Effect of terbutaline on hyperpnoea-induced bronchoconstriction and urinary club cell protein 16 in athletes

This article is made available through the Brunel Open Access Publishing Fund and is distributed by the Creative Commons CC-BY 3.0 license, under which all are free to reuse or distribute the article under the condition that this original publication must be cited.Repeated injury of the airway epithelium caused by hyperpnoea of poorly conditioned air has been proposed as a key factor in the pathogenesis of exercise-induced bronchoconstriction (EIB) in athletes. In animals, the short-acting β2-agonist terbutaline has been shown to reduce dry airflow-induced bronchoconstriction and the associated shedding of airway epithelial cells. Our aim was to test the efficacy of inhaled terbutaline in attenuating hyperpnoea-induced bronchoconstriction and airway epithelial injury in athletes. Twenty-seven athletes with EIB participated in a randomized, double-blind, placebo-controlled, crossover study. Athletes completed an 8-min eucapnic voluntary hyperpnoea (EVH) test with dry air on two separate days 15 min after inhaling 0.5 mg terbutaline or a matching placebo. Forced expiratory volume in 1 s (FEV1) and urinary concentration of the club cell (Clara cell) protein 16 (CC16, a marker of airway epithelial perturbation) were measured before and up to 60 min after EVH. The maximum fall in FEV1 of 17 ± 8% (SD) on placebo was reduced to 8 ± 5% following terbutaline (P < 0.001). Terbutaline gave bronchoprotection (i.e., post-EVH FEV1 fall <10%) to 22 (81%) athletes. EVH caused an increase in urinary excretion of CC16 in both conditions (P < 0.001), and terbutaline significantly reduced this rise (pre- to postchallenge CC16 increase 416 ± 495 pg/μmol creatinine after placebo vs. 315 ± 523 pg/μmol creatinine after terbutaline, P = 0.016). These results suggest that the inhalation of a single therapeutic dose of terbutaline offers significant protection against hyperpnoea-induced bronchoconstriction and attenuates acute airway epithelial perturbation in athletes.World Anti Doping Agenc

Reaction to halothane anaesthesia among heterozygotes at the halothane locus in British Landrace pigs

International audienc

Precision medicine for the discovery of treatable mechanisms in severe asthma

Although the complex disease of asthma has been defined as being heterogeneous, the extent of its endophenotypes remain unclear. The pharmacological approach to initiating treatment has, until recently, been based on disease control and severity. The introduction of antibody therapies targeting the Type2 inflammation pathway for patients with severe asthma has resulted in the recognition of an allergic and an eosinophilic phenotype, which are not mutually exclusive. Concomitantly, molecular phenotyping based on a transcriptomic analysis of bronchial epithelial and sputum cells has identified a Type-2-high inflammation cluster characterised by eosinophilia and recurrent exacerbations, as well as Type-2-low clusters linked with IL-6 trans-signalling, interferon pathways, inflammasome activation and mitochondrial oxidative phosphorylation pathways. Systems biology approaches are establishing the links between these pathways or mechanisms, and clinical and physiologic features. Validation of these pathways contributes to defining endotypes and treatable mechanisms. Precision medicine approaches are necessary to link treatable mechanisms with treatable traits and biomarkers derived from clinical, physiologic and inflammatory features of clinical phenotypes. The deep molecular phenotyping of airway samples along with non-invasive biomarkers linked to bioinformatic and machine learning techniques will enable the rapid detection of molecular mechanisms that transgresses beyond the concept of treatable traits. This article is protected by copyright. All rights reserved

Measurements of nonmethane hydrocarbons in 28 United States cities

Between 1999 and 2005 a sampling campaign was conducted to identify and quantify the major species of atmospheric nonmethane hydrocarbons (NMHCs) in United States cities. Whole air canister samples were collected in 28 cities and analyzed for methane, carbon monoxide (CO) and NMHCs. Ambient mixing ratios exhibited high inter- and intra-city variability, often having standard deviations in excess of 50% of the mean value. For this reason, ratios of individual NMHC to CO, a combustion tracer, were examined to facilitate comparison between cities. Ratios were taken from correlation plots between the species of interest and CO, and most NMHCs were found to have correlation coefficients (r2) greater than 0.6, particularly ethene, ethyne and benzene, highlighting the influence of vehicular emissions on NMHC mixing ratios. Notable exceptions were the short-chain alkanes, which generally had poor correlations with CO. Ratios of NMHC vs. CO were also used to identify those cities with unique NMHC sources. © 2007 Elsevier Ltd. All rights reserved

Lumped dynamic analysis and design of a high-performance reciprocating-piston expander

A spatially - lumped dynamic model of a reciprocating - piston expander is presented in this paper. The model accounts for the three main loss mechanisms in realistic piston machines, namely: pressure losses through the intake and exhaust valves, heat transfer between the gas and the surrounding cylinder walls, and the mass leakage between the compression/expansion chamber and the crankcase throu gh the piston rings. The model also accounts for real - gas effects with the fluid properties calculated from t he NIST database using REFPROP. The numerical calculations are first compared with experimental pressure - volume - temperature data obtained on a cust om reciprocating - piston gas spring over a r ange of oscillation frequencies. The comparison between numerical and experimental results shows good agreement. It also allows the most accurate heat transfer correlation to be selected for calculating the gas - to - wall in - cylinder heat transfer. The semi - heuristic modelling tool is then used to design an expander for specific pressure ratio s and mass flowrate, and to predict the thermodynamic performance of the piston device over a range of part - load conditions

Carbonyl sulfide, dimethyl sulfide and carbon disulfide in the Pearl River Delta of southern China: Impact of anthropogenic and biogenic sources

Reduced sulfur compounds (RSCs) such as carbonyl sulfide (OCS), dimethyl sulfide (DMS) and carbon disulfide (CS2) impact radiative forcing, ozone depletion, and acid rain. Although Asia is a large source of these compounds, until now a long-term study of their emission patterns has not been carried out. Here we analyze 16 months of RSC data measured at a polluted rural/coastal site in the greater Pearl River Delta (PRD) of southern China. A total of 188 canister air samples were collected from August 2001 to December 2002. The OCS and CS2 mixing ratios within these samples were higher in autumn/winter and lower in summer due to the influence of Asian monsoon circulations. Comparatively low DMS values observed in this coastal region suggest a relatively low biological productivity during summer months. The springtime OCS levels in the study region (574 ± 40 pptv) were 25% higher than those on other East Asia coasts such Japan, whereas the springtime CS2 and DMS mixing ratios in the PRD (47 ± 38 pptv and 22 ± 5 pptv, respectively) were 3-30 times lower than elevated values that have been measured elsewhere in East Asia (Japan and Korea) at this time of year. Poor correlations were found among the three RSCs in the whole group of 188 samples, suggesting their complex and variable sources in the region. By means of backward Lagrangian particle release simulations, air samples originating from the inner PRD, urban Hong Kong and South China Sea were identified. The mean mixing ratio of OCS in the inner PRD was significantly higher than that in Hong Kong urban air and South China Sea marine air (p &lt; 0.001), whereas no statistical differences were found for DMS and CS2 among the three regions (p &gt; 0.05). Using a linear regression method based on correlations with the urban tracer CO, the estimated OCS emission in inner PRD (49.6 ± 4.7 Gg yr-1) was much higher than that in Hong Kong (0.32 ± 0.05 Gg yr-1), whereas the estimated CS2 and DMS emissions in the study region accounted for a very few percentage of the total CS2 and DMS emission in China. These findings lay the foundation for better understanding sulfur chemistry in the greater PRD region of southern China. © 2010 Elsevier Ltd

Prevalence, distribution, and severity of cerebral amyloid angiopathy differ between Lewy body diseases and Alzheimer’s disease

\ua9 The Author(s) 2024.Dementia with Lewy bodies (DLB), Parkinson’s disease dementia (PDD), and Parkinson’s disease (PD) collectively known as Lewy body diseases (LBDs) are neuropathologically characterised by α-synuclein deposits (Lewy bodies and Lewy neurites). However, LBDs also exhibit pathology associated with Alzheimer’s disease (AD) (i.e. hyperphosphorylated tau and amyloid β (Aβ). Aβ can be deposited in the walls of blood vessels in the brains of individuals with AD, termed cerebral amyloid angiopathy (CAA). The aim of this study was to investigate the type and distribution of CAA in DLB, PDD, and PD and determine if this differs from AD. CAA type, severity, and topographical distribution was assessed in 94 AD, 30 DLB, 17 PDD, and 11 PD cases, and APOE genotype evaluated in a subset of cases where available. 96.3% AD cases, 70% DLB cases and 82.4% PDD cases exhibited CAA (type 1 or type 2). However only 45.5% PD cases had CAA. Type 1 CAA accounted for 37.2% of AD cases, 10% of DLB cases, and 5.9% of PDD cases, and was not observed in PD cases. There was a hierarchical topographical distribution in regions affected by CAA where AD and DLB displayed the same distribution pattern that differed from PDD and PD. APOE ε4 was associated with severity of CAA in AD cases. Topographical patterns and severity of CAA in DLB more closely resembled AD rather than PDD, and as type 1 CAA is associated with clinical dementia in AD, further investigations are warranted into whether the increased presence of type 1 CAA in DLB compared to PDD are related to the onset of cognitive symptoms and is a distinguishing factor between LBDs. Possible alignment of the the topographical distribution of CAA and microbleeds in DLB warrants further investigation. CAA in DLB more closely resembles AD rather than PDD or PD, and should be taken into consideration when stratifying patients for clinical trials or designing disease modifying therapies

Source origins, modeled profiles, and apportionments of halogenated hydrocarbons in the greater Pearl River Delta region, southern China

We analyze 16-month data of 13 major halocarbons measured at a southern China coastal site in the greater Pearl River Delta (PRD). A total of 188 canister air samples were collected from August 2001 to December 2002. Overall inspection indicated that CH2Cl2, C2Cl 4, and C2HCl3 had similar temporal variations while CFC-11, CFC-12, and CFC-113 showed the same emission patterns during the sampling period. Diurnal variations of halocarbons presented different patterns during ozone episode days, mainly related to emission strength, atmospheric dispersion, and photochemical lifetimes. For further statistics and source appointment, Lagrangian backward particle release simulations were conducted to help understand the potential source regions of all samples and classify them into different categories, including local Hong Kong, inner PRD, continental China, and marine air masses. With the exception of HCFC-142b, the mixing ratios of all halocarbons in marine air were significantly lower than those in urban and regional air (p &lt; 0.01), whereas no significant difference was found between urban Hong Kong and inner PRD regional air, reflecting the dominant impact of the greater PRD regional air on the halocarbon levels. The halocarbon levels in this region were significantly influenced by anthropogenic sources, causing the halocarbon mixing ratios in South China Sea air to be higher than the corresponding background levels, as measured by global surface networks and by airborne missions such as Transport and Chemical Evolution Over the Pacific. Interspecies correlation analysis suggests that CHCl3 is mainly used as a solvent in Hong Kong but mostly as a feedstock for HCFC-22 in the inner PRD. Furthermore, CH3Cl is often used as a refrigerant and emitted from biomass/biofuel burning in the inner PRD. A positive matrix factorization receptor model was applied to the classified halocarbon samples in the greater PRD for source profiles and apportionments. Seven major sources were identified and quantified. Emissions from solvent use were the most significant source of halocarbons (71 ± 9%), while refrigeration was the second largest contributor (18 ± 2%). By further looking at samples from the inner PRD and from urban Hong Kong separately, we found that more solvent was used in the dry cleaning industry in Hong Kong, whereas the contribution of cleaning solvent in the electronic industry was higher in the inner PRD. Besides the two common sources of solvent use and refrigeration, the contributions of biomass/biofuel burning and feedstock in chemical manufacturing was remarkable in the inner PRD but negligible in Hong Kong. These findings are of help to effectively control and phase out the emissions of halocarbons in the greater PRD region of southern China Copyright 2009 by the American Geophysical Union