Increased bioaccumulation of urethane in CYP2E1-/- versus CYP2E1+/+ mice.

Urethane is a fermentation by-product and a potent animal carcinogen. Human exposure to urethane occurs through consumption of alcoholic beverages and fermented foods. Recently, CYP2E1 was identified as the primary enzyme responsible for the metabolism of [(14)C]carbonyl-labeled urethane. Subsequently, attenuation of urethane-induced cell proliferation and genotoxicity in CYP2E1-/- mice was reported. The present work compares the metabolism of single versus multiple exposures of CYP2E1-/- and CYP2E1+/+ mice to (14)C-ethyl-labeled urethane. Urethane was administered as a single 10 or 100 mg/kg gavage dose or at 100 mg/kg/day for 5 consecutive days. CYP2E1+/+ mice administered single or multiple doses exhaled 78 to 88% of dose as (14)CO(2)/day. CYP2E1-/- mice eliminated 30 to 38% of a single dose as (14)CO(2) in 24 h and plateaued after day 3 at approximately 52% of dose/day. The concentrations of urethane-derived radioactivity in plasma and tissues were dose-dependent, increased as a function of the number of doses administered, and were significantly higher in CYP2E1-/- versus CYP2E1+/+ mice. Whereas urethane was the main chemical found in the plasma and tissues of CYP2E1-/- mice, it was not detectable in CYP2E1+/+ mice. In conclusion, multiple dosing led to considerable bioaccumulation of urethane in mice of both genotypes; however, greater retention occurred in CYP2E1-/- versus CYP2E1+/+ mice. Furthermore, greater bioaccumulation of (14)C-ethyl-labeled than [(14)C]carbonyl-labeled urethane was observed in mice. Comparison of the metabolism of ethyl-versus carbonyl-labeled urethane was necessary for tracing the source of CO(2) and led us to propose for the first time that C-hydroxylation is a likely pathway of urethane metabolism.     

Minimally Invasive Treatment of Pilonidal Disease: Crystallized Phenol and Laser Depilation

Pilonidal disease has been treated surgically and by various other methods for many years. The most important problem associated with such treatment is recurrence, but cosmetic outcome is another important issue that cannot be ignored. Today, crystallized phenol is recognized as a treatment option associated with good medical and cosmetic outcomes. We hypothesized that the addition of laser depilation to crystallized phenol treatment of pilonidal disease might increase the rate of success, and this study aimed to determine if the hypothesis was true. Patients who were treated with crystallized phenol and 755-nm alexandrite laser depilation were retrospectively analyzed. In total, 42 (31 male and 11 female) patients were treated with crystallized phenol and alexandrite laser depilation and were followed up between January 2009 and January 2012. In all, 38 patients (90.5%) had chronic disease and 4 (9.5%) had recurrent disease. Among the patients, 26 (61.9%) recovered following 1 crystallized phenol treatment, and the remaining patients had complete remission following repeated treatment. Some patients needed multiple treatments, even up to 8 times. None of the patients had a recurrence during a mean 24 months (range, 6–30 months) of follow-up. Whatever method of treatment is used for pilonidal disease, hair cleaning positively affects treatment outcome. The present results support the hypothesis that the addition of laser depilation (which provides more permanent and effective depilation than other methods) to crystallized phenol treatment (a non-radical, minimally invasive method associated with very good cosmetic results) can increase the effectiveness of the treatment and also reduce the recurrence rate of the disease.     

Protective role of melatonin given either before ischemia or prior to reperfusion on intestinal ischemia-reperfusion damage

Tissue injury resulting from ischemia-reperfusion is of fundamental importance. Experimental evidence suggests that the generation of reactive oxygen species is significantly responsible for this type of injury. In the present study, besides investigating the protective role of melatonin on tissue damage caused by intestinal ischemia-reperfusion, the protective activity of this compound was also analyzed in both pre- and post ischemia melatonin-treated rats. The activities of the main antioxidative enzymes, catalase, superoxide dismutase and glutathione peroxidase in the intestine showed significant (P < 0.05) increases in melatonin-treated animals that were subjected to ischemia/reperfusion compared with those subjected only to ischemia/reperfusion. Also, results clearly indicate that the level of malondialdeyhde, an index of lipid peroxidation, decreased significantly (P < 0.05) when rats subjected to intestinal/reperfusion were given melatonin either before ischemia or before reperfusion.     

ERCP subsequent to retroperitoneal perforation caused by endoscopic sphincterotomy

BACKGROUND: Perforation occurs after endoscopic sphincterotomy in 0.4% of cases. With recognition of a perforation, the procedure usually is aborted and further attempts at ERCP are thought to be precluded by the complication. The aim of this study was to determine the timing and the outcome of ERCP after retroperitoneal perforation caused by endoscopic sphincterotomy when the initial ERCP was incomplete. METHODS: A total of 1787 patients underwent endoscopic sphincterotomy during a period of 29 months. A type II duodenal perforation was recognized in 15 patients, whereupon the ERCP, including further intervention, was halted. Eight patients agreed to undergo a second therapeutic ERCP to complete the treatment of the primary disease. OBSERVATIONS: Therapeutic ERCP was repeated in all patients from 11 to 15 days after the perforation. Treatment was successfully completed in all patients without complication. CONCLUSIONS: Therapeutic ERCP may be repeated and has a high success rate in patients who sustain a perforation caused by endoscopic sphincterotomy.