Bilirubin decreases NOS2 expression via inhibition of NAD(P)H oxidase: implications for protection against endotoxic shock in rats.

We investigated a possible beneficial role for bilirubin, one of the products of heme degradation by the cytoprotective enzyme heme oxygenase-1 in counteracting Escherichia coli endotoxin-mediated toxicity. Homozygous jaundice Gunn rats, which display high plasma bilirubin levels due to deficiency of glucuronyl transferase activity, and Sprague-Dawley rats subjected to sustained exogenous bilirubin administration were more resistant to endotoxin (LPS)-induced hypotension and death compared with nonhyperbilirubinemic rats. LPS-stimulated production of nitric oxide (NO) was significantly decreased in hyperbilirubinemic rats compared with normal animals; this effect was associated with reduction of inducible NO synthase (NOS2) expression in renal, myocardial, and aortic tissues. Furthermore, NOS2 protein expression and activity were reduced in murine macrophages stimulated with LPS and preincubated with bilirubin at concentrations similar to that found in the serum of hyperbilirubinemic animals. This effect was secondary to inhibition of NAD(P)H oxidase since 1) inhibition of NAD(P)H oxidase attenuated NOS2 induction by LPS, 2) bilirubin decreased NAD(P)H oxidase activity in vivo and in vitro, and 3) down-regulation of NOS2 by bilirubin was reversed by addition of NAD(P)H. These findings indicate that bilirubin can act as an effective agent to reduce mortality and counteract hypotension elicited by endotoxin through mechanisms involving a decreased NOS2 induction secondary to inhibition of NAD(P)H oxidase

Cardiorespiratory evaluation in pre and post operative moments of laparoscopic cholecystectomy

PURPOSE: To analyze the changes in both respiratory function and cardiopulmonary exercise tests results in patients subjected to laparoscopic cholecystectomy. METHODS: Fifty patients were evaluated (76% women) and the average age was 47.8±14.2 years. All individuals underwent the measurement of spirometry, manovacuometry, 6-minute walk test (6MWT) and stair-climbing test (SCT). All tests were performed at the first (PO1), fifth (PO5) and thirtieth (PO30) postoperative days. RESULTS: BMI average was 28.8±4.8 kg/m2. Sample comprised 68% non-smokers, 20% current smokers, and 12% former smokers. There was no incidence of postoperative complication whatsoever. There was a significant decrease in spirometric values at PO1, but values were similar to the ones of PRE at PO30. Manovacuometry showed alterations at PO1 displaying values that were similar to the ones of PRE at PO30. 6MWT was significantly shorter at until PO5, but at PO30 values were similar to ones of PRE. As for SCT, values were significantly compromised at PO5 and PO30 since they were similar to the ones of PRE. CONCLUSION: Patients submitted to laparoscopic cholecystectomy present a decrease in cardiorespiratory function on the first postoperative moments but there is a rapid return to preoperative conditions.Sao Paulo State University Botucatu School of MedicineUNESP Botucatu School of MedicineSao Paulo State University Botucatu School of MedicineUNESP Botucatu School of Medicin

European Red List of Marine Fishes

The European Red List is a review of the conservation status of European species according to IUCN regional Red Listing guidelines. It identifies those species that are threatened with extinction at the regional level, so that appropriate conservation action can be taken to improve their status. This Red List publication summarises results for all described native European marine fishes.Postprin