Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension

Background: Endothelin-1 signalling plays an important role in pathogenesis of pulmonary hypertension. Although different endothelin-A receptor antagonists are developed, a novel therapeutic option to cure the disease is still needed. This study aims to investigate the therapeutic efficacy of the selective endothelin-A receptor antagonist TBC3711 in monocrotaline-induced pulmonary hypertension in rats. Methods: Monocrotaline-injected male Sprague-Dawley rats were randomized and treated orally from day 21 to 35 either with TBC3711 (Dose: 30 mg/kg body weight/day) or placebo. Echocardiographic measurements of different hemodynamic and right-heart hypertrophy parameters were performed. After day 35, rats were sacrificed for invasive hemodynamic and right-heart hypertrophy measurements. Additionally, histologic assessment of pulmonary vascular and right-heart remodelling was performed. Results: The novel endothelin-A receptor antagonist TBC3711 significantly attenuated monocrotaline-induced pulmonary hypertension, as evident from improved hemodynamics and right-heart hypertrophy in comparison with placebo group. In addition, muscularization and medial wall thickness of distal pulmonary vessels were ameliorated. The histologic evaluation of the right ventricle showed a significant reduction in fibrosis and cardiomyocyte size, suggesting an improvement in right-heart remodelling. Conclusion: The results of this study suggest that the selective endothelin-A receptor antagonist TBC3711 demonstrates therapeutic benefit in rats with established pulmonary hypertension, thus representing a useful therapeutic approach for treatment of pulmonary hypertension

Practical nutritional recovery strategies for elite soccer players when limited time separates repeated matches

Specific guidelines that aim to facilitate the recovery of soccer players from the demands of training and a congested fixture schedule are lacking; especially in relation to evidence-based nutritional recommendations. The importance of repeated high level performance and injury avoidance while addressing the challenges of fixture scheduling, travel to away venues, and training commitments requires a strategic and practically feasible method of implementing specific nutritional strategies. Here we present evidence-based guidelines regarding nutritional recovery strategies within the context of soccer. An emphasis is placed on providing practically applicable guidelines for facilitation of recovery when multiple matches are played within a short period of time (i.e. 48 h). Following match-play, the restoration of liver and muscle glycogen stores (via consumption of ~1.2 gkg-1h-1 of carbohydrate) and augmentation of protein synthesis (via ~40 g of protein) should be prioritised in the first 20 minutes of recovery. Daily intakes of 6-10 gkg-1 body mass of carbohydrate are recommended when limited time separates repeated matches while daily protein intakes of >1.5 gkg-1 body mass should be targeted; possibly in the form of multiple smaller feedings (e.g., 6 x 20-40 g). At least 150% of the body mass lost during exercise should be consumed within 1 h and electrolytes added such that fluid losses are ameliorated. Strategic use of protein, leucine, creatine, polyphenols and omega-3 supplements could also offer practical means of enhancing post-match recovery. Keywords: soccer, nutrition, recovery, polyphenols, omega-3, creatine, fixture, congestio

Urinary heavy metals, phthalates, perchlorate, nitrate, thiocyanate, hydrocarbons, and polyfluorinated compounds are associated with adult hearing disturbance: USA NHANES, 2011–2012

Background Links between environmental chemicals and human health have emerged, but the effects on hearing were less studied. Therefore, the aim of the present study was to investigate the relationships of different sets of environmental chemicals and the hearing conditions in a national and population-based setting. Methods Data was retrieved from the US National Health and Nutrition Examination Surveys, 2011–2012 including demographics, serum measurements, lifestyle factors, self-reported hearing conditions, and urinary environmental chemical concentrations. Chi-square test, t test, and survey-weighted logistic regression models were performed. Results Among the American adults aged 20–69 (n=5560), 462 (8.3 %) people reported their hearing condition as moderate trouble to deaf. They had higher levels of urinary hydrocarbons and polyfluorinated compounds but not heavy metals, phthalates, arsenic, pesticides, phenols, parabens, perchlorate, nitrate, and thiocyanate concentrations. Also, 466 (10.0 %) people had hearing difficulties during conversation. They had higher levels of urinary cobalt (odds ratio (OR) 1.27, 95 % confidence interval (95%CI) 1.00–1.63), molybdenum (OR 1.45, 95%CI 1.04–2.02), strontium (OR 1.56, 95%CI 1.10–2.21), phthalates, perchlorate (OR 1.27, 95%CI 1.05– 1.54), nitrate (OR 1.60, 1.03–2.49) and thiocyanate (OR 1.22, 95%CI 1.01–1.48) concentrations but not arsenic, pesticides, phenols, parabens, hydrocarbons, and polyfluorinated compounds. Moreover, people who reported difficulties in following conversation with background noise had higher levels of urinary tin concentrations (OR 1.17, 1.00–1.36). Conclusions Urinary heavy metals, phthalates, perchlorate, nitrate, thiocyanate, hydrocarbons, and polyfluorinated compounds were associated with the adult hearing disturbance, although the causality cannot be established. Elimination of these environmental chemicals might need to be considered in future environmental health policy and health intervention programs