Orientador: Madileine Francely Américo / Resumo: Os imunossupressores são utilizados após o transplante de órgãos e no tratamento de doenças autoimunes, desencadeando diversos efeitos colaterais. No esquema tríplice de imunossupressão pós-transplante, cada droga ou a combinação delas podem alterar a estrutura e/ou funcionamento do trato gastrintestinal. Apesar da importância do trato gastrintestinal e de conhecer os efeitos da ingesta oral de imunossupressores, há poucos estudos enfocando esses aspectos e vários desafios éticos para essas avaliações no homem. Desse modo, objetivou-se avaliar as alterações provocadas pela imunossupressão nos parâmetros de esvaziamento gástrico, frequência e amplitude das contrações gástricas, bem como as alterações histológicas no estômago de ratos. Para isso foram utilizados a Biosusceptometria de Corrente Alternada (BAC) e a Eletrogastrografia (EGG). No primeiro capítulo, avaliou-se individualmente sete imunossupressores de diferentes classes (Tacrolimo, Ciclosporina, Micofenolato Mofetil, Azatioprina, Sirolimo, Everolimo e Prednisona) comumente utilizados na terapia imunossupressora. Todos os imunossupressores estudados, exceto o Micofenolato Mofetil causaram alguma alteração nos parâmetros gastrintestinais analisados em ratos. Já o segundo capítulo apresenta os efeitos da terapia imunossupressora combinada, baseada em três classes de imunossupressores (inibidores da calcineurina, antimetabólitos e glicocorticoides). Um dos grupos experimentais recebeu Tacrolimo associado à Micofenolato S... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Immunosuppressants are used after organ transplantation and in the treatment of autoimmune diseases, triggering several side effects. In the triple regimen of post - transplant immunosuppression, each drug or combination of them may alter the structure and / or function of the gastroin testinal tract. Despite the importance of gastrointestinal tract and knowledge of the effects of oral intake of immunosuppressants, there are few studies focusing on these aspects and several ethical challenges for these evaluations in humans. The aim of t his study was to evaluate the effects provoked by immunosuppression in gastric emptying parameters, frequency and amplitude of gastric contractions, as well as the histological aspects in the stomach of rats. Alternating Current Biosusceptometry (BAC) and Electrogastrography (EGG) were used. In the first chapter, seven immunosuppressants from different classes (Tacrolimus, Cyclosporine, Mycophenolate Mofetil, Azathioprine, Sirolimus, Everolimus and Prednisone) commonly used in immunosuppressive therapy were evaluated individually. All immunosuppressants studied except Mycophenolate Mofetil , caused some alteration in the gastrointestinal parameters analyzed in rats. The second chapter presents the effects of combined immunosuppressive therapy based on three c lasses of immunosuppressants (calcineurin inhibitors, antimetabolites and glucocorticoids). One of the experimental groups received Tacrolimus associated with Mycophenolate Sodium and Pr... (Complete abstract click electronic access below) / Doutor

Orientador: José Ricardo de Arruda Miranda / Resumo: Inflammatory bowel disease (IBD) is an idiopathic gastrintestinal tract disease that affects a large part of the world population and has its symptoms related to changes in colon motility. However, the evolution of these changes is not completely understood, and may be related to symptoms that appear in stages when the disease is apparently controlled. The objective of this work was to perform a long-term evaluation of the mechanical and electrical aspects of colonic contractility during the model of inflammation induced by trinitrobenzene sulfonic acid (TNBS) in rats. This work applied an efficient and low invasive methodology associating mechanical, electrical, chemical and histological information. The contractility and inflammatory parameters were acquired in the same animal at six different times: before induction of TNBS (control) and at 2, 5, 8, 11 and 14 days thereafter. The mechanical activities were acquired by Alternating Current Biosusceptometry (ACB) and subdivided in Rhythmic Propagation Ripples (RPR) and Rhythmic Propulsive Motor Complex (RPMC). We recorded the electrical activity by electromyography (EMG) and evaluated the inflammation processes determining the myeloperoxidase activity (MPO) in the feces. Additionally, we compared the thickness of colon layers throughout the inflammation by histopathological analyzes. Our results showed transient changes in MPO activity levels and frequency of RPMC contraction, while RPR and electrical activity underwent perma... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor