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.

Pediatric refracture rates after angulated and completely displaced clavicle shaft fractures.

OBJECTIVES: The purpose of this study was to assess refracture rates after angulation-only and completely displaced clavicle shaft fractures in children. DESIGN: Retrospective chart review. SETTING: Level 1 pediatric trauma center. PATIENTS: Computerized medical records searches identified children treated nonoperatively for clavicle shaft fractures at our institution. Inclusion criteria were age less than 18 years and a minimum of 1-year radiographic follow-up. Statistical methods included Fisher exact test with significant probability values being defined as less than 0.05. RESULTS: Of the 120 angulation-only patients and 41 completely displaced patients meeting criteria for inclusion in our study, we identified a statistically higher (P = 0.002) refracture rate (18%, 21/120) in angulation-only fractures as compared with 0% (0/41) for completely displaced fractures. Subgroup analysis of the angulation-only fractures revealed that fractures angulated less than 40 degrees refractured at a 26% rate (18/69) versus 6% (3/51) of fractures with greater angulation (P = 0.004). CONCLUSIONS: We found that angulation-only shaft fractures had a significantly higher refracture rate than completely displaced fractures. Furthermore, subgroup analysis demonstrated that less-angulated fractures had a higher refracture rate than the more-angulated ones. We feel this somewhat paradoxical finding is analogous to fractures of the forearm shaft, for which greenstick fractures refracture at a higher rate than complete forearm shaft fractures due to less-exuberant callus formation. LEVEL OF EVIDENCE: Prognostic level III. See instructions for authors for a complete description of levels of evidence.