, and alters in vivo responses to psychostimulants

PubMed Central

Mergy, Marc A.; Gowrishankar, Raajaram; Gresch, Paul J.; Gantz, Stephanie C.; Williams, John; Davis, Gwynne L.; Wheeler, C. Austin; Stanwood, Gregg D.; Hahn, Maureen K.; Blakely, Randy D.

2014-01-01

Despite the critical role of the presynaptic dopamine (DA) transporter (DAT, SLC6A3) in DA clearance and psychostimulant responses, evidence that DAT dysfunction supports risk for mental illness is indirect. Recently, we identified a rare, nonsynonymous Slc6a3 variant that produces the DAT substitution Ala559Val in two male siblings who share a diagnosis of attention-deficit hyperactivity disorder (ADHD), with other studies identifying the variant in subjects with bipolar disorder (BPD) and autism spectrum disorder (ASD). Previously, using transfected cell studies, we observed that although DAT Val559 displays normal total and surface DAT protein levels, and normal DA recognition and uptake, the variant transporter exhibits anomalous DA efflux (ADE) and lacks capacity for amphetamine (AMPH)-stimulated DA release. To pursue the significance of these findings in vivo, we engineered DAT Val559 knock-in mice, and here we demonstrate in this model the presence of elevated extracellular DA levels, altered somatodendritic and presynaptic D2 DA receptor (D2R) function, a blunted ability of DA terminals to support depolarization and AMPH-evoked DA release, and disruptions in basal and psychostimulant-evoked locomotor behavior. Together, our studies demonstrate an in vivo functional impact of the DAT Val559 variant, providing support for the ability of DAT dysfunction to impact risk for mental illness. PMID:25331903

Effects of DA-Phen, a dopamine-aminoacidic conjugate, on alcohol intake and forced abstinence.

PubMed

Sutera, Flavia Maria; De Caro, Viviana; Cannizzaro, Carla; Giannola, Libero Italo; Lavanco, Gianluca; Plescia, Fulvio

2016-09-01

The mesolimbic dopamine (DA) system plays a key role in drug reinforcement and is involved in the development of alcohol addiction. Manipulation of the DAergic system represents a promising strategy to control drug-seeking behavior. Previous studies on 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-Phen) showed in vivo effects as a DA-ergic modulator. This study was aimed at investigate DA-Phen effects on operant behavior for alcohol seeking behavior, during reinstatement following subsequent periods of alcohol deprivation. For this purpose, male Wistar rats were tested in an operant paradigm of self-administration; behavioral reactivity and anxiety like-behavior during acute abstinence were evaluated. A characterization of DA-Phen CNS targeting by its quantification in the brain was also carried out. Our findings showed that DA-Phen administration was able to reduce relapse in alcohol drinking by 50% and reversed the alterations in behavioral reactivity and emotionality observed during acute abstinence. In conclusion, DA-Phen can reduce reinstatement of alcohol drinking in an operant-drinking paradigm following deprivation periods and reverse abstinence-induced behavioral phenotype. DA-Phen activity seems to be mediated by the modulation of the DAergic transmission. However further studies are needed to characterize DA-Phen pharmacodynamic and pharmacokinetic properties, and its potential therapeutic profile in alcohol addiction. Copyright © 2016 Elsevier B.V. All rights reserved.

Vinpocetine and α-tocopherol prevent the increase in DA and oxidative stress induced by 3-NPA in striatum isolated nerve endings.

PubMed

Herrera-Mundo, Nieves; Sitges, María

2013-01-01

Vinpocetine is a neuroprotective drug that exerts beneficial effects on neurological symptoms and cerebrovascular disease. 3-nitropropionic acid (3-NPA) is a toxin that irreversibly inhibits succinate dehydrogenase, the mitochondrial enzyme that acts in the electron transport chain at complex II. In previous studies in striatum-isolated nerve endings (synaptosomes), we found that vinpocetine decreased dopamine (DA) at expense of its main metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), and that 3-NPA increased DA, reactive oxygen species (ROS), DA-quinone products formation, and decreased DOPAC. Therefore, in this study, the possible effect of vinpocetine on 3-NPA-induced increase in DA, ROS, lipid peroxidation, and DA-quinone products formation in striatum synaptosomes were investigated, and compared with the effects of the antioxidant α-tocopherol. Results show that the increase in DA induced by 3-NPA was inhibited by both 25 μM vinpocetine and 50 μM α-tocopherol. Vinpocetine, as α-tocopherol, also inhibited 3-NPA-induced increase in ROS (as judged by DCF fluorescence), lipid peroxidation (as judged by TBA-RS formation), and DA-quinone products formation (as judged by the nitroblue tetrazolium reduction method). As in addition to the inhibition of complex II exerted by 3-NPA, 3-NPA increases DA-oxidation products that in turn can inhibit other sites of the respiratory chain, the drop in DA produced by vinpocetine and α-tocopherol may importantly contribute to their protective action from oxidative damage, particularly in DA-rich structures. © 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.

An isoform of myosin XI is responsible for the translocation of endoplasmic reticulum in tobacco cultured BY-2 cells.

PubMed

Yokota, Etsuo; Ueda, Shunpei; Tamura, Kentaro; Orii, Hidefumi; Uchi, Satoko; Sonobe, Seiji; Hara-Nishimura, Ikuko; Shimmen, Teruo

2009-01-01

The involvement of myosin XI in generating the motive force for cytoplasmic streaming in plant cells is becoming evident. For a comprehensive understanding of the physiological roles of myosin XI isoforms, it is necessary to elucidate the properties and functions of each isoform individually. In tobacco cultured BY-2 cells, two types of myosins, one composed of 175 kDa heavy chain (175 kDa myosin) and the other of 170 kDa heavy chain (170 kDa myosin), have been identified biochemically and immunocytochemically. From sequence analyses of cDNA clones encoding heavy chains of 175 kDa and 170 kDa myosin, both myosins have been classified as myosin XI. Immunocytochemical studies using a polyclonal antibody against purified 175 kDa myosin heavy chain showed that the 175 kDa myosin is distributed throughout the cytoplasm as fine dots in interphase BY-2 cells. During mitosis, some parts of 175 kDa myosin were found to accumulate in the pre-prophase band (PPB), spindle, the equatorial plane of a phragmoplast and on the circumference of daughter nuclei. In transgenic BY-2 cells, in which an endoplasmic reticulum (ER)-specific retention signal, HDEL, tagged with green fluorescent protein (GFP) was stably expressed, ER showed a similar behaviour to that of 175 kDa myosin. Furthermore, this myosin was co-fractionated with GFP-ER by sucrose density gradient centrifugation. From these findings, it was suggested that the 175 kDa myosin is a molecular motor responsible for translocating ER in BY-2 cells.

Tonic dopamine induces persistent changes in the transient potassium current through translational regulation

PubMed Central

Rodgers, EW; Krenz, W-D; Baro, DJ

2012-01-01

Neuromodulatory effects can vary with their mode of transmission. Phasic release produces local and transient increases in dopamine (DA) up to micromolar concentrations. Additionally, since DA is released from open synapses and reuptake mechanisms are not nearby, tonic nanomolar DA exists in the extracellular space. Do phasic and tonic transmissions similarly regulate voltage dependent ionic conductances in a given neuron? It was previously shown that DA could immediately alter the transient potassium current (IA) of identified neurons in the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus. Here we show that DA can also persistently alter IA, and that DA’s immediate and persistent effects oppose one another. The lateral pyloric neuron (LP) exclusively expresses type 1 DA receptors (D1Rs). Micromolar DA produces immediate depolarizing shifts in the voltage dependence of LP IA, whereas tonic nanomolar DA produces a persistent increase in LP IA maximal conductance (Gmax) through a translation dependent mechanism involving target of rapamycin (TOR). The pyloric dilator neuron (PD) exclusively expresses type 2 DA receptors (D2Rs). Micromolar DA produces an immediate hyperpolarizing shift in PD IA voltage dependence of activation, whereas tonic DA persistently decreases PD IA Gmax through a translation dependent mechanism not involving TOR. The persistent effects on IA Gmax do not depend on LP or PD activity. These data suggest a role for tonic modulators in the regulation of voltage gated ion channel number; and furthermore, that dopaminergic systems may be organized to limit the amount of change they can impose on a circuit. PMID:21917788

Increases in cytoplasmic dopamine compromise the normal resistance of the nucleus accumbens to methamphetamine neurotoxicity

PubMed Central

Thomas, David M.; Francescutti-Verbeem, Dina M.; Kuhnt, Donald M.

2016-01-01

Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the caudate–putamen (CPu) where long-term DA depletion and microglial activation are most evident. Even damage within the CPu is remarkably heterogenous with lateral and ventral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared of the damage that accompanies binge METH intoxication. Increases in cytoplasmic DA produced by reserpine, L-DOPA or clorgyline prior to METH uncover damage in the NAc as evidenced by microglial activation and depletion of DA, tyrosine hydroxylase (TH), and the DA transporter. These effects do not occur in the NAc after treatment with METH alone. In contrast to the CPu where DA, TH, and DA transporter levels remain depleted chronically, DA nerve ending alterations in the NAc show a partial recovery over time. None of the treatments that enhance METH toxicity in the NAc and CPu lead to losses of TH protein or DA cell bodies in the substantia nigra or the ventral tegmentum. These data show that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of METH to include brain structures not normally targeted for damage by METH alone. The resistance of the NAc to METH-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of METH neurotoxicity by alterations in DA homeostasis is significant in light of the important roles played by this brain structure. PMID:19457119

Pharmacological action of DA-9701 on the motility of feline stomach circular smooth muscle.

PubMed

Nguyen, Thanh Thao; Song, Hyun Ju; Ko, Sung Kwon; Sohn, Uy Dong

2015-03-01

DA-9701, a new prokinetic agent for the treatment of functional dyspepsia, is formulated with Pharbitis semen and Corydalis tuber. This study wasconducted to determine the pharmacological action of DA-9701 and to identify the receptors involved in DA-9701 -induced contractile responsesin the feline gastric corporal, fundic and antral circular smooth muscle. Concentration-response curve to DA-9701 was established. The tissue trips were exposed to methylsergide, ketanserin, ondansetron, GR 113808, atropine and dopamine before administration of DA-9701. The contractile force was determined before and after administration of drugs by a polygraph.DA-9701 enhanced the spontaneous contractile amplitude of antrum, corpus and fundus. However, it did not change the spontaneous contractile frequency of antrum and corpus, but concentration-dependently reduced that of fundus. In the fundus, DA-9701 -induced tonic contractions were inhibited by dopamine, methylsergide, ketanserine, ondansetron or GR 113808 respectively, but not by atropine, indicating that the contractile responses are mediated by multiple receptors: 5-HT2, 5-HT3, 5-HT4, and dopamine receptors. In the corpus, DA-9701-induced contractions were blocked by atropine, dopamine or GR 113808, but not by methysergide, ketanserin or ondansetron, indicating that they are involved in receptors on both, smooth muscles and neurons: 5-HT4 and dopamine receptors. However, contractile responses to DA-9701 are mainly mediated by dopamine receptors in the antrum. These results suggest that DA-9701 has important roles in gastric accommodation by enhancing tonic activity of fundus, and in gastric emptying and gastrointestinal transit by phasic contractions of corpus and antrum mediated by multiple receptors.

Increases in cytoplasmic dopamine compromise the normal resistance of the nucleus accumbens to methamphetamine neurotoxicity.

PubMed

Thomas, David M; Francescutti-Verbeem, Dina M; Kuhn, Donald M

2009-06-01

Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the caudate-putamen (CPu) where long-term DA depletion and microglial activation are most evident. Even damage within the CPu is remarkably heterogenous with lateral and ventral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared of the damage that accompanies binge METH intoxication. Increases in cytoplasmic DA produced by reserpine, L-DOPA or clorgyline prior to METH uncover damage in the NAc as evidenced by microglial activation and depletion of DA, tyrosine hydroxylase (TH), and the DA transporter. These effects do not occur in the NAc after treatment with METH alone. In contrast to the CPu where DA, TH, and DA transporter levels remain depleted chronically, DA nerve ending alterations in the NAc show a partial recovery over time. None of the treatments that enhance METH toxicity in the NAc and CPu lead to losses of TH protein or DA cell bodies in the substantia nigra or the ventral tegmentum. These data show that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of METH to include brain structures not normally targeted for damage by METH alone. The resistance of the NAc to METH-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of METH neurotoxicity by alterations in DA homeostasis is significant in light of the important roles played by this brain structure.

Methylphenidate and Cocaine Self-Administration Produce Distinct Dopamine Terminal Alterations

PubMed Central

Calipari, Erin S.; Ferris, Mark J.; Melchior, James R.; Bermejo, Kristel; Salahpour, Ali; Roberts, David C. S.; Jones, Sara R.

2012-01-01

Methylphenidate (MPH) is a commonly abused psychostimulant prescribed for the treatment of attention deficit hyperactivity disorder. MPH has a mechanism of action similar to cocaine (COC) and is commonly characterized as a dopamine transporter (DAT) blocker. While there has been extensive work aimed at understanding dopamine (DA) nerve terminal changes following COC self-administration, very little is known about the effects of MPH self-administration on the DA system. We used fast scan cyclic voltammetry in nucleus accumbens core slices from animals with a five-day self-administration history of 40 injections/day of either MPH (0.56 mg/kg) or COC (1.5 mg/kg) to explore alterations in baseline DA release and uptake kinetics as well as alterations in the interaction of each compound with the DAT. Although MPH and COC have similar behavioral effects, the consequences of self-administration on DA system parameters were found to be divergent. We show that COC self-administration reduced DAT levels and maximal rates of DA uptake, as well as reducing electrically stimulated release, suggesting decreased DA terminal function. In contrast, MPH self-administration increased DAT levels, DA uptake rates, and DA release, suggesting enhanced terminal function, which was supported by findings of increased metabolite/DA tissue content ratios. Tyrosine hydroxylase mRNA, protein and phosphorylation levels were also assessed in both groups. Additionally, COC self-administration reduced COC-induced DAT inhibition, while MPH self-administration increased MPH-induced DAT inhibition, suggesting opposite pharmacodynamic effects of these two drugs. These findings suggest that the factors governing DA system adaptations are more complicated than simple DA uptake blockade. PMID:22458761

32 CFR 537.16 - Scope for maritime claims.

Code of Federal Regulations, 2010 CFR

2010-07-01

... claims for damage to: (1) DA-accountable properties of a kind that are within the federal maritime jurisdiction. (2) Property under the DA's jurisdiction or DA property damaged by a vessel or floating object... services (including contract salvage and towage) performed by the DA. Claims for salvage services are based...

[In Process Citation].

PubMed

Burgos, Rosa

2016-03-25

La desnutrición relacionada con la enfermedad (DRE) es un problema sanitario de elevada índole que impacta fuertemente en la morbilidad, mortalidad y calidad de vida de los pacientes ancianos ingresados en el hospital. Además, incrementa enormemente el gasto sanitario, sobre todo a través del aumento de la estancia hospitalaria, incremento de las complicaciones y necesidad de centro de convalecencia u otros recursos sanitarios al alta hospitalaria. Conjuntamente con la osteoporosis y la sarcopenia, contribuye de forma directa a la discapacidad y a la pérdida de autonomía del anciano, con las repercusiones familiares y sociales que ello implica.

Los Hispanos: Problemas y Oportunidades. Resumen de la Actual Situacion Demografica, Economica, Social y Politica de los Hispanos en los Estados Unidos y de las Iniciativas Tomadas por la Fundacion Ford Para Hacer Frente a las Necesidades de esta Poblacion en Aumento y Determinar sus Efectos Sobre la Sociedad Estadounidense. Documento de Trabajo de la Fundacion Ford, No. 436.

ERIC Educational Resources Information Center

Ford Foundation, New York, NY.

The Hispanic population's growing impact on American society has caused the Ford Foundation to explore new Foundation initiatives. The 1980 census revealed 14.6 million Hispanics: 60% Mexican American; 14% Puerto Rican; 6% Cuban, and 20% Other. The Hispanic population in the United States is growing and is characterized by diversity; rapid growth…

Dinámica de pulsares jóvenes

NASA Astrophysics Data System (ADS)

Allen, M. P.; Horvath, J. E.

La observación detallada de los pulsos en varios pulsares jóvenes (τ < 105 yr) permitió detectar varios aumentos en la frecuencia de emisión gliches con cambios permanentes en Δ {˙ Ω} / {˙ Ω}. A través de las ecuaciones de movimiento se investiga, utilizando parametrizaciones simples, la hipótesis de que el ángulo entre Ω y el dipolo magnético M sea responsable de ese comportamiento. Se derivan curvas analíticas para la evolución de Ω (t) y se estudia la posibilidad de describir un conjunto de observables (incluyendo el braking index n) con estos modelos.

Da Vinci-assisted abdominal cerclage.

PubMed

Barmat, Larry; Glaser, Gretchen; Davis, George; Craparo, Frank

2007-11-01

To report the first placement of an abdominal cervicoisthmic cerclage using the da Vinci robot. Case report. Tertiary-care hospital. A 39-year-old female with a history of cervical insufficiency who required a cerclage and was not a candidate for transvaginal cerclage placement. Abdominal cervicoisthmic cerclage placement using the da Vinci robot. Ability to safely and successfully place an abdominal cerclage using the da Vinci robot. Abdominal cerclage was successfully placed using the da Vinci robot. The patient had minimal blood loss and was discharged to home on the same day as surgery. Da Vinci robot-assisted abdominal cerclage placement is an innovative application of robotic surgery and may alter the standard of care for women who require this surgery.

Immunoblot patterns of Taenia asiatica taeniasis.

PubMed

Jeon, Hyeong-Kyu; Eom, Keeseon S

2009-03-01

Differential diagnosis of Taenia asiatica infection from other human taeniases by serology has been tested. An enzyme-linked immunoelectrotransfer blot (EITB) was applied to subjected human sera and tapeworm materials. Thirty-eight proteins reactive to serum IgG were observed between 121 and 10 kDa in adult worms, and more than 22 serum-reactive components between 97 kDa and 21.5 kDa were observed in eggs of T. asiatica. Antigens of adult T. asiatica revealed immunoblot bands between 120 and 21.5 kDa against T. asiatica infected sera. Antigens of adult Taenia saginata revealed 110-100, 66, 58-56, and 46 kDa immunoblot bands against T. asiatica infected sera. Antigens of adult Taenia solium also revealed 99-97, 68-66, and 46 kDa bands against T. asiatica infected sera. The immunoblot band of 21.5 kDa exhibited specificity to T. asiatica.

Specific and common antigens of Clonorchis sinensis and Opisthorchis viverrini (Opisthorchidae, Trematoda)

PubMed Central

Choi, Min-Ho; Ryu, Jin-Sook; Lee, Mejeong; Li, Shunyu; Chung, Byung-Suk; Chai, Jong-Yil; Sithithaworn, Paiboon; Tesana, Smarn

2003-01-01

The antigenic characterizations and serological reactions of human liver flukes, Clonorchis sinensis and Opisthorchis viverrini, were analyzed by immunoblot. The antigenic profiles of the crude extract of Clonorchis contained major proteins of 8, 26-28, 34-37, 43, and 70 kDa, and those of Opisthorchis 34-37, 43, 70, and 100 kDa. Of these, the 8, 26-28 and 34-37 kDa bands of Clonorchis and the 100 kDa of Opisthorchis were major components of each excretory-secretory antigen. The 8 and 26-28 kDa bands were specific to Clonorchis but the 100 kDa of Opisthorchis cross-reacted with the sera of clonorchiasis, and the 34-37, 70 and 100 kDa bands cross-reacted with sera of other helminthiases. The frequency and intensity of the immunoblot reactions were positively correlated with the intensity of the liver fluke infection. PMID:12972729

Immunoblot Patterns of Taenia asiatica Taeniasis

PubMed Central

Jeon, Hyeong-Kyu

2009-01-01

Differential diagnosis of Taenia asiatica infection from other human taeniases by serology has been tested. An enzyme-linked immunoelectrotransfer blot (EITB) was applied to subjected human sera and tapeworm materials. Thirty-eight proteins reactive to serum IgG were observed between 121 and 10 kDa in adult worms, and more than 22 serum-reactive components between 97 kDa and 21.5 kDa were observed in eggs of T. asiatica. Antigens of adult T. asiatica revealed immunoblot bands between 120 and 21.5 kDa against T. asiatica infected sera. Antigens of adult Taenia saginata revealed 110-100, 66, 58-56, and 46 kDa immunoblot bands against T. asiatica infected sera. Antigens of adult Taenia solium also revealed 99-97, 68-66, and 46 kDa bands against T. asiatica infected sera. The immunoblot band of 21.5 kDa exhibited specificity to T. asiatica. PMID:19290097

Dopamine in Drosophila: setting arousal thresholds in a miniature brain

PubMed Central

Van Swinderen, Bruno; Andretic, Rozi

2011-01-01

In mammals, the neurotransmitter dopamine (DA) modulates a variety of behaviours, although DA function is mostly associated with motor control and reward. In insects such as the fruitfly, Drosophila melanogaster, DA also modulates a wide array of behaviours, ranging from sleep and locomotion to courtship and learning. How can a single molecule play so many different roles? Adaptive changes within the DA system, anatomical specificity of action and effects on a variety of behaviours highlight the remarkable versatility of this neurotransmitter. Recent genetic and pharmacological manipulations of DA signalling in Drosophila have launched a surfeit of stories—each arguing for modulation of some aspect of the fly's waking (and sleeping) life. Although these stories often seem distinct and unrelated, there are some unifying themes underlying DA function and arousal states in this insect model. One of the central roles played by DA may involve perceptual suppression, a necessary component of both sleep and selective attention. PMID:21208962

Dopamine Receptors and Parkinson's Disease

PubMed Central

Hisahara, Shin; Shimohama, Shun

2011-01-01

Parkinson's disease (PD) is a progressive extrapyramidal motor disorder. Pathologically, this disease is characterized by the selective dopaminergic (DAergic) neuronal degeneration in the substantia nigra. Correcting the DA deficiency in PD with levodopa (L-dopa) significantly attenuates the motor symptoms; however, its effectiveness often declines, and L-dopa-related adverse effects emerge after long-term treatment. Nowadays, DA receptor agonists are useful medication even regarded as first choice to delay the starting of L-dopa therapy. In advanced stage of PD, they are also used as adjunct therapy together with L-dopa. DA receptor agonists act by stimulation of presynaptic and postsynaptic DA receptors. Despite the usefulness, they could be causative drugs for valvulopathy and nonmotor complication such as DA dysregulation syndrome (DDS). In this paper, physiological characteristics of DA receptor familyare discussed. We also discuss the validity, benefits, and specific adverse effects of pharmaceutical DA receptor agonist. PMID:25954517

Using Dynamic Assessment to Evaluate the Expressive Syntax of Children who use Augmentative and Alternative Communication

PubMed Central

King, Marika R.; Binger, Cathy; Kent-Walsh, Jennifer

2015-01-01

The developmental readiness of four 5-year-old children to produce basic sentences using graphic symbols on an augmentative and alternative communication (AAC) device during a dynamic assessment (DA) task was examined. Additionally, the ability of the DA task to predict performance on a subsequent experimental task was evaluated. A graduated prompting framework was used during DA. Measures included amount of support required to produce the targets, modifiability (change in participant performance) within a DA session, and predictive validity of DA. Participants accurately produced target structures with varying amounts of support. Modifiability within DA sessions was evident for some participants, and partial support was provided for the measures of predictive validity. These initial results indicate that DA may be a viable way to measure young children’s developmental readiness to learn how to sequence simple, rule-based messages via aided AAC. PMID:25621928

Peripheral Vascular Resistance Impairment during Isometric Physical Exercise in Normotensive Offspring of Hypertensive Parents.

PubMed

Portela, Natália; Amaral, Josária Ferraz; Mira, Pedro Augusto de Carvalho; Souza, Livia Victorino de; Martinez, Daniel Godoy; Laterza, Mateus Camaroti

2017-07-10

A family history of hypertension is associated with vascular and autonomic abnormalities, as well as an impaired neurohemodynamic response to exercise. To test the hypothesis that normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise. The study included 37 normotensive volunteers of both sexes who were sedentary, eutrophic, and nonsmokers, comprising 23 with (FH+; 24 ± 3 years) and 14 without (FH-; 27 ± 5 years) a family history of hypertension. Blood pressure, heart rate (DIXTAL®), forearm blood flow (Hokanson®), and peripheral vascular resistance were simultaneously measured for 3 minutes during rest and, subsequently, for 3 minutes during an isometric exercise at 30% of maximal voluntary contraction (Jamar®). At rest, the FH+ and FH- groups present similar mean blood pressure (83 ± 7 versus 83 ± 5 mmHg, p = 0.96), heart rate (69 ± 8 bpm versus 66 ± 7 bpm, p = 0.18), forearm blood flow (3 ± 1 mL/min/100 mL versus 2.7 ± 1 mL/min/100 mL, p = 0.16), and peripheral vascular resistance (30 ± 9 units versus 34±9 units, p = 0.21), respectively. Both groups showed a significant and similar increase in mean blood pressure (∆ = 15 ± 7 mmHg versus 14 ± 7 mmHg, p = 0.86), heart rate (∆ = 12 ± 8 bpm versus 13 ± 7 bpm, p = 0.86), and forearm blood flow (∆ = 0.8 ± 1.2 mL/min/100 mL versus 1.4 ± 1.1 mL/min/100 mL, p = 0.25), respectively, during exercise. However, individuals in the FH+ group showed no reduction in peripheral vascular resistance during exercise, which was observed in the FH- group (∆ = -0.4 ± 8.6 units versus -7.2 ± 6.3 units, p = 0.03). Normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise. O histórico familiar para hipertensão arterial está relacionado a anormalidades vasculares e autonômicas, bem como disfunções no comportamento neuro-hemodinâmico durante o exercício físico. Testar a hipótese de que indivíduos normotensos com histórico familiar de hipertensão arterial apresentam resposta prejudicada da resistência vascular periférica durante o exercício físico. Foram avaliados 37 normotensos de ambos os sexos, sedentários, eutróficos e não tabagistas, sendo 23 com histórico familiar positivo (HF+, 24 ± 3 anos) e 14 com histórico familiar negativo (HF-, 27 ± 5 anos) para hipertensão arterial. Foram identificados pressão arterial, frequência cardíaca (DIXTAL®), fluxo sanguíneo muscular do antebraço e resistência vascular periférica local (Hokanson®) por 3 minutos durante o repouso e, em seguida, 3 minutos durante exercício isométrico de preensão palmar a 30% da contração voluntária máxima (Jamar®). Em repouso, os grupos HF+ e HF- apresentaram valores semelhantes de pressão arterial média (83 ± 7 mmHg versus 83 ± 5 mmHg, p = 0,96), frequência cardíaca (69 ± 8 bpm versus 66 ± 7 bpm, p = 0,18), fluxo sanguíneo muscular (3 ± 1 mL/min/199 mL versus 2,7 ± 1 mL/min/100 mL, p = 0,16) e resistência vascular periférica (30 ± 9 unidades versus 34 ± 9 unidades, p = 0,21), respectivamente. Durante o exercício, HF+ e HF- mostraram aumento significativo e semelhante da pressão arterial média (∆ = 15 ± 7 mmHg versus 14 ± 7 mmHg, p = 0,86), frequência cardíaca (∆ = 12 ± 8 bpm versus 13 ± 7 bpm, p = 0,86) e fluxo sanguíneo muscular (∆ = 0,8 ± 1,2 mL/min/100 mL versus 1,4 ± 1,1 mL/min/100 mL, p = 0,25), respectivamente. Entretanto, no grupo HF+ não houve redução significativa da resistência vascular periférica durante o exercício, fato que ocorreu no grupo HF- (∆ = -0,4 ± 8,6 unidades versus -7,2 ± 6,3 unidades, p = 0,03). Indivíduos normotensos com histórico familiar de hipertensão arterial apresentam resposta prejudicada da resistência vascular periférica durante o exercício físico.

Dopamine modulates hemocyte phagocytosis via a D1-like receptor in the rice stem borer, Chilo suppressalis

USDA-ARS?s Scientific Manuscript database

Dopamine (DA) is a signal moiety bridging the nervous and immune systems. DA dysregulation is linked to serious human diseases, including addiction, schizophrenia, and Parkinson's disease. However, DA actions in the immune system remain incompletely understood. In this study, we found that DA modula...

40 CFR 60.42Da - Standard for particulate matter (PM).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Standard for particulate matter (PM). 60.42Da Section 60.42Da Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR....42Da Standard for particulate matter (PM). (a) On and after the date on which the initial performance...

40 CFR 60.42Da - Standard for particulate matter (PM).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 6 2011-07-01 2011-07-01 false Standard for particulate matter (PM). 60.42Da Section 60.42Da Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR....42Da Standard for particulate matter (PM). (a) On and after the date on which the initial performance...

32 CFR 635.13 - Amendment of records.

Code of Federal Regulations, 2010 CFR

2010-07-01

... delegable. If the decision is made to amend an MPR, a supplemental DA Form 3975 will be prepared. The supplemental DA Form 3975 will change information on the original DA Form 3975 and will be mailed to the... file the supplemental DA Form 3975 with the original MPR and notify the requestor of the amendment of...

32 CFR 536.119 - Scope for maritime claims.

Code of Federal Regulations, 2010 CFR

2010-07-01

... vessel of, or in the service of, the Department of the Army (DA) or by other property under the jurisdiction of the DA. (b) Compensation for towage and salvage service, including contract salvage, rendered to a vessel of, or in the service of, the DA or other property under the jurisdiction of the DA. (c...

76 FR 31457 - Airworthiness Directives; Diamond Aircraft Industries GmbH Model DA 42 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-01

... Airworthiness Directives; Diamond Aircraft Industries GmbH Model DA 42 Airplanes AGENCY: Federal Aviation... reportedly found on DA 42 Main Landing Gear (MLG) Damper-to-Trailing Arm joints during standard maintenance... DA 42 Main Landing Gear (MLG) Damper-to-Trailing Arm joints during standard maintenance. Depending on...

76 FR 14346 - Airworthiness Directives; Diamond Aircraft Industries GmbH Model DA 42 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-16

... Industries GmbH Model DA 42 Airplanes AGENCY: Federal Aviation Administration (FAA), Department of... been reportedly found on DA 42 Main Landing Gear (MLG) Damper-to-Trailing Arm joints during standard... condition for the specified products. The MCAI states: Cracks have been reportedly found on DA 42 Main...

Endogenous dopamine (DA) modulates (3H)spiperone binding in vivo in rat brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bischoff, S.; Krauss, J.; Grunenwald, C.

1991-01-01

(3H)spiperone (SPI) binding in vivo, biochemical parameters and behavior were measured after modulating DA levels by various drug treatments. DA releasers and uptake inhibitors increased SPI binding in rat striatum. In other brain areas, the effects were variable, but only the pituitary remained unaffected. Surprisingly, nomifensine decreased SPI binding in frontal cortex. The effects of these drugs were monitored by measuring DA, serotonin (5-HT) and their metabolites in the same rats. The increased SPI binding in striatum was parallel to the locomotor stimulation with the following rank order: amfonelic acid greater than nomifensine greater than D-amphetamine greater than or equalmore » to methylphenidate greater than amineptine greater than bupropion. Decreasing DA levels with reserpine or alpha-methyl-para-tyrosine reduced SPI binding by 45% in striatum only when both drugs were combined. In contrast, reserpine enhanced SPI binding in pituitary. Thus, the amount of releasable DA seems to modulate SPI binding characteristics. It is suggested that in vivo, DA receptors are submitted to dynamic regulation in response to changes in intrasynaptic concentrations of DA.« less

Discourse analysis: A useful methodology for health-care system researches

PubMed Central

Yazdannik, Ahmadreza; Yousefy, Alireza; Mohammadi, Sepideh

2017-01-01

Discourse analysis (DA) is an interdisciplinary field of inquiry and becoming an increasingly popular research strategy for researchers in various disciplines which has been little employed by health-care researchers. The methodology involves a focus on the sociocultural and political context in which text and talk occur. DA adds a linguistic approach to an understanding of the relationship between language and ideology, exploring the way in which theories of reality and relations of power are encoded in such aspects as the syntax, style, and rhetorical devices used in texts. DA is a useful and productive qualitative methodology but has been underutilized within health-care system research. Without a clear understanding of discourse theory and DA it is difficult to comprehend important research findings and impossible to use DA as a research strategy. To redress this deficiency, in this article, represents an introduction to concepts of discourse and DA, DA history, Philosophical background, DA types and analysis strategy. Finally, we discuss how affect to the ideological dimension of such phenomena discourse in health-care system, health beliefs and intra-disciplinary relationship in health-care system. PMID:29296612

Discourse analysis: A useful methodology for health-care system researches.

PubMed

Yazdannik, Ahmadreza; Yousefy, Alireza; Mohammadi, Sepideh

2017-01-01

Discourse analysis (DA) is an interdisciplinary field of inquiry and becoming an increasingly popular research strategy for researchers in various disciplines which has been little employed by health-care researchers. The methodology involves a focus on the sociocultural and political context in which text and talk occur. DA adds a linguistic approach to an understanding of the relationship between language and ideology, exploring the way in which theories of reality and relations of power are encoded in such aspects as the syntax, style, and rhetorical devices used in texts. DA is a useful and productive qualitative methodology but has been underutilized within health-care system research. Without a clear understanding of discourse theory and DA it is difficult to comprehend important research findings and impossible to use DA as a research strategy. To redress this deficiency, in this article, represents an introduction to concepts of discourse and DA, DA history, Philosophical background, DA types and analysis strategy. Finally, we discuss how affect to the ideological dimension of such phenomena discourse in health-care system, health beliefs and intra-disciplinary relationship in health-care system.

Study of Hydroquinone Mediated Cytotoxicity and Hypopigmentation Effects from UVB-Irradiated Arbutin and DeoxyArbutin

PubMed Central

Chang, Nai-Fang; Chen, Yi-Shyan; Lin, Ying-Ju; Tai, Ting-Hsuan; Chen, An-Ni; Huang, Chen-Hsuan; Lin, Chih-Chien

2017-01-01

Arbutin (Arb) and deoxyArbutin (dA) are both effective hypopigmentation agents. However, they are glucoside derivatives of hydroquinone (HQ), which may be decayed into HQ under higher energy environments. Therefore, safety and toxicity are very important issues when considering the usage of these compounds. However, no study has verified the properties of Ultra-Violet B (UVB)-irradiated Arb and dA. In this work, we investigated the cytotoxicity and hypopigmentation effects of UVB-irradiated Arb and dA in Detroit 551 human fibroblast cells and B16-F10 mouse melanoma cells. The results showed that UVB-irradiated Arb and dA have strong cytotoxicity for the fibroblast cells, especially for dA, the caspase-3 is also activated by the treatment of UVB-irradiated dA in Detroit 551 cells. The results correlated with the produced HQ. In addition, UVB-irradiated Arb and dA suppressed the production of melanin in melanoma cells; this is due to the release of HQ that compensates for the UVB triggered Arb and dA decomposition. PMID:28467382

Study of Hydroquinone Mediated Cytotoxicity and Hypopigmentation Effects from UVB-Irradiated Arbutin and DeoxyArbutin.

PubMed

Chang, Nai-Fang; Chen, Yi-Shyan; Lin, Ying-Ju; Tai, Ting-Hsuan; Chen, An-Ni; Huang, Chen-Hsuan; Lin, Chih-Chien

2017-05-03

Arbutin (Arb) and deoxyArbutin (dA) are both effective hypopigmentation agents. However, they are glucoside derivatives of hydroquinone (HQ), which may be decayed into HQ under higher energy environments. Therefore, safety and toxicity are very important issues when considering the usage of these compounds. However, no study has verified the properties of Ultra-Violet B (UVB)-irradiated Arb and dA. In this work, we investigated the cytotoxicity and hypopigmentation effects of UVB-irradiated Arb and dA in Detroit 551 human fibroblast cells and B16-F10 mouse melanoma cells. The results showed that UVB-irradiated Arb and dA have strong cytotoxicity for the fibroblast cells, especially for dA, the caspase-3 is also activated by the treatment of UVB-irradiated dA in Detroit 551 cells. The results correlated with the produced HQ. In addition, UVB-irradiated Arb and dA suppressed the production of melanin in melanoma cells; this is due to the release of HQ that compensates for the UVB triggered Arb and dA decomposition.

Soybean P34 Probable Thiol Protease Probably Has Proteolytic Activity on Oleosins.

PubMed

Zhao, Luping; Kong, Xiangzhen; Zhang, Caimeng; Hua, Yufei; Chen, Yeming

2017-07-19

P34 probable thiol protease (P34) and Gly m Bd 30K (30K) show high relationship with the protease of 24 kDa oleosin of soybean oil bodies. In this study, 9 day germinated soybean was used to separate bioprocessed P34 (P32) from bioprocessed 30K (28K). Interestingly, P32 existed as dimer, whereas 28K existed as monomer; a P32-rich sample had proteolytic activity and high cleavage site specificity (Lys-Thr of 24 kDa oleosin), whereas a 28K-rich sample showed low proteolytic activity; the P32-rich sample contained one thiol protease. After mixing with purified oil bodies, all P32 dimers were dissociated and bound to 24 kDa oleosins to form P32-24 kDa oleosin complexes. By incubation, 24 kDa oleosin was preferentially hydrolyzed, and two hydrolyzed products (HPs; 17 and 7 kDa) were confirmed. After most of 24 kDa oleosin was hydrolyzed, some P32 existed as dimer, and the other as P32-17 kDa HP. It was suggested that P32 was the protease.

The butter flavorant, diacetyl, exacerbates β-amyloid cytotoxicity.

PubMed

More, Swati S; Vartak, Ashish P; Vince, Robert

2012-10-15

Diacetyl (DA), an ubiquitous butter-flavoring agent, was found to influence several aspects of amyloid-β (Aβ) aggregation--one of the two primary pathologies associated with Alzheimer's disease. Thioflavin T fluorescence and circular dichroism spectroscopic measurements revealed that DA accelerates Aβ¹⁻⁴² aggregation into soluble and ultimately insoluble β-pleated sheet structures. DA was found to covalently bind to Arg⁵ of Aβ¹⁻⁴² through proteolytic digestion-mass spectrometric experiments. These biophysical and chemical effects translated into the potentiation of Aβ¹⁻⁴² cytotoxicity by DA toward SH-SY5Y cells in culture. DA easily traversed through a MDR1-MDCK cell monolayer, an in vitro model of the blood-brain barrier. Additionally, DA was found not only to be resistant to but also inhibitory toward glyoxalase I, the primary initiator of detoxification of amyloid-promoting reactive dicarbonyl species that are generated naturally in large amounts by neuronal tissue. In light of the chronic exposure of industry workers to DA, this study raises the troubling possibility of long-term neurological toxicity mediated by DA.

Fluorescent light induces neurodegeneration in the rodent nigrostriatal system but near infrared LED light does not.

PubMed

Romeo, Stefania; Vitale, Flora; Viaggi, Cristina; di Marco, Stefano; Aloisi, Gabriella; Fasciani, Irene; Pardini, Carla; Pietrantoni, Ilaria; Di Paolo, Mattia; Riccitelli, Serena; Maccarone, Rita; Mattei, Claudia; Capannolo, Marta; Rossi, Mario; Capozzo, Annamaria; Corsini, Giovanni U; Scarnati, Eugenio; Lozzi, Luca; Vaglini, Francesca; Maggio, Roberto

2017-05-01

We investigated the effects of continuous artificial light exposure on the mouse substantia nigra (SN). A three month exposure of C57Bl/6J mice to white fluorescent light induced a 30% reduction in dopamine (DA) neurons in SN compared to controls, accompanied by a decrease of DA and its metabolites in the striatum. After six months of exposure, neurodegeneration progressed slightly, but the level of DA returned to the basal level, while the metabolites increased with respect to the control. Three month exposure to near infrared LED light (∼710nm) did not alter DA neurons in SN, nor did it decrease DA and its metabolites in the striatum. Furthermore mesencephalic cell viability, as tested by [ 3 H]DA uptake, did not change. Finally, we observed that 710nm LED light, locally conveyed in the rat SN, could modulate the firing activity of extracellular-recorded DA neurons. These data suggest that light can be detrimental or beneficial to DA neurons in SN, depending on the source and wavelength. Copyright © 2017 Elsevier B.V. All rights reserved.

Different protein profile in amniotic fluid with nervous system malformations by surface-enhanced laser desorption-ionization/time-of-flight mass spectrometry (SELDI-TOF-MS) technology.

PubMed

Ma, Zhe; Liu, Cun; Deng, Biping; Dong, Shaogang; Tao, Guowei; Zhan, Xinfeng; Wang, Chuner; Liu, Shaoping; Qu, Xun

2010-12-01

To detect the distinct proteins in amniotic fluid (AF) between nervous system malformations fetuses and normal fetuses. Surface-enhanced laser desorption-ionization/time-of-flight mass spectrometry was used to characterize AF peptides in AF between nervous system malformations fetuses and normal fetuses. WCX2 protein chips were used to characterize AF peptides in AF. Protein chips were examined in a PBSIIC protein reader, the protein profiling was collected by ProteinChip software version 3.1 (Ciphergen Biosystems, Fremont, CA, USA) and analyzed by Biomarker Wizard software (Ciphergen Biosystems). Nine distinct proteins were identified in AF between nervous system malformations fetuses and normal fetuses. Compared with the control group, three proteins with m/z 4967.5 Da, 5258.0 Da, and 11,717.0 Da were down-regulated, and six proteins with m/z 2540.4 Da, 3107.1 Da, 3396.8 Da, 4590.965 Da, 5589.2 Da and 6429.4 Da up-regulated in nervous system malformations fetuses. The results suggest that there are distinct proteins in protein profiling of AF between nervous system malformations fetuses and normal fetuses. © 2010 The Authors. Journal of Obstetrics and Gynaecology Research © 2010 Japan Society of Obstetrics and Gynecology.

Dopamine Receptors and Neurodegeneration

PubMed Central

Rangel-Barajas, Claudia; Coronel, Israel; Florán, Benjamín

2015-01-01

Dopamine (DA) is one of the major neurotransmitters and participates in a number of functions such as motor coordination, emotions, memory, reward mechanism, neuroendocrine regulation etc. DA exerts its effects through five DA receptors that are subdivided in 2 families: D1-like DA receptors (D1 and D5) and the D2-like (D2, D3 and D4). All DA receptors are widely expressed in the central nervous system (CNS) and play an important role in not only in physiological conditions but also pathological scenarios. Abnormalities in the DAergic system and its receptors in the basal ganglia structures are the basis Parkinson’s disease (PD), however DA also participates in other neurodegenerative disorders such as Huntington disease (HD) and multiple sclerosis (MS). Under pathological conditions reorganization of DAergic system has been observed and most of the times, those changes occur as a mechanism of compensation, but in some cases contributes to worsening the alterations. Here we review the changes that occur on DA transmission and DA receptors (DARs) at both levels expression and signals transduction pathways as a result of neurotoxicity, inflammation and in neurodegenerative processes. The better understanding of the role of DA receptors in neuropathological conditions is crucial for development of novel therapeutic approaches to treat alterations related to neurodegenerative diseases. PMID:26425390

Amphetamine Augments Action Potential-Dependent Dopaminergic Signaling in the Striatum in Vivo

PubMed Central

Ramsson, Eric S.; Covey, Daniel P.; Daberkow, David P.; Litherland, Melissa T.; Juliano, Steven A.; Garris, Paul A.

2011-01-01

Amphetamine (AMPH) is thought to disrupt normal patterns of action potential-dependent dopaminergic signaling by depleting dopamine (DA) vesicular stores and promoting non-exocytotic DA efflux. Voltammetry in brain slices concurrently demonstrates these key drug effects, along with competitive inhibition of neuronal DA uptake. Here we perform comparable kinetic and voltammetric analyses in vivo to determine whether AMPH acts qualitatively and quantitatively similar in the intact brain. Fast-scan cyclic voltammetry measured extracellular DA in dorsal and ventral striata of urethane-anesthetized rats. Electrically evoked recordings were analyzed to determine Km and Vmax for DA uptake and vesicular DA release, while background voltammetric current indexed basal DA concentration. AMPH (0.5, 3, and 10 mg/kg i.p.) robustly increased evoked DA responses in both striatal subregions. The predominant contributor to these elevated levels was competitive uptake inhibition, as exocytotic release was unchanged in the ventral striatum and only modestly decreased in the dorsal striatum. Increases in basal DA levels were not detected. These results are consistent with AMPH augmenting action potential-dependent dopaminergic signaling in vivo across a wide, behaviorally relevant dose range. Future work should be directed at possible causes for the distinct in vitro and in vivo pharmacology of AMPH. PMID:21443523

Purification and sequence analysis of two rat tissue inhibitors of metalloproteinases

NASA Technical Reports Server (NTRS)

Roswit, W. T.; McCourt, D. W.; Partridge, N. C.; Jeffrey, J. J.

1992-01-01

Two protein inhibitors of metalloproteinases (TIMP) were isolated from medium conditioned by the clonal rat osteosarcoma line UMR 106-01. Initial purification of both a 30-kDa inhibitor and a 20-kDa inhibitor was accomplished using heparin-Sepharose chromatography with dextran sulfate elution followed by DEAE-Sepharose and CM-Sepharose chromatography. Purification of the 20-kDa inhibitor to homogeneity was completed with reverse-phase high-performance liquid chromatography. The 20-kDa inhibitor was identified as rat TIMP-2. The 30-kDa inhibitor, although not purified to homogeneity, was identified as rat TIMP-1. Amino terminal amino acid sequence analysis of the 30-kDa inhibitor demonstrated 86% identity to human TIMP-1 for the first 22 amino acids while the sequence of the 20-kDa inhibitor was identical to that of human TIMP-2 for the first 22 residues. Treatment with peptide:N-glycosidase F indicated that the 30-kDa rat inhibitor is glycosylated while the 20-kDa inhibitor is apparently unglycosylated. Inhibition of both rat and human interstitial collagenase by rat TIMP-2 was stoichiometric, with a 1:1 molar ratio required for complete inhibition. Exposure of UMR 106-01 cells to 10(-7) M parathyroid hormone resulted in approximately a 40% increase in total inhibitor production over basal levels.

Characteristics of Dynamic Magnetic Resonance Image Enhancement in Prolactinomas Resistant to Dopamine Agonist Therapy

PubMed Central

Guo, Qinghua; Erickson, Bradley J.; Chang, Alice Y.; Erickson, Dana

2015-01-01

Objective To determine whether dynamic magnetic resonance imaging (dMRI) enhancement parameters could predict dopamine agonist (DA) resistance in prolactinomas. Methods We retrospectively identified patients with prolactinomas who were treated with DA and underwent dMRI from 2001 through 2012 at Mayo Clinic (Rochester, Minnesota). Intensities of the adenoma and pituitary gland were measured by drawing regions of interest on the images. Enhancement ratio, enhancement peak, prepeak slope (PPS), and enhancement time were compared between DA-resistant and DA-responsive groups, between DA-treated and DA-naïve groups, and between the first and follow-up dMRIs. Results We identified 49 patients with prolactinomas, with 6 (12.2%) that showed DA resistance. Thirty-seven patients (75.5%) underwent dMRI while receiving treatment, 12 (25.5%) underwent dMRI before starting therapy, and 10 (20.4%) had follow-up dMRI after DA therapy. The PPS of the tumor was higher in the treatment-resistant group vs the responsive group (mean [SD], 4.42 [3.19] vs 2.65 [1.59]; P=.03), whereas no difference was noted in the pituitary gland (5.79 [2.21] vs 4.06 [2.48]; P=.11). Logistic regression analysis indicated that tumor PPS was associated with DA resistance (odds ratio, 1.71; 95% CI, 1.07-3.27; P=.02). Conclusions dMRI with PPS analysis potentially can be used early in the treatment course to evaluate DA resistance in pituitary prolactinomas. PMID:25551412

Characteristics of dynamic magnetic resonance image enhancement in prolactinomas resistant to dopamine agonist therapy.

PubMed

Guo, Qinghua; Erickson, Bradley J; Chang, Alice Y; Erickson, Dana

2015-03-01

The objective of this study was to determine whether dynamic magnetic resonance imaging (dMRI) enhancement parameters could predict dopamine agonist (DA) resistance in prolactinomas. We retrospectively identified patients with prolactinomas who were treated with DA and underwent dMRI from 2001 through 2012 at Mayo Clinic (Rochester, MN). Intensities of the adenoma and pituitary gland were measured by drawing regions of interest on the images. Enhancement ratio, enhancement peak, prepeak slope (PPS), and enhancement time were compared between DA-resistant and DA-responsive groups, between DA-treated and DA-naive groups, and between the first and follow-up dMRIs. We identified 49 patients with prolactinomas, with 6 (12.2%) showing DA resistance. Thirty-seven patients (75.5%) underwent dMRI while receiving treatment, 12 (25.5%) underwent dMRI before starting therapy, and 10 (20.4%) had follow-up dMRI after DA therapy. The PPS of the tumor was higher in the treatment-resistant group versus the responsive group (mean [SD], 4.42 [3.19] vs 2.65 [1.59]; P = 0.03), whereas no difference was noted in the pituitary gland (5.79 [2.21] vs 4.06 [2.48]; P = 0.11). Logistic regression analysis indicated that tumor PPS was associated with DA resistance (odds ratio, 1.71; 95% confidence interval, 1.07-3.27; P = 0.02). Dynamic MRI with PPS analysis potentially can be used early in the treatment course to evaluate DA resistance in pituitary prolactinomas.

A monoclonal antibody that distinguishes latent and active forms of the proteasome (multicatalytic proteinase complex)

NASA Technical Reports Server (NTRS)

Weitman, D.; Etlinger, J. D.

1992-01-01

Monoclonal antibodies (mAbs) were generated to proteasome purified from human erythrocytes. Five of six proteasome-specific mAbs reacted with three subunits in the molecular mass range of 25-28 kDa, indicating a common epitope. The other mAb (AP5C10) exhibited a more restricted reactivity, recognizing a 32-kDa subunit of the proteasome purified in its latent state. However, when the proteasome is isolated in its active state, AP5C10 reacts with a 28-kDa subunit, evidence for processing of the proteasome subunits during purification. Purified proteasome preparations which exhibited partial latency have both AP5C10 reactive subunits. Although the 32-kDa subunit appears required for latency, loss of this component and generation of the 28-kDa component are not obligatory for activation. The 32- and 28-kDa subunits can each be further resolved into three components by isoelectric focusing. The apparent loss of 4 kDa during the conversion of the 32- to 28-kDa subunit is accompanied by a shift to a more basic pI for each polypeptide. Western blots of the early steps of proteasome purification reveal an AP5C10-reactive protein at 41 kDa. This protein was separated from proteasomes by sizing chromatography and may represent a pool of precursor subunits. Since the 32-kDa subunit appears necessary for latency, it is speculated to play a regulatory role in ATP-dependent proteolytic activity.

Autoradiographic evidence for methamphetamine-induced striatal dopaminergic loss in mouse brain: attenuation in CuZn-superoxide dismutase transgenic mice.

PubMed

Hirata, H; Ladenheim, B; Carlson, E; Epstein, C; Cadet, J L

1996-04-01

Methamphetamine (METH) has long-lasting neurotoxic effects on the nigrostriatal dopamine (DA) system of rodents. METH-induced neurotoxicity is thought to involve release of DA in presynaptic DA terminals, which is associated with increased formation of oxygen-based free radicals. We have recently shown that METH-induced striatal DA depletion is attenuated in transgenic (Tg) mice that express the human CuZn-superoxide dismutase (SOD) enzyme. That study did not specifically address the issue of loss of DA terminals. In the present study, we have used receptor autoradiographic studies of [(125)I]RTI-121-labeled DA uptake sites to evaluate the effects of several doses of METH on striatal DA terminals of Non-Tg as well as of heterozygous and homozygous SOD-Tg mice. In Non-Tg mice, METH caused decreases in striatal DA uptake sites in a dose-dependent fashion. The loss of DA terminals was more prominent in the lateral region than in the medial subdivisions of the striatum. In SOD-Tg mice, the loss of DA terminals caused by METH was attenuated in a gene dosage-dependent fashion, with the homozygous mice showing the greatest protection. Female mice were somewhat more resistant than male mice against these deleterious effects of METH. These results provide further evidence for a role of superoxide radicals in the long-term effects of METH. They also suggest the notion of a gender-specific handling of oxidative stress.

Impact of a web-based prostate cancer treatment decision aid on patient-reported decision process parameters: results from the Prostate Cancer Patient Centered Care trial.

PubMed

Cuypers, Maarten; Lamers, Romy E D; Kil, Paul J M; van de Poll-Franse, Lonneke V; de Vries, Marieke

2018-05-12

To compare patients' evaluation of the treatment decision-making process in localized prostate cancer between counseling that included an online decision aid (DA) and standard counseling. Eighteen Dutch hospitals were randomized to DA counseling (n = 235) or the control group with standard counseling (n = 101) in a pragmatic, cluster randomized controlled trial. The DA was provided to patients at, or soon after diagnosis. Decisional conflict, involvement, knowledge, and satisfaction with information were assessed with a questionnaire after treatment decision-making. Anxiety and depression served as covariates. The levels of decision involvement and conflict were comparable between patients in both groups. Patients with a DA felt more knowledgeable but scored equally well on a knowledge test as patients without a DA. Small significant negative effects were found on satisfaction with information and preparation for decision-making. A preference for print over online and depression and anxiety symptoms was negatively associated with satisfaction and conflict scores in the DA group. The DA aimed to support shared decision-making, while outcomes for a majority of DA users were comparable to patients who received standard counseling. Patients, who are less comfortable with the online DA format or experience anxiety or depression symptoms, could require more guidance toward shared decision-making. To evaluate long-term DA effects, follow-up evaluation on treatment satisfaction and decisional regret will be done.

Electrochemical Detection of Dopamine via Assisted Ion Transfer at Nanopipet Electrode Using Cyclic Voltammetry.

PubMed

Colombo, Michelle L; McNeil, Swami; Iwai, Nicholas; Chang, Albert; Shen, Mei

2016-01-01

We present here the detection of dopamine (DA) at nanopipet electrodes with radii of hundreds of nanometers ranging from 160 nm to 480 nm. Dibenzo-18-crown-6 (DB18C6) was employed as an ionophore to facilitate DA transfer, resulting in a half-wave transfer potential, E 1/2, DA , of -0.322 (±0.020) V vs. E 1/2, TBA . Well-defined steady-state sigmoidal cyclic voltammograms were observed for the transfer of DA. High resolution scanning electron microscopy was used to measure the size and taper angle of the nanopipet electrodes. The detection is linear with concentration of DA ranging from 0.25 mM to 2 mM; calculated diffusion coefficient at nanopipet electrodes with above mentioned sizes is 4.87 (±0.28) × 10 -10 m 2 /s. The effect of the common interferent ascorbic acid on DA detection with nanopipet electrodes was evaluated, where DA detection still shows linear behavior with well-defined sigmoidal CVs with E 1/2, DA being -0.328 (±0.029) V vs. E 1/2, TBA . The diffusion coefficient for DA transfer in MgCl 2 with the presence of 2 mM AA was measured to be 1.93 (±0.59) × 10 -10 m 2 /s on nanoelectrodes with radii from 161 nm to 263 nm, but the physiological concentration of 0.1 mM AA had no effect on DA's diffusion coefficient.

Bursting as a source of non-linear determinism in the firing patterns of nigral dopamine neurons

PubMed Central

Jeong, Jaeseung; Shi, Wei-Xing; Hoffman, Ralph; Oh, Jihoon; Gore, John C.; Bunney, Benjamin S.; Peterson, Bradley S.

2012-01-01

Nigral dopamine (DA) neurons in vivo exhibit complex firing patterns consisting of tonic single-spikes and phasic bursts that encode information for certain types of reward-related learning and behavior. Non-linear dynamical analysis has previously demonstrated the presence of a non-linear deterministic structure in complex firing patterns of DA neurons, yet the origin of this non-linear determinism remains unknown. In this study, we hypothesized that bursting activity is the primary source of non-linear determinism in the firing patterns of DA neurons. To test this hypothesis, we investigated the dimension complexity of inter-spike interval data recorded in vivo from bursting and non-bursting DA neurons in the chloral hydrate-anesthetized rat substantia nigra. We found that bursting DA neurons exhibited non-linear determinism in their firing patterns, whereas non-bursting DA neurons showed truly stochastic firing patterns. Determinism was also detected in the isolated burst and inter-burst interval data extracted from firing patterns of bursting neurons. Moreover, less bursting DA neurons in halothane-anesthetized rats exhibited higher dimensional spiking dynamics than do more bursting DA neurons in chloral hydrate-anesthetized rats. These results strongly indicate that bursting activity is the main source of low-dimensional, non-linear determinism in the firing patterns of DA neurons. This finding furthermore suggests that bursts are the likely carriers of meaningful information in the firing activities of DA neurons. PMID:22831464

Identification of Rice Genes Associated With Enhanced Cold Tolerance by Comparative Transcriptome Analysis With Two Transgenic Rice Plants Overexpressing DaCBF4 or DaCBF7, Isolated From Antarctic Flowering Plant Deschampsia antarctica

PubMed Central

Byun, Mi Young; Cui, Li Hua; Lee, Jungeun; Park, Hyun; Lee, Andosung; Kim, Woo Taek; Lee, Hyoungseok

2018-01-01

Few plant species can survive in Antarctica, the harshest environment for living organisms. Deschampsia antarctica is the only natural grass species to have adapted to and colonized the maritime Antarctic. To investigate the molecular mechanism of the Antarctic adaptation of this plant, we identified and characterized D. antarctica C-repeat binding factor 4 (DaCBF4), which belongs to monocot CBF group IV. The transcript level of DaCBF4 in D. antarctica was markedly increased by cold and dehydration stress. To assess the roles of DaCBF4 in plants, we generated a DaCBF4-overexpressing transgenic rice plant (Ubi:DaCBF4) and analyzed its abiotic stress response phenotype. Ubi:DaCBF4 displayed enhanced tolerance to cold stress without growth retardation under any condition compared to wild-type plants. Because the cold-specific phenotype of Ubi:DaCBF4 was similar to that of Ubi:DaCBF7 (Byun et al., 2015), we screened for the genes responsible for the improved cold tolerance in rice by selecting differentially regulated genes in both transgenic rice lines. By comparative transcriptome analysis using RNA-seq, we identified 9 and 15 genes under normal and cold-stress conditions, respectively, as putative downstream targets of the two D. antarctica CBFs. Overall, our results suggest that Antarctic hairgrass DaCBF4 mediates the cold-stress response of transgenic rice plants by adjusting the expression levels of a set of stress-responsive genes in transgenic rice plants. Moreover, selected downstream target genes will be useful for genetic engineering to enhance the cold tolerance of cereal plants, including rice. PMID:29774046

Influence of Culture Conditions on Expression of the 40-Kilodalton Porin Protein of Vibrio anguillarum Serotype O2

PubMed Central

Davey, Michelle L.; Hancock, Robert E. W.; Mutharia, Lucy M.

1998-01-01

Vibrio anguillarum serotype O2 strains express a 40-kDa outer membrane porin protein. Immunoblot analysis revealed that antigenic determinants of the V. anguillarum O2 40-kDa porin were conserved within bacterial species of the genus Vibrio. The relative amounts of the V. anguillarum O2 40-kDa porin were enhanced by growth of V. anguillarum O2 in CM9 medium containing 5 to 10% sucrose or 0.1 to 0.5 M NaCl. In contrast, the levels of the porin were significantly reduced when cells were grown at 37°C, and a novel 60-kDa protein was also observed. However, the osmolarity or ionic concentration of the growth medium did not influence expression of the 60-kDa protein. Growth in medium containing greater than 0.6 mM EDTA reduced production of the V. anguillarum O2 40-kDa porin and enhanced levels of a novel 19-kDa protein. Thus, expression of the V. anguillarum O2 40-kDa porin was osmoregulated and possibly coregulated by temperature. The N-terminal amino acid sequence of the V. anguillarum O2 40-kDa protein and the effect of environmental factors on the cellular levels of the porin suggested that the V. anguillarum O2 40-kDa porin was functionally similar to the OmpC porin of Escherichia coli. However, pore conductance assays revealed that the V. anguillarum O2 40-kDa porin was a general diffusion porin with a pore size in the range of that of the OmpF porin of E. coli. PMID:9435071

Norepinephrine Activates Dopamine D4 Receptors in the Rat Lateral Habenula

PubMed Central

Root, David H.; Hoffman, Alexander F.; Good, Cameron H.; Zhang, Shiliang; Gigante, Eduardo

2015-01-01

The lateral habenula (LHb) is involved in reward and aversion and is reciprocally connected with dopamine (DA)-containing brain regions, including the ventral tegmental area (VTA). We used a multidisciplinary approach to examine the properties of DA afferents to the LHb in the rat. We find that >90% of VTA tyrosine hydroxylase (TH) neurons projecting to the LHb lack vesicular monoamine transporter 2 (VMAT2) mRNA, and there is little coexpression of TH and VMAT2 protein in this mesohabenular pathway. Consistent with this, electrical stimulation of LHb did not evoke DA-like signals, assessed with fast-scan cyclic voltammetry. However, electrophysiological currents that were inhibited by L741,742, a DA-D4-receptor antagonist, were observed in LHb neurons when DA uptake or degradation was blocked. To prevent DA activation of D4 receptors, we repeated this experiment in LHb slices from DA-depleted rats. However, this did not disrupt D4 receptor activation initiated by the dopamine transporter inhibitor, GBR12935. As the LHb is also targeted by noradrenergic afferents, we examined whether GBR12935 activation of DA-D4 receptors occurred in slices depleted of norepinephrine (NE). Unlike DA, NE depletion prevented the activation of DA-D4 receptors. Moreover, direct application of NE elicited currents in LHb neurons that were blocked by L741,742, and GBR12935 was found to be a more effective blocker of NE uptake than the NE-selective transport inhibitor nisoxetine. These findings demonstrate that NE is released in the rat LHb under basal conditions and that it activates DA-D4 receptors. Therefore, NE may be an important regulator of LHb function. PMID:25716845

Redox changes accompanying storage protein mobilization in moist chilled and warm incubated walnut kernels prior to germination.

PubMed

Shahmoradi, Zeynab; Tamaskani, Fatemeh; Sadeghipour, Hamid Reza; Abdolzadeh, Ahmad

2013-01-01

Alterations in the redox state of storage proteins and the associated proteolytic processes were investigated in moist-chilled and warm-incubated walnut (Juglans regia L.) kernels prior to germination. The kernel total protein labeling with a thiol-specific fluorochrome i.e. monobromobimane (mBBr) revealed more reduction of 29-32 kDa putative glutelins, while in the soluble proteins, both putative glutelins and 41, 55 and 58 kDa globulins contained reduced disulfide bonds during mobilization. Thus, the in vivo more reduced disulfide bonds of storage proteins corresponds to greater solubility. After the in vitro reduction of walnut kernel proteins pre-treated by N-ethyl maleimide (NEM) with dithioerythrethiol (DTT) and bacterial thioredoxin, the 58 kDa putative globulin and a 6 kDa putative albumin were identified as disulfide proteins. Thioredoxin stimulated the reduction of the H(2)O(2)-oxidized 6 kDa polypeptide, but not the 58 kDa polypeptide by DTT. The solubility of 6 kDa putative albumin, 58 and 19-24 kDa putative globulins and glutelins, respectively, were increased by DTT. The in vitro specific mobilization of the 58 kDa polypeptide that occurred at pH 5.0 by the kernel endogenous protease was sensitive to the serine-protease inhibitor phenylmethylsulfonyl fluoride (PMSF) and stimulated by DTT. The specific degradation of the 58 kDa polypeptide might be achieved through thioredoxin-mediated activation of a serine protease and/or reductive unfolding of its 58 kDa polypeptide substrate. As redox changes in storage proteins occurred equally in both moist chilled and warm incubated walnut kernels, the regulatory functions of thioredoxins in promoting seed germination may be due to other germination related processes. Copyright © 2012 Elsevier GmbH. All rights reserved.

Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate

PubMed Central

Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-01-01

The central extended amygdala (CEA) has been conceptualized as a ‘macrosystem’ that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the ‘limbic-associative’ striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning. PMID:28220796

Chronic treatment of DA-8159, a new phosphodiesterase type V inhibitor, attenuates endothelial dysfunction in stroke-prone spontaneously hypertensive rat.

PubMed

Choi, Seul Min; Kim, Jee Eun; Kang, Kyung Koo

2006-02-09

This study examined the effects of chronic treatment of a new phosphodiesterase type 5 inhibitor, DA-8159, on endothelial dysfunction in stroke-prone spontaneously hypertensive rats (SHR-SP). Six-week-old male SHR-SP were divided into 4 groups; vehicle control, DA-8159 1, 3, and 10 mg/kg/day. During a 32-week experimental period, the animals were administered DA-8159 orally and fed a 4% NaCl-loaded diet. The systolic blood pressure was measured every two weeks throughout the experimental period using the tail-cuff method. At the end of experiments, the vascular function (acetylcholine-induced vasodilation) in the endothelium-intact aortic rings was investigated. In addition, the mortality, the left ventricular hypertrophy index, the plasma parameters and the incidence of a cerebral infarction were assessed. In the DA-8159 treated-rats, the vascular reactivity improved significantly in a dose-dependent manner. Although DA-8159 did not alter the elevation of the systolic blood pressure directly, the 3 and 10 mg/kg/day DA-8159 treatment delayed the early death caused by stroke. DA-8159 significantly reduced the left ventricular heart weight/body weight ratio compared with the vehicle control group. Furthermore, the DA-8159 treatment significantly increased the plasma nitric oxide, cGMP, and the total antioxidative status. The DA-8159 treatment also reduced the occurrence of stroke-associated cerebral damage. These results indicate that DA-8159 can ameliorate an endothelial dysfunction-related vascular injury. Therefore, pharmacological intervention aimed at attenuating an endothelial dysfunction is important and might be useful in both preventing and treating endothelial dysfunction-related complications.

Identification of Rice Genes Associated With Enhanced Cold Tolerance by Comparative Transcriptome Analysis With Two Transgenic Rice Plants Overexpressing DaCBF4 or DaCBF7, Isolated From Antarctic Flowering Plant Deschampsia antarctica.

PubMed

Byun, Mi Young; Cui, Li Hua; Lee, Jungeun; Park, Hyun; Lee, Andosung; Kim, Woo Taek; Lee, Hyoungseok

2018-01-01

Few plant species can survive in Antarctica, the harshest environment for living organisms. Deschampsia antarctica is the only natural grass species to have adapted to and colonized the maritime Antarctic. To investigate the molecular mechanism of the Antarctic adaptation of this plant, we identified and characterized D. antarctica C-repeat binding factor 4 ( DaCBF4 ), which belongs to monocot CBF group IV. The transcript level of DaCBF4 in D. antarctica was markedly increased by cold and dehydration stress. To assess the roles of DaCBF4 in plants, we generated a DaCBF4 -overexpressing transgenic rice plant ( Ubi:DaCBF4 ) and analyzed its abiotic stress response phenotype. Ubi:DaCBF4 displayed enhanced tolerance to cold stress without growth retardation under any condition compared to wild-type plants. Because the cold-specific phenotype of Ubi:DaCBF4 was similar to that of Ubi:DaCBF7 (Byun et al., 2015), we screened for the genes responsible for the improved cold tolerance in rice by selecting differentially regulated genes in both transgenic rice lines. By comparative transcriptome analysis using RNA-seq, we identified 9 and 15 genes under normal and cold-stress conditions, respectively, as putative downstream targets of the two D. antarctica CBFs. Overall, our results suggest that Antarctic hairgrass DaCBF4 mediates the cold-stress response of transgenic rice plants by adjusting the expression levels of a set of stress-responsive genes in transgenic rice plants. Moreover, selected downstream target genes will be useful for genetic engineering to enhance the cold tolerance of cereal plants, including rice.

Chemopreventive effects of Korean Angelica vs. its major pyranocoumarins on two lineages of transgenic adenocarcinoma of mouse prostate carcinogenesis

PubMed Central

Tang, Su-Ni; Zhang, Jinhui; Wu, Wei; Jiang, Peixin; Puppala, Manohar; Zhang, Yong; Xing, Chengguo; Kim, Sung-Hoon; Jiang, Cheng; Lü, Junxuan

2015-01-01

We showed previously that daily gavage of Angelica gigas Nakai (AGN) root ethanolic extract starting 8 weeks of age inhibited growth of prostate epithelium and neuroendocrine carcinomas (NE-Ca) in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Since decursin (D) and its isomer decursinol angelate (DA) are major pyranocoumarins in AGN extract, we tested the hypothesis that D/DA represented active/prodrug compounds against TRAMP carcinogenesis. Three groups of male C57BL/6 TRAMP mice were gavage-treated daily with excipient vehicle, AGN (5 mg per mouse) or equimolar D/DA (3 mg per mouse) from 8 weeks to 16 or 28 weeks of age. Measurement of plasma and NE-Ca D, DA and their common metabolite decursinol indicated similar retention from AGN vs. D/DA dosing. The growth of TRAMP dorsolateral prostate (DLP) in AGN-and D/DA-treated mice was inhibited by 66% and 61% at 16 weeks and by 67% and 72% at 28 weeks, respectively. Survival of mice bearing NE-Ca to 28 weeks was improved by AGN, but not by D/DA. Nevertheless, AGN-and D/DA-treated mice had lower NE-Ca burden. Immunohistochemical and mRNA analyses of DLP showed AGN and D/DA exerted similar inhibition of TRAMP epithelial lesion progression and key cell cycle genes. Profiling of NE-Ca mRNA showed a greater scope of modulating angiogenesis, epithelial-mesenchymal-transition, invasion-metastasis and inflammation genes by AGN than D/DA. The data therefore support D/DA as probable active/prodrug compounds against TRAMP epithelial lesions, and they cooperate with non-pyranocoumarin compounds to fully express AGN efficacy against NE-Ca. PMID:26116406

Chemopreventive Effects of Korean Angelica versus Its Major Pyranocoumarins on Two Lineages of Transgenic Adenocarcinoma of Mouse Prostate Carcinogenesis.

PubMed

Tang, Su-Ni; Zhang, Jinhui; Wu, Wei; Jiang, Peixin; Puppala, Manohar; Zhang, Yong; Xing, Chengguo; Kim, Sung-Hoon; Jiang, Cheng; Lü, Junxuan

2015-09-01

We showed previously that daily gavage of Angelica gigas Nakai (AGN) root ethanolic extract starting 8 weeks of age inhibited growth of prostate epithelium and neuroendocrine carcinomas (NE-Ca) in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Because decursin (D) and its isomer decursinol angelate (DA) are major pyranocoumarins in AGN extract, we tested the hypothesis that D/DA represented active/prodrug compounds against TRAMP carcinogenesis. Three groups of male C57BL/6 TRAMP mice were gavage treated daily with excipient vehicle, AGN (5 mg per mouse), or equimolar D/DA (3 mg per mouse) from 8 weeks to 16 or 28 weeks of age. Measurement of plasma and NE-Ca D, DA, and their common metabolite decursinol indicated similar retention from AGN versus D/DA dosing. The growth of TRAMP dorsolateral prostate (DLP) in AGN- and D/DA-treated mice was inhibited by 66% and 61% at 16 weeks and by 67% and 72% at 28 weeks, respectively. Survival of mice bearing NE-Ca to 28 weeks was improved by AGN, but not by D/DA. Nevertheless, AGN- and D/DA-treated mice had lower NE-Ca burden. Immunohistochemical and mRNA analyses of DLP showed that AGN and D/DA exerted similar inhibition of TRAMP epithelial lesion progression and key cell-cycle genes. Profiling of NE-Ca mRNA showed a greater scope of modulating angiogenesis, epithelial-mesenchymal transition, invasion-metastasis, and inflammation genes by AGN than D/DA. The data therefore support D/DA as probable active/prodrug compounds against TRAMP epithelial lesions, and they cooperate with non-pyranocoumarin compounds to fully express AGN efficacy against NE-Ca. ©2015 American Association for Cancer Research.

The causes of parent–offspring transmission of drug abuse: a Swedish population-based study

PubMed Central

Kendler, K. S.; Ohlsson, H.; Sundquist, K.; Sundquist, J.

2014-01-01

Background While drug abuse (DA) is strongly familial, we still have limited knowledge about the causes of its cross-generational transmission. Method We examined DA ascertained from national registers in offspring of three family types from the Swedish population [intact (n=2111074), ‘not-lived-with’ (n = 165315, where biological parents never lived with their offspring) and ‘step’ (n = 124800 offspring)], which reflected, respectively, the effects of genes+rearing, genes only and rearing only. We replicated these results in three high-risk co-relative designs. Results Combined across mothers and fathers, the hazard ratio (HR) for DA in offspring given DA in parents was 3.52 in intact, 2.73 in ‘not-lived-with’ and 1.79 in stepfamilies. In 968 biological full or half-sibling pairs one of whom was reared by and the other never lived with their parent with DA, the HR for DA was greater in the reared than ‘not-lived-with’ child (HR 1.57). In 64 offspring pairs of a parent with DA, the HR for DA was greater in a reared biological v. step-parented non-biological child (HR 3.33). In 321 pairs of offspring of a parent with DA one of whom was a not-lived-with biological child and the second a step-parented non-biological child, the HR for DA was greater in the biological v. stepchild (HR 1.80). Conclusions Both genetic and environmental factors contribute substantially to parent–offspring resemblance for DA. The general population contains informative family constellations that can complement more traditional adoption designs in clarifying the sources of parent–offspring resemblance. PMID:25066684

Dopamine inhibits the function of Gr-1+CD115+ myeloid-derived suppressor cells through D1-like receptors and enhances anti-tumor immunity.

PubMed

Wu, Jin; Zhang, Ruihua; Tang, Ning; Gong, Zizhen; Zhou, Jiefei; Chen, Yingwei; Chen, Kang; Cai, Wei

2015-01-01

MDSCs accumulate in tumor-bearing animals and cancer patients and are a major factor responsible for cancer-induced immunosuppression that limits effective cancer immunotherapy. Strategies aimed at effectively inhibiting the function of MDSCs are expected to enhance host anti-tumor immunity and improve cancer immunotherapy significantly. The neurotransmitter DA has been found to have anti-cancer activity, but the underlying mechanism is poorly understood. In this study, we sought to investigate the therapeutic mechanism and efficacy of DA on the inhibition of cancer development via the regulation of MDSC functions. The regulation of the suppressive function of Gr-1(+)CD115(+) MDSCs by DA was determined by use of murine syngeneic LLC and B16 graft models treated with DA in vivo, as well as Gr-1(+)CD115(+) MDSCs isolated from these model treated with DA ex vivo. Here, we show that Gr-1(+)CD115(+) monocytic MDSCs express D1-like DA receptors. DA dramatically attenuated the inhibitory function of tumor-induced monocytic MDSCs on T cell proliferation and IFN-γ production via D1-like DA receptors and retarded tumor growth. DA and other D1 receptor agonists inhibited IFN-γ-induced NO production by MDSCs from tumor-bearing mice and cancer patients. Decreased NO production was, in part, mediated via the suppression of p-ERK and p-JNK. In conclusion, the neurotransmitter DA potently inhibits the suppressive function of MDSC and enhances anti-tumor immunity. Our finding provides a mechanistic basis for the use of DA or D1-like receptor agonists to overcome tumor-induced immunosuppression in cancer immunotherapy. © Society for Leukocyte Biology.

Reduced striatal dopamine DA D2 receptor function in dominant-negative GSK-3 transgenic mice.

PubMed

Gomez-Sintes, Raquel; Bortolozzi, Analia; Artigas, Francesc; Lucas, José J

2014-09-01

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase with constitutive activity involved in cellular architecture, gene expression, cell proliferation, fate decision and apoptosis, among others. GSK-3 expression is particularly high in brain where it may be involved in neurological and psychiatric disorders such as Alzheimer׳s disease, bipolar disorder and major depression. A link with schizophrenia is suggested by the antipsychotic drug-induced GSK-3 regulation and by the involvement of the Akt/GSK-3 pathway in dopaminergic neurotransmission. Taking advantage of the previous development of dominant negative GSK-3 transgenic mice (Tg) showing a selective reduction of GSK-3 activity in forebrain neurons but not in dopaminergic neurons, we explored the relationship between GSK-3 and dopaminergic neurotransmission in vivo. In microdialysis experiments, local quinpirole (DA D2-R agonist) in dorsal striatum reduced dopamine (DA) release significantly less in Tg mice than in wild-type (WT) mice. However, local SKF-81297 (selective DA D1-R agonist) in dorsal striatum reduced DA release equally in both control and Tg mice indicating a comparable function of DA D1-R in the direct striato-nigral pathway. Likewise, systemic quinpirole administration - acting preferentially on presynaptic DA D2- autoreceptors to modulate DA release-reduced striatal DA release similarly in both control and Tg mice. Quinpirole reduced locomotor activity and induced c-fos expression in globus pallidus (both striatal DA D2-R-mediated effects) significantly more in WT than in Tg mice. Taking together, the present results show that dominant negative GSK-3 transgenic mice show reduced DA D2-R-mediated function in striatum and further support a link between dopaminergic neurotransmission and GSK-3 activity. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Effect of parasitic infection on dopamine biosynthesis in dopaminergic cells

PubMed Central

Martin, H.L.; Alsaady, I.; Howell, G.; Prandovszky, E.; Peers, C.; Robinson, P.; McConkey, G.A.

2015-01-01

Infection by the neurotropic agent Toxoplasma gondii alters rodent behavior and can result in neuropsychiatric symptoms in humans. Little is understood regarding the effects of infection on host neural processes but alterations to dopaminergic neurotransmission are implicated. We have previously reported elevated levels of dopamine (DA) in infected dopaminergic cells however the involvement of the host enzymes and fate of the produced DA were not defined. In order to clarify the effects of infection on host DA biosynthetic enzymes and DA packaging we examined enzyme levels and activity and DA accumulation and release in T. gondii-infected neurosecretory cells. Although the levels of the host tyrosine hydroxylase (TH) and DOPA decarboxylase and AADC (DDC) did not change significantly in infected cultures, DDC was found within the parasitophorous vacuole (PV), the vacuolar compartment where the parasites reside, as well as in the host cytosol in infected dopaminergic cells. Strikingly, DDC was found within the intracellular parasite cysts in infected brain tissue. This finding could provide some explanation for observations of DA within tissue cysts in infected brain as a parasite-encoded enzyme with TH activity was also localized within tissue cysts. In contrast, cellular DA packaging appeared unchanged in single-cell microamperometry experiments and only a fraction of the increased DA was accessible to high potassium-induced release. This study provides some understanding of how this parasite produces elevated DA within dopaminergic cells without the toxic ramifications of free cytosolic DA. The mechanism for synthesis and packaging of DA by T. gondii-infected dopaminergic cells may have important implications for the effects of chronic T. gondii infection on humans and animals. PMID:26297895

Dysfunctions in Dopamine Systems and ADHD: Evidence From Animals and Modeling

PubMed Central

Viggiano, Davide; Vallone, Daniela; Sadile, Adolfo

2004-01-01

Animal models are useful for characterizing neural substrates of neuropsychiatric disorders. Several models have been proposed for the study of Attention Deficit Hyperactivity Disorder (ADHD). The models can be divided into various groups: (i) genetically derived hyperactivity/ inattention, (ii) animal models showing symptoms after pharmacological intervention, and (iii) those based on spontaneous variations in a random population. Spontaneously hypertensive (SHR) and Naples High Excitability (NHE) rats show behavioral traits featuring the main aspects of ADHD in humans but show different changes in dopamine (DA) systems. In fact, the enzyme tyrosine hydroxylase is hyperexpressed in NHE rats and hypoexpressed in SHR. The DA transporter is hyperexpressed in both lines, although in the SHR, DAT activity is low (reduced DA uptake). The DA levels in the striatum and prefrontal cortex are increased in the juvenile SHR, but are decreased in handled young and non-handled older animals. The mRNA of the D1 DA receptor is upregulated in the prefrontal cortex of SHR and downregulated in NHE. The D2 DA receptors are likely to be hypofunctioning in SHR, although the experimental evidence is not univocal, whereas their mRNA is hyperexpressed in NHE. Thus, in SHR both the mesocortical and mesolimbic DA pathways appear to be involved, whereas in NHE only the mesocortical system. To understand the effects of methylphenidate, the elective ADHD drug treatment in humans, in a dysfunctioning DA system, we realized a simple mathematical model of DA regulation based on experimental data from electrophysiological, cyclic voltammetry, and microdialysis studies. This model allows the estimation of a higher firing frequency of DA neurons in SHR rats and suggests that methylphenidate increases attentive processes by regulating the firing rate of DA neurons. PMID:15303308

Cytochrome P450 isoforms in the Metabolism of Decursin and Decursinol Angelate from Korean Angelica

PubMed Central

ZHANG, Jinhui; LI, Li; TANG, Suni; HALE, Thomas W.; XING, Chengguo; JIANG, Cheng; LÜ, Junxuan

2016-01-01

We have shown that the in vitro hepatic microsomal metabolism of pyranocoumarin compound decursinol angelate (DA) to decursinol (DOH) exclusively requires cytochrome P450 enzymes (CYP) whereas the conversion of its isomer decursin (D) to DOH can be mediated by CYP and esterase(s). To provide insight into specific isoforms involved, here we show with recombinant human CYP that 2C19 was the most active at metabolizing D and DA in vitro followed by 3A4. With carboxylesterases (CES), D was hydrolyzed by CES2 but not CES1, and DA was resistant to both CES1 and CES2. In human liver microsomal preparation, general CYP inhibitor 1-aminobenzotriazole (ABT) and respective competitive inhibitors for 2C19 and 3A4, (+)-N-3-benzylnirvanol and ketoconazole, substantially retarded the metabolism of DA and, to a lesser extent, of D. In healthy human subjects from a single-dose pharmacokinetic study, 2C19 extensive metabolizer genotype (2C19*17 allele) tended to have less plasma DA AUC0–48h and poor metabolizer genotype (2C19*2 allele) tended to have greater DA AUC0–48h. In mice given a single dose of D/DA, pretreatment with ABT boosted the plasma and prostate levels of D and DA by more than an order of magnitude. Taken together, our findings suggest that CYP isoforms 2C19 and 3A4 may play a crucial role in the first pass liver metabolism of DA and, to a lesser extent, that of D in humans. Pharmacogenetics with respect to CYP genotypes and interactions among CYP inhibitor drugs and D/DA should therefore be considered in designing future translation studies of DA and/or D. PMID:26394652

Cytochrome P450 Isoforms in the Metabolism of Decursin and Decursinol Angelate from Korean Angelica.

PubMed

Zhang, Jinhui; Li, Li; Tang, Suni; Hale, Thomas W; Xing, Chengguo; Jiang, Cheng; Lü, Junxuan

2015-01-01

We have shown that the in vitro hepatic microsomal metabolism of pyranocoumarin compound decursinol angelate (DA) to decursinol (DOH) exclusively requires cytochrome P450 (CYP) enzymes, whereas the conversion of its isomer decursin (D) to DOH can be mediated by CYP and esterase(s). To provide insight into specific isoforms involved, here we show with recombinant human CYP that 2C19 was the most active at metabolizing D and DA in vitro followed by 3A4. With carboxylesterases (CES), D was hydrolyzed by CES2 but not CES1, and DA was resistant to both CES1 and CES2. In human liver microsomal (HLM) preparation, the general CYP inhibitor 1-aminobenzotriazole (ABT) and respective competitive inhibitors for 2C19 and 3A4, (+)-N-3-benzylnirvanol (NBN) and ketoconazole substantially retarded the metabolism of DA and, to a lesser extent, of D. In healthy human subjects from a single-dose pharmacokinetic (PK) study, 2C19 extensive metabolizer genotype (2C19*17 allele) tended to have less plasma DA AUC0-48h and poor metabolizer genotype (2C19*2 allele) tended to have greater DA AUC0-48h. In mice given a single dose of D/DA, pretreatment with ABT boosted the plasma and prostate levels of D and DA by more than an order of magnitude. Taken together, our findings suggest that CYP isoforms 2C19 and 3A4 may play a crucial role in the first pass liver metabolism of DA and, to a lesser extent, that of D in humans. Pharmacogenetics with respect to CYP genotypes and interactions among CYP inhibitor drugs and D/DA should therefore be considered in designing future translation studies of DA and/or D.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barrett, Christopher A.; Martinez, Alonzo; McNamara, Bruce K.

International Atom Energy Agency (IAEA) safeguard verification measures in gaseous centrifuge enrichment plants (GCEPs) rely on environmental sampling, non-destructive assay (NDA), and destructive assay (DA) sampling and analysis to determine uranium enrichment. UF6 bias defect measurements are made by DA sampling and analysis to assure that enrichment is consistent with declarations. DA samples are collected from a limited number of cylinders for high precision, offsite mass spectrometer analysis. Samples are typically drawn from a sampling tap into a UF6 sample bottle, then packaged, sealed, and shipped under IAEA chain of custody to an offsite analytical laboratory. Future DA safeguard measuresmore » may require improvements in efficiency and effectiveness as GCEP capacities increase and UF6 shipping regulations become increasingly more restrictive. The Pacific Northwest National Laboratory (PNNL) DA sampler concept and Laser Ablation Absorption Ratio Spectrometry (LAARS) assay method are under development to potentially provide DA safeguard tools that increase inspection effectiveness and reduce sample shipping constraints. The PNNL DA sampler concept uses a handheld sampler to collect DA samples for either onsite LAARS assay or offsite laboratory analysis. The DA sampler design will use a small sampling planchet that is coated with an adsorptive film to collect controlled quantities of UF6 gas directly from a cylinder or process sampling tap. Development efforts are currently underway at PNNL to enhance LAARS assay performance to allow high-precision onsite bias defect measurements. In this paper, we report on the experimental investigation to develop adsorptive films for the PNNL DA sampler concept. These films are intended to efficiently capture UF6 and then stabilize the collected DA sample prior to onsite LAARS or offsite laboratory analysis. Several porous material composite films were investigated, including a film designed to maximize the chemical adsorption and binding of gaseous UF6 onto the sampling planchet.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nunes, O. A. C., E-mail: oacn@unb.br

We study the interaction of Dirac Fermions in monolayer graphene on a GaAs substrate in an applied electric field by the combined action of the extrinsic potential of piezoelectric surface acoustical phonons of GaAs (piezoelectric acoustical (PA)) and of the intrinsic deformation potential of acoustical phonons in graphene (deformation acoustical (DA)). We find that provided the dc field exceeds a threshold value, emission of piezoelectric (PA) and deformation (DA) acoustical phonons can be obtained in a wide frequency range up to terahertz at low and high temperatures. We found that the phonon amplification rate R{sup PA,DA} scales with T{sub BG}{supmore » S−1} (S=PA,DA), T{sub BG}{sup S} being the Block−Gru{sup ¨}neisen temperature. In the high-T Block−Gru{sup ¨}neisen regime, extrinsic PA phonon scattering is suppressed by intrinsic DA phonon scattering, where the ratio R{sup PA}/R{sup DA} scales with ≈1/√(n), n being the carrier concentration. We found that only for carrier concentration n≤10{sup 10}cm{sup −2}, R{sup PA}/R{sup DA}>1. In the low-T Block−Gru{sup ¨}neisen regime, and for n=10{sup 10}cm{sup −2}, the ratio R{sup PA}/R{sup DA} scales with T{sub BG}{sup DA}/T{sub BG}{sup PA}≈7.5 and R{sup PA}/R{sup DA}>1. In this regime, PA phonon dominates the electron scattering and R{sup PA}/R{sup DA}<1 otherwise. This study is relevant to the exploration of the acoustic properties of graphene and to the application of graphene as an acoustical phonon amplifier and a frequency-tunable acoustical phonon device.« less

The causes of parent-offspring transmission of drug abuse: a Swedish population-based study.

PubMed

Kendler, K S; Ohlsson, H; Sundquist, K; Sundquist, J

2015-01-01

While drug abuse (DA) is strongly familial, we still have limited knowledge about the causes of its cross-generational transmission. We examined DA ascertained from national registers in offspring of three family types from the Swedish population [intact (n = 2,111,074), 'not-lived-with' (n = 165,315, where biological parents never lived with their offspring) and 'step' (n = 124,800 offspring)], which reflected, respectively, the effects of genes + rearing, genes only and rearing only. We replicated these results in three high-risk co-relative designs. Combined across mothers and fathers, the hazard ratio (HR) for DA in offspring given DA in parents was 3.52 in intact, 2.73 in 'not-lived-with' and 1.79 in stepfamilies. In 968 biological full or half-sibling pairs one of whom was reared by and the other never lived with their parent with DA, the HR for DA was greater in the reared than 'not-lived-with' child (HR 1.57). In 64 offspring pairs of a parent with DA, the HR for DA was greater in a reared biological v. step-parented non-biological child (HR 3.33). In 321 pairs of offspring of a parent with DA one of whom was a not-lived-with biological child and the second a step-parented non-biological child, the HR for DA was greater in the biological v. stepchild (HR 1.80). Both genetic and environmental factors contribute substantially to parent-offspring resemblance for DA. The general population contains informative family constellations that can complement more traditional adoption designs in clarifying the sources of parent-offspring resemblance.

Effect of DA-9701 on the Normal Motility and Clonidine-induced Hypomotility of the Gastric Antrum in Rats

PubMed Central

Kang, Je Wook; Han, Dae Kyeong; Kim, Ock Nyun; Lee, Kwang Jae

2016-01-01

Background/Aims DA-9701 is a novel prokinetic agent. In the present study, we investigated the effect of DA-9701 on the motility of the gastric antrum in the normal and clonidine-induced hypomotility in an in vivo animal model. Methods A strain gauge force transducer was sutured on the gastric antrum to measure the contractile activity in rats. A total of 28 rats were subclassified into the 4 groups: (1) the placebo group, (2) the DA-9701 group, (3) the placebo group in the clonidine-pretreated rats, and (4) the DA-9701 group in the clonidine-pretreated rats. After the basal recording, either placebo (3% [w/v] hydroxypropylmethyl cellulose) or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. In the clonidine-pretreated rats, either placebo or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. Results Oral administration of DA-9701 did not significantly alter the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the placebo group. The administration of clonidine decreased the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the administration of placebo. This reduction of the antral motility by the administration of clonidine was not observed in the clonidine-pretreated DA-9701 group. The percentage of the motility index in the postprandial period was significantly greater in the clonidine-pretreated DA-9701 group, compared with the clonidine-pretreated placebo group. Conclusions DA-9701 improves the hypomotility of the gastric antrum induced by clonidine, suggesting its gastroprokinetic effect in the pathologic condition. PMID:26755679

Differential involvement of dopamine D-1 and D-2 receptors in the circling behaviour induced by apomorphine, SK & F 38393, pergolide and LY 171555 in 6-hydroxydopamine-lesioned rats.

PubMed

Arnt, J; Hyttel, J

1985-01-01

The antagonistic effect of dopamine (DA) D-1 and D-2 antagonists against circling behaviour induced by various DA agonists in 6-OHDA-lesioned rats has been investigated. DA D-1/D-2 selectivity of agonists in vitro was measured by the stimulatory effect on DA-sensitive adenylate cyclase in rat striatal homogenates (D-1), the inhibitory effect on electrically-induced release of 3H-DA in rabbit striatal slices (D-2) and the affinity to 3H-piflutixol (D-1) and 3H-spiroperidol (D-2) binding sites in rat striatal membranes. The contralateral circling behaviour induced by the DA D-1 agonist SK & F 38393 was blocked by the DA D-1 antagonist, SCH 23390, and by the mixed DA D-1/D-2 antagonist cis(Z)-flupentixol, but was not influenced by the DA D-2 antagonists spiroperidol and clebopride. In contrast, circling behaviour induced by the preferential DA D-2 agonists pergolide and LY 171555 was blocked by clebopride, spiroperidol, and cis(Z)-flupentixol, but weakly or not influenced by SCH 23390. Apomorphine-induced circling behaviour was blocked by cis(Z)-flupentixol, partially antagonized by SCH 23390 and clebopride but not inhibited by spiroperidol, although the time-course of circling was changed. Combinations of SCH 23390 with spiroperidol or clebopride in low doses completely blocked the effect of apomorphine. These results indicate that DA D-1 and D-2 receptors mediate circling behaviour through separate mechanisms which can be independently manipulated with respective agonists and antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain.

PubMed

Volkow, N D; Wang, G; Fowler, J S; Logan, J; Gerasimov, M; Maynard, L; Ding, Y; Gatley, S J; Gifford, A; Franceschi, D

2001-01-15

Methylphenidate (Ritalin) is the most commonly prescribed psychoactive drug in children for the treatment of attention deficit hyperactivity disorder (ADHD), yet the mechanisms responsible for its therapeutic effects are poorly understood. Whereas methylphenidate blocks the dopamine transporter (main mechanism for removal of extracellular dopamine), it is unclear whether at doses used therapeutically it significantly changes extracellular dopamine (DA) concentration. Here we used positron emission tomography and [(11)C]raclopride (D2 receptor radioligand that competes with endogenous DA for binding to the receptor) to evaluate whether oral methylphenidate changes extracellular DA in the human brain in 11 healthy controls. We showed that oral methylphenidate (average dose 0.8 +/- 0.11 mg/kg) significantly increased extracellular DA in brain, as evidenced by a significant reduction in B(max)/K(d) (measure of D2 receptor availability) in striatum (20 +/- 12%; p < 0.0005). These results provide direct evidence that oral methylphenidate at doses within the therapeutic range significantly increases extracellular DA in human brain. This result coupled with recent findings of increased dopamine transporters in ADHD patients (which is expected to result in reductions in extracellular DA) provides a mechanistic framework for the therapeutic efficacy of methylphenidate. The increase in DA caused by the blockade of dopamine transporters by methylphenidate predominantly reflects an amplification of spontaneously released DA, which in turn is responsive to environmental stimulation. Because DA decreases background firing rates and increases signal-to-noise in target neurons, we postulate that the amplification of weak DA signals in subjects with ADHD by methylphenidate would enhance task-specific signaling, improving attention and decreasing distractibility. Alternatively methylphenidate-induced increases in DA, a neurotransmitter involved with motivation and reward, could enhance the salience of the task facilitating the "interest that it elicits" and thus improving performance.

The Effect of DA-9701 in Opioid-induced Bowel Dysfunction of Guinea Pig.

PubMed

Hussain, Zahid; Rhee, Kwang Won; Lee, Young Ju; Park, Hyojin

2016-07-30

Opioid induced bowel dysfunction (OIBD) is associated with decreased gastrointestinal (GI) propulsive activity due to intake of opioid analgesics. DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber has promising effects on GI motor function. Therefore, we aim to evaluate the prokinetic effects of DA-9701 in an OIBD model of guinea pig. The ileal and distal colon muscle contraction in presence of different doses of DA-9701, morphine, and combination (morphine + DA-9701) was measured by tissue bath study. The prokinetic effect of DA-9701 was assessed by charcoal transit and fecal pellet output assay in an OIBD model of guinea pig. DA-9701 significantly increased the amplitude and area under the curve of ileal muscle contraction, while there was insignificant effect on the distal colon compared to the control. The maximal amplitude of ileal muscle contraction was acquired at a concentration of 10 μg/mL of DA-9701. In contrast, morphine significantly decreased the amplitude of ileal and distal colon muscle contraction compared to the control. Morphine delayed both upper (P < 0.01) and lower (P < 0.05) GI transit, and delayed GI transit was restored by the administration of DA-9701. Morphine induced reduction of contractility was significantly ameliorated by addition of DA-9701 in both ileal and distal colon muscles. DA-9701 significantly increased the amplitude of contraction of the ileal muscle, however the distal colon muscle contraction was insignificant. Additionally, it restored delayed upper and lower GI transit in an OIBD model of guinea pig, and it might prove to be a useful candidate drug in a clinical trial for OIBD.

Gβγ subunit activation promotes dopamine efflux through the dopamine transporter

PubMed Central

Garcia-Olivares, J; Baust, T; Harris, S; Hamilton, P; Galli, A; Amara, SG; Torres, GE

2018-01-01

The dopamine transporter (DAT) is an important regulator of brain dopamine (DA) homeostasis, controlling the intensity and duration of DA signaling. DAT is the target for psychostimulants—like cocaine and amphetamine—and plays an important role in neuropsychiatric disorders, including attention-deficit hyperactivity disorder and drug addiction. Thus, a thorough understanding of the mechanisms that regulate DAT function is necessary for the development of clinical interventions to treat DA-related brain disorders. Previous studies have revealed a plethora of protein–protein interactions influencing DAT cellular localization and activity, suggesting that the fine-tuning of DA homeostasis involves multiple mechanisms. We recently reported that G-protein beta-gamma (Gβγ) subunits bind directly to DAT and decrease DA clearance. Here we show that Gβγ induces the release of DA through DAT. Specifically, a Gβγ-binding/activating peptide, mSIRK, increases DA efflux through DAT in heterologous cells and primary dopaminergic neurons in culture. Addition of the Gβγ inhibitor gallein or DAT inhibitors prevents this effect. Residues 582 to 596 in the DAT carboxy terminus were identified as the primary binding site of Gβγ. A TAT peptide containing the Gβγ-interacting domain of DAT blocked the ability of mSIRK to induce DA efflux, consistent with a direct interaction of Gβγ with the transporter. Finally, activation of a G-protein-coupled receptor, the muscarinic M5R, results in DAT-mediated DA efflux through a Gβγ-dependent mechanism. Collectively, our data show that Gβγ interacts with DAT to promote DA efflux. This novel mechanism may have important implications in the regulation of brain DA homeostasis. PMID:28894302

Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate.

PubMed

Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-07-01

The central extended amygdala (CEA) has been conceptualized as a 'macrosystem' that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the 'limbic-associative' striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning.

Effect of DA-9701 on the Normal Motility and Clonidine-induced Hypomotility of the Gastric Antrum in Rats.

PubMed

Kang, Je Wook; Han, Dae Kyeong; Kim, Ock Nyun; Lee, Kwang Jae

2016-04-30

DA-9701 is a novel prokinetic agent. In the present study, we investigated the effect of DA-9701 on the motility of the gastric antrum in the normal and clonidine-induced hypomotility in an in vivo animal model. A strain gauge force transducer was sutured on the gastric antrum to measure the contractile activity in rats. A total of 28 rats were subclassified into the 4 groups: (1) the placebo group, (2) the DA-9701 group, (3) the placebo group in the clonidine-pretreated rats, and (4) the DA-9701 group in the clonidine-pretreated rats. After the basal recording, either placebo (3% [w/v] hydroxypropylmethyl cellulose) or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. In the clonidinepretreated rats, either placebo or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. Oral administration of DA-9701 did not significantly alter the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the placebo group. The administration of clonidine decreased the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the administration of placebo. This reduction of the antral motility by the administration of clonidine was not observed in the clonidine-pretreated DA-9701 group. The percentage of the motility index in the postprandial period was significantly greater in the clonidine-pretreated DA-9701 group, compared with the clonidine-pretreated placebo group. DA-9701 improves the hypomotility of the gastric antrum induced by clonidine, suggesting its gastroprokinetic effect in the pathologic condition.

Biochemical and mass spectrometric characterization of the human CB2 cannabinoid receptor expressed in Pichia pastoris--importance of correct processing of the N-terminus.

PubMed

Zhang, Rundong; Kim, Tae-Kang; Qiao, Zhaun-Hong; Cai, Jian; Pierce, William M; Song, Zhao-Hui

2007-10-01

This study was conducted to optimize the expression of human CB2 cannabinoid receptors in methylotrophic yeast Pichia pastoris (P. pastoris). Two major species of expressed CB2 proteins were seen on Western blot, i.e., a 42 kDa band which matches the calculated molecular weight for tagged CB2, and a 52/55 kDa doublet. Treatment of membranes with N-glycosidase F or inclusion of tunicamycin in the culture medium during induction resulted in the disappearance of the 55 kDa, but not the 52 kDa band, suggesting that the 3 kDa extra in the 55 kDa band is due to N-glycosylation, but the 10 kDa extra in the 52 kDa band is not due to N-glycosylation. Anti-FLAG M1 antibody had a much higher preference for the 42 kDa band over the 52/55 kDa doublet, and a 10 kDa fragment recognized by anti-FLAG M2 antibody was generated by CNBr digestion of the 52/55 doublet. These data strongly support the hypothesis that the 10 kDa increase in molecular weight was due to unprocessed alpha-factor sequence. This conclusion was further validated by finding several peptide sequences for alpha-factor fragments at the N-terminal of the CB2 receptor using pepsin/chymotrypsin digestion and LC/MS/MS approaches. Importantly, unprocessed alpha-factor was found to be associated with poor ligand binding. In addition, controlling the level of CB2 protein expression was found to be critical for minimizing the presence of unprocessed alpha-factor sequence. The information gained from this study should aid the proper expression of not only CB2 receptor but also other members of the GPCR family in P. pastoris.

Comprehensive enzymatic analysis of the amylolytic system in the digestive fluid of the sea hare, Aplysia kurodai: Unique properties of two α-amylases and two α-glucosidases.

PubMed

Tsuji, Akihiko; Nishiyama, Nami; Ohshima, Miki; Maniwa, Saori; Kuwamura, Shuji; Shiraishi, Masataka; Yuasa, Keizo

2014-01-01

Sea lettuce (Ulva pertusa) is a nuisance species of green algae that is found all over the world. East-Asian species of the marine gastropod, the sea hare Aplysia kurodai, shows a clear feeding preference for sea lettuce. Compared with cellulose, sea lettuce contains a higher amount of starch as a storage polysaccharide. However, the entire amylolytic system in the digestive fluid of A. kurodai has not been studied in detail. We purified α-amylases and α-glucosidases from the digestive fluid of A. kurodai and investigated the synergistic action of these enzymes on sea lettuce. A. kurodai contain two α-amylases (59 and 80 kDa) and two α-glucosidases (74 and 86 kDa). The 59-kDa α-amylase, but not the 80-kDa α-amylase, was markedly activated by Ca(2+) or Cl(-). Both α-amylases degraded starch and maltoheptaose, producing maltotriose, maltose, and glucose. Glucose production from starch was higher with 80-kDa α-amylase than with 59-kDa α-amylase. Kinetic analysis indicated that 74-kDa α-glucosidase prefers short α-1,4-linked oligosaccharide, whereas 86-kDa α-glucosidase prefers large α-1,6 and α-1,4-linked polysaccharides such as glycogen. When sea lettuce was used as a substrate, a 2-fold greater amount of glucose was released by treatment with 59-kDa α-amylase and 74-kDa α-glucosidase than by treatment with 45-kDa cellulase and 210-kDa β-glucosidase of A. kurodai. Unlike mammals, sea hares efficiently digest sea lettuce to glucose by a combination of two α-amylases and two α-glucosidases in the digestive fluids without membrane-bound maltase-glucoamylase and sucrase-isomaltase complexes.

Dopamine acting at D1-like, D2-like and α1-adrenergic receptors differentially modulates theta and gamma oscillatory activity in primary motor cortex.

PubMed

Özkan, Mazhar; Johnson, Nicholas W; Sehirli, Umit S; Woodhall, Gavin L; Stanford, Ian M

2017-01-01

The loss of dopamine (DA) in Parkinson's is accompanied by the emergence of exaggerated theta and beta frequency neuronal oscillatory activity in the primary motor cortex (M1) and basal ganglia. DA replacement therapy or deep brain stimulation reduces the power of these oscillations and this is coincident with an improvement in motor performance implying a causal relationship. Here we provide in vitro evidence for the differential modulation of theta and gamma activity in M1 by DA acting at receptors exhibiting conventional and non-conventional DA pharmacology. Recording local field potentials in deep layer V of rat M1, co-application of carbachol (CCh, 5 μM) and kainic acid (KA, 150 nM) elicited simultaneous oscillations at a frequency of 6.49 ± 0.18 Hz (theta, n = 84) and 34.97 ± 0.39 Hz (gamma, n = 84). Bath application of DA resulted in a decrease in gamma power with no change in theta power. However, application of either the D1-like receptor agonist SKF38393 or the D2-like agonist quinpirole increased the power of both theta and gamma suggesting that the DA-mediated inhibition of oscillatory power is by action at other sites other than classical DA receptors. Application of amphetamine, which promotes endogenous amine neurotransmitter release, or the adrenergic α1-selective agonist phenylephrine mimicked the action of DA and reduced gamma power, a result unaffected by prior co-application of D1 and D2 receptor antagonists SCH23390 and sulpiride. Finally, application of the α1-adrenergic receptor antagonist prazosin blocked the action of DA on gamma power suggestive of interaction between α1 and DA receptors. These results show that DA mediates complex actions acting at dopamine D1-like and D2-like receptors, α1 adrenergic receptors and possibly DA/α1 heteromultimeric receptors to differentially modulate theta and gamma activity in M1.

Comprehensive enzymatic analysis of the amylolytic system in the digestive fluid of the sea hare, Aplysia kurodai: Unique properties of two α-amylases and two α-glucosidases

PubMed Central

Tsuji, Akihiko; Nishiyama, Nami; Ohshima, Miki; Maniwa, Saori; Kuwamura, Shuji; Shiraishi, Masataka; Yuasa, Keizo

2014-01-01

Sea lettuce (Ulva pertusa) is a nuisance species of green algae that is found all over the world. East-Asian species of the marine gastropod, the sea hare Aplysia kurodai, shows a clear feeding preference for sea lettuce. Compared with cellulose, sea lettuce contains a higher amount of starch as a storage polysaccharide. However, the entire amylolytic system in the digestive fluid of A. kurodai has not been studied in detail. We purified α-amylases and α-glucosidases from the digestive fluid of A. kurodai and investigated the synergistic action of these enzymes on sea lettuce. A. kurodai contain two α-amylases (59 and 80 kDa) and two α-glucosidases (74 and 86 kDa). The 59-kDa α-amylase, but not the 80-kDa α-amylase, was markedly activated by Ca2+ or Cl−. Both α-amylases degraded starch and maltoheptaose, producing maltotriose, maltose, and glucose. Glucose production from starch was higher with 80-kDa α-amylase than with 59-kDa α-amylase. Kinetic analysis indicated that 74-kDa α-glucosidase prefers short α-1,4-linked oligosaccharide, whereas 86-kDa α-glucosidase prefers large α-1,6 and α-1,4-linked polysaccharides such as glycogen. When sea lettuce was used as a substrate, a 2-fold greater amount of glucose was released by treatment with 59-kDa α-amylase and 74-kDa α-glucosidase than by treatment with 45-kDa cellulase and 210-kDa β-glucosidase of A. kurodai. Unlike mammals, sea hares efficiently digest sea lettuce to glucose by a combination of two α-amylases and two α-glucosidases in the digestive fluids without membrane-bound maltase–glucoamylase and sucrase–isomaltase complexes. PMID:25161866

cis-4-Decenoic and decanoic acids impair mitochondrial energy, redox and Ca(2+) homeostasis and induce mitochondrial permeability transition pore opening in rat brain and liver: Possible implications for the pathogenesis of MCAD deficiency.

PubMed

Amaral, Alexandre Umpierrez; Cecatto, Cristiane; da Silva, Janaína Camacho; Wajner, Alessandro; Godoy, Kálita Dos Santos; Ribeiro, Rafael Teixeira; Wajner, Moacir

2016-09-01

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is biochemically characterized by tissue accumulation of octanoic (OA), decanoic (DA) and cis-4-decenoic (cDA) acids, as well as by their carnitine by-products. Untreated patients present episodic encephalopathic crises and biochemical liver alterations, whose pathophysiology is poorly known. We investigated the effects of OA, DA, cDA, octanoylcarnitine (OC) and decanoylcarnitine (DC) on critical mitochondrial functions in rat brain and liver. DA and cDA increased resting respiration and diminished ADP- and CCCP-stimulated respiration and complexes II-III and IV activities in both tissues. The data indicate that these compounds behave as uncouplers and metabolic inhibitors of oxidative phosphorylation. Noteworthy, metabolic inhibition was more evident in brain as compared to liver. DA and cDA also markedly decreased mitochondrial membrane potential, NAD(P)H content and Ca(2+) retention capacity in Ca(2+)-loaded brain and liver mitochondria. The reduction of Ca(2+) retention capacity was more pronounced in liver and totally prevented by cyclosporine A and ADP, as well as by ruthenium red, demonstrating the involvement of mitochondrial permeability transition (mPT) and Ca(2+). Furthermore, cDA induced lipid peroxidation in brain and liver mitochondria and increased hydrogen peroxide formation in brain, suggesting the participation of oxidative damage in cDA-induced alterations. Interestingly, OA, OC and DC did not alter the evaluated parameters, implying lower toxicity for these compounds. Our results suggest that DA and cDA, in contrast to OA and medium-chain acylcarnitines, disturb important mitochondrial functions in brain and liver by multiple mechanisms that are possibly involved in the neuropathology and liver alterations observed in MCAD deficiency. Copyright © 2016 Elsevier B.V. All rights reserved.

Counter-regulation by insulin and isoprenaline of a prominent fat-associated phosphoprotein doublet in rat adipocytes.

PubMed

Mooney, R A; Bordwell, K L

1991-03-01

1. In the adipocyte, phosphorylation/dephosphorylation of regulatory proteins is a common mechanism of metabolic regulation. We have observed a very prominent phosphoprotein doublet of 61 kDa and 63 kDa in rat adipocytes that is markedly responsive to hormones. The 63 kDa band was the predominant phosphoprotein in the cell in response to 0.1 microM-isoprenaline, whereas the 61 kDa band was nearly absent. Insulin alone did not alter 32P incorporation into the doublet, but partially counteracted the effects of isoprenaline, decreasing label in the 63 kDa band by as much as 50% and resulting in the reappearance of the 61 kDa band. 2. Subcellular fractionation demonstrated that both phosphoprotein bands were fat-associated. Neither insulin nor isoprenaline altered this localization. Peptide maps (one-dimensional) of the 61/63 kDa bands demonstrated close sequence similarity. Amino acid analysis revealed the presence of phosphoserine and phosphothreonine. The latter was more prominent in the 61 kDa band. Isoprenaline caused an absolute increase in both phosphoamino acids. 3. Permeabilization of 32P-labelled isoprenaline-treated cells with digitonin initiated rapid dephosphorylation of the 63 kDa band, with reappearance of the 61 kDa band. Insulin increased the rate of dephosphorylation by 2-3-fold when present with isoprenaline before permeabilization. 4. In permeabilized adipocytes, cyclic AMP (1 microM-1 mM) increased phosphorylation of the 61/63 kDa doublet by 4-10-fold in the presence of [gamma-32P]ATP, but insulin had no effect. 5. We conclude that this prominent phosphoprotein, migrating as a 61/63 kDa doublet, is coupled to the cyclic AMP-dependent protein kinase and is associated with an insulin-stimulated phosphoprotein phosphatase activity. This fat-associated phosphoprotein, which is under counter-regulatory hormonal control, may play a role in hormone-dependent lipid metabolism.

The Atypical MAP Kinase SWIP-13/ERK8 Regulates Dopamine Transporters through a Rho-Dependent Mechanism

PubMed Central

Bermingham, Daniel P.; Snider, Sam L.; Miller, David M.

2017-01-01

The neurotransmitter dopamine (DA) regulates multiple behaviors across phylogeny, with disrupted DA signaling in humans associated with addiction, attention-deficit/ hyperactivity disorder, schizophrenia, and Parkinson's disease. The DA transporter (DAT) imposes spatial and temporal limits on DA action, and provides for presynaptic DA recycling to replenish neurotransmitter pools. Molecular mechanisms that regulate DAT expression, trafficking, and function, particularly in vivo, remain poorly understood, though recent studies have implicated rho-linked pathways in psychostimulant action. To identify genes that dictate the ability of DAT to sustain normal levels of DA clearance, we pursued a forward genetic screen in Caenorhabditis elegans based on the phenotype swimming-induced paralysis (Swip), a paralytic behavior observed in hermaphrodite worms with loss-of-function dat-1 mutations. Here, we report the identity of swip-13, which encodes a highly conserved ortholog of the human atypical MAP kinase ERK8. We present evidence that SWIP-13 acts presynaptically to insure adequate levels of surface DAT expression and DA clearance. Moreover, we provide in vitro and in vivo evidence supporting a conserved pathway involving SWIP-13/ERK8 activation of Rho GTPases that dictates DAT surface expression and function. SIGNIFICANCE STATEMENT Signaling by the neurotransmitter dopamine (DA) is tightly regulated by the DA transporter (DAT), insuring efficient DA clearance after release. Molecular networks that regulate DAT are poorly understood, particularly in vivo. Using a forward genetic screen in the nematode Caenorhabditis elegans, we implicate the atypical mitogen activated protein kinase, SWIP-13, in DAT regulation. Moreover, we provide in vitro and in vivo evidence that SWIP-13, as well as its human counterpart ERK8, regulate DAT surface availability via the activation of Rho proteins. Our findings implicate a novel pathway that regulates DA synaptic availability and that may contribute to risk for disorders linked to perturbed DA signaling. Targeting this pathway may be of value in the development of therapeutics in such disorders. PMID:28842414

DA-6034-induced mucin secretion via Ca2+-dependent pathways through P2Y receptor stimulation.

PubMed

Lee, Hun; Kim, Eung Kweon; Kim, Ji Yeon; Yang, Yu-Mi; Shin, Dong Min; Kang, Kyung Koo; Kim, Tae-im

2014-09-11

We evaluated whether DA-6034 is involved in mucin secretion via P2Y receptor activation and/or intracellular Ca2+ concentration ([Ca2+]i) change. Also, we investigated the effect of P2Y receptor inhibitors or Ca2+ chelators on the DA-6034-induced mucin secretion and [Ca2+]i increases. Effects of DA-6034 on mucin expression in primary, cultured, conjunctival epithelial cells was studied using RT-PCR, Western blot analysis, and periodic acid-schiff (PAS) staining. To evaluate thin film layer thickness generated by mucin and fluid secretion, cells were incubated in DA-6034 with/without P2Y antagonists or extracellular/intracellular Ca2+ chelators, and were imaged with confocal microscope using Texas Red-dextran dye. In addition, DA-6034-induced Ca2+-dependent Cl- channels opening was evaluated using perforated patch clamp. Fluo-4/AM was used to measure changes in [Ca2+]i induced by DA-6034 in Ca2+-free or Ca2+-containing buffered condition, as well as P2Y antagonists. DA-6034 induced the expression of mucin genes, production of mucin protein, and increase of number of mucin-secreting cells. P2Y antagonists inhibited DA-6034-induced mucin and fluid secretion, which was also affected by extracellular/intracellular Ca2+ chelators. DA-6034 stimulated Cl- channel opening and [Ca2+]i elevation. Further, [Ca2+]i increases induced by DA-6034 were lacking in either P2Y antagonists or Ca2+-free buffered condition, and diminished when endoplasmic reticulum Ca2+ was depleted by cyclopiazonic acid in Ca2+-free buffered condition. This study demonstrated that DA-6034 has a potential to induce mucin secretion via Ca2+-dependent pathways through P2Y receptors in multilayer, cultured, human conjunctival epithelial cells. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Analysis of suffering at work in Family Health Support Centers.

PubMed

Nascimento, Débora Dupas Gonçalves do; Oliveira, Maria Amélia de Campos

2016-01-01

Analyzing the work process in the Family Health Support Center. An exploratory, descriptive case study using a qualitative approach. Focus groups were conducted with 20 workers of a Family Health Support Center, and the empirical material was subjected to content analysis technique and analyzed in light of Work Psychodynamics. The category of suffering is presented herein as arising from the dialectical contradiction between actual work and prescribed work, from resistance to the Family Health Support Center's proposal and a lack of understanding of their role; due to an immediatist and curative culture of the users and the Family Health Strategy; of the profile, overload and identification with work. The dialectical contradiction between expectations from Family Health Strategy teams and the work in the Family Health Support Center compromises its execution and creates suffering for workers. Analisar o processo de trabalho no Núcleo de Apoio à Saúde da Família. Estudo de caso exploratório, descritivo e de abordagem qualitativa. Grupos focais foram realizados com 20 trabalhadores do Núcleo de Apoio à Saúde da Família, o material empírico foi submetido à técnica de análise de conteúdo e analisado à luz da Psicodinâmica do Trabalho. Apresenta-se aqui a categoria sofrimento que neste estudo decorre da contradição dialética entre o trabalho real e o trabalho prescrito, da resistência à proposta do Núcleo de Apoio à Saúde da Família e da falta de compreensão de seu papel; da cultura imediatista e curativa do usuário e da Estratégia Saúde da Família; do perfil, sobrecarga e identificação com o trabalho. A contradição dialética entre expectativas das equipes da Estratégia Saúde da Família e o trabalho no Núcleo de Apoio à Saúde da Família compromete sua efetivação e gera sofrimento aos trabalhadores.

Identification of a novel 82 kDa proMMP-9 species associated with the surface of leukaemic cells: (auto-)catalytic activation and resistance to inhibition by TIMP-1

PubMed Central

Ries, Christian; Pitsch, Thomas; Mentele, Reinhard; Zahler, Stefan; Egea, Virginia; Nagase, Hideaki; Jochum, Marianne

2007-01-01

MMP-9 (matrix metalloproteinase 9) plays a critical role in tumour progression. Although the biochemical properties of the secreted form of proMMP-9 are well characterized, little is known about the function and activity of cell surface-associated proMMP-9. We purified a novel 82 kDa species of proMMP-9 from the plasma membrane of THP-1 leukaemic cells, which has substantial differences from the secreted 94 kDa proMMP-9. The 82 kDa form was not detected in the medium even upon stimulation with a phorbol ester. It is truncated by nine amino acid residues at its N-terminus, lacks O-linked oligosaccharides present in the 94 kDa proMMP-9, but retains N-linked carbohydrates. Incubation of 94 kDa proMMP-9 with MMP-3 generated the well-known 82 kDa active form, but the 82 kDa proMMP-9 was converted into an active species of 35 kDa, which was also produced by autocatalytic processing in the absence of activating enzymes. The activated 35 kDa MMP-9 efficiently degraded gelatins, native collagen type IV and fibronectin. The enzyme was less sensitive to TIMP-1 (tissue inhibitor of metalloproteinase 1) inhibition with IC50 values of 82 nM compared with 1 nM for the 82 kDa active MMP-9. The synthetic MMP inhibitor GM6001 blocked the activity of both enzymes, with similar IC50 values below 1 nM. The 82 kDa proMMP-9 is also produced in HL-60 and NB4 leukaemic cell lines as well as ex vivo leukaemic blast cells. It is, however, absent from neutrophils and mononuclear cells isolated from peripheral blood of healthy individuals. Thus, the 82 kDa proMMP-9 expressed on the surface of malignant cells may escape inhibition by natural TIMP-1, thereby facilitating cellular invasion in vivo. PMID:17489740

Biosynthesis, processing, and subcellular localization of rat spermbeta-D-galactosidase.

PubMed

Chayko, C A; Orgebin-Crist, M C; Skudlarek, M D; Tulsiani, D R

2000-09-01

During spermatogenesis, spermatids synthesize constituent proteins present in mature spermatozoa; however, little information exists on the molecular processes involved. In previous studies, this laboratory reported the characterization of rat sperm beta-D-galactosidase. In this paper, we report the localization of this enzyme along with its biosynthesis and processing. An antibody against rat luminal fluid beta-D-galactosidase was used to immunolocalize the enzyme in the testis and in epididymal spermatozoa. We found that beta-D-galactosidase is localized within the acrosomal cap of spermatids and in the acrosome and cytoplasmic droplet of epididymal spermatozoa. A combination of germ cell radiolabeling, immunoprecipitation, SDS-PAGE, and autoradiography revealed that spermatids produce two forms of beta-D-galactosidase, 90 and 88 kDa. During pulse-chase analysis, a 56-kDa form appeared. Treatment of beta-D-galactosidase immunoprecipitates from testicular spermatozoa with N-glycanase or Endo H revealed that both the 90- and 88-kDa forms become a 70-kDa polypeptide on SDS-PAGE. Since Endo H or N-glycanase treatment provided similar results, the presence of extensive N-linked high mannose/hybrid-type glycans on these proteins is indicated. Treatment of the 56-kDa form of beta-D-galactosidase with Endo H or N-glycanase resulted in the appearance of 52- and 50-kDa forms, respectively. This result suggests that the 56-kDa form contains N-linked high mannose/hybrid as well as complex oligosaccharides. During epididymal maturation, the 90-kDa form of beta-D-galactosidase persists in caput epididymal spermatozoa and is gradually converted to a major 74-kDa form in cauda spermatozoa. In addition to the 90- to 74-kDa forms, cauda spermatozoa show a 56- to 52-kDa form on Western immunoblots. Since only the high-molecular weight forms of beta-D-galactosidase are present on immunoblots of isolated sperm heads, we suggest that they are acrosomal in origin and that the 56-kDa form, which is processed to 52 kDa in cauda spermatozoa, is associated with the cytoplasmic droplet.

Peer Deviance, Parental Divorce, and Genetic Risk in the Prediction of Drug Abuse in a Nationwide Swedish Sample

PubMed Central

Kendler, Kenneth S.; Ohlsson, Henrik; Sundquist, Kristina; Sundquist, Jan

2014-01-01

IMPORTANCE Peer deviance (PD) strongly predicts externalizing psychopathologic conditions but has not been previously assessable in population cohorts. We sought to develop such an index of PD and to clarify its effects on risk of drug abuse (DA). OBJECTIVES To examine how strongly PD increases the risk of DA and whether this community-level liability indicator interacts with key DA risk factors at the individual and family levels. DESIGN, SETTING, AND PARTICIPANTS Studies of future DA registration in 1 401 698 Swedish probands born from January 1, 1970, through December 31, 1985, and their adolescent peers in approximately 9200 small community areas. Peer deviance was defined as the proportion of individuals born within 5 years of the proband living in the same small community when the proband was 15 years old who eventually were registered for DA. MAIN OUTCOMES AND MEASURES Drug abuse recorded in medical, legal, or pharmacy registry records. RESULTS Peer deviance was associated with future DA in the proband, with rates of DA in older and male peers more strongly predictive than in younger or female peers. The predictive power of PD was only slightly attenuated by adding measures of community deprivation, collective efficacy, or family socioeconomic status. Probands whose parents were divorced were more sensitive to the pathogenic effects of high PD environments. A robust positive interaction was also seen between genetic risk of DA (indexed by rates of DA in first-, second-, and third-degree relatives) and PD exposure. CONCLUSIONS AND RELEVANCE With sufficient data, PD can be measured in populations and strongly predicts DA. In a nationwide sample, risk factors at the level of the individual (genetic vulnerability), family (parental loss), and community (PD) contribute substantially to risk of DA. Individuals at elevated DA risk because of parental divorce or high genetic liability are more sensitive to the pathogenic effects of PD. Although the effect of our PD measure on DA liability cannot be explained by standard measures of community or family risk, we cannot, with available data, discriminate definitively between the effect of true peer effects and other unmeasured risk factors. PMID:24576925

Peer deviance, parental divorce, and genetic risk in the prediction of drug abuse in a nationwide Swedish sample: evidence of environment-environment and gene-environment interaction.

PubMed

Kendler, Kenneth S; Ohlsson, Henrik; Sundquist, Kristina; Sundquist, Jan

2014-04-01

Peer deviance (PD) strongly predicts externalizing psychopathologic conditions but has not been previously assessable in population cohorts. We sought to develop such an index of PD and to clarify its effects on risk of drug abuse (DA). To examine how strongly PD increases the risk of DA and whether this community-level liability indicator interacts with key DA risk factors at the individual and family levels. Studies of future DA registration in 1,401,698 Swedish probands born from January 1, 1970, through December 31, 1985, and their adolescent peers in approximately 9200 small community areas. Peer deviance was defined as the proportion of individuals born within 5 years of the proband living in the same small community when the proband was 15 years old who eventually were registered for DA. Drug abuse recorded in medical, legal, or pharmacy registry records. Peer deviance was associated with future DA in the proband, with rates of DA in older and male peers more strongly predictive than in younger or female peers. The predictive power of PD was only slightly attenuated by adding measures of community deprivation, collective efficacy, or family socioeconomic status. Probands whose parents were divorced were more sensitive to the pathogenic effects of high PD environments. A robust positive interaction was also seen between genetic risk of DA (indexed by rates of DA in first-, second-, and third-degree relatives) and PD exposure. With sufficient data, PD can be measured in populations and strongly predicts DA. In a nationwide sample, risk factors at the level of the individual (genetic vulnerability), family (parental loss), and community (PD) contribute substantially to risk of DA. Individuals at elevated DA risk because of parental divorce or high genetic liability are more sensitive to the pathogenic effects of PD. Although the effect of our PD measure on DA liability cannot be explained by standard measures of community or family risk, we cannot, with available data, discriminate definitively between the effect of true peer effects and other unmeasured risk factors.

Directional Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency: Twelve-Month Results of the DEFINITIVE AR Study.

PubMed

Zeller, Thomas; Langhoff, Ralf; Rocha-Singh, Krishna J; Jaff, Michael R; Blessing, Erwin; Amann-Vesti, Beatrice; Krzanowski, Marek; Peeters, Patrick; Scheinert, Dierk; Torsello, Giovanni; Sixt, Sebastian; Tepe, Gunnar

2017-09-01

Studies assessing drug-coated balloons (DCB) for the treatment of femoropopliteal artery disease are encouraging. However, challenging lesions, such as severely calcified, remain difficult to treat with DCB alone. Vessel preparation with directional atherectomy (DA) potentially improves outcomes of DCB. DEFINITIVE AR study (Directional Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency-A Pilot Study of Anti-Restenosis Treatment) was a multicenter randomized trial designed to estimate the effect of DA before DCB to facilitate the development of future end point-driven randomized studies. One hundred two patients with claudication or rest pain were randomly assigned 1:1 to DA+DCB (n=48) or DCB alone (n=54), and 19 additional patients with severely calcified lesions were treated with DA+DCB. Mean lesion length was 11.2±4.0 cm for DA+DCB and 9.7±4.1 cm for DCB ( P =0.05). Predilation rate was 16.7% for DA+DCB versus 74.1% for DCB; postdilation rate was 6.3% for DA+DCB versus 33.3% for DCB. Technical success was superior for DA+DCB (89.6% versus 64.2%; P =0.004). Overall bail-out stenting rate was 3.7%, and rate of flow-limiting dissections was 19% for DCB and 2% for DA+DCB ( P =0.01). One-year primary outcome of angiographic percent diameter stenosis was 33.6±17.7% for DA+DCB versus 36.4±17.6% for DCB ( P =0.48), and clinically driven target lesion revascularization was 7.3% for DA+DCB and 8.0% for DCB ( P =0.90). Duplex ultrasound patency was 84.6% for DA+DCB, 81.3% for DCB ( P =0.78), and 68.8% for calcified lesions. Freedom from major adverse events at 1 year was 89.3% for DA+DCB and 90.0% for DCB ( P =0.86). DA+DCB treatment was effective and safe, but the study was not powered to show significant differences between the 2 methods of revascularization in 1-year follow-up. An adequately powered randomized trial is warranted. http://www.clinicaltrials.gov. Unique Identifier: NCT01366482. Copyright © 2017 The Author(s).

Directional Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency

PubMed Central

Langhoff, Ralf; Rocha-Singh, Krishna J.; Jaff, Michael R.; Blessing, Erwin; Amann-Vesti, Beatrice; Krzanowski, Marek; Peeters, Patrick; Scheinert, Dierk; Torsello, Giovanni; Sixt, Sebastian; Tepe, Gunnar

2017-01-01

Background— Studies assessing drug-coated balloons (DCB) for the treatment of femoropopliteal artery disease are encouraging. However, challenging lesions, such as severely calcified, remain difficult to treat with DCB alone. Vessel preparation with directional atherectomy (DA) potentially improves outcomes of DCB. Methods and Results— DEFINITIVE AR study (Directional Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency—A Pilot Study of Anti-Restenosis Treatment) was a multicenter randomized trial designed to estimate the effect of DA before DCB to facilitate the development of future end point-driven randomized studies. One hundred two patients with claudication or rest pain were randomly assigned 1:1 to DA+DCB (n=48) or DCB alone (n=54), and 19 additional patients with severely calcified lesions were treated with DA+DCB. Mean lesion length was 11.2±4.0 cm for DA+DCB and 9.7±4.1 cm for DCB (P=0.05). Predilation rate was 16.7% for DA+DCB versus 74.1% for DCB; postdilation rate was 6.3% for DA+DCB versus 33.3% for DCB. Technical success was superior for DA+DCB (89.6% versus 64.2%; P=0.004). Overall bail-out stenting rate was 3.7%, and rate of flow-limiting dissections was 19% for DCB and 2% for DA+DCB (P=0.01). One-year primary outcome of angiographic percent diameter stenosis was 33.6±17.7% for DA+DCB versus 36.4±17.6% for DCB (P=0.48), and clinically driven target lesion revascularization was 7.3% for DA+DCB and 8.0% for DCB (P=0.90). Duplex ultrasound patency was 84.6% for DA+DCB, 81.3% for DCB (P=0.78), and 68.8% for calcified lesions. Freedom from major adverse events at 1 year was 89.3% for DA+DCB and 90.0% for DCB (P=0.86). Conclusions— DA+DCB treatment was effective and safe, but the study was not powered to show significant differences between the 2 methods of revascularization in 1-year follow-up. An adequately powered randomized trial is warranted. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique Identifier: NCT01366482. PMID:28916599

Sensitive determination of dopamine levels via surface-enhanced Raman scattering of Ag nanoparticle dimers.

PubMed

Yu, Xiantong; He, XiaoXiao; Yang, Taiqun; Zhao, Litao; Chen, Qichen; Zhang, Sanjun; Chen, Jinquan; Xu, Jianhua

2018-01-01

Dopamine (DA) is an important neurotransmitter in the hypothalamus and pituitary gland, which can produce a direct influence on mammals' emotions in midbrain. Additionally, the level of DA is highly related with some important neurologic diseases such as schizophrenia, Parkinson, and Huntington's diseases, etc. In light of the important roles that DA plays in the disease modulation, it is of considerable significance to develop a sensitive and reproducible approach for monitoring DA. The objective of this study was to develop an efficient approach to quantitatively monitor the level of DA using Ag nanoparticle (NP) dimers and enhanced Raman spectroscopy. Ag NP dimers were synthesized for the sensitive detection of DA via surface-enhanced Raman scattering (SERS). Citrate was used as both the capping agent of NPs and sensing agent to DA, which is self-assembled on the surface of Ag NP dimers by reacting with the surface carboxyl group to form a stable amide bond. To improve accuracy and precision, the multiplicative effects model for surface-enhanced Raman spectroscopy was utilized to analyze the SERS assays. A low limits of detection (LOD) of 20 pM and a wide linear response range from 30 pM to 300 nM were obtained for DA quantitative detection. The SERS enhancement factor was theoretically valued at approximately 10 7 by discrete dipole approximation. DA was self-assembled on the citrate capped surface of Ag NPs dimers through the amide bond. The adsorption energy was estimated to be 256 KJ/mol using the Langmuir isotherm model. The density functional theory was used to simulate the spectral characteristics of SERS during the adsorption of DA on the surface of the Ag dimers. Furthermore, to improve the accuracy and precision of quantitative analysis of SERS assays with a multiplicative effects model for surface-enhanced Raman spectroscopy. A LOD of 20 pM DA-level was obtained, and the linear response ranged from 30 pM to 300 nM for quantitative DA detection. The absolute relative percentage error was 4.22% between the real and predicted DA concentrations. This detection scheme is expected to have good applications in the prevention and diagnosis of certain diseases caused by disorders in the DA level.

Sensitive determination of dopamine levels via surface-enhanced Raman scattering of Ag nanoparticle dimers

PubMed Central

Yu, Xiantong; He, XiaoXiao; Yang, Taiqun; Zhao, Litao; Chen, Qichen; Zhang, Sanjun; Chen, Jinquan; Xu, Jianhua

2018-01-01

Background Dopamine (DA) is an important neurotransmitter in the hypothalamus and pituitary gland, which can produce a direct influence on mammals’ emotions in midbrain. Additionally, the level of DA is highly related with some important neurologic diseases such as schizophrenia, Parkinson, and Huntington’s diseases, etc. In light of the important roles that DA plays in the disease modulation, it is of considerable significance to develop a sensitive and reproducible approach for monitoring DA. Purpose The objective of this study was to develop an efficient approach to quantitatively monitor the level of DA using Ag nanoparticle (NP) dimers and enhanced Raman spectroscopy. Methods Ag NP dimers were synthesized for the sensitive detection of DA via surface-enhanced Raman scattering (SERS). Citrate was used as both the capping agent of NPs and sensing agent to DA, which is self-assembled on the surface of Ag NP dimers by reacting with the surface carboxyl group to form a stable amide bond. To improve accuracy and precision, the multiplicative effects model for surface-enhanced Raman spectroscopy was utilized to analyze the SERS assays. Results A low limits of detection (LOD) of 20 pM and a wide linear response range from 30 pM to 300 nM were obtained for DA quantitative detection. The SERS enhancement factor was theoretically valued at approximately 107 by discrete dipole approximation. DA was self-assembled on the citrate capped surface of Ag NPs dimers through the amide bond. The adsorption energy was estimated to be 256 KJ/mol using the Langmuir isotherm model. The density functional theory was used to simulate the spectral characteristics of SERS during the adsorption of DA on the surface of the Ag dimers. Furthermore, to improve the accuracy and precision of quantitative analysis of SERS assays with a multiplicative effects model for surface-enhanced Raman spectroscopy. Conclusion A LOD of 20 pM DA-level was obtained, and the linear response ranged from 30 pM to 300 nM for quantitative DA detection. The absolute relative percentage error was 4.22% between the real and predicted DA concentrations. This detection scheme is expected to have good applications in the prevention and diagnosis of certain diseases caused by disorders in the DA level. PMID:29713165

Distinctive Modulation of Dopamine Release in the Nucleus Accumbens Shell Mediated by Dopamine and Acetylcholine Receptors.

PubMed

Shin, Jung Hoon; Adrover, Martin F; Alvarez, Veronica A

2017-11-15

Nucleus accumbens (NAc) shell shows unique dopamine (DA) signals in vivo and plays a unique role in DA-dependent behaviors such as reward-motivated learning and the response to drugs of abuse. A disynaptic mechanism for DA release was reported and shown to require synchronized firing of cholinergic interneurons (CINs) and activation of nicotinic acetylcholine (ACh) receptors (nAChRs) in DA neuron (DAN) axons. The properties of this disynaptic mechanism of DA transmission are not well understood in the NAc shell. In this study, in vitro fast-scan cyclic voltammetry was used to examine the modulation of DA transmission evoked by CINs firing in the shell of mice and compared with other striatal regions. We found that DA signals in the shell displayed significant degree of summation in response to train stimulation of CINs, contrary to core and dorsal striatum. The summation was amplified by a D2-like receptor antagonist and experiments with mice with targeted deletion of D2 receptors to DANs or CINs revealed that D2 receptors in CINs mediate a fast inhibition observed within 100 ms of the first pulse, whereas D2 autoreceptors in DAN terminals are engaged in a slower inhibition that peaks at ∼500 ms. ACh also contributes to the use-dependent inhibition of DA release through muscarinic receptors only in the shell, where higher activity of acetylcholinesterase minimizes nAChR desensitization and promotes summation. These findings show that DA signals are modulated differentially by endogenous DA and ACh in the shell, which may underlie the unique features of shell DA signals in vivo SIGNIFICANCE STATEMENT The present study reports that dopamine (DA) release evoked by activation of cholinergic interneurons displays a high degree of summation in the shell and shows unique modulation by endogenous DA and acetylcholine. Desensitization of nicotinic receptors, which is a prevailing mechanism for use-dependent inhibition in the nucleus accumbens core and dorsal striatum, is also minimal in the shell in part due to elevated acetylcholinesterase activity. This distinctive modulation of DA transmission in the shell may have functional implications in the acquisition of reward-motivated behaviors and reward seeking. Copyright © 2017 the authors 0270-6474/17/3711166-15$15.00/0.

Characterization of Optically and Electrically Evoked Dopamine Release in Striatal Slices from Digenic Knock-in Mice with DAT-Driven Expression of Channelrhodopsin

PubMed Central

2017-01-01

Fast-scan cyclic voltammetry (FCV) is an established method to monitor increases in extracellular dopamine (DA) concentration ([DA]o) in the striatum, which is densely innervated by DA axons. Ex vivo brain slice preparations provide an opportunity to identify endogenous modulators of DA release. For these experiments, local electrical stimulation is often used to elicit release of DA, as well as other transmitters, in the striatal microcircuitry; changes in evoked increases in [DA]o after application of a pharmacological agent (e.g., a receptor antagonist) indicate a regulatory role for the transmitter system interrogated. Optogenetic methods that allow specific stimulation of DA axons provide a complementary, bottom-up approach for elucidating factors that regulate DA release. To this end, we have characterized DA release evoked by local electrical and optical stimulation in striatal slices from mice that genetically express a variant of channelrhodopsin-2 (ChR2). Evoked increases in [DA]o in the dorsal and ventral striatum (dStr and vStr) were examined in a cross of a Cre-dependent ChR2 line (“Ai32” mice) with a DAT::Cre mouse line. In dStr, repeated optical pulse-train stimulation at the same recording site resulted in rundown of evoked [DA]o using heterozygous mice, which contrasted with the stability seen with electrical stimulation. Similar rundown was seen in the presence of a nicotinic acetylcholine receptor (nAChR) antagonist, implicating the absence of concurrent nAChR activation in DA release instability in slices. Rundown with optical stimulation in dStr could be circumvented by recording from a population of sites, each stimulated only once. Same-site rundown was less pronounced with single-pulse stimulation, and a stable baseline could be attained. In vStr, stable optically evoked increases in [DA]o at single sites could be achieved using heterozygous mice, although with relatively low peak [DA]o. Low release could be overcome by using mice with a second copy of the Ai32 allele, which doubled ChR2 expression. The characteristics reported here should help future practitioners decide which Ai32;DAT::Cre genotype and recording protocol is optimal for the striatal subregion to be examined. PMID:28177213

Differential effects of pyrethroid insecticides on extracellular dopamine in the striatum of freely moving rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mubarak Hossain, Muhammad; Suzuki, Tadahiko; United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193

2006-11-15

In order to obtain a more complete understanding of pyrethroid neurotoxicity, effects of the pyrethroid insecticides, allethrin (type I), cyhalothrin (type II) and deltamethrin (type II) on extracellular levels of dopamine (DA) and its metabolites in the striatum of conscious rats were studied by in vivo microdialysis. Rats were treated i.p. with pyrethroids or vehicle. Allethrin had a dual effect on DA release. The increase in the extracellular level of striatal DA by 10 mg/kg allethrin reached a maximum of 178% of baseline but 20 and 60 mg/kg inhibited DA release to 63% and 52% of baseline with a peakmore » effect at 60-80 min after injection. Cyhalothrin 10, 20 and 60 mg/kg inhibited DA release to 65%, 56% and 45% of basal release, respectively, with a peak time of inhibition 40-80 min past injection. Deltamethrin (10 and 20 mg/kg) increased DA release to maximum of 187% and 252% of basal release whereas 60 mg/kg first reduced the efflux for 40 min to 50% of basal release and then increased the efflux to a maximum of 344% of basal release with a peak time of 120 min. Local infusion of 1 {mu}M tetrodotoxin, a Na{sup +} blocker through the dialysis probe completely prevented the effect of allethrin (10 and 60 mg/kg), cyhalothrin (60 mg/kg) and deltamethrin (20 mg/kg) on DA release but only partially blocked the effects of 60 mg/kg deltamethrin. The effect of deltamethrin (60 mg/kg) on DA release was completely prevented by local infusion of 10 {mu}M nimodipine, an L-type Ca{sup ++} channel blocker. All three pyrethroids did not alter the extracellular levels of DOPAC, 3-MT and HVA except that 20 and 60 mg/kg of allethrin and cyhalothrin increased 3-MT levels. Effect of the pyrethroids on synaptosomal DA uptake was also examined. The DA uptake was decreased in rats exposed to 60 mg/kg of allethrin and cyhalothrin but was increased in rats exposed to 60 mg/kg of deltamethrin. Our results demonstrate that striatal DA release and DA uptake are differentially affected by type I and the two type II pyrethroids indicating that dopaminergic circuitry, striatal DA in particular, may be a pyrethroid target and that pyrethroids may be acting on striatal DA by multiple mechanisms.« less

Phosphatidylcholine Coatings Deliver Local Antimicrobials and Reduce Infection in a Murine Model: A Preliminary Study.

PubMed

Harris, Michael A; Beenken, Karen E; Smeltzer, Mark S; Haggard, Warren O; Jennings, J Amber

2017-07-01

Phosphatidylcholine coatings have been shown to elute antibiotics for several days. A recently developed biofilm inhibitor, cis-2-decenoic acid (C2DA), has been shown to exhibit synergistic activity with several common antibiotics. This study aims to evaluate the effectiveness of C2DA and amikacin dual drug delivery from a phosphatidylcholine coating. (1) What are the in vitro elution profiles of amikacin and C2DA from phosphatidylcholine-coated coupons in incubated phosphate-buffered saline? (2) Does the presence of C2DA in eluate samples lower the amount of amikacin needed for bacterial inhibition in overnight bacterial turbidity assays? (3) Does addition of amikacin and C2DA result in decreased colony-forming units (CFUs) on wire implants and bone when compared with phosphatidylcholine coatings alone in a mouse model of periprosthetic joint infection? Effects of loading concentrations were assessed during 7-day in vitro elution studies for coatings containing all mixtures of 0%, 5%, 15%, and 25% wt of amikacin and C2DA (n = 4) through quantitative high-performance liquid chromatography concentration determination and plotting concentration eluted over time. Antimicrobial activity was assessed by overnight turbidity testing of elution study samples against Staphylococcus aureus or Pseudomonas aeruginosa. In vivo efficacy was assessed using phosphatidylcholine-coated wire implants in a murine (mouse) model of infection (n = 3). Wire implants were coated with phosphatidylcholine containing no antimicrobials, amikacin alone, C2DA alone, or amikacin and C2DA and then inserted into the intramedullary femur of each mouse and inoculated with S aureus. The number of viable bacterial colonies on the implant surface and in the surrounding bone was determined after 1 week with the goal of achieving complete bacterial clearance. Total viable CFU count and proportion of samples achieving complete clearance were compared between groups. Elution samples showed a burst response of amikacin and C2DA for 1 to 2 days with C2DA release continuing at low levels through Day 4. All tested eluate samples inhibited P aeruginosa. Samples from coatings containing 25% amikacin or 15% amikacin and any amount of C2DA were able to inhibit S aureus formation, but all coatings with 5% amikacin or 15% amikacin but no C2DA were not inhibitory. All in vivo treatment groups achieved complete bacterial clearance on the wire implant, and the C2DA alone and amikacin alone coatings cleared all CFUs in bone (pin: phosphatidylcholine only one of three; amikacin three of three, C2DA three of three, amikacin + C2DA three of three, p = 0.04 [Fisher's exact test]; bone: coating only: zero of three; amikacin: three of three; C2DA; three of three; C2DA + amikacin: one of three; p = 0.03 [Fisher's exact test]). Phosphatidylcholine coatings elute antimicrobials in vitro under infinite sink conditions for up to 4 days in phosphate-buffered saline and were able to reduce bacterial colonies in a preliminary in vivo model. Turbidity testing with eluate samples containing varying amounts of C2DA and amikacin agrees with previous studies showing synergy between them. Used as an adjunctive to systemic therapy, C2DA-loaded phosphatidylcholine coatings have potential value as a prophylactic infection prevention measure. Future studies may include different antibiotics, animal studies with larger sample sizes and more controls, and advanced coating delivery methods.

Does transition from the da Vinci Si to Xi robotic platform impact single-docking technique for robot-assisted laparoscopic nephroureterectomy?

PubMed

Patel, Manish N; Aboumohamed, Ahmed; Hemal, Ashok

2015-12-01

To describe our robot-assisted nephroureterectomy (RNU) technique for benign indications and RNU with en bloc excision of bladder cuff (BCE) and lymphadenectomy (LND) for malignant indications using the da Vinci Si and da Vinci Xi robotic platform, with its pros and cons. The port placement described for Si can be used for standard and S robotic systems. This is the first report in the literature on the use of the da Vinci Xi robotic platform for RNU. After a substantial experience of RNU using different da Vinci robots from the standard to the Si platform in a single-docking fashion for benign and malignant conditions, we started using the newly released da Vinci Xi robot since 2014. The most important differences are in port placement and effective use of the features of da Vinci Xi robot while performing simultaneous upper and lower tract surgery. Patient positioning, port placement, step-by-step technique of single docking RNU-LND-BCE using the da Vinci Si and da Vinci Xi robot are shown in an accompanying video with the goal that centres using either robotic system benefit from the hints and tips. The first segment of video describes RNU-LND-BCE using the da Vinci Si followed by the da Vinci Xi to highlight differences. There was no need for patient repositioning or robot re-docking with the new da Vinci Xi robotic platform. We have experience of using different robotic systems for single docking RNU in 70 cases for benign (15) and malignant (55) conditions. The da Vinci Xi robotic platform helps operating room personnel in its easy movement, allows easier patient side-docking with the help of its boom feature, in addition to easy and swift movements of the robotic arms. The patient clearance feature can be used to avoid collision with the robotic arms or the patient's body. In patients with challenging body habitus and in situations where bladder cuff management is difficult, modifications can be made through reassigning the camera to a different port with utilisation of the retargeting feature of the da Vinci Xi when working on the bladder cuff or in the pelvis. The vision of the camera used for da Vinci Xi was initially felt to be inferior to that of the da Vinci Si; however, with a subsequent software upgrade this was much improved. The base of the da Vinci Xi is bigger, which does not slide and occasionally requires a change in table placement/operating room setup, and requires side-docking especially when dealing with very tall and obese patients for pelvic surgery. RNU alone or with LND-BCE is a challenging surgical procedure that addresses the upper and lower urinary tract simultaneously. Single docking and single robotic port placement for RNU-LND-BCE has evolved with the development of different generations of the robotic system. These procedures can be performed safely and effectively using the da Vinci S, Si or Xi robotic platform. The new da Vinci Xi robotic platform is more user-friendly, has easy installation, and is intuitive for surgeons using its features. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

32 CFR 516.25 - DA Form 4.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 3 2010-07-01 2010-07-01 true DA Form 4. 516.25 Section 516.25 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION Reporting Legal Proceedings to HQDA § 516.25 DA Form 4. (a) General. The DA Form 4 (See figure C-2...

32 CFR 516.43 - Release of Army and other agency records.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Preservation of originals. To preserve the integrity of DA records, DA personnel will submit properly... otherwise by Litigation Division. (See 28 U.S.C. 1733.) (b) Authentication of copies. Copies of DA records approved for release can be authenticated for introduction in evidence by use of DA Form 4. (See § 516.25...

32 CFR 536.32 - Transfer of claims among armed services branches.

Code of Federal Regulations, 2010 CFR

2010-07-01

... take all actions on the claim. Where the DA is the lead agency, any final action will include other agencies. Similarly, where another agency is the lead agency, that agency will be requested to include DA... another agency has taken denial action on a claim that involves the DA, without informing the DA, and in...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2014 CFR

2014-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2010 CFR

2010-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2011 CFR

2011-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2013 CFR

2013-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

32 CFR 635.23 - DA Form 4833 (Commander's Report of Disciplinary or Administrative Action).

Code of Federal Regulations, 2012 CFR

2012-07-01

... the PMO. The Battalion Commander or the first Lieutenant Colonel in the chain of command is... DA Form 4833 within 45 days of receipt. (1) Appropriate blocks will be checked and blanks annotated... the disposition on DA Form 4833 as appropriate. That portion of the signature block of DA Form 4833...

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Specificity and impact of adrenergic projections to the midbrain dopamine system

PubMed Central

Mejias-Aponte, Carlos A.

2016-01-01

Dopamine (DA) is a neuromodulator that regulates different brain circuits involved in cognitive functions, motor coordination, and emotions. Dysregulation of DA is associated with many neurological and psychiatric disorders such as Parkinson’s disease and substance abuse. Several lines of research have shown that the midbrain DA system is regulated by the central adrenergic system. This review focuses on adrenergic interactions with midbrain DA neurons. It discusses the current neuroanatomy including source of adrenergic innervation, type of synapses, and adrenoceptors expression. It also discusses adrenergic regulation of DA cell activity and neurotransmitter release. Finally, it reviews several neurological and psychiatric disorders where changes in adrenergic system are associated with dysregulation of the midbrain DA system. PMID:26820641

Relationship between Resting Heart Rate, Blood Pressure and Pulse Pressure in Adolescents.

PubMed

Christofaro, Diego Giulliano Destro; Casonatto, Juliano; Vanderlei, Luiz Carlos Marques; Cucato, Gabriel Grizzo; Dias, Raphael Mendes Ritti

2017-05-01

High resting heart rate is considered an important factor for increasing mortality chance in adults. However, it remains unclear whether the observed associations would remain after adjustment for confounders in adolescents. To analyze the relationship between resting heart rate, blood pressure and pulse pressure in adolescents of both sexes. A cross-sectional study with 1231 adolescents (716 girls and 515 boys) aged 14-17 years. Heart rate, blood pressure and pulse pressure were evaluated using an oscillometric blood pressure device, validated for this population. Weight and height were measured with an electronic scale and a stadiometer, respectively, and waist circumference with a non-elastic tape. Multivariate analysis using linear regression investigated the relationship between resting heart rate and blood pressure and pulse pressure in boys and girls, controlling for general and abdominal obesity. Higher resting heart rate values were observed in girls (80.1 ± 11.0 beats/min) compared to boys (75.9 ± 12.7 beats/min) (p ≤ 0.001). Resting heart rate was associated with systolic blood pressure in boys (Beta = 0.15 [0.04; 0.26]) and girls (Beta = 0.24 [0.16; 0.33]), with diastolic blood pressure in boys (Beta = 0.50 [0.37; 0.64]) and girls (Beta = 0.41 [0.30; 0.53]), and with pulse pressure in boys (Beta = -0.16 [-0.27; -0.04]). This study demonstrated a relationship between elevated resting heart rate and increased systolic and diastolic blood pressure in both sexes and pulse pressure in boys even after controlling for potential confounders, such as general and abdominal obesity. A frequência cardíaca de repouso é considerada um importante fator de aumento de mortalidade em adultos. Entretanto, ainda é incerto se as associações observadas permanecem após ajuste para fatores de confusão em adolescentes. Analisar a relação entre frequência cardíaca de repouso, pressão arterial e pressão de pulso em adolescentes dos dois sexos. Estudo transversal com 1231 adolescentes (716 meninas e 515 meninos, idade de 14-17 anos). Frequência cardíaca, pressão arterial e pressão de pulso foram avaliadas com esfigmomanômetro oscilométrico validado para essa população. Peso e altura foram medidos com balança eletrônica e estadiômetro, respectivamente, e a circunferência abdominal, com uma fita inextensível. Análise multivariada com regressão linear investigou a relação entre frequência cardíaca de repouso, pressão arterial e pressão de pulso em meninos e meninas, controlando para obesidade geral e abdominal. Valores maiores de frequência cardíaca de repouso foram observados em meninas (80,1 ± 11,0 bpm) em comparação a meninos (75,9 ± 12,7 bpm) (p ≤ 0,001). Frequência cardíaca de repouso associou-se com pressão arterial sistólica em meninos [Beta = 0,15 (0,04; 0,26)] e meninas [Beta = 0,24 (0,16; 0,33)], com pressão arterial diastólica em meninos [Beta = 0,50 (0,37; 0,64)] e meninas [Beta = 0,41 (0,30; 0,53)], e com pressão de pulso apenas em meninos [Beta = -0,16 (-0,27; -0,04)]. Este estudo demonstrou a relação da frequência cardíaca de repouso elevada com aumento das pressões arteriais sistólica e diastólica em ambos os sexos e com pressão de pulso em meninos, mesmo após controle para potenciais fatores de confusão, como obesidade geral e abdominal.

Toxicity evaluation of glyphosate agrochemical components using Japanese medaka (Oryzias latipes) and DNA microarray gene expression analysis.

PubMed

Uchida, Masaya; Takumi, Shota; Tachikawa, Keiko; Yamauchi, Ryoko; Goto, Yoshiyuki; Matsusaki, Hiromi; Nakamura, Hiroshi; Kagami, Yoshihiro; Kusano, Teruhiko; Arizono, Koji

2012-01-01

Using glyphosate agrochemical components, we investigated their acute toxicity to juvenile Japanese medaka (Oryzias latipes) as well as their toxic impact at gene expression level on the liver tissues of adult medaka using DNA microarray. In our acute toxicity test, juvenile medaka were exposed for 96 hr to each of the following glyphosate agrochemical components: 10~160 mg/l of glyphosate, 1.25~20 mg/l of fatty acid alkanolamide surfactant (DA), and 12~416 mg/l of a fully formulated glyphosate herbicide. As a result, LC(50) values of glyphosate, DA, and the glyphosate herbicide were > 160 mg/l, 8.5 mg/l, and 76.8 mg/l, respectively. On the other hand, adult male medaka fish were exposed to each of the glyphosate agrochemical components for 48 hr at the following concentrations: 16 mg/l of glyphosate, 0.5 mg/l of DA, and 16 mg/l-glyphosate/0.5 mg/l-DA mixture. Interestingly, DNA microarray analysis revealed that there were no significant gene expression changes in the medaka liver after exposure to glyphosate. Nevertheless, 78 and 138 genes were significantly induced by DA and the glyphosate/DA mixture, respectively. Furthermore, we identified five common genes that were affected by DA and glyphosate/DA mixture. These results suggested that glyphosate itself possessed very low toxicity as previously reported by some researchers at least to the small laboratory fish, and the major toxicity of the glyphosate agrochemical resided mainly in DA and perhaps in unintentionally generated byproduct(s) of glyphosate-DA mixture.

The molar hydrodynamic volume changes of factor VIIa due to GlycoPEGylation.

PubMed

Plesner, Bitten; Westh, Peter; Hvidt, Søren; Nielsen, Anders D

2011-06-01

The effects of GlycoPEGylation on the molar hydrodynamic volume of recombinant human rFVIIa were investigated using rFVIIa and two GlycoPEGylated recombinant human FVIIa derivatives, a linear 10kDa PEG and a branched 40kDa PEG, respectively. Molar hydrodynamic volumes were determined by capillary viscometry and mass spectrometry. The intrinsic viscosities of rFVIIa, its two GlycoPEGylated compounds, and of linear 8kDa, 10kDa, 20kDa and branched 40kDa PEG polymers were determined. The measured intrinsic viscosity of rFVIIa is 6.0mL/g, while the intrinsic viscosities of 10kDa PEG-rFVIIa and 40kDa PEG-rFVIIa are 29.5mL/g and 79.0mL/g, respectively. The intrinsic viscosities of the linear PEG polymers are 20, 22.6 and 41.4mL/g for 8, 10, and 20kDa, respectively, and 61.1mL/g for the branched 40kDa PEG. From the results of the intrinsic viscosity and MALDI-TOF measurements it is evident, that the molar hydrodynamic volume of the conjugated protein is not just an addition of the molar hydrodynamic volume of the PEG and the protein. The molar hydrodynamic volume of the GlycoPEGylated protein is larger than the volume of its composites. These results suggest that both the linear and the branched PEG are not wrapped around the surface of rFVIIa but are chains that are significantly stretched out when attached to the protein. Copyright © 2011 Elsevier B.V. All rights reserved.

Electrochemical determination of dopamine and ascorbic acid at a novel gold nanoparticles distributed poly(4-aminothiophenol) modified electrode.

PubMed

Gopalan, Anantha Iyengar; Lee, Kwang-Pill; Manesh, Kalayil Manian; Santhosh, Padmanabhan; Kim, Jun Heon; Kang, Jae Soo

2007-03-15

A modified electrode is fabricated by embedding gold nanoparticles into a layer of electroactive polymer, poly(4-aminothiophenol) (PAT) on the surface of glassy carbon (GC) electrode. Cyclic voltammetry (CV) is performed to deposit PAT and concomitantly deposit Au nanoparticles. Field emission transmission electron microscopic image of the modified electrode, PAT-Au(nano)-ME, indicates the presence of uniformly distributed Au nanoparticles having the sizes of 8-10nm. Electrochemical behavior of the PAT-Au(nano)-ME towards detection of ascorbic acid (AA) and dopamine (DA) is studied using CV. Electrocatalytic determination of DA in the presence of fixed concentration of AA and vice versa, are studied using differential pulse voltammetry (DPV). PAT-Au(nano)-ME exhibits two well defined anodic peaks at the potential of 75 and 400mV for the oxidation of AA and DA, respectively with a potential difference of 325mV. Further, the simultaneous determination of AA and DA is studied by varying the concentration of AA and DA. PAT-Au(nano)-ME exhibits selectivity and sensitivity for the simultaneous determination of AA and DA without fouling by the oxidation products of AA or DA. PAT and Au nanoparticles provide synergic influence on the accurate electrochemical determination of AA or DA from a mixture having any one of the component (AA or DA) in excess. The practical analytical utilities of the PAT-Au(nano)-ME are demonstrated by the determination of DA and AA in dopamine hydrochloride injection and human blood serum samples.

Differential impact of pavlovian drug conditioned stimuli on in vivo dopamine transmission in the rat accumbens shell and core and in the prefrontal cortex.

PubMed

Bassareo, Valentina; De Luca, Maria Antonietta; Di Chiara, Gaetano

2007-04-01

Conditioned stimuli (CSs) by pavlovian association with reinforcing drugs (US) are thought to play an important role in the acquisition, maintenance and relapse of drug dependence. The aim of this study was to investigate by microdialysis the impact of pavlovian drug CSs on behaviour and on basal and drug-stimulated dopamine (DA) in three terminal DA areas: nucleus accumbens shell, core and prefrontal cortex (PFCX). Conditioned rats were trained once a day for 3 days by presentation of Fonzies filled box (FFB, CS) for 10 min followed by administration of morphine (1 mg/kg), nicotine (0.4 mg/kg) or saline, respectively. Pseudo-conditioned rats were presented with the FFB 10 h after drug or saline administration. Rats were implanted with microdialysis probes in the shell, core and PFCX. The effect of stimuli conditioned with morphine and nicotine on DA and on DA response to drugs was studied. Drug CSs elicited incentive reactions and released DA in the shell and PFCX but not in the core. Pre-exposure to morphine CS potentiated DA release to morphine challenge in the shell but not in the core and PFCX. This effect was related to the challenge dose of morphine and was stimulus-specific since a food CS did not potentiate the shell DA response to morphine. Pre-exposure to nicotine CS potentiated DA release in the shell and PFCX. The results show that drug CSs stimulate DA release in the shell and medial PFCX and specifically potentiate the primary stimulant drug effects on DA transmission.

The occurrence of domoic acid linked to a toxic diatom bloom in a new potential vector: the tunicate Pyura chilensis (piure).

PubMed

López-Rivera, Américo; Pinto, Maricela; Insinilla, Andrea; Suárez Isla, Benjamín; Uribe, Eduardo; Alvarez, Gonzalo; Lehane, Mary; Furey, Ambrose; James, Kevin J

2009-11-01

The tunicate Pyura chilensis (Molina, 1782); Phylum Chordata; Subphylum Urochordata; Class Ascidiacea, common local name "piure" or sea squirt; a filter-feeder (plankton and suspended particles) sessile species; may play an important role in monitoring domoic acid (DA) the principal toxic component of Amnesic Shellfish Poisoning (ASP). Significant DA concentrations have been determined in tunicate samples, collected during a recent ASP outbreak in Bahía Inglesa, an important scallop (Argopecten purpuratus) farming area. Several infaunal species were tested for the presence of DA, in addition to the usual scallop monitoring programme. DA was found at sub-toxic levels in filtering bivalves such as mussels (Mytilus chilensis), large mussels (Aulacomya ater) and clams (Protothaca thaca) (6.4, 5.4 and 4.7 microg DA/g tissue respectively). Of particular interest was the observation of significant accumulations of toxic Pseudo-nitzschia sp. diatoms in the internal siphon and atrium spaces of the tunicate. Toxin distribution within major tunicate organs was heterogeneous with 8.7-15.5 microg DA/g in edible tissues, 14.9-17.9 microg DA/g in the fecal material and 13.6-32.7 microg DA/g in the gut content. DA was determined by HPLC-UV and confirmed by diode-array detection and LC-MS/MS analysis. This is the first report of the presence of DA in a tunicate that is regularly consumed by coastal populations. These results confirm the need to include these organisms in sanitation programs for marine toxins.

P2X1 Receptor-Mediated Ca2+ Influx Triggered by DA-9801 Potentiates Nerve Growth Factor-Induced Neurite Outgrowth.

PubMed

Back, Moon Jung; Lee, Hae Kyung; Lee, Joo Hyun; Fu, Zhicheng; Son, Mi Won; Choi, Sang Zin; Go, Hyo Sang; Yoo, Sungjae; Hwang, Sun Wook; Kim, Dae Kyong

2016-11-16

Nerve growth factor (NGF)-induced neuronal regeneration has emerged as a strategy to treat neuronal degeneration-associated disorders. However, direct NGF administration is limited by the occurrence of adverse effects at high doses of NGF. Therefore, development of a therapeutic strategy to promote the NGF trophic effect is required. In view of the lack of understanding of the mechanism for potentiating the NGF effect, this study investigated molecular targets of DA-9801, a well-standardized Dioscorea rhizome extract, which has a promoting effect on NGF. An increase in intracellular calcium ion level was induced by DA-9801, and chelation of extracellular calcium ions with ethylene-bis(oxyethylenenitrilo)tetraacetic acid (EGTA) suppressed the potentiating effect of DA-9801 on NGF-induced neurite outgrowth. In addition, EGTA treatment reduced the DA-9801-induced phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2), the major mediators of neurite outgrowth. To find which calcium ion-permeable channel contributes to the calcium ion influx induced by DA-9801, we treated PC12 cells with various inhibitors of calcium ion-permeable channels. NF449, a P2X1 receptor selective antagonist, significantly abolished the potentiating effect of DA-9801 on NGF-induced neurite outgrowth and abrogated the DA-9801-induced ERK1/2 phosphorylation. In addition, transfection with siRNA of P2X1 receptor significantly reduced the DA-9801-enhanced neurite outgrowth. In conclusion, calcium ion influx through P2X1 receptor mediated the promoting effect of DA-9801 on NGF-induced neurite outgrowth via ERK1/2 phosphorylation.

PCA as a practical indicator of OPLS-DA model reliability.

PubMed

Worley, Bradley; Powers, Robert

Principal Component Analysis (PCA) and Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) are powerful statistical modeling tools that provide insights into separations between experimental groups based on high-dimensional spectral measurements from NMR, MS or other analytical instrumentation. However, when used without validation, these tools may lead investigators to statistically unreliable conclusions. This danger is especially real for Partial Least Squares (PLS) and OPLS, which aggressively force separations between experimental groups. As a result, OPLS-DA is often used as an alternative method when PCA fails to expose group separation, but this practice is highly dangerous. Without rigorous validation, OPLS-DA can easily yield statistically unreliable group separation. A Monte Carlo analysis of PCA group separations and OPLS-DA cross-validation metrics was performed on NMR datasets with statistically significant separations in scores-space. A linearly increasing amount of Gaussian noise was added to each data matrix followed by the construction and validation of PCA and OPLS-DA models. With increasing added noise, the PCA scores-space distance between groups rapidly decreased and the OPLS-DA cross-validation statistics simultaneously deteriorated. A decrease in correlation between the estimated loadings (added noise) and the true (original) loadings was also observed. While the validity of the OPLS-DA model diminished with increasing added noise, the group separation in scores-space remained basically unaffected. Supported by the results of Monte Carlo analyses of PCA group separations and OPLS-DA cross-validation metrics, we provide practical guidelines and cross-validatory recommendations for reliable inference from PCA and OPLS-DA models.

Phosphorylation of the rat hepatic polymeric IgA receptor.

PubMed Central

Larkin, J M; Sztul, E S; Palade, G E

1986-01-01

In vivo labeling with [35S]cysteine has identified three transmembrane forms of the rat hepatic polymeric IgA receptor: (i) a 105-kDa core glycosylated precursor; (ii) a terminally glycosylated 116-kDa intermediate; and (iii) a mature 120-kDa form. In the current study we show that the 120-kDa form is phosphorylated. After in vivo labeling with [32P]orthophosphate, all receptor forms were immunoprecipitated from hepatic total microsomes (TM) (with an antireceptor antiserum), separated by NaDodSO4/PAGE, and detected by autoradiography. The 120-kDa form was selectively phosphorylated, whereas the 116- and 105-kDa forms incorporated no detectable 32P. To determine the topology of the phosphorylation sites, hepatic TM isolated from rats labeled in vivo with either [35S]cysteine or [32P]orthophosphate were treated with trypsin. TM were solubilized and receptors were immunoprecipitated from lysates. With increasing trypsin concentrations, the [35S]cysteine-labeled receptor triplet was degraded to a trypsin-resistant doublet of approximately 95 and 85 kDa, indicating that approximately 20 kDa was removed from the receptor endodomain by trypsin. The same treatment removed all detectable 32P from labeled receptors. Furthermore, no 32P was detected in the 80-kDa biliary form of the receptor. Serine was identified as the only phosphorylated residue in acid hydrolysates of 32P-labeled immunoprecipitated receptor. These findings indicate that (i) the 120-kDa form is the only phosphorylated species of the receptor; and (ii) the phosphorylated residues are serine(s) located in the endodomain of the protein. Images PMID:3460069

Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury

PubMed Central

Hou, Shaoping; Carson, David M.; Wu, Di; Klaw, Michelle C.; Houlé, John D.; Tom, Veronica J.

2016-01-01

Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH)+ neurons in the autonomic nuclei and superficial dorsal horn in L6–S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH)− and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH+ neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D2-like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH+ neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH+ cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH+ neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI. PMID:26655672

Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury.

PubMed

Hou, Shaoping; Carson, David M; Wu, Di; Klaw, Michelle C; Houlé, John D; Tom, Veronica J

2016-11-01

Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH) + neurons in the autonomic nuclei and superficial dorsal horn in L6-S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH) - and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH + neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D 2 -like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH + neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH + cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH + neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI. Published by Elsevier Inc.

Enhanced dopamine release by dopamine transport inhibitors described by a restricted diffusion model and fast scan cyclic voltammetry

PubMed Central

Hoffman, Alexander F.; Spivak, Charles E.; Lupica, Carl R.

2016-01-01

Fast-scan cyclic voltammetry (FSCV) using carbon fiber electrodes is widely used to rapidly monitor changes in dopamine (DA) levels in vitro and in vivo. Current analytical approaches utilize parameters such as peak oxidation current amplitude and decay times to estimate release and uptake processes, respectively. However, peak amplitude changes are often observed with uptake inhibitors, thereby confounding the interpretation of these parameters. To overcome this limitation, we demonstrate that a simple, 5 parameter, two compartment model mathematically describes DA signals as a balance of release (r/ke) and uptake (ku), summed with adsorption (kads and kdes) of DA to the carbon electrode surface. Using non-linear regression, we demonstrate that our model precisely describes measured DA signals obtained in brain slice recordings. The parameters extracted from these curves were then validated using pharmacological manipulations that selectively alter vesicular release or DA transporter (DAT)-mediated uptake. Manipulation of DA release through altered Ca2+/Mg2+ ratio or tetrodotoxin (TTX), reduced the release parameter with no effect on the uptake parameter. The DAT inhibitors methylenedioxypyrovalerone (MDPV), cocaine, and nomifensine significantly reduced uptake and increased vesicular DA release. In contrast, a low concentration of amphetamine reduced uptake but had no effect on DA release. Finally, the kappa-opioid receptor (KOR) agonist U50,488 significantly reduced vesicular DA release but had no effect on uptake. Together, these data demonstrate a novel analytical approach to distinguish the effects of manipulations on DA release or uptake that can be used to interpret FSCV data. PMID:27018734

Enhanced Dopamine Release by Dopamine Transport Inhibitors Described by a Restricted Diffusion Model and Fast-Scan Cyclic Voltammetry.

PubMed

Hoffman, Alexander F; Spivak, Charles E; Lupica, Carl R

2016-06-15

Fast-scan cyclic voltammetry (FSCV) using carbon fiber electrodes is widely used to rapidly monitor changes in dopamine (DA) levels in vitro and in vivo. Current analytical approaches utilize parameters such as peak oxidation current amplitude and decay times to estimate release and uptake processes, respectively. However, peak amplitude changes are often observed with uptake inhibitors, thereby confounding the interpretation of these parameters. To overcome this limitation, we demonstrate that a simple five-parameter, two-compartment model mathematically describes DA signals as a balance of release (r/ke) and uptake (ku), summed with adsorption (kads and kdes) of DA to the carbon electrode surface. Using nonlinear regression, we demonstrate that our model precisely describes measured DA signals obtained in brain slice recordings. The parameters extracted from these curves were then validated using pharmacological manipulations that selectively alter vesicular release or DA transporter (DAT)-mediated uptake. Manipulation of DA release through altering the Ca(2+)/Mg(2+) ratio or adding tetrodotoxin reduced the release parameter with no effect on the uptake parameter. DAT inhibitors methylenedioxypyrovalerone, cocaine, and nomifensine significantly reduced uptake and increased vesicular DA release. In contrast, a low concentration of amphetamine reduced uptake but had no effect on DA release. Finally, the kappa opioid receptor agonist U50,488 significantly reduced vesicular DA release but had no effect on uptake. Together, these data demonstrate a novel analytical approach to distinguish the effects of manipulations on DA release or uptake that can be used to interpret FSCV data.

Bursting as a source of non-linear determinism in the firing patterns of nigral dopamine neurons.

PubMed

Jeong, Jaeseung; Shi, Wei-Xing; Hoffman, Ralph; Oh, Jihoon; Gore, John C; Bunney, Benjamin S; Peterson, Bradley S

2012-11-01

Nigral dopamine (DA) neurons in vivo exhibit complex firing patterns consisting of tonic single-spikes and phasic bursts that encode information for certain types of reward-related learning and behavior. Non-linear dynamical analysis has previously demonstrated the presence of a non-linear deterministic structure in complex firing patterns of DA neurons, yet the origin of this non-linear determinism remains unknown. In this study, we hypothesized that bursting activity is the primary source of non-linear determinism in the firing patterns of DA neurons. To test this hypothesis, we investigated the dimension complexity of inter-spike interval data recorded in vivo from bursting and non-bursting DA neurons in the chloral hydrate-anesthetized rat substantia nigra. We found that bursting DA neurons exhibited non-linear determinism in their firing patterns, whereas non-bursting DA neurons showed truly stochastic firing patterns. Determinism was also detected in the isolated burst and inter-burst interval data extracted from firing patterns of bursting neurons. Moreover, less bursting DA neurons in halothane-anesthetized rats exhibited higher dimensional spiking dynamics than do more bursting DA neurons in chloral hydrate-anesthetized rats. These results strongly indicate that bursting activity is the main source of low-dimensional, non-linear determinism in the firing patterns of DA neurons. This finding furthermore suggests that bursts are the likely carriers of meaningful information in the firing activities of DA neurons. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Onsite Gaseous Centrifuge Enrichment Plant UF6 Cylinder Destructive Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anheier, Norman C.; Cannon, Bret D.; Qiao, Hong

2012-07-17

The IAEA safeguards approach for gaseous centrifuge enrichment plants (GCEPs) includes measurements of gross, partial, and bias defects in a statistical sampling plan. These safeguard methods consist principally of mass and enrichment nondestructive assay (NDA) verification. Destructive assay (DA) samples are collected from a limited number of cylinders for high precision offsite mass spectrometer analysis. DA is typically used to quantify bias defects in the GCEP material balance. Under current safeguards measures, the operator collects a DA sample from a sample tap following homogenization. The sample is collected in a small UF6 sample bottle, then sealed and shipped under IAEAmore » chain of custody to an offsite analytical laboratory. Current practice is expensive and resource intensive. We propose a new and novel approach for performing onsite gaseous UF6 DA analysis that provides rapid and accurate assessment of enrichment bias defects. DA samples are collected using a custom sampling device attached to a conventional sample tap. A few micrograms of gaseous UF6 is chemically adsorbed onto a sampling coupon in a matter of minutes. The collected DA sample is then analyzed onsite using Laser Ablation Absorption Ratio Spectrometry-Destructive Assay (LAARS-DA). DA results are determined in a matter of minutes at sufficient accuracy to support reliable bias defect conclusions, while greatly reducing DA sample volume, analysis time, and cost.« less

Dopamine modulates male sexual behavior in Japanese quail in part via actions on noradrenergic receptors.

PubMed

Cornil, Charlotte A; Dejace, Christel; Ball, Gregory F; Balthazart, Jacques

2005-08-30

In rats, dopamine (DA) facilitates male sexual behavior through its combined action on D1- and D2-like receptors, in the medial preoptic area (MPOA) as well as other brain areas. In Japanese quail, systemic injections of dopaminergic drugs suggested a similar pharmacology but central injections have never been performed. Recent electrophysiological experiments demonstrated that DA effects in the MPOA of quail are mediated mainly through the activation of alpha2-noradrenergic receptors. Previous studies of DA action on behavior used specific dopaminergic agonists/antagonists and therefore unintentionally avoided the potential cross-reaction with alpha2-receptors. The present study was thus designed to investigate directly the effects of DA on male sexual behavior and to test whether the interaction of DA with heterologous receptors affects this behavior. Intracerebroventricular (i.c.v.) injection of DA or NE inhibited copulation in a dose-dependent manner. Systemic injections of yohimbine, an alpha2-noradrenergic antagonist, modulated copulation in a bimodal manner depending on the dose injected. Interestingly, a behaviorally ineffective dose of yohimbine markedly reduced the inhibitory effects of DA when injected 15min before. Together, these results show for the first time that i.c.v. injections of DA itself inhibit male sexual behavior in quail and suggest that the interaction of DA with alpha2-receptors has behavioral significance.

Effect of DA-9701 on Colorectal Distension-Induced Visceral Hypersensitivity in a Rat Model

PubMed Central

Kim, Eun Ran; Min, Byung-Hoon; Lee, Tae Ho; Son, Miwon; Rhee, Poong-Lyul

2014-01-01

Background/Aims DA-9701 is a newly developed drug made from the vegetal extracts of Pharbitidis semen and Co-rydalis tuber. The aim of this study was to evaluate the effect of DA-9701 on colorectal distension (CRD)-induced visceral hypersensitivity in a rat model. Methods Male Sprague-Dawley rats were subjected to neonatal colon irritation (CI) using CRD at 1 week after birth (CI group). At 6 weeks after birth, CRD was applied to these rats with a pressure of 20 to 90 mm Hg, and changes in the mean arterial pressure (MAP) were measured at baseline (i.e., without any drug administration) and after the administration of different doses of DA-9701. Results In the absence of DA-9701, the MAP changes after CRD were significantly higher in the CI group than in the control group at all applied pressures. In the control group, MAP changes after CRD were not significantly affected by the administration of DA-9701. In the CI group, however, the administration of DA-9701 resulted in a significant decrease in MAP changes after CRD. The administration of DA-9701 at a dose of 1.0 mg/kg produced a more significant decrease in MAP changes than the 0.3 mg/kg dose. Conclusions The administration of DA-9701 resulted in a significant increase in pain threshold in rats with CRD-induced visceral hypersensitivity. PMID:25071903

Effect of DA-9701 on colorectal distension-induced visceral hypersensitivity in a rat model.

PubMed

Kim, Eun Ran; Min, Byung-Hoon; Lee, Tae Ho; Son, Miwon; Rhee, Poong-Lyul

2014-07-01

DA-9701 is a newly developed drug made from the vegetal extracts of Pharbitidis semen and Co-rydalis tuber. The aim of this study was to evaluate the effect of DA-9701 on colorectal distension (CRD)-induced visceral hypersensitivity in a rat model. Male Sprague-Dawley rats were subjected to neonatal colon irritation (CI) using CRD at 1 week after birth (CI group). At 6 weeks after birth, CRD was applied to these rats with a pressure of 20 to 90 mm Hg, and changes in the mean arterial pressure (MAP) were measured at baseline (i.e., without any drug administration) and after the administration of different doses of DA-9701. In the absence of DA-9701, the MAP changes after CRD were significantly higher in the CI group than in the control group at all applied pressures. In the control group, MAP changes after CRD were not significantly affected by the administration of DA-9701. In the CI group, however, the administration of DA-9701 resulted in a significant decrease in MAP changes after CRD. The administration of DA-9701 at a dose of 1.0 mg/kg produced a more significant decrease in MAP changes than the 0.3 mg/kg dose. The administration of DA-9701 resulted in a significant increase in pain threshold in rats with CRD-induced visceral hypersensitivity.

DA-6034 Induces [Ca(2+)]i Increase in Epithelial Cells.

PubMed

Yang, Yu-Mi; Park, Soonhong; Ji, Hyewon; Kim, Tae-Im; Kim, Eung Kweon; Kang, Kyung Koo; Shin, Dong Min

2014-04-01

DA-6034, a eupatilin derivative of flavonoid, has shown potent effects on the protection of gastric mucosa and induced the increases in fluid and glycoprotein secretion in human and rat corneal and conjunctival cells, suggesting that it might be considered as a drug for the treatment of dry eye. However, whether DA-6034 induces Ca(2+) signaling and its underlying mechanism in epithelial cells are not known. In the present study, we investigated the mechanism for actions of DA-6034 in Ca(2+) signaling pathways of the epithelial cells (conjunctival and corneal cells) from human donor eyes and mouse salivary gland epithelial cells. DA-6034 activated Ca(2+)-activated Cl(-) channels (CaCCs) and increased intracellular calcium concentrations ([Ca(2+)]i) in primary cultured human conjunctival cells. DA-6034 also increased [Ca(2+)]i in mouse salivary gland cells and human corneal epithelial cells. [Ca(2+)]i increase of DA-6034 was dependent on the Ca(2+) entry from extracellular and Ca(2+) release from internal Ca(2+) stores. Interestingly, these effects of DA-6034 were related to ryanodine receptors (RyRs) but not phospholipase C/inositol 1,4,5-triphosphate (IP3) pathway and lysosomal Ca(2+) stores. These results suggest that DA-6034 induces Ca(2+) signaling via extracellular Ca(2+) entry and RyRs-sensitive Ca(2+) release from internal Ca(2+) stores in epithelial cells.

DA-Raf, a dominant-negative antagonist of the Ras-ERK pathway, is a putative tumor suppressor.

PubMed

Kanno, Emiri; Kawasaki, Osamu; Takahashi, Kazuya; Takano, Kazunori; Endo, Takeshi

2018-01-01

Activating mutations of RAS genes, particularly KRAS, are detected with high frequency in human tumors. Mutated Ras proteins constitutively activate the ERK pathway (Raf-MEK-ERK phosphorylation cascade), leading to cellular transformation and tumorigenesis. DA-Raf1 (DA-Raf) is a splicing variant of A-Raf and contains the Ras-binding domain (RBD) but lacks the kinase domain. Accordingly, DA-Raf antagonizes the Ras-ERK pathway in a dominant-negative fashion and suppresses constitutively activated K-Ras-induced cellular transformation. Thus, we have addressed whether DA-Raf serves as a tumor suppressor of Ras-induced tumorigenesis. DA-Raf(R52Q), which is generated from a single nucleotide polymorphism (SNP) in the RBD, and DA-Raf(R52W), a mutant detected in a lung cancer, neither bound to active K-Ras nor interfered with the activation of the ERK pathway. They were incapable of suppressing activated K-Ras-induced cellular transformation and tumorigenesis in mice, in which K-Ras-transformed cells were transplanted. Furthermore, although DA-Raf was highly expressed in lung alveolar epithelial type 2 (AE2) cells, its expression was silenced in AE2-derived lung adenocarcinoma cell lines with oncogenic KRAS mutations. These results suggest that DA-Raf represents a tumor suppressor protein against Ras-induced tumorigenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Using iPSC-derived human DA neurons from opioid-dependent subjects to study dopamine dynamics.

PubMed

Sheng, Yang; Filichia, Emily; Shick, Elizabeth; Preston, Kenzie L; Phillips, Karran A; Cooperman, Leslie; Lin, Zhicheng; Tesar, Paul; Hoffer, Barry; Luo, Yu

2016-08-01

The dopaminergic (DA) system plays important roles in addiction. However, human DA neurons from drug-dependent subjects were not available for study until recent development in inducible pluripotent stem cells (iPSCs) technology. In this study, we produced DA neurons differentiated using iPSCs derived from opioid-dependent and control subjects carrying different 3' VNTR (variable number tandem repeat) polymorphism in the human dopamine transporter (DAT or SLC6A3). In addition, the effects of valproic acid (VPA) exposures on iPSC-derived human DA neurons are also examined. We present the first evidence suggesting that the 3' VNTR polymorphism in the hDAT gene affects DAT expression level in iPSC-derived human DA neurons. In human DA neurons, which provide an appropriate cellular milieu, VPA treatment alters the expression of several genes important for dopaminergic neuron function including DAT, Nurr1, and TH; this might partly explain its action in regulating addictive behaviors. VPA treatment also significantly increased DA D2 receptor (Drd2) expression, especially in the opioid-dependent iPSC cell lines. Our data suggest that human iPSC-derived DA neurons may be useful in in vitro experimental model to examine the effects of genetic variation in gene regulation, to examine the underlying mechanisms in neurological disorders including drug addiction, and to serve as a platform for therapeutic development.

Death Anxiety in Persons with HIV/AIDS: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Miller, Audrey K.; Lee, Brittany L.; Henderson, Craig E.

2012-01-01

One of the most commonly cited psychological sequelae of HIV/AIDS is anxiety regarding death due to the illness (i.e., death anxiety; DA). However, extant research is inconclusive on several empirical issues, such as DA's relation to HIV/AIDS diagnostic status, the impact of illness-related symptoms on DA, and factors that may protect against DA.…

The Case for Dynamic Assessment in Speech and Language Therapy

ERIC Educational Resources Information Center

Hasson, Natalie

2007-01-01

This paper highlights the appeal of dynamic assessment (DA) for speech and language therapists (SLTs), and describes the usefulness of various DA models and methods. It describes the background to DA, and the uses to which DA has been put, by educational psychologists in the UK, and by SLTs in the USA. The research and development of methods of DA…

32 CFR 635.18 - Identifying criminal incidents and subjects of investigation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... reported as the subject of an offense on DA Form 3975 when credible information exists that the person or... actions will not be based solely on the listing of an individual or legal entity as a subject on DA Form... entity is entered in the subject block of the DA Form 3975, their identity is recorded in DA automated...

Explaining the disease phenotype of intergenic SNP through predicted long range regulation

PubMed Central

Chen, Jingqi; Tian, Weidong

2016-01-01

Thousands of disease-associated SNPs (daSNPs) are located in intergenic regions (IGR), making it difficult to understand their association with disease phenotypes. Recent analysis found that non-coding daSNPs were frequently located in or approximate to regulatory elements, inspiring us to try to explain the disease phenotypes of IGR daSNPs through nearby regulatory sequences. Hence, after locating the nearest distal regulatory element (DRE) to a given IGR daSNP, we applied a computational method named INTREPID to predict the target genes regulated by the DRE, and then investigated their functional relevance to the IGR daSNP's disease phenotypes. 36.8% of all IGR daSNP-disease phenotype associations investigated were possibly explainable through the predicted target genes, which were enriched with, were functionally relevant to, or consisted of the corresponding disease genes. This proportion could be further increased to 60.5% if the LD SNPs of daSNPs were also considered. Furthermore, the predicted SNP-target gene pairs were enriched with known eQTL/mQTL SNP-gene relationships. Overall, it's likely that IGR daSNPs may contribute to disease phenotypes by interfering with the regulatory function of their nearby DREs and causing abnormal expression of disease genes. PMID:27280978

"Click chemistry" in tailor-made polymethacrylates bearing reactive furfuryl functionality: a new class of self-healing polymeric material.

PubMed

Kavitha, A Amalin; Singha, Nikhil K

2009-07-01

This investigation reports the effective use of the Diels-Alder (DA) reaction, a "click reaction" in the preparation of thermally amendable and self-healing polymeric materials having reactive furfuryl functionality. In this case, the DA and retro-DA (rDA) reactions were carried out between the tailor-made homo- and copolymer of furfuryl methacrylate prepared by atom-transfer radical polymerization and a bismaleimide (BM). The kinetic studies of DA and rDA reactions were carried out using Fourier transform infrared spectroscopy. The DA polymers were insoluble in toluene at room temperature. When the DA polymers were heated at 100 degrees C in toluene, it was soluble. This is because of the cleavage between furfuryl functionality and BM. The chemical cross-link density was determined by the Flory-Rehner equation. The cross-linked polymer showed much greater adhesive strength at room temperature, but the adhesive strength was quite low at higher temperature. The self-healing capability was studied by using scanning electron microscopy analysis. The thermal and dynamic mechanical properties of the thermally amendable cross-linked materials were investigated by thermogravimetric analysis and dynamic mechanical analysis.

Reduced dopamine receptors and transporters but not synthesis capacity in normal aging adults: a meta-analysis.

PubMed

Karrer, Teresa M; Josef, Anika K; Mata, Rui; Morris, Evan D; Samanez-Larkin, Gregory R

2017-09-01

Many theories of cognitive aging are based on evidence that dopamine (DA) declines with age. Here, we performed a systematic meta-analysis of cross-sectional positron emission tomography and single-photon emission-computed tomography studies on the average effects of age on distinct DA targets (receptors, transporters, or relevant enzymes) in healthy adults (N = 95 studies including 2611 participants). Results revealed significant moderate to large, negative effects of age on DA transporters and receptors. Age had a significantly larger effect on D1- than D2-like receptors. In contrast, there was no significant effect of age on DA synthesis capacity. The average age reductions across the DA system were 3.7%-14.0% per decade. A meta-regression found only DA target as a significant moderator of the age effect. This study precisely quantifies prior claims of reduced DA functionality with age. It also identifies presynaptic mechanisms (spared synthesis capacity and reduced DA transporters) that may partially account for previously unexplained phenomena whereby older adults appear to use dopaminergic resources effectively. Recommendations for future studies including minimum required samples sizes are provided. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Absorption, distribution, metabolism, and excretion of decursin and decursinol angelate from Angelica gigas Nakai.

PubMed

Kim, Kang Min; Kim, Myo Jeong; Kang, Jae Seon

2009-12-01

The pharmacokinetics of decursin and decursinol angelate (D/DA) was investigated in male SD rats following oral and intravenous administration. D/DA and metabolites obtained from in vitro samples were evaluated by LC/MS. The level of D/DA and metabolized decursinol in the blood following oral and intravenous administration declined according to first-order kinetics, with T1/2 values of 56.67, 58.01 and 57.22 h, respectively, being observed after administration of a dose of 2 mg/kg body weight. The large intestine was the major site of disposition following oral administration. These data indicate that D/DA is rapidly absorbed from the gastrointestinal tract. In in vitro experiment utilizing liver microsomal protein, the major metabolic reaction of D/DA occurred to change decursinol. The cumulative biliary, urinary, and fecal excretion of D/DA in bile duct-cannulated rats was 36.10+/-2.9, 25.35+/-3.8, and 34.20+/-3.2%, respectively, at 72 h after administration. These results indicate that the absorption of D/DA is almost complete, and that its metabolites are primarily excreted into feces through the bile. These results indicate that D/DA is subject to enterohepatic circulation.

Evaluation of cephamycins as supplements to selective agar for detecting Campylobacter spp. in chicken carcass rinses.

PubMed

Chon, Jung-Whan; Kim, Young-Ji; Kim, Hong-Seok; Kim, Dong-Hyeon; Kim, Hyunsook; Song, Kwang-Young; Sung, Kidon; Seo, Kun-Ho

2016-04-16

Although cefoperazone is the most commonly used antibiotic in Campylobacter-selective media, the distribution of cefoperazone-resistant bacteria such as extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli is increasing. Here we evaluated the potential of cephamycins for use as supplements to improve modified charcoal-cefoperazone-deoxycholate agar (mCCDA) by replacing cefoperazone with the same concentrations (32 mg/L) of cefotetan (modified charcoal-cefotetan-deoxycholate agar, mCCtDA) and cefoxitin (modified charcoal-cefoxitin-deoxycholate agar, mCCxDA). In chicken carcass rinse samples, the number of mCCDA plates detecting for Campylobacter (18/70, 26%) was significantly lower than that of mCCtDA (42/70, 60%) or mCCxDA plates (40/70, 57%). The number of mCCDA plates (70/70, 100%) that were contaminated with non-Campylobacter species was significantly higher than that of mCCtDA (20/70, 29%) or mCCxDA plates (21/70, 30%). The most common competing species identified using mCCDA was ESBL-producing E. coli, while Pseudomonas species frequently appeared on mCCtDA and mCCxDA. Copyright © 2016. Published by Elsevier B.V.

Adolescent Stimulation of D2 Receptors Alters the Maturation of Dopamine-dependent Goal-Directed Behavior

PubMed Central

Naneix, Fabien; Marchand, Alain R; Pichon, Anaïs; Pape, Jean- Rémi; Coutureau, Etienne

2013-01-01

Adolescence is a period of high sensitivity to drugs and rewards, characterized by the immaturity of decision-making abilities. A chronic stimulation of reward systems during this period might constitute a factor of vulnerability to the development of psychiatric disorders. However, the long-term consequences of such an exposure have seldom been explored. Here, we investigate at the adult age the effects of chronic dopamine (DA) stimulation during adolescence on both the maturation of DA systems and the cognitive processes underlying goal-directed actions. We first demonstrate that chronic stimulation of D2 receptors by quinpirole during adolescence alters the development of DA systems. This treatment has particularly prominent effects on the mesocortical DA pathway where it decreases DA fibers density, DA concentration, and DA receptors expression. Furthermore, we show that quinpirole-treated rats exhibit specific impairments in instrumental goal-directed behavior, as they fail to adapt their action when action–outcome relationships change in a contingency degradation procedure. These results therefore highlight the vulnerability of DA system and prefrontal areas to prolonged stimulation during adolescence, and its potential long-term impact on cognitive functions. PMID:23443719

Chemogenetic Activation of Midbrain Dopamine Neurons Affects Attention, but not Impulsivity, in the Five-Choice Serial Reaction Time Task in Rats.

PubMed

Boekhoudt, Linde; Voets, Elisa S; Flores-Dourojeanni, Jacques P; Luijendijk, Mieneke Cm; Vanderschuren, Louk Jmj; Adan, Roger Ah

2017-05-01

Attentional impairments and exaggerated impulsivity are key features of psychiatric disorders, such as attention-deficit/hyperactivity disorder, schizophrenia, and addiction. These deficits in attentional performance and impulsive behaviors have been associated with aberrant dopamine (DA) signaling, but it remains unknown whether these deficits result from enhanced DA neuronal activity in the midbrain. Here, we took a novel approach by testing the impact of chemogenetically activating DA neurons in the ventral tegmental area (VTA) or substantia nigra pars compacta (SNc) on attention and impulsivity in the five-choice serial reaction time task (5-CSRTT) in rats. We found that activation of DA neurons in both the VTA and SNc impaired attention by increasing trial omissions. In addition, SNc DA neuron activation decreased attentional accuracy. Surprisingly, enhanced DA neuron activity did not affect impulsive action in this task. These results show that enhanced midbrain DA neuronal activity induces deficits in attentional performance, but not impulsivity. Furthermore, DA neurons in the VTA and SNc have different roles in regulating attention. These findings contribute to our understanding of the neural substrates underlying attention deficits and impulsivity, and provide valuable insights to improve treatment of these symptoms.

Effect of β,β-dimethylacrylshikonin on inhibition of human colorectal cancer cell growth in vitro and in vivo.

PubMed

Fan, Yingying; Jin, Shaoju; He, Jun; Shao, Zhenjun; Yan, Jiao; Feng, Ting; Li, Hong

2012-01-01

In traditional Chinese medicine, shikonin and its derivatives, has been used in East Asia for several years for the prevention and treatment of several diseases, including cancer. We previously identified that β,β-dimethylacrylshikonin (DA) could inhibit hepatocellular carcinoma growth. In the present study, we investigated the inhibitory effects of DA on human colorectal cancer (CRC) cell line HCT-116 in vitro and in vivo. A viability assay showed that DA could inhibit tumor cell growth in a time- and dose-dependent manner. Flow cytometry showed that DA blocks the cell cycle at G(0)/G(1) phase. Western blotting results demonstrated that the induction of apoptosis by DA correlated with the induction of pro-apoptotic proteins Bax, and Bid, and a decrease in the expression of anti-apoptotic proteins Bcl-2 and Bcl-xl. Furthermore, treatment of HCT-116 bearing nude mice with DA significantly retarded the growth of xenografts. Consistent with the results in vitro, the DA-mediated suppression of HCT-116 xenografts correlated with Bax and Bcl-2. Taken together, these results suggest that DA could be a novel and promising approach to the treatment of CRC.

Positron emission tomography molecular imaging of dopaminergic system in drug addiction.

PubMed

Hou, Haifeng; Tian, Mei; Zhang, Hong

2012-05-01

Dopamine (DA) is involved in drug reinforcement, but its role in drug addiction remains unclear. Positron emission tomography (PET) is the first technology used for the direct measurement of components of the dopaminergic system in the living human brain. In this article, we reviewed the major findings of PET imaging studies on the involvement of DA in drug addiction, especially in heroin addiction. Furthermore, we summarized PET radiotracers that have been used to study the role of DA in drug addiction. To investigate presynaptic function in drug addiction, PET tracers have been developed to measure DA synthesis and transport. For the investigation of postsynaptic function, several radioligands targeting dopamine one (D1) receptor and dopamine two (D2) receptor are extensively used in PET imaging studies. Moreover, we also summarized the PET imaging findings of heroin addiction studies, including heroin-induced DA increases and the reinforcement, role of DA in the long-term effects of heroin abuse, DA and vulnerability to heroin abuse and the treatment implications. PET imaging studies have corroborated the role of DA in drug addiction and increase our understanding the mechanism of drug addiction. Copyright © 2012 Wiley Periodicals, Inc.

Dioscorea Extract (DA-9801) Modulates Markers of Peripheral Neuropathy in Type 2 Diabetic db/db Mice.

PubMed

Moon, Eunjung; Lee, Sung Ok; Kang, Tong Ho; Kim, Hye Ju; Choi, Sang Zin; Son, Mi-Won; Kim, Sun Yeou

2014-09-01

The purpose of this study was to investigate the therapeutic effects of DA-9801, an optimized extract of Dioscorea species, on diabetic peripheral neuropathy in a type 2 diabetic animal model. In this study, db/db mice were treated with DA-9801 (30 and 100 mg/kg, daily, p.o.) for 12 weeks. DA-9801 reduced the blood glucose levels and increased the withdrawal latencies in hot plate tests. Moreover, it prevented nerve damage based on increased nerve conduction velocity and ultrastructural changes. Decrease of nerve growth factor (NGF) may have a detrimental effect on diabetic neuropathy. We previously reported NGF regulatory properties of the Dioscorea genus. In this study, DA-9801 induced NGF production in rat primary astrocytes. In addition, it increased NGF levels in the sciatic nerve and the plasma of type 2 diabetic animals. DA-9801 also increased neurite outgrowth and mRNA expression of Tieg1/Klf10, an NGF target gene, in PC12 cells. These results demonstrated the attenuation of diabetic peripheral neuropathy by oral treatment with DA-9801 via NGF regulation. DA-9801 is currently being evaluated in a phase II clinical study.

Pure uptake blockers of dopamine can reduce prolactin secretion: studies with diclofensine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Di Renzo, G.; Amoroso, S.; Taglialatela, M.

1988-01-01

The effects of diclofensine, a pure dopamine (DA) uptake inhibitor on 1) /sup 3/H-DA uptake in rat arcuate-periventricular nucleus-median eminence synaptosomes, 2) basal and K+-evoked endogenous DA release from tuberoinfundibular dopaminergic (TIDA) neurons and 3) in vivo prolactin (PRL) secretion were studied. Diclofensine, in concentrations of 0.01, 0.1 and 1 ..mu..M caused a marked decrease of /sup 3/H-DA uptake. In addition, it was unable to stimulate basal endogenous DA release which, on the contrary, was elicited by d-amphetamine in the same concentration. On the other hand, diclofensine caused a 3 fold enhancement on K+-evoked DA release. Finally, the compound, whenmore » administered in vivo to male rats, significantly reduced basal serum PRL levels. The results of the present study seem to indicate that the pharmacological blockade of DA uptake in TIDA neurons is a condition sufficient to cause a reduction of PRL release.« less

Dopamine, the medial preoptic area, and male sexual behavior.

PubMed

Dominguez, Juan M; Hull, Elaine M

2005-10-15

The medial preoptic area (MPOA), at the rostral end of the hypothalamus, is important for the regulation of male sexual behavior. Results showing that male sexual behavior is impaired following MPOA lesions and enhanced with MPOA stimulation support this conclusion. The neurotransmitter dopamine (DA) facilitates male sexual behavior in all studied species, including rodents and humans. Here, we review data indicating that the MPOA is one site where DA may act to regulate male sexual behavior. DA agonists microinjected into the MPOA facilitate sexual behavior, whereas DA antagonists impair copulation, genital reflexes, and sexual motivation. Moreover, microdialysis experiments showed increased release of DA in the MPOA as a result of precopulatory exposure to an estrous female and during copulation. DA may remove tonic inhibition in the MPOA, thereby enhancing sensorimotor integration, and also coordinate autonomic influences on genital reflexes. In addition to sensory stimulation, other factors influence the release of DA in the MPOA, including testosterone, nitric oxide, and glutamate. Here we summarize and interpret these data.

Respostas religiosas à aids no Brasil: impressões de pesquisa acerca da Pastoral de DST/Aids da Igreja Católica1

PubMed Central

Seffner, Fernando; Silva, Cristiane Gonçalves Meireles da; Maksud, Ívia; Garcia, Jonathan; Rios, Luís Felipe; Natividade, Marcelo; Borges, Priscila Rodrigues; Parker, Richard; Terto, Veriano

2009-01-01

O texto encontra-se estruturado em quatro partes. Na primeira delas, apresentamos um conjunto de considerações e informações acerca da situação da aids no Brasil, das relações entre religião, sexualidade, aids e estado laico, bem como uma descrição mais clara do Projeto Respostas Religiosas ao HIV/Aids no Brasil, do qual este texto apresenta algumas impressões de pesquisa preliminares. A seguir, dedicamos um item a apresentação da Pastoral de DST/Aids, sua história, estrutura e objetivos. No item seguinte problematizamos diversas questões em particular no âmbito das relações Estado e Igreja, relações entre agentes de pastoral e hierarquia da Igreja, e questões ligadas mais diretamente à sexualidade e aids, todas referenciadas ao trabalho da Pastoral de DST/Aids. Ao final, apresentamos a bibliografia e fontes consultadas. PMID:20442806

Morphine disinhibits glutamatergic input to VTA dopamine neurons and promotes dopamine neuron excitation.

PubMed

Chen, Ming; Zhao, Yanfang; Yang, Hualan; Luan, Wenjie; Song, Jiaojiao; Cui, Dongyang; Dong, Yi; Lai, Bin; Ma, Lan; Zheng, Ping

2015-07-24

One reported mechanism for morphine activation of dopamine (DA) neurons of the ventral tegmental area (VTA) is the disinhibition model of VTA-DA neurons. Morphine inhibits GABA inhibitory neurons, which shifts the balance between inhibitory and excitatory input to VTA-DA neurons in favor of excitation and then leads to VTA-DA neuron excitation. However, it is not known whether morphine has an additional strengthening effect on excitatory input. Our results suggest that glutamatergic input to VTA-DA neurons is inhibited by GABAergic interneurons via GABAB receptors and that morphine promotes presynaptic glutamate release by removing this inhibition. We also studied the contribution of the morphine-induced disinhibitory effect on the presynaptic glutamate release to the overall excitatory effect of morphine on VTA-DA neurons and related behavior. Our results suggest that the disinhibitory action of morphine on presynaptic glutamate release might be the main mechanism for morphine-induced increase in VTA-DA neuron firing and related behaviors.

Schizophrenia: an integrated sociodevelopmental-cognitive model

PubMed Central

Howes, Oliver D; Murray, Robin M

2014-01-01

Schizophrenia remains a major burden1. The dopamine (DA) and neurodevelopmental hypotheses attempt to explain the pathogenic mechanisms and origins of the disorder respectively2-4. Recently an alternative, the cognitive model, has gained popularity5. However the first two theories have not been satisfactorily integrated, and the most influential iteration of the cognitive model makes no mention of DA, neurodevelopment, or indeed the brain5. Here we show that developmental alterations secondary to variant genes, early hazards to the brain and childhood adversity, sensitise the DA system, and result in excessive presynaptic DA synthesis and DA release. Social adversity biases the cognitive schema that the individual uses to interpret experiences towards paranoid interpretations. Subsequent stress results in dysregulated DA release, causing the misattribution of salience to stimuli, which are then misinterpreted by the biased cognitive processes. The resulting paranoia and hallucinations in turn cause further stress, and eventually repeated DA dysregulation hard-wires the psychotic beliefs. Finally we consider the implications of this model for understanding and treating schizophrenia. PMID:24315522

Sensitive detection of dopamine via leucodopaminechrome on polyacrylic acid-coated ceria nanorods

NASA Astrophysics Data System (ADS)

Sheng, Weiqin; Zheng, Liang; Liu, Yan; Zhao, Xueqin; Weng, Jian; Zhang, Yang

2017-09-01

The major hurdle in detection of dopamine (DA) by electro-analysis is the presence of physiological interferents with a similar oxidation potential of DA. The conventional method is to enlarge the difference of their oxidation potentials. Here, we report an unconventional method to detect DA via leucodopaminechrome on CeO2 nanorods. Leucodopaminechrome is produced from the cyclization of dopamine-quinone, a product of two-electron oxidation of DA. Thus, its concentration is proportional to the DA concentration. Determining DA is demonstrated by measuring the reduction current of leucodopaminechrome on CeO2 nanorods. CeO2 nanorods demonstrate high electrocatalytic activity for reduction of leucodopaminechrome with a low potential at -0.27 V. The low detection potential of leucodopaminechrome can avoid the interference from ascorbic acid (AA) and uric acid (UA). Therefore, detecting DA via leucodopaminechrome is an effective method to avoid interference from AA and UA, and the suggested biosensor also displays good reproducibility and stability.

Neuroprotective Effect of a New Synthetic Aspirin-decursinol Adduct in Experimental Animal Models of Ischemic Stroke

PubMed Central

Shin, Bich Na; Ahn, Ji Hyeon; Kim, In Hye; Lee, Jae-Chul; Yoo, Ki-Yeon; Hwang, In Koo; Choi, Jung Hoon; Park, Jeong Ho; Lee, Yun Lyul; Suh, Hong-Won; Jun, Jong-Gab; Kwon, Young-Guen; Kim, Young-Myeong; Kwon, Seung-Hae; Her, Song; Kim, Jin Su; Hyun, Byung-Hwa; Kim, Chul-Kyu; Cho, Jun Hwi; Lee, Choong Hyun; Won, Moo-Ho

2013-01-01

Stroke is the second leading cause of death. Experimental animal models of cerebral ischemia are widely used for researching mechanisms of ischemic damage and developing new drugs for the prevention and treatment of stroke. The present study aimed to comparatively investigate neuroprotective effects of aspirin (ASA), decursinol (DA) and new synthetic aspirin-decursinol adduct (ASA-DA) against transient focal and global cerebral ischemic damage. We found that treatment with 20 mg/kg, not 10 mg/kg, ASA-DA protected against ischemia-induced neuronal death after transient focal and global ischemic damage, and its neuroprotective effect was much better than that of ASA or DA alone. In addition, 20 mg/kg ASA-DA treatment reduced the ischemia-induced gliosis and maintained antioxidants levels in the corresponding injury regions. In brief, ASA-DA, a new synthetic drug, dramatically protected neurons from ischemic damage, and neuroprotective effects of ASA-DA may be closely related to the attenuation of ischemia-induced gliosis and maintenance of antioxidants. PMID:24073226

Neuroprotective effect of a new synthetic aspirin-decursinol adduct in experimental animal models of ischemic stroke.

PubMed

Yan, Bing Chun; Park, Joon Ha; Shin, Bich Na; Ahn, Ji Hyeon; Kim, In Hye; Lee, Jae-Chul; Yoo, Ki-Yeon; Hwang, In Koo; Choi, Jung Hoon; Park, Jeong Ho; Lee, Yun Lyul; Suh, Hong-Won; Jun, Jong-Gab; Kwon, Young-Guen; Kim, Young-Myeong; Kwon, Seung-Hae; Her, Song; Kim, Jin Su; Hyun, Byung-Hwa; Kim, Chul-Kyu; Cho, Jun Hwi; Lee, Choong Hyun; Won, Moo-Ho

2013-01-01

Stroke is the second leading cause of death. Experimental animal models of cerebral ischemia are widely used for researching mechanisms of ischemic damage and developing new drugs for the prevention and treatment of stroke. The present study aimed to comparatively investigate neuroprotective effects of aspirin (ASA), decursinol (DA) and new synthetic aspirin-decursinol adduct (ASA-DA) against transient focal and global cerebral ischemic damage. We found that treatment with 20 mg/kg, not 10 mg/kg, ASA-DA protected against ischemia-induced neuronal death after transient focal and global ischemic damage, and its neuroprotective effect was much better than that of ASA or DA alone. In addition, 20 mg/kg ASA-DA treatment reduced the ischemia-induced gliosis and maintained antioxidants levels in the corresponding injury regions. In brief, ASA-DA, a new synthetic drug, dramatically protected neurons from ischemic damage, and neuroprotective effects of ASA-DA may be closely related to the attenuation of ischemia-induced gliosis and maintenance of antioxidants.

Raven surgical robot training in preparation for da vinci.

PubMed

Glassman, Deanna; White, Lee; Lewis, Andrew; King, Hawkeye; Clarke, Alicia; Glassman, Thomas; Comstock, Bryan; Hannaford, Blake; Lendvay, Thomas S

2014-01-01

The rapid adoption of robotic assisted surgery challenges the pace at which adequate robotic training can occur due to access limitations to the da Vinci robot. Thirty medical students completed a randomized controlled trial evaluating whether the Raven robot could be used as an alternative training tool for the Fundamentals of Laparoscopic Surgery (FLS) block transfer task on the da Vinci robot. Two groups, one trained on the da Vinci and one trained on the Raven, were tested on a criterion FLS block transfer task on the da Vinci. After robotic FLS block transfer proficiency training there was no statistically significant difference between path length (p=0.39) and economy of motion scores (p=0.06) between the two groups, but those trained on the da Vinci did have faster task times (p=0.01). These results provide evidence for the value of using the Raven robot for training prior to using the da Vinci surgical system for similar tasks.

Load Segmentation for Convergence of Distribution Automation and Advanced Metering Infrastructure Systems

NASA Astrophysics Data System (ADS)

Pamulaparthy, Balakrishna; KS, Swarup; Kommu, Rajagopal

2014-12-01

Distribution automation (DA) applications are limited to feeder level today and have zero visibility outside of the substation feeder and reaching down to the low-voltage distribution network level. This has become a major obstacle in realizing many automated functions and enhancing existing DA capabilities. Advanced metering infrastructure (AMI) systems are being widely deployed by utilities across the world creating system-wide communications access to every monitoring and service point, which collects data from smart meters and sensors in short time intervals, in response to utility needs. DA and AMI systems convergence provides unique opportunities and capabilities for distribution grid modernization with the DA system acting as a controller and AMI system acting as feedback to DA system, for which DA applications have to understand and use the AMI data selectively and effectively. In this paper, we propose a load segmentation method that helps the DA system to accurately understand and use the AMI data for various automation applications with a suitable case study on power restoration.

A novel quantum dot-laccase hybrid nanobiosensor for low level determination of dopamine.

PubMed

Shamsipur, Mojtaba; Shanehasz, Maryam; Khajeh, Khosro; Mollania, Nasrin; Kazemi, Sayyed Habib

2012-12-07

This work reports a novel nanobiosensor based on a thioglycolic acid (TGA)-capped CdTe quantum dot-laccase (Lac) enzyme system for sensitive detection of dopamine (DA). The enzyme used catalyzes the oxidation of DA to dopamine-o-quinone (DOQ), which can selectively quench the strong luminescence of CdTe nanocrystals at neutral pH. The relationship between luminescence intensity of CdTe nanocrystals and DA concentration is nicely described by the Stern-Volmer equation. At an optimum pH of 7.4, the proposed sensor gives a linear calibration over a DA concentration range of 0.3 to 100 μM, with a limit of detection of 0.16 μM and a response time of 2 min. The relative standard deviation for seven replicate determinations of 6.0 μM of DA was found to be 3.7%. The sensor was successfully applied to the determination of DA in a blood plasma sample and in a DA injection formulation.

Analysis of the Economic Impact of Cardiovascular Diseases in the Last Five Years in Brazil.

PubMed

Siqueira, Alessandra de Sá Earp; Siqueira-Filho, Aristarco Gonçalves de; Land, Marcelo Gerardin Poirot

2017-07-01

There is growing concern about the economic impact of cardiovascular diseases (CVD) in Brazil and worldwide. To estimate the economic impact of CVD in Brazil in the last five years. The information to estimate CVD costs was taken from national databases, adding the direct costs with hospitalizations, outpatient visits and benefits granted by social security. Indirect costs were added to the calculation, such as loss of income caused by CVD morbidity or mortality. CVD mortality accounts for 28% of all deaths in Brazil in the last five years and for 38% of deaths in the productive age range (18 to 65 years). The estimated costs of CVD were R$ 37.1 billion in 2015, a 17% increase in the period from 2010 to 2015. The estimated costs of premature death due to CVD represent 61% of the total cost of CVD, Direct costs with hospitalizations and consultations were 22%, and costs related to the loss of productivity related to the disease were 15% of the total. Health expenditures in Brazil are estimated at 9.5% of GDP and the average cost of CVD was estimated at 0.7% of GDP. CVD costs have increased significantly in the last five years. It is estimated that CVD costs increase as the Brazilian population ages and the prevalence of CVD increases. Existe uma preocupação crescente com o impacto econômico das doenças cardiovasculares (DCV) no Brasil e no mundo. Estimar o impacto econômico das DCV no Brasil nos últimos cinco anos. As informações para estimar os custos em DCV foram retiradas de bancos de dados nacionais, somando os custos diretos com hospitalizações, atendimentos ambulatoriais e benefícios concedidos pela previdência. Custos indiretos foram acrescidos ao cálculo, como a perda de renda causada pela morbidade ou pela mortalidade da DCV. A mortalidade por DCV representa 28% do total de óbitos ocorridos no Brasil nos últimos cinco anos e atinge 38% dos óbitos na faixa etária produtiva (18 a 65 anos). Os custos estimados por DCV foram de R$ 37,1 bilhões de reais no ano de 2015, um aumento percentual de 17% no período de 2010 a 2015. Os custos estimados pela morte prematura por DCV representam 61% do total de custo por DCV, os custos diretos com internações e consultas foram de 22% e os custos pela perda da produtividade relacionados à doença foram de 15% do total. Os gastos com saúde no Brasil são estimados em 9,5% do PIB e o custo médio das DCV foi estimado em 0,7% do PIB. Os custos com DCV vêm aumentando significativamente nos últimos cinco anos. Estima-se que os custos por DCV aumentem à medida que a população brasileira envelhece e que a prevalência de DCV aumenta.

A targeted drug delivery system based on dopamine functionalized nano graphene oxide

NASA Astrophysics Data System (ADS)

Masoudipour, Elham; Kashanian, Soheila; Maleki, Nasim

2017-01-01

The cellular targeting property of a biocompatible drug delivery system can widely increase the therapeutic effect against various diseases. Here, we report a dopamine conjugated nano graphene oxide (DA-nGO) carrier for cellular delivery of the anticancer drug, Methotrexate (MTX) into DA receptor positive human breast adenocarcinoma cell line. The material was characterized using scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy and UV-vis spectroscopy. Furthermore, the antineoplastic action of MTX loaded DA-nGO against DA receptor positive and negative cell lines were explored. The results presented in this article demonstrated that the application of DA functionalized GO as a targeting drug carrier can improve the drug delivery efficacy for DA receptor positive cancer cell lines and promise future designing of carrier conjugates based on it.

Prepuberal intranasal dopamine treatment in an animal model of ADHD ameliorates deficient spatial attention, working memory, amino acid transmitters and synaptic markers in prefrontal cortex, ventral and dorsal striatum.

PubMed

Ruocco, L A; Treno, C; Gironi Carnevale, U A; Arra, C; Mattern, C; Huston, J P; de Souza Silva, M A; Nikolaus, S; Scorziello, A; Nieddu, M; Boatto, G; Illiano, P; Pagano, C; Tino, A; Sadile, A G

2014-09-01

Intranasal application of dopamine (IN-DA) has been shown to increase motor activity and to release DA in the ventral (VS) and dorsal striatum (DS) of rats. The aim of the present study was to assess the effects of IN-DA treatment on parameters of DA and excitatory amino acid (EAA) function in prepuberal rats of the Naples high-excitability (NHE) line, an animal model for attention-deficit hyperactivity disorder (ADHD) and normal random bred (NRB) controls. NHE and NRB rats were daily administered IN-DA (0.075, 0.15, 0.30 mg/kg) or vehicle for 15 days from postnatal days 28-42 and subsequently tested in the Làt maze and in the Eight-arm radial Olton maze. Soluble and membrane-trapped L-glutamate (L-Glu) and L-aspartate (L-Asp) levels as well as NMDAR1 subunit protein levels were determined after sacrifice in IN-DA- and vehicle-treated NHE and NRB rats in prefrontal cortex (PFc), DS and VS. Moreover, DA transporter (DAT) protein and tyrosine hydroxylase (TH) levels were assessed in PFc, DS, VS and mesencephalon (MES) and in ventral tegmental area (VTA) and substantia nigra, respectively. In NHE rats, IN-DA (0.30 mg/kg) decreased horizontal activity and increased nonselective attention relative to vehicle, whereas the lower dose (0.15 mg/kg) increased selective spatial attention. In NHE rats, basal levels of soluble EAAs were reduced in PFc and DS relative to NRB controls, while membrane-trapped EAAs were elevated in VS. Moreover, basal NMDAR1 subunit protein levels were increased in PFc, DS and VS relative to NRB controls. In addition, DAT protein levels were elevated in PFc and VS relative to NRB controls. IN-DA led to a number of changes of EAA, NMDAR1 subunit protein, TH and DAT protein levels in PFc, DS, VS, MES and VTA, in both NHE and NRB rats with significant differences between lines. Our findings indicate that the NHE rat model of ADHD may be characterized by (1) prefrontal and striatal DAT hyperfunction, indicative of DA hyperactivty, and (2) prefrontal and striatal NMDA receptor hyperfunction indicative of net EAA hyperactivty. IN-DA had ameliorative effects on activity level, attention, and working memory, which are likely to be associated with DA action at inhibitory D2 autoreceptors, leading to a reduction in striatal DA hyperactivity and, possibly, DA action on striatal EAA levels, resulting in a decrease of striatal EAA hyperfunction (with persistence of prefrontal EAA hyperfunction). Previous studies on IN-DA treatment in rodents have indicated antidepressant, anxiolytic and anti-parkinsonian effects in relation to enhanced central DAergic activity. Our present results strengthen the prospects of potential therapeutic applications of intranasal  DA by indicating an enhancement of selective attention and working memory in a deficit model.

[Clinical application of Da Vinci surgical system in China].

PubMed

Jin, Zhenyu

2014-01-01

Da Vinci robotic surgical system leads the development of minimally invasive surgical techniques. By using Da Vinci surgical robot for minimally invasive surgery, it brings a lot of advantages to the surgeons. Since 2008, Da Vinci surgeries have been performed in 14 hospitals in domestic cities such as Beijing and Shanghai. Until the end of 2012, 3 551 cases of Da Vinci robotic surgery have been performed, covering various procedures of various surgical departments including the department of general surgery, urology, cardiovascular surgery, thoracic surgery, gynecology, and etc. Robotic surgical technique has made remarkable achievements.

Protection but maintained dysfunction of nigral dopaminergic nerve cell bodies and striatal dopaminergic terminals in MPTP-lesioned mice after acute treatment with the mGluR5 antagonist MPEP.

PubMed

Aguirre, Jose A; Kehr, Jan; Yoshitake, Takashi; Liu, Fang-Ling; Rivera, Alicia; Fernandez-Espinola, Sergio; Andbjer, Beth; Leo, Giuseppina; Medhurst, Andrew D; Agnati, Luigi F; Fuxe, Kjell

2005-02-08

The mGluR5 antagonist MPEP was used to study the role of mGluR5 in MPTP-induced injury of the nigrostriatal DA neurons. The findings indicate that acute blockade of mGluR5 may result in neuroprotective actions against MPTP neurotoxicity on nigral DA cell bodies and striatal DA terminals using stereological analysis of TH immunoreactivity and microdensitometry. Biochemical analysis showed no restoration of DA levels and metabolism indicating a maintained reduction of DA transmission.

Dopamine in the nucleus accumbens core, but not shell, increases during signaled food reward and decreases during delayed extinction.

PubMed

Biesdorf, C; Wang, A-L; Topic, B; Petri, D; Milani, H; Huston, J P; de Souza Silva, M A

2015-09-01

Microdialysis studies in rat have generally shown that appetitive stimuli release dopamine (DA) in the nucleus accumbens (NAc) shell and core. Here we examined the release of DA in the NAc during delivery of reward (food) and during extinction of food reward in the freely moving animal by use of in vivo microdialysis and HPLC. Fifty-two male Wistar rats were trained to receive food reward associated with appearance of cue-lights in a Skinner-box during in vivo microdialysis. Different behavioral protocols were used to assess the effects of extinction on DA and its metabolites. Results Exp. 1: (a) During a 20-min period of cued reward delivery, DA increased significantly in the NAc core, but not shell subregion; (b) for the next 60min period half of the rats underwent immediate extinction (with the CS light presented during non-reward) and the other half did not undergo extinction to the cue lights (CS was not presented during non-reward). DA remained significantly increased in both groups, providing no evidence for a decrease in DA during extinction in either NAc core or shell regions. (c) In half of the animals of the group that was not subjected to extinction, the cue lights were turned on for 30min, thus, initiating extinction to cue CS at a 1h delay from the period of reward. In this group DA in the NAc core, but not shell, significantly decreased. Behavioral analysis showed that while grooming is an indicator of extinction-induced behavior, glances toward the cue-lights (sign tracking) are an index of resistance to extinction. Results Exp. 2: (a) As in Exp. 1, during a 30-min period of cued reward delivery, DA levels again increased significantly in the NAc core but not in the NAc shell. (b) When extinction (the absence of reward with the cue lights presented) was administered 24h after the last reward session, DA again significantly decreased in the NAc core, but not in the NAc shell. (a) These results confirm the importance of DA release in the NAc for reward-related states, with DA increasing in the core, but not shell subregion. (b) They provide first evidence that during the withholding of expected reward, DA decreases in the NAc core, but not shell region. (c) This decrease in DA appears only after a delay between delivery of reward and extinction likely due to it being masked by persisting DA release. We hypothesize the decrease in extinction-induced release of DA in the NAc core to be a marker for the despair/depression that is known to accompany the failure to obtain expected rewards/reinforcers. Copyright © 2015 Elsevier Inc. All rights reserved.

Perfil dos Professores de Ciências Naturais do Recôncavo da Bahia - Alunos da Disciplina Terra e Universo no Curso de Ciências Naturais do Parfor

NASA Astrophysics Data System (ADS)

Lima, S. R.; Cerqueira Júnior, W.; Dutra, G.

2011-12-01

Este trabalho foi desenvolvido pelo projeto Astronomia no Recôncavo da Bahia, no Centro de Formação de Professores da Universidade Federal do Recôncavo da Bahia. Traçamos o perfil de um grupo de professores que lecionam conteúdos de Ciências Naturais no recôncavo, alunos do curso de Licenciatura em Ciências Naturais, oferecido dentro do Plano Nacional de Formação de Professores da Educação Básica. Nosso objetivo era avaliar se eles estão preparados para trabalhar conteúdos de Astronomia e identificar suas dificuldades. Os resultados serviram para orientar o professor da disciplina “Terra e Universo”, oferecida no segundo semestre de 2010. Durante a primeira aula da disciplina Terra e Universo, os alunos responderam a um questionário contendo questões abertas e fechadas, divididas em duas partes. A primeira procurando caracterizar profissionalmente os alunos enquanto professores da rede pública da região do Recôncavo Sul da Bahia e uma segunda parte procurando identificar conhecimentos básicos em Astronomia. Os resultados indicam uma predominância de professores do sexo feminino, com idade superior aos 40 anos, pardos e sem formação específica para o ensino de ciências. A maioria leciona há mais de 15 anos para turmas do 1º ao 5º ano, alguns lecionam para turmas de 6º ao 9º ano. Quase todos nunca participaram de um curso de formação continuada em Astronomia. Além disso, não estão habituados a ler revistas especializadas e nem livros com esta temática. Os que procuram ensinar temas voltados para a Astronomia têm, no livro didático, a maior fonte de informação sobre o assunto. As respostas também indicam uma deficiência em conteúdos básicos como a compreensão da esfericidade da Terra, noções de verticalidade e gravidade, incapacidade de identificar a Terra como um planeta, no Sistema Solar, em uma galáxia, no Universo. Estes resultados ressaltam a importância de disciplinas de Astronomia básica na formação dos professores da região.

On the Origin of Cortical Dopamine: Is it a Co-Transmitter in Noradrenergic Neurons?

PubMed Central

Devoto, Paola; Flore, Giovanna

2006-01-01

Dopamine (DA) and noradrenaline (NA) in the prefrontal cortex (PFC) modulate superior cognitive functions, and are involved in the aetiology of depressive and psychotic symptoms. Moreover, microdialysis studies in rats have shown how pharmacological treatments that induce modifications of extracellular NA in the medial PFC (mPFC), also produce parallel changes in extracellular DA. To explain the coupling of NA and DA changes, this article reviews the evidence supporting the hypothesis that extracellular DA in the cerebral cortex originates not only from dopaminergic terminals but also from noradrenergic ones, where it acts both as precursor for NA and as a co-transmitter. Accordingly, extracellular DA concentration in the occipital, parietal and cerebellar cortex was found to be much higher than expected in view of the scarce dopaminergic innervation in these areas. Systemic administration or intra-cortical perfusion of α2-adrenoceptor agonists and antagonists, consistent with their action on noradrenergic neuronal activity, produced concomitant changes not only in extracellular NA but also in DA in the mPFC, occipital and parietal cortex. Chemical modulation of the locus coeruleus by locally applied carbachol, kainate, NMDA or clonidine modified both NA and DA in the mPFC. Electrical stimulation of the locus coeruleus led to an increased efflux of both NA and DA in mPFC, parietal and occipital cortex, while in the striatum, NA efflux alone was enhanced. Atypical antipsychotics, such as clozapine and olanzapine, or antidepressants, including mirtazapine and mianserine, have been found to increase both NA and DA throughout the cerebral cortex, likely through blockade of α2-adrenoceptors. On the other hand, drugs selectively acting on dopaminergic transmission produced modest changes in extracellular DA in mPFC, and had no effect on the occipital or parietal cortex. Acute administration of morphine did not increase DA levels in the PFC (where NA is diminished), in contrast with augmented dopaminergic neuronal activity; moreover, during morphine withdrawal both DA and NA levels increased, in spite of a diminished dopaminergic activity, both increases being antagonised by clonidine but not quinpirole administration. Extensive 6-hydroxy dopamine lesion of the ventral tegmental area (VTA) decreases below 95% of control both intra- and extracellular DA and DOPAC in the nucleus accumbens, but only partially or not significantly in the mPFC and parietal cortex. The above evidence points to a common origin for NA and DA in the cerebral cortex and suggests the possible utility of noradrenergic system modulation as a target for drugs with potential clinical efficacy on cognitive functions. PMID:18615131

On the origin of cortical dopamine: is it a co-transmitter in noradrenergic neurons?

PubMed

Devoto, Paola; Flore, Giovanna

2006-04-01

Dopamine (DA) and noradrenaline (NA) in the prefrontal cortex (PFC) modulate superior cognitive functions, and are involved in the aetiology of depressive and psychotic symptoms. Moreover, microdialysis studies in rats have shown how pharmacological treatments that induce modifications of extracellular NA in the medial PFC (mPFC), also produce parallel changes in extracellular DA.To explain the coupling of NA and DA changes, this article reviews the evidence supporting the hypothesis that extracellular DA in the cerebral cortex originates not only from dopaminergic terminals but also from noradrenergic ones, where it acts both as precursor for NA and as a co-transmitter.Accordingly, extracellular DA concentration in the occipital, parietal and cerebellar cortex was found to be much higher than expected in view of the scarce dopaminergic innervation in these areas.Systemic administration or intra-cortical perfusion of alpha(2)-adrenoceptor agonists and antagonists, consistent with their action on noradrenergic neuronal activity, produced concomitant changes not only in extracellular NA but also in DA in the mPFC, occipital and parietal cortex.Chemical modulation of the locus coeruleus by locally applied carbachol, kainate, NMDA or clonidine modified both NA and DA in the mPFC.Electrical stimulation of the locus coeruleus led to an increased efflux of both NA and DA in mPFC, parietal and occipital cortex, while in the striatum, NA efflux alone was enhanced.Atypical antipsychotics, such as clozapine and olanzapine, or antidepressants, including mirtazapine and mianserine, have been found to increase both NA and DA throughout the cerebral cortex, likely through blockade of alpha(2)-adrenoceptors. On the other hand, drugs selectively acting on dopaminergic transmission produced modest changes in extracellular DA in mPFC, and had no effect on the occipital or parietal cortex.Acute administration of morphine did not increase DA levels in the PFC (where NA is diminished), in contrast with augmented dopaminergic neuronal activity; moreover, during morphine withdrawal both DA and NA levels increased, in spite of a diminished dopaminergic activity, both increases being antagonised by clonidine but not quinpirole administration.Extensive 6-hydroxy dopamine lesion of the ventral tegmental area (VTA) decreases below 95% of control both intra- and extracellular DA and DOPAC in the nucleus accumbens, but only partially or not significantly in the mPFC and parietal cortex.The above evidence points to a common origin for NA and DA in the cerebral cortex and suggests the possible utility of noradrenergic system modulation as a target for drugs with potential clinical efficacy on cognitive functions.

Co-release of noradrenaline and dopamine in the cerebral cortex elicited by single train and repeated train stimulation of the locus coeruleus

PubMed Central

Devoto, Paola; Flore, Giovanna; Saba, Pierluigi; Fà, Mauro; Gessa, Gian Luigi

2005-01-01

Background Previous studies by our group suggest that extracellular dopamine (DA) and noradrenaline (NA) may be co-released from noradrenergic nerve terminals in the cerebral cortex. We recently demonstrated that the concomitant release of DA and NA could be elicited in the cerebral cortex by electrical stimulation of the locus coeruleus (LC). This study analyses the effect of both single train and repeated electrical stimulation of LC on NA and DA release in the medial prefrontal cortex (mPFC), occipital cortex (Occ), and caudate nucleus. To rule out possible stressful effects of electrical stimulation, experiments were performed on chloral hydrate anaesthetised rats. Results Twenty min electrical stimulation of the LC, with burst type pattern of pulses, increased NA and DA both in the mPFC and in the Occ. NA in both cortices and DA in the mPFC returned to baseline within 20 min after the end of the stimulation period, while DA in the Occ reached a maximum increase during 20 min post-stimulation and remained higher than baseline values at 220 min post-stimulation. Local perfusion with tetrodotoxin (TTX, 10 μM) markedly reduced baseline NA and DA in the mPFC and Occ and totally suppressed the effect of electrical stimulation in both areas. A sequence of five 20 min stimulations at 20 min intervals were delivered to the LC. Each stimulus increased NA to the same extent and duration as the first stimulus, whereas DA remained elevated at the time next stimulus was delivered, so that baseline DA progressively increased in the mPFC and Occ to reach about 130 and 200% the initial level, respectively. In the presence of the NA transport (NAT) blocker desipramine (DMI, 100 μM), multiple LC stimulation still increased extracellular NA and DA levels. Electrical stimulation of the LC increased NA levels in the homolateral caudate nucleus, but failed to modify DA level. Conclusion The results confirm and extend that LC stimulation induces a concomitant release of DA and NA in the mPFC and Occ. The different time-course of LC-induced elevation of DA and NA suggests that their co-release may be differentially controlled. PMID:15865626

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yongjun; Yang, Lingyun

We report an efficient dynamic aperture (DA) optimization approach using multiobjective genetic algorithm (MOGA), which is driven by nonlinear driving terms computation. It was found that having small low order driving terms is a necessary but insufficient condition of having a decent DA. Then direct DA tracking simulation is implemented among the last generation candidates to select the best solutions. The approach was demonstrated successfully in optimizing NSLS-II storage ring DA.

Army Reserve Capabilities-Based Prioritization Study

DTIC Science & Technology

2008-08-15

regulations and procedural guidance are not sufficient to determine the ‘ground truth’ of Planning, Programming, Budgeting and Execution System (PPBES...list), Department of the Army (DA) and Army Reserve Regulations and DA pamphlets. A-3 c. Why this Study Has Not Yet Been Performed/Funded...Memorandum, Management Decision Packages, 1-N list), Department of the Army (DA) and Army Reserve Regulations and DA pamphlets. b. Initial Assessment

Simultaneous characterization of prenylated flavonoids and isoflavonoids in Psoralea corylifolia L. by liquid chromatography with diode-array detection and quadrupole time-of-flight mass spectrometry.

PubMed

Xu, Mei-Juan; Wu, Bin; Ding, Tao; Chu, Ji-Hong; Li, Chang-Yin; Zhang, Jun; Wu, Ting; Wu, Jian; Liu, Shi-Jia; Liu, Shen-Lin; Ju, Wen-Zheng; Li, Ping

2012-10-15

Prenylated flavonoids and isoflavonoids are widely distributed throughout the plant kingdom, with many biological effects. Psoralea corylifolia, which contains many kinds of prenylated components, has been widely used as a medicinal plant in Asia and India for thousands of years. The goal of this study was to characterize the components in P. corylifolia using a liquid chromatography with diode-array detection and quadrupole time-of-flight mass spectrometry (LC-DAD/Q-TOF-MS) method, and to elucidate the fragmentation behavior of the different prenyl substituent groups and their appropriate characteristic pathways in positive ion mode. The calculated accurate masses of the protonated molecules, the fragment ions, the retention behavior, and the data from UV spectra were used for identification of the components in P. corylifolia. A total of 45 compounds, including 43 prenylated components, were identified or tentatively identified in P. corylifolia. Different diagnostic fragment ions and neutral losses were observed in different prenyl substructures: neutral loss of 56 Da (C(4)H(8)) and a fragment ion at m/z 69 (C(5)H(9)(+)) were generated by a prenyl chain; neutral losses of 42 Da (C(3)H(6)), 54 Da (C(4)H(6)), 15 Da (CH(3•)) and 16 Da (CH(4)) were observed in a ring-closed prenyl group; neutral losses of 72 Da (C(4)H(8)O), 60 Da (C(2)H(4)O(2)), 58 Da (C(3)H(6)O) and 18 Da (H(2)O) were detected in a 2,2-dimethyl-3,4-dihydroxydihydropyran ring; neutral losses of 72 Da (C(4)H(8)O), 60 Da (C(3)H(8)O) and 18 Da (H(2)O) were yielded from a 2,2-dimethyl-3-hydroxydihydropyran ring, a 2-(1-hydroxy-1-methylethyl)dihydrofuran ring or a 1-hydroxy-3-methylbut-3-enyl chain. This method can be applied for analysis of prenylated components in P. corylifolia and other herbal medicines. Copyright © 2012 John Wiley & Sons, Ltd.

Counter-regulation by insulin and isoprenaline of a prominent fat-associated phosphoprotein doublet in rat adipocytes.

PubMed Central

Mooney, R A; Bordwell, K L

1991-01-01

1. In the adipocyte, phosphorylation/dephosphorylation of regulatory proteins is a common mechanism of metabolic regulation. We have observed a very prominent phosphoprotein doublet of 61 kDa and 63 kDa in rat adipocytes that is markedly responsive to hormones. The 63 kDa band was the predominant phosphoprotein in the cell in response to 0.1 microM-isoprenaline, whereas the 61 kDa band was nearly absent. Insulin alone did not alter 32P incorporation into the doublet, but partially counteracted the effects of isoprenaline, decreasing label in the 63 kDa band by as much as 50% and resulting in the reappearance of the 61 kDa band. 2. Subcellular fractionation demonstrated that both phosphoprotein bands were fat-associated. Neither insulin nor isoprenaline altered this localization. Peptide maps (one-dimensional) of the 61/63 kDa bands demonstrated close sequence similarity. Amino acid analysis revealed the presence of phosphoserine and phosphothreonine. The latter was more prominent in the 61 kDa band. Isoprenaline caused an absolute increase in both phosphoamino acids. 3. Permeabilization of 32P-labelled isoprenaline-treated cells with digitonin initiated rapid dephosphorylation of the 63 kDa band, with reappearance of the 61 kDa band. Insulin increased the rate of dephosphorylation by 2-3-fold when present with isoprenaline before permeabilization. 4. In permeabilized adipocytes, cyclic AMP (1 microM-1 mM) increased phosphorylation of the 61/63 kDa doublet by 4-10-fold in the presence of [gamma-32P]ATP, but insulin had no effect. 5. We conclude that this prominent phosphoprotein, migrating as a 61/63 kDa doublet, is coupled to the cyclic AMP-dependent protein kinase and is associated with an insulin-stimulated phosphoprotein phosphatase activity. This fat-associated phosphoprotein, which is under counter-regulatory hormonal control, may play a role in hormone-dependent lipid metabolism. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:1848760

A critical evaluation of an asymmetrical flow field-flow fractionation system for colloidal size characterization of natural organic matter.

PubMed

Zhou, Zhengzhen; Guo, Laodong

2015-06-19

Colloidal retention characteristics, recovery and size distribution of model macromolecules and natural dissolved organic matter (DOM) were systematically examined using an asymmetrical flow field-flow fractionation (AFlFFF) system under various membrane size cutoffs and carrier solutions. Polystyrene sulfonate (PSS) standards with known molecular weights (MW) were used to determine their permeation and recovery rates by membranes with different nominal MW cutoffs (NMWCO) within the AFlFFF system. Based on a ≥90% recovery rate for PSS standards by the AFlFFF system, the actual NMWCOs were determined to be 1.9 kDa for the 0.3 kDa membrane, 2.7 kDa for the 1 kDa membrane, and 33 kDa for the 10 kDa membrane, respectively. After membrane calibration, natural DOM samples were analyzed with the AFlFFF system to determine their colloidal size distribution and the influence from membrane NMWCOs and carrier solutions. Size partitioning of DOM samples showed a predominant colloidal size fraction in the <5 nm or <10 kDa size range, consistent with the size characteristics of humic substances as the main terrestrial DOM component. Recovery of DOM by the AFlFFF system, as determined by UV-absorbance at 254 nm, decreased significantly with increasing membrane NMWCO, from 45% by the 0.3 kDa membrane to 2-3% by the 10 kDa membrane. Since natural DOM is mostly composed of lower MW substances (<10 kDa) and the actual membrane cutoffs are normally larger than their manufacturer ratings, a 0.3 kDa membrane (with an actual NMWCO of 1.9 kDa) is highly recommended for colloidal size characterization of natural DOM. Among the three carrier solutions, borate buffer seemed to provide the highest recovery and optimal separation of DOM. Rigorous calibration with macromolecular standards and optimization of system conditions are a prerequisite for quantifying colloidal size distribution using the flow field-flow fractionation technique. In addition, the coupling of AFlFFF with fluorescence EEMs could provide new insights into DOM heterogeneity in different colloidal size fractions. Copyright © 2015 Elsevier B.V. All rights reserved.

Molecular identification of venous progenitors in the dorsal aorta reveals an aortic origin for the cardinal vein in mammals

PubMed Central

Lindskog, Henrik; Kim, Yung Hae; Jelin, Eric B.; Kong, Yupeng; Guevara-Gallardo, Salvador; Kim, Tyson N.; Wang, Rong A.

2014-01-01

Coordinated arterial-venous differentiation is crucial for vascular development and function. The origin of the cardinal vein (CV) in mammals is unknown, while conflicting theories have been reported in chick and zebrafish. Here, we provide the first molecular characterization of endothelial cells (ECs) expressing venous molecular markers, or venous-fated ECs, within the emergent dorsal aorta (DA). These ECs, expressing the venous molecular markers Coup-TFII and EphB4, cohabited the early DA with ECs expressing the arterial molecular markers ephrin B2, Notch and connexin 40. These mixed ECs in the early DA expressed either the arterial or venous molecular marker, but rarely both. Subsequently, the DA exhibited uniform arterial markers. Real-time imaging of mouse embryos revealed EC movement from the DA to the CV during the stage when venous-fated ECs occupied the DA. We analyzed mutants for EphB4, which encodes a receptor tyrosine kinase for the ephrin B2 ligand, as we hypothesized that ephrin B2/EphB4 signaling may mediate the repulsion of venous-fated ECs from the DA to the CV. Using an EC quantification approach, we discovered that venous-fated ECs increased in the DA and decreased in the CV in the mutants, whereas the rest of the ECs in each vessel were unaffected. This result suggests that the venous-fated ECs were retained in the DA and missing in the CV in the EphB4 mutant, and thus that ephrin B2/EphB4 signaling normally functions to clear venous-fated ECs from the DA to the CV by cell repulsion. Therefore, our cellular and molecular evidence suggests that the DA harbors venous progenitors that move to participate in CV formation, and that ephrin B2/EphB4 signaling regulates this aortic contribution to the mammalian CV. PMID:24550118

Constitutive expression of DaCBF7, an Antarctic vascular plant Deschampsia antarctica CBF homolog, resulted in improved cold tolerance in transgenic rice plants.

PubMed

Byun, Mi Young; Lee, Jungeun; Cui, Li Hua; Kang, Yoonjee; Oh, Tae Kyung; Park, Hyun; Lee, Hyoungseok; Kim, Woo Taek

2015-07-01

Deschampsia antarctica is an Antarctic hairgrass that grows on the west coast of the Antarctic peninsula. In this report, we have identified and characterized a transcription factor, D. antarctica C-repeat binding factor 7 (DaCBF7), that is a member of the monocot group V CBF homologs. The protein contains a single AP2 domain, a putative nuclear localization signal, and the typical CBF signature. DaCBF7, like other monocot group V homologs, contains a distinct polypeptide stretch composed of 43 amino acids in front of the AP2 motif. DaCBF7 was predominantly localized to nuclei and interacted with the C-repeat/dehydration responsive element (CRT/DRE) core sequence (ACCGAC) in vitro. DaCBF7 was induced by abiotic stresses, including drought, cold, and salinity. To investigate its possible cellular role in cold tolerance, a transgenic rice system was employed. DaCBF7-overexpressing transgenic rice plants (Ubi:DaCBF7) exhibited markedly increased tolerance to cold stress compared to wild-type plants without growth defects; however, overexpression of DaCBF7 exerted little effect on tolerance to drought or salt stress. Transcriptome analysis of a Ubi:DaCBF7 transgenic line revealed 13 genes that were up-regulated in DaCBF7-overexpressing plants compared to wild-type plants in the absence of cold stress and in short- or long-term cold stress. Five of these genes, dehydrin, remorin, Os03g63870, Os11g34790, and Os10g22630, contained putative CRT/DRE or low-temperature responsive elements in their promoter regions. These results suggest that overexpression of DaCBF7 directly and indirectly induces diverse genes in transgenic rice plants and confers enhanced tolerance to cold stress. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Increasing the use of patient decision aids in orthopaedic care: results of a quality improvement project.

PubMed

Mangla, Mahima; Cha, Thomas D; Dorrwachter, Janet M; Freiberg, Andrew A; Leavitt, Lauren J; Rubash, Harry E; Simmons, Leigh H; Wendell, Emily L; Sepucha, Karen R

2018-05-01

To integrate patient decision aid (DA) delivery to promote shared decision-making and provide more patient-centred care within an orthopaedic surgery department for treatment of hip and knee osteoarthritis, lumbar herniated disc and lumbar spinal stenosis. Different strategies were used across three distinct phases to promote DA delivery. First, we used a quality improvement bonus to generate awareness and interest in the DAs among specialists. Second, we adapted the electronic referral management system to enable DA orders at referral to a specialist. Third, we engaged clinic staff and specialists to design workflows that promoted DA delivery. We tracked the number of patients who received a DA, who ordered the DA, and collected usage data from a subset of patients. Our target was to reach 60% of patients with DAs. In phase 1, 28% (43/155) of spine patients and 37% (114/308) of hip/knee patients received a DA. In phase 2, 54% (64/118) of spine referrals and 58% (189/324) of hip/knee referrals included a request to send a patient a DA. In phase 3, 56% (90/162) of spine patients and 69% (213/307) of hip/knee patients received a DA, significantly more than in phase 1 (P<0.0001). In phase 3, both more DAs were ordered by clinic staff compared with specialists (56% phase 3 vs 34% phase 1, P<0.001) and sent before the visit (74% phase 3 vs 17% phase 1, P<0.001). Patients were more likely to report reviewing the DA when delivered before the visit (63% before vs 50% after, P=0.005). DA implementation into clinic workflow is possible and facilitated by engagement of the entire care team and the support of health information technology. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Subcellular localization and expression pattern of the neurofibromatosis type 2 protein merlin/schwannomin.

PubMed

Schmucker, B; Ballhausen, W G; Kressel, M

1997-01-01

To elucidate the physiological function of the neurofibromatosis type 2 (NF2) tumor suppressor protein merlin/schwannomin, we studied the expression pattern and subcellular localization in human fibroblasts by Western blot analyses and immunofluorescence using a polyclonal antibody raised against the C-terminus of merlin. Three of the six merlin isoforms identified in this study (75 kDa, 58 kDa, 45 kDa) have been reported earlier and can be explained by alternative splicing. In addition, we detected higher molecular weight bands of about 110 kDa, 100 kDa and 84 kDa. Although the merlin bands of 100 kDa and 110 kDa may represent homo- or heterodimers, oligomerization due to formation of disulfide bonds was excluded. Furthermore, the isoforms of 84 kDa and 58 kDa were quantitatively extractable in Lubrol WX, indicating a localization in or close to the plasma membrane. The 45 kDa band, however, was not soluble in Lubrol WX compatible with a localization of this NF2 isoform in the endoplasmic reticulum. Applying confocal laser scanning microscopy, merlin was shown to be located in four subcellular compartments: (i) perinuclear in a compartment resembling endoplasmic reticulum, (ii) in ruffling membranes and at the leading edges, (iii) in filopodia, and (iv) at cell/substrate adhesion points. Codistribution of merlin and F-actin filaments was found in filopodia, ruffling membranes and at the insertion points of stress fibers at cell/substrate adhesion junctions as shown by phalloidin-rhodamine staining. Double immunofluorescence analyses of merlin and moesin revealed a colocalization in filopodia and ruffling membranes. The localization of merlin in the actin-rich cortical cytoskeleton corresponds to the ezrin-radixin-moesin family of proteins suggesting the NF2 protein to contribute to the regulation of cell growth by interaction with cytoskeleton-associated proteins.

Isoform composition and stoichiometry of the approx. 90-kDa heat shock protein associated with glucocorticoid receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mendel, D.B.; Orti, E.

1988-05-15

The authors observed that the approx. 90-kDa non-steroid-binding component of nonactivated glucocorticoid receptors purified from WEHI-7 mouse thymoma cells (which has been identified as the approx. 90-kDa heat shock protein) consistently migrates as a doublet during polyacrylamide gel electrophoresis under denaturing and reducing conditions. It has recently been reported that murine Meth A cells contain a tumor-specific transplantation antigen (TSTA) which is related or identical to the approx. 90-kDa heat shock protein. The observation that TSTA and the approx. 90-kDa heat shock protein isolated from these cells exists as two isoforms of similar molecular mass and charge has suggested thatmore » the doublet observed is also due to the existence of two isoforms. They have therefore conducted this study to determine whether TSTA and the approx. 90-kDa component of glucocorticoid receptors are indeed related, to establish whether the receptor preferentially binds one isoform of the approx. 90-kDa heat shock protein, and to investigate the stoichiometry of the nonactivated receptor complex. They used the BuGr1 and AC88 monoclonal antibodies to purify, respectively, receptor-associated and free approx. 90-kDa heat shock protein from WEHI-7 cells grown for 48 h with (/sup 35/S)methionine to metabolically label proteins to steady state. The long-term metabolic labeling approach has also enabled them to directly determine that the purified non-activated glucocorticoid receptor contains a single steroid-binding protein and two approx. 90-kDa non-steroid-binding subunits. The consistency with which a approx. 1:2 stoichiometric ratio of steroid binding to approx. 90-kDa protein is observed supports the view that the approx. 90-kDa heat shock protein is a true component of nonactivated glucocorticoid-receptor complexes.« less

Single oral dose pharmacokinetics of decursin and decursinol angelate in healthy adult men and women.

PubMed

Zhang, Jinhui; Li, Li; Hale, Thomas W; Chee, Wayne; Xing, Chengguo; Jiang, Cheng; Lü, Junxuan

2015-01-01

The ethanol extract of Angelica gigas Nakai (AGN) root has promising anti-cancer and other bioactivities in rodent models. It is currently believed that the pyranocoumarin isomers decursin (D) and decursinol angelate (DA) contribute to these activities. We and others have documented that D and DA were rapidly converted to decursinol (DOH) in rodents. However, our in vitro metabolism studies suggested that D and DA might be metabolized differently in humans. To test this hypothesis and address a key question for human translatability of animal model studies of D and DA or AGN extract, we conducted a single oral dose human pharmacokinetic study of D and DA delivered through an AGN-based dietary supplement Cogni.Q (purchased from Quality of Life Labs, Purchase, NY) in twenty healthy subjects, i.e., 10 men and 10 women, each consuming 119 mg D and 77 mg DA from 4 vegicaps. Analyses of plasma samples using UHPLC-MS/MS showed mean time to peak concentration (Tmax) of 2.1, 2.4 and 3.3 h and mean peak concentration (Cmax) of 5.3, 48.1 and 2,480 nmol/L for D, DA and DOH, respectively. The terminal elimination half-life (t1/2) for D and DA was similar (17.4 and 19.3 h) and each was much longer than that of DOH (7.4 h). The mean area under the curve (AUC0-48h) for D, DA and DOH was estimated as 37, 335 and 27,579 h∙nmol/L, respectively. Gender-wise, men absorbed the parent compounds faster and took shorter time to reach DOH peak concentration. The human data supported an extensive conversion of D and DA to DOH, even though they metabolized DA slightly slower than rodents. Therefore, the data generated in rodent models concerning anti-cancer efficacy, safety, tissue distribution and pharmacodynamic biomarkers will likely be relevant for human translation. ClinicalTrials.gov NCT02114957.

Single Oral Dose Pharmacokinetics of Decursin and Decursinol Angelate in Healthy Adult Men and Women

PubMed Central

Zhang, Jinhui; Li, Li; Hale, Thomas W.; Chee, Wayne; Xing, Chengguo; Jiang, Cheng; Lü, Junxuan

2015-01-01

The ethanol extract of Angelica gigas Nakai (AGN) root has promising anti-cancer and other bioactivities in rodent models. It is currently believed that the pyranocoumarin isomers decursin (D) and decursinol angelate (DA) contribute to these activities. We and others have documented that D and DA were rapidly converted to decursinol (DOH) in rodents. However, our in vitro metabolism studies suggested that D and DA might be metabolized differently in humans. To test this hypothesis and address a key question for human translatability of animal model studies of D and DA or AGN extract, we conducted a single oral dose human pharmacokinetic study of D and DA delivered through an AGN-based dietary supplement Cogni.Q (purchased from Quality of Life Labs, Purchase, NY) in twenty healthy subjects, i.e., 10 men and 10 women, each consuming 119 mg D and 77 mg DA from 4 vegicaps. Analyses of plasma samples using UHPLC-MS/MS showed mean time to peak concentration (Tmax) of 2.1, 2.4 and 3.3 h and mean peak concentration (Cmax) of 5.3, 48.1 and 2,480 nmol/L for D, DA and DOH, respectively. The terminal elimination half-life (t1/2) for D and DA was similar (17.4 and 19.3 h) and each was much longer than that of DOH (7.4 h). The mean area under the curve (AUC0-48h) for D, DA and DOH was estimated as 37, 335 and 27,579 h∙nmol/L, respectively. Gender-wise, men absorbed the parent compounds faster and took shorter time to reach DOH peak concentration. The human data supported an extensive conversion of D and DA to DOH, even though they metabolized DA slightly slower than rodents. Therefore, the data generated in rodent models concerning anti-cancer efficacy, safety, tissue distribution and pharmacodynamic biomarkers will likely be relevant for human translation. Trial Registration ClinicalTrials.gov NCT02114957 PMID:25695490

Quantitative determination of decursin, decursinol angelate, and decursinol in mouse plasma and tumor tissue using liquid-liquid extraction and HPLC.

PubMed

Li, Li; Zhang, Jinhui; Shaik, Ahmad Ali; Zhang, Yong; Wang, Lei; Xing, Chengguo; Kim, Sung-Hoon; Lü, Junxuan

2012-02-01

The pyranocoumarin compound decursin and its isomer decursinol angelate (DA) are the major hydrophobic phytochemicals in the root of Angelica gigas Nakai (AGN, Korean Angelica), a major traditional medicinal herb. The ethanol extract of AGN and especially the purified decursin and DA have been shown to exhibit antitumor activities by our collaborative team and others. Although decursinol has been identified as a major hydrolysis metabolite of decursin and DA in vivo in previous pharmacokinetic studies with mouse and rat, other recently published results sharply disputed this conclusion. In this study, we set up a practical method for the concurrent analysis of decursin, DA, and decursinol in mouse plasma and tumor tissues by liquid-liquid extraction and HPLC-UV and applied the method to several animal experiments. Plasma or tumor homogenate was extracted directly with ethyl acetate. The extraction efficiency for decursin/DA (quantitated together) and decursinol was between 82-95 % in both mouse plasma and tumor homogenate. The lower limit of quantitation (LLOQ) was approximately 0.25 µg/mL for decursin/DA and 0.2 µg/mL for decursinol in mouse plasma. In a pilot pharmacokinetic study, male C57BL/6 mice were given a single dose of 4.8 mg decursin/DA mixture (~240 mg/kg) per mouse either by oral gavage or intraperitoneal injection. Maximum plasma concentrations for decursin/DA and decursinol were 11.2 and 79.7 µg/mL, respectively, when decursin/DA was administered via intraperitoneal injection, and 0.54 and 14.9 µg/mL via oral gavage. Decursin/DA and decursinol contents in the tumor tissues from nude mouse xenografts correlated very well with those in plasma. Overall, our results confirm the conclusion that the majority of decursin/DA hydrolyze to decursinol in rodent models with a tiny fraction remaining as the intact compounds administered. © Georg Thieme Verlag KG Stuttgart · New York.

Widespread Increases in Malondialdehyde Immunoreactivity in Dopamine-Rich and Dopamine-Poor Regions of Rat Brain Following Multiple, High Doses of Methamphetamine

PubMed Central

Horner, Kristen A.; Gilbert, Yamiece E.; Cline, Susan D.

2011-01-01

Treatment with multiple high doses of methamphetamine (METH) can induce oxidative damage, including dopamine (DA)-mediated reactive oxygen species (ROS) formation, which may contribute to the neurotoxic damage of monoamine neurons and long-term depletion of DA in the caudate putamen (CPu) and substantia nigra pars compacta (SNpc). Malondialdehyde (MDA), a product of lipid peroxidation by ROS, is commonly used as a marker of oxidative damage and treatment with multiple high doses of METH increases MDA reactivity in the CPu of humans and experimental animals. Recent data indicate that MDA itself may contribute to the destruction of DA neurons, as MDA causes the accumulation of toxic intermediates of DA metabolism via its chemical modification of the enzymes necessary for the breakdown of DA. However, it has been shown that in human METH abusers there is also increased MDA reactivity in the frontal cortex, which receives relatively fewer DA afferents than the CPu. These data suggest that METH may induce neuronal damage regardless of the regional density of DA or origin of DA input. The goal of the current study was to examine the modification of proteins by MDA in the DA-rich nigrostriatal and mesoaccumbal systems, as well as the less DA-dense cortex and hippocampus following a neurotoxic regimen of METH treatment. Animals were treated with METH (10 mg/kg) every 2 h for 6 h, sacrificed 1 week later, and examined using immunocytochemistry for changes in MDA-adducted proteins. Multiple, high doses of METH significantly increased MDA immunoreactivity (MDA-ir) in the CPu, SNpc, cortex, and hippocampus. Multiple METH administration also increased MDA-ir in the ventral tegmental area and nucleus accumbens. Our data indicate that multiple METH treatment can induce persistent and widespread neuronal damage that may not necessarily be limited to the nigrostriatal DA system. PMID:21602916

Pharmacokinetics and tolerability of DA-8031, a novel selective serotonin reuptake inhibitor for premature ejaculation in healthy male subjects.

PubMed

Shin, Dongseong; Lee, SeungHwan; Yi, Sojeong; Yoon, Seo Hyun; Cho, Joo-Youn; Bahng, Mi Young; Jang, In-Jin; Yu, Kyung-Sang

2017-01-01

DA-8031 is a selective serotonin reuptake inhibitor under development for the treatment of premature ejaculation. This is the first-in-human study aimed at evaluating the pharmacokinetics and tolerability of DA-8031 and its metabolites (M1, M2, M4, and M5) in the plasma and urine after administration of a single oral dose in healthy male subjects. A dose block-randomized, double-blind, placebo-controlled, single ascending dose study was conducted. Subjects received either placebo or a single dose of DA-8031 at 5, 10, 20, 40, 60, 80, or 120 mg. DA-8031 and its four metabolites were analyzed in the plasma and urine for pharmacokinetic evaluation. The effect of genetic polymorphisms of cytochrome-P450 (CYP) enzymes on the pharmacokinetics of DA-8031 was evaluated. After a single dose, plasma DA-8031 reached the maximum concentration at a median of 2-3 h and was eliminated with terminal elimination half-life of 17.9-28.7 h. The mean renal clearance was 3.7-5.6 L/h. Dose-proportional pharmacokinetics was observed over the dose range of 20-80 mg. Among the metabolites, M4 had the greatest plasma concentration, followed by M5 and M1. Subjects with CYP2D6 intermediate metabolizer had significantly greater dose-normalized C max and AUC 0- t of DA-8031 as well as smaller metabolic ratios than those subjects with CYP2D6 extensive metabolizer. The most common adverse events were nausea, dizziness, and headache, and no serious adverse events were reported. In conclusion, the systemic exposure of DA-8031 was increased proportionally to the dose within 20-80 mg. Genetic polymorphisms of CYP2D6 had an effect on the systemic exposure of DA-8031. DA-8031 was well tolerated after single doses of 80 mg or less.

Beyond reward prediction errors: the role of dopamine in movement kinematics

PubMed Central

Barter, Joseph W.; Li, Suellen; Lu, Dongye; Bartholomew, Ryan A.; Rossi, Mark A.; Shoemaker, Charles T.; Salas-Meza, Daniel; Gaidis, Erin; Yin, Henry H.

2015-01-01

We recorded activity of dopamine (DA) neurons in the substantia nigra pars compacta in unrestrained mice while monitoring their movements with video tracking. Our approach allows an unbiased examination of the continuous relationship between single unit activity and behavior. Although DA neurons show characteristic burst firing following cue or reward presentation, as previously reported, their activity can be explained by the representation of actual movement kinematics. Unlike neighboring pars reticulata GABAergic output neurons, which can represent vector components of position, DA neurons represent vector components of velocity or acceleration. We found neurons related to movements in four directions—up, down, left, right. For horizontal movements, there is significant lateralization of neurons: the left nigra contains more rightward neurons, whereas the right nigra contains more leftward neurons. The relationship between DA activity and movement kinematics was found on both appetitive trials using sucrose and aversive trials using air puff, showing that these neurons belong to a velocity control circuit that can be used for any number of purposes, whether to seek reward or to avoid harm. In support of this conclusion, mimicry of the phasic activation of DA neurons with selective optogenetic stimulation could also generate movements. Contrary to the popular hypothesis that DA neurons encode reward prediction errors, our results suggest that nigrostriatal DA plays an essential role in controlling the kinematics of voluntary movements. We hypothesize that DA signaling implements gain adjustment for adaptive transition control, and describe a new model of the basal ganglia (BG) in which DA functions to adjust the gain of the transition controller. This model has significant implications for our understanding of movement disorders implicating DA and the BG. PMID:26074791

Dopamine suppresses neuronal activity of Helisoma B5 neurons via a D2-like receptor, activating PLC and K channels.

PubMed

Zhong, L R; Artinian, L; Rehder, V

2013-01-03

Dopamine (DA) plays fundamental roles as a neurotransmitter and neuromodulator in the central nervous system. How DA modulates the electrical excitability of individual neurons to elicit various behaviors is of great interest in many systems. The buccal ganglion of the freshwater pond snail Helisoma trivolvis contains the neuronal circuitry for feeding and DA is known to modulate the feeding motor program in Helisoma. The buccal neuron B5 participates in the control of gut contractile activity and is surrounded by dopaminergic processes, which are expected to release DA. In order to study whether DA modulates the electrical activity of individual B5 neurons, we performed experiments on physically isolated B5 neurons in culture and on B5 neurons within the buccal ganglion in situ. We report that DA application elicited a strong hyperpolarization in both conditions and turned the electrical activity from a spontaneously firing state to an electrically silent state. Using the cell culture system, we demonstrated that the strong hyperpolarization was inhibited by the D2 receptor antagonist sulpiride and the phospholipase C (PLC) inhibitor U73122, indicating that DA affected the membrane potential of B5 neurons through the activation of a D2-like receptor and PLC. Further studies revealed that the DA-induced hyperpolarization was inhibited by the K channel blockers 4-aminopyridine and tetraethylammonium, suggesting that K channels might serve as the ultimate target of DA signaling. Through its modulatory effect on the electrical activity of B5 neurons, the release of DA in vivo may contribute to a neuronal output that results in a variable feeding motor program. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Manipulation of dopamine metabolism contributes to attenuating innate high locomotor activity in ICR mice.

PubMed

Yamaguchi, Takeshi; Nagasawa, Mao; Ikeda, Hiromi; Kodaira, Momoko; Minaminaka, Kimie; Chowdhury, Vishwajit S; Yasuo, Shinobu; Furuse, Mitsuhiro

2017-06-15

Attention-deficit hyperactivity disorder (ADHD) is defined as attention deficiency, restlessness and distraction. The main characteristics of ADHD are hyperactivity, impulsiveness and carelessness. There is a possibility that these abnormal behaviors, in particular hyperactivity, are derived from abnormal dopamine (DA) neurotransmission. To elucidate the mechanism of high locomotor activity, the relationship between innate activity levels and brain monoamines and amino acids was investigated in this study. Differences in locomotor activity between ICR, C57BL/6J and CBA/N mice were determined using the open field test. Among the three strains, ICR mice showed the greatest amount of locomotor activity. The level of striatal and cerebellar DA was lower in ICR mice than in C57BL/6J mice, while the level of L-tyrosine (L-Tyr), a DA precursor, was higher in ICR mice. These results suggest that the metabolic conversion of L-Tyr to DA is lower in ICR mice than it is in C57BL/6J mice. Next, the effects of intraperitoneal injection of (6R)-5, 6, 7, 8-tetrahydro-l-biopterin dihydrochloride (BH 4 ) (a co-enzyme for tyrosine hydroxylase) and L-3,4-dihydroxyphenylalanine (L-DOPA) on DA metabolism and behavior in ICR mice were investigated. The DA level in the brain was increased by BH 4 administration, but the increased DA did not influence behavior. However, L-DOPA administration drastically lowered locomotor activity and increased DA concentration in several parts of the brain. The reduced locomotor activity may have been a consequence of the overproduction of DA. In conclusion, the high level of locomotor activity in ICR mice may be explained by a strain-specific DA metabolism. Copyright © 2017 Elsevier B.V. All rights reserved.

Altered neuronal activity in the primary motor cortex and globus pallidus after dopamine depletion in rats.

PubMed

Wang, Min; Li, Min; Geng, Xiwen; Song, Zhimin; Albers, H Elliott; Yang, Maoquan; Zhang, Xiao; Xie, Jinlu; Qu, Qingyang; He, Tingting

2015-01-15

The involvement of dopamine (DA) neuron loss in the etiology of Parkinson's disease has been well documented. The neural mechanisms underlying the effects of DA loss and the resultant motor dysfunction remain unknown. To gain insights into how loss of DA disrupts the electrical processes in the cortico-subcortical network, the present study explores the effects of DA neuron depletion on electrical activity in the primary motor cortex (M1), on the external and the internal segment of the globus pallidus (GPe and GPi respectively), and on their temporal relationships. Comparison of local field potentials (LFPs) in these brain regions from unilateral hemispheric DA neuron depleted rats and neurologically intact rats revealed that the spectrum power of LFPs in 12-70Hz (for M1, and GPe) and in 25-40Hz (for GPi) was significantly greater in the DA depleted rats than that in the control group. These changes were associated with a shortening of latency in LFP activities between M1 and GPe, from several hundred milliseconds in the intact animals to close to zero in the DA depleted animals. LFP oscillations in M1 were significantly more synchronized with those in GPe in the DA depleted rats compared with those in the control rats. By contrast, the synchronization of oscillation in LFP activities between M1 and GPi did not differ between the DA depleted and intact rats. Not surprisingly, rats that had DA neuron depletion spent more time along the ladder compared with the control rats. These data suggest that enhanced oscillatory activity and increased synchronization of LFPs may contribute to movement impairment in the rat model of Parkinson's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Antidepressant-induced Dopamine Receptor Dysregulation: A Valid Animal Model of Manic-Depressive Illness

PubMed Central

Demontis, Francesca; Serra, Francesca; Serra, Gino

2017-01-01

Background: Mania seems to be associated with an increased dopamine (DA) transmission. Antidepressant treatments can induce mania in humans and potentiated DA transmission in animals, by sensitizing DA D2 receptors in the mesolimbic system. We have suggested that the sensitization of D2 receptors may be responsible of antidepressant-induced mania. This review aims to report the experimental evidence that led to the hypothesis that antidepressant-induced DA receptors dysregulation can be considered an animal model of bipolar disorder. Methods: We reviewed papers reporting preclinical and clinical studies on the role of DA in the mechanism of action of antidepressant treatments and in the patho-physiology of mood disorders. Results: A number of preclinical and clinical evidence suggests that mania could be associated with an increased DA activity, while a reduced function of this neurotransmission might underlie depression. Chronic treatment with imipramine induces a sensitization of DA D2 receptors in the mesolimbic system, followed, after drug discontinuation, by a reduced sensitivity associated with an increased immobility time in forced swimming test of depression (FST). Blockade of glutamate NMDA receptors by memantine administration prevents the imipramine effect on DA receptors sensitivity and on the FST. Conclusion: We suggest that chronic treatment with antidepressants induces a behavioural syndrome that mimics mania (the sensitization of DA receptors), followed by depression (desensitization of DA receptors and increased immobility time in the FST), i.e. an animal model of bipolar disorder. Moreover the observation that memantine prevents the “bipolar-like” behavior, suggests that the drug may have an antimanic and mood stabilizing effect. Preliminary clinical observations support this hypothesis. PMID:28503114

β-Phenylethylamine requires the dopamine transporter to increase extracellular dopamine in Caenorhabditis elegans dopaminergic neurons.

PubMed

Hossain, Murad; Wickramasekara, Rochelle N; Carvelli, Lucia

2014-07-01

β-Phenylethylamine (βPEA) is an endogenous amine that has been shown to increase the synaptic levels of dopamine (DA). A number of in vitro and behavioral studies suggest the dopamine transporter (DAT) plays a role in the effects generated by βPEA, however the mechanism through which βPEA affects DAT has not yet been elucidated. Here, we used Caenorhabditis (C.) elegans DAT (DAT-1) expressing LLC-pk1 cells and neuronal cultures to investigate whether the βPEA-induced increase of extracellular DA required DAT-1. Our data show that βPEA increases extracellular dopamine both in DAT-1 transfected cells and cultures of differentiated neurons. RTI-55, a cocaine homologue and DAT inhibitor, completely blocked the βPEA-induced effect in transfected cells. However in neuronal cultures, RTI-55 only partly inhibited the increase of extracellular DA generated by βPEA. These results suggest that βPEA requires DAT-1 and other, not yet identified proteins, to increase extracellular DA when tested in a native system. Furthermore, our results suggest that βPEA-induced increase of extracellular DA does not require functional monoamine vesicles as genetic ablation of the C. elegans homologue vesicular monoamine transporter, cat-1, did not compromise the ability of βPEA to increase extracellular DA. Finally, our electrophysiology data show that βPEA caused fast-rising and self-inactivating amperometric currents in a subset of wild-type DA neurons but not in neurons isolated from dat-1 knockout animals. Taken together, these data demonstrate that in both DA neurons and heterogeneous cultures of differentiated C. elegans neurons, βPEA releases cytoplasmic DA through DAT-1 to ultimately increase the extracellular concentration of DA. Copyright © 2013 Elsevier Ltd. All rights reserved.

β-phenylethylamine Requires the Dopamine Transporter to Increase Extracellular Dopamine in C. elegans Dopaminergic Neurons

PubMed Central

Hossain, Murad; Wickramasekara, Rochelle N.; Carvelli, Lucia

2013-01-01

β-phenylethylamine (βPEA) is an endogenous amine that has been shown to increase the synaptic levels of dopamine (DA). A number of in vitro and behavioral studies suggest the dopamine transporter (DAT) plays a role in the effects generated by βPEA, however the mechanism through which βPEA affects DAT has not yet been elucidated. Here, we used Caenorhabditis (C.) elegans DAT (DAT-1) expressing LLC-pk1 cells and neuronal cultures to investigate whether the βPEA-induced increase of extracellular DA required DAT-1. Our data show that βPEA increases extracellular dopamine both in DAT-1 transfected cells and cultures of differentiated neurons. RTI-55, a cocaine homologue and DAT inhibitor, completely blocked the βPEA-induced effect in transfected cells. However in neuronal cultures, RTI-55 only partly inhibited the increase of extracellular DA generated by βPEA. These results suggest that βPEA requires DAT-1 and other, not yet identified proteins, to increase extracellular DA when tested in a native system. Furthermore, our results suggest that βPEA-induced increase of extracellular DA does not require functional monoamine vesicles as genetic ablation of the C. elegans homologue vesicular monoamine transporter, cat-1, did not compromise the ability of βPEA to increase extracellular DA. Finally, our electrophysiology data show that βPEA caused fast-rising and self-inactivating amperometric currents in a subset of wild-type DA neurons but not in neurons isolated from dat-1 knockout animals. Taken together, these data demonstrate that in both DA neurons and heterogeneous cultures of differentiated C. elegans neurons, βPEA releases cytoplasmic DA through DAT-1 to ultimately increase the extracellular concentration of DA. PMID:24161617

Purification and Characterisation of κ-Carrageenan Oligosaccharides Prepared by κ-Carrageenase from Thalassospira sp. Fjfst-332.

PubMed

Guo, Juanjuan; Zheng, Zhichang; Lu, Xu; Zeng, Shaoxiao; Chen, Chi; Zhang, Longtao; Zheng, Baodong

2018-01-15

κ-Carrageenan oligosaccharides (KCOs) are promising agents for treating inflammatory diseases. However, the lack of purification and structural elucidation of KCOs has limited structure-function evaluation. In this study, using a system coupling medium pressure liquid chromatography (MPLC) with an evaporative light scattering detector (ELSD), four types of KCOs were separated. The total yield of the four KCO powders was ∼5.02% after purification (KCOs/κ-carrageenan, w/w). Their structural identities were characterised by ESI-MS, CID-MS/MS and NMR, as κ-neocarrabiose (α-DA-1,3-G4Srα/β), κ-neocarratetraose (α-DA-1,3-β-G4S-1,4-α-DA-1,3-G4Srα/β), κ-neocarrahexaose (α-DA-1,3-β-G4S-1,4-α-DA-1,3-β-G4S-1,4-α-DA-1,3-G4Srα/β) and heterozygous κ/ι-neocarrahexaose (α-DA/DA2S-1,3-β-G4S-1,4-α-DA-1,3-β-G4S-1,4-α-DA-1,3-G4Srα/β). KCOs showed no cytotoxicity in RAW264.7 macrophages, and the anti-inflammatory activity was closely correlated with the degree of polymerisation and the number of sulfated groups. κ/ι-Neocarrahexaose exhibited the highest inhibition of ROS (Reactive Oxygen Species) production in LPS-induced RAW264.7 macrophages. The MPLC-ELSD system provides a platform for large-scale fabrication of purified KCOs and affords a route to these compounds that may regulate immune defense. Copyright © 2017 Elsevier Ltd. All rights reserved.

Beer self-administration provokes lateralized nucleus accumbens dopamine release in male heavy drinkers.

PubMed

Oberlin, Brandon G; Dzemidzic, Mario; Tran, Stella M; Soeurt, Christina M; O'Connor, Sean J; Yoder, Karmen K; Kareken, David A

2015-03-01

Although striatal dopamine (DA) is important in alcohol abuse, the nature of DA release during actual alcohol drinking is unclear, since drinking includes self-administration of both conditioned flavor stimuli (CS) of the alcoholic beverage and subsequent intoxication, the unconditioned stimulus (US). Here, we used a novel self-administration analog to distinguish nucleus accumbens (NAcc) DA responses specific to the CS and US. Right-handed male heavy drinkers (n = 26) received three positron emission tomography (PET) scans with the D2/D3 radioligand [(11)C]raclopride (RAC) and performed a pseudo self-administration task that separately administered a flavor CS of either a habitually consumed beer or the appetitive control Gatorade®, concomitant with the US of ethanol intoxication (0.06 g/dL intravenous (IV) administration) or IV saline. Scan conditions were Gatorade flavor + saline (Gat&Sal), Gatorade flavor + ethanol (Gat&Eth), and beer flavor + ethanol (Beer&Eth). Ethanol (US) reduced RAC binding (inferring DA release) in the left (L) NAcc [Gat&Sal > Gat&Eth]. Beer flavor (CS) increased DA in the right (R) NAcc [Gat&Eth > Beer&Eth]. The combination of beer flavor and ethanol (CS + US), [Gat&Sal > Beer&Eth], induced DA release in bilateral NAcc. Self-reported intoxication during scanning correlated with L NAcc DA release. Relative to saline, infusion of ethanol increased alcoholic drink wanting. Our findings suggest lateralized DA function in the NAcc, with L NAcc DA release most reflecting intoxication, R NAcc DA release most reflecting the flavor CS, and the conjoint CS + US producing a bilateral NAcc response.

Charge Exchange Reaction in Dopant-Assisted Atmospheric Pressure Chemical Ionization and Atmospheric Pressure Photoionization.

PubMed

Vaikkinen, Anu; Kauppila, Tiina J; Kostiainen, Risto

2016-08-01

The efficiencies of charge exchange reaction in dopant-assisted atmospheric pressure chemical ionization (DA-APCI) and dopant-assisted atmospheric pressure photoionization (DA-APPI) mass spectrometry (MS) were compared by flow injection analysis. Fourteen individual compounds and a commercial mixture of 16 polycyclic aromatic hydrocarbons were chosen as model analytes to cover a wide range of polarities, gas-phase ionization energies, and proton affinities. Chlorobenzene was used as the dopant, and methanol/water (80/20) as the solvent. In both techniques, analytes formed the same ions (radical cations, protonated molecules, and/or fragments). However, in DA-APCI, the relative efficiency of charge exchange versus proton transfer was lower than in DA-APPI. This is suggested to be because in DA-APCI both dopant and solvent clusters can be ionized, and the formed reagent ions can react with the analytes via competing charge exchange and proton transfer reactions. In DA-APPI, on the other hand, the main reagents are dopant-derived radical cations, which favor ionization of analytes via charge exchange. The efficiency of charge exchange in both DA-APPI and DA-APCI was shown to depend heavily on the solvent flow rate, with best efficiency seen at lowest flow rates studied (0.05 and 0.1 mL/min). Both DA-APCI and DA-APPI showed the radical cation of chlorobenzene at 0.05-0.1 mL/min flow rate, but at increasing flow rate, the abundance of chlorobenzene M(+.) decreased and reagent ion populations deriving from different gas-phase chemistry were recorded. The formation of these reagent ions explains the decreasing ionization efficiency and the differences in charge exchange between the techniques. Graphical Abstract ᅟ.

Characterization of dopamine release in the substantia nigra by in vivo microdialysis in freely moving rats.

PubMed

Robertson, G S; Damsma, G; Fibiger, H C

1991-07-01

Dopamine (DA) is released not only from the terminals of the nigrostriatal projection, but also from the dendrites of these neurons, which arborize in the substantia nigra pars reticulata (SNR). Although striatal DA release has been extensively studied by in vivo microdialysis, dendritic DA release in the SNR has not been characterized by this technique. Extracellular DA was monitored simultaneously in the ipsilateral striatum and SNR. The nigral probe was implanted at a 50 degree angle, permitting 2.5 mm of SNR to be dialyzed. Delivery of the tracer Fluoro-Gold into the striatal probe retrogradely labeled tyrosine hydroxylase-positive cell bodies and dendrites in the vicinity of the nigral probe. Hence, it could be demonstrated that dopaminergic neurons near the nigral probe projected to the vicinity of the striatal probe. Addition of 50 mM KCl to the SNR perfusion solution produced a 3.5-fold increase in DA and a 50% reduction in dihydroxyphenylacetic acid (DOPAC) in the SNR; in contrast, this manipulation in the SNR caused DA release in the striatum to be decreased by 20%, while striatal DOPAC was increased by 50%. Local administration of nomifensine (10 microM) in the SNR produced a sevenfold increase in SNR DA but had no effect on striatal DA. Systemic injection of d-amphetamine (2 mg/kg, s.c.) elevated DA in the SNR and striatum five- to sevenfold, while DOPAC was decreased in both structures by at least 40%. To determine the effect of tetrodotoxin (TTX), basal concentrations of DA in the SNR were first elevated threefold by including nomifensine (1 microM) in the nigral perfusion solution.(ABSTRACT TRUNCATED AT 250 WORDS)

[Diagnostic Accuracy of the LiSe-DaZ for Children with Specific Language Impairment].

PubMed

Stephan, T; Keilmann, A

2015-12-01

Currently, only few tests for the development of speech and language exist for bi- or multilingual children in Germany. One of those, the LiSe-DaZ (Linguistic performance measurement - German as a second language), was examined in a prospective study regarding its practicability and the sensitivity to detect children with specific language impairment in a group of children aged 5 to 7 who suffered from a severe language impairment according to clinical tests. 74 children (mean age: 60 months; 46% monolingual German-speaking; 54% bi- or multilingual) with severe specific language impairment were examined with the LiSe-DaZ in addition to the clinical established diagnostic during their in-patient stay in the hospital. The children, on average, showed in the receptive language abilities (LiSe-DaZ vs. TROG-D), the expressive vocabulary (LiSe-DaZ vs. AWST-R or WWT) and in the use of prepositions (LiSe-DaZ vs. Ravensburger Dysgrammatical clinical trial) significantly (p<0,0005) better results in the LiSe-DaZ. Thus, the majority of children were diagnosed as language impaired by clinically established tests whereas the LiSe-DaZ considered the children's language development to be normal. This difference was consistently more prominent for children with German as a second language. Compared with the clinically established tests, the informative value of the LiSe-DaZ turned out to be insufficient. The LiSe-DaZ does not detect children with the need of language therapy. Nevertheless, a norming of the established speech tests for bi- or multilingual children would be desirable to avoid unfounded judgements. © Georg Thieme Verlag KG Stuttgart · New York.

A brief history of levodopa.

PubMed

Hornykiewicz, Oleh

2010-11-01

This article highlights some landmarks in the history of levodopa, beginning with its isolation in 1910-13 from seedlings of Vicia faba to the demonstration, in 1961, of its "miraculous" effect in patients with Parkinson's disease (PD). Midway between these two time points, in 1938, L: -dopa decarboxylase was discovered, the enzyme that produces dopamine (DA) from levodopa. In 1957, DA was shown to occur in the brain, and in 1959 it was found to be enriched in the basal ganglia. At that time the striatal localization of DA, together with studies done in 1957-58 in naive and reserpine-treated animals regarding DA in the brain and the central effects of levodopa, suggested its possible involvement in "extrapyramidal control" and "reserpine parkinsonism". Following these discoveries, a study of (postmortem) brains of patients with basal ganglia disorders, including PD, was started, demonstrating, in 1960, a severe striatal DA deficit specifically in PD, thus furnishing a rational basis for the concept of "DA replacement therapy" with levodopa. Accordingly, in 1961, the first highly successful clinical trial with i.v. levodopa was carried out. In 1963, the DA deficit in the PD substantia nigra was found, indicative of a nigrostriatal DA pathway in the human brain, subsequently established in animal studies in 1964-65. In 1967, the chronic, high dose oral levodopa regimen was introduced in treatment of PD. Besides the above highlights in the history of levodopa, the article also cites critical opinions of world authorities in brain research of the time, harmful to the cause of DA, levodopa and PD. Today, the concept of DA replacement with levodopa is uncontested, with levodopa being the "gold standard" of modern drug treatment of PD.

PKC phosphorylates residues in the N-terminal of the DA transporter to regulate amphetamine-induced DA efflux.

PubMed

Wang, Qiang; Bubula, Nancy; Brown, Jason; Wang, Yunliang; Kondev, Veronika; Vezina, Paul

2016-05-27

The DA transporter (DAT), a phosphoprotein, controls extracellular dopamine (DA) levels in the central nervous system through transport or reverse transport (efflux). Multiple lines of evidence support the claim that PKC significantly contributes to amphetamine-induced DA efflux. Other signaling pathways, involving CaMKII and ERK, have also been shown to regulate DAT mediated efflux. Here we assessed the contribution of putative PKC residues (S4, S7, S13) in the N-terminal of the DAT to amphetamine-induced DA efflux by transfecting DATs containing different serine to alanine (S-A) point mutations into DA pre-loaded HEK-293 cells and incubating these cells in amphetamine (2μM). The effects of a S-A mutation at the non-PKC residue S12 and a threonine to alanine (T-A) mutation at the ERK T53 residue were also assessed for comparison. WT-DATs were used as controls. In an initial experiment, we confirmed that inhibiting PKC with Go6976 (130nM) significantly reduced amphetamine-induced DA efflux. In subsequent experiments, cells transfected with the S4A, S12A, S13A, T53A and S4,7,13A mutants showed a reduction in amphetamine-induced DA efflux similar to that observed with Go6976. Interestingly, cells transfected with the S7A mutant, identified by some as a PKC-PKA residue, showed unperturbed WT-DAT levels of amphetamine-induced DA efflux. These results indicate that phosphorylation by PKC of select residues in the DAT N-terminal can regulate amphetamine-induced efflux. PKC can act either independently or in concert with other kinases such as ERK to produce this effect. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

DA-9701 on gastric motility in patients with Parkinson's disease: A randomized controlled trial.

PubMed

Shin, Cheol Min; Lee, Yoon Jin; Kim, Jong-Min; Lee, Jee Young; Kim, Kyung-Joon; Choi, Yoon Jin; Kim, Nayoung; Lee, Dong Ho

2018-04-21

To evaluate the effect of DA-9701, a novel prokinetic drug, on gastric motility evaluated by magnetic resonance imaging in patients with Parkinson's disease (PD). Forty PD patients were randomly allocated to receive either domperidone or DA-9701. Their gastric functions were evaluated using magnetic resonance imaging before and after 4-week treatment period. Information on levodopa daily dose, disease duration, and Unified PD Rating Scale scores was collected. In 18 patients (domperidone: 9, DA-9701: 9), plasma levodopa concentrations were determined. Primary outcome was assessed by a one-sided 95% confidence interval to show non-inferiority of DA-9701 vs. domperidone with a pre-determined non-inferiority margin of -10%. Thirty-eight participants (19 men and 19 women; mean age, 67.1 years) completed the study protocol (domperidone: DA-9701 = 19:19). Gastric emptying rate at 120 min (2-hr GER) was comparable between the 2 groups; it was not correlated with levodopa daily dose or disease duration or Unified PD Rating Scale scores (all p > 0.05). DA-9701 was not inferior to domperidone in changes of 2-hr GERs before and after the treatment (absolute difference, 4.0 %; one-sided 95% confidence interval, - 3.7 to infinity). However, a significant increase in 2-hr GER was observed only in DA-9701 group (54.5% and 61.8%, before and after treatment, respectively, p < 0.05). Plasma levodopa concentration showed an insignificant but increasing trend in DA-9701 group. There were neither adverse reactions nor deteriorations of parkinsonian symptoms observed in the study participants. DA-9701 can be used for the patients with PD to enhance gastric motility without aggravating PD symptoms (ClinicalTrials.gov number: NCT03022201). Copyright © 2018 Elsevier Ltd. All rights reserved.

Proof of mechanism study of a novel serotonin transporter blocker, DA-8031, using [11C]DASB positron emission tomography and in vivo microdialysis.

PubMed

Park, Hyun Soo; Jung, In Soon; Lim, Nam Hee; Sung, Ji Hyun; Lee, Sukhyang; Moon, Byung Seok; Lee, Byung Chul; Kang, Kyung Koo; Kim, Sang Eun

2014-07-01

To investigate the efficacy of DA-8031, a novel compound for the treatment of premature ejaculation, we measured serotonin transporter (SERT) occupancy by DA-8031, as well as DA-8031-induced changes in extracellular serotonin levels, in the rat brain using positron emission tomography (PET) and 11C-N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine ([11C]DASB) and in vivo microdialysis, respectively. [11C]DASB PET scans were performed in rats with graded doses of DA-8031 (vehicle: 10, 30, and 100 mg/kg). SERT occupancy in the midbrain was determined using binding potentials for [11C]DASB calculated by the multilinear reference tissue model. Extracellular serotonin levels were monitored in the dorsal raphe nucleus of rats after the administration of DA-8031 (10-100 mg/kg) using in vivo microdialysis. PET data indicated a reduction of [11C]DASB binding to SERTs in the midbrain as a function of DA-8031 dose. SERT occupancy for each DA-8031 dose (10-100 mg/kg) ranged between 31% and 84%. The drug dose required for 50% occupancy of SERT was 13.5 mg/kg in the midbrain, comparable with previous preclinical behavioral data (∼10-30 mg/kg). In vivo microdialysis showed that DA-8031 produced a dose-dependent increase in extracellular serotonin levels in the dorsal raphe nucleus (33%-81% increase for doses of 10-100 mg/kg). These preclinical data provide a proof of mechanism for DA-8031 as a novel compound of targeting the SERT for the treatment of premature ejaculation, warranting further clinical trials. They also offer insight into the optimal drug dose needed to exert therapeutic effects while minimizing adverse effects in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Pharmacokinetics and brain distribution of tetrahydropalmatine and tetrahydroberberine after oral administration of DA-9701, a new botanical gastroprokinetic agent, in rats.

PubMed

Jung, Ji Won; Kwon, Yong Sam; Jeong, Jin Seok; Son, Miwon; Kang, Hee Eun

2015-01-01

DA-9701, a new botanical gastroprokinetic agent, has potential for the management of delayed gastric emptying in Parkinson's disease if it has no central anti-dopaminergic activity. Therefore, we examined the pharmacokinetics of DA-9701 components having dopamine D2 receptor antagonizing activity, tetrahydropalmatine (THP) and tetrahydroberberine (THB), following various oral doses (80-328 mg/kg) of DA-9701. The distribution of THP and THB to the brain and/or other tissues was also evaluated after single or multiple oral administrations of DA-9701. Oral administration of DA-9701 yielded dose-proportional area under the plasma concentration-time curve (AUC0-8 h) and maximum plasma concentration (Cmax) values for THP and THB, indicating linear pharmacokinetics (except for THB at the lowest dose). THP and THB's large tissue-to-plasma concentration ratios indicated considerable tissue distribution. High concentrations of THP and THB in the stomach and small intestine suggest an explanation for DA-9701's potent gastroprokinetic activity. The maximum concentrations of THP and THB in brain following multiple oral DA-9701 for 7 d (150 mg/kg/d) was observed at 30 min after the last oral DA-9701 treatment: 131±67.7 ng/g for THP and 6.97±4.03 ng/g for THB. Although both THP and THB pass through the blood-brain barrier, as indicated by brain-to-plasma concentration ratios greater than unity (approximately 2-4), oral administration of DA-9701 at the effective dose in humans is not expected to lead to sufficient brain concentrations to exert central dopamine D2 receptor antagonism.

Efficacy of DA-9701 (Motilitone) in Functional Dyspepsia Compared to Pantoprazole: A Multicenter, Randomized, Double-blind, Non-inferiority Study.

PubMed

Jung, Hye-Kyung; Lee, Kwang Jae; Choi, Myung-Gyu; Park, Hyojin; Lee, Joon Seong; Rhee, Poong-Lyul; Kim, Nayoung; Park, KyungSik; Choi, Suck Chei; Lee, Oh Young; Huh, Kyu Chan; Song, Geun Am; Hong, Su Jin; Sohn, Chong Il; Jung, Hwoon-Yong; Lee, Yong Chan; Rew, Jong Sun; Jee, Sam Ryong; Kwon, Joong Goo

2016-04-30

The effect of proton pump inhibitors (PPI) in Asian functional dyspepsia (FD) patients has not been well established as in Westerncountries. DA-9701, a novel prokinetic agent, stimulates gastric emptying and modulates visceral hypersensitivity in vivo and in human studies. This study was conducted to compare the efficacy of DA-9701 with a conventional PPI in mono or combination therapy in patients with FD. In this double-blind, randomized, non-inferiority trial, 389 patients diagnosed with FD using Rome III criteria were allocated among3 groups: 30-mg DA-9701 t.i.d (means 3 times a day), 40-mg pantoprazole, and 30-mg DA-9701 t.i.d + 40-mg pantoprazole. Theprimary efficacy end-point was a global assessment of the patient binary response or response on a 5-Likert scale after 4 weeks. The global symptomatic improvement was 60.5% in the DA-9701 group, 65.6% in the pantoprazole group, and 63.5% in the DA-9701 + pantoprazole group using a 5-Likert scale at week 4 with no significant difference among 3 groups (P = 0.685). Symptomimprovement measured by binary outcome was significantly achieved in each of the 3 groups, but not different among groups.Patients in all treatment groups reported significant improvement in the response rate and symptoms according to FD subtypes anddyspepsia-related quality of life (P < 0.001), but there were no significant differences among the 3 groups. DA-9701 improves global and individual symptoms and increases dyspepsia-specific quality of life in patients with FD. The efficacyof DA-9701 monotherapy is comparable with pantoprazole and there is no additive effect with combination of DA-9701 andpantoprazole in patients with FD.

Effect of DA-6 and EDTA alone or in combination on uptake, subcellular distribution and chemical form of Pb in Lolium perenne.

PubMed

He, Shanying; Wu, Qiuling; He, Zhenli

2013-11-01

The effects of growth-promoting hormone diethyl aminoethyl hexanoate (DA-6) and EDTA, either alone or in combination applied to original soil or lead (Pb) spiked soil on Pb phytoextraction, subcellular distribution and chemical forms in Lolium perenne were studied. EDTA addition alone significantly reduced plant biomass though it increased Pb accumulation (P<0.05). Foliar spray of DA-6 alone increased both plant biomass and Pb accumulation (P<0.05), with 10μM DA-6 being the most effective. DA-6 combined with EDTA compensated the adverse effect of the latter on plant growth, and resulted in a synergistic effect on Pb uptake and translocation, with the maximum accumulation occurring in the EDTA+10μM DA-6 treatment. At the subcellular level, about 35-66% of Pb was distributed in cell wall and 21-42% in soluble fraction, with a minority present in cellular organelles fraction. EDTA addition alone increased the proportion of Pb in soluble and cellular organelles fraction, while DA-6 detoxified Pb in plant by storing additional Pb in cell wall, and 10μM DA-6 was the most effective. Of the total Pb in plant shoot, 27-52% was NaCl extractable, 22-47% HAc extractable, followed by other fractions. Contrary to EDTA, DA-6 significantly decreased Pb migration in plant. These results suggest that Pb fixation by pectates and proteins in cell wall and compartmentalization by vacuole might be responsible for Pb detoxification in plant, and the combined use of EDTA and 10μM DA-6 appears to be optimal for improving the remediation efficiency of L. perenne for Pb contaminated soil. Copyright © 2013 Elsevier Ltd. All rights reserved.

The newly synthesized pool of dopamine determines the severity of methamphetamine-induced neurotoxicity.

PubMed

Thomas, David M; Francescutti-Verbeem, Dina M; Kuhn, Donald M

2008-05-01

The neurotransmitter dopamine (DA) has long been implicated as a participant in the neurotoxicity caused by methamphetamine (METH), yet, its mechanism of action in this regard is not fully understood. Treatment of mice with the tyrosine hydroxylase (TH) inhibitor alpha-methyl-p-tyrosine (AMPT) lowers striatal cytoplasmic DA content by 55% and completely protects against METH-induced damage to DA nerve terminals. Reserpine, by disrupting vesicle amine storage, depletes striatal DA by more than 95% and accentuates METH-induced neurotoxicity. l-DOPA reverses the protective effect of AMPT against METH and enhances neurotoxicity in animals with intact TH. Inhibition of MAO-A by clorgyline increases pre-synaptic DA content and enhances METH striatal neurotoxicity. In all conditions of altered pre-synaptic DA homeostasis, increases or decreases in METH neurotoxicity paralleled changes in striatal microglial activation. Mice treated with AMPT, l-DOPA, or clorgyline + METH developed hyperthermia to the same extent as animals treated with METH alone, whereas mice treated with reserpine + METH were hypothermic, suggesting that the effects of alterations in cytoplasmic DA on METH neurotoxicity were not strictly mediated by changes in core body temperature. Taken together, the present data reinforce the notion that METH-induced release of DA from the newly synthesized pool of transmitter into the extracellular space plays an essential role in drug-induced striatal neurotoxicity and microglial activation. Subtle alterations in intracellular DA content can lead to significant enhancement of METH neurotoxicity. Our results also suggest that reactants derived from METH-induced oxidation of released DA may serve as neuronal signals that lead to microglial activation early in the neurotoxic process associated with METH.

Monitoring In Vivo Changes in Tonic Extracellular Dopamine Level by Charge-Balancing Multiple Waveform Fast-Scan Cyclic Voltammetry.

PubMed

Oh, Yoonbae; Park, Cheonho; Kim, Do Hyoung; Shin, Hojin; Kang, Yu Min; DeWaele, Mark; Lee, Jeyeon; Min, Hoon-Ki; Blaha, Charles D; Bennet, Kevin E; Kim, In Young; Lee, Kendall H; Jang, Dong Pyo

2016-11-15

Dopamine (DA) modulates central neuronal activity through both phasic (second to second) and tonic (minutes to hours) terminal release. Conventional fast-scan cyclic voltammetry (FSCV), in combination with carbon fiber microelectrodes, has been used to measure phasic DA release in vivo by adopting a background subtraction procedure to remove background capacitive currents. However, measuring tonic changes in DA concentrations using conventional FSCV has been difficult because background capacitive currents are inherently unstable over long recording periods. To measure tonic changes in DA concentrations over several hours, we applied a novel charge-balancing multiple waveform FSCV (CBM-FSCV), combined with a dual background subtraction technique, to minimize temporal variations in background capacitive currents. Using this method, in vitro, charge variations from a reference time point were nearly zero for 48 h, whereas with conventional background subtraction, charge variations progressively increased. CBM-FSCV also demonstrated a high selectivity against 3,4-dihydroxyphenylacetic acid and ascorbic acid, two major chemical interferents in the brain, yielding a sensitivity of 85.40 ± 14.30 nA/μM and limit of detection of 5.8 ± 0.9 nM for DA while maintaining selectivity. Recorded in vivo by CBM-FSCV, pharmacological inhibition of DA reuptake (nomifensine) resulted in a 235 ± 60 nM increase in tonic extracellular DA concentrations, while inhibition of DA synthesis (α-methyl-dl-tyrosine) resulted in a 72.5 ± 4.8 nM decrease in DA concentrations over a 2 h period. This study showed that CBM-FSCV may serve as a unique voltammetric technique to monitor relatively slow changes in tonic extracellular DA concentrations in vivo over a prolonged time period.

Lessons learned - MO&DA at JPL. [Mission Operations and Data Analysis cost reduction of planetary exploration

NASA Technical Reports Server (NTRS)

Handley, Thomas H., Jr.

1993-01-01

The issues of how to avoid future surprise growth in Mission Operations and Data Analysis (MO&DA) costs and how to minimize total MO&DA costs for planetary missions are discussed within the context of JPL mission operations support. It is argued that there is no simple, single solution: the entire Project life-cycle must be addressed. It is concluded that cost models that can predict both MO&DA cost as well as Ground System development costs are needed. The first year MO&DA budget plotted against the total of ground and flight systems developments is shown. In order to better recognize changes and control costs in general, a modified funding line item breakdown is recommended to distinguish between development costs (prelaunch and postlaunch) and MO&DA costs.

DOE Office of Scientific and Technical Information (OSTI.GOV)

El-Labany, S. K., E-mail: skellabany@hotmail.com; Zedan, N. A., E-mail: nesreenplasma@yahoo.com; El-Taibany, W. F., E-mail: eltaibany@hotmail.com, E-mail: eltaibany@du.edu.eg

The nonplanar amplitude modulation of dust acoustic (DA) envelope solitary waves in a strongly coupled dusty plasma (SCDP) has been investigated. By using a reductive perturbation technique, a modified nonlinear Schrödinger equation (NLSE) including the effects of geometry, polarization, and ion superthermality is derived. The modulational instability (MI) of the nonlinear DA wave envelopes is investigated in both planar and nonplanar geometries. There are two stable regions for the DA wave propagation strongly affected by polarization and ion superthermality. Moreover, it is found that the nonlinear DA waves in spherical geometry are the more structurally stable. The larger growth ratemore » of the nonlinear DA MI is observed in the cylindrical geometry. The salient characteristics of the MI in the nonplanar geometries cannot be found in the planar one. The DA wave propagation and the NLSE solutions are investigated both analytically and numerically.« less

Characterization of a major 31-kilodalton peptidoglycan-bound protein of Legionella pneumophila

DOE Office of Scientific and Technical Information (OSTI.GOV)

Butler, C.A.; Hoffman, P.S.

1990-05-01

A 31-kilodalton (kDa) protein was solubilized from the peptidoglycan (PG) fraction of Legionella pneumophila after treatment with either N-acetylmuramidase from the fungus Chalaropsis sp. or with mutanolysin from Streptomyces globisporus. The protein exhibited a ladderlike banding pattern by autoradiography when radiolabeled ((35S)cysteine or (35S)methionine) PG material was extensively treated with hen lysozyme. The banding patterns ranging between 31 and 45 kDa and between 55 and 60 kDa resolved as a single 31-kDa protein when the material was subsequently treated with N-acetylmuramidase. Analysis of the purified 31-kDa protein for diaminopimelic acid by gas chromatography revealed 1 mol of diaminopimelic acid permore » mol of protein. When outer membrane PG material containing the major outer membrane porin protein was treated with N-acetylmuramidase or mutanolysin, both the 28.5-kDa major outer membrane protein and the 31-kDa protein were solubilized from the PG material under reducing conditions. In the absence of 2-mercaptoethanol, a high-molecular-mass complex (100 kDa) was resolved. The results of this study indicate that a 31-kDa PG-bound protein is a major component of the cell wall of L. pneumophila whose function may be to anchor the major outer membrane protein to PG. Finally, a survey of other Legionella species and other serogroups of L. pneumophila suggested that PG-bound proteins may be a common feature of this genus.« less

Genome-Edited, TH-expressing Neuroblastoma Cells as a Disease Model for Dopamine-Related Disorders: A Proof-of-Concept Study on DJ-1-deficient Parkinsonism

PubMed Central

Prasuhn, Jannik; Mårtensson, Christoph U.; Krajka, Victor; Klein, Christine; Rakovic, Aleksandar

2018-01-01

Impairment of the dopaminergic (DA) system is a common cause of several movement disorders including Parkinson’s disease (PD), however, little is known about the underlying disease mechanisms. The recent development of stem-cell-based protocols for the generation of DA neurons partially solved this issue, however, this technology is costly and time-consuming. Commonly used cell lines, i.e., neuroblastoma (SHSY5Y) and PC12 cells are still widely used to investigate PD and significantly contributed to our understanding of mechanisms involved in development of the disease. However, they either do not express DA at all or require additional, only partially efficient differentiations in order to produce DA. Here we generated and characterized transgenic SH-SY5Y cells, ectopically expressing tyrosine hydroxylase (SHTH+), that can be used as a homogenous, DA-producing model to study alterations in DA metabolism and oxidative stress. We demonstrated that SHTH+ produce high levels of DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) making this model suitable to investigate not only alterations in DA synthesis but also its turnover. We also provide evidence for the presence of other enzymes involved in DA synthesis and its turnover in these cells. Finally, we showed that these cells can easily be genetically modified using CRISPR/Cas9 technology in order to study genetically defined forms of movement disorders using DJ1-linked PD as a model. PMID:29379417

Effects of beta-phenylethylamine on dopaminergic neurons of the ventral tegmental area in the rat: a combined electrophysiological and microdialysis study.

PubMed

Ishida, Kota; Murata, Mikio; Katagiri, Nobuyuki; Ishikawa, Masago; Abe, Kenji; Kato, Masatoshi; Utsunomiya, Iku; Taguchi, Kyoji

2005-08-01

The effects of systemic administration of beta-phenylethylamine (beta-PEA) and microiontophoretically applied beta-PEA on the spontaneous discharge of dopamine (DA) neurons in the ventral tegmental area (VTA) of the anesthetized rat were examined. Intravenous administration of beta-PEA (1.0, 2.5, and 5.0 mg/kg) and microiontophoretic applications of beta-PEA caused inhibitory responses in DA neurons. Systemic administration and microiontophoretic applications of beta-PEA induced dose- or current-dependent responses. The systemic beta-PEA-induced inhibitory responses were reversed by pretreatment with the DA D(2) receptor antagonists haloperidol (0.5 mg/kg i.p.) and sulpiride (10 mg/kg i.p). Pretreatment with reserpine (5 mg/kg i.p. 24 h earlier) did not completely block the systemic administration of beta-PEA (2.5 mg/kg) inhibition. A microdialysis study of freely moving rats demonstrated that the extracellular DA level increased significantly in response to local application of beta-PEA (100 muM) in the VTA via a microdialysis probe, and local application of beta-PEA-stimulated somatodendritic DA release in the VTA. The beta-PEA-induced release of DA was calcium ion-independent and was enhanced by pretreatment with pertussis toxin. These findings indicate that beta-phenylethylamine inhibits DA neuron activity via DA D(2) autoreceptors in the rat VTA and that this inhibitory effect is mediated by the somatodendritic DA release.

Striatal dopamine dynamics in mice following acute and repeated toluene exposure.

PubMed

Apawu, Aaron K; Mathews, Tiffany A; Bowen, Scott E

2015-01-01

The abused inhalant toluene has potent behavioral effects, but only recently has progress been made in understanding the neurochemical actions that mediate the action of toluene in the brain. Available evidence suggests that toluene inhalation alters dopamine (DA) neurotransmission, but toluene's mechanism of action is unknown. The present study evaluated the effect of acute and repeated toluene inhalation (0, 2,000, or 4,000 ppm) on locomotor activity as well as striatal DA release and uptake using slice fast-scan cyclic voltammetry. Acutely, 2,000 and 4,000 ppm toluene increased locomotor activity, while neurochemically only 4,000 ppm toluene potentiated electrically evoked DA release across the caudate-putamen and the nucleus accumbens. Repeated administration of toluene resulted in sensitization to toluene's locomotor activity effects. Brain slices obtained from mice repeatedly exposed to toluene demonstrated no difference in stimulated DA release in the caudate-putamen as compared to control animals. Repeated exposure to 2,000 and 4,000 ppm toluene caused a concentration-dependent decrease of 25-50 % in evoked DA release in the nucleus accumbens core and shell relative to air-exposed mice. These voltammetric neurochemical findings following repeated toluene exposure suggest that there may be a compensatory downregulation of the DA system. Acute or repeated toluene exposure had no effect on the DA uptake kinetics. Taken together, these results demonstrate that acute toluene inhalation potentiates DA release, while repeated toluene exposure attenuates DA release in the nucleus accumbens only.

DA-1229, a dipeptidyl peptidase IV inhibitor, protects against renal injury by preventing podocyte damage in an animal model of progressive renal injury.

PubMed

Eun Lee, Jee; Kim, Jung Eun; Lee, Mi Hwa; Song, Hye Kyoung; Ghee, Jung Yeon; Kang, Young Sun; Min, Hye Sook; Kim, Hyun Wook; Cha, Jin Joo; Han, Jee Young; Han, Sang Youb; Cha, Dae Ryong

2016-05-01

Although dipeptidyl peptidase IV (DPPIV) inhibitors are known to have renoprotective effects, the mechanism underlying these effects has remained elusive. Here we investigated the effects of DA-1229, a novel DPPIV inhibitor, in two animal models of renal injury including db/db mice and the adriamycin nephropathy rodent model of chronic renal disease characterized by podocyte injury. For both models, DA-1229 was administered at 300 mg/kg/day. DPPIV activity in the kidney was significantly higher in diabetic mice compared with their nondiabetic controls. Although DA-1229 did not affect glycemic control or insulin resistance, DA-1229 did improve lipid profiles, albuminuria and renal fibrosis. Moreover, DA-1229 treatment resulted in decreased urinary excretion of nephrin, decreased circulating and kidney DPPIV activity, and decreased macrophage infiltration in the kidney. In adriamycin-treated mice, DPPIV activity in the kidney and urinary nephrin loss were both increased, whereas glucagon-like peptide-1 concentrations were unchanged. Moreover, DA-1229 treatment significantly improved proteinuria, renal fibrosis and inflammation associated with decreased urinary nephrin loss, and kidney DPP4 activity. In cultured podocytes, DA-1229 restored the high glucose/angiotensin II-induced increase of DPPIV activity and preserved the nephrin levels in podocytes. These findings suggest that activation of DPPIV in the kidney has a role in the progression of renal disease, and that DA-1229 may exert its renoprotective effects by preventing podocyte injury.

Molecular mechanism: the human dopamine transporter histidine 547 regulates basal and HIV-1 Tat protein-inhibited dopamine transport

PubMed Central

Quizon, Pamela M.; Sun, Wei-Lun; Yuan, Yaxia; Midde, Narasimha M.; Zhan, Chang-Guo; Zhu, Jun

2016-01-01

Abnormal dopaminergic transmission has been implicated as a risk determinant of HIV-1-associated neurocognitive disorders. HIV-1 Tat protein increases synaptic dopamine (DA) levels by directly inhibiting DA transporter (DAT) activity, ultimately leading to dopaminergic neuron damage. Through integrated computational modeling prediction and experimental validation, we identified that histidine547 on human DAT (hDAT) is critical for regulation of basal DA uptake and Tat-induced inhibition of DA transport. Compared to wild type hDAT (WT hDAT), mutation of histidine547 (H547A) displayed a 196% increase in DA uptake. Other substitutions of histidine547 showed that DA uptake was not altered in H547R but decreased by 99% in H547P and 60% in H547D, respectively. These mutants did not alter DAT surface expression or surface DAT binding sites. H547 mutants attenuated Tat-induced inhibition of DA transport observed in WT hDAT. H547A displays a differential sensitivity to PMA- or BIM-induced activation or inhibition of DAT function relative to WT hDAT, indicating a change in basal PKC activity in H547A. These findings demonstrate that histidine547 on hDAT plays a crucial role in stabilizing basal DA transport and Tat-DAT interaction. This study provides mechanistic insights into identifying targets on DAT for Tat binding and improving DAT-mediated dysfunction of DA transmission. PMID:27966610

Annotated type catalogue of the Bulimulidae (Mollusca, Gastropoda, Orthalicoidea) in the Natural History Museum, London

PubMed Central

Breure, Abraham S.H.; Ablett, Jonathan D.

2014-01-01

Abstract The type status is described of 404 taxa classified within the family Bulimulidae (superfamily Orthalicoidea) and kept in the London museum. Lectotypes are designated for Bulimus aurifluus Pfeiffer, 1857; Otostomus bartletti H. Adams, 1867; Helix cactorum d’Orbigny, 1835; Bulimus caliginosus Reeve, 1849; Bulimus chemnitzioides Forbes, 1850; Bulimus cinereus Reeve, 1849; Helix cora d’Orbigny, 1835; Bulimus fallax Pfeiffer, 1853; Bulimus felix Pfeiffer, 1862; Bulimus fontainii d’Orbigny, 1838; Bulimus fourmiersi d’Orbigny, 1837; Bulimus (Mesembrinus) gealei H. Adams, 1867; Bulimus gruneri Pfeiffer, 1846; Bulimus humboldtii Reeve, 1849; Helix hygrohylaea d’Orbigny, 1835; Bulimus jussieui Pfeiffer, 1846; Bulimulus (Drymaeus) binominis lascellianus E.A. Smith, 1895; Helix lichnorum d’Orbigny, 1835; Bulimulus (Drymaeus) lucidus da Costa, 1898; Bulimus luridus Pfeiffer, 1863; Bulimus meleagris Pfeiffer, 1853; Bulimus monachus Pfeiffer, 1857; Bulimus montagnei d’Orbigny, 1837; Helix montivaga d’Orbigny, 1835; Bulimus muliebris Reeve, 1849; Bulimus nigrofasciatus Pfeiffer in Philippi 1846; Bulimus nitelinus Reeve, 1849; Helix oreades d’Orbigny, 1835; Helix polymorpha d’Orbigny, 1835; Bulimus praetextus Reeve, 1849; Bulinus proteus Broderip, 1832; Bulimus rusticellus Morelet, 1860; Helix sporadica d’Orbigny, 1835; Bulimus sulphureus Pfeiffer, 1857; Helix thamnoica var. marmorata d’Orbigny, 1835; Bulinus translucens Broderip in Broderip and Sowerby I 1832; Helix trichoda d’Orbigny, 1835; Bulinus ustulatus Sowerby I, 1833; Bulimus voithianus Pfeiffer, 1847; Bulimus yungasensis d’Orbigny, 1837. The type status of the following taxa is changed to lectotype in accordance with Art. 74.6 ICZN: Bulimulus (Drymaeus) caucaensis da Costa, 1898; Drymaeus exoticus da Costa, 1901; Bulimulus (Drymaeus) hidalgoi da Costa, 1898; Bulimulus (Drymaeus) interruptus Preston, 1909; Bulimulus (Drymaeus) inusitatus Fulton, 1900; Bulimulus latecolumellaris Preston, 1909; Bulimus (Otostomus) napo Angas, 1878; Drymaeus notabilis da Costa, 1906; Drymaeus notatus da Costa, 1906; Bulimulus (Drymaeus) nubilus Preston, 1903; Drymaeus obliquistriatus da Costa, 1901; Bulimus (Drymaeus) ochrocheilus E.A. Smith, 1877; Bulimus (Drymaeus) orthostoma E.A. Smith, 1877; Drymaeus expansus perenensis da Costa, 1901; Bulimulus pergracilis Rolle, 1904; Bulimulus (Drymaeus) plicatoliratus da Costa, 1898; Drymaeus prestoni da Costa, 1906; Drymaeus punctatus da Costa, 1907; Bulimus (Leptomerus) sanctaeluciae E.A. Smith, 1889; Bulimulus (Drymaeus) selli Preston, 1909; Drymaeus subventricosus da Costa, 1901; Bulimulus (Drymaeus) tigrinus da Costa, 1898; Drymaeus volsus Fulton, 1907; Drymaeus wintlei Finch, 1929; Bulimus zhorquinensis Angas, 1879; Bulimulus (Drymaeus) ziczac da Costa, 1898. The following junior subjective synonyms are established: Bulimus antioquensis Pfeiffer, 1855 = Bulimus baranguillanus Pfeiffer, 1853; Drymaeus bellus da Costa, 1906 = Drymaeus blandi Pilsbry, 1897; Bulimus hachensis Reeve 1850 = Bulimus gruneri Pfeiffer, 1846 = Bulimus columbianus Lea, 1838; Bulimus (Otostomus) lamas Higgins 1868 = Bulimus trujillensis Philippi, 1867; Bulimulus (Drymaeus) binominis lascellianus E.A. Smith, 1895 = Bulimulus (Drymaeus) binominis E.A. Smith, 1895; Drymaeus multispira da Costa, 1904 = Helix torallyi d’Orbigny, 1835; Bulimulus (Drymaeus) plicatoliratus Da Costa, 1898 = Bulimus convexus Pfeiffer, 1855; Bulimus sugillatus Pfeiffer, 1857 = Bulimus rivasii d’Orbigny, 1837; Bulimus meridionalis Reeve 1848 [June] = Bulimus voithianus Pfeiffer, 1847. New combinations are: Bostryx montagnei (d’Orbigny, 1837); Bostryx obliquiportus (da Costa, 1901); Bulimulus heloicus (d’Orbigny, 1835); Drymaeus (Drymaeus) lusorius (Pfeiffer, 1855); Drymaeus (Drymaeus) trigonostomus (Jonas, 1844); Drymaeus (Drymaeus) wintlei Finch, 1929; Drymaeus (Mesembrinus) conicus da Costa, 1907; Kuschelenia (Kuschelenia) culminea culminea (d’Orbigny, 1835); Kuschelenia (Kuschelenia) culmineus edwardsi (Morelet, 1863); Kuschelenia (K.) gayi (Pfeiffer, 1857); Kuschelenia (Kuschelenia) tupacii (d’Orbigny, 1835); Kuschelenia (Vermiculatus) anthisanensis (Pfeiffer, 1853); Kuschelenia (Vermiculatus) aquilus (Reeve, 1848); Kuschelenia (Vermiculatus) bicolor (Sowerby I, 1835); Kuschelenia (Vermiculatus) caliginosus (Reeve, 1849); Kuschelenia (Vermiculatus) cotopaxiensis (Pfeiffer, 1853); Kuschelenia (Vermiculatus) filaris (Pfeiffer, 1853); Kuschelenia (Vermiculatus) ochracea (Morelet, 1863); Kuschelenia (Vermiculatus) petiti (Pfeiffer, 1846); Kuschelenia (Vermiculatus) purpuratus (Reeve, 1849); Kuschelenia (Vermiculatus) quechuarum (Crawford, 1939); Naesiotus cinereus (Reeve, 1849); Naesiotus dentritis (Morelet, 1863); Naesiotus fontainii (d’Orbigny, 1838); Naesiotus orbignyi (Pfeiffer, 1846); Protoglyptus pilosus (Guppy, 1871); Protoglyptus sanctaeluciae (E.A. Smith, 1889). Type material of the following taxa is figured herein for the first time: Bulimus cinereus Reeve, 1849; Bulimus coriaceus Pfeiffer, 1857; Bulimulus laxostylus Rolle, 1904; Bulimus pliculatus Pfeiffer, 1857; Bulimus simpliculus Pfeiffer, 1855. PMID:24715782

T227. THE METABOTROPIC GLUTAMATE RECEPTOR SUBTYPE 1 REGULATES STRIATAL DOPAMINE RELEASE VIA AN ENDOCANNABINOID-DEPENDENT MECHANISM: IMPLICATIONS FOR THE TREATMENT OF SCHIZOPHRENIA

PubMed Central

Yohn, Samantha; Covey, Daniel; Foster, Daniel; Moehle, Mark; Galbraith, Jordan; Cheer, Joseph; Lindsley, Craig; Jeffrey Conn, P

2018-01-01

Abstract Background Clinical and preclinical studies suggest that selective activators of the muscarinic M4 receptor have exciting potential as a novel approach for treatment of schizophrenia. M4 reduces striatal dopamine (DA) though release of endocannabinoids (eCB), providing a mechanism for local effects on DA signaling in the striatum. M4 signals through Gαi/o and does not couple to Gαq/11 or induce calcium (Ca++) mobilization. This raises the possibility that M4-induced eCB release and inhibition of DA release may require co-activation of another receptor that activates Gαq/11. If so, this receptor could provide a novel target that may be more proximal to inhibition of DA release. Interestingly, the group 1 metabotropic glutamate (mGlu) receptors (mGlu1 and Glu5), couple to Gαq/11 and activate eCB signaling in multiple brain regions. Methods We tested the hypothesis that M4-induced reductions in DA release and subsequent antipsychotic-effect requires co-activation of group 1 mGlu receptors. The effect of M4 activation on electrically-evoked DA release in striatal slices was assessed using fast-scan cyclic voltammetry (FSCV) in the absence or presence of selective negative allosteric modulators (NAMs) of group 1 mGlu receptor subtypes. To evaluate the potential role of mGlu1, we determined the effects of a selective mGlu1 positive allosteric modulators (PAMs) on striatal DA release and antipsychotic-like activity in rodent models that are dependent on increased DA transmission. Since reductions in DA signaling, including D1 signaling have been implicated in reduced motivation, we also determined the effects of an mGlu1 PAM, M4 PAM, and the typical antipsychotic haloperidol on motivational responding in a progressive ratio (PR) schedule. Results We now present exciting new data in which we found that activation of mGlu1 through application of exogenous agonists or selective stimulation of thalamostriatal afferents induces a reduction of striatal DA release and that selective mGlu1 PAMs have robust antipsychotic-like effects in rodent models. Interestingly, our studies also suggest that mGlu1 activation is required for M4 PAM-induced inhibition of DA release and antipsychotic-like effects. However, in contrast to available antipsychotic agents, the present results and previous studies suggest that mGlu1 and M4 PAMs reduce DA signaling through local release of an eCB from striatal SPNs and activation of CB2 receptors on neighboring DA terminals to reduce DA release. While these studies suggest that the effects of M4 PAMs on DA release require activation of mGlu1, we have also found that these targets have important differences. Most notably, M4 PAMs also directly inhibits D1 signaling in D1-SPN terminals in the substatnia nigra pars reticulata (SNr). Unlike M4, mGlu1 does not directly inhibit DA D1 receptor signaling and does not induce behavioral changes that could be associated with negative symptoms. Discussion Our findings are especially interesting in light of recent findings that multiple loss of function single nucleotide polymorphisms (SNPs) in the human gene encoding mGlu1 (GRM1) are associated with schizophrenia, and points to GRM1/mGlu1 as a gene within the “druggable genome” that could be targeted for treatment of schizophrenia. Recent clinical imaging studies suggesting that symptoms in schizophrenia patients are associated with selective increases in striatal DA signaling and while extrastriatal regions display hypo-dopaminergic function; thus, mGlu1 and M4 PAMs may provide a mechanism for selective inhibition of DA release in striatal regions that are important for antipsychotic efficacy, without further disruptions in extrastriatal DA signaling.

Early experience using the da Vinci Surgical System for the treatment of mediastinal tumors.

PubMed

Kajiwara, Naohiro; Taira, Masahiro; Yoshida, Koichi; Hagiwara, Masaru; Kakihana, Masatoshi; Usuda, Jitsuo; Uchida, Osamu; Ohira, Tatsuo; Kawate, Norihiko; Ikeda, Norihiko

2011-10-01

The da Vinci Surgical System has been used in only a few cases for treating mediastinal tumors in Japan. Recently, we used the da Vinci Surgical System for various types of anterior and middle mediastinal tumors in clinical practice. We report our early experience using the da Vinci Surgical System. Seven patients gave written informed consent to undergo robotic surgery for mediastinal tumor dissection using the da Vinci Surgical System. We evaluated the safety and feasibility of this system for the surgical treatment of mediastinal tumors. Two specialists in thoracic surgery who are certified to use the da Vinci S Surgical System and another specialist acted as an assistant performed the tumor dissection. We were able to access difficult-to-reach areas, such as the mediastinum, safely. All the resected tumors were classified as benign tumors histologically. The average da Vinci setting time was 14.0 min, the average working time was 55.7 min, and the average overall operating time was 125.9 min. The learning curve for the da Vinci setup and manipulation time was short. Robotic surgery enables mediastinal tumor dissection in certain cases more safely and easily than conventional video-assisted thoracoscopic surgery and less invasively than open thoracotomy.

Plant mitochondrial pyruvate dehydrogenase complex: purification and identification of catalytic components in potato.

PubMed Central

Millar, A H; Knorpp, C; Leaver, C J; Hill, S A

1998-01-01

The pyruvate dehydrogenase complex (mPDC) from potato (Solanum tuberosum cv. Romano) tuber mitochondria was purified 40-fold to a specific activity of 5.60 micromol/min per mg of protein. The activity of the complex depended on pyruvate, divalent cations, NAD+ and CoA and was competitively inhibited by both NADH and acetyl-CoA. SDS/PAGE revealed the complex consisted of seven polypeptide bands with apparent molecular masses of 78, 60, 58, 55, 43, 41 and 37 kDa. N-terminal sequencing revealed that the 78 kDa protein was dihydrolipoamide transacetylase (E2), the 58 kDa protein was dihydrolipoamide dehydrogenase (E3), the 43 and 41 kDa proteins were alpha subunits of pyruvate dehydrogenase, and the 37 kDa protein was the beta subunit of pyruvate dehydrogenase. N-terminal sequencing of the 55 kDa protein band yielded two protein sequences: one was another E3; the other was similar to the sequence of E2 from plant and yeast sources but was distinctly different from the sequence of the 78 kDa protein. Incubation of the mPDC with [2-14C]pyruvate resulted in the acetylation of both the 78 and 55 kDa proteins. PMID:9729464

III-Nitride Digital Alloy: Electronics and Optoelectronics Properties of the InN/GaN Ultra-Short Period Superlattice Nanostructures.

PubMed

Sun, Wei; Tan, Chee-Keong; Tansu, Nelson

2017-07-27

The III-Nitride digital alloy (DA) is comprehensively studied as a short-period superlattice nanostructure consisting of ultra-thin III-Nitride epitaxial layers. By stacking the ultra-thin III-Nitride epitaxial layers periodically, these nanostructures are expected to have comparable optoelectronic properties as the conventional III-Nitride alloys. Here we carried out numerical studies on the InGaN DA showing the tunable optoelectronic properties of the III-Nitride DA. Our study shows that the energy gap of the InGaN DA can be tuned from ~0.63 eV up to ~2.4 eV, where the thicknesses and the thickness ratio of each GaN and InN ultra-thin binary layers within the DA structure are the key factors for tuning bandgap. Correspondingly, the absorption spectra of the InGaN DA yield broad wavelength tunability which is comparable to that of bulk InGaN ternary alloy. In addition, our investigation also reveals that the electron-hole wavefunction overlaps are remarkably large in the InGaN DA structure despite the existence of strain effect and build-in polarization field. Our findings point out the potential of III-Nitride DA as an artificially engineered nanostructure for optoelectronic device applications.

Apoptosis induced by β,β-dimethylacrylshikonin is associated with Bcl-2 and NF-κB in human breast carcinoma MCF-7 cells

PubMed Central

XIONG, YAO; MA, XIU-YING; ZHANG, ZIRAN; SHAO, ZHEN-JUN; ZHANG, YUAN-YUAN; ZHOU, LI-MING

2013-01-01

β,β-dimethylacrylshikonin (DA) is a natural naphthoquinone derivative compound of Lithospermum erythrorhizon with various biological activities. The present study aimed to investigate the inhibitory effects and underlying mechanisms of DA in human breast carcinoma MCF-7 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that DA inhibited the proliferation of MCF-7 cells in a dose- and time-dependent manner. The half maximal inhibitory concentration of DA with regard to the proliferation of MCF-7 cells was 0.050±0.016 mM. The characteristics of cell apoptosis, including cell shrinkage, nuclear pyknosis and chromatin condensation, were all observed in DA-treated cells. DA decreased the expression levels of Bcl-2 and increased the expression of Bax and caspase-3 compared with those in the control. DA inhibited the activity of the nuclear factor (NF)-κB pathway, by downregulating the expression of the p65 subunit, and inhibited the Iκb phosphorylation. DA inhibits the proliferation of MCF-7 cells in vitro by inducing apoptosis through the downregulation of Bcl-2, upregulation of Bax and partial inactivation of the NF-κB pathway. PMID:24260077

Explaining the disease phenotype of intergenic SNP through predicted long range regulation.

PubMed

Chen, Jingqi; Tian, Weidong

2016-10-14

Thousands of disease-associated SNPs (daSNPs) are located in intergenic regions (IGR), making it difficult to understand their association with disease phenotypes. Recent analysis found that non-coding daSNPs were frequently located in or approximate to regulatory elements, inspiring us to try to explain the disease phenotypes of IGR daSNPs through nearby regulatory sequences. Hence, after locating the nearest distal regulatory element (DRE) to a given IGR daSNP, we applied a computational method named INTREPID to predict the target genes regulated by the DRE, and then investigated their functional relevance to the IGR daSNP's disease phenotypes. 36.8% of all IGR daSNP-disease phenotype associations investigated were possibly explainable through the predicted target genes, which were enriched with, were functionally relevant to, or consisted of the corresponding disease genes. This proportion could be further increased to 60.5% if the LD SNPs of daSNPs were also considered. Furthermore, the predicted SNP-target gene pairs were enriched with known eQTL/mQTL SNP-gene relationships. Overall, it's likely that IGR daSNPs may contribute to disease phenotypes by interfering with the regulatory function of their nearby DREs and causing abnormal expression of disease genes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Dopamine Burden Triggers Neurodegeneration via Production and Release of TNF-α from Astrocytes in Minimal Hepatic Encephalopathy.

PubMed

Ding, Saidan; Wang, Weikan; Wang, Xuebao; Liang, Yong; Liu, Leping; Ye, Yiru; Yang, Jianjing; Gao, Hongchang; Zhuge, Qichuan

2016-10-01

Dopamine (DA)-induced learning and memory impairment is well documented in minimal hepatic encephalopathy (MHE), but the contribution of DA to neurodegeneration and the involved underlying mechanisms are not fully understood. In this study, the effect of DA on neuronal apoptosis was initially detected. The results showed that MHE/DA (10 μg)-treated rats displayed neuronal apoptosis. However, we found that DA (10 μM) treatment did not induce evident apoptosis in primary cultured neurons (PCNs) but did produce TNF-α in primary cultured astrocytes (PCAs). Furthermore, co-cultures between PCAs and PCNs exposed to DA exhibited increased astrocytic TNF-α levels and neuronal apoptosis compared with co-cultures exposed to the vehicle, indicating the attribution of the neuronal apoptosis to astrocytic TNF-α. We also demonstrated that DA enhanced TNF-α production from astrocytes by activation of the TLR4/MyD88/NF-κB pathway, and secreted astrocytic TNF-α-potentiated neuronal apoptosis through inactivation of the PI3K/Akt/mTOR pathway. Overall, the findings from this study suggest that DA stimulates substantial production and secretion of astrocytic TNF-α, consequently and indirectly triggering progressive neurodegeneration, resulting in cognitive decline and memory loss in MHE.

Human dopamine receptor nanovesicles for gate-potential modulators in high-performance field-effect transistor biosensors

NASA Astrophysics Data System (ADS)

Park, Seon Joo; Song, Hyun Seok; Kwon, Oh Seok; Chung, Ji Hyun; Lee, Seung Hwan; An, Ji Hyun; Ahn, Sae Ryun; Lee, Ji Eun; Yoon, Hyeonseok; Park, Tai Hyun; Jang, Jyongsik

2014-03-01

The development of molecular detection that allows rapid responses with high sensitivity and selectivity remains challenging. Herein, we demonstrate the strategy of novel bio-nanotechnology to successfully fabricate high-performance dopamine (DA) biosensor using DA Receptor-containing uniform-particle-shaped Nanovesicles-immobilized Carboxylated poly(3,4-ethylenedioxythiophene) (CPEDOT) NTs (DRNCNs). DA molecules are commonly associated with serious diseases, such as Parkinson's and Alzheimer's diseases. For the first time, nanovesicles containing a human DA receptor D1 (hDRD1) were successfully constructed from HEK-293 cells, stably expressing hDRD1. The nanovesicles containing hDRD1 as gate-potential modulator on the conducting polymer (CP) nanomaterial transistors provided high-performance responses to DA molecule owing to their uniform, monodispersive morphologies and outstanding discrimination ability. Specifically, the DRNCNs were integrated into a liquid-ion gated field-effect transistor (FET) system via immobilization and attachment processes, leading to high sensitivity and excellent selectivity toward DA in liquid state. Unprecedentedly, the minimum detectable level (MDL) from the field-induced DA responses was as low as 10 pM in real- time, which is 10 times more sensitive than that of previously reported CP based-DA biosensors. Moreover, the FET-type DRNCN biosensor had a rapid response time (<1 s) and showed excellent selectivity in human serum.

Direct voltammetric specific recognition of dopamine using AlIII-DA complexes at the hanging mercury drop electrode.

PubMed

Zhang, Fuping; Zhang, Min; Cheng, Jiongjia; Yang, Li; Ji, Ming; Bi, Shuping

2007-11-01

In this paper, we firstly report the direct voltammetric recognition and determination of dopamine (DA) by using Al(III)-DA complexes at the hanging mercury drop electrode (HMDE). A new sensitive cathodic peak of Al(III)-DA can be detected at -900 mV (vs. SCE) in 0.1 M NH(4)Cl-NH(3).H(2)O-0.1 M KCl buffer solution at pH 8.5. This unique -900 mV cathodic peak arises from the specific interaction between Al(III) and DA on the HMDE, whereas other substances with similar structures, such as L-dopa, epinephrine (EP), norepinephrine (NE), catechols, caffeic acid (CA), trihydric phenols and tiron, do not yield any new peak on the voltammograms in the potential range from -100 to -1200 mV when Al(III) is added. The distinct voltammetric characteristic of the recognition of DA can effectively inhibit the interferences of both ascorbic acid and uric acid in the DA determination by the direct electrochemistry, which is a major difficulty when a solid electrode is used. The proposed method can be anticipated as an effective means for the recognition of DA in the elucidation of the mechanisms of Parkinson's disease (PD) and Alzheimer's disease (AD) in the presence of Al(III).

Rare autism-associated variants implicate syntaxin 1 (STX1 R26Q) phosphorylation and the dopamine transporter (hDAT R51W) in dopamine neurotransmission and behaviors.

PubMed

Cartier, Etienne; Hamilton, Peter J; Belovich, Andrea N; Shekar, Aparna; Campbell, Nicholas G; Saunders, Christine; Andreassen, Thorvald F; Gether, Ulrik; Veenstra-Vanderweele, Jeremy; Sutcliffe, James S; Ulery-Reynolds, Paula G; Erreger, Kevin; Matthies, Heinrich J G; Galli, Aurelio

2015-02-01

Syntaxin 1 (STX1) is a presynaptic plasma membrane protein that coordinates synaptic vesicle fusion. STX1 also regulates the function of neurotransmitter transporters, including the dopamine (DA) transporter (DAT). The DAT is a membrane protein that controls DA homeostasis through the high-affinity re-uptake of synaptically released DA. We adopt newly developed animal models and state-of-the-art biophysical techniques to determine the contribution of the identified gene variants to impairments in DA neurotransmission observed in autism spectrum disorder (ASD). Here, we characterize two independent autism-associated variants in the genes that encode STX1 and the DAT. We demonstrate that each variant dramatically alters DAT function. We identify molecular mechanisms that converge to inhibit reverse transport of DA and DA-associated behaviors. These mechanisms involve decreased phosphorylation of STX1 at Ser14 mediated by casein kinase 2 as well as a reduction in STX1/DAT interaction. These findings point to STX1/DAT interactions and STX1 phosphorylation as key regulators of DA homeostasis. We determine the molecular identity and the impact of these variants with the intent of defining DA dysfunction and associated behaviors as possible complications of ASD.

Tool for Merging Proposals Into DSN Schedules

NASA Technical Reports Server (NTRS)

Khanampornpan, Teerapat; Kwok, John; Call, Jared

2008-01-01

A Practical Extraction and Reporting Language (Perl) script called merge7da has been developed to facilitate determination, by a project scheduler in NASA's Deep Space Network, of whether a proposal for use of the DSN could create a conflict with the current DSN schedule. Prior to the development of merge7da, there was no way to quickly identify potential schedule conflicts: it was necessary to submit a proposal and wait a day or two for a response from a DSN scheduling facility. By using merge7da to detect and eliminate potential schedule conflicts before submitting a proposal, a project scheduler saves time and gains assurance that the proposal will probably be accepted. merge7da accepts two input files, one of which contains the current DSN schedule and is in a DSN-standard format called '7da'. The other input file contains the proposal and is in another DSN-standard format called 'C1/C2'. merge7da processes the two input files to produce a merged 7da-format output file that represents the DSN schedule as it would be if the proposal were to be adopted. This 7da output file can be loaded into various DSN scheduling software tools now in use.

Behavioural and biochemical responses following activation of midbrain dopamine pathways by receptor selective neurokinin agonists.

PubMed

Elliott, P J; Mason, G S; Stephens-Smith, M; Hagan, R M

1991-06-01

Preferential activation of mesolimbic and nigro-striatal dopamine (DA) pathways by receptor-selective and peptidase-resistant neurokinin (NK) agonists is reported. The DA cell body region of the mesolimbic pathway appears to be activated by NK agonists selective for NK-1 and NK-3 receptors whereas the DA cell bodies in the substantia nigra are under an excitatory NK-2 receptor-mediated influence. Stimulation of the mesolimbic DA pathway by NK-1 (Ava[L-Pro9,N-Me-Leu10]SP (7-11) [GR73632]) or NK-3 (Senktide) agonists increase locomotor activity. Additional studies showed that this elevated motor response observed after intra-VTA infusion of GR73632 was accompanied by a corresponding increase in DA turnover in the terminal fields of this pathway. Similarly, unilateral activation of the nigro-striatal DA pathway by NK-2 selective agonists (Ava (D-Pro9) SP (7-11) [GR51667] or [Lys3,Gly8,R-Lac-Leu9]NKA (3-10) [GR64349]) elicit contralateral rotational activity and an increase in DA turnover in the ipsilateral striatum. The rotational response was attenuated by prior administration of an NK-2 antagonist (cyclo (Gln, Trp, Phe, Gly, Leu, Met)] L-659877]) into the nigra. Peripheral injection of haloperidol, a DA antagonist, also blocked the NK-2 agonist induced rotations.

Role of dopamine D2 receptors in human reinforcement learning.

PubMed

Eisenegger, Christoph; Naef, Michael; Linssen, Anke; Clark, Luke; Gandamaneni, Praveen K; Müller, Ulrich; Robbins, Trevor W

2014-09-01

Influential neurocomputational models emphasize dopamine (DA) as an electrophysiological and neurochemical correlate of reinforcement learning. However, evidence of a specific causal role of DA receptors in learning has been less forthcoming, especially in humans. Here we combine, in a between-subjects design, administration of a high dose of the selective DA D2/3-receptor antagonist sulpiride with genetic analysis of the DA D2 receptor in a behavioral study of reinforcement learning in a sample of 78 healthy male volunteers. In contrast to predictions of prevailing models emphasizing DA's pivotal role in learning via prediction errors, we found that sulpiride did not disrupt learning, but rather induced profound impairments in choice performance. The disruption was selective for stimuli indicating reward, whereas loss avoidance performance was unaffected. Effects were driven by volunteers with higher serum levels of the drug, and in those with genetically determined lower density of striatal DA D2 receptors. This is the clearest demonstration to date for a causal modulatory role of the DA D2 receptor in choice performance that might be distinct from learning. Our findings challenge current reward prediction error models of reinforcement learning, and suggest that classical animal models emphasizing a role of postsynaptic DA D2 receptors in motivational aspects of reinforcement learning may apply to humans as well.

Role of Dopamine D2 Receptors in Human Reinforcement Learning

PubMed Central

Eisenegger, Christoph; Naef, Michael; Linssen, Anke; Clark, Luke; Gandamaneni, Praveen K; Müller, Ulrich; Robbins, Trevor W

2014-01-01

Influential neurocomputational models emphasize dopamine (DA) as an electrophysiological and neurochemical correlate of reinforcement learning. However, evidence of a specific causal role of DA receptors in learning has been less forthcoming, especially in humans. Here we combine, in a between-subjects design, administration of a high dose of the selective DA D2/3-receptor antagonist sulpiride with genetic analysis of the DA D2 receptor in a behavioral study of reinforcement learning in a sample of 78 healthy male volunteers. In contrast to predictions of prevailing models emphasizing DA's pivotal role in learning via prediction errors, we found that sulpiride did not disrupt learning, but rather induced profound impairments in choice performance. The disruption was selective for stimuli indicating reward, whereas loss avoidance performance was unaffected. Effects were driven by volunteers with higher serum levels of the drug, and in those with genetically determined lower density of striatal DA D2 receptors. This is the clearest demonstration to date for a causal modulatory role of the DA D2 receptor in choice performance that might be distinct from learning. Our findings challenge current reward prediction error models of reinforcement learning, and suggest that classical animal models emphasizing a role of postsynaptic DA D2 receptors in motivational aspects of reinforcement learning may apply to humans as well. PMID:24713613

Rare Autism-Associated Variants Implicate Syntaxin 1 (STX1 R26Q) Phosphorylation and the Dopamine Transporter (hDAT R51W) in Dopamine Neurotransmission and Behaviors

PubMed Central

Cartier, Etienne; Hamilton, Peter J.; Belovich, Andrea N.; Shekar, Aparna; Campbell, Nicholas G.; Saunders, Christine; Andreassen, Thorvald F.; Gether, Ulrik; Veenstra-Vanderweele, Jeremy; Sutcliffe, James S.; Ulery-Reynolds, Paula G.; Erreger, Kevin; Matthies, Heinrich J.G.; Galli, Aurelio

2015-01-01

Background Syntaxin 1 (STX1) is a presynaptic plasma membrane protein that coordinates synaptic vesicle fusion. STX1 also regulates the function of neurotransmitter transporters, including the dopamine (DA) transporter (DAT). The DAT is a membrane protein that controls DA homeostasis through the high-affinity re-uptake of synaptically released DA. Methods We adopt newly developed animal models and state-of-the-art biophysical techniques to determine the contribution of the identified gene variants to impairments in DA neurotransmission observed in autism spectrum disorder (ASD). Outcomes Here, we characterize two independent autism-associated variants in the genes that encode STX1 and the DAT. We demonstrate that each variant dramatically alters DAT function. We identify molecular mechanisms that converge to inhibit reverse transport of DA and DA-associated behaviors. These mechanisms involve decreased phosphorylation of STX1 at Ser14 mediated by casein kinase 2 as well as a reduction in STX1/DAT interaction. These findings point to STX1/DAT interactions and STX1 phosphorylation as key regulators of DA homeostasis. Interpretation We determine the molecular identity and the impact of these variants with the intent of defining DA dysfunction and associated behaviors as possible complications of ASD. PMID:25774383

Mechanism of isomers and analogues of resveratrol dimers selectively quenching singlet oxygen by UHPLC-ESI-MS2.

PubMed

Yin, Xuefeng; Yu, Jia; Kong, Qingjun; Ren, Xueyan

2017-12-15

Stilbenoids, in particular, resveratrol and its dimers are abundantly present in Vitis vinifera and proved to be quenchers with selective singlet oxygen. However, only a few mechanisms are reported for their complex molecular architectures. Hence, UHPLC combined with accurate MS is employed to investigate the photo-radiation mechanism of resveratrol dimers systematically. Ⅰ: Resorcinol ring exists in Scirpusin A 1, Trans-ε-viniferin 2 and Trans-σ-viniferin 3. The photochemical products were 14Da or 16Da higher than reagents and underwent an endoperoxide intermediate to quinones; Ⅱ: [2+2] cyclization of intra-molecular trans-double bond. The products were 18Da greater than substrates thereby cycloaddited to oxygen heterocyclic; Ⅲ : [4+1], [4+2] cyclization of oxetane formed products were 28Da and 44Da higher than 3, 2 and 1. Ⅳ : 5-phenol-2,3-dihydrobenzofuran ring exists in 2 been oxidized, causing the products at 16Da, 32Da higher than 2. This is the first to reveal the generally regular mechanism of stilbenoids quenching singlet oxygen. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hypothalamic interaction with the mesolimbic DA system in the control of the maternal and sexual behaviors in rats.

PubMed

Stolzenberg, Danielle S; Numan, Michael

2011-01-01

The medial preoptic area (MPOA) of the hypothalamus regulates maternal behavior, male sexual behavior, and female sexual behavior. Functional neuroanatomical evidence indicates that the appetitive aspects of maternal behavior are regulated through MPOA interactions with the mesolimbic dopamine (DA) system; a major focus of this review is to explore whether or not the MPOA participates in the appetitive aspects of sexual behavior via its interaction with the mesolimbic DA system. A second focus of this review is to examine the extent to which estradiol interactions with DA within this circuit regulate all three reproductive behaviors. One mechanism through which estradiol activates male sexual behavior is through the potentiation of DA activity in the MPOA. In the hypothalamus, estradiol has also been found to act in concert with DA, through the activation of similar intracellular signaling pathways, in order to stimulate female sexual behavior. Finally, recent evidence suggests that some effects of estradiol are mediated by direct action of estradiol on the mesolimbic DA system. Copyright © 2010 Elsevier Ltd. All rights reserved.

Electrochemical detection of dopamine using porphyrin-functionalized graphene.

PubMed

Wu, Li; Feng, Lingyan; Ren, Jinsong; Qu, Xiaogang

2012-04-15

A new type of porphyrin-functionalized graphene was synthesized and used for highly selective and sensitive detection of dopamine (DA). The aromatic π-π stacking and electrostatic attraction between positively-charged dopamine and negatively-charged porphyrin-modified graphene can accelerate the electron transfer whereas weakening ascorbic acid (AA) and uric acid (UA) oxidation on the porphyrin-functionalized graphene-modified electrode. Differential pulse voltammetry was used for electrochemical detection, the separation of the oxidation peak potentials for AA-DA, DA-UA and UA-AA is about 188 mV, 144 mV and 332 mV, which allows selectively determining DA. The detection limit of DA can be as low as 0.01 μM. More importantly, the sensor we presented can detect DA in the presence of large excess of ascorbic acid and uric acid. With good sensitivity and selectivity, the present method was applied to the determination of DA in real hydrochloride injection sample, human urine and serum samples, respectively, and the results was satisfactory. Copyright © 2012 Elsevier B.V. All rights reserved.

Functional and Structural Characterization of a Thermostable Phospholipase A2 from a Sparidae Fish (Diplodus annularis).

PubMed

Smichi, Nabil; Othman, Houcemeddine; Achouri, Neila; Noiriel, Alexandre; Arondel, Vincent; Srairi-Abid, Najet; Abousalham, Abdelkarim; Gargouri, Youssef; Miled, Nabil; Fendri, Ahmed

2017-03-22

Novel phospholipase (PLA 2 ) genes from the Sparidae family were cloned. The sequenced PLA 2 revealed an identity with pancreatic PLA 2 group IB. To better understand the structure/function relationships of these enzymes and their evolution, the Diplodus annularis PLA 2 (DaPLA 2 ) was overexpressed in E. coli. The refolded enzyme was purified by Ni-affinity chromatography and has a molecular mass of 15 kDa as determined by MALDI-TOF spectrometry. Interestingly, unlike the pancreatic type, the DaPLA 2 was active and stable at higher temperatures, which suggests its great potential in biotechnological applications. The 3D structure of DaPLA 2 was constructed to gain insights into the functional properties of sparidae PLA 2 . Molecular docking and dynamic simulations were performed to explain the higher thermal stability and the substrate specificity of DaPLA 2 . Using the monolayer technique, the purified DaPLA 2 was found to be active on various phospholipids ranging from 10 to 20 mN·m -1 , which explained the absence of the hemolytic activity for DaPLA 2 .

Effects of aging and divided attention on episodic feeling-of-knowing accuracy.

PubMed

Sacher, Mathilde; Isingrini, Michel; Taconnat, Laurence

2013-10-01

This research investigated the effect of aging on episodic feeling-of-knowing (FOK) using a divided attention (DA) paradigm in order to examine whether DA in younger adults mimics the effects of aging when decreasing either memory encoding or monitoring processes. To that end, four groups of participants were tested on the FOK task: young adults (control group), young adults under DA at encoding, young adults under DA when making FOK judgments, and older adults. Our results showed that DA at encoding in young adults mimicked the effect of aging on memory performance, and also on FOK magnitude and accuracy, supporting the memory-constraint hypothesis (Hertzog et al., 2010). However, our results do not completely contradict the monitoring-deficit hypothesis, as DA during FOK judgments also affected FOK accuracy, but to a lesser extent than the aging effect or DA during encoding. We suggest that the age-related FOK deficit may be due to a lower level of deep encoding, leading to difficulty retrieving target-related contextual details enabling accurate prediction of subsequent recognition. © 2013.

DOE Office of Scientific and Technical Information (OSTI.GOV)

EL-Shamy, E. F., E-mail: emadel-shamy@hotmail.com; Department of Physics, College of Science, King Khalid University, P.O. 9004, Abha; Al-Asbali, A. M., E-mail: aliaa-ma@hotmail.com

A theoretical investigation is carried out to study the propagation and the head-on collision of dust-acoustic (DA) shock waves in a strongly coupled dusty plasma consisting of negative dust fluid, Maxwellian distributed electrons and ions. Applying the extended Poincaré–Lighthill–Kuo method, a couple of Korteweg–deVries–Burgers equations for describing DA shock waves are derived. This study is a first attempt to deduce the analytical phase shifts of DA shock waves after collision. The impacts of physical parameters such as the kinematic viscosity, the unperturbed electron-to-dust density ratio, parameter determining the effect of polarization force, the ion-to-electron temperature ratio, and the effective dustmore » temperature-to-ion temperature ratio on the structure and the collision of DA shock waves are examined. In addition, the results reveal the increase of the strength and the steepness of DA shock waves as the above mentioned parameters increase, which in turn leads to the increase of the phase shifts of DA shock waves after collision. The present model may be useful to describe the structure and the collision of DA shock waves in space and laboratory dusty plasmas.« less

IAP-Based Cell Sorting Results in Homogeneous Transplantable Dopaminergic Precursor Cells Derived from Human Pluripotent Stem Cells.

PubMed

Lehnen, Daniela; Barral, Serena; Cardoso, Tiago; Grealish, Shane; Heuer, Andreas; Smiyakin, Andrej; Kirkeby, Agnete; Kollet, Jutta; Cremer, Harold; Parmar, Malin; Bosio, Andreas; Knöbel, Sebastian

2017-10-10

Human pluripotent stem cell (hPSC)-derived mesencephalic dopaminergic (mesDA) neurons can relieve motor deficits in animal models of Parkinson's disease (PD). Clinical translation of differentiation protocols requires standardization of production procedures, and surface-marker-based cell sorting is considered instrumental for reproducible generation of defined cell products. Here, we demonstrate that integrin-associated protein (IAP) is a cell surface marker suitable for enrichment of hPSC-derived mesDA progenitor cells. Immunomagnetically sorted IAP + mesDA progenitors showed increased expression of ventral midbrain floor plate markers, lacked expression of pluripotency markers, and differentiated into mature dopaminergic (DA) neurons in vitro. Intrastriatal transplantation of IAP + cells sorted at day 16 of differentiation in a rat model of PD resulted in functional recovery. Grafts from sorted IAP + mesDA progenitors were more homogeneous in size and DA neuron density. Thus, we suggest IAP-based sorting for reproducible prospective enrichment of mesDA progenitor cells in clinical cell replacement strategies. Copyright © 2017 Miltenyi Biotec GmbH. Published by Elsevier Inc. All rights reserved.

Ebf2 is required for development of dopamine neurons in the midbrain periaqueductal gray matter of mouse.

PubMed

Yang, Qiaoqiao; Liu, Shuxi; Yin, Min; Yin, Yanqing; Zhou, Guomin; Zhou, Jiawei

2015-11-01

Dopaminergic (DA) neurons in the midbrain ventral periaqueductal gray matter (PAG) play critical roles in various physiological and pathophysiological processes including sleep-wake rhyme, antinociception, and drug addiction. However, the molecular mechanisms underlying their development are poorly understood. Here, we showed that PAG DA neurons arose as early as E15.5 in mouse embryos. During the prenatal period, the majority of PAG DA neurons was distributed in the intermediate and caudal regions of the PAG. In the postnatal brain, ∼50% of PAG DA neurons were preferentially located in the caudal portion of the PAG. Moreover, transcription factor early B-cell factor 2 (Ebf2) was transiently expressed in a subset of DA neurons in embryonic ventral mesencephalon. Functional analysis revealed that loss of Ebf2 in vivo caused a marked reduction in the number of DA neurons in the midbrain PAG but not in the substantia nigra and ventral tegmental area. Thus, Ebf2 is identified as a novel and important regulator selectively required for midbrain PAG DA neuron development. © 2015 Wiley Periodicals, Inc.

The neuroanatomic complexity of the CRF and DA systems and their interface: What we still don't know.

PubMed

Kelly, E A; Fudge, J L

2018-07-01

Corticotropin-releasing factor (CRF) is a neuropeptide that mediates the stress response. Long known to contribute to regulation of the adrenal stress response initiated in the hypothalamic-pituitary axis (HPA), a complex pattern of extrahypothalamic CRF expression is also described in rodents and primates. Cross-talk between the CRF and midbrain dopamine (DA) systems links the stress response to DA regulation. Classically CRF + cells in the extended amygdala and paraventricular nucleus (PVN) are considered the main source of this input, principally targeting the ventral tegmental area (VTA). However, the anatomic complexity of both the DA and CRF system has been increasingly elaborated in the last decade. The DA neurons are now recognized as having diverse molecular, connectional and physiologic properties, predicted by their anatomic location. At the same time, the broad distribution of CRF cells in the brain has been increasingly delineated using different species and techniques. Here, we review updated information on both CRF localization and newer conceptualizations of the DA system to reconsider the CRF-DA interface. Copyright © 2018 Elsevier Ltd. All rights reserved.