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Doctoral Thesis
DOI
10.11606/T.17.2016.tde-06012016-151931
Document
Author
Full name
Marilia Alessi Guena de Camargo
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2015
Supervisor
Committee
Rodrigues, Maria Carolina de Oliveira (President)
Cesar, Thais Borges
Couri, Carlos Eduardo Barra
Jordao Junior, Alceu Afonso
Simoes, Belinda Pinto
Title in Portuguese
Perfil do estresse oxidativo em pacientes com diabetes mellitus do tipo 1 submetidos ao transplante autólogo de células-tronco hematopoéticas, em Ribeirão Preto, SP
Keywords in Portuguese
antioxidantes
diabetes mellitus
estresse oxidativo
transplante autólogo de células-tronco hematopoéticas
Abstract in Portuguese
O estresse oxidativo, induzido por espécies reativas, está diretamente envolvido com a função das células durante o desenvolvimento do diabetes mellitus do tipo 1 (DM1), bem como no desenrolar das complicações relacionadas à hiperglicemia. O transplante autólogo de células-tronco hematopoéticas é uma estratégia de intervenção imunológica que visa preservar a função do pâncreas endócrino, se realizado durante a fase em que o paciente ainda possui importante reserva de células pancreáticas. Dessa forma, o presente estudo objetiva investigar como o estresse oxidativo se comporta nos momentos pré e pós-transplante. Dezoito pacientes transplantados entre 2004 e 2010 foram avaliados retrospectivamente, a partir de amostras de soro criopreservadas imediatamente antes, e 12 meses após o transplante. Esses pacientes também foram subdivididos em respondedores (livres de insulina exógena aos 12 meses pós-transplante) e não-respondedores (em uso de insulina exógena 12 meses pós-transplante). Dados do estresse oxidativo (malonaldeído e isoprostano) e da capacidade antioxidante (glutationa reduzida, superóxido dismutase e tocoferol) foram comparados nos pacientes diabéticos antes e 12 meses pós-transplante, e também com o grupo controle. Dentro do grupo experimental observamos que, 12 meses depois do transplante, os pacientes apresentaram melhora dos níveis de hemoglobina glicada e das doses de insulina exógena e recuperação do peso corporal. Aos 12 meses pós-transplante, o grupo de pacientes respondedores apresentaram níveis de peptídeo-C significativamente maiores do que o de não-respondedores. Quando comparados ao grupo controle, verificamos maiores níveis de glutationa reduzida e isoprostano nos pacientes diabéticos, em ambos os momentos (pré e pós-transplante). Também observamos que níveis de tocoferol (vitamina E) estão reduzidos, abaixo do valor de referência, quando comparados ao grupo controle. Em conclusão, o presente estudo identificou que pacientes com DM1 já possuem alterações no estresse oxidativo marcada pelo aumento do isoprostano e da atividade antioxidante marcada pelo aumento da glutationa reduzida (GSH) poucas semanas após o diagnóstico e que o procedimento não contribuiu para normalizar seus níveis.
Title in English
Oxidative stress profile in patients with type 1 diabetes mellitus treated with autologous hematopoietic stem cells, in Ribeirão Preto, Brazil
Keywords in English
antioxidants
autologous hematopoietic stem cell transplantation
diabetes mellitus
oxidative stress
Abstract in English
Oxidative stress, induced by reactive species, is directly involved with -cell function during the development of type 1 diabetes mellitus (T1DM) and with the development of hyperglycemia-induced complications. Autologous hematopoietic stem cell transplantation (AHSCT) is an immunological therapeutic strategy to preserve the function of the endocrine pancreas, if performed early after T1DM diagnosis, while the patient still has significant residual beta cell mass. Thus, this study aims to investigate how oxidative stress behaves before and after AHSCT and how it may be related with glycemic control. Eighteen patients transplanted between 2004 and 2010, which had serum samples cryopreserved immediately before and 12 months after transplantation, were retrospectively evaluated. These patients were also divided into responders (insulin-free at 12 months posttransplant) and non-responders (in use of insulin 12 months post-transplant). Data on oxidative stress (malondialdehyde and isoprostane levels) and antioxidant capacity (reduced glutathione, superoxide dismutase and tocopherol levels), from diabetic patients, were compared before and 12 months after AHSCT, and also with a healthy control group. We observed that 12 months after transplantation, T1DM patients showed improvement in glycated hemoglobin levels and exogenous insulin doses, besides recovery of pre-diabetes body weight levels. At 12 months posttransplantation, the group of responders had significantly higher C-peptide levels than the non-responders. When compared to the health individuals (control group), we found higher levels of reduced glutathione and isoprostane in T1DM patients, both before and after transplantation. We also observed that tocopherol levels (vitamin E) were reduced below the reference value, when compared to the control group. In conclusion, we found that patients with T1DM present abnormal oxidative stress, marked by increased isoprostane, and antioxidant activity, marked by the increase of reduced glutathione (GSH) already a few weeks after diagnosis and that AHSCT did not contribute to normalize their levels.
 
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Publishing Date
2016-03-14
 
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