Bilirubin prevents acute DSS-induced colitis by inhibiting leukocyte infiltration and suppressing upregulation of inducible nitric oxide synthase.

Bilirubin is thought to exert anti-inflammatory effects by inhibiting vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration and by suppressing the expression of inducible nitric oxide synthase (iNOS). As VCAM-1 and iNOS are important mediators of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice. Male C57BL/6 mice were administered 2.5% DSS in the drinking water for 7 days, while simultaneously receiving intraperitoneal injections of bilirubin (30 mg/kg) or potassium phosphate vehicle. Disease activity was monitored, peripheral blood counts and serum nitrate levels were determined, and intestinal specimens were analyzed for histological injury, leukocyte infiltration, and iNOS expression. The effect of bilirubin on IL-5 production by HSB-2 cells and on Jurkat cell transendothelial migration also was determined. DSS-treated mice that simultaneously received bilirubin lost less body weight, had lower serum nitrate levels, and exhibited reduced disease severity than vehicle-treated animals. Concordantly, histopathological analyses revealed that bilirubin-treated mice manifested significantly less colonic injury, including reduced infiltration of eosinophils, lymphocytes, and monocytes, and diminished iNOS expression. Bilirubin administration also was associated with decreased eosinophil and monocyte infiltration into the small intestine, with a corresponding increase in peripheral blood eosinophilia. Bilirubin prevented Jurkat migration but did not alter IL-5 production. In conclusion, bilirubin prevents DSS-induced colitis by inhibiting the migration of leukocytes across the vascular endothelium and by suppressing iNOS expression.

Assessment of diaphragmatic stressors as risk factors for symptomatic failure of laparoscopic nissen fundoplication.

An important limitation of antireflux surgery is a 5%-10% failure rate. We investigated the correlation between various diaphragm stressors and failure of antireflux surgery. Forty-one study cases who underwent a reoperative antireflux operation from 1997 to 2001 and 50 control patients who had undergone a successful laparoscopic Nissen fundoplication during the same period without clinical or symptomatic evidence of failure were randomly selected for comparison. A retrospective analysis was conducted utilizing a standardized diaphragm stressor questionnaire, addressing the period between the primary and secondary operation. Stressors considered in the study included height, body mass index (BMI), postoperative gagging, vomiting, weight lifting (greater than 100 pounds), coughing, hiccuping, motion sickness, retching, belching, antidepressant use, smoking, preoperative grade of esophagitis, size of hiatal hernia, lower esophageal sphincter pressure, esophageal body pressures, and preoperative response to proton pump inhibitors. Of the potential stressors investigated, the following were significantly associated with surgical failure after adjusting for other variables through multivariate analysis: gagging (P = 0.005), belching (P = 0.02), and hernia size greater than 3 cm (P = 0.04; Table 1). Other potential risk factors show trends as obvious in Fig. 2. Vomiting was significant (P = 0.01) in the earlier models but lost significance when logistic regression was applied. Patients with postoperative gagging and an intraoperative hiatal hernia (greater than 3 cm) have a poorer outcome, whereas patients with postoperative belching have a better long-term outcome.