ABSTRACT:Ionizing radiation has been successfully employed to modify the immunological properties of biomolecules. Very promising results were obtained when crude animal venoms, as well as isolated toxins, were treated with 60Co gamma rays, yielding toxoids with good immunogenicity. The achievement of modified antigens with lower toxicity and preserved or improved immunogenicity can be very useful. Ionizing radiation has already been proven to be a powerful tool to attenuate snake venom toxicity without affecting, and even increasing, their immunogenic properties. However, little is known about the modifications that irradiated molecules undergo and even less about the immunological response that such antigens elicit. In the present work, we investigated the immunological behavior of bothropstoxin-1, a K49 phospholipase, before and after irradiation. Structural modifications of the toxin were analyzed by SDS-PAGE. Isogenic mice were immunized with either the native or the irradiated toxin. The circulating antibodies were isotyped and titrated by ELISA. According to our data, irradiation promoted structural modifications in the toxin characterized by higher molecular weight forms of proteins (aggregates and oligomers). The results also indicated that irradiated toxins were immunogenic and antibodies elicited by them were able to recognize the native toxin in ELISA. These findings suggest that irradiation of toxic proteins can promote significant modifications in their structures; however they still retain many of the original antigenic and immunological properties of native proteins. Also, our data indicate that irradiated proteins induce higher titers of IgG2a and IgG2b, suggesting that Th1 cells are predominantly involved in the immune response.
OBJECTIVES: Several predictors of type 2 diabetes mellitus (T2DM) remission after metabolic surgery have been proposed and used to develop predictive scores. These scores may not be reproducible in diverse geographic regions with different baseline characteristics. This study aimed to identify predictive factors associated with T2DM remission after Roux-en-Y gastric bypass (RYGB) in patients with severe obesity. We hypothesized that the body composition alterations induced by bariatric surgery could also contribute to diabetes remission. METHODS: We retrospectively evaluated 100 patients with severe obesity and T2DM who underwent RYGB between 2014 and 2016 for preoperative factors (age, diabetes duration, insulin use, HbA1c, C-peptide plasma level, and basal insulinemia) to identify predictors of T2DM remission (glycemia<126 mg/dL and/or HbA1c<6.5%) at 3 years postoperatively. The potential preoperative predictors were prospectively applied to 20 other patients with obesity and T2DM who underwent RYGB for validation. In addition, 81 patients with severe obesity (33 with T2DM) underwent body composition evaluations by bioelectrical impedance analysis (InBody 770®) 1 year after RYGB for comparison of body composition changes between patients with and those without T2DM. RESULTS: The retrospective analysis identified only a C-peptide level >3 ng/dL as a positive predictor of 3-year postoperative diabetes remission, which was validated in the prospective phase. There was a significant difference in the postoperative body composition changes between non-diabetic and diabetic patients only in trunk mass. CONCLUSION: Preoperative C-peptide levels can be useful for predicting T2DM remission after RYGB. Trunk mass is the most important difference in postoperative body composition changes between non-diabetic and diabetic patients.
Dissertação apresentada como parte dos requisitos para a obtenção do Grau de Mestre em Ciências na Área de Tecnologia Nuclear -Aplicações Orientadora: Prof a . Dr a . Nanci do Nascimento São Paulo 2009 Dedico este trabalho Aos meus pais, Wagner e Margarida, e aos meus irmãos, Érica e Anderson, por sempre estarem ao meu lado e por todo apoio, compreensão e força que sempre me deram. Ao meu amado Tiago Luiz de Almeida por percorrer esta estrada junto comigo e por ser essa pessoa maravilhosa que fez minha vida ser bem melhor. Um filósofo, muito antigo por sinal, também lhe segredou: "Executa cada ação como se fosse a última de tua vida". Marco Aurélio AGRADECIMENTOS À Deus, primeiramente, por me dar a vida. Ao Instituto de Pesquisa Energéticas e Nucleares (IPEN) e ao Centro de Biotecnologia, onde este trabalho foi realizado, pelo suporte e estrutura que proporcionou. À Dra. Nanci do Nascimento pela oportunidade, atenção e por me guiar no desenvolvimento deste trabalho. Ao Dr. Heitor Franco de Andrade Jr., pelos ensinamentos e ajuda com os gráficos e também por manter as portas de seu laboratório no Instituto de Medicina Tropical de São Paulo sempre abertas. Ao Conselho Nacional de Energia Nuclear (CNEN/IPEN) pela bolsa concedida durante o período em que este trabalho foi realizado. Aos integrantes da Comissão de Pós Graduação do IPEN, pelo empenho e dedicação para oferecer todas as condições necessárias aos pós-graduandos. Aos meus pais pelo apoio interminável, pela força e ensinamento que me deram. Por me guiarem pelos caminhos tortuosos da vida, por acreditarem em mim e pela dedicação e amor com que me criaram. Se sou o que sou hoje eu devo a vocês.Aos meus queridos irmãos, Érica e Anderson, que sempre me ajudaram a crescer como pessoa, pela força e apoio na minha jornada. Por estarem sempre ao meu lado quando eu precisei e por tornarem a minha vida mais feliz e menos difícil, tornando-a mais divertida.Ao meu amado, Tiago Luiz de Almeida, pelo amor, carinho, ajuda, compreensão, força, diversão e por sempre estar ao meu lado em todos os momentos e tornar as coisas mais fáceis de serem feitas.Às minhas queridas avós por estarem sempre dispostas a me ajudar, pelo carinho e por darem o "colinho" que só as vovós possuem.Aos meus tios, Sérgio e Vera, que estiveram comigo durante estes anos, pelas conversas e momentos de alegrias.A toda minha família por me ajudar a crescer e por apoiar nas minhas decisões, além de claro, pelos momentos de descontração.
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