Biochemical evaluation of glycemic levels of long-term tacrolimus therapy in rats

One of the more serious complications following transplantation is the development of post-transplantation diabetes mellitus (PTDM), which has a major impact on the quality of life, with effects ranging from the control of glycemia times to increased susceptibility to infections and cardiovascular complications. It has been suggested that immunosuppressive therapy, mainly tacrolimus therapy, may be an important factor in the development of PTDM. There is a lack of studies that explore the effects of long-term tacrolimus on PTDM in animal protocols. The objective of this study was therefore to evaluate the effects of long-term therapy with tacrolimus in rats. One group was treated with tacrolimus, injected subcutaneously, in a daily dose of 1 mg/kg of body weight. The chosen dose was sufficient to achieve therapeutic tacrolimus serum levels. The experimental periods were 60, 120, 180 and 240 days. One group was used as control and received daily subcutaneous injections of saline solution during all periods. A tendency towards increased glycemia levels during the initial periods (60 and 120 days) was observed. However, at 180 and 240 days, the glycemia levels were not statistically different from that of the control group of the same period. It may thus be concluded that the deleterious effects of tacrolimus therapy on glycemia may be a time-related side effect.

Uma das mais sérias complicações pós-transplante é o desenvolvimento de Diabetes Mellitus Pós-Transplante (DMPT), que irá produzir um grande impacto na qualidade de vida, com variações do controle glicêmico, aumentando a susceptibilidade a infecções e complicações cardiovasculares. Tem sido sugerido que a terapia imunossupressora, principalmente com tacrolimo, pode ser um importante fator no desenvolvimento de DMPT. Existem atualmente poucos estudos explorando os efeitos de um longo período de terapia com tacrolimo sobre DMPT em protocolos animais. Portanto, o objetivo deste estudo foi avaliar o efeito glicêmico de uma terapia por longo período com tacrolimo em ratos. Um grupo foi tratado com tacrolimo com doses diárias subcutâneas de 1 mg/kg de peso corporal. A escolha dessa dose foi suficiente para a obtenção dos níveis séricos terapêuticos desejados com tacrolimo. Os períodos experimentais foram 60, 120, 180 e 240 dias. Outro grupo foi usado como controle e recebeu injeções salinas subcutâneas diariamente durante todos os períodos. Houve uma tendência ao aumento do nível glicêmico nos períodos iniciais (60 e 120 dias). Entretanto, após 180 e 240 dias, os níveis de glicemia não foram estatisticamente diferentes dos obtidos nos grupos controles de mesmo período. Assim, pode-se concluir que os efeitos glicêmicos adversos provocados pela terapia com tacrolimo podem ser relacionados ao tempo.

Evaluation of the natural killer cytotoxicity and the levels of cytokines in rats with type I diabetes mellitus

Type I diabetes mellitus (insulin-dependent DM = IDDM) is a chronic disease characterized by specific destruction of pancreatic beta cells, resulting in an absolute lack of insulin. Immune mechanisms, genetic susceptibility, and environmental factors are all implicated in the pathogenesis of Type 1 diabetes. This study was aimed at determining the efficiency of cytokines, natural killer (NK) cells in the pathophysiology of IDDM. Therefore, we evaluated the plasma levels of cytokines by specific enzyme-linked immunosorbent assay (ELISA) and the cytotoxicity activity of NK cells by anti-candididal index in rats with type I diabetes. We found that the cytotoxicity activity of NK cells in IDDM groups significantly decreased compared to the control groups. The levels of interferon-g (IFN-g) in IDDM groups were slightly higher than in healthy controls. These results indicate that the changes of T H1 type cytokines such as IFN-g and NK cell activity can play a role in the etiology of IDDM. The data may provide new strategies for the treatment of IDDM.

Necrose e apoptose celular após reaplicação de ondas de choque em rins de ratos diabéticos / Cell necrosis and apoptosis after shock waves on kidneys of diabetic rats

O objetivo deste trabalho é estudar as repercussões das ondas de choque e a expressão morfológica da necrose e da apoptose no rim de animal de experimentação .A incidência da litíase urinária é estimada em torno de 3 a 5 por cento da população mundial, comparável à do Diabetes melittus. Cerca de 85 a 90 por cento dos cálculos não eliminados espontaneamente são tratados pelo método da litotripsia extracorpórea, por ondas de choque. Foram utilizados 80 ratos Wistar machos distribuídos em 2 grupos: 40 animais não-diabéticos e 40 animais com diabetes induzida pela aloxana. Estes animais foram redistribuídos em 4 sub-grupos. Os sub-grupos A1 e 131 serviram de controles em relação a A2 e B2, que receberam duas aplicações de 2.000 ondas de choque, com intervalo de 14 entre as aplicações, totalizando 4.000 ondas. Os sub-grupos A3 e 133 serviram de controle em relação a A4 e B4, que receberam uma aplicação de 2.000 ondas de choque, com 14 Kv de intensidade. Todos os animais foram examinados três dias após a aplicação. Os principais parâmetros observados foram: hemorragia subcapsular, hemorragia intersticial, hemorragia glomerular, edema perivascular, infiltrado inflamatório crônico, espessamento mesangial e freqüência do índice de apoptose...

T-lymphocyte mediated injury of beta cells in dual-aetiology diabetes mellitus in Swiss albino mouse.

Earlier we had described a dual aetiology diabetes mellitus (DADM) in mice injected with a sub-diabetogenic dose of streptozotocin (SD-SZN) and afterwards infected with coxsackie B3 virus (CBV). Further experiments were conducted to understand the mechanism of diabetogenesis. In in vitro stimulation and proliferation tests, the splenic lymphocytes (SLC) of mice given either SD-SZN or CBV infection showed lower responses to two T cell mitogens than those of control mice, indicating an immunosuppressive effect. Unexpectedly, SLC of mice given both SD-SZN and CBV showed enhanced response, indicating immunoactivation; they were not stimulated to proliferation in response to CBV antigen, indicating that the immunoactivation was not directed against CBV, but against streptozotocin or cellular elements. When mice were depleted of T cells by injecting with anti-thymocyte serum, the diabetogenic effect of SD-SZN and CBV infection was abrogated, without diminishing the replication of virus in the pancreas. Thus beta cell injury in DADM appears to be T cell-mediated.