Ablation of primary afferent neurons by neonatal capsaicin treatment reduces the susceptibility of the portal hypertensive gastric mucosa to ethanol-induced injury in cirrhotic rats

Primary sensory afferent neurons modulate the hyperdynamic circulation in Cirrhotic rats with portal hypertension.The stomach of cirrhotic rats is prone to damage induced by ethanol, a phenomenon associated with reduced gastric hyperemic response to acid-back diffusion. The aim of this study was to examine the impact of ablation of capsaicin-sensitive neurons and the tachykinin NK(1) receptor antagonist A5330 on the susceptibility of the portal hypertensive gastric mucosa, to ethanol-induced injury and its effects on gastric cyclooxygenase (COX) and nitric oxide synthase (NOS) mRNA expression. Capsaicin was administered to neonatal, male, Wistar rats and the animals were allowed to grow. Cirrhosis was then induced by bile duct ligation in adult rats while controls had sham operation. Ethanol-induced gastric damage was assessed using ex vivo gastric chamber experiments. Gastric blood flow was measured as well as COX/NOS mRNA expression. Topical application of ethanol produced significant gastric damage in cirrhotic rats compared to controls, which was reversed in capsaicin- and A5330-treated animals. Mean arterial and portal pressure was normalized in capsaicin-treated cirrhotic rats. Capsaicin and A5330 administration restored gastric blood flow responses to topical application of ethanol followed by acid in cirrhotic rats. Differential COX and NOS mRNA expression was noted in bile duct ligated rats relative to controls. Capsaicin treatment significantly modified gastric eNOS/iNOS/COX-2 mRNA expression in cirrhotic rats. Capsaicin-sensitive neurons modulate the susceptibility of the portal hypertensive gastric mucosa to injury induced by ethanol via tachykinin NK(1) receptors and signalling of prostaglandin and NO production/release. (c) 2008 Elsevier B.V. All rights reserved.

Efeitos da suplementação de L-arginina e do exercício em cicloergômetro sobre a função endotelial e estresse oxidativo em indivíduos com diabetes tipo 1

Introdução e Objetivo: O fluxo sangüíneo gera estresse de cisalhamento sobre a parede dos vasos induzindo a conversão do aminoácido L-arginina em L-citrulina pela ação da eNOs, liberando o vasodilatador óxido nítrico. O exercício aumenta o fluxo sangüíneo e ativa a eNOs, promovendo vasodilatação. Um aumento no diâmetro do vaso diminuiria os níveis de estresse oxidativo pela diminuição do estresse de cisalhamento. O objetivo deste estudo foi verificar os efeitos da suplementação de L-arginina sobre a função endotelial e estresse oxidativo em indivíduos com diabetes tipo 1. Métodos: Foram avaliados 10 indivíduos do sexo masculino com diabetes do tipo 1 e 20 indivíduos saudáveis para controle, que realizaram teste de cargas progressivas em cicloergômetro para a determinação da carga de exercício, que correspondia a 10% abaixo do 2 º limiar ventilatório. Em uma nova data, os voluntários se exercitaram durante 45 minutos em cicloergômetro, onde foram avaliados parâmetros de função endotelial e estresse oxidativo antes e depois do exercício. Os voluntários foram separados aleatoriamente em dois grupos: L-arginina e placebo. A suplementação de L-arginina foi realizada a partir da ingesta de 7g ao dia na forma de cápsulas; o grupo placebo recebeu amido. Após a suplementação, foi repetido o protocolo de exercício. A função endotelial foi avaliada através da avaliação do fluxo sangüíneo e concentração de nitritos plasmáticos; o estresse oxidativo foi avaliado pelas técnicas do TBARS, carbonil, TRAP e ácido úrico plasmáticos Utilizou-se ANOVA Fatorial de duas vias e teste post hoc de Tukey para análise dos resultados, aceitou-se p<0,05 como significativo. Resultados: Os dados estão expressos em média + erro padrão. Os indivíduos com diabetes do tipo 1 não apresentaram disfunção endotelial quando comparados aos controle, entretanto tiveram parâmetros de estresse oxidativo elevados (TBARS de 1,09 + 0,41 e 2,44 + 0,46 nmolMDA.mg PTN-1, p=0,039; carbonil de 0,148 + 0,02 e 1,48 + 0,20 fM.mg PTN-1, p=0,000 e ácido úrico de 44,55 + 2,06 e 28,10 + 1,57 mg/dl, p=0,000, em controles e diabéticos, respectivamente). O exercício aumentou significativamente o fluxo sangüíneo nos controle e diabéticos ( de 3,53 + 0,35 para 5,46 + 0,35 ml.100ml-1.min-1 no controle, p=0,001 e de 2,66 + 0,33 para 3,77 + 0,36 ml.100ml-1.min-1 nos indivíduos com diabetes, p= 0,000), mas não alterou as concentrações plasmáticas de nitritos nem os parâmetros de estresse oxidativo. Os diabéticos que receberam suplementação com L-arginina tiveram seus valores de fluxo sangüíneo em repouso elevados significativamente (de 3,05 + 0,63 para 4,74 + 0,86 ml.100ml-1.min-1 , p=0,036), efeito não encontrado no grupo controle que recebeu a suplementação. Entretanto, este grupo não apresentou aumento do fluxo sangüíneo após o exercício, conforme observado no momento antes da suplementação. Conclusão: O exercício físico em cicloergômetro aumenta o fluxo sangüíneo sem alterar os parâmetros de estresse oxidativo em indivíduos controle e diabéticos tipo 1. A suplementação com L-arginina aumenta a vasodilatação dependente do endotélio em indivíduos com diabetes do tipo 1, e atenua o aumento do fluxo sangüíneo em resposta ao exercício nestes pacientes. Esta resposta demonstrou uma possível melhora na função endotelial na situação de repouso com a suplementação. Entretanto, restam questões obscuras sobre a resposta de fluxo ao exercício sob o efeito da L-arginina nesta população, sendo necessários estudos adicionais para o esclarecimento.

Panorama da Pesquisa em Direito: I Colóquio

Este livro contém os trabalhos apresentados pelos discentes de programas de pós-graduação strictu sensu do estado de São Paulo durante o I Colóquio, Pesquisa em Direito. A seleção dos discentes e dos textos coube a cada um dos programas de pós-graduação, a partir de um edital preparado em conjunto entre os coordenadores desses programas. É essa seleção que compõe esta obra, editada de forma a oferecer aos leitores cada um dos programas paulistas de pós-graduação em Direito.

Br-IndustrialExpert: um framework para análise de dependabilidade de processos industriais

There is a growing need to develop new tools to help end users in tasks related to the design, monitoring, maintenance and commissioning of critical infrastructures. The complexity of the industrial environment, for example, requires that these tools have flexible features in order to provide valuable data for the designers at the design phases. Furthermore, it is known that industrial processes have stringent requirements for dependability, since failures can cause economic losses, environmental damages and danger to people. The lack of tools that enable the evaluation of faults in critical infrastructures could mitigate these problems. Accordingly, the said work presents developing a framework for analyzing of dependability for critical infrastructures. The proposal allows the modeling of critical infrastructure, mapping its components to a Fault Tree. Then the mathematical model generated is used for dependability analysis of infrastructure, relying on the equipment and its interconnections failures. Finally, typical scenarios of industrial environments are used to validate the proposal

Limites e evolução geodinâmica do Sistema Jaguaribeano, Província Borborema, Nordeste do Brasil

The studied area is geologically located in the Northern Domain of the Borborema Province (Northeast Brazil), limited to the south by the Patos shear zone. Terranes of the Jaguaribeano system are dominant, flanked by the Piranhas (E and S sides) and Central Ceará (NE side) terranes. Its basement comprises gneiss -migmatite terrains of Paleoproterozoic to Archean age (2.6 to 1.9 Ga old), overprinted by neoproterozoic to cambrian tectonotherma l events. Narrow supracrustal belts ( schist belts) display a 1.6 to 1.8 Ga age, as shown by whole - rock Rb-Sr and zircon U-Pb and Pb/Pb dates in acid metavolcanics which dominate in the lower section of these sequences, and in coeval metaplutonics (granitic augen gneisses). From the stratigraphic point of view, three Staterian belts are recognized: 1. Orós Belt - made up by the Orós Group, subdivided in the Santarém (predominantly pure to impure quartzites, micaschists and metacarbonates) and Campo Alegre (metandesites, metabasalts, metarhyolites and metarhyodacites, interlayered with metatuffs and metasediments) formations, and by the Serra do Deserto Magmatic Suite (granitic augen gneisses). 2. Jaguaribe Belt - its lithostratigrahic-lithodemic framework is similar to the one of the Orós Belt, however with a greater expression of the volcano -plutonic components (Campo Alegre Formation and Serra do Deserto Magmatic Suite). The Peixe Gordo Sequence, separately described, is also related to this belt and contain s metasedimentary, metavolcanic (with subordinated volcanoclastics) and metaplutonic units. The first one correlated to the Orós Group and the latter the Serra do Deserto Magmatic Suite. 3. Western Potiguar Belt - represented by the Serra de São José Gro up, subdivided in the Catolezinho (biotite -amphibole gneisses with intercalations of metacarbonates, calcsilicate rocks, amphibolites and quartzite beds to the top) and Minhuins (quartzites, micaschists, metaconglomerates, calcsilicate rocks, acid to the b asic metavolcanics and metatuffs) formations. Its late Paleoproterozoic (Staterian) age was established by a Pb/Pb date on zircons from a granitic orthogneiss of the Catolezinho Formation. The petrographic characteristics and sedimentary structures of the Santarém Formation of the Orós Group point to deltaic to shallow marine depositional systems, overlain by deep water deposits (turbidites). The geodynamic setting of this region encompassed a large depositional basin, probably extending to the east of the Portalegre shear zone and west of the Senador Pompeu shear zone, with possible equivalents in the Jucurutu Formation of the Seridó Belt and in the Ceará Group of central Ceará. The Arneiróz Belt, west Ceará, displays some stratigraphic features and granito ids geochemically akin to the ones of the Orós Belt. The evolutionary setting started with an extensional phase which was more active in the eastern part of this domain (Western Potiguar and part of the Jaguaribe belts), where the rudite and psamite sedime ntation relates to a fluviatile rift environment which evolved to a prograding deltaic system to the west (Orós Group). The basaltic andesitic and rhyolitic volcanics were associated to this extensional phase. During this magmatic event, acid magmas also crystallized at plutonic depths. The Orós Group illustrates the environmental conditions in the western part of this domain. Later on, after a large time gap (1.6 to 1.1 Ga), the region was subjected to an extensional deformational episode marked by 900 Ma old (Sm-Nd data) basic rocks, possibly in connection with the deposition of the Cachoeirinha Group south of the Patos shear zone. In the 800 to 500 Ma age interval, the region was affected by important deformational and metamorphic events coupled with in trusion of granitic rocks of variable size (dykes to batholiths), related to the Brasiliano/Pan -African geotectonic cycle. These events produced structural blocks which differentiate, one from the other, according to the importance of anatectic mobilizatio n, proportion of high-grade supracrustals and the amount of neoproterozoic -cambrian granitoid intrusions. On this basis, a large portion of the Jaguaretama Block/Terrane is relatively well preserved from this late overprint. The border belts of the Jagua retama Block (Western Potiguar and Arneiroz) display kyanite-bearing (medium pressure) mineral associations, while in the inner part of the block there is a north-south metamorphic zoning marked by staurolite or sillimanite peak metamorphic conditions. Regarding the deformations of the Staterian supracrustal rocks, second and third phases were the most important, diagnosed as having developed in a progressive tectonic process. In the general, more vigorous conditions of PT are related to the interval tardi - phase 2 early-phase 3, whose radiometric ages and regional structuring indicators places it in the Brasiliano/Pan-African Cycle. In the Staterian geodynamic setting of Brazilian Platform , these sequences are correlated to the lower Espinhaço Supergroup (p.ex., Rio dos Remédios and Paraguaçu groups, a paleproterozoic rift system in the São Francisco Craton), the Araí and Serra da Mesa groups (north of Goiás, in the so -called Goiás Central Massif), and the Uatumã Group (in the Amazonian Craton). Granitic ( augen gneisses) plutonics are also known from these areas, as for example the A-type granites intrusive in the Araí and Serra da Mesa groups, dated at 1.77 Ga. Gravimetric and geological data place the limits of the Jaguaribeano System (terranes) along the Senador Pompeu Shear Zone (western border) and the Portalegre- Farias Brito shear zone (eastern and southern). However, the same data area not conclusive as regards the interpretation of those structures as suture of the terrane docking process. The main features of those shear zones and of involved lothological associations, appear to favour an intracontinental transpressional -transcurrent regime, during Neoproterozoic-Cambrian times, marking discontinuities along which different crustal blocks were laterally dispersed. Inside of this orogenic system and according to the magnetic data (total field map), the most important terrane boundary appears to be the Jaguaribe shear zone. The geochronological data, on some tectonostratigraphic associations (partly represented by the Ceará and Jucurutu groups), still at a preliminary level, besides the lack of granitic zonation and other petrotectonic criteria, do not allow to propose tectonic terrane assembly diagrams for the studied area

Putative antinociceptive action of nitric oxide in the caudal part of the spinal trigeminal nucleus during chronic carrageenan-induced arthritis in the rat temporomandibular joint

In order to investigate a putative role for nitric oxide (NO) in the central nociceptive processing following carrageenan-induced arthritis in the rat temporomandibular joint (TMJ), we analyzed the immunoreactivity, gene expression and activity of nitric oxide synthases (NOS) in the caudal part of the spinal trigeminal nucleus (Sp5C) during the acute (24 h), chronic (15 days) and chronic-active (14 days-24 h) arthritis. In addition, evaluation of head-withdrawal threshold was carried out in all phases of arthritis under chronic inhibition of nNOS with the selective inhibitor 7-nitroindazole (7-NI). Neurons with nNOS-like immunoreactivity (nNOS-LI) were concentrated mainly in the lamina II of the Sp5C, showing no significant statistical difference during arthritis. Only a discrete percentage of nNOS-LI neurons expressed Fos immunoreactivity. The mRNA expression for both nNOS and endothelial nitric oxide synthases (eNOS) presented no noticeable differences among the groups. No expression of inducible nitric oxide synthase (iNOS) was detected in the Sp5C by either immunohistochemistry or reverse-transcription polymerase chain reaction (RTPCR). Ca(2+)-dependent NOS activity in the ipsilateral Sp5C was significantly higher (108.3 +/- 49.2%; P<0.01) in animals during the chronic arthritis. Interestingly, this increased activity was completely abolished 24 h later, in the chronic-active arthritis. Finally, head-withdrawal threshold decreased significantly in the chronic arthritis in animals under 7-NI chronic inhibition. In conclusion, nNOS immunoreactivity and mRNA expression are stable in the Sp5C during TMJ arthritis evolution, but its activity significantly increases in the chronic-phases supporting an antinociceptive role of the nNOS as evidenced by pain threshold experiment. (C) 2009 Elsevier B.V. All rights reserved.

Efeito do exercício físico e do polimorfismo T-786C na pressão arterial e no fluxo sanguíneo de idosas

FUNDAMENTO: O polimorfismo T-786C do gene da sintetase do óxido nítrico endotelial (eNOS) e a produção de ânion superóxido podem diminuir a produção e biodisponibilidade do óxido nítrico, comprometendo o grau de vasodilatação, podendo este efeito ser revertido pelo exercício físico. OBJETIVO: Investigar a influência do treinamento aeróbico e do polimorfismo T-786C nas concentrações dos metabólitos do óxido nítrico (NOx), no fluxo sanguíneo (FS) e na pressão arterial (PA). MÉTODOS: Trinta e duas idosas pré-hipertensas (59 ± 6 anos) foram separadas em dois grupos de acordo com o polimorfismo T-786C (TT e TC+CC). Foram analisadas as concentrações de NOx (plasma) e fluxo sanguíneo por pletismografia de oclusão venosa em repouso, 1, 2 e 3 minutos pós-oclusão (FS-0, FS-1, FS-2, FS-3, respectivamente). As avaliações foram realizadas antes e após 6 meses de um programa de exercício aeróbico. RESULTADOS: Nas avaliações pré-treinamento, os níveis de NOx foram menores no grupo TC+CC em relação ao grupo TT. O grupo TT apresentou correlações entre NOx e FS-0 (r = 0,6) e pressão arterial diastólica (PAD) e FS-0 (r = -0,7), porém nenhuma correlação foi encontrada no grupo TC+CC. Nas avaliações pós-treinamento, ocorreram correlações entre NOx e FS-0 (r = 0,6) e nas mudanças do NOx e PAD (r = -0,6) no grupo TT. Também foram obtidas correlações entre PAD e FS-1 (r = -0,8), PAD e FS-2 (r = -0,6), PAD e FS-3 (r = -0,6), nas mudanças entre NOx e FS-1 (r = 0,8) e mudanças do NOx e PAD (r = -0,7) no grupo TC+CC. CONCLUSÃO: Conclui-se que 6 meses de exercício aeróbico podem contribuir para aumentar as relações existentes entre NO, PA e FS em idosas portadores do alelo C.

Interaction between Advanced Glycation End Products Formation and Vascular Responses in Femoral and Coronary Arteries from Exercised Diabetic Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Pulmonary Disease in Hamsters Infected with Leptospira interrogans: Histopathologic Findings and Cytokine mRNA Expressions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Oxidative Stress Impairs Vasorelaxation Induced by the Soluble Guanylyl Cyclase Activator BAY 41-2272 in Spontaneously Hypertensive Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Diet-induced obesity impairs AKT signalling in the retina and causes retinal degeneration

Retinopathy, a common complication of diabetes, is characterized by an unbalanced production of nitric oxide (NO), a process regulated by nitric oxide synthase (NOS). We hypothesized that retinopathy might stem from changes in the insulin receptor substrate (IRS)/PI3K/AKT pathway and/or expression of NOS isoforms. Thus, we analysed the morphology and apoptosis index in retinas of obese rats in whom insulin resistance had been induced by a high-fat diet (HFD). Immunoblotting analysis revealed that the retinal tissue of HFD rats had lower levels of AKT1, eNOS and nNOS protein than those of samples taken from control animals. Furthermore, immunohistochemical analyses indicated higher levels of iNOS and 4-hydroxynonenal and a larger number of apoptotic nuclei in HFD rats. Finally, both the inner and outer retinal layers of HFD rats were thinner than those in their control counterparts. When considered alongside previous results, these patterns suggest two major ways in which HFD might impact animals: direct activity of ingested fatty acids and/or via insulin-resistance-induced changes in intracellular pathways. We discuss these possibilities in further detail and advocate the use of this animal model for further understanding relationships between retinopathy, metabolic syndrome and type 2 diabetes. © 2012 John Wiley & Sons, Ltd.

Isolation, homology modeling and renal effects of a C-type natriuretic peptide from the venom of the Brazilian yellow scorpion (Tityus serrulatus)

Mammalian natriuretic peptides (NPs) have been extensively investigated for use as therapeutic agents in the treatment of cardiovascular diseases. Here, we describe the isolation, sequencing and tridimensional homology modeling of the first C-type natriuretic peptide isolated from scorpion venom. In addition, its effects on the renal function of rats and on the mRNA expression of natriuretic peptide receptors in the kidneys are delineated. Fractionation of Tityusserrulatus venom using chromatographic techniques yielded a peptide with a molecular mass of 2190.64Da, which exhibited the pattern of disulfide bridges that is characteristic of a C-type NP (TsNP, T. serrulatus Natriuretic Peptide). In the isolated perfused rat kidney assay, treatment with two concentrations of TsNP (0.03 and 0.1μg/mL) increased the perfusion pressure, glomerular filtration rate and urinary flow. After 60min of treatment at both concentrations, the percentages of sodium, potassium and chloride transport were decreased, and the urinary cGMP concentration was elevated. Natriuretic peptide receptor-A (NPR-A) mRNA expression was down regulated in the kidneys treated with both concentrations of TsNP, whereas NPR-B, NPR-C and CG-C mRNAs were up regulated at the 0.1μg/mL concentration. In conclusion, this work describes the isolation and modeling of the first natriuretic peptide isolated from scorpion venom. In addition, examinations of the renal actions of TsNP indicate that its effects may be related to the activation of NPR-B, NPR-C and GC-C. © 2013 Elsevier Ltd.

Alteraciones climáticas en Bolivia: impactos observados en el primer trimestre de 2007

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La economía del cambio climático en Centroamérica: impactos potenciales en la aridez y los meses secos: serie técnica 2012

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