Mechanisms for suppressing NADPH oxidase in the vascular wall

Oxidative stress underlies many forms of vascular disease as well as tissue injury following ischemia and reperfusion. The major source of oxidative stress in the artery wall is an NADPH oxidase. This enzyme complex as expressed in vascular cells differs from that in phagocytic leucocytes both in biochemical structure and functions. The crucial flavin-containing catalytic subunits, Nox1 and Nox4, are not found in leucocytes, but are highly expressed in vascular cells and upregulated with vascular remodeling, such as that found in hypertension and atherosclerosis. The difference in catalytic subunits offers the opportunity to develop “vascular specific” NADPH oxidase inhibitors that do not compromise the essential physiological signaling and phagocytic functions carried out by reactive oxygen and nitrogen species.  Nitric oxide and targeted inhibitors of NADPH oxidase that block the source of oxidative stress in the vasculature are more likely to prevent the deterioration of vascular function that leads to stroke and heart attack, than are conventional antioxidants. The roles of Nox isoforms in other inflammatory conditions are yet to be explored.ver (aqui)

Role of Nicotinamide Adenine Dinucleotide Phosphate Oxidase 1 in Oxidative Burst Response to Toll-Like Receptor 5 Signaling in Large Intestinal Epithelial Cells

The NADPH oxidase 1 (Nox1) is a gp91^phox homologue preferentially expressed in the colon. We have established primary cultures of guinea pig large intestinal epithelial cells giving 90% purity of surface mucous cells. These cells spontaneously released superoxide anion (O₂^-) of 160 nmol/mg protein/h and expressed the Nox1, p22^phox,p67^phox, and Rac1 mRNAs, but not the gp91^phox, Nox4, p47^phox, p40^phox, and Rac2mRNAs. They also expressed novel homologues of p47^phox and p67^phox (p41^nox and p51^nox, respectively). Human colon cancer cell lines (T84 and Caco2 cells) expressed theNox1, p22^phox, p51^nox, and Rac1 mRNAs, but not the other NADPH component mRNAs, and secreted only small amounts of O₂^- (<2 nmol/mg protein/h). Cotransfection of p41^noxand p51^nox cDNAs in T84 cells enhanced PMA-stimulated O₂^- release 5-fold. Treatment of the transfected T84 cells with recombinant flagellin (rFliC) from Salmonella enteritidisfurther augmented the O₂^- release in association with the induction of Nox1 protein. The enhanced O₂^- production by cotransfection of p41^nox and p51^nox vectors further augmented the rFliC-stimulated IL-8 release from T84 cells. T84 cells expressed the Toll-like receptor 5, and rFliC rapidly phosphorylated TGF--activated kinase 1 and TGF--activated kinase 1-binding protein 1. A potent inhibitor for NF-κB (pyrrolidine dithiocarbamate) significantly blocked the rFliC-primed increase in O₂^- production and induction of Nox1 protein. These results suggest that p41^nox and p51^nox are involved in the Nox1 activation in surface mucous cells of the colon, and besides that, epithelial cells discern pathogenicities among bacteria to appropriately operate Nox1 for the host defense. ver (aqui)

Cursos recomendados e reconhecidos pela CAPES

Constam da relação abaixo apresentada os programas e cursos de pós-graduação que obtiveram nota igual ou superior a "3" na avaliação da CAPES e que, portanto, atendem ao requisito básico estabelecido pela legislação vigente para serem reconhecidos pelo Ministério da Educação por meio do Conselho Nacional de Educação (CNE) e, em decorrência, expedirem diplomas de mestrado e/ou doutorado com validade nacional. Nela são incluídos os programas e cursos cujos atos de reconhecimento ou de renovação de reconhecimento já foram oficializados pelo Ministro da Educação (Cursos reconhecidos) como também aqueles cujas propostas foram recentemente aprovadas pela CAPES e encaminhadas ao CNE para a instrução de seus processos de reconhecimento (Cursos recomendados).

Escolha a opção que mais facilita a sua procura:

• Por Área de Avaliação
• Por Nota
• Por Região/Instituição

Prêmio Nobel de Medicina 2011.

No dia 03 de outubro de 2011, três pesquisadores dividiram o Prêmio Nobel. Dois deles na linha de imunidade inata, Bruce A. Beutler e Jules A. Hoffmann e um deles,  Ralph M. Steinman (falecido de câncer 3 dias antes da cerimônia do Prêmio),  na linha de imunidade adaptativa. Todos os 3 pesquisadores desenvolveram conceitos que hoje consideramos corriqueiros, mas que revolucionaram o modo como entendemos a resposta imune frente a diversas formas de agressão. A imunidade inata e a imunidade aprendida não são independentes uma da outra. Cada sistema atua em relação com o outro e influi sobre ele, direta ou indiretamente, por meio da indução de citocinas - mensageiros. Raramente um estímulo desencadeia uma só resposta. O que faz é iniciar várias, algumas das quais podem atuar conjuntamente ou ocasionalmente competir entre si (figura 1). Os vencedores do Prêmio Nobel descobriram também passos importantes das respostas imunes. No caso da imunidade inata,  eles explicitaram um dos seus mecanismos básicos que é a ligação do Lipopolissacáride (LPS) de um determinado agente infeccioso ao seu receptor - Toll-like receptor -  presente em algumas células do sistema imunológico, ativando a cascata imunológica inata (figura 2). Na resposta imune adaptativa, o falecido Dr Steinman constatou a existência  e isolou a famosa célula apresentadora de antígeno ou célula dendrítica. Esta é a célula que “processa” o antígeno e o apresenta aos linfócitos T e B ativando-os e criando a memória imunológica específica de cada indivíduo.  Estas descobertas foram determinantes para o Prêmio Nobel 2011.

Fig 1: resumo de imunidade inata e adaptativa

Fig 2: Papel dos LPS e do TLR na imunidade inata e das células dendríticas na imunidade adaptativa.

II Simpósio em Citometria de Fluxo - CPqAM/FIOCRUZ-PE

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Antioxidant supplementation for the treatment of acute lung injury: a meta-analysis

This meta-analysis was performed to evaluate the evidence  supporting  antioxidant supplementation as an adjunct therapy to prevent  oxidative damage  and  improve the clinical outcomes (mortality, length of hospital stay  and duration of mechanical ventilation).The  search strategy for  randomized controlled trials RCTs) involved the participation of two  researchers  who  independently assessed  the methodological quality of  each  full-text article  that was available  in  the PubMed,  ISI WEB of Knowledge and  ScienceDirect databases. We  extracted  110  studies from  the past  10 years, but  only 30  articles  met  the methodological criteria  (RCT,  blinded  and  statistically  significant results),  for a total of  241  animals  and 256  patients. This study found an odds ratio (OR) of 0.45 [95% confidence interval (CI): 0.26 to 0.79] for death in the experimental group compared with placebo (six trials, n = 256), an OR of 0.46 [95% CI:  0.26 to 0.87]  for  hospitalization time and an OR of 0.63 [95% CI: 0.35 to 1.12] for mechanical ventilation time between groups, Conflicting  evidence makes it impossible to recommend the routine use of antioxidant supplementation in critically ill patients.

VI Congresso Brasileiro de Células-tronco e Terapia Celular

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Congresso da Sociedade Brasileira de Imunologia

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FESBE 2011

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I São Paulo Advanced School on Redox Processes in Biomedicine

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Effect of a neonatal low-protein diet on the morphology of myotubes in culture and the expression of key proteins that regulate myogenesis in young and adult rats

To investigate the effects of a neonatal low-protein diet on the morphology of myotubes in culture and the expression of key proteins that regulate myogenesis in young and adult rats. Methods: Male Wistar rats (n = 18) were suckled by mothers fed diets containing 17% protein (controls, C) or 8% protein (undernourished, UN). All rats were fed a normal protein diet after weaning. Muscles were removed from the legs of 42-, 60- and 90-day-old rats. Muscle cells were cultured to assess cell number, morphology and the expression of major proteins involved in myogenesis (Pax7, cadherins, β1 integrin, IL-4Rα and myogenin) by western blotting. IL-4 levels in culture supernatants were measured by ELISA. Results: Offspring from mothers fed a low-protein diet showed a lower body weight gain. Cell number and myotube expansion were reduced in cultured muscle cells from UN, but the expression of myogenic marker proteins was unaltered. Conclusions:   Dietary restriction during lactation had no impact on the synthesis of myogenic marker proteins, and myocyte differentiation occurred normally in the muscles of offspring aged 42, 60 or 90 days. Nevertheless, the number and morphology of the myotubes are altered.VER ARTIGO (aqui)

Effects of nasal continuous positive airway pressure treatment on oxidative stress and adiponectin levels in obese patients with obstructive sleep apnea.

Obesity and obstructive sleep apnea (OSA) are both associated with the prevalence of major cardiovascular illnesses and certain common factors they are considered responsible for, such as stress oxidative increase, sympathetic tonus and resistance to insulin. The aim of the present study was to compare the effect of continuous positive airway pressure (CPAP) on oxidative stress and adiponectin levels in obese patients with and without OSA. Twenty-nine obese patients were categorized into 3 groups: group 1: 10 individuals without OSA (apnea-hypopnea index, AHI <or=5) who did not have OSA diagnosed at polysomnography; group 2: 10 patients with moderate to severe OSA (AHI >or=20) who did not use CPAP; group 3: 9 patients with moderate to severe OSA (AHI >or=20) who used CPAP. Group 3 showed significant differences before and after the use of CPAP, in the variables of diminished production of superoxide, and increased nitrite and nitrate synthesis and adiponectin levels. Positive correlations were seen between the AHI and the superoxide production, between the nitrite and nitrate levels and the adiponectin levels, between superoxide production and the HOMA-IR, and between AHI and the HOMA-IR. Negative correlations were found between AHI and the nitrite and nitrate levels, between the superoxide production and that of nitric oxide, between the superoxide production and the adiponectin levels, between AHI and the adiponectin levels, and between the nitrite and nitrate levels and the HOMA-IR. This study demonstrates that the use of CPAP can reverse the increased superoxide production, the diminished serum nitrite, nitrate and plasma adiponectin levels, and the metabolic changes existing in obese patients with OSA. VER (click)

Cytotoxicity of current adhesive systems: in vitro testing on cell cultures of primary murine macrophages.

The aim of this study was to evaluate, in vitro, the potential cytotoxicity of dentinal adhesives on alveolar macrophages of Wistar rats, after diffusion through dentin. The cytotoxicity of adhesives [single bond plus (SB), clearfil SE bond (CF) and Xeno V (XE)] applied to the occlusal surface of human dentin disks adapted to a dentin barrier test device were analyzed. The sets placed on a monolayer of cells were incubated for 24, 48 and 72h. Culture medium and Escherichia coli lipopolysaccharides (LPS) were used as negative and positive controls, respectively. Cellular cytotoxicity was evaluated by observing the cell survival rate (MTT assay) and nitric oxide production (NO). The data were analyzed by one-way factorial ANOVA and Tukey's and Tamhane's paired comparisons T2 (α=0.05). All the adhesive systems reduced the percentage of live cells by over 50%, compared with the control group. Within the same period of time, there was a statistically significant difference between the adhesives and LPS compared with the negative control group. SB presented a statistically significant difference between 24h and 72h, and XE between 48h and 72h. The quantity of NO produced in 24h did not differ statistically between the NC and adhesive groups. After 48h there was a significant difference between SB/CF and XE/NC. At 72h only CF showed a significant difference from each of the other groups. LPS differed statistically from all the other groups at all the evaluation times. Components of the adhesives tested may permeate the dentin in sufficient concentrations to cause death and damage to cell metabolism in the alveolar macrophages of rats, which indicates potential cytotoxicity to pulpal cells. TO SEE (click here) ou vídeo