Udenafil, a Phosphodiesterase 5 Inhibitor, Reduces Body Weight in High-Fat-Fed Mice

PURPOSE: High-fat (HF) feeding induces hypothalamic leptin resistance via the activation of toll-like receptor 4 (TLR4). TLR4 deficiency confers resistance to diet-induced obesity. Udenafil, an anti-impotence drug, inhibits TLR4 in airway epithelial cells in vitro. In this study, we evaluated whether udenafil suppressed the hypothalamic expression of TLR4 and reduced body weight. MATERIALS AND METHODS: The hypothalamic expression of TLR4, phosphodiesterase 5 (PDE5), nuclear factor-κB (NF-κB), and myeloid differentiation primary response gene 88 (Myd88) was analyzed by real-time polymerase chain reaction after treating mice for 2 days with udenafil (0, 12, 120, or 600 µg/d). Furthermore, the hypothalamic expression of TLR4, pro-opiomelanocortin (POMC), and neuropeptide Y (NPY) was analyzed after 9 days' treatment with udenafil and/or leptin. We also measured body weight and food intake following 9 days of udenafil and/or leptin treatment in control- and HF-fed mice. RESULTS: Udenafil suppressed hypothalamic TLR4 mRNA expression dose-dependently. The changes were associated with decreased PDE5, NF-κB, and Myd88 expression. Udenafil treatment for 9 days reduced body weight and caloric intake in HF-fed mice. This may have been associated with the suppression of NPY expression that was elevated by HF feeding. POMC expression was not affected by udenafil. However, udenafil did not augment the effects of leptin on the reduction of body weight and caloric intake in HF-fed mice. CONCLUSIONS: These results suggested that udenafil reduced body weight by suppressing hypothalamic TLR4 mRNA expression in HF-fed mice and the combination effect of udenafil and leptin was additive rather than synergistic.

Clinical Review of Acute Mesenteric Ischemia

PURPOSE: The purpose of this study was to review our clinical experiences of acute mesenteric ischemic disease at the Masan Samsung hospital. METHOD: Retrospectively reviewed the medical records of 20 patients with acute mesenteric ischemic disease from 1998 through 2003 in terms of clinical characteristics, image findings, management and results. RESULT: The mean age of patients was 63.5 years and the male female ratio was 1.5:1. Coexisting diseases were atrial fibrillation (n=10), hypertension (n=9), myocardial infarction (n=2), DM (n=4). The clinical manifestations were abdominal pain, abdominal distension, peritoneal irritation signs, vomiting and melena. The presenting signs were nonspecific. Laboratory findings were nonspecific and not helpful for diagnosis of acute mesenteric ischemia. Abdominal CT and SMA angiography were accurate and sensitive diagnostic tools. Seventeen cases were SMA occlusion (1 case: SMA dissection) and 3 cases were SMV occlusion. Operative procedures were resection of bowel (12 cases) and thromboembolectomy (5 cases). Non operative procedure was anticoagulation (3 cases). One patient refused surgery. CONCLUSION: Both clinical and laboratory data were non-specific and delayed diagnosis was the main cause of the overall mortality rate of 35% (7 cases). The mortality rate for patients undergoing surgery for acute mesenteric ischemic disease was high, but early diagnosis and intensive care may be reduced mortality.