Effect of propofol and etomidate on normoxic and chronically hypoxic pulmonary artery

BACKGROUND: Chronic alveolar hypoxia results in sustained arterial constriction, and increase in pulmonary vascular resistance leading to pulmonary artery hypertension (PAHT). The aim of this study was to investigate the effect of propofol and etomidate on pulmonary artery (PA) reactivity in chronically hypoxic (CH) rats, a model of pulmonary arterial hypertension (PAHT), in normoxic animals, and human PA. METHODS: CH rats were maintained 14 days at 380 mmHg pressure in a hypobaric chamber. Human tissue was retrieved from histological lung pieces from patients undergoing resection for carcinoma. Cumulative concentrations of anaesthetics were tested on isolated vascular rings precontracted with phenylephrine (PHE) or 100 mM KCl. Statistical comparisons were done by ANOVA, followed, when needed, by Student t tests with Bonferroni correction as post-hoc tests. RESULTS: In normoxic rat PA, maximal relaxation (R(max)) induced by etomidate and propofol was 101.3 ± 0.8% and 94.0 ± 2.3%, respectively, in KCl-precontracted rings, and 63.3 ± 9.7% and 46.1 ± 9.1%, respectively, in PHE-precontracted rings (n = 7). In KCl-precontracted human PA, R(max )was 84.7 ± 8.6 % and 66.5 ± 11.8%, for etomidate and propofol, respectively, and 154.2 ± 22.4 % and 51.6 ± 15.1 %, respectively, in PHE-precontracted human PA (n = 7). In CH rat PA, the relaxant effect of both anaesthetics was increased in PHE-precontracted and, for etomidate only, in KCl-precontracted PA. In aorta, CH induced no change in the relaxant effect of anaesthetics. CONCLUSION: Propofol and etomidate have relaxant properties in PA from human and normoxic rat. The relaxant effect is specifically accentuated in PA from CH rat, mainly via an effect on the pharmacomechanical coupling. Etomidate appears to be more efficient than propofol at identical concentration, but, taking into account clinical concentrations, etomidate is less potent than propofol, which effect was in the range of clinical doses. Although these findings provide experimental support for the preferential use of etomidate for haemodynamic stability in patients suffering from PAHT, the clinical relevance of the observations requires further investigation

Electronic Cigarettes Regulation in the UK: A Case Study in Evidence Informed Policy Making

This chapter argues that policy debates on electronic cigarettes (e-cigarettes) are structured around competing evidence claims between proponents and sceptics, who remain bitterly divided on the issue. The confusion and intransigence which has emerged between these camps is, in part, the result of an insufficiently nuanced understanding of the value-centred and highly political nature of the policy process, and the highly circumscribed (yet nonetheless important) role which evidence can play within this. Key policy actors, often from biomedical backgrounds, or trained in the natural sciences, have been unable to recognise the limits of evidence to resolve protracted policy controversies such as that surrounding e-cigarettes. The chapter highlights the value of insights, derived from interpretative social science, about the multiple potential framings of an issue and the need for reflexivity on the part of policy actors to move beyond the current impasse

The FixK₂Protein Is Involved in Regulation of Symbiotic Hydrogenase Expression in<i>Bradyrhizobium japonicum</i>

ABSTRACTThe roles of the nitrogen fixation regulatory proteins NifA, FixK1, and FixK2in the symbiotic regulation of hydrogenase structural gene expression inBradyrhizobium japonicumhave been investigated. Bacteroids from FixJ and FixK2mutants have little or no hydrogenase activity, and extracts from these mutant bacteroids contain no hydrogenase protein. Bacteroids from a FixK1mutant exhibit wild-type levels of hydrogenase activity. In β-galactosidase transcriptional assays with NifA and FixK2expression plasmids, the FixK2protein induces transcription from thehuppromoter to levels similar to those induced by HoxA, the transcriptional activator of free-living hydrogenase expression. The NifA protein does not activate transcription at the hydrogenase promoter. Therefore, FixK2is involved in the transcriptional activation of symbiotic hydrogenase expression. By using β-galactosidase transcriptional fusion constructs containing successive truncations of thehuppromoter, the region of thehuppromoter required for regulation by FixK2was determined to be between 29 and 44 bp upstream of the transcription start site.</jats:p

The FixK2 protein is involved in regulation of symbiotic hydrogenase expression in Bradyrhizobium japonicum

The roles of the nitrogen fixation regulatory proteins NifA, FixK1, and FixK2 in the symbiotic regulation of hydrogenase structural gene expression in Bradyrhizobium japonicum have been investigated. Bacteroids from FixJ and FixK2 mutants have little or no hydrogenase activity, and extracts from these mutant bacteroids contain no hydrogenase protein. Bacteroids from a FixK1 mutant exhibit wild-type levels of hydrogenase activity. In beta-galactosidase transcriptional assays with NifA and FixK2 expression plasmids, the FixK2 protein induces transcription from the hup promoter to levels similar to those induced by HoxA, the transcriptional activator of free-living hydrogenase expression. The NifA protein does not activate transcription at the hydrogenase promoter. Therefore, FixK2 is involved in the transcriptional activation of symbiotic hydrogenase expression. By using beta-galactosidase transcriptional fusion constructs containing successive truncations of the hup promoter, the region of the hup promoter required for regulation by FixK2 was determined to be between 29 and 44 bp upstream of the transcription start site.https://ezproxy.stevenson.edu/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=mnh&AN=9620982&site=eds-live&scope=sit