LB30057, A Direct Thrombin Inhibitor, Inhibits Vascular Smooth Muscle Cell proliferation in vitro and the Neointimal Hyperplasia in Rat Carotid Injury Model

BACKGROUND: Recent data showed prolonged administration of direct thrombin inhibitor might be needed to counteract the persistent thrombin activity and reduce the neointimal hyperplasia after arterial injury. We hypothesized that prolonged administration of LB30057, orally active direct thrombin inhibitor, might inhibit the vascular smooth muscle cell (SMC) proliferation in vitro and neointimal hyperplasia in rat carotid injury model. METHODS: In phase I, thrombin stimulated [methyl-3H] thymidine uptake was measured after LB30057 administration in cell culture study using rat aortic SMC. In phase II, LB30057 (low-dose: 5mg/kg, bid: mid-dose: 25mg/kg, bid: high-dose: 50mg/kg, bid) or placebo was administrated orally twice a day starting from 30minutes before injury until sacrifice for 14days in separated 2 sets of experiment. The histo-morphometric analysis for lumen area, intimal area, medial area, intima-to-medial ratio was performed. RESULTS: In vitro rat aortic SMC culture study, LB30057 inhibited thrombin-induced thymidine uptake. The mean neointimal area was significantly less in high-dose and mid-dose group than placebo group (high-dose vs. placebo: 0.14+/-0.02mm2 vs. 0.25+/-0.02mm2: mid-dose vs. placebo: 0.16+/-0.02mm2 vs. 0.29+/-0.03mm2, p<0.005) respectively and the mean ratio of neointima to medial area were significantly less in high-dose and mid-dose group than in placebo group (high-dose vs. placebo: 1.20+/-0.57 vs. 1.94+/-0.67, mid-dose vs. placebo: 1.58+/-0.29 vs. 2.39+/-0.27, p<0.05). There was no significant difference in the mean area of internal elastic lamina, external elastic lamina and mean luminal area between groups. In 2nd set experiment, the mean neointimal area (placebo: 0.29+/-0.03mm2, mid-dose: 0.16+/-0.02mm2: p<0.005), the mean area of internal elastic lamina and external elastic lamina were significantly less in mid-dose group than in placebo group. The mean ratio of neointima to medial area was significantly less in mid-dose group(1.58+/-0.29) than in placebo group (2.39+/-0.27) (p<0.05). CONCLUSION: LB30057 inhibits SMC proliferation in a dose dependent manner. Prolonged 14-day oral administration of LB30057 is effective in reducing the neointimal hyperplasia in rat carotid balloon injury model.

Two Cases of Acute Respiratory Distress Syndrome with Pulmonary Hemorrhage Induced by Injection of Silicone at Perineum / 결핵

Silicone fluid is a biomaterial widely used in modern cosmetic procedures because there are few side effects, considerable chemical stability and predictable physical properties. However, many local and systemic adverse reactions have reported. In particular some serious pulmonary complications have been reported such as pulmonary thromboembolism, acute respiratory distress syndrome with some cases leading to mortality. Most of the serious complicated cases were induced by an illegal silicone fluid injection. We experienced two cases of acute respiratory distress syndrome with pulmonary hemorrhage induced by an illegal silicone fluid injection. The patients were 41 & 51 year old women, who complained of dyspnea. The chest X-ray and HRCT scan findings showed a bilateral ground glass attenuation on the bilateral dependent portion of the upper and middle lung zone. The patients clinical symptoms and the radiologic and other laboratory findings were compatible with acute respiratory distress syndrome induced by the silicon fluid injection. Here we report two cases of acute respiratory distress syndrome with pulmonary hemorrhage induced by an illegal silicone injection with a review of the relevant literature.

A Case of Theophylline-Induced Hepatitis / 대한간학회지

Theophylline has been widely used in the treatment of asthma and chronic obstructive lung disease. To date, there have been very few reports on hepatotoxicity due to theophylline. We diagnosed, through biochemical testing and a liver biopsy, a case of acute cholestatic hepatitis developed after oral consumption of theophylline. A 43 year-old man was admitted to the department of internal medicine due to jaundice and pruritus which developed after ten days administration of oral theophylline (Etheophyl ). Liver function tests showed elevated serum bilirubin at 13.2 mg/dL with AST and ALT of 71 U/L and 194 U/L. Alkaline phosphatase and gamma-GTP were also elevated at 175 U/L and 301 U/L. There was no evidence of viral or autoimmune hepatitis in laboratory tests. The patient's symptoms and liver function tests were improved after conservative treatment. After 9 months oral theophylline was readministered for the control of relapsed asthma. Then, jaundice and pruritus again developed again. A liver biopsy showed a few lymphocytes and eosinophilic inflammatory cell infiltration in portal tract and cholestasis in the lobule. Drug-induced hepatitis was diagnosed with a typical clinical course; the exclusion of all possible causes of acute hepatic dysfunction; and a positive response to accidental readministration of drug. We report this case with a review of the literature.