Chronic ethanol intake modulates vascular levels of endothelin-1 receptor and enhances the pressor response to endothelin-1 in anaesthetized rats.

BACKGROUND AND PURPOSE: The contribution of endothelin-1 (ET-1) to vascular hyper-reactivity associated with chronic ethanol intake, a major risk factor in several cardiovascular diseases, remains to be investigated. EXPERIMENTAL APPROACH: The biphasic haemodynamic responses to ET-1 (0.01-0.1 nmol kg(-1), i.v.) or to the selective ETB agonist, IRL1620 (0.001-1.0 nmol kg(-1), i.v.), with or without ETA or ETB antagonists (BQ123 (c(DTrp-Dasp-Pro-Dval-Leu)) at 1 and 2.5 mg kg(-1) and BQ788 (N-cis-2,6-dimethyl-piperidinocarbonyl-L-gamma-methylleucyl1-D-1methoxycarbonyltryptophanyl-D-norleucine) at 0.25 mg kg(-1), respectively) were tested in anaesthetized rats, after 2 weeks' chronic ethanol treatment. Hepatic parameters and ET receptor protein levels were also determined. KEY RESULTS: The initial hypotensive responses to ET-1 or IRL1620 were unaffected by chronic ethanol intake, whereas the subsequent pressor effects induced by ET-1, but not by IRL1620, were potentiated. BQ123 at 2.5 but not 1 mg kg(-1) reduced the pressor responses to ET-1 in ethanol-treated rats. Conversely, BQ788 (0.25 mg kg(-1)) potentiated ET-1-induced increases in mean arterial blood pressure in control as well as in ethanol-treated rats. Interestingly, in the latter group, increases in heart rate, induced by ET-1 at a dose of 0.025 mg kg(-1) were enhanced following ETB receptor blockade. Finally, we observed higher levels of ETA receptor in the heart and mesenteric artery and a reduction of ETB receptor protein levels in the aorta and kidney from rats chronically treated with ethanol. CONCLUSIONS AND IMPLICATIONS: Increased vascular reactivity to ET-1 and altered protein levels of ETA and ETB receptors could play a role in the pathogenesis of cardiovascular complications associated with chronic ethanol consumption.

Characterization of the non-adrenergic/non-cholinergic response to perivascular nerve stimulation in the double-perfused mesenteric bed of the mouse.

BACKGROUND AND PURPOSE: Calcitonin gene-related peptide (CGRP), a capsaicin-sensitive neuromodulator of splanchnic vascular tone in several animal species, remains poorly investigated in mouse models. We therefore assessed whether endogenous CGRP is a non-adrenergic/non-cholinergic (NANC) neuromodulator in the mesenteric vascular bed of the mouse. EXPERIMENTAL APPROACH: Arterial and venous changes in perfusion pressure in response to perivascular nerve stimulation (PNS) were monitored in the mouse mesenteric bed under basal conditions or precontracted with KCl (artery) or U46619 (vein) in circuits pretreated with guanethidine, atropine, indomethacin and prazosin. Arterial responses to NANC were also characterized with a CGRP1 antagonist, halphaCGRP8-37. Finally, the PNS-induced release of arterial CGRP was measured by enzyme immunoassay. KEY RESULTS: HalphaCGRP8-37 enhanced PNS-induced arterial increases in perfusion pressure under basal tone. PNS-induced stimulation of NANC triggered an halphaCGRP8-37 or capsaicin- sensitive reduction in perfusion pressure of the pre-contracted arterial bed only. Chemical removal of the endothelium inhibited PNS- and halphaCGRP- induced reduction in perfusion pressure in the arterial mesenteric bed. Responses to NANC nerves were reduced by guanylate and adenylate cyclase inhibitors (1H-[1,2,4]oxadiazole[4,3-a] quinoxalin-1-one (ODQ)) and [9-(tetrahydro-2-furanyl)-9H-purin-6-amine] (SQ 22,536), respectively. A neuronal NOS inhibitor (7-nitroindazole; 7-NI) also enhanced the response to NANC in vessels from wild-type, eNOS KO but not iNOS KO mice. Finally, PNS enhanced the release of immunoreactive CGRP from the perfused arterial mesenteric bed. CONCLUSIONS AND IMPLICATIONS: Our study demonstrates a role for CGRP in the NANC-dependent reduction in perfusion pressure of the arterial but not venous mesenteric bed of the mouse.

[Infection after total hip replacement by Staphylococcus caprae. Case report and review of the literature]. / Infection sur prothèse totale de hanche à Staphylococcus caprae. Cas clinique et revue de la littérature.

We report a case of Staphylococcus caprae bone and joint infection, that illustrate difficulties to diagnose coagulase-negative staphylococci (CNS) orthopedic surgery infections, specially following implantation of prostheses. Four of 5 strains successivelly isolated from deep and/or peri-operative specimens during late infection after total hip replacement (THR) have been identified, using commercial systems and conventionnal tests, as S. caprae. Identity of biochemical profile, antibiotype and pulsotype of the 4 isolates confirmed the pathogenicity of this animal CNS, rarely described as a human pathogen. Analysis of the 24 S. caprae human cases previously described evidence a relation ship between this bacteria and bone and joint infections, with implantation of prosthetic material as supplementary risk factor. S. caprae, whose major identification criteria are resumed, may have previously been misidentified as some similar CNS; this bacteria is probably part of our normal flora but may be recognized as an opportunistic pathogen, responsible for both nosocomial and community acquired infections.

Computer-assisted instruction using electronic mail.

A major challenge to nursing staff development departments is how to reach individual staff members with new information in a limited period of time. Attendance at classroom instruction is not always feasible. The use of electronic mail to provide instruction to learners can be an effective teaching strategy. Advantages are immediate accessibility to the learner and the opportunity to tailor the program to meet specific hospital requirements or individual learning needs. Tips on how to develop and send instructional modules through electronic mail are included in this article.