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We reported earlier that β-cell-specific overexpression of glutathione peroxidase (GPx)-1 significantly ameliorated hyperglycemia in diabetic mice and prevented glucotoxicity-induced db/db deterioration of β-cell mass and function. We have now ascertained whether early treatment of Zucker diabetic fatty (ZDF) rats with ebselen, an oral GPx mimetic, will prevent β-cell deterioration. No other antihyperglycemic treatment was given. Ebselen ameliorated fasting hyperglycemia, sustained nonfasting insulin levels, lowered nonfasting glucose levels, and lowered HbA1c levels with no effects on body weight. Ebselen doubled β-cell mass, prevented apoptosis, prevented expression of oxidative stress markers, and enhanced intranuclear localization of pancreatic and duodenal homeobox (Pdx)-1 and v-maf musculoaponeurotic brosarcoma oncogene family, protein A (MafA), two critical insulin transcription factors. Minimal β-cell replication was observed in both groups. These findings indicate that prevention of oxidative stress is the mechanism whereby ebselen prevents apoptosis and preserves intranuclear Pdx-1 and MafA, which, in turn, is a likely explanation for the beneficial effects of ebselen on β-cell mass and function. Since ebselen is an oral antioxidant currently used in clinical trials, it is a novel therapeutic candidate to ameliorate fasting hyperglycemia and further deterioration of β -cell mass and function in humans undergoing the onset of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Classical congenital adrenal hyperplasia (CAH) is characterized by the defects in cortisol and aldosterone secretion, and accompanied with adrenal hyperandrogenism. It is likely that the impaired adrenocortical function and intermittent treatment-related hypercortisolism may predispose patients to the development of metabolic syndrome in adulthood. Our aim was to assess the impact of hyperandrogenism on metabolic profiles in CAH women without glucocorticosteroid treatment. We evaluated the clinical characteristics and metabolic profiles in 30 untreated Chinese female adults with simple virilizing congenital adrenal hyperplasia (SV-CAH). Mutation analysis was performed by sequencing the entire 21-hydroxylase gene ( CYP21A2). As compared with the controls, CAH patients had higher BMI (BMI, 21.5 ± 2.1 vs. 20.0 ± 1.8 kg/m, P < 0.05), higher 2 h post-load plasma glucose levels (6. 35 ± 1.74 vs. 5. 35 ± 1.17 mmol/l, P < 0.05), higher serum triglycerides (TG) (1.12 ± 0.64 vs. 0.63 ± 0.15 mmol/l, P < 0.01), and lower high-density lipoprotein cholesterol (HDL-c) (1.30 ± 0.39 vs. 1.67 ± 0.29 mmol/l, P < 0.01). Moreover, CAH patients had higher fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) (1.81 ± 0.99 vs. 1.24 ± 0.50, P < 0.05), while ΔIns30/ΔGlu30 showed no statistically significant difference in two groups. In addition, a marked reduction of serum adiponectin levels were observed in CAH patients (7.0 ± 3.3 vs. 13.2 ± 4.8 μg/ml, P < 0.001), however, serum CRP levels were not different between patients and the controls. Further regression analysis showed that higher serum testosterone concentrations were associated with metabolic disorder indexes and reduction of serum adiponectin. Our study demonstrates that untreated CAH patients are prone to have metabolic disorders in association with elevated serum testosterone levels and reduced insulin insensitivity. [ABSTRACT FROM AUTHOR]

Infliximab (IFX) is an anti-tumor necrosis factor chimeric antibody that is effective for treatment of autoimmune disorders such as Crohn's disease and ulcerative colitis (UC). IFX is well tolerated with a low incidence of adverse effects such as infections, skin reactions, autoimmunity, and malignancy. Dermatological manifestations can appear as infusion reaction, vasculitis, cutaneous infections, psoriasis, eczema, and skin cancer. Here, we present an unusual case of extensive and sporadic subcutaneous ecchymosis in a 69-year-old woman with severe UC, partial colectomy and cecostomy, following her initial dose of IFX. The reaction occurred during infliximab infusion, and withdrawal of IFX led to gradual alleviation of her symptoms. We concluded that Henoch-Schönlein purpura, a kind of leukocytoclastic vasculitis, might have contributed to the development of the bruising. Although the precise mechanisms of the vasculitis are still controversial, such a case highlights the importance of subcutaneous adverse effects in the management of UC with IFX.

Inflammatory bowel disease (IBD) includes Crohn's disease and ulcerative colitis. The exact etiology and pathology of IBD remain unknown. Available evidence suggests that an abnormal immune response against the microorganisms in the intestine is responsible for the disease in genetically susceptible individuals. Dysregulation of immune response in the intestine plays a critical role in the pathogenesis of IBD, involving a wide range of molecules including cytokines. On the other hand, besides T helper (Th) 1 and Th2 cell immune responses, other subsets of T cells, namely Th17 and regulatory T cells, are likely associated with disease progression. Studying the interactions between various constituents of the innate and adaptive immune systems will certainly open new horizons of the knowledge about the immunologic mechanisms in IBD.