Increased collagen synthesis rate during wound healing in muscle

Wound healing in muscle involves the deposition of collagen, but it is not known whether this is achieved by changes in the synthesis or the degradation of collagen. We have used a reliable flooding dose method to measure collagen synthesis rate in vivo in rat abdominal muscle following a surgical incision. Collagen synthesis rate was increased by 480% and 860% on days 2 and 7 respectively after surgery in the wounded muscle compared with an undamaged area of the same muscle. Collagen content was increased by approximately 100% at both day 2 and day 7. These results demonstrate that collagen deposition during wound healing in muscle is achieved entirely by an increase in the rate of collagen synthesis

Original Research Oral Quercetin Supplementation and Blood Oxidative Capacity in Response to Ultramarathon Competition

Previous research indicates that ultramarathon exercise can result in blood oxidative stress. The purpose of this investigation was to examine the efficacy of oral supplementation with quercetin, a naturally occurring compound with known antioxidant properties, as a potential countermeasure against blood oxidative stress during an ultramarathon competition. In double-blind fashion, 63 participants received either oral quercetin (250 mg, 4×/day; 1,000 mg/day total) or quercetin-free supplements 3 weeks before and during the 160-km Western States Endurance Run. Blood drawn before and immediately after (quercetin finishers n = 18, quercetin-free finishers n = 21) the event was analyzed for changes in blood redox status and oxidative damage. Results show that quercetin supplementation did not affect race performance. In response to the ultramarathon challenge, aqueous-phase antioxidant capacity (ferric-reducing ability of plasma) was similarly elevated in athletes in both quercetin and quercetin-free treatments and likely reflects significant increases in plasma urate levels. Alternatively, trolox-equivalent antioxidant capacity was not altered by exercise or quercetin. Accordingly, neither F2-isoprostances nor protein carbonyls were influenced by either exercise or quercetin supplementation. In the absence of postrace blood oxidative damage, these findings suggest that oral quercetin supplementation does not alter blood plasma lipid or aqueous-phase antioxidant capacity or oxidative damage during an ultramarathon challenge

Blood Leukocyte mRNA Expression for IL-10, IL-1Ra, and IL-8, but Not IL-6, Increases After Exercise

The primary purpose of this project was to study exercise-induced leukocyte cytokine mRNA expression. Changes in plasma cytokine levels and blood leukocyte mRNA expression for interleukin-6 (IL-6), IL-8, IL- 10, and IL-1 receptor antagonist (IL-1Ra) were measured in 12 athletes following 2 h of intensive cycling (64% Wattsmax) while ingesting a carbohydrate or placebo beverage (randomized and double blinded). Blood samples were collected 30 min preexercise and immediately and 1 h postexercise. Carbohydate compared with placebo ingestion attenuated exercise-induced changes in plasma cortisol (8.8% vs. 62%, respectively), epinephrine (–9.2% vs. 138%), IL-6 (10-fold vs. 40-fold), IL-10 (8.9-fold vs. 26-fold, and IL-1Ra (2.1-fold vs. 5.6-fold). Significant time effects were measured for blood leukocyte IL-8 (2.4-fold increase 1 h postexercise), IL-10 (2.7-fold increase), IL-1Ra (2.2-fold increase), and IL-6 (0.8-fold decrease) mRNA content, with no significant differences between Cho and Pla test conditions. In summary, gene expression for IL-8, IL-10, and IL-1Ra, but not IL-6, is increased in blood leukocytes taken from athletes following 2 h of intensive cycling and is not influenced by carbohydrate compared with placebo ingestion. mRNA expression was high enough to indicate a substantial contribution of blood leukocytes to plasma levels of IL-8, IL-10, and IL-1Ra during prolonged exercise

Genetic partitioning of interleukin-6 signalling in mice dissociates Stat3 from Smad3-mediated lung fibrosis

Idiopathic pulmonary fibrosis (IPF) is a fatal disease that is unresponsive to current therapies and characterized by excessive collagen deposition and subsequent fibrosis. While inflammatory cytokines, including interleukin (IL)-6, are elevated in IPF, the molecular mechanisms that underlie this disease are incompletely understood, although the development of fibrosis is believed to depend on canonical transforming growth factor (TGF)-β signalling. We examined bleomycin-induced inflammation and fibrosis in mice carrying a mutation in the shared IL-6 family receptor gp130. Using genetic complementation, we directly correlate the extent of IL-6-mediated, excessive Stat3 activity with inflammatory infiltrates in the lung and the severity of fibrosis in corresponding gp130757F mice. The extent of fibrosis was attenuated in B lymphocyte-deficient gp130757F;µMT−/− compound mutant mice, but fibrosis still occurred in their Smad3−/− counterparts consistent with the capacity of excessive Stat3 activity to induce collagen 1α1 gene transcription independently of canonical TGF-β/Smad3 signalling. These findings are of therapeutic relevance, since we confirmed abundant STAT3 activation in fibrotic lungs from IPF patients and showed that genetic reduction of Stat3 protected mice from bleomycin-induced lung fibrosis

Successive Bouts of Cycling Stimulates Genes Associated with Mitochondrial Biogenesis

Exercise increases mRNA for genes involved in mitochondrial biogenesis and oxidative enzyme capacity. However, little is known about how these genes respond to consecutive bouts of prolonged exercise. We examined the effects of 3 h of intensive cycling performed on three consecutive days on the mRNA associated with mitochondrial biogenesis in trained human subjects. Forty trained cyclists were tested for VO2max (54.7 ± 1.1 ml kg−1 min−1). The subjects cycled at 57% wattsmax for 3 h using their own bicycles on CompuTrainer™ Pro Model trainers (RacerMate, Seattle, WA) on three consecutive days. Muscle biopsies were obtained from the vastus lateralis pre- and post-exercise on days one and three. Muscle samples were analyzed for mRNA content of peroxisome proliferator receptor gamma coactivator-1 alpha (PGC-1α), sirtuin 1 (Sirt-1), cytochrome c, and citrate synthase. Data were analyzed using a 2 (time) × 2 (day) repeated measures ANOVA. Of the mRNA analyzed, the following increased from pre to post 3 h rides: cytochrome c (P = 0.006), citrate synthase (P = 0.03), PGC-1α (P \u3c 0.001), and Sirt-1 (P = 0.005). The following mRNA showed significant effects from days one to three: cytochrome c (P \u3c 0.001) and citrate synthase (P = 0.01). These data show that exhaustive cycling performed on three consecutive days resulted in both acute and chronic stimuli for mRNA associated with mitochondrial biogenesis in already trained subjects. This is the first study to illustrate an increase in sirtuin-1 mRNA with acute and chronic exercise. These data contribute to the understanding of mRNA expression during both acute and successive bouts of prolonged exercise

Effect of low dose, short-term creatine supplementation on muscle power output in elite youth soccer players

Background: To determine the effects of a low dose, short-term Creatine monohydrate (Cr) supplementation (0.03 g.kg.d-1 during 14 d) on muscle power output in elite youth soccer players. Methods: Using a two-group matched, double blind, placebo-controlled design, nineteen male soccer players (mean age = 17.0 ± 0.5 years) were randomly assigned to either Cr (N = 9) or placebo (N = 10) group. Before and after supplementation, participants performed a 30s Wingate Anaerobic Test (WAnT) to assess peak power output (PPO), mean power output (MPO), fatigue index (FI), and total work. Results: There were significant increases in both PPO and MPO after the Cr supplementation period (P ≤ 0.05) but not the placebo period. There were also significant increases in total work, but not FI, after the Cr supplementation and placebo periods (P ≤ 0.05). Notably, there were differences in total work between the Cr and placebo groups after (P ≤ 0.05) but not before the 14 d supplementation period. Conclusion: There is substantial evidence to indicate that a low-dose, short-term oral Cr supplementation beneficially affected muscle power output in elite youth soccer players

Quercetin Ingestion Does Not Alter Cytokine Changes in Athletes Competing in the Western States Endurance Run

The purpose of this study was to measure the influence of quercetin on plasma cytokines, leukocyte cytokine mRNA, and related variables in ultramarathoners competing in the 160-km Western States Endurance Run (WSER). Sixty-three runners were randomized to quercetin and placebo groups and under double-blinded methods ingested 1000 mg/day quercetin for 3 weeks before the WSER. Thirty-nine of the 63 subjects (n = 18 for quercetin, n = 21 for placebo) finished the race and provided blood samples the morning before the race and 15–30 min postrace. Significant prerace to postrace WSER increases were measured for nine proinflammatory and anti-inflammatory plasma cytokines, cortisol (quercetin = 94%, placebo = 96%), serum C-reactive protein (CRP) (mean ± SE absolute increase, quercetin = 31.8 ± 4.2, placebo = 38.2 ± 5.0 mg/L), and creatine kinase (CK) (quercetin = 21,575 ± 3,977, placebo = 19,455 ± 3,969 U/L), with no significant group differences. Interleukin-6 (IL-6) mRNA did not change post-WSER, with a significant decrease measured for leukocyte IL-8 mRNA (0.21 ± 0.03-fold and 0.25 ± 0.04-fold change from rest, quercetin and placebo, respectively) and significant increases for IL-1Ra mRNA (1.43 ± 0.18-fold and 1.40 ± 0.16-fold change, quercetin and placebo, respectively) and IL-10 mRNA (12.9 ± 3.9-fold and 17.2 ± 6.1-fold change, quercetin and placebo, respectively), with no significant differences between groups. In conclusion, quercetin ingestion (1 g/day) by ultramarathon athletes for 3 weeks before a competitive 160-km race significantly increased plasma quercetin levels but failed to attenuate muscle damage, inflammation, increases in plasma cytokine and hormone levels, and alterations in leukocyte cytokine mRNA expression

Genetic partitioning of interleukin-6 signalling in mice dissociates Stat3 from Smad3-mediated lung fibrosis

Idiopathic pulmonary fibrosis (IPF) is a fatal disease that is unresponsive to current therapies and characterized by excessive collagen deposition and subsequent fibrosis. While inflammatory cytokines, including interleukin (IL)-6, are elevated in IPF, the molecular mechanisms that underlie this disease are incompletely understood, although the development of fibrosis is believed to depend on canonical transforming growth factor (TGF)-beta signalling. We examined bleomycin-induced inflammation and fibrosis in mice carrying a mutation in the shared IL-6 family receptor gp130. Using genetic complementation, we directly correlate the extent of IL-6-mediated, excessive Stat3 activity with inflammatory infiltrates in the lung and the severity of fibrosis in corresponding gp130757F mice. The extent of fibrosis was attenuated in B lymphocyte-deficient gp130757F;mu MT-/- compound mutant mice, but fibrosis still occurred in their Smad3-/- counterparts consistent with the capacity of excessive Stat3 activity to induce collagen 1a1 gene transcription independently of canonical TGF-beta/Smad3 signalling. These findings are of therapeutic relevance, since we confirmed abundant STAT3 activation in fibrotic lungs from IPF patients and showed that genetic reduction of Stat3 protected mice from bleomycin-induced lung fibrosis

The association between farming activities, precipitation, and the risk of acute gastrointestinal illness in rural municipalities of Quebec, Canada: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Increasing livestock density and animal manure spreading, along with climate factors such as heavy rainfall, may increase the risk of acute gastrointestinal illness (AGI). In this study we evaluated the association between farming activities, precipitation and AGI.</p> <p>Methods</p> <p>A cross-sectional telephone survey of randomly selected residents (n = 7006) of 54 rural municipalities in Quebec, Canada, was conducted between April 2007 and April 2008. AGI symptoms and several risk factors were investigated using a phone questionnaire. We calculated the monthly prevalence of AGI, and used multivariate logistic regression, adjusting for several demographic and risk factors, to evaluate the associations between AGI and both intensive farming activities and cumulative weekly precipitation. Cumulative precipitation over each week, from the first to sixth week prior to the onset of AGI, was analyzed to account for both the delayed effect of precipitation on AGI, and the incubation period of causal pathogens. Cumulative precipitation was treated as a four-category variable: high (≥90^thpercentile), moderate (50^thto <90^thpercentile), low (10^thto <50^thpercentile), and very low (<10^thpercentile) precipitation.</p> <p>Results</p> <p>The overall monthly prevalence of AGI was 5.6% (95% CI 5.0%-6.1%), peaking in winter and spring, and in children 0-4 years old. Living in a territory with intensive farming was negatively associated with AGI: adjusted odds ratio (OR) = 0.70 (95% CI 0.51-0.96). Compared to low precipitation periods, high precipitation periods in the fall (September, October, November) increased the risk of AGI three weeks later (OR = 2.20; 95% CI 1.09-4.44) while very low precipitation periods in the summer (June, July, August) increased the risk of AGI four weeks later (OR = 2.19; 95% CI 1.02-4.71). Further analysis supports the role of water source on the risk of AGI.</p> <p>Conclusions</p> <p>AGI poses a significant burden in Quebec rural municipalities with a peak in winter. Intensive farming activities were found to be negatively associated with AGI. However, high and very low precipitation levels were positively associated with the occurrence of AGI, especially during summer and fall. Thus, preventive public health actions during such climate events may be warranted.</p