76 FR 64882 - Inquiry Into Disbursement Process for the Universal Service Fund Low Income Program

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-19

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 54 [WC Docket Nos. 03-109 and 11-42; DA 11-1593] Inquiry Into Disbursement Process for the Universal Service Fund Low Income Program AGENCY: Federal...; DA 11-1593, issued September 23, 2011. The complete text of the Public Notice is available for...

The effects of nitric oxide-cGMP pathway stimulation on dopamine in the medial preoptic area and copulation in DHT-treated castrated male rats

PubMed Central

Sato, Satoru M.; Wersinger, Scott R.; Hull, Elaine M.

2007-01-01

Dopamine (DA) in the medial preoptic area (MPOA) provides important facilitative influence on male rat copulation. We have shown that the nitric oxide-cGMP (NO-cGMP) pathway modulates MPOA DA levels and copulation. We have also shown that systemic estradiol (E2) maintains neuronal NO synthase (nNOS) immunoreactivity in the MPOA of castrates, as well as relatively normal DA levels. This effect of E2 on nNOS probably accounts for at least some of the previously demonstrated behavioral facilitation by intra-MPOA E2 administration in castrates. Therefore, we hypothesized that stimulation of the MPOA NO-cGMP pathway in dihydrotestosterone (DHT)-treated castrates should restore DA levels and copulatory behaviors. Reverse-dialysis of a NO donor, sodium nitroprusside (SNP), increased extracellular DA in the MPOA of DHT-treated castrates and restored the ability to copulate to ejaculation in half of the animals. A cGMP analog, 8-Br-cGMP, also increased extracellular DA, though not as robustly, but did not restore copulatory ability. The effectiveness of the NO donor in restoring copulation and MPOA DA levels is consistent with our hypothesis. However, the lack of behavioral effects of 8-Br-cGMP, despite its increase in MPOA DA, suggests that NO may have additional mediators in the MPOA in the regulation of copulation. Furthermore, the suboptimal copulation seen in the NO donor-treated animals suggests the importance of extra-MPOA systems in the regulation of copulation. PMID:17467707

The experience of rural families in the face of cancer.

PubMed

Girardon-Perlini, Nara Marilene Oliveira; Ângelo, Margareth

2017-01-01

To understand the meanings of cancer within the experience of rural families and how such meanings influence family dynamics. Qualitative study guided by Symbolic Interactionism as a theoretical framework and Grounded Theory as a methodological framework. Six rural families (18 participants) undergoing the experience of having a relative with cancer participated in the interview. Constant comparative analysis of data allowed the elaboration of an explanatory substantive theory, defined by the main category Caregiving to support the family world, which represents the family's symbolic actions and strategies to reconcile care for the patient and care for family life. Throughout the experience, rural families seek to preserve the interconnected symbolic elements that provide support for the family world: family unit, land, work and care. Compreender os significados do câncer presentes na experiência de famílias rurais e como esses significados influenciam a dinâmica familiar. Estudo qualitativo orientado pelo Interacionismo Simbólico como referencial teórico e pela Teoria Fundamentada nos Dados como referencial metodológico. Participaram, por meio de entrevista, seis famílias rurais (18 participantes) que estavam vivendo a experiência de ter um familiar com câncer. A análise comparativa constante dos dados permitiu a elaboração de uma teoria substantiva explicativa da experiência, definida pela categoria central Cuidando para manter o mundo da família amparado, que representa as ações e estratégias simbólicas da família visando a conciliar o cuidado do familiar doente e o cuidado da vida familiar. Ao longo da experiência, a família rural procura preservar os elementos simbólicos que, conectados, constituem o amparo do mundo da família: a unidade familiar, a terra, o trabalho e o cuidado.

O que bilíngues bimodais têm a nos dizer sobre desenvolvimento bilíngue?

PubMed Central

de Quadros, Ronice Müller; Lillo-Martin, Diane; Pichler, Deborah Chen

2013-01-01

O objetivo deste trabalho é apresentar o que as pesquisas que estamos desenvolvendo com crianças ouvintes, filhas de pais surdos, adquirindo Língua Brasileira de Sinais (Libras) e Português e Língua de Sinais Americana (ASL) e Inglês (Lillo-Martin et al. 2010) têm a nos dizer sobre desenvolvimento bilíngue. Os dados deste estudo fazem parte de um banco de dados de interações espontâneas coletadas longitudinalmente, alternando contextos de aquisição da Libras e do português como língua alvo, no Brasil e dados coletados longitudinalmente. nos mesmos contextos, de crianças adquirindo ASL e inglês1. Além disso, há também dados do estudo experimental com testes aplicados nos dois pares de línguas que se agregam ao presente estudo. Uma visão geral dos estudos desenvolvidos sobre a aquisição bilíngue bimodal por crianças ouvintes, filhas de pais surdos, será apresentada e, então, serão expostos alguns aspectos linguísticos deste tipo de aquisição, considerando as discussões sobre aquisição bilíngue a partir da pesquisa realizada. PMID:24431480

The Mechanism of Helium-Induced Preconditioning: A Direct Role for Nitric Oxide in Rabbits

PubMed Central

Pagel, Paul S.; Krolikowski, John G.; Pratt, Phillip F.; Shim, Yon Hee; Amour, Julien; Warltier, David C.; Weihrauch, Dorothee

2008-01-01

BACKGROUND Helium produces preconditioning against myocardial infarction by activating prosurvival signaling, but whether nitric oxide (NO) generated by endothelial NO synthase plays a role in this phenomenon is unknown. We tested the hypothesis that NO mediates helium-induced cardioprotection in vivo. METHODS Rabbits (n = 62) instrumented for hemodynamic measurement were subjected to a 30-min left anterior descending coronary artery occlusion and 3 h reperfusion, and received 0.9% saline (control) or three cycles of 70% helium–30% oxygen administered for 5 min interspersed with 5 min of an air–oxygen mixture before left anterior descending coronary artery occlusion in the absence or presence of pretreatment with the nonselective NOS inhibitor N-nitro-l-arginine methyl ester (L-NAME; 10 mg/kg), the selective inducible NOS inhibitor aminoguanidine hydrochloride (AG; 300 mg/kg), or selective neuronal NOS inhibitor 7-nitroindazole (7-NI; 50 mg/kg). In additional rabbits, the fluorescent probe 4,5-diaminofluroscein diacetate (DAF-2DA) and confocal laser microscopy were used to detect NO production in the absence or presence of helium with or without L-NAME pretreatment. RESULTS Helium reduced (P < 0.05) infarct size (24% ± 4% of the left ventricular area at risk; mean ± sd) compared with control (46% ± 3%). L-NAME, AG, and 7-NI did not alter myocardial infarct size when administered alone. L-NAME, but not 7-NI or AG, abolished helium-induced cardioprotection. Helium enhanced DAF-2DA fluorescence compared with control (26 ± 8 vs 15 ± 5 U, respectively). Pretreatment with L-NAME abolished these helium-induced increases in DAF-2DA fluorescence. CONCLUSIONS The results indicate that cardioprotection by helium is mediated by NO that is probably generated by endothelial NOS in vivo. PMID:18713880

Effects of advancing gestation and non-Caucasian race on ductus arteriosus gene expression

PubMed Central

Waleh, Nahid; Barrette, Anne Marie; Dagle, John M.; Momany, Allison; Jin, Chengshi; Hills, Nancy K.; Shelton, Elaine L.; Reese, Jeff; Clyman, Ronald I.

2015-01-01

Objective To identify genes affected by advancing gestation and racial/ethnic origin in human ductus arteriosus (DA). Study design We collected three sets of DA tissue (n=93, n=89, n=91; total = 273 fetuses) from second trimester pregnancies. We examined four genes, with DNA polymorphisms that distribute along racial lines, to identify "Caucasian" and "Non-Caucasian" DA. We used RT-PCR to measure RNA expression of 48 candidate genes involved in functional closure of the DA, and used multivariable regression analyses to examine the relationships between advancing gestation, "Non-Caucasian" race, and gene expression. Results Mature gestation and Non-Caucasian race are significant predictors for identifying infants who will close their patent DA when treated with indomethacin. Advancing gestation consistently altered gene expression in pathways involved with oxygen-induced constriction (e.g., calcium-channels, potassium-channels, and endothelin signaling), contractile protein maturation, tissue remodeling, and prostaglandin and nitric oxide signaling in all three tissue sets. None of the pathways involved with oxygen-induced constriction appeared to be altered in "Non-Caucasian" DA. Two genes, SLCO2A1 and NOS3, (involved with prostaglandin reuptake/metabolism and nitric oxide production, respectively) were consistently decreased in "Non-Caucasian" DA. Conclusions Prostaglandins and nitric oxide are the most important vasodilators opposing DA closure. Indomethacin inhibits prostaglandin production, but not nitric oxide production. Because decreased SLCO2A1 and NOS3 expression can lead to increased prostaglandin and decreased nitric oxide concentrations, we speculate that prostaglandin-mediated vasodilation may play a more dominant role in maintaining the "Non-Caucasian" PDA, making it more likely to close when inhibited by indomethacin. PMID:26265282

Uma Visão do Universo Segundo um Grupo de Alunos do Ensino Médio de São Paulo

NASA Astrophysics Data System (ADS)

Elias, D. S.; Araújo, M.; Amaral, L. H.; Voelzke, M. R.; Araújo, M.

2005-08-01

A astronomia, embora seja uma ciência popular, com inúmeras descobertas de interesse público, ainda é apresentada desconsiderando-se os aspectos históricos e científicos relacionados ao seu desenvolvimento, sendo geralmente veiculada nos meios de comunicação de maneira pouco esclarecedora e não raro com imprecisões. Neste trabalho analisou-se a concepção de um grupo de estudantes de Ensino Médio sobre conceitos de astronomia, visando identificar sua visão de mundo a respeito do Universo, envolvendo idéias sobre espaço e tempo. Para issso, foi aplicado um questionário em três escolas da grande São Paulo em um espaço amostral de 270 alunos. Constatou-se que, embora o ensino de astronomia esteja previsto nos PCNEM, os resultados obtidos na pesquisa mostram que há grande deficiência no conhecimento dos temas investigados. Nesse sentido, verificou-se que apenas 20% dos alunos eram capazes de relacionar a sucessão das semanas com as fases da lua, enquanto 28% associaram as estações do ano à inclinação do eixo de rotação da Terra. Por outro lado, somente 23% dos alunos tinham noções das distâncias entre os objetos celestes próximos da Terra e 56% conseguiram relacionar o Big Bang com a origem do Universo. Finalmente, constatou-se que 37% reconheciam o ano-luz como uma unidade de distância e 60% reconheciam o Sol como sendo uma estrela. Apesar de 60% dos alunos indicarem que a escola é a principal fonte para aquisição dos conhecimentos de astronomia, conclui-se que seus conceitos nessa área ainda são inadequados, havendo necessidade de ampliação e aprimoramento da abordagem desses conteúdos nos ambientes escolares.

Sport physiology, dopamine and nitric oxide - Some speculations and hypothesis generation.

PubMed

Landers, J G; Esch, Tobias

2015-12-01

Elite Spanish professional soccer players surprisingly showed a preponderance of an allele coding for nitric oxide synthase (NOS) that resulted in lower nitric oxide (NO) compared with Spanish endurance and power athletes and sedentary men. The present paper attempts a speculative explanation. Soccer is an "externally-paced" (EP) sport and team work dependent, requiring "executive function skills". We accept that time interval estimation skill is, in part, also an executive skill. Dopamine (DA) is prominent among the neurotransmitters with a role in such skills. Polymorphisms affecting dopamine (especially DRD2/ANKK1-Taq1a which leads to lower density of dopamine D2 receptors in the striatum, leading to increased striatal dopamine synthesis) and COMT val 158 met (which prolongs the action of dopamine in the cortex) feature both in the time interval estimation and the executive skills literatures. Our paper may be a pioneering attempt to stimulate empirical efforts to show how genotypes among soccer players may be connected via neurotransmitters to certain cognitive abilities that predict sporting success, perhaps also in some other externally-paced team sports. Graphing DA levels against time interval estimation accuracy and also against certain executive skills reveals an inverted-U relationship. A pathway from DA, via endogenous morphine and mu3 receptors on endothelia, to the generation of NO in tiny quantities has been demonstrated. Exercise up-regulates DA and this pathway. With somewhat excessive exercise, negative feedback from NO down-regulates DA, hypothetically keeping it near the peak of the inverted-U. Other research, not yet done on higher animals or humans, shows NO "fine-tuning" movement. We speculate that Caucasian men, playing soccer recreationally, would exemplify the above pattern and their nitric oxide synthase (NOS) would reflect the norm of their community, whereas professional players of soccer and perhaps other EP sports, with DA boosted by very frequent and intense practice and extra stress from public scrutiny, would potentially have their negative feedback system overwhelmed, were it not that many of them carry the C allele of the NOS3-786T/C polymorphism. Then, even very high DA would not result in so much NO as to shut the system down. We add some evolutionary speculations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Protection from inorganic mercury effects on the in vivo dopamine release by ionotropic glutamate receptor antagonists and nitric oxide synthase inhibitors.

PubMed

Vidal, Lucía; Durán, Rafael; Faro, Lilian F; Campos, Francisco; Cervantes, Rosa C; Alfonso, Miguel

2007-09-05

The possible role of ionotropics glutamate receptors on the HgCl(2)-induced dopamine (DA) release from rat striatum was investigated by using in vivo brain microdialysis technique after administration of selective NMDA and AMPA/Kainate receptors antagonists dizocilpine (MK-801), D (-)-2-amino-5-phoshonopentanoic acid (AP5), and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Moreover, we have also studied the effects of nitric oxide synthase (NOS) inhibitors L-nitro-arginine methyl ester (L-NAME) and 7-nitro-indazol (7-NI) on HgCl(2)-induced DA release. Intraestriatal infusion of 1mM HgCl(2) increased striatal DA to 1717.2+/-375.4% respect to basal levels. Infusion of 1mM HgCl(2) in 400 microM MK-801 pre-treated animals produced an increase on striatal DA levels 61% smaller than that induced in non-pre-treated animals. In the case of AP5, this treatment reduced 92% the increase produced by HgCl(2) as compared to non-pre-treated rats. Nevertheless, the administration of CNQX did not produce any effect on HgCl(2)-induced dopamine release. Intrastriatal infusion of 1mM HgCl(2) in 100 microM L-NAME pre-treated animals produced an increase on extracellular DA levels 82% smaller than produced by HgCl(2) alone. In addition, the pre-treatment with 7-NI reduced 90% the increase produced by infusion of HgCl(2) alone in rats. Thus, HgCl(2)-induced DA release could be produced at last in part, by overstimulation of NMDA receptors with NO production, since administration of NMDA receptor antagonists and NOS inhibitors protected against HgCl(2) effects on DA release.

Vascular and renal effects of dopamine during extracellular volume expansion: Role of nitric oxide pathway.

PubMed

Costa, María A; Elesgaray, Rosana; Loria, Analía; Balaszczuk, Ana María; Arranz, Cristina

2006-02-28

The aim of the study was to determine the possible role of NO-system activation in vascular and renal effects of the dopaminergic system and the probable interaction between both systems during acute volume expansion in rats. Expanded (10% bw) and non-expanded anaesthetized male Wistar rats were treated with haloperidol, a DA receptor antagonist (3 mg/kg bw, ip). Mean arterial pressure, diuresis, natriuresis, renal plasma flow, glomerular filtration rate, nitrites and nitrates excretion (NOx) were determined. NADPH diaphorase activity was measured using a histochemistry technique in kidney, aorta and renal arteries. NOS activity in kidney and aorta from expanded and non-expanded animals was determined with L-[U14C]-arginine substrate, in basal conditions and after DA (1 microM) administration. The hypotensive effect of L-arg and hypertension induced by L-NAME were not modified by haloperidol. This blocker reverted the increase in diuresis, natriuresis and RPF induced by L-arg in both groups. Dopaminergic blockade induced a decrease in NOx excretion and in NADPH-diaphorase activity in glomeruli, proximal tubule and medullar collecting duct and in endothelium and vascular smooth muscle of renal arteries. DA induced an increase in NOS activity in renal medulla and cortex in both groups, but no changes in the aorta were observed. Our results suggest that renal DA would be associated with the renal response induced by NO during extracellular volume expansion. NO-system activation would be one of the mechanisms involved in renal DA activity during saline load, but NO appears not to be involved in DA vascular effects.

11. "TEST STANDS NOS. 11, 13, & 15; CONCRETE STRUCTURAL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

11. "TEST STANDS NOS. 1-1, 1-3, & 1-5; CONCRETE STRUCTURAL SECTIONS AND DETAILS." Specifications No. OC12-50-10; Drawing No. 60-09-04; no sheet number within title block. D.O. SERIES 1109/15, Rev. E. Stamped: RECORD DRAWING - AS CONSTRUCTED. Below stamp: Contract DA-04353 Eng. 177, Rev. E; Date: 21 Dec. 1951. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Test Stand 1-5, Test Area 1-115, northwest end of Saturn Boulevard, Boron, Kern County, CA

13. "TEST STANDS NOS. 11, 13, & 15; CONCRETE STRUCTURAL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

13. "TEST STANDS NOS. 1-1, 1-3, & 1-5; CONCRETE STRUCTURAL SECTIONS AND DETAILS." Specifications No. OC12-50-10; Drawing No. 60-09-04; no sheet number within title block. D.O. SERIES 1109/18, Rev. D. Stamped: RECORD DRAWING - AS CONSTRUCTED. Below stamp: Contract DA-04353 Eng. 177, Rev. D, no change; Date: 18 Dec. 1951. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Test Stand 1-5, Test Area 1-115, northwest end of Saturn Boulevard, Boron, Kern County, CA

15. "TEST STANDS NOS. 11, 13, & 15; STRUCTURAL STEEL; ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

15. "TEST STANDS NOS. 1-1, 1-3, & 1-5; STRUCTURAL STEEL; PLAN & DETAILS." Specifications No. ENG 04-353-50-10; Drawing No. 60-09-04; no sheet number within title block. D.O. SERIES 1109/34, Rev. A. Stamped: RECORD DRAWING - AS CONSTRUCTED. Below stamp: Contract DA-04353 Eng. 177, Rev. A, no change; Date: 21 Dec. 1951. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Test Stand 1-5, Test Area 1-115, northwest end of Saturn Boulevard, Boron, Kern County, CA

9. "TEST STANDS NOS. 11, 13, & 15; CONCRETE STRUCTURAL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

9. "TEST STANDS NOS. 1-1, 1-3, & 1-5; CONCRETE STRUCTURAL SECTIONS AND DETAILS." Specifications No. ENG 04-35350-10; Drawing No. 60-09-04; no sheet number within title block. D.O. SERIES 1109/13. Stamped: RECORD DRAWING - AS CONSTRUCTED. Below stamp: Contract DA-04353 Eng. 177, no change; Date: 17 Dec. 1951. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Test Stand 1-5, Test Area 1-115, northwest end of Saturn Boulevard, Boron, Kern County, CA

10. "TEST STANDS NOS. 11, 13, & 15; CONCRETE STRUCTURAL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

10. "TEST STANDS NOS. 1-1, 1-3, & 1-5; CONCRETE STRUCTURAL SECTIONS AND DETAILS." Specifications No. OC12-50-10; Drawing No. 60-09-04; no sheet number within title block. D.O. SERIES 1109/14, Rev. B. Stamped: RECORD DRAWING - AS CONSTRUCTED. Below stamp: Contract DA-04353 Eng. 177, Rev. B; Date: 21 Dec. 1951. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Test Stand 1-5, Test Area 1-115, northwest end of Saturn Boulevard, Boron, Kern County, CA

16. "TEST STANDS NOS. 11, 13, & 15; STRUCTURAL STEEL; ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

16. "TEST STANDS NOS. 1-1, 1-3, & 1-5; STRUCTURAL STEEL; ELEVATIONS AND SECTIONS." Specifications No. ENG 04353-50-10; Drawing No. 60-09-04; no sheet number within title block. D.O. SERIES 1109/35, Rev. A. Stamped: RECORD DRAWING - AS CONSTRUCTED. Below stamp: Contract DA-04-353 Eng. 177, Rev. A; Date: 29 Dec. 1951. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Test Stand 1-5, Test Area 1-115, northwest end of Saturn Boulevard, Boron, Kern County, CA

12. "TEST STANDS NOS. 11, 13, & 15; CONCRETE STRUCTURAL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

12. "TEST STANDS NOS. 1-1, 1-3, & 1-5; CONCRETE STRUCTURAL SECTIONS AND DETAILS." Specifications No. OC12-50-10; Drawing No. 60-09-06; no sheet number within title block. D.O. SERIES 1109/16, Rev. E. Stamped: RECORD DRAWING - AS CONSTRUCTED. Below stamp: Contract DA-04353 Eng. 177, Rev. E; Date: 26 Dec. 1951. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Test Stand 1-5, Test Area 1-115, northwest end of Saturn Boulevard, Boron, Kern County, CA

14. "TEST STANDS NOS. 11, 13, & 15; MISCELLANEOUS DETAILS." ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

14. "TEST STANDS NOS. 1-1, 1-3, & 1-5; MISCELLANEOUS DETAILS." Specifications No. OC12-50-10; Drawing No. 60-09-04; no sheet number within title block. D.O. SERIES 1109/22, Rev. D. Stamped: RECORD DRAWING - AS CONSTRUCTED. Below stamp: Contract DA-04-353 Eng. 177, Rev. D, no change; Date: 17 Dec. 1951. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Test Stand 1-5, Test Area 1-115, northwest end of Saturn Boulevard, Boron, Kern County, CA

Interfering with memory for faces: The cost of doing two things at once.

PubMed

Wammes, Jeffrey D; Fernandes, Myra A

2016-01-01

We inferred the processes critical for episodic retrieval of faces by measuring susceptibility to memory interference from different distracting tasks. Experiment 1 examined recognition of studied faces under full attention (FA) or each of two divided attention (DA) conditions requiring concurrent decisions to auditorily presented letters. Memory was disrupted in both DA relative to FA conditions, a result contrary to a material-specific account of interference effects. Experiment 2 investigated whether the magnitude of interference depended on competition between concurrent tasks for common processing resources. Studied faces were presented either upright (configurally processed) or inverted (featurally processed). Recognition was completed under FA, or DA with one of two face-based distracting tasks requiring either featural or configural processing. We found an interaction: memory for upright faces was lower under DA when the distracting task required configural than featural processing, while the reverse was true for memory of inverted faces. Across experiments, the magnitude of memory interference was similar (a 19% or 20% decline from FA) regardless of whether the materials in the distracting task overlapped with the to-be-remembered information. Importantly, interference was significantly larger (42%) when the processing demands of the distracting and target retrieval task overlapped, suggesting a processing-specific account of memory interference.

Endothelial nitric oxide synthase expression in systemic and pulmonary circulation of streptozotocin induced diabetic rats: comparison using image analysis.

PubMed

Sridulyakul, P; Chakraphan, D; Bhattarakosol, P; Patumraj, S

2003-01-01

To compare the level of endothelial nitric oxide synthase (eNOS) expression produced in heart and lung vascular tissue, the protein content was determined using Western blot analysis with the enhancement of image processing. Heart and lung extracts from 12 and 24 weeks from control (CON) and streptozotocin-induced diabetic (DM) rats were collected for Western blot analysis. Using monoclonal antibody against rat eNOS protein (140 kDa), the eNOS-protein bands were detected with enhanced chemiluminescence (ECL; Amersham) and exposured to film (Hyperfilm-ECL; Amersham). Images of eNOS bands on each film were then scanned and saved to digital files. Using Global Lab Image software, the number of pixels in each digital file was counted and calibrated for eNOS-protein content. For the CON and DM groups, the mean values of eNOS-protein contents were calculated and expressed as a percentage of total protein content, 5 micrograms. It was found that the eNOS level in DM hearts was significantly decreased, as compared to age-matched CON hearts. On the other hand, eNOS levels in DM lungs was increased, compared to CON lungs. Therefore, it may be concluded that high, not low, flow-mediated eNOS expression is a good measure of hyperglycemic-induced endothelial dysfunction.

Poly(ADP-ribose) polymerase-1 and its cleavage products differentially modulate cellular protection through NF-kB-dependent signaling

PubMed Central

Castri, Paola; Lee, Yang-ja; Ponzio, Todd; Maric, Dragan; Spatz, Maria; Bembry, Joliet; Hallenbeck, John

2014-01-01

Poly(ADP-ribose) polymerase-1 (PARP-1) and its cleavage products regulate cell viability and NF-kB activity when expressed in neurons. PARP-1 cleavage generates a 24kDa (PARP-124) and an 89kDa fragment (PARP-189). Compared to WT (PARP-1WT), the expression of an uncleavable PARP-1 (PARP-1UNCL) or of PARP-124 conferred protection from oxygen/glucose deprivation (OGD) or OGD/restoration of oxygen and glucose (ROG) damage in vitro, whereas expression of PARP-189 was cytotoxic. Viability experiments were performed in SH-SY5Y, a human neuroblastoma cell line, as well as in rat primary cortical neurons. Following OGD, the higher viability in the presence of PARP-1UNCL or PARP-124 was not accompanied with decreased formation of poly(ADP-riboses) or higher NAD levels. PARP-1 is a known cofactor for NF-kB, hence we investigated whether PARP-1 cleavage influences the inflammatory response. All PARP-1 constructs mimicked PARP-1WT in regards to induction of NF-kB translocation into the nucleus and its increased activation during ischemic challenge. However, expression of PARP-189 construct induced significantly higher NF-kB activity than PARP-1WT; and the same was true for NF-kB-dependent iNOS promoter binding activity. At a protein level, PARP-1UNCL and PARP-124 decreased iNOS (and lower levels of iNOS transcript) and COX-2, and increased Bcl-xL. The increased levels of NF-kB and iNOS transcriptional activities, seen with cytotoxic PARP-189, were accompanied by higher protein expression of COX-2 and iNOS (and higher levels of iNOS transcript) and lower protein expression of Bcl-xL. Taken together, these findings suggest that PARP-1 cleavage products may regulate cellular viability and inflammatory responses in opposing ways during in vitro models of “ischemia”. PMID:24333653

DaCHS: Data Center Helper Suite

NASA Astrophysics Data System (ADS)

Demleitner, Markus

2018-04-01

DaCHS, the Data Center Helper Suite, is an integrated package for publishing astronomical data sets to the Virtual Observatory. Network-facing, it speaks the major VO protocols (SCS, SIAP, SSAP, TAP, Datalink, etc). Operator-facing, many input formats, including FITS/WCS, ASCII files, and VOTable, can be processed to publication-ready data. DaCHS puts particular emphasis on integrated metadata handling, which facilitates a tight integration with the VO's Registry

Effects of 7-Nitroindazole, an NOS Inhibitor on Methamphetamine-Induced Dopaminergic and Serotonergic Neurotoxicity in Micea.

PubMed

Ali, Syed F; Itzhak, Yossef

1998-05-01

Methamphetamine (METH) is one of the major drugs of abuse that is postulated to cause neurotoxicity by depleting dopamine (DA) and its metabolites, high-affinity DA uptake sites, and the activity of tyrosine hydroxylase. The present study was undertaken to investigate whether the relatively selective, neuronal nitric oxide synthase (NOS) inhibitor, 7-nitroindazole (7-NI), protects against METH-induced neurotoxicity. Male Swiss Webster mice received the following injections intraperitoneally (i.p.) 3 times (every 3 hr): (i) vehicle/saline, (ii) 7-NI (25 mg/kg)/saline, (iii) vehicle/METH (5 mg/kg), and (iv) 7-NI (25 mg/kg)/METH (5 mg/kg). On the second day, groups (i) and (iii) received two vehicle injections and groups (ii) and (iv) received two 7-NI injections (25 mg/kg each). The administration of vehicle/METH resulted in 68, 44 and 55% decreases in the concentration of DA, dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA), respectively, and a 48% decrease in the number of [ 3 H]mazindol binding sites in the striatum compared to control values. The treatment with 7-NI (group iv) provided a full protection against the depletion of DA and its metabolites, and the loss of dopamine transporter binding sites. Multiple injection of METH caused a significant decrease in the concentration of serotonin (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA). Treatment with 7-NI partially blocked the depletion of 5-HT and completely blocked the reduction in 5-HIAA levels. The administration of 7-NI/saline (group ii) affected neither the tissue concentration of DA, 5-HT and their metabolites (DOPAC, HVA and 5-HIAA) nor the binding parameters of [ 3 H]-mazindol compared to control (vehicle/saline) values. 7-NI had no significant effect on the animals' body temperature, and it did not affect METH-induced hyperthermia. These findings indicate a role for nitric oxide in METH-induced neurotoxicity and also suggest that blockage of NOS may be beneficial for the management of Parkinson's disease.

Effects of 7-nitroindazole, an NOS inhibitor on methamphetamine-induced dopaminergic and serotonergic neurotoxicity in mice.

PubMed

Ali, S F; Itzhak, Y

1998-05-30

Methamphetamine (METH) is one of the major drugs of abuse that is postulated to cause neurotoxicity by depleting dopamine (DA) and its metabolites, high-affinity DA uptake sites, and the activity of tyrosine hydroxylase. The present study was undertaken to investigate whether the relatively selective, neuronal nitric oxide synthase (NOS) inhibitor, 7-nitroindazole (7-NI), protects against METH-induced neurotoxicity. Male Swiss Webster mice received the following injections intraperitoneally (i.p.) 3 times (every 3 hr): (i) vehicle/saline, (ii) 7-NI (25 mg/kg)/saline, (iii) vehicle/METH (5 mg/kg), and (iv) 7-NI (25 mg/kg)/METH (5 mg/kg). On the second day, groups (i) and (iii) received two vehicle injections and groups (ii) and (iv) received two 7-NI injections (25 mg/kg each). The administration of vehicle/METH resulted in 68, 44 and 55% decreases in the concentration of DA, dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA), respectively, and a 48% decrease in the number of [3H]mazindol binding sites in the striatum compared to control values. The treatment with 7-NI (group iv) provided a full protection against the depletion of DA and its metabolites, and the loss of dopamine transporter binding sites. Multiple injection of METH caused a significant decrease in the concentration of serotonin (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA). Treatment with 7-NI partially blocked the depletion of 5-HT and completely blocked the reduction in 5-HIAA levels. The administration of 7-NI/saline (group ii) affected neither the tissue concentration of DA, 5-HT and their metabolites (DOPAC, HVA and 5-HIAA) nor the binding parameters of [3H]-mazindol compared to control (vehicle/saline) values. 7-NI had no significant effect on the animals' body temperature, and it did not affect METH-induced hyperthermia. These findings indicate a role for nitric oxide in METH-induced neurotoxicity and also suggest that blockage of NOS may be beneficial for the management of Parkinson's disease.

Amygdala response to faces parallels social behavior in Williams syndrome

PubMed Central

Snyder, Abraham Z.; Haist, Frank; Raichle, Marcus E.; Bellugi, Ursula; Stiles, Joan

2009-01-01

Individuals with Williams syndrome (WS), a genetically determined disorder, show relatively strong face-processing abilities despite poor visuospatial skills and depressed intellectual function. Interestingly, beginning early in childhood they also show an unusually high level of interest in face-to-face social interaction. We employed functional magnetic resonance imaging (fMRI) to investigate physiological responses in face-sensitive brain regions, including ventral occipito-temporal cortex and the amygdala, in this unique genetic disorder. Participants included 17 individuals with WS, 17 age- and gender-matched healthy adults (chronological age-matched controls, CA) and 17 typically developing 8- to 9-year-old children (developmental age controls, DA). While engaged in a face discrimination task, WS participants failed to recruit the amygdala, unlike both CA and DA controls. WS fMRI responses in ventral occipito-temporal cortex, however, were comparable to those of DA controls. Given the integral role of the amygdala in social behavior, the failure of WS participants to recruit this region during face processing may be a neural correlate of the abnormally high sociability that characterizes this disorder. PMID:19633063

Overall contextual view of Building Nos. 92, 391, and 392, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Overall contextual view of Building Nos. 92, 391, and 392, taken from pier side, crane rails along bravo piers in foreground, palm tree and street light at right center, view facing east-northeast - U.S. Naval Base, Pearl Harbor, Marine Railway No. 1 Accessories House & Apprentice Welding School, Additions, Intersection of Avenue B & Sixth Street, Pearl City, Honolulu County, HI

Post-transcriptional regulation of inducible nitric oxide synthase in chronic lymphocytic leukemia B cells in pro- and antiapoptotic culture conditions.

PubMed

Tiscornia, A C; Cayota, A; Landoni, A I; Brito, C; Oppezzo, P; Vuillier, F; Robello, C; Dighiero, G; Gabús, R; Pritsch, O

2004-01-01

Functional inducible NOS (iNOS) may be involved in the prolonged lifespan of chronic lymphocytic leukemia cells (B-CLL), although the exact mechanisms implicated remain elusive as yet. In this work, we have examined iNOS expression in normal B lymphocytes and B-CLL cells in pro- and antiapoptotic conditions. Our results demonstrate: (1) The existence of a new splice variant characterized by a complete deletion of exon 14 (iNOS 13-16(14del)), which was preferentially detected in normal B lymphocytes and may represent an isoform that could play a role in the regulation of enzyme activity. (2) The existence of another alternatively spliced iNOS mRNA transcript involving a partial deletion of the flavodoxin region (iNOS 13-16(neg)) was correlated to a decreased B-CLL cell viability. The 9-beta-D-arabinofuranosyl-2-fluoradenine or fludarabine (F-ara) treatment induced iNOS 13-16(neg) transcript variants, whereas IL-4 enhanced both the transcription of variants, including these exons (iNOS 13-16(pos)), and the expression of a 122 kDa iNOS protein. These results suggest that in B-CLL, a regulation process involving nitric oxide (.- NO) levels could occur by a post-transcriptional mechanism mediated by soluble factors. Our results also provide an insight into a new complementary proapoptotic action of F-ara in B-CLL by the induction of particular iNOS splice variants, leading to the activation of a caspase-3-dependent apoptotic pathway.

Ensino de gravitação clássica no nível médio: uma proposta de abordagem e resultados preliminares

NASA Astrophysics Data System (ADS)

Medeiros, G. C. M.; Jafelice, L. C.

2003-08-01

O ensino de gravitação clássica é comumente realizado de maneira formal e descontextualizado da experiência com a força-peso e da história do tema. Fustigados por anos de experiência de ensino no assunto, nem sempre com bons resultados, propomos uma abordagem ancorada nos eixos: a) contextualização histórica; e b) reconhecimento do peso como a força de atração gravitacional. O primeiro eixo integra o tema no desenvolvimento cultural do ser humano, praticando a interdisciplinaridade. O segundo eixo embasa construtivamente a abordagem, levando o aluno a realizar experiências e a vivenciar o reconhecimento de uma força universal. A abordagem foi construída através das etapas: 1) análise crítica do tema em livros didáticos; 2) elaboração de um curso para professores das várias disciplinas do ensino médio, identificando conexões para a prática da interdisciplinaridade; 3) elaboração de material didático; e 4) avaliação da eficácia da abordagem. No trabalho discutimos em detalhe as quatro etapas. Como resultados, adiantamos que: tabulamos a abordagem de gravitação nos livros didáticos, ainda muito tradicional e carecedora de atividades criativas que poderiam melhor explorar esse assunto; mapeamos, junto aos professores, padrões de conceitos espontâneos e erros associados ao tema; e, no curso, adaptamos e testamos a eficiência de materiais instrucionais existentes e criamos outros novos (e.g., para trabalhar excentricidades das órbitas planetárias), além disto elaboramos roteiros e figuras para tratamentos qualitativo e quantitativo da lei da gravitação universal. As avaliações feitas pelos professores foram muito animadoras. O espaço da presente reunião será aproveitado para socializar a proposta e os resultados obtidos e para submeter o projeto à análise crítica. (PPGECNM/UFRN; PRONEX/FINEP; NUPA/USP; Temáticos/FAPESP)

77 FR 29703 - Product List Changes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-18

... POSTAL REGULATORY COMMISSION [Docket Nos. MC2012-20 and CP2012-26; Order No. 1343] Product List Changes AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... proposed changes in the Mail Classification Schedule with the addition underlined; Attachment D--a...

77 FR 29393 - Product List Changes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-17

... POSTAL REGULATORY COMMISSION [Docket Nos. MC2012-18 and CP2012-24; Order No. 1341] Product List Changes AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... changes in the Mail Classification Schedule with the addition underlined; Attachment D--a Statement of...

77 FR 29702 - Product List Changes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-18

... POSTAL REGULATORY COMMISSION [Docket Nos. MC2012-21 and CP2012-27; Order No. 1344] Product List Changes AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... proposed changes in the Mail Classification Schedule with the addition underlined; Attachment D--a...

77 FR 64446 - Wireless Microphones Proceeding

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-22

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Parts 15, 74, and 90 [WT Docket Nos. 08-166, 08-167, ET Docket No. 10-24; DA 12-1570] Wireless Microphones Proceeding AGENCY: Federal Communications Commission.... [ssquf] Federal Communications Commission's Web site: http://www.fcc.gov/cgb/ecfs2/ . Follow the...

Quality of life of individuals with cleft lip and palate pre- and post-surgical correction of dentofacial deformity.

PubMed

Beluci, Marli Luiz; Genaro, Katia Flores

2016-04-01

To assesses the quality of life and the impact of oral health conditions in the pre- and post-surgical correction of dentofacial deformity of individuals with cleft lip and palate. Quantitative and prospective study in a referral hospital in the period from June 2011 to May 2013. A total of 50 participants responded the questionnaires World Health Organization Quality of Life - Bref (WHOQOL-Bref) and Oral Health Impact Profile - 14 (OHIP-14), approximately 3 days before and 3 to 12 months after surgery. The "t" test for paired samples and Wilcoxon test were used for statistical analysis with a significance level of 5%. After surgery, differences were found in the domains: Physical, Psychological, Environmental and General Questions of the WHOQOL-Bref and domains: Psychological Discomfort, Psychological Disability, Social Disability, Handicap and Overall Score of OHIP-14. Surgical correction of dentofacial deformity improved quality of life and had positive impact of oral health condition. Avaliar a qualidade de vida e o impacto das condições de saúde oral nos períodos pré e pós-correção cirúrgica da deformidade dentofacial de indivíduos com fissura labiopalatina operada. Estudo quantitativo e prospectivo, realizado em um hospital de referência, no período de junho de 2011 a maio de 2013. Participaram 50 indivíduos que responderam aos questionários World Health Organization Quality of Life - Bref (WHOQOL-Bref) e Oral Health Impact Profile - 14 (OHIP-14), aproximadamente 3 dias antes e entre 3 e 12 meses após a cirurgia. Os testes "t" para amostras pareadas e de Wilcoxon foram usados para análise estatística, com nível de significância de 5%. Após a cirurgia, foram encontradas diferenças nos domínios: Físico, Psicológico, Meio Ambiente e nas Questões Gerais do WHOQOL-Bref e nos domínios: Desconforto Psicológico, Limitação Psicológica, Limitação Social, Incapacidade e no Escore Geral do OHIP-14. A correção cirúrgica da deformidade dentofacial propiciou melhora da qualidade de vida e impacto positivo da condição da saúde oral.

Development and evaluation of a decision aid for patients considering first‐line chemotherapy for metastatic breast cancer

PubMed Central

Chiew, Kimberly S.; Shepherd, Heather; Vardy, Janette; Tattersall, Martin H.N.; Butow, Phyllis N.; Leighl, Natasha B.

2007-01-01

Abstract Objective  Treatment decisions in advanced breast cancer are complex, with enhanced quality of life and survival among important treatment goals. Patients with metastatic breast cancer face the decision of whether or not to have chemotherapy, and many wish to be involved in this decision. We report the development and evaluation of a decision aid (DA) designed to assist patients facing this treatment decision. Design and sample  Women with metastatic breast cancer (n = 17) and medical oncologists in Australia and Canada (n = 7) were invited to evaluate the DA. Intervention  A DA was developed for patients with hormone‐resistant metastatic breast cancer considering chemotherapy. The DA presented options of supportive care, with or without chemotherapy. Potential benefits and side effects of different chemotherapy regimens, and evidence‐based prognostic estimates were described, and a values clarification exercise included. Main outcome measures  Patient questionnaires evaluating information and decision involvement preferences, attitudes toward the DA and oncologist feedback regarding attitudes toward the DA. Results  Seventeen patients participated; fifteen desired as much information about their illness as possible; sixteen wished to be actively involved in the decision‐making process. The majority rated the DA as highly acceptable, clear and informative, and would recommend it to others facing this treatment decision. Conclusion  This is the first DA for patients with advanced metastatic breast cancer considering chemotherapy. A randomized trial is underway to evaluate its role in clinical decision‐making. PMID:18297781

Escleroterapia de safena associada a enxerto de pele no tratamento de úlceras venosas

PubMed Central

de Oliveira, Alexandre Faraco; de Oliveira, Horácio

2017-01-01

Resumo Contexto Úlceras são a resultante final de varizes associadas a refluxo de veias safenas. Objetivo Demonstrar a possibilidade de associar dois procedimentos, a escleroterapia com espuma de veias safenas e o enxerto de pele parcial, para o tratamento de pacientes com úlceras venosas relacionadas a refluxo de veias safenas. Métodos Foram tratados 20 membros em 20 pacientes, todos com ulcerações relacionadas a refluxo de veias safenas. Realizamos o enxerto de pele expandida, seguido da escleroterapia ecoguiada com espuma de polidocanol nas veias associadas às úlceras, através de punção ou dissecção da veia. Resultados Em todos os casos, houve melhora dos sintomas relacionados à úlcera e cicatrização da lesão. Em 11 casos, obtivemos a viabilidade do enxerto de pele por completo; em quatro casos, houve cicatrização de cerca de 50% da lesão; e nos cinco casos restantes, houve cicatrização de aproximadamente 75% da lesão. A primeira ultrassonografia de controle revelou esclerose completa dos vasos tratados em 19 dos 20 casos e esclerose parcial sem refluxo detectável em um caso. Na segunda ultrassonografia, realizada após 45 dias, observamos esclerose completa de 15 casos; em cinco casos, houve esclerose parcial, dos quais três sem refluxo detectável e dois com refluxo em segmentos isolados associados a varizes. A complicação mais frequente foi a pigmentação nos trajetos venosos, observada em 13 pacientes. Um caso apresentou trombose assintomática de veias musculares da perna. Conclusão Essa associação de procedimentos consiste em uma opção válida com potencial para promover um tratamento mais breve e de menor custo. PMID:29930660

GPER activation is effective in protecting against inflammation-induced nigral dopaminergic loss and motor function impairment.

PubMed

Mendes-Oliveira, Julieta; Lopes Campos, Filipa; Videira, Rita Alexandra; Baltazar, Graça

2017-08-01

Increasing evidence suggest that excessive inflammatory responses from overactivated microglia play a critical role in Parkinson's disease (PD), contributing to, or exacerbating, nigral dopaminergic (DA) degeneration. Recent results from our group and others demonstrated that selective activation of G protein-coupled estrogen receptor (GPER) with the agonist G1 can protect DA neurons from 1-methyl-4-phenylpyridinium (MPP + ) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxins. However, it is not known whether modulation of microglial responses is one of the mechanisms by which G1 exerts its DA neuroprotective effects. We analyzed, in the N9 microglial cell line, the effect of G1 on microglial activation induced by lipopolysaccharide (LPS) exposure. The results revealed that G1 significantly decrease phagocytic activity, expression of inducible nitric oxide synthase (iNOS) and release of nitric oxide (NO) induced by LPS. To determine the relevance of this anti-inflammatory effect to the protection of nigral DA cells, the effect of G1 was analyzed in male mice injected unilaterally in the substantia nigra (SN) with LPS. Although G1 treatment did not decrease LPS-induced increase of ionized calcium binding adaptor molecule 1 (iba-1) positive cells it significantly reduced interleukin-1beta (IL-1β), cluster of differentiation 68 (CD68) and iNOS mRNA levels, and totally inhibited nigral DA cell loss and, as a consequence, protected the motor function. In summary, our findings demonstrated that the G1 agonist is able to modulate microglial responses and to protect DA neurons and motor functions against a lesion induced by an inflammatory insult. Since G1 lacks the feminizing effects associated with agonists of the classical estrogen receptors (ERs), the use of G1 to selectively activate the GPER may be a promising strategy for the development of new therapeutics for the treatment of PD and other neuroinflammatory diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Professionals and interfamily violence against children and adolescents: in between legal and conceptual precepts.

PubMed

Schek, Gabriele; Silva, Mara Regina Santos da; Lacharité, Carl; Bueno, Maria Emilia Nunes

2016-01-01

To identify the conceptions of professionals regarding interfamily violence against children and adolescents. A qualitative study conducted with 15 professionals who had taken children and adolescents under their care as a result of interfamily violence. Data were collected between November, 2013, and March, 2015, through semi-structured interviews. Data were organized and analyzed using the Textual Discourse Analysis technique. The professional discourse highlighted that some legal aspects regarding the handling of interfamily violence against children and adolescents are neglected; an omission supported by the justification of professionals to preserve the family. We highlight the confrontation between the concept of family as a caregiver and the family that commits violence against children, in addition to the positioning of professionals, which does not include the family or the aggressor in the intervention process in facing situations of interfamily violence attended to by the services. Acting against interfamily violence requires professionals to do away with some pre-established concepts in ordee to put the actual needs of victims and families into evidence. Identificar, com base no discurso dos profissionais, suas concepções a respeito da violência intrafamiliar contra crianças e adolescentes. Estudo qualitativo, realizado com 15 profissionais, que tiveram sob seus cuidados crianças e adolescentes atendidas em decorrência da violência intrafamiliar. Os dados foram coletados entre novembro de 2013 e março de 2015, por meio de entrevistas semiestruturadas. Os dados foram organizados e analisados utilizando a técnica de Análise Textual Discursiva. O discurso dos profissionais colocou em evidência que alguns aspectos legais em relação ao manejo da violência intrafamiliar contra crianças e adolescentes são negligenciados, omissão respaldada pela justificativa dos profissionais de preservar a família. Destaca-se o confronto entre a concepção de família como cuidadora e a família que violenta os filhos, além do posicionamento dos profissionais, os quais não incluem a família e o agressor nos processos de intervenção frente às situações de violência intrafamiliar atendidas nos serviços. Atuar frente à violência intrafamiliar requer do profissional romper com algumas concepções preestabelecidas para colocar em evidência as reais necessidades de vítimas e famílias.

1. GENERAL VIEW OF WESLEY PARK FACING NORTH, SHOWING SOUTH ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. GENERAL VIEW OF WESLEY PARK FACING NORTH, SHOWING SOUTH FACADE OF AUDITORIUM, WEST FACADES OF COTTAGES (Nos. 84-89, see site plan included with historical data), AND SOUTH FACADES OF COTTAGES ON MORRIS AVENUE (in background) - South Seaville Methodist Camp Meeting Grounds, Dennisville Road, West of U.S. Highway 9, South Seaville, Cape May County, NJ

Developing a science teacher education course that supports student teachers' thinking and teaching about the nature of science

NASA Astrophysics Data System (ADS)

Sorensen, Pete; Newton, Len; McCarthy, Sue

2012-04-01

Background and purpose . This paper reports on part of an ongoing research project in England concerning the Nature of Science (NOS). The particular focus is on the initial thinking of the graduate scientists starting a one-year, Postgraduate Certificate of Education (PGCE) course and the way the course approaches adopted influence their views and understanding of NOS and their teaching. The research is set against a wealth of literature indicating that teachers find it difficult to teach curricula that emphasise NOS. Thus a key impetus for research in this area has been to look for ways that beginning teachers might be better prepared to face such challenges. Sample The paper draws on data from three cohorts of secondary PGCE students in a university-schools partnership, involving a total of 169 students. Design and method The research lies within a design research tradition. It has used mixed methods, involving written tasks, interviews and focus groups, with an iterative approach where the outcomes from one cohort have been used to inform course developments in successive years. Results The results from these cohorts suggest that, while the students starting the course have a less restricted view of NOS than indicated by some other studies, in most cases there is a lack of breadth and depth to their understanding. There is some evidence that the use of specific tasks focusing on NOS in university-based sessions may be helping to develop and deepen understanding. However, the impact of current approaches remains fairly limited and attempts to develop teaching practices often face considerable barriers in the school-based practicum. Conclusions Graduate science students' understanding of NOS as they embark on the PGCE is not highly developed. Hence, the emphasis on aspects of NOS in the school curriculum presents a considerable challenge. This study suggests that there is a need to both further develop an explicit focus on NOS in university-based sessions and to develop closer relationships between schools and university faculty in seeking to support developments in classroom practice in this difficult area.

Intimate partner violence and incidence of common mental disorder.

PubMed

Mendonça, Marcela Franklin Salvador de; Ludermir, Ana Bernarda

2017-04-10

To investigate the association of intimate partner violence against women reported in the last 12 months and seven years with the incidence of common mental disorders. A prospective cohort study with 390 women from 18 to 49 years, registered in the Family Health Program of the city of Recife, State of Pernambuco; from July 2013 to December 2014. The Self Reporting Questionnaire-20 (SRQ-20) assessed mental health. Intimate partner violence consists of concrete acts of psychological, physical or sexual violence that the partner inflicts on the woman. Poisson regression was used to estimate crude and adjusted relative risks (RR) of the association between common mental disorders and intimate partner violence. The incidence of common mental disorders was 44.6% among women who reported intimate partner violence in the last 12 months and 43.4% among those who reported in the past seven years. Mental disorders remained associated with psychological violence (RR = 3.0; 95%CI 1.9-4.7 and RR = 1.8; 95%CI 1.0-3.7 in the last 12 months, and seven years, respectively), even in the absence of physical or sexual violence. When psychological violence were related to physical or sexual violence, the risk of common mental disorders was even higher, both in the last 12 months (RR = 3.1; 95%CI 2.1-4.7) and in the last seven years (RR = 2.5; 95%CI 1.7-3.8). Intimate partner violence is associated with the incidence of common mental disorders in women. The treatment of the consequences of IPV and support for women in seeking protection for themselves for public services is essential. Investigar a associação da violência por parceiros íntimos relatada contra as mulheres nos últimos 12 meses e últimos sete anos com a incidência dos transtornos mentais comuns. Estudo de coorte prospectivo com 390 mulheres de 18 a 49 anos, cadastradas no Programa Saúde da Família da cidade do Recife, PE, entre julho de 2013 e dezembro de 2014. A saúde mental foi avaliada pelo Self Reporting Questionnaire-20 (SRQ-20). A violência por parceiro íntimo foi definida por atos concretos de violência psicológica, física ou sexual infligidos à mulher pelo parceiro. A regressão de Poisson foi utilizada para estimar os riscos relativos (RR) brutos e ajustados da associação entre transtorno mental comum e violência por parceiro íntimo. A incidência dos transtornos mentais comuns foi de 44,6% entre as mulheres que relataram violência nos últimos 12 meses e de 43,4% nas que relataram violência nos últimos sete anos. Os transtornos mentais mantiveram-se associados à violência psicológica (RR = 3,0; IC95% 1,9-4,7 e RR = 1,8; IC95% 1,0-3,7 nos últimos 12 meses, e sete anos, respectivamente), mesmo na ausência de violência física ou sexual. Quando a violência psicológica esteve combinada com violência física ou sexual, o risco dos transtornos mentais comuns foi ainda mais elevado, tanto nos últimos 12 meses (RR = 3,1; IC95% 2,1-4,7) quanto nos últimos sete anos (RR = 2,5; IC95% 1,7-3,8). A violência por parceiro íntimo está associada à incidência de transtornos mentais comuns nas mulheres. É fundamental o tratamento das consequências da VPI e o apoio às mulheres na busca de proteção para si pelos serviços públicos.

Corn silk induces nitric oxide synthase in murine macrophages.

PubMed

Kim, Kyung A; Choi, Sang Kyu; Choi, Hye Seon

2004-12-31

Corn silk has been purified as an anticoagulant previously and the active component is a polysaccharide with a molecular mass of 135 kDa. It activates murine macrophages to induce nitric oxide synthase (NOS) and generate substantial amounts of NO in time and dose-dependent manners. It was detectable first at 15 h after stimulation by corn silk, peaked at 24 h, and undetectable by 48 h. Induction of NOS is inhibited by pyrolidine dithiocarbamate (PDTC) and genistein, an inhibitor of nuclear factor kappa B (NF-kappaB) and tyrosine kinase, respectively, indicating that iNOS stimulated by corn silk is associated with tyrosine kinase and NF-kappaB signaling pathways. IkappaB-alpha degradation was detectible at 10 min, and the level was restored at 120 min after treatment of corn silk. Corn silk induced nuclear translocation of NF-kappaB by phosphorylation and degradation of IkappaB-alpha.

78 FR 70238 - Survey of Urban Rates

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-25

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 54 [WC Docket Nos. 10-90; DA 13-598] Survey of Urban...: 3060-1192. OMB Approval Date: October 22, 2013. OMB Expiration Date: October 31, 2016. Title: Survey of... America Fund. The Order adopts the form and content for a survey of urban rates for fixed voice and fixed...

75 FR 25278 - National Institute on Drug Abuse; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-07

... personal privacy. Name of Committee: National Institute on Drug Abuse Special Emphasis Panel; N44DA-10-5542... Institute on Drug Abuse, NIH, 6101 Executive Blvd., Room 220, MSC 8401, Bethesda, MD 20852, 301-435-1432, [email protected] . (Catalogue of Federal Domestic Assistance Program Nos.: 93.279, Drug Abuse and...

76 FR 74017 - Empowering Consumers to Prevent and Detect Billing for Unauthorized Charges (“Cramming...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-30

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 64 [CG Docket Nos. 11-116 and 09-158; CC Docket No. 98-170; FCC 11-106; DA 11-1860] Empowering Consumers to Prevent and Detect Billing for Unauthorized Charges (``Cramming''); Consumer Information and Disclosure; Truth-in-Billing and Billing Format AGENCY...

PubMed

Silva, Cristiane Gonçalves da; Santos, Alessandro Oliveira; Licciardi, Daniele Carli; Paiva, Vera; Parker, Richard

2008-01-01

Esse artigo descreve como jovens religiosos e autoridades religiosas de sua comunidade compreendem a sexualidade, considerando suas experiências pessoais e como membros de comunidades religiosas. A análise pretende contribuir para que políticas públicas dedicadas à promoção da saúde sexual da juventude considerem a religiosidade, no contexto de um estado laico e da promoção do direito à prevenção. Foram realizadas 26 entrevistas abertas e semidirigidas em diferentes comunidades da região metropolitana da cidade de São Paulo (comunidades católicas, da umbanda, do candomblé e de diferentes denominações evangélicas) sobre iniciação sexual, casamento, gravidez, contracepção e prevenção das DST/Aids, homossexualidade, aborto e direitos humanos. Observou-se como jovens e autoridades religiosas convivem com a tensão entre tradição e modernidade e os distintos discursos sobre a sexualidade. Como sujeitos religiosos (do discurso religioso) e sujeitos sexuais (de discursos sobre sexualidade), devem ser incorporados pelos programas como sujeitos de direito nos termos de sua religiosidade.

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

Thin films for gas sensors

NASA Astrophysics Data System (ADS)

Pires, Jose Miguel Alves Correia

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

Anti-inflammatory action of high molecular weight Mytilus edulis hydrolysates fraction in LPS-induced RAW264.7 macrophage via NF-κB and MAPK pathways.

PubMed

Kim, Young-Sang; Ahn, Chang-Bum; Je, Jae-Young

2016-07-01

Anti-inflammatory Mytilus edulis hydrolysates (MEHs) were prepared by peptic hydrolysis and MEH was further fractionated into three fractions based on molecular weight, namely >5kDa, 1-5kDa, and <1kDa. The >5kDa peptide fraction exerted the highest nitric oxide (NO) inhibitory activity and inhibited prostaglandin E2 (PGE2) secretion in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Pretreatment with the >5kDa peptide fraction markedly inhibited LPS-stimulated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and gene expressions. Stimulation by LPS induced the production of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and -1β (IL-1β), whereas co-treatment with the >5kDa peptide fraction suppressed pro-inflammatory cytokine production. The >5kDa peptide fraction inhibited the translocation of NF-κB (nuclear factor-kappa B) through the prevention of IκBα (inhibitory factor kappa B alpha) phosphorylation and degradation and also inhibited the MAPK signaling pathway in LPS-stimulated RAW264.7 macrophages. Copyright © 2016 Elsevier Ltd. All rights reserved.

Católicos, fidelidade conjugal e AIDS: entre a cruz da doutrina moral e as espadas do cotidiano sexual dos adeptos1

PubMed Central

Rios, Luis Felipe; de Aquino, Francisca Luciana; Muñoz-Laboy, Miguel; Oliveira, Cinthia; Parker, Richard

2009-01-01

Neste artigo discutimos a visão da Igreja Católica sobre sexualidade na interface com a epidemia do HIV/AIDS. Nossa reflexão está embasada em pesquisa etnográfica que envolveu dois meses de observação participante do cotidiano de católicos de um bairro popular da Região Metropolitana do Recife, além de contar com entrevistas a onze dos leigos engajados nos serviços religiosos da igreja do bairro e a oito sacerdotes que realizam seus trabalhos religiosos em outras localidades. Nelas abordamos diferentes temáticas relacionadas ao enfrentamento da epidemia da AIDS. Nesse contexto, conjugalidade e fidelidade se afiguram como importantes analisadores de como aqueles lidam com a epidemia, em uma variedade de re-descrições práticas e de re-interpretações conceptuais das assertivas do discurso moral religioso – ainda que, muitos impasses permaneçam em aberto em termos das prerrogativas da Igreja e seus possíveis rebatimentos na saúde sexual dos adeptos. PMID:21765650

Donor/Acceptor Molecular Orientation-Dependent Photovoltaic Performance in All-Polymer Solar Cells.

PubMed

Zhou, Ke; Zhang, Rui; Liu, Jiangang; Li, Mingguang; Yu, Xinhong; Xing, Rubo; Han, Yanchun

2015-11-18

The correlated donor/acceptor (D/A) molecular orientation plays a crucial role in solution-processed all-polymer solar cells in term of photovoltaic performance. For the conjugated polymers PTB7-th and P(NDI2OD-T2), the preferential molecular orientation of neat PTB7-th films kept face-on regardless of the properties of processing solvents. However, an increasing content of face-on molecular orientation in the neat P(NDI2OD-T2) films could be found by changing processing solvents from chloronaphthalene (CN) and o-dichlorobenzene (oDCB) to chlorobenzene (CB). Besides, the neat P(NDI2OD-T2) films also exhibited a transformation of preferential molecular orientation from face-on to edge-on when extending film drying time by casting in the same solution. Consequently, a distribution diagram of molecular orientation for P(NDI2OD-T2) films was depicted and the same trend could be observed for the PTB7-th/P(NDI2OD-T2) blend films. By manufacture of photovoltaic devices with blend films, the relationship between the correlated D/A molecular orientation and device performance was established. The short-circuit current (Jsc) of devices processed by CN, oDCB, and CB enhanced gradually from 1.24 to 8.86 mA/cm(2) with the correlated D/A molecular orientation changing from face-on/edge-on to face-on/face-on, which could be attributed to facile exciton dissociation at D/A interface with the same molecular orientation. Therefore, the power conversion efficiency (PCE) of devices processed by CN, oDCB, and CB improved from 0.53% to 3.52% ultimately.

The future of PanDA in ATLAS distributed computing

NASA Astrophysics Data System (ADS)

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

2015-12-01

Experiments at the Large Hadron Collider (LHC) face unprecedented computing challenges. Heterogeneous resources are distributed worldwide at hundreds of sites, thousands of physicists analyse the data remotely, the volume of processed data is beyond the exabyte scale, while data processing requires more than a few billion hours of computing usage per year. The PanDA (Production and Distributed Analysis) system was developed to meet the scale and complexity of LHC distributed computing for the ATLAS experiment. In the process, the old batch job paradigm of locally managed computing in HEP was discarded in favour of a far more automated, flexible and scalable model. The success of PanDA in ATLAS is leading to widespread adoption and testing by other experiments. PanDA is the first exascale workload management system in HEP, already operating at more than a million computing jobs per day, and processing over an exabyte of data in 2013. There are many new challenges that PanDA will face in the near future, in addition to new challenges of scale, heterogeneity and increasing user base. PanDA will need to handle rapidly changing computing infrastructure, will require factorization of code for easier deployment, will need to incorporate additional information sources including network metrics in decision making, be able to control network circuits, handle dynamically sized workload processing, provide improved visualization, and face many other challenges. In this talk we will focus on the new features, planned or recently implemented, that are relevant to the next decade of distributed computing workload management using PanDA.

Feasibility and acceptability of a decision aid designed for people facing advanced or terminal illness: a pilot randomized trial.

PubMed

Matlock, Dan D; Keech, Tarah A E; McKenzie, Marlene B; Bronsert, Michael R; Nowels, Carolyn T; Kutner, Jean S

2014-02-01

Patients nearing the end of their lives face an array of difficult decisions. This study was designed to assess the feasibility and acceptability of a decision aid (DA) designed for patients facing advanced or terminal illness. We conducted a pilot randomized clinical trial of Health Dialog's Looking Ahead: choices for medical care when you're seriously ill DA (booklet and DVD) applied to patients on a hospital-based palliative care (PC) service. University of Colorado Hospital - December 2009 and May 2010. All adult, English-speaking patients or their decision makers were potentially eligible. Patients were not approached if they were in isolation, did not speak English or if any provider felt that they were not appropriate because of issues such as family conflict or actively dying. All participants received a standard PC consultation. Participants in the intervention arm also received a copy of the DA. Measurements Primary outcomes included decision conflict and knowledge. Participants in the intervention arm also completed an acceptability questionnaire and qualitative exit interviews. Of the 239 patients or decision makers, 51(21%) enrolled in the trial. The DA had no significant effect on decision conflict or knowledge. Exit interviews indicated it was acceptable and empowering, although they wished they had access to the DA earlier. While the DA was acceptable, feasibility was limited by late-life illness challenges. Future trials of this DA should be performed on patients earlier in their illness trajectory and should include additional outcome measures such as self-efficacy and confidence. © 2011 John Wiley & Sons Ltd.

Variação temporal do gradiente radial de o/h a partir de uma amostra de nebulosas planetárias

NASA Astrophysics Data System (ADS)

Maciel, W. J.; Costa, R. D. D.; Uchida, M. M. M.

2003-08-01

Gradientes radiais de abundância são observados no disco de nossa Galáxia e também em outras galáxias espirais. No caso da Galáxia, o principal problema relativo aos gradientes é sua variação temporal, que constitui um dos principais vínculos aos modelos de evolução química da Galáxia. As nebulosas planetárias são particularmente interessantes no estudo dos gradientes e suas variações, tanto espaciais como temporais. São objetos brilhantes, podendo ser observadas a grandes distâncias, e têm abundâncias relativamente precisas de diversos elementos químicos. Além disso, sendo originadas de estrelas com massas entre 0.8 e 8 massas solares na sequência principal, incluem objetos com idades e populações diferentes, o que as torna especialmente interessantes ao estudo da variação temporal dos gradientes. Neste trabalho, apresentamos resultados recentes sobre a variação temporal do gradiente de O/H a partir de uma amostra contendo cerca de 200 nebulosas, para as quais obtivemos distâncias por métodos estatísticos. As abundâncias foram parcialmente obtidas a partir de observações em Itajubá e La Silla, sendo as restantes obtidas da literatura. Os resultados mostram, pela primeira vez, evidências de um achatamento do gradiente de O/H, de -0.11 dex/kpc para -0.06 dex/kpc nos últimos 9 giga-anos ou de -0.08 dex/kpc para -0.06 dex/kpc nos últimos 5 giga-anos. Esses valores apresentam um bom acordo com alguns modelos recentes para a evolução química da Galáxia. (FAPESP/CNPq)

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.

Influence of the ventilatory mode on acute adverse effects and facial thermography after noninvasive ventilation.

PubMed

Pontes, Suzy Maria Montenegro; Melo, Luiz Henrique de Paula; Maia, Nathalia Parente de Sousa; Nogueira, Andrea da Nóbrega Cirino; Vasconcelos, Thiago Brasileiro; Pereira, Eanes Delgado Barros; Bastos, Vasco Pinheiro Diógenes; Holanda, Marcelo Alcantara

2017-01-01

To compare the incidence and intensity of acute adverse effects and the variation in the temperature of facial skin by thermography after the use of noninvasive ventilation (NIV). We included 20 healthy volunteers receiving NIV via oronasal mask for 1 h. The volunteers were randomly divided into two groups according to the ventilatory mode: bilevel positive airway pressure (BiPAP) or continuous positive airway pressure (CPAP). Facial thermography was performed in order to determine the temperature of the face where it was in contact with the mask and of the nasal dorsum at various time points. After removal of the mask, the volunteers completed a questionnaire about adverse effects of NIV. The incidence and intensity of acute adverse effects were higher in the individuals receiving BiPAP than in those receiving CPAP (16.1% vs. 5.6%). Thermographic analysis showed a significant cooling of the facial skin in the two regions of interest immediately after removal of the mask. The more intense acute adverse effects occurred predominantly among the participants in whom the decrease in the mean temperature of the nasal dorsum was lower (14.4% vs. 7.2%). The thermographic visual analysis of the zones of cooling and heating on the face identified areas of hypoperfusion or reactive hyperemia. The use of BiPAP mode was associated with a higher incidence and intensity of NIV-related acute adverse effects. There was an association between acute adverse effects and less cooling of the nasal dorsum immediately after removal of the mask. Cutaneous thermography can be an additional tool to detect adverse effects that the use of NIV has on facial skin. Comparar a incidência e a intensidade de efeitos adversos agudos e a variação da temperatura da pele da face através da termografia após a aplicação de ventilação não invasiva (VNI). Foram incluídos 20 voluntários sadios, de ambos os gêneros, submetidos à VNI com máscara oronasal por 1 h e divididos aleatoriamente em dois grupos de acordo com o modo ventilatório: bilevel positive airway pressure (BiPAP) ou continuous positive airway pressure (CPAP). A termografia da face foi realizada para determinar a temperatura na região de contato da máscara e no dorso do nariz em momentos diferentes. Os voluntários preencheram um questionário de efeitos adversos após a retirada da VNI. A incidência e a intensidade dos efeitos adversos agudos foram maiores naqueles submetidos a BiPAP em relação aos submetidos a CPAP (16,1% vs. 5,6%). A análise termográfica evidenciou um esfriamento significativo da pele facial nas duas regiões de estudo imediatamente após a retirada da máscara. Os efeitos adversos agudos em maior intensidade ocorreram predominantemente no grupo de participantes cuja redução da temperatura média no dorso do nariz foi menor (14,4% vs. 7,2%). A análise visual termográfica de zonas de esfriamento e aquecimento na face identificou regiões de hipoperfusão ou hiperemia reativa. O uso do modo BiPAP associou-se a maior incidência e intensidade de efeitos adversos agudos associados à VNI. Houve associação entre efeitos adversos agudos e menor esfriamento da pele do dorso do nariz imediatamente após a retirada da máscara. A termografia cutânea pode ser uma ferramenta adicional na detecção de efeitos adversos na pele da face associados ao uso da VNI.

Questões mais freqüentes na área de astronomia

NASA Astrophysics Data System (ADS)

Segundo, H. A. S.; Garcia, G. C.; Caretta, C. A.; Lima, F. P.

2003-08-01

É amplamente reconhecido que as pessoas em geral têm grande fascínio e interesse pela Astronomia. Por outro lado, o conteúdo dessa área incluído no ensino formal está longe de ser abrangente e suficiente para suprir a demanda. Esse interesse permite otimizar a divulgação e o ensino não formal de Astronomia aliando a adequação do conteúdo à expectativa das pessoas. Nesse intuito, nosso trabalho busca mapear que assuntos da Astronomia despertam mais a atenção e o interesse das pessoas e o quanto disso é estimulado pela mídia, que freqüentemente aproveita-se desse interesse de forma sensacionalista, trazendo contribuições positivas e negativas. Para esta avaliação, utilizamos as pesquisas específicas e de caracterização do público que freqüentou o MAst nos anos de 2001 a 2003, pesquisa das matérias de Astronomia veiculadas na mídia escrita da cidade do Rio de Janeiro no mesmo período, além da base de dados do programa Pergunte a um astrônomo, realizado no Observatório Nacional nos anos de 1997 a 1999. Para a análise dos dados, dividimos as perguntas em dez categorias, cada uma com suas subcategorias, tomando como referência as divisões, comissões e grupos de trabalho da IAU. Apresentamos neste trabalho os resultados dessa pesquisa, que incluem, entre outros, a predominância de questões nas categorias Observação do Céu e Sistemas Planetários enquanto nos jornais dominam as notícias de Sistemas Planetários e Espaço & Astronáutica. Outro resultado interessante indicou que as dúvidas de crianças do ensino fundamental se concentram em algumas categorias enquanto as questões de adultos são mais distribuídas por todas as categorias. Os resultados dessa pesquisa serão aplicados diretamente no aperfeiçoamento das atividades do Programa de Observação de Céu, bem como na elaboração de novos projetos e eventos realizados no MAst.

Challenges and strategies for effectively teaching the nature of science: A qualitative case study

NASA Astrophysics Data System (ADS)

Koehler, Catherine M.

This year long, qualitative, case study examines two, experienced, high school, biology teachers as they facilitated nature of science (NOS) understandings in their classrooms. This study explored three research questions: (1) In what ways do experienced teachers' conceptions of NOS evolve over one full year as a result of participating in a course that explicitly address NOS teaching and learning? (2) In what ways do experienced teachers' pedagogical practices evolve over one full year as a result of participating in a course that explicitly address NOS teaching and learning?, and (3) What are the challenges facing experienced teachers in their attempts to implement NOS understandings in their science, high school classrooms? This study was conducted in two parts. In Part I (fall 2004 semester), the participants were enrolled in a graduate course titled, Teaching the Nature of Science , where they were introduced to: (1) NOS, (2) a strategy, the Model for Teaching NOS (MTNOS), which helped them facilitate teaching NOS understandings through inquiry-based activities, and (3) participated in "real" science activities that reinforced their conceptions of NOS. In Part II (spring 2005 semester), classroom observations were made to uncover how these teachers implemented inquiry-based activities emphasizing NOS understanding in their classrooms. Their conceptions of NOS were measured using the Views of the Nature of Science questionnaire. Results demonstrated that each teacher's conceptions of NOS shifted slightly during course the study, but, for one, this was not a permanent shift. Over the year, one teacher's pedagogical practices changed to include inquiry-based lessons using MTNOS; the other, although very amenable to using prepared inquiry-based lessons, did not change her pedagogical practices. Both reported similar challenges while facilitating NOS understanding. The most significant challenges included: (1) time management; (2) the perception that NOS was a content area, and (3) using an inquiry-based model in their classroom. This study describes a curricular and pedagogical model for lesson planning and implementation of inquiry-based activities that promotes NOS understandings in the classroom. It defines the challenges encountered while fostering these understandings, and suggests that NOS needs to be integrated across the educational life span of all students.

Face, content, and construct validity of four, inanimate training exercises using the da Vinci ® Si surgical system configured with Single-Site ™ instrumentation.

PubMed

Jarc, Anthony M; Curet, Myriam

2015-08-01

Validated training exercises are essential tools for surgeons as they develop technical skills to use robot-assisted minimally invasive surgical systems. The purpose of this study was to show face, content, and construct validity of four, inanimate training exercises using the da Vinci (®) Si surgical system configured with Single-Site (™) instrumentation. New (N = 21) and experienced (N = 6) surgeons participated in the study. New surgeons (11 Gynecology [GYN] and 10 General Surgery [GEN]) had not completed any da Vinci Single-Site cases but may have completed multiport cases using the da Vinci system. They participated in this study prior to attending a certification course focused on da Vinci Single-Site instrumentation. Experienced surgeons (5 GYN and 1 GEN) had completed at least 25 da Vinci Single-Site cases. The surgeons completed four inanimate training exercises and then rated them with a questionnaire. Raw metrics and overall normalized scores were computed using both video recordings and kinematic data collected from the surgical system. The experienced surgeons significantly outperformed new surgeons for many raw metrics and the overall normalized scores derived from video review (p < 0.05). Only one exercise did not achieve a significant difference between new and experienced surgeons (p = 0.08) when calculating an overall normalized score using both video and advanced metrics derived from kinematic data. Both new and experienced surgeons rated the training exercises as appearing, to train and measure technical skills used during da Vinci Single-Site surgery and actually testing the technical skills used during da Vinci Single-Site surgery. In summary, the four training exercises showed face, content, and construct validity. Improved overall scores could be developed using additional metrics not included in this study. The results suggest that the training exercises could be used in an overall training curriculum aimed at developing proficiency in technical skills for surgeons new to da Vinci Single-Site instrumentation.

Acute Ethanol Intake Induces NAD(P)H Oxidase Activation and Rhoa Translocation in Resistance Arteries.

PubMed

Simplicio, Janaina A; Hipólito, Ulisses Vilela; Vale, Gabriel Tavares do; Callera, Glaucia Elena; Pereira, Camila André; Touyz, Rhian M; Tostes, Rita de Cássia; Tirapelli, Carlos R

2016-11-01

The mechanism underlying the vascular dysfunction induced by ethanol is not totally understood. Identification of biochemical/molecular mechanisms that could explain such effects is warranted. To investigate whether acute ethanol intake activates the vascular RhoA/Rho kinase pathway in resistance arteries and the role of NAD(P)H oxidase-derived reactive oxygen species (ROS) on such response. We also evaluated the requirement of p47phox translocation for ethanol-induced NAD(P)H oxidase activation. Male Wistar rats were orally treated with ethanol (1g/kg, p.o. gavage) or water (control). Some rats were treated with vitamin C (250 mg/kg, p.o. gavage, 5 days) before administration of water or ethanol. The mesenteric arterial bed (MAB) was collected 30 min after ethanol administration. Vitamin C prevented ethanol-induced increase in superoxide anion (O2-) generation and lipoperoxidation in the MAB. Catalase and superoxide dismutase activities and the reduced glutathione, nitrate and hydrogen peroxide (H2O2) levels were not affected by ethanol. Vitamin C and 4-methylpyrazole prevented the increase on O2- generation induced by ethanol in cultured MAB vascular smooth muscle cells. Ethanol had no effect on phosphorylation levels of protein kinase B (Akt) and eNOS (Ser1177 or Thr495 residues) or MAB vascular reactivity. Vitamin C prevented ethanol-induced increase in the membrane: cytosol fraction ratio of p47phox and RhoA expression in the rat MAB. Acute ethanol intake induces activation of the RhoA/Rho kinase pathway by a mechanism that involves ROS generation. In resistance arteries, ethanol activates NAD(P)H oxidase by inducing p47phox translocation by a redox-sensitive mechanism. O mecanismo da disfunção vascular induzido pelo consumo de etanol não é totalmente compreendido. Justifica-se, assim a identificação de mecanismos bioquímicos e moleculares que poderiam explicar tais efeitos. Investigar se a ingestão aguda de etanol ativa a via vascular RhoA/Rho quinase em artérias de resistência e o papel das espécies reativas de oxigênio (ERO) derivadas da NAD(P)H oxidase nessa resposta. Nós também avaliamos se ocorreu translocação da p47phox e ativação da NAD(P)H oxidase após o consumo agudo de etanol. Ratos Wistar machos foram tratados com etanol via oral (1g/kg, p.o. gavagem) ou água (controle). Alguns ratos foram tratados com vitamina C (250 mg/kg, p.o. gavagem, 5 dias) antes de água ou etanol. O leito arterial mesentérico (LAM) foi coleado 30 min após a administração de etanol. A vitamina C preveniu o aumento da geração de ânion superóxido (O2 -) e lipoperoxidação no LAM induzidos pelo etanol. A atividade da catalase (CAT), da superóxido dismutase (SOD) e os níveis de glutationa reduzida(GSH), nitrato e peróxido de hidrogênio (H2O2) não foram afetados após a ingestão aguda de etanol. A vitamina C e o 4-metilpirazol preveniram o aumento na geração de O2 - induzido pelo etanol em cultura de células do músculo liso vascular (CMLV). O etanol não afetou a fosforilação da proteína quinase B (Akt) e nem da óxido nítrico sintase endotelial (eNOS) (nos resíduos de Ser1177 ou Thr495) ou a reatividade vascular do LAM. A vitamina C preveniu o aumento da razão membrana:citosol da p47phox e a expressão da RhoA no LAM de rato induzido pelo etanol. A ingestão aguda de etanol induz a ativação da via RhoA/Rho quinase por um mecanismo que envolve a geração de ERO. Nas artérias de resistência, o etanol ativa NAD(P)H oxidase induzindo a translocação da p47phox por um mecanismo redox-sensível.

Religiosidade, juventude e sexualidade: entre a autonomia e a rigidez1

PubMed Central

Silva, Cristiane Gonçalves da; Santos, Alessandro Oliveira; Licciardi, Daniele Carli; Paiva, Vera; Parker, Richard

2009-01-01

Esse artigo descreve como jovens religiosos e autoridades religiosas de sua comunidade compreendem a sexualidade, considerando suas experiências pessoais e como membros de comunidades religiosas. A análise pretende contribuir para que políticas públicas dedicadas à promoção da saúde sexual da juventude considerem a religiosidade, no contexto de um estado laico e da promoção do direito à prevenção. Foram realizadas 26 entrevistas abertas e semidirigidas em diferentes comunidades da região metropolitana da cidade de São Paulo (comunidades católicas, da umbanda, do candomblé e de diferentes denominações evangélicas) sobre iniciação sexual, casamento, gravidez, contracepção e prevenção das DST/Aids, homossexualidade, aborto e direitos humanos. Observou-se como jovens e autoridades religiosas convivem com a tensão entre tradição e modernidade e os distintos discursos sobre a sexualidade. Como sujeitos religiosos (do discurso religioso) e sujeitos sexuais (de discursos sobre sexualidade), devem ser incorporados pelos programas como sujeitos de direito nos termos de sua religiosidade. PMID:21886456

77 FR 41955 - Empowering Consumers To Prevent and Detect Billing for Unauthorized Charges (“Cramming...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-17

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 64 [CG Docket Nos. 11-116 and 09-158; CC Docket No. 98-170; FCC 12-42; DA 12-1039] Empowering Consumers To Prevent and Detect Billing for Unauthorized..., which extends the reply comment filing deadline established in the FNPRM, FCC 12-42, published at 77 FR...

Immunostimulative Activity of Low Molecular Weight Chitosans in RAW264.7 Macrophages

PubMed Central

Wu, Ning; Wen, Zheng-Shun; Xiang, Xing-Wei; Huang, Yan-Na; Gao, Yang; Qu, You-Le

2015-01-01

Chitosan and its derivatives such as low molecular weight chitosans (LMWCs) have been reported to exert many biological activities, such as antioxidant and antitumor effects. However, complex and molecular weight dependent effects of chitosan remain controversial and the mechanisms that mediate these complex effects are still poorly defined. This study was carried out to investigate the immunostimulative effect of different molecular weight chitosan in RAW264.7 macrophages. Our data suggested that two LMWCs (molecular weight of 3 kDa and 50 kDa) both possessed immunostimulative activity, which was dependent on dose and, at the higher doses, also on the molecular weight. LMWCs could significantly enhance the the pinocytic activity, and induce the production of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interferon-γ (IFN-γ), nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in a molecular weight and concentration-dependent manner. LMWCs were further showed to promote the expression of the genes including iNOS, TNF-α. Taken together, our findings suggested that LMWCs elicited significantly immunomodulatory response through up-regulating mRNA expression of proinflammatory cytokines and activated RAW264.7 macrophage in a molecular weight- and concentration-dependent manner. PMID:26437419

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

Tão perto de casa, tão longe de nós: etnografia das novas margens no centro da urbe

PubMed Central

Fernandes, Por Luís

2011-01-01

Philippe Bourgois é, desde 2007, “Richard Perry University professor” no Departamento de Antropologia e de Medicina Familiar e de Práticas Comunitárias na Universidade da Pensilvânia. Esteve durante largos anos ligado ao Departamento de Antropologia, História e Medicina Social da Universidade da Califórnia, São Francisco. A publicação, em 1995, de In Search of Respect: Selling Crack in El Barrio1 projectaria o seu nome muito para além dos Estados Unidos: uma etnografia no coração porto-riquenho do Harlem, em torno dos actores e dos ambientes da venda de crack. Seguir-se-ia um longo trabalho de terreno em acampamentos de dependentes de heroína em São Francisco, orientando o seu trabalho para as formas mais radicais da pobreza e da marginalidade nos EUA. É deste trabalho de terreno que sai o seu último livro, Righteous Dopefiend2. Em Junho de 2007 esteve em Lisboa para participar na 3.a edição do “Ethnografeast”. Foi então que aproveitámos a oportunidade para ouvir um percurso invulgar contado pelo próprio: uma longa conversa no Hotel Zurique, cujo nome só vem ao caso por evocar o país onde passou uma parte da infância. PMID:22013286

Osthole relaxes pulmonary arteries through endothelial phosphatidylinositol 3-kinase/Akt-eNOS-NO signaling pathway in rats.

PubMed

Yao, Li; Lu, Ping; Li, Yumei; Yang, Lijing; Feng, Hongxuan; Huang, Yong; Zhang, Dandan; Chen, Jianguo; Zhu, Daling

2013-01-15

Pulmonary arterial hypertension is a life-threatening disease lacking effective therapies. Osthole is a natural coumarin compound isolated from Angelica pubescens Maxim., which possesses hypotensive effect. Although its effects on isolated thoracic aorta (systemic circulating system) are clarified, it remains unclear whether Osthole relaxes isolated pulmonary arteries (PAs) (pulmonary circulating system). The aim of this study was to investigate the effects of Osthole on isolated PAs and the underlying mechanisms. We examined PA relaxation induced by Osthole in isolated human and rat PA rings with force-electricity transducers, the expression and activity of endothelial nitric oxide synthase (eNOS) and protein kinase B (Akt) with western blot, and nitric oxide (NO) production using DAF-FM DA fluorescent indicator. The results showed that Osthole elicited a dose-dependent vasorelaxation activity with phenylephrine-precontracted human and rat PA rings, which can be diminished by endothelium denudation and inhibition of eNOS, while having no effect on rat mesenteric arteries. Osthole increased NO release as well as activation of Akt and eNOS, indicated with increased phosphorylations of Akt at Ser-473 and eNOS at Ser-1177 in endothelial cells. PI3K inhibitor LY294002 also blocked Osthole induced vasodilation. In summary, dilative effect of Osthole was dependent on endothelial integrity and NO production, and was mediated by endothelial PI3K/Akt-eNOS-NO pathway. These may provide a new pulmonary vasodilator for the therapy of pulmonary arterial hypertension. Copyright © 2012 Elsevier B.V. All rights reserved.

Adherence to dietary recommendations for preschoolers: clinical trial with teenage mothers.

PubMed

Soldateli, Betina; Vigo, Alvaro; Giugliani, Elsa Regina Justo

2016-12-22

To assess the effect of educational dietary intervention offered in the child's first year of life, as well as teenage mothers and grandmothers in carrying out the dietary recommendations at four to seven years. Randomized clinical trial initiated in 2006, in Porto Alegre, RS, involving 323 teenage mothers and grandmothers who cohabited. The intervention consisted of six counseling sessions on breastfeeding and healthy complementary feeding. The first session occurred in the maternity ward and the other ones in the households of mothers at seven, 15, 30, 60, and 120 days of the child's life. The information about the child's diet were obtained on a monthly basis in the first six months, every two months in the second half-year, and at four to seven years, using a food frequency questionnaire. To assess the adequacy of food consumption to the recommendations from the Ministry of Health, we elaborated a score system that would reflect the compliance with the Ten Steps for Healthy Toddlers from 2 to 10 Years. The average scores of intervention and control groups were compared using the t-test. Low adherence to recommendations on child nutrition was found in the study population, with no difference in implementation the steps between the groups. The score on the compliance with the steps was similar in both groups (9.6 [SD = 1.63] and 9.3 [SD = 1.60] in the intervention and control groups, respectively) and no influence of the cohabitation with the grandmother was found. Educational dietary intervention in the first four months of the child's life for teenage mothers and grandmothers had no effect on the compliance with the recommendations at four to seven years of the child's life. Avaliar o efeito de intervenção alimentar educativa oferecida, no primeiro ano de vida da criança, a mães adolescentes e avós maternas, no cumprimento das recomendações alimentares aos quatro a sete anos. Ensaio clínico randomizado iniciado em 2006, em Porto Alegre, RS, envolvendo 323 mães adolescentes e avós maternas, quando em coabitação. A intervenção consistiu em seis sessões de aconselhamento sobre aleitamento materno e alimentação complementar saudável. A primeira sessão ocorreu na maternidade e as demais, nos domicílios das mães aos sete, 15, 30, 60 e 120 dias de vida da criança. As informações sobre alimentação da criança foram obtidas mensalmente nos primeiros seis meses de vida, a cada dois meses no segundo semestre, e aos quatro a sete anos, por meio de questionário de frequência alimentar. Para avaliar a adequação do consumo alimentar às recomendações do Ministério da Saúde, elaborou-se um sistema de escore que refletisse o cumprimento dos Dez Passos Para Uma Alimentação Saudável Para Crianças de 2 a 10 Anos. As médias dos escores dos grupos intervenção e controle foram comparadas por meio do teste t. Houve baixa adesão às recomendações sobre alimentação infantil na população estudada, sem diferença no cumprimento dos passos entre os grupos. O escore relativo ao cumprimento dos passos foi semelhante nos dois grupos (9,6 [DP = 1,63] e 9,3 [DP = 1,60] nos grupos intervenção e controle, respectivamente) e não houve influência da coabitação com a avó materna. Intervenção alimentar educativa nos primeiros quatro meses de vida da criança para mães adolescentes e avós maternas não teve efeito no cumprimento das recomendações alimentares aos quatro a sete anos de vida.

Health literacy in pregnant women facing prenatal screening may explain their intention to use a patient decision aid: a short report.

PubMed

Delanoë, Agathe; Lépine, Johanie; Leiva Portocarrero, Maria Esther; Robitaille, Hubert; Turcotte, Stéphane; Lévesque, Isabelle; Wilson, Brenda J; Giguère, Anik M C; Légaré, France

2016-07-11

It has been suggested that health literacy may impact the use of decision aids (DAs) among patients facing difficult decisions. Embedded in the pilot test of a questionnaire, this study aimed to measure the association between health literacy and pregnant women's intention to use a DA to decide about prenatal screening. We recruited a convenience sample of 45 pregnant women in three clinical sites (family practice teaching unit, birthing center and obstetrical ambulatory care clinic). We asked participating women to complete a self-administered questionnaire assessing their intention to use a DA to decide about prenatal screening and assessed their health literacy levels using one subjective and two objective scales. Two of the three scales discriminated between levels of health literacy (three numeracy questions and three health literacy questions). We found a positive correlation between pregnant women's intention to use a DA and subjective health literacy (Spearman coefficient, Rho 0.32, P = 0.04) but not objective health literacy (Spearman coefficient, Rho 0.07, P = 0.65). Hence subjective health literacy may affect the intention to use a DA among pregnant women facing a decision about prenatal screening. Special attention should be given to pregnant women with lower health literacy levels to increase their intention to use a DA and ensure that every pregnant women can give informed and value-based consent to prenatal screening.

Massa do gás e das estrelas em aglomerados: eficiência da formação estelar

NASA Astrophysics Data System (ADS)

Laganá, T. F.; Lima Neto, G. B.

2003-08-01

Os aglomerados de galáxias apresentam um interesse especial para a cosmologia observacional. Eles são as maiores estruturas ligadas pela gravitação no Universo e relaxadas na região central. A comparação entre a massa do gás intra-aglomerado (responsável por ~25% da massa total, inferida a partir de observações em raios-X), a massa contida nas estrelas (i.e., nas galáxias) e a massa total (incluindo a matéria escura não bariônica), nos dá informações importantes sobre os processos de formação e evolução de aglomerados. Por exemplo, a razão entre a massa do gás e a massa total é uma medida da fração de bárions no Universo (razão entre a matéria bariônica e matéria escura) e, utilizando a densidade de bárions predita pela nucleosíntese primordial, podemos deduzir a densidade de matéria escura no Universo (cf. White et al. 1993). O objetivo deste trabalho é obter as razões entre as massas do gás, estelar (contida nas galáxias), e a total (massa dinâmica). As massas do gás e total são obtidas a partir das análises fotométrica e espectroscópica em raios-X enquanto que a massa estelar é obtida pela análise fotométrica das galáxias. Esta análise foi aplicada ao aglomerado Abell 496 observado pelo satélite XMM-Newton. A massa contida nas galáxias foi estimada a partir da função de luminosidade obtida por Durret et al. (2002). Para determinar as massas dinâmica e do gás nos precisamos determinar os perfis radiais de densidade e temperatura. Nós apresentaremos aqui estes resultados e suas implicações na eficiência da formação estelar em Abell 496.

Influence of multi-deposition multi-annealing on time-dependent dielectric breakdown characteristics of PMOS with high-k/metal gate last process

NASA Astrophysics Data System (ADS)

Wang, Yan-Rong; Yang, Hong; Xu, Hao; Wang, Xiao-Lei; Luo, Wei-Chun; Qi, Lu-Wei; Zhang, Shu-Xiang; Wang, Wen-Wu; Yan, Jiang; Zhu, Hui-Long; Zhao, Chao; Chen, Da-Peng; Ye, Tian-Chun

2015-11-01

A multi-deposition multi-annealing technique (MDMA) is introduced into the process of high-k/metal gate MOSFET for the gate last process to effectively reduce the gate leakage and improve the device’s performance. In this paper, we systematically investigate the electrical parameters and the time-dependent dielectric breakdown (TDDB) characteristics of positive channel metal oxide semiconductor (PMOS) under different MDMA process conditions, including the deposition/annealing (D&A) cycles, the D&A time, and the total annealing time. The results show that the increases of the number of D&A cycles (from 1 to 2) and D&A time (from 15 s to 30 s) can contribute to the results that the gate leakage current decreases by about one order of magnitude and that the time to fail (TTF) at 63.2% increases by about several times. However, too many D&A cycles (such as 4 cycles) make the equivalent oxide thickness (EOT) increase by about 1 Å and the TTF of PMOS worsen. Moreover, different D&A times and numbers of D&A cycles induce different breakdown mechanisms. Project supported by the National High Technology Research and Development Program of China (Grant No. SS2015AA010601) and the National Natural Science Foundation of China (Grant Nos. 61176091 and 61306129).

Spatiotemporal alterations of cortical network activity by selective loss of NOS-expressing interneurons.

PubMed

Shlosberg, Dan; Buskila, Yossi; Abu-Ghanem, Yasmin; Amitai, Yael

2012-01-01

Deciphering the role of GABAergic neurons in large neuronal networks such as the neocortex forms a particularly complex task as they comprise a highly diverse population. The neuronal isoform of the enzyme nitric oxide synthase (nNOS) is expressed in the neocortex by specific subsets of GABAergic neurons. These neurons can be identified in live brain slices by the nitric oxide (NO) fluorescent indicator diaminofluorescein-2 diacetate (DAF-2DA). However, this indicator was found to be highly toxic to the stained neurons. We used this feature to induce acute phototoxic damage to NO-producing neurons in cortical slices, and measured subsequent alterations in parameters of cellular and network activity. Neocortical slices were briefly incubated in DAF-2DA and then illuminated through the 4× objective. Histochemistry for NADPH-diaphorase (NADPH-d), a marker for nNOS activity, revealed elimination of staining in the illuminated areas following treatment. Whole cell recordings from several neuronal types before, during, and after illumination confirmed the selective damage to non-fast-spiking (FS) interneurons. Treated slices displayed mild disinhibition. The reversal potential of compound synaptic events on pyramidal neurons became more positive, and their decay time constant was elongated, substantiating the removal of an inhibitory conductance. The horizontal decay of local field potentials (LFPs) was significantly reduced at distances of 300-400 μm from the stimulation, but not when inhibition was non-selectively weakened with the GABA(A) blocker picrotoxin. Finally, whereas the depression of LFPs along short trains of 40 Hz stimuli was linearly reduced with distance or initial amplitude in control slices, this ordered relationship was disrupted in DAF-treated slices. These results reveal that NO-producing interneurons in the neocortex convey lateral inhibition to neighboring columns, and shape the spatiotemporal dynamics of the network's activity.

EVALUATION OF POSTGRADUATES STRICTO SENSU: MONITORING POLICY FOR INTERNATIONAL GRADUATES.

PubMed

Lima, Wilma Terezinha Anselmo

2015-01-01

Search for references in relationship to international alumni on the website of the postgraduate programs of all postgraduate courses at Ribeirão Preto Medical School - FMRP. Verify with more attention to the ones with 5, 6 and 7 notes, and also the same search on the website of courses with notes 5, 6 and 7 of CAPES - Medicine III. Of the 22 programs of FMRP only three had any information on the site about the destiny of the postgraduates; they were: Surgical Clinics, Genetics, and Basic and Applied Immunology. Programs in the area of ​​Medicine III, notes 5, 6 and 7, only Ophthalmology and Visual Programs and Translational Sciences Surgery, both of UNIFESP, presented such information. It is urgent: to create project and funding evaluation mechanisms that are approved by different sources; to stimulate more efficient controls in relation to teachers and their students who participate in these projects; and to stimulate the interaction of teachers and students with the institution and the program. Verificar a existência de referências aos egressos internacionais nos sites dos programas de pós-graduação de todos os cursos de pós-graduação da Faculdade de Medicina de Ribeirão Preto - FMRP. Verificar com mais atenção aos cursos notas 5, 6 e 7, e também a mesma busca nos sites dos cursos com notas 5, 6 e 7 da Medicina III da CAPES. Dos 22 programas da FMRP apenas três tinham no site alguma informação sobre o destino dos egressos, foram eles: Clínica Cirúrgica, Genética e Imunologia Básica e Aplicada. Dos programas da área de Medicina III, notas 5, 6 e 7 apenas os programas de Oftalmologia e Ciências Visuais e Cirurgia Translacional, ambos da UNIFESP, apresentavam informações sobre o destino dos seus egressos. É urgente criar mecanismos de avaliação para os projetos de incentivo e fomento à pesquisa dos diferentes órgãos; estimular controles mais eficientes e atualizados em relação aos docentes e seus respectivos discentes que participam desses projetos; e estimular a interação dos docentes e discentes com a instituição e o programa.

De novo mutation in the dopamine transporter gene associates dopamine dysfunction with autism spectrum disorder.

PubMed

Hamilton, P J; Campbell, N G; Sharma, S; Erreger, K; Herborg Hansen, F; Saunders, C; Belovich, A N; Sahai, M A; Cook, E H; Gether, U; McHaourab, H S; Matthies, H J G; Sutcliffe, J S; Galli, A

2013-12-01

De novo genetic variation is an important class of risk factors for autism spectrum disorder (ASD). Recently, whole-exome sequencing of ASD families has identified a novel de novo missense mutation in the human dopamine (DA) transporter (hDAT) gene, which results in a Thr to Met substitution at site 356 (hDAT T356M). The dopamine transporter (DAT) is a presynaptic membrane protein that regulates dopaminergic tone in the central nervous system by mediating the high-affinity reuptake of synaptically released DA, making it a crucial regulator of DA homeostasis. Here, we report the first functional, structural and behavioral characterization of an ASD-associated de novo mutation in the hDAT. We demonstrate that the hDAT T356M displays anomalous function, characterized as a persistent reverse transport of DA (substrate efflux). Importantly, in the bacterial homolog leucine transporter, substitution of A289 (the homologous site to T356) with a Met promotes an outward-facing conformation upon substrate binding. In the substrate-bound state, an outward-facing transporter conformation is required for substrate efflux. In Drosophila melanogaster, the expression of hDAT T356M in DA neurons-lacking Drosophila DAT leads to hyperlocomotion, a trait associated with DA dysfunction and ASD. Taken together, our findings demonstrate that alterations in DA homeostasis, mediated by aberrant DAT function, may confer risk for ASD and related neuropsychiatric conditions.

Interior view of west end entry showing entry hallway and ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Interior view of west end entry showing entry hallway and double-door frame, view facing south - U.S. Naval Base, Pearl Harbor, Administration Annex, Near Russell Avenue (previously Avenue E), between of Facility Nos. 1C & 1E , Pearl City, Honolulu County, HI

Neuronal nitric oxide synthase mediates insulin- and oxidative stress-induced glucose uptake in skeletal muscle myotubes.

PubMed

Kellogg, Dean L; McCammon, Karen M; Hinchee-Rodriguez, Kathryn S; Adamo, Martin L; Roman, Linda J

2017-09-01

Previously published studies strongly suggested that insulin- and exercise-induced skeletal muscle glucose uptake require nitric oxide (NO) production. However, the signal transduction mechanisms by which insulin and contraction regulated NO production and subsequent glucose transport are not known. In the present study, we utilized the myotube cell lines treated with insulin or hydrogen peroxide, the latter to mimic contraction-induced oxidative stress, to characterize these mechanisms. We found that insulin stimulation of neuronal nitric oxide synthase (nNOS) phosphorylation, NO production, and GLUT4 translocation were all significantly reduced by inhibition of either nNOS or Akt2. Hydrogen peroxide (H 2 O 2 ) induced phosphorylation of nNOS at the same residue as did insulin, and also stimulated NO production and GLUT4 translocation. nNOS inhibition prevented H 2 O 2 -induced GLUT4 translocation. AMP activated protein kinase (AMPK) inhibition prevented H 2 O 2 activation and phosphorylation of nNOS, leading to reduced NO production and significantly attenuated GLUT4 translocation. We conclude that nNOS phosphorylation and subsequently increased NO production are required for both insulin- and H 2 O 2 -stimulated glucose transport. Although the two stimuli result in phosphorylation of the same residue on nNOS, they do so through distinct protein kinases. Thus, insulin and H 2 O 2 -activated signaling pathways converge on nNOS, which is a common mediator of glucose uptake in both pathways. However, the fact that different kinases are utilized provides a basis for the use of exercise to activate glucose transport in the face of insulin resistance. Copyright © 2017. Published by Elsevier Inc.

Impact of neoadjuvant therapy in downstaging of lower rectal adenocarcinoma and the role of pelvic magnetic resonance in staging.

PubMed

Magri, Karina Dagre; Bin, Fang Chia; Formiga, Fernanda Bellotti; Manzione, Thiago da Silveira; Gomes, Caroline Merci Caliari de Neves; Candelári, Paulo de Azeredo Passos; Ortiz, Jorge Alberto; Klug, Wilmar Artur; Mandia, José; Capelhuchnik, Peretz

2016-01-01

to evaluate the effect of neoadjuvant therapy on the stage (TNM) of patients with rectal adenocarcinoma and validate the use of MRI as a method of determining locoregional stage. we conducted a retrospective study of 157 patients with lower rectum adenocarcinoma, whom we divided into two groups: Group 1, 81 patients (52%) who had undergone surgical treatment initially, with the purpose to analyze the accuracy of locoregional staging by pelvic magnetic resonance imaging throug the comparison of radiological findings with pathological ones; Group 2, 76 patients (48%), who had been submitted to neoadjuvant therapy (chemotherapy and radiation) prior to definitive surgical treatment, so as to evaluate its effects on the stage by comparing clinical and radiological findings with pathology. In group 1, the accuracy of determining tumor depth (T) and lymph node involvement (N) was 91.4% and 82.7%, respectively. In group 2, neoadjuvant therapy decreased the T stage, N stage and TNM stage in 51.3%, 21% and 48.4% of cases, respectively. neoadjuvant therapy in patients with rectal adenocarcinoma is effective in decreasing disease stage, and pelvic magnetic resonance imaging is effective for locoregional staging. avaliar o efeito da terapia neoadjuvante, nos pacientes portadores de adenocarcinoma de reto, sobre o estádio (TNM) e validar o emprego da ressonância magnética como método de determinação do estádio locorregional. estudo retrospectivo de 157 pacientes com diagnóstico de adenocarcinoma de reto baixo, que foram divididos em dois grupos: Grupo 1, 81 pacientes (52%), submetidos ao tratamento cirúrgico de princípio, cuja finalidade foi analisar a acurácia da determinação do estádio locorregional pela ressonância magnética da pelve, através da comparação entre os achados radiológicos e os achados anatomopatológicos; Grupo 2, 76 pacientes (48%), encaminhados à terapia neoadjuvante (quimioterapia e radioterapia), antes do tratamento cirúrgico definitivo, com o intuito de avaliar seus efeitos sobre o estádio, através da comparação dos achados clínico-radiológicos com os anatomopatológicos. no grupo 1, a acurácia da determinação da profundidade da lesão (T) e do comprometimento linfonodal (N), foram de 91,4% e 82,7%, respectivamente. No grupo 2, a terapia neoadjuvante diminuiu o estádio T, estádio N e o estádio TNM em 51,3%, 21% e 48,4% dos casos, respectivamente. a terapia neoadjuvante nos pacientes com adenocarcinoma de reto é efetiva na diminuição do estádio e a ressonância magnética da pelve é eficaz na determinação do estádio locorregional.

Changes in the nitric oxide system in the shore crab Hemigrapsus sanguineus (Crustacea, Decapoda) CNS induced by a nociceptive stimulus.

PubMed

Dyuizen, Inessa V; Kotsyuba, Elena P; Lamash, Nina E

2012-08-01

Using NADPH-diaphorase (NADPH-d) histochemistry, inducible nitric oxide synthase (iNOS)-immunohistochemistry and immunoblotting, we characterized the nitric oxide (NO)-producing neurons in the brain and thoracic ganglion of a shore crab subjected to a nociceptive chemical stimulus. Formalin injection into the cheliped evoked specific nociceptive behavior and neurochemical responses in the brain and thoracic ganglion of experimental animals. Within 5-10 min of injury, the NADPH-d activity increased mainly in the neuropils of the olfactory lobes and the lateral antenna I neuropil on the side of injury. Later, the noxious-induced expression of NADPH-d and iNOS was detected in neurons of the brain, as well as in segmental motoneurons and interneurons of the thoracic ganglion. Western blotting analysis showed that an iNOS antiserum recognized a band at 120 kDa, in agreement with the expected molecular mass of the protein. The increase in nitrergic activity induced by nociceptive stimulation suggests that the NO signaling system may modulate nociceptive behavior in crabs.

Overview taken from the corner of Avenue E (Russell Avenue) ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Overview taken from the corner of Avenue E (Russell Avenue) and Central Avenue. Facility 167 in background. View facing northwest - U.S. Naval Base, Pearl Harbor, Administration Annex, Near Russell Avenue (previously Avenue E), between of Facility Nos. 1C & 1E , Pearl City, Honolulu County, HI

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

Increased nitric oxide production in platelets from severe chronic renal failure patients.

PubMed

Siqueira, Mariana Alves de Sá; Brunini, Tatiana M C; Pereira, Natália Rodrigues; Martins, Marcela Anjos; Moss, Monique Bandeira; Santos, Sérgio F; Lugon, Jocemir R; Mendes-Ribeiro, Antônio C

2011-02-01

Nitric oxide (NO) production occurs through oxidation of the amino acid L-arginine by NO synthase (NOS). NO inhibits platelet activation by increasing the levels of cyclic guanosine monophosphate (cGMP), thus maintaining vascular homeostasis. Our group previously demonstrated (da Silva et al. 2005) an enhancement of the L-arginine-NO-cGMP pathway in platelets taken from chronic renal failure (CRF) patients on haemodialysis associated with reduced platelet aggregation. We investigate the platelet L-arginine-NO-cGMP pathway, platelet function, and inflammation from patients in CRF on conservative treatment. A total of 42 CRF patients and 42 controls (creatinine clearance = 27 ± 3 vs. 93 ± 1 mL per min per 1.73 m2, respectively) participated in this study. NOS activity and expression and cGMP concentration were measured in platelets. Platelet aggregation induced by collagen or ADP was evaluated and plasma levels of fibrinogen were determined by the Clauss method. A marked increase in basal NOS activity was seen in undialysed CRF patients compared with controls, accompanied by an elevation of fibrinogen plasma levels. There were no differences in expression of NOS and in cGMP levels. In this context, platelet aggregation was not affected. We provide the first evidence of increased intraplatelet NO biosynthesis in undialysed CRF patients, which can be an early marker of future haemostatic abnormalities during dialysis treatment.

Profilaxia de tromboembolismo venoso na gestação

PubMed Central

de Oliveira, André Luiz Malavasi Longo; Marques, Marcos Arêas

2016-01-01

Resumo O tromboembolismo venoso é importante causa de morbidade e mortalidade obstétrica. Durante a gestação, o risco de sua ocorrência aumenta entre cinco e dez vezes quando comparado ao de mulheres não gestantes de mesma idade. Associado a esse fato, a gestante apresenta algumas limitações para o diagnóstico clínico (alta frequência de dor e edema nos membros inferiores), ecográfico (menor sensibilidade e especificidade no diagnóstico de trombose venosa de ilíaca com a evolução da gestação) e laboratorial (o D-dímero apresenta aumento progressivo no decorrer da gravidez). Uma estratificação criteriosa de risco de tromboembolismo venoso de cada mulher antes da gestação pode diminuir a incidência dessa doença, frequente e de difícil diagnóstico na gravidez, e suas complicações. PMID:29930607

Angiotensin-I converting enzyme inhibitory peptides from antihypertensive skate (Okamejei kenojei) skin gelatin hydrolysate in spontaneously hypertensive rats.

PubMed

Ngo, Dai-Hung; Kang, Kyong-Hwa; Ryu, BoMi; Vo, Thanh-Sang; Jung, Won-Kyo; Byun, Hee-Guk; Kim, Se-Kwon

2015-05-01

The aim of this study was to investigate antihypertensive effect of bioactive peptides from skate (Okamejei kenojei) skin gelatin. The Alcalase/protease gelatin hydrolysate below 1 kDa (SAP) exhibited the highest angiotensin-I converting enzyme (ACE) inhibition compared to other hydrolysates. SAP can decrease systolic blood pressure significantly in spontaneously hypertensive rats. SAP inhibited vasoconstriction via PPAR-γ expression, activation and phosphorylation of eNOS in lungs. Moreover, the expression levels of endothelin-1, RhoA, α-smooth muscle actin, cleaved caspase 3 and MAPK were decreased by SAP in lungs. Vascularity, muscularization and cellular proliferation in lungs were detected by immunohistochemical staining. Finally, two purified peptides (LGPLGHQ, 720Da and MVGSAPGVL, 829Da) showed potent ACE inhibition with IC50 values of 4.22 and 3.09 μM, respectively. These results indicate that bioactive peptides isolated from skate skin gelatin may serve as candidates against hypertension and could be used as functional food ingredients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fall and its association with the frailty syndrome in the elderly: systematic review with meta-analysis.

PubMed

Fhon, Jack Roberto Silva; Rodrigues, Rosalina Aparecida Partezani; Neira, Wilmer Fuentes; Huayta, Violeta Magdalena Rojas; Robazzi, Maria Lucia do Carmo Cruz

2016-01-01

To analyze the prevalence of falls and frailty syndrome and the association between these two syndromes in the elderly population. Systematic review, without restriction of dates, in English, Portuguese and Spanish languages, in the databases PubMed, CINAHL, LILACS and in the SciElo virtual library. The association between both variables was extracted from the studies (Odds Ratio and 95% Confidence Intervals). The review included 19 studies published between 2001 and 2015. The prevalence of falls in the frail elderly population was between 6.7% and 44%; in the pre-frail, between 10.0% and 52.0%, and in the non-frail, between 7.6% and 90.4%. The association between both variables presented a value of OR 1.80 (95% CI 1.51-2.13). There is evidence that falls are associated to the frailty in the elderly. Other factors may influence this association, such as age, sex, data collection instrument of the studies, place where they live and the process of senescence. Analisar a prevalência de quedas e da síndrome da fragilidade e a associação entre essas duas síndromes na população idosa. Revisão sistemática, sem restrição de datas, nos idiomas inglês, português e espanhol, nas bases de dados PubMed, CINAHL, LILACS e na biblioteca virtual SciElo. A associação entre ambas as variáveis foi extraída dos próprios artigos (Odds Ratio e os Intervalos de Confiança de 95%). Foram incluídos na revisão 19 artigos publicados entre 2001 e 2015. A prevalência de queda no idoso frágil esteve entre 6,7% e 44%; nos pré-frágeis, entre 10,0% e 52,0%, e nos não frágeis, entre 7,6% e 90,4%. A associação entre ambas as variáveis apresentou o valor de OR 1,80 (IC 95% 1,51-2,13). Há evidências de que a queda está associada à fragilidade do idoso. Outros fatores podem influenciar essa associação, como idade, sexo, instrumento de coleta de dados dos estudos, local onde vive e o próprio processo de senescência.

Argumentation, critical thinking, nature of science and socioscientific issues: a dialogue between two researchers

NASA Astrophysics Data System (ADS)

Yacoubian, Hagop A.; Khishfe, Rola

2018-05-01

The purpose of this paper is to compare and contrast between two theoretical frameworks for addressing nature of science (NOS) and socioscientific issues (SSI) in school science. These frameworks are critical thinking (CT) and argumentation (AR). For the past years, the first and second authors of this paper have pursued research in this area using CT and AR as theoretical frameworks, respectively. Yacoubian argues that future citizens need to develop a critical mindset as they are guided to (1) practice making judgments on what views of NOS to acquire and (2) practice making decisions on SSI through applying their NOS understandings. Khishfe asserts that AR is an important component of decision making when dealing with SSI and the practice in AR in relation to controversial issues is needed for informed decision making. She argues that AR as a framework may assist in the development of more informed understandings of NOS. In this paper, the authors delve into a dialogue for (1) elucidating strengths and potential of each framework, (2) highlighting challenges that they face in their research using the frameworks in question, (3) exploring the extent to which the frameworks can overlap, and (4) proposing directions for future research.

77 FR 33097 - Application To Participate in an Auction for Mobility Fund Phase I Support and Application for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-05

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Parts 1 and 54 [WC Docket No. 10-90, 07-135, 05-337, 03-109; GN Docket No. 09-51; CC Docket Nos. 01-92, 96-45; and WT Docket No. 10-208; FCC 11-161 and DA 12....1005(a) and (b); 54.1006(a) through (e); 54.1007(a) and (b); 54.1008(a) and (e), published at 76 FR...

The proportion of the face in younger adults using the thumb rule of Leonardo da Vinci.

PubMed

Oguz, O

1996-01-01

The present study was conducted to examine whether the thumb rule of Leonardo da Vinci could be an objective method in the determination of the natural and artistic proportions of human face. In this study, a sample of 400 subjects (200 male and 200 female, 22-25 years old) was used. Measurements were made of the length of thumb, the length of ear, the approximate distances between the hair line and the glabella or eyebrows, between the glabella or eyebrows and the tip of the nose and the distance between the nose and the chin, and the distance between the ear and the lateral aspect of the eye. The results obtained in the males and females showed significant (p < 0.01) correlations between the length of thumb and the proportions of the face examined in the study. Additionally, the height of the face was found to be almost three times the length of the thumb. However, the measurements obtained from female subjects were on average smaller than those taken from males. The results obtained in this experiment could be of value in understanding of the evaluation of the face for the people working in plastic surgery or art.

Test-retest reliability of Brazilian version of Memorial Symptom Assessment Scale for assessing symptoms in cancer patients.

PubMed

Menezes, Josiane Roberta de; Luvisaro, Bianca Maria Oliveira; Rodrigues, Claudia Fernandes; Muzi, Camila Drumond; Guimarães, Raphael Mendonça

2017-01-01

To assess the test-retest reliability of the Memorial Symptom Assessment Scale translated and culturally adapted into Brazilian Portuguese. The scale was applied in an interview format for 190 patients with various cancers type hospitalized in clinical and surgical sectors of the Instituto Nacional de Câncer José de Alencar Gomes da Silva and reapplied in 58 patients. Data from the test-retest were double typed into a Microsoft Excel spreadsheet and analyzed by the weighted Kappa. The reliability of the scale was satisfactory in test-retest. The weighted Kappa values obtained for each scale item had to be adequate, the largest item was 0.96 and the lowest was 0.69. The Kappa subscale was also evaluated and values were 0.84 for high frequency physic symptoms, 0.81 for low frequency physical symptoms, 0.81 for psychological symptoms, and 0.78 for Global Distress Index. High level of reliability estimated suggests that the process of measurement of Memorial Symptom Assessment Scale aspects was adequate. Avaliar a confiabilidade teste-reteste da versão traduzida e adaptada culturalmente para o português do Brasil do Memorial Symptom Assessment Scale. A escala foi aplicada em forma de entrevista em 190 pacientes com diversos tipos de câncer internados nos setores clínicos e cirúrgicos do Instituto Nacional de Câncer José de Alencar Gomes da Silva e reaplicada em 58 pacientes. Os dados dos testes-retestes foram inseridos num banco de dados por dupla digitação independente em Excel e analisados pelo Kappa ponderado. A confiabilidade da escala mostrou-se satisfatória nos testes-retestes. Os valores do Kappa ponderado obtidos para cada item da escala apresentaram-se adequados, sendo o maior item de 0,96 e o menor de 0,69. Também se avaliou o Kappa das subescalas, sendo de 0,84 para sintomas físicos de alta frequência, de 0,81 para sintomas físicos de baixa frequência, de 0,81 também para sintomas psicológicos, e de 0,78 para Índice Geral de Sofrimento. Altos níveis de confiabilidade estimados permitem concluir que o processo de aferição dos itens do Memorial Symptom Assessment Scale foi adequado.

Resilience of the health team in caring for people with mental disorders in a psychiatric hospital.

PubMed

Brolese, Débora Felippe; Lessa, Greice; Santos, José Luís Guedes Dos; Mendes, Jucimara da Silva; Cunha, Kamylla Santos da; Rodrigues, Jeferson

2017-08-17

Evaluating and understanding the resilience process of the health team in caring for people with mental disorders in a psychiatric hospital. A mixed-method study with concomitant triangulation of data from a cross-sectional study, with health professionals, and Grounded Theory in the data. Quantitative data were collected using the Resilience Scale and analyzed using descriptive and inferential statistics. Qualitative data were obtained from interviews and analyzed using initial and focused coding. 40 health professionals participated in the study. Mean responses of the participants in the resilience scale were 99.80 ± 12.86 points, with a minimum of 35 and a maximum of 114 points. From the qualitative data, we can highlight the professionals' commitment in developing competencies in caring for people with mental disorders; valorization of teamwork and positive impact on work for the re-signification of the meaning of life. Understanding this process of resilience enables developing strategies to improve the quality of life of workers in psychiatric hospitals. Avaliar e compreender o processo de resiliência da equipe de saúde no cuidado a pessoas com transtornos mentais em um hospital psiquiátrico. Estudo de método misto com triangulação concomitante de dados de um estudo transversal, com profissionais de saúde, e uma Teoria Fundamentada nos Dados. Os dados quantitativos foram coletados a partir da Escala de Resiliência e analisados por meio de estatística descritiva e inferencial. Os dados qualitativos foram obtidos a partir de entrevistas e analisados mediante codificação inicial e focalizada. Participaram da pesquisa 40 profissionais de saúde. Na escala de resiliência, a média das respostas dos participantes foi 99,80±12,86 pontos, o mínimo foi de 35 e o máximo de 114 pontos. Nos dados qualitativos, destacaram-se o empenho dos profissionais para o desenvolvimento de competências para o cuidado de pessoas com transtornos mentais, a valorização do trabalho em equipe e o impacto positivo no trabalho para a ressignificação do sentido da vida. Conclusão: O entendimento desse processo de resiliência possibilita o desenvolvimento de estratégias para a melhoria da qualidade de vida dos trabalhadores que atuam em hospitais psiquiátricos.

p38 mitogen-activated protein kinase is involved in arginase-II-mediated eNOS-Uncoupling in Obesity

PubMed Central

2014-01-01

Background Endothelial nitric oxide synthase (eNOS)-uncoupling links obesity-associated insulin resistance and type-II diabetes to the increased incidence of cardiovascular disease. Studies have indicated that increased arginase is involved in eNOS-uncoupling through competing with the substrate L-arginine. Given that arginase-II (Arg-II) exerts some of its biological functions through crosstalk with signal transduction pathways, and that p38 mitogen-activated protein kinase (p38mapk) is involved in eNOS-uncoupling, we investigated here whether p38mapk is involved in Arg-II-mediated eNOS-uncoupling in a high fat diet (HFD)-induced obesity mouse model. Methods Obesity was induced in wild type (WT) and Arg-II-deficient (Arg-II-/-) mice on C57BL/6 J background by high-fat diet (HFD, 55% fat) for 14 weeks starting from age of 7 weeks. The entire aortas were isolated and subjected to 1) immunoblotting analysis of the protein level of eNOS, Arg-II and p38mapk activation; 2) arginase activity assay; 3) endothelium-dependent and independent vasomotor responses; 4) en face staining of superoxide anion and NO production with Dihydroethidium and 4,5-Diaminofluorescein Diacetate, respectively, to assess eNOS-uncoupling. To evaluate the role of p38mapk, isolated aortas were treated with p38mapk inhibitor SB203580 (10 μmol/L, 1 h) prior to the analysis. In addition, the role of p38mapk in Arg-II-induced eNOS-uncoupling was investigated in cultured human endothelial cells overexpressing Arg-II in the absence or presence of shRNA against p38mapk. Results HFD enhanced Arg-II expression/activity and p38mapk activity, which was associated with eNOS-uncoupling as revealed by decreased NO and enhanced L-NAME-inhibitable superoxide in aortas of WT obese mice. In accordance, WT obese mice revealed decreased endothelium-dependent relaxations to acetylcholine despite of higher eNOS protein level, whereas Arg-II-/- obese mice were protected from HFD-induced eNOS-uncoupling and endothelial dysfunction, which was associated with reduced p38mapk activation in aortas of the Arg-II-/- obese mice. Moreover, overexpression of Arg-II in human endothelial cells caused eNOS-uncoupling and augmented p38mapk activation. The Arg-II-induced eNOS-uncoupling was prevented by silencing p38mapk. Furthermore, pharmacological inhibition of p38mapk recouples eNOS in isolated aortas from WT obese mice. Conclusions Taking together, we demonstrate here for the first time that Arg-II causes eNOS-uncoupling through activation of p38 mapk in HFD-induced obesity. PMID:25034973

World Perspective Case Descriptions on Educational Programs for Adults: Chile.

ERIC Educational Resources Information Center

Donoso, Patricio; Gajardo, Marcela

This document contains two case studies of adult education programs in Chile. Both case studies begin with a "face sheet" on which is recorded basic information about the program and the description. The first case study, prepared by Patricio Donoso, reports on Centro El Canelo de Nos, an inservice center for educators who work with…

Overview taken from Facility 2 looking east down Avenue E ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Overview taken from Facility 2 looking east down Avenue E (Russell Avenue). Facility 1 is on left, Facility 1G and 1C in center. View facing east - U.S. Naval Base, Pearl Harbor, Administration Annex, Near Russell Avenue (previously Avenue E), between of Facility Nos. 1C & 1E , Pearl City, Honolulu County, HI

Analytically determining frequency and amplitude of spontaneous alpha oscillation in Jansenʼs neural mass model using the describing function method

NASA Astrophysics Data System (ADS)

Xu, Yao; Zhang, Chun-Hui; Niebur, Ernst; Wang, Jun-Song

2018-04-01

Not Available Project supported by the National Natural Science Foundation of China (Grant No. 61473208), the Tianjin Research Program of Application Foundation and Advanced Technology, China (Grant No. 15JCYBJC47700), the National Institutes of Health, USA (Grant Nos. R01DA040990 and R01EY027544), and the Project of Humanities and Social Sciences from the Ministry of Education, China (Grant No. 17YJAZH092).

Reading: Students' Attitudes and Interests in Fourth, Fifth, and Sixth Grades in Official Portuguese Schools in the USA (A Leitura: Atitudes e Preferencias dos Educandos do 4th, 5th, e 6th Anos de Escolaridade nas Escolas Oficiais Portuguesas nos Estados Unidos da America).

ERIC Educational Resources Information Center

Castanho, Maria da Graca Borges

A study investigated attitudes and preferences concerning reading among fourth-, fifth-, and sixth-grade students in Portuguese-language schools in the United States. Extrinsic factors influencing students (parents, teachers) were also analyzed. The research took place in 10 schools in 5 states. Data were obtained using questionnaires (students)…

Construyendo modelos confiables de estrellas rías

NASA Astrophysics Data System (ADS)

Mauas, P. J.; Falchi, A.

Se estudian las aproximaciones que se realizan usualmente al calcular modelos de estrellas frías (redistribución completa para la lí nea Lyman-α, despreciar el ``line-blanketing", suponer los metales en LTE), y cómo influyen en los distintos observables. Asimismo, se evalúa cuál es la información que cada observable nos da sobre la atmósfera de la estrella, y cuáles son las incertidumbres de cada modelo.

Control of the interparticle spacing in superparamagnetic iron oxide nanoparticle clusters by surface ligand engineering

NASA Astrophysics Data System (ADS)

Dan, Wang; Bingbing, Lin; Taipeng, Shen; Jun, Wu; Fuhua, Hao; Chunchao, Xia; Qiyong, Gong; Huiru, Tang; Bin, Song; Hua, Ai

2016-07-01

Polymer-mediated self-assembly of superparamagnetic iron oxide (SPIO) nanoparticles allows modulation of the structure of SPIO nanocrystal cluster and their magnetic properties. In this study, dopamine-functionalized polyesters (DA-polyester) were used to directly control the magnetic nanoparticle spacing and its effect on magnetic resonance relaxation properties of these clusters was investigated. Monodisperse SPIO nanocrystals with different surface coating materials (poly(ɛ-caprolactone), poly(lactic acid)) of different molecular weights containing dopamine (DA) structure (DA-PCL2k, DA-PCL1k, DA-PLA1k)) were prepared via ligand exchange reaction, and these nanocrystals were encapsulated inside amphiphilic polymer micelles to modulate the SPIO nanocrystal interparticle spacing. Small-angle x-ray scattering (SAXS) was applied to quantify the interparticle spacing of SPIO clusters. The results demonstrated that the tailored magnetic nanoparticle clusters featured controllable interparticle spacing providing directly by the different surface coating of SPIO nanocrystals. Systematic modulation of SPIO nanocrystal interparticle spacing can regulate the saturation magnetization (M s) and T 2 relaxation of the aggregation, and lead to increased magnetic resonance (MR) relaxation properties with decreased interparticle spacing. Project supported by the National Key Basic Research Program of China (Grant No. 2013CB933903), the National Key Technology R&D Program of China (Grant No. 2012BAI23B08), and the National Natural Science Foundation of China (Grant Nos. 20974065, 51173117, and 50830107).

How Elementary Teachers' Beliefs About the Nature of Science Mediate Implementing Prescribed Science Curricula in Their Classrooms

NASA Astrophysics Data System (ADS)

Giglio, Kathleen Rose Fitzgerald

This is an in depth study of two elementary school teachers, who are generalists because they teach multiple subjects to their classes, in addition to science, respectively in grade 3 and grade 6. The teachers taught and their students learned using a contemporary understanding of the nature of science (NOS), which they learned by actually doing science investigations, rather than being explicitly told about NOS (contrary to what some scholars claim). Neither teacher completed any formal/informal science training/experiences, especially connected to the construct NOS. Even though the teachers did not explicitly reference NOS in the classroom, their teaching about NOS was made possible through their implementation of the FOSS ( Full Option Science System) curriculum. Although their students enthusiastically demonstrated competence in both science process and content, as prescribed by the FOSS curriculum, the teachers' felt undermined by the state mandated assessments and the inclusion of student performance as a criterion for the state teacher evaluation system. This research was designed to answer the following questions: (1) What are elementary teachers' conceptions about NOS? (2) How are the teachers' NOS views manifested in their implementation of the FOSS program and their choices of instructional methods/materials? (3) What factors may have enhanced or hindered how the teachers sustained their NOS conceptions as they implemented the FOSS program? To explicate the relationship between teachers' views of NOS and the extent to which constructivist practices were employed in their science instruction, a multiple research methodology using grounded theory as the foundation and employing both quantitative and qualitative measures, was needed. Sources of quantitative data were written survey results using the Student Understanding of Science and Scientific Inquiry Questionnaire (SUSSI; Liang et al., 2008) Likert scale responses and constructed responses. Face validity was determined through correlation of teachers' NOS conceptions from their written responses with their verbal responses during semi-structured interviews. Sources of qualitative data were coding of field notes (audiotapes of interviews and classroom observations) and artifacts (instructional materials and student work). Following qualitative analysis, data were compared and validated through triagulation, and the results were summarized. The results indicate that teachers may develop contemporary NOS conceptions without explicit instruction and may fortify such perceptions in their students by teaching science using FOSS investigations without explicitly mentioning NOS (also contrary to what some scholars claim). These results have important implications for the successful implementation of the Next Generation Science Standards and future elementary science teacher education programs.

Nursing team's conceptions about the families of hospitalized children.

PubMed

Macedo, Isabela Fornerolli de; Souza, Tania Vignuda de; Oliveira, Isabel Cristina Dos Santos; Cibreiros, Sylvia Alves; Morais, Rita de Cássia Melão de; Vieira, Rosana Fidelis Coelho

2017-01-01

to describe nursing team care and discuss the nursing team's conception of companion families of hospitalized children. The study was based on the theoretical framework of Collière's theory of nursing care identity. this was a qualitative study with 14 members of a nursing team, conducted through an unstructured group interview. Thematic data analysis was employed. habitual and repair care was delegated to families, regardless of the child's clinical condition. the team's official discourse about the families of hospitalized children, as recommended by the literature, refers to the family's alterity and participation in care provision, with sights on discharge and defending family participation as beneficial to children. In practice, however, the nursing staff makes concessions about the presence of chaperoning families and delegates care. descrever os cuidados da equipe de enfermagem e discutir as concepções da equipe de enfermagem frente à família acompanhante da criança hospitalizada. O referencial teórico está vinculado à identidade do cuidado de enfermagem de Collière. Estudo qualitativo com quatorze membros da equipe de enfermagem, utilizando a técnica de entrevista não diretiva em grupo. Foi realizada análise temática dos dados. os cuidados habituais e de reparação prestados à criança estão sendo delegados à família, independentemente da situação clínica da criança. o discurso oficial da equipe de enfermagem frente à família acompanhante da criança hospitalizada, preconizado pela literatura, refere-se à alteridade e à participação da família nos cuidados à criança, prevendo sua alta e justificando a participação como benéfica para a criança. Em contrapartida, na prática, a enfermagem faz concessões sobre a permanência da família e delega os cuidados.

De novo mutations in NALCN cause a syndrome characterized by congenital contractures of the limbs and face, hypotonia, and developmental delay.

PubMed

Chong, Jessica X; McMillin, Margaret J; Shively, Kathryn M; Beck, Anita E; Marvin, Colby T; Armenteros, Jose R; Buckingham, Kati J; Nkinsi, Naomi T; Boyle, Evan A; Berry, Margaret N; Bocian, Maureen; Foulds, Nicola; Uzielli, Maria Luisa Giovannucci; Haldeman-Englert, Chad; Hennekam, Raoul C M; Kaplan, Paige; Kline, Antonie D; Mercer, Catherine L; Nowaczyk, Malgorzata J M; Klein Wassink-Ruiter, Jolien S; McPherson, Elizabeth W; Moreno, Regina A; Scheuerle, Angela E; Shashi, Vandana; Stevens, Cathy A; Carey, John C; Monteil, Arnaud; Lory, Philippe; Tabor, Holly K; Smith, Joshua D; Shendure, Jay; Nickerson, Deborah A; Bamshad, Michael J

2015-03-05

Freeman-Sheldon syndrome, or distal arthrogryposis type 2A (DA2A), is an autosomal-dominant condition caused by mutations in MYH3 and characterized by multiple congenital contractures of the face and limbs and normal cognitive development. We identified a subset of five individuals who had been putatively diagnosed with "DA2A with severe neurological abnormalities" and for whom congenital contractures of the limbs and face, hypotonia, and global developmental delay had resulted in early death in three cases; this is a unique condition that we now refer to as CLIFAHDD syndrome. Exome sequencing identified missense mutations in the sodium leak channel, non-selective (NALCN) in four families affected by CLIFAHDD syndrome. We used molecular-inversion probes to screen for NALCN in a cohort of 202 distal arthrogryposis (DA)-affected individuals as well as concurrent exome sequencing of six other DA-affected individuals, thus revealing NALCN mutations in ten additional families with "atypical" forms of DA. All 14 mutations were missense variants predicted to alter amino acid residues in or near the S5 and S6 pore-forming segments of NALCN, highlighting the functional importance of these segments. In vitro functional studies demonstrated that NALCN alterations nearly abolished the expression of wild-type NALCN, suggesting that alterations that cause CLIFAHDD syndrome have a dominant-negative effect. In contrast, homozygosity for mutations in other regions of NALCN has been reported in three families affected by an autosomal-recessive condition characterized mainly by hypotonia and severe intellectual disability. Accordingly, mutations in NALCN can cause either a recessive or dominant condition characterized by varied though overlapping phenotypic features, perhaps based on the type of mutation and affected protein domain(s). Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Comparação entre cirurgia aberta e endovascular no tratamento do aneurisma da artéria poplítea: uma revisão

PubMed Central

Gonçalves, Ana Fernanda Fagundes; Pelek, Carlos Augusto; Nogueira, Lorena Slusarz; de Carvalho, Renan Francisco; Stumpf, Matheo Augusto Morandi; Gomes, Ricardo Zanetti; Kluthcovsky, Ana Claudia Garabeli Cavalli

2018-01-01

Resumo Os aneurismas de artéria poplítea correspondem a 70% dos aneurismas periféricos e o tratamento é cirúrgico, com controvérsias sobre os resultados da via endovascular. Este estudo objetivou realizar uma revisão da literatura sobre a comparação entre cirurgia aberta e endovascular no tratamento dos aneurismas da artéria poplítea. A pesquisa foi realizada utilizando os termos apropriados nos portais de periódicos LILACS e MEDLINE, com a seleção de 15 artigos. Um total de 5.166 procedimentos cirúrgicos foram comparados, sendo 3.930 cirurgias abertas e 1.236 cirurgias endovasculares. A cirurgia aberta com bypass venoso continua sendo o padrão-ouro. A cirurgia endovascular apresenta menor tempo de internação e é uma opção viável em pacientes eletivos, com baixa expectativa de vida, alto risco cirúrgico, comorbidades e mais idosos, desde que tenham anatomia favorável para o procedimento. Contudo, são necessários estudos de longo prazo para estabelecer os reais benefícios e indicações das duas técnicas, como o ensaio clínico randomizado controlado.

An Analytical Overview of Spirituality in NANDA-I Taxonomies.

PubMed

Mesquita, Ana Cláudia; Caldeira, Sílvia; Chaves, Erika; Carvalho, Emilia Campos de

2017-03-01

To discuss the approach of spirituality in NANDA-I taxonomies, based on the elements that characterize this phenomenon. This study was based on concepts that are usually adopted in the literature for defining spirituality and on the analysis of the NANDA-I taxonomies from I to III. Spirituality is included in all taxonomies but all three are missing some attributes to guarantee the completeness of this dimension for nursing diagnosis. Taxonomy III makes different approaches to spirituality and some inconsistencies. Contribute to the development and review of the new proposal for taxonomy. Discutir a abordagem à espiritualidade nas taxonomias da NANDA-I, baseada nos elementos que caracterizam este fenômeno. MÉTODOS: Este estudo foi baseado em conceitos usualmente adotados na literatura de enfermagem para definir espiritualidade e na análise das taxonomias da NANDA-I, desde a I à III. A espiritualidade está incluída nas taxonomias, porém estas carecem de atributos do seu conceito. CONCLUSÕES: A taxonomia III faz diferentes abordagens à espiritualidade, porém com algumas inconsistências identificadas. IMPLICAÇÕES PARA A ENFERMAGEM: Esta análise pode contribuir para o desenvolvimento e revisão da taxonomia III. © 2017 NANDA International, Inc.

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.

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.

Historical short stories as nature of science instruction in secondary science classrooms: Science teachers' implementation and students' reactions

NASA Astrophysics Data System (ADS)

Reid-Smith, Jennifer Ann

This study explores the use of historical short stories as nature of science (NOS) instruction in thirteen secondary science classes. The stories focus on the development of science ideas and include statements and questions to draw students' and teachers' attention to key NOS ideas and misconceptions. This study used mixed methods to examine how teachers implement the stories, factors influencing teachers' implementation, the impact on students' NOS understanding, students' interest in the stories and factors correlated with their interest. Teachers' implementation decisions were influenced by their NOS understanding, curricula, time constraints, perceptions of student ability and resistance, and student goals. Teachers implementing stories at a high-level of effectiveness were more likely to make instructional decisions to mitigate constraints from the school environment and students. High-level implementers frequently referred to their learning goals for students as a rationale for implementing the stories even when facing constraints. Teachers implementing at a low-level of effectiveness were more likely to express that constraints inhibited effective implementation. Teachers at all levels of implementation expressed concern regarding the length of the stories and time required to fully implement the stories. Additionally, teachers at all levels of implementation expressed a desire for additional resources regarding effective story implementation and reading strategies. Evidence exists that the stories can be used to improve students' NOS understanding. However, under what conditions the stories are effective is still unclear. Students reported finding the stories more interesting than textbook readings and many students enjoyed learning about scientists and the development of science idea. Students' interest in the stories is correlated with their attitudes towards reading, views of effective science learning, attributions of academic success, and interest in a science-related career. If NOS instructional materials are to be used effectively, designers must take into account the needs of classroom teachers by limiting the length of the materials and providing additional teacher support resources. Many teachers will likely require professional development opportunities to build their NOS understanding, develop a compelling rationale for teaching NOS and using the stories, observe modeling of effective implementation, and collaborate with other teachers regarding how to mitigate constraints.

Capturing the sublimity of a free radical gas.

PubMed

Leong, S K

1999-12-01

This paper reviews the work related to nitric oxide (NO) done by the author and his postgraduates and colleagues in the past 7 years in the National University of Singapore. Our work shows that (i) NADPH-d and NO synthase (NOS) are often but not always identical; (ii) NO (as indicated by NADPH-d histochemistry and NOS immunohistochemistry) is generated in some endocrine (thyroid, parathyroid and ultimobranchial glands) and immune (thymus and bursa of Fabricius) organs and the cochlea. It is noted from the above studies that NO could possibly regulate blood flow through the various organs via its presence in the vascular endothelial cells and also via nitrergic neurons innervating the blood vessels. It could also regulate the activity of the secretary cells of these organs by being present in them, as well as acting through nitrergic neurons closely related to them. The paper also examines the Janus-faced nature of NO as a neuroprotective and neurodestructive agent, and the apparent noninvolvement of peroxynitrite and inducible NOS in neuronal death occurring in the red nucleus and nucleus dorsalis after spinal cord hemisection.

Regiones de formación de estrellas masivas en las Nubes de Magallanes

NASA Astrophysics Data System (ADS)

Barbá, R.; Maíz Apellániz, J.; Rubio, M.; Walborn, N.

Las Nubes de Magallanes son un laboratorio formidable para el estudio de regiones de formación estelar. A diferencia de lo que sucede en el plano galáctico, ambas galaxias contienen poco polvo que nos afecte la visión directa de dichas regiones. Por otra parte, la menor metalicidad de las Nubes, nos permiten hacer un estudio comparativo de la formación estelar en ambientes de baja metalicidad. El presente trabajo da una revisión de los progresos notables que hemos alcanzado en el conocimiento del contenido estelar de algunas regiones de formación de estrellas masivas en ambas Nubes, en base a la utilización de imágenes del Telescopio Espacial Hubble, Gemini Sur, y Very Large Telescope, entre otros. En especial, nos concentramos en 30 Doradus y N11 en la Nube Mayor, y en NGC 346 en la Nube Menor. Nuevas imágenes de N11 obtenidas en los últimos meses con la Advanced Camera for Surveys del Hubble (óptico), y con Flamingos en Gemini Sur (infrarrojo), nos han permitido descubrir un nuevo `jet' con origen en una fuente infrarroja sumergida en un pilar polvoriento similar al objeto Herbig-Haro de M20 en nuestra galaxia. Este `jet' (junto a otros tres que hemos descubierto en 30 Doradus), es el cuarto ejemplo confirmado de `jet' asociado a una protoestrella fuera de nuestra galaxia. Además, presentamos el descubrimiento del primer objeto estelar joven masivo de la Nube Menor confirmado espectroscópicamente.

Valsartan regulates the interaction of angiotensin II type 1 receptor and endothelial nitric oxide synthase via Src/PI3K/Akt signalling.

PubMed

Su, Kuo-Hui; Tsai, Jin-Yi; Kou, Yu Ru; Chiang, An-Na; Hsiao, Sheng-Huang; Wu, Yuh-Lin; Hou, Hsin-Han; Pan, Ching-Chian; Shyue, Song-Kun; Lee, Tzong-Shyuan

2009-06-01

Valsartan, a selective angiotensin II type 1 receptor (AT1R) blocker, has beneficial effects in the cardiovascular system in part by its increase of nitric oxide (NO) bioavailability, yet the mechanisms are unclear. We investigated the molecular mechanisms underlying this effect in endothelial cells (ECs). NO production was examined by Griess reagent assay, DAF-2 DA fluorescence staining and cGMP ELISA kits. Protein interaction was determined by western blotting and immunoprecipitation. Treating bovine or human aortic ECs with valsartan increased NO production, as evidenced by elevated level of stable NO metabolites and intracellular cGMP. Valsartan increased the phosphorylation but not the protein level of endothelial NO synthase (eNOS). Inhibition of phosphoinositide-3 kinase (PI3K)/Akt and Src pathways by specific inhibitors suppressed valsartan-induced NO release. In addition, valsartan increased the tyrosine residue phosphorylation of AT1R, which was attenuated by inhibition of Src but not PI3K activities. Valsartan also suppressed the interaction of eNOS and AT1R, which was blocked by Src or PI3K inhibition. Valsartan-induced NO production in ECs is mediated through Src/PI3K/Akt-dependent phosphorylation of eNOS. Valsartan-induced AT1R phosphorylation depends on Src but not PI3K, whereas valsartan-induced suppression of AT1R-eNOS interaction depends on Src/PI3K/Akt signalling. These results indicate a novel vasoprotective mechanism of valsartan in upregulating NO production in ECs.

Biaxial seismic behaviour of reinforced concrete columns =

NASA Astrophysics Data System (ADS)

Rodrigues, Hugo Filipe Pinheiro

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

Structural characteristics of surface-functionalized nitrogen-doped diamond-like carbon films and effective adjustment to cell attachment

NASA Astrophysics Data System (ADS)

Liu, Ai-Ping; Liu, Min; Yu, Jian-Can; Qian, Guo-Dong; Tang, Wei-Hua

2015-05-01

Nitrogen-doped diamond-like carbon (DLC:N) films prepared by the filtered cathodic vacuum arc technology are functionalized with various chemical molecules including dopamine (DA), 3-Aminobenzeneboronic acid (APBA), and adenosine triphosphate (ATP), and the impacts of surface functionalities on the surface morphologies, compositions, microstructures, and cell compatibility of the DLC:N films are systematically investigated. We demonstrate that the surface groups of DLC:N have a significant effect on the surface and structural properties of the film. The activity of PC12 cells depends on the particular type of surface functional groups of DLC:N films regardless of surface roughness and wettability. Our research offers a novel way for designing functionalized carbon films as tailorable substrates for biosensors and biomedical engineering applications. Project supported by the National Natural Science Foundation of China (Grant Nos. 51272237, 51272231, and 51010002) and the China Postdoctoral Science Foundation (Grant Nos. 2012M520063, 2013T60587, and Bsh1201016).

Science Teacher Educators' Engagement with Pedagogical Content Knowledge and Scientific Inquiry in Predominantly Paper-Based Distance Learning Programs

ERIC Educational Resources Information Center

Fraser, William J.

2017-01-01

This article focuses on the dilemmas science educators face when having to introduce Pedagogical Content Knowledge (PCK) to science student teachers in a predominantly paper-based distance learning environment. It draws on the premise that science education is bound by the Nature of Science (NOS), and by the Nature of Scientific Inquiry (NOSI).…

Interpersonal, Nonverbal, and Small Group Communication: Abstracts of Doctoral Dissertations Published in "Dissertation Abstracts International," July through December 1985 (Vol. 46 Nos. 1 through 6).

ERIC Educational Resources Information Center

ERIC Clearinghouse on Reading and Communication Skills, Urbana, IL.

This collection of abstracts is part of a continuing series providing information on recent doctoral dissertations. The 18 titles deal with a variety of topics, including the following: (1) ways of conceptualizing and evaluating group discussion; (2) participant observations of communication themes in families facing death; (3) perceptions of…

Gathering Strength: Canada's Aboriginal Action Plan. A Progress Report = Rassembler nos forces: Le plan d'action du Canada pour les questions autochtones. Rapport d'etape.

ERIC Educational Resources Information Center

Department of Indian Affairs and Northern Development, Ottawa (Ontario).

Gathering Strength is an integrated government-wide plan to address the key challenges facing Canada's Aboriginal people. Following an initial section on reconciliation of historic grievances, this report describes initiatives in the four areas addressed by the action plan: (1) partnerships (all schools received public awareness materials;…

Small-molecule inhibitors at the PSD-95/nNOS interface protect against glutamate-induced neuronal atrophy in primary cortical neurons.

PubMed

Doucet, M V; O'Toole, E; Connor, T; Harkin, A

2015-08-20

Glutamate and nitric oxide (NO) are important regulators of dendrite and axon development in the central nervous system. Excess glutamatergic stimulation is a feature of many pathological conditions and manifests in neuronal atrophy and shrinkage with eventual neurodegeneration and cell death. Here we demonstrate that treatment of cultured primary cortical rat neurons for 24h with glutamate (500μM) or N-methyl-d-aspartate (NMDA) (100-500μM) combined with glycine suppresses neurite outgrowth. A similar reduction of neurite outgrowth was observed with the NO precursor l-arginine and NO donor sodium nitroprusside (SNP) (100 and 300μM). The NMDA-receptor (NMDA-R) antagonists ketamine and MK-801 (10nM) counteracted the NMDA/glycine-induced reduction in neurite outgrowth and the neuronal NO synthase (nNOS) inhibitor 1-[2-(trifluoromethyl)phenyl] imidazole (TRIM) (100nM) counteracted both the NMDA/glycine and l-arginine-induced decreases in neurite outgrowth. Furthermore, targeting soluble guanylate cyclase (sGC), a downstream target of NO, with the sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10μM) also protected against l-arginine-induced decreases in neurite outgrowth. Since the NMDA-R is functionally coupled to nNOS via the postsynaptic protein 95kDa (PSD-95), inhibitors of the PSD-95/nNOS interaction were tested for their ability to protect against glutamate-induced suppression in neurite outgrowth. Treatment with the small-molecule inhibitors of the PSD-95/nNOS interface 2-((1H-benzo[d] [1,2,3]triazol-5-ylamino) methyl)-4,6-dichlorophenol (IC87201) (10 and 100nM) and 4-(3,5-dichloro-2-hydroxy-benzylamino)-2-hydroxybenzoic acid (ZL-006) (10 and 100nM) attenuated NMDA/glycine-induced decreases in neurite outgrowth. These data support the hypothesis that targeting the NMDA-R/PSD-95/nNOS interaction downstream of NMDA-R promotes neurotrophic effects by preventing neurite shrinkage in response to excess glutamatergic stimulation. The PSD-95/nNOS interface may be an attractive target for treating deficits in neuronal outgrowth and atrophy associated with excessive glutamatergic neurotransmission in neurodevelopmental and neurodegenerative conditions. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Insights into the Modulation of Dopamine Transporter Function by Amphetamine, Orphenadrine, and Cocaine Binding

PubMed Central

Cheng, Mary Hongying; Block, Ethan; Hu, Feizhuo; Cobanoglu, Murat Can; Sorkin, Alexander; Bahar, Ivet

2015-01-01

Human dopamine (DA) transporter (hDAT) regulates dopaminergic signaling in the central nervous system by maintaining the synaptic concentration of DA at physiological levels, upon reuptake of DA into presynaptic terminals. DA translocation involves the co-transport of two sodium ions and the channeling of a chloride ion, and it is achieved via alternating access between outward-facing (OF) and inward-facing states of DAT. hDAT is a target for addictive drugs, such as cocaine, amphetamine (AMPH), and therapeutic antidepressants. Our recent quantitative systems pharmacology study suggested that orphenadrine (ORPH), an anticholinergic agent and anti-Parkinson drug, might be repurposable as a DAT drug. Previous studies have shown that DAT-substrates like AMPH or -blockers like cocaine modulate the function of DAT in different ways. However, the molecular mechanisms of modulation remained elusive due to the lack of structural data on DAT. The newly resolved DAT structure from Drosophila melanogaster opens the way to a deeper understanding of the mechanism and time evolution of DAT–drug/ligand interactions. Using a combination of homology modeling, docking analysis, molecular dynamics simulations, and molecular biology experiments, we performed a comparative study of the binding properties of DA, AMPH, ORPH, and cocaine and their modulation of hDAT function. Simulations demonstrate that binding DA or AMPH drives a structural transition toward a functional form predisposed to translocate the ligand. In contrast, ORPH appears to inhibit DAT function by arresting it in the OF open conformation. The analysis shows that cocaine and ORPH competitively bind DAT, with the binding pose and affinity dependent on the conformational state of DAT. Further assays show that the effect of ORPH on DAT uptake and endocytosis is comparable to that of cocaine. PMID:26106364

Building a Virtual Learning Environment to Foster Blended Learning Experiences in an Institute of Application in Brazil

ERIC Educational Resources Information Center

da Silva Marques Ribeiro, Andrea; Rodrigues Oliveira, Esequiel; Fortes Mello, Rodrigo

2017-01-01

Blended learning, the combination of face-to-face teaching with a virtual learning environment (VLE), is the theme of this study that aims at describing and analyzing the implementation of a VLE in the Institute of Application Fernando Rodrigues da Silveira, an academic unit of the State University of Rio de Janeiro. This study's main contribution…

Effects of incretin agonists on endothelial nitric oxide synthase expression and nitric oxide synthesis in human coronary artery endothelial cells exposed to TNFα and glycated albumin.

PubMed

Garczorz, Wojciech; Francuz, Tomasz; Siemianowicz, Krzysztof; Kosowska, Agnieszka; Kłych, Agnieszka; Aghdam, Mohammad Reza F; Jagoda, Krystyna

2015-02-01

There have been a number of beneficial effects of incretin agonists on the cardiovascular system. Glycated albumin (GA) and tumor necrosis factor (TNFα) may lead to endothelial dysfunction. Due to reports of cardioprotective effects of incretin agonist, we wanted to determine if GLP-1 and exendin-4 can reverse diminished production of nitric oxide (NO) after treatment with TNFα and GA. The objective of our experiment was to study the interaction between incretin agonists and proinflammatory substances like TNFα and GA on production of NO in HCAEC. Human vascular endothelial cells from the coronary artery (HCAEC) were used. The mRNA expression and protein level of endothelial nitric oxide synthase (eNOS) and inducible (iNOS) were quantified. NO production was measured in cells using DAF-FM/DA and flow cytometry. TNFα (10 ng/mL) decreased eNOS: mRNA by 90% and protein level by 31%. TNFα also decreased NO by 33%. GA (500 μg/mL) neither affected eNOS expression nor the protein level, but inhibited nearly all formation of NO in endothelium. GLP-1 (100 nM) and exendin-4 (1 and 10nM) decreased the amount of NO compared to control. Incubation of HCAEC with TNFα and incretin agonists did not change or moderately reduce the amount of NO compared to TNFα alone. TNFα and GA decrease production of NO in HCAEC, presumably by inducing reactive oxygen species or eNOS uncoupling. Incretin agonists in tested concentrations in the presence of l-arginine were not able to reverse this effect and instead led to a further reduction in NO production. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Innovation in healthcare services: notes on the limits of field research.

PubMed

Costa, Laís Silveira

2016-11-03

The contemporary context of population aging, itsthe population's different health and disease characteristics, and the growing incorporation of technologies by healthcare systems have highlighted the need to adjust the healthcare structure as a whole. The defense of a democratic and sustainable system reveals the importance of understanding how changes in healthcare take place. The current article aims to contribute to the understanding of innovation in healthcare services. The study's results indicate that the existence of certain knowledge gaps means that public policies tend to overlook a whole rangeseries of innovations normally associated with social changes, with a consequentwith an impact on human development, social cohesion, equality, and equity, allcentral issues that are central toin the field of collective public healthcare field. The article concludes that the lack of a mature theoretical framework negatively impacts the formulation of such policies, further aggravated in Brazil by growing differences in quality and access between population segments that depend on the public and private healthcare systems. Resumo: O contexto contemporâneo de envelhecimento e as características de saúde e doença da população, aliados à crescente incorporação tecnológica nos sistemas de saúde têm pontuado a necessidade de adequação da estrutura de atenção. A defesa de um sistema democrático e sustentável evidencia a importância de entender como são estabelecidos os processos relacionados às mudanças na saúde. Neste cenário, o presente artigo visa aprofundar o entendimento sobre inovação nos serviços de saúde. Os resultados da pesquisa indicaram que lacunas no conhecimento levam políticas públicas a negligenciarem uma série de inovações normalmente associadas a mudanças sociais com impacto no desenvolvimento humano, coesão social, igualdade e equidade, temas centrais ao campo da saúde coletiva. E conclui que a falta de um referencial teórico maduro tem impactos deletérios para a formulação dessas políticas, quadro agravado no Brasil, onde são observadas diferenças crescentes na qualidade e disponibilidade de acesso entre os segmentos populacionais dependentes dos sistemas públicos e privados.

Validation of Robotic Surgery Simulator (RoSS).

PubMed

Kesavadas, Thenkurussi; Stegemann, Andrew; Sathyaseelan, Gughan; Chowriappa, Ashirwad; Srimathveeravalli, Govindarajan; Seixas-Mikelus, Stéfanie; Chandrasekhar, Rameella; Wilding, Gregory; Guru, Khurshid

2011-01-01

Recent growth of daVinci Robotic Surgical System as a minimally invasive surgery tool has led to a call for better training of future surgeons. In this paper, a new virtual reality simulator, called RoSS is presented. Initial results from two studies - face and content validity, are very encouraging. 90% of the cohort of expert robotic surgeons felt that the simulator was excellent or somewhat close to the touch and feel of the daVinci console. Content validity of the simulator received 90% approval in some cases. These studies demonstrate that RoSS has the potential of becoming an important training tool for the daVinci surgical robot.

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

NASA Astrophysics Data System (ADS)

Balan, Catalin

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

Dopamine D(1) receptor deletion strongly reduces neurotoxic effects of methamphetamine.

PubMed

Ares-Santos, S; Granado, N; Oliva, I; O'Shea, E; Martin, E D; Colado, M I; Moratalla, R

2012-02-01

Methamphetamine (METH) is a potent, highly addictive psychostimulant consumed worldwide. In humans and experimental animals, repeated exposure to this drug induces persistent neurodegenerative changes. Damage occurs primarily to dopaminergic neurons, accompanied by gliosis. The toxic effects of METH involve excessive dopamine (DA) release, thus DA receptors are highly likely to play a role in this process. To define the role of D(1) receptors in the neurotoxic effects of METH we used D(1) receptor knock-out mice (D(1)R(-/-)) and their WT littermates. Inactivation of D(1)R prevented METH-induced dopamine fibre loss and hyperthermia, and increases in gliosis and pro-inflammatory molecules such as iNOS in the striatum. In addition, D(1)R inactivation prevented METH-induced loss of dopaminergic neurons in the substantia nigra. To explore the relationship between hyperthermia and neurotoxicity, METH was given at high ambient temperature (29 °C). In this condition, D(1)R(-/-) mice developed hyperthermia following drug delivery and the neuroprotection provided by D(1)R inactivation at 23 °C was no longer observed. However, reserpine, which empties vesicular dopamine stores, blocked hyperthermia and strongly potentiated dopamine toxicity in D(1)R(-/-) mice, suggesting that the protection afforded by D(1)R inactivation is due to both hypothermia and higher stored vesicular dopamine. Moreover, electrical stimulation evoked higher DA overflow in D(1)R(-/-) mice as demonstrated by fast scan cyclic voltammetry despite their lower basal DA content, suggesting higher vesicular DA content in D(1)R(-/-) than in WT mice. Altogether, these results indicate that the D(1)R plays a significant role in METH-induced neurotoxicity by mediating drug-induced hyperthermia and increasing the releasable cytosolic DA pool. Copyright © 2011. Published by Elsevier Inc.

Alterações Induzidas Pelo Exercício no Número, Função e Morfologia de Monócitos de Ratos

PubMed Central

GUERESCHI, MARCIA G.; PRESTES, JONATO; DONATTO, FELIPE F.; DIAS, RODRIGO; FROLLINI, ANELENA B.; FERREIRA, CLÍLTON KO.; CAVAGLIERI, CLAUDIA R.; PALANCH, ADRIANNE C.

2008-01-01

O propósito desse estudo foi verificar as alterações histofisiológicas em monócitos e macrófagos induzidas por curtos períodos de exercícios. Ratos Wistar (idade = 2 meses, peso corporal = 200g) foram divididos em sete grupos (n=6 cada): controle sedentário (C), grupos exercitados (natação) na intensidade leve por 5 (5L), 10 (10L) e 15 minutos (15L), e grupos exercitados em intensidade moderada por 5 (5M), 10 (10M) e 15 minutes (15M). Na intensidade moderada os animais carregaram uma carga de 5% do peso corporal dos mesmos em seus respectivos dorsos. Os monócitos sangüíneos foram avaliados quanto à quantidade e morfologia e os macrófagos peritoneais foram analisados quanto à quantidade e atividade fagocitária. Os dados foram analisados usando ANOVA e Tukey’s post hoc test (p ≤ 0,05). Os grupos de intensidade leve e 5M apresentaram aumento nos níveis dos monócitos quando comparados com o controle. Foi observado aumento na área celular dos monócitos para os grupos 5L, 10L, 5M e 10M; a área nuclear aumentou para os grupos 10L, 5M e 10M em comparação com o controle. Houve aumento nos macrófagos peritoneais para os grupos 15L, 10M, 15M e diminuição no grupo 5M. A capacidade fagocitária dos macrófagos aumentou nos grupos de intensidade leve e para o grupo 10M. O exercício realizado por curtos períodos modulou o número e função dos macrófagos, assim como o número e morfologia dos monócitos, sendo tais alterações dependentes da intensidade. A soma das respostas agudas observadas nesse estudo pode exercer um efeito protetor contra doenças, podendo ser utilizada para a melhora da saúde e qualidade de vida.

Polysaccharides from Smilax glabra inhibit the pro-inflammatory mediators via ERK1/2 and JNK pathways in LPS-induced RAW264.7 cells.

PubMed

Lu, Chuan-li; Wei, Zhu; Min, Wang; Hu, Meng-mei; Chen, Wen-long; Xu, Xiao-jie; Lu, Chuan-jian

2015-05-20

The rhizomes of Smilax glabra have been used as both food and folk medicine in many countries for a long time. However, little research has been reported on polysaccharides of S. glabra. In the present study, two polysaccharide fractions, SGP-1 and SGP-2, were isolated from the rhizomes of S. glabra with the number average molecular weights of 1.72 × 10(2)kDa and 1.31 × 10(2)kDa, and the weight average molecular weights of 1.31 × 10(5)kDa and 1.18 × 10(5)kDa, respectively, and their mainly monosaccharide compositions were both galactose and rhamnose (2.5:1). Both SGP-1 and SGP-2 significantly suppressed the release of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) from LPS-induced RAW 264.7 cells, as well as the mRNA expression of inducible nitric oxide synthase (iNOS), TNF-α and IL-6. Additionally, SGP-1 and SGP-2 repressed the extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK). These findings strongly suggested polysaccharides were also the anti-inflammatory active ingredient for S. glabra, and the potential of SGP-1 and SGP-2 as the anti-inflammatory agents. Copyright © 2015. Published by Elsevier Ltd.

Inventory on the dietary assessment tools available and needed in africa: a prerequisite for setting up a common methodological research infrastructure for nutritional surveillance, research, and prevention of diet-related non-communicable diseases.

PubMed

Pisa, Pedro T; Landais, Edwige; Margetts, Barrie; Vorster, Hester H; Friedenreich, Christine M; Huybrechts, Inge; Martin-Prevel, Yves; Branca, Francesco; Lee, Warren T K; Leclercq, Catherine; Jerling, Johann; Zotor, Francis; Amuna, Paul; Al Jawaldeh, Ayoub; Aderibigbe, Olaide Ruth; Amoussa, Waliou Hounkpatin; Anderson, Cheryl A M; Aounallah-Skhiri, Hajer; Atek, Madjid; Benhura, Chakare; Chifamba, Jephat; Covic, Namukolo; Dary, Omar; Delisle, Hélène; El Ati, Jalila; El Hamdouchi, Asmaa; El Rhazi, Karima; Faber, Mieke; Kalimbira, Alexander; Korkalo, Liisa; Kruger, Annamarie; Ledo, James; Machiweni, Tatenda; Mahachi, Carol; Mathe, Nonsikelelo; Mokori, Alex; Mouquet-Rivier, Claire; Mutie, Catherine; Nashandi, Hilde Liisa; Norris, Shane A; Onabanjo, Oluseye Olusegun; Rambeloson, Zo; Saha, Foudjo Brice U; Ubaoji, Kingsley Ikechukwu; Zaghloul, Sahar; Slimani, Nadia

2018-01-02

To carry out an inventory on the availability, challenges, and needs of dietary assessment (DA) methods in Africa as a pre-requisite to provide evidence, and set directions (strategies) for implementing common dietary methods and support web-research infrastructure across countries. The inventory was performed within the framework of the "Africa's Study on Physical Activity and Dietary Assessment Methods" (AS-PADAM) project. It involves international institutional and African networks. An inventory questionnaire was developed and disseminated through the networks. Eighteen countries responded to the dietary inventory questionnaire. Various DA tools were reported in Africa; 24-Hour Dietary Recall and Food Frequency Questionnaire were the most commonly used tools. Few tools were validated and tested for reliability. Face-to-face interview was the common method of administration. No computerized software or other new (web) technologies were reported. No tools were standardized across countries. The lack of comparable DA methods across represented countries is a major obstacle to implement comprehensive and joint nutrition-related programmes for surveillance, programme evaluation, research, and prevention. There is a need to develop new or adapt existing DA methods across countries by employing related research infrastructure that has been validated and standardized in other settings, with the view to standardizing methods for wider use.

Leonardo da Vinci meets celiac disease.

PubMed

Zanchi, Chiara; Ventura, Giovanna; Di Leo, Grazia; Orzes, Nicoletta; Ronfani, Luca; Not, Tarcisio; Ventura, Alessandro

2013-02-01

Leonardo da Vinci's face symmetry derives from 3 equal craniofacial segments: trichion-nasion (tn), which represents the superior third of the face, nasion-subnasal (ns) that is the medium third of the face, and subnasal-gnathion (sg) that is the length of the lower third of the face. It has been reported that adult subjects with celiac disease (CD) can be identified on the basis of a greater extension of the forehead in comparison to the medium third of the face, with a high tn/ns ratio. The aim of the present study was to investigate the correlation between facial asymmetry and CD in childhood and adulthood. We studied 126 biopsy-proven patients with CD (76 children and 50 adults) and 102 healthy controls (43 children and 59 adults). Their faces were photographed; the pictures were edited using a software program to calculate the facial segments. The tn length was significantly different between adult celiac and adult controls (7.43 ± 1.46 cm vs 6.38 ± 1.73 cm, P = 0.001). The cutoff of 6.5 cm tn, derived from receiver operating characteristic curve analysis, identified 43 of 50 patients (sensitivity 86%), but 34 of 59 controls were positive (specificity 54.2%). The positive predictive value was 56%; however, the tn/ns ratio was not significantly different between celiacs and controls. Neither the tn length nor the tn/ns ratio in celiacs correlated to the time of gluten exposure. Adults, but not children, with celiac disease show a forehead extension significantly greater than controls, but this test's specificity appears too low to be used in the screening of CD.

Study of hydrogen in phthalocyanine semiconductors using muSR technique =

NASA Astrophysics Data System (ADS)

Duarte, Joao Pedro Piroto Pereira

Este trabalho apresenta um estudo experimental dos semicondutores organicos Ftalocianina (H2Pc), Ftalocianina de Zinco (ZnPc) e Ftalocianina de Cobre (CuPc) por tecnicas de µSR, tendo-se obtido informacao detalhada sobre a estrutura electronica dos estados de carga formados pelo muao positivo nos tres compostos, e sobre as interaccoes dinamicas a que esses estados se encontram sujeitos. Os resultados do estudo indicam que nas ftalocianias com caracter nao magneticas H2Pc e ZnPc se da a formacao de tres radicais muonicos paramagneticos distintos. A estrutura hiperfina destes radicais, referidos como estados I, II e III, foi caracterizada atraves da medida dos parametros de acoplamento hipefino em conjunto com a parameterizacao da sua dependencia com a temperatura. Uma quarta componente paramagnetica do sinal µSR foi tambem identificada, mas sobre a qual nao foi possivel retirar conclusoes definitivas quanto a sua origem. Verificou-se que os parametros de acoplamento hiperfino isotropicos dos tres estados identificados se encontram numa regiao de valores entre os 100 e os 150MHz para os estados I e II, enquanto que para o estado III esta quantidade toma valores em torno de 10 MHz. A estrutura electronica de todos os estados possui simetria axial, caracterizada por parametros dipolares de cerca de 15MHz para os estados I e II, e 20MHz para o estado III. A origem dos estados I e II foi determinada como sendo devida a adicao de muonio a uma das ligacoes duplas existentes nos aneis benzenicos da periferia das moleculas de ftalocianina recorrendo a calculos de estrutura electronica, tendo-se verificado a existencia de um acoplamento entre a interaccao hiperfina desses estados e modos vibracionais desses aneis. A problematica da localizacao do estado III tambem foi abordada, tomando-se como hipotese mais provavel uma posicao intersticial entre duas moleculas de ftalocianina. O estudo das interaccoes dinamicas de spin destes tres estados revelou que o estado III esta sujeito a um fenomeno de spin exchange, originado pela colisao com portadores de carga presentes no material. A taxa de spin-flip relativa a esta interaccao foi deduzida a partir de medidas µSR em geometria de campo longitudinal, tendo sida determinada a barreira energetica existente para a difusao de portadores de carga entre moleculas de ftalocianina localizadas dentro da mesma estrutura colunar tanto na H2Pc, como na ZnPc. Por fim, o sinal µSR da ftalocianina com caracter magnetico CuPc foi tambem caracterizado. Foram identificadas duas componentes de caracter aparentemente diamagnetico com taxas de relaxacao separadas por cerca de duas ordens de grandeza, atribuidas a duas configuracoes distintas para o emparelhamento entre o electrao do radical muonico, e o electrao com spin desemparelhado localizado no atomo de cobre. Os dois emparelhamentos diferentes geram um ambiente puramente diamagnetico para o muao, o que origina a componente de relaxacao lenta, e uma configuracao na qual existe uma densidade de spin flutuante na posicao do muao, responsavel pela componente de relaxacao elevada.

Effects of prayer on the vital signs of patients with chronic kidney disease: randomized controlled trial.

PubMed

Brasileiro, Thaila Oliveira Zatiti; Prado, Andressa Anunciação de Oliveira; Assis, Bianca Bacelar de; Nogueira, Denismar Alves; Lima, Rogério Silva; Chaves, Erika de Cassia Lopes

2017-07-20

To assess the effect of prayer on blood pressure, heart rate and respiratory rate in patients with chronic kidney disease and learn their perception of the intervention. A randomized controlledtrial, double blind with a sample of volunteers, randomized into an intervention group (n=42) and a control group (n=37). Questionnaires addressing socio-demographic, clinical and spiritual characteristics and the Duke University Religious Index were applied. Blood pressure, heart rate and respiratory rate were measured. The prayer was conducted at three different moments on alternating weeks. The qualitative data were organized and analyzed through Thematic Analysis. The sample consisted of 95 randomized volunteers. In the intra-group analysis, a statistically significant reduction (P<0001) of blood pressure, heart rate and respiratory rate was observed in all evaluations of the people who were prayed for. The qualitative analysis resulted in the themes Prayer in a "Place of Suffering" and Positive Evaluation and in the sub-themes Relief from Suffering, Hope for Improvement, and Coping with Hemodialysis. CONCLUSIONPrayer reduced blood pressure, heart rate and respiratory rate in patients who suffer from chronic kidney disease, and the volunteers' evaluation of the intervention was positive.BrazilianClinicalTrials Registry: RBR-2zv39y. Avaliar o efeito da prece sobre a pressão arterial, a frequência cardíaca e respiratória em paciente com insuficiência renal crônica e conhecer sua percepção a respeito da intervenção. Ensaio clínico controlado, randomizado, duplo cego com uma amostra de voluntários, randomizados em grupo intervenção (n=42) e grupo controle (n=37). Foram aplicados, por meio de entrevista, um questionário de características sociodemográficas, clínicas e espirituais e o Índice de Religiosidade da Universidade de Duke, além da mensuração da pressão arterial, frequência cardíaca e respiratória. A prece foi ministrada em três momentos diferentes, durantes semanas alternadas. Os dados qualitativos foram organizados e analisados por meio da Análise Temática. A amostra totalizou 95 voluntários randomizados.Na análiseintragruposfoi observada uma redução estatisticamente significativa (P<0001) dos valores de pressão arterial, frequência cardíaca e respiratória em todas as análises das pessoas que receberam a prece. Aanálise qualitativa resultou nos temasA Prece em um "Lugar de Sofrimento" e Avaliação Positiva e nos subtemas Alívio do Sofrimento, Esperança de Superação, Enfrentamento do Tratamento Hemodialítico. A prece reduziu os valores da pressão arterial, frequência cardíaca e respiratória de pacientes com insuficiência renal crônica e a avaliação dos voluntários em relação à intervenção foi positiva. Registro Brasileiro de Ensaios Clínicos: RBR-2zv39y.

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

PubMed

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

2016-01-01

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

Determinação de regiões de órbitas diretas estáveis ao redor da Lua

NASA Astrophysics Data System (ADS)

de Melo, C. F.; Winter, O. C.; Vieira Neto, E.

2003-08-01

Neste Trabalho estamos investigando regiões do sistema Terra-Lua que contêm órbitas diretas estáveis ao redor da Lua visando a utilização destas órbitas em futuras missões de veículos espaciais como alternativas de trajetórias com baixo custo de manutenção. Adotando-se o problema restrito de três corpos, Terra-Lua-partícula, a localização e a extensão destas regiões de estabilidade foram investigadas numericamente considerando como estável toda órbita que permanece ao redor a Lua por, no mínimo, 1000 dias com energia de dois corpos da partícula em relação à Lua negativa. A estabilidade de tais regiões está associada a duas famílias de órbitas periódicas simples H1 e H2 e a órbitas quase-periódicas associadas a elas. Uma vez identificadas as regiões de estabilidade passamos a analisá-las introduzindo, paulatinamente, outras interações relevantes ao sistema como as perturbações do Sol (via problema restrito de quatro corpos), das marés, da pressão de radiação e do achatamento terrestre. Os resultados encontrados até o momento mostram que a perturbação do Sol é a única que reduz significativamente o tamanho das regiões de estabilidade. Também estamos investigando o comportamento de tais regiões quando características intrínsecas do sistema como as excentricidades das órbitas da Terra e da Lua e a inclinação da órbita Lua são consideradas. Com este estudo estamos reunindo informações que nos permitirão compreender a evolução das regiões de estabilidade no sistema Terra-Lua, bem como estabelecer parâmetros adequados para a utilização das trajetórias estáveis em futuras missões espaciais. Agradecimentos: Este projeto conta com o apoio do CNPq, da Capes e da Fapesp.

Estudo de não gaussianidade nas anisotropias da RCF medidas Wmap

NASA Astrophysics Data System (ADS)

Andrade, A. P. A.; Wuensche, C. A.; Ribeiro, A. L. B.

2003-08-01

A investigação do campo de flutuações da Radiação Cósmica de Fundo (RCF) pode oferecer um importante teste para os modelos cosmológicos que descrevem a origem e a evolução das flutuações primordiais. De um lado, apresenta-se o modelo inflacionário que prevê um espectro de flutuações adiabáticas distribuídas segundo uma gaussiana e, de outro, os modelos de defeitos topológicos (dentre outros) que descrevem um mecanismo para a geração de flutuações de isocurvatura que obedecem a uma distribuição não gaussiana. Este trabalho tem como objetivo caracterizar traços do modelo não gaussiano de campo misto (entre flutuações adiabáticas e de isocurvatura) nos mapas do Wilkinson Microwave Anisotropy Probe (WMAP). Simulações das anisotropias da RCF no contexto de mistura indicam traços marcantes na distribuição das flutuações de temperatura, mesmo quando consideradas pequenas contribuições do campo de isocurvatura (da ordem de 0.001). O efeito da mistura entre os campos resulta na transferência de potência de flutuações em escalas angulares intermediárias para flutuações em pequenas escalas angulares. Este efeito pode ser caracterizado pela relação entre as amplitudes dos primeiros picos acústicos no espectro de potência da RCF. Neste trabalho, investigamos a contribuição do campo de isocurvatura, no contexto de mistura, sobre as observações recentes da RCF realizadas pelo WMAP. As previsões do modelo de campo misto, uma vez confrontadas com as observações em pequenas escalas angulares, podem ajudar a revelar a natureza das flutuações primordiais.

Ultrafast electron transfer at organic semiconductor interfaces: Importance of molecular orientation

DOE PAGES

Ayzner, Alexander L.; Nordlund, Dennis; Kim, Do -Hwan; ...

2014-12-04

Much is known about the rate of photoexcited charge generation in at organic donor/acceptor (D/A) heterojunctions overaged over all relative arrangements. However, there has been very little experimental work investigating how the photoexcited electron transfer (ET) rate depends on the precise relative molecular orientation between D and A in thin solid films. This is the question that we address in this work. We find that the ET rate depends strongly on the relative molecular arrangement: The interface where the model donor compound copper phthalocyanine is oriented face-on with respect to the fullerene C 60 acceptor yields a rate that ismore » approximately 4 times faster than that of the edge-on oriented interface. Our results suggest that the D/A electronic coupling is significantly enhanced in the face-on case, which agrees well with theoretical predictions, underscoring the importance of controlling the relative interfacial molecular orientation.« less

Nitric oxide, stress, and depression.

PubMed

McLeod, T M; López-Figueroa, A L; López-Figueroa, M O

2001-01-01

Stress and depression have a significant impact on modern society. Even though their symptomatology is well characterized, little is known about the molecular mechanisms underlying these disturbing disorders. While the role of neurotransmitters such as serotonin, norepinephrine (NE), dopamine (DA), corticotropin-releasing hormone (CRH), and arginine vasopressin (AVP) has been extensively studied, new evidence suggests a role for the unique neurotransmitter nitric oxide (NO). This highly diffusible and reactive molecule is synthesized by at least three enzyme subtypes of NO synthase (NOS). The commonly known neuronal NOS subtype is localized in areas of the brain related to stress and depression. The limbic-hypothalamic-pituitary-adrenal (LHPA) axis is the core of this system. These interrelated pathways have in common the production, and negative feedback, of glucocorticoids. Within these areas, NO is suggested to play a role in modulating the release of other neurotransmitters, acting as a cellular communicator in plasticity and development, and/or acting as a vasodilator in regulation of blood flow. This article summarizes some of the recent advances in the understanding of the role of NO in stress and depression.

Face, content and concurrent validity of the Mimic® dV-Trainer for robot-assisted endoscopic surgery: a prospective study.

PubMed

Egi, H; Hattori, M; Tokunaga, M; Suzuki, T; Kawaguchi, K; Sawada, H; Ohdan, H

2013-01-01

The aim of this study was to determine whether any correlation exists between the performance of the Mimic® dV-Trainer (Mimic Technologies, Seattle, Wash., USA) and the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, Calif., USA). Twelve participants were recruited, ranging from residents to consultants. We used four training tasks, consisting of 'Pick and Place', 'Peg Board', 'Thread the Rings' and 'Suture Sponge', from the software program of the Mimic dV-Trainer. The performance of the participants was recorded and measured. Additionally, we prepared the same tasks for the da Vinci Surgical System. All participants completed the tasks using the da Vinci Surgical System and were assessed according to time, the Objective Structured Assessment of Technical Skill checklist and the global rating score for endoscopic suturing assessed by two independent blinded observers. After performing these tasks, the participants completed a questionnaire that evaluated the Mimic dV-Trainer's face and content validity. The final results for each participant for the Mimic dV-Trainer and the da Vinci Surgical System were compared. All participants ranked the Mimic dV-Trainer as a realistic training platform that is useful for residency training. There was a significant relationship between the Mimic dV-Trainer and the da Vinci Surgical System in all four tasks. We verified the reliability of the assessment of the checklist and the global rating scores for endoscopic suturing assessed by the two blinded observers using Cronbach's alpha test (r = 0.803, 0.891). We evaluated the concurrent validity of the Mimic dV-Trainer and the da Vinci Surgical System. Our results suggest the possibility that training using the Mimic dV-Trainer may therefore be able to improve the operator's performance during live robot-assisted surgery. © 2013 S. Karger AG, Basel.

Low oxygen tension increased fibronectin fragment induced catabolic activities--response prevented with biomechanical signals.

PubMed

Parker, Eleanor; Vessillier, Sandrine; Pingguan-Murphy, Belinda; Abas, Wan; Bader, Dan L; Chowdhury, Tina T

2013-10-25

The inherent low oxygen tension in normal cartilage has implications on inflammatory conditions associated with osteoarthritis (OA). Biomechanical signals will additionally contribute to changes in tissue remodelling and influence the inflammatory response. In this study, we investigated the combined effects of oxygen tension and fibronectin fragment (FN-f) on the inflammatory response of chondrocytes subjected to biomechanical signals. Chondrocytes were cultured under free-swelling conditions at 1%, 5% and 21% oxygen tension or subjected to dynamic compression in an ex vivo 3D/bioreactor model with 29 kDa FN-f, interleukin-1beta (IL-1β) and/or the nitric oxide synthase (NOS) inhibitor for 6 and 48 hours. Markers for catabolic activity (NO, PGE2), tissue remodelling (GAG, MMPs) and cytokines (IL-1β, IL-6 and TNFα) were quantified by biochemical assay. Aggrecan, collagen type II, iNOS and COX-2 gene expression were examined by real-time quantitative PCR. Two-way ANOVA and a post hoc Bonferroni-corrected t-test were used to analyse data. Both FN-fs and IL-1β increased NO, PGE2 and MMP production (all P< 0.001). FN-f was more active than IL-1β with greater levels of NO observed at 5% than 1% or 21% oxygen tension (P < 0.001). Whilst FN-f reduced GAG synthesis at all oxygen tension, the effect of IL-1β was significant at 1% oxygen tension. In unstrained constructs, treatment with FN-f or IL-1β increased iNOS and COX-2 expression and reduced aggrecan and collagen type II (all P < 0.001). In unstrained constructs, FN-f was more effective than IL-1β at 5% oxygen tension and increased production of NO, PGE2, MMP, IL-1β, IL-6 and TNFα. At 5% and 21% oxygen tension, co-stimulation with compression and the NOS inhibitor abolished fragment or cytokine-induced catabolic activities and restored anabolic response. The present findings revealed that FN-fs are more potent than IL-1β in exerting catabolic effects dependent on oxygen tension via iNOS and COX-2 upregulation. Stimulation with biomechanical signals abolished catabolic activities in an oxygen-independent manner and NOS inhibitors supported loading-induced recovery resulting in reparative activities. Future investigations will utilize the ex vivo model as a tool to identify key targets and therapeutics for OA treatments.

Thirdhand smoke: when the danger is more than you can see or smell.

PubMed

Figueiró, Luciana Rizzieri; Ziulkoski, Ana Luiza; Dantas, Denise Conceição Mesquita

2016-12-01

Recent discussion has focused on another form of exposure to tobacco - thirdhand smoke (THS) - consisting of residual pollutants from cigarette smoke that remain in environments. The main concern with THS is based on the presence and persistence of many toxic compounds, some specific nitrosamines from tobacco that have carcinogenic activity. Little is known about THS, and few people are aware of its existence and potential health repercussions, thus highlighting the need to shed light on the subject and incorporate it into the public health debate, as was done with passive smoking several years ago. THS is a form of passive smoking, together with secondary or involuntary exposure to cigarette smoke. Recentemente, passou a ser discutida mais uma forma de exposição ao tabaco - thirdhand smoke (THS) - que consiste nos poluentes residuais da fumaça de cigarro que permanecem nos ambientes. A principal preocupação com o THS é embasada na presença e longa persistência de muitos compostos tóxicos, algumas nitrosaminas específicas do tabaco que têm atividade carcinogênica. Além de se saber pouco sobre o THS, poucos sabem de sua existência e preocupante repercussão na saúde. Coloca-se em destaque a necessidade de trazê-lo à luz e incluí-lo nas discussões, assim como foi feito com o tabagismo passivo alguns anos atrás, até mesmo porque o THS se caracteriza como uma forma de tabagismo passivo junto à exposição secundária ou involuntária da fumaça de cigarro.

6-Shogaol, an active compound of ginger, protects dopaminergic neurons in Parkinson's disease models via anti-neuroinflammation

PubMed Central

Park, Gunhyuk; Kim, Hyo Geun; Ju, Mi Sun; Ha, Sang Keun; Park, Yongkon; Kim, Sun Yeou; Oh, Myung Sook

2013-01-01

Aim: 6-Shogaol [1-(4-hydroxy-methoxyphenyl)-4-decen-one], a pungent compound isolated from ginger, has shown various neurobiological and anti-inflammatory effects. The aim of this study was to examine the effects of 6-shogaol on neuroinflammatory-induced damage of dopaminergic (DA) neurons in Parkinson's disease (PD) models. Methods: Cultured rat mesencephalic cells were treated with 6-shogaol (0.001 and 0.01 μmol/L) for 1 h, then with MPP+(10 μmol/L) for another 23 h. The levels of TNF-α and NO in medium were analyzed spectrophotometrically. C57/BL mice were administered 6-shogaol (10 mg·kg−1·d−1, po) for 3 d, and then MPTP (30 mg/kg, ip) for 5 d. Seven days after the last MPTP injection, behavioral testings were performed. The levels of tyrosine hydroxylase (TH) and macrophage antigen (MAC)-1 were determined with immunohistochemistry. The expression of iNOS and COX-2 was measured using RT PCR. Results: In MPP+-treated rat mesencephalic cultures, 6-shogaol significantly increased the number of TH-IR neurons and suppressed TNF-α and NO levels. In C57/BL mice, treatment with 6-shogaol reversed MPTP-induced changes in motor coordination and bradykinesia. Furthermore, 6-shogaol reversed MPTP-induced reductions in TH-positive cell number in the substantia nigra pars compacta (SNpc) and TH-IR fiber intensity in stratum (ST). Moreover, 6-shogaol significantly inhibited the MPTP-induced microglial activation and increases in the levels of TNF-α, NO, iNOS, and COX-2 in both SNpc and ST. Conclusion: 6-Shogaol exerts neuroprotective effects on DA neurons in in vitro and in vivo PD models. PMID:23811724

6-Shogaol, an active compound of ginger, protects dopaminergic neurons in Parkinson's disease models via anti-neuroinflammation.

PubMed

Park, Gunhyuk; Kim, Hyo Geun; Ju, Mi Sun; Ha, Sang Keun; Park, Yongkon; Kim, Sun Yeou; Oh, Myung Sook

2013-09-01

6-Shogaol [1-(4-hydroxy-methoxyphenyl)-4-decen-one], a pungent compound isolated from ginger, has shown various neurobiological and anti-inflammatory effects. The aim of this study was to examine the effects of 6-shogaol on neuroinflammatory-induced damage of dopaminergic (DA) neurons in Parkinson's disease (PD) models. Cultured rat mesencephalic cells were treated with 6-shogaol (0.001 and 0.01 μmol/L) for 1 h, then with MPP(+)(10 μmol/L) for another 23 h. The levels of TNF-α and NO in medium were analyzed spectrophotometrically. C57/BL mice were administered 6-shogaol (10 mg·kg(-1)·d(-1), po) for 3 d, and then MPTP (30 mg/kg, ip) for 5 d. Seven days after the last MPTP injection, behavioral testings were performed. The levels of tyrosine hydroxylase (TH) and macrophage antigen (MAC)-1 were determined with immunohistochemistry. The expression of iNOS and COX-2 was measured using RT PCR. In MPP(+)-treated rat mesencephalic cultures, 6-shogaol significantly increased the number of TH-IR neurons and suppressed TNF-α and NO levels. In C57/BL mice, treatment with 6-shogaol reversed MPTP-induced changes in motor coordination and bradykinesia. Furthermore, 6-shogaol reversed MPTP-induced reductions in TH-positive cell number in the substantia nigra pars compacta (SNpc) and TH-IR fiber intensity in stratum (ST). Moreover, 6-shogaol significantly inhibited the MPTP-induced microglial activation and increases in the levels of TNF-α, NO, iNOS, and COX-2 in both SNpc and ST. 6-Shogaol exerts neuroprotective effects on DA neurons in in vitro and in vivo PD models.

Sobre a largura da última superfície de espalhamento

NASA Astrophysics Data System (ADS)

Nobre, M. A. S.; Pires, N.; Lima, J. A. S.

2003-08-01

De acordo com o modelo do "Big-Bang", no universo primordial a matéria estava em equilíbrio térmico com a radiação. Com a expansão a temperatura da radiação cai. Quando a temperatura chega em torno dos 4.000K, os espalhamentos diminuem, começando a recombinação dos prótons e elétrons em Hidrogênio neutro (era conhecida como da recombinação). Ao final da recombinação, os fótons se propagam livremente sofrendo, em princípio, somente os efeitos do "redshift" cosmológico. Esses fótons nos alcançam hoje como a radiação cósmica de fundo (RCF), e parecem vir de uma superfície esférica ao nosso redor, tal que o raio dela é a distância que ele viajou desde seu último espalhamento na época da recombinação. Naturalmente, esse processo não ocorreu abruptamente, implicando na existência de uma largura no espaço dos "redshifts" que deve depender do modelo cosmológico específico e dos processos físicos considerados. Neste trabalho analisamos os efeitos de diferentes modelos - a saber, aqueles com decaimento do vácuo L(t), criação de matéria, quintessência e gás de Chaplygin - sobre a última superfície de espalhamento da RCF, em particular sua largura e a função visibilidade, que determina a probabilidade de um fóton ter tido seu último espalhamento num "redshift" z. No caso particular dos modelos com decaimento do vácuo, existe uma forte dependência da função visibilidade com L(t). Tais efeitos poderão ser testados através da análise dos resultados de experimentos mais precisos que estão atualmente em andamento, como por exemplo, o WMAP.

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

Health technology assessment (HTA) organizations: dimensions of the institutional and political framework.

PubMed

Novaes, Hillegonda Maria Dutilh; Soárez, Patrícia Coelho de

2016-11-03

Health technology assessment (HTA) is consolidated as a scientific and technological practice. The aim of this study is to identify HTA organizations from different settings and analyze their relevant dimensions in terms of effectiveness/impact, in order to address the challenges they face in Brazil. Narrative literature review based on data and websites of HTA organizations. There are well-established activity development processes in all organizations. These activities have specific features in their profile, in the process of technology assessment, decision and implementation of technologies that influence their potential impact on health systems. Agencies share in common the challenges of ranking the technologies to be assessed, and the implementation of their recommendations. Technical and political strengthening of the institutionalization of HTA in Brazil may foster scientific, technological and innovation policies, effectively impacting health policies. Resumo: A avaliação de tecnologias em saúde (ATS) está consolidada enquanto prática científica e tecnológica. O objetivo do estudo é identificar organizações de ATS de diferentes contextos e analisá-las de acordo com dimensões relevantes na avaliação de sua efetividade/impacto, buscando contribuir com os desafios enfrentados no contexto nacional. Revisão narrativa da literatura, realizada em bases de dados e web sites de organizações de ATS. Existem processos de desenvolvimento das atividades bem estabelecidos em todas as organizações. Elas apresentam particularidades no seu perfil, nos processos de avaliação, decisão e implementação das tecnologias que influenciam o seu impacto potencial sobre os sistemas de saúde. As agências compartilham os desafios de priorização das tecnologias a serem avaliadas e implementação das suas recomendações. O fortalecimento técnico e político do processo de institucionalização da ATS no contexto nacional poderá contribuir com as políticas científicas, tecnológicas e de inovação, impactando de forma efetiva as políticas de saúde.

Critical incidents connected to nurses' leadership in Intensive Care Units.

PubMed

Lima, Elaine Cantarella; Bernardes, Andrea; Baldo, Priscila Lapaz; Maziero, Vanessa Gomes; Camelo, Silvia Helena Henriques; Balsanelli, Alexandre Pazetto

2017-01-01

The goal of this study is to analyze nurses' leadership in intensive care units at hospitals in the state of São Paulo, Brazil, in the face of positive and negative critical incidents. Exploratory, descriptive study, conducted with 24 nurses by using the Critical Incident Technique as a methodological benchmark. Results were grouped into 61 critical incidents distributed into categories. Researchers came to the conclusion that leadership-related situations interfere with IC nurses' behaviors. Among these situations they found: difficulty in the communication process; conflicts in the daily exercise of nurses' activities; people management; and the setting of high quality care targets. Researchers identified a mixed leadership model, leading them to the conclusion that nurses' knowledge and practice of contemporary leadership theories/styles are crucial because they facilitate the communication process, focusing on behavioral aspects and beliefs, in addition to valuing flexibility. This positively impacts the organization's results. Analisar a liderança do enfermeiro em Centros de Terapia Intensiva de hospitais localizados no interior do estado de São Paulo, diante de incidentes críticos positivos e negativos. Estudo exploratório, descritivo, realizado com 24 enfermeiros, que utilizou a Técnica do Incidente Crítico como referencial metodológico. Os resultados foram agrupados em 61 incidentes críticos distribuídos em categorias. Identificou-se que situações relacionadas à liderança interferem no comportamento do enfermeiro de Terapia Intensiva, dentre elas: dificuldade no processo de comunicação, conflitos existentes no dia a dia do exercício profissional, gerenciamento de pessoas e estabelecimento de metas para o alcance da assistência qualificada. Encontrou-se um modelo misto de liderança, o que permite concluir que o conhecimento e a prática dos enfermeiros acerca de teorias/estilos contemporâneos de liderança tornam-se fundamentais, pois facilitam o processo de comunicação, focando nos aspectos comportamentais e crenças, e valorizam a flexibilidade, impactando positivamente os resultados da organização.

A fonte ionizante do disco de acreção no núcleo de NGC1097

NASA Astrophysics Data System (ADS)

Silva, R. N.; Storchi-Bergmann, T.

2003-08-01

Observações em raios-X revelam o "coração" dos núcleos ativos de galáxias, pois esse tipo de radiação provém das suas regiões mais internas, próximas ao buraco negro central. Neste trabalho apresentamos observações em raios-X da região central da galáxia NGC1097, que hospeda um buraco negro supermassivo e um disco de acreção cuja emissão vem sendo observada há dez anos através da linha de emissão Ha larga (10000 km/s) e de duplo pico. As observações em raios-X - que foram obtidas com o Telescópio Chandra - foram combinadas com observações no ultravioleta obtidas com o Telescópio Espacial Hubble e são usadas para estudar as características da fonte central que ioniza o disco de acreção. A distribuição espectral de energia é comparada com a predita por modelos, em particular o de uma estrutura "ADAF" ("advection dominated accretion flow") na parte interna do disco. Tal estrutura produz um espectro de emissão de linhas estreitas tipo LINER, como observado em NGC1097 e em rádio-galáxias que apresentam linhas de Balmer largas de duplo pico. Apresentamos também uma comparação entre outros LINERs com linhas de emissão largas de duplo pico, disponíveis na literatura ou nos arquivos do Chandra e do Telescópio Espacial Hubble e discutimos as correspondentes implicações para modelos da fonte central.

Teaching astronomy mediated by information and communication technologies: a preliminary approach

NASA Astrophysics Data System (ADS)

Rosa, R. H. L.; Voelzke, M. R.

2014-08-01

O presente trabalho é parte preliminar de um estudo mais amplo em nível de doutorado sobre o ensino de astronomia mediado pelas tecnologias da informação e comunicação, utilizando dispositivos compactos, móveis e pessoais. Este estudo também faz parte do projeto institucional do CEFETMG sobre ambientes diversificados de aprendizagem sob fomento da agência estadual FAPEMIG (Fundação de Amparo à Pesquisa do Estado de Minas Gerais). Esta apresentação aborda o resultado das concepções prévias de estudantes em relação a conhecimentos básicos de astronomia, ligados à percepção e observação direta do céu. Três turmas de estudantes de 1ª série e uma turma de 3ª série do ensino integrado médio técnico da Educação Básica, Técnica e Tecnológica (EBTT) do CEFETMG Campus II - Belo Horizonte/MG foram submetidas a uma avaliação prévia através de questionário estruturado. Este questionário foi elaborado de forma a abordar a percepção dos estudantes em relação aos recursos gráficos (figuras e desenhos) representativos de conhecimentos básicos de astronomia, comuns em livros didáticos. Após a análise dos resultados desta avaliação, organizou-se uma estratégia de intervenção didática em sala de aula sobre o conteúdo de astronomia, utilizando-se de recursos de mediação baseados nas tecnologias da informação e comunicação. Os temas selecionados para esta estratégia didática foram relacionados aos assuntos básicos de astronomia em que ocorreu maior nível de desconhecimento dos estudantes. Os estudantes foram submetidos a avaliação posterior elaborada com os mesmos pressupostos da avaliação prévia. A análise dos resultados foi realizada a partir dos pressupostos da aprendizagem significativa (Ausubel; Novak e Hanesian, 1983). O ensino de astronomia por mediação das tecnologias da informação e comunicação indica uma alternativa preliminar aos trabalhos de campo usuais orientados na prática escolar, tais como, visita a planetários e a observatórios. Os estudantes ficaram muito sensibilizados pela possibilidade de percepção do céu em tempo real e à luz do dia dentro da sala de aula no contexto escolar. Os resultados deste levantamento preliminar indicam que os níveis de ensino fundamental e médio não foram capazes de internalizar conhecimentos básicos de astronomia, a despeito das orientações específicas contidas nos documentos oficiais da educação básica brasileira (Brasil, 1997 e 2000). Os estudantes pesquisados apresentaram conhecimentos e concepções rudimentares sobre o tema astronomia básica, indicando a ausência de abordagem do tema astronomia, tampouco de observação direta do céu em trabalhos de campo escolares na educação básica. Finalmente, esta abordagem didática suscitou nos estudantes grande interesse para futuros trabalhos de observação de campo. D.P. Ausubel; J.D. Novak; H. Hanesian. Psicología Educativa: un punto de vista cognoscitivo. México: Trillas, 1983. BRASIL. Secretaria de Educação Básica. Parâmetros Curriculares Nacionais: Ensino Fundamental (PCN), 1997, e Ensino Médio (PCNEM), 2000. Brasília. MEC/SEB.

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

PubMed

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

2016-01-01

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

(Un)receptiveness in interactions with professionals: experiences of parents of children with retinopathy of prematurity.

PubMed

Facio, Beatriz Castanheira; Marski, Bruna de Souza Lima; Higarashi, Ieda Harumi; Misko, Maira Deguer; Silveira, Aline Oliveira; Wernet, Monika

2016-01-01

To analyze the influence of health professionals' receptiveness on parental care of children with retinopathy of prematurity (ROP). A qualitative study developed under the theoretical framework of Symbolic Interactionism and using a narrative research methodology. Six women and three men, being parents of children with retinopathy of prematurity were individually interviewed in depth. From the scope of information, emotions and their rights, the parents experienced receptiveness from some professionals and unreceptiveness from others. The predominance of unreceptive attitudes in the parental narratives originated the following analysis themes: Informational (un)receptiveness, Emotional (un)receptiveness, and (Un)receptiveness of rights. The study supports human and comprehensive healthcare in the context of retinopathy of prematurity by pointing out the interactive process with health professionals as a potential stressor of parental care. The results signal a nuclear of attitudinal changes and reinforce challenges to the child and family-centered approach. Analisar a influência do acolhimento do profissional de saúde no cuidado parental junto ao filho com retinopatia da prematuridade. Estudo qualitativo desenvolvido sob o referencial teórico do Interacionismo Simbólico e metodológico da pesquisa de narrativas. Foram entrevistados em profundidade e individualmente seis mulheres e três homens, pais de crianças com retinopatia da prematuridade. Os pais vivenciam, nos âmbitos informacional, emocional e de direitos, acolhimento com alguns profissionais e destrato com outros. A predominância da postura de desacolhimento nas narrativas parentais deu origem aos temas de análise: (Des)acolhimento informacional, (Des)acolhimento emocional, e (Des)acolhimento de direitos. O estudo oferece subsídios ao cuidado humano e integral em saúde no contexto da retinopatia da prematuridade ao apontar o processo interativo com os profissionais de saúde enquanto potencial estressor do cuidado parental. Os resultados sinalizam núcleos de mudanças atitudinais e reforçam desafios à abordagem centrada na criança e família.

Ambiente e formação estelar em galáxias

NASA Astrophysics Data System (ADS)

Mateus, A., Jr.; Sodré, L., Jr.

2003-08-01

Estudamos o ambiente de galáxias com formação estelar inicialmente a partir de uma amostra limitada em volume proveniente do 2dF Galaxy Redshift Survey. Discriminamos as galáxias com formação estelar com base em distintas classes espectrais, utilizando para esta classificação as larguras equivalentes das linhas [OII]l3727 e Hd. O ambiente é caracterizado pela densidade espacial local de galáxias. Mostramos que a fração de galáxias com formação estelar é bastante reduzida em ambientes densos, enquanto a de galáxias passivas aumenta nestas regiões. Por outro lado, quando analisamos a fração de galáxias que apresentam um surto recente de formação estelar, notamos que ela independe do ambiente, sendo que em regiões mais densas alguns destes objetos apresentam distorções em sua morfologia. Estes resultados são confrontados com a análise da dependência ambiental da taxa de formação estelar, estimada pela emissão em Ha, de uma amostra extraída do Sloan Digital Sky Survey. Um declínio gradual da formação estelar também é observado nesta análise, sugerindo que as interações por efeitos de maré sejam responsáveis pela redução da formação estelar em ambientes densos através da remoção do reservatório de gás das galáxias. No entanto, estas interações também podem induzir surtos de formação estelar nas galáxias, além de peculiaridades morfológicas observadas nos objetos que habitam regiões mais densas.

Bladder carcinogenesis in rats subjected to ureterosigmoidostomy and treated with L-lysine.

PubMed

Dornelas, Conceição Aparecida; Santos, Alessandra Marques Dos; Correia, Antonio Lucas Oliveira; Juanes, Camila de Carvalho; Coelho, João Paulo Ferreira; Cunha, Bianca Lopes; Maciel, André Vinicius Vieira; Jamacaru, Francisco Vagnaldo Fechine

2016-01-01

to evaluate the effect of L-lysine in the bladder and intestinal epithelia in rats submitted to vesicosigmoidostomy. we divided forty Wistar rats into four groups: group I - control group (Sham); group II - submitted to vesicosigmoidostomy and treated with L-lysine 150mg/kg; group III - submitted only to vesicosigmoidostomy; and group IV - received L-lysine 150mg/kg. After eight weeks the animals were sacrificed. in the bladders of all operated animals we observed simple, papillary and nodular hyperplasia of transitional cells, transitional cell papillomas and squamous metaplasia. As for the occurrence of aberrant crypt foci in the colons of operated animals, we did not observe statistically significant differences in any of the distal, proximal and medium fragments, or in all fragments together (p=1.0000). Although statistically there was no promotion of carcinogenesis in the epithelia of rats treated with L-lysine in the observed time, it was clear the histogenesis of bladder carcinogenesis in its initial phase in all operated rats, this being probably associated with chronic infection and tiny bladder stones. o objetivo deste trabalho é avaliar o efeito da L-lisina nos epitélios vesical e intestinal de ratas submetidas à vesicossigmoidostomia. quarenta ratas Wistar, foram divididas em quatro grupos: grupo I- grupo controle (Sham); grupo II- submetido à vesicossigmoidostomia e tratado com L-lisina 150mg/kg; grupo III- submetido apenas à vesicossigmoidostomia; e grupo IV- recebeu L-lisina 150mg/kg. Após oito semanas os animais foram sacrificados. na bexiga de todos os animais operados observou-se hiperplasia simples, papilar e nodular de células transicionais, papiloma de células transicionais e metaplasia escamosa. Quanto à ocorrência de focos de criptas aberrantes nos colos dos animais operados, não foi evidenciado diferença estatística significante em nenhum dos fragmentos distal, proximal e médio, e todos juntos (P=1,0000). apesar de, estatisticamente, não ter havido promoção de carcinogênese nos epitélios dos ratos tratados com L-lisina, no tempo observado, é nítida a histogênese da carcinogênese de bexiga em sua fase inicial, no epitélio vesical, em todos os ratos operados, estando esta provavelmente associada à infecção crônica e aos diminutos cálculos vesicais.

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 of Mexican Arnica (Heterotheca inuloides Cass) and Rosemary (Rosmarinus officinalis) Extracts on Dopamine and Selected Biomarkers of Oxidative Stress in Stomach and Brain of Salmonella typhimurium Infected rats.

PubMed

Guzmàn, David Calderón; Herrera, Maribel Ortiz; Brizuela, Norma Osnaya; Mejía, Gerardo Barragàn; García, Ernestina Hernàndez; Olguín, Hugo Juàrez; Peraza, Armando Valenzuela; Ruíz, Norma Labra; Del Angel, Daniel Santamaría

2017-01-01

The effects of some natural products on dopamine (DA) and 5-hydroxyindole acetic acid (5-HIAA) in brain of infected models are still unclear. The purpose of this study was to measure the effect of Mexican arnica/rosemary (MAR) water extract and oseltamivir on both biogenic amines and some oxidative biomarkers in the brain and stomach of young rats under infection condition. Female Wistar rats (weight 80 g) in the presence of MAR or absence (no-MAR) were treated as follows: group 1, buffer solution (controls); oseltamivir (100 mg/kg), group 2; culture of Salmonella typhimurium ( S.Typh ) (1 × 10 6 colony-forming units/rat) group 3; oseltamivir (100 mg/kg) + S.Typh (same dose) group 4. Drug and extracts were administered intraperitoneally every 24 h for 5 days, and S.Typh was given orally on days 1 and 3. On the fifth day, blood was collected to measure glucose and hemoglobin. The brains and stomachs were obtained to measure levels of DA, 5-HIAA, glutathione (GSH), TBARS, H 2 O 2 , and total ATPase activity using validated methods. DA levels increased in MAR group treated with oseltamivir alone but decreased in no-MAR group treated with oseltamivir plus S.Typh . 5-HIAA, GSH, and H 2 O 2 decreased in this last group, and ATPase activity increased in MAR group treated with oseltamivir plus S.Typh . TBARS (lipid peroxidation) increased in MAR group that received oseltamivir alone. Most of the biomarkers were not altered significantly in the stomach. MAR extract alters DA and metabolism of 5-HIAA in the brain of young animals infected. Antioxidant capacity may be involved in these effects. The purpose of this study was to measure the effect of Mexican arnica/rosemary water extract and oseltamivir on both biogenic amines and some oxidative biomarkers in the brain and stomach of young rats under infection condition. Results: Mexican arnica and rosemary extract alter dopamine and metabolism of 5-HIAA in the brain of young animals infected. Antioxidant capacity may be involved in these effects. Abbreviations used: AS: Automated system, ATP: Adenosine triphosphate, CNS: Central nervous system, CFU: Colony-forming unit, DA: Dopamine EDTA: Ethylenediaminetetraacetic acid, 5-HIAA: Äcido 5-hidroxindolacético (serotonina), GABA: γ-aminobutyric acid, GSH: Glutathione, H2O2: Hidrogen peroxide, HCLO4: Perchloric acid, iNOS: Inducible nitric oxide synthase, LPS: Lipopolysaccharides, MAR: Arnica/Rosemary, NaCl: Sodium Chloride, NOGSH: nitrosoglutathione, NOS: Nitric oxide, OPT: Ortho-phtaldialdehyde, Pbs: Phosphate buffered saline, pH: potential of Hydrogen, Pi: Inorganic phosphate, ROS: Reactive oxygen species, RNSs: Reactive nitrogen species Tba: Thiobarbaturic acid, TBARS: Thiobarbituric aid reactive, Tca: Trichloroacetic, Tris-HCL: Tris hydrochloride, TSA: Trypticasein Soya Agar.

Assessment of Mexican Arnica (Heterotheca inuloides Cass) and Rosemary (Rosmarinus officinalis) Extracts on Dopamine and Selected Biomarkers of Oxidative Stress in Stomach and Brain of Salmonella typhimurium Infected rats

PubMed Central

Guzmàn, David Calderón; Herrera, Maribel Ortiz; Brizuela, Norma Osnaya; Mejía, Gerardo Barragàn; García, Ernestina Hernàndez; Olguín, Hugo Juàrez; Peraza, Armando Valenzuela; Ruíz, Norma Labra; Del Angel, Daniel Santamaría

2017-01-01

Background: The effects of some natural products on dopamine (DA) and 5-hydroxyindole acetic acid (5-HIAA) in brain of infected models are still unclear. Objective: The purpose of this study was to measure the effect of Mexican arnica/rosemary (MAR) water extract and oseltamivir on both biogenic amines and some oxidative biomarkers in the brain and stomach of young rats under infection condition. Methods: Female Wistar rats (weight 80 g) in the presence of MAR or absence (no-MAR) were treated as follows: group 1, buffer solution (controls); oseltamivir (100 mg/kg), group 2; culture of Salmonella typhimurium (S.Typh) (1 × 106 colony-forming units/rat) group 3; oseltamivir (100 mg/kg) + S.Typh (same dose) group 4. Drug and extracts were administered intraperitoneally every 24 h for 5 days, and S.Typh was given orally on days 1 and 3. On the fifth day, blood was collected to measure glucose and hemoglobin. The brains and stomachs were obtained to measure levels of DA, 5-HIAA, glutathione (GSH), TBARS, H2O2, and total ATPase activity using validated methods. Results: DA levels increased in MAR group treated with oseltamivir alone but decreased in no-MAR group treated with oseltamivir plus S.Typh. 5-HIAA, GSH, and H2O2 decreased in this last group, and ATPase activity increased in MAR group treated with oseltamivir plus S.Typh. TBARS (lipid peroxidation) increased in MAR group that received oseltamivir alone. Most of the biomarkers were not altered significantly in the stomach. Conclusion: MAR extract alters DA and metabolism of 5-HIAA in the brain of young animals infected. Antioxidant capacity may be involved in these effects. SUMMARY The purpose of this study was to measure the effect of Mexican arnica/rosemary water extract and oseltamivir on both biogenic amines and some oxidative biomarkers in the brain and stomach of young rats under infection condition. Results: Mexican arnica and rosemary extract alter dopamine and metabolism of 5-HIAA in the brain of young animals infected. Antioxidant capacity may be involved in these effects. Abbreviations used: AS: Automated system, ATP: Adenosine triphosphate, CNS: Central nervous system, CFU: Colony-forming unit, DA: Dopamine EDTA: Ethylenediaminetetraacetic acid, 5-HIAA: Äcido 5-hidroxindolacético (serotonina), GABA: γ-aminobutyric acid, GSH: Glutathione, H2O2: Hidrogen peroxide, HCLO4: Perchloric acid, iNOS: Inducible nitric oxide synthase, LPS: Lipopolysaccharides, MAR: Arnica/Rosemary, NaCl: Sodium Chloride, NOGSH: nitrosoglutathione, NOS: Nitric oxide, OPT: Ortho-phtaldialdehyde, Pbs: Phosphate buffered saline, pH: potential of Hydrogen, Pi: Inorganic phosphate, ROS: Reactive oxygen species, RNSs: Reactive nitrogen species Tba: Thiobarbaturic acid, TBARS: Thiobarbituric aid reactive, Tca: Trichloroacetic, Tris-HCL: Tris hydrochloride, TSA: Trypticasein Soya Agar PMID:28539708

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

NASA Astrophysics Data System (ADS)

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

2003-08-01

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

Perfil das alterações vasculares periféricas em dependentes de crack acompanhados em Centro de Atenção Psicossocial para Álcool e Drogas (CAPS-AD)

PubMed Central

da Costa, Antônio Fagundes; Baldaçara, Leonardo Rodrigo; da Silva, Sílvio Alves; Tavares, Ana Célia de Freitas Ramos; Orsolin, Ederson de Freitas; Prehl, Vinícius Barros; Gondo, Fernando Hirohito Beltran; Santana, Hernani Lopes

2016-01-01

Resumo Contexto O consumo de crack é um dos grandes desafios em saúde pública, e o uso dessa droga tem efeitos diretos na saúde de seus usuários. Objetivos Avaliar o perfil das alterações vasculares em pacientes com dependência de crack em Centro de Atenção Psicossocial para Álcool e Drogas (CAPS-AD) e observar os possíveis efeitos vasculares periféricos. Métodos Trata-se de um estudo observacional, descritivo, de corte transversal. Os pacientes da amostra foram submetidos a um questionário objetivo para avaliar questões demográficas, padrão de uso da droga, coexistência de diabetes melito, hipertensão arterial ou tabagismo, exame físico e ecográfico. Os dados foram sumarizados e analisados estatisticamente com teste qui-quadrado ou teste exato de Fisher. Resultados A média de idade da amostra foi de 33,29 (±7,15) anos, e 74% eram do gênero masculino. A média de idade de início de uso da droga foi de 23,4 (±7,78) anos, com tempo médio de uso de 9,58 (±5,64) anos. O consumo médio diário de pedras de crack foi de 21,45 (±8,32) pedras. A alteração de pulsos em membros inferiores foi mais frequente em mulheres. A prevalência do espessamento da parede arterial nos membros inferiores foi de 94,8%. O tempo de uso da droga apresentou associação estatística (p = 0,0096) com alteração do padrão de curva espectral das artérias dos membros inferiores. Conclusões Há alterações vasculares periféricas em usuários de crack. O tempo de uso da droga exerceu um maior impacto nesse sistema, o que sugere associação entre o uso do crack e a diminuição de fluxo arterial.

Populações estelares do bojo galáctico

NASA Astrophysics Data System (ADS)

Escudero, A. V.; Costa, R. D. D.; Maciel, W. J.

2003-08-01

Os estudos mais recentes do bojo galáctico têm enfocado essencialmente as abundâncias químicas de elementos pesados, como o ferro, obtidos a partir das estrelas nas regiões centrais da galáxia. Elementos leves, como hélio, nitrogênio, oxigênio e argônio ainda são pouco estudados nestas regiões, devido à difícil determinação de suas abundâncias a partir de estrelas. Nestas condições as nebulosas planetárias desempenham um importante papel, pois permitem a determinação de abundâncias destes elementos usando técnicas de espectroscopia nebular. Neste trabalho, reportamos a análise das abundâncias químicas de uma nova amostra de nebulosas planetárias do bojo, bem como os resultados preliminares de um código numérico destinado a modelar a evolução química desta região. Usamos como vínculos observacionais os resultados obtidos das nebulosas planetárias, bem como de abundâncias estelares da região do bojo, obtidas da literatura. A partir deste modelo da evolução química e dos vínculos observacionais foi possível fazer um diagnóstico mais preciso das populações que constituem o bojo galáctico. O estudo destas populações que compõem a região central de nossa galáxia é de extrema importância para o maior entendimento da evolução química e dinâmica da galáxia como um todo. Por isto, verificamos a importância dos modelos de formação simples e mista utilizados para explicar características da população da região central da galáxia. Algumas destas características são: uma grande dispersão nos valores das abundâncias químicas e um grande espalhamento nas correlações entre as abundâcias de nitrogênio e oxigênio. Estas peculiaridades são dificilmente reproduzidas por modelos de formação simples, e portanto são importantes indícios da validade dos modelos de formação mista, tais como um rápido colapso do bojo seguido de uma evolução secular. (FAPESP, CNPq)

West Europe Report

DTIC Science & Technology

1985-07-15

Lisbon TAL & QUAL in Portuguese 17 May 85 p 3 [Text] Manuel da Costa Bras, Lt Col in the reserves and High Commissioner against Corruption, is facing...people around Gen Eanes, starting with Lt Col Melo Antunes. The PRD itself has already announced many times that it would not oppose such an

32 CFR 516.28 - Policy.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 3 2011-07-01 2009-07-01 true Policy. 516.28 Section 516.28 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS... current or former DA personnel who face criminal charges or civil litigation in their individual capacity...

A nitric oxide burst precedes apoptosis in angiosperm and gymnosperm callus cells and foliar tissues.

PubMed

Pedroso, M C; Magalhaes, J R; Durzan, D

2000-06-01

Leaves and callus of Kalanchoë daigremontiana and Taxus brevifolia were used to investigate nitric oxide-induced apoptosis in plant cells. The effect of nitric oxide (NO) was studied by using a NO donor, sodium nitroprusside (SNP), a nitric oxide-synthase (NOS) inhibitor, N:(G)-monomethyl-L-arginine (NMMA), and centrifugation (an apoptosis-inducing treatment in these species). NO production was visualized in cells and tissues with a specific probe, diaminofluorescein diacetate (DAF-2 DA). DNA fragmentation was detected in situ by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) method. In both species, NO was detected diffused in the cytosol of epidermal cells and in chloroplasts of guard cells and leaf parenchyma cells. Centrifugation increased NO production, DNA fragmentation and subsequent cell death by apoptosis. SNP mimicked centrifugation results. NMMA significantly decreased NO production and apoptosis in both species. The inhibitory effect of NMMA on NO production suggests that a putative NOS is present in Kalanchoë and Taxus cells. The present results demonstrated the involvement of NO on DNA damage leading to cell death, and point to a potential role of NO as a signal molecule in these plants.

Inhibitory effect of Styrax Japonica Siebold et al. Zuccarini glycoprotein (38 kDa) on interleukin-1β and induction proteins in chromium(VI)-treated BNL CL.2 cells.

PubMed

Lee, Jin; Lim, Kye-Taek

2012-08-01

Chromium(VI) [Cr(VI)] induces chronic inflammation in hepatocytes. Inflammation has been shown to play an important role in tumorigenesis, tumor progression, and metastasis. To examine the effects of the Styrax Japonica Siebold et al. Zuccarini (SJSZ) glycoprotein on inflammation in BNL CL.2 cells, we evaluated the activities of c-Jun NH(2)-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), nuclear factor (NF)-κB (p50 and p65), and inflammation-related factors [cyclooxygenase (COX)-2, inducible nitric oxide syntheses (iNOS) and interleukin (IL)-1β] in Cr-induced BNL CL.2 cells using immunoblot analysis and RT-PCR. We also used two-dimensional gel electrophoresis (2-DE) to compare between treatments. To determine which proteins are induced by Cr(VI), we evaluated total protein lysates using 2-DE. After Cr(VI) treatment, total protein lysates were prepared and resolved by 2-DE. The results obtained from this study demonstrated that the SJSZ glycoprotein (50 μg/ml) inhibits expression of JNK, ERK, NF-κB, and the expression of COX-2, iNOS, and IL-1β. Moreover, the results obtained from 2DE showed that four proteins out of nine proteins were relatively expressed strongly, while the rest of them were relatively appeared weakly on the gel. Taken together, these data indicate that the SJSZ glycoprotein prevents expression of COX-2, iNOS, and IL-1β by blocking NF-κB and MAPKs in Cr(VI)-induced BNL CL.2 cells.

Orofacial esthetics and dental anxiety: associations with oral and psychological health.

PubMed

Carlsson, Viktor; Hakeberg, Magnus; Blomkvist, Klas; Wide Boman, Ulla

2014-11-01

Severe dental anxiety (DA) is associated with both oral health and psychosocial consequences in what has been described as a vicious circle of DA. The aim of this study was to investigate self-rated orofacial esthetics in patients with DA and its relationship to psychological and oral health. A consecutive sample of 152 adult patients who were referred or self-referred to a specialized dental anxiety clinic filled out the Orofacial Esthetic Scale (OES) as well as measurements on DA, self-rated oral health and general anxiety and depression. Clinical measures of dental status were also obtained. Compared with the general population, patients with DA had lower ratings of satisfaction on all aspects of their orofacial esthetics, which included the teeth, gingiva, mouth and face, as well as a global orofacial assessment. Furthermore, the perception of the orofacial appearance was related both to dental status and self-rated oral health, as well as to general anxiety and depression. The level of dissatisfaction with the orofacial appearance was similar for both genders, but women reported more regular dental care and better dental status. The results of this study clearly show less satisfaction with dental and facial appearance in patients with DA, and that the self-rating of orofacial esthetics is related to both oral and psychological health. The OES can be used to assess orofacial esthetics in patients with DA.

Medical Students' Death Anxiety: Severity and Association With Psychological Health and Attitudes Toward Palliative Care.

PubMed

Thiemann, Pia; Quince, Thelma; Benson, John; Wood, Diana; Barclay, Stephen

2015-09-01

Death anxiety (DA) is related to awareness of the reality of dying and death and can be negatively related to a person's psychological health. Physicians' DA also may influence their care for patients approaching death. Doctors face death in a professional context for the first time at medical school, but knowledge about DA among medical students is limited. This study examined medical students' DA in relation to: 1) its severity, gender differences, and trajectory during medical education and 2) its associations with students' attitudes toward palliative care and their psychological health. Four cohorts of core science and four cohorts of clinical students at the University of Cambridge Medical School took part in a questionnaire survey with longitudinal follow-up. Students who provided data on the revised Collett-Lester Fear of Death Scale were included in the analysis (n = 790). Medical students' DA was moderate, with no gender differences and remained very stable over time. High DA was associated with higher depression and anxiety levels and greater concerns about the personal impact of providing palliative care. The associations between high DA and lower psychological health and negative attitudes toward palliative care are concerning. It is important to address DA during medical education to enhance student's psychological health and the quality of their future palliative care provision. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Reconstrução tridimensional de arcos magnéticos por tomografia

NASA Astrophysics Data System (ADS)

Simões, P. J. A.; Costa, J. E. R.

2003-08-01

Uma explosão solar é uma variação súbita do brilho que ocorre nas regiões ativas da atmosfera solar. Estas regiões são constituídas por um plasma magnetizado com intensa indução magnética e em cenários bem complexos como visto recentemente através de experimentos embarcados em satélites operando instrumentos em raios X moles e ultra-violeta distante. A energia magnética, que pode ser armazenada por um período de horas até dias em configurações magnéticas estressadas, é subitamente lançada na atmosfera solar e transferida para partículas como elétrons, prótons e núcleos pesados, que são acelerados e/ou aquecidos, produzindo radiação eletromagnética. A proposta final deste projeto é determinar as características espaciais de alta resolução da emissão e polarização girossincrotrônica de explosões solares em ambientes complexos de campos magnéticos. Os recentes resultados da emissão difusa em EUV apresentado pelos satélites TRACE e SOHO dos arcos magnéticos conectando as diferentes polaridades magnéticas sobre as regiões ativas possibilitam novas abordagens sobre o papel do campo magnético na emissão em rádio. Nesta etapa apresentamos os resultados da reconstrução da geometria tridimensional das linhas de força destes arcos utilizando técnicas tomográficas, a partir de imagens de alta resolução espacial obtidas pelo instrumento EIT (Extreme ultraviolet Imaging Telescope), além da modelagem das induções magnéticas por um campo dipolar e as densidades de partículas aceleradas. Utilizamos para a reconstrução geométrica, imagens tomadas em vários ângulos dos arcos devido à rotacão solar. Com estes resultados, daremos continuidade ao projeto, com os cálculos da transferência radiativa nos modos ordinário e extraordinário de propagação da radiação girossincrotrônica de explosões solares.

Tendências de teses e dissertações sobre ensino de astronomia no Brasil

NASA Astrophysics Data System (ADS)

Bretones, P. S.; Megid Neto, J.

2003-08-01

Neste trabalho são apresentados os resultados de uma pesquisa do tipo estado da arte sobre teses e dissertações defendidas no Brasil e relativas ao ensino de Astronomia. Teve por objetivo identificar essa produção e conhecer as principais tendências da pesquisa nesse campo. O procedimento inicial consistiu de um levantamento bibliográfico junto ao Centro de Documentação em Ensino de Ciências (CEDOC) da Faculdade de Educação da UNICAMP e ao Banco de Teses da CAPES disponível na Internet. Foram localizadas 13 dissertações de mestrado e 3 teses de doutorado, as quais foram estudadas em função dos seguintes aspectos: instituição, ano de defesa, nível escolar abrangido no estudo, foco temático do estudo e gênero de trabalho acadêmico. Deste conjunto de pesquisas, 13 (81,3%) delas foram defendidas a partir da segunda metade dos anos 90, indicando uma preocupação mais recente com temas relativos ao ensino de Astronomia no conjunto da produção acadêmica em programas de pós-graduação no Brasil. Verificou-se que 43,7% dos trabalhos foram produzidas na USP e 18,8% na UNICAMP. Quanto ao nível escolar abrangido nos estudos, predominaram os estudos direcionados ao Ensino Fundamental de 5a a 8a séries (62,5%). No que diz respeito ao foco temático das pesquisas, as principais tendências voltaram-se: 56,3% para Conteúdo e Método; 43,8% para Concepções do Professor; 37,5% para Currículo e Programas; 37,5% para Recursos Didáticos. Quanto ao gênero de trabalho acadêmico, verificou-se que 43,8% são de Pesquisa Experimental e 31,3% de Pesquisa de Análise de Conteúdo. Estudos de revisão bibliográfica como este visam colaborar com a divulgação ampla da produção acadêmica em determinada área, traçando algumas de suas tendências. Ao mesmo tempo possibilita, a partir de investigações decorrentes, apontar as suas contribuições para o ensino e sinalizar com necessidades a serem supridas por futuras pesquisas.

Avaliação dos efeitos do subgalato de bismuto na proliferação de miofibroblastos

PubMed Central

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

2016-01-01

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

Angiolymphatic invasion as a prognostic fator in resected N0 pancreatic adenocarcinoma.

PubMed

Almeida, Ricardo Vitor Silva de; Pacheco, Adhemar Monteiro; Silva, Rodrigo Altenfelder; Moricz, André de; Campos, Tércio de

2017-01-01

Pancreatic adenocarcinoma remains one of the worst digestive cancers. Surgical resection is the main target when treating a patient with curative intent. To assess angiolymphatic invasion as a prognostic factor in resected pN0 pancreatic cancer. Thirty-eight patients were submitted to pancreatoduodenectomy due to head pancreatic cancer. Tumor size, margins, lymph nodes, pTNM staging, angiolymphatic and perineural invasion were described in the pathologists' reports. Most patients were female. Overall median survival was 13 months. Gemcitabine was the regimen of choice for chemotherapy in selected patients; however, it did not improve overall survival. pR0 resection had better survival compared with pR1. Within the pN0 group, survival was significantly better in patients without angiolymphatic invasion. Angiolymphatic invasion in N0 pancreatoduodenectomy can be demonstrated by the Hematoxylin-Eosin stain and may predict a poor prognosis factor for those patients. Adenocarcinoma pancreático continua sendo um dos piores cânceres do aparelho digestivo. A ressecção cirúrgica é o principal objetivo quando se trata de intenção curativa. Avaliar a invasão angiolinfática como um fator prognóstico no câncer da cabeça do pâncreas ressecado pN0. Trinta e oito pacientes foram submetidos a duodenopancreatectomia por câncer da cabeça do pâncreas. Tamanho do tumor, margens, linfonodos, estadiamento pTNM, invasão angiolinfática e perineural foram descritos nos laudos anatomopatológicos. A maioria foi de mulheres. A sobrevida mediana global foi de 13 meses. Gencitabina foi a droga de escolha para quimioterapia nos pacientes selecionados, entretanto não aumentou a sobrevida global. Pacientes com ressecção pR0 tiveram sobrevida global superior quando comparados com ressecção pR1. Dentro do grupo de pacientes com pN0, a sobrevida foi significativamente melhor no grupo de pacientes que não apresentavam invasão angiolinfática. A invasão angiolinfática da duodenopancreatectomia N0 pode ser demonstrada utilizando apenas a hematoxilina-eosina e pode predizer prognóstico ruim para estes pacientes.

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

PubMed

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

2017-09-01

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

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

PubMed

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

2017-01-01

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

Elderly with knee osteoarthritis should perform nutritional assessment: integrative literature review.

PubMed

Souza, Isabelle Ferreira da Silva; Oliveira Neta, Rosa Sá de; Gazzola, Juliana Maria; Souza, Marcelo Cardoso de

2017-01-01

To review scientific literature to assess nutritional status of elderly patients with osteoarthritis in the last 16 years. This is an integrative literature review that included articles published in national and international journals indexed in PubMed, SciELO and BIREME. We selected 14 articles, and English language was predominant. The year of publication of articles ranged from 2006 to 2016, and most of papers were cross-sectional studies. To gather papers and for posterior evaluate, we used a validated data collection instrument and the included studies were critical analyzed by reading, gathering and analysis of articles. Studies suggested that there is a positive correlation between obesity and knee osteoarthritis. Obesity is one of the most important modifiable factors in worsening of osteoarthritis symptoms. RESUMO O objetivo da pesquisa foi revisar a produção científica referente à avaliação do estado nutricional de idosos com osteoartrite nos últimos 16 anos. Assim, o estudo foi uma revisão integrativa da literatura, realizada com a busca de artigos publicados em periódicos nacionais e internacionais indexados no PubMed, na SciELO e na BIREME. Foram selecionados 14 artigos, e o idioma inglês foi preponderante. O período de publicação dos artigos variou de 2006 a 2016, com predominância de estudos do tipo transversais. Para reunir os artigos e para posterior avaliação, foi utilizado um instrumento de coleta de dados validado, e as análises críticas dos estudos incluídos foram realizadas por meio da leitura, do agrupamento e da análise dos artigos. As pesquisas sugeriram que existe correlação positiva entre obesidade e osteoartrite de joelhos. Além disto, a obesidade é um dos fatores mais significativos e modificáveis no agravamento dos sintomas da osteoartrite.

Determinação da massa de júpiter a partir das órbitas de seus satélites: um experimento didático

NASA Astrophysics Data System (ADS)

Schlickmann, M. S.; Saito, R. K.; Becker, D. A.; Rezende, M. F., Jr.; Cid Fernandes, R.

2003-08-01

Este trabalho apresenta o roteiro piloto de uma prática observacional em astronomia, junto com os primeiros resultados obtidos nesta fase de implementacão. O projeto, que será executado em duas etapas, visa introduzir noções de Astronomia a alunos do Ensino Médio e iniciantes nos cursos de Física. O experimento consiste em medir as órbitas dos satélites Galileanos e, a partir da análise dos dados coletados, verificar a validade da Lei das órbitas de Kepler, determinando a massa do planeta Júpiter. Em uma primeira etapa, as observações serão feitas utilizando um telescópio Meade LX200 10" e câmera CCD para obter uma seqüência de imagens do planeta, que possibilitará medir o movimento de seus satélites. A segunda etapa terá início a partir do funcionamento do telescópio em modo robótico, com a possibilidade de observações via internet por instituições de ensino. Para o desenvolvimento deste experimento foram inicialmente coletadas várias imagens de Júpiter obtidas com os instrumentos citados acima. Estas imagens serviram como base para confecção dos roteiros para a experiência no nível médio e superior. Os roteiros serão inicialmente apresentados em uma home-page. Nela também se buscará uma contextualização histórica da experiência bem como o estabelecimento de relações com professores e alunos, propostas metodológicas e a disponibilização dos programas computacionais necessários para a utilização "on-line" pelos usuários. O projeto conta com apoio da Fundação VITAE.

Dopamine signaling and myopia development: What are the key challenges.

PubMed

Zhou, Xiangtian; Pardue, Machelle T; Iuvone, P Michael; Qu, Jia

2017-11-01

In the face of an "epidemic" increase in myopia over the last decades and myopia prevalence predicted to reach 2.5 billion people by the end of this decade, there is an urgent need to develop effective and safe therapeutic interventions to slow down this "myopia booming" and prevent myopia-related complications and vision loss. Dopamine (DA) is an important neurotransmitter in the retina and mediates diverse functions including retina development, visual signaling, and refractive development. Inspired by the convergence of epidemiological and animal studies in support of the inverse relationship between outdoor activity and risk of developing myopia and by the close biological relationship between light exposure and dopamine release/signaling, we felt it is timely and important to critically review the role of DA in myopia development. This review will revisit several key points of evidence for and against DA mediating light control of myopia: 1) the causal role of extracellular retinal DA levels, 2) the mechanism and action of dopamine D1 and D2 receptors and 3) the roles of cellular/circuit retinal pathways. We examine the experiments that show causation by altering DA, DA receptors and visual pathways using pharmacological, transgenic, or visual environment approaches. Furthermore, we critically evaluate the safety issues of a DA-based treatment strategy and some approaches to address these issues. The review identifies the key questions and challenges in translating basic knowledge on DA signaling and myopia from animal studies into effective pharmacological treatments for myopia in children. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Evaluation of the implementation of the directly observed treatment strategy for tuberculosis in a large city.

PubMed

Lavôr, Débora Cristina Brasil da Silva; Pinheiro, Jair Dos Santos; Gonçalves, Maria Jacirema Ferreira

2016-04-01

To assess the degree of implementation of the Directly Observed Treatment, Short-course - DOTS for tuberculosis (TB) in a large city. Assessment of the implementation of the logic model, whose new cases of infectious pulmonary TB were recruited from specialized clinics and followed-up in basic health units. The judgment matrix covering the five components of the DOTS strategy were used. The result of the logic model indicates DOTS was partially implemented. In external, organizational and implementation contexts, the DOTS strategy was partially implemented; and, the effectiveness was not implemented. The partial implementation of the DOTS strategy in the city of Manaus did not reflect in TB control compliance, leading to low effectiveness of the program. Avaliar o grau de implantação da estratégia de tratamento diretamente observado (Directly Observed Treatment, Short-course - DOTS) para tuberculose (TB) em um município de grande porte. Avaliação de implantação por meio de modelo lógico, cujos casos novos de TB pulmonar bacilífera foram recrutados em ambulatórios especializados e acompanhados nas unidades básicas de saúde. Utilizou-se matriz de julgamento que abrange os cinco componentes da estratégia DOTS. O resultado do modelo lógico indica DOTS implantada parcialmente. Nos contextos externo, organizacional e de implantação, a estratégia DOTS está implantada parcialmente; e, na efetividade não está implantada. A implantação parcial da estratégia DOTS, na cidade de Manaus, reflete na não conformidade do controle da TB, levando à baixa efetividade do programa.

BRAZILIAN CONSENSUS FOR MULTIMODAL TREATMENT OF COLORECTAL LIVER METASTASES. MODULE 3: CONTROVERSIES AND UNRESECTABLE METASTASES.

PubMed

Torres, Orlando Jorge Martins; Marques, Márcio Carmona; Santos, Fabio Nasser; Farias, Igor Correia de; Coutinho, Anelisa Kruschewsky; Oliveira, Cássio Virgílio Cavalcante de; Kalil, Antonio Nocchi; Mello, Celso Abdon Lopes de; Kruger, Jaime Arthur Pirola; Fernandes, Gustavo Dos Santos; Quireze, Claudemiro; Murad, André M; Silva, Milton José de Barros E; Zurstrassen, Charles Edouard; Freitas, Helano Carioca; Cruz, Marcelo Rocha; Weschenfelder, Rui; Linhares, Marcelo Moura; Castro, Leonaldson Dos Santos; Vollmer, Charles; Dixon, Elijah; Ribeiro, Héber Salvador de Castro; Coimbra, Felipe José Fernandez

2016-01-01

In the last module of this consensus, controversial topics were discussed. Management of the disease after progression during first line chemotherapy was the first discussion. Next, the benefits of liver resection in the presence of extra-hepatic disease were debated, as soon as, the best sequence of treatment. Conversion chemotherapy in the presence of unresectable liver disease was also discussed in this module. Lastly, the approach to the unresectable disease was also discussed, focusing in the best chemotherapy regimens and hole of chemo-embolization. RESUMO Neste último módulo do consenso, abordou-se alguns temas controversos. O primeiro tópico discutido foi o manejo da doença após progressão na primeira linha de quimioterapia, com foco em se ainda haveria indicação cirúrgica neste cenário. A seguir, o painel debruçou-se sobre as situações de ressecção da doença hepática na presença de doença extra-hepática, assim como, qual a melhor sequência de tratamento. O tratamento de conversão para doença inicialmente irressecável também foi abordado neste módulo, incluindo as importantes definições de quando se pode esperar que a doença se torne ressecável e quais esquemas terapêuticos seriam mais efetivos à luz dos conhecimentos atuais sobre a biologia tumoral e taxas de resposta objetiva. Por último, o tratamento da doença não passível de ressecção foi discutida, focando-se nos melhores esquemas a serem empregados e seu sequenciamento, bem como o papel da quimioembolização no manejo destes pacientes.

Peculiaridades observadas no espectro da estrela magnética HD 190073 - candidata a estrela do tipo Ae de Herbig

NASA Astrophysics Data System (ADS)

Franco, G. A. P.; Pogodin, M. A.; Lopes, D. F.

2003-08-01

Apresentaremos os resultados de uma investigação espectroscópica cooperativa da estrela magnética HD 190073. As observações foram conduzidas no Observatório do Pico dos Dias (LNA/MCT), European Southern Observatory (ESO, Chile), e Crimean Astrophysical Observatory (CrAO, Ucrânia), entre 1998 e 2002. Discutiremos em detalhe um dos padrões mais marcantes do espectro desse objeto - as multicomponentes em absorção das linhas Ca ii K e H. De acordo com nossos resultados, a estrutura complexa desse perfil permaneceu constante durante várias decadas (dos anos 30 até os anos 80) após o que apresentou mudanças marcantes nos anos 90. Essa variabilidade apresenta óbvia contradição com a interpretação tradicional desse fenômeno como o resultado de espalhamento ressonante atuando seletivamente sobre o vento estelar em distâncias diferentes. Propomos uma explicação alternativa com base em uma topologia especí fica do campo magnético estelar. Essa hipótese permite, também, explicar uma série de outras peculiaridades observadas no envoltório de HD 190073, tais como: (a) a baixa velocidade de rotação pode ser o resultado da interação entre a magnetosfera estelar e um disco equatorial hipotético; (b) o gás circumstelar acumulado em loops magnéticos em latitudes intermediárias pode estimular a formação de regiões gasosas densas a distâncias intermediárias da estrela, onde linhas em emissão com perfil simples são formadas.

High molecular weight glutenin subunits in some durum wheat cultivars investigated by means of mass spectrometric techniques.

PubMed

Muccilli, Vera; Lo Bianco, Marisol; Cunsolo, Vincenzo; Saletti, Rosaria; Gallo, Giulia; Foti, Salvatore

2011-11-23

The primary structures of high molecular weight glutenin subunits (HMW-GS) of 5 Triticum durum Desf. cultivars (Simeto, Svevo, Duilio, Bronte, and Sant'Agata), largely cultivated in the south of Italy, and of 13 populations of the old spring Sicilian durum wheat landrace Timilia (Triticum durum Desf.) (accession nos. 1, 2, 3, 4, 7, 8, 9, 13, 14, 15, SG1, SG2, and SG3) were investigated using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) and reversed-phase high performance liquid chromatography/nanoelectrospray ionization mass spectrometry (RP-HPLC/nESI-MS/MS). M(r) of the intact proteins determined by MALDI mass spectrometry showed that all the 13 populations of Timilia contained the same two HMW-GS with 75.2 kDa and 86.4 kDa, whereas the other durum wheat cultivars showed the presence of the expected HMW-GS 1By8 and 1Bx7 at 75.1 kDa and 83.1 kDa, respectively. By MALDI mass spectrometry of the tryptic digestion peptides of the isolated HMW-GS of Timilia, the 1Bx and 1By subunits were identified as the NCBInr Acc. No AAQ93629, and AAQ93633, respectively. Sequence verification for HMW-GS 1Bx and 1By both in Simeto and Timilia was obtained by MALDI mass mapping and HPLC/nESI-MSMS of the tryptic peptides. The Bx subunit of Timila presents a sequence similarity of 96% with respect to Simeto, with differences in the insertion of 3 peptides of 5, 9, and 15 amino acids, for a total insertion of 29 amino acids and 25 amino acid substitutions. These differences in the amino acidic sequence account for the determined Δm of 3294 Da between the M(r) of the 1Bx subunits in Timilia and Simeto. Sequence alignment between the two By subunits shows 10 amino acid substitutions and is consistent with the Δm of 148 Da found in the MALDI mass spectra of the intact subunits.

Characterisation of gas and particle emissions from wildfires =

NASA Astrophysics Data System (ADS)

Vicente, Ana Margarida Proenca

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

Risk factors for cardiovascular disease in patients with COPD: mild-to-moderate COPD versus severe-to-very severe COPD.

PubMed

Caram, Laura Miranda de Oliveira; Ferrari, Renata; Naves, Cristiane Roberta; Coelho, Liana Sousa; Vale, Simone Alves do; Tanni, Suzana Erico; Godoy, Irma

2016-01-01

To assess and compare the prevalence of comorbidities and risk factors for cardiovascular disease (CVD) in COPD patients according to disease severity. The study included 25 patients with mild-to-moderate COPD (68% male; mean age, 65 ± 8 years; mean FEV1, 73 ± 15% of predicted) and 25 with severe-to-very severe COPD (males, 56%; mean age, 69 ± 9 years; mean FEV1, 40 ± 18% of predicted). Comorbidities were recorded on the basis of data obtained from medical charts and clinical evaluations. Comorbidities were registered on the basis of data obtained from medical charts and clinical evaluations. The Charlson comorbidity index was calculated, and the Hospital Anxiety and Depression Scale (HADS) score was determined. Of the 50 patients evaluated, 38 (76%) had been diagnosed with at least one comorbidity, 21 (42%) having been diagnosed with at least one CVD. Twenty-four patients (48%) had more than one CVD. Eighteen (36%) of the patients were current smokers, 10 (20%) had depression, 7 (14%) had dyslipidemia, and 7 (14%) had diabetes mellitus. Current smoking, depression, and dyslipidemia were more prevalent among the patients with mild-to-moderate COPD than among those with severe-to-very severe COPD (p < 0.001, p = 0.008, and p = 0.02, respectively). The prevalence of high blood pressure, diabetes mellitus, alcoholism, ischemic heart disease, and chronic heart failure was comparable between the two groups. The Charlson comorbidity index and HADS scores did not differ between the groups. Comorbidities are highly prevalent in COPD, regardless of its severity. Certain risk factors for CVD, themselves classified as diseases (including smoking, dyslipidemia, and depression), appear to be more prevalent in patients with mild-to-moderate COPD. Avaliar e comparar a prevalência de comorbidades e de fatores de risco de doença cardiovascular (DCV) em pacientes com DPOC de acordo com a gravidade da doença. O estudo incluiu 25 pacientes com DPOC leve/moderada (homens: 68%; média de idade: 65 ± 8 anos; média de VEF1: 73 ± 15% do previsto) e 25 com DPOC grave/muito grave (homens: 56%; média de idade: 69 ± 9 anos; média de VEF1, 40 ± 18% do previsto). As comorbidades foram registradas com base nos dados dos prontuários médicos e avaliações clínicas. O índice de comorbidades de Charlson foi calculado, e a pontuação na Hospital Anxiety and Depression Scale (HADS) foi determinada. Dos 50 pacientes avaliados, 38 (76%) receberam diagnóstico de pelo menos uma comorbidade, sendo que 21 (42%) receberam diagnóstico de pelo menos uma DCV. Vinte e quatro pacientes (48%) apresentavam mais de uma DCV. Dezoito pacientes (36%) eram fumantes, 10 (20%) tinham depressão, 7 (14%) apresentavam dislipidemia, e 7 (14%) tinham diabetes mellitus. Tabagismo atual, depressão e dislipidemia foram mais prevalentes nos pacientes com DPOC leve/moderada que naqueles com DPOC grave/muito grave (p < 0,001, p = 0,008 e p = 0,02, respectivamente). A prevalência de pressão arterial elevada, diabetes mellitus, alcoolismo, doença isquêmica do coração e insuficiência cardíaca crônica foi semelhante nos dois grupos. O índice de comorbidades de Charlson e a pontuação na HADS não diferiram entre os grupos. Comorbidades são muito prevalentes na DPOC, independentemente da gravidade da doença. Certos fatores de risco de DCV, eles próprios considerados doenças (incluindo tabagismo, dislipidemia e depressão), parecem ser mais prevalentes nos pacientes com DPOC leve/moderada.

Effects of methylphenidate during emotional processing in amphetamine users: preliminary findings.

PubMed

Bottelier, M A; Schouw, M L J; de Ruiter, M B; Ruhe, H G; Lindauer, R J L; Reneman, L

2015-12-01

D-amphetamine (dAMPH) and methylphenidate (MPH) are stimulants used in the treatment of Attention Deficit Hyperactivity Disorder (ADHD). Preclinical studies have shown that in healthy animals, dAMPH induces dopamine (DA) dysfunction, as evidenced for instance by loss of DA levels and its transporters. It has also been suggested that DA plays an important role in emotional processing, and that altered DA-ergic intervention may modulate amygdala function. To explore the role of the DA system in emotional processing we examined emotional processing using functional magnetic resonance imaging (fMRI) in eight male recreational users of dAMPH and eight male healthy controls. We compared brain activation between both groups during an emotional face-processing task with and without an oral MPH challenge. All subjects were abstinent for at least 2 weeks during the baseline scan. The second scan was performed on the same day 1½ hours after receiving an oral dose of 35 mg MPH. A significant Valence*Group interaction (p = .037) indicated amygdala hyperreactivity to fearful facial expressions in dAMPH users that was robust against adjustment for age (p = .015). Furthermore, duration of amphetamine use in years was positively correlated with amygdala reactivity in dAMPH users (r = .76; p = .029). These exploratory findings are in line with previous findings suggesting that DA plays a role in emotional processing.

Estriol-induced fibrinolysis due to the activation of plasminogen to plasmin by nitric oxide synthesis in platelets.

PubMed

Jana, Pradipta; Maiti, Smarajit; Kahn, Nighat N; Sinha, Asru K

2015-04-01

Estriol, an oestrogen, at 0.6 nmol/l was reported to inhibit ADP-induced platelet aggregation through nitric oxide synthesis. As nitric oxide has been reported to cause fibrinolysis due to the activation of plasminogen to plasmin, the role of estriol as a fibrinolytic agent was investigated. Also, the mechanism of estriol-induced nitric oxide synthesis in anucleated platelets was investigated. The estriol-induced lysis of platelet-rich plasma (PRP) clot was determined by photography of the clot lysis and by the assay of fibrin degradation products in the lysate and was obtained by SDS-PAGE. Nitric oxide was determined by methemoglobin method. The platelet membrane protein was isolated from the platelets by using Triton X-100 (0.05% v/v). The binding of estriol to the protein was determined by Scatchard plot by using an ELISA for estriol. Estriol at 0.6 nmol/l was found to lyse the clotted PRP due to fibrinolysis that produced fibrin degradation products in the lysate. The amino acid analysis of the platelet membrane protein, which resembles with nitric oxide synthase (NOS) activity, was activated nearly 10-fold over the control in the presence of estriol and was identified to be a human serum albumin precursor (Mr. 69 kDa) that binds to estriol with Kd1 of 6.0 × 10 mol/l and 39 ± 2 molecules of estriol bound the NOS molecule. The estriol-induced nitric oxide is capable of inducing fibrinolysis of the clotted PRP. The binding of estriol to platelet membrane NOS activated the enzyme in the absence of DNA in the platelet.

Health Policy on the pages of Revista de Saúde Pública.

PubMed

Bousquat, Aylene; Tanaka, Oswaldo Yoshimi

2016-11-10

We carried out a narrative review of the scientific production in the area of Policy, Planning and Management in Revista de Saúde Pública (RSP), between 1967 and 2015. All the fascicles of RSP, in the period, were accessed via SciELO platform, which provides all articles online. We selected and classified the articles according to the main topics of scientific production in the area of Policy, Planning and Management. Revista de Saúde Pública has published 343 articles on this subject, with significant growth in the last two decades. The most discussed topics were Health Economics, Primary Health-care, Access and Use of Health Services, and Evaluation of Services and Programs. In the last decade, the topics of Policy and Access to Medicines and Public-Private Relationship, including judicialization, gained importance. The pages of RSP embraced the vast and diverse production of Policy, Planning and Management in its first 50 years, contributing to the consolidation of the area in Brazil. RESUMO Foi realizada revisão narrativa da produção científica do campo de Política, Planejamento e Gestão veiculada na Revista de Saúde Pública (RSP), entre 1967 e 2015. Todos os fascículos da RSP, no período, foram acessados via plataforma SciELO, que disponibiliza todos os artigos online. Foram selecionados e classificados os artigos segundo os principais temas da produção científica da área de Política, Planejamento e Gestão. Foram publicados 343 artigos, com crescimento expressivo nas últimas duas décadas. Economia da Saúde, Atenção Primária à Saúde, Acesso e Utilização de Serviços de Saúde e Avaliação de Serviços e Programas foram os temas mais abordados. Na última década, os temas Política e Acesso a Medicamentos e Relação Público-Privado, incluindo a judicialização, ganharam importância. As páginas da RSP abrigaram vasta e diversa produção de Política, Planejamento e Gestão nos seus primeiros 50 anos, contribuindo para consolidação da área no Brasil.

Evaluation of the performance of actions and outcomes in primary health care.

PubMed

Miclos, Paula Vitali; Calvo, Maria Cristina Marino; Colussi, Claudia Flemming

2017-01-01

The objective of this study has been to evaluate the performance of the primary care of Brazilian municipalities in relation to health actions and outcomes. This is an evaluative, cross-sectional research, with a quantitative approach, aimed at the identification of the efficiency frontier of the primary care in health actions and outcomes in Brazilian municipalities. Secondary data have been collected from the Programa Nacional de Melhoria do Acesso e da Qualidade da Atenção Básica (National Program for Improving Access and Quality of Primary Care) and the Department of Informatics of the Brazilian Unified Health System, in 2012. The data envelopment analysis tool has been used for variable returns to scale with product orientation. Municipalities have been analyzed by population size, and small municipalities have presented a high percentage of inefficiency for both models. The analysis of efficiency has indicated the existence of a higher percentage of effective municipalities in the model of health actions than in the model of health outcomes. Avaliar o desempenho da atenção básica dos municípios brasileiros quanto a ações e resultados em saúde. Pesquisa avaliativa, transversal, com abordagem quantitativa, para identificar a fronteira de eficiência da atenção básica em ações e resultados em saúde nos municípios brasileiros. Foi realizada coleta de dados secundários a partir do Programa Nacional de Melhoria do Acesso e da qualidade da Atenção Básica e do Departamento de Informática do Sistema Único de Saúde, no ano de 2012. Utilizou-se a ferramenta análise envoltória de dados para retornos variáveis de escala com orientação para produto. Os municípios foram analisados por porte populacional e verificou-se que para ambos os modelos, os municípios de pequeno porte apresentaram alto percentual de ineficiência. A análise da eficiência indicou a existência de um percentual maior de municípios eficientes no modelo de ações em saúde do que no modelo de resultados em saúde.

A atuação do Observatório Nacional registrada nos relatórios ministeriais 1889 a 1930

NASA Astrophysics Data System (ADS)

Rodrigues, T.

2003-08-01

O período republicano até 1930 foi marcante na história do Observatório Nacional. Diversas reformas levaram a instituição a três ministérios diferentes e mudaram a ênfase do seu trabalho. A tão aguardada mudança para uma nova sede, em São Cristóvão, em 1920, não foi suficiente para que a instituição acompanhasse o ritmo tomado pela astronomia no mundo e se firmasse como ambiente de pesquisa. Uma análise simplificada poderia caracterizar um período de produção científica insignificante, dado o distanciamento da instituição dos novos rumos da astrofísica e da rápida inovação dos instrumentos, além do pequeno volume de publicações. Era uma época em que ainda não existiam os mecanismos formais de apoio e avaliação da atividade científica. Esse trabalho procura identificar a real atividade do Observatório no conteúdo dos Relatórios Ministeriais que, ao final de cada ano, apresentava as atividades, sucessos e problemas enfrentados pela instituição. Questões como instrumental e recursos humanos necessários; entraves burocráticos e financeiros; e articulações com outros observatórios se complementaram entre si ao longo desses anos para definir o perfil institucional e alguns aspectos fundamentais para a construção da astronomia no país. É possível concluir que a ênfase em serviços geográficos e de meteorologia, ao lado da inadequação dos instrumentos e do local, quase fizeram desaparecer a pesquisa em astronomia. Porém, vale destacar a sobrevivência de alguns trabalhos, como, por exemplo, variação de latitude e observação de estrelas duplas que mantiveram importante intercâmbio com outros grupos de pesquisa, demonstrando o constante esforço dos astrônomos e das diretorias em defesa da atividade científica.

Possible role of the 38 kDa protein, lacking in the gastrula-arrested Xenopus mutant, in gastrulation.

PubMed

Tanaka, Tetsuya S; Ikenishi, Kohji

2002-02-01

An acidic, 38 kDa protein that is present in Xenopus wild-type embryos has been previously shown to be lacking in gastrula-arrested mutant embryos. To gain understanding of the role of this protein, its spatio-temporal distribution and involvement in gastrulation was investigated using the monoclonal antibody (9D10) against it. The protein was prominent in the cortical cytoplasm of cells facing the outside in the animal hemisphere of embryos until the gastrula stage, and in ciliated epithelial cells of embryos at stages later than the late neurula. When the 9D10 antibody was injected into fertilized wild-type eggs, they cleaved normally, but most of them had arrested development, always at the early stage of gastrulation, as in the mutant embryos. In contrast, the majority of the control antibody-injected eggs gastrulated normally and developed further. Cytoskeletal F-actin, which was mainly observed in the area beneath the plasma membrane facing the outside of the epithelial layer of not only the dorsal involuting marginal zone but also the dorsal, vegetal cell mass of the control antibody-injected embryos at the early gastrula stage, was scarcely recognized in the corresponding area of the 9D10 antibody-injected embryos. It is likely that the paucity of the F-actin caused by the 9D10 antibody inhibition of the 38 kDa protein might lead to a failure of cell movement in gastrulation, resulting in developmental arrest.

Characterization and Anti-Inflammatory Potential of an Exopolysaccharide from Submerged Mycelial Culture of Schizophyllum commune

PubMed Central

Du, Bin; Yang, Yuedong; Bian, Zhaoxiang; Xu, Baojun

2017-01-01

Background and Purpose: Mushroom polysaccharides have attracted attention in food and pharmacology fields because of their many biological activities. The structure characterization and anti-inflammatory activity of exopolysaccharide from Schizophyllum commune were evaluated in present study. Methods: An exopolysaccharide from a submerged mycelial fermentation of S. commune was obtained using DEAE-52 cellulose and Sephadex G-150 chromatography. The molecular weight (MW), monosaccharide compositions, chemical compositions, methylation analysis, circular dichroism studies, Fourier transform infrared spectroscopy, nuclear magnetic resonance (NMR) spectra, scanning electron microscopy (SEM), and atomic force microscopy were investigated. Results: It was a homogeneous protein-bound heteropolysaccharide with MW of 2,900 kDa. The exopolysaccharide contained a β-(1→3) glycosidic backbone, (1→4)- and (1→6)- glycosidic side chain, and high amount of glucose. The anti-inflammatory activity of exopolysaccharide was assessed by inhibiting the production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), and 5- lipoxygenase (5-LOX) from macrophages. This exopolysaccharide significantly (p < 0.05) inhibited lipopolysaccharides-induced iNOS expression levels in the cells in a dose-dependent manner. Conclusion: It indicated significant anti-inflammatory effects, which showed that exopolysaccharide might be exploited as an effective anti-inflammatory agent for application in NO-related disorders such as inflammation and cancer. PMID:28555107

Transection of the hepatic parenchyma associated or not with the contralateral portal vein branch ligature and its effect in liver regeneration.

PubMed

Wiederkehr, Henrique de Aguiar; Wiederkehr, Julio Cesar; Collaço, Luiz Martins; Sousa, Eros Luiz de; Salvalaggio, Paolo; Carvalho, Caroline Aragão de; Wiederkehr, Barbara de Aguiar; Marques, Camila Aparecida Moraes; Rosa, Francielle França da; Nanni, Felipe de Negreiros; Fuchs, Taíse

2017-01-01

To analyze the influence of portal vein ligation in hepatic regeneration by immunohistochemical criteria. Ten pigs divided into two groups of five animals underwent hepatectomy in two stages, and the groups were differentiated by ligation or not of the left portal vein tributary, which is responsible for vascularization of the left lateral and medial lobes of the pig liver. Five days after the procedure, the animals underwent liver biopsies for further analysis of histological and immunohistochemical with marker Ki67. The group submitted to hepatectomy with vascular ligation showed an increase of approximately 4% of hepatocytes in regeneration status, as well as a greater presence of Kupffer and inflammatory cells as compared to control. As a result of positive cell replication observed through the Ki67 marker, we can suspect that the ligation of a tributary of the portal vein associated with liver resection promoted a greater stimulus of liver regeneration when compared to liver resection alone. Analisar a influência da ligadura da tributária da veia porta no estímulo regenerativo hepático por meio de critérios imuno-histoquímicos. Dez suínos, divididos em dois grupos de cinco animais, foram submetidos à hepatectomia em dois estágios, sendo que os grupos foram diferenciados pela ligadura ou não da tributária da veia porta, responsável pela vascularização dos lobos lateral e medial esquerdos do fígado do suíno. Cinco dias após o procedimento, os animais foram reabordados para retirada de amostras hepáticas para posterior análise de histológica e imunoistoquímica com o marcador Ki67. O grupo submetido à hepatectomia com ligadura vascular apresentou incremento de 4% aproximadamente de hepatócitos em processo de regeneração, bem como grande número de células de Kupffer e células inflamatórias, quando comparado ao controle. Em virtude da análise positiva da replicação celular observada por meio do marcador Ki67, pode-se observar que a ligadura de uma tributária da veia porta promoveu um maior estímulo de regeneração hepática, efeito observado com menor intensidade no grupo submetido apenas à ressecção hepática.

A Influência da Escola e da Mídia na Obtenção dos Conhecimentos Astronômicos

NASA Astrophysics Data System (ADS)

da Cunha, W. S.; Voelzke, M. R.; Amaral, L. H.

2006-08-01

O universo em que vivemos possui segredos jamais imaginados pelo homem, fruto da pequena proporção que ocupamos diante de um cosmos infinito. A astronomia funciona como um instrumento que sacia a sede humana em desvendar esses segredos, estudando as galáxias, quasares, pulsares além da existência de todos os elementos que preenchem o espaço cósmico, o vácuo, não mais vazio como se pensou em outros tempos. A mídia explora esse campo de forma mística e também científica. A difusão adequada e dentro dos padrões educacionais vigentes, de conceitos astronômicos, se faz necessária, devido sua presença nos conteúdos escolares, centros de ciência e na mídia, de modo geral. A reforma do Currículo Básico da Escola Pública da maioria dos Estados brasileiros introduziu conceitos astronômicos desde a pré-escola até o Ensino Médio. Num estudo realizado com 1.032 alunos do Ensino Médio de seis escolas estaduais, revelou-se através da aplicação de um questionário que abordava conheciment os básicos em astronomia, como estes foram adquiridos e qual era a infra-estrutura oferecida pela escola: para 66,2% dos entrevistados o professor já fez alguma apresentação a respeito de astronomia. O presente estudo revelou também que 44,5% dos alunos entrevistados adquiriram seus conhecimentos astronômicos na escola, 28,1% através da televisão e 27,4% afirmaram que seus conhecimentos foram obtidos através de outros tipos de mídia (internet, filmes e revistas). Embora o estudo revele claramente que há certo equilíbrio na forma em que os alunos obtiveram seus conhecimentos astronômicos, a mídia ainda explora e muitas vezes desperta o interesse pela astronomia com assuntos que não fazem parte de nosso cotidiano como, por exemplo, o homem na Lua, os projetos espaciais e a primeira viagem de um astronauta brasileiro no espaço. Porém, em certos casos, a mídia pode promover conhecimentos incompletos ou mesmo equivocados sobre os conceitos que envolvam a astronomia, como por exemplo a propagação do som no vácuo observado na maioria dos filmes de f icção científica ou da existência das estações do ano em função da distância da Terra ao Sol, em conformidade com o questionário aplicado.

Dopamine transport by the serotonin transporter: a mechanistically distinct mode of substrate translocation

PubMed Central

Larsen, Mads Breum; Sonders, Mark S.; Mortensen, Ole Valente; Larson, Gaynor A.; Zahniser, Nancy R.; Amara, Susan G.

2011-01-01

The serotonin transporter (SERT) is the principal mechanism for terminating serotonin (5HT) signals in the nervous system and is a site of action for a variety of psychoactive drugs including antidepressants, amphetamines, and cocaine. Here we show that human SERTs (hSERTs) and rat SERTs are capable of robust dopamine (DA) uptake through a process that differs mechanistically from 5HT transport in several unanticipated ways. DA transport by hSERT has a higher maximum velocity than 5HT transport, requires significantly higher Na+ and Cl− concentrations to sustain transport, is inhibited non-competitively by 5HT and is more sensitive to SERT inhibitors, including selective serotonin reuptake inhibitors (SSRIs). We use a thiol reactive methane thiosulfonate (MTS) reagent to modify a conformationally-sensitive cysteine residue to demonstrate that hSERT spends more time in an outward facing conformation when transporting DA than when transporting 5HT. Co-transfection of an inactive or an MTS-sensitive SERT with wild type SERT subunits reveals an absence of cooperative interactions between subunits during DA, but not 5HT transport. To establish the physiological relevance of this mechanism for DA clearance, we show using in vivo high-speed chronoamperometry that SERT has the capacity to clear extracellularly applied DA in the hippocampal CA3 region of anesthetized rats. Together, these observations suggest the possibility that SERT serves as a DA transporter in vivo and highlight the idea that there can be distinct modes of transport of alternative physiological substrates by SERT. PMID:21525301

SCIENTIFIC LEADERS FOR THE FUTURE: PRIMARY AND SECONDARY EDUCATION.

PubMed

Nascimento, Fernanda Amorim de Morais; Gregório, Bianca Martins; Souza, Diogo Benchimol de; Sampaio, Francisco José Barcellos; Ferreira, Lydia Masako

2015-01-01

To present a high school insertion pilot project in post graduate programs (PPG) and discuss the mechanisms for the formation of leaders in science. This study presents a review and pilot project. Bibliographic search occurred in sites of CAPES, MEC, SciELO and library of virtual books from January/ 2014 to February/2015. The pilot is in PPG-Medicine III Translational Surgery/UNIFESP and Pathophysiology and Surgical Sciences / UERJ. The junior undergraduate students (ICj) came from public school and develop scientific activities: scientific meetings, graduation and inclusion in research projects. The evaluation will occur at the end of one year, with the results essays, reports and participation in scientific events. In Brazil, one of the main challenges of education is the high average years of study. The PNPG (2011-2020) shows the insertion of basic education in all PPG. In the Pathophysiology and Surgical Sciences/UERJ there are currently 11 high school students who have followed the scientific meetings and are being prepared for the inclusion in research projects. There was 30% of absence, owing to the high school hours. This result and the experience allow creating future alternatives to enhance the integration project. The leadership in science is formed from a complex relationship between basic education and investment in research. PPG-Medicine III courses follow the vanguard with initiatives focused on scientific and technological development. Thus, projects involving basic education students represent promoter model and environment leaders. Apresentar um projeto piloto de inserção do ensino médio em programas de pós-graduação (PPG) e discutir os mecanismos para a formação de líderes em ciência. Realizou-se um estudo de revisão e apresentação de piloto. A busca bibliográfica ocorreu nos sites da CAPES, MEC, Scielo e biblioteca de livros virtuais, de janeiro/2014 a fevereiro/2015. O piloto ocorre nos PPG-Medicina III em Cirurgia Translacional/UNIFESP e Fisiopatologia e Ciências Cirúrgicas/UERJ. Os alunos de iniciação científica júnior (ICj) são oriundos de escola pública e desenvolvem atividades científicas: participação em reuniões científicas, graduação e inserção nos projetos de pesquisa. A avaliação ocorrerá ao final de um ano, com redações dos resultados, relatórios e participações em eventos científicos. No Brasil, um dos principais desafios da educação é a alta média de anos de estudo. O PNPG (2011-2020) apresenta a inserção da educação básica em todos os PPG. Na Fisiopatologia e Ciências Cirúrgicas/UERJ há atualmente 11 alunos do ensino médio, que já acompanharam as reuniões científicas e preparam-se para a inserção em projetos de pesquisa. Houve 30% de desistência, devido à alta carga horária escolar. Esse resultado e a experiência vivenciada permite criar alternativas futuras para aprimorar o projeto de inserção. A liderança em ciências é formada a partir de uma complexa relação entre educação básica e investimentos na pesquisa. Cursos de PPG-Medicina III seguem na vanguarda com iniciativas focadas no desenvolvimento científico e tecnológico. Assim, projetos envolvendo alunos da educação básica representam modelo e ambiente promotor de líderes.

Animal bite injuries to the face : A Case Report.

PubMed

Simao, Niverso Rodrigues; Borba, Alexandre Meireles; da Silva, Andre Luis Fernandes; Vieira, Evanice Menezes Marcal; Carvalhosa, Artur Aburad; Bandeca, Matheus Coelho; Borges, Alvaro Henrique

2013-08-01

Traumatic lacerations to the skin are problems frequently seen and treated by emergency centers around the world. Among all wounds, dog and cat bites are commonly seen. As in many mammals, different species of microorganisms are found in dog and cat mouths with a potential pathological effect to humans, as represented by rabies. The injuries have disfiguration effect with possible psychological repercussion to the patient. This article aimed presenting up to date considerations regarding the management of animal bite injuries to the face, exemplified by a case report that should be the interest of all professions that deal with facial tissues, as dentists do. How to cite this article: Simao NR, Borba AM, da Silva ALF, Vieira EMM, Carvalhosa AA, Bandeca MC, Borges AH. Animal bite injuries to the face: A Case Report. J Int Oral Health 2013; 5(4):68-72.

PanDA: Exascale Federation of Resources for the ATLAS Experiment at the LHC

NASA Astrophysics Data System (ADS)

Barreiro Megino, Fernando; Caballero Bejar, Jose; De, Kaushik; Hover, John; Klimentov, Alexei; Maeno, Tadashi; Nilsson, Paul; Oleynik, Danila; Padolski, Siarhei; Panitkin, Sergey; Petrosyan, Artem; Wenaus, Torre

2016-02-01

After a scheduled maintenance and upgrade period, the world's largest and most powerful machine - the Large Hadron Collider(LHC) - is about to enter its second run at unprecedented energies. In order to exploit the scientific potential of the machine, the experiments at the LHC face computational challenges with enormous data volumes that need to be analysed by thousand of physics users and compared to simulated data. Given diverse funding constraints, the computational resources for the LHC have been deployed in a worldwide mesh of data centres, connected to each other through Grid technologies. The PanDA (Production and Distributed Analysis) system was developed in 2005 for the ATLAS experiment on top of this heterogeneous infrastructure to seamlessly integrate the computational resources and give the users the feeling of a unique system. Since its origins, PanDA has evolved together with upcoming computing paradigms in and outside HEP, such as changes in the networking model, Cloud Computing and HPC. It is currently running steadily up to 200 thousand simultaneous cores (limited by the available resources for ATLAS), up to two million aggregated jobs per day and processes over an exabyte of data per year. The success of PanDA in ATLAS is triggering the widespread adoption and testing by other experiments. In this contribution we will give an overview of the PanDA components and focus on the new features and upcoming challenges that are relevant to the next decade of distributed computing workload management using PanDA.

Primary health care assessment from the users' perspectives: a systematic review.

PubMed

Paula, Weslla Karla Albuquerque Silva de; Samico, Isabella Chagas; Caminha, Maria de Fátima Costa; Filho, Malaquias Batista; Silva, Suzana Lins da

2016-04-01

Analyze the evaluation of the attributes of primary care made by users of basic units of Brazilian health by using PCATool instrument adapted to Brazil. A systematic literature review conducted in the PubMed database, IBECS, LILACS, SciELO and BDTD. 4,405 documents were found, selected 23 full texts. After Full reading and application of eligibility criteria, 14 articles were evaluated. The studies showed that primary care performs well in longitudinality attributes, completeness and coordination and worse performance on attributes access first contact, family counseling and community orientation, even in the basic units with the Family Health. The users of basic health units assessed as unsatisfactory attributes considered essential for a health care more equitable and competing for user autonomy and social control. It is inferred that there are still obstacles hindering user access to basic health services and care actions are still being developed without favoring user participation and the community context in which they live. Analisar a avaliação dos atributos da Atenção Básica feita por usuários de unidades básicas de saúde brasileiras, mediante utilização de adaptações do instrumento PCATool para o Brasil. Revisão sistemática da literatura realizada nas bases de dados Medline/PubMed, LILACS, IBECS, SciELO e BDTD. Foram encontrados 4.405 documentos, sendo selecionados 23 textos completos. Após leitura integral e aplicação dos critérios de elegibilidade, 14 artigos foram avaliados. Os estudos apontaram que a Atenção Básica tem bom desempenho nos atributos longitudinalidade, integralidade e coordenação e pior desempenho nos atributos acesso de primeiro contato, orientação familiar e a orientação comunitária, mesmo nas unidades básicas com Saúde da Família. Os usuários das unidades básicas de saúde avaliaram como insatisfatórios atributos considerados fundamentais para uma atenção à saúde mais equânime e concorrente para autonomia do usuário e controle social. Infere-se que ainda existem obstáculos que dificultam o acesso dos usuários aos serviços básicos de saúde e que ações do cuidado ainda estejam sendo desenvolvidas sem privilegiar a participação do usuário e o contexto comunitário onde vivem.

Estudo em microondas do aprisionamento e precipitação de elétrons em explosões solares

NASA Astrophysics Data System (ADS)

Rosal, A. C.; Costa, J. E. R.

2003-08-01

Uma explosão solar é uma variação rápida e intensa do brilho que ocorre nas chamadas regiões ativas da atmosfera, constituídas por um plasma magnetizado com intensa indução magnética. Os modelos de explosões solares atuais, discutidos na literatura, apresentam características de aprisionamento e precipitação de elétrons em ambientes magnéticos simplificados. Neste trabalho, nos propusemos a separar a emissão dos elétrons aprisionados da emissão dos elétrons em precipitação apenas a partir da emissão em microondas, melhorando portanto o controle sobre o conjunto de parâmetros inferidos. A emissão em microondas da população em precipitação é bastante fraca e portanto da nossa base de dados de 130 explosões observadas pelo Rádio Polarímetro de Nobeyama, em sete freqüências, apenas para 32 foi possível separar as duas componentes de emissão com uma boa razão sinal/ruído. A partir de estudos das escalas de tempo das emissões devidas à variação gradual da emissão no aprisionamento e da variação rápida da emissão dos elétrons em precipitação foi possível obter a separação utilizando um filtro temporal nas emissões resultantes. Em nossa análise destas explosões estudamos os espectros girossincrotrônicos da emissão gradual, a qual associamos provir do topo dos arcos magnéticos e da emissão de variação rápida associada aos elétrons em precipitação. Estes espectros foram calculados e dos quais inferimos que a indução magnética efetiva do topo e dos pés foi em média, Btopo = 236 G e Bpés = 577 G, inferidas das freqüências de pico dos espectros em ntopo = 11,8 GHz e npés = 14,6 GHz com leve anisotropia (pequeno alargamento espectral). O índice espectral da distribuição não-térmica de elétrons d, inferido do índice espectral de fótons da emissão em regime opticamente fino, foi de dtopo = 3,3 e dpés = 3,9. Estes parâmetros são típicos da maioria das análises realizadas em ambiente único de emissão e a relação dos índices espectrais, dpés > dtopo prioriza as interpretações com difusão em ângulo de passo devida a colisões Coulombianas. Nesta difusão o déficit de elétrons energéticos na precipitação seria uma conseqüência natural da dependência em e-3/2 das colisões elétron-próton (onde e é a energia dos elétrons).

ANALYSIS OF BIOMECHANICAL PARAMETERS IN COLONIC ANASTOMOSIS.

PubMed

Iwanaga, Tiago Cavalcanti; Aguiar, José Lamartine de Andrade; Martins-Filho, Euclides Dias; Kreimer, Flávio; Silva-Filho, Fernando Luiz; Albuquerque, Amanda Vasconcelos de

2016-01-01

The use of measures in colonic anastomoses to prevent dehiscences is of great medical interest. Sugarcane molasses, which has adequate tolerability and compatibility in vivo, has not yet been tested for this purpose. To analyze the biomechanical parameters of colonic suture in rats undergoing colectomy, using sugarcane molasses polysaccharide as tape or gel. 45 Wistar rats (Rattus norvegicus albinus) were randomized into three groups of 15 animals: irrigation of enteric sutures with 0.9% saline solution; application of sugarcane molasses polysaccharide as tape; and sugarcane molasses polysaccharide as gel. The rats underwent colon ressection, with subsequent reanastomosis using polypropylene suture; they were treated according to their respective groups. Five rats from each group were evaluated at different times after the procedure: 30, 90 and 180 days postoperatively. The following variables were evaluated: maximum rupture force, modulus of elasticity and specific deformation of maximum force. The biomechanical variables among the scheduled times and treatment groups were statistically calculated. The characteristics of maximum rupture force and modulus of elasticity of the specimens remained identical, regardless of treatment with saline, polysaccharide gel or tape, and treatment time. However, it was found that the specific deformation of maximum force of the intestinal wall was higher after 180 days in the group treated with sugarcane polysaccharide gel (p=0.09). Compared to control, it was detected greater elasticity of the intestinal wall in mice treated with sugarcane polysaccharide gel, without changing other biomechanical characteristics, regardless of type or time of treatment. A aplicação de produtos em anastomoses colônicas que possam prevenir o surgimento de deiscências são de grande interesse médico. O emprego do polissacarídeo de melaço de cana-de-açúcar (Saccharum officinarum), que possui adequada tolerabilidade e compatibilidade in vivo, ainda não foi testado para este fim. Analisar os parâmetros biomecânicos em suturas colônicas de ratos submetidos à colectomia esquerda após aplicação de fita ou gel do polissacarídeo do melaço da cana-de-açúcar no sítio cirúrgico. Quarenta e cinco ratos (Rattus norvegicus albinus da linhagem Wistar) foram sorteados em três grupos de 15 submetidos a: irrigação das suturas entéricas com soro fisiológico a 0,9%; aplicação de fita de polissacarídeo do melaço da cana-de-açúcar; e aplicação do gel do mesmo melaço. Os ratos foram submetidos à colectomia esquerda com anastomose primária, e tratados segundo os respectivos grupos. Cinco ratos de cada grupo foram avaliados em diferentes tempos após o procedimento: 30º, 90º e 180º dias de pós-operatório. Foram avaliadas as variáveis de força máxima de ruptura, módulo de elasticidade e deformação específica da força máxima. As variáveis biomecânicas entre os tempos de coleta da pesquisa e os grupos de tratamento foram analisados estatisticamente. As características biomecânicas de força máxima de ruptura e o módulo de elasticidade do corpo de prova permaneceram idênticas, independente do tratamento com soro, fita ou gel de polissacarídeo, e do tempo de tratamento. No entanto, foi evidenciada maior deformação específica da força máxima da parede intestinal, aos 180 dias nos ratos tratados com gel de polissacarídeo de cana-de-açúcar. (p=0,09). Em relação ao controle, foi detectada maior elasticidade da parede intestinal nos ratos tratados com gel de polissacarídeo de cana-de-açúcar, sem alteração de outras características biomecânicas, independente do tipo ou tempo de tratamento.

Mapping the potential beverage quality of coffee produced in the Zona da Mata, Minas Gerais, Brazil.

PubMed

Silva, Samuel de Assis; de Queiroz, Daniel Marçal; Ferreira, Williams Pinto Marques; Corrêa, Paulo Cesar; Rufino, José Luis Dos Santos

2016-07-01

Detailed knowledge of coffee production systems enables optimization of crop management, harvesting and post-harvest techniques. In this study, coffee quality is mapped as a function of coffee variety, altitude and terrain aspect attributes. The work was performed in the Zona da Mata, Minas Gerais, Brazil. A large range of coffee quality grades was observed for the Red Catuai variety. For the Yellow Catuai variety, no quality grades lower than 70 were observed. Regarding the terrain aspect, samples from the southeast-facing slope (SEFS) and the northwest-facing slope (NWFS) exhibited distinct behaviors. The SEFS samples had a greater range of quality grades than did the NWFS samples. The highest grade was obtained from an NWFS point. The lowest quality values and the largest range of grades were observed at lower altitudes. The extracts from the highest-altitude samples did not produce any low-quality coffee. The production site's position and altitude are the primary variables that influenced the coffee quality. The study area has micro-regions with grades ranging from 80 to 94. These areas have the potential for producing specialty coffees. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

A randomized-controlled trial of intensive case management emphasizing the recovery model among patients with severe and enduring mental illness.

PubMed

O'Brien, S; McFarland, J; Kealy, B; Pullela, A; Saunders, J; Cullen, W; Meagher, D

2012-09-01

There is increasing interest in the application of recovery principles in mental health services. We studied the implementation of a programme of intensive case management (ICM) emphasizing recovery principles in a community mental health service in Ireland. Eighty service attenders with severe and enduring illness characterized by significant ongoing disability were randomized into (1) a group receiving a programme of ICM and (2) a group receiving treatment as usual (TAU). Groups were compared before and after the programme for general psychopathology using the Brief Psychiatric Rating Scale (BPRS) (clinician rated) and How are You? scale (self-rated). The Functional Analysis of Care Environments (FACE) scale provided assessment of multiple functional domains. The overall group (mean age 44.5 ± 13.2 years; 60% male) had mean total Health of the Nation Outcome Scale (HoNOS) scale scores of 10.5 ± 4.6, with problems in social functioning especially prominent (mean social subscale score 5.0 ± 2.7). The ICM group were younger (p < 0.01) with higher baseline scores on the HoNOS social subscale and BPRS (p < 0.05). An analysis of covariance, controlling for these baseline differences, indicated greater improvement in BPRS scores (p = 0.001), How are You? scores (p = 0.02) and FACE domains for cognition, symptoms and interpersonal relationships (all p < 0.001) in the ICM group. The ICM group underwent greater changes in structured daily activities that were linked to improved BPRS scores (p = 0.01). A programme of ICM emphasizing recovery principles resulted in significant improvement across psychopathological and functional domains. Improvements were linked to enhanced engagement with structured daily activities. Recovery-oriented practices can be integrated into existing mental health services and provided alongside traditional models of care.

Stimulation of the Rat Subthalamic Nucleus is Neuroprotective Following Significant Nigral Dopamine Neuron Loss

PubMed Central

Spieles-Engemann, A. L.; Behbehani, M. M.; Collier, T. J.; Wohlgenant, S. L.; Steece-Collier, K.; Paumier, K.; Daley, B. F.; Gombash, S.; Madhavan, L.; Mandybur, G. T.; Lipton, J.W.; Terpstra, B.T.; Sortwell, C.E.

2010-01-01

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is efficacious in treating the motor symptoms of Parkinson’s disease (PD). However, the impact of STN-DBS on the progression of PD is unknown. Previous preclinical studies have demonstrated that STN-DBS can attenuate the degeneration of a relatively intact nigrostriatal system from dopamine (DA)-depleting neurotoxins. The present study examined whether STN-DBS can provide neuroprotection in the face of prior significant nigral DA neuron loss similar to PD patients at the time of diagnosis. STN-DBS between two and four weeks after intrastriatal 6-hydroxydopamine (6-OHDA) provided significant sparing of DA neurons in the SN of rats. This effect was not due to inadvertent lesioning of the STN and was dependent upon proper electrode placement. Since STN-DBS appears to have significant neuroprotective properties, initiation of STN-DBS earlier in the course of PD may provide added neuroprotective benefits in addition to its ability to provide symptomatic relief. PMID:20307668

iNOS-dependent sweating and eNOS-dependent cutaneous vasodilation are evident in younger adults, but are diminished in older adults exercising in the heat

PubMed Central

Fujii, Naoto; Meade, Robert D.; Alexander, Lacy M.; Akbari, Pegah; Foudil-bey, Imane; Louie, Jeffrey C.; Boulay, Pierre

2015-01-01

Nitric oxide synthase (NOS) contributes to sweating and cutaneous vasodilation during exercise in younger adults. We hypothesized that endothelial NOS (eNOS) and neuronal NOS (nNOS) mediate NOS-dependent sweating, whereas eNOS induces NOS-dependent cutaneous vasodilation in younger adults exercising in the heat. Further, aging may upregulate inducible NOS (iNOS), which may attenuate sweating and cutaneous vasodilator responses. We hypothesized that iNOS inhibition would augment sweating and cutaneous vasodilation in exercising older adults. Physically active younger (n = 12, 23 ± 4 yr) and older (n = 12, 60 ± 6 yr) adults performed two 30-min bouts of cycling at a fixed rate of metabolic heat production (400 W) in the heat (35°C). Sweat rate and cutaneous vascular conductance (CVC) were evaluated at four intradermal microdialysis sites with: 1) lactated Ringer (control), 2) nNOS inhibitor (nNOS-I, NPLA), 3) iNOS inhibitor (iNOS-I, 1400W), or 4) eNOS inhibitor (eNOS-I, LNAA). In younger adults during both exercise bouts, all inhibitors decreased sweating relative to control, albeit a lower sweat rate was observed at iNOS-I compared with eNOS-I and nNOS-I sites (all P < 0.05). CVC at the eNOS-I site was lower than control in younger adults throughout the intermittent exercise protocol (all P < 0.05). In older adults, there were no differences between control and iNOS-I sites for sweating and CVC during both exercise bouts (all P > 0.05). We show that iNOS and eNOS are the main contributors to NOS-dependent sweating and cutaneous vasodilation, respectively, in physically active younger adults exercising in the heat, and that iNOS inhibition does not alter sweating or cutaneous vasodilation in exercising physically active older adults. PMID:26586908

iNOS-dependent sweating and eNOS-dependent cutaneous vasodilation are evident in younger adults, but are diminished in older adults exercising in the heat.

PubMed

Fujii, Naoto; Meade, Robert D; Alexander, Lacy M; Akbari, Pegah; Foudil-Bey, Imane; Louie, Jeffrey C; Boulay, Pierre; Kenny, Glen P

2016-02-01

Nitric oxide synthase (NOS) contributes to sweating and cutaneous vasodilation during exercise in younger adults. We hypothesized that endothelial NOS (eNOS) and neuronal NOS (nNOS) mediate NOS-dependent sweating, whereas eNOS induces NOS-dependent cutaneous vasodilation in younger adults exercising in the heat. Further, aging may upregulate inducible NOS (iNOS), which may attenuate sweating and cutaneous vasodilator responses. We hypothesized that iNOS inhibition would augment sweating and cutaneous vasodilation in exercising older adults. Physically active younger (n = 12, 23 ± 4 yr) and older (n = 12, 60 ± 6 yr) adults performed two 30-min bouts of cycling at a fixed rate of metabolic heat production (400 W) in the heat (35°C). Sweat rate and cutaneous vascular conductance (CVC) were evaluated at four intradermal microdialysis sites with: 1) lactated Ringer (control), 2) nNOS inhibitor (nNOS-I, NPLA), 3) iNOS inhibitor (iNOS-I, 1400W), or 4) eNOS inhibitor (eNOS-I, LNAA). In younger adults during both exercise bouts, all inhibitors decreased sweating relative to control, albeit a lower sweat rate was observed at iNOS-I compared with eNOS-I and nNOS-I sites (all P < 0.05). CVC at the eNOS-I site was lower than control in younger adults throughout the intermittent exercise protocol (all P < 0.05). In older adults, there were no differences between control and iNOS-I sites for sweating and CVC during both exercise bouts (all P > 0.05). We show that iNOS and eNOS are the main contributors to NOS-dependent sweating and cutaneous vasodilation, respectively, in physically active younger adults exercising in the heat, and that iNOS inhibition does not alter sweating or cutaneous vasodilation in exercising physically active older adults. Copyright © 2016 the American Physiological Society.

Implementação de um algoritmo para a limpeza de mapas da RCFM

NASA Astrophysics Data System (ADS)

Souza, C. L.; Wuensche, C. A.

2003-08-01

A Radiação Cósmica de Fundo em Microondas (RCFM), descoberta por Penzias e Wilson em 1965, é uma das ferramentas mais poderosas para o estudo da cosmologia. Com a descoberta de flutuações de temperatura na RCFM, da ordem de uma parte em 105, pelo COBE (1992), uma nova era teve início. Nos últimos onze anos, diversos instrumentos fizeram novas medidas de alta precisão, refinando os resultados apresentados pelo COBE, culminando com os resultados recentes do satélite WMAP. A análise de dados da RCFM, especialmente no caso de experimentos com pequena cobertura do céu, apresenta uma série de dificuldades devido a emissões de contaminantes externos, tais como a emissão da Galáxia e de fontes pontuais, e de ruídos intrínsecos tanto ao sistema de detecção quanto à estratégia de observação do céu. Uma das soluções típicas para a filtragem de dados brutos de um experimento para medir flutuações de temperatura é aplicar um gabarito (template) e um filtro passa alta ao produzir mapas simplificados (sem considerar matrizes de correlação ou covariância). No caso de experimentos que utilizam detectores HEMT, essa combinação de filtros remove, satisfatoriamente, ruídos do tipo 1/f gerados pela instabilidade no ganho do detector acoplado ao movimento do instrumento, definido pela estratégia de observação. Entretanto, o sinal resultante medido, tanto em simulações quanto em séries temporais reais, sugere que parte do sinal cosmológico pode estar sendo removido junto com o ruído dos detectores. Este trabalho descreve as etapas para a produção de um mapa típico (simulado) e os testes preliminares de um algoritmo para remover ruídos do tipo 1/f introduzidos pela estratégia de observação sem prejudicar a qualidade do sinal cosmológico presente no mapa.

Propriedades de estruturas temporais rápidas submilimétricas durante uma grande explosão solar

NASA Astrophysics Data System (ADS)

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

2003-08-01

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

Guide of attributes of the nurse's political competence: a methodological study.

PubMed

Melo, Wesley Soares de; Oliveira, Paulo Jorge Ferreira de; Monteiro, Flávia Paula Magalhães; Santos, Francisca Carla Dos Angelos; Silva, Maria Janaína Nogueira da; Calderon, Carolina Jimenez; Fonseca, Lilian Nara Amaral da; Simão, Ana Adélia Chaves

2017-01-01

To build and validate a guide of attributes of the nurse's political competence. Methodological research. This study comprised the construction of the instrument through literature review; experts validation of pre-established attributes for composing the guide; and clinical validation in the nurses work environment/reality. The data collection took place in the months from August to October 2014, and the analysis was based on the content analysis of Bardin and use of Epi info 3.5. All ethical precepts have been complied with. From 29 attributes found in the literature, 25 have been validated by experts. Clinical/practical validation involved the participation of 43 nurses, who observed that the attributes are not articulated with the professional practices developed by them. The attributes of the nurse's political competence were identified with support of literature. It is concluded that the professionals still have limited and fragmented perception of political competence, expressing difficulty/limitation. Construir e validar um guia de atributos da competência política do enfermeiro. Pesquisa metodológica. O estudo compreendeu a construção do instrumento por meio de revisão da literatura; validação, por especialistas, dos atributos preestabelecidos para composição do guia; e validação clínica no ambiente/realidade de trabalho dos enfermeiros. A coleta dos dados ocorreu nos meses de agosto a outubro de 2014, e a análise baseou-se na análise de conteúdo de Bardin e utilização do Epi info 3.5. Foram respeitados todos os preceitos éticos. Dos 29 atributos encontrados na literatura, 25 foram validados pelos especialistas. A validação clínica/prática envolveu a participação de 43 enfermeiros, os quais observaram que os atributos não apresentam articulação com as práticas profissionais por eles desenvolvidas. Identificados os atributos da competência política do enfermeiro com apoio da literatura. Conclui-se que os profissionais ainda possuem percepção limitada e fragmentada da competência política, manifestando dificuldade/limitação.

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

PubMed Central

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

2017-01-01

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

Silibinin attenuates MPP⁺-induced neurotoxicity in the substantia nigra in vivo.

PubMed

Jung, Un Ju; Jeon, Min-Tae; Choi, Myung-Sook; Kim, Sang Ryong

2014-05-01

Parkinson's disease (PD) is characterized by degeneration of the nigrostriatal dopaminergic (DA) pathway. The cause of neuronal death in PD is largely unknown, but it is becoming clear that inflammation plays a significant role in the pathophysiology of PD. Silibinin is a major flavonoid in milk thistle which has an anti-inflammatory activity. We investigated whether silibinin could have neuroprotective effects on DA neurons in the 1-methyl-4-phenylpyridinium ion (MPP(+))-treated animal model of PD in vivo. To address this question, animals received intraperitoneal (i.p.) injections 10, 50, or 100 mg/kg of silibinin, starting 1 day before MPP(+) injection and continued daily until 6 days post-lesion for tyrosine hydroxylase (TH) staining, or until 1 hour prior to the MPP(+) injection to examine the expression levels of inflammatory proteins. Finally, their brains were harvested at the indicated time points for the analyses. Silibinin treatment with 10 mg/kg had no significantly neuroprotective effects in the substantia nigra (SN). However, 50 and 100 mg/kg of silibinin ameliorated the MPP(+)-induced neurotoxicity in the SN in a dose-dependent manner, and the increased levels of inflammatory molecules such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and inducible nitric oxide synthase (iNOS) by MPP(+) treatment were attenuated by treatment with 100 mg/kg of silibinin. These results indicate that silibinin could be a useful and beneficial natural product offering promise for the prevention of DA neuronal degeneration involved in PD.

Animal bite injuries to the face : A Case Report

PubMed Central

Simao, Niverso Rodrigues; Borba, Alexandre Meireles; da Silva, Andre Luis Fernandes; Vieira, Evanice Menezes Marcal; Carvalhosa, Artur Aburad; Bandeca, Matheus Coelho; Borges, Alvaro Henrique

2013-01-01

Traumatic lacerations to the skin are problems frequently seen and treated by emergency centers around the world. Among all wounds, dog and cat bites are commonly seen. As in many mammals, different species of microorganisms are found in dog and cat mouths with a potential pathological effect to humans, as represented by rabies. The injuries have disfiguration effect with possible psychological repercussion to the patient. This article aimed presenting up to date considerations regarding the management of animal bite injuries to the face, exemplified by a case report that should be the interest of all professions that deal with facial tissues, as dentists do. How to cite this article: Simao NR, Borba AM, da Silva ALF, Vieira EMM, Carvalhosa AA, Bandeca MC, Borges AH. Animal bite injuries to the face: A Case Report. J Int Oral Health 2013; 5(4):68-72. PMID:24155623

Um Projeto de Intervenção nos Espaços de Exposições do Planetário do Parque do Ibirapuera

NASA Astrophysics Data System (ADS)

Elias, D. S.; Amaral, L. H.; de Araújo, C. F., Jr.; Matsuura, O. T.; Voelzke, M. R.

2005-08-01

Cada vez mais a humanidade, em sua imensa maioria, está alheia às próprias conquistas. A insatisfação com esta realidade tem levado muitos pesquisadores, instituições, empresas e governos a procurar formas alternativas de acompanhar e transmitir todo este acervo científico cultural à sociedade, buscando a melhoria da qualidade da divulgação científica e contribuindo para o processo de cultura e alfabetização científica. Não há tempo nem espaço nos limitados planos curriculares do ensino médio e mesmo nos programas de ensino que propiciem a cultura científica e o acompanhamento do vertiginoso progresso científico e tecnológico atual. Neste sentido, a educação formal escolar precisa ser complementada ou acrescida de uma educação informal, extra-escolar, que possa oferecer à sociedade o que a escola não pode oferecer. A interação do público com museus, feiras de ciências, planetários, exposições científicas e/ou culturais é de grande importância para a aquisição e difusão de conhecimentos relacionados ao mundo científico. Reconhecidamente como um modelo de alfabetização científica esses ambientes promovem uma interação social capaz de propiciar de forma efetiva uma melhor relação ensino-aprendizagem com o público. Partindo desta realidade a Universidade Cruzeiro do Sul e a Escola Municipal de Astronomia (EMA) vêm desenvolvendo um projeto de intervenção no espaço em torno do Planetário do Parque do Ibirapuera com o objetivo de se implantar um ambiente de aprendizagem motivador e desafiador que promova a popularização de conteúdos relacionados à astronomia, astrofísica e cosmologia. Busca-se, também, a aproximação e interação do público com exposições que estão sendo implementadas no planetário. Considerando que se trata de um projeto de mestrado em fase inicial o objetivo do presente trabalho é apresentar a concepção básica e os critérios que estão sendo utilizados do ponto de vista pedagógico para as indicações dos objetos e experimentos que serão expostos, procurando formas de construir, expor e apresen! tá-los d e maneira mais eficiente em termos de uma aprendizagem significativa. (Apoio: Fundação Vitae, CNPq)

Código para imageamento indireto de estrelas em sistemas binarios: simulação de variações elipsoidais e do perfil das linhas

NASA Astrophysics Data System (ADS)

Souza, T. R.; Baptista, R.

2003-08-01

As estrelas secundárias em variáveis cataclí smicas (VCs) e binárias-x de baixa massa (BXBMs) são cruciais para o entendimento da origem, evolução e comportamento destas binárias interagentes. Elas são estrelas magneticamente ativas submetidas a condições ambientais extremas [e.g., estão muito próximas de uma fonte quente e irradiante; têm rotação extremamente rápida e forma distorcida; estão perdendo massa a taxas de 10-8-10-10 M¤/ano] que contribuem para que suas propriedades sejam distintas das de estrelas de mesma massa na seqüência principal. Por outro lado, o padrão de irradiação na face da secundária fornece informação sobre a geometria das estruturas de acréscimo em torno da estrela primária. Assim, a obtenção de imagens da superfície destas estrelas é de grande interesse astrofísico. A Tomografia Roche usa as variações no perfil das linhas de emissão/absorção da estrela secundária em função da fase orbital para mapear a distribuição de brilho em sua superfície. Neste trabalho apresentamos os resultados iniciais do desenvolvimento de um programa para o mapeamento da distribuição de brilho na superfí cie das estrelas secundárias em VCs e BXBMs com técnicas de astro-tomografia. Presentemente temos em operação um código que simula as variações no perfil das linhas em conseqüência de efeito Doppler resultante da combinação de rotação e translação de uma estrela em forma de lobo de Roche em torno do centro de massa da binária, em função da distribuição de brilho na superfície desta estrela. O código igualmente produz a curva de luz resultante das variações de aspecto da estrela em função da fase orbital (variações elipsoidais).

On ambiente de binárias de pequena massa em formação: o caso do glóbulo cometário CG30 e IRAS08076-3556

NASA Astrophysics Data System (ADS)

Hickel, G. R.; Vilas-Boas, J. W. S.

2003-08-01

Neste trabalho, combinamos observações de polarização linear no óptico (banda R), dados no infravermelho distante (IRAS) e observações de transições moleculares em radiofreqüências (CO e espécies isotópicas, HCN e HCO+) para analisar o glóbulo cometário (GC) CG30 (na região da IRAS Vela Shell), que apresenta objetos Herbig-Haro e ejeções de matéria, além de uma fonte pontual IRAS em seu interior. Os objetivos deste estudo são: determinar a eficiência de formação estelar nos glóbulos cometários, através da relação entre a massa total do GC e da massa das estrelas em formação; determinar como o campo magnético influencia na formação de estrelas no interior destes objetos; e analisar as modificações que ejeções de matéria de estrelas em formação causam no gás e no campo magnético dos GCs. Combinando nossos dados com trabalhos já publicados, mostramos que CG30 tem uma eficiência de formação estelar em torno de 3%; que o campo magnético é importante na manutenção da estrutura global do GC e demonstra sinais de torção e compressão; e que a ejeção bipolar de matéria das estrelas do par formam uma ejeção quadripolar, a qual influencia na densidade e temperatura do gás e no grau de polarização dos grãos de poeira associados ao gás do GC.

Fiber-optic components for optical communicatios and sensing =

NASA Astrophysics Data System (ADS)

Marques, Carlos Alberto Ferreira

Nos ultimos anos, a Optoelectronica tem sido estabelecida como um campo de investigacao capaz de conduzir a novas solucoes tecnologicas. As conquistas abundantes no campo da optica e lasers, bem como em comunicacoes opticas tem sido de grande importancia e desencadearam uma serie de inovacoes. Entre o grande numero de componentes opticos existentes, os componentes baseados em fibra optica sao principalmente relevantes devido a sua simplicidade e a elevada de transporte de dados da fibra optica. Neste trabalho foi focado um destes componentes opticos: as redes de difraccao em fibra optica, as quais tem propriedades opticas de processamento unicas. Esta classe de componentes opticos e extremamente atraente para o desenvolvimento de dispositivos de comunicacoes opticas e sensores. O trabalho comecou com uma analise teorica aplicada a redes em fibra e foram focados os metodos de fabricacao de redes em fibra mais utilizados. A inscricao de redes em fibra tambem foi abordado neste trabalho, onde um sistema de inscricao automatizada foi implementada para a fibra optica de silica, e os resultados experimentais mostraram uma boa aproximacao ao estudo de simulacao. Tambem foi desenvolvido um sistema de inscricao de redes de Bragg em fibra optica de plastico. Foi apresentado um estudo detalhado da modulacao acustico-optica em redes em fibra optica de silica e de plastico. Por meio de uma analise detalhada dos modos de excitacao mecanica aplicadas ao modulador acustico-optico, destacou-se que dois modos predominantes de excitacao acustica pode ser estabelecidos na fibra optica, dependendo da frequencia acustica aplicada. Atraves dessa caracterizacao, foi possivel desenvolver novas aplicacoes para comunicacoes opticas. Estudos e implementacao de diferentes dispositivos baseados em redes em fibra foram realizados, usando o efeito acustico-optico e o processo de regeneracao em fibra optica para varias aplicacoes tais como rapido multiplexador optico add-drop, atraso de grupo sintonizavel de redes de Bragg, redes de Bragg com descolamento de fase sintonizaveis, metodo para a inscricao de redes de Bragg com perfis complexos, filtro sintonizavel para equalizacao de ganho e filtros opticos notch ajustaveis.

Minimum Map of Social Institutional Network: a multidimensional strategy for research in Nursing.

PubMed

Carlos, Diene Monique; Pádua, Elisabete Matallo Marchesini de; Nakano, Ana Márcia Spanó; Ferriani, Maria das Graças Carvalho

2016-06-01

To analyze the use of methodological strategies in qualitative research - Minimum Maps of Social Institutional Network, as proposed to understand the phenomena in the multidimensional perspective. Methodological theoretical essay in which we aimed to reflect on the use of innovative methodological strategies in nursing research, supported in Complex Paradigm fundamentals. The minimum map of Social Institutional External Network aims to identify institutional linkages and gaps for the intervention work of the surveyed institutions. The use of these maps provided important advances in know-how qualitative research in Health and Nursing. In this perspective, the use of minimum Social Intitutional Network maps can be stimulated and enhanced to meet the current demands of the contemporary world, particularly for its flexibility in adapting to various research subjects; breadth and depth of discussion; and possibilities with health services. Analisar o uso de estratégias metodológicas em pesquisas qualitativas - Mapa mínimo da Rede Social Institucional, como proposta para compreender os fenômenos na perspectiva multidimensional. Ensaio teórico metodológico em que buscou-se refletir sobre o uso de estratégias metodológicas inovadoras de pesquisa na enfermagem, sustentada nos fundamentos do Pensamento Complexo. O mapa mínimo da Rede Social Institucional Externa tem o objetivo de identificar os vínculos institucionais e lacunas para o trabalho de intervenção das instituições pesquisadas. O uso destes mapas proporcionou avanços importantes no saber-fazer pesquisa qualitativa em Saúde e Enfermagem. Nessa perspectiva, o uso de mapas mínimos da Rede Social Institucional pode ser estimulado e potencializado para responder às atuais demandas da contemporaneidade, em especial pela sua flexibilidade na adequação a diversos objetos de pesquisa; amplitude e profundidade de discussão; e possibilidades de articulação com a prática dos serviços.

Polymorphisms in IL-10 and INF-γ genes are associated with early atherosclerosis in coronary but not in carotid arteries: A study of 122 autopsy cases of young adults.

PubMed

Esperança, José Carlos P; Miranda, William R R; Netto, José B; Lima, Fabiane S; Baumworcel, Leonardo; Chimelli, Leila; Silva, Rosane; Ürményi, Turán P; Cabello, Pedro H; Rondinelli, Edson; Faffe, Débora S

2015-06-01

Atherosclerosis is a complex disease, involving both genetic and environmental factors. However, the influence of genetic variations on its early development remains unclear. This study examined the association of 12 different polymorphisms with atherosclerosis severity in anterior descending coronary (DA, n = 103) and carotid arteries (CA, n = 66) of autopsied young adults (< 30 years old). Histological sections (H-E) were classified according to the American Heart Association. Polymorphisms in ACE, TNF-α (- 308G/A and - 238 G/A), IFN-γ (+ 874 A/T), MMP-9 (- 1562 C/T), IL-10 (- 1082 A/G and - 819 C/T), NOS3 (894 G/T), ApoA1 (rs964184), ApoE (E2E3E4 isoforms), and TGF-β (codons 25 and 10) genes were genotyped by gel electrophoresis or automatic DNA sequencing. Firearm projectile or car accident was the main cause of death, and no information about classical risk factors was available. Histological analysis showed high prevalence of type III atherosclerotic lesions in both DA (69%) and CA (39%) arteries, while severe type IV and V lesions were observed in 14% (DA) and 33% (CA). Allele frequencies and genotype distributions were determined. Among the polymorphisms studied, IFN-γ and IL-10 (- 1082 A/G) were related to atherosclerosis severity in DA artery. No association between genotypes and lesion severity was found in CA. In conclusion, we observed that the high prevalence of early atherosclerosis in young adults is associated with IFN-γ (p < 0.001) and IL-10 (p = 0.013) genotypes. This association is blood vessel dependent. Our findings suggest that the vascular system presents site specialization, and specific genetic variations may provide future biomarkers for early disease identification.

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.

Localization and quantitative co-localization of enamelin with amelogenin.

PubMed

Gallon, Victoria; Chen, Lisha; Yang, Xiudong; Moradian-Oldak, Janet

2013-08-01

Enamelin and amelogenin are vital proteins in enamel formation. The cooperative function of these two proteins controls crystal nucleation and morphology in vitro. We quantitatively analyzed the co-localization between enamelin and amelogenin by confocal microscopy and using two antibodies, one raised against a sequence in the porcine 32 kDa enamelin region and the other raised against full-length recombinant mouse amelogenin. We further investigated the interaction of the porcine 32 kDa enamelin and recombinant amelogenin using immuno-gold labeling. This study reports the quantitative co-localization results for postnatal days 1-8 mandibular mouse molars. We show that amelogenin and enamelin are secreted into the extracellular matrix on the cuspal slopes of the molars at day 1 and that secretion continues to at least day 8. Quantitative co-localization analysis (QCA) was performed in several different configurations using large (45 μm height, 33 μm width) and small (7 μm diameter) regions of interest to elucidate any patterns. Co-localization patterns in day 8 samples revealed that enamelin and amelogenin co-localize near the secretory face of the ameloblasts and appear to be secreted approximately in a 1:1 ratio. The degree of co-localization decreases as the enamel matures, both along the secretory face of ameloblasts and throughout the entire thickness of the enamel. Immuno-reactivity against enamelin is concentrated along the secretory face of ameloblasts, supporting the theory that this protein together with amelogenin is intimately involved in mineral induction at the beginning of enamel formation. Copyright © 2013 Elsevier Inc. All rights reserved.

Elementary teachers' perceptions about the effective features of explicit-reflective nature of science instruction

NASA Astrophysics Data System (ADS)

Adibelli-Sahin, Elif; Deniz, Hasan

2017-04-01

This qualitative study explored elementary teachers' perceptions about the effective features of explicit-reflective nature of science (NOS) instruction. Our participants were four elementary teachers from a public charter school located in the Southwestern U.S.A. The four elementary teachers participated in an academic year-long professional development about NOS which consisted of NOS training and NOS teaching phases. After each phase of the professional development, we specifically asked our participants which features of the explicit-reflective NOS instruction they found effective in improving their NOS conceptions by presenting pre- and post-profiles of their NOS conceptions. We identified nine features perceived by the participants as effective components of explicit-reflective NOS instruction: (1) specific focus on NOS content, (2) participation in hands-on NOS activities, (3) introductory NOS readings, (4) multiple types/forms of reflection, (5) multiple exposure to NOS content, (6) structural consistency in the presentation of NOS content, (7) the evaluation of secondary NOS data from elementary students, (8) the analysis of national and state science standards in terms of NOS content, and (9) NOS teaching experience.

Development and pilot‐testing of a Decision Aid for use among Chinese women facing breast cancer surgery

PubMed Central

Au, Angel H.Y.; Lam, Wendy W.T.; Chan, Miranda C.M.; Or, Amy Y.M.; Kwong, Ava; Suen, Dacita; Wong, Annie L.; Juraskova, Ilona; Wong, Teresa W.T.; Fielding, Richard

2011-01-01

Abstract Background  Women choosing breast cancer surgery encounter treatment decision‐making (TDM) difficulties, which can cause psychological distress. Decision Aids (DAs) may facilitate TDM, but there are no DAs designed for Chinese populations. We developed a DA for Chinese women newly diagnosed with breast cancer, for use during the initial surgical consultation. Aims  Conduct a pilot study to assess the DA acceptability and utility among Chinese women diagnosed with breast cancer. Methods  Women preferred the DA in booklet format. A booklet was developed and revised and evaluated in two consecutive pilot studies (P1 and P2). On concluding their initial diagnostic consultation, 95 and 38 Chinese women newly diagnosed with breast cancer received the draft and revised draft DA booklet, respectively. Four‐day post‐consultation, women had questionnaires read out to them and to which they responded assessing attitudes towards the DA and their understanding of treatment options. Results  The original DA was read/partially read by 66/22% (n = 84) of women, whilst the revised version was read/partially read by 74/16% (n = 35), including subliterate women (χ2 = 0.76, P = 0.679). Knowledge scores varied with the extent the booklet was read (P1: F = 12.68, d.f. 2, P < 0.001; P2: F = 3.744, d.f. 2, P = 0.034). The revised, shorter version was graphically rich and resulted in improved perceived utility, [except for the ‘treatment options’ (χ2 = 5.50, P = 0.019) and ‘TDM guidance’ (χ2 = 8.19, P = 0.004) sections] without increasing anxiety (F = 0.689, P = 0.408; F = 3.45, P = 0.073). Conclusion  The DA was perceived as acceptable and useful for most women. The DA effectiveness is currently being evaluated using a randomized controlled trial. PMID:21223468

Differences in water soluble non-digestible polysaccharides and anti-inflammatory activities of fruiting bodies from two cultivated Xylaria nigripes strains.

PubMed

Chen, Ching-Fu; Su, Chun-Han; Lai, Ming-Nan; Ng, Lean-Teik

2018-05-12

Polysaccharides including β-glucans are important bioactive components of mushroom. Xylaria nigripes is a popular medicinal fungus that has been used for treating trauma, insomnia and mental illness. This study examined the physicochemical characteristics and anti-inflammatory activities of water soluble non-digestible polysaccharides (TXNP and CXNP) from fruiting bodies of two cultivated X. nigripes strains (TXN and CXN). Results showed that both TXNP and CXNP possessed relatively similar FT-IR spectra. TXNP had a triple helix conformation and molecular weight of 853.8 kDa, whereas the molecular weight of CXNP was 14.7 kDa. The monosaccharide composition of TXNP was predominantly glucose, whereas CXNP contained xylose, mannose and glucose. Although both TXNP and CXNP dose-dependently suppressed the production of NO, IL-1β, TNF-α and PGE2, as well as the expression of iNOS, COX-2 and NF-κB in the lipopolysaccharide-induced RAW264.7 macrophages, the potency of TXNP was stronger. This study reveals that under similar conditions of cultivation and extraction procedures, the different physicochemical characteristics of polysaccharides from TXN and CXN may have contributed to the differences in their anti-inflammatory potency. Copyright © 2018. Published by Elsevier B.V.

Perfil de temperatura dos funis magnetosféricos de estrelas T Tauri com aquecimento alfvênico

NASA Astrophysics Data System (ADS)

Vasconcelos, M. J.

2003-08-01

Estrelas T Tauri Clássicas são objetos jovens circundados por discos de gás e poeira e que apresentam uma intensa atividade magnética. Seu espectro mostra linhas de emissão alargadas que são razoavelmente reproduzidas nos modelos de acresção magnetosférica. No entanto, o perfil de temperatura dos funis magnéticos é desconhecido. Aquecimento magnético compressional e difusão ambipolar foram considerados para estas estruturas, porém as temperaturas obtidas não são suficientes para explicar as observações. Neste trabalho, examinamos o aquecimento gerado pelo amortecimento de ondas Alfvén através de quatro mecanismos, os amortecimentos não-linear, turbulento, viscoso-resistivo e colisional como função da freqüência da onda. Inicialmente, a temperatura é ajustada para reproduzir as observações e o grau de turbulência requerido para que o mecanismo seja viável é calculado. Os resultados mostram que este é compatível com os dados observacionais. Apresentam-se, também, resultados preliminares do cálculo auto-consistente do perfil de temperatura dos funis, levando-se em conta fontes de aquecimento Alfvênica e fontes de resfriamento.

Kidney ischemia and reperfunsion syndrome: effect of lidocaine and local postconditioning.

PubMed

Yamaki, Igor Nagai; Pontes, Ruy Victor Simões; Costa, Felipe Lobato DA Silva; Yamaki, Vitor Nagai; Teixeira, Renan Kleber Costa; Yasojima, Edson Yuzur; Brito, Marcus Vinicius Henriques

2016-01-01

to evaluate the effects of blocking the regulation of vascular tone on the ischemia and reperfusion syndrome in rats through the use of lidocaine in the postconditioning technique. we randomized 35 rats into seven groups of five animals: Group 1- Control; Group 2- Ischemia and Reperfusion; Group 3- Ischemia, Reperfusion and Saline; Group 4- Ischemic Postconditioning; Group 5- Ischemic Postconditioning and Saline; Group 6- Lidocaine; Group 7- Ischemic Postconditioning and Lidocaine. Except for the control group, all the others were submitted to renal ischemia for 30 minutes. In postconditioning groups, we performed ischemia and reperfusion cycles of five minutes each, applied right after the main ischemia. In saline and lidocaine groups, we instilled the substances at a rate of two drops per minute. To compare the groups, we measured serum levels of urea and creatinine and also held renal histopathology. The postconditioning and postconditioning + lidocaine groups showed a decrease in urea and creatinine values. The lidocaine group showed only a reduction in creatinine values. In histopathology, only the groups submitted to ischemic postconditioning had decreased degree of tubular necrosis. Lidocaine did not block the effects of postconditioning on renal ischemia reperfusion syndrome, and conferred better glomerular protection when applied in conjunction with ischemic postconditioning. avaliar os efeitos do bloqueio da regulação do tônus vascular por meio do uso da lidocaína na técnica de pós-condicionamento isquêmico na síndrome de isquemia e reperfusão renal em ratos. trinta e cinco ratos foram randomizados em sete grupos de cinco animais: Grupo 1- Controle; Grupo 2- Isquemia e Reperfusão; Grupo 3- Isquemia, Reperfusão e Solução Salina; Grupo 4- Pós-condicionamento Isquêmico; Grupo 5- Pós-condicionamento Isquêmico e Solução Salina; Grupo 6- Lidocaína; Grupo 7- Pós-condicionamento Isquêmico e lidocaína. Com exceção do grupo controle, todos os demais foram submetidos à isquemia renal de 30 minutos. Nos grupos de pós-condicionamento, foi realizado o ciclo de isquemia e reperfusão de cinco minutos cada, aplicado logo após a isquemia principal. Nos grupos salina e lidocaína foram instiladas as substâncias numa taxa de duas gotas por minuto. Para comparar os grupos, foram dosados os níveis séricos de ureia e creatinina e análise histopatológica renal. os grupos pós-condicionamento e pós-condicionamento + lidocaína apresentaram uma redução nos valores de ureia e creatinina. O grupo lidocaína apresentou apenas uma redução nos valores de creatinina. Na análise histopatológica, apenas os grupos submetidos ao pós-condicionamento isquêmico apresentaram redução do grau de necrose tubular. a lidocaína não bloqueou os efeitos do pós-condicionamento na síndrome de isquemia e reperfusão renal, mas conferiu melhor na proteção glomerular quando aplicada em conjunto com o pós-condicionamento isquêmico.

Validation of the da Vinci Surgical Skill Simulator across three surgical disciplines: A pilot study

PubMed Central

Alzahrani, Tarek; Haddad, Richard; Alkhayal, Abdullah; Delisle, Josée; Drudi, Laura; Gotlieb, Walter; Fraser, Shannon; Bergman, Simon; Bladou, Frank; Andonian, Sero; Anidjar, Maurice

2013-01-01

Objective: In this paper, we evaluate face, content and construct validity of the da Vinci Surgical Skills Simulator (dVSSS) across 3 surgical disciplines. Methods: In total, 48 participants from urology, gynecology and general surgery participated in the study as novices (0 robotic cases performed), intermediates (1–74) or experts (≥75). Each participant completed 9 tasks (Peg board level 2, match board level 2, needle targeting, ring and rail level 2, dots and needles level 1, suture sponge level 2, energy dissection level 1, ring walk level 3 and tubes). The Mimic Technologies software scored each task from 0 (worst) to 100 (best) using several predetermined metrics. Face and content validity were evaluated by a questionnaire administered after task completion. Wilcoxon test was used to perform pair wise comparisons. Results: The expert group comprised of 6 attending surgeons. The intermediate group included 4 attending surgeons, 3 fellows and 5 residents. The novices included 1 attending surgeon, 1 fellow, 13 residents, 13 medical students and 2 research assistants. The median number of robotic cases performed by experts and intermediates were 250 and 9, respectively. The median overall realistic score (face validity) was 8/10. Experts rated the usefulness of the simulator as a training tool for residents (content validity) as 8.5/10. For construct validity, experts outperformed novices in all 9 tasks (p < 0.05). Intermediates outperformed novices in 7 of 9 tasks (p < 0.05); there were no significant differences in the energy dissection and ring walk tasks. Finally, experts scored significantly better than intermediates in only 3 of 9 tasks (matchboard, dots and needles and energy dissection) (p < 0.05). Conclusions: This study confirms the face, content and construct validities of the dVSSS across urology, gynecology and general surgery. Larger sample size and more complex tasks are needed to further differentiate intermediates from experts. PMID:23914275

Shear stress increases nitric oxide production in thick ascending limbs

PubMed Central

Cabral, Pablo D.; Hong, Nancy J.

2010-01-01

We showed that luminal flow stimulates nitric oxide (NO) production in thick ascending limbs. Ion delivery, stretch, pressure, and shear stress all increase when flow is enhanced. We hypothesized that shear stress stimulates NO in thick ascending limbs, whereas stretch, pressure, and ion delivery do not. We measured NO in isolated, perfused rat thick ascending limbs using the NO-sensitive dye DAF FM-DA. NO production rose from 21 ± 7 to 58 ± 12 AU/min (P < 0.02; n = 7) when we increased luminal flow from 0 to 20 nl/min, but dropped to 16 ± 8 AU/min (P < 0.02; n = 7) 10 min after flow was stopped. Flow did not increase NO in tubules from mice lacking NO synthase 3 (NOS 3). Flow stimulated NO production by the same extent in tubules perfused with ion-free solution and physiological saline (20 ± 7 vs. 24 ± 6 AU/min; n = 7). Increasing stretch while reducing shear stress and pressure lowered NO generation from 42 ± 9 to 17 ± 6 AU/min (P < 0.03; n = 6). In the absence of shear stress, increasing pressure and stretch had no effect on NO production (2 ± 8 vs. 8 ± 8 AU/min; n = 6). Similar results were obtained in the presence of tempol (100 μmol/l), a O2− scavenger. Primary cultures of thick ascending limb cells subjected to shear stresses of 0.02 and 0.55 dyne/cm2 produced NO at rates of 55 ± 10 and 315 ± 93 AU/s, respectively (P < 0.002; n = 7). Pretreatment with the NOS inhibitor l-NAME (5 mmol/l) blocked the shear stress-induced increase in NO production. We concluded that shear stress rather than pressure, stretch, or ion delivery mediates flow-induced stimulation of NO by NOS 3 in thick ascending limbs. PMID:20719980

Genetics of Aggression in Alzheimer’s Disease (AD)

PubMed Central

Lukiw, Walter J.; Rogaev, Evgeny I.

2017-01-01

Alzheimer’s disease (AD) is a terminal, age-related neurological syndrome exhibiting progressive cognitive and memory decline, however AD patients in addition exhibit ancillary neuropsychiatric symptoms (NPSs) and these include aggression. In this communication we provide recent evidence for the mis-regulation of a small family of genes expressed in the human hippocampus that appear to be significantly involved in expression patterns common to both AD and aggression. DNA array- and mRNA transcriptome-based gene expression analysis and candidate gene association and/or genome-wide association studies (CGAS, GWAS) of aggressive attributes in humans have revealed a surprisingly small subset of six brain genes that are also strongly associated with altered gene expression patterns in AD. These genes encoded on five different chromosomes (chr) include the androgen receptor (AR; chrXq12), brain-derived neurotrophic factor (BDNF; chr11p14.1), catechol-O-methyl transferase (COMT; chr22q11.21), neuronal specific nitric oxide synthase (NOS1; chr12q24.22), dopamine beta-hydroxylase (DBH chr9q34.2) and tryptophan hydroxylase (TPH1, chr11p15.1 and TPH2, chr12q21.1). Interestingly, (i) the expression of three of these six genes (COMT, DBH, NOS1) are highly variable; (ii) three of these six genes (COMT, DBH, TPH1) are involved in DA or serotonin metabolism, biosynthesis and/or neurotransmission; and (iii) five of these six genes (AR, BDNF, COMT, DBH, NOS1) have been implicated in the development, onset and/or propagation of schizophrenia. The magnitude of the expression of genes implicated in aggressive behavior appears to be more pronounced in the later stages of AD when compared to MCI. These recent genetic data further indicate that the extent of cognitive impairment may have some bearing on the degree of aggression which accompanies the AD phenotype. PMID:28443016

Brassica juncea nitric oxide synthase like activity is stimulated by PKC activators and calcium suggesting modulation by PKC-like kinase.

PubMed

Talwar, Pooja Saigal; Gupta, Ravi; Maurya, Arun Kumar; Deswal, Renu

2012-11-01

Nitric oxide (NO) is an important signaling molecule having varied physiological and regulatory roles in biological systems. The fact that nitric oxide synthase (NOS) is responsible for NO generation in animals, prompted major search for a similar enzyme in plants. Arginine dependent NOS like activity (BjNOSla) was detected in Brassica juncea seedlings using oxyhemoglobin and citrulline assays. BjNOSla showed 25% activation by NADPH (0.4 mM) and 40% by calcium (0.4 mM) but the activity was flavin mononucleotide (FMN), flavin dinucleotide (FAD) and calmodulin (CaM) independent. Pharmacological approach using mammalian NOS inhibitors, NBT (300 μM) and l-NAME (5 mM), showed significant inhibition (100% and 67% respectively) supporting that the BjNOSla operates via the oxidative pathway. Most of the BjNOSla activity (80%) was confined to shoot while root showed only 20% activity. Localization studies by NADPH-diaphorase and DAF-2DA staining showed the presence of BjNOSla in guard cells. Kinetic analysis showed positive cooperativity with calcium as reflected by a decreased K(m) (∼13%) and almost two fold increase in V(max). PMA (438 nM), a kinase activator, activated BjNOSla ∼1.9 fold while its inactive analog 4αPDD was ineffective. Calcium and PMA activated the enzyme to ∼3 folds. Interestingly, 1,2-DG6 (2.5 μM) and PS (1 μM) with calcium activated the enzyme activity to ∼7 fold. A significant inhibition of BjNOSla by PKC inhibitors-staurosporine (∼90%) and calphostin-C (∼40%), further supports involvement of PKC-like kinase. The activity was also enhanced by abiotic stress conditions (7-46%). All these findings suggest that BjNOSla generates NO via oxidative pathway and is probably regulated by phosphorylation. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Patients or volunteers? The impact of motivation for trial participation on the efficacy of patient decision Aids: a secondary analysis of a Cochrane systematic review.

PubMed

Brown, James G; Joyce, Kerry E; Stacey, Dawn; Thomson, Richard G

2015-05-01

Efficacy of patient decision aids (PtDAs) may be influenced by trial participants' identity either as patients seeking to benefit personally from involvement or as volunteers supporting the research effort. To determine if study characteristics indicative of participants' trial identity might influence PtDA efficacy. We undertook exploratory subgroup meta-analysis of the 2011 Cochrane review of PtDAs, including trials that compared PtDA with usual care for treatment decisions. We extracted data on whether participants initiated the care pathway, setting, practitioner interactions, and 6 outcome variables (knowledge, risk perception, decisional conflict, feeling informed, feeling clear about values, and participation). The main subgroup analysis categorized trials as "volunteerism" or "patienthood" on the basis of whether participants initiated the care pathway. A supplementary subgroup analysis categorized trials on the basis of whether any volunteerism factors were present (participants had not initiated the care pathway, had attended a research setting, or had a face-to-face interaction with a researcher). Twenty-nine trials were included. Compared with volunteerism trials, pooled effect sizes were higher in patienthood trials (where participants initiated the care pathway) for knowledge, decisional conflict, feeling informed, feeling clear, and participation. The subgroup difference was statistically significant for knowledge only (P = 0.03). When trials were compared on the basis of whether volunteerism factors were present, knowledge was significantly greater in patienthood trials (P < 0.001), but there was otherwise no consistent pattern of differences in effects across outcomes. There is a tendency toward greater PtDA efficacy in trials in which participants initiate the pathway of care. Knowledge acquisition appears to be greater in trials where participants are predominantly patients rather than volunteers. © The Author(s) 2015.

Efficient generation of hPSC-derived midbrain dopaminergic neurons in a fully defined, scalable, 3D biomaterial platform

PubMed Central

Adil, Maroof M.; Rodrigues, Gonçalo M. C.; Kulkarni, Rishikesh U.; Rao, Antara T.; Chernavsky, Nicole E.; Miller, Evan W.; Schaffer, David V.

2017-01-01

Pluripotent stem cells (PSCs) have major potential as an unlimited source of functional cells for many biomedical applications; however, the development of cell manufacturing systems to enable this promise faces many challenges. For example, there have been major recent advances in the generation of midbrain dopaminergic (mDA) neurons from stem cells for Parkinson’s Disease (PD) therapy; however, production of these cells typically involves undefined components and difficult to scale 2D culture formats. Here, we used a fully defined, 3D, thermoresponsive biomaterial platform to rapidly generate large numbers of action-potential firing mDA neurons after 25 days of differentiation (~40% tyrosine hydroxylase (TH) positive, maturing into 25% cells exhibiting mDA neuron-like spiking behavior). Importantly, mDA neurons generated in 3D exhibited a 30-fold increase in viability upon implantation into rat striatum compared to neurons generated on 2D, consistent with the elevated expression of survival markers FOXA2 and EN1 in 3D. A defined, scalable, and resource-efficient cell culture platform can thus rapidly generate high quality differentiated cells, both neurons and potentially other cell types, with strong potential to accelerate both basic and translational research. PMID:28091566

Auditory-visual speech integration by prelinguistic infants: perception of an emergent consonant in the McGurk effect.

PubMed

Burnham, Denis; Dodd, Barbara

2004-12-01

The McGurk effect, in which auditory [ba] dubbed onto [ga] lip movements is perceived as "da" or "tha," was employed in a real-time task to investigate auditory-visual speech perception in prelingual infants. Experiments 1A and 1B established the validity of real-time dubbing for producing the effect. In Experiment 2, 4 1/2-month-olds were tested in a habituation-test paradigm, in which an auditory-visual stimulus was presented contingent upon visual fixation of a live face. The experimental group was habituated to a McGurk stimulus (auditory [ba] visual [ga]), and the control group to matching auditory-visual [ba]. Each group was then presented with three auditory-only test trials, [ba], [da], and [(delta)a] (as in then). Visual-fixation durations in test trials showed that the experimental group treated the emergent percept in the McGurk effect, [da] or [(delta)a], as familiar (even though they had not heard these sounds previously) and [ba] as novel. For control group infants [da] and [(delta)a] were no more familiar than [ba]. These results are consistent with infants' perception of the McGurk effect, and support the conclusion that prelinguistic infants integrate auditory and visual speech information. Copyright 2004 Wiley Periodicals, Inc.

Toward the S3DVAR data assimilation software for the Caspian Sea

NASA Astrophysics Data System (ADS)

Arcucci, Rossella; Celestino, Simone; Toumi, Ralf; Laccetti, Giuliano

2017-07-01

Data Assimilation (DA) is an uncertainty quantification technique used to incorporate observed data into a prediction model in order to improve numerical forecasted results. The forecasting model used for producing oceanographic prediction into the Caspian Sea is the Regional Ocean Modeling System (ROMS). Here we propose the computational issues we are facing in a DA software we are developing (we named S3DVAR) which implements a Scalable Three Dimensional Variational Data Assimilation model for assimilating sea surface temperature (SST) values collected into the Caspian Sea with observations provided by the Group of High resolution sea surface temperature (GHRSST). We present the algorithmic strategies we employ and the numerical issues on data collected in two of the months which present the most significant variability in water temperature: August and March.

Upregulation of endothelial nitric oxide synthase (eNOS) and its upstream regulators in Opisthorchis viverrini associated cholangiocarcinoma and its clinical significance.

PubMed

Suksawat, Manida; Techasen, Anchalee; Namwat, Nisana; Yongvanit, Puangrat; Khuntikeo, Narong; Titapun, Attapon; Koonmee, Supinda; Loilome, Watcharin

2017-08-01

Endothelial nitric oxide synthase (eNOS) is an isoform of the enzyme nitric oxide synthase (NOS) which is constitutively expressed in endothelial cells and plays important roles in vasodilation. We previously reported the importance of eNOS activation in cholangiocarcinoma (CCA) tissues and cell lines. The present study aims to investigate the relative abundance of eNOS and phosphorylated eNOS (P-eNOS) and their upstream regulators VEGFR3, VEGFC, EphA3 and ephrin-A1, in the Opisthorchis viverrini (Ov)/N-nitrosodimethylamine (NDMA)-induced hamster CCA model and in human CCA by semiquantitative immunohistochemical analysis of the relevant tissues. Results from the hamster model suggested an increase in eNOS and P-eNOS and upstream regulators during CCA genesis. In human CCA, high immunohistochemical staining intensity of all investigated proteins was associated with the presence of metastasis. A pairwise analysis of the staining data for eNOS and its upstream regulators showed that a concurrent increase in eNOS/VEGFR3, eNOS/ephrin-A1, eNOS/VEGFC and eNOS/EphA3 was significantly associated with metastasis. An increase in eNOS/VEGFR3, eNOS/ephrin-A1 was also associated with non-papillary type CCA. Additionally, an increase in eNOS and P-eNOS was significantly correlated with a high micro-vessel level (P=0.04). Our results indicate that the development of CCA involves upregulation of eNOS and P-eNOS and their regulators. This may drive angiogenesis and metastasis in CCA. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

White Dwarfs in the SDSS Photometric Footprint

NASA Astrophysics Data System (ADS)

Gentile Fusillo, N. P.; Girven, J.; Gänsicke, B.

2013-01-01

Attempts to create a homogeneous catalogue of white dwarfs have always been faced with the challenge posed by the intrinsic faintness of these objects. In recent years, thanks to large area surveys like the Sloan Digital Sky Survey (SDSS), the size of the known white dwarf population has increased dramatically, but, in order to carry out a statical study on the population of white dwarfs, it is necessary to have a reliable and well-defined selection method. We present a method which uses cuts in colour-colour space to select from DR7 16785 bright (g ≤ 19) photometric DA white dwarf candidates (Girven et al. 2011). The selection is 62% efficient in returning DA white dwarfs and produces a DA sample which is 95% complete for Teff > 8000 K. This sample contains 4636 spectroscopically confirmed DA white dwarfs; i.e. a ˜70% increase compared to Eisenstein et al.'s sample. As a first application of the SDSS DR7 DA candidates sample we cross correlated it with Data Release 8 of UKIDSS Large Area Survey with the aim of identifying white dwarfs which exhibit an infrared excess consistent with the presence of low mass stellar companions or dusty debris discs. Our current work aims to extend the photometric selection to all types of white dwarfs, using reduced proper motion as a further constrain. We expect to find a total of ˜20 000 photometric white dwarf candidates with g ≤ 19 in the footprint of SDSS DR8.

Limited English Proficient Students: Progress of 2008-09 High School Cohort. Data Trends. D&A Report No. 13.14

ERIC Educational Resources Information Center

Baenen, Nancy

2013-01-01

Students with Limited English Proficiency (LEP) entering U.S. schools in grade 9 face a tight timeline to simultaneously learn English and graduate from high school in four or five years. This study focuses on student outcomes and progress indicators for the cohort of ninth graders new to WCPSS in 2008-09 who had limited English proficiency. Based…

Expression analysis of NOS family and HSP genes during thermal stress in goat ( Capra hircus)

NASA Astrophysics Data System (ADS)

Yadav, Vijay Pratap; Dangi, Satyaveer Singh; Chouhan, Vikrant Singh; Gupta, Mahesh; Dangi, Saroj K.; Singh, Gyanendra; Maurya, Vijay Prakash; Kumar, Puneet; Sarkar, Mihir

2016-03-01

Approximately 50 genes other than heat shock protein (HSP) expression changes during thermal stress. These genes like nitric oxide synthase (NOS) need proper attention and investigation to find out their possible role in the adaptation to thermal stress in animals. So, the present study was undertaken to demonstrate the expressions of inducible form type II NOS (iNOS), endothelial type III NOS (eNOS), constitutively expressed enzyme NOS (cNOS), HSP70, and HSP90 in peripheral blood mononuclear cells (PBMCs) during different seasons in Barbari goats. Real-time polymerase chain reaction, western blot, and immunocytochemistry were applied to investigate messenger RNA (mRNA) expression, protein expression, and immunolocalization of examined factors. The mRNA and protein expressions of iNOS, eNOS, cNOS, HSP70, and HSP90 were significantly higher ( P < 0.05) during peak summer, and iNOS and eNOS expressions were also observed to be significantly higher ( P < 0.05) during peak winter season as compared with moderate season. The iNOS, eNOS, cNOS, HSP70, and HSP90 were mainly localized in plasma membrane and cytoplasm of PBMCs. To conclude, data generated in the present study indicate the possible involvement of the NOS family genes in amelioration of thermal stress so as to maintain cellular integrity and homeostasis in goats.

Deficient ryanodine receptor S-nitrosylation increases sarcoplasmic reticulum calcium leak and arrhythmogenesis in cardiomyocytes.

PubMed

Gonzalez, Daniel R; Beigi, Farideh; Treuer, Adriana V; Hare, Joshua M

2007-12-18

Altered Ca(2+) homeostasis is a salient feature of heart disease, where the calcium release channel ryanodine receptor (RyR) plays a major role. Accumulating data support the notion that neuronal nitric oxide synthase (NOS1) regulates the cardiac RyR via S-nitrosylation. We tested the hypothesis that NOS1 deficiency impairs RyR S-nitrosylation, leading to altered Ca(2+) homeostasis. Diastolic Ca(2+) levels are elevated in NOS1(-/-) and NOS1/NOS3(-/-) but not NOS3(-/-) myocytes compared with wild-type (WT), suggesting diastolic Ca(2+) leakage. Measured leak was increased in NOS1(-/-) and NOS1/NOS3(-/-) but not in NOS3(-/-) myocytes compared with WT. Importantly, NOS1(-/-) and NOS1/NOS3(-/-) myocytes also exhibited spontaneous calcium waves. Whereas the stoichiometry and binding of FK-binding protein 12.6 to RyR and the degree of RyR phosphorylation were not altered in NOS1(-/-) hearts, RyR2 S-nitrosylation was substantially decreased, and the level of thiol oxidation increased. Together, these findings demonstrate that NOS1 deficiency causes RyR2 hyponitrosylation, leading to diastolic Ca(2+) leak and a proarrhythmic phenotype. NOS1 dysregulation may be a proximate cause of key phenotypes associated with heart disease.

Using History of Science to Teach Nature of Science to Elementary Students

NASA Astrophysics Data System (ADS)

Fouad, Khadija E.; Masters, Heidi; Akerson, Valarie L.

2015-11-01

Science lessons using inquiry only or history of science with inquiry were used for explicit reflective nature of science (NOS) instruction for second-, third-, and fourth-grade students randomly assigned to receive one of the treatments. Students in both groups improved in their understanding of creative NOS, tentative NOS, empirical NOS, and subjective NOS as measured using VNOS-D as pre- and post-test surveys. Social and cultural context of science was not accessible for the students. Students in second, third, and fourth grades were able to attain adequate views of empirical NOS, the role of observation and inference, creative and imaginative NOS, and subjective NOS. Students were not able to express adequate views of socially and culturally embedded NOS. Most gains in NOS eroded by the next school year, except for tentative NOS for both groups and creative NOS for the inquiry group.

Using a Professional Development Program for Enhancing Chilean Biology Teachers' Understanding of Nature of Science (NOS) and Their Perceptions About Using History of Science to Teach NOS

NASA Astrophysics Data System (ADS)

Pavez, José M.; Vergara, Claudia A.; Santibañez, David; Cofré, Hernán

2016-05-01

A number of authors have recognized the importance of understanding the nature of science (NOS) for scientific literacy. Different instructional strategies such as decontextualized, hands-on inquiry, and history of science (HOS) activities have been proposed for teaching NOS. This article seeks to understand the contribution of HOS in enhancing biology teachers' understanding of NOS, and their perceptions about using HOS to teach NOS. These teachers ( N = 8), enrolled in a professional development program in Chile are, according to the national curriculum, expected to teach NOS, but have no specific NOS and HOS training. Teachers' views of NOS were assessed using the VNOS-D+ questionnaire at the beginning and at the end of two modules about science instruction and NOS. Both the pre- and the post-test were accompanied by interviews, and in the second session we collected information about teachers' perceptions of which interventions had been more significant in changing their views on NOS. Finally, the teachers also had to prepare a lesson plan for teaching NOS that included HOS. Some of the most important study results were: significant improvements were observed in teachers' understanding of NOS, although they assigned different levels of importance to HOS in these improvements; and although the teachers improved their understanding of NOS, most had difficulties in planning lessons about NOS and articulating historical episodes that incorporated NOS. The relationship between teachers' improved understanding of NOS and their instructional NOS skills is also discussed.

Feature extraction with deep neural networks by a generalized discriminant analysis.

PubMed

Stuhlsatz, André; Lippel, Jens; Zielke, Thomas

2012-04-01

We present an approach to feature extraction that is a generalization of the classical linear discriminant analysis (LDA) on the basis of deep neural networks (DNNs). As for LDA, discriminative features generated from independent Gaussian class conditionals are assumed. This modeling has the advantages that the intrinsic dimensionality of the feature space is bounded by the number of classes and that the optimal discriminant function is linear. Unfortunately, linear transformations are insufficient to extract optimal discriminative features from arbitrarily distributed raw measurements. The generalized discriminant analysis (GerDA) proposed in this paper uses nonlinear transformations that are learnt by DNNs in a semisupervised fashion. We show that the feature extraction based on our approach displays excellent performance on real-world recognition and detection tasks, such as handwritten digit recognition and face detection. In a series of experiments, we evaluate GerDA features with respect to dimensionality reduction, visualization, classification, and detection. Moreover, we show that GerDA DNNs can preprocess truly high-dimensional input data to low-dimensional representations that facilitate accurate predictions even if simple linear predictors or measures of similarity are used.

Noscapinoids bearing silver nanocrystals augmented drug delivery, cytotoxicity, apoptosis and cellular uptake in B16F1, mouse melanoma skin cancer cells.

PubMed

Soni, Naina; Jyoti, Kiran; Jain, Upendra Kumar; Katyal, Anju; Chandra, Ramesh; Madan, Jitender

2017-06-01

Noscapine (Nos) and reduced brominated analogue of noscapine (Red-Br-Nos) prevent cellular proliferation and induce apoptosis in cancer cells either alone or in combination with other chemotherapeutic drugs. However, owing to poor physicochemical properties, Nos and Red-Br-Nos have demonstrated their anticancer activity at higher and multiple doses. Therefore, in present investigation, silver nanocrystals of noscapinoids (Nos-Ag 2+ nanocrystals and Red-Br-Nos-Ag 2+ nanocrystals) were customized to augment drug delivery, cytotoxicity, apoptosis and cellular uptake in B16F1 mouse melanoma cancer cells. Nos-Ag 2+ nanocrystals and Red-Br-Nos-Ag 2+ nanocrystals were prepared separately by precipitation method. The mean particle size of Nos-Ag 2+ nanocrystals was measured to be 25.33±3.52nm, insignificantly (P>0.05) different from 27.43±4.51nm of Red-Br-Nos-Ag 2+ nanocrystals. Furthermore, zeta-potential of Nos-Ag 2+ nanocrystals was determined to be -25.3±3.11mV significantly (P<0.05) different from -15.2±3.33mV of Red-Br-Nos-Ag 2+ nanocrystals. The shape of tailored nanocrystals was slightly spherical and or irregular in shape. The architecture of Nos-Ag 2+ nanocrystals and Red-Br-Nos-Ag 2+ nanocrystals was crystalline in nature. FT-IR spectroscopy evinced the successful interaction of Ag 2+ nanocrystals with Nos and Red-Br-Nos, respectively. The superior therapeutic efficacy of tailored nanocrystals was measured in terms of enhanced cytotoxicity, apoptosis and cellular uptake. The Nos-Ag 2+ nanocrystals and Red-Br-Nos-Ag 2+ nanocrystals exhibited an IC 50 of 16.6μM and 6.5μM, significantly (P<0.05) lower than 38.5μM of Nos and 10.3μM of Red-Br-Nos, respectively. Finally, cellular morphological alterations in B16F1 cells upon internalization of Nos-Ag 2+ nanocrystals and Red-Br-Nos-Ag 2+ nanocrystals provided the evidences for accumulation within membrane-bound cytoplasmic vacuoles and in enlarged lysosomes and thus triggered mitochondria mediated apoptosis via caspase activation. Preliminary investigations substantiated that Nos-Ag 2+ nanocrystals and Red-Br-Nos-Ag 2+ nanocrystals must be further explored and utilized for the delivery of noscapinoids to melanoma cancer cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The ECS(SPSB) E3 ubiquitin ligase is the master regulator of the lifetime of inducible nitric-oxide synthase.

PubMed

Matsumoto, Kazuma; Nishiya, Tadashi; Maekawa, Satoshi; Horinouchi, Takahiro; Ogasawara, Kouetsu; Uehara, Takashi; Miwa, Soichi

2011-05-27

The ubiquitin-proteasome pathway is an important regulatory system for the lifetime of inducible nitric-oxide synthase (iNOS), a high-output isoform compared to neuronal NOS (nNOS) and endothelial NOS (eNOS), to prevent overproduction of NO that could trigger detrimental effects such as cytotoxicity. Two E3 ubiquitin ligases, Elongin B/C-Cullin-5-SPRY domain- and SOCS box-containing protein [ECS(SPSB)] and the C-terminus of Hsp70-interacting protein (CHIP), recently have been reported to target iNOS for proteasomal degradation. However, the significance of each E3 ubiquitin ligase for the proteasomal degradation of iNOS remains to be determined. Here, we show that ECS(SPSB) specifically interacted with iNOS, but not nNOS and eNOS, and induced the subcellular redistribution of iNOS from dense regions to diffused expression as well as the ubiquitination and proteasomal degradation of iNOS, whereas CHIP neither interacted with iNOS nor had any effects on the subcellular localization, ubiquitination, and proteasomal degradation of iNOS. These results differ from previous reports. Furthermore, the lifetime of the iNOS(N27A) mutant, a form of iNOS that does not bind to ECS(SPSB), was substantially extended in macrophages. These results demonstrate that ECS(SPSB), but not CHIP, is the master regulator of the iNOS lifetime. Copyright © 2011 Elsevier Inc. All rights reserved.

Pedagogical Reflections by Secondary Science Teachers at Different NOS Implementation Levels

NASA Astrophysics Data System (ADS)

Herman, Benjamin C.; Clough, Michael P.; Olson, Joanne K.

2017-02-01

This study investigated what 13 secondary science teachers at various nature of science (NOS) instruction implementation levels talked about when they reflected on their teaching. We then determined if differences exist in the quality of those reflections between high, medium, and low NOS implementers. This study sought to answer the following questions: (1) What do teachers talk about when asked general questions about their pedagogy and NOS pedagogy and (2) what qualitative differences, if any, exist within variables across teachers of varying NOS implementation levels? Evidence derived from these teachers' reflections indicated that self-efficacy and perceptions of general importance for NOS instruction were poor indicators of NOS implementation. However, several factors were associated with the extent that these teachers implemented NOS instruction, including the utility value they hold for NOS teaching, considerations of how people learn, understanding of NOS pedagogy, and their ability to accurately and deeply self-reflect about teaching. Notably, those teachers who effectively implemented the NOS at higher levels value NOS instruction for reasons that transcend immediate instructional objectives. That is, they value teaching NOS for achieving compelling ends realized long after formal schooling (e.g., lifelong socioscientific decision-making for civic reasons), and they deeply reflect about how to teach NOS by drawing from research about how people learn. Low NOS implementers' simplistic notions and reflections about teaching and learning appeared to be impeding factors to accurate and consistent NOS implementation. This study has implications for science teacher education efforts that promote NOS instruction.

Da Vinci Xi and Si platforms have equivalent perioperative outcomes during robot-assisted partial nephrectomy: preliminary experience.

PubMed

Abdel Raheem, Ali; Sheikh, Abulhasan; Kim, Dae Keun; Alatawi, Atalla; Alabdulaali, Ibrahim; Han, Woong Kyu; Choi, Young Deuk; Rha, Koon Ho

2017-03-01

The aims of this study were to compare the perioperative outcomes of da Vinci Xi to Si during robotic-assisted partial nephrectomy (RAPN) and to discuss the feasibility of our novel port placement scheme for the da Vinci Xi platform, to overcome the existing kinetic and technical difficulties we faced with the linear port placement in patients with a small body habitus. A retrospective data analysis of patients who underwent RPN using da Vinci Xi (n = 18) was carried out. The outcomes of the Xi group were compared with the Si group (n = 18) selected using a case-matched methodology. For da Vinci Xi, we applied the universal linear port placement in 12 patients and our modified port placement in the remaining 6 patients. The Xi group had a shorter mean docking time of 17.8 ± 2.6 min compared to the Si group of 20.5 ± 2.1 min (p = 0.002); otherwise, no significant difference was present with regard to the remaining perioperative variables (p > 0.05). The modified Xi port placement had a shorter mean console time of 70.8 ± 9.7 min compared to the universal linear port placement of 89.3 ± 17.2 min (p = 0.03). Moreover, it provided a broader field of vision with excellent robotic arms movement, minimizing collisions and allowing an easier and comfortable surgical assist. Da Vinci Xi appears to be feasible and safe during RPN with similar outcomes to Si. The novel Xi port placement makes surgery easier in patients with low BMI.

Irisin protects against endothelial injury and ameliorates atherosclerosis in apolipoprotein E-Null diabetic mice.

PubMed

Lu, Junyan; Xiang, Guangda; Liu, Min; Mei, Wen; Xiang, Lin; Dong, Jing

2015-12-01

The circulating irisin increases energy expenditure and improves insulin resistance in mice and humans. The improvement of insulin resistance ameliorates atherosclerosis. Therefore, we hypothesized that irisin alleviates atherosclerosis in diabetes. Endothelial function was measured by acetylcholine-induced endothelium-dependent vasodilation using aortic rings in apolipoprotein E-Null (apoE(-/-)) streptozotocin-induced diabetic mice. Atherosclerotic lesion was evaluated by plaque area and inflammatory response in aortas. In addition, the endothelium-protective effects of irisin were also further investigated in primary human umbilical vein endothelial cells (HUVECs) in vitro. The in vivo experiments showed that irisin treatment significantly improved endothelial dysfunction, decreased endothelial apoptosis, and predominantly decreased atherosclerotic plaque area of both en face and cross sections when compared with normal saline-treated diabetic mice. Moreover, the infiltrating macrophages and T lymphocytes within plaque and the mRNA expression levels of inflammatory cytokines in aortas were also significantly reduced by irisin treatment in mice. The in vitro experiments revealed that irisin inhibited high glucose-induced apoptosis, oxidative stress and increased antioxidant enzymes expression in HUVECs, and pretreatment with LY294002, l-NAME, AMPK-siRNA or eNOS-siRNA, attenuated the protection of irisin on HUVECs apoptosis induced by high glucose. In addition, the in vivo and in vitro experiments showed that irisin increased the phosphorylation of AMPK, Akt and eNOS in aortas and cultured HUVECs. The present study indicates that systemic administration of irisin may be protected against endothelial injury and ameliorated atherosclerosis in apoE(-/-) diabetic mice. The endothelium-protective action of irisin was through activation of AMPK-PI3K-Akt-eNOS signaling pathway. Irisin could be therapeutic for atherosclerotic vascular diseases in diabetes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Renal actions of atrial natriuretic peptide in spontaneously hypertensive rats: the role of nitric oxide as a key mediator.

PubMed

Elesgaray, Rosana; Caniffi, Carolina; Savignano, Lucía; Romero, Mariana; Mac Laughlin, Myriam; Arranz, Cristina; Costa, María A

2012-06-01

Atrial natriuretic peptide (ANP) is an important regulator of blood pressure (BP). One of the mechanisms whereby ANP impacts BP is by stimulation of nitric oxide (NO) production in different tissues involved in BP control. We hypothesized that ANP-stimulated NO is impaired in the kidneys of spontaneously hypertensive rats (SHR) and this contributes to the development and/or maintenance of high levels of BP. We investigated the effects of ANP on the NO system in SHR, studying the changes in renal nitric oxide synthase (NOS) activity and expression in response to peptide infusion, the signaling pathways implicated in the signaling cascade that activates NOS, and identifying the natriuretic peptide receptors (NPR), guanylyl cyclase receptors (NPR-A and NPR-B) and/or NPR-C, and NOS isoforms involved. In vivo, SHR and Wistar-Kyoto rats (WKY) were infused with saline (0.05 ml/min) or ANP (0.2 μg·kg(-1)·min(-1)). NOS activity and endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) NOS expression were measured in the renal cortex and medulla. In vitro, ANP-induced renal NOS activity was determined in the presence of iNOS and nNOS inhibitors, NPR-A/B blockers, guanine nucleotide-regulatory (G(i)) protein, and calmodulin inhibitors. Renal NOS activity was higher in SHR than in WKY. ANP increased NOS activity, but activation was lower in SHR than in WKY. ANP had no effect on expression of NOS isoforms. ANP-induced NOS activity was not modified by iNOS and nNOS inhibitors. NPR-A/B blockade blunted NOS stimulation via ANP in kidney. The renal NOS response to ANP was reduced by G(i) protein and calmodulin inhibitors. We conclude that ANP interacts with NPR-C, activating Ca-calmodulin eNOS through G(i) protein. NOS activation also involves NPR-A/B. The NOS response to ANP was diminished in kidneys of SHR. The impaired NO system response to ANP in SHR participates in the maintenance of high blood pressure.

A proposed contents astronomy for basic education

NASA Astrophysics Data System (ADS)

Albrecht, E.; Voelzke, M. R.

2014-08-01

A Astronomia é um tema que sempre exerceu fascínio sobre as pessoas de um modo geral. Conhecer e estudar o que há nos “céus”, além de nossos olhos, continua sendo instigador e de grande interesse. Baseado nestas justificativas desenvolveu-se uma pesquisa de Doutorado, na qual, o objetivo principal foi investigar sobre a presença dos conteúdos de Astronomia nas Propostas Curriculares da região Sul do Brasil, a saber, os estados de Paraná, Rio Grande do Sul e Santa Catarina e, posterior comparação com os Parâmetros Curriculares Nacionais (PCN) que trazem propostas de conteúdos para toda a Educação Básica brasileira. Tal investigação pautou-se na abordagem de caráter qualitativo e utilizouse para tal da Análise de Conteúdos (Bardin, 2011), que possibilitou a construção de quatro categorias, nas quais os conteúdos astronômicos foram agrupados: Terra, Sistema Solar, Via Láctea e Universo. Após a leitura, coleta de dados, construção de categorias, observou-se a dicotomia na apresentação destes conteúdos. As propostas curriculares analisadas foram as de Geografia, Ciências e Física dos estados do Paraná (2008), Rio Grande do Sul (2009) e de Santa Catarina (1998), responsáveis pelo trabalho com Astronomia nestes estados. No Ensino Fundamental, a proposta curricular do estado do Paraná apresenta conteúdos ligados à Astronomia desde o sexto ano até o nono ano, como conteúdo do primeiro bimestre, o que também é apresentado na proposta curricular do estado do Rio Grande do Sul, porém, este, não divide os conteúdos por bimestre e nem por ano, mas por ciclos, sexto e sétimo anos como primeiro ciclo e oitavo e nono anos como segundo ciclo, deixando livre para o professor estruturar sua sequência de conteúdos. A proposta curricular de Santa Catarina não apresenta estes conteúdos de maneira explícita, não divide dos conteúdos nem por ano, nem por série, traz uma sequência de conteúdos para serem trabalhados ao longo dos quatro anos, nos quais, aparecem timidamente alguns conteúdos de Astronomia. Para o Ensino Médio, as propostas curriculares do Paraná e de Santa Catarina parecem que se repetem, apresentando apenas o conteúdo Gravitação Universal, na primeira série do Ensino Médio, já a proposta curricular do Rio Grande do Sul, traz uma sequência que é proposta nos PCN (Brasil, 1998; 1999; 2002), na qual aparece o tema em questão, porém, em todos os anos, em todas as propostas, não há um detalhamento do que, de como trabalhar os conteúdos. O detalhamento facilita a prática pedagógica, pois, conteúdos simples como as Estações do Ano, Fases da Lua, sequer são citados nas propostas curriculares pesquisadas. Outro aspecto observado é que os conteúdos de um modo geral não trazem uma sequência e não primam por partir do entorno do aluno, daquilo que ele conhece para estruturar novos conceitos. Tais aspectos dificultam o fazer pedagógico, pois, por ser uma região com características culturais semelhantes, era esperado que as propostas fossem mais próximas, o! que facilitaria em muito, por exemplo, transferências dentro de um mesmo estado ou interestaduais. Pautando-se no que foi observado, na falta de especificidade dos conteúdos, clareza, sequência dos conteúdos e propostas de trabalho é proposto uma sequência de conteúdos de Astronomia, com materiais e recursos, pois, como apontado por Langhi e Nardi (2009), é necessário fornecer além da informação, do conteúdo, o como fazer. Tal proposta não visa estabelecer-se como regra, mas como suporte ao professor para facilitar sua prática pedagógica e tornar o trabalho com Astronomia presente nas escolas brasileiras. Bardin, L. Análise de conteúdo. Tradução Luís Antero Reto, Augusto Pinheiro. São Paulo: Edições 70, 2011. 279 p. Langhi, R; Nardi, R. Ensino da astronomia no Brasil: educação formal, informal, não-formal e divulgação científica. Revista Brasileira de Ensino de Física, v. 31, n. 4, p. 4402-1 a 4402-11, 2009.

Sociodemographic and health factors associated with mortality in community-dwelling elderly.

PubMed

Borim, Flávia Silva Arbex; Francisco, Priscila Maria Stolses Bergamo; Neri, Anita Liberalesso

2017-05-04

The objective of this study is to identify factors associated with mortality, with emphasis on gender and age differences. This is a cross-sectional study, which uses data from the FIBRA-2008-2009 network in Campinas, State of São Paulo, Brazil, with information on non-institutionalized residents of the urban area and the Mortality Information System. The dependent variable has been death, in 2013. The associations have been tested by odds ratio (OR) and their 95% confidence intervals, and the analyses have been conducted using the program Stata 12.0. Average age has been 72.3 years, 69.3% have been women, and 8.9% have died. We have found greater OR for mortality in individuals aged ≥ 75 years, classified as pre-frail or frail, and in those who have reported heart disease. In this study, the analysis of specific subgroups has allowed us to better understand the relationship between the factors associated with death in the elderly. With the exception of age, strategies based on primary and secondary care, focused on priority groups, can have a positive impact on the reduction of mortality among the elderly. Identificar fatores associados à mortalidade, com ênfase nas diferenças de gênero e idade. Trata-se de estudo transversal, utilizando dados provenientes da rede FIBRA-2008-2009 em Campinas, SP, com informações de pessoas não institucionalizadas residentes na área urbana e pelo Sistema de Informações de Mortalidade. A variável dependente foi a ocorrência de óbito, verificada em 2013. As associações foram testadas pelas razões de chances (OR) e respectivos intervalos de confiança de 95%, e as análises conduzidas no programa Stata 12.0. A média de idade foi 72,3 anos, 69,3% eram mulheres e 8,9% foram a óbito. Encontrou-se maior OR para mortalidade nos indivíduos com idade ≥ 75 anos, nos classificados como pré-frágil ou frágil e naqueles que referiram doença do coração. Neste estudo, a análise para os subgrupos específicos permitiu melhor compreender a relação entre fatores que se associam ao óbito no idoso. Com exceção da idade, estratégias baseadas no cuidado específico de atenção primária e secundária, direcionadas a grupos prioritários, podem ter um impacto positivo na redução da mortalidade entre os idosos.

Fotometria superficial BVRI de 18 galáxias fracas

NASA Astrophysics Data System (ADS)

Saraiva, M. F. O.; Silva, P. R.

2003-08-01

Conhecer as propriedades de galáxias a diferentes redshifts é uma questão fundamental para entender o problema da formação e evolução das galáxias, e desde a década passada tem se intensificado fortemente o estudo de galáxias muito distantes. No entanto parece haver um interesse menor em galáxias a distâncias intermediárias, que aparecem como objetos de fundo em imagens de objetos próximos, e que são igualmente importantes. Examinando imagens BVRI de longa exposição, ótimo sinal/ruído, grande campo (46'x46'), das vizinhanças de NGC 7479, detectamos 18 galáxias fracas (18 < B < 21) nessas imagens. Neste trabalho, apresentamos a fotometria superficial desses objetos. Determinamos coordenadas equatoriais, magnitudes e cores integradas, perfis de brilho e de cor, e parâmetros isofotais calculados por ajuste de ellipses, dentro do limite permitido pela baixa resolução espacial dos dados (1,35 segarc/pixel). Nosso objetivo é procurar correlações entre as propriedades das galáxias e, tentativamente, comparar esses dados com aqueles de galáxias de redshift conhecido, disponíveis na literatura, para estimar suas distâncias (a partir da relação cor x redshift) e suas morfologias. Uma análise preliminar nesse sentido mostrou que as cores aparentes B-V, V-R e V-I dos objetos da nossa amostra, a menos de duas exceções, ocupam regiões bem definidas nos diagramas cor-cor, e não apresentam diferenças notáveis em relação às cores típicas de galáxias próximas.

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

Unexpected Heterodivalent Recruitment of NOS1AP to nNOS Reveals Multiple Sites for Pharmacological Intervention in Neuronal Disease Models.

PubMed

Li, Li-Li; Melero-Fernandez de Mera, Raquel M; Chen, Jia; Ba, Wei; Kasri, Nael Nadif; Zhang, Mingjie; Courtney, Michael J

2015-05-13

The protein NOS1AP/CAPON mediates signaling from a protein complex of NMDA receptor, PSD95 and nNOS. The only stroke trial for neuroprotectants that showed benefit to patients targeted this ternary complex. NOS1AP/nNOS interaction regulates small GTPases, iron transport, p38MAPK-linked excitotoxicity, and anxiety. Moreover, the nos1ap gene is linked to disorders from schizophrenia, post-traumatic stress disorder, and autism to cardiovascular disorders and breast cancer. Understanding protein interactions required for NOS1AP function, therefore, has broad implications for numerous diseases. Here we show that the interaction of NOS1AP with nNOS differs radically from the classical PDZ docking assumed to be responsible. The NOS1AP PDZ motif does not bind nNOS as measured by multiple methods. In contrast, full-length NOS1AP forms an unusually stable interaction with nNOS. We mapped the discrepancy between full-length and C-terminal PDZ motif to a novel internal region we call the ExF motif. The C-terminal PDZ motif, although neither sufficient nor necessary for binding, nevertheless promotes the stability of the complex. It therefore potentially affects signal transduction and suggests that functional interaction of nNOS with NOS1AP might be targetable at two distinct sites. We demonstrate that excitotoxic pathways can be regulated, in cortical neuron and organotypic hippocampal slice cultures from rat, either by the previously described PDZ ligand TAT-GESV or by the ExF motif-bearing region of NOS1AP, even when lacking the critical PDZ residues as long as the ExF motif is intact and not mutated. This previously unrecognized heterodivalent interaction of nNOS with NOS1AP may therefore provide distinct opportunities for pharmacological intervention in NOS1AP-dependent signaling and excitotoxicity. Copyright © 2015 the authors 0270-6474/15/357349-16$15.00/0.

Application of Three-Dimensional Models for the Teaching of Time Zones. (Breton Title: Aplicação de Modelos Tridimensionais Para o Ensino de Fusos Horários.) Aplicación de Modelos Tridimensionales Para la Enseñanza de Husos Horarios

NASA Astrophysics Data System (ADS)

Azevedo Sobreira, Paulo Henrique

2012-07-01

There are several interesting astronomical topics that must be addressed in the High School and Elementary/Middle School in the disciplines of Geography and of Sciences. Among them, the topic of time zones which is one of the most important to understand the correlation of the Earth's rotation and its implications on daily activities of citizens in local scale, regional and global scales which involve problems of time differences. For the teaching of time zones in the lessons of Geography, for example, there are bi-dimensional representations of thematic maps of world time zones, textbooks and atlas. It happens that teachers face some difficulties to permit its students to view three-dimensionally this astronomical phenomenon from the textbooks available in schools. The aim of this paper is to present two proposals with low-cost materials, which allow the preparation of three-dimensional models for the teaching of time zones. Há vários temas astronômicos interessantes que devem ser trabalhados nos Ensinos Médio e Fundamental, nas disciplinas de Geografia e de Ciências. Entre eles, o tema dos fusos horários que é um dos mais importantes para se correlacionar a rotação da Terra e suas implicações nas atividades cotidianas dos cidadãos em escala local, regional e global, que envolvem problemas de diferenças horárias. Para o ensino dos fusos horários nas aulas de Geografia, por exemplo, há representações bidimensionais de mapas temáticos de fusos horários mundiais, nos livros didáticos e nos atlas. Ocorre que os professores enfrentam algumas dificuldades para possibilitar aos seus alunos a visão tridimensional deste fenômeno astronômico, a partir dos materiais didáticos disponíveis nas escolas. O objetivo deste trabalho é apresentar duas propostas para a confecção de materiais de baixo custo, que possibilitem a elaboração de modelos tridimensionais para o ensino dos fusos horários. Hay algunos temas astronómicos interesantes que se deben trabajar en la enseñanza media y básica, en las asignaturas de Geografía y de Ciencias. Entre ellos, el de los husos horarios que es uno de los más importantes para correlacionar la rotación de la Tierra y sus implicaciones en las actividades diarias de los ciudadanos en escala local, regional y global, y en general, cuestiones que implican problemas de las diferencias horarias. Para la enseñanza de los husos horarios en las clases de Geografía, por ejemplo, hay representaciones bidimensionales de los mapas temáticos de husos horarios mundiales, en libros y atlas didácticos. Sin embargo, los profesores se enfrentan con algunas dificultades para hacer posible que sus alumnos tengan una visión tridimensional de este fenómeno astronómico, usando los materiales didácticos disponibles en las escuelas. El objetivo de este trabajo es presentar la construcción de dos propuestas de materiales de bajo costo, que hacen posible la elaboración de modelos tridimensionales para la enseñanza de los husos horarios.

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.

Rerouting the Pathway for the Biosynthesis of the Side Ring System of Nosiheptide: The Roles of NosI, NosJ, and NosK

PubMed Central

2017-01-01

Nosiheptide (NOS) is a highly modified thiopeptide antibiotic that displays formidable in vitro activity against a variety of Gram-positive bacteria. In addition to a central hydroxypyridine ring, NOS contains several other modifications, including multiple thiazole rings, dehydro-amino acids, and a 3,4-dimethylindolic acid (DMIA) moiety. The DMIA moiety is required for NOS efficacy and is synthesized from l-tryptophan in a series of reactions that have not been fully elucidated. Herein, we describe the role of NosJ, the product of an unannotated gene in the biosynthetic operon for NOS, as an acyl carrier protein that delivers 3-methylindolic acid (MIA) to NosK. We also reassign the role of NosI as the enzyme responsible for catalyzing the ATP-dependent activation of MIA and MIA’s attachment to the phosphopantetheine moiety of NosJ. Lastly, NosK catalyzes the transfer of the MIA group from NosJ-MIA to a conserved serine residue (Ser102) on NosK. The X-ray crystal structure of NosK, solved to 2.3 Å resolution, reveals that the protein is an α/β-fold hydrolase. Ser102 interacts with Glu210 and His234 to form a catalytic triad located at the bottom of an open cleft that is large enough to accommodate the thiopeptide framework. PMID:28343381

Posttranslational inactivation of endothelial nitric oxide synthase in the transgenic sickle cell mouse penis

PubMed Central

Musicki, Biljana; Champion, Hunter C.; Hsu, Lewis L.; Bivalacqua, Trinity J.; Burnett, Arthur L.

2017-01-01

INTRODUCTION Sickle cell disease (SCD)-associated priapism is characterized by endothelial nitric oxide synthase (eNOS) dysfunction in the penis. However, the mechanism of decreased eNOS function/activation in the penis in association with SCD is not known. AIMS Our hypothesis in the present study was that eNOS is functionally inactivated in the SCD penis in association with impairments in eNOS posttranslational phosphorylation and the enzyme’s interactions with its regulatory proteins. METHODS Sickle cell transgenic (sickle) mice were used as an animal model of SCD. Wild type (WT) mice served as controls. Penes were excised at baseline for molecular studies. eNOS phosphorylation on Ser-1177 (positive regulatory site) and Thr-495 (negative regulatory site), total eNOS, and phosphorylated AKT (upstream mediator of eNOS phosphorylation on Ser-1177) expressions, and eNOS interactions with heat shock protein 90 (HSP90) and caveolin-1 were measured by Western blot. Constitutive NOS catalytic activity was measured by conversion of L-[14C]arginine-to-L-[14C]citrulline in the presence of calcium. MAIN OUTCOME MEASURES Molecular mechanisms of eNOS dysfunction in the sickle mouse penis. RESULTS eNOS phosphorylated on Ser-1177, an active portion of eNOS, was decreased in the sickle mouse penis compared to WT penis. eNOS interaction with its positive protein regulator HSP90, but not with its negative protein regulator caveolin-1, and phosphorylated AKT expression, as well as constitutive NOS activity, were also decreased in the sickle mouse penis compared to WT penis. eNOS phosphorylated on Thr-495, total eNOS, HSP90, and caveolin-1 protein expressions in the penis were not affected by SCD. CONCLUSION These findings provide a molecular basis for chronically reduced eNOS function in the penis by SCD, which involves decreased eNOS phosphorylation on Ser-1177 and decreased eNOS-HSP90 interaction. PMID:21143412

A Safe and Easy Introduction of Darbepoetin-Alpha in Patients Receiving Maintenance Hemodialysis and Epoetin Monotherapy: A “Half-and-Half” Combination Therapy☆

PubMed Central

Shimamatsu, Kazumasa; Inamasu, Hiroko

2013-01-01

Background In hemodialysis (HD) patients requiring anemia management, the 3-fold longer terminal half-life (25.3 hours) of darbepoetin-alpha (DA) results in reduced dose frequency when compared with recombinant human erythropoietin (EPO) -alpha or -beta by intravenous administration (8.5 hours). However, this might become a disadvantage in the face of rapid withdrawal of the drug against hemoglobin (Hb) overshoot and/or cycling. Objective A “half-and-half” combination therapy of DA and EPO was used to avoid a possible Hb overshoot due to the full conversion from EPO to DA. Methods Thirty-two stable patients receiving HD (13 men, 19 women) and EPO monotherapy were enrolled and prospectively followed for 9 months. The mean (SD) patient age was 63.2 (11.3) years. The HD duration was 10.7 (8.2) years. The DA doses (in micrograms) of 1/200 of halves of previous weekly EPO doses (in international units) were given intravenously on the second HD day of a week. The remaining half doses of previous weekly EPO doses were dividedly administered intravenously on the first and the third HD days of the week. The target Hb was 11 g/dL. Results The “half-and-half” combination with DA and EPO resulted in no episodes of Hb overshoot. The Hb values did not exceed 13 g/dL throughout the follow-up period. The mean (SD) dose of 3984 (2175) IU/wk EPO was converted to a combination of 1688 (894) IU/wk EPO and 13.4 (7.9) μg/wk DA at baseline. Thereafter, the mean (SD) doses became 304 (656) IU/wk EPO and 16.0 (8.4) μg/wk DA at 3 months, and 532 (912) IU/wk and 15.8 (9.0) μg/wk, respectively, at 9 months. The total combination doses of DA/EPO (as EPO equivalents) were significantly reduced to 80% to 84% of the original EPO doses after 2 months of introduction of the DA/EPO combination. Conclusions A “half-and-half” combination therapy may be a safe and easy method to merge DA into EPO monotherapy without Hb overshoot or dramatic cycling. PMID:24384988

Rock billboards on the basaltic cliff along the Route 66 ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Rock billboards on the basaltic cliff along the Route 66 alignment, ca. 1926. The sign on the left is for "La Bajada Service Shop" (faint "da" visible), "Santa Fe Camp" in the center, and a petroglyph at far right. View facing northwest. - La Bajada Historic Trails and Roads, Approximately 1 mile East/Northeast of intersection of State Highway 16 and Indian Service Road 841, La Bajada, Santa Fe County, NM

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.

Determining the Shape of the Orbit of Mars in the High School. (Spanish Title: Determinación de la Forma de la Órbita de Marte en la Escuela Secundaria.) Determinando a Forma da Órbita de Marte no Ensino Médio

NASA Astrophysics Data System (ADS)

Dutra, Carlos Maximiliano; Rossini Goulart, Andressa

2014-12-01

In the present work, in order to supply the lacks of practical activities related to the content of Kepler's Laws in high school physics textbooks, we present a practical activity to determine the shape of the orbit of Mars. In this activity the student can experience the discovery the shape of the orbit of Mars in a way similar to that realized by Johannes Kepler combining the physical concepts with geometry. We applied the activity to eighteen high school teachers participating in a Postgraduate Course in Science Education. After two hours of work the group obtained the shape of the orbit of Mars and estimated its orbital parameters with a relative error less than 14%. En el presente trabajo y con el objetivo de reducir la escasez de actividades prácticas relacionadas con el contenido de las leyes de Kepler en libros de texto de física de la escuela secundaria, se presenta una actividad práctica para determinar la forma de la órbita de Marte. En esta actividad el estudiante puede vivir la experiencia de descubrir la forma de la órbita de Marte de una manera similar a la realizada por Johannes Kepler combinando los conceptos físicos con la geometría. Aplicamos la actividad a dieciocho maestros de escuelas secundarias en un Curso de Especialización en Enseñanza de las Ciencias. Después de dos horas de trabajo el grupo obtuvo la forma de la órbita de Marte com error inferior al 14% en los parámetros orbitales. No presente trabalho, visando suprir a deficiência de atividades práticas relacionadas ao conteúdo de Leis de Kepler nos livros-textos de Física do 1º ano do Ensino Médio, apresentamos uma atividade prática de determinação da órbita de Marte. O aluno, combinando conceitos físicos com a geometria poderá vivenciar a experiência da descoberta da forma da órbita de Marte de modo similar ao realizado por Johannes Kepler. Aplicamos a metodologia proposta junto a dezoito professores do Curso de Especialização em Educação em Ciências e obtivemos em um trabalho de duas horas de duração o traçado da órbita de Marte com resultados numéricos médios que reproduzem com erro inferior a 14% os parâmetros orbitais de referência da órbita de Marte.

Comparative study of abdominal cavity temporary closure techniques for damage control.

PubMed

Ribeiro, Marcelo A F; Barros, Emily Alves; Carvalho, Sabrina Marques DE; Nascimento, Vinicius Pereira; Cruvinel, José; Fonseca, Alexandre Zanchenko

2016-01-01

The damage control surgery, with emphasis on laparostomy, usually results in shrinkage of the aponeurosis and loss of the ability to close the abdominal wall, leading to the formation of ventral incisional hernias. Currently, various techniques offer greater chances of closing the abdominal cavity with less tension. Thus, this study aims to evaluate three temporary closure techniques of the abdominal cavity: the Vacuum-Assisted Closure Therapy - VAC, the Bogotá Bag and the Vacuum-pack. We conducted a systematic review of the literature, selecting 28 articles published in the last 20 years. The techniques of the bag Bogotá and Vacuum-pack had the advantage of easy access to the material in most centers and low cost, contrary to VAC, which, besides presenting high cost, is not available in most hospitals. On the other hand, the VAC technique was more effective in reducing stress at the edges of lesions, removing stagnant fluids and waste, in addition to acting at the cellular level by increasing proliferation and cell division rates, and showed the highest rates of primary closure of the abdominal cavity. RESUMO A cirurgia de controle de danos, com ênfase em peritoneostomia, geralmente resulta em retração da aponeurose e perda da capacidade de fechar a parede abdominal, levando à formação de hérnias ventrais incisionais. Atualmente, várias técnicas oferecem maiores chances de fechamento da cavidade abdominal, com menor tensão. Deste modo, este estudo tem por objetivo avaliar três técnicas de fechamento temporário da cavidade abdominal: fechamento a vácuo (Vacuum-Assisted Closure Therapy - VAC), Bolsa de Bogotá e Vacuum-pack. Realizou-se uma revisão sistemática da literatura com seleção de 28 artigos publicados nos últimos 20 anos. As técnicas de Bolsa de Bogotá e Vacuum-pack tiveram como vantagem o acesso fácil ao material, na maioria dos centros, e baixo custo, ao contrário do que se observa na terapia a vácuo, VAC, que além de apresentar alto custo, não está disponível em grande parte dos hospitais. A técnica VAC, por outro lado, foi mais eficaz na redução da tensão nas bordas das lesões, ao remover fluidos estagnados e detritos, além de exercer ação a nível celular, aumentando as taxas de proliferação e divisão celular, e apresentou as maiores taxas de fechamento primário da cavidade abdominal.

Urinary tract infection in iNOS-deficient mice with focus on bacterial sensitivity to nitric oxide.

PubMed

Poljakovic, Mirjana; Persson, Katarina

2003-01-01

Inducible nitric oxide synthase (iNOS)-deficient mice were used to examine the role of iNOS in Escherichia coli-induced urinary tract infection (UTI). The toxicity of nitric oxide (NO)/peroxynitrite to bacteria and host was also investigated. The nitrite levels in urine of iNOS+/+ but not iNOS/ mice increased after infection. No differences in bacterial clearance or persistence were noted between the genotypes. In vitro, the uropathogenic E. coli 1177 was sensitive to 3-morpholinosydnonimine, whereas the avirulent E. coli HB101 was sensitive to both NO and 3-morpholinosydnonimine. E. coli HB101 was statistically (P < 0.05) more sensitive to peroxynitrite than E. coli 1177. Nitrotyrosine immunoreactivity was observed in infected bladders of both genotypes and in infected kidneys of iNOS+/+ mice. Myeloperoxidase, neuronal (n)NOS, and endothelial (e)NOS immunoreactivity was observed in inflammatory cells of both genotypes. Our results indicate that iNOS/ and iNOS+/+ mice are equally susceptible to E. coli-induced UTI and that the toxicity of NO to E. coli depends on bacterial virulence. Furthermore, myeloperoxidase and nNOS/eNOS may contribute to nitrotyrosine formation in the absence of iNOS.

Towards a Philosophically and a Pedagogically Reasonable Nature of Science Curriculum

NASA Astrophysics Data System (ADS)

Yacoubian, Hagop Azad

This study, primarily theoretical in nature, explores a philosophically and pedagogically reasonable way of addressing nature of science (NOS) in school science. NOS encompasses what science is and how scientific knowledge develops. I critically evaluate consensus frameworks of NOS in school science, which converge contentious philosophical viewpoints into general NOS-related ideas. I argue that they (1) lack clarity in terms of how NOS-related ideas could be applied for various ends, (2) portray a distorted image of the substantive content of NOS and the process of its development, and (3) lack a developmental trajectory for how to address NOS at different grade levels. As a remedy to these problems, I envision a NOS curriculum that (1) explicates and targets both NOS as an educational end and NOS as a means for socioscientific decision making, (2) has critical thinking as its foundational pillar, and (3) provides a developmental pathway for NOS learning using critical thinking as a progression unit. Next, I illustrate a framework for addressing NOS in school science referred to as the critical thinking—nature of science (CT-NOS) framework. This framework brings together the first two of the three elements envisioned in the NOS curriculum. I address the third element by situating the CT-NOS framework in a developmental context, borrowing from the literature on learning progressions in science and using critical thinking as a progression unit. Finally, I present an empirical study of experienced secondary science teachers’ views of a NOS lesson prepared using the CT-NOS framework. The teachers attended a professional development workshop at which the lesson, and the characteristics of the CT-NOS framework, were presented. The analysis of the qualitative data revealed that most teachers found the lesson to be somewhat feasible for a secondary science classroom, useful or somewhat useful to their students, and interesting. The teachers focused on 14 features of the lesson in their judgments and recommendations. The study revealed a number of teacher challenges generally related to critical thinking and its teaching as well as to the distinction between critical thinking about NOS and critical thinking with NOS.

Astrossismologia e o satélite COROT

NASA Astrophysics Data System (ADS)

Andrade, L. B. P.; Janot Pacheco, E.

2003-08-01

Este trabalho centra-se em atividades na fase de pré-lançamento do satélite COROT, da agência espacial francesa (CNES), a ser lançado em 2005. O satélite será dedicado à sismologia estelar e à procura de exoplanetas. Nosso programa de trabalho centra-se em dois pontos principais: (1) efetuar uma procura detalhada nos campos COROT de alvos astrofísicos de especial interesse; (2) participar das análises espectroscópicas prévias de alvos selecionados para determinação de parâmetros físicos das estrelas com a maior precisão possível. Na presente etapa, priorizou-se o primeiro ponto do projeto. Foi feito um levantamento geral dos objetos astrofísicos encontrados nos dois campos de observação, centrados em 06H50M e 18H50M, com raios de 10 minutos. Concluiu-se que as estrelas B-Be deverão ser observadas no campo sismológico, enquanto que as anãs brancas deverão sê-lo no campo exoplanetário. Objetos a serem observados foram escolhidos de forma a estarem próximos de alvos principais dos programas centrais do satélite. Paralelamente, estudos e pesquisas bibliográficas foram feitos para compreender os assuntos de interesse principal, ou seja, as pulsações não-radiais de estrelas Ob-Be

Intimate partner violence reported by female and male users of healthcare units.

PubMed

Barros, Claudia Renata Dos Santos; Schraiber, Lilia Blima

2017-02-16

To analyze nonfatal violence suffered and committed by adult men and women, in an intimate relationship. The participants in the research were women aged between 15 and 49 years and men between 18 and 60 years, interviewed by face-to-face questionnaire application. The sample selection was of consecutive type, according to the order of arrival of the users. We conducted temporarily independent investigations and covered different health services to avoid couples and relationships in which the retaliation could be overvalued. To improve the comparison, we also examined reports of men and women from the same service, i.e., a service that was common to both investigations. We compared the situations suffered by women according to their reports and cross-linked the information to what men, according to their own reports, do against intimate partners or ex-partners. We also examined the cross-linked situation in reverse: the violence committed by women against their partners, according to their reports, in comparison with the violence suffered by men, also according to their reports, even if, in this case, the exam refers only to physical violence. The variables were described using mean, standard deviation, frequencies and proportions, and the hypothesis testing used was: Fisher's exact and Pearson's Chi-square tests, adopting a significance level of 5%. Victimization was greater among women, regardless of the type of violence, when perpetrated by intimate partner. The perception of violence was low in both genders; however, women reported more episodes of multiple recurrences of any violence and sexual abuse suffered than men acknowledged to have perpetrated. The study in its entirety shows significant gender differences, whether about the prevalence of violence, whether about the perception of these situations. Analisar as violências não fatais sofridas e praticadas por homens e mulheres adultos, em situação de parceria íntima. Os sujeitos da pesquisa foram mulheres entre 15 a 49 anos e homens entre 18 a 60 anos, entrevistados por aplicação de questionário face a face. A seleção amostral foi do tipo consecutivo, captando-se os participantes por ordem de chegada ao serviço. Foram conduzidos como investigações temporalmente independentes e abrangendo diferentes serviços, para evitar o estudo em casais, nos quais o revide poderia estar supervalorizado. Para adensar um pouco mais a comparação, também examinamos relatos de homens e mulheres pertencentes a um mesmo serviço, ou seja, um serviço que foi participante comum às duas investigações. Comparamos as situações sofridas pelas mulheres segundo seus relatos e, de modo entrecruzado, as situações que os homens, segundo seus relatos, praticam contra as mulheres, suas parceiras íntimas ou ex-parceiras. Também examinamos a situação entrecruzada reversa: a violência praticada pelas mulheres contra seus parceiros, segundo seus próprios relatos, comparativamente à violência sofrida pelos homens, segundo seus relatos, ainda que, neste caso, o exame se refere apenas à violência física. As variáveis foram descritas por meio de média, desvio padrão, frequências e proporções e os testes de hipóteses utilizados foram: Exato de Fisher e Qui-quadrado de Pearson, adotando-se nível de significância de 5%. A vitimização foi maior entre as mulheres, independentemente do tipo de violência, quando perpetrada por parceiro íntimo. A percepção da violência foi baixa em ambos os sexos; entretanto, mulheres relataram mais episódios de múltiplas recorrências de quaisquer violências e de violência sexual sofrida do que os homens reconheceram que perpetraram. O estudo em seu todo mostra importantes diferenças de gênero, quer quanto às prevalências das violências, quer quanto à percepção dessas situações.

Vascular endothelial dysfunction in Duchenne muscular dystrophy is restored by bradykinin through upregulation of eNOS and nNOS

PubMed Central

Dabiré, Hubert; Barthélémy, Inès; Blanchard-Gutton, Nicolas; Sambin, Lucien; Sampedrano, Carolina Carlos; Gouni, Vassiliki; Unterfinger, Yves; Aguilar, Pablo; Thibaud, Jean-Laurent; Ghaleh, Bijan; Bizé, Alain; Pouchelon, Jean-Louis; Blot, Stéphane; Berdeaux, Alain; Hittinger, Luc; Chetboul, Valérie; Su, Jin Bo

2012-01-01

Little is known about the vascular function and expression of endothelial and neuronal nitric oxide synthases (eNOS and nNOS) in Duchenne muscular dystrophy (DMD). Bradykinin is involved in the regulation of eNOS expression induced by angiotensin-converting enzyme inhibitors. We characterized the vascular function and eNOS and nNOS expression in a canine model of DMD and evaluated the effects of chronic bradykinin treatment. Vascular function was examined in conscious golden retriever muscular dystrophy (GRMD) dogs with left ventricular dysfunction (measured by echocardiography) and in isolated coronary arteries. eNOS and nNOS proteins in carotid arteries were measured by western blot and cyclic guanosine monophosphate (cGMP) content was analyzed by radioimmunoassay. Compared with controls, GRMD dogs had an impaired vasodilator response to acetylcholine. In isolated coronary artery, acetylcholine-elicited relaxation was nearly absent in placebo-treated GRMD dogs. This was explained by reduced nNOS and eNOS proteins and cGMP content in arterial tissues. Chronic bradykinin infusion (1 μg/min, 4 weeks) restored in vivo and in vitro vascular response to acetylcholine to the level of control dogs. This effect was NO-mediated through upregulation of eNOS and nNOS expression. In conclusion, this study is the first to demonstrate that DMD is associated with NO-mediated vascular endothelial dysfunction linked to an altered expression of eNOS and nNOS, which can be overcome by bradykinin. PMID:22193759

MGE-derived nNOS+ interneurons promote fear acquisition in nNOS-/- mice.

PubMed

Zhang, Lin; Yuan, Hong-Jin; Cao, Bo; Kong, Cheng-Cheng; Yuan, Fang; Li, Jun; Ni, Huan-Yu; Wu, Hai-Yin; Chang, Lei; Liu, Yan; Luo, Chun-Xia

2017-12-02

Neuronal nitric oxide synthase (nNOS) 1 , mainly responsible for NO release in central nervous system (CNS) 2 , plays a significant role in multiple physiological functions. However, the function of nNOS + interneurons in fear learning has not been much explored. Here we focused on the medial ganglionic eminences (MGE) 3 -derived nNOS + interneurons in fear learning. To determine the origin of nNOS + interneurons, we cultured neurons in vitro from MGE, cortex, lateral ganglionic eminence (LGE) 4 , caudal ganglionic eminences (CGE) 5 and preoptic area (POA) 6 . The results showed that MGE contained the most abundant precursors of nNOS + interneurons. Moreover, donor cells from E12.5 embryos demonstrated the highest positive rate of nNOS + interneurons compared with other embryonic periods (E11.5, E12, E13, E13.5 and E14). Additionally, these cells from E12.5 embryos showed long axonal and abundant dendritic arbors after 10 days culture, indicating the capability to disperse and integrate in host neural circuits after transplantation. To investigate the role of MGE-derived nNOS + interneurons in fear learning, donor MGE cells were transplanted into dentate gyrus (DG) 7 of nNOS knock-out (nNOS -/- ) or wild-type mice. Results showed that the transplantation of MGE cells promoted the acquisition of nNOS -/- but not the wild-type mice, suggesting the importance of nNOS + neurons in fear acquisition. Moreover, we transplanted MGE cells from nNOS -/- mice or wild-type mice into DG of the nNOS -/- mice and found that only MGE cells from wild-type mice but not the nNOS -/- mice rescued the deficit in acquisition of the nNOS -/- mice, further confirming the positive role of nNOS + neurons in fear learning. Copyright © 2017 Elsevier Inc. All rights reserved.

Uso de modelos mecânicos em curso informal de astronomia para deficientes visuais. Resgate de uma experiência

NASA Astrophysics Data System (ADS)

Tavares, E. T., Jr.; Klafke, J. C.

2003-08-01

O presente trabalho propõe-se a resgatar uma experiência que teve lugar no Planetário de São Paulo nos anos 60. Em 1962, o Sr. Acácio, então com 37 anos, deficiente visual desde os 27, passou a assistir às aulas ministradas pelo Prof. Aristóteles Orsini aos integrantes do corpo de servidores do Planetário. O Sr. Acácio era o único deficiente da turma e, embora possuísse conhecimentos básicos e relativamente avançados de matemática, enfrentava dificuldades na compreensão e acompanhamento da exposição, como também em estudos posteriores. Com o intuito de auxiliá-lo na superação desses problemas, o Prof. Orsini solicitou a construção de modelos mecânicos que, através do sentido do tato, permitissem o acompanhamento das aulas e a transposição do modelo para o "constructo" mental. Essa prática mostrou-se tão eficaz que facilitou sobejamente o aprendizado da matéria pelo sujeito. O Sr. Acácio passou a integrar o corpo de professores do Planetário/Escola Municipal de Astrofísica, tendo ficado responsável pelo curso de "Introdução à Astronomia" por vários anos. Além disso, a experiência foi tão bem sucedida que alguns dos modelos tiveram seus elementos constitutivos pintados diferencialmente para serem utilizados em cursos regulares do Planetário, tornando-se parte integrante do conjunto de recursos didáticos da instituição. É pensando nessa eficácia, tanto em seu objetivo original permitir o aprendizado de um deficiente visual quanto no subsidiário recurso didático sistemático da instituição que decidimos resgatar essa experiência. Estribados nela, acreditamos ser extremamente produtivo, em termos educacionais, o aperfeiçoamento dos modelos originais, agora resgatados e restaurados, e a criação de outros que pudessem ser utilizados no ensino dessa ciência a deficientes visuais.

Incidence and factors related to delirium in an intensive care unit.

PubMed

Mori, Satomi; Takeda, Juliana Rumy Tsuchihashi; Carrara, Fernanda Souza Angotti; Cohrs, Cibelli Rizzo; Zanei, Suely Sueko Viski; Whitaker, Iveth Yamaguchi

2016-01-01

To identify the incidence of delirium, compare the demographic and clinical characteristics of patients with and without delirium, and verify factors related to delirium in critical care patients. Prospective cohort with a sample made up of patients hospitalized in the Intensive Care Unit (ICU) of a university hospital. Demographic, clinical variables and evaluation with the Confusion Assessment Method for Intensive Care Unit to identify delirium were processed to the univariate analysis and logistic regression to identify factors related to the occurrence of delirium. Of the total 149 patients in the sample, 69 (46.3%) presented delirium during ICU stay, whose mean age, severity of illness and length of ICU stay were statistically higher. The factors related to delirium were: age, midazolam, morphine and propofol. Results showed high incidence of ICU delirium associated with older age, use of sedatives and analgesics, emphasizing the need for relevant nursing care to prevent and identify early, patients presenting these characteristics. Identificar a incidência de delirium, comparar as características demográficas e clínicas dos pacientes com e sem delirium e verificar os fatores relacionados ao delirium em pacientes internados em Unidade de Terapia Intensiva (UTI). Coorte prospectiva, cuja amostra foi constituída de pacientes internados em UTI de um hospital universitário. Variáveis demográficas, clínicas e da avaliação com o Confusion Assessment Method for Intensive Care Unit para identificação de delirium foram processadas para análise univariada, e regressão logística para identificar fatores relacionados à ocorrência do delirium. Do total de 149 pacientes da amostra, 69 (46,3%) apresentaram delirium durante a internação na UTI, observando-se que a média da idade, o índice de gravidade e o tempo de permanência nas UTI foram estatisticamente maiores. Os fatores relacionados ao delirium foram: idade, midazolam, morfina e propofol. Os resultados mostraram elevada incidência de delirium na UTI e sua ocorrência associada às idades mais avançadas e o uso de sedativos e analgésicos, ressaltando-se a importância da atuação do enfermeiro na prevenção e identificação precoce do quadro nos pacientes com essas características.

Cometa Hyakutake (C/1996 B2): análise do gás e características físicas das partículas de poeira

NASA Astrophysics Data System (ADS)

Sanzovo, G. C.; de Almeida, A. A.; Boczko, R.

2003-08-01

A completa caracterização e compreensão do núcleo de um cometa novo é de fundamental importância para a elucidação dos processos físicos e químicos atuantes na época da formação do Sistema Solar. O Cometa Hyakutake, conjuntamente com o Cometa Hale-Bopp representam os objetos mais brilhantes que visitaram o Sistema Solar Interno nos últimos 20 anos. Neste Trabalho, nós aplicamos o Método Semi-Empírico das Magnitudes Visuais (MSEMV) à aproximadamente 4000 dados observacionais que correlacionam a magnitude visual absoluta com a distância heliocêntrica para o Cometa Hyakutake nas fases pré- e pós-periélicas. Como produto da aplicação desse método, conseguimos caracterizar dimensionalmente seu núcleo e área ativa efetiva. As taxas de produção dos radicais CN, C2 e C3, obtidos a partir de dados disponíveis na literatura, revelam que, além de muito brilhante, o Hyakutake é um cometa "normal" no sentido de Cochran (1986). Desse modo, deduzimos as taxas de perdas de água (em moléculas/s) a partir da análise de sua magnitude visual aparente, e as convertemos em taxas de perdas de gás (em g/s), despreendido pelo nucleo cometário. Com o auxílio do modelo fotométrico clássico da poeira, realizamos uma análise sistemática e uniforme dessa componente cometária, a partir dos fluxos observacionais no contínuo, para os comprimentos de onda 365,0 e 484,5 nm, assumindo que esses fluxos são o resultado da radiação solar espalhada por grãos de partículas micrométricos presentes na coma. Com isso, pudemos obter as taxas de produção (em g/s), cores (relativas à cor neutra solar), e as dimensões efetivas médias das partículas de poeira, bem como as razões poeira-gás.

Espectroscopia infravermelha de núcleos ativos de galáxias: resultados adicionais

NASA Astrophysics Data System (ADS)

Rodríguez Ardila, A.; Viegas, S.; Pastoria, M. G.

2003-08-01

Apresentamos resultados parciais de um levantamento espectroscópico na região do infravermelho próximo (NIR) realizado em 30 núcleos ativos de galáxias (AGN), incluindo vários objetos selecionados do catálogo PG com z de até 0.55. O objetivo é estudar a natureza do contínuo observado e as condições físicas do gas emissor. Todas as fontes de tipo 1 apresentam uma mudança na inclinação do contínuo na região de 1.2mm, associada ao término da contribuição do contínuo emitido pelo AGN e ao início da contribuição do contínuo emitido pela poeira quente atribuída ao tórus que rodeia a fonte central. O índice espectral associado à segunda contribuição varia apreciavelmente de objeto para objeto. Este resultado é comparado com distribuições espectrais de energia preditas por modelos de toroides para testar a validez do modelo unificado. A partir das linhas de FeII observado nos espectros deriva-se, pela primeira vez nessa região espectral, um template empírico de FeII para estudar a intensidade e a origem dessa emissão. A intensidade do FeII é estudada em conjunto com aquela da região visível e comparada às predições de modelos teóricos que incluem fluorescência de Lya, excitação colisional e auto-fluorescência como mecanismos dominantes de exitação. Encontra-se que os dois primeiros processos dominam na formação do espectro de FeII observado. Indicadores de avermelhamento, entre eles Brg/Pab, Pab/Pag, Pab/Pad e [FeII] 1.257/1.644 mm são utilizados para mapear a distribuição de poeira nas regiões emissoras de linhas. Encontra-se valores de extinção Av~3 associados ao último indicador e valores significativamente menores (Av~1.5) para os restantes, o que sugere que o [FeII] se forma em uma região separada da maior parte do gás emissor de linhas estreitas.

Structure-based design of bacterial nitric oxide synthase inhibitors

DOE PAGES

Holden, Jeffrey K.; Kang, Soosung; Hollingsworth, Scott A.; ...

2014-12-18

Inhibition of bacterial nitric oxide synthase (bNOS) has the potential to improve the efficacy of antimicrobials used to treat infections by Gram-positive pathogens Staphylococcus aureus and Bacillus anthracis. However, inhibitor specificity toward bNOS over the mammalian NOS (mNOS) isoforms remains a challenge because of the near identical NOS active sites. One key structural difference between the NOS isoforms is the amino acid composition of the pterin cofactor binding site that is adjacent to the NOS active site. Previously, we demonstrated that a NOS inhibitor targeting both the active and pterin sites was potent and functioned as an antimicrobial. Here wemore » present additional crystal structures, binding analyses, and bacterial killing studies of inhibitors that target both the active and pterin sites of a bNOS and function as antimicrobials. Lastly, these data provide a framework for continued development of bNOS inhibitors, as each molecule represents an excellent chemical scaffold for the design of isoform selective bNOS inhibitors.« less

População estelar jovem em galáxias irregulares próximas

NASA Astrophysics Data System (ADS)

Guimarães, T. A.; Telles, E.

2003-08-01

A análise do conteúdo estelar de galáxias próximas através da fotometria das suas estrelas resolvidas nos fornece informações importantes sobre a história de formação estelar e os processos de formação estelar em galáxias, que estão diretamente ligados ao estudo de evolução de galáxias. Quando nenhuma estrela puder ser resolvida o método mais poderoso consiste na análise do conteúdo estelar integrado das galáxias através das suas cores integradas em conjunto com informação espectroscópica que combinados com modelos de síntese evolutiva podem restringir simultaneamente a função de massa inicial (IMF) e a taxa de formação estelar (SFR). Nesse contexto, galáxias do tipo tardio, em particular, irregulares, são relevantes por várias razões: elas são objetos relativamente simples, com alta atividade de formação estelar e são objetos relativamente jovens (geralmente apresentam baixas abundâncias de elementos pesados e grande quantidade de gás). Apresentamos uma análise fotométrica de uma amostra de 7 galáxias do tipo tardio do universo local (NGC 2366, NGC 4395, NGC 4656, NGC 4214, NGC 4236, HOII, IC2574) que foram observadas com uma boa resolução espacial nas bandas B, V e R no telescópio Isaac Newton de 2.5m de Roque de los Muchachos nas Ilhas Canárias, Espanha. A distribuição espacial da população estelar jovem dessas galáxias é discutida sobre os pontos de vista dos íindices de cor integrados e dos seus diagramas cor magnitude, que comparados com isócronas teóricas, nos fornecem informações sobre os eventos de formação estelar, como por exemplo, indicações sobre a idade dos mesmos. As principais conclusões do trabalho podem ser resumidas em: (i) As galáxias irregulares possuem formação estelar recente (FE) espalhada ocorrendo nos últimos 50 Manos; (ii) A formação estelar em galáxias irregulares não é auto-propagante em escalas globais ( > 100 pc) ; (iii) A FE pode ser auto-regulável em escalas espaciais de poucas dezenas de parsec; (iv) As galáxias irregulares sofreram um evento principal de FE há 1010 anos atrás, o que implica que houve um momento na evolução do universo onde a maior parte das estrelas se formaram em galáxias.

Flow control of micro-ramps on supersonic forward-facing step flow

NASA Astrophysics Data System (ADS)

Qing-Hu, Zhang; Tao, Zhu; Shihe, Yi; Anping, Wu

2016-05-01

The effects of the micro-ramps on supersonic turbulent flow over a forward-facing step (FFS) was experimentally investigated in a supersonic low-noise wind tunnel at Mach number 3 using nano-tracer planar laser scattering (NPLS) and particle image velocimetry (PIV) techniques. High spatiotemporal resolution images and velocity fields of supersonic flow over the testing model were captured. The fine structures and their spatial evolutionary characteristics without and with the micro-ramps were revealed and compared. The large-scale structures generated by the micro-ramps can survive the downstream FFS flowfield. The micro-ramps control on the flow separation and the separation shock unsteadiness was investigated by PIV results. With the micro-ramps, the reduction in the range of the reversal flow zone in streamwise direction is 50% and the turbulence intensity is also reduced. Moreover, the reduction in the average separated region and in separation shock unsteadiness are 47% and 26%, respectively. The results indicate that the micro-ramps are effective in reducing the flow separation and the separation shock unsteadiness. Project supported by the National Natural Science Foundation of China (Grant Nos. 11172326 and 11502280).

Inducible Nitric Oxide Synthase in Heart Tissue and Nitric Oxide in Serum of Trypanosoma cruzi-Infected Rhesus Monkeys: Association with Heart Injury

PubMed Central

Carvalho, Cristiano Marcelo Espinola; Silverio, Jaline Coutinho; da Silva, Andrea Alice; Pereira, Isabela Resende; Coelho, Janice Mery Chicarino; Britto, Constança Carvalho; Moreira, Otacílio Cruz; Marchevsky, Renato Sergio; Xavier, Sergio Salles; Gazzinelli, Ricardo Tostes; da Glória Bonecini-Almeida, Maria; Lannes-Vieira, Joseli

2012-01-01

Background The factors contributing to chronic Chagas' heart disease remain unknown. High nitric oxide (NO) levels have been shown to be associated with cardiomyopathy severity in patients. Further, NO produced via inducible nitric oxide synthase (iNOS/NOS2) is proposed to play a role in Trypanosoma cruzi control. However, the participation of iNOS/NOS2 and NO in T. cruzi control and heart injury has been questioned. Here, using chronically infected rhesus monkeys and iNOS/NOS2-deficient (Nos2 −/−) mice we explored the participation of iNOS/NOS2-derived NO in heart injury in T. cruzi infection. Methodology Rhesus monkeys and C57BL/6 and Nos2 −/− mice were infected with the Colombian T. cruzi strain. Parasite DNA was detected by polymerase chain reaction, T. cruzi antigens and iNOS/NOS2+ cells were immunohistochemically detected in heart sections and NO levels in serum were determined by Griess reagent. Heart injury was assessed by electrocardiogram (ECG), echocardiogram (ECHO), creatine kinase heart isoenzyme (CK-MB) activity levels in serum and connexin 43 (Cx43) expression in the cardiac tissue. Results Chronically infected monkeys presented conduction abnormalities, cardiac inflammation and fibrosis, which resembled the spectrum of human chronic chagasic cardiomyopathy (CCC). Importantly, chronic myocarditis was associated with parasite persistence. Moreover, Cx43 loss and increased CK-MB activity levels were primarily correlated with iNOS/NOS2+ cells infiltrating the cardiac tissue and NO levels in serum. Studies in Nos2 −/− mice reinforced that the iNOS/NOS2-NO pathway plays a pivotal role in T. cruzi-elicited cardiomyocyte injury and in conduction abnormalities that were associated with Cx43 loss in the cardiac tissue. Conclusion T. cruzi-infected rhesus monkeys reproduce features of CCC. Moreover, our data support that in T. cruzi infection persistent parasite-triggered iNOS/NOS2 in the cardiac tissue and NO overproduction might contribute to CCC severity, mainly disturbing of the molecular pathway involved in electrical synchrony. These findings open a new avenue for therapeutic tools in Chagas' heart disease. PMID:22590660

Post-translational regulation of endothelial nitric oxide synthase (eNOS) by estrogens in the rat vagina.

PubMed

Musicki, Biljana; Liu, Tongyun; Strong, Travis D; Lagoda, Gwen A; Bivalacqua, Trinity J; Burnett, Arthur L

2010-05-01

Estrogens control vaginal blood flow during female sexual arousal mostly through nitric oxide (NO). Although vascular effects of estrogens are attributed to an increase in endothelial NO production, the mechanisms of endothelial NO synthase (eNOS) regulation by estrogens in the vagina are largely unknown. Our hypothesis was that estrogens regulate eNOS post-translationally in the vagina, providing a mechanism to affect NO bioavailability without changes in eNOS protein expression. We measured eNOS phosphorylation and eNOS interaction with caveolin-1 and heat shock protein 90 (HSP90) in the distal and proximal vagina of female rats at diestrus, 7 days after ovariectomy and 2 days after replacement of ovariectomized rats with estradiol-17beta (15 microg). Molecular mechanisms of eNOS regulation by estrogen in the rat vagina. We localized phospho-eNOS (Ser-1177) immunohistochemically to the endothelium lining blood vessels and vaginal sinusoids. Estrogen withdrawal decreased phosphorylation of eNOS on its positive regulatory site (Ser-1177) and increased eNOS binding to its negative regulator caveolin-1 (without affecting eNOS/HSP90 interaction), and they were both normalized by estradiol replacement. Protein expressions of phosphorylated Akt (protein kinase B) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) were not affected by estrogen status, suggesting that the effect of estrogens on eNOS (Ser-1177) phosphorylation was not mediated by activated AKT or ERK1/2. eNOS phosphorylation on its negative regulatory site (Ser-114) was increased in the vagina by estrogen withdrawal and normalized by estradiol replacement, implying that the maintenance of low phosphorylation of eNOS on this site by estradiol may limit eNOS interaction with caveolin-1 and preserve the enzyme's activity. Total eNOS, inducible NOS, caveolin-1, and HSP90 protein expressions were not affected by ovariectomy or estradiol replacement in the distal or proximal vagina. These results define novel estrogen signaling mechanisms in the vagina which involve eNOS phosphorylation and eNOS-caveolin-1 interaction.

Post-translational Regulation of Endothelial Nitric Oxide Synthase (eNOS) by Estrogens in the Rat Vagina

PubMed Central

Musicki, Biljana; Liu, Tongyun; Strong, Travis D.; Lagoda, Gwen A.; Bivalacqua, Trinity J.; Burnett, Arthur L.

2010-01-01

Introduction Estrogens control vaginal blood flow during female sexual arousal mostly through nitric oxide (NO). Although vascular effects of estrogens are attributed to an increase in endothelial NO production, the mechanisms of endothelial NO synthase (eNOS) regulation by estrogens in the vagina are largely unknown. Aims Our hypothesis was that estrogens regulate eNOS post-translationally in the vagina, providing a mechanism to affect NO bioavailability without changes in eNOS protein expression. Methods We measured eNOS phosphorylation and eNOS interaction with caveolin-1 and heat shock protein 90 (HSP90) in the distal and proximal vagina of female rats at diestrus, 7 days after ovariectomy and 2 days after replacement of ovariectomized rats with estradiol-17β (15 μg). Main Outcome Measures Molecular mechanisms of eNOS regulation by estrogen in the rat vagina. Results We localized phospho-eNOS (Ser-1177) immunohistochemically to the endothelium lining blood vessels and vaginal sinusoids. Estrogen withdrawal decreased phosphorylation of eNOS on its positive regulatory site (Ser-1177) and increased eNOS binding to its negative regulator caveolin-1 (without affecting eNOS/HSP90 interaction), and they were both normalized by estradiol replacement. Protein expressions of phosphorylated Akt (protein kinase B) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) were not affected by estrogen status, suggesting that the effect of estrogens on eNOS (Ser-1177) phosphorylation was not mediated by activated AKT or ERK1/2. eNOS phosphorylation on its negative regulatory site (Ser-114) was increased in the vagina by estrogen withdrawal and normalized by estradiol replacement, implying that the maintenance of low phosphorylation of eNOS on this site by estradiol may limit eNOS interaction with caveolin-1 and preserve the enzyme's activity. Total eNOS, inducible NOS, caveolin-1, and HSP90 protein expressions were not affected by ovariectomy or estradiol replacement in the distal or proximal vagina. Conclusions These results define novel estrogen signaling mechanisms in the vagina which involve eNOS phosphorylation and eNOS-caveolin-1 interaction. PMID:20233295

How the nature of science is presented to elementary students in science read-alouds

NASA Astrophysics Data System (ADS)

Rivera, Seema

Students as early as elementary school age are capable of learning the aspects of the nature of science (NOS), and the National Benchmarks incorporate the NOS as part of the learning objectives for K--2 students. Learning more about elementary science instruction can aid in understanding how the NOS can be taught or potentially integrated into current teaching methods. Although many teaching methods exist, this study will focus on read-alouds because they are recommended for and are very common in elementary schools. The read-aloud practice is particularly helpful to young students because most of these students have a higher listening comprehension than reading comprehension. One of the main components of the read-aloud practice is the discourse that takes place about the trade book. Both explicit and implicit messages are communicated to students by teachers' language and discussion that takes place in the classroom. Therefore, six multisite naturalistic case studies were conducted to understand elementary teachers' understanding of the NOS, students' understandings of the NOS, trade book representations of the NOS, and read-aloud practices and understandings in upstate New York. The findings of the study revealed that teachers and students held mostly naive and mixed understandings of the NOS. The trade books that had explicit connections to the NOS helped teachers discuss NOS related issues, even when the teachers did not hold strong NOS views. Teachers who held more informed NOS views were able to ask students NOS related questions. All teachers showed they need guidance on how to translate their NOS views into discussion and see the significance of the NOS in their classroom. Explicit NOS instruction can improve student understanding of the NOS, however the focus should be not only on teachers and their NOS understanding but also on the books used. These results show that quality trade books with explicit connections to the NOS are a useful instructional tool in elementary science classrooms. The results of the study encourage more science education research in the science read-aloud practice. Keywords: NOS, read-aloud, elementary

Intraprotein Electron Transfer in Inducible Nitric Oxide Synthase Holoenzyme

PubMed Central

Feng, Changjian; Dupont, Andrea L.; Nahm, Nickolas J.; Spratt, Donald E.; Hazzard, James T.; Weinberg, J. Brice; Guillemette, J. Guy; Tollin, Gordon; Ghosh, Dipak K.

2008-01-01

Intraprotein electron transfer (IET) from flavin mononucleotide (FMN) to heme is essential in nitric oxide (NO) synthesis by NO synthase (NOS). Our previous laser flash photolysis studies provided a direct determination of the kinetics of the FMN–heme IET in a truncated oxyFMN construct of murine inducible NOS (iNOS), in which only the oxygenase and FMN domains along with the calmodulin (CaM) binding site are present [Feng et al. (2006) J. Am. Chem. Soc. 128, 3808-3811]. Here we report the kinetics of the IET in a human iNOS oxyFMN construct, a human iNOS holoenzyme and a murine iNOS holoenzyme, using CO photolysis in comparative studies on partially reduced NOS and a NOS oxygenase construct that lacks the FMN domain. The IET rate constants for the human and murine iNOS holoenzymes are 34 ± 5 s-1 and 35 ± 3 s-1, respectively, thereby providing a direct measurement of this IET between the catalytically significant redox couples of FMN and heme in the iNOS holoenzyme. These values are approximately an order of magnitude smaller than that in the corresponding iNOS oxyFMN construct, suggesting that in the holoenzyme the rate-limiting step in the IET is the conversion of the shielded electron-accepting (input) state to a new electron-donating (output) state. The fact that there is no rapid IET component in the kinetic traces obtained with the iNOS holoenzyme implies that the enzyme remains mainly in the input state. The IET rate constant value for the iNOS holoenzyme is similar to that obtained for a CaM-bound neuronal NOS (nNOS) holoenzyme, suggesting that CaM activation effectively removes the inhibitory effect of the unique autoregulatory insert in nNOS. PMID:18830722

Mechanism and Kinetics of Inducible Nitric Oxide Synthase Auto-S-Nitrosation and Inactivation†

PubMed Central

Smith, Brian C.; Fernhoff, Nathaniel B.; Marletta, Michael A.

2012-01-01

Nitric oxide (NO), the product of the nitric oxide synthase (NOS) reaction, was previously shown to result in S-nitrosation of the NOS Zn2+-tetrathiolate and inactivation of the enzyme. To probe the potential physiological significance of NOS S-nitrosation, the inactivation timescale of the inducible NOS isoform (iNOS) was determined and found to directly correlate with an increase in iNOS S-nitrosation. A kinetic model of NOS inactivation in which arginine is treated as a suicide substrate was developed. In this model, NO synthesized at the heme cofactor is partitioned between release into solution (NO release pathway) and NOS S-nitrosation followed by NOS inactivation (inactivation pathway). Experimentally determined progress curves of NO formation were fit to the model. The NO release pathway was perturbed through addition of the NO traps oxymyoglobin (MbO2) and β2 H-NOX, which yielded partition ratios between NO release and inactivation of ~100 at 4 μM MbO2 and ~22,000 at saturating trap concentrations. The results suggest that a portion of the NO synthesized at the heme cofactor reacts with the Zn2+-tetrathiolate without being released into solution. Perturbation of the inactivation pathway through addition of the reducing agents GSH or TCEP resulted in a concentration-dependent decrease in iNOS S-nitrosation that directly correlated with protection from iNOS inactivation. iNOS inactivation was most responsive to physiological concentrations of GSH with an apparent Km value of 13 mM. NOS turnover that leads to NOS S-nitrosation might be a mechanism to control NOS activity, and NOS S-nitrosation could play a role in the physiological generation of nitrosothiols. PMID:22242685

The influence of authentic scientific research experiences on teachers' conceptions of the nature of science (NOS) and their NOS teaching practices

NASA Astrophysics Data System (ADS)

Moriarty, Meghan A.

This study explored the influence of teachers' authentic scientific research experiences (ASREs) on teachers' conceptions of the nature of science (NOS) and teachers' NOS instruction. Twelve high school biology teachers participated in this study. Six of the participants had authentic scientific research experience (ASRE) and six had not participated in authentic scientific research. Data included background surveys, modified Views of the Nature of Science (VNOS) questionnaires, interviews, and teaching observations. Data was coded based on the eight NOS understandings outlined in 2013 in the Next Generation Science Standards (NGSS). Evidence from this study indicates participating in authentic scientific research as a member of a scientific community has dual benefits of enabling high school science teachers with informed understandings of the NOS and positioning them to teach with the NOS. However, these benefits do not always result from an ASRE. If the nature of the ASRE is limited, then it may limit teachers' NOS understandings and their NOS teaching practices. The results of this study suggest that participation in ASREs may be one way to improve teachers' NOS understandings and teaching practices if the experiences themselves offer a comprehensive view of the NOS. Because ASREs and other science learning experiences do not always offer such experiences, pre-service teacher education and professional development opportunities may engage science teachers in two ways: (1) becoming part of a scientific community may enable them to teach with NOS and (2) being reflective about what being a scientist means may improve teachers' NOS understandings and better position them to teach about NOS.. Keywords: nature of science, authentic scientific research experiences, Next Generation Science Standards, teaching about NOS, teaching with NOS.

"There were more decisions and more options than just yes or no": Evaluating a decision aid for advanced cancer patients and their family caregivers.

PubMed

Bakitas, Marie; Dionne-Odom, J Nicholas; Jackson, Lisa; Frost, Jennifer; Bishop, Margaret F; Li, Zhongze

2017-02-01

Few decision aids are available for patients with a serious illness who face many treatment and end-of-life decisions. We evaluated the Looking Ahead: Choices for Medical Care When You're Seriously Ill® patient decision aid (PtDA), one component of an early palliative care clinical trial. Our participants included individuals with advanced cancer and their caregivers who had participated in the ENABLE (Educate, Nurture, Advise, Before Life Ends) early palliative care telehealth randomized controlled trial (RCT) conducted in a National Cancer Institute-designated cancer center, a U.S. Department of Veterans Affairs medical center, and affiliated outreach clinics in rural New England. ENABLE included six weekly patient and three weekly family caregiver structured sessions. Participants watched the Looking Ahead PtDA prior to session 3, which covered content on decision making and advance care planning. Nurse coaches employed semistructured interviews to obtain feedback from consecutive patient and caregiver participants approximately one week after viewing the Looking Ahead PtDA program (booklet and DVD). Between April 1, 2011, and October 31, 2012, 57 patients (mean age = 64), 42% of whom had lung and 23% gastrointestinal cancer, and 20 caregivers (mean age = 59), 80% of whom were spouses, completed the PtDA evaluation. Participants reported a high degree of satisfaction with the PtDA format, as well as with its length and clarity. They found the format of using patient interviews "validating." The key themes were: (1) "the earlier the better" to view the PtDA; (2) feeling empowered, aware of different options, and an urgency to participate in advance care planning. The Looking Ahead PtDA was well received and helped patients with a serious illness realize the importance of prospective decision making in guiding their treatment pathways. We found that this PtDA can help seriously ill patients prior to the end of life to understand and discuss future healthcare decision making. However, systems to routinely provide PtDAs to seriously ill patients are yet not well developed.

Posttranscriptional regulation of human iNOS by the NO/cGMP pathway.

PubMed

Pérez-Sala, D; Cernuda-Morollón, E; Díaz-Cazorla, M; Rodríguez-Pascual, F; Lamas, S

2001-03-01

Nitric oxide (NO) and cGMP may exert positive or negative effects on inducible NO synthase (iNOS) expression. We have explored the influence of the NO/cGMP pathway on iNOS levels in human mesangial cells. Inhibition of NOS activity during an 8-h stimulation with IL-1beta plus tumor necrosis factor (TNF)-alpha reduced iNOS levels, while NO donors amplified iNOS induction threefold. However, time-course studies revealed a subsequent inhibitory effect of NO donors on iNOS protein and mRNA levels. This suggests that NO may contribute both to iNOS induction and downregulation. Soluble guanylyl cyclase (sGC) activation may be involved in these effects. Inhibition of sGC attenuated IL-1beta/TNF-alpha-elicited iNOS induction and reduced NO-driven amplification. Interestingly, cGMP analogs also modulated iNOS protein and mRNA levels in a biphasic manner. Inhibition of transcription unveiled a negative posttranscriptional modulation of the iNOS transcript by NO and cGMP at late times of induction. Supplementation with 8-bromo-cGMP (8-BrcGMP) reduced iNOS mRNA stability by 50%. These observations evidence a complex feedback regulation of iNOS expression, in which posttranscriptional mechanisms may play an important role.

Visualizing inducible nitric-oxide synthase in living cells with a heme-binding fluorescent inhibitor.

PubMed

Panda, Koustubh; Chawla-Sarkar, Mamta; Santos, Cecile; Koeck, Thomas; Erzurum, Serpil C; Parkinson, John F; Stuehr, Dennis J

2005-07-19

The study of nitric-oxide synthase (NOS) physiology is constrained by the lack of suitable probes to detect NOS in living cells or animals. Here, we characterized a fluorescent inducible NOS (iNOS) inhibitor called PIF (pyrimidine imidazole FITC) and examined its utility for microscopic imaging of iNOS in living cells. PIF binding to iNOS displayed high affinity, isoform selectivity, and heme specificity, and was essentially irreversible. PIF was used to successfully image iNOS expressed in RAW264.7 cells, HEK293T cells, human A549 epithelial cells, and freshly obtained human lung epithelium. PIF was used to estimate a half-life for iNOS of 1.8 h in HEK293T cells. Our work reveals that fluorescent probes like PIF will be valuable for studying iNOS cell biology and in understanding the pathophysiology of diseases that involve dysfunctional iNOS expression.

Observational study of the development and evaluation of a fertility preservation patient decision aid for teenage and adult women diagnosed with cancer: the Cancer, Fertility and Me research protocol

PubMed Central

Jones, G L; Hughes, J; Mahmoodi, N; Greenfield, D; Brauten-Smith, G; Skull, J; Gath, J; Yeomanson, D; Baskind, E; Snowden, J A; Velikova, G; Collins, K; Stark, D; Phillips, R; Lane, S; Bekker, H L

2017-01-01

Introduction Women diagnosed with cancer and facing potentially sterilising cancer treatment have to make time-pressured decisions regarding fertility preservation with specialist fertility services while undergoing treatment of their cancer with oncology services. Oncologists identify a need for resources enabling them to support women's fertility preservation decisions more effectively; women report wanting more specialist information to make these decisions. The overall aim of the ‘Cancer, Fertility and Me’ study is to develop and evaluate a new evidence-based patient decision aid (PtDA) for women with any cancer considering fertility preservation to address this unmet need. Methods and analysis This is a prospective mixed-method observational study including women of reproductive age (16 years +) with a new diagnosis of any cancer across two regional cancer and fertility centres in Yorkshire, UK. The research involves three stages. In stage 1, the aim is to develop the PtDA using a systematic method of evidence synthesis and multidisciplinary expert review of current clinical practice and patient information. In stage 2, the aim is to assess the face validity of the PtDA. Feedback on its content and format will be ascertained using questionnaires and interviews with patients, user groups and key stakeholders. Finally, in stage 3 the acceptability of using this resource when integrated into usual cancer care pathways at the point of cancer diagnosis and treatment planning will be evaluated. This will involve a quantitative and qualitative evaluation of the PtDA in clinical practice. Measures chosen include using count data of the PtDAs administered in clinics and accessed online, decisional and patient-reported outcome measures and qualitative feedback. Quantitative data will be analysed using descriptive statistics, paired sample t-tests and CIs; interviews will be analysed using thematic analysis. Ethics and dissemination Research Ethics Committee approval (Ref: 16/EM/0122) and Health Research Authority approval (Ref: 194751) has been granted. Findings will be published in open access peer-reviewed journals, presented at conferences for academic and health professional audiences, with feedback to health professionals and program managers. The Cancer, Fertility and Me patient decision aid (PtDA) will be disseminated via a diverse range of open-access media, study and charity websites, professional organisations and academic sources. External endorsement will be sought from the International Patient Decision Aid Standards (IPDAS) Collaboration inventory of PtDAs and other relevant professional organisations, for example, the British Fertility Society. Trial registration number NCT02753296; pre-results. PMID:28289046

Stromal cell-derived factor 2 is critical for Hsp90-dependent eNOS activation.

PubMed

Siragusa, Mauro; Fröhlich, Florian; Park, Eon Joo; Schleicher, Michael; Walther, Tobias C; Sessa, William C

2015-08-18

Endothelial nitric oxide synthase (eNOS) catalyzes the conversion of l-arginine and molecular oxygen into l-citrulline and nitric oxide (NO), a gaseous second messenger that influences cardiovascular physiology and disease. Several mechanisms regulate eNOS activity and function, including phosphorylation at Ser and Thr residues and protein-protein interactions. Combining a tandem affinity purification approach and mass spectrometry, we identified stromal cell-derived factor 2 (SDF2) as a component of the eNOS macromolecular complex in endothelial cells. SDF2 knockdown impaired agonist-stimulated NO synthesis and decreased the phosphorylation of eNOS at Ser(1177), a key event required for maximal activation of eNOS. Conversely, SDF2 overexpression dose-dependently increased NO synthesis through a mechanism involving Akt and calcium (induced with ionomycin), which increased the phosphorylation of Ser(1177) in eNOS. NO synthesis by iNOS (inducible NOS) and nNOS (neuronal NOS) was also enhanced upon SDF2 overexpression. We found that SDF2 was a client protein of the chaperone protein Hsp90, interacting preferentially with the M domain of Hsp90, which is the same domain that binds to eNOS. In endothelial cells exposed to vascular endothelial growth factor (VEGF), SDF2 was required for the binding of Hsp90 and calmodulin to eNOS, resulting in eNOS phosphorylation and activation. Thus, our data describe a function for SDF2 as a component of the Hsp90-eNOS complex that is critical for signal transduction in endothelial cells. Copyright © 2015, American Association for the Advancement of Science.

Enhancing eNOS activity with simultaneous inhibition of IKKβ restores vascular function in Ins2(Akita+/-) type-1 diabetic mice.

PubMed

Krishnan, Manickam; Janardhanan, Preethi; Roman, Linda; Reddick, Robert L; Natarajan, Mohan; van Haperen, Rien; Habib, Samy L; de Crom, Rini; Mohan, Sumathy

2015-10-01

The balance of nitric oxide (NO) versus superoxide generation has a major role in the initiation and progression of endothelial dysfunction. Under conditions of high glucose, endothelial nitric oxide synthase (eNOS) functions as a chief source of superoxide rather than NO. In order to improve NO bioavailability within the vessel wall in type-1 diabetes, we investigated treatment strategies that improve eNOS phosphorylation and NO-dependent vasorelaxation. We evaluated methods to increase the eNOS activity by (1) feeding Ins2(Akita) spontaneously diabetic (type-1) mice with l-arginine in the presence of sepiapterin, a precursor of tetrahydrobiopterin; (2) preventing eNOS/NO deregulation by the inclusion of inhibitor kappa B kinase beta (IKKβ) inhibitor, salsalate, in the diet regimen in combination with l-arginine and sepiapterin; and (3) independently increasing eNOS expression to improve eNOS activity and associated NO production through generating Ins2(Akita) diabetic mice that overexpress human eNOS predominantly in vascular endothelial cells. Our results clearly demonstrated that diet supplementation with l-arginine, sepiapterin along with salsalate improved phosphorylation of eNOS and enhanced vasorelaxation of thoracic/abdominal aorta in type-1 diabetic mice. More interestingly, despite the overexpression of eNOS, the in-house generated transgenic eNOS-GFP (TgeNOS-GFP)-Ins2(Akita) cross mice showed an unanticipated effect of reduced eNOS phosphorylation and enhanced superoxide production. Our results demonstrate that enhancement of endogenous eNOS activity by nutritional modulation is more beneficial than increasing the endogenous expression of eNOS by gene therapy modalities.

Targeted overexpression of endothelial nitric oxide synthase in endothelial cells improves cerebrovascular reactivity in Ins2Akita-type-1 diabetic mice.

PubMed

Chandra, Saurav B; Mohan, Sumathy; Ford, Bridget M; Huang, Lei; Janardhanan, Preethi; Deo, Kaiwalya S; Cong, Linlin; Muir, Eric R; Duong, Timothy Q

2016-06-01

Reduced bioavailability of nitric oxide due to impaired endothelial nitric oxide synthase (eNOS) activity is a leading cause of endothelial dysfunction in diabetes. Enhancing eNOS activity in diabetes is a potential therapeutic target. This study investigated basal cerebral blood flow and cerebrovascular reactivity in wild-type mice, diabetic mice (Ins2(Akita+/-)), nondiabetic eNOS-overexpressing mice (TgeNOS), and the cross of two transgenic mice (TgeNOS-Ins2(Akita+/-)) at six months of age. The cross was aimed at improving eNOS expression in diabetic mice. The major findings were: (i) Body weights of Ins2(Akita+/-) and TgeNOS-Ins2(Akita+/-) were significantly different from wild-type and TgeNOS mice. Blood pressure of TgeNOS mice was lower than wild-type. (ii) Basal cerebral blood flow of the TgeNOS group was significantly higher than cerebral blood flow of the other three groups. (iii) The cerebrovascular reactivity in the Ins2(Akita+/-) mice was significantly lower compared with wild-type, whereas that in the TgeNOS-Ins2(Akita+/-) was significantly higher compared with the Ins2(Akita+/-) and TgeNOS groups. Overexpression of eNOS rescued cerebrovascular dysfunction in diabetic animals, resulting in improved cerebrovascular reactivity. These results underscore the possible role of eNOS in vascular dysfunction in the brain of diabetic mice and support the notion that enhancing eNOS activity in diabetes is a potential therapeutic target. © The Author(s) 2015.

Stromal cell–derived factor 2 is critical for Hsp90-dependent eNOS activation

PubMed Central

Siragusa, Mauro; Fröhlich, Florian; Park, Eon Joo; Schleicher, Michael; Walther, Tobias C.; Sessa, William C.

2016-01-01

Endothelial nitric oxide synthase (eNOS) catalyzes the conversion of l-arginine and molecular oxygen into l-citrulline and nitric oxide (NO), a gaseous second messenger that influences cardiovascular physiology and disease. Several mechanisms regulate eNOS activity and function, including phosphorylation at Ser and Thr residues and protein-protein interactions. Combining a tandem affinity purification approach and mass spectrometry, we identified stromal cell–derived factor 2 (SDF2) as a component of the eNOS macromolecular complex in endothelial cells. SDF2 knockdown impaired agonist-stimulated NO synthesis and decreased the phosphorylation of eNOS at Ser1177, a key event required for maximal activation of eNOS. Conversely, SDF2 overexpression dose-dependently increased NO synthesis through a mechanism involving Akt and calcium (induced with ionomycin), which increased the phosphorylation of Ser1177 in eNOS. NO synthesis by iNOS (inducible NOS) and nNOS (neuronal NOS) was also enhanced upon SDF2 overexpression. We found that SDF2 was a client protein of the chaperone protein Hsp90, interacting preferentially with the M domain of Hsp90, which is the same domain that binds to eNOS. In endothelial cells exposed to vascular endothelial growth factor (VEGF), SDF2 was required for the binding of Hsp90 and calmodulin to eNOS, resulting in eNOS phosphorylation and activation. Thus, our data describe a function for SDF2 as a component of the Hsp90-eNOS complex that is critical for signal transduction in endothelial cells. PMID:26286023

Functional significance of differential eNOS translocation

PubMed Central

Sánchez, Fabiola A.; Savalia, Nirav B.; Durán, Ricardo G.; Lal, Brajesh K.; Boric, Mauricio P.; Durán, Walter N.

2006-01-01

Nitric oxide (NO) regulates flow and permeability. ACh and platelet-activating factor (PAF) lead to endothelial NO synthase (eNOS) phosphorylation and NO release. While ACh causes only vasodilation, PAF induces vasoconstriction and hyperpermeability. The key differential signaling mechanisms for discriminating between vasodilation and hyperpermeability are unknown. We tested the hypothesis that differential translocation may serve as a regulatory mechanism of eNOS to determine specific vascular responses. We used ECV-304 cells permanently transfected with eNOS-green fluorescent protein (ECVeNOS-GFP) and demonstrated that the agonists activate eNOS and reproduce their characteristic endothelial permeability effects in these cells. We evaluated eNOS localization by lipid raft analysis and immunofluorescence microscopy. After PAF and ACh, eNOS moves away from caveolae. eNOS distributes both in the plasma membrane and Golgi in control cells. ACh (10−5 M, 10−4 M) translocated eNOS preferentially to the trans-Golgi network (TGN) and PAF (10−7 M) preferentially to the cytosol. We suggest that PAF-induced eNOS translocation preferentially to cytosol reflects a differential signaling mechanism related to changes in permeability, whereas ACh-induced eNOS translocation to the TGN is related to vasodilation. PMID:16679407

Piezoresponse force microscopy of ferroelectric relaxors =

NASA Astrophysics Data System (ADS)

Kiselev, Dmitry

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

Role of Nitric Oxide Isoforms in Vascular and Alveolar Development and Lung Injury in Vascular Endothelial Growth Factor Overexpressing Neonatal Mice Lungs.

PubMed

Syed, Mansoor A; Choo-Wing, Rayman; Homer, Robert J; Bhandari, Vineet

2016-01-01

The role of vascular endothelial growth factor (VEGF)-induced 3 different nitric oxide synthase (NOS) isoforms in lung development and injury in the newborn (NB) lung are not known. We hypothesized that VEGF-induced specific NOS pathways are critical regulators of lung development and injury. We studied NB wild type (WT), lung epithelial cell-targeted VEGF165 doxycycline-inducible overexpressing transgenic (VEGFTG), VEGFTG treated with a NOS1 inhibitor (L-NIO), VEGFTG x NOS2-/- and VEGFTG x NOS3+/- mice in room air (RA) for 7 postnatal (PN) days. Lung morphometry (chord length), vascular markers (Ang1, Ang2, Notch2, vWF, CD31 and VE-cadherin), cell proliferation (Ki67), vascular permeability, injury and oxidative stress markers (hemosiderin, nitrotyrosine and 8-OHdG) were evaluated. VEGF overexpression in RA led to increased chord length and vascular markers at PN7, which were significantly decreased to control values in VEGFTG x NOS2-/- and VEGFTG x NOS3+/- lungs. However, we found no noticeable effect on chord length and vascular markers in the VEGFTG / NOS1 inhibited group. In the NB VEGFTG mouse model, we found VEGF-induced vascular permeability in the NB murine lung was partially dependent on NOS2 and NOS3-signaling pathways. In addition, the inhibition of NOS2 and NOS3 resulted in a significant decrease in VEGF-induced hemosiderin, nitrotyrosine- and 8-OHdG positive cells at PN7. NOS1 inhibition had no significant effect. Our data showed that the complete absence of NOS2 and partial deficiency of NOS3 confers protection against VEGF-induced pathologic lung vascular and alveolar developmental changes, as well as injury markers. Inhibition of NOS1 does not have any modulating role on VEGF-induced changes in the NB lung. Overall, our data suggests that there is a significant differential regulation in the NOS-mediated effects of VEGF overexpression in the developing mouse lung.

Health and innovation: economic dynamics and Welfare State in Brazil.

PubMed

Gadelha, Carlos Augusto Grabois; Braga, Patrícia Seixas da Costa

2016-11-03

The effective enforcement of the access to healthcare as fundamental right requires an important theoretical and political effort at linking the often contradictory economic and social dimensions of development. This study suggests the need for a systemic view of policies related to the industrial base and innovation in health and the construction of the Brazilian Unified National Health System (SUS). The authors investigate the relations between health, innovation, and development, seeking to show and update the political, economic, and social determinants of the recent Brazilian experience with the Health Economic-Industrial Complex (HEIC). They discuss how the agenda for innovation and domestic industrial production in health gained a central place in the project for construction of the SUS. The article thus seeks to link inherent issues from the agenda for development, production, and innovation to social policy in healthcare, as observed in recent years, and based on this analysis, points to political and conceptual challenges for implementing the SUS, especially as regards strengthening its technological and industrial base. As a byproduct, the article develops an analytical and factual focus on the consolidation of the HEIC in Brazil, both as a dynamic vector of industrial development, generating investment, income, employment, and innovations, and as a decisive element for reducing vulnerability and structural dependence in health. The authors aim to show that strengthening the SUS and orienting it to social needs is an essential part of building a social Welfare State in Brazil. Resumo: A efetivação da saúde como um direito fundamental exige importante esforço, teórico e político, de articulação das dimensões econômicas e sociais, por vezes contraditórias, do desenvolvimento. Este trabalho indica a necessidade de um olhar sistêmico das políticas relacionadas à base produtiva e de inovação em saúde e à construção do Sistema Único de Saúde (SUS). Investiga as relações entre saúde, inovação e desenvolvimento, buscando mostrar e atualizar os determinantes políticos, econômicos e sociais da experiência brasileira recente relacionada ao Complexo Econômico-Industrial da Saúde (CEIS). Mostra como a agenda da inovação e da produção nacional em saúde ganhou centralidade no projeto de construção do SUS. O artigo procura, assim, articular questões inerentes à agenda do desenvolvimento, da produção e da inovação com a política social em saúde, tal como observado nos últimos anos e, valendo-se de sua análise, aponta desafios políticos e conceituais para a efetivação do SUS, em especial no que se refere ao fortalecimento de sua base tecnológica e produtiva. Como desdobramento, desenvolve um enfoque analítico e factual que relaciona a consolidação do CEIS no Brasil tanto como um vetor dinâmico do desenvolvimento industrial, gerando investimento, renda, emprego e inovações, quanto como elemento decisivo para a redução da vulnerabilidade e da dependência estrutural em saúde. Procura mostrar que seu fortalecimento e direcionamento para as necessidades sociais é parte essencial da construção de um Estado de Bem-Estar Social no Brasi.

Resposta do detector de ondas gravitacionais Mario Schenberg ao "ringdown" de buraco negros

NASA Astrophysics Data System (ADS)

Costa, C. A.; Aguiar, O. D.; Magalhães, N. S.

2003-08-01

Acredita-se que quando duas estrelas de nêutrons coalescem, elas, eventualmente, formam um buraco negro com massa igual a soma das massas dos objetos originais. Durante a formação do buraco negro, o espaço-tempo em torno do sistema sofre perturbações que se propagam na forma de radiação gravitacional. A forma de onda associada a radiação gravitacional, durante este estágio, aproxima-se a uma senóide exponencialmente amortecida. Este tipo de sinal é conhecido como "ringdown", e seu comportamento e parametrização são muito bem conhecidos. Neste trabalho, simulamos computacionalmente sinais provenientes do "ringdown" de buracos negros, com a finalidade de testar o desempenho do detector de ondas gravitacionais Mario Schenberg em observá-los, quando entrar em funcionamento. Este primeiro teste teórico ajudou-nos a criar estratégias de detecção de sinais imersos no ruído instrumental. Calculamos a relação sinal-ruído como uma função da frequência, bem como sua integral dentro da faixa de sensibilidade do detector. Os resultados obtidos mostraram que o detector Schenberg terá sensibilidade suficiente para detectar este tipo de sinal, proveniente de fontes astrofísicas localizadas dentro de um raio de ~100kpc.

Natural antisense transcript-targeted regulation of inducible nitric oxide synthase mRNA levels.

PubMed

Yoshigai, Emi; Hara, Takafumi; Araki, Yoshiro; Tanaka, Yoshito; Oishi, Masaharu; Tokuhara, Katsuji; Kaibori, Masaki; Okumura, Tadayoshi; Kwon, A-Hon; Nishizawa, Mikio

2013-04-01

Natural antisense transcripts (asRNAs) are frequently transcribed from mammalian genes. Recently, we found that non-coding asRNAs are transcribed from the 3' untranslated region (3'UTR) of the rat and mouse genes encoding inducible nitric oxide synthase (iNOS), which catalyzes the production of the inflammatory mediator nitric oxide. The iNOS asRNA stabilizes iNOS mRNA by interacting with the mRNA 3'UTR. Furthermore, single-stranded 'sense' oligonucleotides corresponding to the iNOS mRNA sequence were found to reduce iNOS mRNA levels by interfering with mRNA-asRNA interactions in rat hepatocytes. This method was named natural antisense transcript-targeted regulation (NATRE) technology. In this study, we detected human iNOS asRNA expressed in hepatocarcinoma and colon carcinoma tissues. The human iNOS asRNA harbored a sequence complementary to an evolutionarily conserved region of the iNOS mRNA 3'UTR. When introduced into hepatocytes, iNOS sense oligonucleotides that were modified by substitution with partial phosphorothioate bonds and locked nucleic acids or 2'-O-methyl nucleic acids greatly reduced levels of iNOS mRNA and iNOS protein. Moreover, sense oligonucleotides and short interfering RNAs decreased iNOS mRNA to comparable levels. These results suggest that NATRE technology using iNOS sense oligonucleotides could potentially be used to treat human inflammatory diseases and cancers by reducing iNOS mRNA levels. Copyright © 2013 Elsevier Inc. All rights reserved.

Activation of eNOS in endothelial cells exposed to ionizing radiation involves components of the DNA damage response pathway

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

Nagane, Masaki; Yasui, Hironobu; Sakai, Yuri

2015-01-02

Highlights: • eNOS activity is increased in BAECs exposed to X-rays. • ATM is involved in this increased eNOS activity. • HSP90 modulates the radiation-induced activation of ATM and eNOS. - Abstract: In this study, the involvement of ataxia telangiectasia mutated (ATM) kinase and heat shock protein 90 (HSP90) in endothelial nitric oxide synthase (eNOS) activation was investigated in X-irradiated bovine aortic endothelial cells. The activity of nitric oxide synthase (NOS) and the phosphorylation of serine 1179 of eNOS (eNOS-Ser1179) were significantly increased in irradiated cells. The radiation-induced increases in NOS activity and eNOS-Ser1179 phosphorylation levels were significantly reduced bymore » treatment with either an ATM inhibitor (Ku-60019) or an HSP90 inhibitor (geldanamycin). Geldanamycin was furthermore found to suppress the radiation-induced phosphorylation of ATM-Ser1181. Our results indicate that the radiation-induced eNOS activation in bovine aortic endothelial cells is regulated by ATM and HSP90.« less

Relief evolution of the Continental Rift of Southeast Brazil revealed by in situ-produced 10Be concentrations in river-borne sediments

NASA Astrophysics Data System (ADS)

Salgado, André Augusto Rodrigues; Rezende, Eric de Andrade; Bourlès, Didier; Braucher, Régis; da Silva, Juliana Rodrigues; Garcia, Ricardo Alexandrino

2016-04-01

This study aims to quantify the denudation dynamics of the Brazilian passive margin along a segment of the Continental Rift of Southeast Brazil. The denudation rates of 30 basins that drain both horsts of the continental rift, including the mountain ranges of the Serra do Mar (seaside horst); and the Serra da Mantiqueira (continental horst); were derived from 10Be concentrations measured in sand-sized river sediment. The mean denudation rate ranges from 9.2 m Ma-1 on the plateau of the Serra do Mar to 37.1 m Ma-1 along the oceanic escarpment of the Serra do Mar. The seaward-facing scarps of both mountain ranges exhibit mean denudation rates that are approximately 1.5 times those of the inland-facing scarps. The escarpments of the horst nearer to the ocean (Serra do Mar) exhibit higher denudation rates (mean 30.2 m Ma-1) than the escarpments of the continental horst (Serra da Mantiqueira) (mean 16.5 m Ma-1). The parameters that impact these denudation rates include the catchment relief, the slope gradient, the rock and the climate. The incongruent combination of a mountainous landscape and moderate to low 10Be-based denudation rates averaging at ∼20 m Ma-1 suggests a reduction in intraplate tectonic activity beginning in the Middle Quaternary or earlier.

Enhanced XOR activity in eNOS-deficient mice: Effects on the nitrate-nitrite-NO pathway and ROS homeostasis.

PubMed

Peleli, Maria; Zollbrecht, Christa; Montenegro, Marcelo F; Hezel, Michael; Zhong, Jianghong; Persson, Erik G; Holmdahl, Rikard; Weitzberg, Eddie; Lundberg, Jon O; Carlström, Mattias

2016-10-01

Xanthine oxidoreductase (XOR) is generally known as the final enzyme in purine metabolism and as a source of reactive oxygen species (ROS). In addition, this enzyme has been suggested to mediate nitric oxide (NO) formation via reduction of inorganic nitrate and nitrite. This NO synthase (NOS)-independent pathway for NO generation is of particular importance during certain conditions when NO bioavailability is diminished due to reduced activity of endothelial NOS (eNOS) or increased oxidative stress, including aging and cardiovascular disease. The exact interplay between NOS- and XOR-derived NO generation is not fully elucidated yet. The aim of the present study was to investigate if eNOS deficiency is associated with changes in XOR expression and activity and the possible impact on nitrite, NO and ROS homeostasis. Plasma levels of nitrate and nitrite were similar between eNOS deficient (eNOS -/- ) and wildtype (wt) mice. XOR activity was upregulated in eNOS -/- compared with wt, but not in nNOS -/- , iNOS -/- or wt mice treated with the non-selective NOS inhibitor L-NAME. Following an acute dose of nitrate, plasma nitrite increased more in eNOS -/- compared with wt, and this augmented response was abolished by the selective XOR inhibitor febuxostat. Livers from eNOS -/- displayed higher nitrite reducing capacity compared with wt, and this effect was attenuated by febuxostat. Dietary supplementation with nitrate increased XOR expression and activity, but concomitantly reduced superoxide generation. The latter effect was also seen in vitro after nitrite administration. Treatment with febuxostat elevated blood pressure in eNOS -/- , but not in wt mice. A high dose of dietary nitrate reduced blood pressure in naïve eNOS -/- mice, and again this effect was abolished by febuxostat. In conclusion, eNOS deficiency is associated with an upregulation of XOR facilitating the nitrate-nitrite-NO pathway and decreasing the generation of ROS. This interplay between XOR and eNOS is proposed to play a significant role in NO homeostasis and blood pressure regulation. Copyright © 2016 Elsevier Inc. All rights reserved.

Mechanism of Inducible Nitric-oxide Synthase Dimerization Inhibition by Novel Pyrimidine Imidazoles*

PubMed Central

Nagpal, Latika; Haque, Mohammad M.; Saha, Amit; Mukherjee, Nirmalya; Ghosh, Arnab; Ranu, Brindaban C.; Stuehr, Dennis J.; Panda, Koustubh

2013-01-01

Overproduction of nitric oxide (NO) by inducible nitric-oxide synthase (iNOS) has been etiologically linked to several inflammatory, immunological, and neurodegenerative diseases. As dimerization of NOS is required for its activity, several dimerization inhibitors, including pyrimidine imidazoles, are being evaluated for therapeutic inhibition of iNOS. However, the precise mechanism of their action is still unclear. Here, we examined the mechanism of iNOS inhibition by a pyrimidine imidazole core compound and its derivative (PID), having low cellular toxicity and high affinity for iNOS, using rapid stopped-flow kinetic, gel filtration, and spectrophotometric analysis. PID bound to iNOS heme to generate an irreversible PID-iNOS monomer complex that could not be converted to active dimers by tetrahydrobiopterin (H4B) and l-arginine (Arg). We utilized the iNOS oxygenase domain (iNOSoxy) and two monomeric mutants whose dimerization could be induced (K82AiNOSoxy) or not induced (D92AiNOSoxy) with H4B to elucidate the kinetics of PID binding to the iNOS monomer and dimer. We observed that the apparent PID affinity for the monomer was 11 times higher than the dimer. PID binding rate was also sensitive to H4B and Arg site occupancy. PID could also interact with nascent iNOS monomers in iNOS-synthesizing RAW cells, to prevent their post-translational dimerization, and it also caused irreversible monomerization of active iNOS dimers thereby accomplishing complete physiological inhibition of iNOS. Thus, our study establishes PID as a versatile iNOS inhibitor and therefore a potential in vivo tool for examining the causal role of iNOS in diseases associated with its overexpression as well as therapeutic control of such diseases. PMID:23696643

Daily cycling of nitric oxide synthase (NOS) in the hippocampus of pigeons (C. livia)

PubMed Central

2013-01-01

Background Nitric oxide synthase (NOS) is essential for the synthesis of nitric oxide (NO), a non-conventional neurotransmitter with an important role in synaptic plasticity underlying processes of hippocampus-dependent memory and in the regulation of biological clocks and circadian rhythms. Many studies have shown that both the NOS cytosolic protein content and its enzymatic activity present a circadian variation in different regions of the rodent brain, including the hippocampus. The present study investigated the daily variation of NOS enzymatic activity and the cytosolic content of nNOS in the hippocampus of pigeons. Results Adult pigeons kept under a skeleton photoperiod were assigned to six different groups. Homogenates of the hippocampus obtained at six different times-of-day were used for NOS analyses. Both iNOS activity and nNOS cytosolic protein concentrations were highest during the subjective light phase and lowest in the subjective dark phase of the circadian period. ANOVA showed significant time differences for iNOS enzymatic activity (p < 0.05) and for nNOS protein content (p < 0.05) in the hippocampus. A significant daily rhythm for both iNOS and nNOS was confirmed by analysis with the Cosinor method (p < 0.05). The present findings indicate that the enzymatic activity of iNOS and content of nNOS protein in the hippocampus of pigeons exhibit a daily rhythm, with acrophase values occurring during the behavioral activity phase. Conclusions The data corroborate the reports on circadian variation of NOS in the mammalian hippocampus and can be considered indicative of a dynamic interaction between hippocampus-dependent processes and circadian clock mechanisms. PMID:24176048

Teaching Nature of Science to K-2 Students: What understandings can they attain?

NASA Astrophysics Data System (ADS)

Akerson, Valarie; Donnelly, Lisa A.

2010-01-01

This study explored the influence of a Saturday Science program that used explicit reflective instruction through contextualized and decontextualized guided and authentic inquiry on K-2 students' views of nature of science (NOS). The six-week program ran for 2.5 hours weekly and emphasized NOS in a variety of science content areas, culminating in an authentic inquiry designed and carried out by the K-2 students. The Views of Nature of Science Form D was used to interview K-2 students pre- and post-instruction. Copies of student work were retained for content analysis. Videotapes made of each week's science instruction were reviewed to ensure that explicit reflective NOS instruction took place. Explicit NOS teaching strategies included (1) introducing NOS through decontextualized activities, (2) embedding NOS into science content through contextualized activities, (3) using children's literature, (4) debriefings and embedded NOS assessments, and (5) guided and student-designed inquiries. Results indicate that K-2 students improved their NOS views over the course of the program, suggesting that they are developmentally ready for these concepts. Students developed adequate views of the distinction between observation and inference, the creative NOS, the tentative NOS, the empirical NOS, and to a lesser degree, the subjective NOS.

Association of a NOS3 gene polymorphism with Behçet's disease but not with Vogt-Koyanagi-Harada syndrome in Han Chinese.

PubMed

Zhou, Yan; Yu, Hongsong; Hou, Shengping; Fang, Jing; Qin, Jieying; Yuan, Gangxiang; Kijlstra, Aize; Yang, Peizeng

2016-01-01

Previous studies have identified that nitric oxide synthase (NOS) genes are associated with several immune-mediated diseases. This study aimed to investigate whether NOS2 and NOS3 gene polymorphisms are associated with Behçet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Han Chinese population. An association analysis of NOS2/rs4795067, NOS3/rs1799983 and NOS3/rs1800779 was performed in 733 patients with BD, 800 patients with VKH syndrome, and 1,359 controls using PCR restriction fragment length polymorphism (PCR-RFLP) assay. Statistical analysis was performed with the chi-square test followed by the Bonferroni correction. The result showed a decreased frequency of the NOS3/rs1799983 GG genotype and an increased frequency of NOS3/rs1799983 GT genotype in the patients with BD (Bonferroni correction test [Pc]=0.02, odds ratio [OR]=0.74; Pc=2.1×10(-3), OR=1.57, respectively). No significant association was found between rs1799983 and VKH syndrome. NOS2/ rs4795067 and NOS3/rs1800779 were not associated with either BD or VKH syndrome. Our findings suggest that a NOS3/rs1799983polymorphism is associated with susceptibility to BD in Han Chinese.

[Effects of glycosides of Tripterygium wilfordii, methyltestosterone and zhuanggushenjin capsule on nitric oxide synthase in rat testes].

PubMed

Ren, Ya-Ping; Sun, Li; Jiang, Wei; Hu, Chun-Ping

2005-05-01

To investigate the effects of glycosides of tripterygium wilfordii (GTW), methyltestosterone and Zhuanggushenjin capsule on nitric oxide synthase (NOS) in rat testes. Forty-five rats were equally divided into 5 groups, and respectively given GTW [10 mg/(kg x d)], methyltestosterone [2 mg/(kg x d)], Zhuanggushenjin capsule [0.3 g/(kg x d)], distilled water plus Tween 80 (control I), and distilled water alone (control II) for 4 weeks. At the end of the 5th week, the immunochemical ABC method was used to observe the effects of the three drugs on the NOS positive Leydig cells of the rats. Compared with control II, the GTW group had a significant decrease in the numbers of nNOS and eNOS positive Leydig cells, the methyltestosterone group showed an increase in the number of nNOS but a decrease in that of eNOS positive Leydig cells, and the Zhuanggushenjin group had an increase in the numbers of both nNOS and eNOS positive Leydig cells. GTW can reduce NO production by inhibiting eNOS and nNOS, and hence influence the spermatogenic process. Zhuanggushenjin capsule plays an important role in improving male sexual function by enhancing nNOS and eNOS expression and NO synthesis.

Efficacy of bacterial cellulose membrane for the treatment of lower limbs chronic varicose ulcers: a randomized and controlled trial.

PubMed

Cavalcanti, Luciana Marins; Pinto, Flávia Cristina Morone; Oliveira, Glícia Maria DE; Lima, Salvador Vilar Correia; Aguiar, José Lamartine DE Andrade; Lins, Esdras Marques

2017-01-01

to evaluate the efficacy of Bacterial Cellulose (BC) membrane dressings in the treatment of lower limb venous ulcers. we carried out a prospective, randomized, controlled study of 25 patients with chronic venous ulcer disease in the lower limbs from the Angiology and Vascular Surgery Service of the Federal University of Pernambuco Hospital and from the Salgado Polyclinic of the County Health Department, Caruaru, Pernambuco. We randomly assigned patients to two groups: control group, receiving dressings with triglyceride oil (11 patients) and experimental group, treated with BC membrane (14 patients). We followed the patients for a period of 120 days. There was a reduction in the wound area in both groups. There were no infections or reactions to the product in any of the groups. Patients in the BC group showed decreased pain and earlier discontinuation of analgesic use. BC membrane can be used as a dressing for the treatment of varicose ulcers of the lower limbs. avaliar a eficácia de curativos com membrana de Celulose Bacteriana (CB) no tratamento de úlceras venosas de membros inferiores. estudo prospectivo, randomizado e controlado de 25 pacientes com úlceras decorrentes de doença venosa crônica nos membros inferiores provenientes do Serviço de Angiologia e Cirurgia Vascular do Hospital de Clínicas da Universidade Federal de Pernambuco e da Policlínica do Salgado da Secretaria Municipal de Saúde, Caruaru, Pernambuco. Os pacientes foram distribuídos aleatoriamente em dois grupos: grupo controle, que recebeu curativos com óleo de triglicerídeos (11 pacientes) e grupo experimental, tratado com membrana de CB (14 pacientes). Os pacientes foram acompanhados por um período de 120 dias. houve uma redução na área de ferida em ambos os grupos. Não houve infecção ou reações ao produto em nenhum dos grupos. Pacientes do grupo CB mostraram diminuição da dor e interrupção mais precoce do uso de analgésicos. a membrana de CB pode ser usada como curativo para o tratamento de úlceras varicosas dos membros inferiores.

Astronomia cultural e meio ambiente segundo uma abordagem holística

NASA Astrophysics Data System (ADS)

Jafelice, L. C.

2003-08-01

Neste trabalho ampliamos a discussão da abordagem holística para o ensino de astronomia que temos desenvolvido nos últimos anos, analisamos novos resultados e apresentamos exemplos práticos para interessados em experimentá-la. A constatação básica a orientar este enfoque é que cursos introdutórios em astronomia costumam ser excessiva e prematuramente técnicos, além de assumirem uma visão tradicional, muito estreita, do que seja educação científica, herdada da era cartesiana e positivista da ciência. Fundamentamos porque é importante que elementos de astronomia cultural ofereçam o mote e constituam o eixo norteador daqueles cursos e porque é urgente revermos a visão que temos da relação entre astronomia e meio ambiente. Um ponto central nesta abordagem é explorar formas de reativar e atualizar uma relação orgânica com o meio e excitar a consciência de nossa inevitável e profunda interdependência com ele em nível cósmico. Neste trabalho exemplificamos a possibilidade de concretização desta proposta em três diferentes situações: disciplinas de cursos de licenciatura em geografia e em física; escolas de nível fundamental; e, neste caso ainda a ser implementada, comunidades carentes. Estes casos envolvem públicos e espaços diferenciados para educação formal e não-formal. Dos casos já implementados, destacamos os resultados alcançados pelos alunos: enriquecimento cultural, aprendizagem significativa de conteúdos astronômicos tradicionais; mudanças de comportamento, incorporando contato diário com o céu; e freqüentes vivências de sentimentos empáticos que redirecionam a relação com a natureza e a consciência ecológica global. Além disto, para interessados em aplicar esta proposta, também socializamos procedimentos e cuidados para a implementação de ações alternativas consonantes com a mesma. (PPGECNM/UFRN; PRONEX/FINEP; NUPA/USP; Temáticos/FAPESP)

Nature of Science Progression in School Year 1-9: a Case Study of Teachers' Suggestions and Rationales

NASA Astrophysics Data System (ADS)

Leden, Lotta; Hansson, Lena

2017-07-01

The inclusion of nature of science (NOS) in science education has for a long time been regarded as crucial. There is, however, a lack of research on appropriate NOS aspects for different educational levels. An even more neglected area of research is that focusing on teachers' perspectives on NOS teaching at different levels. The aim of this article is to examine NOS progression in the light of teachers' suggestions and rationales. In order to obtain teachers' informed perspectives, we chose to involve six teachers (teaching grades 1-9) in a 3-year research project. They took part in focus group discussions about NOS and NOS teaching as well as implemented jointly planned NOS teaching sessions. Data that this article builds on was collected at the end of the project. The teachers' suggestions for NOS progression often relied on adding more NOS issues at every stage, thereby creating the foundations of a broader but not necessarily deeper understanding of NOS. Five rationales, for if/when specific NOS issues are appropriate to introduce, emerged from the analysis of the teacher discussions. Some of these rationales, including practice makes perfect and increasing levels of depth can potentially accommodate room for many NOS issues in the science classroom, while maturity and experience instead has a restricting effect on NOS teaching. Also, choice of context and teaching approaches play an important role in teachers' rationales for whether specific NOS issues should be included or not at different stages. The article discusses the implications for teacher education and professional development.

Elementary school science teachers' reflection for nature of science: Workshop of NOS explicit and reflective on force and motion learning activity

NASA Astrophysics Data System (ADS)

Patho, Khanittha; Yuenyong, Chokchai; Chamrat, Suthida

2018-01-01

The nature of science has been part of Thailand's science education curriculum since 2008. However, teachers lack of understanding about the nature of science (NOS) and its teaching, particularly element school science teachers. In 2012, the Science Institute of Thailand MOE, started a project of Elementary Science Teacher Professional Development to enhance their thinking about the Nature of Science. The project aimed to enhance teachers' understanding of NOS, science teaching for explicit and reflective NOS, with the aim of extending their understanding of NOS to other teachers. This project selected 366 educational persons. The group was made up of a teacher and a teacher supervisor from 183 educational areas in 74 provinces all Thailand. The project provided a one week workshop and a year's follow up. The week-long workshop consisted of 11 activities of science teaching for explicit reflection on 8 aspects of NOS. Workshop of NOS explicit and reflective on force and motion learning activity is one of eight activities. This activity provided participants to learn force and motion and NOS from the traditional toy "Bang-Poh". The activity tried to enhance participants to explicit NOS for 5 aspects including empirical basis, subjectivity, creativity, observation and inference, and sociocultural embeddedness. The explicit NOS worksheet provided questions to ask participants to reflect their existing ideas about NOS. The paper examines elementary school science teachers' understanding of NOS from the force and motion learning activity which provided explicit reflection on 5 NOS aspects. An interpretive paradigm was used to analyse the teachers' reflections in a NOS worksheet. The findings indicated that majority of them could reflect about the empirical basis of science and creativity but few reflected on observation and inference, or sociocultural embeddedness. The paper will explain the teachers' NOS thinking and discuss the further enhancing of their understanding and organizing NOS explicit and reflective science teaching.

Feasibility and dosimetry studies for 18F-NOS as a potential PET radiopharmaceutical for inducible nitric oxide synthase in humans.

PubMed

Herrero, Pilar; Laforest, Richard; Shoghi, Kooresh; Zhou, Dong; Ewald, Gregory; Pfeifer, John; Duncavage, Eric; Krupp, Kitty; Mach, Robert; Gropler, Robert

2012-06-01

Nitric oxide (NO), the end product of the inducible form of NO synthase (iNOS), is an important mediator of a variety of inflammatory diseases. Therefore, a radiolabeled iNOS radiopharmaceutical for assessing iNOS protein concentration as a marker for its activity would be of value to the study and treatment of NO-related diseases. We recently synthesized an (18)F-radiolabeled analog of the reversible NOS inhibitor, 2-amino-4-methylpyridine ((18)F-NOS), and confirmed its utility in a murine model of lung inflammation. To determine its potential for use in humans, we measured (18)F-NOS myocardial activity in patients after orthotopic heart transplantation (OHT) and correlated it with pathologic allograft rejection, tissue iNOS levels, and calculated human radiation dosimetry. Two groups were studied-a kinetic analysis group and a dosimetry group. In the kinetic analysis group, 10 OHT patients underwent dynamic myocardial (18)F-NOS PET/CT, followed by endomyocardial biopsy. Myocardial (18)F-NOS PET was assessed using volume of distribution; standardized uptake values at 10 min; area under the myocardial moment curve (AUMC); and mean resident time at 5, 10, and 30 min after tracer injection. Tissue iNOS levels were measured by immunohistochemistry. In the dosimetry group, the biodistribution and radiation dosimetry were calculated using whole-body PET/CT in 4 healthy volunteers and 12 OHT patients. The combined time-activity curves were used for residence time calculation, and organ doses were calculated with OLINDA. Both AUMC at 10 min (P < 0.05) and tissue iNOS (P < 0.0001) were higher in patients exhibiting rejection than in those without rejection. Moreover, the (18)F-NOS AUMC at 10 min correlated positively with tissue iNOS at 10 min (R(2) = 0.42, P < 0.05). (18)F-NOS activity was cleared by the hepatobiliary system. The critical organ was the bladder wall, with a dose of 95.3 μGy/MBq, and an effective dose of 15.9 μSv/MBq was calculated. Myocardial (18)F-NOS activity is increased in organ rejection (a condition associated with increased iNOS levels) and correlates with tissue iNOS measurements with acceptable radiation exposure. Although further modifications to improve the performance of (18)F-NOS are needed, these data show the feasibility of PET of iNOS in the heart and other tissues.

Development of a benthic multimetric index for the Serra da Bocaina bioregion in Southeast Brazil.

PubMed

Baptista, D F; Henriques-Oliveira, A L; Oliveira, R B S; Mugnai, R; Nessimian, J L; Buss, D F

2013-08-01

Brazil faces a challenge to develop biomonitoring tools to be used in water quality assessment programs, but few multimetric indices were developed so far. This study is part of an effort to test and implement programs using benthic macroinvertebrates as bioindicators in Rio de Janeiro State. Our aim was first to test the Multimetric Index for Serra dos Órgãos (SOMI) for a different area--Serra da Bocaina (SB)--in the same ecoregion. We sampled 27 streams of different sizes and altitudes in the SB region. Despite the environmental similarities, results indicated biological differences between reference sites of the two regions. Considering these differences, we decided to develop an index specific for the SB region, the Serra da Bocaina Multimetric Index (MISB). We tested twenty-two metrics for sensitivity to impairment and redundancy, and six metrics were considered valid to integrate the MISB: Family Richness, Trichoptera Richness, % Coleoptera, % Diptera, IBE-IOC index, EPT / Chironomidae ratio. A test of the MISB in eleven sites indicated it was more related to land-use and water physico-chemical parameters than with altitude or stream width, being a useful tool for the monitoring and assessment of streams in the bioregion.

Influence of heart failure on resting lung volumes in patients with COPD.

PubMed

Souza, Aline Soares de; Sperandio, Priscila Abreu; Mazzuco, Adriana; Alencar, Maria Clara; Arbex, Flávio Ferlin; Oliveira, Mayron Faria de; O'Donnell, Denis Eunan; Neder, José Alberto

2016-01-01

To evaluate the influence of chronic heart failure (CHF) on resting lung volumes in patients with COPD, i.e., inspiratory fraction-inspiratory capacity (IC)/TLC-and relative inspiratory reserve-[1 - (end-inspiratory lung volume/TLC)]. This was a prospective study involving 56 patients with COPD-24 (23 males/1 female) with COPD+CHF and 32 (28 males/4 females) with COPD only-who, after careful clinical stabilization, underwent spirometry (with forced and slow maneuvers) and whole-body plethysmography. Although FEV1, as well as the FEV1/FVC and FEV1/slow vital capacity ratios, were higher in the COPD+CHF group than in the COPD group, all major "static" volumes-RV, functional residual capacity (FRC), and TLC-were lower in the former group (p < 0.05). There was a greater reduction in FRC than in RV, resulting in the expiratory reserve volume being lower in the COPD+CHF group than in the COPD group. There were relatively proportional reductions in FRC and TLC in the two groups; therefore, IC was also comparable. Consequently, the inspiratory fraction was higher in the COPD+CHF group than in the COPD group (0.42 ± 0.10 vs. 0.36 ± 0.10; p < 0.05). Although the tidal volume/IC ratio was higher in the COPD+CHF group, the relative inspiratory reserve was remarkably similar between the two groups (0.35 ± 0.09 vs. 0.44 ± 0.14; p < 0.05). Despite the restrictive effects of CHF, patients with COPD+CHF have relatively higher inspiratory limits (a greater inspiratory fraction). However, those patients use only a part of those limits, probably in order to avoid critical reductions in inspiratory reserve and increases in elastic recoil. Avaliar a influência da insuficiência cardíaca crônica (ICC) nos volumes pulmonares de repouso em pacientes com DPOC, ou seja, fração inspiratória -capacidade inspiratória (CI)/CPT - e reserva inspiratória relativa - [1 - (volume pulmonar inspiratório final/CPT)]. Após cuidadosa estabilização clínica, 56 pacientes com DPOC (24 alocados no grupo DPOC+ICC; 23 homens/1 mulher) e 32 (28 homens/4 mulheres) com DPOC isolada foram submetidos à espirometria forçada e lenta e pletismografia de corpo inteiro. Os pacientes do grupo DPOC+ICC apresentaram maior VEF1, VEF1/CVF e VEF1/capacidade vital lenta; porém, todos os principais volumes "estáticos" - VR, capacidade residual funcional (CRF) e CPT - foram menores que aqueles do grupo DPOC (p < 0,05). A CRF diminuiu mais do que o VR, determinando assim menor volume de reserva expiratória no grupo DPOC+ICC que no grupo DPOC. Houve redução relativamente proporcional da CRF e da CPT nos dois grupos; logo, a CI também foi similar. Consequentemente, a fração inspiratória no grupo DPOC+ICC foi maior que no grupo DPOC (0,42 ± 0,10 vs. 0,36 ± 0,10; p < 0,05). Embora a razão volume corrente/CI fosse maior no grupo DPOC+ICC, a reserva inspiratória relativa foi notadamente similar entre os grupos (0,35 ± 0,09 vs. 0,44 ± 0,14; p < 0,05). Apesar dos efeitos restritivos da ICC, pacientes com DPOC+ICC apresentam elevações relativas dos limites inspiratórios (maior fração inspiratória). Entretanto, esses pacientes utilizam apenas parte desses limites, com o provável intuito de evitar reduções críticas da reserva inspiratória e maior trabalho elástico.

Multifaceted NOS Instruction: Contextualizing Nature of Science with Documentary Films

ERIC Educational Resources Information Center

Bloom, Mark; Binns, Ian C.; Koehler, Catherine

2015-01-01

This research focuses on inservice science teachers' conceptions of nature of science (NOS) before and after a two-week intensive summer professional development (PD). The PD combined traditional explicit NOS instruction, numerous interactive interventions that highlighted NOS aspects, along with documentary films that portrayed NOS in context of…

The NosX and NirX Proteins of Paracoccus denitrificans Are Functional Homologues: Their Role in Maturation of Nitrous Oxide Reductase

PubMed Central

Saunders, Neil F. W.; Hornberg, Jorrit J.; Reijnders, Willem N. M.; Westerhoff, Hans V.; de Vries, Simon; van Spanning, Rob J. M.

2000-01-01

The nos (nitrous oxide reductase) operon of Paracoccus denitrificans contains a nosX gene homologous to those found in the nos operons of other denitrifiers. NosX is also homologous to NirX, which is so far unique to P. denitrificans. Single mutations of these genes did not result in any apparent phenotype, but a double nosX nirX mutant was unable to reduce nitrous oxide. Promoter-lacZ assays and immunoblotting against nitrous oxide reductase showed that the defect was not due to failure of expression of nosZ, the structural gene for nitrous oxide reductase. Electron paramagnetic resonance spectroscopy showed that nitrous oxide reductase in cells of the double mutant lacked the CuA center. A twin-arginine motif in both NosX and NirX suggests that the NosX proteins are exported to the periplasm via the TAT translocon. PMID:10960107

Intracellular formation of ”undisruptable” dimers of inducible nitric oxide synthase

PubMed Central

Kolodziejski, Pawel J.; Rashid, Mohammad B.; Eissa, N. Tony

2003-01-01

Overproduction of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathogenesis of many diseases. iNOS is active only as a homodimer. Dimerization of iNOS represents a potentially critical target for therapeutic intervention. In this study, we show that intracellular iNOS forms dimers that are ”undisruptable” by boiling, denaturants, or reducing agents. Undisruptable (UD) dimers are clearly distinguishable from the easily dissociated dimers formed by iNOS in vitro. UD dimers do not form in Escherichia coli-expressed iNOS and could not be assembled in vitro, which suggests that an in vivo cellular process is required for their formation. iNOS UD dimers are not affected by intracellular depletion of H4B. However, the mutation of Cys-115 (critical for zinc binding) greatly affects the formation of UD dimers. This study reveals insight into the mechanisms of in vivo iNOS dimer formation. UD dimers represent a class of iNOS dimers that had not been suspected. This unanticipated finding revises our understanding of the mechanisms of iNOS dimerization and lays the groundwork for future studies aimed at modulating iNOS activity in vivo. PMID:14614131

Intracellular formation of "undisruptable" dimers of inducible nitric oxide synthase.

PubMed

Kolodziejski, Pawel J; Rashid, Mohammad B; Eissa, N Tony

2003-11-25

Overproduction of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathogenesis of many diseases. iNOS is active only as a homodimer. Dimerization of iNOS represents a potentially critical target for therapeutic intervention. In this study, we show that intracellular iNOS forms dimers that are "undisruptable" by boiling, denaturants, or reducing agents. Undisruptable (UD) dimers are clearly distinguishable from the easily dissociated dimers formed by iNOS in vitro. UD dimers do not form in Escherichia coli-expressed iNOS and could not be assembled in vitro, which suggests that an in vivo cellular process is required for their formation. iNOS UD dimers are not affected by intracellular depletion of H4B. However, the mutation of Cys-115 (critical for zinc binding) greatly affects the formation of UD dimers. This study reveals insight into the mechanisms of in vivo iNOS dimer formation. UD dimers represent a class of iNOS dimers that had not been suspected. This unanticipated finding revises our understanding of the mechanisms of iNOS dimerization and lays the groundwork for future studies aimed at modulating iNOS activity in vivo.

Requirement of phosphorylatable endothelial nitric oxide synthase at Ser-1177 for vasoinhibin-mediated inhibition of endothelial cell migration and proliferation in vitro.

PubMed

García, Celina; Nuñez-Anita, Rosa Elvira; Thebault, Stéphanie; Arredondo Zamarripa, David; Jeziorsky, Michael C; Martínez de la Escalera, Gonzalo; Clapp, Carmen

2014-03-01

Endothelial nitric oxide synthase (eNOS)-derived nitric oxide is a major vasorelaxing factor and a mediator of vasopermeability and angiogenesis. Vasoinhibins, a family of antiangiogenic prolactin fragments that include 16 K prolactin, block most eNOS-mediated vascular effects. Vasoinhibins activate protein phosphatase 2A, causing eNOS inactivation through dephosphorylation of eNOS at serine residue 1179 in bovine endothelial cells and thereby blocking vascular permeability. In this study, we examined whether human eNOS phosphorylation at S1177 (analogous to bovine S1179) influences other actions of vasoinhibins. Bovine umbilical vein endothelial cells were stably transfected with human wild-type eNOS (WT) or with phospho-mimetic (S1177D) or non-phosphorylatable (S1177A) eNOS mutants. Vasoinhibins inhibited the increases in eNOS activity, migration, and proliferation following the overexpression of WT eNOS but did not affect these responses in cells expressing S1177D and S1177A eNOS mutants. We conclude that eNOS inhibition by dephosphorylation of S1177 is fundamental for the inhibition of endothelial cell migration and proliferation by vasoinhibins.

Induction of calcium-dependent nitric oxide synthases by sex hormones.

PubMed

Weiner, C P; Lizasoain, I; Baylis, S A; Knowles, R G; Charles, I G; Moncada, S

1994-05-24

We have examined the effects of pregnancy and sex hormones on calcium-dependent and calcium-independent nitric oxide synthases (NOSs) in the guinea pig. Pregnancy (near term) caused a > 4-fold increase in the activity of calcium-dependent NOS in the uterine artery and at least a doubling in the heart, kidney, skeletal muscle, esophagus, and cerebellum. The increase in NOS activity in the cerebellum during pregnancy was inhibited by the estrogen-receptor antagonist tamoxifen. Treatment with estradiol (but not progesterone) also increased calcium-dependent NOS activity in the tissues examined from both females and males. Testosterone increased calcium-dependent NOS only in the cerebellum. No significant change in calcium-independent NOS activity was observed either during pregnancy or after the administration of any sex hormone. Both pregnancy and estradiol treatment increased the amount of mRNAs for NOS isozymes eNOS and nNOS in skeletal muscle, suggesting that the increases in NOS activity result from enzyme induction. Thus both eNOS and nNOS are subject to regulation by estrogen, an action that could explain some of the changes that occur during pregnancy and some gender differences in physiology and pathophysiology.

Effects of simulated microgravity on arterial nitric oxide synthase and nitrate and nitrite content

NASA Technical Reports Server (NTRS)

Ma, Jin; Kahwaji, Chadi I.; Ni, Zhenmin; Vaziri, Nosratola D.; Purdy, Ralph E.

2003-01-01

The aim of the present work was to investigate the alterations in nitric oxide synthase (NOS) expression and nitrate and nitrite (NOx) content of different arteries from simulated microgravity rats. Male Wistar rats were randomly assigned to either a control group or simulated microgravity group. For simulating microgravity, animals were subjected to hindlimb unweighting (HU) for 20 days. Different arterial tissues were removed for determination of NOS expression and NOx. Western blotting was used to measure endothelial NOS (eNOS) and inducible NOS (iNOS) protein content. Total concentrations of NOx, stable metabolites of nitric oxide, were determined by the chemiluminescence method. Compared with controls, isolated vessels from simulated microgravity rats showed a significant increase in both eNOS and iNOS expression in carotid arteries and thoracic aorta and a significant decrease in eNOS and iNOS expression of mesenteric arteries. The eNOS and iNOS content of cerebral arteries, as well as that of femoral arteries, showed no differences between the two groups. Concerning NOx, vessels from HU rats showed an increase in cerebral arteries, a decrease in mesenteric arteries, and no change in carotid artery, femoral artery and thoracic aorta. These data indicated that there were differential alterations in NOS expression and NOx of different arteries after hindlimb unweighting. We suggest that these changes might represent both localized adaptations to differential body fluid redistribution and other factors independent of hemodynamic shifts during simulated microgravity.

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.

A novel Bluetongue virus serotype 3 strain in Tunisia, November 2016.

PubMed

Sghaier, S; Lorusso, A; Portanti, O; Marcacci, M; Orsini, M; Barbria, M E; Mahmoud, A S; Hammami, S; Petrini, A; Savini, G

2017-06-01

Since 1998, southern Europe has experienced multiple incursions of different serotypes and topotypes of Bluetongue virus, a vector-borne transmitted virus, the causative agent of Bluetongue (BT), a major disease of ruminants. Some of these incursions originated from northern Africa, likely because of wind-blown dissemination of infected midges. In this report, we describe the detection and whole genome characterization of a novel BTV-3 strain identified in a symptomatic sheep in Tunisia. Sequences were immediately deposited with the GenBank Database under Accession Nos KY432369-KY432378. Alert and preparedness are requested to face the next vector seasons in northern Africa and the potential incursion of this novel strain in southern Europe. © 2017 Blackwell Verlag GmbH.

Resveratrol protects from lipopolysaccharide-induced inflammation in the uterus and prevents experimental preterm birth.

PubMed

Bariani, María Victoria; Correa, Fernando; Leishman, Emma; Domínguez Rubio, Ana Paula; Arias, Andreína; Stern, Aníbal; Bradshaw, Heather B; Franchi, Ana María

2017-08-01

Is resveratrol able to prevent the lipopolysaccharide (LPS)-induced preterm labor in 15-day pregnant BALB/c mice? Resveratrol prevented the LPS-induced onset of preterm labor in 64% of the cases and showed anti-inflammatory and tocolytic effects by downregulating COX-2 and iNOS expression and NOS activity, and by changing the uterine prostaglandin and endocannabinoid profiling. Genital tract infections by Gram-negative bacteria are a common complication in human pregnancy and have been shown to increase risk of preterm delivery. Bacterial LPS elicits a strong maternal inflammatory response that results in preterm delivery and fetal death in a murine model endotoxin-induced preterm labor. An in vivo animal study was conducted. On Day 15 of pregnancy, mice received at 8:00 h a dose of vehicle (40% ethanol in saline solution) or resveratrol (3 mg/kg in vehicle) via oral gavage followed by two doses of LPS or vehicle administered intraperitoneally (i.p.), the first one at 10:00 h (0.17 mg/kg in 0.1 ml of sterile saline solution) and the second at 13:00 h (0.5 mg/kg in 0.1 ml of sterile saline solution). The mice were closely observed for any signs of morbidity (piloerection, decreased movement, and diarrhea), vaginal bleeding or preterm delivery. The beginning of preterm delivery was defined by early delivery of the first pup. Normal term labor occurs on Day 19 of gestation. Time of labor, pregnancy outcome and morphological features were evaluated after LPS and/or resveratrol administration. Uterine stripes were collected 5 h after the last LPS injection and prostaglandin and endocannabinoid profiling was analyzed by mass spectrometry. Nitric oxide synthase (NOS) activity was measured by radioconversion assay. Cyclooxygenase-2 (Cox-2) and 15-hydroxyprostaglandin dehydrogenase (15-Pgdh) mRNA levels were analyzed by RT-PCR whilst the protein expression of inducible nitric oxide synthase (iNOS), COX-1 and COX-2 were studied by western blot. In vivo treatment of 15-day pregnant BALB/c mice with resveratrol prevented the LPS-induced preterm birth in 64% of the cases, whereas only 15% of mice with LPS alone escaped preterm birth. Treatment with resveratrol resulted in a reduced NOS activity (P < 0.05) in the uterus of LPS-treated mice. Similarly, resveratrol reduced the expression of LPS-induced pro-inflammatory agents such as iNOS (P < 0.05), COX-2 (P < 0.05), prostaglandin E2 (PGE2) (P < 0.05) and anandamide (AEA) (P < 0.05). Moreover, resveratrol administration resulted in changes in the uterine endocannabinoid profiling altered by LPS. N/A. Since our experimental design involves the use of mice, the extrapolation of the results presented here to humans is limited. Our findings provide evidence for the tocolytic effects of resveratrol. Dr Ana María Franchi was funded by Agencia Nacional para la Promoción Científica y Tecnológica (PICT 2013/0097) and by Consejo Nacional de Investigaciones Científicas y Técnicas (PIP 2012/0061). Dr Heather B. Bradshaw was funded by NIH (DA006668). The authors have no competing interests. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Proteomic identification of plant proteins probed by mammalian nitric oxide synthase antibodies.

PubMed

Butt, Yoki Kwok-Chu; Lum, John Hon-Kei; Lo, Samuel Chun-Lap

2003-03-01

Several studies suggest that a mammalian-like nitric oxide synthase (NOS) exists in plants. Researchers have attempted to verify its presence using two approaches: (i) determination of NOS functional activity and (ii) probing with mammalian NOS antibodies. However, up to now, neither a NOS-like gene nor a protein has been found in plants. While there is still some controversy over whether the NOS functional activity seen is due to nitrate reductase, using the mammalian NOS antibodies in western blot analysis, several groups have reported the presence of immunoreactive protein bands in plant homogenates. Based on these results, immunohistochemical studies using these antibodies have also been used to localize NOS in plant tissues. However, plant NOS has never been positively identified or characterized. Thus, we used a proteomic approach to verify the identities of plant proteins that cross-reacted with the mammalian NOS antibodies. Proteins extracted from maize (Zea mays L.) embryonic axes were separated by two-dimensional gel electrophoresis and subjected to western blot analysis with the mammalian neuronal NOS and inducible NOS antibodies. Twenty immunoreactive protein spots recognized on a corresponding Coomassie blue-stained two-dimensional gel were subjected to tryptic digestion, followed by identification using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Fifteen proteins were successfully identified and they have described functions that are unrelated to NO metabolism. The remaining five proteins could not be identified. The amino acid sequences of these identified proteins and those used to raise the antibodies were aligned. However, no homologous region could be found. Our results demonstrate that the mammalian NOS antibodies recognize many NOS-unrelated plant proteins. Therefore, it is inappropriate to infer the presence of plant NOS using this immunological technique.

Nitric oxide synthase expression in foetal placentas of cows with retained fetal membranes.

PubMed

Shixin, Fu; Li, Zhang; Chunhai, Luo; Chuang, Xu; Cheng, Xia; Zhe, Wang; Xiaobing, Li

2011-10-01

The objectives of this study were to investigate relationship of retained fetal membranes (RFM) to expression of NOS and NOS mRNA and to analyze pathohistological changes and the distribution of nitric oxide synthase (NOS) in foetal placentas of cows with RFM. Twenty cows were assigned to two groups, a control group (no retained fetal membranes, NRFM, n = 10) and a diseased group (RFM, n = 10). The endpoint method was used to detect the nitric oxide (NO) content and nitric oxide synthase (NOS) activity in foetal placental tissue fluid and the fluorescent quantitation PCR was used to measure the expression of NOS mRNA. Immunohistochemistry and hematoxylin-eosin staining were used to observe pathohistological changes. Tissue from RFM cows showed fibronecrosis of the chorionic villi, and a decreased number of trophoblastic cells. The majority of trophoblastic cells displayed vacuolar degeneration. Interstitium vessels were distended and congested. Expression of induced nitric oxide synthase (iNOS) protein and iNOS mRNA was significantly higher (P < 0.05) in the cytoplasm of placental villus trophoblastic cells in the RFM group. But expression of endothelial nitric oxide synthase (eNOS) protein and eNOS mRNA was significantly lower (P<0.05) in the RFM group. The NO content and NOS activity of cows with RFM were significantly higher (P < 0.05). A high expression of iNOS protein and iNOS mRNA in the cow foetal placenta could produce high content of NO, which might inhibit uterine contraction. So over expression of iNOS protein and iNOS mRNA might be an important agent of retained fetal membranes in cows, and it may be a potential diagnosis biomarker. Copyright © 2010 Elsevier Ltd. All rights reserved.

Inhibition of the L-arginine-nitric oxide pathway mediates the antidepressant effects of ketamine in rats in the forced swimming test.

PubMed

Zhang, Guang-Fen; Wang, Nan; Shi, Jin-Yun; Xu, Shi-Xia; Li, Xiao-Min; Ji, Mu-Huo; Zuo, Zhi-Yi; Zhou, Zhi-Qiang; Yang, Jian-Jun

2013-09-01

Converging evidence shows that the acute administration of a sub-anaesthetic dose ketamine produces fast-acting and robust antidepressant properties in patients suffering from major depressive disorder. However, the underlying mechanisms have not been fully elucidated. The present study aimed to investigate the role of the L-arginine-nitric oxide pathway in the antidepressant effects of ketamine in rats performing the forced swimming test (FST). Ketamine (10 mg/kg) significantly decreased immobility times in the FST and the activities of total nitric oxide synthases (T-NOS), inducible NOS (iNOS), and endothelial NOS (eNOS) in the rat hippocampus. Interestingly, the plasma activities of T-NOS, iNOS, and eNOS increased after administration of ketamine. Furthermore, the activities of neuronal NOS (nNOS) did not change significantly in either the hippocampus or plasma after ketamine administration. The antidepressant effects of ketamine were prevented by pre-treatment with l-arginine (750 mg/kg). Pre-treatment with the NOS inhibitor L-NG-nitroarginine methyl ester at a sub-antidepressant dose of 50 mg/kg and ketamine at a sub-antidepressant dose of 3 mg/kg reduced immobility time in the FST compared to treatment with either drug alone. None of the drugs affected crossing and rearing scores in the open field test. These results suggest that the L-arginine-nitric oxide pathway is involved in the antidepressant effects of ketamine observed in rats in the FST and this involvement is characterised by the inhibition of brain T-NOS, iNOS, and eNOS activities. Copyright © 2013 Elsevier Inc. All rights reserved.

Biphasic Modulation of NOS Expression, Protein and Nitrite Products by Hydroxocobalamin Underlies Its Protective Effect in Endotoxemic Shock: Downstream Regulation of COX-2, IL-1β, TNF-α, IL-6, and HMGB1 Expression

PubMed Central

Sampaio, André L. F.; Dalli, Jesmond; Brancaleone, Vincenzo; D'Acquisto, Fulvio; Perretti, Mauro; Wheatley, Carmen

2013-01-01

Background. NOS/•NO inhibitors are potential therapeutics for sepsis, yet they increase clinical mortality. However, there has been no in vivo investigation of the (in vitro) •NO scavenger, cobalamin's (Cbl) endogenous effects on NOS/•NO/inflammatory mediators during the immune response to sepsis. Methods. We used quantitative polymerase chain reaction (qPCR), ELISA, Western blot, and NOS Griess assays, in a C57BL/6 mouse, acute endotoxaemia model. Results. During the immune response, pro-inflammatory phase, parenteral hydroxocobalamin (HOCbl) treatment partially inhibits hepatic, but not lung, iNOS mRNA and promotes lung eNOS mRNA, but attenuates the LPS hepatic rise in eNOS mRNA, whilst paradoxically promoting high iNOS/eNOS protein translation, but relatively moderate •NO production. HOCbl/NOS/•NO regulation is reciprocally associated with lower 4 h expression of TNF-α, IL-1β, COX-2, and lower circulating TNF-α, but not IL-6. In resolution, 24 h after LPS, HOCbl completely abrogates a major late mediator of sepsis mortality, high mobility group box 1 (HMGB1) mRNA, inhibits iNOS mRNA, and attenuates LPS-induced hepatic inhibition of eNOS mRNA, whilst showing increased, but still moderate, NOS activity, relative to LPS only. experiments (LPS+D-Galactosamine) HOCbl afforded significant, dose-dependent protection in mice Conclusions. HOCbl produces a complex, time- and organ-dependent, selective regulation of NOS/•NO during endotoxaemia, corollary regulation of downstream inflammatory mediators, and increased survival. This merits clinical evaluation. PMID:23781123

Relationship Between Soil Type and N2O Reductase Genotype (nosZ) of Indigenous Soybean Bradyrhizobia: nosZ-minus Populations are Dominant in Andosols

PubMed Central

Shiina, Yoko; Itakura, Manabu; Choi, Hyunseok; Saeki, Yuichi; Hayatsu, Masahito; Minamisawa, Kiwamu

2014-01-01

Bradyrhizobium japonicum strains that have the nosZ gene, which encodes N2O reductase, are able to mitigate N2O emissions from soils (15). To examine the distribution of nosZ genotypes among Japanese indigenous soybean bradyrhizobia, we isolated bradyrhizobia from the root nodules of soybean plants inoculated with 32 different soils and analyzed their nosZ and nodC genotypes. The 1556 resultant isolates were classified into the nosZ+/nodC+ genotype (855 isolates) and nosZ−/nodC+ genotype (701 isolates). The 11 soil samples in which nosZ− isolates significantly dominated (P < 0.05; the χ2 test) were all Andosols (a volcanic ash soil prevalent in agricultural fields in Japan), whereas the 17 soil samples in which nosZ+ isolates significantly dominated were mainly alluvial soils (non-volcanic ash soils). This result was supported by a principal component analysis of environmental factors: the dominance of the nosZ− genotype was positively correlated with total N, total C, and the phosphate absorption coefficient in the soils, which are soil properties typical of Andosols. Internal transcribed spacer sequencing of representative isolates showed that the nosZ+ and nosZ− isolates of B. japonicum fell mainly into the USDA110 (BJ1) and USDA6 (BJ2) groups, respectively. These results demonstrated that the group lacking nosZ was dominant in Andosols, which can be a target soil type for an N2O mitigation strategy in soybean fields. We herein discussed how the nosZ genotypes of soybean bradyrhizobia depended on soil types in terms of N2O respiration selection and genomic determinants for soil adaptation. PMID:25476067

Relationship between soil type and N₂O reductase genotype (nosZ) of indigenous soybean bradyrhizobia: nosZ-minus populations are dominant in Andosols.

PubMed

Shiina, Yoko; Itakura, Manabu; Choi, Hyunseok; Saeki, Yuichi; Hayatsu, Masahito; Minamisawa, Kiwamu

2014-01-01

Bradyrhizobium japonicum strains that have the nosZ gene, which encodes N2O reductase, are able to mitigate N2O emissions from soils (15). To examine the distribution of nosZ genotypes among Japanese indigenous soybean bradyrhizobia, we isolated bradyrhizobia from the root nodules of soybean plants inoculated with 32 different soils and analyzed their nosZ and nodC genotypes. The 1556 resultant isolates were classified into the nosZ+/nodC+ genotype (855 isolates) and nosZ-/nodC+ genotype (701 isolates). The 11 soil samples in which nosZ- isolates significantly dominated (P < 0.05; the χ(2) test) were all Andosols (a volcanic ash soil prevalent in agricultural fields in Japan), whereas the 17 soil samples in which nosZ+ isolates significantly dominated were mainly alluvial soils (non-volcanic ash soils). This result was supported by a principal component analysis of environmental factors: the dominance of the nosZ- genotype was positively correlated with total N, total C, and the phosphate absorption coefficient in the soils, which are soil properties typical of Andosols. Internal transcribed spacer sequencing of representative isolates showed that the nosZ+ and nosZ- isolates of B. japonicum fell mainly into the USDA110 (BJ1) and USDA6 (BJ2) groups, respectively. These results demonstrated that the group lacking nosZ was dominant in Andosols, which can be a target soil type for an N2O mitigation strategy in soybean fields. We herein discussed how the nosZ genotypes of soybean bradyrhizobia depended on soil types in terms of N2O respiration selection and genomic determinants for soil adaptation.

Intraprotein electron transfer between the FMN and heme domains in endothelial nitric oxide synthase holoenzyme

PubMed Central

Feng, Changjian; Taiakina, Valentina; Ghosh, Dipak K.; Guillemette, J. Guy; Tollin, Gordon

2011-01-01

Intraprotein electron transfer (IET) from flavin mononucleotide (FMN) to heme is an essential step in nitric oxide (NO) synthesis by NO synthase (NOS). The IET kinetics in neuronal and inducible NOS (nNOS and iNOS) holoenzymes have been previously determined in our laboratories by laser flash photolysis [reviewed in: C.J. Feng, G. Tollin, Dalton Trans., (2009) 6692-6700]. Here we report the kinetics of the IET in a bovine endothelial NOS (eNOS) holoenzyme in the presence and absence of added calmodulin (CaM). The IET rate constant in the presence of CaM is estimated to be ~ 4.3 s-1. No IET was observed in the absence of CaM, indicating that CaM is the primary factor in controlling the FMN–heme IET in the eNOS enzyme. The IET rate constant value for the eNOS holoenzyme is approximately 10 times smaller than those obtained for the iNOS and CaM-bound nNOS holoenzymes. Possible mechanisms underlying the difference in IET kinetics among the NOS isoforms are discussed. Because the rate-limiting step in the IET process in these enzymes is the conformational change from input state to output state, a slower conformational change (than in the other isoforms) is most likely to cause the slower IET in eNOS. PMID:21864726

The ontogeny of nanos homologue expression in the oligochaete annelid Tubifex tubifex.

PubMed

Mohri, Ki-Ichi; Nakamoto, Ayaki; Shimizu, Takashi

2016-01-01

We have cloned and characterized the expression of a nanos homologue (designated Ttu-nos) from the oligochaete annelid Tubifex tubifex. Ttu-nos mRNA is distributed broadly throughout the early cleavage stages. Ttu-nos is expressed in most if not all of the early blastomeres, in which Ttu-nos RNA associates with pole plasms. Ttu-nos transcripts are concentrated to 2d and 4d cells. Shortly after 2d(111) (derived from 2d cell) divides into a bilateral pair of NOPQ proteloblasts, Ttu-nos RNA vanishes from the embryo, which is soon followed by the resumption of Ttu-nos expression in nascent primary blast cells produced by teloblasts. The resumption of Ttu-nos expression occurs only in a subset of teloblast lineages (viz., M, N and Q). After Ttu-nos expression is retained in the germ band for a while, it disappears in anterior-to-posterior progression. At the end of embryogenesis, there is no trace of Ttu-nos expression. Thereafter, growing juveniles do not show any sign of Ttu-nos expression, either. The first sign of Ttu-nos expression is detected in oocytes in the ovary of young adults (ca 40 days after hatching), and its expression continues in growing oocytes that undergo yolk deposition and maturation in the ovisac. Copyright © 2015 Elsevier B.V. All rights reserved.

The Impact of a Course on Nature of Science Pedagogical Views and Rationales. Comparing Preservice Teachers in Their First Versus Second Experience

NASA Astrophysics Data System (ADS)

Kruse, Jerrid W.; Easter, Jaclyn M.; Edgerly, Hallie S.; Seebach, Colin; Patel, Neal

2017-08-01

This study explored changes in preservice teachers' (PSTs) nature of science pedagogical (NOSP) views and nature of science (NOS) rationales using pre- and post-course written responses as well as interview data. Through systematic analysis, themes were generated and compared to the NOS literature. Comparisons between pre- and post-course data demonstrate improved and deepened NOS views, NOSP views that are more aligned with NOS literature, and a greater number of rationales for including NOS. All participants were enrolled in the "Inquiry and Natures of Science, Technology, and Engineering" (INSTE) course. However, six participants were enrolled in INSTE as their first course in which NOS and NOSP were addressed. The other six participants were enrolled in INSTE as their second course in which NOS and NOSP were addressed, with science methods as their first course in which NOS and NOSP were addressed. By comparing participants enrolled in INSTE as their first course to those enrolled in INSTE as their second course, we observed that NOS understanding seemed to develop in a first experience alongside some NOS rationales, but NOSP views lagged for participants in INSTE as their first course. Participants enrolled in INSTE as their second course developed more robust and literature-aligned NOSP views and more multifaceted NOS rationales. Therefore, this study bolsters arguments that teachers need to receive extended NOS and NOSP instruction.

Abundance of endothelial nitric oxide synthase in newborn intrapulmonary arteries.

PubMed Central

Hislop, A. A.; Springall, D. R.; Buttery, L. D.; Pollock, J. S.; Haworth, S. G.

1995-01-01

A monoclonal antibody to endothelial NOS (eNOS) was used to demonstrate the distribution and density of eNOS in the developing porcine lung. Lung tissue from large white pigs aged from less than 5 minutes to 3 months was immunostained and, using light microscopy, distribution of eNOS was assessed by a semiquantitative scoring system. At all ages eNOS was located on the endothelial cells of pulmonary and bronchial arteries and veins. Immunoreactivity for eNOS was greater in the larger, more proximal pulmonary arteries than at the periphery. In the lung of newborn pigs immunoreactivity for eNOS was present in arteries of all sizes but some showed no positive staining. At 2-3 days of age almost all arteries showed positive immunoreactivity. By 3 months of age the amount of eNOS had decreased and was less than that seen in the newborn. The highest level of eNOS was seen immediately after birth when the pulmonary arteries are dilating. eNOS may therefore play an important part in adaptation to extra-uterine life. Images Figure 3 Figure 1 Figure 2 PMID:7552590

Working with the nature of science in physics class: turning ‘ordinary’ classroom situations into nature of science learning situations

NASA Astrophysics Data System (ADS)

Hansson, Lena; Leden, Lotta

2016-09-01

In the science education research field there is a large body of literature on the ‘nature of science’ (NOS). NOS captures issues about what characterizes the research process as well as the scientific knowledge. Here we, in line with a broad body of literature, use a wide definition of NOS including also e.g. socio-cultural aspects. It is argued that NOS issues, for a number of reasons, should be included in the teaching of science/physics. Research shows that NOS should be taught explicitly. There are plenty of suggestions on specific and separate NOS activities, but the necessity of discussing NOS issues in connection to specific science/physics content and to laboratory work, is also highlighted. In this article we draw on this body of literature on NOS and science teaching, and discuss how classroom situations in secondary physics classes could be turned into NOS-learning situations. The discussed situations have been suggested by secondary teachers, during in-service teacher training, as situations from every-day physics teaching, from which NOS could be highlighted.

The Science Teachers and Their way of Thinking about Astronomy. (Spanish Title: Los Profesores de Ciencias y Sus Formas de Pensar la Astronomía.) Os Professores de Ciências e Suas Formas de Pensar a Astronomia

NASA Astrophysics Data System (ADS)

Leite, Cristina; Hosoume, Yassuko

2007-12-01

The research presented in this article is about the way science teachers from Elementary School think about astronomical elements. Its methodology is based on semi-structured interviews, which were video recorded. The research is centered in a three-dimensional perspective of astronomical Earth, the Sun, the Moon, the planets and the stars, and also the conceptions about sky and Universe. The esults indicate a Universe that contains: Sun, stars, planets and Moon; where the Solar System is a little part of the whole. Sometimes they think that the Solar System is the Universe. The objects are in the sky or in the Universe, which, for many of them, is only the space above the Earth. The flat shape of astronomical objects and the spatial structure of the Universe are striking features. Many of them think that Sun and stars are different: the Sun is a hot object and the stars are cold ones. These results worry us and they certainly indicate how urgent it is to plan Professional Development in Astronomy for teachers, after all the PCN's emphasize that this subject is important to be taught. El objeto de investigación de este artículo es la manera de pensar sobre los elementos de la Astronomía de los profesores de Ciencias en la enseñanza fundamental. La metodología consiste en entrevistas semi-estructuradas, filmadas en video y centradas en la tridimensionalidad de los elementos astronómicos, para posibilitar un mapeamiento de las concepciones sobre las formas y dimensiones de la Tierra, del Sol, de la Luna, de los planetas y de las estrellas, como también de la concepción de cielo y de Universo en su totalidad. Los resultados indican un Universo conteniendo: Sol, estrellas, planetas y Luna, donde el Sistema Solar se ubica como parte. Algunas veces, el Universo es concebido como el propio Sistema Solar. Los objetos están en el cielo o en el Universo, que, para muchos, se restringe al espacio que está arriba de la Tierra. La forma plana de los objetos astronómicos y la estructura espacial del montaje del Universo son características fundamentales. Muchos indican Sol y estrellas como cosas distintas: el Sol es un objeto caliente y las estrellas son frías. Esos resultados nos preocupan y ciertamente señalan una urgencia de programas de formación continuada para profesores en el contenido de astronomía, pues los PCN's (Parámetros Curriculares Nacionales) recomiendan con énfasis la enseñanza de este contenido. O modo de pensar dos professores de Ciências do ensino fundamental sobre os elementos da Astronomia é o objeto de pesquisa presente neste artigo, cuja metodologia consiste em entrevistas semiestruturadas, filmadas em vídeo e centradas numa perspectiva tridimensional dos elementos astronômicos, possibilitando um mapeamento das concepções das formas e das dimensões da Terra, do Sol, da Lua, dos planetas e das estrelas, bem como da concepção de céu e de Universo como um todo. Os resultados indicam um Universo contendo: Sol, estrelas, planetas e Lua, onde o Sistema Solar é parte do todo. Algumas vezes o Universo é concebido como o próprio Sistema Solar. Os objetos estão no céu ou no Universo o qual, para muitos, se restringe ao espaço que está acima da Terra. A forma plana dos objetos astronômicos e a estrutura espacial da montagem do Universo são características marcantes. Muitos indicam Sol e estrelas como coisas diferentes: Sol é um objeto quente e as estrelas são frias. Esses resultados nos preocupam e certamente sinalizam uma urgência de programas de formação continuada para professores no conteúdo de astronomia, uma vez que os PCN's indicam fortemente o ensino desse conteúdo.

RELATIONSHIP BETWEEN ESOPHAGITIS GRADES AND HELICOBACTER PYLORI.

PubMed

Ribeiro, Patrícia Fernanda Saboya; Kubrusly, Luiz Fernandao; Nassif, Paulo Afonso Nunes; Ribeiro, Irma Cláudia Saboya; Bertoldi, Andressa de Souza; Batistão, Venessa Caroline

2016-01-01

The Helicobacter pylori infection (HP) is related to the development of gastric lesions and lymphoma; however, it is not known if there is a relation with gastroesophageal reflux disease and reflux esophagitis. To evaluate HP's relationship with esophagitis in patients undergoing upper endoscopy. Observational, retrospective and cross-sectional study, being evaluated 9576 patients undergoing outpatient endoscopic examination during the period between January and December 2015. Were included patients with any esophageal alteration at the examination; greater than 18; of both genders; independent of the complaint or the reason for the examination, illness or drug use. Were excluded those with active bleeding during the examination and in use of anticoagulants. The variables gender, age, esophagitis and result of the urease test, were studied. For statistical analysis was used the Epi Info software 7.1.5.2. Most of the samples consisted of women and the overall average age was 46.54±16.32 years. The presence of infection was balanced for gender: 1204 (12.56%) women and 952 (13.92%) men. Relating degree of esophagitis HP- and HP+ was observed that the type A was the most common (58.79%, n=1460); 604 (24.32%) had grade B; 334 (13.45%) grade C, and 85 (3.42%) grade D. In the relation between the grade of esophagitis with gender, esophagitis A was predominant in women and present in 929 (63.33%), followed by type B, 282 (46.68%), 136 C (40.71%) and D 30 (35.29%). In men 531 (36.36%) showed type A, 322 (53.31%) B, 198 (59.28%) C, and 55 (64.70%) D. Among the groups 40-50 and over 60 years there was a significant difference in whether have or not have HP+. There is no significant difference between HP infection and the different grades of esophagitis. A infecção pelo Helicobacter pylori (HP) é relacionada com o desenvolvimento de lesões e linfoma gástricos; porém, ainda não se sabe ao certo se há relação dele com a doença do refluxo gastroesofágico e esofagite de refluxo. Avaliar a relação do HP com as esofagites em pacientes submetidos à endoscopia digestiva alta. Estudo observacional, retrospectivo e transversal, sendo avaliados 9576 pacientes submetidos ao exame endoscópico ambulatorial durante o período compreendido entre janeiro e dezembro de 2015. Foram incluídos pacientes que apresentaram alguma alteração esofágica ao exame; maiores que 18 anos; de ambos os gêneros; independente da queixa ou da razão para a realização do exame, doença ou uso de medicamentos. Excluíram-se os com sangramento ativo durante o exame e em uso de anticoagulantes. Foram avaliadas as variáveis gênero, idade, esofagite e resultado do teste da urease. Para a análise estatística utilizou-se o software Epi Info 7.1.5.2. A maioria das amostras foi composta por mulheres e a idade média geral foi de 46,54±16,32 anos. A presença da infecção foi equilibrada para a variável gênero: 1204 (12,56%) mulheres e 952 (13,92%) homens. Relacionando os graus da esofagite com HP+ e HP- observou-se que o tipo A foi o mais comum (58,79% da amostra, n=1460), que 604 (24,32%) possuíam o grau B; 334 (13,45%) o grau C e 85 (3,42%) o grau D. Já na relação entre os graus de esofagite com o gênero, a esofagite A foi predominante nas mulheres e presente em 929 (63,33%), seguido pelo tipo B, com 282 (46,68%), C com 136 (40,71%) e D com 30 (35,29%) mulheres. Nos homens 531 (36,36%) apresentam o tipo A, 322 (53,31%) o B, 198 (59,28%) o C e 55 (64,70%) o D. Entre os grupos de 40 a 50 anos e acima de 60 anos houve diferença significativa em ter ou não HP+. Não há diferença significativa entre infecção por HP nos diferentes graus de esofagite.

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

PubMed

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

2017-02-01

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

Gene Therapy With Inducible Nitric Oxide Synthase Protects Against Myocardial Infarction via a Cyclooxygenase-2—Dependent Mechanism

PubMed Central

Li, Qianhong; Guo, Yiru; Xuan, Yu-Ting; Lowenstein, Charles J.; Stevenson, Susan C.; Prabhu, Sumanth D.; Wu, Wen-Jian; Zhu, Yanqing; Bolli, Roberto

2013-01-01

Although the inducible isoform of NO synthase (iNOS) mediates late preconditioning (PC), it is unknown whether iNOS gene transfer can replicate the cardioprotective effects of late PC, and the role of this protein in myocardial ischemia is controversial. Thus, the cDNA for human iNOS was cloned behind the Rous sarcoma virus (RSV) promoter to create adenovirus (Ad) 5/iNOS lacking E1, E2a, and E3 regions. Intramyocardial injection of Ad5/iNOS in mice increased local iNOS protein expression and activity and markedly reduced infarct size. The infarct-sparing effects of Ad5/iNOS were at least as powerful as those of ischemic PC. The increased iNOS expression was associated with increased cyclooxygenase-2 (COX-2) protein expression and prostanoid levels. Pretreatment with the COX-2–selective inhibitor NS-398 completely abrogated the infarct-sparing actions of Ad5/iNOS, demonstrating that COX-2 is an obligatory downstream effector of iNOS-dependent cardioprotection. We conclude that gene transfer of iNOS (an enzyme commonly thought to be detrimental) affords powerful cardioprotection the magnitude of which is equivalent to that of late PC. This is the first report that upregulation of iNOS, in itself, is sufficient to reduce infarct size. The results provide proof-of-principle for gene therapy against ischemia/reperfusion injury, which increases local myocardial NO synthase levels without the need for continuous intravenous infusion of NO donors and without altering systemic hemodynamics. The data also reveal the existence of a close coupling between iNOS and COX-2, whereby induction of the former enzyme leads to secondary induction of the latter, which in turn mediates the cytoprotective effects of iNOS. We propose that iNOS and COX-2 form a stress-responsive functional module that mitigates ischemia/reperfusion injury. PMID:12702642

The protein inhibitor of nNOS (PIN/DLC1/LC8) binding does not inhibit the NADPH-dependent heme reduction in nNOS, a key step in NO synthesis

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

Parhad, Swapnil S.; Jaiswal, Deepa; TIFR Centre for Interdisciplinary Sciences, 21 Brundavan Colony, Narsingi, Hyderabad 500075

The neuronal nitric oxide synthase (nNOS) is an essential enzyme involved in the synthesis of nitric oxide (NO), a potent neurotransmitter. Although previous studies have indicated that the dynein light chain 1 (DLC1) binding to nNOS could inhibit the NO synthesis, the claim is challenged by contradicting reports. Thus, the mechanism of nNOS regulation remained unclear. nNOS has a heme-bearing, Cytochrome P450 core, and the functional enzyme is a dimer. The electron flow from NADPH to Flavin, and finally to the heme of the paired nNOS subunit within a dimer, is facilitated upon calmodulin (CaM) binding. Here, we show thatmore » DLC1 binding to nNOS-CaM complex does not affect the electron transport from the reductase to the oxygenase domain. Therefore, it cannot inhibit the rate of NADPH-dependent heme reduction in nNOS, which results in L-Arginine oxidation. Also, the NO release activity does not decrease with increasing DLC1 concentration in the reaction mix, which further confirmed that DLC1 does not inhibit nNOS activity. These findings suggest that the DLC1 binding may have other implications for the nNOS function in the cell. - Highlights: • The effect of interaction of nNOS with DLC1 has been debatable with contradicting reports in literature. • Purified DLC1 has no effect on electron transport between reductase and oxygenase domain of purified nNOS-CaM. • The NO release activity of nNOS was not altered by DLC1, supporting that DLC1 does not inhibit the enzyme. • These findings suggest that the DLC1 binding may have other implications for the nNOS function in the cell.« less

Constitutive NOS uncoupling and NADPH oxidase upregulation in the penis of type 2 diabetic men with erectile dysfunction

PubMed Central

Musicki, Biljana; Burnett, Arthur L.

2016-01-01

Erectile dysfunction (ED) associated with type 2 diabetes mellitus (T2DM) involves dysfunctional nitric oxide (NO) signaling and increased oxidative stress in the penis. However, the mechanisms of endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) dysregulation, and the sources of oxidative stress, are not well defined, particularly at the human level. The objective of this study was to define whether uncoupled eNOS and nNOS, and NADPH oxidase upregulation, contribute to the pathogenesis of ED in T2DM men. Penile erectile tissue was obtained from 9 T2DM patients with ED who underwent penile prosthesis surgery for ED, and from 6 control patients without T2DM or ED who underwent penectomy for penile cancer. The dimer-to-monomer protein expression ratio, an indicator of uncoupling for both eNOS and nNOS, total protein expressions of eNOS and nNOS, as well as protein expressions of NADPH oxidase catalytic subunit gp91phox (an enzymatic source of oxidative stress) and 4-hydroxy-2-nonenal [4-HNE] and nitrotyrosine (markers of oxidative stress) were measured by Western blot in this tissue. In the erectile tissue of T2DM men, eNOS and nNOS uncoupling and protein expressions of NADPH oxidase subunit gp91phox, 4-HNE- and nitrotyrosine-modified proteins were significantly (p<0.05) increased compared to control values. Total eNOS and nNOS protein expressions were not significantly different between the groups. In conclusion, mechanisms of T2DM-associated ED in the human penis may involve uncoupled eNOS and nNOS and NADPH oxidase upregulation. Our description of molecular factors contributing to the pathogenesis of T2DM-associated ED at the human level is relevant for advancing clinically therapeutic approaches to restore erectile function in T2DM patients. PMID:28076881

Low shear stress induces vascular eNOS uncoupling via autophagy-mediated eNOS phosphorylation.

PubMed

Zhang, Jun-Xia; Qu, Xin-Liang; Chu, Peng; Xie, Du-Jiang; Zhu, Lin-Lin; Chao, Yue-Lin; Li, Li; Zhang, Jun-Jie; Chen, Shao-Liang

2018-05-01

Uncoupled endothelial nitric oxide synthase (eNOS) produces O 2 - instead of nitric oxide (NO). Earlier, we reported rapamycin, an autophagy inducer and inhibitor of cellular proliferation, attenuated low shear stress (SS) induced O 2 - production. Nevertheless, it is unclear whether autophagy plays a critical role in the regulation of eNOS uncoupling. Therefore, this study aimed to investigate the modulation of autophagy on eNOS uncoupling induced by low SS exposure. We found that low SS induced endothelial O 2 - burst, which was accompanied by reduced NO release. Furthermore, inhibition of eNOS by L-NAME conspicuously attenuated low SS-induced O 2 - releasing, indicating eNOS uncoupling. Autophagy markers such as LC3 II/I ratio, amount of Beclin1, as well as ULK1/Atg1 were increased during low SS exposure, whereas autophagic degradation of p62/SQSTM1 was markedly reduced, implying impaired autophagic flux. Interestingly, low SS-induced NO reduction could be reversed by rapamycin, WYE-354 or ATG5 overexpression vector via restoration of autophagic flux, but not by N-acetylcysteine or apocynin. eNOS uncoupling might be ascribed to autophagic flux blockade because phosphorylation of eNOS Thr495 by low SS or PMA stimulation was also regulated by autophagy. In contrast, eNOS acetylation was not found to be regulated by low SS and autophagy. Notably, although low SS had no influence on eNOS Ser1177 phosphorylation, whereas boosted eNOS Ser1177 phosphorylation by rapamycin were in favor of the eNOS recoupling through restoration of autophagic flux. Taken together, we reported a novel mechanism for regulation of eNOS uncoupling by low SS via autophagy-mediated eNOS phosphorylation, which is implicated in geometrical nature of atherogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

A study of elementary teachers' conceptions of nature of science and their beliefs about the developmental appropriateness and importance of nature of science throughout a professional development program

NASA Astrophysics Data System (ADS)

Adibelli, Elif

This qualitative study aimed to explore the changes in elementary science teachers' conceptions of nature of science (NOS) and their beliefs about the developmental appropriateness and importance of NOS after participating in an academic, year-long professional development program (PDP) as well as the factors facilitating these changes. The PDP consisted of two phases. In the first phase, the participants received NOS training designed with an explicit-reflective instructional approach. In the second phase, the participants implemented several NOS training activities in their classrooms. Four elementary science teachers who volunteered and completed all components of the PDP (i.e., the NOS training and the NOS teaching) comprised the participants of the present study. A multiple-embedded case study design was employed to explore the changes in the elementary science teachers' conceptions of NOS and their beliefs about the developmental appropriateness and importance of NOS. The study data were collected from multiple sources. The primary data sources included (a) Views of Nature of Science Elementary School Version 2 (VNOS-D2) questionnaire (Lederman & Khishfe, 2002), (b) Ideas about Science for Early Elementary (K-4) Students questionnaire (Sweeney, 2010), and (c) follow-up semi-structured interviews. The secondary data sources included videotaping of meetings with teachers, reflective field notes, and artifacts produced by teachers and their students. Data were analyzed using Yin's (1994, 2003) analytic tactics of pattern matching, explanation building, and cross-case synthesis. The findings of the study revealed that the elementary science teachers showed gradual, but substantial changes in their conceptions, and beliefs about the developmental appropriateness and importance of the NOS aspects over the course of participation in the PDP. Moreover, the participants identified nine components in the PDP that facilitated these changes in their conceptions, and beliefs about the developmental appropriateness and importance of the NOS aspects. These components were (a) specific focus on the NOS content, (b) participation in hands-on activities on NOS, (c) educational readings on NOS, (d) multiple types/ formats of reflection, (e) multiple exposure to the NOS content, (f) structural consistency in the presentation of the NOS content, (g) the evaluation of secondary student data, (h) the analysis of national and state science standards in terms of NOS, and (i) the implementation of the NOS activities in the classroom. Based on the findings of this study, it may be concluded that explicit-reflective NOS instruction coupled with NOS teaching is sufficient to evolve and crystallize teachers' conceptions and beliefs about the developmental appropriateness and importance of the NOS aspects.

Nitric Oxide Synthase-3 Promotes Embryonic Development of Atrioventricular Valves

PubMed Central

Liu, Yin; Lu, Xiangru; Xiang, Fu-Li; Lu, Man; Feng, Qingping

2013-01-01

Nitric oxide synthase-3 (NOS3) has recently been shown to promote endothelial-to-mesenchymal transition (EndMT) in the developing atrioventricular (AV) canal. The present study was aimed to investigate the role of NOS3 in embryonic development of AV valves. We hypothesized that NOS3 promotes embryonic development of AV valves via EndMT. To test this hypothesis, morphological and functional analysis of AV valves were performed in wild-type (WT) and NOS3−/− mice at postnatal day 0. Our data show that the overall size and length of mitral and tricuspid valves were decreased in NOS3−/− compared with WT mice. Echocardiographic assessment showed significant regurgitation of mitral and tricuspid valves during systole in NOS3−/− mice. These phenotypes were all rescued by cardiac specific NOS3 overexpression. To assess EndMT, immunostaining of Snail1 was performed in the embryonic heart. Both total mesenchymal and Snail1+ cells in the AV cushion were decreased in NOS3−/− compared with WT mice at E10.5 and E12.5, which was completely restored by cardiac specific NOS3 overexpression. In cultured embryonic hearts, NOS3 promoted transforming growth factor (TGFβ), bone morphogenetic protein (BMP2) and Snail1expression through cGMP. Furthermore, mesenchymal cell formation and migration from cultured AV cushion explants were decreased in the NOS3−/− compared with WT mice. We conclude that NOS3 promotes AV valve formation during embryonic heart development and deficiency in NOS3 results in AV valve insufficiency. PMID:24204893

Circulating Blood eNOS Contributes to the Regulation of Systemic Blood Pressure and Nitrite Homeostasis

PubMed Central

Wood, Katherine C.; Cortese-Krott, Miriam M.; Kovacic, Jason C.; Noguchi, Audrey; Liu, Virginia B.; Wang, Xunde; Raghavachari, Nalini; Boehm, Manfred; Kato, Gregory J.; Kelm, Malte; Gladwin, Mark T.

2013-01-01

Objective Mice genetically deficient in endothelial nitric oxide synthase (eNOS−/−) are hypertensive with lower circulating nitrite levels, indicating the importance of constitutively produced nitric oxide (NO•) to blood pressure regulation and vascular homeostasis. While the current paradigm holds that this bioactivity derives specifically from expression of eNOS in endothelium, circulating blood cells also express eNOS protein. A functional red cell eNOS that modulates vascular NO• signaling has been proposed. Approach and Results To test the hypothesis that blood cells contribute to mammalian blood pressure regulation via eNOS-dependent NO• generation, we cross-transplanted WT and eNOS−/− mice, producing chimeras competent or deficient for eNOS expression in circulating blood cells. Surprisingly, we observed a significant contribution of both endothelial and circulating blood cell eNOS to blood pressure and systemic nitrite levels, the latter being a major component of the circulating NO• reservoir. These effects were abolished by the NOS inhibitor L-NAME and repristinated by the NOS substrate L-Arginine, and were independent of platelet or leukocyte depletion. Mouse erythrocytes were also found to carry an eNOS protein and convert 14C-Arginine into 14C-Citrulline in a NOS-dependent fashion. Conclusions These are the first studies to definitively establish a role for a blood borne eNOS, using cross transplant chimera models, that contributes to the regulation of blood pressure and nitrite homeostasis. This work provides evidence suggesting that erythrocyte eNOS may mediate this effect. PMID:23702660

Cardiovascular responses and neurotransmitter changes during static muscle contraction following blockade of inducible nitric oxide synthase (iNOS) within the ventrolateral medulla.

PubMed

Ally, Ahmmed; Phattanarudee, Siripan; Kabadi, Shruti; Patel, Maitreyee; Maher, Timothy J

2006-05-23

The enzyme nitric oxide synthase (NOS) which is necessary for the production of nitric oxide from L-arginine exists in three isoforms: neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS). Our previous studies have demonstrated the roles of nNOS and eNOS within the rostral (RVLM) and caudal ventrolateral medulla (CVLM) in modulating cardiovascular responses during static skeletal muscle contraction via altering localized glutamate and GABA levels (Brain Res. 977 (2003) 80-89; Neuroscience Res. 52 (2005) 21-30). In this study, we investigated the role of iNOS within the RVLM and CVLM on cardiovascular responses and glutamatergic/GABAergic neurotransmission during the exercise pressor reflex. Bilateral microdialysis of a selective iNOS antagonist, aminoguanidine (AGN; 1.0 microM), for 60 min into the RVLM attenuated increases in mean arterial pressure (MAP), heart rate (HR), and extracellular glutamate levels during a static muscle contraction. Levels of GABA within the RVLM were increased. After 120 min of discontinuation of the drug, MAP and HR responses and glutamate/GABA concentrations recovered to baseline values during a subsequent muscle contraction. In contrast, bilateral application of AGN (1.0 microM) into CVLM potentiated cardiovascular responses and glutamate concentration while attenuating levels of GABA during a static muscle contraction. All values recovered after 120 min of discontinuation of the drug. These results demonstrate that iNOS within the ventrolateral medulla plays an important role in modulating cardiovascular responses and glutamatergic/GABAergic neurotransmission that regulates the exercise pressor reflex.

Participation of hippocampal nitric oxide synthase and soluble guanylate cyclase in the modulation of behavioral responses elicited by the rat forced swimming test.

PubMed

Sales, Amanda J; Hiroaki-Sato, Vinícius A; Joca, Sâmia R L

2017-02-01

Systemic or hippocampal administration of nitric oxide (NO) synthase inhibitors induces antidepressant-like effects in animals, implicating increased hippocampal levels of NO in the neurobiology of depression. However, the role played by different NO synthase in this process has not been clearly defined. As stress is able to induce neuroinflammatory mechanisms and trigger the expression of inducible nitric oxide synthase (iNOS) in the brain, as well as upregulate neuronal nitric oxide synthase (nNOS) activity, the aim of the present study was to investigate the possible differential contribution of hippocampal iNOS and nNOS in the modulation of the consequences of stress elicited by the forced swimming test. Male Wistar rats received intrahippocampal injections, immediately after the pretest or 1 h before the forced swimming test, of selective inhibitors of nNOS (N-propyl-L-arginine), iNOS (1400W), or sGC (ODQ), the main pharmacological target for NO. Stress exposure increased nNOS and phospho-nNOS levels at all time points, whereas iNOS expression was increased only 24 h after the pretest. All drugs induced an antidepressant-like effect. However, whereas the nNOS inhibitor was equally effective when injected at different times, the iNOS inhibitor was more effective 24 h after the pretest. These results suggest that hippocampal nNOS and iNOS contribute to increase in NO levels in response to stress, although with a differential time course after stress exposure.

Understanding of the life experience of homeless women.

PubMed

Biscotto, Priscilla Ribeiro; Jesus, Maria Cristina Pinto de; Silva, Marcelo Henrique da; Oliveira, Deíse Moura de; Merighi, Miriam Aparecida Barbosa

2016-01-01

To understand the life experience of homeless women. A social phenomenological study was conducted with 10 women assisted by a shelter. The analysis of the interviews was based on the theoretical framework of social phenomenology of Alfred Schütz and thematic literature. The participants face adversities in the street context, with emphasis on the risk of physical and sexual abuse, and seek shelters as a possibility for minimizing difficulties experienced. They hope to leave the streets; however, they see themselves trapped in this social reality, due to the addiction to alcohol and other drugs. The understanding of the life experience of homeless women shows daily confrontations and reveals the conflict between the desire for leaving and remaining on the streets, given the complexity of the reality that keeps them in this condition. Compreender a vivência de mulheres em situação de rua. Pesquisa fenomenológica social realizada com 10 mulheres assistidas por um albergue. A análise das entrevistas ancorou-se no referencial teórico da fenomenologia social de Alfred Schütz e literatura temática. As participantes enfrentam adversidades no contexto da rua, com destaque para o risco de violência física e sexual, e buscam o albergue como possibilidade de minimizar as dificuldades vivenciadas. Elas têm como expectativa sair da rua, porém se veem presas a esta realidade social em virtude do vício em álcool e outras drogas. A compreensão da vivência de mulheres em situação de rua aponta enfrentamentos cotidianos e revela o conflito entre o desejo de sair e permanecer na rua, dada a complexidade da realidade que as mantém nesta condição.

Caveolin-1 down-regulates inducible nitric oxide synthase via the proteasome pathway in human colon carcinoma cells

PubMed Central

Felley-Bosco, Emanuela; Bender, Florent C.; Courjault-Gautier, Françoise; Bron, Claude; Quest, Andrew F. G.

2000-01-01

To investigate whether caveolin-1 (cav-1) may modulate inducible nitric oxide synthase (iNOS) function in intact cells, the human intestinal carcinoma cell lines HT29 and DLD1 that have low endogenous cav-1 levels were transfected with cav-1 cDNA. In nontransfected cells, iNOS mRNA and protein levels were increased by the addition of a mix of cytokines. Ectopic expression of cav-1 in both cell lines correlated with significantly decreased iNOS activity and protein levels. This effect was linked to a posttranscriptional mechanism involving enhanced iNOS protein degradation by the proteasome pathway, because (i) induction of iNOS mRNA by cytokines was not affected and (ii) iNOS protein levels increased in the presence of the proteasome inhibitors N-acetyl-Leu-Leu-Norleucinal and lactacystin. In addition, a small amount of iNOS was found to cofractionate with cav-1 in Triton X-100-insoluble membrane fractions where also iNOS degradation was apparent. As has been described for endothelial and neuronal NOS isoenzymes, direct binding between cav-1 and human iNOS was detected in vitro. Taken together, these results suggest that cav-1 promotes iNOS presence in detergent-insoluble membrane fractions and degradation there via the proteasome pathway. PMID:11114180

Intracerebroventricular injection of neuronal and inducible nitric oxide synthase inhibitors does not influence febrile response in rats during turpentine abscess.

PubMed

Soszynski, D; Chelminiak, M

2007-12-01

The purpose of this study was to investigate the role of neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS) in the brain during development of fever in response to localized tissue inflammation caused by injection of turpentine in freely moving biotelemetered rats. To determine the role of both NOSs in turpentineinduced fever, we injected vinyl-L-NIO (N(5) - (1-Imino-3-butenyl) - ornithine (vLNIO), a selective nNOS inhibitor, and aminoguanidine hydrochloride, a selective iNOS inhibitor, intracerebroventricularly (i.c.v.) 5 h after turpentine injection. Rats responded with fever to intramuscular injection of 20 mul of turpentine that commenced about 5 - 6 h after injection and reached peak value between 9 - 11 h post-turpentine. The inhibition of nNOS as well as iNOS in the brain did not affect fever induced by turpentine. Fevers in control rats (treated i.c.v. with pyrogen-free water) and iNOS or nNOS inhibitor-i.c.v. treated rats injected with turpentine were essentially the same. Furthermore, on the basis of these data, we concluded that iNOS and nNOS inside the brain do not participate in generation of fever to turpentine in rats.

Zinc regulates iNOS-derived nitric oxide formation in endothelial cells.

PubMed

Cortese-Krott, Miriam M; Kulakov, Larissa; Opländer, Christian; Kolb-Bachofen, Victoria; Kröncke, Klaus-D; Suschek, Christoph V

2014-01-01

Aberrant production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathogenesis of endothelial dysfunction and vascular disease. Mechanisms responsible for the fine-tuning of iNOS activity in inflammation are still not fully understood. Zinc is an important structural element of NOS enzymes and is known to inhibit its catalytical activity. In this study we aimed to investigate the effects of zinc on iNOS activity and expression in endothelial cells. We found that zinc down-regulated the expression of iNOS (mRNA+protein) and decreased cytokine-mediated activation of the iNOS promoter. Zinc-mediated regulation of iNOS expression was due to inhibition of NF-κB transactivation activity, as determined by a decrease in both NF-κB-driven luciferase reporter activity and expression of NF-κB target genes, including cyclooxygenase 2 and IL-1β. However, zinc did not affect NF-κB translocation into the nucleus, as assessed by Western blot analysis of nuclear and cytoplasmic fractions. Taken together our results demonstrate that zinc limits iNOS-derived high output NO production in endothelial cells by inhibiting NF-κB-dependent iNOS expression, pointing to a role of zinc as a regulator of iNOS activity in inflammation.

Removal of a putative inhibitory element reduces the calcium-dependent calmodulin activation of neuronal nitric-oxide synthase.

PubMed

Montgomery, H J; Romanov, V; Guillemette, J G

2000-02-18

Neuronal nitric-oxide synthase (NOS) and endothelial NOS are constitutive NOS isoforms that are activated by binding calmodulin in response to elevated intracellular calcium. In contrast, the inducible NOS isoform binds calmodulin at low basal levels of calcium in resting cells. Primary sequence comparisons show that each constitutive NOS isozyme contains a polypeptide segment within its reductase domain, which is absent in the inducible NOS enzyme. To study a possible link between the presence of these additional polypeptide segments in constitutive NOS enzymes and their calcium-dependent calmodulin activation, three deletion mutants were created. The putative inhibitory insert was removed from the FMN binding regions of the neuronal NOS holoenzyme and from two truncated neuronal NOS reductase enzymes in which the calmodulin binding region was either included or deleted. All three mutant enzymes showed reduced incorporation of FMN and required reconstitution with exogenous FMN for activity. The combined removal of both the calmodulin binding domain and the putative inhibitory insert did not result in a calmodulin-independent neuronal NOS reductase. Thus, although the putative inhibitory element has an effect on the calcium-dependent calmodulin activation of neuronal NOS, it does not have the properties of the typical autoinhibitory domain found in calmodulin-activated enzymes.

iNOS Activity Modulates Inflammation, Angiogenesis, and Tissue Fibrosis in Polyether-Polyurethane Synthetic Implants.

PubMed

Cassini-Vieira, Puebla; Araújo, Fernanda Assis; da Costa Dias, Filipi Leles; Russo, Remo Castro; Andrade, Silvia Passos; Teixeira, Mauro Martins; Barcelos, Luciola Silva

2015-01-01

There is considerable interest in implantation techniques and scaffolds for tissue engineering and, for safety and biocompatibility reasons, inflammation, angiogenesis, and fibrosis need to be determined. The contribution of inducible nitric oxide synthase (iNOS) in the regulation of the foreign body reaction induced by subcutaneous implantation of a synthetic matrix was never investigated. Here, we examined the role of iNOS in angiogenesis, inflammation, and collagen deposition induced by polyether-polyurethane synthetic implants, using mice with targeted disruption of the iNOS gene (iNOS(-/-)) and wild-type (WT) mice. The hemoglobin content and number of vessels were decreased in the implants of iNOS(-/-) mice compared to WT mice 14 days after implantation. VEGF levels were also reduced in the implants of iNOS(-/-) mice. In contrast, the iNOS(-/-) implants exhibited an increased neutrophil and macrophage infiltration. However, no alterations were observed in levels of CXCL1 and CCL2, chemokines related to neutrophil and macrophage migration, respectively. Furthermore, the implants of iNOS(-/-) mice showed boosted collagen deposition. These data suggest that iNOS activity controls inflammation, angiogenesis, and fibrogenesis in polyether-polyurethane synthetic implants and that lack of iNOS expression increases foreign body reaction to implants in mice.

Heterogeneous distribution of type I nitric oxide synthase in pulmonary vasculature of ovine fetus.

PubMed

Tzao, C; Nickerson, P A; Russell, J A; Noble, B K; Steinhorn, R H

2000-11-01

The nitric oxide/guanosine 3',5'-cyclic monophosphate pathway plays an essential role in mediating pulmonary vasodilation at birth. Small resistance arteries in the fetal lung are vessels of major significance in the regulation of pulmonary vascular tone. The present study is to determine that type I nitric oxide synthase (NOS-I) is present in ovine fetal pulmonary vasculature and that NOS-I is distributed heterogeneously in ovine fetal pulmonary circulation. We used reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry and NOS-I immunohistochemistry to localize NOS-I in fetal sheep lungs and showed a colocalization for NADPH-d activity with NOS-I immunoreactivity. Strong NOS-I immunoreactivity was observed exclusively in the endothelium of the terminal bronchiole and respiratory bronchiole-associated arteries. As a comparison, adult sheep lung did not show positive immunoreactivity in the pulmonary endothelium. NOS-I was absent in the umbilical or systemic arteries from the ovine fetus, whereas abundant NOS-III immunoreactivity was present in these arteries. We conclude that NOS-I is present uniquely in the ovine fetal pulmonary circulation as opposed to the adult pulmonary or the fetal systemic circulation. NOS-I is distributed heterogeneously in the ovine pulmonary vasculature. We speculate that NOS-I plays an active role in the regulation of perinatal pulmonary circulation.

Zinc regulates iNOS-derived nitric oxide formation in endothelial cells

PubMed Central

Cortese-Krott, Miriam M.; Kulakov, Larissa; Opländer, Christian; Kolb-Bachofen, Victoria; Kröncke, Klaus-D.; Suschek, Christoph V.

2014-01-01

Aberrant production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathogenesis of endothelial dysfunction and vascular disease. Mechanisms responsible for the fine-tuning of iNOS activity in inflammation are still not fully understood. Zinc is an important structural element of NOS enzymes and is known to inhibit its catalytical activity. In this study we aimed to investigate the effects of zinc on iNOS activity and expression in endothelial cells. We found that zinc down-regulated the expression of iNOS (mRNA+protein) and decreased cytokine-mediated activation of the iNOS promoter. Zinc-mediated regulation of iNOS expression was due to inhibition of NF-κB transactivation activity, as determined by a decrease in both NF-κB-driven luciferase reporter activity and expression of NF-κB target genes, including cyclooxygenase 2 and IL-1β. However, zinc did not affect NF-κB translocation into the nucleus, as assessed by Western blot analysis of nuclear and cytoplasmic fractions. Taken together our results demonstrate that zinc limits iNOS-derived high output NO production in endothelial cells by inhibiting NF-κB-dependent iNOS expression, pointing to a role of zinc as a regulator of iNOS activity in inflammation. PMID:25180171

[Expression and antagonist role of endothelin and nitric oxide synthase in atherosclerotic plaque].

PubMed

Song, L; Wang, D; Wang, T

1997-02-01

To study the pathogenetic mechanism of atherosclerotic plaque, the action of mediation and antagonism of endothelin (ET) and nitric oxide synthase (NOS) was investigated. In situ hybridization, RT-PCR on endothelin and NOS, cytochemistry on NOS were measured using the rabbit atherosclerosis model and cultured vascular smooth muscle cells (VSMC) from normal rabbit. Transcription of endothelin mRNA increased and transcription of NOS mRNA decreased in astherosclerotic plaque: compared with normal aorta, expression of ET gene in plaque was increased by 1.2 times and the expression of NOS gene was decreased by 22.2%; cytochemistry combined with image pattern analysis showed that ET could inhibit NOS protien synthesis in VSMC; type A receptor antagonist of ET could inhibit the role of ET which causes a decrease of NOS protein in VSMC. The imbalance between NOS and ET, namely abnormal increase of ET and/or obvious decrease of NOS, is related to atherosclerotic plaque formation.

Neuronal NOS localises to human airway cilia.

PubMed

Jackson, Claire L; Lucas, Jane S; Walker, Woolf T; Owen, Holly; Premadeva, Irnthu; Lackie, Peter M

2015-01-30

Airway NO synthase (NOS) isoenzymes are responsible for rapid and localised nitric oxide (NO) production and are expressed in airway epithelium. We sought to determine the localisation of neuronal NOS (nNOS) in airway epithelium due to the paucity of evidence. Sections of healthy human bronchial tissue in glycol methacrylate resin and human nasal polyps in paraffin wax were immunohistochemically labelled and reproducibly demonstrated nNOS immunoreactivity, particularly at the proximal portion of cilia; this immunoreactivity was blocked by a specific nNOS peptide fragment. Healthy human epithelial cells differentiated at an air-liquid interface (ALI) confirmed the presence of all three NOS isoenzymes by immunofluorescence labelling. Only nNOS immunoreactivity was specific to the ciliary axonemeand co-localised with the cilia marker β-tubulin in the proximal part of the ciliary axoneme. We report a novel localisation of nNOS at the proximal portion of cilia in airway epithelium and conclude that its independent and local regulation of NO levels is crucial for normal cilia function. Copyright © 2014 Elsevier Inc. All rights reserved.

MORTALITY OF URGENCY VERSUS ELECTIVE VIDEOLAPAROSCOPIC CHOLECYSTECTOMY FOR ACUTE CHOLECYSTITIS.

PubMed

Felício, Saulo José Oliveira; Matos, Ediriomar Peixoto; Cerqueira, Antonio Maurício; Farias, Kurt Wolfgang Schindler Freire de; Silva, Ramon de Assis; Torres, Mateus de Oliveira

2017-01-01

Surgical approach is still controversial in patients with acute cholecystitis: to treat clinically the inflammatory process and operate electively later or to operate immediately on an emergency basis? To test the hypothesis that urgent laparoscopic cholecystectomy in acute cholecystitis has a higher mortality than elective laparoscopic cholecystectomy. From the data available in Datasus, mortality was compared between patients undergoing elective laparoscopic cholecystectomy for cholelithiasis and in urgency. Calculations were made of the relative reduction in risk of death, absolute reduction of risk of death and number needed to treat. From 2009 to 2014 in Brazil, there were 250.439 laparoscopic cholecystectomy and 74.6% were electives. Mortality in the emergency group was 4.8 times higher compared to the elective group (0.0023% vs. 0.00048%). Despite the relative reduction in risk of death (RRR) was 83%, in the calculation of absolute risk was found 0.0018 and number needed to treat of 55,555. Despite the relative risk reduction for mortality was high comparing elective vs. urgent basis, the absolute risk reduction was minimal, since this outcome is very low in both groups, suggesting that mortality should not have much influence on surgical decision. Continua controversa a conduta nos pacientes com colecistite aguda: compensar o processo inflamatório e operar eletivamente ou operar imediatamente em caráter de urgência? Testar a hipótese de que a colecistectomia videolaparoscópica de urgência por colecistite aguda apresenta maior mortalidade que a colecistectomia videolaparoscópica eletiva. A partir dos dados disponíveis no Datasus, foi comparada a mortalidade entre os pacientes submetidos à colecistectomia videolaparoscópica eletiva por colelitíase e a de urgência. Foram realizados cálculos da redução relativa de risco de morte, redução absoluta do risco de morte e número necessário para tratar . De 2009 a 2014 no Brasil, foram realizadas 250.439 colecistectomias videolaparoscópicas sendo 74,6% eletivas. A mortalidade no grupo de emergência foi 4,8 vezes mais elevada em comparação com o grupo eletivo (0,0023% vs. 0,00048%). Apesar da redução relativa do risco de morte (RRR) ser de 83%, no cálculo do risco absoluto encontrou-se 0,0018 e número necessário para tratar de 55.555. Apesar da redução relativa de risco para mortalidade ser alta comparando o caráter eletivo vs. urgência, a redução de risco absoluto é mínima, já que esse desfecho é muito baixo nos dois grupos, sugerindo que a mortalidade não deve ter muita influência na tomada de decisão cirúrgica.

METRICS DEVELOPMENT FOR PATENTS.

PubMed

Veiga, Daniela Francescato; Ferreira, Lydia Masako

2015-01-01

To develop a proposal for metrics for patents to be applied in assessing the postgraduate programs of Medicine III - Capes. From the reading and analysis of the 2013 area documents of all the 48 areas of Capes, a proposal for metrics for patents was developed to be applied in Medicine III programs. Except for the areas Biotechnology, Food Science, Biological Sciences III, Physical Education, Engineering I, III and IV and Interdisciplinary, most areas do not adopt a scoring system for patents. The proposal developed was based on the criteria of Biotechnology, with adaptations. In general, it will be valued, in ascending order, the deposit, the granting and licensing/production. It will also be assigned higher scores to patents registered abroad and whenever there is a participation of students. This proposal can be applied to the item Intellectual Production of the evaluation form, in subsection Technical Production/Patents. The percentage of 10% for academic programs and 40% for Masters Professionals should be maintained. The program will be scored as Very Good when it reaches 400 points or over; Good, between 200 and 399 points; Regular, between 71 and 199 points; Weak up to 70 points; Insufficient, no punctuation. Desenvolver uma proposta de métricas para patentes a serem aplicadas na avaliação dos Programas de Pós-Graduação da Área Medicina III - Capes. A partir da leitura e análise dos documentos de área de 2013 de todas as 48 Áreas da Capes, desenvolveu-se uma proposta de métricas para patentes, a ser aplicada na avaliação dos programas da área. Constatou-se que, com exceção das áreas Biotecnologia, Ciência de Alimentos, Ciências Biológicas III, Educação Física, Engenharias I, III e IV e Interdisciplinar, a maioria não adota sistema de pontuação para patentes. A proposta desenvolvida baseou-se nos critérios da Biotecnologia, com adaptações. De uma forma geral, foi valorizado, em ordem crescente, o depósito, a concessão e o licenciamento/produção. Também foi atribuída maior pontuação a patentes registradas no exterior e com participação de discentes. Esta proposta poderá ser aplicada ao item Produção Intelectual da ficha de avaliação, no subitem Produções Técnicas, patentes e outras produções consideradas relevantes. Deverá ser mantida, neste subitem, a porcentagem de 10% para os programas acadêmicos e 40% para os mestrados profissionais. Será considerado Muito Bom o programa que obtiver 400 pontos/triênio ou mais, Bom entre 200 e 399 pontos; Regular entre 71 e 199 pontos; Fraco até 70 pontos; e Deficiente sem pontuação.

Effects of endogenous nitric oxide and of DETA NONOate in arteriogenesis.

PubMed

Troidl, Kerstin; Tribulova, Silvia; Cai, Wei-Jun; Rüding, Inka; Apfelbeck, Hanna; Schierling, Wilma; Troidl, Christian; Schmitz-Rixen, Thomas; Schaper, Wolfgang

2010-02-01

Previous studies showed that targeted endothelial nitric oxide synthase (eNOS) disruption in mice with femoral artery occlusion does not impede and transgenic eNOS overexpression does not stimulate collateral artery growth after femoral artery occlusion, suggesting that nitric oxide from eNOS does not play a role in arteriogenesis. However, pharmacologic nitric oxide synthase inhibition with L-NAME markedly blocks arteriogenesis, suggestive of an important role of nitric oxide. To solve the paradox, we studied targeted deletion of eNOS and of inducible nitric oxide synthase (iNOS) in mice and found that only iNOS knockout could partially inhibit arteriogenesis. However, the combination of eNOS knockout and treatment with the iNOS inhibitor L-NIL completely abolished arteriogenesis. mRNA transcription studies (reverse transcriptase-polymerase chain reaction) performed on collateral arteries of rats showed that eNOS and especially iNOS (but not neural nitric oxide synthase) become upregulated in shear stress-stimulated collateral vessels, which supports the hypothesis that nitric oxide is necessary for arteriogenesis but that iNOS plays an important part. This was strengthened by the observation that the nitric oxide donor DETA NONOate strongly stimulated collateral artery growth, activated perivascular monocytes, and increased proliferation markers. Shear stress-induced nitric oxide may activate the innate immune system and activate iNOS. In conclusion, arteriogenesis is completely dependent on the presence of nitric oxide, a large part of it coming from mononuclear cells.

Adolescent pregnancy and transition to adulthood in young users of the SUS.

PubMed

Vieira, Elisabeth Meloni; Bousquat, Aylene; Barros, Claudia Renata Dos Santos; Alves, Maria Cecilia Goi Porto

2017-03-30

The objective of this study is to contextualize adolescent pregnancy from milestones associated with the process of transition from youth to adulthood. This is a cross-sectional study conducted with 200 adolescents, users of the Brazilian Unified Health System. The sample size for the estimation of proportions has been calculated assuming a population ratio of 0.50 and 95% confidence level. The dependent variables - planned pregnancy, living with a partner, and having left the parents' house - have been considered as markers of transition from dependence to independence, from youth to adulthood. In the analysis of the associated factors, we have used the Poisson model with robust variance. Average age was 17.3 years, and most adolescents lived with a partner; approximately half of the adolescents got pregnant from their first partner and the average age of first sexual intercourse was 14.6 years. Only 19% of the adolescents were studying and most dropped out of school before the beginning of the pregnancy. In the bivariate and multiple analysis, we could see that the relationship with a partner for more than two years was associated with the three dependent variables. The path of transition to adulthood has been the establishment of a link with a partner and consequent pregnancy, suggesting a clear pattern of male guardianship. The changing role of women in society observed in recent decades, which means choosing a professional career, defining the number of children, and choosing their partner(s), has not reached these young persons. Contextualizar a gestação em adolescentes a partir de marcos associados ao processo de transição da juventude para a vida adulta. Estudo transversal realizado com 200 adolescentes usuárias do Sistema Único de Saúde. O tamanho da amostra para a estimação de proporções foi calculado considerando uma proporção populacional de 0,50, e nível de confiança de 95%. As variáveis dependentes - gestação planejada, morar com o parceiro e ter saído da casa dos pais - foram consideradas marcadores da transição da dependência para a independência, da juventude para a vida adulta. Na análise dos fatores associados, utilizou-se o modelo de Poisson com variância robusta. A idade média foi 17,3 anos, a maioria coabitava com o companheiro; aproximadamente metade engravidou do primeiro parceiro e a idade média da primeira relação sexual foi 14,6 anos. Apenas 19% das jovens estudavam e o abandono escolar foi, na maior parte, anterior ao início da gestação. Nas análises bivariadas e na análise múltipla, observou-se que relacionar-se com o parceiro há mais de dois anos se associou às três variáveis dependentes. O caminho de transição para a vida adulta foi o estabelecimento de um vínculo com um parceiro e consequente maternidade, sugerindo padrão claro de tutela masculina. A mudança do papel da mulher na sociedade observada nos últimas décadas, que implica optar por uma carreira profissional, definir número de filhos e escolher o(s) parceiro(s),não chegou a parcela dessas jovens.

Improving Flood Prediction By the Assimilation of Satellite Soil Moisture in Poorly Monitored Catchments.

NASA Astrophysics Data System (ADS)

Alvarez-Garreton, C. D.; Ryu, D.; Western, A. W.; Crow, W. T.; Su, C. H.; Robertson, D. E.

2014-12-01

Flood prediction in poorly monitored catchments is among the greatest challenges faced by hydrologists. To address this challenge, an increasing number of studies in the last decade have explored methods to integrate various existing observations from ground and satellites. One approach in particular, is the assimilation of satellite soil moisture (SM-DA) into rainfall-runoff models. The rationale is that satellite soil moisture (SSM) can be used to correct model soil water states, enabling more accurate prediction of catchment response to precipitation and thus better streamflow. However, there is still no consensus on the most effective SM-DA scheme and how this might depend on catchment scale, climate characteristics, runoff mechanisms, model and SSM products used, etc. In this work, an operational SM-DA scheme was set up in the poorly monitored, large (>40,000 km2), semi-arid Warrego catchment situated in eastern Australia. We assimilated passive and active SSM products into the probability distributed model (PDM) using an ensemble Kalman filter. We explored factors influencing the SM-DA framework, including relatively new techniques to remove model-observation bias, estimate observation errors and represent model errors. Furthermore, we explored the advantages of accounting for the spatial distribution of forcing and channel routing processes within the catchment by implementing and comparing lumped and semi-distributed model setups. Flood prediction is improved by SM-DA (Figure), with a 30% reduction of the average root-mean-squared difference of the ensemble prediction, a 20% reduction of the false alarm ratio and a 40% increase of the ensemble mean Nash-Sutcliffe efficiency. SM-DA skill does not significantly change with different observation error assumptions, but the skill strongly depends on the observational bias correction technique used, and more importantly, on the performance of the open-loop model before assimilation. Our findings imply that proper pre-processing of SSM is important for the efficacy of the SM-DA and assimilation performance is critically affected by the quality of model calibration. We therefore recommend focusing efforts on these two factors, while further evaluating the trade-offs between model complexity and data availability.

Requirement for STAT1 in LPS-induced gene expression in macrophages.

PubMed

Ohmori, Y; Hamilton, T A

2001-04-01

This study examines the role of the signal transducer and activator of transcription 1 (STAT1) in induction of lipopolysaccharide (LPS)-stimulated gene expression both in vitro and in vivo. LPS-induced expression of an interferon (IFN)-inducible 10-kDa protein (IP-10), IFN regulatory factor-1 (IRF-1), and inducible nitric oxide synthase (iNOS) mRNAs was severely impaired in macrophages prepared from Stat1-/- mice, whereas levels of tumor necrosis factor alpha and KC (a C-X-C chemokine) mRNA in LPS-treated cell cultures were unaffected. A similar deficiency in LPS-induced gene expression was observed in livers and spleens from Stat1-/- mice. The reduced LPS-stimulated gene expression seen in Stat1-/- macrophages was not the result of reduced activation of nuclear factor kappaB. LPS stimulated the delayed activation of both IFN-stimulated response element and IFN-gamma-activated sequence binding activity in macrophages from wild-type mice. Activation of these STAT1-containing transcription factors was mediated by the intermediate induction of type I IFNs, since the LPS-induced IP-10, IRF-1, and iNOS mRNA expression was markedly reduced in macrophages from IFN-alpha/betaR-/- mice and blocked by cotreatment with antibodies against type I IFN. These results indicate that indirect activation of STAT1 by LPS-induced type I IFN participates in promoting optimal expression of LPS-inducible genes, and they suggest that STAT1 may play a critical role in innate immunity against gram-negative bacterial infection.

9.73% Efficiency Nonfullerene All Organic Small Molecule Solar Cells with Absorption-Complementary Donor and Acceptor.

PubMed

Bin, Haijun; Yang, Yankang; Zhang, Zhi-Guo; Ye, Long; Ghasemi, Masoud; Chen, Shanshan; Zhang, Yindong; Zhang, Chunfeng; Sun, Chenkai; Xue, Lingwei; Yang, Changduk; Ade, Harald; Li, Yongfang

2017-03-29

In the last two years, polymer solar cells (PSCs) developed quickly with n-type organic semiconductor (n-OSs) as acceptor. In contrast, the research progress of nonfullerene organic solar cells (OSCs) with organic small molecule as donor and the n-OS as acceptor lags behind. Here, we synthesized a D-A structured medium bandgap organic small molecule H11 with bithienyl-benzodithiophene (BDTT) as central donor unit and fluorobenzotriazole as acceptor unit, and achieved a power conversion efficiency (PCE) of 9.73% for the all organic small molecules OSCs with H11 as donor and a low bandgap n-OS IDIC as acceptor. A control molecule H12 without thiophene conjugated side chains on the BDT unit was also synthesized for investigating the effect of the thiophene conjugated side chains on the photovoltaic performance of the p-type organic semiconductors (p-OSs). Compared with H12, the 2D-conjugated H11 with thiophene conjugated side chains shows intense absorption, low-lying HOMO energy level, higher hole mobility and ordered bimodal crystallite packing in the blend films. Moreover, a larger interaction parameter (χ) was observed in the H11 blends calculated from Hansen solubility parameters and differential scanning calorimetry measurements. These special features combined with the complementary absorption of H11 donor and IDIC acceptor resulted in the best PCE of 9.73% for nonfullerene all small molecule OSCs up to date. Our results indicate that fluorobenzotriazole based 2D conjugated p-OSs are promising medium bandgap donors in the nonfullerene OSCs.

Teachers' Ways of Talking about Nature of Science and Its Teaching

ERIC Educational Resources Information Center

Leden, Lotta; Hansson, Lena; Redfors, Andreas; Ideland, Malin

2015-01-01

Nature of science (NOS) has for a long time been regarded as a key component in science teaching. Much research has focused on students' and teachers' views of NOS, while less attention has been paid to teachers' perspectives on NOS teaching. This article focuses on in-service science teachers' ways of talking about NOS and NOS teaching, e.g. what…

"Non alcoholic fatty liver disease and eNOS dysfunction in humans".

PubMed

Persico, Marcello; Masarone, Mario; Damato, Antonio; Ambrosio, Mariateresa; Federico, Alessandro; Rosato, Valerio; Bucci, Tommaso; Carrizzo, Albino; Vecchione, Carmine

2017-03-07

NAFLD is associated to Insulin Resistance (IR). IR is responsible for Endothelial Dysfunction (ED) through the impairment of eNOS function. Although eNOS derangement has been demonstrated in experimental models, no studies have directly shown that eNOS dysfunction is associated with NAFLD in humans. The aim of this study is to investigate eNOS function in NAFLD patients. Fifty-four NAFLD patients were consecutively enrolled. All patients underwent clinical and laboratory evaluation and liver biopsy. Patients were divided into two groups by the presence of NAFL or NASH. We measured vascular reactivity induced by patients' platelets on isolated mice aorta rings. Immunoblot assays for platelet-derived phosphorylated-eNOS (p-eNOS) and immunohistochemistry for hepatic p-eNOS have been performed to evaluate eNOS function in platelets and liver specimens. Flow-mediated-dilation (FMD) was also performed. Data were compared with healthy controls. Twenty-one (38, 8%) patients had NAFL and 33 (61, 7%) NASH. No differences were found between groups and controls except for HOMA and insulin (p < 0.0001). Vascular reactivity demonstrated a reduced function induced from NAFLD platelets as compared with controls (p < 0.001), associated with an impaired p-eNOS in both platelets and liver (p < 0.001). NAFL showed a higher impairment of eNOS phosphorylation in comparison to NASH (p < 0.01). In contrast with what observed in vitro, the vascular response by FMD was worse in NASH as compared with NAFL. Our data showed, for the first time in humans, that NAFLD patients show a marked eNOS dysfunction, which may contribute to a higher CV risk. eNOS dysfunction observed in platelets and liver tissue didn't match with FMD.

Differential cholinoceptor modulation of nitric oxide isoforms in experimentally-induced inflammation of dental pulp tissue.

PubMed

De Couto Pita, A; Passafaro, D; Ganzinelli, S; Borda, E; Sterin-Borda, L

2009-06-01

The aim of the study was to investigate the role of muscarinic acetylcholine receptor (mAChR) activity in the regulation of endothelial (e), neuronal (n) and inducible (i) nitric oxide synthase (NOS) activity and expression in experimentally induced inflammation of rat dental pulp tissue. Inflammation was induced by application of bacterial lipopolysaccharide (LPS) to the pulp. Extirpated pulp-tissue samples were incubated in saline solution until the various experiments were performed. Saline-treated pulp and healthy pulp tissues were used as controls. NOS activity was measured by the production of [U-(14)C]-citrulline from [U-(14)C]-arginine. Nitrite/nitrate assay was evaluated by the conversion of nitrate to nitrite in the presence of nicotinamide adenine dinucleotide phosphate. i-nos, e-nos and n-nos mRNA levels were measured using reverse-transcriptase polymerase chain reaction by co-amplification of target cDNA with a single set of primers. Application of LPS to the pulp increased NOS activity and nitrate production (P < 0.001), generated by iNOS over-activity and expression. Pilocarpine acting on mAChRs triggered a biphasic action on NOS activity and NO accumulation. At low concentrations, pilocarpine induced a negative effect associated with a decrease in i-nos mRNA level, whilst at high concentration, it produced a positive effect associated with increased e-nos and n-nos mRNA levels. In control pulp tissue, only the positive effect of pilocarpine was observed. Irreversible pulpitis changes mAChR conformation increasing its efficiency of coupling to transducing molecules that in turn induce activate iNOS. The capacity of pilocarpine to prevent NO accumulation and iNOS activity, by acting on mAChR mutation induced by pulpitis, might be useful therapeutically as a local treatment.

Inhibitor-κB kinase attenuates Hsp90-dependent endothelial nitric oxide synthase function in vascular endothelial cells

PubMed Central

Konopinski, Ryszard; Krishnan, Manickam; Roman, Linda; Bera, Alakesh; Hongying, Zheng; Habib, Samy L.; Mohan, Sumathy

2015-01-01

Endothelial nitric oxide (NO) synthase (eNOS) is the predominant isoform that generates NO in the blood vessels. Many different regulators, including heat shock protein 90 (Hsp90), govern eNOS function. Hsp90-dependent phosphorylation of eNOS is a critical event that determines eNOS activity. In our earlier study we demonstrated an inhibitor-κB kinase-β (IKKβ)-Hsp90 interaction in a high-glucose environment. In the present study we further define the putative binding domain of IKKβ on Hsp90. Interestingly, IKKβ binds to the middle domain of Hsp90, which has been shown to interact with eNOS to stimulate its activity. This new finding suggests a tighter regulation of eNOS activity than was previously assumed. Furthermore, addition of purified recombinant IKKβ to the eNOS-Hsp90 complex reduces the eNOS-Hsp90 interaction and eNOS activity, indicating a competition for Hsp90 between eNOS and IKKβ. The pathophysiological relevance of the IKKβ-Hsp90 interaction has also been demonstrated using in vitro vascular endothelial growth factor-mediated signaling and an Ins2Akita in vivo model. Our study further defines the preferential involvement of α- vs. β-isoforms of Hsp90 in the IKKβ-eNOS-Hsp90 interaction, even though both Hsp90α and Hsp90β stimulate NO production. These studies not only reinforce the significance of maintaining a homeostatic balance of eNOS and IKKβ within the cell system that regulates NO production, but they also confirm that the IKKβ-Hsp90 interaction is favored in a high-glucose environment, leading to impairment of the eNOS-Hsp90 interaction, which contributes to endothelial dysfunction and vascular complications in diabetes. PMID:25652452

Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice.

PubMed

Chen, Yong; Boettger, Michael K; Reif, Andreas; Schmitt, Angelika; Uçeyler, Nurcan; Sommer, Claudia

2010-03-02

Although it has been largely demonstrated that nitric oxide synthase (NOS), a key enzyme for nitric oxide (NO) production, modulates inflammatory pain, the molecular mechanisms underlying these effects remain to be clarified. Here we asked whether cytokines, which have well-described roles in inflammatory pain, are downstream targets of NO in inflammatory pain and which of the isoforms of NOS are involved in this process. Intraperitoneal (i.p.) pretreatment with 7-nitroindazole sodium salt (7-NINA, a selective neuronal NOS inhibitor), aminoguanidine hydrochloride (AG, a selective inducible NOS inhibitor), L-N(G)-nitroarginine methyl ester (L-NAME, a non-selective NOS inhibitor), but not L-N(5)-(1-iminoethyl)-ornithine (L-NIO, a selective endothelial NOS inhibitor), significantly attenuated thermal hyperalgesia induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA). Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed a significant increase of nNOS, iNOS, and eNOS gene expression, as well as tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1beta), and interleukin-10 (IL-10) gene expression in plantar skin, following CFA. Pretreatment with the NOS inhibitors prevented the CFA-induced increase of the pro-inflammatory cytokines TNF and IL-1beta. The increase of the anti-inflammatory cytokine IL-10 was augmented in mice pretreated with 7-NINA or L-NAME, but reduced in mice receiving AG or L-NIO. NNOS-, iNOS- or eNOS-knockout (KO) mice had lower gene expression of TNF, IL-1beta, and IL-10 following CFA, overall corroborating the inhibitor data. These findings lead us to propose that inhibition of NOS modulates inflammatory thermal hyperalgesia by regulating cytokine expression.

In vivo detection of inducible nitric oxide synthase in rodent gliomas.

PubMed

Towner, Rheal A; Smith, Nataliya; Doblas, Sabrina; Garteiser, Philippe; Watanabe, Yasuko; He, Ting; Saunders, Debra; Herlea, Oana; Silasi-Mansat, Robert; Lupu, Florea

2010-03-01

Increased iNOS expression is often found in brain tumors, such as gliomas. The goal of this study was to develop and assess a novel molecular MRI (mMRI) probe for in vivo detection of iNOS in rodent models for gliomas (intracerebral implantation of rat C6 or RG2 cells or ethyl nitrosourea-induced glioma). The probe we used incorporated a Gd-DTPA (gadolinium(III) complex of diethylenetriamine-N,N,N',N'',N''-pentaacetate) backbone with albumin and biotin moieties and covalent binding of an anti-iNOS antibody (Ab) to albumin (anti-iNOS probe). We used mMRI with the anti-iNOS probe to detect in vivo iNOS levels in gliomas. Nonimmune normal rat IgG coupled to albumin-Gd-DTPA-biotin was used as a control nonspecific contrast agent. By targeting the biotin component of the anti-iNOS probe with streptavidin Cy3, fluorescence imaging confirmed the specificity of the probe for iNOS in glioma tissue. iNOS levels in glioma tumors were also confirmed via Western blots and immunohistochemistry. The presence of plasma membrane-associated iNOS in glioma cells was established by transmission electron microscopy and gold-labeled anti-iNOS Ab. The more aggressive RG2 glioma was not found to have higher levels of iNOS compared to C6. Differences in glioma vascularization and blood-brain barrier permeability between the C6 and the RG2 gliomas are discussed. In vivo assessment of iNOS levels associated with tumor development is quite feasible in heterogeneous tissues with mMRI. (c) 2009 Elsevier Inc. All rights reserved.

Trigeminal Pain Molecules, Allodynia, and Photosensitivity Are Pharmacologically and Genetically Modulated in a Model of Traumatic Brain Injury

PubMed Central

Daiutolo, Brittany V.; Tyburski, Ashley; Clark, Shannon W.

2016-01-01

Abstract The pain-signaling molecules, nitric oxide synthase (NOS) and calcitonin gene-related peptide (CGRP), are implicated in the pathophysiology of post-traumatic headache (PTH) as they are for migraine. This study assessed the changes of inducible NOS (iNOS) and its cellular source in the trigeminal pain circuit, as well as the relationship between iNOS and CGRP after controlled cortical impact (CCI) injury in mice. The effects of a CGRP antagonist (MK8825) and sumatriptan on iNOS messenger RNA (mRNA) and protein were compared to vehicle at 2 weeks postinjury. Changes in CGRP levels in the trigeminal nucleus caudalis (TNC) in iNOS knockouts with CCI were compared to wild-type (WT) mice at 3 days and 2 weeks post injury. Trigeminal allodynia and photosensitivity were measured. MK8825 and sumatriptan increased allodynic thresholds in CCI groups compared to vehicle (p < 0.01), whereas iNOS knockouts were not different from WT. Photosensitivity was attenuated in MK8825 mice and iNOS knockouts compared to WT (p < 0.05). MK8825 and sumatriptan reduced levels of iNOS mRNA and iNOS immunoreactivity in the TNC and ganglia (p < 0.01). Differences in iNOS cellular localization were found between the trigeminal ganglia and TNC. Although the knockout of iNOS attenuated CGRP at 3 days (p < 0.05), it did not reduce CGRP at 2 weeks. CGRP immunoreactivity was found in the meningeal layers post-CCI, while negligible in controls. Findings support the importance of interactions between CGRP and iNOS in mediating allodynia, as well as the individual roles in photosensitivity. Mitigating prolonged increases in CGRP may be a promising intervention for treating acute PTH. PMID:26472135

Plasma membrane calcium ATPase 4b inhibits nitric oxide generation through calcium-induced dynamic interaction with neuronal nitric oxide synthase.

PubMed

Duan, Wenjuan; Zhou, Juefei; Li, Wei; Zhou, Teng; Chen, Qianqian; Yang, Fuyu; Wei, Taotao

2013-04-01

The activation and deactivation of Ca(2+)- and calmodulindependent neuronal nitric oxide synthase (nNOS) in the central nervous system must be tightly controlled to prevent excessive nitric oxide (NO) generation. Considering plasma membrane calcium ATPase (PMCA) is a key deactivator of nNOS, the present investigation aims to determine the key events involved in nNOS deactivation of by PMCA in living cells to maintain its cellular context. Using time-resolved Förster resonance energy transfer (FRET), we determined the occurrence of Ca(2+)-induced protein-protein interactions between plasma membrane calcium ATPase 4b (PMCA4b) and nNOS in living cells. PMCA activation significantly decreased the intracellular Ca(2+) concentrations ([Ca(2+)]i), which deactivates nNOS and slowdowns NO synthesis. Under the basal [Ca(2+)]i caused by PMCA activation, no protein-protein interactions were observed between PMCA4b and nNOS. Furthermore, both the PDZ domain of nNOS and the PDZ-binding motif of PMCA4b were essential for the protein-protein interaction. The involvement of lipid raft microdomains on the activity of PMCA4b and nNOS was also investigated. Unlike other PMCA isoforms, PMCA4 was relatively more concentrated in the raft fractions. Disruption of lipid rafts altered the intracellular localization of PMCA4b and affected the interaction between PMCA4b and nNOS, which suggest that the unique lipid raft distribution of PMCA4 may be responsible for its regulation of nNOS activity. In summary, lipid rafts may act as platforms for the PMCA4b regulation of nNOS activity and the transient tethering of nNOS to PMCA4b is responsible for rapid nNOS deactivation.

Partial eNOS deficiency causes spontaneous thrombotic cerebral infarction, amyloid angiopathy and cognitive impairment.

PubMed

Tan, Xing-Lin; Xue, Yue-Qiang; Ma, Tao; Wang, Xiaofang; Li, Jing Jing; Lan, Lubin; Malik, Kafait U; McDonald, Michael P; Dopico, Alejandro M; Liao, Francesca-Fang

2015-06-24

Cerebral infarction due to thrombosis leads to the most common type of stroke and a likely cause of age-related cognitive decline and dementia. Endothelial nitric oxide synthase (eNOS) generates NO, which plays a crucial role in maintaining vascular function and exerting an antithrombotic action. Reduced eNOS expression and eNOS polymorphisms have been associated with stroke and Alzheimer's disease (AD), the most common type of dementia associated with neurovascular dysfunction. However, direct proof of such association is lacking. Since there are no reports of complete eNOS deficiency in humans, we used heterozygous eNOS(+/-) mice to mimic partial deficiency of eNOS, and determine its impact on cerebrovascular pathology and perfusion of cerebral vessels. Combining cerebral angiography with immunohistochemistry, we found thrombotic cerebral infarctions in eNOS(+/-) mice as early as 3-6 months of age but not in eNOS(+/+) mice at any age. Remarkably, vascular occlusions in eNOS(+/-) mice were found almost exclusively in three areas: temporoparietal and retrosplenial granular cortexes, and hippocampus this distribution precisely matching the hypoperfused areas identified in preclinical AD patients. Moreover, progressive cerebral amyloid angiopaphy (CAA), blood brain barrier (BBB) breakdown, and cognitive impairment were also detected in aged eNOS(+/-) mice. These data provide for the first time the evidence that partial eNOS deficiency results in spontaneous thrombotic cerebral infarctions that increase with age, leading to progressive CAA and cognitive impairments. We thus conclude that eNOS(+/-) mouse may represent an ideal model of ischemic stroke to address early and progressive damage in spontaneously-evolving chronic cerebral ischemia and thus, study vascular mechanisms contributing to vascular dementia and AD.

Development, health, and international policy: the research and innovation dimension.

PubMed

Buss, Paulo Marchiori; Chamas, Claudia; Faid, Miriam; Morel, Carlos

2016-11-03

This text main objective is to discuss development and health from the perspective of the influence of global health governance, using as the tracer the dimension of research, development, and innovation policies in health, which relate to both important inputs for the health system, like drugs and medicines, vaccines, diagnostic reagents, and equipment, and innovative concepts and practices for the improvement of health systems and public health. The authors examine the two main macro-processes that influence development and health: the post-2015 Development Agenda and the process under way in the World Health Organization concerning research and development, intellectual property, and access to health inputs. The article concludes, first, that much remains to be done for the Agenda to truly represent a coherent and viable international political pact, and that the two macro-processes related to innovation in health need to be streamlined. But this requires democratization of participation by the main stakeholders - patients and the general population of the poorest countries - since this is the only way to overcome a "zero sum" result in the clash in the current debates among member State representatives. Resumo: O objetivo central deste texto é discutir desenvolvimento e saúde sob a ótica da influência da governança da saúde global, utilizando como traçador a dimensão das políticas de pesquisa, desenvolvimento e inovação em saúde, que se referem, de um lado, a insumos importantes para o sistema de saúde - como fármacos e medicamentos, vacinas, reativos para diagnóstico e equipamentos e, de outro, a conceitos e práticas inovadoras para o aperfeiçoamento dos sistemas de saúde e da saúde pública. Examina os dois principais macroprocessos que influenciam o desenvolvimento e a saúde: a Agenda do Desenvolvimento para o pós-2015 e o processo sobre pesquisa e desenvolvimento, propriedade intelectual e acesso a insumos em saúde em curso na Organização Mundial da Saúde. Conclui que muito há que ser feito para que a referida Agenda possa representar um pacto político internacional coerente e viável, e que os dois macroprocessos relacionados com a inovação em saúde precisam ser agilizados, mas para isto torna-se necessária a democratização da participação dos maiores interessados - os pacientes e, de modo geral, a população dos países mais pobres - pois só desta maneira será superada a "soma zero" em que se encontra o embate entre os representantes de Estados-membros nos debates atuais.

Use of cuff tear arthroplasty head prosthesis for rotator cuff arthropathy treatment in elderly patients with comorbidities.

PubMed

Carvalho, Cassiano Diniz; Andreoli, Carlos Vicente; Pochini, Alberto de Castro; Ejnisman, Benno

2016-01-01

To evaluate the clinical and functional behavior of patients undergoing cuff tear arthroplasty at different stages of the disease. Cuff tear arthroplasty hemiarthroplasties were performed in 34 patients with rotator cuff arthropathy and associated comorbidities, classified according to Seebauer. The mean age was 76.3 years, and the sample comprised 23 females (67.6%) and 11 males (32.4%). The mean follow-up period was 21.7 months, and evaluations were performed using the Visual Analog Scale for pain and the Constant scale. There were no statistically significant differences in the mean reduction in the Visual Analog Scale or in the Constant scale increase between the female and male groups. The variation between the pre- and postoperative Visual Analog Scale and Constant scale evaluations was significant. There was also no statistically significant difference between the Seebauer classification groups regarding the mean Visual Analog Scale reduction, or the mean Constant scale increase. Cuff tear arthroplasty shoulder hemiarthroplasty is a good option for rotator cuff arthropathy in patients with comorbidities. Avaliar o comportamento clínico e funcional dos pacientes submetidos à artroplastia do tipo cuff tear arthroplasty para o tratamento da artropatia do manguito rotador em diferentes estágios da afecção. Foram realizadas 34 hemiartroplastias do tipo cuff tear arthroplasty em 34 pacientes com artropatia do manguito rotador e comorbidades associadas, classificadas de acordo com Seebauer. A média de idade foi de 76,3 anos, sendo 23 pacientes do sexo feminino (67,6%) e 11 do sexo masculino (32,4%). O seguimento médio foi de 21,7 meses e a avaliação foi realizada por meio da Escala Visual Analógica da dor e pela escala de Constant. Não houve diferença estatisticamente significante entre os grupos feminino e masculino, tanto nas médias de redução na Escala Visual Analógica quanto nas de aumento na escala de Constant. A variação entre as avaliações da Escala Visual Analógica e da escala de Constant pré e pós-operatórias foi significante. Não houve diferença estatisticamente significante entre os grupos de classificação de Seebauer quanto às médias de redução na Escala Visual Analógica e nem quanto às médias de aumento na escala de Constant, e não houve casos de infecção. A hemiartroplastia do ombro tipo cuff tear arthroplasty é boa uma opção nos pacientes com artropatia do manguito rotador, especialmente em pacientes com comorbidades.

Air Force Operational Medicine: Using the Enterprise Estimating Supplies Program to Develop Materiel Solutions for the Expeditionary Medical Support (EMEDS). Volume 4. EMEDS+25

DTIC Science & Technology

2011-03-28

TRICHOMONIASIS NOS 1 Infectious 580.9 ACUTE NEPHRITIS NOS 1 Genitourinary 582.9 CHRONIC NEPHRITIS NOS 1 Genitourinary 075 INFECTIOUS MONONUCLEOSIS 1...CALCULUS OF KIDNEY 2 075 INFECTIOUS MONONUCLEOSIS 2 870.9 OPN WND OCULAR ADNEX NOS 1 780.6 FEVER 2 Total patients 85 EMEDS+25 Materiel Solutions H-1...008.8 VIRAL ENTERITIS NOS 38 Infectious 462 ACUTE PHARYNGITIS 19 Respiratory 780.6 FEVER 14 Ill-defined 692.9 DERMATITIS NOS 13 Skin 110.4

Modulation of NO and ROS production by AdiNOS transduced vascular cells through supplementation with L-Arg and BH4: implications for gene therapy of restenosis.

PubMed

Forbes, Scott P; Alferiev, Ivan S; Chorny, Michael; Adamo, Richard F; Levy, Robert J; Fishbein, Ilia

2013-09-01

Gene therapy with viral vectors encoding for NOS enzymes has been recognized as a potential therapeutic approach for the prevention of restenosis. Optimal activity of iNOS is dependent on the intracellular availability of L-Arg and BH4 via prevention of NOS decoupling and subsequent ROS formation. Herein, we investigated the effects of separate and combined L-Arg and BH4 supplementation on the production of NO and ROS in cultured rat arterial smooth muscle and endothelial cells transduced with AdiNOS, and their impact on the antirestenotic effectiveness of AdiNOS delivery to balloon-injured rat carotid arteries. Supplementation of AdiNOS transduced endothelial and vascular smooth muscle cells with L-Arg (3.0 mM), BH4 (10 μM) and especially their combination resulted in a significant increase in NO production as measured by nitrite formation in media. Formation of ROS was dose-dependently increased following transduction with increasing MOIs of AdiNOS. Exposure of RASMC to AdiNOS tethered to meshes via a hydrolyzable cross-linker, modeling viral delivery from stents, resulted in increased ROS production, which was decreased by supplementation with BH4 but not L-Arg or L-Arg/BH4. Enhanced cell death, caused by AdiNOS transduction, was also preventable with BH4 supplementation. In the rat carotid model of balloon injury, intraluminal delivery of AdiNOS in BH4-, L-Arg-, and especially in BH4 and L-Arg supplemented animals was found to significantly enhance the antirestenotic effects of AdiNOS-mediated gene therapy. Fine-tuning of iNOS function by L-Arg and BH4 supplementation in the transduced vasculature augments the therapeutic potential of gene therapy with iNOS for the prevention of restenosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Modulation of NO and ROS production by AdiNOS transduced vascular cells through supplementation with L-Arg and BH4: Implications for gene therapy of restenosis

PubMed Central

Forbes, Scott P.; Alferiev, Ivan S.; Chorny, Michael; Adamo, Richard F.; Levy, Robert J.; Fishbein, Ilia

2013-01-01

Objective Gene therapy with viral vectors encoding for NOS enzymes has been recognized as a potential therapeutic approach for the prevention of restenosis. Optimal activity of iNOS is dependent on the intracellular availability of L-Arg and BH4 via prevention of NOS decoupling and subsequent ROS formation. Herein, we investigated the effects of separate and combined L-Arg and BH4 supplementation on the production of NO and ROS in cultured rat arterial smooth muscle and endothelial cells transduced with AdiNOS, and their impact on the antirestenotic effectiveness of AdiNOS delivery to balloon-injured rat carotid arteries. Methods and Results Supplementation of AdiNOS transduced endothelial and vascular smooth muscle cells with L-Arg (3.0 mM), BH4 (10 μM) and especially their combination resulted in a significant increase in NO production as measured by nitrite formation in media. Formation of ROS was dose-dependently increased following transduction with increasing MOIs of AdiNOS. Exposure of RASMC to AdiNOS tethered to meshes via a hydrolysable cross-linker, modeling viral delivery from stents, resulted in increased ROS production, which was decreased by supplementation with BH4 but not L-Arg or L-Arg/BH4. Enhanced cell death, caused by AdiNOS transduction, was also preventable with BH4 supplementation. In the rat carotid model of balloon injury, intraluminal delivery of AdiNOS in BH4-, L-Arg-, and especially in BH4 and L-Arg supplemented animals was found to significantly enhance the antirestenotic effects of AdiNOS-mediated gene therapy. Conclusions Fine-tuning of iNOS function by L-Arg and BH4 supplementation in the transduced vasculature augments the therapeutic potential of gene therapy with iNOS for the prevention of restenosis. PMID:23958248

[Influence of hepatocyte growth factor on iNOS, NO and IL-1β in the cerebrum during cerebral ischemia/reperfusion in rats].

PubMed

He, Fang; Ye, Bei; Chen, Jianzhen; Sun, Xiaoyan; Li, Chang

2014-01-01

To explore the effect of hepatocyte growth factor (HGF) on inducible nitric oxide synthase (iNOS), NO and interleukin-1β (IL-1β) in the cerebrum of rats subjected to cerebral ischemia/reperfusion (I/R). Sprague-Dawley rats were randomly divided into 5 groups: a sham group, an I/R group,an HGF1 group, an HGF2 group, and an HGF3 group. The latter 3 groups were respectively injected 15, 30 and 60 μg/kg HGF. The focal cerebral I/R model was established by sutureoccluded method. After 1.5 h ischemia followed by 24 h reperfusion, the iNOS activity and NO content in the ischemic cerebral tissue were assessed. The expression of iNOS mRNA and IL-1β mRNA was detected. The level of iNOS protein and IL-1β content were determined. In addition, cultured cerebral cortical neurons in vitro were exposed to I/R. Then the expression of iNOS and IL-1β protein in the neurons was detected, and NO content was assessed. The iNOS activity and NO content in the ischemic cerebral tissue were increased. The expression of iNOS mRNA and IL-1β mRNA was upregulated. The level of iNOS protein and IL- 1β content were increased. Administration of HGF decreased the iNOS activity and NO content, and downregulated the expression of iNOS mRNA, IL-1β mRNA, iNOS protein and IL-1β content in the ischemic cerebral tissue. HGF decreased the expression of IL-1β, iNOS protein and NO content in the cortical neurons exposed to I/R in vitro. HGF can inhibit the expression of IL-1β and decrease the expression of iNOS and content of NO, which is probably one of the mechanisms mediating the protection of HGF against cerebral ischemia injury.

The reciprocal relationship between heme oxygenase and nitric oxide synthase in the organs of lipopolysaccharide-treated rodents.

PubMed

Furuichi, Masayuki; Yokozuka, Motoi; Takemori, Ken; Yamanashi, Yoshitaka; Sakamoto, Atsuhiro

2009-08-01

The production of nitric oxide (NO) by inducible NO synthase (NOS) and carbon monoxide (CO) by inducible heme oxygenase (HO) contributes greatly to endotoxemia. Reciprocal relationships have been proposed between the NO/NOS and CO/HO systems. However, the interaction between these systems during endotoxemia is unclear, and it is unknown whether the interactive behavior differs among organs. Using endotoxic rats, we studied the effects of the inducible NOS (iNOS) inhibitor L-canavanine (CAN), and the HO inhibitor zinc protoporphyrin (ZPP) on gene expression and protein levels of iNOS, endothelial NOS (eNOS), inducible HO (HO-1), and constitutive HO (HO-2) in the brain, lung, heart, liver and kidney tissue. Intravenous injection of LPS significantly increased iNOS and HO-1 gene expression in all organs. The effects of LPS on eNOS gene expression differed among organs, with increased expression in the liver and kidney, and no change in the lung, brain and heart. ZPP administration down-regulated the LPS-induced increase in HO-1 expression and produced a further increase in iNOS expression in all organs. These data suggest that the CO/HO system modifies the NO/NOS system in endotoxic organs, and that there were only minor organ-specific behaviors in terms of the relationship between these systems in the organs examined.

Inducible nitric oxide synthase inhibits oxygen consumption in collateral-dependent myocardium.

PubMed

Chen, Yingjie; Zhang, Ping; Li, Jingxin; Xu, Xin; Bache, Robert J

2014-02-01

Following coronary artery occlusion growth of collateral vessels can provide an effective blood supply to the dependent myocardium. The ischemia, which results in growth of collateral vessels, recruits an inflammatory response with expression of cytokines and growth factors, upregulation of endothelial nitric oxide (NO) synthase (eNOS) in vascular endothelial cells, and expression of inducible nitric oxide synthase (iNOS) in both vessels and cardiac myocytes. Because NO is a potent collateral vessel dilator, this study examined whether NO derived from iNOS or constitutive NOS regulates myocardial blood flow (MBF) in the collateral region. Nonselective NOS inhibition with N(G)-nitro-l-arginine (LNA) caused vasoconstriction with a significant decrease in MBF to the collateral region during exercise. In contrast, the highly selective iNOS inhibitor 1400W caused a 21 ± 5% increase of MBF in the collateral region. This increase in MBF following selective iNOS blockade was proportionate to an increase in myocardial O2 consumption (MVo2). The results suggest that NO produced by iNOS inhibits MVo2 in the collateralized region, so that the increase in MBF following iNOS blockade was the result of metabolic vasodilation secondary to an increase in MVo2. Thus the coordinated expression of iNOS to restrain MVo2 and eNOS to maintain collateral vasodilation act to optimize the O2 supply-demand relationship and protect the collateralized myocardium from ischemia.

Artichoke, cynarin and cyanidin downregulate the expression of inducible nitric oxide synthase in human coronary smooth muscle cells.

PubMed

Xia, Ning; Pautz, Andrea; Wollscheid, Ursula; Reifenberg, Gisela; Förstermann, Ulrich; Li, Huige

2014-03-24

Artichoke (Cynara scolymus L.) is one of the world's oldest medicinal plants with multiple health benefits. We have previously shown that artichoke leaf extracts and artichoke flavonoids upregulate the gene expression of endothelial-type nitric oxide synthase (eNOS) in human endothelial cells. Whereas NO produced by the eNOS is a vasoprotective molecule, NO derived from the inducible iNOS plays a pro-inflammatory role in the vasculature. The present study was aimed to investigate the effects of artichoke on iNOS expression in human coronary artery smooth muscle cells (HCASMC). Incubation of HCASMC with a cytokine mixture led to an induction of iNOS mRNA expression. This iNOS induction was concentration- and time-dependently inhibited by an artichoke leaf extract (1-100 µg/mL, 6 h or 24 h). Consistently, the artichoke leaf extract also reduced cytokine-induced iNOS promoter activation and iNOS protein expression. In addition, treatment of HCASMC with four well-known artichoke compounds (cynarin > cyanidin > luteolin ≈ cynaroside) led to a downregulation iNOS mRNA and protein expression, with cynarin being the most potent one. In conclusion, artichoke contains both eNOS-upregulating and iNOS-downregulating compounds. Such compounds may contribute to the beneficial effects of artichoke and may per se have therapeutic potentials.

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Exploring Elementary Science Methods Course Contexts to Improve Preservice Teachers' NOS of Science Conceptions and Understandings of NOS Teaching Strategies

ERIC Educational Resources Information Center

Akerson, Valarie L.; Weiland, Ingrid; Rogers, Meredith Park; Pongsanon, Khemmawaddee; Bilican, Kader

2014-01-01

We explored adaptations to an elementary science methods course to determine how varied contexts could improve elementary preservice teachers' conceptions of NOS as well as their ideas for teaching NOS to elementary students. The contexts were (a) NOS Theme in which the course focused on the teaching of science through the consistent teaching…

Relationship between students' understandings of nature of science and instructional context

NASA Astrophysics Data System (ADS)

Khishfe, Rola Fouad

The study investigated and compared two different instructional approaches (integrated and nonintegrated), which address the explicit teaching of nature of science (NOS), in relation to improving students' understanding of NOS. Participants were three teachers and their students---a total of 129---which comprised six groups of 89 ninth and 40 10th/11th graders. Each teacher taught two intact sections of the same grade level within a specific science discipline (environmental science, chemistry, or biology). The treatment for all groups spanned five to six weeks and involved teaching a unit, which included both the regular science content and NOS. Participants in each of the two intact classes were taught by the same teacher about their regular science content, with the difference being the context in which NOS was explicitly taught (integrated or nonintegrated). In the integrated group, NOS instruction was related to the science content addressed in the unit. In the nonintegrated group, NOS was taught through a set of generic (non content-embedded) activities that specifically addressed NOS aspects and were "interspersed" across the science content addressed in the unit. An open-ended questionnaire, in conjunction with semi-structured interviews, was used to assess participants' views prior to and following instruction. Data analysis involved a systematic process consistent with analytic induction. Results showed general improvements in participants' views of NOS regardless of whether or not NOS was integrated within the regular science content. The results of this study do not support the appealing assumption held by many science educators that integrating NOS within the context of the science content would better enhance the learning of NOS. However, the results suggest the possibility of an interaction between the type of change (naive to transitional, transitional to informed, naive to informed, no changes, regression) in students' views and the explicit instructional approach (integrated or nonintegrated) to teach NOS. Moreover, the findings suggest the transferability of NOS understandings among various contexts, with the consequence that learning NOS might not be context-dependent. Implications for the teaching and learning of NOS are discussed.

The novel imidazopyridine 2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine (BYK191023) is a highly selective inhibitor of the inducible nitric-oxide synthase.

PubMed

Strub, Andreas; Ulrich, Wolf-Rüdiger; Hesslinger, Christian; Eltze, Manfrid; Fuchss, Thomas; Strassner, Jochen; Strand, Susanne; Lehner, Martin D; Boer, Rainer

2006-01-01

We have identified imidazopyridine derivatives as a novel class of NO synthase inhibitors with high selectivity for the inducible isoform. 2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine (BYK191023) showed half-maximal inhibition of crudely purified human inducible (iNOS), neuronal (nNOS), and endothelial (eNOS) NO synthases at 86 nM, 17 microM, and 162 microM, respectively. Inhibition of inducible NO synthase was competitive with l-arginine, pointing to an interaction of BYK191023 with the catalytic center of the enzyme. In radioligand and surface plasmon resonance experiments, BYK191023 exhibited an affinity for iNOS, nNOS, and eNOS of 450 nM, 30 microM, and >500 microM, respectively. Inhibition of cellular nitrate/nitrite synthesis in RAW, rat mesangium, and human embryonic kidney 293 cells after iNOS induction showed 40- to 100-fold higher IC(50) values than at the isolated enzyme, in agreement with the much higher l-arginine concentrations in cell culture media and inside intact cells. BYK191023 did not show any toxicity in various rodent and human cell lines up to high micromolar concentrations. The inhibitory potency of BYK191023 was tested in isolated organ models of iNOS (lipopolysaccharide-treated and phenylephrine-precontracted rat aorta; IC(50) = 7 microM), eNOS (arecaidine propargyl ester-induced relaxation of phenylephrine-precontracted rat aorta; IC(50) > 100 microM), and nNOS (field-stimulated relaxation of phenylephrine-precontracted rabbit corpus cavernosum; IC(50) > 100 microM). These data confirm the high selectivity of BYK191023 for iNOS over eNOS and nNOS found at isolated enzymes. In summary, we have identified a new highly selective iNOS inhibitor structurally unrelated to known compounds and l-arginine. BYK191023 is a valuable tool for the investigation of iNOS-mediated effects in vitro and in vivo.

Assessment of the effectiveness of physical activity interventions in the Brazilian Unified Health System.

PubMed

Ribeiro, Evelyn Helena Corgosinho; Garcia, Leandro Martin Totaro; Salvador, Emanuel Péricles; Costa, Evelyn Fabiana; Andrade, Douglas Roque; Latorre, Maria do Rosario Dias de Oliveira; Florindo, Alex Antonio

2017-06-26

To assess the effect of interventions on the levels of physical activity of healthy adults, users of the Brazilian Unified Health System and attended by the Family Health Strategy. Non-randomized experimental study with 157 adults allocated in three groups: 1) physical exercise classes (n = 54), 2) health education (n = 54), 3) control (n = 49). The study lasted for18 months, with 12 months of interventions and six months of follow-up after intervention. Assessments took place at the beginning, in the 12 months, and in the 18 months of study. Physical activity has been assessed by questionnaires and accelerometry. For the analyses, we have used the intention-to-treat principle and generalized estimating equations. After 12 months, both intervention groups have increased the minutes of weekly leisure time physical activity and annual scores of physical exercise, leisure and transport-related physical activity. The exercise class group has obtained the highest average annual physical exercises score when compared to the other groups (p < 0.001). In the follow-up period, the exercise class group reduced its annual score (average: -0.3; 95%CI -0.5--0.1), while the health education group increased this score (average: 0.2; 95%CI 0.1-0.4). There have been no differences in the levels of physical activity measured by accelerometry. The interventions have been effective in increasing the practice of physical activity. However, we have observed that the health education intervention was more effective for maintaining the practice of physical activity in the period after intervention. We recommend the use of both interventions to promote physical activity in the Brazilian Unified Health System, according to the local reality of professionals, facilities, and team objectives. Avaliar o efeito de intervenções nos níveis de atividade física de adultos saudáveis, usuários do Sistema Único de Saúde e atendidos pela Estratégia de Saúde da Família. Estudo experimental, não randomizado, com 157 adultos alocados em três grupos: 1) classes de exercícios físicos (n = 54); 2) educação em saúde (n = 54); 3) controle (n = 49). O estudo teve duração de 18 meses, sendo 12 meses de intervenções e seis meses de acompanhamento pós-intervenção. As avaliações ocorreram no início, nos 12 e nos 18 meses de estudo. A atividade física foi avaliada por questionários e por acelerometria. Para as análises, utilizaram-se o princípio de intenção de tratar e equações de estimativas generalizadas. Após 12 meses, ambos os grupos de intervenção aumentaram os minutos semanais de atividade física no lazer e os escores anuais de exercícios físicos, de lazer e de deslocamento. O grupo das classes de exercícios físicos obteve maior média de escore anual de exercícios físicos em comparação com os outros grupos (p < 0,001). No período pós-intervenção, o grupo de classes de exercícios físicos reduziu o escore anual de exercícios físicos (média: -0,3; IC95% -0,5--0,1), enquanto o grupo de educação em saúde aumentou este escore (média: 0,2; IC95% 0,1-0,4). Não houve diferenças nos níveis de atividade física mensurados por acelerometria. As intervenções foram efetivas para aumentar a prática de atividade física. No entanto, observou-se que a intervenção de educação em saúde foi mais efetiva para a manutenção da prática de atividade física no período pós-intervenção. Recomenda-se a utilização de ambas as intervenções para a promoção da atividade física no Sistema Único de Saúde, de acordo com as realidades locais de profissionais, instalações e objetivos das equipes.

Effects of developmental methylphenidate (MPH) treatment on monoamine neurochemistry of male and female rats.

PubMed

Panos, John J; O'Callaghan, James P; Miller, Diane B; Ferguson, Sherry A

2014-01-01

Attention Deficit Hyperactivity Disorder (ADHD) is estimated to affect 4-5% of the adult human population (Kessler et al., 2006; Willcutt, 2012). Often prescribed to attenuate ADHD symptoms (Nair and Moss, 2009), methylphenidate hydrochloride (MPH) can have substantial positive effects. However, there is a paucity of literature regarding its use during pregnancy. Thus, adult women with ADHD face a difficult decision when contemplating pregnancy. In this study, pregnant Sprague-Dawley rats were orally treated a total of 0 (water), 6 (low), 18 (medium), or 42 (high) mg MPH/kg body weight/day (divided into three doses) on gestational days 6-21 (i.e., the low dose received 2 mg MPH/kg body weight 3×/day). Offspring were orally treated with the same daily dose as their dam (divided into two doses) on postnatal days (PNDs) 1-21. One offspring/sex/litter was sacrificed at PND 22 or PND 104 (n=6-7/age/sex/treatment group) and the striatum was quickly dissected and frozen. High Performance Liquid Chromatography (HPLC) coupled to a Photo Diode Array detector (PDA) was used to analyze monoamine content in the striatum of one side while a sandwich ELISA was used to analyze tyrosine hydroxylase (TH) from the other side. Age significantly affected monoamine and metabolite content as well as turnover ratios (i.e., DA, DOPAC, HVA, DOPAC/DA, HVA/DA, 5-HT and 5-HIAA); however, there were no significant effects of sex. Adult rats of the low MPH group had higher DA levels than control adults (p<0.05). At both ages, subjects of the low MPH group had higher TH levels than controls (p<0.05), although neither effect (i.e., higher DA or TH levels) exhibited an apparent dose-response. PND 22 subjects of the high MPH treatment group had higher ratios of HVA/DA and DOPAC/DA than same-age control subjects (p<0.05). The increased TH levels of the low MPH group may be related to the increased DA levels of adult rats. While developmental MPH treatment appears to have some effects on monoamine system development, further studies are required to determine if these alterations manifest as functional changes in behavior. Published by Elsevier Inc.

Views of nature of science questionnaire: Toward valid and meaningful assessment of learners' conceptions of nature of science

NASA Astrophysics Data System (ADS)

Lederman, Norm G.; Abd-El-Khalick, Fouad; Bell, Randy L.; Schwartz, Renée S.

2002-08-01

Helping students develop informed views of nature of science (NOS) has been and continues to be a central goal for kindergarten through Grade 12 (K-12) science education. Since the early 1960s, major efforts have been undertaken to enhance K-12 students and science teachers' NOS views. However, the crucial component of assessing learners' NOS views remains an issue in research on NOS. This article aims to (a) trace the development of a new open-ended instrument, the Views of Nature of Science Questionnaire (VNOS), which in conjunction with individual interviews aims to provide meaningful assessments of learners' NOS views; (b) outline the NOS framework that underlies the development of the VNOS; (c) present evidence regarding the validity of the VNOS; (d) elucidate the use of the VNOS and associated interviews, and the range of NOS aspects that it aims to assess; and (e) discuss the usefulness of rich descriptive NOS profiles that the VNOS provides in research related to teaching and learning about NOS. The VNOS comes in response to some calls within the science education community to go back to developing standardized forced-choice paper and pencil NOS assessment instruments designed for mass administrations to large samples. We believe that these calls ignore much of what was learned from research on teaching and learning about NOS over the past 30 years. The present state of this line of research necessitates a focus on individual classroom interventions aimed at enhancing learners' NOS views, rather than on mass assessments aimed at describing or evaluating students' beliefs.

NO-Synthase Activity in Patients with Coronary Heart Disease Associated with Hypertension of Different Age Groups.

PubMed

Besedina, Anna

2016-01-01

Coronary heart disease is the leading cause of death and disability worldwide. Hypertension is a major independent risk factor for the development of CHD. Abnormalities in NO generation or activity have been proposed as a major mechanism of CHD. The purpose of this article is to determine the activity of eNOS and iNOS in patients with isolated CHD and CHD associated with HT of different age groups. Fifty patients with isolated CHD and 42 patients with CHD associated with HT were enrolled in this study. NOS activity was determined by nitrite anion formed in the reaction. A statistically significant increase in iNOS activity is observed in elderly donors. In patients with isolated coronary heart disease cNOS activity is statistically significantly reduced with respect to the control group. The reduction of enzymatic activity of cNOS is more expressed in elderly patients than in middle-aged patients with coronary heart disease. Alterations in eNOS activity are more expressed in patients with coronary heart disease associated with hypertension than in patients with isolated coronary heart disease. Against the background of cNOS inhibition in the patients, a sharp increase in iNOS activity is observed. It has been shown that disturbance of endothelial function in patients with coronary heart disease associated with hypertension is characterized by reduced endothelial NO synthesis by cNOS and increased systemic NO synthesis due to increased iNOS activity. It has been found that the lack of endothelial NO and hyperproduction of »harmful« NO by iNOS are more expressed in elderly patients.

DISSECTING STRUCTURAL AND ELECTRONIC EFFECTS IN INDUCIBLE NITRIC OXIDE SYNTHASE

PubMed Central

Hannibal, Luciana; Page, Richard C.; Haque, Mohammad Mahfuzul; Bolisetty, Karthik; Yu, Zhihao; Misra, Saurav; Stuehr, Dennis J.

2015-01-01

Nitric oxide synthases (NOS) are haem-thiolate enzymes that catalyse the conversion of L-Arginine (LArg) into NO and citrulline. Inducible NOS (iNOS) is responsible for delivery of NO in response to stressors during inflammation. The catalytic performance of iNOS is proposed to rely mainly on the haem midpoint potential and the ability of the substrate L-Arg to provide an H-bond for oxygen activation (O-O scission). We present a comparative study of native iNOS versus iNOS-mesohaem, and investigate the formation of a low-spin ferric haem-aquo or -hydroxo species (P) in iNOS mutant W188H substituted with mesohaem. iNOS-mesohaem and W188H-mesohaem were stable and dimeric, and presented substrate-binding affinities comparable to their native counterparts. Single turnover reactions catalysed by iNOSoxy with LArg (first reaction step) or N-hydroxyarginine (second reaction step) showed that mesohaem substitution triggered faster rates of FeIIO2 conversion and altered other key kinetic parameters. We elucidated the first crystal structure of a NOS substituted with mesohaem and found essentially identical features compared to the structure of iNOS carrying native haem. This facilitated the dissection of structural and electronic effects. Mesohaem substitution substantially reduced the build-up of species P in W188H iNOS during catalysis, thus increasing its proficiency toward NO synthesis. The marked structural similarities of iNOSoxy containing native haem or mesohaem indicate that the kinetic behaviour observed in mesohaem-substituted iNOS is most heavily influenced by electronic effects rather than structural alterations. PMID:25608846

Differential regulation of glomerular and interstitial endothelial nitric oxide synthase expression in the kidney of hibernating ground squirrel.

PubMed

Sandovici, Maria; Henning, Robert H; Hut, Roelof A; Strijkstra, Arjen M; Epema, Anne H; van Goor, Harry; Deelman, Leo E

2004-09-01

Hibernating animals transiently reduce renal function during their hypothermic periods (torpor), while completely restoring it during their periodical rewarming to euthermia (arousal). Moreover, structural integrity of the kidney is preserved throughout the hibernation. Nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) is a crucial vasodilatory mediator and a protective factor in the kidney. We investigated renal NOS expression in hibernating European ground squirrels after 1 day and 7 days of torpor (torpor short, TS, and torpor long, TL, respectively), at 1.5 and at 10 h of rewarming (arousal short, AS, and arousal long, AL, respectively), and in continuously euthermic animals after hibernation (EU). For that purpose, we performed NOS activity assay, immunohistochemistry and real-time PCR analysis. Immunohistochemistry revealed a decreased glomerular eNOS expression in hibernating animals (TS, TL, AS, and AL) compared to non-hibernating animals (EU, p < 0.05), whereas no difference was found in the expression of interstitial eNOS. Expression of iNOS and nNOS did not differ between all groups. The reduced glomerular eNOS was associated with a significantly lower eNOS mRNA levels and NOS activity of whole kidney during torpor and arousal (TS, TL, AS, and AL) compared to EU. In all methods used, torpid and aroused squirrels did not differ. These results demonstrate differential regulation of eNOS in glomeruli and interstitium of hibernating animals, which is unaffected during arousal. The differential regulation of eNOS may serve to reduce ultrafiltration without jeopardizing tubular structures during hibernation.

Folic acid modulates eNOS activity via effects on posttranslational modifications and protein–protein interactions☆

PubMed Central

Taylor, Sarah Y.; Dixon, Hannah M.; Yoganayagam, Shobana; Price, Natalie; Lang, Derek

2013-01-01

Folic acid enhances endothelial function and improves outcome in primary prevention of cardiovascular disease. The exact intracellular signalling mechanisms involved remain elusive and were therefore the subject of this study. Particular focus was placed on folic acid-induced changes in posttranslational modifications of endothelial nitric oxide synthase (eNOS). Cultured endothelial cells were exposed to folic acid in the absence or presence of phosphatidylinositol-3' kinase/Akt (PI3K/Akt) inhibitors. The phosphorylation status of eNOS was determined via western blotting. The activities of eNOS and PI3K/Akt were evaluated. The interaction of eNOS with caveolin-1, Heat-Shock Protein 90 and calmodulin was studied using co-immunoprecipitation. Intracellular localisation of eNOS was investigated using sucrose gradient centrifugation and confocal microscopy. Folic acid promoted eNOS dephosphorylation at negative regulatory sites, and increased phosphorylation at positive regulatory sites. Modulation of phosphorylation status was concomitant with increased cGMP concentrations, and PI3K/Akt activity. Inhibition of PI3K/Akt revealed specific roles for this kinase pathway in folic acid-mediated eNOS phosphorylation. Regulatory protein and eNOS protein associations were altered in favour of a positive regulatory effect in the absence of bulk changes in intracellular eNOS localisation. Folic acid-mediated eNOS activation involves the modulation of eNOS phosphorylation status at multiple residues and positive changes in important protein–protein interactions. Such intracellular mechanisms may in part explain improvements in clinical vascular outcome following folic acid treatment. PMID:23796957

Interaction of AR and iNOS in lens epithelial cell: A new pathogenesis and potential therapeutic targets of diabetic cataract.

PubMed

Li, Xue; Liu, Wenping; Huang, Xinduo; Xiong, Jianping; Wei, Xiaoyong

2017-02-01

Although there is significant interest in revealing the role of aldose reductase (AR) and inducible nitric oxide synthase (iNOS) in diabetic cataract (DC), the interaction of AR and iNOS remains unknown. The aim of this study is to investigate the pathogenesis mechanisms and explore as a new potential therapeutic targets for DC. This study investigated the interaction of AR-iNOS through the methods of enzyme kinetics, molecular docking and molecular dynamics simulation, co-immunoprecipitation and fluorescence resonance energy transfer (FRET). The IC50 of AR for inhibition of iNOS activity is 0.04 μM, and the IC50 of iNOS for inhibition of AR activity is 0.042 μM through enzyme kinetics; the interface showed that ARG99 on AR and GLU317 on iNOS played the key roles in the interaction of AR-iNOS predicted by molecular docking and molecular dynamics simulation. Co-immunoprecipitation of protein complexes in human lens epithelial cell (HLEC) demonstrated that AR could association with iNOS in cell; and the interaction distance of AR-iNOS was 6.50 ± 0.22 nm detected by FRET. This study exhibited a direct inhibition interaction between AR and iNOS in HLECs. It is the first report of inhibition interaction between AR and iNOS, suggesting a new pathophysiological mechanism and providing a new insight into the therapeutic mechanism of DC. Copyright © 2017 Elsevier Inc. All rights reserved.

Transfer of Nature of Science Understandings into Similar Contexts: Promises and Possibilities of an Explicit Reflective Approach

NASA Astrophysics Data System (ADS)

Khishfe, Rola

2013-11-01

The purpose of this study was to (a) investigate the effectiveness of explicit nature of science (NOS) instruction in the context of controversial socioscientific issues and (b) explore whether the transfer of acquired NOS understandings, which were explicitly taught in the context of one socioscientific context, into other similar contexts (familiar and unfamiliar) was possible. Participants were 10th grade students in two intact sections at one high school. The treatment involved teaching a six-week unit about genetic engineering. For one group (non-NOS group), there was no explicit instruction about NOS. For the other group (NOS group), explicit instruction about three NOS aspects (subjective, empirical, and tentative) was dispersed across the genetic engineering unit. A questionnaire including two open-ended scenarios, in conjunction with semi-structured interviews, was used to assess the change in participants' understandings of NOS and their ability to transfer their acquired understandings into similar contexts. The first scenario involved a familiar context about genetically modified food and the second one focused on an unfamiliar context about water fluoridation. Results showed no improvement in NOS understandings of participants in the non-NOS group in relation to the familiar and unfamiliar contexts. On the other hand, there was a general improvement in the NOS understandings of participants in the NOS group in relation to both the familiar and unfamiliar contexts. Implications about the transfer of participants' acquired NOS understandings on the basis of the distance between the context of learning and that of application are highlighted and discussed in link with the classroom learning environment.

Preliminary results of in situ laser-induced breakdown spectroscopy for the first wall diagnostics on EAST

NASA Astrophysics Data System (ADS)

Hu, Zhenhua; Li, Cong; Xiao, Qingmei; Liu, Ping; Fang, Ding; Mao, Hongmin; Wu, Jing; Zhao, Dongye; Ding, Hongbin; Luo, Guang-Nan; EAST Team

2017-02-01

Post-mortem methods cannot fulfill the requirement of monitoring the lifetime of the plasma facing components (PFC) and measuring the tritium inventory for the safety evaluation. Laser-induced breakdown spectroscopy (LIBS) is proposed as a promising method for the in situ study of fuel retention and impurity deposition in a tokamak. In this study, an in situ LIBS system was successfully established on EAST to investigate fuel retention and impurity deposition on the first wall without the need of removal tiles between plasma discharges. Spectral lines of D, H and impurities (Mo, Li, Si, … ) in laser-induced plasma were observed and identified within the wavelength range of 500-700 nm. Qualitative measurements such as thickness of the deposition layers, element depth profile and fuel retention on the wall are obtained by means of in situ LIBS. The results demonstrated the potential applications of LIBS for in situ characterization of fuel retention and co-deposition on the first wall of EAST. Supported by the National Magnetic Confinement Fusion Science Program of China (Nos. 2013GB105002, 2015GB109001, and 2013GB109005), National Natural Science Foundation of China (Nos. 11575243, 11605238, 11605023), Chinesisch-Deutsches Forschungs Project (GZ765), and Korea Research Council of Fundamental Science and Technology (KRCF) under the international collaboration & research in Asian countries (PG1314).

SOD1 suppresses maternal hyperglycemia-increased iNOS expression and consequent nitrosative stress in diabetic embryopathy

PubMed Central

Weng, Hongbo; Li, Xuezheng; Reece, E. Albert; Yang, Peixin

2012-01-01

Objectives Hyperglycemia induces oxidative stress and increases inducible nitric oxide synthase (iNOS) expression. We hypothesized that oxidative stress is responsible for hyperglycemia-induced iNOS expression. Study Design iNOS-luciferase activities, nitrosylated protein, lipidperoxidation markers 4-HNE and MDA were determined in PYS-2 cells exposed to 5 mM glucose or high glucose (25 mM) with or without SOD1 (copper zinc superoxide dismutase 1) treatment. Levels of iNOS protein and mRNA, nitrosylated protein, and cleaved caspase-3 and -8 were assessed in wild-type embryos and SOD1 overexpressing embryos from non-diabetic and diabetic dams. Results SOD1 treatment diminished high glucose-induced oxidative stress, as evidenced by 4-HNE and MDA reductions, and it blocked high glucose-increased iNOS expression, iNOS-luciferase activities, and nitrosylated protein. in vivo SOD1 overexpression suppressed hyperglycemia-increased iNOS expression and nitrosylated protein, and it blocked caspase-3 and -8 cleavage. Conclusions We conclude that oxidative stress induces iNOS expression, nitrosative stress, and apoptosis in diabetic embryopathy. PMID:22425406

SOD1 suppresses maternal hyperglycemia-increased iNOS expression and consequent nitrosative stress in diabetic embryopathy.

PubMed

Weng, Hongbo; Li, Xuezheng; Reece, E Albert; Yang, Peixin

2012-05-01

Hyperglycemia induces oxidative stress and increases inducible nitric oxide synthase (iNOS) expression. We hypothesized that oxidative stress is responsible for hyperglycemia-induced iNOS expression. iNOS-luciferase activities, nitrosylated protein, and lipid peroxidation markers 4-hydroxynonenal and malondialdehyde were determined in parietal yolk sac-2 cells exposed to 5 mmol/L glucose or high glucose (25 mmol/L) with or without copper zinc superoxide dismutase 1 (SOD1) treatment. Levels of iNOS protein and messenger RNA, nitrosylated protein, and cleaved caspase-3 and -8 were assessed in wild-type embryos and SOD1-overexpressing embryos from nondiabetic and diabetic dams. SOD1 treatment diminished high glucose-induced oxidative stress, as evidenced by 4-hydroxynonenal and malondialdehyde reductions, and it blocked high glucose-increased iNOS expression, iNOS-luciferase activities, and nitrosylated protein. In vivo SOD1 overexpression suppressed hyperglycemia-increased iNOS expression and nitrosylated protein, and it blocked caspase-3 and -8 cleavage. We conclude that oxidative stress induces iNOS expression, nitrosative stress, and apoptosis in diabetic embryopathy. Copyright © 2012 Mosby, Inc. All rights reserved.

Exploring How Second Grade Elementary Teachers Translate Their Nature of Science Views into Classroom Practice After a Graduate Level Nature of Science Course

NASA Astrophysics Data System (ADS)

Deniz, Hasan; Adibelli, Elif

2015-12-01

The main purpose of this study was to explore the factors mediating the translation of second grade teachers' nature of science (NOS) views into classroom practice after completing a graduate level NOS course. Four second grade in-service elementary teachers comprised the sample of this study. Data were collected from several sources during the course of this study. The primary data sources were (a) assessment of the elementary teachers' NOS views before and after the graduate level NOS course using the Views of Nature of Science Questionnaire Version B (VNOS-B) (Lederman et al., 2002) coupled with interviews, and (b) a classroom observation and videotaped recording of the elementary teachers' best NOS lessons coupled with interview. We identified three distinct but related factors that mediated the translation of NOS views into classroom practice: the teachers' perspectives about the developmental appropriateness of the NOS aspect, the teachers' selection of target NOS aspects, and the relative importance placed by teachers on each NOS aspect.

Sleep Behaviors and Sleep Quality in Children with Autism Spectrum Disorders

PubMed Central

Souders, Margaret C.; Mason, Thorton B. A.; Valladares, Otto; Bucan, Maja; Levy, Susan E.; Mandell, David S.; Weaver, Terri E.; Pinto-Martin, Jennifer

2009-01-01

Study Objectives: (1) Compare sleep behaviors of children with autism spectrum disorders (ASD) with sleep behaviors of typically developing (TD) children using the Children's Sleep Habits Questionnaire (CSHQ); (2) compare sleep quality—defined as mean activity, sleep latency, number of awakenings, sleep efficiency and total sleep time—of the cohort of children with ASD and TD, as measured by 10 nights of actigraphy; and (3) estimate the prevalence of sleep disturbances in the ASD and TD cohorts. Design: Descriptive cross-sectional study. Setting: The Children's Hospital of Philadelphia. Participants: Randomly selected children from the Regional Autism Center. The ASD cohort of 59 children, aged 4 to 10 years, (26 with autism, 21 with pervasive developmental disorder-not otherwise specified [PDD-NOS], and 12 with Asperger disorder) were compared with 40 TD control subjects. Measurements and Results: The CSHQ, sleep diaries, and 10 nights of actigraphy using the Sadeh algorithm of children with ASD and TD control subjects were compared. CSHQ showed 66.1% of parents of children with ASD (62.5% autism, 76.2% PDD-NOS, 58.3% Asperger disorder) and 45% of parents of the control subjects reported that their children had sleep problems. Actigraphic data showed that 66.7% of children with ASD (75% autism, 52.4% PDD-NOS, 75% Asperger disorder) and 45.9% of the control subjects had disturbed sleep. Conclusions: The prevalence estimate of 45% for mild sleep disturbances in the TD cohort highlights pediatric sleep debt as a public health problem of concern. The prevalence estimate of 66% for moderate sleep disturbances in the ASD cohort underscores the significant sleep problems that the families of these children face. The predominant sleep disorders in the ASD cohort were behavioral insomnia sleep-onset type and insomnia due to PDD. Citation: Souders MC; Mason TBA; Valladares O; Bucan M; Levy SE; Mandell DS; Weaver TE; Pinto-Martin D. Sleep behaviors and sleep quality in children with autism spectrum disorders. SLEEP 2009;32(12):1566-1578. PMID:20041592

NEW TECHNIQUE FOR OBESITY SURGERY: INTERNAL GASTRIC PLICATION TECHNIQUE USING INTRAGASTRIC SINGLE-PORT (IGS-IGP) IN EXPERIMENTAL MODEL.

PubMed

Müller, Verena; Fikatas, Panagiotis; Gül, Safak; Noesser, Maximilian; Fuehrer, Kirs Ten; Sauer, Igor; Pratschke, Johann; Zorron, Ricardo

2017-01-01

Bariatric surgery is currently the most effective method to ameliorate co-morbidities as consequence of morbidly obese patients with BMI over 35 kg/m2. Endoscopic techniques have been developed to treat patients with mild obesity and ameliorate comorbidities, but endoscopic skills are needed, beside the costs of the devices. To report a new technique for internal gastric plication using an intragastric single port device in an experimental swine model. Twenty experiments using fresh pig cadaver stomachs in a laparoscopic trainer were performed. The procedure was performed as follow in ten pigs: 1) volume measure; 2) insufflation of the stomach with CO2; 3) extroversion of the stomach through the simulator and installation of the single port device (Gelpoint Applied Mini) through a gastrotomy close to the pylorus; 4) performance of four intragastric handsewn 4-point sutures with Prolene 2-0, from the gastric fundus to the antrum; 5) after the performance, the residual volume was measured. Sleeve gastrectomy was also performed in further ten pigs and pre- and post-procedure gastric volume were measured. The internal gastric plication technique was performed successfully in the ten swine experiments. The mean procedure time was 27±4 min. It produced a reduction of gastric volume of a mean of 51%, and sleeve gastrectomy, a mean of 90% in this swine model. The internal gastric plication technique using an intragastric single port device required few skills to perform, had low operative time and achieved good reduction (51%) of gastric volume in an in vitro experimental model. A cirurgia bariátrica é atualmente o método mais efetivo para melhorar as co-morbidades decorrentes da obesidade mórbida com IMC acima de 35 kg/m2. Técnicas endoscópicas foram desenvolvidas para tratar pacientes com obesidade leve e melhorar as comorbidades, mas habilidades endoscópicas são necessárias, além dos custos. Relatar uma nova técnica para a plicatura gástrica interna utilizando um dispositivo intragástrico de portal único em modelo experimental de suínos. Foram realizados 20 experimentos utilizando estômagos de cadáver de porco fresco em um instrutor laparoscópico. O procedimento foi realizado da seguinte forma em dez porcos: 1) medida de volume; 2) insuflação do estômago com CO2; 3) extroversão do estômago através do simulador e instalação do dispositivo de uma única via (Gelpoint Applied Mini) através de uma gastrotomia próxima ao piloro; 4) realização de quatro suturas de quatro pontos intra-gástricas com Prolene 2-0, desde o fundo gástrico até o antro; 5) medição do volume residual. A gastrectomia vertical foi também realizada em mais dez suínos e o volume gástrico pré e pós-procedimento foi medido. A técnica de plicatura gástrica interna foi realizada com sucesso nos dez experimentos com suínos. O tempo médio do procedimento foi de 27±4 min. Produziu redução do volume gástrico em média de 51%, e a gastrectomia vertical em média de 90% neste modelo suíno. A técnica de plicatura gástrica interna, utilizando um dispositivo intragástrico de uma única via, exigiu poucas habilidades para ser realizada, teve baixo tempo operatório e obteve boa redução (51%) do volume gástrico em um modelo experimental in vitro.

Observational study of the development and evaluation of a fertility preservation patient decision aid for teenage and adult women diagnosed with cancer: the Cancer, Fertility and Me research protocol.

PubMed

Jones, G L; Hughes, J; Mahmoodi, N; Greenfield, D; Brauten-Smith, G; Skull, J; Gath, J; Yeomanson, D; Baskind, E; Snowden, J A; Jacques, R M; Velikova, G; Collins, K; Stark, D; Phillips, R; Lane, S; Bekker, H L

2017-03-13

Women diagnosed with cancer and facing potentially sterilising cancer treatment have to make time-pressured decisions regarding fertility preservation with specialist fertility services while undergoing treatment of their cancer with oncology services. Oncologists identify a need for resources enabling them to support women's fertility preservation decisions more effectively; women report wanting more specialist information to make these decisions. The overall aim of the 'Cancer, Fertility and Me' study is to develop and evaluate a new evidence-based patient decision aid (PtDA) for women with any cancer considering fertility preservation to address this unmet need. This is a prospective mixed-method observational study including women of reproductive age (16 years +) with a new diagnosis of any cancer across two regional cancer and fertility centres in Yorkshire, UK. The research involves three stages. In stage 1, the aim is to develop the PtDA using a systematic method of evidence synthesis and multidisciplinary expert review of current clinical practice and patient information. In stage 2, the aim is to assess the face validity of the PtDA. Feedback on its content and format will be ascertained using questionnaires and interviews with patients, user groups and key stakeholders. Finally, in stage 3 the acceptability of using this resource when integrated into usual cancer care pathways at the point of cancer diagnosis and treatment planning will be evaluated. This will involve a quantitative and qualitative evaluation of the PtDA in clinical practice. Measures chosen include using count data of the PtDAs administered in clinics and accessed online, decisional and patient-reported outcome measures and qualitative feedback. Quantitative data will be analysed using descriptive statistics, paired sample t-tests and CIs; interviews will be analysed using thematic analysis. Research Ethics Committee approval (Ref: 16/EM/0122) and Health Research Authority approval (Ref: 194751) has been granted. Findings will be published in open access peer-reviewed journals, presented at conferences for academic and health professional audiences, with feedback to health professionals and program managers. The Cancer, Fertility and Me patient decision aid (PtDA) will be disseminated via a diverse range of open-access media, study and charity websites, professional organisations and academic sources. External endorsement will be sought from the International Patient Decision Aid Standards (IPDAS) Collaboration inventory of PtDAs and other relevant professional organisations, for example, the British Fertility Society. NCT02753296; pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Phospho-eNOS Ser-1176 is associated with the nucleoli and the Golgi complex in C6 rat glioma cells.

PubMed

Klinz, Franz-Josef; Herberg, Natalie; Arnhold, Stefan; Addicks, Klaus; Bloch, Wilhelm

2007-06-29

Enzymatic activity of endothelial nitric oxide synthase (eNOS) is controlled by posttranslational modifications, protein-protein interactions, and subcellular localization. For example, N-terminal fatty acid modifications target eNOS to the Golgi complex where it becomes phosphorylated. We show here by immunofluorescence analysis that phospho-eNOS Ser-1176 is enriched in the perinuclear region of interphase C6 rat glioma cells. Confocal double immunofluorescence microscopy with the Golgi marker protein 58K revealed that phospho-eNOS Ser-1176 is associated with the Golgi complex. Surprisingly, we observed several spots in the nucleus of C6 cells that were positive for phospho-eNOS Ser-1176. Confocal double immunofluorescence analysis with the nucleolus marker protein fibrillarin revealed that within the nucleus phospho-eNOS Ser-1176 is exclusively associated with the nucleoli. It is known that in mitotic cells nucleoli are lost during prophase and rebuild during telophase. In agreement with this, we find no nucleoli-like distribution of phospho-eNOS Ser-1176 in metaphase and anaphase C6 glioma cells. Our finding that phospho-eNOS Ser-1176 is selectively associated with the nucleoli points to a so far unknown role for eNOS in interphase glioma cells.

[Expressional change of nitric oxide synthases in dorsal root ganglia of cats after selective dorsal rhizotomy].

PubMed

Qin, Hua-li; Zhou, Xue; Zhang, Wei; Chen, Si-xiu

2004-01-01

To examine the expressional change of nitric oxide synthase (NOS) in the injured dorsal root ganglia (DRG) and the ipsilateral adjacent uninjured DRG after selective dorsal rhizotomy. Immunochemical ABC method was used to detect the distribution of immunoreaction complex of NOS isoforms--nNOS and eNOS, and quantitative analysis was conducted to get the number of nNOS-immunoreactivity (nNOS-IR) neurons in normal DRG, dorsal rhizotomized DRG and spared DRG from adult cats on the 6th day after operation. This operating model was made by rhizotomizing unilateral L1-L5 dorsal roots and leaving L6 as a spared root. nNOS-immunoreactants were mainly distributed in the small-sized neurons in the DRG of cat. The percentage of nNOS-expressing small-sized neurons increased in the deafferentated L5 DRG (29.74%) when compared with the contralateral DRG (19.35%), and it also increased in the spared DRG (24.22%), compared with the contralateral DRG (18.61%). eNOS-IR was not observed in the DRG of adult cats. nNOS/NO up-regulated in DRG neurons is involved in a wide variety of biological functions under physiological and lesion-induced pathophysiological conditions in nerve system.

Maternal Nanos-Dependent RNA Stabilization in the Primordial Germ Cells of Drosophila Embryos.

PubMed

Sugimori, Seiko; Kumata, Yuji; Kobayashi, Satoru

2018-01-01

Nanos (Nos) is an evolutionary conserved protein expressed in the germline of various animal species. In Drosophila, maternal Nos protein is essential for germline development. In the germline progenitors, or the primordial germ cells (PGCs), Nos binds to the 3' UTR of target mRNAs to repress their translation. In contrast to this prevailing role of Nos, here we report that the 3' UTR of CG32425 mRNA mediates Nos-dependent RNA stabilization in PGCs. We found that the level of mRNA expressed from a reporter gene fused to the CG32425 3' UTR was significantly reduced in PGCs lacking maternal Nos (nos PGCs) as compared with normal PGCs. By deleting the CG32425 3' UTR, we identified the region required for mRNA stabilization, which includes Nos-binding sites. In normal embryos, CG32425 mRNA was maternally supplied into PGCs and remained in this cell type during embryogenesis. However, as expected from our reporter assay, the levels of CG32425 mRNA and its protein product expressed in nos PGCs were lower than in normal PGCs. Thus, we propose that Nos protein has dual functions in translational repression and stabilization of specific RNAs to ensure proper germline development. © 2017 Japanese Society of Developmental Biologists.

Nitric oxide synthase during early embryonic development in silkworm Bombyx mori: Gene expression, enzyme activity, and tissue distribution.

PubMed

Kitta, Ryo; Kuwamoto, Marina; Yamahama, Yumi; Mase, Keisuke; Sawada, Hiroshi

2016-12-01

To elucidate the mechanism for embryonic diapause or the breakdown of diapause in Bombyx mori, we biochemically analyzed nitric oxide synthase (NOS) during the embryogenesis of B. mori. The gene expression and enzyme activity of B. mori NOS (BmNOS) were examined in diapause, non-diapause, and HCl-treated diapause eggs. In the case of HCl-treated diapause eggs, the gene expression and enzyme activity of BmNOS were induced by HCl treatment. However, in the case of diapause and non-diapause eggs during embryogenesis, changes in the BmNOS activity and gene expressions did not coincide except 48-60 h after oviposition in diapause eggs. The results imply that changes in BmNOS activity during the embryogenesis of diapause and non-diapause eggs are regulated not only at the level of transcription but also post-transcription. The distribution and localization of BmNOS were also investigated with an immunohistochemical technique using antibodies against the universal NOS; the localization of BmNOS was observed mainly in the cytoplasm of yolk cells in diapause eggs and HCl-treated diapause eggs. These data suggest that BmNOS has an important role in the early embryonic development of the B. mori. © 2016 Japanese Society of Developmental Biologists.

Face, content, construct, and concurrent validity of a novel robotic surgery patient-side simulator: the Xperience™ Team Trainer.

PubMed

Xu, Song; Perez, Manuela; Perrenot, Cyril; Hubert, Nicolas; Hubert, Jacques

2016-08-01

To determine the face, content, construct, and concurrent validity of the Xperience™ Team Trainer (XTT) as an assessment tool of robotic surgical bed-assistance skills. Subjects were recruited during a robotic surgery curriculum. They were divided into three groups: the group RA with robotic bed-assistance experience, the group LS with laparoscopic surgical experience, and the control group without bed-assistance or laparoscopic experience. The subjects first performed two standard FLS exercises on a laparoscopic simulator for the assessment of basic laparoscopic skills. After that, they performed three virtual reality exercises on XTT, and then performed similar exercises on physical models on a da Vinci(®) box trainer. Twenty-eight persons volunteered for and completed the tasks. Most expert subjects agreed on the realism of XTT and the three exercises, and also their interest for teamwork and bed-assistant training. The group RA and the group LS demonstrated a similar level of basic laparoscopic skills. Both groups performed better than the control group on the XTT exercises (p < 0.05). The performance superiority of the group RA over LS was observed but not statistically significant. Correlation of performance was determined between the tests on XTT and on da Vinci(®) box trainer. The introduction of XTT facilitates the training of bedside assistants and emphasizes the importance of teamwork, which may change the paradigm of robotic surgery training in the near future. As an assessment tool of bed-assistance skills, XTT proves face, content, and concurrent validity. However, these results should be qualified considering the potential limitations of this exploratory study with a relatively small sample size. The training modules remain to be developed, and more complex and discriminative exercises are expected. Other studies will be needed to further determine construct validity in the future.

Analysis of the Economic Impact of Cardiovascular Diseases in the Last Five Years in Brazil.

PubMed

Siqueira, Alessandra de Sá Earp; Siqueira-Filho, Aristarco Gonçalves de; Land, Marcelo Gerardin Poirot

2017-07-01

There is growing concern about the economic impact of cardiovascular diseases (CVD) in Brazil and worldwide. To estimate the economic impact of CVD in Brazil in the last five years. The information to estimate CVD costs was taken from national databases, adding the direct costs with hospitalizations, outpatient visits and benefits granted by social security. Indirect costs were added to the calculation, such as loss of income caused by CVD morbidity or mortality. CVD mortality accounts for 28% of all deaths in Brazil in the last five years and for 38% of deaths in the productive age range (18 to 65 years). The estimated costs of CVD were R$ 37.1 billion in 2015, a 17% increase in the period from 2010 to 2015. The estimated costs of premature death due to CVD represent 61% of the total cost of CVD, Direct costs with hospitalizations and consultations were 22%, and costs related to the loss of productivity related to the disease were 15% of the total. Health expenditures in Brazil are estimated at 9.5% of GDP and the average cost of CVD was estimated at 0.7% of GDP. CVD costs have increased significantly in the last five years. It is estimated that CVD costs increase as the Brazilian population ages and the prevalence of CVD increases. Existe uma preocupação crescente com o impacto econômico das doenças cardiovasculares (DCV) no Brasil e no mundo. Estimar o impacto econômico das DCV no Brasil nos últimos cinco anos. As informações para estimar os custos em DCV foram retiradas de bancos de dados nacionais, somando os custos diretos com hospitalizações, atendimentos ambulatoriais e benefícios concedidos pela previdência. Custos indiretos foram acrescidos ao cálculo, como a perda de renda causada pela morbidade ou pela mortalidade da DCV. A mortalidade por DCV representa 28% do total de óbitos ocorridos no Brasil nos últimos cinco anos e atinge 38% dos óbitos na faixa etária produtiva (18 a 65 anos). Os custos estimados por DCV foram de R$ 37,1 bilhões de reais no ano de 2015, um aumento percentual de 17% no período de 2010 a 2015. Os custos estimados pela morte prematura por DCV representam 61% do total de custo por DCV, os custos diretos com internações e consultas foram de 22% e os custos pela perda da produtividade relacionados à doença foram de 15% do total. Os gastos com saúde no Brasil são estimados em 9,5% do PIB e o custo médio das DCV foi estimado em 0,7% do PIB. Os custos com DCV vêm aumentando significativamente nos últimos cinco anos. Estima-se que os custos por DCV aumentem à medida que a população brasileira envelhece e que a prevalência de DCV aumenta.

Low-level laser therapy and Calendula officinalis in repairing diabetic foot ulcers.

PubMed

Carvalho, Ana Flávia Machado de; Feitosa, Maura Cristina Porto; Coelho, Nayana Pinheiro Machado de Freitas; Rebêlo, Veruska Cronemberger Nogueira; Castro, Juçara Gonçalves de; Sousa, Patrícia Regina Gomes de; Feitosa, Valrian Campos; Arisawa, Emilia Angela Lo Schiavo

2016-01-01

To evaluate the effects of low-level laser therapy isolated and associated with Calendula officinalis oil in treating diabetic foot ulcers. An experimental, randomized, controlled, prospective, interventional clinical case study using a quantitative approach. The sample consisted of 32 diabetic patients of both genders. Participants were randomly divided into four groups. Doppler Ultrasound evaluation of the Ankle-Brachial Index, brief pain inventory and analog pain scale were performed at baseline and after 30 days. Reduced pain was observed in the Low-level laser therapy and Low-level laser therapy associated with Essential Fatty Acids groups (p<0.01). Regarding the Ankle-Brachial Index and Doppler Ultrasound, all groups remained stable. By analyzing lesion area reduction, Low-level laser therapy associated with Essential fatty acids group showed a significance of p=0.0032, and the Low-level laser therapy group showed p=0.0428. Low-level laser therapy, performed alone or associated with the Calendula officinalis oil was effective in relieving pain and accelerating the tissue repair process of diabetic foot. Avaliar os efeitos da Terapia a Laser de Baixa Intensidade isolada e associada ao óleo de Calendula officinalis no reparo de úlceras em pé diabético. Estudo de caso clínico, experimental, controlado, randomizado, prospectivo, intervencional, de caráter quantitativo. A amostra foi composta de 32 pacientes diabéticos, de ambos os gêneros. Os participantes foram distribuídos aleatoriamente em quatro grupos. Ultrassom Doppler, avaliação do Índice Tornozelo-Braquial, Inventário breve de dor e escala de dor analógica foram realizados no início e após 30 dias. Houve redução da dor nos grupos Terapia a Laser de Baixa Intensidade e Terapia a Laser de Baixa intensidade associada aos Ácidos Graxos Essenciais, com p<0,01. Quanto ao Índice Tornozelo-Braquial e Ultrassom Doppler, todos os grupos mantiveram-se estáveis. Na análise da redução de área da lesão, o grupo Terapia a Laser de Baixa Intensidade associada aos Ácidos Graxos Essenciais apresentou uma significância p=0,0032, e o grupo Terapia a Laser de Baixa Intensidade, p=0,0428. A Terapia a Laser de Baixa Intensidade, realizada tanto isoladamente quanto associada ao óleo de Calendula officinalis, foi eficaz no alívio da dor e na aceleração do processo de reparo tecidual de pé diabético.

GLP-2: A POORLY UNDERSTOOD MEDIATOR ENROLLED IN VARIOUS BARIATRIC/METABOLIC SURGERY-RELATED PATHOPHYSIOLOGIC MECHANISMS.

PubMed

Cazzo, Everton; Gestic, Martinho Antonio; Utrini, Murillo Pimentel; Chaim, Felipe David Mendonça; Geloneze, Bruno; Pareja, José Carlos; Chaim, Elinton Adami; Magro, Daniéla Oliveira

2016-01-01

Glucagon-like peptide-2 (GLP-2) is a gastrointestinal hormone whose effects are predominantly trophic on the intestinal mucosa. Critically evaluate the current literature on the influence of bariatric/metabolic surgery on the levels of GLP-2 and its potential clinical implications. s: Narrative review through online research on the databases Medline and Lilacs. There were six prospective human studies, two cross-sectional human studies, and three experimental animal studies selected. There is evidence demonstrating significant increase in the levels of GLP-2 following gastric bypass, Scopinaro operation, and sleeve gastrectomy. There are no differences between gastric bypass and sleeve gastrectomy in regards to the increase in the GLP-2 levels. There is no correlation between the postoperative levels of GLP-2 and the occurrence of adequate or insufficient postoperative weight loss. GLP-2 plays significant roles on the regulation of nutrient absorption, permeability of gut mucosa, control of bone resorption, and regulation of satiety. The overall impact of these effects potentially exerts a significant adaptive or compensatory effect within the context of varied bariatric surgical techniques. O peptídeo semelhante ao glucagon-2 (GLP-2) é hormônio gastrointestinal com efeitos predominantemente tróficos sobre a mucosa intestinal. Avaliar criticamente a literatura atual a respeito da cirurgia bariátrica/metabólica sobre os níveis de GLP-2 e suas potenciais implicações clínicas. Revisão narrativa realizada através de pesquisa on-line nas bases de dados Medline e LILACS. Foram selecionados seis estudos prospectivos em humanos, dois transversais em humanos e três experimentais em animais. Existem evidências demonstrando aumento significativo nos níveis de GLP-2 após o bypass gástrico, a operação de Scopinaro e a gastrectomia vertical. Não foram observadas diferenças entre o bypass gástrico e a gastrectomia vertical em relação ao aumento do GLP-2. Não há correlação entre os níveis de GLP-2 e a ocorrência de perda de peso pós-operatória adequada ou insuficiente. O GLP-2 desempenha importantes papel sobre a regulação da absorção de nutrientes, permeabilidade da mucosa intestinal, controle da reabsorção óssea e regulação da saciedade. O impacto combinado destes efeitos potencialmente exerce efeito adaptativo ou compensatório importante no contexto das diferentes técnicas bariátricas.

Does the nature of science influence college students' learning of biological evolution?

NASA Astrophysics Data System (ADS)

Butler, Wilbert, Jr.

This quasi-experimental, mixed-methods study assessed the influence of the nature of science (NOS) instruction on college students' learning of biological evolution. In this research, conducted in two introductory biology courses, in each course the same instruction was employed, with one important exception: in the experimental section students were involved in an explicit, reflective treatment of the nature of science (Explicit, reflective NOS), in the traditional treatment section, NOS was implicitly addressed (traditional treatment). In both sections, NOS aspects of science addressed included is tentative, empirically based, subjective, inferential, and based on relationship between scientific theories and laws. Students understanding of evolution, acceptance of evolution, and understanding of the nature of science were assessed before, during and after instruction. Data collection entailed qualitative and quantitative methods including Concept Inventory for Natural Selection (CINS), Measure of Acceptance of the Theory of Evolution (MATE) survey, Views of nature of Science (VNOS-B survey), as well as interviews, classroom observations, and journal writing to address understand students' views of science and understanding and acceptance of evolution. The quantitative data were analyzed via inferential statistics and the qualitative data were analyzed using grounded theory. The data analysis allowed for the construction and support for four assertions: Assertion 1: Students engaged in explicit and reflective NOS specific instruction significantly improved their understanding of the nature of science concepts. Alternatively, students engaged in instruction using an implicit approach to the nature of science did not improve their understanding of the nature of science to the same degree. The VNOS-B results indicated that students in the explicit, reflective NOS class showed the better understanding of the NOS after the course than students in the implicit NOS class. The increased understanding of NOS demonstrated by students in the explicit, reflective NOS class compared to students in the implicit NOS class can be attributed to the students' engagement in explicit and reflective NOS instruction that was absent in the implicit NOS class. Post VNOS results from students in the explicit, reflective NOS class showed marked improvement in the targeted aspects of NOS (empirical nature of scientific knowledge, inferential nature of scientific knowledge, subjective nature of scientific knowledge, the distinction between scientific law and theory, and the tentative nature of scientific knowledge) compared to the result of the pretest while the scores of students in the implicit NOS class demonstrated little change. Assertion 2: Students in the explicit, reflective NOS class section made greater gains in their understanding of evolution than students in the traditional class. The explicit, reflective NOS class demonstrated a statistically significant improvement in their understanding of biological evolution after the course, while the changes observed in the implicit NOS group were not found to be statistically significant---this despite that the manner in which evolution was taught was held constant across the two sections. Thus, the explicit, reflective NOS approach to the teaching of biological evolution seems to be more effective than many discussed in the literature in supporting student learning about evolution. Assertion 3: The conceptual gains by students in the explicit, reflective NOS course section were allowed by the affective "room" that a sophisticated understanding of the nature of the nature of science provides in a classroom. The data collected from this study collectively indicate that a sophisticated understanding of NOS allows students to recognize the boundaries of science. We argue that an explicit and reflective engagement of the NOS aspects helps the students understand the defining aspects of science better. Assertion 4: A change in students' understanding of evolution does not necessitate a change in students' acceptance of evolution. The results showed that students engaged in explicit and reflective NOS specific instruction significantly improved their understanding of NOS concepts and the understanding of evolution. However, there was not a significant change in acceptance of evolution related to the change in understanding. These results demonstrate that the nature of science instruction plays an important role in the teaching and learning of biological evolution. Nevertheless, this NOS instruction must be explicit and reflective in nature. Students that engage explicitly and reflectively on specific tenets of NOS not only developed a better understanding of the NOS aspects but also a better understanding of biological evolution. Therefore, science teachers in elementary, middle, secondary and post-secondary education should consider implementing an explicit, reflective approach to the nature of science into their science curriculum not only for teaching evolution but for other controversial topics as well. (Abstract shortened by UMI.)

Superoxide and peroxynitrite generation from inducible nitric oxide synthase in macrophages

PubMed Central

Xia, Yong; Zweier, Jay L.

1997-01-01

Superoxide (O2⨪) and nitric oxide (NO) act to kill invading microbes in phagocytes. In macrophages NO is synthesized by inducible nitric oxide synthase (iNOS, NOS 2) from l-arginine (l-Arg) and oxygen; however, O2⨪ was thought to be produced mainly by NADPH oxidase. Electron paramagnetic resonance (EPR) spin trapping experiments performed in murine macrophages demonstrate a novel pathway of O2⨪ generation. It was observed that depletion of cytosolic l-Arg triggers O2⨪ generation from iNOS. This iNOS-mediated O2⨪ generation was blocked by the NOS inhibitor N-nitro-l-arginine methyl ester or by l-Arg, but not by the noninhibitory enantiomer N-nitro-d-arginine methyl ester. In l-Arg-depleted macrophages iNOS generates both O2⨪ and NO that interact to form the potent oxidant peroxynitrite (ONOO−), which was detected by luminol luminescence and whose formation was blocked by superoxide dismutase, urate, or l-Arg. This iNOS-derived ONOO− resulted in nitrotyrosine formation, and this was inhibited by iNOS blockade. iNOS-mediated O2⨪ and ONOO− increased the antibacterial activity of macrophages. Thus, with reduced l-Arg availability iNOS produces O2⨪ and ONOO− that modulate macrophage function. Due to the existence of l-Arg depletion in inflammation, iNOS-mediated O2⨪ and ONOO− may occur and contribute to cytostatic/cytotoxic actions of macrophages. PMID:9192673

Inducible nitric oxide synthase inhibits oxygen consumption in collateral-dependent myocardium

PubMed Central

Chen, Yingjie; Zhang, Ping; Li, Jingxin; Xu, Xin

2013-01-01

Following coronary artery occlusion growth of collateral vessels can provide an effective blood supply to the dependent myocardium. The ischemia, which results in growth of collateral vessels, recruits an inflammatory response with expression of cytokines and growth factors, upregulation of endothelial nitric oxide (NO) synthase (eNOS) in vascular endothelial cells, and expression of inducible nitric oxide synthase (iNOS) in both vessels and cardiac myocytes. Because NO is a potent collateral vessel dilator, this study examined whether NO derived from iNOS or constitutive NOS regulates myocardial blood flow (MBF) in the collateral region. Nonselective NOS inhibition with NG-nitro-l-arginine (LNA) caused vasoconstriction with a significant decrease in MBF to the collateral region during exercise. In contrast, the highly selective iNOS inhibitor 1400W caused a 21 ± 5% increase of MBF in the collateral region. This increase in MBF following selective iNOS blockade was proportionate to an increase in myocardial O2 consumption (MV̇o2). The results suggest that NO produced by iNOS inhibits MV̇o2 in the collateralized region, so that the increase in MBF following iNOS blockade was the result of metabolic vasodilation secondary to an increase in MV̇o2. Thus the coordinated expression of iNOS to restrain MV̇o2 and eNOS to maintain collateral vasodilation act to optimize the O2 supply-demand relationship and protect the collateralized myocardium from ischemia. PMID:24322607

Representing Nature of Science in a Science Textbook: Exploring author-editor-publisher interactions

NASA Astrophysics Data System (ADS)

DiGiuseppe, Maurice

2014-05-01

Current reforms in elementary and secondary science education call for students and teachers to develop more informed views of the nature of science (NOS)-a process in which science textbooks play a significant role. This paper reports on a case study of the development of representations of the NOS in a senior high school chemistry textbook by the book's author, editor, and publisher. The study examines the multiple discourses that arose as the developers reflected on their personal and shared understandings of NOS; squared these with mandated curricula, the educational needs of chemistry students and teachers, and the exigencies of large-scale commercial textbook publishing. As a result, the team developed and incorporated, in the textbook, representations of NOS they believed were the most pedagogically suitable. Analysis of the data in this study indicates that a number of factors significantly influenced the development of representations of NOS, including representational accuracy (the degree to which representations of NOS conformed to informed views of the NOS), representational consistency (the degree to which representations of NOS in different parts of the book conveyed the same meaning), representational appropriateness (the age-, grade-, and reading-level appropriateness of the NOS representations), representational alignment (the degree to which NOS representations aligned with mandated curriculum), representational marketability (the degree to which NOS representations would affect sales of the textbook), and 'Workplace Resources' factors including availability of time, relevant expertise, and opportunities for professional development.

cAMP inhibits inducible nitric oxide synthase expression and NF-kappaB-binding activity in cultured rat hepatocytes.

PubMed

Harbrecht, B G; Taylor, B S; Xu, Z; Ramalakshmi, S; Ganster, R W; Geller, D A

2001-08-01

The inducible nitric oxide synthase (iNOS) is strongly expressed following inflammatory stimuli. Adenosine 3',5'-cyclic monophosphate (cAMP) increases iNOS expression and activity in a number of cell types but decreases cytokine-stimulated iNOS expression in hepatocytes. The mechanisms for this effect are unknown. Rat hepatocytes were stimulated with cytokines to induce iNOS and cultured with cAMP agonists dibutyryl-cAMP (dbcAMP), 8-bromo-cAMP, and forskolin (FSK). Nitric oxide synthesis was assessed by supernatant nitrite levels and iNOS expression was measured by Northern and Western blot analyses. Nuclear factor kappaB binding was assessed by electromobility shift assay. Cyclic AMP dose dependently decreased NO synthesis in response to a combination of proinflammatory cytokines or interleukin-1beta (IL-1beta) alone. The adenylate cyclase inhibitor SQ 22,536 increased cytokine- or IL-1beta-stimulated NO synthesis. dbcAMP decreased iNOS mRNA expression and iNOS protein expression. Both dbcAMP and glucagon decreased iNOS promoter activity in rat hepatocytes transfected with the murine iNOS promoter and decreased DNA binding of the transcription factor NF-kappaB. These data suggest that cAMP is important in hepatocyte iNOS expression and agents that alter cAMP levels may profoundly alter the response of hepatocytes to inflammatory stimuli through effects onthe iNOS promoter region and NF-kappaB. Copyright 2001 Academic Press.

Retinoic acid-induced nNOS expression depends on a novel PI3K/Akt/DAX1 pathway in human TGW-nu-I neuroblastoma cells.

PubMed

Nagl, Florian; Schönhofer, Katrin; Seidler, Barbara; Mages, Jörg; Allescher, Hans-Dieter; Schmid, Roland M; Schneider, Günter; Saur, Dieter

2009-11-01

Neuronal nitric oxide synthase (nNOS)-derived nitric oxide (NO) acts as a neurotransmitter and intracellular signaling molecule in the central and peripheral nervous system. NO regulates multiple processes like neuronal development, plasticity, and differentiation and is a mediator of neurotoxicity. The nNOS gene is highly complex with 12 alternative first exons, exon 1a-1l, transcribed from distinct promoters, leading to nNOS variants with different 5'-untranslated regions. Transcriptional control of the nNOS gene is not understood in detail. To investigate regulation of nNOS gene expression by retinoic acid (RA), we used the human neuroblastoma cell line TGW-nu-I as a model system. We show that RA induces nNOS transcription in a protein synthesis-dependent fashion. We identify the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and the atypical orphan nuclear receptor DAX1 (NR0B1) as critical mediators involved in RA-induced nNOS gene transcription. RA treatment increases DAX1 expression via PI3K/Akt signaling. Upregulation of DAX1 expression in turn induces nNOS transcription in response to RA. These results identify nNOS as a target gene of a novel RA/PI3K/Akt/DAX1-dependent pathway in human neuroblastoma cells and stress the functional importance of the transcriptional regulator DAX1 for nNOS gene expression in response to RA treatment.

Petroleomics: the next grand challenge for chemical analysis.

PubMed

Marshall, Alan G; Rodgers, Ryan P

2004-01-01

Ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry has recently revealed that petroleum crude oil contains heteroatom-containing (N,O,S) organic components having more than 20,000 distinct elemental compositions (C(c)H(h)N(n)O(o)S(s)). It is therefore now possible to contemplate the ultimate characterization of all of the chemical constituents of petroleum, along with their interactions and reactivity, a concept we denote as "petroleomics". Such knowledge has already proved capable of distinguishing petroleum and its distillates according to their geochemical origin and maturity, distillation cut, extraction method, catalytic processing, etc. The key features that have opened up this new field have been (a) ultrahigh-resolution FT-ICR mass analysis, specifically, the capability to resolve species differing in elemental composition by C(3) vs SH(4) (i.e., 0.0034 Da); (b) higher magnetic field to cover the whole mass range at once; (c) dynamic range extension by external mass filtering; and (d) plots of Kendrick mass defect vs nominal Kendrick mass as a means for sorting different compound "classes" (i.e., numbers of N, O, and S atoms), "types" (rings plus double bonds), and alkylation ((-CH(2))(n)) distributions, thereby extending to >900 Da the upper limit for unique assignment of elemental composition based on accurate mass measurement. The same methods are also being applied successfully to analysis of humic and fulvic acids, coals, and other complex natural mixtures, often without prior or on-line chromatographic separation.

Propriedades físicas de condensações densas no Escorpião

NASA Astrophysics Data System (ADS)

Vilas-Boas, J. W. S.; Barbosa, P. R., Jr.; Hickel, G. R.

2003-08-01

O conhecimento das propriedade físicas das condensações das nuvens escuras e sua relação com a dinâmica das núvens é um dos caminhos para o entendimento dos mecanismos de formação de estrelas de massas pequenas. Nesse trabalho, 8 condensações da nuvem escura do Escorpião foram observadas através de transições das moléculas de 13CO, C18O e NH3, utilizando-se os radiotelescopios de 15 m do SEST e 64 m de PARKES. Embora localizadas na superfície de uma bolha com velocidade de expansão entre 12 km/s e 15 km/s (Vilas-Boas et al), as linhas de monóxido de carbono apresentaram características típicas daquelas observadas em nuvens escuras. Em apenas uma condensação, contendo um objeto Pre-Sequência Principal (PMS), foi detectada emissão da molécula de amônia. A comparação direta entre as propriedades dessas condensações densas (núcleos) e aquelas identificadas na Musca, que se caracteriza por ser uma núvem de baixa atividade de formação estelar, mostra que elas têm propriedades idênticas e que as eficiências de formação estelar nos núcleos de ambas as nuvens são similares.

GTP cyclohydrolase I gene transfer augments intracellular tetrahydrobiopterin in human endothelial cells: effects on nitric oxide synthase activity, protein levels and dimerisation.

PubMed

Cai, Shijie; Alp, Nicholas J; McDonald, Denise; Smith, Ian; Kay, Jonathan; Canevari, Laura; Heales, Simon; Channon, Keith M

2002-09-01

Tetrahydrobiopterin (BH4) is an essential cofactor for endothelial nitric oxide synthase (eNOS) activity. BH4 levels are regulated by de novo biosynthesis; the rate-limiting enzyme is GTP cyclohydrolase I (GTPCH). BH4 activates and promotes homodimerisation of purified eNOS protein, but the intracellular mechanisms underlying BH4-mediated eNOS regulation in endothelial cells remain less clear. We aimed to investigate the role of BH4 levels in intracellular eNOS regulation, by targeting the BH4 synthetic pathway as a novel strategy to modulate intracellular BH4 levels. We constructed a recombinant adenovirus, AdGCH, encoding human GTPCH. We infected human endothelial cells with AdGCH, investigated the changes in intracellular biopterin levels, and determined the effects on eNOS enzymatic activity, protein levels and dimerisation. GTPCH gene transfer in EAhy926 endothelial cells increased BH4 >10-fold compared with controls (cells alone or control adenovirus infection), and greatly enhanced NO production in a dose-dependent, eNOS-specific manner. We found that eNOS was principally monomeric in control cells, whereas GTPCH gene transfer resulted in a striking increase in eNOS homodimerisation. Furthermore, the total amounts of both native eNOS protein and a recombinant eNOS-GFP fusion protein were significantly increased following GTPCH gene transfer. These findings suggest that GTPCH gene transfer is a valid approach to increase BH4 levels in human endothelial cells, and provide new evidence for the relative importance of different mechanisms underlying BH4-mediated eNOS regulation in intact human endothelial cells. Additionally, these observations suggest that GTPCH may be a rational target to augment endothelial BH4 and normalise eNOS activity in endothelial dysfunction states.

Therapeutic effect of enhancing endothelial nitric oxide synthase (eNOS) expression and preventing eNOS uncoupling

PubMed Central

Förstermann, Ulrich; Li, Huige

2011-01-01

Nitric oxide (NO) produced by the endothelium is an important protective molecule in the vasculature. It is generated by the enzyme endothelial NO synthase (eNOS). Similar to all NOS isoforms, functional eNOS transfers electrons from nicotinamide adenine dinucleotide phosphate (NADPH), via the flavins flavin adenine dinucleotide and flavin mononucleotide in the carboxy-terminal reductase domain, to the heme in the amino-terminal oxygenase domain. Here, the substrate L-arginine is oxidized to L-citrulline and NO. Cardiovascular risk factors such as diabetes mellitus, hypertension, hypercholesterolaemia or cigarette smoking reduce bioactive NO. These risk factors lead to an enhanced production of reactive oxygen species (ROS) in the vessel wall. NADPH oxidases represent major sources of this ROS and have been found upregulated in the presence of cardiovascular risk factors. NADPH-oxidase-derived superoxide avidly reacts with eNOS-derived NO to form peroxynitrite (ONOO-). The essential NOS cofactor (6R-)5,6,7,8-tetrahydrobiopterin (BH4) is highly sensitive to oxidation by this ONOO-. In BH4 deficiency, oxygen reduction uncouples from NO synthesis, thereby converting NOS to a superoxide-producing enzyme. Among conventional drugs, compounds interfering with the renin-angiotensin-aldosterone system and statins can reduce vascular oxidative stress and increase bioactive NO. In recent years, we have identified a number of small molecules that have the potential to prevent eNOS uncoupling and, at the same time, enhance eNOS expression. These include the protein kinase C inhibitor midostaurin, the pentacyclic triterpenoids ursolic acid and betulinic acid, the eNOS enhancing compounds AVE9488 and AVE3085, and the polyphenolic phytoalexin trans-resveratrol. Such compounds enhance NO production from eNOS also under pathophysiological conditions and may thus have therapeutic potential. PMID:21198553

Nitric Oxide Synthase and Cyclooxygenase Pathways: A Complex Interplay in Cellular Signaling.

PubMed

Sorokin, Andrey

2016-01-01

The cellular reaction to external challenges is a tightly regulated process consisting of integrated processes mediated by a variety of signaling molecules, generated as a result of modulation of corresponding biosynthetic systems. Both, nitric oxide synthase (NOS) and cyclooxygenase (COX) systems, consist of constitutive forms (NOS1, NOS3 and COX-1), which are mostly involved in housekeeping tasks, and inducible forms (NOS2 and COX-2), which shape the cellular response to stress and variety of bioactive agents. The complex interplay between NOS and COX pathways can be observed at least at three levels. Firstly, products of NOS and Cox systems can mediate the regulation and the expression of inducible forms (NOS2 and COX-2) in response of similar and dissimilar stimulus. Secondly, the reciprocal modulation of cyclooxygenase activity by nitric oxide and NOS activity by prostaglandins at the posttranslational level has been shown to occur. Mechanisms by which nitric oxide can modulate prostaglandin synthesis include direct S-nitrosylation of COX and inactivation of prostaglandin I synthase by peroxynitrite, product of superoxide reaction with nitric oxide. Prostaglandins, conversely, can promote an increased association of dynein light chain (DLC) (also known as protein inhibitor of neuronal nitric oxide synthase) with NOS1, thereby reducing its activity. The third level of interplay is provided by intracellular crosstalk of signaling pathways stimulated by products of NOS and COX which contributes significantly to the complexity of cellular signaling. Since modulation of COX and NOS pathways was shown to be principally involved in a variety of pathological conditions, the dissection of their complex relationship is needed for better understanding of possible therapeutic strategies. This review focuses on implications of interplay between NOS and COX for cellular function and signal integration.

Insights into the arginine paradox: evidence against the importance of subcellular location of arginase and eNOS

PubMed Central

Elms, Shawn; Chen, Feng; Wang, Yusi; Qian, Jin; Askari, Bardia; Yu, Yanfang; Pandey, Deepesh; Iddings, Jennifer; Caldwell, Ruth B.

2013-01-01

Reduced production of nitric oxide (NO) is one of the first indications of endothelial dysfunction and precedes overt cardiovascular disease. Increased expression of Arginase has been proposed as a mechanism to account for diminished NO production. Arginases consume l-arginine, the substrate for endothelial nitric oxide synthase (eNOS), and l-arginine depletion is thought to competitively reduce eNOS-derived NO. However, this simple relationship is complicated by the paradox that l-arginine concentrations in endothelial cells remain sufficiently high to support NO synthesis. One mechanism proposed to explain this is compartmentalization of intracellular l-arginine into distinct, poorly interchangeable pools. In the current study, we investigated this concept by targeting eNOS and Arginase to different intracellular locations within COS-7 cells and also BAEC. We found that supplemental l-arginine and l-citrulline dose-dependently increased NO production in a manner independent of the intracellular location of eNOS. Cytosolic arginase I and mitochondrial arginase II reduced eNOS activity equally regardless of where in the cell eNOS was expressed. Similarly, targeting arginase I to disparate regions of the cell did not differentially modify eNOS activity. Arginase-dependent suppression of eNOS activity was reversed by pharmacological inhibitors and absent in a catalytically inactive mutant. Arginase did not directly interact with eNOS, and the metabolic products of arginase or downstream enzymes did not contribute to eNOS inhibition. Cells expressing arginase had significantly lower levels of intracellular l-arginine and higher levels of ornithine. These results suggest that arginases inhibit eNOS activity by depletion of substrate and that the compartmentalization of l-arginine does not play a major role. PMID:23792682

AP-1 Inhibition by SR 11302 Protects Human Hepatoma HepG2 Cells from Bile Acid-Induced Cytotoxicity by Restoring the NOS-3 Expression

PubMed Central

González-Rubio, Sandra; Linares, Clara I.; Aguilar-Melero, Patricia; Rodríguez-Perálvarez, Manuel; Montero-Álvarez, José L.

2016-01-01

The harmful effects of bile acid accumulation occurring during cholestatic liver diseases have been associated with oxidative stress increase and endothelial nitric oxide synthase (NOS-3) expression decrease in liver cells. We have previously reported that glycochenodeoxycholic acid (GCDCA) down-regulates gene expression by increasing SP1 binding to the NOS-3 promoter in an oxidative stress dependent manner. In the present study, we aimed to investigate the role of transcription factor (TF) AP-1 on the NOS-3 deregulation during GCDCA-induced cholestasis. The cytotoxic response to GCDCA was characterized by 1) the increased expression and activation of TFs cJun and c-Fos; 2) a higher binding capability of these at position -666 of the NOS-3 promoter; 3) a decrease of the transcriptional activity of the promoter and the expression and activity of NOS-3; and 4) the expression increase of cyclin D1. Specific inhibition of AP-1 by the retinoid SR 11302 counteracted the cytotoxic effects induced by GCDCA while promoting NOS-3 expression recovery and cyclin D1 reduction. NOS activity inhibition by L-NAME inhibited the protective effect of SR 11302. Inducible NOS isoform was no detected in this experimental model of cholestasis. Our data provide direct evidence for the involvement of AP-1 in the NOS-3 expression regulation during cholestasis and define a critical role for NOS-3 in regulating the expression of cyclin D1 during the cell damage induced by bile acids. AP-1 appears as a potential therapeutic target in cholestatic liver diseases given its role as a transcriptional repressor of NOS-3. PMID:27490694

Consistency of the Health of the Nation Outcome Scales (HoNOS) at inpatient-to-community transition.

PubMed

Luo, Wei; Harvey, Richard; Tran, Truyen; Phung, Dinh; Venkatesh, Svetha; Connor, Jason P

2016-04-27

The Health of the Nation Outcome Scales (HoNOS) are mandated outcome-measures in many mental-health jurisdictions. When HoNOS are used in different care settings, it is important to assess if setting specific bias exists. This article examines the consistency of HoNOS in a sample of psychiatric patients transitioned from acute inpatient care and community centres. A regional mental health service with both acute and community facilities. 111 psychiatric patients were transferred from inpatient care to community care from 2012 to 2014. Their HoNOS scores were extracted from a clinical database; Each inpatient-discharge assessment was followed by a community-intake assessment, with the median period between assessments being 4 days (range 0-14). Assessor experience and professional background were recorded. The difference of HoNOS at inpatient-discharge and community-intake were assessed with Pearson correlation, Cohen's κ and effect size. Inpatient-discharge HoNOS was on average lower than community-intake HoNOS. The average HoNOS was 8.05 at discharge (median 7, range 1-22), and 12.16 at intake (median 12, range 1-25), an average increase of 4.11 (SD 6.97). Pearson correlation between two total scores was 0.073 (95% CI -0.095 to 0.238) and Cohen's κ was 0.02 (95% CI -0.02 to 0.06). Differences did not appear to depend on assessor experience or professional background. Systematic change in the HoNOS occurs at inpatient-to-community transition. Some caution should be exercised in making direct comparisons between inpatient HoNOS and community HoNOS scores. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Crataegus Special Extract WS 1442 Effects on eNOS and microRNA 155.

PubMed

Wang, Xinwen; Liang, Yan; Shi, Jian; Zhu, Hao-Jie; Bleske, Barry E

2018-04-16

Increased expression of microRNA 155 (miR-155) results in a decrease in endothelial nitric oxide synthase (eNOS) expression and impaired endothelial function. Factors that have been shown to increase expression of miR-155 may be mitigated by WS 1442, an extract of hawthorn leaves and flowers ( Crataegus special extract) that contains a range of pharmacologically active substances including oligomeric proanthocyanidins and flavonoids. The purpose of this study is to determine the effect of WS 1442 on the expression of miR-155 and eNOS in the presence of tumor necrosis factor (TNF- α ). Human umbilical vein endothelial cells (HUVECs) were studied after the exposure to TNF- α , with or without simvastatin (positive control) and WS 1442. The expression levels of eNOS, phosphorylated eNOS, and miR-155 in the different HUVEC treatment groups were determined by western blot and quantitative real-time polymerase chain reaction, respectively. To evaluate the effect of WS 1442 on the eNOS activity, the medium and intracellular nitrate/nitrite (NO) concentrations were also analyzed using a colorimetric Griess assay kit. The results demonstrated that TNF- α upregulated miR-155 expression and decreased eNOS expression and NO concentrations. WS 1442 also increased miR-155 expression and decreased eNOS expression but, unlike TNF- α , increased phosphorylated eNOS expression and NO concentrations. Surprisingly, WS 1442 increased miR-155 expression; however, WS 1442 mitigated the overall negative effect of miR-155 on decreasing eNOS expression by increasing expression of phosphorylated eNOS and resulting in an increase in NO concentrations. In the setting where miR-155 may be expressed, WS 1442 may offer vascular protection by increasing the expression of phosphorylated eNOS. Georg Thieme Verlag KG Stuttgart · New York.

Peroxynitrite induces destruction of the tetrahydrobiopterin and heme in endothelial nitric oxide synthase: transition from reversible to irreversible enzyme inhibition†

PubMed Central

Chen, Weiguo; Druhan, Lawrence J.; Chen, Chun-An; Hemann, Craig; Chen, Yeong-Renn; Berka, Vladimir; Tsai, Ah-Lim; Zweier, Jay L.

2010-01-01

Endothelial nitric oxide synthase (eNOS) is an important regulator of vascular and cardiac function. Peroxynitrite (ONOO−) inactivates eNOS, but questions remain regarding the mechanisms of this process. It has been reported that inactivation is due to oxidation of the eNOS zinc-thiolate cluster, rather than the cofactor tetrahydrobiopterin (BH4); however, this remains highly controversial. Therefore, we investigated the mechanisms of ONOO−-induced eNOS dysfunction and their dose-dependence. Exposure of human eNOS to ONOO− resulted in a dose-dependent loss of activity with a marked destabilization of the eNOS dimer. HPLC analysis indicated that both free and eNOS-bound BH4 were oxidized during exposure to ONOO−; however, full oxidation of protein bound biopterin required higher ONOO− levels. Additionally, ONOO− triggered changes in UV/Visible spectrum and heme content of the enzyme. Pre-incubation of eNOS with BH4 decreased dimer destabilization and heme alteration. Addition of BH4 to the ONOO−-destabilized eNOS dimer only partially rescued enzyme function. In contrast to ONOO− treatment, incubation with the zinc chelator TPEN with removal of enzyme-bound zinc did not change the eNOS activity or stability of the SDS-resistant eNOS dimer, demonstrating that the dimer stabilization induced by BH4 does not require zinc occupancy of the zinc-thiolate cluster. While ONOO− treatment was observed to induce loss of Zn-binding this can not account for the loss of enzyme activity. Therefore, ONOO−-induced eNOS inactivation is primarily due to oxidation of BH4 and irreversible destruction of the heme/heme-center. PMID:20184376

Unexpected nondenitrifier nitrous oxide reductase gene diversity and abundance in soils

PubMed Central

Sanford, Robert A.; Wagner, Darlene D.; Wu, Qingzhong; Chee-Sanford, Joanne C.; Thomas, Sara H.; Cruz-García, Claribel; Rodríguez, Gina; Massol-Deyá, Arturo; Krishnani, Kishore K.; Ritalahti, Kirsti M.; Nissen, Silke; Konstantinidis, Konstantinos T.; Löffler, Frank E.

2012-01-01

Agricultural and industrial practices more than doubled the intrinsic rate of terrestrial N fixation over the past century with drastic consequences, including increased atmospheric nitrous oxide (N2O) concentrations. N2O is a potent greenhouse gas and contributor to ozone layer destruction, and its release from fixed N is almost entirely controlled by microbial activities. Mitigation of N2O emissions to the atmosphere has been attributed exclusively to denitrifiers possessing NosZ, the enzyme system catalyzing N2O to N2 reduction. We demonstrate that diverse microbial taxa possess divergent nos clusters with genes that are related yet evolutionarily distinct from the typical nos genes of denitirifers. nos clusters with atypical nosZ occur in Bacteria and Archaea that denitrify (44% of genomes), do not possess other denitrification genes (56%), or perform dissimilatory nitrate reduction to ammonium (DNRA; (31%). Experiments with the DNRA soil bacterium Anaeromyxobacter dehalogenans demonstrated that the atypical NosZ is an effective N2O reductase, and PCR-based surveys suggested that atypical nosZ are abundant in terrestrial environments. Bioinformatic analyses revealed that atypical nos clusters possess distinctive regulatory and functional components (e.g., Sec vs. Tat secretion pathway in typical nos), and that previous nosZ-targeted PCR primers do not capture the atypical nosZ diversity. Collectively, our results suggest that nondenitrifying populations with a broad range of metabolisms and habitats are potentially significant contributors to N2O consumption. Apparently, a large, previously unrecognized group of environmental nosZ has not been accounted for, and characterizing their contributions to N2O consumption will advance understanding of the ecological controls on N2O emissions and lead to refined greenhouse gas flux models. PMID:23150571

Role of neuronal and inducible nitric oxide synthases in the guinea pig ileum myenteric plexus during in vitro ischemia and reperfusion.

PubMed

Giaroni, C; Marchet, S; Carpanese, E; Prandoni, V; Oldrini, R; Bartolini, B; Moro, E; Vigetti, D; Crema, F; Lecchini, S; Frigo, G

2013-02-01

Intestinal ischemia and reperfusion (I/R) injury leads to abnormalities in motility, namely delay of transit, caused by damage to myenteric neurons. Alterations of the nitrergic transmission may occur in these conditions. This study investigated whether an in vitro I/R injury may affect nitric oxide (NO) production from the myenteric plexus of the guinea pig ileum and which NO synthase (NOS) isoform is involved. The distribution of the neuronal (n) and inducible (i) NOS was determined by immunohistochemistry during 60 min of glucose/oxygen deprivation (in vitro ischemia) followed by 60 min of reperfusion. The protein and mRNA levels of nNOS and iNOS were investigated by Western-immunoblotting and real time RT-PCR, respectively. NO levels were quantified as nitrite/nitrate. After in vitro I/R the proportion of nNOS-expressing neurons and protein levels remained unchanged. nNOS mRNA levels increased 60 min after inducing ischemia and in the following 5 min of reperfusion. iNOS-immunoreactive neurons, protein and mRNA levels were up-regulated during the whole I/R period. A significant increase of nitrite/nitrate levels was observed in the first 5 min after inducing I/R and was significantly reduced by N(ω) -propyl-l-arginine and 1400 W, selective inhibitors of nNOS and iNOS, respectively. Our data demonstrate that both iNOS and nNOS represent sources for NO overproduction in ileal myenteric plexus during I/R, although iNOS undergoes more consistent changes suggesting a more relevant role for this isoform in the alterations occurring in myenteric neurons following I/R. © 2012 Blackwell Publishing Ltd.

Unaltered radial maze performance and brain acetylcholine of the endothelial nitric oxide synthase knockout mouse.

PubMed

Dere, E; Frisch, C; De Souza Silva, M A; Gödecke, A; Schrader, J; Huston, J P

2001-01-01

Proceeding from previous findings of a beneficial effect of endothelial nitric oxide synthase (eNOS) gene inactivation on negatively reinforced water maze performance, we asked whether this improvement in place learning capacities also holds for a positively reinforced radial maze task. Unlike its beneficial effects on the water maze task, eNOS gene inactivation did not facilitate radial maze performance. The acquisition performance over the days of place learning did not differ between eNOS knockout (eNOS-/-) and wild-type mice (eNOS+/+). eNOS-/- mice displayed a slight and eNOS+/+ mice a more severe working memory deficit in the place learning version of the radial maze compared to the genetic background C57BL/6 strain. Possible differential effects of eNOS inactivation, related to differences in reinforcement contingencies between the Morris water maze and radial maze tasks, behavioral strategy requirements, or to different emotional and physiological concomitants inherent in the two tasks are discussed. These task-unique characteristics might be differentially affected by the reported anxiogenic and hypertensional effects of eNOS gene inactivation. Post-mortem determination of acetylcholine concentrations in diverse brain structures revealed that acetylcholine and choline contents were not different between eNOS-/- and eNOS+/+ mice, but were increased in eNOS+/+ mice compared to C57BL/6 mice in the frontal cortex. Our findings demonstrate that phenotyping of learning and memory capacities should not rely on one learning task only, but should include tasks employing both negative and positive reinforcement contingencies in order to allow valid statements regarding differences in learning capacities between rodent strains.

Identificação de radiofontes puntiformes presentes na região observada pelo telescópio BEAST

NASA Astrophysics Data System (ADS)

Oliveira, M. S.; Wuensche, C. A.; Leonardi, R.; Tello, C.

2003-08-01

Radiofontes extragalácticas são um dos principais contaminantes nas medidas da Radiação Cósmica de Fundo (RCF) em freqüências abaixo de 200 GHz. O estudo de seu comportamento espectral permite determinar a contribuição destas fontes às anisotropias intrísincas da RCF. Um dos experimentos recentes concebidos para estudar a RCF é o BEAST (Background Emission Anisotropy Scanning Telescope), cujos primeiros resultados foram publicados em fevereiro de 2003. Nos últimos meses, geramos mapas do céu nas freqüências de 30 GHz e 41 GHz, para um total de 648 horas de observação entre julho e outubro de 2002. Identificamos 4 fontes puntiformes extragalácticas na região do céu situada entre 0h < RA < 24 h e +32° < DEC < +42°, com relação S/R > 4,3 e situadas a pelo menos 25° acima do Plano Galáctico. Suas contrapartidas em 5 GHz, segundo o catálogo GB6, são: J1613+3412, J1635+3808, J0927+3902 e J1642+3948. Estas fontes também foram identificadas pelo satélite WMAP sendo que três coincidem com as observadas pelo BEAST dentro da incerteza do feixe do telescópio e a quarta encontra-se bastante próxima (J1613+3412), embora não seja coincidente. As estimativas preliminares de fluxos obtidas para esses objetos são, respectivamente, 0,51; 0,97; 1,08 e 1,6 Jy em 41 GHz. Usando estes resultados e medidas de fluxos em outras frequências existentes na literatura, apresentamos uma estimativa dos índices espectrais destes objetos no intervalo de frequências entre 4,85 GHz e 41 GHz.

Observações espectroscópicas da candidata a pós-AGB IRAS 19386+0155

NASA Astrophysics Data System (ADS)

Lorenz-Martins, S.; Pereira, C. B.

2003-08-01

Nesse trabalho apresentamos a análise fotosférica da estrela candidata a pós-AGB IRAS 19386+0155. Com os dados obtidos no espectrógrafo FEROS foram determinados os parâmetros atmosféricos e abundâncias fotosféricas utilizando o código MOOG. A análise do espectro mostrou que IRAS 19386+0155 possui os seguintes parâmetros atmosféricos : Teff = 6800K, log g = 1.4, [M/H] = -1.5 e Vt = 8.4 km/s. O padrão de abundância obtido para os elementos mais leves (Carbono, Nitrogênio e Oxigênio) e elementos a (Magnésio, Silício e Cálcio) foi inferior ao solar (log C = 7.74, log N = 7.28, Log O = 8.43, log Mg = 7.14, log Si = 7.54 e log Ca = 5.91). Uma inspeção visual do espectro ISO deste objeto revela a presença de poeira fria na forma de silicatos cristalinos. Embora as bandas mais marcantes de silicatos amorfos (em 10 mm e 18mm) não sejam observadas, a emissão em 21 mm, presente em algumas pós-AGBs também não está presente. O espectro ISO parece revelar um meio rico em oxigênio, mas a forma da distribuição de energia no infravermelho não obedece ao padrão apresentado por outras pós-AGBs. Nossos resultados nos levam a sugerir que IRAS 19386+0155 talvez faça parte de um sistema binário, uma vez que outras pós-AGBs que são membros de sistemas binários apresentam padrão de abundância semelhante.

Caloric restriction improves endothelial dysfunction during vascular aging: Effects on nitric oxide synthase isoforms and oxidative stress in rat aorta.

PubMed

Zanetti, Michela; Gortan Cappellari, Gianluca; Burekovic, Ismet; Barazzoni, Rocco; Stebel, Marco; Guarnieri, Gianfranco

2010-11-01

Aging is characterized by activation of inducible over endothelial nitric oxide synthase (iNOS and eNOS), impaired antioxidant activity and increased oxidative stress, which reduces nitric oxide bioavailability and causes endothelial dysfunction. Caloric restriction (CR) blunts oxidative stress. We investigated whether CR impacts endothelial dysfunction in aging and the underlying mechanisms. Aortas from young (YC, 6 months of age) and old (OC, 24 months of age) rats ad-libitum fed and from old rats caloric-restricted for 3-weeks (OR, 26%) were investigated. Endothelium-dependent vasorelaxation was impaired in OC, associated with reduced eNOS and increased iNOS expression (P<0.05). Aortic nitrite was similar in OC and YC, but the contribution of calcium-independent NOS to total NOS activity was increased whereas that of calcium-dependent NOS was reduced (p≤0.0003). Plasma thiobarbituric acid-reactive substances (TBARS) were elevated in OC as well as aortic nitrotyrosine (P<0.05). Expression of manganese superoxide dismutase (MnSOD) and total SOD activity were impaired in OC (P<0.05 vs. YC), whereas copper-zinc (CuZn) SOD expression was similar in OC and YC. CR restored endothelial dysfunction in old rats, reduced iNOS expression, total nitrite and calcium-independent NOS activity in aorta (P<0.05) without changes in eNOS expression and calcium-dependent NOS activity. Sirtuin-1 expression did not differ among groups. Plasma TBARS and aortic nitrotyrosine were reduced (P<0.05) in OR compared with OC. In OR CuZnSOD protein and SOD activity increased (P<0.05) without changes in MnSOD expression. Short-term CR improves age-related endothelial dysfunction. Reversal of altered iNOS/eNOS ratio, reduced oxidative stress and increased SOD enzyme activity rather than enhanced NO production appear to be involved in this effect. Copyright © 2010 Elsevier Inc. All rights reserved.

iNOS expression in CD4+ T cells limits Treg induction by repressing TGFβ1: combined iNOS inhibition and Treg depletion unmask endogenous antitumor immunity.

PubMed

Jayaraman, Padmini; Alfarano, Matthew G; Svider, Peter F; Parikh, Falguni; Lu, Geming; Kidwai, Sarah; Xiong, Huabao; Sikora, Andrew G

2014-12-15

Expression of inducible nitric oxide synthase (iNOS) in different cellular compartments may have divergent effects on immune function. We used a syngeneic tumor model to functionally characterize the role of iNOS in regulation of CD4(+)FOXP3(+) regulatory T cells (Treg), and optimize the beneficial effects of iNOS inhibition on antitumor immunity. Wild-type (WT) or iNOS knockout mice bearing established MT-RET-1 melanoma were treated with the small-molecule iNOS inhibitor L-NIL and/or cyclophosphamide alone or in combination. The effect of iNOS inhibition or knockout on induction of Treg from mouse and human CD4(+) T cells in ex vivo culture was determined in parallel in the presence or absence of TGFβ1-depleting antibodies, and TGFβ1 levels were assessed by ELISA. Whereas intratumoral myeloid-derived suppressor cells (MDSC) were suppressed by iNOS inhibition or knockout, systemic and intratumoral FOXP3(+) Treg levels increased in tumor-bearing mice. iNOS inhibition or knockout similarly enhanced induction of Treg from activated cultured mouse splenocytes or purified human or mouse CD4(+) T cells in a TGFβ1-dependent manner. Although either iNOS inhibition or Treg depletion with low-dose cyclophosphamide alone had little effect on growth of established MT-RET1 melanoma, combination treatment potently inhibited MDSC and Treg, boosted tumor-infiltrating CD8(+) T-cell levels, and arrested tumor growth in an immune-dependent fashion. iNOS expression in CD4(+) T cells suppresses Treg induction by inhibiting TGFβ1 production. Our data suggest that iNOS expression has divergent effects on induction of myeloid and lymphoid-derived regulatory populations, and strongly support development of combinatorial treatment approaches that target these populations simultaneously. ©2014 American Association for Cancer Research.

Elk-3 is a transcriptional repressor of nitric-oxide synthase 2.

PubMed

Chen, Yen-Hsu; Layne, Matthew D; Chung, Su Wol; Ejima, Kuniaki; Baron, Rebecca M; Yet, Shaw-Fang; Perrella, Mark A

2003-10-10

The inducible isoform of nitric-oxide synthase (NOS2), a key enzyme catalyzing the dramatic increase in nitric oxide by lipopolysaccharide (LPS), plays an important role in the pathophysiology of endotoxemia and sepsis. Recent evidence suggests that Ets transcription factors may contribute to NOS2 induction by inflammatory stimuli. In this study, we investigated the role of Ets transcription factors in the regulation of NOS2 by LPS and transforming growth factor (TGF)-beta 1. Transient transfection assays in macrophages showed that Ets-2 produced an increase in NOS2 promoter activity, whereas the induction by Ets-1 was modest and NERF2 had no effect. Elk-3 (Net/Erp/Sap-2a) markedly repressed NOS2 promoter activity in a dose-dependent fashion, and overexpression of Elk-3 blunted the induction of endogenous NOS2 message. Mutation of the Net inhibitory domain of Elk-3, but not the C-terminal-binding protein interaction domain, partially alleviated this repressive effect. We also found that deletion of the Ets domain of Elk-3 completely abolished its repressive effect on the NOS2 promoter. LPS administration to macrophages led to a dose-dependent decrease in endogenous Elk-3 mRNA levels, and this decrease in Elk-3 preceded the induction of NOS2 mRNA. In a mouse model of endotoxemia, the expression of Elk-3 in kidney, lung, and heart was significantly down-regulated after systemic administration of LPS, and this down-regulation also preceded NOS2 induction. Moreover, TGF-beta 1 significantly increased endogenous Elk-3 mRNA levels that had been down-regulated by LPS in macrophages. This increase in Elk-3 correlated with a TGF-beta 1-induced down-regulation of NOS2. Taken together, our data suggest that Elk-3 is a strong repressor of NOS2 promoter activity and mRNA levels and that endogenous expression of Elk-3 inversely correlates with NOS2. Thus, Elk-3 may serve as an important mediator of NOS2 gene expression.

Methamphetamine- and 1-methyl-4-phenyl- 1,2,3, 6-tetrahydropyridine-induced dopaminergic neurotoxicity in inducible nitric oxide synthase-deficient mice.

PubMed

Itzhak, Y; Martin, J L; Ali, S F

1999-12-15

Previous studies have suggested a role for the retrograde messenger, nitric oxide (NO), in methamphetamine (METH)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- induced dopaminergic neurotoxicity. Since evidence supported the involvement of the neuronal nitric oxide synthase (nNOS) isoform in the dopaminergic neurotoxicity, the present study was undertaken to investigate whether the inducible nitric oxide synthase (iNOS) isoform is also associated with METH- and MPTP-induced neurotoxicity. The administration of METH (5mg/kg x 3) to iNOS deficient mice [homozygote iNOS(-/-)] and wild type mice (C57BL/6) resulted in significantly smaller depletion of striatal dopaminergic markers in the iNOS(-/-) mice compared with the wild-type mice. METH-induced hyperthermia was also significantly lower in the iNOS(-/-) mice than in wild-type mice. In contrast to the outcome of METH administration, MPTP injections (20 mg/kg x 3) resulted in a similar decrease in striatal dopaminergic markers in iNOS(-/-) and wild-type mice. In the set of behavioral experiments, METH-induced locomotor sensitization was investigated. The acute administration of METH (1.0 mg/kg) resulted in the same intensity of locomotor activity in iNOS(-/-) and wild-type mice. Moreover, 68 to 72 h after the exposure to the high-dose METH regimen (5 mg/kg x 3), a marked sensitized response to a challenge injection of METH (1.0 mg/kg) was observed in both the iNOS(-/-) and wild-type mice. The finding that iNOS(-/-) mice were unprotected from MPTP-induced neurotoxicity suggests that the partial protection against METH-induced neurotoxicity observed was primarily associated with the diminished hyperthermic effect of METH seen in the iNOS(-/-) mice. Moreover, in contrast to nNOS deficiency, iNOS deficiency did not affect METH-induced behavioral sensitization. Copyright 1999 Wiley-Liss, Inc.

Placental Vesicles Carry Active Endothelial Nitric Oxide Synthase and Their Activity is Reduced in Preeclampsia.

PubMed

Motta-Mejia, Carolina; Kandzija, Neva; Zhang, Wei; Mhlomi, Vuyane; Cerdeira, Ana Sofia; Burdujan, Alexandra; Tannetta, Dionne; Dragovic, Rebecca; Sargent, Ian L; Redman, Christopher W; Kishore, Uday; Vatish, Manu

2017-08-01

Preeclampsia, a multisystem hypertensive disorder of pregnancy, is associated with increased systemic vascular resistance. Placentae from patients with preeclampsia have reduced levels of endothelial nitric oxide synthase (eNOS) and, thus, less nitric oxide (NO). Syncytiotrophoblast extracellular vesicles (STBEV), comprising microvesicles (STBMV) and exosomes, carry signals from the syncytiotrophoblast to the mother. We hypothesized that STBEV-bound eNOS (STBEV-eNOS), capable of producing NO, are released into the maternal circulation. Dual-lobe ex vivo placental perfusion and differential centrifugation was used to isolate STBEV from preeclampsia (n=8) and normal pregnancies (NP; n=11). Plasma samples of gestational age-matched preeclampsia and NP (n=6) were used to isolate circulating STBMV. STBEV expressed placental alkaline phosphatase, confirming placental origin. STBEV coexpressed eNOS, but not inducible nitric oxide synthase, confirmed using Western blot, flow cytometry, and immunodepletion. STBEV-eNOS produced NO, which was significantly inhibited by N   G -nitro-l-arginine methyl ester (eNOS inhibitor; P <0.05) but not by N -(3-(aminomethyl) bezyl) acetamidine) (inducible nitric oxide synthase inhibitor). STBEV-eNOS catalytic activity was confirmed by visualizing eNOS dimerization. STBEV-eNOS was more abundant in uterine vein compared with peripheral blood, indicating placental origin. STBEV isolated from preeclampsia-perfused placentae had lower levels of STBEV-eNOS (STBMV; P <0.05) and overall lower NO activity (STBMV, not significant; syncytiotrophoblast extracellular exosomes, P <0.05) compared with those from NP. Circulating plasma STBMV from preeclampsia women had lower STBEV-eNOS expression compared with that from NP women ( P <0.01). This is the first observation of functional eNOS expressed on STBEV from NP and preeclampsia placentae, as well as in plasma. The lower STBEV-eNOS NO production seen in preeclampsia may contribute to the decreased NO bioavailability in this disease. © 2017 The Authors.

Hypothermia translocates nitric oxide synthase from cytosol to membrane in snail neurons.

PubMed

Rószer, Tamás; Kiss-Tóth, Eva; Rózsa, Dávid; Józsa, Tamás; Szentmiklósi, A József; Bánfalvi, Gáspár

2010-11-01

Neuronal nitric oxide (NO) levels are modulated through the control of catalytic activity of NO synthase (NOS). Although signals limiting excess NO synthesis are being extensively studied in the vertebrate nervous system, our knowledge is rather limited on the control of NOS in neurons of invertebrates. We have previously reported a transient inactivation of NOS in hibernating snails. In the present study, we aimed to understand the mechanism leading to blocked NO production during hypothermic periods of Helix pomatia. We have found that hypothermic challenge translocated NOS from the cytosol to the perinuclear endoplasmic reticulum, and that this cytosol to membrane trafficking was essential for inhibition of NO synthesis. Cold stress also downregulated NOS mRNA levels in snail neurons, although the amount of NOS protein remained unaffected in response to hypothermia. Our studies with cultured neurons and glia cells revealed that glia-neuron signaling may inhibit membrane binding and inactivation of NOS. We provide evidence that hypothermia keeps NO synthesis "hibernated" through subcellular redistribution of NOS.

l-Arginine normalizes NOS activity and zinc-MT homeostasis in the kidney of mice chronically exposed to inorganic mercury.

PubMed

Piacenza, Francesco; Malavolta, Marco; Cipriano, Catia; Costarelli, Laura; Giacconi, Robertina; Muti, Elisa; Tesei, Silvia; Pierpaoli, Sara; Basso, Andrea; Bracci, Massimo; Bonacucina, Viviana; Santarelli, Lory; Mocchegiani, Eugenio

2009-09-28

Inorganic mercury (HgCl2) exposure provokes damage in many organs, especially kidney. Inducible nitric oxide synthase (iNOS) expression, total NOS activity and the profiles of zinc (Zn), copper (Cu) and Hg as well as their distribution when bound to specific intracellular proteins, including metallothioneins (MT), were studied during HgCl2 exposure and after l-arginine treatment in C57BL/6 mouse kidney. HgCl2 exposure modulates differently iNOS expression and NOS activity, increasing iNOS expression but, conversely, decreasing total NOS activity in the mouse kidney. Moreover, during Hg exposure an increased MT production occurs. The kidney damage leads to a loss of urinary proteins, increased plasma creatinine and high Zn mobilization with consequent increased urinary Zn excretion. l-arginine treatment recovers NOS activity and induces a normalization of MT induction, plasma creatinine values and urinary proteins excretion, suggesting that l-arginine may limit kidney damages by Hg exposure.

Activity and expression of nitric oxide synthase in pork skeletal muscles.

PubMed

Liu, Rui; Li, Yu-pin; Zhang, Wan-gang; Fu, Qing-quan; Liu, Nian; Zhou, Guang-hong

2015-01-01

The objective of this study was to investigate the biochemical changes of nitric oxide synthase (NOS) in pork skeletal muscles during postmortem storage. Longissimus thoracis (LT), psoas major (PM) and semimembranosus (SM) muscles of pork were removed immediately after slaughter and stored under vacuum condition at 4°C for 0, 1 and 3d. Results showed that all three muscles exhibited NOS activity until 1d while SM muscle retained NOS activity after 3d of storage. The content of nNOS in SM muscle was stable across 3d of storage while decreased intensity of nNOS was detected at 1 and 3d of aging in PM and LT muscles due to the degradation of calpain. Immunostaining showed that nNOS was located at not only sarcolemma but also cytoplasm at 0 and 1d of storage. Our data suggest that postmortem muscles possess NOS activity and nNOS expression depends on muscle type. Copyright © 2014 Elsevier Ltd. All rights reserved.

Arctigenin promotes degradation of inducible nitric oxide synthase through CHIP-associated proteasome pathway and suppresses its enzyme activity.

PubMed

Yao, Xiangyang; Li, Guilan; Lü, Chaotian; Xu, Hui; Yin, Zhimin

2012-10-01

Arctigenin, a natural dibenzylbutyrolactone lignan compound, has been reported to possess anti-inflammatory properties. Previous works showed that arctigenin decreased lipopolysaccharide (LPS)-induced iNOS at transcription level. However, whether arctigenin could regulate iNOS at the post-translational level is still unclear. In the present study, we demonstrated that arctigenin promoted the degradation of iNOS which is expressed under LPS stimulation in murine macrophage-like RAW 264.7 cells. Such degradation of iNOS protein is due to CHIP-associated ubiquitination and proteasome-dependency. Furthermore, arctigenin decreased iNOS phosphorylation through inhibiting ERK and Src activation, subsequently suppressed iNOS enzyme activity. In conclusion, our research displays a new finding that arctigenin can promote the ubiqitination and degradation of iNOS after LPS stimulation. iNOS activity regulated by arctigenin is likely to involve a multitude of crosstalking mechanisms. Copyright © 2012 Elsevier B.V. All rights reserved.

ROLE OF ENDOTHELIAL NITRIC OXIDE SYNTHETASE IN ARTERIOGENESIS AFTER STROKE IN MICE

PubMed Central

CUI, X.; CHOPP, M.; ZACHAREK, A.; ZHANG, C.; ROBERTS, C.; CHEN, J.

2009-01-01

Arteriogenesis supports restored perfusion in the ischemic brain and improves long-term functional outcome after stroke. We investigate the role of endothelial nitric oxide synthetase (eNOS) and an NO donor, [(Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) aminio] diazen-1-ium-1, 2-diolate (DETA-NONOate), in promoting arteriogenesis after stroke. Adult wild-type (WT, n=18) and eNOS-knockout (eNOS-/-, n=36) mice were subjected to transient (2.5 hours) right middle cerebral artery occlusion (MCAo) and were treated with or without DETA-NONOate (0.4 mg/kg) 24 hours after MCAo. Functional evaluation was performed. Animals were sacrificed 3 days after MCAo for arterial cell culture studies, or 14 days for immunohistochemical analysis. Consistent with previous studies, eNOS-/- mice exhibited a higher mortality rate (p<0.05, n=18/group) and more severe neurological functional deficit after MCAo than WT mice (p<0.05, n=12/group). Decreased arteriogenesis, was evident in eNOS-/- mice compared with WT mice, as demonstrated by reduced vascular smooth muscle cell (VSMC) proliferation, arterial density and diameter in the ischemic brain. eNOS-/- mice treated with DETA-NONOate had a significantly decreased mortality rate and improved functional recovery, and exhibited enhanced arteriogenesis identified by increased VSMC proliferation, and upregulated arterial density and diameter compared to eNOS-/- mice after stroke (p<0.05, n=12/group). To elucidate the mechanisms underlying eNOS/NO mediated arteriogenesis, VSMC migration was measured in vitro. Arterial cell migration significantly decreased in the cultured common carotid artery (CCA) derived from eNOS-/- mice 3 days after MCAo compared to WT arterial cells. DETA-NONOate-treatment significantly attenuated eNOS-/--induced decrease of arterial cell migration compared to eNOS-/- control artery (p<0.05. n=6/group). Using VSMC culture, DETA-NONOate significantly increased VSMC migration, while inhibition of NOS significantly decreased VSMC migration (p<0.05. n=6/group). Our data indicated that eNOS not only promotes vascular dilation but also increases VSMC proliferation and migration, and thereby enhances arteriogenesis after stroke. Therefore, increase eNOS may play an important role in regulating of arteriogenesis after stroke. PMID:19154781

Role of endothelial nitric oxide synthetase in arteriogenesis after stroke in mice.

PubMed

Cui, X; Chopp, M; Zacharek, A; Zhang, C; Roberts, C; Chen, J

2009-03-17

Arteriogenesis supports restored perfusion in the ischemic brain and improves long-term functional outcome after stroke. We investigate the role of endothelial nitric oxide synthetase (eNOS) and a nitric oxide (NO) donor, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate (DETA-NONOate), in promoting arteriogenesis after stroke. Adult wild-type (WT, n=18) and eNOS-knockout (eNOS(-/-), n=36) mice were subjected to transient (2.5 h) right middle cerebral artery occlusion (MCAo) and were treated with or without DETA-NONOate (0.4 mg/kg) 24 h after MCAo. Functional evaluation was performed. Animals were sacrificed 3 days after MCAo for arterial cell culture studies, or 14 days for immunohistochemical analysis. Consistent with previous studies, eNOS(-/-) mice exhibited a higher mortality rate (P<0.05, n=18/group) and more severe neurological functional deficit after MCAo than WT mice (P<0.05, n=12/group). Decreased arteriogenesis, was evident in eNOS(-/-) mice compared with WT mice, as demonstrated by reduced vascular smooth muscle cell (VSMC) proliferation, arterial density and diameter in the ischemic brain. eNOS(-/-) mice treated with DETA-NONOate had a significantly decreased mortality rate and improved functional recovery, and exhibited enhanced arteriogenesis identified by increased VSMC proliferation, and upregulated arterial density and diameter compared to eNOS(-/-) mice after stroke (P<0.05, n=12/group). To elucidate the mechanisms underlying eNOS/NO mediated arteriogenesis, VSMC migration was measured in vitro. Arterial cell migration significantly decreased in the cultured common carotid artery (CCA) derived from eNOS(-/-) mice 3 days after MCAo compared to WT arterial cells. DETA-NONOate-treatment significantly attenuated eNOS(-/-)-induced decrease of arterial cell migration compared to eNOS(-/-) control artery (P<0.05; n=6/group). Using VSMC culture, DETA-NONOate significantly increased VSMC migration, while inhibition of NOS significantly decreased VSMC migration (P<0.05; n=6/group). Our data indicated that eNOS not only promotes vascular dilation but also increases VSMC proliferation and migration, and thereby enhances arteriogenesis after stroke. Therefore, increase eNOS may play an important role in regulating of arteriogenesis after stroke.

Cloning, expression, and characterization of recombinant nitric oxide synthase-like protein from Bacillus anthracis

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

Midha, Shuchi; Mishra, Rajeev; Aziz, M.A.

2005-10-14

Nitric oxide synthase (NOS) is amongst a family of evolutionarily conserved enzymes, involved in a multi-turnover process that results in NO as a product. The significant role of NO in various pathological and physiological processes has created an interest in this enzyme from several perspectives. This study describes for the first time, cloning and expression of a NOS-like protein, baNOS, from Bacillus anthracis, a pathogenic bacterium responsible for causing anthrax. baNOS was expressed in Escherichia coli as a soluble and catalytically active enzyme. Homology models generated for baNOS indicated that the key structural features that are involved in the substratemore » and active site interaction have been highly conserved. Further, the behavior of baNOS in terms of heme-substrate interactions and heme-transitions was studied in detail. The optical perturbation spectra of the heme domain demonstrated that the ligands perturb the heme site in a ligand specific manner. baNOS forms a five-coordinate, high-spin complex with L-arginine analogs and a six-coordinate low-spin complex with inhibitor imidazole. Studies indicated that the binding of L-arginine, N {sup {omega}}-hydroxy-L-arginine, and imidazole produces various spectroscopic species that closely correspond to the equivalent complexes of mammalian NOS. The values of spectral binding constants further corroborated these results. The overall conservation of the key structural features and the correlation of heme-substrate interactions in baNOS and mammalian NOS, thus, point towards an interesting phenomenon of convergent evolution. Importantly, the NO generated by NOS of mammalian macrophages plays a potent role in antimicrobicidal activity. Because of the existence of high structural and behavioral similarity between mammalian NOS and baNOS, we propose that NO produced by B. anthracis may also have a pivotal pathophysiological role in anthrax infection. Therefore, this first report of characterization of a NOS-like protein from a pathogenic bacterium opens up avenues for further studies in understanding the importance of this protein in pathogenicity.« less

The nature of science and the preservice elementary teacher: Changes in understanding and practice

NASA Astrophysics Data System (ADS)

Rivas, Michael Gerald

This action research project studies preservice elementary teachers in a science methods course. The purpose of this research project was to enhance preservice teachers' understanding of specific nature of science (NOS) tenets so as to promote equity and access within the elementary science classroom. In particular, I chose five NOS tenets that were listed in the first chapter of the AAAS (1989) document titled, "The Nature of Science," and connected them to equitable educational goals and practices. The theoretical framework guiding this study came from bodies of scholarship relating to the NOS, social constructivism, and action research. This study addressed the following three questions: (1) What opportunities were provided the preservice teachers so that they could enhance their understandings of the NOS? (2) What were the changes in preservice teachers' understanding of the NOS as a result? (3) How did the prospective teachers' understandings of the NOS translate into their classroom practice? The analysis revealed that the science methods course's operational curriculum consisted of implicit and explicit teaching of the NOS, as well as intended and untended NOS tenets. The prospective teachers initially held a limited view of the NOS, but by the end of the course their view had been enhanced. In addition, the participants made direct connections between their new understandings of the NOS and equity and access in the science classroom. In their teaching, the preservice teachers as a group implicitly taught all five of the NOS tenets. In fact, a majority taught three of the five intended tenets. Explicitly, only one tenet was taught, but it was taught with a direct connection to making the science classroom more inclusive. The findings of this study indicate that preservice teachers can have their views of the NOS enhanced even though they may have experienced years of deficient science instruction. They pointed out that this enhanced view of the NOS can be translated into classroom practice. The findings also showed that a direct connection can be made between understandings of the NOS and issues of equity and access at the elementary level.

Development and Nature of Preservice Chemistry Teachers' Pedagogical Content Knowledge for Nature of Science

NASA Astrophysics Data System (ADS)

Demirdöğen, Betül; Hanuscin, Deborah L.; Uzuntiryaki-Kondakci, Esen; Köseoğlu, Fitnat

2016-08-01

The purpose of this case study is to delve into the complexities of the early development of preservice chemistry teachers' science teaching orientations, knowledge of learners, knowledge of instructional strategies, and knowledge of assessment during a two-semester intervention designed to enhance their pedagogical content knowledge (PCK) for teaching nature of science (NOS). Thirty preservice chemistry teachers enrolled in a Research in Science Education course participated in the study. Qualitative data sources included responses to an open-ended instrument, interviews, observations, and artifacts such as lesson plans and reflection papers. Through the in-depth analysis of explicit PCK and constant comparative method of analysis, we identified the influence of the intervention on participants' PCK for NOS. Analysis of data revealed four major themes related to the nature of preservice chemistry teachers' NOS teaching practices and their PCK for NOS: (1) prerequisite knowledge and beliefs are necessary to teach NOS, (2) there is a developmental progression of PCK for NOS from knowledge to application level, (3) teachers need some comfort in their NOS understanding to teach NOS, and (4) the higher integration of PCK components leads to successful NOS teaching practices. Implications for science teacher education and research are discussed.

Exposure to diesel exhaust up-regulates iNOS expression in ApoE knockout mice

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

Bai Ni; James Hogg Research Centre, Providence Heart and Lung Institute, St. Paul's Hospital, University of British Columbia, Vancouver, BC; Kido, Takashi

Traffic related particulate matter air pollution is a risk factor for cardiovascular events; however, the biological mechanisms are unclear. We hypothesize that diesel exhaust (DE) inhalation induces up-regulation of inducible nitric oxide synthase (iNOS), which is known to contribute to vascular dysfunction, progression of atherosclerosis and ultimately cardiovascular morbidity and mortality. Methods: ApoE knockout mice (30-week) were exposed to DE (at 200 {mu}g/m{sup 3} of particulate matter) or filtered-air (control) for 7 weeks (6 h/day, 5 days/week). iNOS expression in the blood vessels and heart was evaluated by immunohistochemistry and western blotting analysis. To examine iNOS activity, thoracic aortae weremore » mounted in a wire myograph, and vasoconstriction stimulated by phenylephrine (PE) was measured with and without the presence of the specific inhibitor for iNOS (1400 W). NF-{kappa}B (p65) activity was examined by ELISA. The mRNA expression of iNOS and NF-{kappa}B (p65) was determined by real-time PCR. Results: DE exposure significantly enhanced iNOS expression in the thoracic aorta (4-fold) and heart (1.5 fold). DE exposure significantly attenuated PE-stimulated vasoconstriction by {approx} 20%, which was partly reversed by 1400 W. The mRNA expression of iNOS and NF-{kappa}B was significantly augmented after DE exposure. NF-{kappa}B activity was enhanced 2-fold after DE inhalation, and the augmented NF-{kappa}B activity was positively correlated with iNOS expression (R{sup 2} = 0.5998). Conclusions: We show that exposure to DE increases iNOS expression and activity possibly via NF-{kappa}B-mediated pathway. We suspect that DE exposure-caused up-regulation of iNOS contributes to vascular dysfunction and atherogenesis, which could ultimately lead to urban air pollution-associated cardiovascular morbidity and mortality. - Highlights: > Exposed ApoE knockout mice (30-week) to diesel exhaust (DE) for 7 weeks. > Examine iNOS expression and activity in the blood vessels and heart. > DE exposure enhanced iNOS protein and mRNA expression in the aorta and heart. > iNOS activity was also increased after DE exposure. > This up-regulation of iNOS may contribute to vascular dysfunction and atherogenesis.« less

The influence of explicit versus implicit instructional approaches during a technology-based curriculum on students' understanding of nature of science (NOS)

NASA Astrophysics Data System (ADS)

Al-Saidi, Ahmed Mohammad

The purpose of this study was to examine the effect of an explicit versus an implicit instructional approach during technology-based curriculum on students' understanding of the nature of science (NOS) within an introductory biology course. The study emphasized the inferential and tentative nature of science. The intervention or explicit group was involved in inquiry activities followed by discussions that were directly geared towards the target aspects of NOS. The implicit group was engaged in the same activities but received instruction devoid of direct reference to the NOS aspects. Students in both groups spent identical amount of time on task. Selected items of the Views of Nature of Science Questionnaire (VNOS) together with semi-structured interviews were used to evaluate students' NOS conceptions before and at the end of the intervention, which lasted two weeks. A quantitative analysis using chi-square of students' pre-intervention NOS views as provided by the VNOS questionnaires revealed that there was not a statistically significant difference between implicit and explicit groups in both targeted NOS aspects, with (p = 0.18) and (p = 0.34) for inferential and tentative NOS, respectively. However the same analysis indicated statistical significance difference for post-intervention between implicit and explicit groups, yielding (p < 0.02) and (p < 0.002) for both inferential and tentative NOS, respectively. A qualitative analysis of students' pre and post-intervention views of the target aspects of NOS as well as semi-structured interviews for both groups was also conducted. Before intervention, the number of informed NOS responses in both groups was not considerably different. However, analysis of post-intervention NOS views indicated that more students in the explicit group demonstrated informed views of the NOS aspects than in the implicit group. Therefore, the analysis of the data indicated that, in this particular study, engaging students in inquiry-based activities followed by explicit discussion that is geared toward NOS aspects was more effective than merely involving them in implicit, inquiry-based instruction. The imperative finding of the present study provides evidence that teaching the NOS could be achieved through short-intensive discussion and does not necessarily require separate and independent courses.

Deficiency of iNOS-derived NO accelerates lipid accumulation-independent liver fibrosis in non-alcoholic steatohepatitis mouse model.

PubMed

Nozaki, Yuichi; Fujita, Koji; Wada, Koichiro; Yoneda, Masato; Kessoku, Takaomi; Shinohara, Yoshiyasu; Imajo, Kento; Ogawa, Yuji; Nakamuta, Makoto; Saito, Satoru; Masaki, Naohiko; Nagashima, Yoji; Terauchi, Yasuo; Nakajima, Atsushi

2015-04-01

Although many of the factors and molecules closely associated with non-alcoholic steatohepatitis (NASH) have been reported, the role of inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) on the progression of NASH remains unclear. We therefore investigated the role of iNOS-derived NO in NASH pathogenesis with a long-term follow-up study using systemic iNOS-knockout mice under high-fat diet (HFD) conditions. iNOS-knockout and wild-type mice were fed a basal or HFD for 10 or 48 weeks. Lipid accumulation, fibrosis, and inflammation were evaluated, and various factors and molecules closely associated with NASH were analyzed. Marked fibrosis and inflammation (indicators of NASH) were observed in the livers of iNOS-knockout mice compared to wild-type mice after 48 weeks of a HFD; however, lipid accumulation in iNOS-knockout mice livers was less than in the wild-type. Increased expressions of various cytokines that are transcriptionally controlled by NF-kB in iNOS-deficient mice livers were observed during HFD conditions. iNOS-derived NO may play a protective role against the progression to NASH during an HFD by preventing fibrosis and inflammation, which are mediated by NF-kB activation in Kupffer cells. A lack of iNOS-derived NO accelerates progression to NASH without excessive lipid accumulation.

Endothelial nitric oxide synthase is dynamically expressed during bone marrow stem cell differentiation into endothelial cells.

PubMed

Liu, Zhenguo; Jiang, Yuehua; Hao, Hong; Gupta, Kalpna; Xu, Jian; Chu, Ling; McFalls, Edward; Zweier, Jay; Verfaillie, Catherine; Bache, Robert J

2007-09-01

This study was designed to investigate the developmental expression of endothelial nitric oxide synthase (eNOS) during stem cell differentiation into endothelial cells and to examine the functional status of the newly differentiated endothelial cells. Mouse adult multipotent progenitor cells (MAPCs) were used as the source of stem cells and were induced to differentiate into endothelial cells with vascular endothelial growth factor (VEGF) in serum-free medium. Expression of eNOS in the cells during differentiation was evaluated with real-time PCR, nitric oxide synthase (NOS) activity, and Western blot analysis. It was found that eNOS, but no other NOS, was present in undifferentiated MAPCs. eNOS expression disappeared in the cells immediately after induction of differentiation. However, eNOS expression reoccurred at day 7 during differentiation. Increasing eNOS mRNA, protein content, and activity were observed in the cells at days 14 and 21 during differentiation. The differentiated endothelial cells formed dense capillary networks on growth factor-reduced Matrigel. VEGF-stimulated phosphorylation of extracellular signal-regulated kinase (ERK)-1 and ERK-2 occurred in these cells, which was inhibited by NOS inhibitor N(G)-nitro-L-arginine methyl ester. In conclusion, these data demonstrate that eNOS is present in MAPCs and is dynamically expressed during the differentiation of MAPCs into endothelial cells in vitro.

Post-Translational Modification of Constitutive Nitric Oxide Synthase in the Penis

PubMed Central

Musicki, Biljana; Ross, Ashley E.; Champion, Hunter C.; Burnett, Arthur L.; Bivalacqua, Trinity J.

2009-01-01

Erectile dysfunction (ED) is a common men's health problem characterized by the consistent inability to sustain an erection sufficient for sexual intercourse. Basic science research on erectile physiology has been devoted to investigating the pathogenesis of ED and has led to the conclusion that ED is predominately a disease of vascular origin and/or neurogenic dysfunction. The constitutive forms of nitric oxide synthase [NOS; endothelial NOS (eNOS) and neuronal NOS (nNOS)] are important enzymes involved in the production of nitric oxide (NO) and thus regulate penile vascular homeostasis. Given the impact of endothelial- and neuronal-derived NO in penile vascular biology, a great deal of research over the past decade has focused on the role of NO synthesis from the endothelium and nitrergic nerve terminal in normal erectile physiology as well as in disease states. Loss of the functional integrity of the endothelium and subsequent endothelial dysfunction plays an integral role in the occurrence of ED. Therefore, molecular mechanisms involved in dysregulation of these NOS isoforms in the development of ED are essential to discovering the pathogenesis of ED in various disease states. This communication reviews the role of eNOS and nNOS in erectile physiology and discusses the alterations in eNOS and nNOS via post-translation modification in various vascular diseases of the penis. PMID:19342700

Impact of Chinese Culture on Pre-service Science Teachers' Views of the Nature of Science

NASA Astrophysics Data System (ADS)

Wan, Dongsheng; Zhang, Hongshia; Wei, Bing

2018-04-01

This study examines Chinese pre-service teachers' (N = 30) views on the nature of science (NOS) and how Chinese culture influences their views. Participants were from two teachers' universities in eastern China. As an exploratory and interpretive study, a scenario-based interview approach was adopted. The results indicated that the participants held unique views about the five key aspects of NOS. Many participants have alternative and contemporary views of NOS, but few possess classical views. In fact, teachers adopted features of the Confucian Doctrine of the Mean either consciously or unconsciously to account for their views of NOS. This research reflects that the Doctrine of the Mean affected Chinese teachers' views of NOS, making them rather deficient in their understandings of classical NOS. Based on empirical data, it is argued that science teacher training in China should focus on the content and objectives of classical NOS, rather than just teaching contemporary views of NOS. Taking Chinese culture into consideration, science teacher education in China cannot entirely import the strategies of teaching the classical views of NOS from the developed world, but should develop, design and contextualize local strategies that are suitable for the training of Chinese science teachers. Some issues for further investigation of learners' views of NOS in non-Western contexts are suggested as implications from this study.

mNos2 deletion and human NOS2 replacement in Alzheimer disease models.

PubMed

Colton, Carol A; Wilson, Joan G; Everhart, Angela; Wilcock, Donna M; Puoliväli, Jukka; Heikkinen, Taneli; Oksman, Juho; Jääskeläinen, Olli; Lehtimäki, Kimmo; Laitinen, Teemu; Vartiainen, Nina; Vitek, Michael P

2014-08-01

Understanding the pathophysiologic mechanisms underlying Alzheimer disease relies on knowledge of disease onset and the sequence of development of brain pathologies. We present a comprehensive analysis of early and progressive changes in a mouse model that demonstrates a full spectrum of characteristic Alzheimer disease-like pathologies. This model demonstrates an altered immune redox state reminiscent of the human disease and capitalizes on data indicating critical differences between human and mouse immune responses, particularly in nitric oxide levels produced by immune activation of the NOS2 gene. Using the APPSwDI(+)/(+)mNos2(-/-) (CVN-AD) mouse strain, we show a sequence of pathologic events leading to neurodegeneration,which include pathologically hyperphosphorylated tau in the perforant pathway at 6 weeks of age progressing to insoluble tau, early appearance of β-amyloid peptides in perivascular deposits around blood vessels in brain regions known to be vulnerable to Alzheimer disease, and progression to damage and overt loss in select vulnerable neuronal populations in these regions. The role of species differences between hNOS2 and mNos2 was supported by generating mice in which the human NOS2 gene replaced mNos2. When crossed with CVN-AD mice, pathologic characteristics of this new strain (APPSwDI(+)/(-)/HuNOS2(tg+)/(+)/mNos2(-/-)) mimicked the pathologic phenotypes found in the CVN-AD strain.

The mTOR kinase inhibitor rapamycin decreases iNOS mRNA stability in astrocytes

PubMed Central

2011-01-01

Background Reactive astrocytes are capable of producing a variety of pro-inflammatory mediators and potentially neurotoxic compounds, including nitric oxide (NO). High amounts of NO are synthesized following up-regulation of inducible NO synthase (iNOS). The expression of iNOS is tightly regulated by complex molecular mechanisms, involving both transcriptional and post-transcriptional processes. The mammalian target of rapamycin (mTOR) kinase modulates the activity of some proteins directly involved in post-transcriptional processes of mRNA degradation. mTOR is a serine-threonine kinase that plays an evolutionarily conserved role in the regulation of cell growth, proliferation, survival, and metabolism. It is also a key regulator of intracellular processes in glial cells. However, with respect to iNOS expression, both stimulatory and inhibitory actions involving the mTOR pathway have been described. In this study the effects of mTOR inhibition on iNOS regulation were evaluated in astrocytes. Methods Primary cultures of rat cortical astrocytes were activated with different proinflammatory stimuli, namely a mixture of cytokines (TNFα, IFNγ, and IL-1β) or by LPS plus IFNγ. Rapamycin was used at nM concentrations to block mTOR activity and under these conditions we measured its effects on the iNOS promoter, mRNA and protein levels. Functional experiments to evaluate iNOS activity were also included. Results In this experimental paradigm mTOR activation did not significantly affect astrocyte iNOS activity, but mTOR pathway was involved in the regulation of iNOS expression. Rapamycin did not display any significant effects under basal conditions, on either iNOS activity or its expression. However, the drug significantly increased iNOS mRNA levels after 4 h incubation in presence of pro-inflammatory stimuli. This stimulatory effect was transient, since no differences in either iNOS mRNA or protein levels were detected after 24 h. Interestingly, reduced levels of iNOS mRNA were detected after 48 hours, suggesting that rapamycin can modify iNOS mRNA stability. In this regard, we found that rapamycin significantly reduced the half-life of iNOS mRNA, from 4 h to 50 min when cells were co-incubated with cytokine mixture and 10 nM rapamycin. Similarly, rapamycin induced a significant up-regulation of tristetraprolin (TTP), a protein involved in the regulation of iNOS mRNA stability. Conclusion The present findings show that mTOR controls the rate of iNOS mRNA degradation in astrocytes. Together with the marked anti-inflammatory effects that we previously observed in microglial cells, these data suggest possible beneficial effects of mTOR inhibitors in the treatment of inflammatory-based CNS pathologies. PMID:21208419

nNOS expression in the brain of rats after burn and the effect of the ACE inhibitor captopril.

PubMed

Demiralay, Ebru; Saglam, Ibrahim Yaman; Ozdamar, Emine Nur; Sehirli, Ahmet Ozer; Sener, Goksel; Saglam, Esra

2013-08-01

To investigate the role of endogenous neuronal nitric oxide synthase (nNOS) on brain injury after burn and the effects of the captopril. Wistar albino rats (200-250 g) were exposed on the dorsal surface to 90°C (burn) or 25°C (sham) water for 10 s. The ACE group was treated with intraperitoneal 10 mg/kg captopril immediately after burn and this treatment was repeated twice daily. At the end of the 24 h brain samples were taken. nNOS was studied in brain areas by immunohistochemistry. There was no difference between the cerebellar and hypothalamic areas the nNOS expression of all groups. nNOS expression increased in the frontal cortex, striatum and midbrain in the burn group compared to the control group. In the frontal cortex, nNOS expression significantly decreased after ACE inhibitor treatment (p<0.05). The striatal nNOS of the ACE group significantly increased when compared to the control group (p=0.001). In the midbrain of the animals, nNOS decreased in the ACE group. Hippocampal nNOS expression did not change after burn and significantly increased after ACE inhibitor therapy (p<0.05). Our data showed that the pathophysiological events following burn appear to be related to an acute inflammatory reaction which is associated with nNOS in the frontal cortex, striatum and midbrain, and captopril treatment abrogates the nNOS response in the frontal cortex and midbrain. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

Influence of elastin-derived peptides, glucose, LDL and oxLDL on nitric oxide synthase expression in human umbilical artery endothelial cells.

PubMed

Garczorz, Wojciech; Francuz, Tomasz; Gmiński, Jan; Likus, Wirginia; Siemianowicz, Krzysztof; Jurczak, Teresa; Strzałka-Mrozik, Barbara

2011-01-01

Endothelial dysfunction plays an important role in the development of atherosclerosis. Elastin-derived peptides (EDP), hyperglycemia, hypercholesterolemia and oxidized LDL have a proven proatherosclerotic potential. Nitric oxide generated by endothelial nitric oxide synthase (eNOS; EC 1.14.13.39) is an important vasorelaxant. Here we studied the influence of those proatherosclerotic factors on eNOS gene and protein expression in artery-derived endothelial cells. Human umbilical artery endothelial cells (HUAEC) were incubated with or without: glucose (270 mg/dl), LDL (200 mg/dl), oxidized LDL (oxLDL 25 mg/dl) or κ-elastin (0.5 and 2.5 µg/ml). Gene expression was assessed by real time RT-PCR, whilst the eNOS protein by ELISA. In cells incubated with 2.5 µg/ml of κ-elastin, a 31 % increase of eNOS mRNA expression was observed, but the protein level remained unchanged. OxLDL, LDL and glucose decreased the eNOS protein level by 74 %, 37 % and 29 %, respectively. OxLDL decreased eNOS mRNA by 42 %. LDL non-significantly decreased eNOS mRNA expression. An elevated glucose level did not affect the eNOS mRNA expression. Hyperglycemia and an elevated level of LDL, particularly oxLDL, decreased the level of eNOS protein in endothelial cells. As κ-elastin did not decrease the expression of eNOS gene in HUAEC, the proatherogenic properties of elastin-derived peptides are unlikely to be due to their influence on eNOS.

Dissecting structural and electronic effects in inducible nitric oxide synthase.

PubMed

Hannibal, Luciana; Page, Richard C; Haque, Mohammad Mahfuzul; Bolisetty, Karthik; Yu, Zhihao; Misra, Saurav; Stuehr, Dennis J

2015-04-01

Nitric oxide synthases (NOSs) are haem-thiolate enzymes that catalyse the conversion of L-arginine (L-Arg) into NO and citrulline. Inducible NOS (iNOS) is responsible for delivery of NO in response to stressors during inflammation. The catalytic performance of iNOS is proposed to rely mainly on the haem midpoint potential and the ability of the substrate L-Arg to provide a hydrogen bond for oxygen activation (O-O scission). We present a study of native iNOS compared with iNOS-mesohaem, and investigate the formation of a low-spin ferric haem-aquo or -hydroxo species (P) in iNOS mutant W188H substituted with mesohaem. iNOS-mesohaem and W188H-mesohaem were stable and dimeric, and presented substrate-binding affinities comparable to those of their native counterparts. Single turnover reactions catalysed by iNOSoxy with L-Arg (first reaction step) or N-hydroxy-L-arginine (second reaction step) showed that mesohaem substitution triggered higher rates of Fe(II)O₂ conversion and altered other key kinetic parameters. We elucidated the first crystal structure of a NOS substituted with mesohaem and found essentially identical features compared with the structure of iNOS carrying native haem. This facilitated the dissection of structural and electronic effects. Mesohaem substitution substantially reduced the build-up of species P in W188H iNOS during catalysis, thus increasing its proficiency towards NO synthesis. The marked structural similarities of iNOSoxy containing native haem or mesohaem indicate that the kinetic behaviour observed in mesohaem-substituted iNOS is most heavily influenced by electronic effects rather than structural alterations.

The effect of high protein diet and exercise on irisin, eNOS, and iNOS expressions in kidney.

PubMed

Tastekin, Ebru; Palabiyik, Orkide; Ulucam, Enis; Uzgur, Selda; Karaca, Aziz; Vardar, Selma Arzu; Yilmaz, Ali; Aydogdu, Nurettin

2016-08-01

Long-term effects of high protein diets (HPDs) on kidneys are still not sufficiently studied. Irisin which increases oxygen consumption and thermogenesis in white fat cells was shown in skeletal muscles and many tissues. Nitric oxide synthases (NOS) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. We aimed to investigate the effects of HPD, irisin and NO expression in kidney and relation of them with exercise and among themselves. Animals were grouped as control, exercise, HPD and exercise combined with HPD (exercise-HPD). Rats were kept on a HPD for 5 weeks and an exercise program was given them as 5 exercise and 2 rest days per week exercising on a treadmill with increasing speed and angle. In our study, while HPD group had similar total antioxidant capacity (TAC) levels with control group, exercise and exercise-HPD groups had lower levels (p < 0.05). Kidneys of exercising rats had no change in irisin or eNOS expression but their iNOS expression had increased (p < 0.001). HPD-E group has not been observed to cause kidney damage and not have a significant effect on rat kidney irisin, eNOS, or iNOS expression. Localization of irisin, eNOS, and iNOS staining in kidney is highly selective and quite clear in this study. Effects of exercise and HPD on kidney should be evaluated with different exercise protocols and contents of the diet. İrisin, eNOS, and iNOS staining localizations should be supported with various research studies.

Design of Chemistry Teacher Education Course on Nature of Science

NASA Astrophysics Data System (ADS)

Vesterinen, Veli-Matti; Aksela, Maija

2013-09-01

To enhance students' understanding of nature of science (NOS), teachers need adequate pedagogical content knowledge related to NOS. The educational design research study presented here describes the design and development of a pre-service chemistry teacher education course on NOS instruction. The study documents two iterative cycles of problem analysis, design, implementation, and evaluation. The main aims of the study were (1) to create an in-depth and detailed description of the process used in the development of the course and the design solutions produced, and (2) to evaluate how the design solutions affected participants' commitment to teach NOS. Based on the problem analysis based on challenges recognized from the previous research, three design solutions were produced: (1) definition of central dimensions of domain-specific NOS for chemistry education, (2) teaching cycle for explicit and structured opportunities for reflection and discussion, and (3) design assignments to translate NOS understanding into classroom practice. The major data-sources used in the evaluation of the design solutions were the four in-depth interviews conducted after the course. Based on the evaluation, the design solutions supported internalizing understanding of NOS and transforming the understanding to instruction. Supporting the implementation of new innovative teaching practices such as NOS instruction in pre-service teacher education is a challenge. However, the success of the participants in implementing NOS instruction demonstrates, that a pre-service teacher education course can be successful in producing early adopters of NOS instruction and thus might be one of the first steps in injecting NOS instruction into the curriculum.

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

Chung, E.; Chen, G.; Gardiner, M.

The etiological role of the gene for neuronal nitric oxide synthase (NOS1) in infantile pyloric stenosis (PS) was investigated by analysis of two intragenic polymorphisms (NOS1a and NOS1b) in 27 families. There was significant overall transmission disequilibrium between PS and NOS1a (P=.006). Consideration of each allele independently revealed a highly significant tendency for allele 7 (210 bp) to be preferentially transmitted to the affected offspring (P=.0006). These observations suggest that NOS1 is a susceptibility locus for PS. 38 refs., 1 fig., 3 tabs.

Using human sera to identify a 52-kDa exoantigen of Penicillium chrysogenum and implications of polyphasic taxonomy of anamorphic ascomycetes in the study of antigenic proteins.

PubMed

Wilson, Aaron M; Luo, Wen; Miller, J David

2009-11-01

We are interested in isolating and identifying antigenic fungal proteins from species that grow on damp building materials. The indoor clade of Penicillium chrysogenum, the so-called Fleming clade, is the most common species of Penicillium on moldy building materials. We have identified a 52-kDa marker protein for the indoor clade of P. chrysogenum not present in a taxonomically diverse selection of fungi. It is found in high concentrations in protein extracted from the fungus grown on paper-faced gypsum wallboard. During this process, we illuminated the variability in response to patient sera and of strains of the fungus collected over a wide geographic area. From a collection of sera from all over the USA, 25 of the 48 patients reacted to the 52-kDa protein from this prescreened collection of sera. Most strain/antibody combinations had proportionate ELISA response associated with the presence of the target. However, approximately 25% of the strain/patient serum combinations included people who responded to many common allergens from the Penicillia. All the P. chrysogenum strains tested produced the target protein. However, there was considerable variability in patient IgG response to 32-, 30-, and 18-kDa antigens and in their production by the various clade 4 strains. The target protein was not found in spores or culture extracts of a wide selection of relevant fungi. It appears that the previous studies have been conducted on strains of the fungus from the three clades not those associated with the built environment.

[The virtual environment of a research group: the tutors' perspective].

PubMed

Prado, Cláudia; Casteli, Christiane Pereira Martins; Lopes, Tania Oliveira; Kobayashi, Rika M; Peres, Heloísa Helena Ciqueto; Leite, Maria Madalena Januário

2012-02-01

The Grupo de Estudos e Pesquisas de Tecnologia da Informação nos Processos de Trabalho em Enfermagem (Study and Research Group for Information Technology in the Nursing Working Processes, GEPETE) has the purpose of producing and socializing knowledge in information technology and health and nursing communication, making associations with research groups in this field and promoting student participation. This study was performed by the group tutors with the objective to report on the development of the virtual learning environment (VLE) and the tutors' experience as mediators of a research group using the Moodle platform. To do this, a VLE was developed and pedagogical mediation was performed following the theme of mentoring. An initial diagnosis was made of the difficulties in using this technology in interaction and communication, which permitted the proposal of continuing to use the platform as a resource to support research activities, offer lead researchers the mechanisms to socialize projects and offer the possibility of giving advice at a distance.

Populações estelares em galáxias HII

NASA Astrophysics Data System (ADS)

Westera, P.; Cuisinier, F.; Telles, E.; Kehrig, C.

2003-08-01

Analisamos o conteúdo estelar de 74 galáxias HII a partir do contínuo observado nos espectros ópticos dessas galáxias, utilizando métodos de síntese de população estelar. Descobrimos que todas as galáxias para as quais encontramos soluções contêm uma população estelar velha que domina a massa estelar, e numa maioria dessas também encontramos evidência de uma população de idade intermediaria além da geração jovem que está se formando agora. Concluímos que a formação estelar dessas galáxias se realiza em surtos individuais, Esses surtos são interrompidos por longos períodos de inatividade, com os primeiros consumindo a maior parte do gás. Sugerimos, portanto, que as galáxias HII sejam galáxias anãs normais flagradas em um período de surto.

Clinicopathological analysis in PTCL-NOS with CADM1 expression.

PubMed

Kato, Takeharu; Miyoshi, Hiroaki; Kobayashi, Seiichiro; Yoshida, Noriaki; Imaizumi, Yoshitaka; Seto, Masao; Uchimaru, Kaoru; Miyazaki, Yasushi; Ohshima, Koichi

2017-11-01

Peripheral T cell lymphoma, not otherwise specified (PTCL-NOS), is a heterogeneous disease with respect to clinicopathological features. Cell adhesion molecule 1 (CADM1) has been reported to be ectopically expressed in adult T cell leukaemia/lymphoma (ATLL). However, the frequency of CADM1 expression remains unknown in peripheral T cell lymphomas. In the current study, CADM1 expression was analysed in 88 PTCL-NOS patients. CADM1 was expressed in 14 of 88 (15.9%) PTCL-NOS cases, and its expression was associated with C-C chemokine receptor type 4 (CCR4) expression and nuclear atypia. CADM1-positive PTCL-NOS cases (10/74) had a significantly poorer prognosis than CADM1-negative cases (64/74) (P = 0.001). Multivariate analysis confirmed that CADM1 expression was an independent prognostic factor in PTCL-NOS. These findings suggest that CADM1 expression is a novel prognostic factor for PTCL-NOS.

Inducible nitric oxide expression correlates with the level of inflammation in periapical cysts.

PubMed

Matsumoto, Mariza Akemi; Ribeiro, Daniel Araki

2007-10-01

In an attempt to elucidate if inducible nitric oxide expression (iNOS) is correlated with the level of inflammation in periapical cysts with accuracy, the goal of this study was to evaluate the expression of iNOS in these ones. 30 cases were included in this study being iNOS evaluated by means of immunohistochemistry. Statistical analysis was performed by Kruskal-Wallis non-parametric test followed by the post-hoc Dunn's test. iNOS stain was detected throughout the epithelium, subepithelial fibroblasts and macrophages in all cases, indistinctly. Nevertheless, iNOS immunostaining in periapical cysts was different according to the levels of inflammation, being the strongest effect associated with intense inflammatory infiltrate. Taken together, our results indicate that immunoreactivity of iNOS was expressed in several cellular types present in periapical cyst, being positively correlated with the level of inflammation. Therefore, iNOS expression plays an important role in the pathogenesis of periapical cysts.

The Tentativeness of Scientific Theories: Conceptions of Pre-Service Science Teachers

ERIC Educational Resources Information Center

Jain, Jasmine; Abdullah, Nabilah; Lim, Beh Kian

2014-01-01

The recognition of sound understanding of Nature of Science (NOS) in promoting scientific literacy among individuals has heightened the need to probe NOS conceptions among various groups. However, the nature of quantitative studies in gauging NOS understanding has left the understanding on few NOS aspects insufficiently informed. This paper aimed…

Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B

PubMed Central

Lee, Chih-Yung Sean; Lu, Tu

2017-01-01

Nanos RNA-binding proteins are required for germline development in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of primordial germ cells (PGCs) lacking the nanos homologs nos-1 and nos-2 in C. elegans. nos-1nos-2 PGCs fail to silence hundreds of transcripts normally expressed in oocytes. We find that this misregulation is due to both delayed turnover of maternal transcripts and inappropriate transcriptional activation. The latter appears to be an indirect consequence of delayed turnover of the maternally-inherited transcription factor LIN-15B, a synMuvB class transcription factor known to antagonize PRC2 activity. PRC2 is required for chromatin reprogramming in the germline, and the transcriptome of PGCs lacking PRC2 resembles that of nos-1nos-2 PGCs. Loss of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These findings suggest that Nanos promotes germ cell fate by downregulating maternal RNAs and proteins that would otherwise interfere with PRC2-dependent reprogramming of PGC chromatin. PMID:29111977

Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B.

PubMed

Lee, Chih-Yung Sean; Lu, Tu; Seydoux, Geraldine

2017-11-07

Nanos RNA-binding proteins are required for germline development in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of primordial germ cells (PGCs) lacking the nanos homologs nos-1 and nos-2 in C. elegans. nos-1nos-2 PGCs fail to silence hundreds of transcripts normally expressed in oocytes. We find that this misregulation is due to both delayed turnover of maternal transcripts and inappropriate transcriptional activation. The latter appears to be an indirect consequence of delayed turnover of the maternally-inherited transcription factor LIN-15B, a synMuvB class transcription factor known to antagonize PRC2 activity. PRC2 is required for chromatin reprogramming in the germline, and the transcriptome of PGCs lacking PRC2 resembles that of nos-1nos-2 PGCs. Loss of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These findings suggest that Nanos promotes germ cell fate by downregulating maternal RNAs and proteins that would otherwise interfere with PRC2-dependent reprogramming of PGC chromatin.

Effect of dexamethasone on endothelial nitric oxide synthase in experimental congenital diaphragmatic hernia

PubMed Central

Okoye, B.; Losty, P.; Fisher, M.; Wilmott, I.; Lloyd, D.

1998-01-01

AIMS—To study the effect of prenatal glucocorticoid treatment on endothelial nitric oxide synthase (eNOS) expression in rats with congenital diaphragmatic hernia (CDH).
METHODS—CDH was induced in fetal rats by the maternal administration of nitrofen on day 9.5 of gestation. Dexamethasone was administered on days 18.5 and 19.5 before delivery of the fetuses on days 20.5and 21.5. Pulmonary eNOS protein expression was studied by western immunoblotting and immunohistochemistry.
RESULTS—On day 20.5, eNOS expression was significantly reduced in CDH pups compared with normal control rats. Dexamethasone treated CDH pups had eNOS concentrations equivalent to those of normal animals. By day 21.5, however, there was no detectable difference in eNOS expression between the experimental groups.
CONCLUSIONS—eNOS is deficient in near term (day 20.5) CDH rats. Dexamethasone restores eNOS expression in these animals to that seen in normal rat lungs. At term, the precise role of eNOS in the pathophysiology of CDH remains uncertain.

 PMID:9713033

Is the Health of the Nation Outcome Scales appropriate for the assessment of symptom severity in patients with substance-related disorders?

PubMed

Andreas, Sylke; Harries-Hedder, Karin; Schwenk, Wolfgang; Hausberg, Maria; Koch, Uwe; Schulz, Holger

2010-07-01

The Health of the Nation Outcome Scales (HoNOS) is an internationally established clinician-rated instrument. The aim of the study was to assess the psychometric properties in inpatients with substance-related disorders. The HoNOS was applied in a multicenter, consecutive sample of 417 inpatients. Interrater reliability coefficients, confirmatory factor analysis, and regression tree analyses were calculated to assess the reliability and validity of the HoNOS. The factor validity of the HoNOS and its total score could not be confirmed. After training, all items of the HoNOS revealed sufficient values of interrater reliabilities. As the results of the regression tree analyses showed, the single items of the HoNOS were one of the most important predictor of service utilization. The HoNOS can be recommended for obtaining detailed ratings of the problems of inpatients with substance-related disorders as a clinical application in routine mental health care at present. Further studies should include comparisons of HoNOS and Addiction Severity Index. Copyright 2010 Elsevier Inc. All rights reserved.

Measurement of O-GlcNAcylated endothelial nitric oxide synthase by using 2',5'-ADP-Sepharose pull-down assay.

PubMed

Long, Yang; Yan, Jianghong; Luo, Suxin; Liu, Zhenguo; Xia, Yong

2017-11-15

Endothelial nitric oxide synthase (eNOS) plays central roles in cardiovascular regulation and disease. eNOS function is critically affected by O-linked N-acetylglucosamine (O-GlcNAc) modification. The present method for measuring O-GlcNAcylated eNOS relies on immunoprecipitation. Such method exhibits low detection efficiency and is also costly. We here report a simplified assay by employing the high binding affinity of eNOS with the 2',5'-ADP-Sepharose resins. Together with the O-GlcNAc antibody, this assay readily allows the detection of O-GlcNAcylated eNOS in both cultured endothelial cells and rat vascular tissues. By using this assay, we demonstrate that eNOS O-GlcNAcylation is markedly elevated in the vessels of diabetic rats. Thus, a 2',5'-ADP-Sepharose-based pull-down assay is developed to measure O-GlcNAcylated eNOS. This assay is simple and efficient in detecting O-GlcNAcylated eNOS in cultured cells and animal tissues under both normal and disease conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Translation, cross-cultural adaptation and validation of the Diabetes Empowerment Scale - Short Form.

PubMed

Chaves, Fernanda Figueredo; Reis, Ilka Afonso; Pagano, Adriana Silvina; Torres, Heloísa de Carvalho

2017-03-23

To translate, cross-culturally adapt and validate the Diabetes Empowerment Scale - Short Form for assessment of psychosocial self-efficacy in diabetes care within the Brazilian cultural context. Assessment of the instrument's conceptual equivalence, as well as its translation and cross-cultural adaptation were performed following international standards. The Expert Committee's assessment of the translated version was conducted through a web questionnaire developed and applied via the web tool e-Surv. The cross-culturally adapted version was used for the pre-test, which was carried out via phone call in a group of eleven health care service users diagnosed with type 2 diabetes mellitus. The pre-test results were examined by a group of experts, composed by health care consultants, applied linguists and statisticians, aiming at an adequate version of the instrument, which was subsequently used for test and retest in a sample of 100 users diagnosed with type 2 diabetes mellitus via phone call, their answers being recorded by the web tool e-Surv. Internal consistency and reproducibility of analysis were carried out within the statistical programming environment R. Face and content validity were attained and the Brazilian Portuguese version, entitled Escala de Autoeficácia em Diabetes - Versão Curta, was established. The scale had acceptable internal consistency with Cronbach's alpha of 0.634 (95%CI 0.494- 0.737), while the correlation of the total score in the two periods was considered moderate (0.47). The intraclass correlation coefficient was 0.50. The translated and cross-culturally adapted version of the instrument to spoken Brazilian Portuguese was considered valid and reliable to be used for assessment within the Brazilian population diagnosed with type 2 diabetes mellitus. The use of a web tool (e-Surv) for recording the Expert Committee responses as well as the responses in the validation tests proved to be a reliable, safe and innovative method. Traduzir, adaptar culturalmente e validar o Diabetes Empowerment Scale - Short Form para aplicação no contexto cultural brasileiro. A análise do instrumento, para avaliar a equivalência conceitual e de itens, bem como sua tradução e adaptação cultural, foram realizadas de acordo com a metodologia padrão. A etapa de avaliação pelo comitê de juízes foi conduzida por meio de questionário eletrônico, desenvolvido e aplicado pela ferramenta web e-Surv. A versão adaptada foi utilizada durante o pré-teste, aplicado via ligação telefônica, a um grupo de 11 usuários com diabetes melito tipo 2. Os resultados do pré-teste foram examinados por profissionais da área da saúde, linguística aplicada e estatística, para obtenção de uma versão adequada do instrumento. Em seguida, foi aplicada no teste e reteste em amostra de 100 usuários com diabetes, por ligação telefônica, com registro das respostas dos usuários por meio da ferramenta e-Surv. As análises de consistência interna e reprodutibilidade foram realizadas no ambiente de programação estatística R. Foi possível obter validade de face e de conteúdo do instrumento, que resultou na versão em português, intitulada Escala de Autoeficácia em Diabetes - Versão Curta. A escala apresentou consistência interna aceitável, com alfa de Cronbach igual a 0,634 (IC95% 0,494-0,737), enquanto a concordância do escore total nos dois momentos foi considerada moderada (0,47). O coeficiente de correlação intraclasse teve o valor de 0,50. O processo de tradução e de adaptação para a língua portuguesa falada no Brasil gerou uma versão do instrumento considerada válida e confiável para a população brasileira. A utilização do e-Surv para o registro dos dados coletados do comitê de juízes, assim como das respostas dos testes de validação, mostrou-se uma metodologia confiável, segura e inovadora.

The oldest anatomical handmade skull of the world c. 1508: 'the ugliness of growing old' attributed to Leonardo da Vinci.

PubMed

Missinne, Stefaan J

2014-06-01

The author discusses a previously unknown early sixteenth-century renaissance handmade anatomical miniature skull. The small, naturalistic skull made from an agate (calcedonia) stone mixture (mistioni) shows remarkable osteologic details. Dr. Saban was the first to link the skull to Leonardo. The three-dimensional perspective of and the search for the senso comune are discussed. Anatomical errors both in the drawings of Leonardo and this skull are presented. The article ends with the issue of physiognomy, his grotesque faces, the Perspective Communis and his experimenting c. 1508 with the stone mixture and the human skull. Evidence, including the Italian scale based on Crazie and Braccia, chemical analysis leading to a mine in Volterra and Leonardo's search for the soul in the skull are presented. Written references in the inventory of Salai (1524), the inventory of the Villa Riposo (Raffaello Borghini 1584) and Don Ambrogio Mazenta (1635) are reviewed. The author attributes the skull c. 1508 to Leonardo da Vinci.

The Nature of Science and the Next Generation Science Standards: Analysis and Critique

NASA Astrophysics Data System (ADS)

McComas, William F.; Nouri, Noushin

2016-08-01

This paper provides a detailed analysis of the inclusion of aspects of nature of science (NOS) in the Next Generation Science Standards (NGSS). In this new standards document, NOS elements in eight categories are discussed in Appendix H along with illustrative statements (called exemplars). Many, but not all, of these exemplars are linked to the standards by their association with either the "practices of science" or "crosscutting concepts," but curiously not with the recommendations for science content. The study investigated all aspects of NOS in NGSS including the accuracy and inclusion of the supporting exemplar statements and the relationship of NOS in NGSS to other aspects of NOS to support teaching and learning science. We found that while 92 % of these exemplars are acceptable, only 78 % of those written actually appear with the standards. "Science as a way of knowing" is a recommended NOS category in NGSS but is not included with the standards. Also, several other NOS elements fail to be included at all grade levels thus limiting their impact. Finally, NGSS fails to include or insufficiently emphasize several frequently recommended NOS elements such as creativity and subjectivity. The paper concludes with a list of concerns and solutions to the challenges of NOS in NGSS.

Piper sarmentosum increases nitric oxide production in oxidative stress: a study on human umbilical vein endothelial cells.

PubMed

Ugusman, Azizah; Zakaria, Zaiton; Hui, Chua Kien; Nordin, Nor Anita Megat Mohd

2010-07-01

Nitric oxide produced by endothelial nitric oxide synthase (eNOS) possesses multiple anti-atherosclerotic properties. Hence, enhanced expression of eNOS and increased Nitric oxide levels may protect against the development of atherosclerosis. Piper sarmentosum is a tropical plant with antioxidant and anti-inflammatory activities. This study aimed to investigate the effects of Piper sarmentosum on the eNOS and Nitric oxide pathway in cultured human umbilical vein endothelial cells (HUVECs). HUVECS WERE DIVIDED INTO FOUR GROUPS: control, treatment with 180 microM hydrogen peroxide (H(2)O(2)), treatment with 150 microg/mL aqueous extract of Piper sarmentosum, and concomitant treatment with aqueous extract of PS and H(2)O(2) for 24 hours. Subsequently, HUVECs were harvested and eNOS mRNA expression was determined using qPCR. The eNOS protein level was measured using ELISA, and the eNOS activity and Nitric oxide level were determined by the Griess reaction. Human umbilical vein endothelial cells treated with aqueous extract of Piper sarmentosum showed a marked induction of Nitric oxide. Treatment with PS also resulted in increased eNOS mRNA expression, eNOS protein level and eNOS activity in HUVECs. Aqueous extract of Piper sarmentosum may improve endothelial function by promoting NO production in HUVECs.

Association of endothelial nitric oxide synthase gene polymorphism with the risk of Henoch-Schönlein purpura/Henoch-Schönlein purpura nephritis.

PubMed

Zhong, Weiqiang; Zhou, Tian-Biao; Jiang, Zongpei

2015-04-01

Association between endothelial nitric oxide synthase (eNOS) gene polymorphism and Henoch-Schönlein purpura (HSP)/Henoch-Schönlein purpura nephritis (HSPN) risk is still controversial. A meta-analysis was performed to evaluate the association between eNOS gene polymorphism and HSP/HSPN susceptibility. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic database. Three articles were identified for the analysis of association between eNOS gene polymorphism and HSPN/HSP risk. eNOS G894T gene polymorphism was not associated with HSPN susceptibility and the risk of patients with HSP developing into HSPN. Interestingly, eNOS G894T T allele and GG genotype were associated with HSP susceptibility, but not the TT genotype. eNOS T786C TT genotype was associated with HSPN susceptibility, but not C allele and CC genotype. Furthermore, eNOS T786C gene polymorphism was not associated with HSP risk and the risk of patients with HSP developing into HSPN. In conclusion, eNOS T786C TT genotype was associated with and eNOS G894T T allele and GG genotype were associated with HSP susceptibility. However, more studies should be performed in the future.

The metabolism of carbadox, olaquindox, mequindox, quinocetone and cyadox: an overview.

PubMed

Liu, Zhao-Ying; Sun, Zhi-Liang

2013-12-01

The aim of this article is to get an overview of the metabolism of quinoxaline 1,4-di-N-oxides (QdNOs) used in food animals. The derivatives of QdNOs (carbadox, olaquindox, mequindox, quinocetone, and cyadox) are the potent synthetic antimicrobial agents that are used for improving the feed efficiency and controlling dysentery in food-producing animals. Studies have demonstrated that the toxicity of QdNOs is closely associated with the production of their metabolism, especially with the production of their reduced metabolites. To the best of our knowledge, no one has systematically compiled the metabolism data of QdNOs. Therefore, the metabolism of QdNOs in animals has been discussed in the review for the first time. These drugs undergo extensive metabolism prior to excretion. N-oxide group reduction is the major metabolic pathway of QdNOs. Moreover, the N1- and N4-oxide reductions of QdNOs by different reducing mechanisms are also described. Obvious differences in metabolic pathways for QdNOs were observed owing to the differences on the side chain of these drugs. Therefore, understanding the metabolic pathways of QdNOs in animals will provide the guides for further studies of metabolism and toxicology of these drugs, and will also provide abundant information for the food safety assessment.

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

PubMed

Ewerling, Fernanda; Barros, Aluísio J D

2017-03-02

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

SURGERY AND CARDIOVASCULAR SURGERY JOURNALS ANALYSIS.

PubMed

Schanaider, Alberto

2015-01-01

To analyze critically the effectiveness and value of bibliometric indicators in journals of Surgery or Cardiovacular Surgery in the context of the postgraduate programs of CAPES Medicine III. A sampling with 16 academic programs and one professional master of Medicine III, encompassing the General and Digestive System Surgery, Cardiovascular Surgery and Multidisciplinary courses with such contents, was evaluated. Thomson Reuters/ISI (JCR), Elsevier/Scopus (SJR), and also Scielo databases were used. Only in seven programs, the teachers had an average of Qualis A1 articles greater than the others strata. Eleven journals in the surgical area are in stratum A1 (5%) and it reaches 25% in Cardiovascular Surgery. Among the six journals with the largest number of publications Qualis A1 in area Medicine III, five are from non-specific areas. The Acta Cirúrgica Brasileira represented 58% of the publications in the stratum A2. There are some obstacles in the Qualis classification with little uniformity among the Medicine areas I, II and III. A permanent committee should be set to update the Qualis, composed by the three medical areas. It should be considered using other index databases and the unification of the Qualis criteria for journals in medicine. Rating criteria of multi and transdisciplinary journals need to be reviewed. It is essential an institutional financial support for national journals chosen by peers aiming to provide a full computerization process and a professional reviewer of the English language, in order to increase the impact factor. Analisar criticamente a eficácia e valor de indicadores bibliométricos dos periódicos da Cirurgia e Cirurgia Cardiovascular no contexto dos Programas de Pós-Graduação da área Medicina III da CAPES. Foi avaliada uma amostragem com 16 programas acadêmicos e um mestrado profissional da área de Medicina III, compreendendo a Cirurgia Geral e do Aparelho Digestivo, a Cirurgia Cardiovascular e Cursos Multidisciplinares com estes conteúdos. Utilizaram-se as bases de dados Thomson Reuters/ISI (JCR), Elsevier/Scopus (SJR), além do Scielo. Somente nos programas 7, os docentes têm média de artigos Qualis A1 maior ou igual que os demais estratos. Apenas 11 periódicos da área de Cirurgia estão no estrato A1 (5%) e na Cirurgia Cardiovascular são 25%. Dos seis periódicos com o maior número de publicações na área Medicina III, Qualis A1, cinco não são específicos da área. A Acta Cirúrgica Brasileira representou 58% das publicações no estrato A2. Há alguns óbices na classificação Qualis com pouca uniformidade entre as Medicinas I, II e III. Se impõe a criação de um comitê permanente para atualização do Qualis, composto pelas três áreas da Medicina. Deve-se ponderar a utilização de outras bases de indexação e a unificação dos critérios Qualis para as revistas das áreas de medicina. Critérios de classificação dos periódicos multi e transdisciplinares precisam ser revistos. É imprescindível suporte financeiro institucional aos periódicos nacionais escolhidos pelos pares visando informatização completa e prover revisão profissional da língua inglesa, tendo como meta a elevação do fator de impacto.

iNOS inhibits hair regeneration in obese diabetic (ob/ob) mice.

PubMed

Sasaki, Mari; Shinozaki, Shohei; Morinaga, Hironobu; Kaneki, Masao; Nishimura, Emi; Shimokado, Kentaro

2018-07-02

Previous studies have shown that androgenic alopecia is associated with metabolic syndrome and diabetes. However, the detailed mechanism whereby diabetes causes alopecia still remains unclear. We focused on the inflammatory response that is caused by diabetes or obesity, given that inflammation is a risk factor for hair loss. Inducible nitric oxide synthase (iNOS) is known to be upregulated under conditions of acute or chronic inflammation. To clarify the potential role of iNOS in diabetes-related alopecia, we generated obese diabetic iNOS-deficient (ob/ob; iNOS-KO mice). We observed that ob/ob; iNOS-KO mice were potentiated for the transition from telogen (rest phase) to anagen (growth phase) in the hair cycle compared with iNOS-proficient ob/ob mice. To determine the effect of nitric oxide (NO) on the hair cycle, we administered an iNOS inhibitor intraperitoneally (compound 1400 W, 10 mg/kg) or topically (10% aminoguanidine) in ob/ob mice. We observed that iNOS inhibitors promoted anagen transition in ob/ob mice. Next, we administered an NO donor (S-nitrosoglutathione, GSNO), to test whether NO has the telogen elongation effects. The NO donor was sufficient to induce telogen elongation in wild-type mice. Together, our data indicate that iNOS-derived NO plays a role in telogen elongation under the inflammatory conditions associated with diabetes in mice. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

An initial examination of Singaporean seventh and eighth graders' views of nature of science

NASA Astrophysics Data System (ADS)

Lin, Tzung-Jin; Goh, Amos Yoong Shin; Chai, Ching Sing; Tsai, Chin-Chung

2013-07-01

Background and purpose . Research in nature of science (NOS) among Asia-Pacific countries such as Singapore is arguably scarce. This study aimed to survey Singaporean secondary school students' views of NOS with a newly developed instrument named Students' Views of Nature of Science (SVNOS), which included various key aspects of NOS that are generally agreed upon by the science education community. Moreover, the relations between some demographic factors, including gender and grade, and students' views of NOS were explored. Sample, design and method In total, 359 Singaporean seventh and eighth graders were invited to participate in this survey. The reliability, validity and structure of the SVNOS instrument were ensured by confirmatory factor analysis. A two-way multivariate analysis of variance was then conducted to determine the interaction effects between the gender variable and the grade-level variable. Results and conclusion The results indicated that the SVNOS instrument is reliable and valid to assess students' views of NOS regarding seven distinct NOS dimensions. The male students were more prone to have constructivist-oriented views of NOS in the most of the SVNOS dimensions, while the female students conveyed more non-objective views of NOS. In addition, the eighth graders revealed more empiricist-oriented views of NOS than the seventh graders in several SVNOS dimensions. This result seems to contradict the results of previous studies that students' views of NOS may reflect a developmental trend with their increasing educational experiences.

Endothelial nitric oxide synthase in hypoxic newborn porcine pulmonary vessels

PubMed Central

Hislop, A; Springall, D; Oliveira, H; Pollock, J; Polak, J; Haworth, S

1997-01-01

AIMS—To determine if the failure of neonatal pulmonary arteries to dilate is due to a lack of nitric oxide synthase (NOS).
METHODS—A monoclonal antibody to endothelial NOS was used to demonstrate the distribution and density of NOS in the developing porcine lung after a period in hypobaric hypoxia. Newborn piglets were made hypertensive by exposure to hypobaric hypoxia (50.8 kPa) from < 5 minutes of age to 2.5 days of age, 3-6 days of age or 14-17 days of age. A semiquantitative scoring system was used to assess the distribution of endothelial NOS by light microscopy.
RESULTS—NOS was present in the arteries in all hypoxic animals. However, hypoxia from birth caused a reduction in NOS compared with those lungs normal at birth and those normal at 3 days. Hypoxia from 3-6 days led to a high density of NOS compared with normal lungs at 6 days. Hypoxia from 14-17 days had little effect on the amount of NOS. On recovery in room air after exposure to hypoxia from birth there was a transient increase in endothelial NOS after three days of recovery, mirroring that seen at three days in normal animals.
CONCLUSIONS—Suppression of NOS production in the first few days of life may contribute to pulmonary hypertension in neonates.

 Keywords: pulmonary circulation; nitric oxide synthase; hypoxia; endothelium; piglets PMID:9279177

NOS1-derived nitric oxide promotes NF-κB transcriptional activity through inhibition of suppressor of cytokine signaling-1

PubMed Central

Baig, Mirza Saqib; Zaichick, Sofia V.; Mao, Mao; de Abreu, Andre L.; Bakhshi, Farnaz R.; Hart, Peter C.; Saqib, Uzma; Deng, Jing; Chatterjee, Saurabh; Block, Michelle L.; Vogel, Stephen M.; Malik, Asrar B.; Consolaro, Marcia E.L.; Christman, John W.; Minshall, Richard D.

2015-01-01

The NF-κB pathway is central to the regulation of inflammation. Here, we demonstrate that the low-output nitric oxide (NO) synthase 1 (NOS1 or nNOS) plays a critical role in the inflammatory response by promoting the activity of NF-κB. Specifically, NOS1-derived NO production in macrophages leads to proteolysis of suppressor of cytokine signaling 1 (SOCS1), alleviating its repression of NF-κB transcriptional activity. As a result, NOS1−/− mice demonstrate reduced cytokine production, lung injury, and mortality when subjected to two different models of sepsis. Isolated NOS1−/− macrophages demonstrate similar defects in proinflammatory transcription on challenge with Gram-negative bacterial LPS. Consistently, we found that activated NOS1−/− macrophages contain increased SOCS1 protein and decreased levels of p65 protein compared with wild-type cells. NOS1-dependent S-nitrosation of SOCS1 impairs its binding to p65 and targets SOCS1 for proteolysis. Treatment of NOS1−/− cells with exogenous NO rescues both SOCS1 degradation and stabilization of p65 protein. Point mutation analysis demonstrated that both Cys147 and Cys179 on SOCS1 are required for its NO-dependent degradation. These findings demonstrate a fundamental role for NOS1-derived NO in regulating TLR4-mediated inflammatory gene transcription, as well as the intensity and duration of the resulting host immune response. PMID:26324446

Effect of deuterium-depleted water on selected cardiometabolic parameters in fructose-treated rats.

PubMed

Rehakova, R; Klimentova, J; Cebova, M; Barta, A; Matuskova, Z; Labas, P; Pechanova, O

2016-10-24

Deuterium-depleted water (DDW) has a lower concentration of deuterium than occurs naturally (less than 145 ppm). While effects of DDW on cancer started to be intensively studied, the effects on cardiovascular system are completely unknown. Thus, we aimed to analyze the effects of DDW (55+/-5 ppm) administration to 12-week-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) treated with 15 % fructose for 6 weeks. Blood pressure (BP) and selected biochemical parameters were measured together with determination of nitric oxide synthase (NOS) activity and iNOS and eNOS protein expressions in the left ventricle (LV) and aorta. Neither DDW nor fructose had any significant effect on BP in both strains. DDW treatment decreased total cholesterol and triglyceride levels in WKY, but it was not able to prevent increase in the same parameters elevated due to fructose treatment in SHR. Both fructose and DDW increased insulin level in WKY. Fructose did not affect NOS activity either in WKY or SHR. DDW increased NOS activity in LV of both WKY and SHR, while it decreased NOS activity and iNOS expression in the aorta of SHR with or without fructose treatment. In conclusion, DDW treatment significantly modified biochemical parameters in WKY together with NOS activity elevation in the heart. On the other hand, it did not affect biochemical parameters in SHR, but decreased NOS activity elevated due to iNOS upregulation in the aorta.

Analysis of Nature of Science Included in Recent Popular Writing Using Text Mining Techniques

NASA Astrophysics Data System (ADS)

Jiang, Feng; McComas, William F.

2014-09-01

This study examined the inclusion of nature of science (NOS) in popular science writing to determine whether it could serve supplementary resource for teaching NOS and to evaluate the accuracy of text mining and classification as a viable research tool in science education research. Four groups of documents published from 2001 to 2010 were analyzed: Scientific American, Discover magazine, winners of the Royal Society Winton Prize for Science Books, and books from NSTA's list of Outstanding Science Trade Books. Computer analysis categorized passages in the selected documents based on their inclusions of NOS. Human analysis assessed the frequency, context, coverage, and accuracy of the inclusions of NOS within computer identified NOS passages. NOS was rarely addressed in selected document sets but somewhat more frequently addressed in the letters section of the two magazines. This result suggests that readers seem interested in the discussion of NOS-related themes. In the popular science books analyzed, NOS presentations were found more likely to be aggregated in the beginning and the end of the book, rather than scattered throughout. The most commonly addressed NOS elements in the analyzed documents are science and society and empiricism in science. Only one inaccurate presentation of NOS were identified in all analyzed documents. The text mining technique demonstrated exciting performance, which invites more applications of the technique to analyze other aspects of science textbooks, popular science writing, or other materials involved in science teaching and learning.

Calcium-mediated signaling and calmodulin-dependent kinase regulate hepatocyte-inducible nitric oxide synthase expression.

PubMed

Zhang, Baochun; Crankshaw, Will; Nesemeier, Ryan; Patel, Jay; Nweze, Ikenna; Lakshmanan, Jaganathan; Harbrecht, Brian G

2015-02-01

Induced nitric oxide synthase (iNOS) is induced in hepatocytes by shock and inflammatory stimuli. Excessive NO from iNOS mediates shock-induced hepatic injury and death, so understanding the regulation of iNOS will help elucidate the pathophysiology of septic shock. In vitro, cytokines induce iNOS expression through activation of signaling pathways including mitogen-activated protein kinases and nuclear factor κB. Cytokines also induce calcium (Ca(2+)) mobilization and activate calcium-mediated intracellular signaling pathways, typically through activation of calmodulin-dependent kinases (CaMK). Calcium regulates NO production in macrophages but the role of calcium and calcium-mediated signaling in hepatocyte iNOS expression has not been defined. Primary rat hepatocytes were isolated, cultured, and induced to produce NO with proinflammatory cytokines. Calcium mobilization and Ca(2+)-mediated signaling were altered with ionophore, Ca(2+) channel blockers, and inhibitors of CaMK. The Ca(2+) ionophore A23187 suppressed cytokine-stimulated NO production, whereas Ethylene glycol tetraacetic acid and nifedipine increased NO production, iNOS messenger RNA, and iNOS protein expression. Inhibition of CaMK with KN93 and CBD increased NO production but the calcineurin inhibitor FK 506 decreased iNOS expression. These data demonstrate that calcium-mediated signaling regulates hepatocyte iNOS expression and does so through a mechanism independent of calcineurin. Changes in intracellular calcium levels may regulate iNOS expression during hepatic inflammation induced by proinflammatory cytokines. Copyright © 2015 Elsevier Inc. All rights reserved.

A noninhibitory mutant of the caveolin-1 scaffolding domain enhances eNOS-derived NO synthesis and vasodilation in mice

PubMed Central

Bernatchez, Pascal; Sharma, Arpeeta; Bauer, Philip M.; Marin, Ethan; Sessa, William C.

2011-01-01

Aberrant regulation of eNOS and associated NO release are directly linked with various vascular diseases. Caveolin-1 (Cav-1), the main coat protein of caveolae, is highly expressed in endothelial cells. Its scaffolding domain serves as an endogenous negative regulator of eNOS function. Structure-function analysis of Cav-1 has shown that phenylalanine 92 (F92) is critical for the inhibitory actions of Cav-1 toward eNOS. Herein, we show that F92A–Cav-1 and a mutant cell–permeable scaffolding domain peptide called Cavnoxin can increase basal NO release in eNOS-expressing cells. Cavnoxin reduced vascular tone ex vivo and lowered blood pressure in normal mice. In contrast, similar experiments performed with eNOS- or Cav-1–deficient mice showed that the vasodilatory effect of Cavnoxin is abolished in the absence of these gene products, which indicates a high level of eNOS/Cav-1 specificity. Mechanistically, biochemical assays indicated that noninhibitory F92A–Cav-1 and Cavnoxin specifically disrupted the inhibitory actions of endogenous Cav-1 toward eNOS and thereby enhanced basal NO release. Collectively, these data raise the possibility of studying the inhibitory influence of Cav-1 on eNOS without interfering with the other actions of endogenous Cav-1. They also suggest a therapeutic application for regulating the eNOS/Cav-1 interaction in diseases characterized by decreased NO release. PMID:21804187

Angiotensin-(1-7) upregulates central nitric oxide synthase in spontaneously hypertensive rats.

PubMed

Cerrato, Bruno D; Frasch, Alejandra P; Nakagawa, Pablo; Longo-Carbajosa, Nadia; Peña, Clara; Höcht, Cristian; Gironacci, Mariela M

2012-05-09

Increased blood pressure in hypertension is hypothesized to be caused by high sympathetic nervous system (SNS) activity. Since Ang (1-7) exerts an inhibitory neuromodulatory effect on the SNS through a NO-mediated mechanism, we tested the hypothesis that Ang (1-7) alters centrally nitric oxide synthase (NOS) activity and expression in spontaneously hypertensive rats (SHR). Since NOS activity is altered in relation to the development of hypertension in rats, we evaluated the effect of Ang-(1-7) on hypothalamic NOS activity in two different ages in SHR, corresponding to a prehypertensive phase (3-4 weeks) and a established hypertension (13-14 weeks) and compared with age-matched Wistar-Kyoto (WKY) rats. NOS activity was measured by the conversion of [³H]L-arginine to citrulline. Ang-(1-7) caused an impairment in NOS activity in prehypertensive SHR (26 ± 4% reduction), while it induced an increase in NOS activity at established hypertension (48 ± 9% increase). In contrast, Ang-(1-7) did not modify NOS activity in age-matched WKY rats. In another set of experiments, Ang-(1-7) was injected into the anterior hypothalamic area, mean arterial blood pressure (MAP) was registered and after 30, 60 and 180 min nNOS expression was evaluated by Western-blot. Ang-(1-7) decreased MAP after 10 min of injection and this effect was blocked by a NOS inhibitor. nNOS expression increased after 180 min of Ang-(1-7) intrahypothalamic injection in both WKY and SHR (WKY: 3.6-fold increase above basal; SHR: 1.85-fold increase above basal). Our results suggest that Ang-(1-7) upregulates hypothalamic NOS in a hypertensive state as a compensatory and protective mechanism to combat hypertension. Copyright © 2012 Elsevier B.V. All rights reserved.

Community Composition of Nitrous Oxide Consuming Bacteria in the Oxygen Minimum Zone of the Eastern Tropical South Pacific

PubMed Central

Sun, Xin; Jayakumar, Amal; Ward, Bess B.

2017-01-01

The ozone-depleting and greenhouse gas, nitrous oxide (N2O), is mainly consumed by the microbially mediated anaerobic process, denitrification. N2O consumption is the last step in canonical denitrification, and is also the least O2 tolerant step. Community composition of total and active N2O consuming bacteria was analyzed based on total (DNA) and transcriptionally active (RNA) nitrous oxide reductase (nosZ) genes using a functional gene microarray. The total and active nosZ communities were dominated by a limited number of nosZ archetypes, affiliated with bacteria from marine, soil and marsh environments. In addition to nosZ genes related to those of known marine denitrifiers, atypical nosZ genes, related to those of soil bacteria that do not possess a complete denitrification pathway, were also detected, especially in surface waters. The community composition of the total nosZ assemblage was significantly different from the active assemblage. The community composition of the total nosZ assemblage was significantly different between coastal and off-shore stations. The low oxygen assemblages from both stations were similar to each other, while the higher oxygen assemblages were more variable. Community composition of the active nosZ assemblage was also significantly different between stations, and varied with N2O concentration but not O2. Notably, nosZ assemblages were not only present but also active in oxygenated seawater: the abundance of total and active nosZ bacteria from oxygenated surface water (indicated by nosZ gene copy number) was similar to or even larger than in anoxic waters, implying the potential for N2O consumption even in the oxygenated surface water. PMID:28702012

Gene transfer of inducible nitric oxide synthase complementary DNA regresses the fibrotic plaque in an animal model of Peyronie's disease.

PubMed

Davila, Hugo H; Magee, Thomas R; Vernet, Dolores; Rajfer, Jacob; Gonzalez-Cadavid, Nestor F

2004-11-01

The goal of the present study was to investigate the antifibrotic role of inducible nitric oxide synthase (iNOS) in Peyronie's disease (PD) by determining whether a plasmid expressing iNOS (piNOS) injected into a PD-like plaque can induce regression of the plaque. A PD-like plaque was induced with fibrin in the penile tunica albuginea of mice and then injected with a luciferase-expressing plasmid (pLuc), either alone or with piNOS, following luciferase expression in vivo by bioluminescence imaging. Rats were treated with either piNOS, an empty control plasmid (pC), or saline. Other groups were treated with pC or piNOS, in the absence of fibrin. Tissue sections were stained for collagen, transforming growth factor (TGF) beta1, and plasminogen-activator inhibitor (PAI-1) as profibrotic factors; copper-zinc superoxide dismutase (CuZn SOD) as scavenger of reactive oxygen species (ROS); and nitrotyrosine to detect nitric oxide reaction with ROS. Quantitative image analysis was applied. Both iNOS and xanthine oxido-reductase (XOR; oxidative stress) were estimated by Western blot analysis. Luciferase reporter expression was restricted to the penis, peaked at 3 days after injection, but continued for at least 3 wk. In rats receiving piNOS, iNOS expression also peaked at 3 days, but expression decreased at the end of treatment, when a considerable reduction of plaque size occurred. Protein nitrotyrosine, XOR, and CuZn SOD increased, and TGFbeta1 and PAI-1 decreased. The piNOS gene transfer regressed the PD plaque and expression of profibrotic factors, supporting the view that endogenous iNOS induction in PD is defense mechanism by the tissue against fibrosis.

Transactivation of inducible nitric oxide synthase gene by Kruppel-like factor 6 regulates apoptosis during influenza A virus infection

PubMed Central

Mgbemena, Victoria; Segovia, Jesus A.; Chang, Te-Hung; Tsai, Su-Yu; Cole, Garry T.; Hung, Chiung-Yu; Bose, Santanu

2012-01-01

Influenza A virus (flu) is a respiratory tract pathogen causing high morbidity and mortality among the human population. Nitric oxide (NO) is a cellular mediator involved in tissue damage due to apoptosis of target cells and resulting enhancement of local inflammation. Inducible nitric oxide (iNOS) is involved in the production of NO following infection. Although NO is a key player in the development of exaggerated lung disease during flu infection, the underlying mechanism including the role of NO in apoptosis during infection has not been reported. Similarly, the mechanism of iNOS gene induction during flu infection is not well defined in terms of host trans-activator(s) required for iNOS gene expression. In the current study we have identified kruppel-like factor 6 (KLF6) as a critical transcription factor essential for iNOS gene expression during flu infection. We have also underscored the requirement of iNOS in inducing apoptosis during infection. KLF6 gene silencing in human lung epithelial cells resulted in drastic loss of NO production, iNOS-promoter specific luciferase activity and expression of iNOS mRNA following flu infection. Chromatin immuno-precipitation assay revealed a direct interaction of KLF6 with iNOS promoter during both in vitro and in vivo flu infection of human lung cells and mouse respiratory tract, respectively. Significant reduction in flu mediated apoptosis was noted in KLF6 silenced cells, cells treated with iNOS inhibitor and in primary murine macrophages derived from iNOS knock-out (KO) mice. A similar reduction in apoptosis was noted in the lungs following intra-tracheal flu infection of iNOS KO mice. PMID:22711891

Inducible nitric oxide synthase (iNOS) in gingival tissues of chronic periodontitis with and without diabetes: immunohistochemistry and RT-PCR study.

PubMed

Shaker, Olfat; Ghallab, Noha A; Hamdy, Ebtehal; Sayed, Safinaz

2013-10-01

There is few data concerning the pathogenesis and contribution of inducible nitric oxide synthase (iNOS) in the inflammatory reactions of the periodontium in the course of diabetes. This study evaluated the expression of iNOS in the gingival biopsies of periodontitis patients with and without type 2 diabetes. 80 subjects were evaluated in four groups: patients with chronic periodontitis and diabetes, patients with chronic periodontitis, periodontally healthy patients with diabetes, and systemically and periodontally healthy control subjects. Gingival biopsies were subjected to immunohistochemistry as well as reverse transcription polymerase chain reaction (RT-PCR) for determination of iNOS. All diseased gingival tissues had a significant increase in iNOS expression by immunohistochemistry (P<0.001) compared to controls. There was no significant difference observed between patients with both diabetes and periodontitis and diabetic patients regarding iNOS(+) cells. Meanwhile, these two groups had significantly increased iNOS(+) cells when compared to periodontitis patients (P<0.001). There are significantly higher levels of iNOS mRNA expression of all patient groups compared to controls (P<0.0001). In addition, samples from patients with diabetes and periodontitis showed significantly higher levels of iNOS mRNA expression compared to samples from periodontitis patients and diabetic patients (P<0.0001) yet, without noting statistically significant differences between the latter two groups. Although iNOS expression was prominent in the gingiva of patients with diabetes and periodontitis, periodontitis patients and diabetic patients, the higher mRNA for iNOS observed in diabetes and periodontitis may indicate a possible involvement of this mediator in the periodontal destruction of type 2 diabetes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neuronal nitric oxide synthase immunopositive neurons in cat claustrum--a light and electron microscopic study.

PubMed

Hinova-Palova, Dimka; Edelstein, Lawrence; Paloff, Adrian; Hristov, Stanislav; Papantchev, Vassil; Ovtscharoff, Wladimir

2008-08-01

Nitric oxide is a unique neurotransmitter, which participates in many physiological and pathological processes in the organism. Nevertheless there are little data about the neuronal Nitric Oxide Synthase immunoreactive (nNOS-ir) neurons and fibers in the dorsal claustrum (DC) of a cat. In this respect the aims of this study were: (1) to demonstrate nNOS-ir in the neurons and fibers of the DC; (2) to describe their light microscopic morphology and distribution; (3) to investigate and analyze the ultrastructure of the nNOS-ir neurons, fibers and synaptic terminals; (4) to verify whether the nNOS-ir neurons consist a specific subpopulation of claustral neurons; (5) to verify whether the nNOS-ir neurons have a specific pattern of organization throughout the DC. For demonstration of the nNOS-ir the Avidin-Biotin-Peroxidase Complex method was applied. Immunopositive for nNOS neurons and fibers were present in all parts of DC. On the light microscope level nNOS-ir neurons were different in shape and size. According to the latter they were divided into three groups-small (with diameter under 15 microm), medium-sized (with diameter from 16 to 20 microm) and large (with diameter over 21 microm). Some of nNOS-ir neurons were lightly-stained while others were darkly-stained. On the electron microscope level the immunoproduct was observed in neurons, dendrites and terminal boutons. Different types of nNOS-ir neurons differ according to their ultrastructural features. Three types of nNOS-ir synaptic boutons were found. As a conclusion we hope that the present study will contribute to a better understanding of the functioning of the DC in cat and that some of the data presented could be extrapolated to other mammals, including human.

Neuroanatomical Relationship of nNOS to GnRH and Kisspeptin Neurons in Adult Female Sheep and Primates.

PubMed

Bedenbaugh, Michelle; McCosh, Rick; Lopez, Justin; Connors, John; Goodman, Robert L; Hileman, Stan

2018-06-21

Background: Neuronal intermediates that communicate estrogen and progesterone feedback to gonadotropin-releasing hormone (GnRH) neurons are essential for modulating reproductive cyclicity. Individually, kisspeptin and nitric oxide (NO) influence GnRH secretion. However, it is possible these two neuronal intermediates interact with one another to affect reproductive cyclicity. We investigated the neuroanatomical relationship of one isoform of the enzyme that synthesizes NO, neuronal nitric oxide synthase (nNOS), to kisspeptin and GnRH in adult female rhesus monkeys and sheep using dual-label immunofluorescence. Additionally, we evaluated if the phase of the reproductive cycle would affect these relationships. Overall, no effect of stage of cycle was observed for any variable in this study. In the arcuate nucleus (ARC) of sheep, 98.8±3.5% of kisspeptin neurons colocalized with nNOS, and kisspeptin close-contacts were observed onto nNOS neurons. In contrast to ewes, no colocalization was observed between kisspeptin and nNOS in the infundibular arcuate nucleus (INF ARC) of primates, but kisspeptin fibers were apposed to nNOS neurons. In the preoptic area (POA) of ewes, 15.0±4.2% of GnRH neurons colocalized with nNOS. In primates, 38.8±10.1% of GnRH neurons in the mediobasal hypothalamus (MBH) colocalized with nNOS, and GnRH close-contacts were observed onto nNOS neurons in both sheep and primates. Although species differences were observed, this work establishes a neuroanatomical framework between nNOS and kisspeptin and nNOS and GnRH in adult female nonhuman primates and sheep.
. ©2018S. Karger AG, Basel.

Phenotyping of nNOS neurons in the postnatal and adult female mouse hypothalamus.

PubMed

Chachlaki, Konstantina; Malone, Samuel A; Qualls-Creekmore, Emily; Hrabovszky, Erik; Münzberg, Heike; Giacobini, Paolo; Ango, Fabrice; Prevot, Vincent

2017-10-15

Neurons expressing nitric oxide (NO) synthase (nNOS) and thus capable of synthesizing NO play major roles in many aspects of brain function. While the heterogeneity of nNOS-expressing neurons has been studied in various brain regions, their phenotype in the hypothalamus remains largely unknown. Here we examined the distribution of cells expressing nNOS in the postnatal and adult female mouse hypothalamus using immunohistochemistry. In both adults and neonates, nNOS was largely restricted to regions of the hypothalamus involved in the control of bodily functions, such as energy balance and reproduction. Labeled cells were found in the paraventricular, ventromedial, and dorsomedial nuclei as well as in the lateral area of the hypothalamus. Intriguingly, nNOS was seen only after the second week of life in the arcuate nucleus of the hypothalamus (ARH). The most dense and heavily labeled population of cells was found in the organum vasculosum laminae terminalis (OV) and the median preoptic nucleus (MEPO), where most of the somata of the neuroendocrine neurons releasing GnRH and controlling reproduction are located. A great proportion of nNOS-immunoreactive neurons in the OV/MEPO and ARH were seen to express estrogen receptor (ER) α. Notably, almost all ERα-immunoreactive cells of the OV/MEPO also expressed nNOS. Moreover, the use of EYFP Vglut2 , EYFP Vgat , and GFP Gad67 transgenic mouse lines revealed that, like GnRH neurons, most hypothalamic nNOS neurons have a glutamatergic phenotype, except for nNOS neurons of the ARH, which are GABAergic. Altogether, these observations are consistent with the proposed role of nNOS neurons in physiological processes. © 2017 Wiley Periodicals, Inc.

Nature of Science and Science Content Learning. The Relation Between Students' Nature of Science Understanding and Their Learning About the Concept of Energy

NASA Astrophysics Data System (ADS)

Michel, Hanno; Neumann, Irene

2016-12-01

Besides viewing knowledge about the nature of science (NOS) as important for its own value with respect to scientific literacy, an adequate understanding of NOS is expected to improve science content learning by fostering the ability to interrelate scientific concepts and, thus, coherently acquire scientific content knowledge. However, there is a lack of systematic investigations, which clarify the relations between NOS and science content learning. In this paper, we present the results of a study, conducted to investigate how NOS understanding relates to students' acquisition of a proper understanding of the concept of energy. A total of 82 sixth and seventh grade students received an instructional unit on energy, with 41 of them receiving generic NOS instruction beforehand. This NOS instruction, however, did not result in students having higher scores on the NOS instrument. Thus, correlational analyses were performed to investigate how students' NOS understanding prior to the energy unit related to their learning about science content. Results show that a more adequate understanding of NOS might relate to students' perspective on the concept of energy and might support them in understanding the nature of energy as a theoretical concept. Students with higher NOS understanding, for example, seemed to be more capable of learning how to relate the different energy forms to each other and to justify why they can be subsumed under the term of energy. Further, we found that NOS understanding may also be related to students' approach toward energy degradation—a concept that can be difficult for students to master—while it does not seem to have a substantive impact on students' learning gain regarding energy forms, transformation, or conservation.