The Effect of Nitrate Supplementation on Cycling Performance in the Heat in Well-Trained Cyclists

Purpose: The aim of this study was to determine the effect of NO₃⁻ consumption on measures of perception, thermoregulation and cycling performance in hot conditions. Methods: Using a randomised, double-blind, crossover-design, 8 well-trained cyclists (mean ± SD: age: 25 ± 8 y, V̇O2peak: 64 ± 5 ml·kg⁻¹·min⁻¹) performed 2 separate trials, in hot (35°C, 60% relative humidity) environments, having ingested either 140 ml NO3--rich beetroot juice ~8 mmol NO₃⁻ (NIT), or placebo (PLA), daily for 3-days with a 7-day washout period separating trials. Trials consisted of 2 × 10 min bouts at 40 and 60% peak power output (PPO) to determine physiological and perceptual responses in the heat, followed by a 4 km cycling time-trial. Results: Basal [nitrite] was substantially elevated in NIT (2.70 ± 0.98 μM) vs PLA (1.10 ± 0.61 μM) resulting in a most likely (ES = 1.58 ± 0.93) increase after 3-days. There was a very likely trivial increase in rectal temperature [Tᵣₑ] in NIT at 40% (PLA;37.4 ± 0.2°C vs NIT;37.5 ± 0.3°C, 0.1 ± 0.2°C) and 60% (PLA;37.8 ± 0.2°C vs NIT;37.9 ± 0.3°C, 0.1 ± 0.2°C) PPO. Cycling performance was similar between trials (PLA;336 ± 45 W vs NIT;337 ± 50 W, CV±95%CL; 0.2 ± 2.5%). Outcomes for heart rate, and perceptual measures were unclear across the majority of time-points. Conclusions: Three days of NO₃⁻ supplementation, resulted in small increases in Tᵣₑ during low- to moderate-intensity exercise, however this did not appear to influence 4 km cycling time-trial performance in hot climates

‘Priming’ exercise and O2 uptake kinetics during treadmill running

We tested the hypothesis that priming exercise would speed kinetics during treadmill running. Eight subjects completed a square-wave protocol, involving two bouts of treadmill running at 70% of the difference between the running speeds at lactate threshold (LT) and max, separated by 6-min of walking at 4 km h−1, on two occasions. Oxygen uptake was measured breath-by-breath and subsequently modelled using non-linear regression techniques. Heart rate and blood lactate concentration were significantly elevated prior to the second exercise bout compared to the first. However, kinetics was not significantly different between the first and second exercise bouts (mean ± S.D., phase II time constant, Bout 1: 16 ± 3 s vs. Bout 2: 16 ± 4 s; slow component amplitude, Bout 1: 0.24 ± 0.10 L min−1vs. Bout 2: 0.20 ± 0.12 L min−1; mean response time, Bout 1: 34 ± 4 s vs. Bout 2: 34 ± 6 s; P > 0.05 for all comparisons). These results indicate that, contrary to previous findings with other exercise modalities, priming exercise does not alter kinetics during high-intensity treadmill running, at least in physically active young subjects. We speculate that the relatively fast kinetics and the relatively small slow component in the control (‘un-primed’) condition negated any enhancement of kinetics by priming exercise in this exercise modality

Reproducibility of onset and recovery oxygen uptake kinetics in moderately impaired patients with chronic heart failure

Oxygen (O2) kinetics reflect the ability to adapt to or recover from exercise that is indicative of daily life. In patients with chronic heart failure (CHF), parameters of O2 kinetics have shown to be useful for clinical purposes like grading of functional impairment and assessment of prognosis. This study compared the goodness of fit and reproducibility of previously described methods to assess O2 kinetics in these patients. Nineteen CHF patients, New York Heart Association class II–III, performed two constant-load tests on a cycle ergometer at 50% of the maximum workload. Time constants of O2 onset- and recovery kinetics (τ) were calculated by mono-exponential modeling with four different sampling intervals (5 and 10 s, 5 and 8 breaths). The goodness of fit was expressed as the coefficient of determination (R2). Onset kinetics were also evaluated by the mean response time (MRT). Considering O2 onset kinetics, τ showed a significant inverse correlation with peak- \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document} \ifmmode\expandafter\dot\else\expandafter\.\fi{V}{\text{O}}_{2} \end{document} (R = −0.88, using 10 s sampling intervals). The limits of agreement of both τ and MRT, however, were not clinically acceptable. O2 recovery kinetics yielded better reproducibility and goodness of fit. Using the most optimal sampling interval (5 breaths), a change of at least 13 s in τ is needed to exceed normal test-to-test variations. In conclusion, O2 recovery kinetics are more reproducible for clinical purposes than O2 onset kinetics in moderately impaired patients with CHF. It should be recognized that this observation cannot be assumed to be generalizable to more severely impaired CHF patients

A simple and rapid approach for screening of SARS-coronavirus genotypes: an evaluation study

BACKGROUND: The Severe Acute Respiratory Syndrome (SARS) was a newly emerged infectious disease which caused a global epidemic in 2002–2003. Sequence analysis of SARS-coronavirus isolates revealed that specific genotypes predominated at different periods of the epidemic. This information can be used as a footprint for tracing the epidemiology of infections and monitor viral evolution. However, direct sequencing analysis of a large number of clinical samples is cumbersome and time consuming. We present here a simple and rapid assay for the screening of SARS-coronavirus genotypes based on the use of fluorogenic oligonucleotide probes for allelic discrimination. METHODS: Thirty SARS patients were recruited. Allelic discrimination assays were developed based on the use of fluorogenic oligonucleotide probes (TaqMan). Genotyping of the SARS-coronavirus isolates obtained from these patients were carried out by the allelic discrimination assays and confirmed by direct sequencing. RESULTS: Genotyping based on the allelic discrimination assays were fully concordant with direct sequencing. All of the 30 SARS-coronavirus genotypes studied were characteristic of genotypes previously documented to be associated with the latter part of the epidemic. Seven of the isolates contained a previously reported major deletion but in patients not epidemiologically related to the previously studied cohort. CONCLUSION: We have developed a simple and accurate method for the characterization and screening of SARS-coronavirus genotypes. It is a promising tool for the study of epidemiological relationships between documented cases during an outbreak

Efeitos do treinamento muscular inspiratório em universitários tabagistas e não tabagistas

O hábito de fumar pode reduzir a capacidade aeróbica, aumentar a resistência ao fluxo aéreo e afetar a função dos músculos respiratórios. O objetivo deste estudo foi comparar os efeitos do Treinamento Muscular Inspiratório (TMI) entre dois grupos: tabagistas e não tabagistas. Participaram 44 voluntários universitários, divididos em dois grupos: tabagistas (GT), composto por 20 indivíduos (25,60±7,01 anos) e não tabagistas, constituindo o Grupo Controle (GC), composto por 24 voluntários (24,08±7,52 anos). Ambos os grupos foram submetidos ao TMI, por meio do uso do manovacuômetro aneroide, com duração de 6 semanas, sendo 3 sessões semanais, totalizando 18 sessões. Os resultados mostraram diferença estatisticamente significativa (p<0,05) pós-TMI no GC para as variáveis: Pressão Inspiratória Máxima (PImáx), Pico de Fluxo Expiratório (PFE), Pressão Arterial Média ao repouso (PAM pré-TC6) e Teste de Caminhada de Seis Minutos (TC6). No GT, houve diferença estatisticamente significativa pós-TMI para as variáveis: PImáx, PFE, TC6 e saturação periférica de oxigênio após o TC6 (SpO2 pós-imediata). A comparação das médias das variáveis entre GT e GC mostrou diferença estatisticamente significativa no pós-TMI para as variáveis PImáx e PFE. A variável TC6 não apresentou diferença estatisticamente significativa. Conclui-se que o TMI proporcionou um aumento significativo da força muscular inspiratória, melhora da função pulmonar e melhora do desempenho físico nos indivíduos estudados

Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis

Objective: To investigate whether antidrug antibodies and/or drug non-trough levels predict the long-term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.  Methods: A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme-linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non-trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.  Results: Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.  Conclusion: Pharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months

Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis

Toll-like receptors (TLRs) are a family of transmembrane pattern recognition receptors (PRR) that play a key role in innate and adaptive immunity by recognizing structural components unique to bacteria, fungi and viruses. TLR4 is the most studied of the TLRs, and its primary exogenous ligand is lipopolysaccharide, a component of Gram-negative bacterial walls. In the absence of exogenous microbes, endogenous ligands including damage-associated molecular pattern molecules from damaged matrix and injured cells can also activate TLR4 signaling. In humans, single nucleotide polymorphisms of the TLR4 gene have an effect on its signal transduction and on associated risks of specific diseases, including cirrhosis. In liver, TLR4 is expressed by all parenchymal and non-parenchymal cell types, and contributes to tissue damage caused by a variety of etiologies. Intact TLR4 signaling was identified in hepatic stellate cells (HSCs), the major fibrogenic cell type in injured liver, and mediates key responses including an inflammatory phenotype, fibrogenesis and anti-apoptotic properties. Further clarification of the function and endogenous ligands of TLR4 signaling in HSCs and other liver cells could uncover novel mechanisms of fibrogenesis and facilitate the development of therapeutic strategies