18 research outputs found

    ATLAS detector and physics performance: Technical Design Report, 1

    Get PDF

    A new role of AMP-activated protein kinase in regulating proliferation of mesenchymal stem cells

    No full text
    Purpose: Natriuretic peptides (NPs) administered during early reperfusion are protective in models of myocardial infarction. A previous study examining the endogenous components of B-type natriuretic peptide (BNP) protection of reperfused myocardium, implicated both sarcolemmal (s) KATP and mitochondrial (m) KATP channels. The indirect evidence characterising the relationship between BNP signalling and KATP was obtained using sulphonylurea receptor inhibitors in a rat isolated heart model of ischaemia-reperfusion injury. Here we seek to further examine the relationship between NPs and sKATP openings using single channel electrophysiology. Given our previous findings and the overarching consensus that cardioprotective autacoids open KATP channels, it was hypothesised that NPs elicit sKATP opening. Methods: Cardiomyocyte isolation. Left ventricular cardiomyocytes were isolated from male Sprague-Dawley rat hearts subjected to enzymatic digestion with Liberase Blendzyme DL. Cardiomyocytes were cultured overnight in Medium 199, prior to patch clamp. Single channel patch clamp. Single channel recordings at room temperature (22°C) were made from cell attached patches bathed in Na+ Locke, pH 7.2. The recording pipette contained high KCl (140 mM), pH 7.2. Recordings (45 sec) were made over a range of patch potentials (0, -30, -60, -90, -120 mV), in the absence (control) and in the presence of bath applied BNP (10, 100 nM and 1 µM), pinacidil (200 µM) or pinacidil vehicle (DMSO, 0.25%). Recordings were also made with BNP and pinacidil applied concomitantly. Data are mean ± S.E.M. Results: The current voltage relationship of sKATP under control conditions was linear at –ve patch potentials, the mean conductance being 52.9 ± 1.8 pS (n = 18 hearts, n = 35 cells). Pinacidil caused a four fold increase in sKATP open probability compared to control. Mean channel conductance in the presence of pinacidil was 59.9 ± 1.9 pS (n = 16 hearts, n = 44 cells). Interestingly BNP at all concentrations had negligible effects on sKATP open probability and unitary conductance. However, BNP at all concentrations and patch potentials inhibited pinacidil induced sKATP openings, restoring channel open probability to baseline. Conclusion: These data illustrate the inhibitory effect of NP signalling on sKATP function in the cardiomyocyte under normoxia. They are concordant with the inhibitory effect of atrial NP on KATP in the pancreatic beta cell, but are in apparent conflict with the current cardioprotection paradigm. However, differential effects on sKATP and mKATP and the effects of hypoxia-reoxygenation require further exploration

    Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial

    No full text
    Background Rosiglitazone is a thiazolidinedione that reduces insulin resistance and might preserve insulin secretion. The aim of this study was to assess prospectively the drugs ability to prevent type 2 diabetes in individuals at high risk of developing the condition

    ATLAS

    No full text

    ATLAS

    No full text

    Predictors of embolism and death in left-sided infective endocarditis: the European Society of Cardiology EURObservational Research Programme European Infective Endocarditis registry

    No full text
    International audienceBackground and Aims Even though vegetation size in infective endocarditis (IE) has been associated with embolic events (EEs) and mortality risk, it is unclear whether vegetation size associated with these potential outcomes is different in left-sided IE (LSIE). This study aimed to seek assessing the vegetation cut-off size as predictor of EE or 30-day mortality for LSIE and to determine risk predictors of these outcomes. Methods The European Society of Cardiology EURObservational Research Programme European Infective Endocarditis is a prospective, multicentre registry including patients with definite or possible IE throughout 2016–18. Cox multivariable logistic regression analysis was performed to assess variables associated with EE or 30-day mortality. Results There were 2171 patients with LSIE (women 31.5%). Among these affected patients, 459 (21.1%) had a new EE or died in 30 days. The cut-off value of vegetation size for predicting EEs or 30-day mortality was >10 mm [hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.13–1.69, P = .0015]. Other adjusted predictors of risk of EE or death were as follows: EE on admission (HR 1.89, 95% CI 1.54–2.33, P < .0001), history of heart failure (HR 1.53, 95% CI 1.21–1.93, P = .0004), creatinine >2 mg/dL (HR 1.59, 95% CI 1.25–2.03, P = .0002), Staphylococcus aureus (HR 1.36, 95% CI 1.08–1.70, P = .008), congestive heart failure (HR 1.40, 95% CI 1.12–1.75, P = .003), presence of haemorrhagic stroke (HR 4.57, 95% CI 3.08–6.79, P < .0001), alcohol abuse (HR 1.45, 95% CI 1.04–2.03, P = .03), presence of cardiogenic shock (HR 2.07, 95% CI 1.29–3.34, P = .003), and not performing left surgery (HR 1.30 95% CI 1.05–1.61, P = .016) (C-statistic = .68). Conclusions Prognosis after LSIE is determined by multiple factors, including vegetation size

    ATLAS detector and physics performance: Technical Design Report, 2

    No full text

    ATLAS calorimeter performance

    No full text
    corecore