No abstract

In type 2 diabetes, chronic hyperglycemia is suggested to be detrimental to pancreatic β cells, causing impaired insulin secretion. IL-1β is a proinflammatory cytokine acting during the autoimmune process of type 1 diabetes. IL-1β inhibits β cell function and promotes Fas-triggered apoptosis in part by activating the transcription factor NF-κB. Recently, we have shown that increased glucose concentrations also induce Fas expression and β cell apoptosis in human islets. The aim of the present study was to test the hypothesis that IL-1β may mediate the deleterious effects of high glucose on human β cells. In vitro exposure of islets from nondiabetic organ donors to high glucose levels resulted in increased production and release of IL-1β, followed by NF-κB activation, Fas upregulation, DNA fragmentation, and impaired β cell function. The IL-1 receptor antagonist protected cultured human islets from these deleterious effects. β cells themselves were identified as the islet cellular source of glucose-induced IL-1β. In vivo, IL-1β–producing β cells were observed in pancreatic sections of type 2 diabetic patients but not in nondiabetic control subjects. Similarly, IL-1β was induced in β cells of the gerbil Psammomys obesus during development of diabetes. Treatment of the animals with phlorizin normalized plasma glucose and prevented β cell expression of IL-1β. These findings implicate an inflammatory process in the pathogenesis of glucotoxicity in type 2 diabetes and identify the IL-1β/NF-κB pathway as a target to preserve β cell mass and function in this condition

To assess the clinical and echocardiographic time course, prognosis, and possible etiology of HIV-associated primary pulmonary hypertension (PPH), we prospectively followed all 19 patients in whom PPH was diagnosed in our centers. Women (12 cases) and injecting drug use (16 cases) predominated; the median CD4 lymphocytes count was 83/microliter (range, 1 to 740). Matched control subjects without PPH were identified within the Swiss HIV Cohort Study. Frozen serum samples of both groups were then reanalyzed for autoimmune parameters, neopterin, beta-2-microglobulin, and thyroid-stimulating hormone. The median follow up of the patients was 1.3 yr. Follow-up Doppler echocardiography was available in 13 patients. The RVSP-RAP pressure gradient decreased by 3.2 mm Hg for those six patients who received antiretroviral treatment but increased by 19.0 mm Hg for untreated patients (p = 0.026). PPH was the cause of eight of 17 deaths. The probability of surviving was significantly decreased in patients with PPH in comparison with the control subjects; the median survival was 1.3 versus 2.6 yr (p < 0.05). Patients with PPH had significantly higher anticardiolipin IgM, anti SS-B, and neopterin, but all other laboratory values did not differ between cases and control subjects. In conclusion, HIV-associated PPH contributed significantly to mortality. Antiretroviral treatment may exert a beneficial effect on the pressure gradient. A possible role of an autoimmune phenomenon in the pathogenesis could not be substantiated.

Elevated troponin is a mortality risk factor for medical intensive care patients admitted for reasons other than ACS. It is associated with decreased left ventricular function and higher levels of TNF-alpha and IL-6.

Background: S100 proteins are low-molecular-weight calcium-binding proteins and appear to play an important role in various cellular processes such as cell division and differentiation. In histopathology, S100 is widely accepted as the marker of choice for immunohistochemical identification of malignant melanoma. When S100 was detected in the serum of patients with malignant melanoma, it was suggested that serum S100 may be a useful marker for the stage of disease. Objective: The aim of this study was to examine serum S100 concentrations of patients with different stages of malignant melanoma and to determine the value of serum S100 in the follow-up of melanoma patients during treatment. Methods: Sera were obtained from 73 melanoma patients in different stages of the disease. The control group consisted of 130 healthy subjects. In 4 patients with metastatic melanoma, serum SI00 was measured serially. Serum levels were measured by a commercially available immunoradiometric assay. Results: While only 1 out of 25 stage I/II patients and 3 of 14 patients with lymph node metastases (stage III, 21.4%) showed detectable serum SI00 levels, 27 of 34 patients with disseminated disease (stage IV, 79.4%) had elevated serum SI00. Interestingly, rising levels of serum S100 in the serial measurement indicated progression of the disease, and a complete decline reflected 2 patient remissions. Conclusion: The data support the value of serum S100 as a clinical marker for progression of metastatic melanoma and serological monitoring during systemic therapies.