Indirect evidence for stimulation of nitric oxide release by tumour necrosis factor-α in human veins in vivo

Objectives: The detrimental haemodynamic changes observed in septicaemia are generalised vasodilation, arterial hypotension, and hyporesponsiveness to vasopressor compounds, all of which could be explained by the release of an endogenous vasodilator. Experimental and clinical evidence suggests that tumour necrosis factor-α (TNF) induces the expression of vascular nitric oxide (NO) synthase within hours and that NO released from smooth muscle cells could be involved in the pathogenesis of septic shock. The aim of this study was to investigate the role of NO in the vascular effects of TNF. Methods: Using the dorsal hand vein compliance technique, the effect of the NO synthase inhibitor L-NG-monomethyl-arginine (L-NMMA) on α1-adrenergic responsiveness (phenylephrine 1.25-8000 ng/min) was studied after prolonged local venous infusion of TNF (8.7 μg in 5 h) in 9 volunteers and in 6 volunteers without previous cytokine exposure. Results: Mean (±s.e.) maximum phenylephrine constriction (Emax) was 73 ± 6% and log dose-rates exerting 50% of Emax (log ED50) were 3.2 ± 0.09 (geometric mean: 1535 ng/min). Local co-administration of L-NMMA at a dose sufficiently high to block NO formation (3.4 μmol/min) increased venous sensitivity to phenylephrine threefold (log ED50 2.8 ± 0.1, P < 0.015; geometric mean: 574 ng/min) whereas Emax was similar (73 ± 5%). In the controls the phenylephrine dose-response relationship remained unaffected by simultaneous administration of L-NMMA. Conclusions: As no basal release of NO occurs in hand veins without previous exposure to TNF these results provide direct evidence for induction of NO formation in the human vasculature and consecutive resistance to α-adrenergic venoconstriction. NO might, therefore, be a key mediator of haemodynamic impairment in humans under conditions with known elevations of circulating TNF, such as a septic shoc

Constraining the expansion rate of the Universe using low-redshift ellipticals as cosmic chronometers

We present a new methodology to determine the expansion history of the Universe analyzing the spectral properties of early type galaxies (ETG). We found that for these galaxies the 4000\AA break is a spectral feature that correlates with the relative ages of ETGs. In this paper we describe the method, explore its robustness using theoretical synthetic stellar population models, and apply it using a SDSS sample of $\sim$14 000 ETGs. Our motivation to look for a new technique has been to minimise the dependence of the cosmic chronometer method on systematic errors. In particular, as a test of our method, we derive the value of the Hubble constant $H_0 = 72.6 \pm 2.8$ (stat) $\pm2.3$ (syst) (68% confidence), which is not only fully compatible with the value derived from the Hubble key project, but also with a comparable error budget. Using the SDSS, we also derive, assuming w=constant, a value for the dark energy equation of state parameter $w = -1 \pm 0.2$ (stat) $\pm0.3$ (syst). Given the fact that the SDSS ETG sample only reaches $z \sim 0.3$, this result shows the potential of the method. In future papers we will present results using the high-redshift universe, to yield a determination of H(z) up to $z \sim 1$.Comment: 25 pages, 17 figures, JCAP accepte

Acute Cough Due to Acute Bronchitis in Immunocompetent Adult Outpatients: CHEST Expert Panel Report

Background: Evidence for the diagnosis and management of cough due to acute bronchitis in immunocompetent adult outpatients was reviewed as an update to the 2006 “Chronic Cough Due to Acute Bronchitis: American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines.” Methods: Acute bronchitis was defined as an acute lower respiratory tract infection manifested predominantly by cough with or without sputum production, lasting no more than 3 weeks with no clinical or any recent radiographic evidence to suggest an alternative explanation. Two clinical population, intervention, comparison, outcome questions were addressed by systematic review in July 2017: (1) the role of investigations beyond the clinical assessment of patients presenting with suspected acute bronchitis, and (2) the efficacy and safety of prescribing medication for cough in acute bronchitis. An updated search was undertaken in May 2018. Results: No eligible studies relevant to the first question were identified. For the second question, only one relevant study met eligibility criteria. This study found no difference in number of days with cough between patients treated with an antibiotic or an oral nonsteroidal antiinflammatory agent compared with placebo. Clinical suggestions and research recommendations were made based on the consensus opinion of the CHEST Expert Cough Panel. Conclusions: The panelists suggested that no routine investigations be ordered and no routine medications be prescribed in immunocompetent adult outpatients first presenting with cough due to suspected acute bronchitis, until such investigations and treatments have been shown to be safe and effective at making cough less severe or resolve sooner. If the cough due to suspected acute bronchitis persists or worsens, a reassessment and consideration of targeted investigations should be considered.</p

COMET P/2016 WM48 (Lemmon)

Available from the Minor Planet Center

Observations and Orbits of Comets

Minor Planet Electronic Circ., No. 2017-N58 (2017).Available from the Minor Planet Center