Chronic intermittent hypoxia increases rat sternohyoid muscle NADPH oxidase expression with attendant modest oxidative stress

Chronic intermittent hypoxia (CIH) causes upper airway muscle dysfunction. We hypothesized that the superoxide generating NADPH oxidase (NOX) is upregulated in CIH-exposed muscle causing oxidative stress. Adult male Wistar rats were exposed to intermittent hypoxia (5% O2 at the nadir for 90 s followed by 210 s of normoxia), for 8 h per day for 14 days. The effect of CIH exposure on the expression of NOX subunits, total myosin and 4-hydroxynonenal (4-HNE) protein adducts in sternohyoid muscle was determined by western blotting and densitometry. Sternohyoid protein free thiol and carbonyl group contents were determined by 1D electrophoresis using specific fluorophore probes. Aconitase and glutathione reductase activities were measured as indices of oxidative stress. HIF-1α content and key oxidative and glycolytic enzyme activities were determined. Contractile properties of sternohyoid muscle were determined ex vivo in the absence and presence of apocynin (putative NOX inhibitor). We observed an increase in NOX 2 and p47 phox expression in CIH-exposed sternohyoid muscle with decreased aconitase and glutathione reductase activities. There was no evidence, however, of increased lipid peroxidation or protein oxidation in CIH-exposed muscle. CIH exposure did not affect sternohyoid HIF-1α content or aldolase, lactate dehydrogenase, or glyceraldehyde-3-phosphate dehydrogenase activities. Citrate synthase activity was also unaffected by CIH exposure. Apocynin significantly increased sternohyoid force and power. We conclude that CIH exposure upregulates NOX expression in rat sternohyoid muscle with concomitant modest oxidative stress but it does not result in a HIF-1α-dependent increase in glycolytic enzyme activity. Constitutive NOX activity decreases sternohyoid force and power. Our results implicate NOX-dependent reactive oxygen species in CIH-induced upper airway muscle dysfunction which likely relates to redox modulation of key regulatory proteins in excitation-contraction coupling

Energy Trends: September 2020

Energy Trends and Energy Prices are produced by the Department for Business, Energy and Industrial Strategy (BEIS) on a quarterly basis. Both periodicals are published concurrently in June, September, December and March. The September editions cover the second quarter of the current year

Sensorimotor control of breathing in the mdx mouse model of Duchenne muscular dystrophy

Patients with Duchenne muscular dystrophy (DMD) hypoventilate with consequential arterial blood gas derangement relevant to disease progression. Whereas deficits in DMD diaphragm are recognized, there is a paucity of knowledge in respect of the neural control of breathing in dystrophinopathies. We sought to perform an analysis of respiratory control in a model of DMD, the mdx mouse. In 8-week-old male wild-type and mdx mice, ventilation and metabolism, carotid body afferent activity, diaphragm muscle force-generating capacity, and muscle fibre size, distribution and centronucleation were determined. Diaphragm EMG activity and responsiveness to chemostimulation was determined. During normoxia, mdx mice hypo-ventilated, owing to a reduction in tidal volume. Basal CO2 production was not different between wild-type and mdx mice. Carotid sinus nerve responses to hyperoxia were blunted in mdx, suggesting hypoactivity. However, carotid body, ventilatory and metabolic responses to hypoxia were equivalent in wild-type and mdx mice. Diaphragm force was severely depressed in mdx mice, with evidence of fibre remodelling and damage. Diaphragm EMG responses to chemoactivation were enhanced in mdx mice. We conclude that there is evidence of chronic hypoventilation in young mdx mice. Diaphragm dysfunction confers mechanical deficiency in mdx resulting in impaired capacity to generate normal tidal volume at rest and decreased absolute ventilation during chemoactivation. Enhanced mdx diaphragm EMG responsiveness suggests compensatory neuroplasticity facilitating respiratory motor output, which may extend to accessory muscles of breathing. Our results may have relevance to emerging treatments for human DMD aiming to preserve ventilatory capacity

Long-term exposure to air pollution and hospital admissions for ischemic stroke. A register-based case-control study using modelled NOx as exposure proxy

Background: Long-term exposure to air pollution is a hypothesized risk factor for ischemic stroke. In a large case-control study with a complete study base, we investigated whether hospital admissions for ischemic stroke were associated with residential concentrations of outdoor NOx, as a proxy for exposure to air pollution, in the region of Scania, Southern Sweden. Methods: We used a two-phase case-control study design, including as first-phase controls all individuals born between 1923 and 1965 and residing in Scania in 2002 (N=556 912). We defined first-phase cases as first-time ischemic stroke patients residing in Scania and registered in the Swedish stroke register between 2001 and 2005 (N=4 904) and second-phase cases as cases for whom we had information on smoking status, diabetes, and medication for hypertension (N=4 375). For the controls, information on these covariables was collected from a public health survey, resulting in 4 716 second-phase controls. With a geographical information system and an emission database, individual residential outdoor annual mean NOx concentration was modelled. The data were analyzed with logistic regression. Results: We found no evident association between NOx and ischemic stroke. For example, the odds ratio for ischemic stroke associated with the NOx category 20-30 mu g/m(3) compared to the reference category of <10 mu g/m(3) was 0.95 (95% CI 0.86-1.06). Conclusion: In this study area, with generally low levels of air pollution, using a complete study base, high-quality ascertainment of cases, and individually modelled exposure, we did not observe any clear association between NOx and ischemic stroke hospital admissions

Access Rate to the Emergency Department for Venous Thromboembolism in Relationship with Coarse and Fine Particulate Matter Air Pollution

Particulate matter (PM) air pollution has been associated with cardiovascular and respiratory disease. Recent studies have proposed also a link with venous thromboembolism (VTE) risk. This study was aimed to evaluate the possible influence of air pollution-related changes on the daily flux of patients referring to the Emergency Department (ED) for VTE, dissecting the different effects of coarse and fine PM. From July 1st, 2007, to June 30th, 2009, data about ED accesses for VTE and about daily concentrations of PM air pollution in Verona district (Italy) were collected. Coarse PM (PM10-2.5) was calculated by subtracting the finest PM2.5 from the whole PM10. During the index period a total of 302 accesses for VTE were observed (135 males and 167 females; mean age 68.3±16.7 years). In multiple regression models adjusted for other atmospheric parameters PM10-2.5, but not PM2.5, concentrations were positively correlated with VTE (beta-coefficient = 0.237; P = 0.020). During the days with high levels of PM10-2.5 (≥75th percentile) there was an increased risk of ED accesses for VTE (OR 1.69 with 95%CI 1.13–2.53). By analysing days of exposure using distributed lag non-linear models, the increase of VTE risk was limited to PM10-2.5 peaks in the short-term period. Consistently with these results, in another cohort of subjects without active thrombosis (n = 102) an inverse correlation between PM10-2.5 and prothrombin time was found (R = −0.247; P = 0.012). Our results suggest that short-time exposure to high concentrations of PM10-2.5 may favour an increased rate of ED accesses for VTE through the induction of a prothrombotic state

A class-wide phylogenetic assessment of Dothideomycetes

We present a comprehensive phylogeny derived from 5 genes, nucSSU, nucLSU rDNA, TEF1, RPB1 and RPB2, for 356 isolates and 41 families (six newly described in this volume) in Dothideomycetes. All currently accepted orders in the class are represented for the first time in addition to numerous previously unplaced lineages. Subclass Pleosporomycetidae is expanded to include the aquatic order Jahnulales. An ancestral reconstruction of basic nutritional modes supports numerous transitions from saprobic life histories to plant associated and lichenised modes and a transition from terrestrial to aquatic habitats are confirmed. Finally, a genomic comparison of 6 dothideomycete genomes with other fungi finds a high level of unique protein associated with the class, supporting its delineation as a separate taxon

Cumulative exposure to air pollution and long term outcomes after first acute myocardial infarction: A population-based cohort study. Objectives and methodology

<p>Abstract</p> <p>Background</p> <p>Cardiovascular disease is a leading cause of morbidity and mortality worldwide and epidemiological studies have consistently shown an increased risk for cardiovascular events in relation to exposure to air pollution. The Israel Study of First Acute Myocardial Infarction was designed to longitudinally assess clinical outcomes, psychosocial adjustment and quality of life in patients hospitalized with myocardial infarction. The current study, by introducing retrospective air pollution data, will examine the association between exposure to air pollution and outcome in myocardial infarction survivors. This report will describe the methods implemented and measures employed. The study specifically aims to examine the relationship between residential exposure to air pollution and long-term risk of recurrent coronary event, heart failure, stroke, cardiac and all-cause death in a geographically defined cohort of patients with myocardial infarction.</p> <p>Methods/Design</p> <p>All 1521 patients aged ≤65 years, admitted with first myocardial infarction between February 1992 and February 1993 to the 8 hospitals serving the population of central Israel, were followed for a median of 13 years. Data were collected on sociodemographic, clinical and environmental factors. Data from air quality monitoring stations will be incorporated retrospectively. Daily measures of air pollution will be summarised, allowing detailed maps to be developed in order to reflect chronic exposure for each participant.</p> <p>Discussion</p> <p>This study addresses some of the gaps in understanding of the prognostic importance of air pollution exposure after myocardial infarction, by allowing a sufficient follow-up period, using a well-defined community cohort, adequately controlling for multiple and multilevel confounding factors and providing extensive data on various outcomes.</p