Remission from insulin dependency in insulin-treated recent-onset type I (insulin-dependent) diabetic patients can result from a partial recovery of insulin secretion, an improvement in tissue sensitivity to insulin, or both. The same hypothesis must be analyzed when remission occurs in cyclosporin A (CsA)-treated patients. In this study, plasma C-peptide levels were serially measured in the basal state and after stimulation in 219 recent-onset type I diabetic patients; 129 received CsA, and all patients were similarly monitored and insulin treated. The results were analyzed in view of the occurrence of remission. Remission was defined as good metabolic control in the absence of hypoglycemic treatment for greater than or equal to 1 mo. Remission occurred in 44% of the CsA-treated group and lasted for mean +/- SE 10.0 +/- 0.9 mo vs. 21.6% in the non-CsA-treated group with a duration of 4.4 +/- 0.8 mo. Plasma C-peptide levels were initially dramatically lower than normal in both groups in the basal and stimulated states. C-peptide levels increased significantly later, at 3 and 6 mo, in both groups. C-peptide values were proportional to the rates of remission in both groups. In the non-CsA-treated group, C-peptide levels later decreased, and these patients inexorably relapsed to insulin dependency. In contrast, in the CsA-treated group, the initial recovery in insulin secretory capacity was maintained over the 18-24 mo of the study. Furthermore, higher remission rates and longer-lasting remission were obtained in patients who reached higher C-peptide levels at the 3rd mo of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
Background: Volatile anesthetic preconditioning (APC) protects against myocardial ischemia-reperfusion (IR) injury, but the precise mechanisms underlying this phenomenon remain undefined. To investigate the molecular mechanism of APC in myocardial protection, the activation of nuclear factor (NF) [kappa]B and its regulated inflammatory mediators expression were examined in the current study.
Methods: Hearts from male rats were isolated, Langendorff perfused, and randomly assigned to one of three groups: (1) the control group: hearts were continuously perfused for 130 min; (2) the IR group: 30 min of equilibration, 15 min of baseline, 25 min of ischemia, 60 min of reperfusion; and (3) the APC + IR group: 30 min of equilibration, 10 min of sevoflurane exposure and a 5-min washout, 25 min of global ischemia, 60 min of reperfusion. Tissue samples were acquired at the end of reperfusion. NF-[kappa]B activity was determined by electrophoretic mobility shift assay. The NF-[kappa]B inhibitor, I[kappa]B-[alpha], was determined by Western blot analysis. Myocardial inflammatory mediators, including tumor necrosis factor [alpha], interleukin 1, intercellular adhesion molecule 1, and inducible nitric oxide synthase, were also assessed by Western blot analysis.
Results: Nuclear factor [kappa]B-DNA binding activity was significantly increased at the end of reperfusion in rat myocardium, and cytosolic I[kappa]B-[alpha] was decreased. Supershift assay revealed the involvement of NF-[kappa]B p65 and p50 subunits. APC with sevoflurane attenuated NF-[kappa]B activation and reduced the expression of tumor necrosis factor [alpha], interleukin 1, intercellular adhesion molecule 1, and inducible nitric oxide synthase. APC also reduced infarct size and creatine kinase release and improved myocardial left ventricular developed pressure during IR. 相似文献