Percepção Astronômica de Alunos do Ensino Médio da Rede Estadual de São Paulo

NASA Astrophysics Data System (ADS)

de Oliveira, E. F.; Voelzke, M. R.; Amaral, L. H.

2005-08-01

Embora a astronomia seja uma das ciências mais antigas da humanidade e muitos dos conceitos astronômicos serem populares, principalmente nesta época de alta globalização do conhecimento por intermédio de eficientes meios de comunicação e de obtenção da informação, notadamente através da internet, observa-se que uma parcela significativa dos estudantes encontra-se à margem dessas informações. O presente trabalho visa analisar o nível de conhecimento básico dos alunos de Ensino Médio da rede estadual da cidade de Suzano quanto aos fenômenos astronômicos que os rodeiam, tais como a sucessão dos dias e das estações do ano, além de questioná-los sobre fatos genéricos tais como: quais são os astros que se encontram mais próximos do planeta Terra, o que vem a ser o Sol, o Big Bang, um ano-luz, uma estrela cadente, a estrela de Bélem e o que ocasionou a extinção dos dinossauros. Para tanto foi elaborado um formulário constando de questões de múltipla escolha, o qual foi aplicado no primeiro colegial noturno da Escola Estadual Batista Renzi. Num espaço amostral de 34 alunos constatou-se que apenas 29,4% compreendiam a sucessão dos dias da semana, que apenas 20,6% explicaram corretamente as estações do ano, que apenas 20,6% tinham idéia de quais são os objetos celestes mais próximos da Terra, em contraposição 67,6% sabiam classificar corretamente o Sol como estrela, 55,9% relacionavam o Big Bang à origem do universo, apenas 20,6% identificavam um ano-luz como unidade de distância, 32,4% reconheciam uma estrela cadente como meteoro, 41,2% consideravam a estrela de Belém como um cometa e 50,0% explicaram corretamente a extinção dos dinossauros. A presente análise será expandida para as demais classes de primeiro colegial, não somente do período noturno, mas também do diurno da Escola Estadual Batista Renzi, bem como o formulário será devidamente ampliado. Já nesta primeira fase nota-se claramente o pequeno discernimento de eventos astronômicos dos alunos e principalmente a grande confusão sobre o significado correto de termos astronômicos populares.

Age-related changes in bone architecture.

PubMed

Giordano, Vincenzo; Franco, José Sérgio; Koch, Hilton Augusto; Labronici, Pedro José; Pires, Robinson Esteves S; Amaral, Ney Pecegueiro DO

2016-01-01

: to evaluate the histologic and morphometric characteristics of bone biopsies of the anterior iliac crest of patients of different age groups. : we studied 30 bone samples from the iliac crest, using brightfield optical microscopy. We divided the samples by donors' age groups in three groups: Group 1 (n = 10), subjects aged between 25 and 39 years; Group 2 (n = 10), subjects aged between 40 and 64 years; Group 3 (n = 10), individuals aged 65 years and over. We randomly divided the samples into two sets with 15 specimens. In the first study segment (n = 15), we used histological to assess the osteogenic property of the graft, through the analysis of cell reserve in the periosteum, the number of osteocytes in the lacunae and the number of Haversian and Volkmann's canals. In the second study segment (n = 15), we investigated the morphology of osteoconductive property of the graft, through quantification of the trabecular meshwork (Vv) and trabecular area (Sv). : histologically, we observed degeneration of bone occurring with age, characterized by thinning of the periosteum, with gradual replacement of the steogenic layer by fibrous tissue, small amount of Haversian and Volkmann's canals, osteocyte lacunae voids and fine spongy bone trabeculae, allowing ample medullary space, usually occupied by fat cells and adipocytes. Morphologically, with respect to the quantification of the trabecular meshwork (Vv), we found statistically significant differences between Groups 1 and 3 and between Groups 2 and 3, with reduction of the trabecular meshwork of about 45% in the elderly over 65 years old ; there was no statistically significant difference between Groups 1 and 2. There was also no statistical difference between the Groups regarding Sv. : the results of this experiment suggest that, in the elderly (over 65 years old), the osteogenic property of autologous bone graft decreases and the osteoconductive property is compromised. avaliar as características histológicas e morfométricas de biópsias ósseas da região anterior da crista ilíaca de pacientes de diferentes faixas etárias. foram estudadas 30 amostras de osso da crista ilíaca, utilizando-se microscopia óptica de campo claro. As amostras foram divididas pela faixa etária dos doadores em três grupos: Grupo 1 (n = 10), indivíduos com idade entre 25 e 39 anos; Grupo 2 (n = 10), indivíduos com idade entre 40 e 64 anos; Grupo 3 (n = 10), indivíduos com idade igual ou superior a 65 anos. As amostras foram separadas aleatoriamente em dois conjuntos com 15 peças. No primeiro segmento do estudo (n = 15), foi avaliada histologicamente a propriedade osteogênica do enxerto, através da análise da reserva celular no periósteo, do número de osteócitos nas lacunas e da quantidade de canais de Havers e de Volkmann. No segundo segmento do estudo (n = 15), investigou-se morfologicamente a propriedade osteocondutora do enxerto, através da quantificação da rede trabecular (Vv) e da área trabecular (Sv). histologicamente, observou-se que ocorre degeneração do tecido ósseo com a idade, caracterizada pelo adelgaçamento do periósteo, com substituição gradual da camada osteogênica por tecido fibroso, pequena quantidade de canais de Havers e de Volkmann, osteoplastos vazios e trabéculas finas de osso esponjoso, permitindo amplo espaço medular, em geral ocupado por células lipídicas e adipócitos. Morfologicamente, com relação à quantificação da rede trabecular (Vv), foi observada diferença estatisticamente significante entre os Grupos 1 e 3 e entre os Grupos 2 e 3, com redução da rede trabecular de cerca de 45% no idoso acima de 65 anos de idade; não foi observada diferença estatisticamente significante entre os Grupos 1 e 2. Não foi observada diferença estatística entre os grupos quanto à Sv. os achados do presente experimento sugerem que nos indivíduos idosos (acima de 65 anos de idade), a propriedade osteogênica do enxerto ósseo autólogo diminui e a propriedade osteocondutora está comprometida.

Health education with older adults: action research with primary care professionals.

PubMed

Mendonça, Francielle Toniolo Nicodemos Furtado de; Santos, Álvaro da Silva; Buso, Ana Luisa Zanardo; Malaquias, Bruna Stephanie Sousa

2017-01-01

To assess the development and implementation of permanent education action. Quantitative-qualitative research based on action research in three phases (diagnosis of reality, implementation of activity and evaluation), performed with health professionals and managers of basic health units. The evaluation was on the perception of changes immediately following the activity and after 120 days. In the first phase, 110 professionals took part, 36.4% of whom indicated the existence of groups for older adults at work. In the second phase, 98 professionals participated, pointing out interferences of the group in the life of older adults, items of importance and facilitation in forming groups and developing reality-based activities. The third phase showed, in the quantitative analysis, positive impact of the training, and in the qualitative analysis, reassessment of groups, greater knowledge and confidence in managing groups and increased respect for older adults. Permanent education opens pathways for the construction of differentiated care for older adults based on respect and health promotion. Avaliar o desenvolvimento e implementação de uma ação de educação permanente. Pesquisa quantitativo-qualitativa baseada na pesquisa-ação em 3 fases (diagnóstico da realidade, implementação de atividade e avaliação), realizada com profissionais de saúde e gerentes de unidades básicas. A avaliação se deu pela percepção de mudanças imediatamente à atividade e após 120 dias. Na 1ª fase, participaram 110 profissionais, dos quais 36,4% apontaram a existência de grupos para idosos no trabalho. Na 2ª fase, participaram 98 profissionais, que apontaram interferências do grupo na vida do idoso, itens de importância e facilitação para construção de grupos e atividade baseada na realidade. A 3ª fase mostrou, na análise quantitativa, impacto positivo do treinamento; e, na qualitativa, releitura dos grupos e manejo com mais conhecimento, segurança e respeito ao idoso. A educação permanente abre caminhos para a construção da atenção diferenciada aos idosos pautada no respeito e na promoção da saúde.

Controle orbital de satélites artificiais com propulsão e uso de gravidade lunar

NASA Astrophysics Data System (ADS)

Torres, K. S.; de Almeida Prado, A. F. B.

2003-08-01

A redução do custo de combustível de uma manobra é atualmente a grande prioridade de todos os programas espaciais existentes no mundo. As manobras assistidas pela gravidade são uma ótima forma de se contornar o problema pois proporcionam economias com vasto impacto no custo final da missão. Neste trabalho é feito um estudo particular do controle orbital de um satélite artificial da Terra usando a gravidade da Lua. O objetivo é estudar uma técnica econômica para uma mudança de plano de um satélite que está em órbita em volta da Terra. A idéia principal desta abordagem é enviar primeiramente o veículo espacial em direção à Lua usando uma manobra mono-impulsiva para que assim o campo gravitacional da Lua possa fazer a mudança de plano desejada (sem custo de combustível) e só então retornar o veículo aos valores iniciais de semi-eixo e excentricidade usando uma manobra bi-impulsiva tipo Hohmann. Para tanto, é assumido que a espaçonave inicia em uma órbita circular coplanar à órbita da lua em torno da Terra e a meta é colocá-la em uma órbita similar que difere da órbita inicial somente pela inclinação. São usadas equações analíticas baseadas na abordagem Patched Conics para se calcular a variação na velocidade, momento angular, energia e inclinação do veículo espacial que realiza esta manobra. Várias simulações são feitas para se avaliar as economias de combustível envolvidas.

Análise da medição do raio solar em ultravioleta

NASA Astrophysics Data System (ADS)

Saraiva, A. C. V.; Giménez de Castro, C. G.; Costa, J. E. R.; Selhorst, C. L.; Simões, P. J. A.

2003-08-01

A medição acurada do raio solar em qualquer banda do espectro eletromagnético é de relevância na formulação e calibração de modelos da estrutura e atmosfera solar. Esses modelos atribuem emissão do contínuo do Sol calmo em microondas à mesma região da linha Ha do Hell. Apresentamos a medição do raio solar em UV com imagens do EIT (Extreme Ultraviolet Image Telescope) entre 1996 e 2002, no comprimento de onda 30,9 nm (Ha do Hell), que se forma na região de transição/cromosfera solar. A técnica utilizada para o cálculo do raio UV foi baseada na transformada Wavelet B3spline. Fizemos um banco de dados com 1 imagem por dia durante o período citado. Obtivemos como resultado o raio médio da ordem de 975.61" e uma diminuição do mesmo para o período citado variando em média -0,45" /ano. Comparamos estes dados com os valores obtidos pelo ROI (Radio Observatório de Itapetinga) em 22/48 GHz e Nobeyama Radio Heliograph em 17 GHz mostrando que os raios médios são muito próximos o que indica que a região de formação nessas freqüências é a mesma conforme os modelos. Comparamos os resultados também com outros índices de atividade solar.

A teoria da percolação aplicada às galáxias aneladas peculiares

NASA Astrophysics Data System (ADS)

Poppe, P. C. R.; Martin, V. A. F.; de Medeiros, N. G. F.; Faúndez-Abans, M.; Oliveira-Abans, M.

2003-08-01

Formulado no final da década de 50, o modelo de percolação concentra-se em descrever o meio poroso, que será visto neste trabalho como uma rede de canais aleatórios, por onde escoa um fluido determinístico. Se o número de canais for suficientemente grande, então eles estarão ligados e o meio se tornará permeável à passagem do fluido. Neste caso, dizemos que houve a percolação do fluido. Reformulando o modelo acima, podemos escrever um código particularmente adaptado para simulações em Galáxias, onde iremos supor que os canais formam um reticulado, e que cada sítio da rede representa um poro que será interpretado como uma região ativa de formação estelar. Para cada elo teremos um pequeno canal ligando dois sítios vizinhos, que poderá, após um tempo "t", induzir ou não a formação de uma região ativa no poro vizinho. Para simular a passagem desta região ativa através dos poros, diremos que um elo está aberto com probabilidade p e fechado com probabilidade 1-p. Dessa forma, passamos a imaginar configurações de elos abertos e fechados, onde cada configuração ocorre com uma certa probabilidade, dada por p|A|(1-p)|F|, onde |A| é o número de elos abertos e |F| o número de elos fechados da configuração. A expressão anterior só tem importância física se |A| e |F| forem ambos finitos, pois, caso contrário, a probabilidade de ocorrência de uma dada configuração será sempre nula. Neste trabalho, foram considerados dados cinemáticos publicados na literatura bem como aqueles obtidos pelos autores a partir de observações fotométricas realizadas no Observatório de Las Campanãs, em 1994, para a Galáxia Anelada Peculiar HRG 03401. Mostraremos que para certos valores de p, situados entre 0,5 e 0,6, os clusters assim formados irão simular, de maneira coerente, o referido objeto.

ANÁLISE DA INSERÇÃO DOS TEMAS DE HUMANIDADES E ÉTICA, COM METODOLOGIA DE APRENDIZAGEM BASEADA EM PROBLEMAS, EM CURRICULO MÉDICO INTEGRADO EM ESCOLA PÚBLICA NO DISTRITO FEDERAL, BRASIL

PubMed Central

Novaes, Maria Rita Carvalho Garbi; Novaes, Luiz Carlos Garcez; Guilhem, Dirce; Lolas, Fernando; Silveira, Carla; Guiotti, Murilo

2009-01-01

Objetivo Realizar uma análise da inserção da ética e humanidades no currículo do Curso de Medicina da Escola Superior em Ciências da Saúde - ESCS, escola pública do Distrito Federal, Brasil, de forma a contribuir com o processo de gestão curricular. Metodologia O Estudo é de coorte e documental. Foram pesquisados 37 termos relacionados à ética e 36 referentes à humanização nos objetivos educacionais e conteúdo dos módulos temáticos, habilidades e atitudes e interação ensino-serviço-comunidade, de 1a a 4a série e no programa do internato no currículo (ano 2006) e no projeto pedagógico do Curso de Medicina (2001). Resultados Maior inserção da humanização, ética e bioética na 1a e 2a série, quando comparado à inserção na 3a e 4a série e no internato, (IC95%-α=0,034, pvalue=0,007). Unidade de habilidades e atitudes: freqüência das 3 temáticas no currículo da 1a a 4a séries (IC95%-α=0,026, pvalue=0,013). Quando comparada a inserção entre o internato e as quatro primeiras séries, observa-se que nestas a inserção da temática humanização é superior (IC95%-α=0,042, pvalue=0,029). Conclusão O currículo desenvolvido no ano de 2006 na ESCS apresentou correlação com o projeto pedagógico do curso e contemplou a temática de forma abrangente, em todas as séries e internato. PMID:20396594

A distância e o conteúdo estelar da região HII gigante G333.1-0.4 - vínculos para a taxa de formação estelar da galáxia

NASA Astrophysics Data System (ADS)

Figuerêdo, E.; Damineli, A.; Blum, R.; Conti, P.

2003-08-01

Neste trabalho apresentamos imagens de alta resolução angular da região HII gigante G333.1-0.4 obtidas através dos filtros J, H e K no telescópio de 4-m do CTIO. Este trabalho faz parte de um estudo de regiões HII gigantes no infravermelho próximo que tem por objetivo estudar a natureza da formação de estrelas massivas e traçar a estrutura espiral de nossa galáxia. Nossa determinação da distância é baseada no método da paralaxe espectroscópica de estrelas OB localizadas na seqüência principal de idade zero (ZAMS) do Diagrama HR. No caso de G333.1-0.4, a magnitude aparente das estrelas localizadas na ZAMS indica que a distância não pode ser maior do que o limite inferior determinado por técnica rádio (2,8 kpc). Resultados semelhantes foram encontrados para regiões estudadas anteriormente, reforçando a idéia de que a taxa de formação estelar na Via Láctea é menor do que o determinado a partir de dados rádio. Nossos resultados mais recentes sobre o conteúdo estelar de G333.1-0.4 revelaram vários objetos que possuem cores bastante avermelhadas (H-K > 2,0). Nós identificamos estes objetos usando os diagramas cor-cor e cor-magnitude dos aglomerados. Estes objetos apresentam um forte excesso em emissão na banda K e possivelmente se tratam de estrelas do tipo OB envolvidas por um disco/envelope circumestelar espesso. O estudo da função de massa inical desta região, em conjunto com resultados de nossos trabalhos anteriores, aponta para uma IMF independente da posição galática. A contagem de estrelas nos fornece um valor para o número de fótons no contínuo de Lyman que corrobora com a afirmação de que G333.1-0.4 se encontra mais próxima da menor distância determinada por rádio.

Assessment on the ownership and use of mosquito nets in Mozambique.

PubMed

Arroz, Jorge Alexandre Harrison; Chirrute, Francisco; Mendis, Chandana; Chande, Marta Honesta; Kollhoff, Veronique

2016-12-22

To assess the ownership and use of mosquito nets in 2014, in Mozambique. This observational and cross-sectional study assessed, in February and March 2015, 69 districts (nine of 11 provinces of Mozambique) that have benefited from the mass distribution of mosquito nets. The Lot Quality Assurance Sampling methodology was used. Each locality was denominated supervision area. The Lot Quality Assurance Sampling opts for a minimum of 19 households (in this case, we decided for a minimum of 100 households per district) from each supervision area to assess an indicator (in this case, two indicators were assessed: ownership and use of mosquito nets). Two questions guided the research: a) received a mosquito net; b) used a mosquito net the night before. A total of 6,725 households were assessed. Eighty three percent of them had received mosquito nets in the campaign. Of the 6,232 respondents, 82.0% said they used mosquito nets the night before. The districts of the provinces with low coverage of ownership and use were Tete (69.5% and 60.0%, respectively), Zambezia (79.0% and 60.0%, respectively), and Gaza (81.6% and 70.7%, respectively). The largest coverage of ownership and use were observed in the districts of Nampula (96.7% and 93.8%, respectively) and Niassa (86.0% and 85.4% respectively). In the districts assessed, the progression of ownership and use of mosquito nets is satisfactory. Nampula and Niassa are the only provinces where ownership and use are at desired levels. Avaliar a posse e o uso das redes mosquiteiras no ano de 2014 em Moçambique. Este estudo observacional transversal avaliou, em fevereiro e março de 2015, 68 distritos (nove das 11 províncias de Moçambique) que se beneficiaram da distribuição de redes em massa. Usou-se a metodologia Lot Quality Assurance Sampling. Cada localidade foi designada de área de supervisão. O Lot Quality Assurance Sampling opta por um mínimo de 19 agregados familiares (neste caso decidiu-se um mínimo de 100 agregados familiares por distrito) de cada área de supervisão, a fim de avaliar um indicador (neste caso dois indicadores foram avaliados: posse e uso de redes mosquiteiras). Duas perguntas nortearam a pesquisa: a) recebeu rede; b) usou rede na noite anterior. Foram avaliados 6.725 agregados familiares . Desses, 83,0% tinham recebido redes na campanha. Dos 6.232 inqueridos, 82,0% disseram que usaram na noite anterior. As províncias com distritos com menores coberturas de posse e uso foram Tete (69,5% e 60,0%, respectivamente), Zambézia (79,0% e 60,0%, respectivamente) e Gaza (81,6% e 70,7%, respectivamente). As maiores coberturas de posse e uso foram observadas nos distritos de Nampula (96,7% e 93,8%, respectivamente) e Niassa (86,0% e 85,4%, respectivamente). Nos distritos avaliados, a progressão para a posse e uso de redes mosquiteiras é satisfatória. Nampula e Niassa são as únicas províncias onde a posse e o uso estão em níveis desejados.

RedeR: R/Bioconductor package for representing modular structures, nested networks and multiple levels of hierarchical associations

PubMed Central

2012-01-01

Visualization and analysis of molecular networks are both central to systems biology. However, there still exists a large technological gap between them, especially when assessing multiple network levels or hierarchies. Here we present RedeR, an R/Bioconductor package combined with a Java core engine for representing modular networks. The functionality of RedeR is demonstrated in two different scenarios: hierarchical and modular organization in gene co-expression networks and nested structures in time-course gene expression subnetworks. Our results demonstrate RedeR as a new framework to deal with the multiple network levels that are inherent to complex biological systems. RedeR is available from http://bioconductor.org/packages/release/bioc/html/RedeR.html. PMID:22531049

Atomic layer deposition of metal oxide by non-aqueous sol-gel chemistry =

NASA Astrophysics Data System (ADS)

Marichy, Catherine

O trabalho apresentado neste manuscrito foi desenvolvido no ambito do programa doutoral intitulado “Deposicao de Camadas Atomicas (ALD) de oxido de metais por sol-gel nao-aquoso”. O objectivo deste trabalho foi a preparacao de hetero-estruturas funcionais por ALD e a sua caracterizacao. Foi desenvolvido um novo processo de deposicao de oxido de estanho a temperatura baixa-moderada, utilizando um metodo ALD nao-aquoso, o qual foi aplicado com sucesso ao revestimento controlado das paredes internas e externas de nanotubos de carbono. Uma vez que a preparacao de nanomateriais funcionais requer uma elevada exatidao do processo de deposicao, foi demonstrada a deposicao precisa de filmes que se adaptem a forma do substrato ou de filmes nano-estruturados constituidos por particulas em varios substratos. Alem disso, foram depositados com grande exatidao varios oxidos de metal em nanotubos de carbono e demonstrou-se a possibilidade de ajustar o revestimento feito por ALD atraves do controlo da funcionalizacao da superficie do substrato nano-estruturado de carbono. As hetero-estruturas obtidas foram posteriormente aplicadas como sensores de gases. O melhoramento verificado na sensibilidade foi atribuido a formacao de heterojuncoes p-n entre o filme de oxido de metais e o suporte. O trabalho desenvolvido tendo como objetivo o controlo do revestimento por ALD atraves da funcionalizacao da superficie do suporte e certamente de interesse para o design de hetero-estruturas funcionais baseadas em substratos de carbono. De facto, durante o ultimo periodo do programa de doutoramento, este conceito foi alargado a funcionalizacao e revestimento com oxidos de metal de fibras de carbono preparadas por “electrospinning”, de forma a melhorar a estabilidade e a atividade eletrocatalitica de catalisadores a base de Pt. Este trabalho foi realizado maioritariamente na Universidade de Aveiro mas tambem na Universidade Nacional de Seul e beneficiou de varias colaboracoes internacionais devido a natureza multidisciplinar da area de investigacao em que esta inserido.

Quotidian of accompanying family members in an environment of care: the emergence of hospital tribes.

PubMed

Passos, Silvia da Silva Santos; Pereira, Álvaro; Nitschke, Rosane Gonçalves

2016-01-01

Compreender o relacionamento no quotidiano dos familiares acompanhantes nos cenários de cuidado que se aproximam da metáfora da tribo no ambiente hospitalar. Estudo qualitativo com dados coletados a partir de entrevistas semiestruturadas e observação com 16 familiares acompanhantes de pessoas hospitalizadas com dependência para o autocuidado. Os dados foram submetidos à análise temática e analisados através da metáfora da tribo proposta pela sociologia compreensiva. Os familiares formam um agrupamento social em torno do cuidado onde encontramos as características das tribos: a ambiência emocional; a solidariedade baseada nos vínculos de simpatia e ajuda mútua; a nebulosa afetual no processo interacional; a lógica da fusão nas relações tácteis e a comunhão/religiosidade no processo de ligação numa identidade coletiva. Os familiares na presença do trágico criam agrupamentos sociais que se assemelham a tribos cujo totem é o cuidado. Understand the quotidian relationships of accompanying family members in an environment of care, which are close to the metaphor of a tribe in hospital environment. METHODQualitative study with data gathered from semi-structured interviews and observations with 16 family members accompanying hospitalized individuals with dependence on self-care. Data were submitted to thematic analysis, and analyzed through the metaphor of "tribe" proposed by comprehensive sociology. Family members build up social clusters around caring, where we find traits typical of tribes: emotional ambience; solidarity based on links of sympathy and mutual assistance; an affectual nebula in the process of interaction; a logic of fusion in tactile relations; and communion/religiosity in the process of connecting in a collective identity. In the presence of tragedy, families build social clusters similar to tribes having care as a totem.

Developments in REDES: The rocket engine design expert system

NASA Technical Reports Server (NTRS)

Davidian, Kenneth O.

1990-01-01

The Rocket Engine Design Expert System (REDES) is being developed at the NASA-Lewis to collect, automate, and perpetuate the existing expertise of performing a comprehensive rocket engine analysis and design. Currently, REDES uses the rigorous JANNAF methodology to analyze the performance of the thrust chamber and perform computational studies of liquid rocket engine problems. The following computer codes were included in REDES: a gas properties program named GASP, a nozzle design program named RAO, a regenerative cooling channel performance evaluation code named RTE, and the JANNAF standard liquid rocket engine performance prediction code TDK (including performance evaluation modules ODE, ODK, TDE, TDK, and BLM). Computational analyses are being conducted by REDES to provide solutions to liquid rocket engine thrust chamber problems. REDES is built in the Knowledge Engineering Environment (KEE) expert system shell and runs on a Sun 4/110 computer.

Developments in REDES: The Rocket Engine Design Expert System

NASA Technical Reports Server (NTRS)

Davidian, Kenneth O.

1990-01-01

The Rocket Engine Design Expert System (REDES) was developed at NASA-Lewis to collect, automate, and perpetuate the existing expertise of performing a comprehensive rocket engine analysis and design. Currently, REDES uses the rigorous JANNAF methodology to analyze the performance of the thrust chamber and perform computational studies of liquid rocket engine problems. The following computer codes were included in REDES: a gas properties program named GASP; a nozzle design program named RAO; a regenerative cooling channel performance evaluation code named RTE; and the JANNAF standard liquid rocket engine performance prediction code TDK (including performance evaluation modules ODE, ODK, TDE, TDK, and BLM). Computational analyses are being conducted by REDES to provide solutions to liquid rocket engine thrust chamber problems. REDES was built in the Knowledge Engineering Environment (KEE) expert system shell and runs on a Sun 4/110 computer.

Experiences in the Family Health Strategy: demands and vulnerabilities in the territory.

PubMed

Pinto, Antonio Germane Alves; Jorge, Maria Salete Bessa; Marinho, Mirna Neyara Alexandre de Sá Barreto; Vidal, Emery Ciana Figueirêdo; Aquino, Priscila de Souza; Vidal, Eglídia Carla Figueirêdo

2017-01-01

To understand the daily demands of Family Health Strategy in clinical practice of the team and social vulnerabilities of community territory. Research with qualitative approach, in a critical-reflexive perspective, held with two teams of the Family Health Strategy, in the city of Fortaleza, State of Ceará, Brazil. The participants were 22 users and 19 health professionals from the basic health network. Data from the interviews and observation were analyzed under the assumptions of critical hermeneutics. We highlight the unveiling of sufferings and daily clashes, the influence of social determinants on health and psychosocial demands, limits and possibilities of everyday clinical practice. The clinic attention must recognize the perceptions and living conditions by listening and promoting health in the community. Compreender as demandas cotidianas da Estratégia Saúde da Família na prática clínica da equipe e as vulnerabilidades sociais do território comunitário. Pesquisa com abordagem qualitativa, numa perspectiva crítico-reflexiva, realizada com duas equipes da Estratégia Saúde da Família, no município de Fortaleza, Estado do Ceará, Brasil. Os participantes foram 22 usuários e 19 profissionais de saúde da rede básica de saúde. Os dados das entrevistas e observação foram analisados sob os pressupostos da hermenêutica crítica. Evidenciam-se o desvelamento de sofrimentos e enfrentamentos cotidianos, a influência dos determinantes sociais na saúde e as demandas psicossociais, limites e possibilidades da prática clínica cotidiana. Considera-se que a atenção clínica deve reconhecer as percepções e condições de vida pela escuta e ações de promoção de saúde na comunidade.

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

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.

United States Air Force Statistical Digest, Fiscal Year 1962, Seventeenth Edition

DTIC Science & Technology

1962-09-30

belOW’Is a revision of ’lable 44, FY 1961 GAINS Not Beyond Eco From TYPE, M:lDEL, AND SERIES Pro- MAP, From Redes - Com-Total due- USA, Other i_- Total... Redes - mer- ebec- Recla-tion and t10n i_- cia! lete ma- USN tion Sale t10n ..FIR8l’ ’HALF FY 1962 (1 July W& . . ill 446 18 20 ~ 1,451 281 8 1 .21...LOSSES BY TV e; --- GAINS 110’ .7ŕ’" Eco From TYPE, MODEL, ANDSERlES; Pro- MAP, From Redes - Com- Total duc- USA, other tgne- Total Redes - A>_ Hecla.t10n

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

Band Gap Transition Studies of U:ThO2 Using Cathodoluminescence

DTIC Science & Technology

2014-03-27

BAND GAP TRANSITION STUDIES OF U:THO2 USING CATHODOLUMINESCENCE THESIS Joshua D. Reding , Second Lieutenant, USAF AFIT-ENP-14-M-31 DEPARTMENT OF THE...Education and Training Command in Partial Fulfillment of the Requirements for the Degree of Master of Science in Applied Physics Joshua D. Reding , B.S...STUDIES OF U:THO2 USING CATHODOLUMINESCENCE Joshua D. Reding , B.S. Second Lieutenant, USAF Approved: //signed// Robert L. Hengehold, PhD (Chair) //signed

Redes En Acción. Increasing Hispanic participation in cancer research, training, and awareness.

PubMed

Ramirez, Amelie G; Talavera, Gregory A; Marti, Jose; Penedo, Frank J; Medrano, Martha A; Giachello, Aida L; Pérez-Stable, Eliseo J

2006-10-15

Hispanics are affected by many health care disparities. The National Cancer Institute (NCI), through its Special Populations Branch, is supporting networking and capacity-building activities designed to increase Hispanic participation and leadership in cancer research. Redes En Acción established a national network of cancer research centers, community-based organizations, and federal partners to facilitate opportunities for junior Hispanic scientists to participate in training and research projects on cancer control. Since 2000, Redes En Acción has established a network of more than 1800 Hispanic leaders involved in cancer research and education. The project has sustained 131 training positions and submitted 29 pilot projects to NCI for review, with 16 awards for a total of $800,000, plus an additional $8.8 million in competing grant funding based on pilot study results to date. Independent research has leveraged an additional $32 million in non-Redes funding, and together the national and regional network sites have participated in more than 1400 community and professional awareness events. In addition, the program conducted extensive national survey research that provided the basis for the Redes En Acción Latino Cancer Report, a national agenda on Hispanic cancer issues. Redes En Acción has increased participation in cancer control research, training, and awareness among Hispanic scientists and within Hispanic communities. Cancer 2006. (c) 2006 American Cancer Society.

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.

Western Foreign Fighters in Syria: An Empirical Analysis of Recruitment and Mobilization Mechanisms

DTIC Science & Technology

2015-06-01

Malet, Foreign Fighters, 5. 16 Ibid., 4–6. 17 See for example Ines von Behr, Anaïs Reding , Charlie Edwards, and Luke Gribbon, “Radicalization in the...summary see Ines von Behr, Anaïs Reding , Charlie Edwards, and Luke Gribbon, “Radicalization in the Digital Era: The Use of the Internet in 15 Cases of...12; <http://www.lexisnexis.com.libproxy.nps.edu/hottopics/lnacademic> [April 11, 2015]. 134 von Behr, Reding , Edwards, and Gribbon

Eventos de Desconexao na Cauda de Plasma do Cometa P/Halley

NASA Astrophysics Data System (ADS)

Voelzke, M. R.; Fahr, H. J.

2001-08-01

Observacoes cometárias e de vento solar sao comparadas com o propósito de determinar-se as condicoes do vento solar associadas aos eventos de desconexao (DEs) observados em caudas de plasma cometárias. Os dados cometários sao provenientes do The International Halley Watch Atlas of Large-Scale Phenomena. A análise visual sistemática das imagens do atlas revelou, entre outras estruturas morfológicas, 47 DEs ao longo da cauda de plasma do P/Halley. Estes 47 DEs registrados em 47 imagens distintas permitiram a descoberta de 19 origens de DEs, ou seja, o tempo em que as desconexoes iniciaram foi calculado. Os dados do vento solar sao provenientes de medidas feitas in situ pela sonda espacial IMP-8, as quais foram usadas para elaborar a variacao da velocidade do vento solar, densidade e pressao dinâmica durante o intervalo analisado. O presente trabalho compara as atuais teorias conflitantes, baseadas nos mecanismos de formacao, com o intuito de explicar o fenômeno cíclico dos DEs, ou seja, os efeitos de producao iônica, os efeitos de pressao e os efeitos de reconexao magnética sao analisados. Para cada uma das 19 origens de DEs comparou-se a densidade com a respectiva velocidade do vento solar com o intuito de determinar-se uma possível correlacao entre estas origens e os efeitos de pressao dinâmica. Quando da ocorrência de 6 origens de DEs o IMP-8 nao realizou medidas, nos outros 13 casos 10 origens (77%) mostraram uma anticorrelacao entre velocidade e densidade e apenas 3 (23%) revelaram uma tendência similar entre velocidade e densidade. Portanto, a análise inicial demonstra uma fraca correlacao entre as origens dos DEs e os efeitos de pressao.

Topic 1.1.2, Unsteady Aerodynamics: Time-Varying Compressible Dynamic Stall Mechanisms Due to Freestream Mach Oscillations

DTIC Science & Technology

2014-12-31

separation during the pitch-up motion – thus interrupting the vortex shedding that is characteristic of deep dynamic stall (Ericsson and Reding , 1984). The...Aircraft, Vol. 31, No. 4, pp. 782-786. Ericsson, L. E. and Reding , J. P., (1971) “Dynamic Stall Simulation Problems,” Journal of Aircraft, Vol. 8, No...7, pp. 579-583. Ericsson, L. E. and Reding , J. P., (1984) “Shock-Induced Dynamic Stall,” Journal of Aircraft, Vol. 21, No. 5, pp. 316-321. Favier

The family experience of care in chronic situation.

PubMed

Bellato, Roseney; Araújo, Laura Filomena Santos de; Dolina, Janderléia Valéria; Musquim, Cleciene Dos Anjos; Corrêa, Geovana Hagata de Lima Souza Thaines

2016-06-01

An essay that aims to reflect on the family experience of care in chronic situation, increasing the understanding of the family as the primary caregiver. It is based on comprehensive approach in studies conducted in three matrix searches from family care experiences. We have taken three axes to organize our reflections: a) conformation of family care in chronic situation, highlighting the multiple costs incurred to the family, which can exhaust the potential of care and establish or increase its vulnerability if it is not backed by networks support and sustenance; b) family rearrangements for the care, giving visibility to care cores in which many loved family members share the care, dynamic, plural and changeable way; c) self care modeling family care, pointing to the range of possibilities of the person taking care of diseased conditions supported by people close to them. We learn that the family takes care of itself in everyday life and in the illness experience, creating networks that can provide you support and sustenance. Thus, professionals in health practices should shape up in a longitudinal and very personal way, by reference to the family care, supporting him in what is his own. Ensaio que tem por objetivo refletir sobre a experiência familiar de cuidado na situação crônica, ampliando a compreensão da família como cuidadora primária. Embasa-se em estudos de abordagem compreensiva realizados em três pesquisas matriciais que abordaram experiências familiares de cuidado. Tomamos três eixos para organizar nossas reflexões: a) conformação do cuidado familiar na situação crônica, destacando os múltiplos custos gerados à família, que podem exaurir seus potenciais de cuidado, instaurando ou ampliando sua vulnerabilidade se não for amparada por redes de apoio e sustentação; b) rearranjos familiares para o cuidado, dando visibilidade aos núcleos de cuidado compartilhados pelos diversos entes familiares, de modo dinâmico, plural e mutável; c) cuidado próprio modelando o cuidado familiar, apontando a gama de condições de possibilidades da pessoa adoecida se cuidar apoiada pelas pessoas que lhe são próximas. Compreendemos que a família cuida de si e de seus entes no bojo da vida, assim como na experiência de adoecimento, tecendo redes que a sustentem ao longo do tempo. As práticas profissionais em saúde precisam modelar-se, então, tendo por referência o cuidado familiar, amparando-o naquilo que lhe seja próprio.

76 FR 59180 - Agency Information Collection Activities: Proposed Request and Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-23

... criteria. Respondents complete Form SSA-1026-REDE under the following circumstances: (1) When individuals...,420 SSA-1026-OCR-SM-REDE 225,000 1 18 67,500 Total 236,400 70,920 II. SSA submitted the information...

Spin-Transfer-Torque Nano-Oscillators: Fabrication, Characterization and Dynamics

NASA Astrophysics Data System (ADS)

Costa, Jose Diogo Teixeira Barbosa

Este trabalho aborda algumas propriedades magneticas e estruturais de nanoparticulas de oxidos e oxidos-hidroxidos de ferro crescidos em matrizes hibridas orgânicas-inorgânicas. As matrizes hibridas, denominadas di-ureasils e obtidas pelo processo sol-gel, sao compostas por uma rede siliciosa ligada covalentemente por pontes ureia a cadeias orgânicas de diferente peso molecular. A estrutura local dos di-ureasils nao dopados esta modelada como grupos de dominios siliciosos com dimensoes nanometricas, estruturalmente correlacionados no seio de uma matriz rica em polimero. Neste trabalho mostra-se que os di-ureasils permitem o crescimento controlado de oxidos e oxidos-hidroxidos de ferro, incluindo a magnetite, maguemite, oxihidroxinitrato de ferro e ferrihidrite. O crescimento das nanoparticulas de ferrihidrite da-se em condicoes acidas a superficie dos dominios siliciosos, junto aos grupos carbonilo, que funcionam como pontos de nucleacao. Desse modo da-se uma nucleacao heterogenea, onde o tamanho das nanoparticulas depende da concentracao de ferro (entre 1 e 6% em massa), sendo a concentracao de particulas constante. As propriedades magneticas das nanoparticulas de ferrihidrite revelam a existencia de interaccoes antiferromagneticas e de momentos descompensados. A contribuicao destas duas componentes nas curvas de magnetizacao em funcao do campo magnetico pode ser separada usando um metodo aqui proposto, o que permite um adequado estudo da evolucao do momento magnetico com a temperatura. O estudo das propriedades magneticas dinâmicas das particulas de ferrihidrite, atraves de susceptibilidade ac, medidas de relaxacao e medidas de efeito Mossbauer, permitiu estudar a evolucao das interaccoes dipolares em funcao da concentracao de ferro, bem como determinar a distribuicao de barreiras de energia de anisotropia no caso em que essas interaccoes sao desprezaveis. E apresentado um novo metodo para comparacao desta distribuicao com a distribuicao de tamanhos, que permitiu concluir que os momentos magneticos descompensados estao aleatoriamente distribuidos em volume. Usando baixas concentracoes de agua, foi possivel crescer fases de oxihidroxinitrato de ferro com diferentes graus de cristalinidade, sendo algumas precursoras da ferrihidrite (como observado noutros trabalhos) e sendo outras novas fases. O crescimento de nanoparticulas de maguemite e magnetite acontece apos incorporacao de ioes de Fe2+ e Fe3+ seguidos de tratamento basico e termico. Estes sistemas apresentam propriedades magneticas tipicas de nanoparticulas superparamagneticas sem interaccoes dipolares. As propriedades magneticas dependem criticamente da existencia de grupos isocianato livres, que actuarao como pontos de nucleacao. None

Structural and Magnetic Studies on Iron Oxide Nanoparticles in Hybrid Matrices =

NASA Astrophysics Data System (ADS)

Silva, Nuno Joao de Oliveira

Este trabalho aborda algumas propriedades magneticas e estruturais de nanoparticulas de oxidos e oxidos-hidroxidos de ferro crescidos em matrizes hibridas orgânicas-inorgânicas. As matrizes hibridas, denominadas di-ureasils e obtidas pelo processo sol-gel, sao compostas por uma rede siliciosa ligada covalentemente por pontes ureia a cadeias orgânicas de diferente peso molecular. A estrutura local dos di-ureasils nao dopados esta modelada como grupos de dominios siliciosos com dimensoes nanometricas, estruturalmente correlacionados no seio de uma matriz rica em polimero. Neste trabalho mostra-se que os di-ureasils permitem o crescimento controlado de oxidos e oxidos-hidroxidos de ferro, incluindo a magnetite, maguemite, oxihidroxinitrato de ferro e ferrihidrite. O crescimento das nanoparticulas de ferrihidrite da-se em condicoes acidas a superficie dos dominios siliciosos, junto aos grupos carbonilo, que funcionam como pontos de nucleacao. Desse modo da-se uma nucleacao heterogenea, onde o tamanho das nanoparticulas depende da concentracao de ferro (entre 1 e 6% em massa), sendo a concentracao de particulas constante. As propriedades magneticas das nanoparticulas de ferrihidrite revelam a existencia de interaccoes antiferromagneticas e de momentos descompensados. A contribuicao destas duas componentes nas curvas de magnetizacao em funcao do campo magnetico pode ser separada usando um metodo aqui proposto, o que permite um adequado estudo da evolucao do momento magnetico com a temperatura. O estudo das propriedades magneticas dinâmicas das particulas de ferrihidrite, atraves de susceptibilidade ac, medidas de relaxacao e medidas de efeito Mossbauer, permitiu estudar a evolucao das interaccoes dipolares em funcao da concentracao de ferro, bem como determinar a distribuicao de barreiras de energia de anisotropia no caso em que essas interaccoes sao desprezaveis. E apresentado um novo metodo para comparacao desta distribuicao com a distribuicao de tamanhos, que permitiu concluir que os momentos magneticos descompensados estao aleatoriamente distribuidos em volume. Usando baixas concentracoes de agua, foi possivel crescer fases de oxihidroxinitrato de ferro com diferentes graus de cristalinidade, sendo algumas precursoras da ferrihidrite (como observado noutros trabalhos) e sendo outras novas fases. O crescimento de nanoparticulas de maguemite e magnetite acontece apos incorporacao de ioes de Fe2+ e Fe3+ seguidos de tratamento basico e termico. Estes sistemas apresentam propriedades magneticas tipicas de nanoparticulas superparamagneticas sem interaccoes dipolares. As propriedades magneticas dependem criticamente da existencia de grupos isocianato livres, que actuarao como pontos de nucleacao. None

Procedures for measuring and verifying gastric tube placement in newborns: an integrative review.

PubMed

Dias, Flávia de Souza Barbosa; Emidio, Suellen Cristina Dias; Lopes, Maria Helena Baena de Moraes; Shimo, Antonieta Keiko Kakuda; Beck, Ana Raquel Medeiros; Carmona, Elenice Valentim

2017-07-10

to investigate evidence in the literature on procedures for measuring gastric tube insertion in newborns and verifying its placement, using alternative procedures to radiological examination. an integrative review of the literature carried out in the Cochrane, LILACS, CINAHL, EMBASE, MEDLINE and Scopus databases using the descriptors "Intubation, gastrointestinal" and "newborns" in original articles. seventeen publications were included and categorized as "measuring method" or "technique for verifying placement". Regarding measuring methods, the measurements of two morphological distances and the application of two formulas, one based on weight and another based on height, were found. Regarding the techniques for assessing placement, the following were found: electromagnetic tracing, diaphragm electrical activity, CO2 detection, indigo carmine solution, epigastrium auscultation, gastric secretion aspiration, color inspection, and evaluation of pH, enzymes and bilirubin. the measuring method using nose to earlobe to a point midway between the xiphoid process and the umbilicus measurement presents the best evidence. Equations based on weight and height need to be experimentally tested. The return of secretion into the tube aspiration, color assessment and secretion pH are reliable indicators to identify gastric tube placement, and are the currently indicated techniques. investigar, na literatura, evidências sobre procedimentos de mensuração da sonda gástrica em recém-nascidos e de verificação do seu posicionamento, procedimentos alternativos ao exame radiológico. revisão integrativa da literatura nas bases Biblioteca Cochrane, LILACS, CINAHL, EMBASE, MEDLINE e Scopus, utilizando os descritores "intubação gastrointestinal" e "recém-nascido" em artigos originais. dezessete publicações foram incluídas e categorizadas em "método de mensuração" ou "técnica de verificação do posicionamento". Como métodos de mensuração, foram encontrados os de tomada de duas distâncias morfológicas e os de aplicação de duas fórmulas, uma baseada no peso e outra na altura. Para técnicas de verificação do posicionamento, encontrou-se traçado eletromagnético, atividade elétrica do diafragma, detecção de CO2, solução de índigo carmim, ausculta do epigástrio, aspiração de secreção gástrica, inspeção da cor, avaliação de pH, enzimas e bilirrubina. o método de mensuração que utiliza as medidas do nariz ao lóbulo da orelha ao ponto médio entre apêndice xifoide e cicatriz umbilical apresenta melhores evidências. As equações baseadas em peso e altura necessitam ser testadas experimentalmente. O retorno de secreção na aspiração da sonda, avaliação da cor e do pH da secreção são indicadores confiáveis na identificação do posicionamento da sonda gástrica, e são as técnicas atualmente indicadas. investigar, en la literatura, evidencias sobre procedimientos de medición de la sonda gástrica en recién nacidos y de verificación de su posicionamiento, procedimientos alternativos al examen radiológico. revisión integradora de la literatura en las bases Biblioteca Cochrane, LILACS, CINAHL, EMBASE, MEDLINE y Scopus, utilizando los descriptores "intubación gastrointestinal" y "recién nacido" en artículos originales. diecisiete publicaciones fueron incluidas y categorizadas en "método de medición" o "técnica de verificación del posicionamiento". Como métodos de medición, fueron encontrados los de medida de dos distancias morfológicas y los de aplicación de dos fórmulas (una basada en el peso y otra en la altura). Para las técnicas de verificación del posicionamiento, se encontró: trazado electromagnético, actividad eléctrica del diafragma, detección de CO2, solución de índigo carmín, auscultación del epigastrio, aspiración de secreción gástrica, inspección del color, evaluación de pH, enzimas y bilirrubina. el método de medición que utiliza las medidas de la nariz al lóbulo de la oreja al punto medio entre apéndice xifoideo y cicatriz umbilical, presenta las mejores evidencias. Las ecuaciones basadas en peso y altura necesitan ser comprobadas experimentalmente. El retorno de secreción en la aspiración de la sonda, evaluación del color y del pH de la secreción son indicadores confiables en la identificación del posicionamiento de la sonda gástrica, y son las técnicas actualmente indicadas.

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.

Improvement of nursing students' learning outcomes through scenario-based skills training.

PubMed

Uysal, Nurcan

2016-08-08

this study analyzed the influence of scenario-based skills training on students' learning skills. the author evaluated the nursing skills laboratory exam papers of 605 sophomores in nursing programs for seven years. The study determined the common mistakes of students and the laboratory work was designed in a scenario-based format. The effectiveness of this method was evaluated by assessing the number of errors the students committed and their achievement scores in laboratory examinations. This study presents the students' common mistakes in intramuscular and subcutaneous injection and their development of intravenous access skills, included in the nursing skills laboratory examination. an analysis of the students' most common mistakes revealed that the most common was not following the principles of asepsis for all three skills (intramuscular, subcutaneous injection, intravenous access) in the first year of the scenario-based training. The students' exam achievement scores increased gradually, except in the fall semester of the academic year 2009-2010. The study found that the scenario-based skills training reduced students' common mistakes in examinations and enhanced their performance on exams. this method received a positive response from both students and instructors. The scenario-based training is available for use in addition to other skills training methods. en este estudio fue analizada la influencia de la capacitación basada en escenarios en las capacidades de aprendizaje de los alumnos. el autor evaluó los textos de exámenes de laboratorio de habilidades de enfermería producidos por 605 alumnos de segundo año en cursos de enfermería durante siete años. El estudio determinó los errores comunes de los alumnos y el trabajo en laboratorio adoptó el formato basado en escenarios. La eficacia de ese método fue evaluada mediante la cantidad de errores que los alumnos cometieron y sus notas de desempeño en exámenes de laboratorio. Este estudio presenta los errores comunes de los alumnos en la ejecución de inyecciones intramuscular y subcutánea y su desarrollo de capacidades de acceso intravenoso, tratadas en el examen de laboratorio de habilidades de enfermería. un análisis de los errores más comunes de los alumnos reveló que el más común fue el no seguimiento de los principios de asepsia para las tres habilidades ((intramuscular, inyección subcutánea, acceso intravenoso) en el primer año de la capacitación basada en escenarios. Las notas de desempeño de los alumnos en la prueba aumentaron gradualmente, excepto en el semestre de otoño del año académico 2009-2010. Fue observado que la capacitación basada en escenarios redujo los errores comunes de los alumnos en los exámenes y aumentó su desempeño en las pruebas. tanto los alumnos como los profesores respondieron positivamente a ese método. La capacitación basada en escenarios está disponible para uso en combinación con otros métodos de capacitación. neste estudo se analisou a influência da formação de capacidades baseada em cenários nas capacidades de aprendizagem de alunos. o autor avaliou os textos de exames de laboratório de habilidades de enfermagem produzidos por 605 alunos de segundo ano em cursos de enfermagem durante sete anos. O estudo determinou os erros comuns dos alunos e o trabalho em laboratório adotou o formato baseado em cenários. A eficácia desse método foi avaliada mediante o número de erros que os alunos cometeram e suas notas de desempenho em exames de laboratório. Este estudo apresenta os erros comuns dos alunos na execução de injeções intramuscular e subcutânea e seu desenvolvimento de habilidades de acesso intravenoso, tratadas no exame de laboratório de habilidades de enfermagem. uma análise dos erros mais comuns dos alunos revelou que o mais comum foi o não seguimento dos princípios de assepsia para as três habilidades (intramuscular, injeção subcutânea, acesso intravenoso) no primeiro ano da capacitação baseada em cenários. As notas de desempenho dos alunos no exame aumentaram gradualmente, exceto no semestre de outono do ano académico 2009-2010. Observou-se que a capacitação baseada em cenários reduziu os erros comuns dos alunos nos exames e aumentou seu desempenho nas provas. tanto os alunos como os professores responderam positivamente a esse método. A capacitação baseada em cenários está disponível para uso em combinação com outros métodos de capacitação.

Association of tuberculosis with multimorbidity and social networks.

PubMed

Valenzuela-Jiménez, Hiram; Manrique-Hernández, Edgar Fabian; Idrovo, Alvaro Javier

2017-01-01

The combination of tuberculosis with other diseases can affect tuberculosis treatment within populations. In the present study, social network analysis of data retrieved from the Mexican National Epidemiological Surveillance System was used in order to explore associations between the number of contacts and multimorbidity. The node degree was calculated for each individual with tuberculosis and included information from 242 contacts without tuberculosis. Multimorbidity was identified in 49.89% of individuals. The node degrees were highest for individuals with tuberculosis + HIV infection (p < 0.04) and lowest for those with tuberculosis + pulmonary edema (p < 0.07). Social network analysis should be used as a standard method for monitoring tuberculosis and tuberculosis-related syndemics. RESUMO A combinação de tuberculose e outras doenças pode afetar o tratamento da tuberculose nas populações. No presente estudo, a análise de redes sociais de dados extraídos do Sistema Nacional de Vigilância Epidemiológica do México foi usada para explorar as relações entre o número de contatos e a multimorbidade. O grau do nó foi calculado para cada indivíduo com tuberculose e incluiu informações a respeito de 242 contatos sem tuberculose. A multimorbidade foi identificada em 49,89% dos indivíduos. Os maiores graus dos nós foram os referentes a indivíduos com tuberculose + infecção pelo HIV (p < 0,04), e os menores foram os referentes a indivíduos com tuberculose + edema pulmonar (p < 0,07). A análise de redes sociais deve ser usada como método-padrão para monitorar a tuberculose e a sindemia relacionada com a tuberculose.

Particulate Meso-scale Mechanics Diagnostics: Magnetic Sensors for Dynamic State Orientation

DTIC Science & Technology

2013-12-01

Research Laboratory for giving this opportunity to work at the Eglin AFB, FL. REFERENCES 1. Brian D. Reding , “Development of Particulate Materials...Measurements," Sandia Report, 1984. 15. I.N. Tansel, B. Reding , W. L. Cooper, “Lagrangian Point State Estimation with Optimized, Redundant Induction Coil

An Evaluation of the Implementation and Perceived Utility of the Airman Resilience Training Program

DTIC Science & Technology

2014-01-01

and participating in structured activities.4 The participant felt that this was an ideal time to address the rede - ployment integration stress topics...Utility of the Airman Resilience Training Program Another staff member asserted that it was important to normalize symptoms of rede - ployment integration

Nursing supervision for care comprehensiveness.

PubMed

Chaves, Lucieli Dias Pedreschi; Mininel, Vivian Aline; Silva, Jaqueline Alcântara Marcelino da; Alves, Larissa Roberta; Silva, Maria Ferreira da; Camelo, Silvia Helena Henriques

2017-01-01

To reflect on nursing supervision as a management tool for care comprehensiveness by nurses, considering its potential and limits in the current scenario. A reflective study based on discourse about nursing supervision, presenting theoretical and practical concepts and approaches. Limits on the exercise of supervision are related to the organization of healthcare services based on the functional and clinical model of care, in addition to possible gaps in the nurse training process and work overload. Regarding the potential, researchers emphasize that supervision is a tool for coordinating care and management actions, which may favor care comprehensiveness, and stimulate positive attitudes toward cooperation and contribution within teams, co-responsibility, and educational development at work. Nursing supervision may help enhance care comprehensiveness by implying continuous reflection on including the dynamics of the healthcare work process and user needs in care networks. refletir a supervisão de enfermagem como instrumento gerencial do enfermeiro para integralidade do cuidado, considerando suas potencialidades e limitações no cenário atual. estudo reflexivo baseado na formulação discursiva sobre a supervisão de enfermagem, apresentando conceitos e enfoques teóricos e/ou práticos. limitações no exercício da supervisão estão relacionadas à organização dos serviços de saúde embasada no modelo funcional e clínico de atenção, assim como possíveis lacunas no processo de formação do enfermeiro e sobrecarga de trabalho. Quanto às potencialidades, destaca-se a supervisão como instrumento de articulação de ações assistenciais e gerenciais, que pode favorecer integralidade da atenção, estimular atitudes de cooperação e colaboração em equipe, além da corresponsabilização e promoção da educação no trabalho. supervisão de enfermagem pode contribuir para fortalecimento da integralidade do cuidado, pressupondo reflexão contínua, para contemplar a dinamicidade do processo de trabalho em saúde e necessidades dos usuários nas redes de atenção.

Análise sobre o Conhecimento de um Grupo de Alunos do Ensino Médio da Rede Estadual de São Paulo sobre Termos e Fenômenos Astronômicos do Cotidiano

NASA Astrophysics Data System (ADS)

de Oliveira, E. F.; Voelzke, M. R.; Amaral, L. H.

2007-08-01

Embora os Parâmetros Curriculares Nacionais do Ensino Médio (PCN-EM) e as orientações complementares a esses Parâmetros (PCN+) apontem a importância de uma abordagem significativa de conceitos relacionados à astronomia nas aulas de Física, muitos estudantes terminam o Ensino Médio (EM) sem compreender a razão de certos acontecimentos de origem celeste, ainda que estes façam parte de seu cotidiano. Este trabalho tem por objetivo analisar os conhecimentos básicos em astronomia dos alunos de EM da escola estadual Batista Renzi, bem como investigar os meios através dos quais estes conhecimentos foram adquiridos. Para tanto foi elaborado um questionário de múltipla escolha aplicado a 310 alunos distribuídos entre as três séries do EM dos períodos matutino e noturno. Dessa forma, observou-se que apenas 34,5% relacionaram as estações do ano à inclinação do eixo de rotação da Terra, 21,3% indicaram a influência gravitacional da Lua e do Sol como responsáveis pelo fenômeno das marés, 24,5% indicaram corretamente quais são os objetos celestes mais próximos da Terra, 36,1% identificaram ano-luz como uma medida de distância e 34,2% reconheceram uma estrela cadente como meteoro. Em contrapartida, 67,1% compreendiam a sucessão entre dia e noite, 73,9% identificaram o Sol como estrela e 52,3% relacionaram o Big Bang à origem do Universo. Além disso, foram comparadas as respostas de alunos de diferentes séries e períodos, observando-se, dentre outras coisas, que os estudantes do terceiro ano apresentam um percentual de acertos semelhante ao dos alunos do primeiro, caracterizando que a abordagem de tópicos relacionados à astronomia no EM não tem contribuído para uma maior compreensão dos fenômenos e conceitos.

RedeAmericas: building research capacity in young leaders for sustainable growth in community mental health services in Latin America.

PubMed

Yang, L; Pratt, C; Valencia, E; Conover, S; Fernández, R; Burrone, M S; Cavalcanti, M T; Lovisi, G; Rojas, G; Alvarado, R; Galea, S; Price, L N; Susser, E

2017-01-01

The purpose of this paper is to describe the development and initial accomplishments of a training program of young leaders in community mental health research as part of a Latin American initiative known as RedeAmericas. RedeAmericas was one of five regional 'Hubs' funded by the National Institute of Mental Health (NIMH) to improve community mental health care and build mental health research capacity in low- and middle-income countries. It included investigators in six Latin American cities - Santiago, Chile; Medellín, Colombia; Rio de Janeiro, Brazil; and Córdoba, Neuquén, and Buenos Aires in Argentina - working together with a team affiliated with the Global Mental Health program at Columbia University in New York City. One component of RedeAmericas was a capacity-building effort that included an Awardee program for early career researchers in the mental health field. We review the aims of this component, how it developed, and what was learned that would be useful for future capacity-building efforts, and also comment on future prospects for maintaining this type of effort.

Data Sharing: A New Editorial Initiative of the International Committee of Medical Journal Editors. Implications for the Editors´ Network.

PubMed

Alfonso, Fernando; Adamyan, Karlen; Artigou, Jean-Yves; Aschermann, Michael; Boehm, Michael; Buendia, Alfonso; Chu, Pao-Hsien; Cohen, Ariel; Cas, Livio Dei; Dilic, Mirza; Doubell, Anton; Echeverri, Dario; Enç, Nuray; Ferreira-González, Ignacio; Filipiak, Krzysztof J; Flammer, Andreas; Fleck, Eckart; Gatzov, Plamen; Ginghina, Carmen; Goncalves, Lino; Haouala, Habib; Hassanein, Mahmoud; Heusch, Gerd; Huber, Kurt; Hulín, Ivan; Ivanusa, Mario; Krittayaphong, Rungroj; Lau, Chu-Pak; Marinskis, Germanas; Mach, François; Moreira, Luiz Felipe; Nieminen, Tuomo; Oukerraj, Latifa; Perings, Stefan; Pierard, Luc; Potpara, Tatjana; Reyes-Caorsi, Walter; Rim, Se-Joong; Rødevand, Olaf; Saade, Georges; Sander, Mikael; Shlyakhto, Evgeny; Timuralp, Bilgin; Tousoulis, Dimitris; Ural, Dilek; Piek, J J; Varga, Albert; Lüscher, Thomas F

2017-05-01

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship - emphasizing the importance of responsibility and accountability-, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors´ Network of the European Society of Cardiology. Resumo O Comitê Internacional de Editores de Revistas Médicas (ICMJE) fornece recomendações para aprimorar o padrão editorial e a qualidade científica das revistas biomédicas. Tais recomendações variam desde requisitos técnicos de uniformização até assuntos editoriais mais complexos e elusivos, como os aspectos éticos do processo científico. Recentemente, foram propostos registro de ensaios clínicos, divulgação de conflitos de interesse e novos critérios de autoria, enfatizando a importância da responsabilidade e da responsabilização. No último ano, lançou-se uma nova iniciativa editorial para fomentar o compartilhamento dos dados de ensaios clínicos. Esta revisão discute essa nova iniciativa visando a aumentar a conscientização de leitores, investigadores, autores e editores filiados à Rede de Editores da Sociedade Europeia de Cardiologia.

Transferências orbitais dentro do modelo quase bicircular no sistema Terra-Lua-Sol

NASA Astrophysics Data System (ADS)

Corrêa, A. A.; de Almeida Prado, A. F. B.; Stuchi, T. J.; Beaugé, C.

2003-08-01

O problema quase bicircular planar consiste na determinação da dinâmica de um corpo, de massa desprezível, que se move sob o campo gravitacional de três corpos. No caso estudado, o quarto corpo é considerado um satélite artificial e os demais são a Terra, a Lua e o Sol, formando o sistema de três corpos. Este modelo permite a construção de uma hamiltoniana similar a do problema restrito de três corpos (PRTC), incluindo termos periódicos não autônomos, provenientes da presença do Sol, portanto pode ser entendido como uma perturbação ao PRTC. Suas órbitas periódicas aparecem isoladas e possuem o mesmo período solar. Os pontos de equilíbrio colineares possuem o mesmo caráter de estabilidade linear dos pontos lagrangianos (L1, L2 e L3) do PRTC, sendo do tipo sela x centro x centro, instável na direção x e estáveis nas direções y e z. As órbitas periódicas tridimensionais ao redor do ponto colinear é chamada órbita Halo. O objetivo deste trabalho é determinar órbitas de transferências de baixo consumo de combustível para um veículo espacial partindo de uma órbita de estacionamento ao redor da Terra em direção a uma órbita Halo do ponto L1, situado entre a Terra e Lua. Esta tarefa pode ser transformada no problema de valor de contorno: dado um ponto inicial na órbita de estacionamento, um ponto final na órbita halo e o tempo de transferência, deseja-se obter a trajetória que liga estes dois pontos e que minimize os incrementos de velocidade do veículo. Essas transferências são realizadas baseadas no método de Lambert e analisadas de modo a fornecer um baixo consumo. Posteriormente, é feita uma comparação de consumo com as órbitas de transferência equivalentes do PRTC.

Authentication Architecture for Region-Wide e-Health System with Smartcards and a PKI

NASA Astrophysics Data System (ADS)

Zúquete, André; Gomes, Helder; Cunha, João Paulo Silva

This paper describes the design and implementation of an e-Health authentication architecture using smartcards and a PKI. This architecture was developed to authenticate e-Health Professionals accessing the RTS (Rede Telemática da Saúde), a regional platform for sharing clinical data among a set of affiliated health institutions. The architecture had to accommodate specific RTS requirements, namely the security of Professionals' credentials, the mobility of Professionals, and the scalability to accommodate new health institutions. The adopted solution uses short-lived certificates and cross-certification agreements between RTS and e-Health institutions for authenticating Professionals accessing the RTS. These certificates carry as well the Professional's role at their home institution for role-based authorization. Trust agreements between e-Health institutions and RTS are necessary in order to make the certificates recognized by the RTS. As a proof of concept, a prototype was implemented with Windows technology. The presented authentication architecture is intended to be applied to other medical telematic systems.

The effect of training in reduced energy density eating and food self-monitoring accuracy on weight loss maintenance.

PubMed

Lowe, Michael R; Tappe, Karyn A; Annunziato, Rachel A; Riddell, Lynnette J; Coletta, Maria C; Crerand, Canice E; Didie, Elizabeth R; Ochner, Christopher N; McKinney, Shortie

2008-09-01

Failure to maintain weight losses in lifestyle change programs continues to be a major problem and warrants investigation of innovative approaches to weight control. The goal of this study was to compare two novel group interventions, both aimed at improving weight loss maintenance, with a control group. A total of 103 women lost weight on a meal replacement-supplemented diet and were then randomized to one of three conditions for the 14-week maintenance phase: cognitive-behavioral treatment (CBT); CBT with an enhanced food monitoring accuracy (EFMA) program; or these two interventions plus a reduced energy density eating (REDE) program. Assessments were conducted periodically through an 18-month postintervention. Outcome measures included weight and self-reported dietary intake. Data were analyzed using completers only as well as baseline-carried-forward imputation. Participants lost an average of 7.6 +/- 2.6 kg during the weight loss phase and 1.8 +/- 2.3 kg during the maintenance phase. Results do not suggest that the EFMA intervention was successful in improving food monitoring accuracy. The REDE group decreased the energy density (ED) of their diets more so than the other two groups. However, neither the REDE nor the EFMA condition showed any advantage in weight loss maintenance. All groups regained weight between 6- and 18-month follow-ups. Although no incremental weight maintenance benefit was observed in the EFMA or EFMA + REDE groups, the improvement in the ED of the REDE group's diet, if shown to be sustainable in future studies, could have weight maintenance benefits.

Environmental Assessment (EA): Proposed Construction of a Munitions Flight Maintenance Facility, Hill Air Force Base, Utah

DTIC Science & Technology

2008-07-01

1997) Ozone(031 /·-c.,.. ?i Ogden C.ty Ma1 tenance Area (Redes~gnated 2001) er ~~.., Sa Laice Oty Ma1 enance Alea (RedeSIQreled 1999) Pr...disposal. 3.4 Vegetation Hill AFB is located in a geographic region that would typically support a mountain -brush type native plant community. Dominant

Environmental Assessment (EA): Proposed Construction of a Munitions Flight Maintenance Facility, Hill Air Force Base, Utah

DTIC Science & Technology

2008-07-01

031 /·-c.,.. ?i Ogden C.ty Ma1 tenance Area (Redes~gnated 2001) er ~~.., Sa Laice Oty Ma1 enance Alea (RedeSIQreled 1999) Pr<MYOrem...Vegetation Hill AFB is located in a geographic region that would typically support a mountain -brush type native plant community. Dominant vegetation

Problem Articulation and the Processes of Assistance: An Activity Theoretic View of Mediation in Game Play

ERIC Educational Resources Information Center

Stone, Lynda D.; Gutierrez, Kris D.

2007-01-01

In this article, we study a local adaptation of the Fifth Dimension [Cole, M. (1996). "Cultural psychology: A once and future discipline." Cambridge: Cambridge University Press] known as Las Redes (i.e., Networks of Collaboration in the Fifth Dimension) to examine how the multiple activity systems of Las Redes, e.g. the undergraduate course and…

Is there any link between accreditation programs and the models of organizational excellence?

PubMed

Berssaneti, Fernando Tobal; Saut, Ana Maria; Barakat, Májida Farid; Calarge, Felipe Araujo

2016-01-01

To evaluate whether accredited health organizations perform better management practices than non-accredited ones. The study was developed in two stages: a literature review, and a study of multiple cases in 12 healthcare organizations in the state of São Paulo, Brazil. It surveyed articles comparing hospital accreditation with the EFQM (European Foundation for Quality Management) model of excellence in management. According to the pertinent literature, the accreditation model and the EFQM model are convergent and supplementary in some aspects. With 99% confidence, one can say that there is evidence that accredited organizations scored better in the evaluation based on the EFQM model in comparison to non-accredited organizations. This result was also confirmed in the comparison of results between the categories Facilitators and Results in the EFQM model. There is convergence between the accreditation model and the EFQM excellence model, suggesting that accreditation helps the healthcare sector to implement the best management practices already used by other business sectors. Avaliar se as organizações de saúde acreditadas possuem melhores práticas de gestão do que as não acreditadas. A pesquisa foi dividida em duas etapas: revisão da literatura e estudo de casos múltiplos com 12 organizações de saúde, localizadas no estado de São Paulo ‒ Brasil. Foram pesquisados artigos que comparavam a acreditação hospitalar com o modelo de excelência em gestão da EFQM (European Foundation for Quality Management), sendo que a literatura pertinente considera que o modelo de acreditação e o modelo da EFQM são convergentes e, ao mesmo tempo, complementares em determinados aspectos. Com 99% de confiança, pode-se afirmar que há evidência de que as organizações com acreditação obtiveram uma pontuação maior na avaliação baseada no modelo EFQM comparativamente às organizações não acreditadas. Este resultado também se confirmou na comparação dos resultados das categorias Facilitadores e Resultados do modelo EFQM. Há uma convergência entre o modelo de acreditação e o modelo de excelência da EFQM, sugerindo que a acreditação contribui para o setor de saúde implementar as melhores práticas de gestão já difundidas em outros setores de negócio.

Telescópio de patrulhamento solar em 12 GHz

NASA Astrophysics Data System (ADS)

Utsumi, F.; Costa, J. E. R.

2003-08-01

O telescópio de patrulhamento solar é um instrumento dedicado à observação de explosões solares com início de suas operações em janeiro de 2002, trabalhando próximo ao pico de emissão do espectro girossincrotrônico (12 GHz). Trata-se de um arranjo de três antenas concebido para a detecção de explosões e determinação em tempo real da localização da região emissora. Porém, desde sua implementação em uma montagem equatorial movimentada por um sistema de rotação constante (15 graus/hora) o rastreio apresentou pequenas variações de velocidade e folgas nas caixas de engrenagens. Assim, tornou-se necessária a construção de um sistema de correção automática do apontamento que era de fundamental importância para os objetivos do projeto. No segundo semestre de 2002 empreendemos uma série de tarefas com o objetivo de automatizar completamente o rastreio, a calibração, a aquisição de dados, controle de ganhos, offsets e transferência dos dados pela internet através de um projeto custeado pela FAPESP. O rastreio automático é realizado através de um inversor que controla a freqüência da rede de alimentação do motor de rastreio podendo fazer micro-correções na direção leste-oeste conforme os radiômetros desta direção detectem uma variação relativa do sinal. Foi adicionado também um motor na direção da declinação para correção automática da variação da direção norte-sul. Após a implementação deste sistema a precisão do rastreio melhorou para um desvio máximo de 30 segundos de arco, o que está muito bom para este projeto. O Telescópio se encontra em funcionamento automático desde março de 2003 e já conta com várias explosões observadas após a conclusão desta fase de automação. Estamos apresentando as explosões mais intensas do período e com as suas respectivas posições no disco solar.

Cateteres venosos centrais de inserção periférica: alternativa ou primeira escolha em acesso vascular?

PubMed Central

Di Santo, Marcelo Kalil; Takemoto, Diogo; Nascimento, Robert Guimarães; Nascimento, Ariele Milano; Siqueira, Érika; Duarte, Caio Túlio; Jovino, Marco Antônio Caldas; Kalil, Jorge Agle

2017-01-01

Resumo Contexto Os cateteres venosos centrais de inserção periférica (PICC) são dispositivos intravenosos, introduzidos através de uma veia superficial ou profunda da extremidade superior ou inferior até o terço distal da veia cava superior ou proximal da veia cava inferior. Apresentam maior segurança para infusão de soluções vesicantes/irritantes e hiperosmolares, antibioticoterapia, nutrição parenteral prolongada (NPT) e uso de quimioterápicos; demonstram reduzido risco de infecção em comparação a outros cateteres vasculares e maior relação custo/benefício se comparados ao cateter venoso de inserção central (CVCIC). Objetivos Apresentar os resultados de implantes de PICCs ecoguiados e posicionados por fluoroscopia realizados no Hospital e Maternidade São Luiz (HMSL) Itaim, Rede D’or, Brasil. Métodos Estudo prospectivo, não randomizado, realizado entre fevereiro de 2015 e novembro de 2016. Utilizou-se protocolo pré-estabelecido pela instituição em casos de solicitação de acesso vascular. Foram analisadas indicações, doenças prevalentes, tipo do cateter implantado, sucesso técnico, complicações relacionadas ao cateter, e estabelecidos critérios de inclusão e exclusão. Resultados Solicitados 256 acessos vasculares, sendo implantados 236 PICCs (92,1%) e 20 CVCICs (7,9%). Principais indicações: antibioticoterapia prolongada (52,0%), NPT (19,3%) e acesso venoso difícil (16,0%). Houve sucesso técnico em 246 cateteres implantados (96,1%). A veia basílica direita foi a principal veia puncionada em 192 pacientes (75,0%), seguida da braquial direita em 28 pacientes (10,9%). Conclusões O implante dos PICCs ecoguiados e posicionados por fluoroscopia demonstrou baixa incidência de complicações, reduzidos índices de infecção e é seguro e eficaz em casos de acessos vasculares difíceis, sendo esses cateteres considerados dispositivos de escolha em acesso vascular central.

Care production for tuberculosis cases:analysis according to the elements of the Chronic Care Model.

PubMed

Silva, Daiane Medeiros da; Farias, Hérika Brito Gomes de; Villa, Tereza Cristina Scatena; Sá, Lenilde Duarte de; Brunello, Maria Eugênia Firmino; Nogueira, Jordana de Almeida

2016-04-01

To analyze the care provided to tuberculosis cases in primary health care services according to the elements of the Chronic Care Model. Cross-sectional study conducted in a capital city of the northeastern region of Brazil involving 83 Family Health Strategy professionals.A structured tool adapted to tuberculosis-related care in Brazil was applied.Analysis was based on the development of indicators with capacity to produce care varying between limited and optimum. The organization of care for tuberculosis and supported self-care presented reasonable capacity.In the coordination with the community, the presence of the community agent presented optimum capacity.Partnership with organizations of the community and involvement of experts presented limited capacity.The qualification of professionals, the system for scheduling and monitoring tuberculosis in the community, and the clinical information system presented basic capacity. The capacity of the primary health care services to produce tuberculosis-related care according to the elements of the Chronic Care Model is still limited.Overcoming the fragmentation of care and prioritizing a systemic operation between actions and services of the health care network remains as a major challenge. Analisar,segundo os elementos doChronicCareModel,a produção do cuidado aos casos de tuberculose nos serviços de Atenção Primária à Saúde. Estudo transversal, realizado em capital do nordeste brasileiro, envolvendo 83 profissionais da Estratégia Saúde da Família. Aplicou-se um instrumento estruturado, adaptado para atenção à tuberculose no Brasil. A análise pautou-se na construção de indicadores, cujacapacidade para produção de cuidados variou entre limitada a ótima. A organização da atenção à tuberculose e o autocuidado apoiado apresentaram capacidade razoável. Na articulação com a comunidade, a presençadoagente comunitário de saúde apresentou capacidade ótima. A parceria com organizações da comunidade e o envolvimento de especialistas obtiveram capacidade limitada. A capacitação dos profissionais, o sistema de agendamento e monitoramento da tuberculose na comunidade e o sistema de informação clínica alcançaram capacidade básica. A capacidade dos serviços da Atenção Primária à Saúde para produção do cuidado aos casos de tuberculose,segundo os elementos doChronicCareModel,ainda é limitada.Superar a fragmentação do cuidado e priorizar um funcionamento sistêmico entre ações e serviços da rede de atenção à saúde é ainda um grande desafio.

Mental health in the Family Health Strategy as perceived by health professionals.

PubMed

Souza, Jacqueline de; Almeida, Letícia Yamawaka de; Luis, Margarita Antonia Villar; Nievas, Andreia Fernanda; Veloso, Tatiana Maria Coelho; Barbosa, Sara Pinto; Giacon, Bianca Cristina Ciccone; Assad, Francine Baltazar

2017-01-01

to analyze the management of mental health needs in primary care as perceived by Family Health Strategy professionals. this was a qualitative descriptive exploratory study developed within the coverage area of five family health teams. The data were collected using observation, group interviews, individual semi-structured interviews, and focus groups. Content analysis was conducted using text analysis software and interpretation was based on the corresponding analytical structures. numerous and challenging mental health demands occur in this setting, for which the teams identified care resources; however, they also indicated difficulties, especially related to the operationalization and integration of such resources. there is a need for a care network sensitive to mental health demands that are better coordinated and more effectively managed. analisar o manejo das necessidades de saúde mental na atenção primária à saúde de acordo com a percepção dos profissionais da Estratégia Saúde da Família. estudo qualitativo, descritivo exploratório, desenvolvido no território de abrangência de cinco equipes de saúde da família. Os participantes foram cinco enfermeiras, cinco coordenadores e 17 agentes comunitários de saúde. Os dados foram coletados utilizando observação, entrevistas grupais, entrevistas individuais semiestruturadas e grupos focais. Fez-se a análise de conteúdo com o auxílio de um Software de análise textual, e a interpretação baseou-se nas estruturas analíticas correspondentes. inúmeras e desafiadoras demandas de saúde mental têm sido acolhidas nesse setting, para as quais as equipes identificaram recursos de atendimento; no entanto, apontaram dificuldades, sobretudo relacionadas à operacionalização e integração destes recursos. destaca-se a necessidade de uma rede de cuidados sensível a tais demandas, mais articulada e gerida de modo eficaz.

Estudo de propriedades estruturais e opticas de multicamadas epitaxiais emissoras de luz baseadas em InGaN/GaN

NASA Astrophysics Data System (ADS)

Pereira, Sergio Manuel de Sousa

Esta tese apresenta os resultados de uma investigacao experimental em filmes epitaxiais emissores de luz baseados em InxGa1-xN. O InxGa1-xN e uma liga semicondutora ternaria do grupo III-N muito utilizada como camada activa numa gama de dispositivos optoelectronicos em desenvolvimento, incluindo diodos emissores de luz (LEDs) e diodos laser (LDs), para operacao na regiao do visivel e ultravioleta do espectro electromagnetico. Neste estudo, caracterizam-se as propriedade opticas e estruturais de camadas simples e pocos quânticos multiplos (Multiple Quantum Wells, MQWs) de InxGa1-xN/GaN, com enfase nas suas propriedades fisicas fundamentais. O objectivo central do trabalho prende-se com a compreensao mais profunda dos processos fisicos que estao por tras das suas propriedades opticas, preenchendo o fosso existente entre aplicacoes tecnologicas e o conhecimento cientifico. Nomeadamente, a tese aborda os problemas da medicao da fraccao de InN (x) em multicamadas ultrafinas sujeitas a tensoes, a influencia da composicao e das tensoes microscopicas nas propriedades opticas e estruturais. A questao relativa a segregacao de fases em multicamadas de InxGa1-xN/GaN e tambem discutida a luz dos resultados obtidos. A metodologia seguida assenta na integracao de resultados obtidos por tecnicas complementares atraves de uma analise sistematica e multidisciplinar. Esta abordagem passa pela combinacao de: 1) Crescimento de amostras por deposicao epitaxial em fase de vapor organometalico (MOVPE) com caracteristicas especificas de forma a tentar isolar parâmetros estruturais, tais como espessura e composicao; 2) Caracterizacao nanoestrutural por microscopia de forca atomica (AFM), microscopica electronica de varrimento (SEM), difraccao de raios-X e retro-dispersao de Rutherford (RBS); 3) Caracterizacao optica a escalas complementares por: espectroscopia de absorcao optica (OA), fotoluminescencia (PL), catodoluminescencia (CL) e microscopia confocal (CM) com analise espectral. Com base nos resultados obtidos, a tese propoe modelos de interpretacao para as propriedades estruturais e opticas, dando enfase as suas correlacoes. Em particular, estabelece-se a necessidade de considerar fenomenos relacionados com tensoes microscopicas na interpretacao dos resultados experimentais. Com este trabalho fica clara a necessidade de um conhecimento detalhado das caracteristicas nanoestruturais para interpretar as propriedades opticas das ligas de InxGa1-xN. None

Astronomical Perception of the Secondary School's Students in São Paulo's State School in Suzano City. (Spanish Title: Percepción Astronómica de Alumnos de la Enseñanza Media de la Red Estatal de San Pablo en la Ciudad de Suzano.) Percepção Astronômica de um Grupo de Alunos do Ensino Médio da Rede Estadual de São Paulo da Cidade de Suzano

NASA Astrophysics Data System (ADS)

França de Oliveira, Edilene; Voelzke, Marcos Rincon; Amaral, Luis Henrique

2007-12-01

Although Astronomy is one of the oldest Sciences in the world and many of its concepts are popular, it is possible to observe that a major part of the students do not know about them. This work aims to analyse the basic knowledge of the secondary school's students of a state school in the city of Suzano, related to the astronomical phenomena, which surround them. It was carried out a questionnaire of multiple choice to 34 students from the first grade, night classes, of the state school Batista Renzi. From the sample, 34 students, only 29.4% of them could understand the succession of the days; 20.6% could explain the seasons of the year and 20.6% had some idea about celestial objects nearer to the Earth. In turn, 67.6% correctly classified the Sun as a star; 55.9% related the Big Bang to the origin of Universe; only 20.6% identified the light-year as an unit of distance and 32.4% recognized a falling star as a meteor. The actual analysis was expanded to more 310 students of other classes, grades and periods of the same school. In this first stage, it can be noted the students' little discernment of the astronomical events and mainly the great confusion about the appropriate meaning of popular astronomical terms. Aunque la Astronomía es una de las ciencias más antiguas de la humanidad y muchos de los conceptos astronómicos son populares, se observa que una parcela significativa de los estudiantes se encuentra al margen de estas informaciones. El presente trabajo pretende analizar el nivel de conocimiento básico de los alumnos de la Enseñanza Media de la Red Estatal de la ciudad de Suzano con relación a los fenómenos astronómicos que los rodean. Con este objetivo fue elaborado un formulario constando de preguntas de selección múltipla, aplicado en el primer año nocturno de la Escuela Estatal Batista Renzi. En un universo de 34 alumnos se constató que solamente 29,4% comprendían la sucesión de los días; 20,6% explicaron correctamente las estaciones del año y 20,6% tenían la idea de cuales son los objetos celestes más cercanos de la Tierra. En contraposición, 67,6% clasificaron correctamente el Sol como una estrella; 55,9% relacionaron el Big Bang al origen del Universo; solamente 20,6% identificaron un año-luz como unidad de distancia y 32,4% reconocieron una estrella fugaz como meteoro. El presente análisis fue expandido para otros grupos de la Enseñanza Media, no solamente del período nocturno, sino también diurno de la misma escuela. En esta primera fase se nota el pequeño conocimiento de los alumnos sobre eventos astronómicos y principalmente la gran confusión sobre el significado correcto de los términos astronómicos populares. Embora a Astronomia seja uma das ciências mais antigas da humanidade e muitos dos conceitos astronômicos serem populares, observa-se que uma parcela significativa dos estudantes encontra-se à margem dessas informações. O presente trabalho visa analisar o nível de conhecimento básico dos alunos do Ensino Médio da Rede Estadual da cidade de Suzano quanto aos fenômenos astronômicos que os rodeiam. Para tanto foi elaborado um formulário constando de questões de múltipla escolha, aplicado no primeiro ano noturno da Escola Estadual Batista Renzi. Num espaço amostral de 34 alunos constatou-se que apenas 29,4% compreendiam a sucessão dos dias; 20,6% explicaram corretamente as estações do ano e 20,6% tinham idéia de quais são os objetos celestes mais próximos da Terra. Em contraposição, 67,6% classificaram corretamente o Sol como estrela; 55,9% relacionaram o Big Bang à origem do Universo; apenas 20,6% identificaram um ano-luz como unidade de distância e 32,4% reconheceram uma estrela cadente como meteoro. A presente análise foi expandida para mais 310 alunos de outras classes de Ensino Médio, não somente do período noturno, mas também diurno da mesma escola. Nesta primeira fase nota-se o pequeno discernimento dos alunos sobre eventos astronômicos e principalmente a grande confusão sobre o significado correto de termos astronômicos populares.

Rainfall Erosivity Database on the European Scale (REDES): A product of a high temporal resolution rainfall data collection in Europe

NASA Astrophysics Data System (ADS)

Panagos, Panos; Ballabio, Cristiano; Borrelli, Pasquale; Meusburger, Katrin; Alewell, Christine

2016-04-01

The erosive force of rainfall is expressed as rainfall erosivity. Rainfall erosivity considers the rainfall amount and intensity, and is most commonly expressed as the R-factor in the (R)USLE model. The R-factor is calculated from a series of single storm events by multiplying the total storm kinetic energy with the measured maximum 30-minutes rainfall intensity. This estimation requests high temporal resolution (e.g. 30 minutes) rainfall data for sufficiently long time periods (i.e. 20 years) which are not readily available at European scale. The European Commission's Joint Research Centre(JRC) in collaboration with national/regional meteorological services and Environmental Institutions made an extensive data collection of high resolution rainfall data in the 28 Member States of the European Union plus Switzerland in order to estimate rainfall erosivity in Europe. This resulted in the Rainfall Erosivity Database on the European Scale (REDES) which included 1,541 rainfall stations in 2014 and has been updated with 134 additional stations in 2015. The interpolation of those point R-factor values with a Gaussian Process Regression (GPR) model has resulted in the first Rainfall Erosivity map of Europe (Science of the Total Environment, 511, 801-815). The intra-annual variability of rainfall erosivity is crucial for modelling soil erosion on a monthly and seasonal basis. The monthly feature of rainfall erosivity has been added in 2015 as an advancement of REDES and the respective mean annual R-factor map. Almost 19,000 monthly R-factor values of REDES contributed to the seasonal and monthly assessments of rainfall erosivity in Europe. According to the first results, more than 50% of the total rainfall erosivity in Europe takes place in the period from June to September. The spatial patterns of rainfall erosivity have significant differences between Northern and Southern Europe as summer is the most erosive period in Central and Northern Europe and autumn in the Mediterranean area. This spatio-temporal analysis of rainfall erosivity at European scale is very important for policy makers and farmers for soil conservation, optimization of agricultural land use and natural hazards prediction. REDES is also used in combination with future rainfall data from WorldClim to run climate change scenarios. The projection of REDES combined with climate change scenarios (HADGEM2, RCP4.5) and using a robust geo-statistical model resulted in a 10-20% increase of the R-factor in Europe till 2050.

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.

The mental health care model in Brazil: analyses of the funding, governance processes, and mechanisms of assessment.

PubMed

Trapé, Thiago Lavras; Campos, Rosana Onocko

2017-03-23

This study aims to analyze the current status of the mental health care model of the Brazilian Unified Health System, according to its funding, governance processes, and mechanisms of assessment. We have carried out a documentary analysis of the ordinances, technical reports, conference reports, normative resolutions, and decrees from 2009 to 2014. This is a time of consolidation of the psychosocial model, with expansion of the health care network and inversion of the funding for community services with a strong emphasis on the area of crack cocaine and other drugs. Mental health is an underfunded area within the chronically underfunded Brazilian Unified Health System. The governance model constrains the progress of essential services, which creates the need for the incorporation of a process of regionalization of the management. The mechanisms of assessment are not incorporated into the health policy in the bureaucratic field. There is a need to expand the global funding of the area of health, specifically mental health, which has been shown to be a successful policy. The current focus of the policy seems to be archaic in relation to the precepts of the psychosocial model. Mechanisms of assessment need to be expanded. Analisar o estágio atual do modelo de atenção à saúde mental do Sistema Único de Saúde, segundo seu financiamento, processos de governança e mecanismos de avaliação. Foi realizada uma análise documental de portarias, informes técnicos, relatórios de conferência, resoluções e decretos de 2009 a 2014. Trata-se de um momento de consolidação do modelo psicossocial, com ampliação da rede assistencial, inversão de financiamento para serviços comunitários com forte ênfase na área de crack e outras drogas. A saúde mental é uma área subfinanciada dentro do subfinanciamento crônico do Sistema Único de Saúde. O modelo de governança constrange o avanço de serviços essenciais, havendo a necessidade da incorporação de um processo de regionalização da gestão. Os mecanismos avaliativos no campo burocrático se mostram pouco incorporados à política de saúde. É necessário ampliar o financiamento global da saúde e específico da saúde mental, que vem se constituindo como uma política exitosa. O foco atual da política se mostra anacrônico aos preceitos do modelo psicossocial. Aponta-se a necessidade de ampliação de mecanismos avaliativos.

Percepção astronómica de um grupo de alunos do ensino médio de uma escola da rede estadual de São Paulo

NASA Astrophysics Data System (ADS)

de Oliveria, E. F.; Voelzke, M. R.

2009-03-01

Sendo a Astronomia uma das cièncias mais antigas da humanidade, e considerando sua importáncia histórica e cultural, é de extrema releváncia que tópicos relacionados a ela sejam tratados nas escolas. Embora os Parámetros Curriculares Nacionais do Ensino Médio (PCN-EM) e as Orientaçiacute;es Complementares aos Parámetros (PCN+) apontem a importáncia de uma abordagem significativa de conceitos relacionados à Astronomia nas aulas de Física, muitos estudantes terminam o Ensino Médio (EM) sem compreender a razão de certos acontecimentos de origem celeste, ainda que estes façam parte de seu cotidiano e sejam alvos da curiosidade natural dos jovens. Da observação dessa curiosidade em alunos de uma escola pública paulista, na cidade de Suzano, surgiu o interesse em investigar os conhecimentos básicos em Astronomia dos alunos do Ensino Médio desta escola, constituindo-se este como principal objetivo desta pesquisa. Para tanto foi elaborado um questionário de múltipla escolha aplicado inicialmente a 34 alunos do primeiro ano e, posteriormente, a mais 310, distribuídos entre as très séries do Ensino Médio dos períodos matutino e noturno. Dessa forma, observou-se que 73,9% dos estudantes identificaram o Sol como sendo uma estrela, 67,1% mostraram compreender a sucessão entre dia e noite e 52,3% relacionaram o Big Bang à origem do Universo. Em contrapartida, apenas 34,5% relacionaram as estaçíes do ano à inclinação do eixo de rotação da Terra, 21,3% indicaram a influència gravitacional simultánea da Lua e do Sol como responsável pelo fenòmeno das marés, 24,5% indicaram corretamente quais são os objetos celestes mais próximos da Terra, 36,1% identificaram ano-luz como uma medida de distáncia e 34,2% reconheceram as estrelas cadentes como meteoros, evidenciando-se assim o pequeno discernimento dos estudantes quanto aos fenòmenos e termos astronòmicos do cotidiano. Além disso, foram comparadas as respostas de alun! os de diferentes séries e períodos, observando-se, dentre ou tras coi sas, que os estudantes do terceiro ano apresentam um percentual de acertos semelhante ao dos alunos do primeiro, caracterizando que a abordagem de tópicos relacionados à astronomia no Ensino Médio não tem contribuído de forma significativa para uma maior compreensão dos fenòmenos e conceitos.

Tuberculosis control in people living with HIV/AIDS.

PubMed

Magnabosco, Gabriela Tavares; Lopes, Lívia Maria; Andrade, Rubia Laine de Paula; Brunello, Maria Eugênia Firmino; Monroe, Aline Aparecida; Villa, Tereza Cristina Scatena

2016-09-09

to analyze the offering of health actions and services for the control of tuberculosis for people living with HIV/AIDS being followed up in the Specialized Care Services for HIV/AIDS in Ribeirão Preto, SP, Brazil. quantitative, exploratory survey study. Participated 253 people living with HIV/AIDS followed up by this service, considering as inclusion criteria: individuals older than 18 years living in the city and not inmates. Data collection was conducted from January 2012 to May 2013 through interviews with the support of a specific instrument. Data were analyzed using indicators and a composite index. the offering of services for the control of tuberculosis in people living with HIV/AIDS by municipal services was considered as intermediate, reinforcing the need for better planning for comprehensive assistance, coordination of professionals in teams and among the services network, in addition to professional training and continuing education. it is necessary to implement strategies that promote shared actions between TB and HIV / AIDS programs and between different services in order to strengthen the local care network, aimed at producing an individualized care, comprehensive and responsive. analisar a oferta das ações e serviços de saúde para o controle da tuberculose nas pessoas vivendo com HIV/aids em seguimento pelos Serviços de Atenção Especializada ao HIV/aids de Ribeirão Preto, SP, Brasil. estudo quantitativo, exploratório, do tipo inquérito. Participaram 253 pessoas vivendo com HIV/aids em seguimento nos serviços, considerando os critérios de inclusão: indivíduos maiores de 18 anos, residentes no município e não pertencentes ao sistema prisional. A coleta de dados foi realizada no período de janeiro/2012 a maio/2013, por meio de entrevistas com apoio de um instrumento específico. Os dados foram analisados mediante indicadores e índice composto. a oferta de ações e serviços para o controle da tuberculose nas pessoas vivendo com HIV/aids pelos serviços do município foi considerada regular, reforçando a necessidade de melhor planejamento da assistência de forma integral, articulação dos profissionais nas equipes e entre os serviços da rede, além da formação profissional e educação permanente. faz-se necessário a implementação de estratégias que favoreçam ações compartilhadas entre os programas de tuberculose e HIV/aids e entre os diferentes serviços, com o intuito de fortalecer a rede local de atenção objetivando a produção de um cuidado singular, integral e resolutivo. analizar la oferta de acciones y servicios de salud para el control de la tuberculosis en las personas viviendo con VIH-SIDA acompañadas por los Servicios de Atención Especializada al VIH-SIDA de Ribeirao Preto, SP, Brasil. estudio cuantitativo, exploratorio, de tipo encuesta. Participaron 253 personas viviendo con VIH-SIDA seguidas por estos servicios, considerando como criterios de inclusión: individuos mayores de 18 años, residentes en el municipio y no ser del sistema de prisiones. La recolección de datos fue realizada en el periodo de enero de 2012 a mayo de 2013, por medio de entrevistas guiadas por un instrumento especifico. Los datos fueron analizados mediante indicadores y un índice compuesto. la oferta de acciones y servicios para el control de la tuberculosis en personas viviendo con VIH-SIDA fue considerada intermedia, reforzando la necesidad de mejorar la planificación de la asistencia en forma integral, la articulación de los profesionales en los equipos y entre los servicios de la red, además de la formación profesional y la educación permanente. se hace necesaria la implementación de estrategias que favorezcan las acciones compartidas entre los programas de tuberculosis y VIH-SIDA y entre los diferentes servicios, con el fin de fortalecer la red local de atención para producir un cuidado personalizado, integral y resolutivo.

DIETARY MANAGEMENT FOR DYSLIPIDEMIA IN LIVER TRANSPLANT RECIPIENTS.

PubMed

Pinto, Andressa S; Chedid, Marcio F; Guerra, Léa T; Cabeleira, Daiane D; Kruel, Cleber D P

2016-01-01

Dyslipidemia occurs in approximately 70% of all liver transplant (LT) recipients, and no prior control studies have demonstrated any dietary intervention to change it. To analyze the effects of a dietary intervention on the lipid profile of dyslipidemic LT recipients. All LT recipients with dyslipidemia on clinical follow-up were enrolled. Anthropometric evaluation, food history, body composition (bioimpedance) and assessment of basal metabolism through indirect calorimetry were performed. Patients met with a dietitian and an individualized diet based on estimate of basal metabolism and consisting of 25% of the total energy value in total fat and <200 mg/day of cholesterol was prescribed. Total cholesterol (TC), HDL-cholesterol (HDL), LDL-cholesterol (LDL), triglycerides (TG) and anthropometric measures were measured at baseline and six months after intervention. Fifty-thee out of 56 patients concluded follow-up; age was 59±10 years; 29 were men (51.8%). The analysis pre- and post-intervention were, respectively: TC 238.9±30 and 165.1±35, p<0.001; LDL 154±33 and 90±29, p<0.001; and TG 168 (IQR=51-200) and 137 (IQR=94-177), p=<0.001. They were all modified at six months following intervention. At baseline, none of the patients had normal TC, and only 12 (22.7%) had optimal/near optimal LDL. Following dietary intervention, 45 patients (84.9%) reached normal TC and 50 (94.4%) had optimal/near optimal LDL. HDL and anthropometric measures were not modified. Dietary counseling with prescription of individualized diet based on estimate of basal metabolism through indirect calorimetry was able to manage dyslipidemia in most LT recipients; so, all dyslipidemic LT recipients must be enrolled on a dietary program. A dislipidemia ocorre em aproximadamente 70% de todos os pacientes transplantados de fígado em acompanhamento ambulatorial. Não há relato prévio de qualquer intervenção dietética que houvesse controlado a dislipidemia nesse grupo de pacientes. Analisar os efeitos de uma intervenção dietética no perfil lipídico de pacientes transplantados hepáticos dislipidêmicos em acompanhamento ambulatorial. Foram incluídos todos os pacientes adultos transplantados hepáticos com dislipidemia e em acompanhamento ambulatorial em nossa instituição. Avaliação antropométrica, anamnese alimentar, composição corporal (bioimpedância) e cálculo do metabolismo basal (calorimetria indireta) foram realizados. Pacientes foram atendidos por uma nutricionista e uma dieta individualizada baseada no metabolismo basal e consistindo de 25% do valor energético em gorduras totais e menos de 200 mg/dia de colesterol foi prescrita. Colesterol total (CT), HDL-colesterol (HDL), LDL-colesterol (LDL), triglicerídeos (TG) e medidas antropométricas foram medidos antes do início da dieta, sendo repetidos seis meses após o início da intervenção dietética. Cinquenta e três pacientes concluíram o seguimento e tinham idade 59±10 anos e 29 eram homens (51,8%). CT pré-intervenção=238,9±30; pós-intervenção=165,1±35, p<0.001; LDL pré-intervenção=154±33; pós-intervenção=90±29, p<0.001 e TG pré-intervenção=168, IQR=151-200; pós-intervenção=137, IQR=94-177, p=<0.001 sofreram modificações significativas seis meses após a intervenção. Antes do estudo, nenhum dos pacientes apresentava níveis séricos normais para o CT, e apenas 12 pacientes (22,7%) tinham níveis séricos ótimo ou quase ótimos para o LDL. Seis meses após o início da intervenção, 45 pacientes (84,9%) alcançaram níveis séricos normais de CT e 50 (94,4%) níveis séricos ótimos ou quase ótimos de LDL. Os níveis séricos de HDL e as medidas antropométricas não sofreram modificações significativas. Aconselhamento dietético com prescrição de dieta individualizada baseada no cálculo do metabolismo basal mostrou-se efetivo no manejo da dislipidemia em pacientes transplantados hepáticos em seguimento ambulatorial. Assim, todos os pacientes transplantados hepáticos com dislipidemia devem ser incluídos em um programa de intervenção dietética sob orientação de nutricionista.

Health care networks implementation and regional governance challenges in the Legal Amazon Region: an analysis of the QualiSUS-Rede Project.

PubMed

Casanova, Angela Oliveira; Cruz, Marly Marques; Giovanella, Ligia; Alves, Glaydes Dos Reis; Cardoso, Gisela Cordeiro Pereira

2017-04-01

This paper aims to analyze the potential, limits and challenges of regional governance in the implementation process of health care networks in three Brazilian regions: Alto Solimões (Amazonas), Belém (Pará) and an interstate region comprising Tocantins, Pará and Maranhão states (Topama). The study is based on the evaluation study on the implementation of the Quality Health Care Network Development and Improvement Project (QualiSUS-Rede). This is a qualitative multiple case study with the analysis of official documents and use of semi-structured interviews with key stakeholders conducted from July to December 2014. Governance review encompassed three components: stakeholders involved, especially local steering groups and their regional coordination capacity; strategies used for strengthening regional governance, anchored on the intervention's modeling; and implementation of local health care networks. Results point that the regional managing commissions were the main governance strategy and that the QualiSUS-Rede Project strengthened regional governance and integration differently in every case, depending on stakeholders' administration and consensus capacity on regional and political priorities.

The genesis of the AIDS policy and AIDS Space in Brazil (1981-1989).

PubMed

Barros, Sandra Garrido de; Vieira-da-Silva, Ligia Maria

2016-07-21

To analyze the genesis of the policy for controlling AIDS in Brazil. Socio-historical study (1981-1989), based on Bordieu's genetic sociology, by document analysis, bibliographical review, and in-depth interviews. It consisted of a connection between the analysis of the paths of 33 agents involved in the creation of a social space focusing on AIDS-related issues and the historical possibility conditions of the drafting of a specific policy. AIDS Space is a gathering point for the paths of agents from several social fields (medical, scientific, political, and bureaucratic fields). A specific space for relationships, which enabled the drafting of a policy for controlling the AIDS epidemic, but also a place where the authority to talk about the meaning of the disease, the methods to prevent and treat it was under dispute. The analysis showed how the various structures (democratic administrations in Sao Paulo and at the national level, with public health officers taking important positions) and the lack of a specific therapy contributed to social agents of different ranks and backgrounds to initially set prevention as a priority. The rise of the sanitary movement, the organization of SUS, and the dominance of the medical field at the AIDS Space contributed to foster treatment as a part of the measures to control the epidemic. These conditions allowed drafting a policy based on the integrality of care, by linking prevention and treatment in the following decade, with important participation from state bureaucracy and researchers. Analisar a gênese da política de controle da aids no Brasil. Estudo sócio-histórico (1981-1989), orientado pela sociologia genética de Bourdieu, por meio de análise documental, revisão bibliográfica e entrevistas em profundidade. Consistiu na articulação entre a análise das trajetórias de 33 agentes envolvidos na criação de um espaço social voltado para as questões relativas à aids e as condições históricas de possibilidade para a formulação de uma política específica. O Espaço Aids constituiu-se como produto do encontro da trajetória de agentes de diversos campos sociais (médico, científico, político e burocrático). Um espaço específico de relações, que possibilitou a formulação de uma política para o controle da epidemia da aids, mas onde também estava em disputa a autoridade de falar sobre o significado da doença, suas formas de prevenção e tratamento. A análise mostrou como as estruturas (governos democráticos no estado de São Paulo e no âmbito nacional, com sanitaristas assumindo posições importantes) e a ausência de terapia específica contribuíram para que agentes sociais com disposições e formações diversas formulassem uma política que priorizou inicialmente a prevenção. A ascensão do movimento sanitário, a constituição do SUS e a dominância do campo médico no Espaço Aids contribuíram para a valorização do tratamento, como parte das medidas de controle da epidemia. Essas condições possibilitaram a formulação de uma política baseada na integralidade das ações, articulando prevenção e tratamento, na década seguinte, com importante participação da burocracia estatal e de pesquisadores.

A bone tissue engineering strategy based on starch scaffolds and bone marrow cells cultured in a flow perfusion bioreactor

NASA Astrophysics Data System (ADS)

Gomes, Maria Manuela Estima

A Engenharia de Tecidos e uma area cientifica em continua expansao. Os desenvolvimentos conseguidos por esta area tem contribuido significativamente para diversos avancos no campo da Medicina Regenerativa. Esta ciencia interdisciplinar combina os conhecimentos de diversas outras areas, tao distintas como a Engenharia de Materiais e a Biologia, com o objectivo de desenvolver substitutos sinteticos para tecidos humanos. Para se atingir este objectivo utilizam-se, de uma forma generica, combinacoes especificas de celulas e de um material de suporte tridimensional com propriedades adequadas, gerando um material hibrido cujas caracteristicas podem ainda ser moduladas atraves do sistema de cultura usado. A presente tese e centrada no desenvolvimento de estrategias de engenharia de tecido osseo baseadas na cultura in vitro de celulas previamente "semeadas" num suporte tridimensional ("scaffold"). Esta estrategia permite que as celulas adiram ao suporte, proliferem e segreguem matriz extracelular especifica do tecido osseo, ate se obter um substituto artificial funcional com caracteristicas do tecido original, que pode finalmente ser transplantado para tratar o defeito em causa. Para que uma estrategia deste tipo seja bem sucedida, pelo menos tres componentes fundamentais devem ser cuidadosamente estudados: o material de suporte (scaffold), as celulas a usar e o sistema de cultura in vitro. Dai que os principais objectivos desta tese estejam relacionados com estes tres aspectos, nomeadamente: • Desenvolvimento de scaffolds biodegradaveis a partir de polimeros a base de amido de milho que induzam a adesao e proliferacao celular e que apresentem propriedades adequadas, tais como a porosidade e interconectividade entre poros, de forma a proporcionar um ambiente que favoreca o desenvolvimento in vitro de um material hibrido com caracteristicas similares ao osso humano. • Estudo da utilizacao de celulas da medula ossea como uma potencial fonte de celulas para engenharia do tecido osseo, uma vez que estas celulas podem ser facilmente recolhidas do proprio paciente a tratar por metodos nao-invasivos (bioppsia) e em quantidades suficientes. Alem disso, tratando-se de uma fonte de celulas autologas (obtidas do proprio paciente) permitem evitar os riscos de transmissao de doencas contagiosas e/ou de rejeicao pelo sistema imunologico. • Estudo da influencia das condicoes de cultura in vitro geradas por um bioreactor de perfusao (em comparacao com os metodos tradicionais de cultura em condicoes estaticas) no desenvolvimento dos materiais hibridos, compostos pelas celulas e scaffolds, assim como as interaccoes do ambiente proporcionado por este sistema de cultura com as diferentes estruturas/arquitecturas e porosidades dos scaffolds utilizados. Estes objectivos convergem para o objectivo geral desta tese que consistiu no desenvolvimento de uma terapia de engenharia do tecido osseo alternativa as existentes e com potencial para vir a ser posteriormente utilizada na pratica clinica. Este objectivo foi avaliado atraves do estudo da funcionalidade dos materiais hibridos obtidos em diferentes condicoes de cultura in vitro (e utilizando diferentes scaffolds), partindo do principio que o sistema de perfusao poderia eventualmente superar as limitacoes de difusao tipicas dos sistema de cultura estatica e simultaneamente proporcionar estimulos mecânicos as celulas, semelhantes aos encontrados em condicoes fisiologicas. (Abstract shortened by ProQuest.).

Lanthanide oxide and phosphate nanoparticles for thermometry and bimodal imaging =

NASA Astrophysics Data System (ADS)

Debasu, Mengistie Leweyehu

Nesta tese relatam-se estudos de fotoluminescencia de nanoparticulas de oxidos e fosfatos dopados com ioes trivalentes de lantanideos, respectivamente, nanobastonetes de (Gd,Eu)2O3 e (Gd,Yb,Er)2O3 e nanocristais de (Gd,Yb,Tb)PO4, demonstrando-se tambem aplicacoes destes materiais em revestimentos inteligentes, sensores de temperatura e bioimagem. Estuda-se a transferencia de energia entre os sitios de Eu3+ C2 e S6 dos nanobastonetes Gd2O3. A contribuicao dos mecanismos de transferencia de energia entre sitios para o tempo de subida 5D0(C2) e descartada a favor da relaxacao directa 5D1(C2) 5D0(C2) (i.e., transferencia de energia entre niveis). O maior tempo de decaimento do nivel 5D0(C2) nos nanobastonetes, relativamente ao valor medido para o mesmo material na forma de microcristais, e atribuido, quer a existencia de espacos livres entre nanobastonetes proximos (factor de enchimento ou fraccao volumica), quer a variacao do indice de refraccao efectivo do meio em torno dos ioes Eu3+. A dispersao de nanobastonetes de (Gd,Eu)2O3 em tres resinas epoxi comerciais atraves da cura por UV permite obter nanocompositos epoxi- (Gd,Eu)2O3. Relatam-se estudos cineticos e das propriedades termicas e de fotoluminescencia destes nanocompositos. Estes, preservam as tipicas propriedades de emissao do Eu3+, mostrando o potencial do metodo de cura por UV para obter revistimentos inteligentes e fotoactivos. Considera-se um avanco significativo a realizacao de uma nanoplataforma optica, incorporando aquecedor e termometro e capaz de medir uma ampla gama de temperaturas (300-2000 K) a escala nano, baseada em nanobastonetes de (Gd,Yb,Er)2O3 (termometros) cuja superficie se encontra revestida com nanoparticulas de ouro. A temperature local e calculada usando, quer a distribuicao de Boltzmann (300-1050 K) do racio de intensidades da conversao ascendente 2H11=2!4I15=2/4S3=2!4I15=2, quer a lei de Planck (1200-2000 K) para uma emissao de luz branca atribuida a radiacao do corpo negro. Finalmente, estudam-se as propriedades de fotoluminescencia correspondentes as conversoes ascendente e descendente de energia em nanocristais de (Gd,Yb,Tb)PO4 sintetizados por via hidrotermica. A relaxividade (ressonancia magnetica) do 1H destes materiais sao investigadas, tendo em vista possiveis aplicacoes em imagem bimodal (luminescencia e ressonancia magnetica nuclear).

Seismic ground motion scenarios in Lower Tagus Valley Basin

NASA Astrophysics Data System (ADS)

Borges, José; Torres, Ricardo; Furtado, José; Silva, Hugo; Caldeira, Bento; Pinto, Carlos; Bezzeghoud, Mourad; Carvalho, João

2013-04-01

Throughout its history the Lower Tagus Valley (LTV) has been struck by several earthquakes which produced important material damage and loss of lives: The 1st of November 1755 Lisbon earthquake and the 1969 earthquake (Mw=7.3), located in the SW Iberia Margin and the 1344, 1531 and 1909 (M= 6 to 7) with epicenter located inside the LTV basin. Since this region is the most highly populated region in Portugal, it is expected that an earthquake of similar magnitude of those that have occurred in the past will cause an enormous destruction and casualties. This fact makes LTV a high priority area for earthquake research in Portugal. In order to overcome the problems related to the absence of geological outcrops, low slip-rates (<0,4 mm/year) and the processes of sedimentation and erosion, we use in this work seismic reflection profiles, potential field data, soundings, wells and geological cartography to obtain a map of the main seismogenic structures and to characterize their seismic potential [1]. Moreover, a 3D structural model has been developed for de LTV based on Seismic reflection, Seismic Noise and potential field data [2,3]. In order to improve assessment of the seismic hazard in the LTV basin, we simulate long-period (0-1 Hz) ground motion time histories for a suite of scenarios earthquakes (Mw =5.5 to 7) within the basin, using fault geometries and the 3D seismic velocity structure based on the previous mentioned works. References [1] Pinto, Carlos C. (2011). Identification of Seismogenic Structures in the Lower Tagus Basin. Master Thesis, Universidade de Évora, 128 pp. [2] Torres, R.J.G., (2012). Modelo de velocidade da Bacia do Vale do Tejo: uma abordagem baseada no estudo do ruído sísmico ambiental, Master Thesis, Universidade de Évora, 83pp. [3] Furtado, J.A (2010). Confirmação do modelo da estrutura 3D do Vale Inverior do Tejo a partir de dados de ruído sísmico ambiente, Master Thesis, Universidade de Évora, 136pp.

Observações das explosões cósmicas de raios gama GRB021004 e GRB021211 com o satélite HETE

NASA Astrophysics Data System (ADS)

Braga, J.; Ricker, G.; Hurley, K.; Lamb, D.; Grew, G.; et al.

2003-08-01

O High Energy Transient Explorer (HETE) é o primeiro satélite inteiramente dedicado ao estudo das explosões cósmicas de raios gama (ECRGs). Lançado em 9 de outubro de 2000, o HETE possui instrumentação capaz de observar as ECRGs desde o UV até raios gama e localizá-las com precisão de ~ 1-10 minutos de arco. As localizações das ECRGs detectadas são disseminadas rapidamente (em alguns segundos) pela Internet através de uma rede de estações de recepção ao longo do equador. A participação brasileira nesse projeto se dá através da montagem e operação de uma estação de recepção em Natal, RN, e da participação na equipe científica da missão. Neste trabalho são apresentados resultados da observação pelo HETE de duas ECRGs: GRB 021004 e GRB 021211. A GRB021004 foi detectada em raios gama pelo HETE em 4 de outubro de 2002 e localizada em raios-X em apenas 48 s, quando a emissão de raios gama ainda estava se processando. A explosão, relativamente brilhante e longa, durou aproximadamente 100 s. Um transiente óptico de magnitude 15 foi detectado no local da explosão nove minutos após o evento, e observações realizadas após 7 horas determinaram um desvio para o vermelho de absorção de 1,6. O GRB021004 foi o burst mais bem observado até o momento e suas observações em vários comprimentos de onda têm sido fundamentais para o aprimoramento dos modelos de ECRGs. O GRB21211, um burst brilhante e rico em raios-X, foi detectado em 11 de dezembro de 2002 e localizado em raios-X em 22 s após o início do evento. A duração do burst foi de 2,3 s em altas energias (85 a 400 keV) e de 8,5 s em baixas energias (2 a 10 keV). Caso essa explosão não tivesse sido rapidamente localizada pelo HETE, ela teria sido classificada como "opticamente escura", já que o transiente óptico decaiu rapidamente de R < 14 a R»19 dentro dos primeiros 20 minutos e já estava mais fraco do que R»23 depois de 24 horas da ocorrência do burst. Serão discutidas as implicações desse resultado nos modelos de afterglows de ECRGs.

Life-cycle optimization model for distributed generation in buildings

NASA Astrophysics Data System (ADS)

Safaei, Amir

O setor da construcao e responsavel por uma grande parte do consumo de energia e emissoes na Uniao Europeia. A Geracao Distribuida (GD) de energia, nomeadamente atraves de sistemas de cogeracao e tecnologias solares, representa um papel importante no futuro energetico deste setor. A otimizacao do funcionamento dos sistemas de cogeracao e uma tarefa complexa, devido as diversas variaveis em jogo, designadamente: os diferentes tipos de necessidades energeticas (eletricidade, aquecimento e arrefecimento), os precos dinamicos dos combustiveis (gas natural) e da eletricidade, e os custos fixos e variaveis dos diferentes sistemas de GD. Tal torna-se mais complexo considerando a natureza flutuante das tecnologias solares termicas e fotovoltaicas. Ao mesmo tempo, a liberalizacao do mercado da eletricidade permite exportar para a rede, a electricidade gerada localmente. Adicionalmente, a operacao estrategica de um sistema de GD deve atender aos quadros politicos nacionais, se tiver como objetivo beneficiar de tais regimes. Alem disso, considerando os elevados impactes ambientais do setor da construcao, qualquer avaliacao energetica de edificios rigorosa deve tambem integrar aspetos ambientais, utilizando uma abordagem de Ciclo de Vida (CV). Uma avaliacao de Ciclo de Vida (ACV) completa de um sistema de GD deve incluir as fases relativas a operacao e construcao do sistema, bem como os impactes associados a producao dos combustiveis. Foram analisadas as emissoes da producao de GN, as quais variam de acordo com a origem, tipo (convencional ou nao-convencional), e estado (na forma de GN Liquefeito (GNL) ou gas). Do mesmo modo, o impacte dos sistemas solares e afetado pela meteorologia e radiacao solar, de acordo com a sua localizacao geografica. Sendo assim, uma avaliacao adequada dos sistemas de GD exige um modelo de ACV adequado a localizacao geografica (Portugal), integrando tambem a producao de combustivel (GN), tendo em conta as suas diferentes fontes de abastecimento. O principal objetivo desta tese de doutoramento foi desenvolver um modelo para otimizar o desenho e operacao de sistemas de GD para o setor da construcao de edificios comerciais em Portugal, considerando os respetivos Impactes de Ciclo de Vida (IAVC) e Custos de Ciclo de Vida (CCV), de modo a satisfazer as necessidades energeticas do edificio. Tres tipos de tecnologias de cogeracao (Micro-Turbinas, Motores de combustao interna, e Celulas combustiveis de Oxido solido), e dois tipos de tecnologias de energia solar, solar termica e fotovoltaica, constituem os sistemas de GD que sao acoplados aos sistemas convencionais. Foi desenvolvido um modelo de CV, tendo em conta todos os impactes relacionados com a construcao e operacao dos sistemas de energia, bem como os processos a montante relacionados com a producao do GN. Em particular, o mix de GN consumido em Portugal em 2011 foi identificado (60% da Nigeria, 40% da Argelia) e os impactes relativos a cada uma das vias de abastecimento foram avaliados separadamente para quatro categorias de impacte ambiental: Consumo de Energia Primaria (CEP), Gases com Efeito de Estufa (GEE), acidificacao, e eutrofizacao. Devido a importancia das emissoes de GEE na formulacao de politicas, foi tambem realizada uma analise de incerteza as emissoes de GEE do GN fornecido a Portugal. Foi desenvolvido um modelo matematico, em linguagem de Programacao General Algebraic Modeling System (GAMS), que utiliza os resultados da ACV dos sistemas de energia e as suas implicacoes economicas para minimizar o CCV e IACV ao longo de um horizonte de planeamento definido pelo decisor. Foram derivadas fronteiras otimas de Pareto, representando as relacoes entre o tipo de IACV (CEP, GEE, acidificacao, eutrofizacao) e CCV decorrentes da satisfacao das necessidades energeticas do edificio. Para aumentar a robustez do modelo, dada a incerteza dos precos dos combustiveis (GN e eletricidade), foi desenvolvido um modelo de custos robusto para os sistemas de GD, que e menos afetado por perturbacoes relativas aos custos de combustivel. A aplicacao do modelo proposto foi testada num caso de estudo real, um edificio comercial localizado na cidade de Coimbra, em Portugal.

EFFECTIVE INDICATORS FOR SCIENCE INTERNATIONALIZATION.

PubMed

Cunha-Melo, José Renan da

2015-01-01

To review of concepts and actions that aim to analyze the effects of internationalization of science and education, with emphasis in the medical field and its basement in development policies adopted by nations, exploring the potential for international interdisciplinary cooperation of each laboratory, department, university or institute. Search of indicators to assess the degree of internationalization of universities and research institutes in several interconnected levels: organizational, regional, sectoral and global, and policy-making in science, technology innovation and higher education. Scientific research is still carried out individually, but is now much more closely integrated with other social processes. The scientist is no longer a stranger who is allowed to surrender to his hobby to do what it wants. Internationalization of research and medical education, although it is among the topics of greatest need, as the globalized world, is difficult activity to be assessed. The leaders seem to have understood that the knowledge societies, leading to economic policy based on knowledge, can result in economic and social progress of nations. This fact has motivated increasingly the incentive to actions aimed at addressing global problems (eg health, climate change) by funding research that generates new knowledge. The consensus is that the internationalization of science is desirable and necessary for the sustainable development of nations. However it cannot be done only by encouraging and promoting the outward students and researchers abroad. It is necessary, in addition, offer conditions to foreign researchers and students teachers to work in collaboration with Brazilian and raise the country to international scientific standards. Apresentar revisão dos conceitos e ações que objetivam analisar os efeitos da internacionalização da ciência e da educação, com ênfase na área médica e seu embasamento nas políticas de desenvolvimento adotadas pelas nações, explorando o potencial para cooperação internacional interdisciplinar de cada laboratório, departamento, universidade ou instituto. Procura de indicadores que possam avaliar o grau de internacionalização das universidades e institutos de pesquisa em vários níveis interconectados: organizacional, regional, setorial e global e para definição de políticas nas áreas de ciência, tecnologia inovação e educação superior. A pesquisa científica ainda é realizada individualmente, mas está atualmente muito mais intimamente integrada a outros processos sociais. O cientista não é mais um estranho que tem permissão para entregar-se ao seu passatempo de fazer aquilo que bem entende. Internacionalização da pesquisa e da educação médica, embora esteja entre os tópicos de maior reconhecimento como sendo necessidade do mundo globalizado, é atividade difícil de ser avaliada. Os governantes parecem ter entendido que as sociedades do conhecimento, induzindo a política econômica baseada no conhecimento pode resultar em progresso econômico e social das nações. Esse fato tem motivado de forma crescente o incentivo às ações que visam a abordagem de problemas globais (e.g. saúde, mudanças climáticas) pelo financiamento da pesquisa que gera conhecimento novo. É consenso que a internacionalização da ciência é desejável e necessária para o desenvolvimento sustentável das nações. Entretanto ela não pode ser feita somente incentivando e fomentando a ida de estudantes e pesquisadores para o exterior. É preciso, em adição, oferecer condições a professores pesquisadores e estudantes estrangeiros para que possam atuar em colaboração com os brasileiros e elevar o país aos padrões científicos internacionais.

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.

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.

Factors associated with the implementation of programs for drug abuse prevention in schools.

PubMed

Pereira, Ana Paula Dias; Paes, Ângela Tavares; Sanchez, Zila M

2016-08-04

To analyze if characteristics of managers, schools, and curriculum are associated with the implementation of programs for drug abuse prevention in elementary and high schools. Cross-sectional study, with random sample of 263 school managers. Data were collected between 2012 and 2013 by a program that sends forms via internet. A closed self-filling questionnaire was applied online. Statistical analysis included Chi-square tests and logistic regression models. The outcome variable was the presence of program for drug abuse prevention inserted in the daily life and educational program of the school. The explanatory variables were divided into: demographic data of the manager; characteristics of the school and of the curriculum; health education; and drug use in the school. We found that 42.5% (95%CI 36.1-49.1) of the evaluated schools had programs for drug abuse prevention. With the multiple logistic regression model, we observed that the more time the manager has worked with education, the chance of the school having a program increased at about 4.0%. Experimenting with innovative teaching techniques also increased at about six times the chance of the school developing a program for drug abuse prevention. The difficulties in the implementation of the programs were more present in state and municipal schools, when compared with private schools, due to, for instance: lack of teaching materials, lack of money, and competing demands for teaching other subjects. The implementation of programs for drug abuse prevention in the city of Sao Paulo is associated with the experience of the manager in education and with the teaching strategies of the school. Analisar se características dos dirigentes, das escolas e do currículo escolar estão associadas à implantação de programas de prevenção ao uso de drogas nas escolas do ciclo fundamental II e médio. Estudo transversal, com amostra aleatória sistemática de 263 dirigentes escolares. Os dados foram coletados nos anos de 2012 e 2013 por meio de um programa de envio de formulários pela internet. Aplicou-se questionário fechado, de autopreenchimento on-line. A análise estatística incluiu testes Qui-quadrado e modelos de regressão logística. A variável desfecho foi a presença de programa de prevenção ao uso de drogas inserido no cotidiano e no programa pedagógico da escola. As variáveis explicativas foram divididas em: dados demográficos do dirigente; características da escola e do currículo; educação em saúde; e consumo de drogas na escola. Constatou-se que 42,5% (IC95% 36,1-49,1) das escolas avaliadas possuíam programa de prevenção ao uso de drogas. Com o modelo de regressão logística múltipla, observou-se que, a cada ano de atuação do dirigente na educação, a chance de a escola ter um programa aumentava em aproximadamente 4,0%. O fato de experimentar técnicas de ensino inovadoras também aumentou em cerca de seis vezes a chance de a escola desenvolver um programa de prevenção ao uso de drogas. As dificuldades na implantação dos programas foram mais presentes nas redes estadual e municipal, quando comparadas à rede privada, destacando-se: a falta de material didático, a falta de dinheiro e as demandas concorrentes para ensino de outras disciplinas. A implantação de programas de prevenção ao uso de drogas no município de São Paulo está associada à experiência do dirigente escolar na educação e nas estratégias de ensino da escola.

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

Systematic Review of Health Economic Evaluation Studies Developed in Brazil from 1980 to 2013.

PubMed

Decimoni, Tassia Cristina; Leandro, Roseli; Rozman, Luciana Martins; Craig, Dawn; Iglesias, Cynthia P; Novaes, Hillegonda Maria Dutilh; de Soárez, Patrícia Coelho

2018-01-01

Brazil has sought to use economic evaluation to support healthcare decision-making processes. While a number of health economic evaluations (HEEs) have been conducted, no study has systematically reviewed the quality of Brazilian HEE. The objective of this systematic review was to provide an overview regarding the state of HEE research and to evaluate the number, characteristics, and quality of reporting of published HEE studies conducted in a Brazilian setting. We systematically searched electronic databases (MEDLINE, EMBASE, Latin American, and Caribbean Literature on Health Sciences Database, Scientific Electronic Library Online, NHS Economic Evaluation Database, health technology assessment Database, Bireme, and Biblioteca Virtual em Saúde Economia da Saúde ); citation indexes (SCOPUS, Web of Science), and Sistema de Informação da Rede Brasileira de Avaliação de Tecnologia em Saúde . Partial and full HEEs published between 1980 and 2013 that referred to a Brazilian setting were considered for inclusion. In total, 535 studies were included in the review, 36.8% of these were considered to be full HEE. The category of healthcare technologies more frequently assessed were procedures (34.8%) and drugs (28.8%) which main objective was treatment (72.1%). Forty-four percent of the studies reported their funding source and 36% reported a conflict of interest. Overall, the full HEE quality of reporting was satisfactory. But some items were generally poorly reported and significant improvement is required: (1) methods used to estimate healthcare resource use quantities and unit costs, (2) methods used to estimate utility values, (3) sources of funding, and (4) conflicts of interest. A steady number of HEE have been published in Brazil since 1980. To improve their contribution to inform national healthcare policy efforts need to be made to enhance the quality of reporting of HEEs and promote improvements in the way HEEs are designed, implemented (i.e., using sound methods for HEEs) and reported.

Innovation, development, and financing of institutions of Higher Education in health.

PubMed

Poz, Mario Roberto Dal; Couto, Maria Helena Costa; Franco, Thais de Andrade Vidaurre

2016-11-03

The article analyzes the configuration and trends in institutions of Higher Education and their relationship as components of the Health Economic-Industrial Complex (HEIC). The expansion of higher education is part of the transition from elite to mass systems, with tensions between quantitative and qualitative aspects. Such changes reflect different cultures and are related to international phenomena such as globalization, economic transformations, the development of new information and communication technologies, and the emergence of an international knowledge network. The scale and content of these changes vary according to the expansion and institutional reconfiguration of educational systems, as well as the link between state and society. Market expansion for private higher education stirs competition, shapes business clusters, modifies training processes, and raises new public policy challenges. Resumo: Este artigo analisa a configuração e as tendências das instituições de Ensino Superior de saúde no seu relacionamento enquanto componentes do Complexo Econômico Industrial da Saúde (CEIS). A expansão do Ensino Superior é parte da transição de sistemas de elite para sistemas de massa, com tensionamentos entre aspectos quantitativos e qualitativos. Essas mudanças refletem diferentes culturas e se relacionam com fenômenos de escopo mundial como globalização, transformações econômicas, desenvolvimento de novas tecnologias de comunicação e informação, e emergência de uma rede internacional de conhecimento. A escala e o conteúdo dessas mudanças variam com a ampliação dos sistemas de ensino e na reconfiguração institucional, bem como na articulação entre Estado e sociedade. A ampliação do mercado privado no ensino acirra a competitividade, conformando conglomerados empresariais, alterando processos de formação e forjando novos desafios para as políticas públicas.

Use of health services by Brazilian older adults with and without functional limitation.

PubMed

Silva, Alexandre Moreira de Melo; Mambrini, Juliana Vaz de Melo; Peixoto, Sérgio Viana; Malta, Deborah Carvalho; Lima-Costa, Maria Fernanda

2017-06-01

To analyze the use of health services and the quality of medical care received by Brazilian older adults with and without functional limitation. The main analyses were based on a national sample representing 23,815 participants of the National Survey on Health (PNS) aged 60 years or older. Functional limitation was defined by the difficulty to perform at least one out of ten basic or instrumental activities of daily living. Potential confounding variables included predisposing and enabling factors of the use of health services. The prevalence of functional limitation was 30.1% (95%CI 29.2-31.4). The number of doctor visits and hospitalizations in the past 12 months showed statistically significant associations with functional limitation, both for users of the public system (OR = 2.48 [95%CI 2.13-2.88] for three or more doctor visits and OR = 2.58 [95%CI 2.15-3.09] for one or more hospitalizations) and of the private system (OR = 2.56 [95%CI 1.50-4.36] and OR = 2.22 [95%CI 1.64-3.00], respectively). The propensity to use basic health units was higher among users of the private system with functional limitations (OR = 2.01 [95%CI 1.12-3.59]). Only two out of seven indicators of the quality of medical care received were associated with functional limitation, in the perception of users of public and private systems. The public system users with functional limitations did worse evaluation of the freedom for choosing the doctor and waiting time for an appointment, when compared with users of the same system without these limitations (OR = 0.81 [95%CI 0.67-0.99] and OR = 0.76 [95%CI 0.62-0.93], respectively). Older adults with functional limitations use more health services in comparison with those without such limitations. The magnitude of the association between functional limitation and number of doctor visits and hospitalizations was similar in the public and private health systems. Analisar o uso de serviços de saúde e a qualidade da atenção médica recebida por idosos brasileiros com e sem limitação funcional. As análises principais foram baseadas em amostra nacional representativa de 23.815 participantes da Pesquisa Nacional de Saúde com 60 anos ou mais. A limitação funcional foi definida pela dificuldade para realizar pelo menos uma entre dez atividades básicas ou instrumentais da vida diária. Potenciais variáveis de confusão incluíram fatores predisponentes e facilitadores do uso de serviços de saúde. A prevalência da limitação funcional foi de 30,1% (IC95% 29,2-31,4). O número de consultas médicas e a ocorrência de hospitalizações nos últimos 12 meses apresentaram associações estatisticamente significantes com a limitação funcional, tanto entre usuários do sistema público (OR = 2,48 [IC95% 2,13-2,88] para três ou mais consultas e OR = 2,58 [IC95% 2,15-3,09] para uma ou mais hospitalizações) quanto do sistema privado (OR = 2,56 [IC95% 1,50-4,36] e OR = 2,22 [IC95% 1,64-3,00], respectivamente). A propensão ao uso da unidade básica de saúde foi maior entre usuários do sistema privado com limitações funcionais (OR = 2,01 [IC95% 1,12-3,59]). Entre sete indicadores da qualidade da atenção médica recebida, na percepção dos usuários dos sistemas público e privado, somente dois apresentaram associação com a limitação funcional. Os usuários do sistema público com limitações funcionais fizeram pior avaliação da liberdade para escolha do médico e do tempo de espera para a consulta, em comparação aos usuários do mesmo sistema sem essas limitações (OR = 0,81 [IC95% 0,67-0,99] e OR = 0,76 [IC95% 0,62-0,93], respectivamente). Idosos com limitações funcionais utilizam mais serviços de saúde em comparação aos seus pares sem essas limitações. A magnitude da associação entre a limitação funcional e o número de consultas médicas e de hospitalizações foi semelhante nos sistemas público e privado de saúde.

Evaluation of Reference Centers for Special Immunobiologicals implementation.

PubMed

Nóbrega, Laura Andrade Lagôa; Novaes, Hillegonda Maria Dutilh; Sartori, Ana Marli Christovam

2016-09-01

To describe the Reference Centers for Special Immunobiologicals and evaluate their implementation considering formal regulations. We conducted a program evaluation, of evaluative research type. From August 2011 to January 2012, a questionnaire was applied to the 42 Reference Centers for Special Immunobiologicals existing in the Country, approaching the structure, human resources, and developed activities dimensions. We conducted a descriptive analysis of data and used a clustering for binary data with the squared Euclidean distance, by the farthest neighbor method, to aggregate services with similar features. We observed great diversity among the services in the three dimensions. The clustering resulted in five service profiles, named according to their characteristics. 1) Best structure: 12 Reference Centers for Special Immunobiologicals with the highest proportion of services with the minimum of rooms recommended, purpose-built vaccine refrigerators, preventive maintenance of the cold chain, and oxygen source. 2) Immunobiologicals distributor: six Reference Centers for Special Immunobiologicals that distributed more than applied immunogens; no doctor present for more than half of the working hours and no purpose-built vaccine refrigerators . 3) Incipient implementation: five Reference Centers for Special Immunobiologicals with inadequate structure, such as absence of purpose-built vaccine refrigerators, preventive maintenance of the cold chain and oxygen source; none had computer. 4) Vaccination rooms: 13 Reference Centers for Special Immunobiologicals, everyone did routine immunization, most participated in vaccination campaigns. 5) Teaching and research: six services, all inserted into teaching hospitals, developed researches and received trainees; most had doctors in more than half of the working hours. The evaluation of the Reference Centers for Special Immunobiologicals implementation was based on the profiles found and considered the official regulations: services categorized as "better structure" and "teaching and research" were considered implemented; "immunobiologicals distributor" and "vaccination room" services, partially implemented, and the ones with the "incipient implementation" profile, not implemented. The results of this evaluation can contribute to the reformulation of the services, considering the current context. Descrever os Centros de Referência para Imunobiológicos Especiais e avaliar sua implantação considerando as regulamentações formais. Foi realizada uma avaliação de programa, tipo pesquisa avaliativa. De agosto de 2011 a janeiro de 2012, foi aplicado questionário aos responsáveis pelos 42 Centros de Referência para Imunobiológicos Especiais existentes no País, abordando as dimensões estrutura, recursos humanos e atividades desenvolvidas. Foi feita análise descritiva dos dados e utilizado agrupamento para dados binários com uso da distância euclidiana quadrática, pelo método do vizinho mais distante, para agregar serviços com características semelhantes. Observou-se grande diversidade entre os serviços nas três dimensões. O agrupamento resultou em cinco perfis de serviços, denominados de acordo com suas características. 1) Melhor estrutura: 12 Centros de Referência para Imunobiológicos Especiais com a maior proporção de serviços com o mínimo de salas preconizado, câmaras de vacinas, manutenção preventiva da rede de frio e fonte de oxigênio. 2) Dispensador de imunobiológicos: seis Centros de Referência para Imunobiológicos Especiais que mais dispensavam do que aplicavam imunógenos; sem médico presente por mais da metade do expediente do serviço e sem câmara de vacinas. 3) Implantação incipiente: cinco Centros de Referência para Imunobiológicos Especiais com estrutura inadequada, como ausência de câmaras de vacinas, de manutenção preventiva da rede de frio e de fonte de oxigênio; nenhum possuía computador. 4) Sala de vacinas: 13 Centros de Referência para Imunobiológicos Especiais, todos faziam imunização de rotina, a maioria participava de campanhas de vacinação. 5) Ensino e pesquisa: seis serviços, todos inseridos em hospitais de ensino, desenvolviam pesquisas e recebiam estagiários; a maioria possuía médicos em mais da metade do expediente. A avaliação de implantação dos Centros de Referência para Imunobiológicos Especiais baseou-se nos perfis encontrados e considerou as regulamentações oficiais: os serviços categorizados como "melhor estrutura" e "ensino e pesquisa" foram considerados implantados; os serviços "dispensador de imunobiológicos" e "sala de vacinas", parcialmente implantados e os do perfil "implantação incipiente", não implantados. Os resultados dessa avaliação podem contribuir para a reformulação dos serviços, considerando o contexto atual.

Attitude and knowledge about foot health: a spanish view.

PubMed

López-López, Daniel; García-Mira, Ricardo; Palomo-López, Patricia; Sánchez-Gómez, Rubén; Ramos-Galván, José; Tovaruela-Carrión, Natalia; García-Sánchez, Matilde

2017-04-06

to explore attitudes towards patients' self-reported data about foot health-related beliefs from a behavioural and attitudinal perspective. a sample of 282 participants of a mean age of 39.46 ± 16.026 came to a health centre where self-reported demographic, clinical characteristics and beliefs relating to foot health data were registered, informants' completed all the stages of the research process. the results of the analysis revealed an 8-factor factorial structure based on (1) podiatric behaviours, (2) the intention to carry out protective behaviour, (3) attitudinal beliefs, (4) normative beliefs, (5) needs, (6) apathy, (7) self-care, and (8) the general perception of foot health. They all explained 62.78% of the variance, and were considered as independent variables in a regression analysis to determine which provided the best explanations for the importance attributed to foot health. the participants in the study revealed a positive attitude in relation to foot health care and responsible behaviour. explorar as atitudes em relação aos dados auto-relatados dos pacientes sobre crenças relacionadas à saúde do pé, desde uma perspectiva comportamental e atitudinal. uma amostra de 282 participantes com idade média de 39,46 ± 16,026 chegaram a um centro de saúde onde foram registradas características demográficas, clínicas e crenças auto-relatadas referentes a dados de saúde do pé, os quais completaram todas as fases do processo de pesquisa. os resultados da análise revelaram uma estrutura fatorial de 8 fatores baseada em (1) comportamentos podiátricos, (2) a intenção de realizar comportamentos protetores, (3) crenças atitudinais, (4) crenças normativas, (6) apatia, (7) autocuidado, e (8) a percepção geral da saúde do pé. Todos eles explicaram 62,78% da variância e foram considerados como variáveis ​​independentes em uma análise de regressão para determinar quais forneceram as melhores explicações para a importância atribuída à saúde do pé. os participantes do estudo revelaram uma atitude positiva em relação à saúde do pé e comportamento responsável. explorar las actitudes relacionadas con datos autoinformados sobre las creencias de la salud del pie desde una perspectiva actitudinal. una muestra de 282 participantes edad media 39.46 ± 16.026 acudieron a un centro de salud donde se registraron datos autoinformados de las características demográficas, características clínicas y creencias relacionadas con la salud del pie, completándose todas las etapas del proceso de investigación. los resultados del análisis revelaron una estructura factorial de 8 factores basado en (1) conductas podológicas, (2) la intención de llevar a cabo una conducta de protección, (3) las creencias actitudinales, (4) las creencias normativas, (5) las necesidades, (6) la apatía, (7) el autocuidado, y (8) la percepción general de salud podal. Todos ellos explicaron un 62,78% de la varianza, y fueron considerados como variables independientes en una ecuación de regresión para determinar cuáles de ellos explicaban mejor la importancia atribuida a la salud del pie. los participantes en el estudio revelaron una actitud positiva en relación al cuidado de la salud del pie y al comportamiento responsable.

Informal and paid care for Brazilian older adults (National Health Survey, 2013).

PubMed

Lima-Costa, Maria Fernanda; Peixoto, Sérgio Viana; Malta, Deborah Carvalho; Szwarcwald, Célia Landmann; Mambrini, Juliana Vaz de Melo

2017-06-01

To describe the prevalence and sociodemographic factors associated with informal and paid care for Brazilian older adults with functional limitations. Of the 23,815 participants of the National Health Survey aged 60 or older, 5,978 reported needing help to perform activities of daily living and were included in this analysis. The dependent variable was the source of care, categorized as exclusively informal (unpaid), exclusively formal (paid), mixed or none. The socio-demographic variables were age (60-64, 65-74, ≥ 75 years old), gender and number of residents in the household (1, 2, ≥ 3). The multivariate analysis was based on binomial and multinomial logistic regressions. Informal care predominated (81.8%), followed by paid (5.8%) or mixed (6.8%) and no care (5.7%). The receipt of care from any source increased gradually with the number of residents in a same household, regardless of age and gender (OR = 4.85 and 9.74 for 2 and ≥ 3, respectively). Age was positively associated with receiving any care while the male gender showed a negative association. The number of residents in the household showed the strongest association with informal care (OR = 10.94 for ≥ 3 residents), compared with paid (OR = 5.48) and mixed (OR = 4.16) care. Informal care is the main source of help for community-dwelling older adults with functional limitations. In a context of rapid population aging and decline in family size, the results reinforce the need for policies to support long-term care for older Brazilians. Descrever a prevalência e fatores sociodemográficos associados à ajuda informal e remunerada a idosos com limitações funcionais. Dos 23.815 participantes com 60 anos ou mais da Pesquisa Nacional de Saúde, 5.978 declararam necessitar de ajuda para realizar atividades da vida diária e foram incluídos nesta análise. A variável dependente foi a fonte de ajuda, categorizada como exclusivamente informal (não remunerada), exclusivamente remunerada, mista ou nenhuma. Os fatores sociodemográficos foram idade (60-64, 65-74, ≥ 75 anos), sexo e número de moradores no domicílio (1, 2, ≥ 3). A análise multivariada foi baseada nas regressões logísticas binomial e multinomial. A ajuda informal predominou (81,8%), seguida pela remunerada (5,8%) ou mista (6,8%) e nenhuma (5,7%). A propensão ao recebimento da ajuda por qualquer fonte aumentou gradativamente com o número de moradores no domicílio, independentemente da idade e do sexo (OR = 4,85 e 9,74 para 2 e ≥ 3 moradores, respectivamente). A idade apresentou associação positiva e o sexo masculino apresentou associação negativa com o recebimento de qualquer ajuda. O número de moradores no domicílio apresentou associação mais forte com a ajuda informal (OR = 10,94 para ≥ 3 moradores), em comparação à ajuda remunerada (OR = 5,48) e mista (OR = 4,16). O cuidado informal é a principal fonte de ajuda domiciliar aos idosos com limitações funcionais. Em um contexto de rápido envelhecimento populacional e diminuição do tamanho das famílias, os resultados reforçam a necessidade de políticas para garantir o cuidado domiciliar aos idosos com limitações funcionais.

Medical Recording Tools for Biodosimetry in Radiation Incidents

DTIC Science & Technology

2005-01-01

assistant) devices. To ac- complish this, the second edition of the AFRRI handbook will be redesigned, using Adobe FrameMaker desk- top publishing...Handbook will be redes- igned for display on hand-held computer devices, using Adobe FrameMaker desktop publishing software. Portions of the text

A social and ecological assessment of tropical land uses at multiple scales: the Sustainable Amazon Network

EPA Science Inventory

Science has a critical role to play in guiding more sustainable development trajectories. Here we present the Sustainable Amazon Network (Rede Amazônia Sustentável, RAS): a multi-disciplinary research initiative involving more than 30 partner organisations working to assess both ...

Rede und Gesinnung (Speech and Ways of Thinking)

ERIC Educational Resources Information Center

Kienzle, Bertram

1974-01-01

Analyzes some of the basic ideas in Georg Franklin's book "Versuch einer neuen Lehre von den vornehmsten Gegenstanden der deutschen Sprachlehre; nach den Regeln der Vernunftlehre in sechs Abhandlungen verfasst" (1778) and compares them to those of such modern linguists and philosophers a s Searle, Austin and Wunderlich. Concludes that…

COST-EFFECTIVENESS OF PERIOPERATIVE IMMUNONUTRITION IN GASTROINTESTINAL ONCOLOGIC SURGERY: A SYSTEMATIC REVIEW.

PubMed

Reis, Audrey Machado Dos; Kabke, Geórgia Brum; Fruchtenicht, Ana Valéria Gonçalves; Barreiro, Taiane Dias; Moreira, Luis Fernando

2016-01-01

Costs, length of hospital staying and morbidity are frequently and significantly increased as a result of infections and other complications following surgical procedure for gastrointestinal tract cancer. Recently, improving host defence mechanisms have become a target of interest. Immunonutrition aims at improving immunity, most likely providing key nutrients to maintain T-lymphocyte and other host defence. To evaluate the immunonutrition in cancer patients who are operated by digestive diseases and assess the cost-effectiveness of this supplementation. This study consisted of a systematic review of the literature based on reference analyses retrieved from current databases such as PubMed, Lilacs and SciELO. The search strategy was defined by terms related to immunonutrition [immunonutrition, arginine, omega-3 and nucleotides] in combination with [costs, cost-effective and cost-effectiveness] as well as [gastrointestinal cancer surgery, oesophageal, gastric or pancreatic surgery] in English, Portuguese or Spanish language. For cost analyses, currencies used in the manuscripts were all converted to American dollars (US$) in order to uniform and facilitate comparison. Six prospective randomized studies were included in this review. The cost-effectiveness was positive in most of studies, demonstrating that this diet can significantly reduce hospital costs in the North hemisphere. However, similar studies needed to be carried to determine such results among us. Custos, tempo de hospitalização e morbidade estão frequentemente aumentados na presença de infecções e outras complicações decorrentes de procedimentos cirúrgicos para o câncer gastrointestinal. Recentemente, a melhora de mecanismos de defesa do hospedeiro tem se tornado um alvo de interesse. Nutrição adequada está fortemente relacionada com competência imune e redução de infeções. Imunonutrição objetiva a melhora da imunidade, principalmente para manutenção de linfócitos-T e outras defesas. Avaliar a imunonutrição em pacientes oncológicos que são operados por doenças do aparelho digestivo e avaliar a relação custo-eficácia desta suplementação. Revisão sistemática da literatura baseada nas bases de dados PubMed, Lilacs e SciELO. A busca foi realizada com combinação de descritores em inglês e português relacionados ao tema da revisão: [immunonutrition, arginine, omega-3, nucleotides] combinado com [costs, cost-effective, cost-effectiveness] e [gastrointestinal cancer surgery, oesophageal, gastric or pancreatic surgery]. Para análise de custos, moedas usadas nos artigos foram todas convertidas para dólar americano. Seis estudos randomizados prospectivos foram incluídos nesta revisão. O custo-benefício foi positivo na maioria dos estudos, sugerindo que este tipo de dieta reduz significativamente os custos hospitalares nos países do hemisfério norte. Contudo, estudos similares de custo-benefício devem ser realizados para definir o real custo-benefício em nosso meio.

Pragma- und textilinguistische Untersuchungsmethoden zur indirekten Rede im Englischen (Pragmatic and Text-Linguistic Research Methods on Indirect Discourse in English)

ERIC Educational Resources Information Center

Ziegesar, Detlef von

1976-01-01

Examines the mechanisms involved in changing from direct to indirect discourse, taking as a starting point research findings in linguistic pragmatics, which involve the practical application of speech symbol use between speaker and hearer. (Text is in German.) (IFS/WGA)

Effects of Alloy Chemistry Changes on Sacrificial Aluminum Anode Performance, Tri-Service Committee on Corrosion Proceedings

DTIC Science & Technology

1994-06-01

Notes 14. Abstract 15. Subject Terms Tri-Service Conference on Corrosion A • PON ... i 19. Limitation 20. # of 21. Responsible Person...review of the text. REFERENCES 1. Reding , J.’ J.J. Newport III and J.R. Minderhout; US Patent 3,321,306, "Galvanic Anode Alloy and Products Produced

Creative and Critical Thinking in the Arts and Sciences: Some Examples of Congruence

ERIC Educational Resources Information Center

Karakas, Scott L.

2010-01-01

In his landmark 1959 Rede lecture and subsequent publication, physicist Charles Percy Snow expressed concerns over what he saw as a growing rift between scientific and literary scholarly communities (Snow 1959). In the 50 years since that time, scholars and other commentators have expended a great deal of intellectual capital in the analysis of…

Velocity and structural model of the Lower Tagus Basin according to the study of environmental seismic noise

NASA Astrophysics Data System (ADS)

Gomes Torres, Ricardo Jorge; Furtado, José Augusto; Gonçalves Silva, Hugo; Borges, José Fernando; Caldeira, Bento; Bezzeghoud, Mourad; Carvalho, João

2013-04-01

Along his history the Lower Tagus Valley (LTV) region was shaken by several earthquakes, some of them produced in large ruptures of offshore structures located southwest of the Portuguese coastline. Among these is the Lisbon earthquake of 1 November 1755 (M~8.5-8.7), and other moderates earthquakes that were produced by local sources such as the 1344 (M6.0), 1531 (M7.1) and 1909 (M6.0) earthquakes. Previous simulations [1] have shown high velocity amplification in the region. The model used in the simulations was updated from low to high resolution using all the new available geophysical and geotechnical data on the area (seismic reflection, aeromagnetic, gravimetric, deep wells and geological outcrops) [2]. To confirm this model in the areas where it was derived by potential field methods we use broadband ambient noise measurements collected in about 200 points along seven profiles on the LTV basin, six perpendicular and one parallel to the basin axis. We applied the horizontal to vertical (H/V) spectral ratio method [3] to the seismic noise profiles in order to estimate the distribution of amplification in the basin. The H/V curves obtained reveals the existence of two low frequency peaks centered on 0.2 and 1 Hz [4]. These peaks are strongly related with the thickness of Cenozoic and alluvial sediments. The velocity model obtained by inversion of the H/V curves is in good agreement with borehole data, and results obtained using seismic reflection and gravimetric methods. However, aeromagnetic data overestimates the depth of the base of Cenozoic in the areas where it overlies directly the paleozoic basement, which we attribute either to the existence of Mesozoic units or higher magnetic susceptibilities than expected for the Paleozoic. References: [1] Bezzeghoud, M., Borges, J.F., M., Caldeira (2011). Ground motion simulations of the SW Iberia margin: rupture directivity and earth structure effects. Natural Hazards, pages 1-17. doi:10.1007/s11069-011-9925-2 [2] Torres, R.J.G., (2012). Modelo de velocidade da Bacia do Vale do Tejo: uma abordagem baseada no estudo do ruído sísmico ambiental, Master Thesis, Universidade de Évora, 83pp. [3] Nakamura, Y., 1989. A method for dynamic characteristics estimations of subsurface using microtremors on the ground surface, Quarterly Report, RTRI, Japan, v. 30, p. 25-33. [4] J.A. Furtado, Confirmação do modelo da estrutura 3D do Vale Inverior do Tejo a partir de dados de ruído sísmico ambiente, Master Thesis, Universidade de Évora, 136pp, 2010.

Development of lithium disilicate based glass-ceramics =

NASA Astrophysics Data System (ADS)

Fernandes, Hugo Alexandre Goncalves da Rocha

O principal objectivo deste estudo foi o desenvolvimento de vitroceramicos a base de dissilicato de litio no sistema Li2O-K2O-Al2O3-SiO2 contendo uma razao molar SiO2/Li2O muito afastada da do dissilicato de litio (Li2Si2O5) usando composicoes simples e a tecnica tradicional de fusao-vazamento de vidro de forma a obter materiais com propriedades mecanicas, termicas, quimicas e electricas superiores que permitam a utilizacao destes materiais em diversas aplicacoes funcionais. Investigou-se o fenomeno de separacao de fases, a cristalizacao e as relacoes estrutura-propriedades de vidros nos sistemas Li2O-SiO2, Li2O-Al2O3-SiO2 e Li2O-K2O-Al2O3-SiO2. Os vidros nos sistemas Li2O-SiO2 e Li2O-Al2O3-SiO2 apresentaram fraca densificacao e resultaram em materiais frageis, contrastando com a boa sinterizacao dos vidros no sistema Li2O-K2O-Al2O3-SiO2. Pequenas adicoes de Al2O3 e K2O ao sistema Li2O-SiO2 permitiram controlar a separacao de fases devido a formacao de especies de Al(IV) que confirmaram o papel de Al2O3 como formador de rede. Os compactos de po de vidro das composicoes contendo Al2O3 e K2O tratados termicamente resultaram em vitroceramicos bem densificados, apresentando dissilicato de litio como a principal fase cristalina, e valores de resistencia mecanica a flexao, resistencia quimica e condutividade electrica (173-224 MPa, 25-50 mg/cm2 e 2´10-18 S/cm, respectivamente) que possibilitam a utilizacao destes materiais em diversas aplicacoes funcionais. A adicao de P2O5, TiO2 e ZrO2 ao sistema Li2O-K2O-Al2O3-SiO2 como agentes nucleantes revelou que os vidros contendo apresentaram cristalizacao em volume, com a formacao de metassilicato de litio a temperaturas mais baixas e dissilicato de litio para as temperaturas mais elevadas, enquanto a adicao de zirconia reduz o grau de segregacao, aumenta a polimerizacao da matriz vitrea e desloca o valor de Tg para temperaturas superiores, inibindo a cristalizacao.

Outsourcing and "dismantling" of steady jobs at hospitals.

PubMed

Souza, Helton Saragor de; Mendes, Áquilas Nogueira

2016-04-01

To relate hospitals' organizational structure as the core of a web of outsourced services and flexible employment bonds among healthcare professionals in the context of finance capitalism, analyzing work arrangements based mainly on the type of employment bond. Qualitative research through ethnography, interviews, data analysis, and case studies. The case studies were concentrated in 3 hospitals located in the São Paulo metropolitan region under different management types: public administration; outsourced administration via a healthcare social organization (HSO); and private administration. This study highlights a trend in outsourcing, dismantling of steady jobs, and shaping working relations asymmetrically in terms of healthcare professions. These aspects are characteristic of contemporary capitalism and post-Fordist work organization. In this context, the state under sponsorship cripples the very existence of an effective human resources policy, creating a favorable environment for outsourcing and flexibility of employment bonds among healthcare workers. Relacionar a estrutura organizativa dos hospitais como núcleo de uma rede de serviços subcontratados e a flexibilização dos vínculos contratuais dos profissionais de saúde no contexto de capitalismo financeirizado, analisando os regimes de trabalho condicionados centralmente pelo vínculo empregatício. Pesquisa qualitativa através de etnografia, realização de entrevistas, análise de dados e utilização de estudo de caso. Os estudos de caso concentram-se em três hospitais localizados Região Metropolitana de São Paulo com gestões distintas: administração pública; administração terceirizada para Organização Social de Saúde (OSS); e administração privada. Destacamos a tendência da terceirização, do desmonte do emprego estável e a conformação de relações trabalhistas assimétricas para as profissões em saúde. Esses aspectos são característicos do período do capitalismo contemporâneo e da organização pós-fordista do trabalho. Nesse contexto, o subfinanciamento do Estado inviabiliza uma política de recursos humanos efetiva, configurando o ambiente propício para as terceirizações e flexibilidade do vínculo empregatício para os trabalhadores de saúde.

Social representations of the health care of the Mbyá-Guarani indigenous population by health workers.

PubMed

Falkenberg, Mirian Benites; Shimizu, Helena Eri; Bermudez, Ximena Pamela Díaz

2017-02-06

to analyze the social representations of health care of the Mbyá-Guarani ethnic group by multidisciplinary teams from the Special Indigenous Health District in the south coast of Rio Grande do Sul state (Distrito Sanitário Especial Indígena Litoral Sul do Rio Grande do Sul), Brazil. a qualitative method based on the theory of social representations was used. Data were collected via semi-structured interviews with 20 health workers and by participant observation. The interviews were analyzed with ALCESTE software, which conducts a lexical content analysis using quantitative techniques for the treatment of textual data. there were disagreements in the health care concepts and practices between traditional medicine and biomedicine; however, some progress has been achieved in the area of intermedicality. The ethnic boundaries established between health workers and indigenous peoples based on their representations of culture and family, together with the lack of infrastructure and organization of health actions, are perceived as factors that hinder health care in an intercultural context. a new basis for the process of indigenous health care needs to be established by understanding the needs identified and by agreement among individuals, groups, and health professionals via intercultural exchange. analisar as representações sociais do cuidado em saúde entre trabalhadores que atuam em equipes multidisciplinares no Distrito Sanitário Especial Indígena Litoral Sul do Rio Grande do Sul, junto à etnia Mbyá-Guarani. utilizou-se método qualitativo, fundamentado na teoria das Representações Sociais. Os dados foram coletados por meio de entrevistas semiestruturadas com 20 trabalhadores e da observação participante. As entrevistas analisadas com o software ALCESTE, o qual realiza a análise lexical de conteúdo por meio de técnicas quantitativas de tratamento de dados textuais. verificou-se que existe tensão entre as concepções e práticas de cuidado da medicina tradicional e da biomedicina, mas observam-se alguns avanços na perspectiva da intermedicalidade. Fronteiras étnicas estabelecidas entre os trabalhadores e os indígenas, baseadas em suas representações de cultura e família, da mesma maneira que a falta de infraestrutura e os modos de organização do trabalho em saúde são percebidos como fatores que dificultam o cuidado em contextos de interculturalidade. é preciso estabelecer novas bases para o processo de cuidar em saúde indígena, a partir da compreensão das necessidades representadas, negociadas entre sujeitos individuais e coletivos e os profissionais nas instituições de saúde em um diálogo intercultural de múltiplas vozes. analizar las representaciones sociales de la atención de la salud del grupo étnico Mbyá-Guaraní por equipos multidisciplinarios del Distrito Sanitario Especial Indígena en la costa sur del estado de Rio Grande do Sul (Distrito Sanitário Especial Indígena Litoral Sul do Rio Grande do Sul), Brasil. se utilizó un método cualitativo basado en la teoría de las representaciones sociales. Los datos fueron recogidos a través de entrevistas semi-estructuradas con 20 trabajadores de la salud y por observación de los participantes. Las entrevistas fueron analizadas con el programa ALCESTE, que realiza un análisis de contenido léxico utilizando técnicas cuantitativas para el tratamiento de datos textuales. hubo desacuerdos en los conceptos y prácticas de atención médica entre medicina tradicional y biomedicina; sin embargo, se han logrado algunos avances en el área de la intermedicina. Las barreras étnicas establecidas entre los trabajadores de la salud y los pueblos indígenas basados en sus representaciones de la cultura y la familia, junto con la falta de infraestructura y organización de las acciones de salud, son percibidas como factores que obstaculizan la atención sanitaria en un contexto intercultural. es necesario establecer una nueva base para el proceso de atención de salud indígena mediante la comprensión de las necesidades identificadas y por acuerdo entre individuos, grupos y profesionales de la salud a través del intercambio intercultural.

Needs of family caregivers in home care for older adults.

PubMed

Bierhals, Carla Cristiane Becker Kottwitz; Santos, Naiana Oliveira Dos; Fengler, Fernanda Laís; Raubustt, Kamila Dellamora; Forbes, Dorothy Anne; Paskulin, Lisiane Manganelli Girardi

2017-04-06

to reveal the felt and normative needs of primary family caregivers when providing instrumental support to older adults enrolled in a Home Care Program in a Primary Health Service in the South of Brazil. using Bradshaw's taxonomy of needs to explore the caregiver's felt needs (stated needs) and normative needs (defined by professionals), a mixed exploratory study was conducted in three steps: Descriptive quantitative phase with 39 older adults and their caregiver, using a data sheet based on patient records; Qualitative exploratory phase that included 21 caregiver interviews, analyzed by content analysis; Systematic observation, using an observation guide with 16 caregivers, analyzed by descriptive statistics. the felt needs were related to information about instrumental support activities and subjective aspects of care. Caregivers presented more normative needs related to medications care. understanding caregivers' needs allows nurses to plan interventions based on their particularities. identificar as necessidades sentidas e normativas dos cuidadores familiares principais no apoio instrumental a idosos registrados em um Programa de Atenção Domiciliar em uma Unidade Básica de Saúde no Sul do Brasil. usando a Taxonomia de Necessidades de Bradshaw para explorar as necessidades sentidas (necessidades declaradas) e normativas (definidas por profissionais), desenvolveu-se um estudo exploratório misto em três etapas: Etapa descritiva quantitativa, envolvendo 39 idosos e seus cuidadores, com a ajuda de um folha de dados baseada no prontuário do paciente; Etapa exploratória qualitativa, baseada em entrevistas com 21 cuidadores, analisadas mediante a análise de conteúdo; Observação sistemática, aplicando um roteiro de observação a 16 cuidadores, com análise estatística descritiva. as necessidades sentidas estavam relacionadas a informações sobre atividades de apoio instrumental e aspectos subjetivos do cuidado. Os cuidadores apresentaram maior número de necessidades normativas associadas ao cuidado com as medicações. compreender as necessidades dos cuidadores permite aos enfermeiros planejar intervenções baseadas em suas particularidades. descubrir las necesidades sentidas y normativas de los cuidadores primarios familiares en la prestación de apoyo instrumental a ancianos registrados en un Programa de Atención Domiciliaria en una Unidad Básica de Salud en el sur de Brasil. usando la Taxonomía de Necesidades de Bradshaw para explorar las necesidades sentidas (necesidades declaradas) y normativas (definidas por profesionales), fue desarrollado un estudio exploratorio mixto en tres etapas: Etapa descriptiva cuantitativa, involucrando 39 ancianos y sus cuidadores, mediante una hoja de datos basada en el archivo del paciente; Etapa exploratoria cualitativa, basada en entrevistas con 21 cuidadores, analizadas mediante el análisis de contenido; Observación sistemática, aplicando un manual de observación a 16 cuidadores, con análisis estadístico descriptivo. las necesidades sentidas estaban relacionadas a informaciones sobre actividades de apoyo instrumental y aspectos subjetivos de la atención. Los cuidadores presentaron mayor número de necesidades normativas asociadas al cuidado con medicaciones. comprender las necesidades de los cuidadores permite a los enfermeros planificar intervenciones basadas en sus particularidades.

Bilingual Education. Papers Presented at the Language Teaching Conference (3rd, La Trobe University, May 3-4, 1974).

ERIC Educational Resources Information Center

Rado, Marta, Ed.

The conference was held to alert teachers and other interested persons to the complexities of linguistic diversity in Australia, with attention focused on the immigrant child. This report includes the individual conference papers, presented by Marta Rado, Bert Townsend, Michael Clyne, Alan Matheson, and Rede Lar, and the comments of symposium and…

"The Two Cultures" and the Historical Perspective on Science as a Culture

ERIC Educational Resources Information Center

Rocherberg, Francesca

2007-01-01

In the Rede lecture of 1959, C.P.Snow speaks in terms of two cultures, one of science, the other of literary intellectuals. Snow's discussion presupposes that science represents a culture of its own, independent of and superior to the arts and humanities, and unified within itself. At our present distance from this claim, Snow's point of view can…

An Epidemiologic Study of Genetic Variation in Hormonal Pathways in Relation to the Effect of Hormone Replacement Therapy on Breast Cancer Risk

DTIC Science & Technology

2007-04-01

active learning techniques in Introduction to Epidemiology Ongoing5 W81XWH-06-1-0312 Reding, Kerryn 7 TASK STATUS of FUTURE TASKS Task 3...Apply for and obtain IRB renewal Ongoing task Task 4: Training-related Work (Months 13-36) a. Present research findings on active learning at

Towards estimates of future rainfall erosivity in Europe based on REDES and WorldClim datasets

NASA Astrophysics Data System (ADS)

Panagos, Panos; Ballabio, Cristiano; Meusburger, Katrin; Spinoni, Jonathan; Alewell, Christine; Borrelli, Pasquale

2017-05-01

The policy requests to develop trends in soil erosion changes can be responded developing modelling scenarios of the two most dynamic factors in soil erosion, i.e. rainfall erosivity and land cover change. The recently developed Rainfall Erosivity Database at European Scale (REDES) and a statistical approach used to spatially interpolate rainfall erosivity data have the potential to become useful knowledge to predict future rainfall erosivity based on climate scenarios. The use of a thorough statistical modelling approach (Gaussian Process Regression), with the selection of the most appropriate covariates (monthly precipitation, temperature datasets and bioclimatic layers), allowed to predict the rainfall erosivity based on climate change scenarios. The mean rainfall erosivity for the European Union and Switzerland is projected to be 857 MJ mm ha-1 h-1 yr-1 till 2050 showing a relative increase of 18% compared to baseline data (2010). The changes are heterogeneous in the European continent depending on the future projections of most erosive months (hot period: April-September). The output results report a pan-European projection of future rainfall erosivity taking into account the uncertainties of the climatic models.

Towards estimates of future rainfall erosivity in Europe based on REDES and WorldClim datasets.

PubMed

Panagos, Panos; Ballabio, Cristiano; Meusburger, Katrin; Spinoni, Jonathan; Alewell, Christine; Borrelli, Pasquale

2017-05-01

The policy requests to develop trends in soil erosion changes can be responded developing modelling scenarios of the two most dynamic factors in soil erosion, i.e. rainfall erosivity and land cover change. The recently developed Rainfall Erosivity Database at European Scale (REDES) and a statistical approach used to spatially interpolate rainfall erosivity data have the potential to become useful knowledge to predict future rainfall erosivity based on climate scenarios. The use of a thorough statistical modelling approach (Gaussian Process Regression), with the selection of the most appropriate covariates (monthly precipitation, temperature datasets and bioclimatic layers), allowed to predict the rainfall erosivity based on climate change scenarios. The mean rainfall erosivity for the European Union and Switzerland is projected to be 857 MJ mm ha -1  h -1  yr -1 till 2050 showing a relative increase of 18% compared to baseline data (2010). The changes are heterogeneous in the European continent depending on the future projections of most erosive months (hot period: April-September). The output results report a pan-European projection of future rainfall erosivity taking into account the uncertainties of the climatic models.

Primary Health Care as a guide for assistance to infants at risk of neurodevelopmental disorders.

PubMed

Molini-Avejonas, Daniela Regina; Rondon-Melo, Silmara; Batista, Estela Ramos; Souza, Amanda Calsolari de; Dias, Daniela Cardilli; Samelli, Alessandra Gianella

2018-01-01

Purpose Characterize infants at risk of neurodevelopmental disorders according to sociodemographic and health profiles and describe their monitoring in Basic Health Units (UBS) under different management models. Methods Data were collected from medical records of infants at risk of neurodevelopmental disorders in the west region of the city of Sao Paulo from August 2013 to February 2014 (phase 1 - characterization; phase 2 - monitoring). Results Of the 225 individuals assessed in the first phase of the study, 51.1% were female and 7.11% were twins. Adolescent (45.2%), brown (50.56%), single (46.09%), complete primary education (47.60%) mothers were predominant. The mean number of prenatal visits was 7.12. Most mothers had vaginal delivery (62.22%) at mean gestational age of 37.05 weeks. Mean Apgar scores at the 1st and 5th minutes were 7.13 and 8.80, respectively. Mean weight at birth was 2597.21g., with 50.22% of newborns weighting ≤2500g. In its second phase, the study describes and compares the follow-up of 55 infants according to the UBS management model: 28 in UBS/"Estratégia Saúde da Família" (UBS/ESF) and 27 in traditional UBS (UBS/T). UBS/ESF presented higher mean of consultations (p=0.006). Longer interval between consultations was observed at UBS/T. No records of development milestones were found in 56% of the sample. Growth measures were better registered at UBS/ESF. In both management models, the number of consultations was smaller and the interval between them was shorter than those recommended by the Brazilian Ministry of Health. Conclusion According to the recommended guidelines of the "Rede Cegonha" public policy, gaps in the monitoring of infants at risk of neurodevelopmental disorders are still observed.

Textlinguistik und Schulunterricht. Am Beispiel der Behandlung der indirekten Rede im Englischen. (Text Linguistics and Instruction in the Schools: Example: The Treatment of Indirect Discourse in English).

ERIC Educational Resources Information Center

Kueper, Christoph

1979-01-01

Compares sentence grammar with text linguistics, giving a survey of the treatment of indirect discourse in school grammars, and finding them inadequate. Recommends rules derived from text linguistics in spite of their greater complexity, because they do not hold the student to mechanical recasting of sentences. (IFS/WGA)

Granting Credit for College Proficiency and Regents External Degree Examinations in New York State: A Summary of Institutional Policies, 1981-82.

ERIC Educational Resources Information Center

New York State Education Dept., Albany. Bureau of Independent Study and Programs Development.

A guide is presented for students on the policies and practices of public and private New York colleges and universities in regard to granting credit, course waiver, or advanced standing to those who pass the College Proficiency Examinations (CPEs) and the Regents External Degree Examinations (REDEs). A chart indicates, for each institution and…

Die Indirekte Rede als Diskursstrategie: Innovative Lehrmethoden zum Konjunktiv I (Indirect Speech as a Discourse Strategy: Innovative Teaching Methods for the Subjunctive).

ERIC Educational Resources Information Center

Gramberg, Anne-Kathrin; Heinze, Karin U.

1993-01-01

This article talks about the subjunctive of indirect speech, in which its important functions and meanings are depicted. An analysis of the instructional materials used in the first and second years of language study, followed by practical curriculum recommendations, demonstrates how this grammatical phenomenon can be established in an advanced…

Analisis experimental de la propagacion en redes de area corporal para la banda de ultra wideband. experimental characterization of the propagation in ultra wideband body area networks

NASA Astrophysics Data System (ADS)

Garcia Serna, Ruben Gregorio

Diferentes dispositivos capaces de obtener informacion sobre parametros fisiologicos, cinematicos o contextuales del cuerpo pueden interconectarse de manera inalambrica dando lugar a las denominadas Redes de Area Corporal Inalambricas (WBAN, Wireless Body Area Networks). De entre las posibles tecnologias para establecer los enlaces, Ultra Wideband (UWB) esta captando cada vez un mayor interes debido a caracteristicas tales como el bajo nivel de potencia de transmision requerido (bajo nivel de exposicion a campos electromagneticos), el alto ancho de banda disponible y la alta resolucion temporal/espacial. El diseno de sistemas centrados en el cuerpo requiere de modelos de canal que describan de manera precisa la propagacion de senales en este tipo de entornos. Esta tesis se plantea con el objetivo de contribuir al estudio experimental de la propagacion en sistemas centrados en el cuerpo operando en la banda UWB. En primer lugar, se presenta un marco introductorio a las redes WBAN, sus elementos constitutivos, bandas de frecuencia, estandarizacion y modelos de canal. Ademas, se introducen los fundamentos de la tecnologia UWB y sus aplicaciones en este area. Seguidamente, se analiza en terminos de las perdidas de propagacion y la dispersion de retardo la propagacion en el canal off-body entre un transmisor fijo y un dispositivo receptor colocado sobre la superficie del cuerpo de un sujeto. Se considera la influencia de diferentes aspectos, tales como el entorno de medidas, la posicion de colocacion de una antena sobre el cuerpo y la postura adoptada por un sujeto. Finalmente, se analiza el canal de propagacion in-body considerando el movimiento relativo entre dos dispositivos causado por efecto de la respiracion. Las condiciones de propagacion en el interior del cuerpo se emulan por medio de un phantom liquido para UWB y la caracterizacion se plantea tanto en frecuencia, en terminos del modelado de la forma y el ensanchamiento del espectro Doppler, como en tiempo, por medio del estudio de la funcion de autocorrelacion y el tiempo de coherencia del canal.

Geo-statistical model of Rainfall erosivity by using high temporal resolution precipitation data in Europe

NASA Astrophysics Data System (ADS)

Panagos, Panos; Ballabio, Cristiano; Borrelli, Pasquale; Meusburger, Katrin; Alewell, Christine

2015-04-01

Rainfall erosivity (R-factor) is among the 6 input factors in estimating soil erosion risk by using the empirical Revised Universal Soil Loss Equation (RUSLE). R-factor is a driving force for soil erosion modelling and potentially can be used in flood risk assessments, landslides susceptibility, post-fire damage assessment, application of agricultural management practices and climate change modelling. The rainfall erosivity is extremely difficult to model at large scale (national, European) due to lack of high temporal resolution precipitation data which cover long-time series. In most cases, R-factor is estimated based on empirical equations which take into account precipitation volume. The Rainfall Erosivity Database on the European Scale (REDES) is the output of an extensive data collection of high resolution precipitation data in the 28 Member States of the European Union plus Switzerland taking place during 2013-2014 in collaboration with national meteorological/environmental services. Due to different temporal resolutions of the data (5, 10, 15, 30, 60 minutes), conversion equations have been applied in order to homogenise the database at 30-minutes interval. The 1,541 stations included in REDES have been interpolated using the Gaussian Process Regression (GPR) model using as covariates the climatic data (monthly precipitation, monthly temperature, wettest/driest month) from WorldClim Database, Digital Elevation Model and latitude/longitude. GPR has been selected among other candidate models (GAM, Regression Kriging) due the best performance both in cross validation (R2=0.63) and in fitting dataset (R2=0.72). The highest uncertainty has been noticed in North-western Scotland, North Sweden and Finland due to limited number of stations in REDES. Also, in highlands such as Alpine arch and Pyrenees the diversity of environmental features forced relatively high uncertainty. The rainfall erosivity map of Europe available at 500m resolution plus the standard error and the erosivity density (Rainfall erosivity per mm of precipitation) are available in the European Soil Data Centre (ESDAC). The highest erosivity has been found in the mediterrean countries (Italy, Western Greece, Spain, Northern Portugal), South Austria, Slovenia, Croatia and Western United Kingdom.

The Expected Cardiovascular Benefit of Plasma Cholesterol Lowering with or Without LDL-C Targets in Healthy Individuals at Higher Cardiovascular Risk.

PubMed

Cesena, Fernando Henpin Yue; Laurinavicius, Antonio Gabriele; Valente, Viviane A; Conceição, Raquel D; Santos, Raul D; Bittencourt, Marcio S

2017-06-01

There is controversy whether management of blood cholesterol should be based or not on LDL-cholesterol (LDL-c) target concentrations. To compare the estimated impact of different lipid-lowering strategies, based or not on LDL-c targets, on the risk of major cardiovascular events in a population with higher cardiovascular risk. We included consecutive individuals undergoing a routine health screening in a single center who had a 10-year risk for atherosclerotic cardiovascular disease (ASCVD) ≥ 7.5% (pooled cohort equations, ACC/AHA, 2013). For each individual, we simulated two strategies based on LDL-c target (≤ 100 mg/dL [Starget-100] or ≤ 70 mg/dL [Starget-70]) and two strategies based on percent LDL-c reduction (30% [S30%] or 50% [S50%]). In 1,897 subjects (57 ± 7 years, 96% men, 10-year ASCVD risk 13.7 ± 7.1%), LDL-c would be lowered from 141 ± 33 mg/dL to 99 ± 23 mg/dL in S30%, 71 ± 16 mg/dL in S50%, 98 ± 9 mg/dL in Starget-100, and 70 ± 2 mg/dL in Starget-70. Ten-year ASCVD risk would be reduced to 8.8 ± 4.8% in S50% and 8.9 ± 5.2 in Starget-70. The number of major cardiovascular events prevented in 10 years per 1,000 individuals would be 32 in S30%, 31 in Starget-100, 49 in S50%, and 48 in Starget-70. Compared with Starget-70, S50% would prevent more events in the lower LDL-c tertile and fewer events in the higher LDL-c tertile. The more aggressive lipid-lowering approaches simulated in this study, based on LDL-c target or percent reduction, may potentially prevent approximately 50% more hard cardiovascular events in the population compared with the less intensive treatments. Baseline LDL-c determines which strategy (based or not on LDL-c target) is more appropriate at the individual level. Há controvérsias sobre se o controle do colesterol plasmático deve ou não se basear em metas de concentração de colesterol LDL (LDL-c). Comparar o impacto estimado de diferentes estratégias hipolipemiantes, baseadas ou não em metas de LDL-c, sobre o risco de eventos cardiovasculares maiores em uma população de risco cardiovascular mais elevado. Foram incluídos indivíduos consecutivamente submetidos a uma avaliação rotineira de saúde em um único centro e que apresentavam um risco em 10 anos de doença cardiovascular aterosclerótica (DCVAS) ≥ 7,5% ("pooled cohort equations", ACC/AHA, 2013). Para cada indivíduo, foram simuladas duas estratégias baseadas em meta de LDL-c (≤ 100 mg/dL [Emeta-100] ou ≤ 70 mg/dL [Emeta-70]) e duas estratégias baseadas em redução percentual do LDL-c (30% [E30%] ou 50% [E50%]). Em 1.897 indivíduos (57 ± 7 anos, 96% homens, risco em 10 anos de DCVAS 13,7 ± 7,1%), o LDL-c seria reduzido de 141 ± 33 mg/dL para 99 ± 23 mg/dL na E30%, 71 ± 16 mg/dL na E50%, 98 ± 9 mg/dL na Emeta-100 e 70 ± 2 mg/dL na Emeta-70. O risco em 10 anos de DCVAS seria reduzido para 8,8 ± 4,8% na E50% e para 8,9 ± 5,2 na Emeta-70. O número de eventos cardiovasculares maiores prevenidos em 10 anos por 1.000 indivíduos seria de 32 na E30%, 31 na Emeta-100, 49 na E50% e 48 na Emeta-70. Em comparação com a Emeta-70, a E50% evitaria mais eventos no tercil inferior de LDL-c e menos eventos no tercil superior de LDL-c. As abordagens hipolipemiantes mais agressivas simuladas neste estudo, com base em meta de LDL-c ou redução percentual, podem potencialmente prevenir cerca de 50% mais eventos cardiovasculares graves na população em comparação com os tratamentos menos intensivos. Os níveis basais de LDL-c determinam qual estratégia (baseada ou não em meta de LDL-c) é mais apropriada para cada indivíduo.

[Promising networks, fruitful inquiry].

PubMed

Frenk, Silvestre

2014-01-01

This supplement of the Revista Médica del Instituto Mexicano del Seguro Social includes 10 original contributions, and also six current themes, all of them related to childhood obesity. It is the result of an institutional program that it has been identified as Redes de Investigación Institucional, and it has been promoted and developed by the Coordinación de Investigación of the Instituto Mexicano del Seguro Social.

Conservation of Information: Reverse Engineering Dark Social Systems

DTIC Science & Technology

2010-01-01

Factbook, retrieved 5/20/10 from www.cia.gov). 25 For example, Air- America , a politically liberal talk radio network, said that it would cease operations...attractive targets than mid- America ; see Reding, 2009). Obama Clinton Clinton Obama Lawless et al.: Conservation of Information 13 approached it...indefinitely sustain the control of the Communist Party--i.e., censoring Google--is increasingly at odds with Network China, which is thriving by

Seasonal variation and climate change impact in Rainfall Erosivity across Europe

NASA Astrophysics Data System (ADS)

Panagos, Panos; Borrelli, Pasquale; Meusburger, Katrin; Alewell, Christine; Ballabio, Cristiano

2017-04-01

Rainfall erosivity quantifies the climatic effect on water erosion and is of high importance for soil scientists, land use planners, agronomists, hydrologists and environmental scientists in general. The rainfall erosivity combines the influence of rainfall duration, magnitude, frequency and intensity. Rainfall erosivity is calculated from a series of single storm events by multiplying the total storm kinetic energy with the measured maximum 30-minute rainfall intensity. This estimation requests high temporal resolution (e.g. 30 minutes) rainfall data for sufficiently long time periods (i.e. 20 years). The European Commission's Joint Research Centr(JRC) in collaboration with national/regional meteorological services and Environmental Institutions made an extensive data collection of high resolution rainfall data in the 28 Member States of the European Union plus Switzerland to estimate rainfall erosivity in Europe. This resulted in the Rainfall Erosivity Database on the European Scale (REDES) which included 1,675 stations. The interpolation of those point erosivity values with a Gaussian Process Regression (GPR) model has resulted in the first Rainfall Erosivity map of Europe (Science of the Total Environment, 511: 801-815). In 2016, REDES extended with a monthly component, which allowed developing monthly and seasonal erosivity maps and assessing rainfall erosivity both spatially and temporally for European Union and Switzerland. The monthly erosivity maps have been used to develop composite indicators that map both intra-annual variability and concentration of erosive events (Science of the Total Environment, 579: 1298-1315). Consequently, spatio-temporal mapping of rainfall erosivity permits to identify the months and the areas with highest risk of soil loss where conservation measures should be applied in different seasons of the year. Finally, the identification of the most erosive month allows recommending certain agricultural management practices (crop residues, reduced tillage) in regions with high erosivity. Besides soil erosion mapping, the intra-annual analysis of rainfall erosivity is an important step towards flood prevention, hazard mitigation, ecosystem services, land use change and agricultural production. The application of REDES in combination with moderate climate change scenarios scenario (HadGEM RCP 4.5) resulted in predictions of erosivity in 2050. The overall increase of rainfall erosivity in Europe by 18% until 2050 are in line with projected increases of 17% for the U.S.A. The predicted mean rise of erosivity is also expected to increase the threat of soil erosion in Europe. The most noticeable increase of erosivity is projected for North-Central Europe, the English Channel, The Netherlands and Northern France. On the contrary, the Mediterranean basin show mixed trends. The success story with the compilation of REDES and first rainfall erosivity map of Europe was a driver to implement a Global Rainfall Erosivity Database (GloREDa). During the last 3 years, JRC was leading an effort to collect high temporal resolution rainfall data worldwide. In collaboration with 50 scientists worldwide and 100+ Meteorological and environmental Organisations, we have developed a Global Erosivity Database. In this database, we managed to include calculated erosivity values for 3,625 stations covering 63 countries worldwide.

Cultural adaptation and validation of an instrument on barriers for the use of research results.

PubMed

Ferreira, Maria Beatriz Guimarães; Haas, Vanderlei José; Dantas, Rosana Aparecida Spadoti; Felix, Márcia Marques Dos Santos; Galvão, Cristina Maria

2017-03-02

to culturally adapt The Barriers to Research Utilization Scale and to analyze the metric validity and reliability properties of its Brazilian Portuguese version. methodological research conducted by means of the cultural adaptation process (translation and back-translation), face and content validity, construct validity (dimensionality and known groups) and reliability analysis (internal consistency and test-retest). The sample consisted of 335 nurses, of whom 43 participated in the retest phase. the validity of the adapted version of the instrument was confirmed. The scale investigates the barriers for the use of the research results in clinical practice. Confirmatory factorial analysis demonstrated that the Brazilian Portuguese version of the instrument is adequately adjusted to the dimensional structure the scale authors originally proposed. Statistically significant differences were observed among the nurses holding a Master's or Doctoral degree, with characteristics favorable to Evidence-Based Practice, and working at an institution with an organizational cultural that targets this approach. The reliability showed a strong correlation (r ranging between 0.77 and 0.84, p<0.001) and the internal consistency was adequate (Cronbach's alpha ranging between 0.77 and 0.82). the Brazilian Portuguese version of The Barriers Scale was valid and reliable in the group studied. efectuar la adaptación cultural del instrumento The Barriers to Research Utilization Scale, y analizar propiedades métricas de validez y confiabilidad de su versión para portugués brasileño. investigación metodológica conducida mediante el proceso de adaptación cultural (traducción y retrotraducción), validez de faz y contenido, validez de constructo (dimensionalidad y grupos conocidos) y análisis de fiabilidad (consistencia interna y test-retest). La muestra incluyó 335 enfermeros, de los cuales 43 participaron de la etapa retest. la validez de la versión adaptada del instrumento fue confirmada, la escala investiga las barreras para la utilización de resultados de investigación en la práctica clínica. El análisis factorial confirmatorio demostró que la versión del instrumento para el portugués brasileño está adecuadamente ajustado a la estructura dimensional originalmente propuesta por los autores de la escala. Fueron observadas diferencias estadísticamente significantes entre los enfermeros con título de maestría o doctorado, con características favorables a la Práctica Basada en Evidencias, y actuantes en institución con cultura organizacional dirigida hacia tal aproximación. La fiabilidad presentó correlación fuerte (r variando entre 0,77 y 0,84, p<0,001) y la consistencia interna fue adecuada (alfa de Cronbach variando entre 0,77 y 0,82). la versión para el portugués brasileño del instrumento The Barriers Scale se mostró válida y confiable en el grupo estudiado. realizar adaptação cultural do instrumento The Barriers to Research Utilization Scale, e analisar propriedades métricas de validade e confiabilidade da sua versão para o português brasileiro. pesquisa metodológica conduzida por meio do processo de adaptação cultural (tradução e retrotradução), validade de face e conteúdo, validade de construto (dimensionalidade e grupos conhecidos) e análise da confiabilidade (consistência interna e teste-reteste). A amostra foi composta de 335 enfermeiros, desses, 43 participaram da etapa reteste. a validade da versão adaptada do instrumento foi confirmada, a escala investiga as barreiras para a utilização de resultados de pesquisa na prática clínica. A análise fatorial confirmatória demonstrou que a versão do instrumento para o português brasileiro está adequadamente ajustada à estrutura dimensional originalmente proposta pelos autores da escala. Observou-se diferenças estatisticamente significantes entre os enfermeiros mestres ou doutores, com características favoráveis a Prática Baseada em Evidências, e atuantes em instituição com cultura organizacional direcionada para tal abordagem. A confiabilidade apresentou correlação forte (r variando entre 0,77e 0,84, p<0,001) e a consistência interna foi adequada (alfa de Cronbach variando entre 0,77 e 0,82) . a versão para o português brasileiro do instrumento The Barriers Scale demonstrou-se válida e confiável no grupo estudado.

THE ROLE OF METABOLIC SURGERY FOR PATIENTS WITH OBESITY GRADE I ANDCLINICALLY UNCONTROLLED TYPE 2 DIABETES.

PubMed

Campos, Josemberg; Ramos, Almino; Szego, Thomaz; Zilberstein, Bruno; Feitosa, Heládio; Cohen, Ricardo

2016-07-07

Even considering the advance of the medical treatment in the last 20 years with new and more effective drugs, the outcomes are still disappointing as the control of obesity and type 2 Diabetes Mellitus (T2DM) with a large number of patients under the medical treatment still not reaching the desired outcomes. To present a Metabolic Risk Score to better guide the surgical indication for T2DM patients with body mass index (BMI) where surgery for obesity is still controversial. Research was conducted in PubMed, Medline, PubMed Central, Scielo and Lilacs between 2003-2015 correlating headings: metabolic surgery, obesity and type 2 diabetesmellitus. In addition, representatives of the societiesinvolved, as an expert panel, issued opinions. Forty-five related articles were analyzed by evidence-based medicine criteria. Grouped opinions sought to answer the following questions: Why metabolic and not bariatric surgery?; Mechanisms involved in glycemic control; BMI as a single criterion for surgical indication for uncontrolled T2DM; Results of metabolic surgery studies in BMI<35 kg/m2; Safety of metabolic surgery in patients with BMI<35 kg/m2; Long-term effects of surgery in patients with baseline BMI<35 kg/m2 and Proposal for a Metabolic Risk Score. Metabolic surgery has well-defined mechanisms of action both in experimental and human studies. Gastrointestinal interventions in T2DM patients with IMC≤35 kg/m2 has similar safety and efficacy when compared to groups with greater BMIs, leading to the improvement of diabetes in a superior manner than clinical treatment and lifestyle changes, in part through weight loss independent mechanisms . There is no correlation between baseline BMI and weight loss in the long term with the success rate after any surgical treatment. Gastrointestinal surgery treatment may be an option for patients with T2DM without adequate clinical control, with a BMI between 30 and 35, after thorough evaluation following the parameters detailed in Metabolic Risk Score defined by the surgical societies. Roux-en-Y gastric bypass (RYGB), because of its well known safety and efficacy and longer follow-up studies, is the main surgical technique indicated for patients eligible for surgery through the Metabolic Risk Score. The vertical sleeve gastrectomy may be considered if there is an absolute contraindication for the RYGB. T2DM patients should be evaluated by the multiprofessional team that will assess surgical eligibility, preoperative work up, follow up and long term monitoring for micro and macrovascular complications. Mesmo considerando o avanço do tratamento clínico ocorrido nos últimos 20 anos, com novos e mais eficientes medicamentos, os dados ainda são desanimadores quanto ao controle da obesidade e da diabete melito tipo 2(DMT2),com grande parcela de doentes em tratamento clínico ficando fora da meta desejada de controle. Apresentar proposta de Escore de Risco Metabólico para melhor orientar a indicação cirúrgica do diabete em pacientes com índice de massa corpórea (IMC) mais baixo nos quais o uso de procedimento cirúrgico para obesidade ainda é controverso. Foi realizada pesquisa nas bases de dados PubMed, Medline, PubMed Central, Scielo e Lilacs entre 2003-2015 correlacionando os descritores:cirurgia metabólica, obesidade e diabete melito tipo 2. Adicionalmente, representantes das sociedades envolvidas emitiram opiniões em pontos nos quais não existia na literatura trabalhos com graus de evidência elevados. Foram encontrados 45 artigos relacionadosque foram analisados pelos critérios da medicina baseada em evidências.As opiniões agrupadas procuraram responder as seguintes questões: Porque cirurgia metabólica e não bariátrica?;Mecanismos envolvidos no controle glicêmico; IMC como critério isolado de indicação cirúrgica para o DMT2 não controlado; Resultados de estudos de cirurgia metabólica em IMC<35 kg/m2; Segurança da cirurgia metabólica em pacientes com IMC<35 kg/m2; Efeitos em longo prazo da cirurgia em pacientes com IMC inicial <35 kg/m2; Proposta de Escore de Risco Metabólico. A cirurgia metabólica tem mecanismos de ação bem definidos tanto em estudos experimentais quanto em seres humanos. As intervenções gastrointestinais em diabéticos com IMC≤35 kg/m2 possuem segurança e eficácia semelhantes aos grupos com IMCs maiores, levando a melhora do diabete de forma superior aos tratamentos clínicos e mudanças de estilo de vida, em parte através de mecanismos independentes da perda ponderal. Não há correlação entre o IMC inicial e perda ponderal em longo prazo com os índices de sucesso do tratamento cirúrgico. O tratamento cirúrgico é opção para os pacientes portadores de DMT2 sem adequado controle clínico, com IMC entre 30 e 35, após minuciosa avaliação seguindo os parâmetros dispostos no Escore de Risco Metabólico aqui proposto. DGYR é a técnica indicada para os pacientes selecionados no Escore, existindo a possibilidade de indicação da gastrectomia vertical para os casos em que exista contraindicação para ela. O paciente deve ser avaliado por equipe multiprofissional envolvida na indicação, preparo e acompanhamento após as operações e acompanhados com monitorização de complicações micro e macrovasculares.

THE ROLE OF METABOLIC SURGERY FOR PATIENTS WITH OBESITY GRADE I AND TYPE 2 DIABETES NOT CONTROLLED CLINICALLY.

PubMed

Campos, Josemberg; Ramos, Almino; Szego, Thomaz; Zilberstein, Bruno; Feitosa, Heládio; Cohen, Ricardo

Even considering the advance of the medical treatment in the last 20 years with new and more effective drugs, the outcomes are still disappointing as the control of obesity and type 2 Diabetes Mellitus (T2DM) with a large number of patients under the medical treatment still not reaching the desired outcomes. To present a Metabolic Risk Score to better guide the surgical indication for T2DM patients with body mass index (BMI) where surgery for obesity is still controversial. Research was conducted in Pubmed, Medline, Pubmed Central, Scielo and Lilacs between 2003-2015 correlating headings: metabolic surgery, obesity and type 2 diabetes mellitus. In addition, representatives of the societies involved, as an expert panel, issued opinions. Forty-five related articles were analyzed by evidence-based medicine criteria. Grouped opinions sought to answer the following questions: Why metabolic and not bariatric surgery?; Mechanisms involved in glycemic control; BMI as a single criterion for surgical indication for uncontrolled T2DM; Results of metabolic surgery studies in BMI<35 kg/m2; Safety of metabolic surgery in patients with BMI<35 kg/m2; Long-term effects of surgery in patients with baseline BMI<35 kg/m2 and Proposal for a Metabolic Risk Score. Metabolic surgery has well-defined mechanisms of action both in experimental and human studies. Gastrointestinal interventions in T2DM patients with IMC≤35 kg/m2 has similar safety and efficacy when compared to groups with greater BMIs, leading to the improvement of diabetes in a superior manner than clinical treatment and lifestyle changes, in part through weight loss independent mechanisms . There is no correlation between baseline BMI and weight loss in the long term with the success rate after any surgical treatment. Gastrointestinal surgery treatment may be an option for patients with T2DM without adequate clinical control, with a BMI between 30 and 35, after thorough evaluation following the parameters detailed in Metabolic Risk Score defined by the surgical societies. Roux-en-Y gastric bypass (RYGB), because of its well known safety and efficacy and longer follow-up studies, is the main surgical technique indicated for patients eligible for surgery through the Metabolic Risk Score. The vertical sleeve gastrectomy may be considered if there is an absolute contraindication for the RYGB. T2DM patients should be evaluated by the multiprofessional team that will assess surgical eligibility, preoperative work up, follow up and long term monitoring for micro and macrovascular complications. Mesmo considerando o avanço do tratamento clínico ocorrido nos últimos 20 anos, com novos e mais eficientes medicamentos, os dados ainda são desanimadores quanto ao controle da obesidade e da diabete melito tipo 2 (DMT2),com grande parcela de doentes em tratamento clínico ficando fora da meta desejada de controle. Apresentar proposta de Escore de Risco Metabólico para melhor orientar a indicação cirúrgica do diabete em pacientes com índice de massa corpórea (IMC) mais baixo nos quais o uso de procedimento cirúrgico para obesidade ainda é controverso. Foi realizada pesquisa nas bases de dados Pubmed, Medline, Pubmed Central, Scielo e Lilacs entre 2003-2015 correlacionando os descritores:cirurgia metabólica, obesidade e diabete melito tipo 2. Adicionalmente, representantes das sociedades envolvidas emitiram opiniões em pontos nos quais não existia na literatura trabalhos com graus de evidência elevados. Foram encontrados 45 artigos relacionados que foram analisados pelos critérios da medicina baseada em evidências. As opiniões agrupadas procuraram responder as seguintes questões: Porque cirurgia metabólica e não bariátrica?; Mecanismos envolvidos no controle glicêmico; IMC como critério isolado de indicação cirúrgica para o DMT2 não controlado; Resultados de estudos de cirurgia metabólica em IMC<35 kg/m2; Segurança da cirurgia metabólica em pacientes com IMC<35 kg/m2; Efeitos em longo prazo da cirurgia em pacientes com IMC inicial <35 kg/m2; Proposta de Escore de Risco Metabólico. A cirurgia metabólica tem mecanismos de ação bem definidos tanto em estudos experimentais quanto em seres humanos. As intervenções gastrointestinais em diabéticos com IMC≤35 kg/m2 possuem segurança e eficácia semelhantes aos grupos com IMCs maiores, levando a melhora do diabete de forma superior aos tratamentos clínicos e mudanças de estilo de vida, em parte através de mecanismos independentes da perda ponderal. Não há correlação entre o IMC inicial e perda ponderal em longo prazo com os índices de sucesso do tratamento cirúrgico. O tratamento cirúrgico é opção para os pacientes portadores de DMT2 sem adequado controle clínico, com IMC entre 30 e 35, após minuciosa avaliação seguindo os parâmetros dispostos no Escore de Risco Metabólico aqui proposto. DGYR é a técnica indicada para os pacientes selecionados no Escore, existindo a possibilidade de indicação da gastrectomia vertical para os casos em que exista contraindicação para ela. O paciente deve ser avaliado por equipe multiprofissional envolvida na indicação, preparo e acompanhamento após as operações e acompanhados com monitorização de complicações micro e macrovasculares.

The Concept of Comprehensive Security: A Distinctive Feature of a Shared Security Culture in Europe

DTIC Science & Technology

2007-12-01

Sicherheitsbegriff, ed. Bundesakademie für Sicherheitspolitik (Hamburg: Mittler, 2001), 18. 92. Emil Kirchner and James Sperling , “The New Security Threats in...im 21. Jahrhundert - Keine allein militärische Aufgabe. Rede von Heidi Wegener, MdB, am 23.03.2006 im Marshall Center. www.marshallcenter.org/site...Wenger (Zürich: Forschungsstelle für Sicherheitspolitik, 2005), 11 217. Kurt R. Spillmann, " Von der bewaffneten Neutralität zur kooperativen

Memorias Conferencia Internacional IEEE Mexico 1971, Sobre Sistemas, Redes Y Computadoras. Volumen I and Volumen II. (Proceedings of International Conference of IEEE Concerning Systems, Networks, and Computers. Volume I and Volume II.

ERIC Educational Resources Information Center

Concheiro, A. Alonso, Ed.; And Others

The following papers in English from this international conference may be of particular interest to those in the field of education. T. Nakahara, A. Tsukamota, and M. Matsumoto describe a computer-aided design technique for an economical urban cable television system. W. D. Wasson and R. K. Chitkara outline a recognition scheme based on analysis…

Security Assistance Rationales: The Soviet Union and Eastern Europe.

DTIC Science & Technology

1983-12-01

of knowledge and as an analytical prism, it reflects an image of the existing social order and the distinctive analytical instruments (dialectical laws...desiderata through reliance on an external factor; the Soviet Union. In the case of Romania, Ceausescu rede - fined the parties desiderata more in line with...forces in the world. For in a climate of anti-Soviet hatred, attacks on socialism and on world peace can be more easily perpetrated. The history of

Economic evaluation of the Programs Rede Farmácia de Minas do SUS versus Farmácia Popular do Brasil.

PubMed

Garcia, Marina Morgado; Guerra, Augusto Afonso; Acúrcio, Francisco de Assis

2017-01-01

We conducted an economic assessment of the Pharmaceutical Assistance - Rede Farmácia de Minas Gerais-RFMG and Farmácia Popular do Brasil-FPB to ascertain which of the two models stands out as the most efficient. To do this, a model, which consisted of a study of incurred costs in both programs, up to the dispensing of medicine to citizens, was developed. The uncertainties of the proposed model were tested using the Monte Carlo method. If the entire population initially estimated in the RFMG were attended in the FPB, there would be an additional cost of R$ 139,324,050.19. The sensitivity analysis appeared to be favorable to the RFMG. A total of 10000 simulations were carried out, resulting in a median value of R$ 114,053,709.99 for the RFMG and R$ 254,106,120.65 for the FPB. The current National Drug Policy emphasizes the need to strengthen pharmaceutical services beyond the mere acquisition and delivery of pharmaceutical products. The public healthcare service model, consistent with the principles and guidelines of the SUS, seems to be more appropriate in ensuring complete and universal quality healthcare services to the citizens. The economic study conducted reinforces this fact, as it appears to be a more efficient alternative of the direct use of resources in the public health network.

Vietnam Head Injury Study - Phase III: A 30-Year Post-Injury Follow-Up Study

DTIC Science & Technology

2007-08-01

Michael Koenigs1, Edward D. Huey1, Vanessa Raymont1,2, Bobby Cheon2, Jeffrey Solomon3, Eric M. Wassermann1, & Jordan Grafman1 1Cognitive Neuroscience...Currently, Dr. Vanessa Raymont and colleagues are about to submit a manuscript to the journal Brain entitled, “Demographic, Structural and Genetic...PENETRATING HEAD INJURY Vanessa Raymont1&2, Amanda Greathouse1&2, Katherine Reding1&2, Robert Lipsky3, Andres Salazar2, and Jordan Grafman2* 1

Combat Squadrons of the Air Force, World War II,

DTIC Science & Technology

1982-01-01

1952. Inactivated on 1 Jul 1957. Redes- of a paddle wheel river boat, Air Force ignated 7o2d Troop Carrier Squadron blue, the windows lighted Air Force ...782d Bombard- hitched to a red wagon with wheels red, ment Squadron (Heavy) on 19 May hub yellow, tires and axles black, the 1943. Activated on 1 Aug...AD-A128 026 COMBAT SQUADRONS OF TOE AIR FORCE WORLD WAR IU) 1OFFICEOF AIR FORCE HISTORY WASHINGTON DC M MAURER UNCLASSIFIED F/G 15/7 NL

SERUM LEPTIN LEVENS AND HEPATOCELLULAR CARCINOMA: REVIEW ARTICLE.

PubMed

Andrighetto, Luiza Vitelo; Poziomyck, Aline Kirjner

2016-01-01

Hepatocellular carcinoma is one of the most frequent types of malignant tumors in the world. There is growing evidence of the relationship between it development and obesity. The mechanism that links obesity to cancer is still not fully understood; however, it is essential to the understanding the adipose tissue in metabolic changes related to obesity and hepatocellular carcinoma. To review the influence of serum leptin levels in patients with hepatocelular carcinoma. Systematic review of the literature based on the methodology of the Cochrane Institute. The search for articles was in the database: Science Direct, Scielo, Medline, Lilacs e Pubmed. The key words used were hepatocellular carcinoma, leptin, adipokine. After evaluation of individual studies, were selected seven studies. The results previously studied are still inconsistent and contradictory, and leptin can be effectively involved in the occurrence and development of hepatocellular carcinoma. Therefore, it is necessary to develop prospective, well-designed and conducted focusing on the role and specific mechanisms of this hormone in patients with hepatocellular carcinoma, so that new correlations can be properly supported. O carcinoma hepatocelular é um dos tipos mais frequentes de tumores malignos no mundo. Há crescentes evidências da relação entre o seu desenvolvimento e a obesidade. O mecanismo que os relaciona ainda não é completamente entendido. Entretanto é essencial a compreensão do tecido adiposo nas alterações metabólicas relacionadas à obesidade e ao câncer. Revisar a influência dos níveis séricos de leptina em pacientes com carcinoma hepatocelular. Trata-se de revisão bibliográfica baseada na metodologia do Instituto Cochrane; a busca de dados foi realizada na base de dados Science Direct, Scielo, Medline, Lilacs e Pubmed, empregando as seguintes descritores: hepatocellular carcinoma, leptin, adipokine. Após avaliação individual dos artigos selecionaram-se sete estudos. Os resultados ainda são inconsistentes e contraditórios, e a leptina pode estar efetivamente envolvida na ocorrência e no desenvolvimento do carcinoma hepatocelular. Faz-se necessário o desenvolvimento de estudos prospectivos, bem desenhados e conduzidos sobre o papel e mecanismos específicos deste hormônio em pacientes com carcinoma hepatocelular para que novas correlações sejam devidamente comprovadas.

Correlação de longo alcance em sistemas binários de raios-x usando remoção de flutuações

NASA Astrophysics Data System (ADS)

Pereira, M. G.; Moret, M. A.; Zebende, G. F.; Nogueira, E., Jr.

2003-08-01

Neste trabalho é proposta uma metodologia de analise de series temporais de fontes astrofísicas, baseada no método proposto por Peng et al. (1994) e Liu et al. (1999), o qual consiste na idéia de que uma série temporal correlacionada pode ser mapeada por um processo de busca de auto-similaridades em diversas escalas de tempo n. Removendo as eventuais tendências e integrando o sinal observado, é obtida uma medida do desvio médio quadrático das flutuações do sinal integrado F(n)~na, onde a representa o fator de escala associado com a auto-similaridade da correlação de longo alcance do sinal. Baseado nos valores obtidos de a, é possível distinguir entre os casos de sinais não-correlacionados, tipo ruído branco (a = 0,5), sinal anti-persistentes (a < 0,5) e sinal persistente (a > 0,5). Usando esta metodologia, foram analisadas 129 curvas de luz de sistemas binários de raios-X, provenientes do banco de dados públicos de observações feitas pelo instrumento All Sky Monitor, a bordo do satélite Rossi X-Ray Timing Explorer (ASM-RXTE). Foram identificadas a presença de a'0,5 em mais de 90% dos sistemas estudados, implicando em dizer que as flutuações de intensidade observadas apresentam correlação de auto-similaridade, sem entretanto, indícios de apresentarem uma escala de tempo característica das flutuações de intensidade. Sistemas onde são observadas erupções (flares), apresentam sistematicamente a > 0,5, característica esta, possivelmente associada com persistência das flutuações de densidade de disco ou taxa de acréscimo de massa. Os sistemas com curvas de luz onde nao são observadas as erupções apresentam uma distribuição normal centrada em a~0,62+/-0,10. Referências ¾ Peng, C.-K., Buldyrev, S.V., Havlin, S., Simons, M., Stanley, H.E., e Goldberg, A.L., Phys. Rev. E, (49), 1685 (1994). ¾ Liu, Y., Gopikrishnan, P., Cizeau, P., Meyer, M., Peng,C.-K., e Stanley, H.E., Phys. Rev. E, (60), 1390 (1999).

Development of a virtual learning environment for cardiorespiratory arrest training.

PubMed

Silva, Anazilda Carvalho da; Bernardes, Andrea; Évora, Yolanda Dora Martinez; Dalri, Maria Célia Barcellos; Silva, Alexandre Ribeiro da; Sampaio, Camila Santana Justo Cintra

2016-01-01

To develop a Virtual Learning Environment (VLE) aiming at the training of nursing team workers and emergency vehicle drivers in Basic Life Support (BLS) to attend Cardiorespiratory arrest, and to evaluate the quality of its contents among specialists in the area of Emergency and Urgent care. Applied research of technological development. The methodology used was based on the Instructional Design Model (ADDIE), which structures the teaching-learning planning in different stages (analysis, design, development, implementation and evaluation). The VLE was composed of texts elaborated from bibliographic research, links, edited video from a simulation scenario in the laboratory and questions to evaluate the fixation of the content, organized in modules. After its development, it was evaluated as adequate to satisfy the needs of the target public, by eight expert judges, which was made available for electronic access. The VLE has potential as a tool for training and qualification in BLS, as it can be easily integrated with other pedagogical approaches and strategies with active methodologies. Desenvolver um Ambiente Virtual de Aprendizagem (AVA) visando à capacitação de trabalhadores da equipe de enfermagem e condutores de veículo de emergência em Suporte Básico de Vida (SBV) no atendimento à Parada Cardiorrespiratória, e avaliar a qualidade do seu conteúdo junto a especialistas na área de Urgência e Emergência. Pesquisa aplicada, de produção tecnológica. A metodologia utilizada foi baseada no Modelo de Design Instrucional (ADDIE), que estrutura o planejamento de ensino-aprendizagem em estágios distintos (analysis, design, development, implementation and evaluation). O AVA foi composto por textos elaborados a partir de pesquisa bibliográfica, links, vídeo construído a partir de um cenário de simulação em laboratório e questões para avaliar a fixação do conteúdo, organizados em módulos. Após a sua construção, foi avaliado como adequado para satisfazer às necessidades do público-alvo, por oito juízes especialistas, sendo disponibilizado para acesso eletrônico. O AVA tem potencial como ferramenta para formação e capacitação em SBV porser facilmente integrado a outras abordagens pedagógicas e estratégias com metodologias ativas.

Analytical study of nozzle performance for nuclear thermal rockets

NASA Technical Reports Server (NTRS)

Davidian, Kenneth O.; Kacynski, Kenneth J.

1991-01-01

Nuclear propulsion has been identified as one of the key technologies needed for human exploration of the Moon and Mars. The Nuclear Thermal Rocket (NTR) uses a nuclear reactor to heat hydrogen to a high temperature followed by expansion through a conventional convergent-divergent nozzle. A parametric study of NTR nozzles was performed using the Rocket Engine Design Expert System (REDES) at the NASA Lewis Research Center. The REDES used the JANNAF standard rigorous methodology to determine nozzle performance over a range of chamber temperatures, chamber pressures, thrust levels, and different nozzle configurations. A design condition was set by fixing the propulsion system exit radius at five meters and throat radius was varied to achieve a target thrust level. An adiabatic wall was assumed for the nozzle, and its length was assumed to be 80 percent of a 15 degree cone. The results conclude that although the performance of the NTR, based on infinite reaction rates, looks promising at low chamber pressures, finite rate chemical reactions will cause the actual performance to be considerably lower. Parameters which have a major influence on the delivered specific impulse value include the chamber temperature and the chamber pressures in the high thrust domain. Other parameters, such as 2-D and boundary layer effects, kinetic rates, and number of nozzles, affect the deliverable performance of an NTR nozzle to a lesser degree. For a single nozzle, maximum performance of 930 seconds and 1030 seconds occur at chamber temperatures of 2700 and 3100 K, respectively.

Automatic Generation of Taylor Series in Pascal-SC: Basic Operations and Applications to Ordinary Differential Equations.

DTIC Science & Technology

1983-03-01

facilities built into the language compiler itself can be used to generate _imanchAe-C-d, for the evaluatiomn la ’ fficients.) Examples of such languages...Dy mtt ss. I I I I I I I I I,ase.TC11) - 0 1 I =- M 3 (SM) By Mse rede a• I RA IQ BZ yrcrec Table 4.1. Resolution of Cases for e. Consider a series...von Gudenberg. Gesmte Arithmetik des PASCAL-SC Rechners: Benutzerhandbuch. Institute for Applied Mathematics, University of Karlsruhe, 1981. -33- 4

A national agenda for Latino cancer prevention and control.

PubMed

Ramirez, Amelie G; Gallion, Kipling J; Suarez, Lucina; Giachello, Aida L; Marti, Jose R; Medrano, Martha A; Pérez-Stable, Eliseo J; Talavera, Gregory A; Trapido, Edward J

2005-06-01

Although cancer is a leading cause of morbidity and premature death among Latinos, there is limited knowledge of cancer-related issues and priorities of greatest significance to the Latino population, the largest minority group in the nation. This information is vital in helping to guide Latino cancer research, training, and awareness efforts at national, regional, and local levels. To help identify cancer issues of greatest relevance to Latinos, Redes En Accion, The National Hispanic/Latino Cancer Network, a major network among the National Cancer Institute's Special Populations Networks, conducted a survey of 624 key opinion leaders from around the country. Respondents were asked to rank the three cancer sites most important to Latinos in their region and the five issues of greatest significance for this population's cancer prevention and control. Recommendations were prioritized for three specific areas: 1) research, 2) training and/or professional education, and 3) awareness and/or public education. Among cancers, breast carcinoma was ranked number one, followed in order by cervical and lung carcinomas. The issues of greatest significance to Latinos were 1) access to cancer screening and care, 2) tobacco use, 3) patient-doctor communication, 4) nutrition, and 5) risk communication. This survey solicited information from scientists, health care professionals, leaders of government agencies, professional and community-based organizations, and other stakeholders in Latino health. The results laid the foundation for a national Redes En Accion Latino cancer agenda, thus providing a useful tool for individuals and organizations engaged in cancer prevention and control efforts among the Hispanic-Latino population.

Evaluation of dose reduction versus standard dosing for maintenance of remission in patients with spondyloarthritis and clinical remission with anti-TNF (REDES-TNF): study protocol for a randomized controlled trial.

PubMed

Pontes, Caridad; Gratacós, Jordi; Torres, Ferran; Avendaño, Cristina; Sanz, Jesús; Vallano, Antoni; Juanola, Xavier; de Miguel, Eugenio; Sanmartí, Raimon; Calvo, Gonzalo

2015-08-20

Dose reduction schedules of tumor necrosis factor antagonists (anti-TNF) as maintenance therapy in patients with spondyloarthritis are used empirically in clinical practice, despite the lack of clinical trials providing evidence for this practice. To address this issue the Spanish Society of Rheumatology (SER) and Spanish Society of Clinical Pharmacology (SEFC) designed a 3-year multicenter, randomized, open-label, controlled clinical trial (2 years for inclusion and 1 year of follow-up). The study is expected to include 190 patients with axial spondyloarthritis on stable maintenance treatment (≥4 months) with any anti-TNF agent at doses recommended in the summary of product characteristics. Patients will be randomized to either a dose reduction arm or maintenance of the dosing regimen as per the official labelling recommendations. Randomization will be stratified according to the anti-TNF agent received before study inclusion. Patient follow-up, visit schedule, and examinations will be maintained as per normal clinical practice recommendations according to SER guidelines. The study aims to test the hypothesis of noninferiority of the dose reduction strategy compared with standard treatment. The first patients were recruited in July 2012, and study completion is scheduled for the end of April 2015. The REDES-TNF study is a pragmatic clinical trial that aims to provide evidence to support a medical decision now made empirically. The study results may help inform clinical decisions relevant to both patients and healthcare decision makers. EudraCT 2011-005871-18 (21 December 2011).

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

UH-60A External Stores Support System Fixed Provision Fairings Drag Determination

DTIC Science & Technology

1984-05-01

irori I Sif Iii. ,,moin’!1.tIit~l -,v- .v.t m ;Irttiit or oiut poit pon , it ons~ 11 r;i1 Tfre, ion, 1 Aii𔃻u’ of ; i rI Jp ~ur ra f t a ttirue Ptti’b...ltoin in ha I I cenrte red f li ght by refer. n4,41 . ’I e .v ifr.i if Ilateral I cci’ I ercmet er at a p rede te~rmi ntd rCr "’nf I Itr f’ F- rsit or

Aplicación de técnicas de análisis de redes sociales y de co-ocurrencia de palabras en la determinación de frentes de investigación

NASA Astrophysics Data System (ADS)

Boeris, C. E.

A bibliometric study of the scientific production of the IAR researchers has been performed, with the aim of determining the institute's research fronts and groups of researchers working on these fronts. Methods of analysis of co-occurrence of words, authorship analysis and social network analysis (SNA) has been applied by extracting keywords and the names of the authors on the base of published works. The results support the existence of two research fronts within the institution. FULL TEXT IN SPANISH

Engine Rotor Dynamics, Synchronous and Nonsynchronous Whirl Control

DTIC Science & Technology

1979-02-01

models and experimental tests, a method of design optimization was de -, loped to obtain the best trade-off between all the rotor design variables...onsnchrorous What Task X Dphrmiaatoos * Conxduct u rede Study to Determine Sat Comnpromise Damper Support F~ure 1, Rotor Dyna micso Powe agrbin Overview 12 Tlsv...Program - Pj,k-I + l P-l -2 +. + 2 " 1jk Pjjkll + 1+’- + + 2 flJk Pj+I,k (20) where Rj,k = f3,j-,d- + f4j.k de and f3j, k I f4j,k are the functions

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

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.

Contribution of Oswaldo Paulo Forattini to public health: analysis of scientific production.

PubMed

Reis, Juliana Gonçalves; Kobayashi, Keilla Miki; Ueno, Helene Mariko; Ribeiro, Cristiane Martins; Cardoso, Telma Abdalla de Oliveira

2016-12-22

To analyze the main characteristics of the scientific production of Oswaldo Paulo Forattini, researcher and, for 40 years, editor of Revista de Saúde Pública. Descriptive study with bibliometric approach conducted in three steps. (1) identification of bibliographic records using the following search strategy: "Oswaldo Paulo Forattini" OR "Forattini OP" OR "Forattini" up information sources Google Scholar, Web of Science, and PubMed, in July 2016, which retrieved 867 records. (2) composition of research corpus, in which we included 351 bibliographic records of articles, books, book chapters, editorials, book reviews, informative notes and annual reports of the RSP and excluded 516 duplicates and acknowledgement notes, obituary notes, and nonretrievable citations. (3) data organization and analysis, in which we built databases for descriptive analysis and development of the MeSH coauthors and terms networks in VOSviewer software. For analysis of editorials, three reviewers read the full text of each editorial and categorized them according to subject, historical context and perspectives, relating them with historical milestones. Forattini's scientific production occurred from 1946 to 2009, most consisting of articles (n = 218; 62.1%), editorials (n = 43; 12.3%), and books (n = 13; 3.7%). The main subjects were Culicidae (36.8%), Triatominae (12.5%), and Epidemiology (10.0%). The coauthors of articles were his professors, colleagues of his generation, and graduate students. His editorials addressed critical reflections on the production of knowledge, research priorities, and factors that contributed to or hindered progress. The scope of subjects is broad, referring to socioeconomic and scientific development, public health issues in developed countries, or global health. The analysis shows Forattini's commitment with public health, research with vectors, training of researchers, and scientific communication. Analisar as principais características da produção científica de Oswaldo Paulo Forattini, pesquisador e, por 40 anos, editor da Revista de Saúde Pública. Estudo descritivo com abordagem bibliométrica realizado em três etapas. (1) Identificação dos registros bibliográficos, utilizando a seguinte estratégia de busca: "Oswaldo Paulo Forattini" OR "Forattini OP" OR "Forattini O" nas fontes de informação Google Scholar, Web of Science e PubMed, em julho de 2016, o que recuperou 867 registros. (2) Composição do corpus da pesquisa, na qual foram incluídos 351 registros bibliográficos de artigos, livros, capítulos de livros, editoriais, resenhas de livros, notas informativas e relatórios anuais da RSP e excluídos 516 duplicatas e notas de agradecimento, notas de obituários e citações não recuperáveis. (3) Organização e análise dos dados, na qual foram construídos bancos de dados para análise descritiva e elaboração das redes de coautores e de termos do MeSH no software VOSviewer. Para análise dos editoriais, três revisores leram o texto completo de cada editorial e os categorizaram segundo assunto, contexto histórico e perspectivas, relacionando-o com marcos históricos. A produção científica de Forattini ocorreu de 1946 a 2009, a maioria composta por artigos (n = 218; 62,1%), editoriais (n = 43; 12,3%) e livros (n = 13; 3,7%). Os principais assuntos foram Culicidae (36,8%), Triatominae (12,5%) e Epidemiologia (10,0%). Os coautores dos artigos foram seus mestres, colegas de sua geração e alunos de pós-graduação. Seus editoriais abordaram reflexões críticas sobre a produção de conhecimento, prioridades em pesquisa e fatores que contribuíam ou desfavoreciam o progresso. O escopo dos assuntos é amplo, remetendo ao desenvolvimento científico e socioeconômico, questões de saúde pública em países desenvolvidos ou saúde global. A análise mostra o comprometimento de Forattini com a saúde pública, na pesquisa com vetores, na formação de pesquisadores e na comunicação científica.

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.

Many Miles to Go: A Systematic Review of the State of Cost-Utility Analyses in Brazil.

PubMed

Campolina, Alessandro G; Rozman, Luciana M; Decimoni, Tassia C; Leandro, Roseli; Novaes, Hillegonda M D; De Soárez, Patrícia Coelho

2017-04-01

Little is known about the quality and quantity of cost-utility analyses (CUAs) in Brazil. The objective of this study was to provide a systematic review of published CUAs of healthcare technologies in Brazil. We performed a systematic review of economic evaluations studies published in MEDLINE, EMBASE, LILACS (Latin American and Caribbean Health Sciences Literature), SciELO (Scientific Electronic Library Online), NHS EED (National Health Service Economic Evaluation Database), HTA (Health Technology Assessment) Database, Web of Science, Scopus, Bireme (Biblioteca Regional de Medicina), BVS ECOS (Health Economics database of the Brazilian Virtual Library of Health), and SISREBRATS (Sistema de Informação da Rede Brasileira de Avaliação de Tecnologias em Saúde [Brazilian Network for the Evaluation of Health Technologies]) from 1980 to 2013. Articles were included if they were CUAs according to the classification devised by Drummond et al. Two independent reviewers screened articles for relevance and carried out data extraction. Disagreements were resolved through discussion or through consultation with a third reviewer. We performed a qualitative narrative synthesis. Of the 535 health economic evaluations (HEEs) relating to Brazil, only 40 were CUAs and therefore included in the analysis. Most studies adhered to methodological guidelines for quality of reporting and 77.5% used quality-adjusted life-years (QALYs) as the health outcome. Of these studies, 51.6% did not report the population used to elicit preferences for outcomes and 45.2% used a specific population such as expert opinion. The preference elicitation method was not reported in 58.1% of these studies. The majority (80.6%) of studies did not report the instrument used to derive health state valuations and no publication reported whether tariffs (or preference weights) were national or international. No study mentioned the methodology used to estimate QALYs. Many published Brazilian cost-utility studies adhere to key recommended general methods for HEE; however, the use of QALY calculations is far from being the current international standard. Development of health preferences research can contribute to quality improvement of health technology assessment reports in Brazil.

Um enfoque antropológico para o ensino de astronomia no nível médio

NASA Astrophysics Data System (ADS)

Costa, G. B.; Jafelice, L. C.

2003-08-01

Há uma enorme carência de materiais didático-pedagógicos em astronomia para professores do ensino médio, sobretudo materiais que explorem também aspectos humanísticos. A origem do Universo é um bom exemplo desta constatação central. Embora tal origem teve explicações culturais diversas, os professores não têm informações sobre isso e muito menos material que trabalhe diferentes visões de mundo e treinamento que os capacite a abordá-las devidamente. Conseqüentemente o ensino de astronomia costuma ser tecnicista e dissociado do aspecto humano que alimenta o grande interesse e curiosidade que esses temas despertam. Aqui apresentamos propostas visando contribuir para reverter esse quadro e trabalhamos distintas visões de Universo: espontâneas, autóctones e científicas. Desenvolvemos práticas, materiais instrucionais e textos para viabilizar a adoção de um enfoque antropológico para o ensino de astronomia no nível médio, no qual as culturas humanística e científica sejam integradas de uma maneira contextualizada e eficaz para aquele ensino. Estas propostas foram aplicadas em um curso de treinamento para professores da rede pública de diferentes disciplinas. A receptividade dos professores à abordagem proposta e os resultados alcançados foram muito estimulantes. Destes, destacamos: produção de roteiros de atividades; desenvolvimento de práticas didático-pedagógicas específicas (e.g., encenação de mitos; dança primordial guarani; "criação" de constelações e interpretações pluriculturais; etc.); e sugestões concretas para a efetiva realização de um ensino interdisciplinar contextualizado, onde questões cosmogônicas servem de mote para iniciar tal ensino. Discutimos estes resultados e como o enfoque adotado pode instrumentalizar os professores para leituras de mundo que incluem naturalmente aspectos culturais, sociais e históricos associados aos temas estudados. (PPGECNM/UFRN; PRONEX/FINEP; NUPA/USP; Temáticos/FAPESP)

Condom use and alcohol consumption in adolescents and youth.

PubMed

Mola, Rachel; Pitangui, Ana Carolina Rodarti; Barbosa, Sháyra Anny Moura; Almeida, Layane Sá; Sousa, Mayara Ruth Marinho de; Pio, Wellypâmela Pauliny de Lima; Araújo, Rodrigo Cappato de

2016-01-01

To determine the association between not using the male condom and alcohol consumption in adolescents and schoolchildren. An epidemiological study, with a cross-sectional, descriptive, and correlation design carried out from March to July 2014. The sample consisted of students in public primary and secondary education, aged between 12 and 24 years. The social and demographic survey and the Youth Risk Behavior Survey questionnaire were used. The study included 1,275 students, of these; 37.0% reported having had sexual relations. The prevalent age of sexual initiation was 14-16 years 55.7% and 65.6% used condom in the last sexual intercourse. Regarding the lack of condom use at the last intercourse, girls showed an association with drunkenness in the previous 30 days (2.19; 95%CI: 1.06-4.54). In females, the non-use of condoms was associated with drunkenness in the previous 30 days. Identificar os fatores associados ao não uso de preservativo masculino e ao consumo de bebida alcoólica em adolescentes e jovens escolares. Estudo epidemiológico, com delineamento transversal, descritivo e correlacional, desenvolvido de março a julho de 2014. A amostra foi composta por estudantes dos Ensinos Fundamental e Médio da rede pública estadual, com idades entre 12 e 24 anos. Empregaram-se o inquérito sociodemográfico e o questionário Youth Risk Behavior Survey. Foram incluídos 1.275 estudantes; 37,0% deles relataram terem tido relação sexual. A idade prevalente de iniciação sexual foi de 14 a 16 anos, com 55,7%; 65,6% usaram preservativo na última relação. Com relação ao não uso de preservativo na última relação, as meninas apresentaram associação com bebedeira nos últimos 30 dias (2,19; IC95%: 1,06-4,54). O não uso de preservativos esteve associado com bebedeira nos últimos 30 dias nas meninas.

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.

The Soviet Naval Indian Ocean Squadron. Raison d’Etre: Action or Reaction?

DTIC Science & Technology

1983-09-01

THESIS * THE SOVIET NAVAL INDIAN OCEAN SQUADRON R-AISON D’ETRE: ACTION OR. REACTION? by C) Allen Marvin Stout C..) La ~j September 1983 Thesis Advisor...but the anti-carrier forces were allowed to rede - ploy elsewhere. The bcttom line, then, is as expected. The Squadron has both active and reactive... Pon so bl tS 0 S 0 0 0 20 0 0 0 0 0 1 S 1 6 I ~ ~ O ofnbmt soesUB 0 6 S @0 0a 1 2 5 S 1 5 I Iba IOT Ilw om Djiout aI ~ IcbSitm I Ia 110

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®.

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

The situation of nursing education in Latin America and the Caribbean towards universal health.

PubMed

Cassiani, Silvia Helena De Bortoli; Wilson, Lynda Law; Mikael, Sabrina de Souza Elias; Peña, Laura Morán; Grajales, Rosa Amarilis Zarate; McCreary, Linda L; Theus, Lisa; Agudelo, Maria Del Carmen Gutierrez; Felix, Adriana da Silva; Uriza, Jacqueline Molina de; Gutierrez, Nathaly Rozo

2017-05-11

to assess the situation of nursing education and to analyze the extent to which baccalaureate level nursing education programs in Latin America and the Caribbean are preparing graduates to contribute to the achievement of Universal Health. quantitative, descriptive/exploratory, cross-sectional study carried out in 25 countries. a total of 246 nursing schools participated in the study. Faculty with doctoral level degrees totaled 31.3%, without Brazil this is reduced to 8.3%. The ratio of clinical experiences in primary health care services to hospital-based services was 0.63, indicating that students receive more clinical experiences in hospital settings. The results suggested a need for improvement in internet access; information technology; accessibility for the disabled; program, faculty and student evaluation; and teaching/learning methods. there is heterogeneity in nursing education in Latin America and the Caribbean. The nursing curricula generally includes the principles and values of Universal Health and primary health care, as well as those principles underpinning transformative education modalities such as critical and complex thinking development, problem-solving, evidence-based clinical decision-making, and lifelong learning. However, there is a need to promote a paradigm shift in nursing education to include more training in primary health care. avaliar a situação da educação em enfermagem e analisar o quanto os programas de educação em enfermagem, no nível de Bacharelado na América Latina e no Caribe, estão preparando graduados a contribuir para o alcance da Saúde Universal. estudo quantitativo, descritivo/exploratório, transversal, realizado em 25 países. um total de 246 escolas de enfermagem participaram do estudo. O corpo docente com nível de Doutorado totalizou 31,3%; sem o Brasil o número fica reduzido a 8,3%. A razão entre experiências clínicas nos serviços de atenção primária à saúde e nos serviços hospitalares foi de 0,63, indicando que os estudantes têm mais experiências clínicas nos cenários hospitalares. Os resultados sugeriram necessidade de aprimoramento relacionada ao acesso à Internet; tecnologia da informação; acesso para portadores de deficiências; avaliação do programa, do corpo docente e dos estudantes; e aos métodos de ensino/aprendizagem. há heterogeneidade na educação em enfermagem na América Latina e no Caribe. Os currículos de enfermagem incluem, geralmente, os princípios e valores da Saúde Universal e da atenção primária à saúde, bem como aqueles princípios subjacentes às modalidades de educação transformativa, como o desenvolvimento de pensamento crítico e complexo, a solução de problemas, a tomada de decisão clínica baseada em evidências, e aprendizagem contínua. No entanto, é preciso promover uma mudança de paradigma na educação em enfermagem que inclua mais treinamento na atenção primária à saúde. evaluar la situación de la educación en enfermería y analizar en qué grado los programas de educación de enfermería a nivel de grado en América Latina y el Caribe están preparando a los graduados para contribuir al logro de la Salud Universal. se llevó a cabo un estudio transversal, cuantitativo, descriptivo y exploratorio en 25 países. participaron en el estudio 246 escuelas de enfermería. El porcentaje de profesores con títulos de doctorado fue de 31,3%; pero, si se excluye a Brasil esta cifra se reduce a 8,3%. La proporción de la experiencia clínica adquirida en los servicios de atención primaria de salud en relación con la adquirida en servicios hospitalarios fue de 0,63, lo que indica que los estudiantes adquieren la mayor parte de su experiencia clínica en entornos hospitalarios. Los resultados mostraron una necesidad de mejorar el acceso a internet; la tecnología de la información; la accesibilidad para las personas discapacitadas; la evaluación de los programas, de los profesores y de los estudiantes; y los métodos de enseñanza y aprendizaje. hay heterogeneidad en la educación en enfermería en América Latina y el Caribe. En general, los programas de estudios de enfermería han adoptado los principios y los valores de la Salud Universal y la atención primaria de salud, así como los principios que sustentan las modalidades de educación transformadora, como son el desarrollo del pensamiento crítico y complejo, la solución de problemas, la toma de decisiones clínicas basadas en la evidencia y el aprendizaje a lo largo de toda la vida. Sin embargo, hay necesidad de promover un cambio en el paradigma de la educación en enfermería, a fin de que abarque más capacitación en la atención primaria de salud.

Assessment in the primary care of the State of São Paulo, Brazil: incipient actions in sexual and reproductive health.

PubMed

Nasser, Mariana Arantes; Nemes, Maria Ines Battistella; Andrade, Marta Campagnoni; Prado, Rogério Ruscitto do; Castanheira, Elen Rose Lodeiro

2017-08-17

The objective of this study is to assess performance in sexual and reproductive health of primary health care services of the Brazilian Unified Health System, in the State of São Paulo, Brazil. An evaluative framework was built for sexual and reproductive health with the categorization of 99 indicators in three domains: sexual and reproductive health promotion (25), sexually transmitted infections/AIDS prevention and care (43), and reproductive health care (31). This framework was applied to assess the services responses to the questionnaire of Quality Evaluation of Primary Health Care in the Municipalities of São Paulo State (QualiAB), in 2010. Percentages were calculated for positive responses to indicators and performance in the sexual and reproductive health dimension, according to domains, and their contribution to the overall score in sexual and reproductive health (Friedman), relative participation (Dunn), and correlation (Spearman) was verified. Overall, 2,735 services participated in the study. They were located in 586 municipalities (distributed throughout the 17 regional health departments of São Paulo), of which 70.6% had fewer than 100,000 inhabitants. The overall average performance of these services for sexual and reproductive health is 56.8%. The actions are characterized by: prenatal with adequate beginning and exams, better organization for immediate rather than for late postnatal care, and selective reproductive planning for some contraceptives; prevention based on specific protection, limitations in the prevention of congenital syphilis, in the treatment of sexually transmitted infections, and in the screening of cervical and breast cancer; specific educational activities, with a restricted vulnerability approach, focus on sexuality over reproduction. The domain of reproductive health has greater participation in the overall score, followed by prevention/care and promotion. The three domains are correlated; the domain of prevention/care has the highest correlation with the other ones. The implementation of sexual and reproductive health in primary health care in the services studied is incipient. The revision of the purpose of the work, the dissemination of technologies, and the investing in permanent education are needed. The evaluative framework built can be used by the sexual and reproductive health program services and management in primary health care, thereby contributing to their actions. Avaliar o desempenho em saúde sexual e reprodutiva de serviços de atenção primária à saúde do Sistema Único de Saúde, no estado de São Paulo. Construiu-se quadro avaliativo para a saúde sexual e reprodutiva com a categorização de 99 indicadores em três domínios: promoção à saúde sexual e reprodutiva (25), prevenção e assistência às doenças sexualmente transmissíveis/aids (43), e atenção à saúde reprodutiva (31). Esse quadro foi aplicado para avaliar as respostas dos serviços ao questionário Avaliação da Qualidade da Atenção Básica em Municípios de São Paulo (QualiAB), em 2010. Calcularam-se as porcentagens de respostas positivas aos indicadores e o desempenho na dimensão saúde sexual e reprodutiva, segundo os domínios; e verificou-se sua contribuição para o escore geral em saúde sexual e reprodutiva (Friedman), participação relativa (Dunn) e correlação (Spearman). Participaram 2.735 serviços, localizados em 586 municípios (distribuídos nos 17 departamentos regionais de saúde paulistas), dos quais 70,6% municípios com menos de 100.000 habitantes. A média geral do desempenho desses serviços para saúde sexual e reprodutiva é 56,8%. As ações são caracterizadas por: pré-natal com início e exames adequados, melhor organização para puerpério imediato do que tardio, e planejamento reprodutivo seletivo para alguns contraceptivos; prevenção baseada em proteção específica, limites na prevenção da sífilis congênita, no tratamento de doenças sexualmente transmissíveis, no rastreamento do câncer cervical e mamário; atividades educativas pontuais, com restrita abordagem das vulnerabilidades, predomínio do enfoque da sexualidade centrado na reprodução. O domínio saúde reprodutiva tem maior participação no escore geral, seguido de prevenção/assistência e promoção. Os três domínios estão correlacionados; o domínio prevenção/assistência apresenta as maiores correlações com os demais. A implementação da saúde sexual e reprodutiva na atenção primária à saúde nos serviços estudados é incipiente. É necessário rever finalidades do trabalho, disseminar tecnologias e investir em educação permanente. O quadro avaliativo construído pode ser utilizado pelos serviços e pela gestão do programa de saúde sexual e reprodutiva na atenção primária à saúde e contribuir para suas ações.

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.

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.

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.

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.

Astronomy in High School: Using a Mini-Planetarium to Understand Details of the Apparent Movement of Stars. (Spanish Title: Astronomía en la Escuela Secundaria: Comprendiendo los Detalles del Movimiento Aparente de Las Estrellas con un Miniplanetario.) Astronomia no Ensino Médio: Compreendendo Detalhes do Movimento Aparente das Estrelas com um Miniplanetário

NASA Astrophysics Data System (ADS)

dos Santos Leão, Demetrius

2013-07-01

The aim of this article is to present part of the results obtained by the intervention made from the author's Master degree project, which consisted in the development of a set of Astronomy classes for first year of High School students from a private school in the "Distrito Federal", Brasilia, Brazil, making use of a didactical material called mini-planetarium (MP) as the main resource. Using Paulo Freire's contextualization and dialogicity ideas as a theoretical framework guided by these lessons, it was proposed to the students the assembly and application of that resource in a planetarium session. During the project, some subjects such as the apparent trajectory of stars through Brasilia's sky, the location of the cardinal points beginning from the Southern Cross constellation, the color of stars and the stars being seen from a particular place were emphasized. It was found that the students showed an improvement of their understanding about these subjects, as well as a significant excitement with the developed methodology. El objetivo de este trabajo es presentar algunos de los resultados obtenidos en el proyecto de la tesis de maestría del autor, que incluyó el desarrollo de algunas clases de Astronomía, con estudiantes del primer año del bachillerato de una escuela privada del Distrito Federal (Brasilia, Brasil), utilizando como materia prima didáctica el recurso llamado miniplanetario (MP). Utilizando como base teórica orientadora de esas clases las ideas de contextualización y dialógica de Paulo Freire, fue propuesto a los estudiantes el montaje y la utilización de este recurso en una función de planetario. Durante el proyecto, se enfatizaron asuntos tales como la trayectoria aparente de las estrellas del cielo de Brasilia, la ubicación de los puntos cardinales a partir de la constelación de la Cruz del Sur, los colores de las estrellas y las estrellas vistas desde una localidad determinada. Se constató que los estudiantes mostraron una mejora en la comprensión de estas cuestiones y demostraron un gran interés por esta metodología. O objetivo deste artigo é apresentar parte dos resultados obtidos com a intervenção feita como projeto da dissertação de mestrado do autor, que consistiu no desenvolvimento de um conjunto de aulas de Astronomia, com alunos do 1º Ano do Ensino Médio de uma escola da rede privada do Distrito Federal (Brasília, Brasil), empregando como recurso principal um material didático chamado miniplanetário (MP). Utilizando como pressuposto teórico norteador dessas aulas as ideias de contextualização e dialogicidade de Paulo Freire, foi proposta aos estudantes a montagem e utilização desse recurso em uma sessão de planetário. Durante o projeto, enfatizaram-se assuntos como a trajetória aparente das estrelas para o céu de Brasília, a localização dos pontos cardeais a partir da constelação do Cruzeiro do Sul, as cores das estrelas e as estrelas vistas de uma determinada localidade. Apurou-se que os alunos apresentaram melhoria na compreensão desses assuntos, bem como demonstraram expressiva empolgação com essa metodologia desenvolvida.

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.

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).

Perceptional gaps among women, husbands and family members about intentions for birthplace: a cross-sectional study.

PubMed

Shimpuku, Yoko; Madeni, Frida Elikana; Horiuchi, Shigeko; Leshabari, Sebalda Charles

2017-01-30

women are more likely to give birth at a health facility when their families agree with the birthplace. However, in rural areas of Tanzania, women are often marginalized from decision-making. This study predicted birthplace intention and identified factors to reduce perceptional gaps among pregnant women, husbands and family members. explanatory cross-sectional survey was conducted in three villages in North Eastern Tanzania. Participants were 138 pregnant women and their families who answered the Birth Intention Questionnaire (BIQ), measuring knowledge, attitude, perceived behavioral control, subjective norms and intention for birthplace. Descriptive analysis, ANOVA, Chi-square, and multiple linear regression was used to analyze the data. the regression model showed that knowledge, perceived behavioral control, and subjective norms predicted intention for birthplace (R2 = .28). While 81% of pregnant women thought their husbands were decision-makers for their birth, only 38% of husbands and 37% of family members agreed. Pregnant women had significantly lower scores on the item "I will prepare for childbirth with my family" compared with husbands (p < .01) and other family members (p < .001). providing evidence-based birth preparation and reducing the identified perceptual gaps may enhance women's intention to deliver at health facilities. as mulheres são mais propensas a dar à luz em um centro de saúde quando suas famílias estão de acordo com o local de nascimento. No entanto, nas áreas rurais da Tanzânia, as mulheres são muitas vezes marginalizadas do processo de decisão. Este estudo fez previsoes de intenção para o local do parto e fatores para reduzir as lacunas de percepção entre as mulheres grávidas, seus maridos e familiares identificados. estudo transversal explicativo realizado em três aldeias no nordeste da Tanzânia. Os participantes foram 138 mulheres grávidas e suas famílias que responderam ao Questionário de Intenção sobre Parto (BIQ), medindo o conhecimento, atitude, percepcão de controle comportamental, normas subjetivas e intenção para lugar de parto. Análise descritivas, ANOVA, Qui-quadrado e regressão linear múltipla foram utilizados para analisar os dados. o modelo de regressão mostrou que o conhecimento, percepcão de controle comportamental e normas subjetivas previram intenção de lugar de parto (R2 = 0,28). Enquanto 81% das mulheres grávidas pensavam que seus maridos eram os decisores para seu parto, apenas 38% dos maridos e 37% dos membros da família concordaram. As mulheres grávidas tiveram escores significativamente mais baixos sobre o item "Vou me preparar para o parto com a minha família", em comparação com os maridos (p < 0,01) e outros membros da família (p < 0,001). Proporcionar preparação para o parto baseada em evidencias e a redução das lacunas de percepção identificadas podem melhorar a intenção das mulheres para dar à luz em unidades de saúde. las mujeres son más propensas a dar a luz en un centro de salud cuando sus familias están de acuerdo con el lugar de parto. Sin embargo, en las zonas rurales de Tanzania, las mujeres son a menudo marginadas de la toma de decisiones. Este estudio predijo la intención del lugar de parto y los factores identificados para reducir la brecha de percepción entre las mujeres embarazadas, esposos y miembros de la familia. encuesta transversal explicativa llevada a cabo en tres aldeas en el noreste de Tanzania. Los participantes fueron 138 mujeres embarazadas y sus familias, que respondieron al Cuestionario sobre Intención del Parto (BIQ), que mide el conocimiento, la actitud, percepción de control del comportamiento, las normas subjetivas y la intención de lugar de parto. Se utilizaron análisis descriptivo, ANOVA, Chi-cuadrado y regresión lineal múltiple para analizar los datos. el modelo de regresión mostró que el conocimiento, la percepción de control del comportamiento, y las normas subjetivas predijeron la intencion del lugar de parto (R2 = 0,28). Mientras que el 81% de las mujeres embarazadas pensaba que sus maridos estaban encargados de tomar decisiones para el nacimiento, sólo el 38% de los esposos y el 37% de los miembros de la familia estuvieron de acuerdo. Las mujeres embarazadas tenían puntuaciones significativamente más bajas en el tema "Me prepararé para el parto con mi familia", en comparación con los maridos (p < 0,01) y otros miembros de la familia (p < 0,001). proporcionar la preparación al parto basada en la evidencia y reducir las brechas de percepción identificadas pueden mejorar intención de las mujeres a dar a luz en centros de salud.

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

Variability in biochemical components of the mussel (Mytilus galloprovincialis) cultured after Prestige oil spill.

PubMed

Peteiro, Laura G; Labarta, Uxío; Fernández-Reiriz, María José

2007-05-01

The biochemical composition (proteins, carbohydrates, glycogen, total lipids and lipid classes) of the mussel Mytilus galloprovincialis was investigated during an experimental culture using mussel seed from areas with different degree of exposure to the Prestige oil spill. The aim of the study was to identify alterations in the biochemical composition of mussel seed from natural populations commonly used in Galicia for mussel raft culture that might be linked to previous oil exposure. We have selected three mussel seed populations from Pindo, Miranda and Redes, that were characterised in a previous study according to the oil exposure three months after the spill. These populations were transplanted to a raft culture system in the Ría de Ares-Betanzos where our experimental culture followed standard commercial techniques from March 2003 to February 2004. Mussels from Pindo (characterised as the most affected area by the oil spill) showed marked differences in lipid composition with regard to other populations in the content of triacylglycerols, (P<0.001), free fatty acids (P<0.001) and phospholipids (P<0.05) at the onset of the culture. Although these differences in lipid composition might reflect their previous exposition to hydrocarbons, this pattern did not last longer most likely due to depuration of hydrocarbons stored in the tissues or by the development of certain tolerance to PAHs. These significant differences were not detected between Miranda (designed as hardly affected area) and Redes (designed as reference area) which may reflect that Miranda mussels were not affected or only hardly affected by the spill. With the exception of the onset of the culture, biochemical composition showed similar patterns in all mussel populations. Then, the fact of being cultured in a common environment seemed to be more responsible for the long-term variability in the energetic reserve than the origin of the populations or their previous biochemical status.

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

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...

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

Effectiveness of teaching strategies on the development of critical thinking in undergraduate nursing students: a meta-analysis.

PubMed

Oliveira, Larissa Bertacchini de; Díaz, Leidy Johanna Rueda; Carbogim, Fábio da Costa; Rodrigues, Adriano Rogério Baldacin; Püschel, Vilanice Alves de Araújo

2016-04-01

To evaluate the effectiveness of teaching strategies used for development of critical thinking (CT) in undergraduate nursing students. Systematic review with meta-analysis based on the recommendations of the Joanna Briggs Institute . Searches were conducted in the following databases: PubMed, CINAHL, EMBASE, Web of Science, SCOPUS, LILACS, Cochrane CENTRAL, PsycINFO, ERIC, and a database of theses from four continents. The initial selection and evaluation of studies and assessment of methodological quality was performed by two reviewers independently. Twelve randomized clinical trials were included in the study. In the meta-analysis of the four studies included that evaluated the strategy of problem-based learning (PBL), compared to lectures, the effectiveness of PBL was demonstrated with statistical significance (SMD = 0.21 and 95% CI = 0.01 to 0.42; p = 0.0434) for the development of CT in undergraduate nursing students, and the studies were homogeneous (chi-square = 6.10, p = 0.106). The effectiveness of PBL was demonstrated in the increase of overall CT scores. Further studies need to be conducted in order to develop, implement and evaluate teaching strategies that are guided in high methodological rigor, and supported in theoretical models of teaching and learning. Avaliar a efetividade das estratégias de ensino utilizadas para o desenvolvimento do pensamento crítico (PC) em estudantes de graduação em Enfermagem. Revisão sistemática com metanálise baseada nas recomendações do Joanna Briggs Institute. A busca foi realizada nas bases de dados PubMed, CINAHL, EMBASE, Web of Science, SCOPUS, LILACS, Cochrane CENTRAL, PsycINFO e ERIC e de banco de teses dos quatro continentes. A seleção e avaliação inicial dos estudos e a avaliação da qualidade metodológica foi realizada por dois revisores de forma independente. Incluídos 12 ensaios clínico randomizados. Na metanálise, dos quatro estudos incluídos que avaliaram a estratégia do Problem Based Learning (PBL), comparada a palestras, foi demonstrada a efetividade do PBL, estatisticamente significativa (SMD=0,21 e 95% IC=0,01-0,42; p=0,0434) para o desenvolvimento do PC em estudantes de graduação em Enfermagem e os estudos eram homogêneos (Qui-quadrado=6,10, p=0,106). Foi demonstrada a efetividade do PBL no aumento dos escores de PC global. Novos estudos precisam ser feitos com o objetivo de desenvolver, implementar e avaliar estratégias de ensino, que sejam pautadas em alto rigor metodológico e amparadas em modelos teóricos de ensino-aprendizagem.

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.

Ship Production Symposium Held in Long Beach, California on September 11-13, 1985. Volume 2 (The National Shipbuilding Research Program)

DTIC Science & Technology

1985-09-01

t h e long- term we are comple te ly redes ign ing the Weapon Systems F i le c o m p u t e r s o f t w a r e s o t h a t i t i s f u l l y ...sidewall 6) ability to repair surface defects by carbon arcing and grinding -572- LIST OF REFERENCES 1) Kimura, S., Ichihara, I., and Nagai, Y ...5.5 inch/min) (50/60 Hz) Stroke: 350mm (I 3.8 inch) electric inching method M o u n t i n g A s s e m b l y ) Vertical Head adjustment Slide speed

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

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.

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.

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

Gastric wall changes after intragastric balloon placement: a preliminary experience.

PubMed

Périssé, Luís Gustavo Santos; Ecbc-Rj, Paulo Cézar Marques Périssé; Ribeiro, Kelson Ferreira

2016-01-01

: to evaluate the thickness of the gastric wall at the time of intra gastric balloon (IGB) placement, at the time of its withdrawal and one month after withdrawal. : fifteen morbidly obese patients underwent the introduction of IGB under general anesthesia. In all patients, there was infusion of 500ml of distilled water in the balloon for the test. Measurements of the thickness of the gastric wall were made in the antrum, body and proximal body, using a radial echoendoscope with a frequency of 12MHz and maximum zoom, and its own balloon inflated with 5ml of distilled water. : the presence of IGB led to increased wall thickness of the gastric body by expanding the muscle layer. These changes were apparently transient, since 30 days after the balloon withdrawal there was a tendency to return of the wall thickness values ​​observed before the balloon insertion. : the use of intragastric balloon for the treatment of obesity determines transient increase in the wall thickness of the gastric body caused by expanded muscle layer. avaliar a espessura da parede gástrica no momento do posicionamento do balão intragástrico (BIG), no momento de sua retirada e um mês após a retirada. quinze pacientes obesos mórbidos foram submetidos à introdução de BIG sob anestesia geral. Em todos os pacientes foi feita infusão de 500 ml de água destilada e o balão foi insuflado com 5ml de água destilada. As medidas da espessura da parede gástrica foram feitas no antro, corpo e corpo alto utilizando-se um ecoendoscópio radial com frequência de 12MHz e zoom máximo. a presença do BIG levou ao aumento da espessura da parede do corpo gástrico pelo aumento de espessura da sua camada muscular. Estas alterações são aparentemente transitórias já que após 30 dias da retirada do balão existiu uma tendência de retorno da espessura da parede aos valores observados antes do seu posicionamento. a utilização do balão intragástrico para tratamento da obesidade determina aumento transitório da espessura da parede do corpo gástrico causado pelo aumento da camada muscular.

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.