Aims: Statins have been identified as a potentially interesting treatment against sepsis. Here, we study the vascular reactivity of aortae from rats treated with lipopolysaccharide (LPS), 4 mg · kg–1, following chronic administration of simvastatin (SV) 10 mg · kg–1. Methods: The rats were treated with either vehicle or SV for 4 weeks before administration of LPS. After 18 h, the systolic blood pressure (SBP) was measured using a tail cuff and vascular and endothelial responses of aortic rings to several agonists were studied in an organ bath. Results: LPS injection decreased the SBP by 38 mm Hg and vascular response to phenylephrine (Phe) by 60%. Plasma nitrates and nitrites (NOx) were 3-fold higher after LPS. This attenuated response to Phe was prevented by incubation with either the inducible-nitric-oxide-synthase (iNOS)-selective inhibitor 1400W or the endothelial nitric oxide synthase (eNOS)/iNOS nonselective blocker L-NAME. The presence of endothelium did not alter these findings. Administering LPS to SV-treated rats also decreased the SBP and increased the NOx concentration. The impaired response to Phe was restored by blocking NO synthesis in endothelium-denuded but not in intact aortic rings. The response to acetylcholine demonstrated an enhanced reduction in arteries from the SV + LPS group compared with the LPS group. The inhibition of iNOS prevented acetylcholine-induced relaxation in rings from LPS-treated rats but not in those from the SV + LPS group. Conclusion: These results suggest that statins may reduce iNOS-mediated NO production in endothelial but not in vascular smooth-muscle cells.
Electronic training devices: discussion on the pros and cons of their use in dogs as a basis for the position statement of the European Society of Veterinary Clinical Ethology (ESVCE). Article type: Review Article.
Classification of patients according to their risk of poor outcomes in Clostridioides difficile infection (CDI) would enable implementation of costly new treatment options in a subset of patients at higher risk of poor outcome. In a previous study, we found that low toxin B amplification cycle thresholds (C t ) were independently associated with poor outcome CDI. Our objective was to perform a multicentre external validation of a PCR-toxin B C t as a marker of poor outcome CDI. We carried out a multicentre study (14 hospitals) in which the characteristics and outcome of patients with CDI were evaluated. A subanalysis of the results of the amplification curve of real-time PCR gene toxin B (XpertTM C. difficile) was performed. A total of 223 patients were included. The median age was 73.0 years, 50.2% were female, and the median Charlson index was 3.0. The comparison of poor outcome and nonepoor outcome CDI episodes revealed, respectively, the following results: median age (years), 77.0 vs 72.0 (p ¼ 0.009); patients from nursing homes, 24.4% vs 10.8% (p ¼ 0.039); median leukocytes (cells/ml), 10,740.0 vs 8795.0 (p ¼ 0.026); and median PCR-toxin B C t , 23.3 vs 25.4 (p ¼ 0.004). Multivariate analysis showed that a PCR-toxin B C t cutoff <23.5 was significantly and independently associated with poor outcome CDI (p ¼ 0.002; OR, 3.371; 95%CI, 1.565e7.264). This variable correctly classified 68.5% of patients. The use of this microbiological marker could facilitate early selection of patients who are at higher risk of poor outcome and are more likely to benefit from newer and more costly therapeutic options.
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