RESUMO
BACKGROUND: Triple immunosuppressive therapy is associated with several gastrointestinal disorders. The aim of this study was to investigate the effects induced by the triple immunosuppressive therapy on the gastrointestinal tract of rats. METHODS: Male Wistar rats were randomly assigned into three experimental groups: Control: filtered water; TAC + MPS + PRED: treated with Tacrolimus plus Mycophenolate Sodium plus Prednisone; and CSA + AZA + PRED: treated with Cyclosporine plus Azathioprine plus Prednisone. The treatment was done for 14 days by gavage. Gastric emptying and contractility were evaluated by the Alternating Current Biosusceptometry (ACB) and Electrogastrography (EGG). Histological, biochemical and hematological analyses were also performed. RESULTS: Gastric emptying time was slower in the CSA + AZA + PRED group in comparison with control (p<0.01) and TAC + MPS + PRED groups (p<0.001). Animals treated with TAC + MPS + PRED showed accelerated gastric emptying (p<0.05) compared to control. The amplitude of gastric contractions in both immunosuppressed groups was higher than observed in the control. The frequency of gastric contractions for the CSA + AZA + PRED group was also increased (p<0.01). Results obtained by EGG were similar to those recorded with the ACB. The thickness of the circular layer from stomach muscle decreased in both immunosuppressed groups, while the longitudinal layer was reduced only in the CSA + AZA + PRED group. CONCLUSION: Triple immunosuppressive therapy alters gastric motility, compromises the muscular layers and the association between CSA, AZA, and PRED provokes the major alterations in the structure and gastric function. Specific gastrointestinal side effects resulting from different immunosuppressive therapies still need to be elucidated in order to provide more effective and personalized therapy for patients.
Assuntos
Gastroenteropatias/induzido quimicamente , Gastroenteropatias/imunologia , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/imunologia , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Animais , Azatioprina/administração & dosagem , Azatioprina/efeitos adversos , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Quimioterapia Combinada , Esvaziamento Gástrico/efeitos dos fármacos , Esvaziamento Gástrico/imunologia , Gastroenteropatias/patologia , Masculino , Ratos , Ratos Wistar , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversosRESUMO
AIDS is inexorably involving all parts of the country and all strata of society, with 10% of the urban and 3% of the rural population infected with HIV. It is increasingly a disease of women and children. The major cofactors for transmission are also sexually transmitted. For most developing countries, in spite of all education efforts, the "silent epidemic" of AIDS continues. AIDS is known but not understood; counselling modifies behavior in only 10-20% of at-risk persons. Under optimal conditions, HIV discordant females have seroconversion rates of 4.7% per year and pregnancy rates of 10.4% per year. The recent political unrest in Zaire and Haiti will further enhance the spread of AIDS in these countries. Despite these difficult periods, the work can and must continue. After all, during our 10th year of collaboration with a Haitian private research group, the Haitian government and Cornell University, Haiti has known seven different political rulers. Finally, I want to make a pledge on behalf of the millions of people who face a certain death from HIV infection and AIDS and who will never make the front page of any newspaper. For these people, you can make a difference. You must give us the tools to carry on this fight. The clinical trials must be done where they are most needed: the developing countries. Vaccines represent the only viable alternative despite the recognized obstacles of viral heterogeneity, immunogenicity, and delivery.