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Int Immunopharmacol ; 11(8): 1024-31, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21371583

RESUMO

Heart failure and sudden death are the most common causes of death in patients with Chagas' disease. The main drug available for Chagas treatment is benznidazole, which eradicates Trypanosoma cruzi parasites during the acute stage of infection. However, its effectiveness during the chronic phase remains unclear. Ganglioside GM1 administration in chronically infected patients resulted to be an effective treatment for the cardiac manifestations of Chagas' disease. However, the precise mechanisms of GM1-induced improvement during chronic T. cruzi infection still remain unknown. The aim of the present study was to evaluate the potential benefits of ganglioside GM1 treatment during the chronic stage of murine chagasic infection, analyzing its influence on myocardial pathology as well as its immunomodulatory effects. The results obtained showed that GM1 therapy diminished the extent of myocardial fibrosis induced by T. cruzi in chronically infected mice. In addition, GM1 treatment resulted in a significant reduction in the myocardial expression of the fibrogenic cytokine TGF-ß as well as the proinflammatory cytokines and chemokines IFN-γ, TNF-α and CCL5/RANTES. Our experimental data indicate that GM1 could be a promising immunomodulatory agent with capacity to limit the inflammatory process leading to myocardial tissue damage in chronic chagasic patients.


Assuntos
Cardiomiopatia Chagásica/tratamento farmacológico , Gangliosídeo G(M1)/farmacologia , Fatores Imunológicos/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Cardiomiopatia Chagásica/genética , Cardiomiopatia Chagásica/imunologia , Cardiomiopatia Chagásica/patologia , Quimiocina CCL5/antagonistas & inibidores , Quimiocina CCL5/genética , Feminino , Fibrose/tratamento farmacológico , Fibrose/genética , Fibrose/patologia , Interferon gama/antagonistas & inibidores , Interferon gama/genética , Camundongos , Camundongos Endogâmicos BALB C , Miocárdio/metabolismo , Miocárdio/patologia , Fator de Crescimento Transformador beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/genética , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética
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