45 resultados para A1-A


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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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

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

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Endometriosis is a continuous and progressive disease with a poorly understood aetiology, pathophysiology and natural history. This study evaluated the histological differences between eutopic and ectopic endometria (abdominal wall endometriosis) and the expression of mast cell proteases (tryptase and chymase), annexin A1 (ANXA1) and formyl peptide receptor 1 (FPR1). Ectopic endometrium from 18 women with abdominal wall endometriosis and eutopic endometrium from 10 women without endometriosis were obtained. The endometrial samples were analysed by histopathology, immunohistochemistry and ultrastructural immunogold labeling to determine mast cell heterogeneity (tryptase and chymase positive cells) and the expression levels of ANXA1 and FPR1. Histopathological analysis of the endometriotic lesions showed a glandular pattern of mixed differentiation and an undifferentiated morphology with a significant influx of inflammatory cells and a change in mast cell heterogeneity, as evidenced by a significant increase in the number of chymase-positive cells and endogenous chymase expression. The undifferentiated glandular pattern of endometriotic lesions was positively associated with a marked increase and co-localization of ANXA1 and FPR1 in the epithelial cells. In conclusion, the co-upregulated expression of mast cell chymase and ANXA1–FPR1 system in ectopic endometrium suggests their involvement in the development of endometriotic lesions.

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Immunosuppressive drugs have a critical role in inhibiting tissue damage and allograft rejection.Studies have demonstrated the anti-infl ammatory effects of the annexin A1 (AnxA1) in the regulationof transmigration and apoptosis of leucocytes. In the present study, an experimental skin allograftmodel was used to evaluate a potential protective effect of AnxA1 in transplantation survival. Micewere used for the skin allograft model and pharmacological treatments were carried out using eitherthe AnxA1 mimetic peptide Ac2-26, with or without cyclosporine A (CsA), starting 3 days beforesurgery until rejection. Graft survival, skin histopathology, leucocyte transmigration and expressionof AnxA1 and AnxA5 post-transplantation were analysed. Pharmacological treatment with Ac2-26increased skin allograft survival related with inhibition of neutrophil transmigration and inductionof apoptos is, thereby reducing the tissue damage compared with control animals. Moreover, AnxA1and AnxA5 expression increased after Ac2-26 treatment in neutrophils. Interestingly, thecombination of Ac2-26 and cyclosporine A showed similar survival of transplants when compared withthe cyclosporine A group, which could be attributed to a synergistic effect of both drugs. Investigationsin vitro revealed that cyclosporine A inhibited extracellular-signal-regulated kinase (ERK) phosphory-lation induced by Ac2-26 in neutrophils. Overall, the results suggest that AnxA1 has an essential role inaugmenting the survival of skin allograft, mainly owing to inhibition of neutrophil transmigration andenhancement of apoptosis. This effect may lead to the development of new therapeutic approachesrelevant to transplant rejection.

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

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A vespa social Polybia paulista (Hymenoptera, Vespidae) é bastante abundante e endêmica nos Estados de São Paulo e sul de Minas Gerais. Os indivíduos da espécie causam um elevado número de acidentes de importância médica. Após a ferroada a vítima pode experimentar reações imunológicas locais e/ou sistêmicas, que em alguns casos podem conduzir a anafilaxia e morte. O diagnóstico e terapia de alergia à ferroada de P. paulista é baseado no uso de extrato de veneno bruto o que se associa à ocorrência de reatividade cruzada e reações imunológicas adversas durante a imunoterapia. O uso de alérgenos recombinantes (r) tem-se mostrado como uma alternativa interessante para reduzir o impacto destas desvantagens. Neste trabalho, foram avaliadas diferentes condições para otimizar a expressão recombinante e solubilização dos corpúsculos de inclusão da fosfolipase A1 (Poly p 1) (70kDa) do veneno de P. paulista previamente obtida mediante expressão heteróloga no sistema procariótico, Escherichia coli. Os resultados aqui obtidos contribuirão para aumentar as quantidades do r Poly p 1 necessárias para sua avaliação bioquímica e imunológica, e finalmente para melhorar os resultados do diagnóstico e imunoterapia específica de alergia ao veneno de P. paulista