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

Bleomycin-induced lung injury in the rat: effects of the platelet-activating factor (PAF) receptor antagonist BN 52021 and platelet depletion.

Bleomycin is a highly effective antitumor agent, but pulmonary toxicity, characterized by an acute inflammatory reaction and associated pulmonary edema, limits clinical use of the drug. Platelets and platelet-activating factor (PAF), a membrane-derived phospholipid, have been implicated in the mechanisms that can mediate pulmonary microvascular injury. We sought to investigate the role of PAF in bleomycin-induced lung injury in the rat, using the PAF receptor antagonist BN 52021; and the role of platelets though the use of an anti-platelet antibody. Lung injury was induced by intratracheal bleomycin (1.5 mg) and assessed by measurements of lung wet weight and total pulmonary extravascular albumin space (TPEAS). Bleomycin caused a significant increase in both indices after 48 hr, compared with control animals (p less than 0.05). A single dose of BN 52021 (20 mg/kg orally) significantly reduced the bleomycin-induced increase in lung weight, but not the rise in TPEAS (p greater than 0.05). Increasing the dose of BN 52021 (20 mg/kg/12 hr, orally) had no additional effect. Reducing circulating platelet numbers by approximately 75% had no effect on either the increase in lung weight or TPEAS, observed 48 hr after bleomycin (p greater than 0.05). PAF may partially contribute to the acute inflammatory reaction seen after intratracheal bleomycin in rats

Editorial Redox Biology of Exercise

Redox biology is probably the most rapidly expanding field in biology. Indeed, the number of conferences, journals, and books devoted to redox biology is increasing and it is very often seen that major biology journals publish special issues on this area (e.g., Exercise is perhaps one of the most characteristic examples demonstrating that reactive species are not necessarily "harmful" entities, considering that the well-known benefits of regular exercise on muscle function and health are accompanied by repeated episodes of oxidative and nitrosative stress. In addition, an ongoing debate exists in the literature regarding the implications of antioxidant supplementation on physical performance and redox homeostasis. Considering that the redox biology of exercise is by nature multidisciplinary, this special issue is compiled of original and review articles combining chemical, analytical, biochemical, nutritional, physiological, and medical aspects relevant to reactive species biology. Reading through these papers the multiple facets of exercise redox biology are revealed. The review article by E. C. Gomes et al. presents the current state of knowledge on the redox biology of exercise. It provides a comprehensive perspective on the contribution of various intracellular and extracellular sources and the identity of oxidants produced by exercising animals and humans. It also focuses on the possible role of these exercise-induced oxidants in important training adaptations such as angiogenesis, mitochondria biogenesis, and muscle hypertrophy. This article lays the groundwork for the other articles of the special issue that address oxidant effects on exercise performance and redox homeostasis and diseases. Specifically, H. Pan et al. indicated that electrical stimulation of skeletal muscle cells increased the production of reactive species as well as the mRNA and protein levels of interleukin-6. The authors hypothesized that reactive species generation induced by skeletal muscle contraction may be one of the factors regulating musclederived interleukin-6 production and release. Using a more physiological relevant methodology, S. Mrakic-Sposta et al. employed an electron paramagnetic resonance technique for the rapid and noninvasive measurement of reactive species concentration directly in fresh human peripheral blood. Using this innovative approach, they reported that short-term high-intensity exercise increased reactive species production whereas the resting levels of reactive species decreased following supplementation with the antioxidant cofactor α-lipoic acid

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

NIDCAP improves brain function and structure in preterm infants with severe intrauterine growth restriction

Objective: The effect of NIDCAP (Newborn Individualized Developmental Care and Assessment Program) was examined on the neurobehavioral, electrophysiological and neurostructural development of preterm infants with severe intrauterine growth restriction (IUGR). Study Design: A total of 30 infants, 27–33 weeks gestation, were randomized to control (C; N=17) or NIDCAP/experimental (E; N=13) care. Baseline health and demographics were assessed at intake; electroencephalography (EEG) and magnetic resonance imaging (MRI) at 35 and 42 weeks postmenstrual age; and health, growth and neurobehavior at 42 weeks and 9 months corrected age (9 months). Results: C and E infants were comparable in health and demographics at baseline. At follow-up, E infants were healthier, showed significantly improved brain development and better neurobehavior. Neurobehavior, EEG and MRI discriminated between C and E infants. Neurobehavior at 42 weeks correlated with EEG and MRI at 42 weeks and neurobehavior at 9 months. Conclusion: NIDCAP significantly improved IUGR preterm infants' neurobehavior, electrophysiology and brain structure. Longer-term outcome assessment and larger samples are recommended

Importance of amino acid composition to improve skin collagen protein synthesis rates in UV-irradiated mice

Skin collagen metabolism abnormalities induced by ultraviolet (UV) radiation are the major causes of skin photoaging. It has been shown that the one-time exposure of UV irradiation decreases procollagen mRNA expression in dermis and that chronic UV irradiation decreases collagen amounts and induces wrinkle formation. Amino acids are generally known to regulate protein metabolism. Therefore, we investigated the effects of UV irradiation and various orally administered amino acids on skin collagen synthesis rates. Groups of 4–5 male, 8-week-old HR-1 hairless mice were irradiated with UVB (66 mJ/cm2) twice every other day, then fasted for 16 h. The fractional synthesis rate (FSR; %/h) of skin tropocollagen was evaluated by incorporating l-[ring-2H5]-phenylalanine. We confirmed that the FSR of dermal tropocollagen decreased after UVB irradiation. The FSR of dermal tropocollagen was measured 30 min after a single oral administration of amino acids (1 g/kg) to groups of 5–16 UVB-irradiated mice. Branched-chain amino acids (BCAA, 1.34 ± 0.32), arginine (Arg, 1.66 ± 0.39), glutamine (Gln, 1.75 ± 0.60), and proline (Pro, 1.48 ± 0.26) did not increase the FSR of skin tropocollagen compared with distilled water, which was used as a control (1.56 ± 0.30). However, essential amino acids mixtures (BCAA + Arg + Gln, BCAA + Gln, and BCAA + Pro) significantly increased the FSR (2.07 ± 0.58, 2.04 ± 0.54, 2.01 ± 0.50 and 2.07 ± 0.59, respectively). This result suggests that combinations of BCAA and glutamine or proline are important for restoring dermal collagen protein synthesis impaired by UV irradiation

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

Localization and potential role of matrix metalloproteinase-1 and tissue inhibitors of metalloproteinase-1 and -2 in different phases of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) can evolve in prematurely born infants who require mechanical ventilation because of hyaline membrane disease (HMD). The development of BPD can be divided in an acute, a regenerative, a transitional, and a chronic phase. During these different phases, extensive remodeling of the lung parenchyma with re-epithelialization of the alveoli and formation of fibrosis occurs. Matrix metalloproteinase-1 (MMP-1) is an enzyme that is involved in re-epithelialization processes, and dysregulation of MMP-1 activity contributes to fibrosis. Localization of MMP-1 and its inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, were investigated in lung tissue obtained from infants who died during different phases of BPD development. In all studied cases (n = 50) type-II pneumocytes were found to be immunoreactive for MMP-1, TIMP-1, and TIMP-2. During the acute and regenerative phase of BPD, type-II pneumocytes re-epithelialize the injured alveoli. This may suggest that MMP-1 and its inhibitors, expressed by type-II pneumocytes, play a role in the re-epithelialization process after acute lung injury. Although MMP-1 staining intensity remained constant in type-II pneumocytes during BPD development, TIMP-1 increased during the chronic fibrotic phase. This relative elevation of TIMP-1 compared with MMP-1 is indicative for reduced collagenolytic activity by type-II pneumocytes in chronic BPD and may contribute to fibrosis. Fibrotic foci in chronic BPD contained fibroblasts immunoreactive for MMP-1 and TIMP-1 and -2. This may indicate that decreased collagen turnover by fibroblasts contributes to fibrosis in BPD development