Aerobic capacity and skeletal muscle function in children with asthma

Background Peripheral muscle strength and endurance are decreased in patients with chronic pulmonary diseases and seem to contribute to patients' exercise intolerance. However, the authors are not aware of any studies evaluating peripheral muscle function in children with asthma. It seems to be implied that children with asthma have lower aerobic fitness, but there are limited studies comparing the aerobic capacity of children with and without asthma. The present study aimed to evaluate muscle strength and endurance in children with persistent asthma and their association with aerobic capacity and inhaled corticosteroid consumption. Methods Forty children with mild persistent asthma (MPA) or severe persistent asthma (SPA) (N=20 each) and 20 children without asthma (control group) were evaluated. Upper (pectoralis and latissimus dorsi) and lower (quadriceps) muscle strength and endurance were assessed, and cardiopulmonary exercise testing was performed. Inhaled corticosteroid consumption during the last 6 and 24 months was also quantified. Results Children with SPA presented a reduction in peak oxygen consumption (VO(2)) (28.2 +/- 8.1 vs 34.7 +/- 6.9 ml/kg/min; p<0.01) and quadriceps endurance (43.1 +/- 6.7 vs 80.9 +/- 11.9 repetitions; p<0.05) compared with the control group, but not the MPA group (31.5 +/- 6.1 ml/kg/min and 56.7 +/- 47.7 repetitions respectively; p>0.05). Maximal upper and lower muscle strength was preserved in children with both mild and severe asthma (p>0.05). Finally, the authors observed that lower muscle endurance weakness was not associated with reductions in either peak VO(2) (r=0.22, p>0.05) or corticosteroid consumption (r=-0.31, p>0.05) in children with asthma. Conclusion The findings suggest that cardiopulmonary exercise and lower limb muscle endurance should be a priority during physical training programs for children with severe asthma.

Influence of Laser Photobiomodulation on Collagen IV During Skeletal Muscle Tissue Remodeling After Injury in Rats

Objective: The aim of the present study was to determine the effect of GaAlAs low-level laser therapy (LLLT) on collagen IV remodeling of the tibialis anterior (TA) muscle in rats after cryolesion. Background: Considerable interest exists in skeletal muscle regeneration in situations such as repair after exercise-induced muscle injury, after muscle transplantation, in muscular dystrophy, exercise-induced muscle injury, and the recovery of strength after atrophy due to disuse. A number of studies have demonstrated the potential of LLLT in facilitating the muscle-healing process; however, no consensus is found in the literature regarding the best laser-irradiation parameters. Methods: Adult male Wistar rats (n = 45) were used and randomly divided into three groups: control (n = 5); nontreated cryolesioned group (n = 20), and LLLT-cryolesioned group (n = 20). The cryolesioned groups were analyzed at 1, 7, 14, and 21 days after the injury procedure. Laser irradiation was performed 3 times per week on the injured region by using the GaAlAs laser (660 nm; beam spot of 0.04 cm(2), output power of 20 mW, power density of 500 mW/cm(2), and energy density of 5 J/cm(2), for 10 sec). The muscles were removed, frozen, cryosectioned, and then stained with hematoxylin-eosin for the visualization of general morphology or used for immunohistochemical analysis of collagen IV. Results: It was demonstrated that LLLT promotes an increase in collagen IV immunolabeling in skeletal muscle in the first 7 days after acute trauma caused by cryoinjury, but does not modify the duration of the tissue-repair process. Even with LLLT, the injured muscle tissue needs similar to 21 days to achieve the same state of organization as that in the noninjured muscle. Conclusion: The collagen IV content is modulated in regenerating skeletal muscle under LLLT, which might be associated with better tissue outcome, although the histologic analysis did not detect tissue improvement in the LLLT group.

Effect of 655-nm Low-Level Laser Therapy on Exercise-Induced Skeletal Muscle Fatigue in Humans

Objective: To investigate if development of skeletal muscle fatigue during repeated voluntary biceps contractions could be attenuated by low-level laser therapy (LLLT). Background Data: Previous animal studies have indicated that LLLT can reduce oxidative stress and delay the onset of skeletal muscle fatigue. Materials and Methods: Twelve male professional volleyball players were entered into a randomized double-blind placebo-controlled trial, for two sessions (on day 1 and day 8) at a 1-wk interval, with both groups performing as many voluntary biceps contractions as possible, with a load of 75% of the maximal voluntary contraction force (MVC). At the second session on day 8, the groups were either given LLLT (655 nm) of 5 J at an energy density of 500 J/cm(2) administered at each of four points along the middle of the biceps muscle belly, or placebo LLLT in the same manner immediately before the exercise session. The number of muscle contractions with 75% of MVC was counted by a blinded observer and blood lactate concentration was measured. Results: Compared to the first session (on day 1), the mean number of repetitions increased significantly by 8.5 repetitions (+/- 1.9) in the active LLLT group at the second session (on day 8), while in the placebo LLLT group the increase was only 2.7 repetitions (+/- 2.9) (p = 0.0001). At the second session, blood lactate levels increased from a pre-exercise mean of 2.4 mmol/L (+/- 0.5 mmol/L), to 3.6 mmol/L (+/- 0.5 mmol/L) in the placebo group, and to 3.8 mmol/L (+/- 0.4 mmol/L) in the active LLLT group after exercise, but this difference between groups was not statistically significant. Conclusion: We conclude that LLLT appears to delay the onset of muscle fatigue and exhaustion by a local mechanism in spite of increased blood lactate levels.

beta-Hydroxy-beta-methylbutyrate (HM beta) supplementation stimulates skeletal muscle hypertrophy in rats via the mTOR pathway

beta-Hydroxy-beta-methylbutyrate (HM beta) supplementation is used to treat cancer, sepsis and exercise-induced muscle damage. However, its effects on animal and human health and the consequences of this treatment in other tissues (e. g., fat and liver) have not been examined. The purpose of this study was to evaluate the effects of HM beta supplementation on skeletal muscle hypertrophy and the expression of proteins involved in insulin signalling. Rats were treated with HM beta (320 mg/kg body weight) or saline for one month. The skeletal muscle hypertrophy and insulin signalling were evaluated by western blotting, and hormonal concentrations were evaluated using ELISAs. HM beta supplementation induced muscle hypertrophy in the extensor digitorum longus (EDL) and soleus muscles and increased serum insulin levels, the expression of the mammalian target of rapamycin (mTOR) and phosphorylation of p70S6K in the EDL muscle. Expression of the insulin receptor was increased only in liver. Thus, our results suggest that HM beta supplementation can be used to increase muscle mass without adverse health effects.

Human multipotent adipose-derived stem cells restore dystrophin expression of Duchenne skeletal-muscle cells in vitro

Background information. DMD (Duchenne muscular dystrophy) is a devastating X-linked disorder characterized by progressive muscle degeneration and weakness. The use of cell therapy for the repair of defective muscle is being pursued as a possible treatment for DMD. Mesenchymal stem cells have the potential to differentiate and display a myogenic phenotype in vitro. Since liposuctioned human fat is available in large quantities, it may be an ideal source of stem cells for therapeutic applications. ASCs (adipose-derived stem cells) are able to restore dystrophin expression in the muscles of mdx (X-linked muscular dystrophy) mice. However, the outcome when these cells interact with human dystrophic muscle is still unknown. Results. We show here that ASCs participate in myotube formation when cultured together with differentiating human DMD myoblasts, resulting in the restoration of dystrophin expression. Similarly, dystrophin was induced when ASCs were co-cultivated with DMD myotubes. Experiments with GFP (green fluorescent protein)-positive ASCs and DAPI (4,6-diamidino-2-phenylindole)-stained DMD myoblasts indicated that ASCs participate in human myogenesis through cellular fusion. Conclusions. These results show that ASCs have the potential to interact with dystrophic muscle cells, restoring dystrophin expression of DMD cells in vitro. The possibility of using adipose tissue as a source of stem cell therapies for muscular diseases is extremely exciting.

Effect of eccentric exercise velocity on akt/mtor/p70(s6k) signaling in human skeletal muscle

It has been suggested that muscle tension plays a major role in the activation of intracellular pathways for skeletal muscle hypertrophy via an increase in mechano growth factor (MGF) and other downstream targets. Eccentric exercise (EE) imposes a greater amount of tension on the active muscle. In particular, high-speed EE seems to exert an additional effect on muscle tension and, thus, on muscle hypertrophy. However, little is known about the effect of EE velocity on hypertrophy signaling. This study investigated the effect of acute EE-velocity manipulation on the Akt/mTORCI/p70(S6K) hypertrophy pathway. Twenty subjects were assigned to either a slow (20 degrees.s(-1); ES) or fast EE (210 degrees.s(-1); EF) group. Biopsies were taken from vastus lateralis at baseline (B), immediately after (T1), and 2 h after (T2) the completion of 5 sets of 8 repetitions of eccentric knee extensions. Akt, mTOR, and p70(S6K) total protein were similar between groups, and did not change postintervention. Further, Akt and p70(S6K) protein phosphorylation were higher at T2 than at B for ES and EF. MGF messenger RNA was similar between groups, and only significantly higher at T2 than at B in ES. The acute manipulation of EE velocity does not seem to differently influence intracellular hypertrophy signaling through the Akt/mTORCI/p70S6K pathway.

Aerobic exercise training improves skeletal muscle function and Ca(2+) handling-related protein expression in sympathetic hyperactivity-induced heart failure

Bueno CR Jr, Ferreira JC, Pereira MG, Bacurau AV, Brum PC. Aerobic exercise training improves skeletal muscle function and Ca(2+) handling-related protein expression in sympathetic hyperactivity-induced heart failure. J Appl Physiol 109: 702-709, 2010. First published July 1, 2010; doi: 10.1152/japplphysiol.00281.2010.-The cellular mechanisms of positive effects associated with aerobic exercise training on overall intrinsic skeletal muscle changes in heart failure (HF) remain unclear. We investigated potential Ca(2+) abnormalities in skeletal muscles comprising different fiber compositions and investigated whether aerobic exercise training would improve muscle function in a genetic model of sympathetic hyperactivity-induced HF. A cohort of male 5-mo-old wild-type (WT) and congenic alpha(2A)/alpha(2C) adrenoceptor knockout (ARKO) mice in a C57BL/6J genetic background were randomly assigned into untrained and trained groups. Exercise training consisted of a 8-wk running session of 60 min, 5 days/wk (from 5 to 7 mo of age). After completion of the exercise training protocol, exercise tolerance was determined by graded treadmill exercise test, muscle function test by Rotarod, ambulation and resistance to inclination tests, cardiac function by echocardiography, and Ca(2+) handling-related protein expression by Western blot. alpha(2A)/alpha(2C)ARKO mice displayed decreased ventricular function, exercise intolerance, and muscle weakness paralleled by decreased expression of sarcoplasmic Ca(2+) release-related proteins [alpha(1)-, alpha(2)-, and beta(1)-subunits of dihydropyridine receptor (DHPR) and ryanodine receptor (RyR)] and Ca(2+) reuptake-related proteins [sarco(endo) plasmic reticulum Ca(2+)-ATPase (SERCA) 1/2 and Na(+)/Ca(2+) exchanger (NCX)] in soleus and plantaris. Aerobic exercise training significantly improved exercise tolerance and muscle function and reestablished the expression of proteins involved in sarcoplasmic Ca(2+) handling toward WT levels. We provide evidence that Ca(2+) handling-related protein expression is decreased in this HF model and that exercise training improves skeletal muscle function associated with changes in the net balance of skeletal muscle Ca(2+) handling proteins.

Experimental chronic low-frequency resistance training produces skeletal muscle hypertrophy in the absence of muscle damage and metabolic stress markers

Volitional animal resistance training constitutes an important approach to modeling human resistance training. However, the lack of standardization protocol poses a frequent impediment to the production of skeletal muscle hypertrophy and the study of related physiological variables (i.e., cellular damage/inflammation or metabolic stress). Therefore, the purposes of the present study were: (1) to test whether a long-term and low frequency experimental resistance training program is capable of producing absolute increases in muscle mass; (2) to examine whether cellular damage/inflammation or metabolic stress is involved in the process of hypertrophy. In order to test this hypothesis, animals were assigned to a sedentary control (C, n = 8) or a resistance trained group (RT, n = 7). Trained rats performed 2 exercise sessions per week (16 repetitions per day) during 12 weeks. Our results demonstrated that the resistance training strategy employed was capable of producing absolute mass gain in both soleus and plantaris muscles (12%, p<0.05). Furthermore, muscle tumor necrosis factor (TNF-alpha) protein expression (soleus muscle) was reduced by 24% (p<0.01) in trained group when compared to sedentary one. Finally, serum creatine kinase (CK) activity and serum lactate concentrations were not affected in either group. Such information may have practical applications if reproduced in situations where skeletal muscle hypertrophy is desired but high mechanical stimuli of skeletal muscle and inflammation are not. Copyright (C) 2010 John Wiley & Sons, Ltd.

Aerobic exercise training improves Ca(2+) handling and redox status of skeletal muscle in mice

Exercise training is known to promote relevant changes in the properties of skeletal muscle contractility toward powerful fibers. However, there are few studies showing the effect of a well-established exercise training protocol on Ca(2+) handling and redox status in skeletal muscles with different fiber-type compositions. We have previously standardized a valid and reliable protocol to improve endurance exercise capacity in mice based on maximal lactate steady-state workload (MLSSw). The aim of this study was to investigate the effect of exercise training, performed at MLSSw, on the skeletal muscle Ca(2+) handling-related protein levels and cellular redox status in soleus and plantaris. Male C57BL/6J mice performed treadmill training at MLSSw over a period of eight weeks. Muscle fiber-typing was determined by myosin ATPase histochemistry, citrate synthase activity by spectrophotometric assay, Ca(2+) handling-related protein levels by Western blot and reduced to oxidized glutathione ratio (GSH:GSSG) by high-performance liquid chromatography. Trained mice displayed higher running performance and citrate synthase activity compared with untrained mice. Improved running performance in trained mice was paralleled by fast-to-slow fiber-type shift and increased capillary density in both plantaris and soleus. Exercise training increased dihydropyridine receptor (DHPR) alpha 2 subunit, ryanodine receptor and Na(+)/Ca(2+) exchanger levels in plantaris and soleus. Moreover, exercise training elevated DHPR beta 1 subunit and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) 1 levels in plantaris and SERCA2 levels in soleus of trained mice. Skeletal muscle GSH content and GSH:GSSG ratio was increased in plantaris and soleus of trained mice. Taken together, our findings indicate that MLSSw exercise-induced better running performance is, in part, due to increased levels of proteins involved in skeletal muscle Ca(2+) handling, whereas this response is partially dependent on specificity of skeletal muscle fiber-type composition. Finally, we demonstrated an augmented cellular redox status and GSH antioxidant capacity in trained mice.

Exercise training changes IL-10/TNF-alpha ratio in the skeletal muscle of post-MI rats

Heart failure (HF) is associated with changes in the skeletal muscle (SM) which might be a consequence of the unbalanced local expression of pro- (TNF-alpha) and anti- (IL-10) inflammatory cytokines, leading to inflammation-induced myopathy, and SM wasting. This local effect of HF on SM may, on the other hand, contribute to systemic inflammation, as this tissue actively secretes cytokines. Since increasing evidence points out to an anti-inflammatory effect of exercise training, the goal of the present study was to investigate its effect in rats with HF after post-myocardial infarction (MI), with special regard to the expression of TNF-alpha and IL-10 in the soleus and extensor digitorum longus (EDL), muscles with different fiber composition. Wistar rats underwent left thoracotomy with ligation of the left coronary artery, and were randomly assigned to either a sedentary (Sham-operated and MI sedentary) or trained (Sham-operated and MI trained) group. Animals in the trained groups ran on a treadmill (0% grade at 13-20 m/min) for 60 min/day, 5 days/week, for 8-10 weeks. The training protocol was able to reverse the changes induced by MI, decreasing TNF-alpha protein (26%, P < 0.05) and mRNA (58%, P < 0.05) levels in the soleus, when compared with the sedentary MI group. Training also increased soleus IL-10 expression (2.6-fold, P < 0.001) in post-MI HF rats. As a consequence, the IL-10/TNF-alpha ratio was increased. This ""anti-inflammatory effect"" was more pronounced in the soleus than in the EDL, suggesting a fiber composition dependent response. (C) 2009 Elsevier Ltd. All rights reserved.

Physical Training Leads to Remodeling of Diaphragm Muscle in Asthma Model

Matrix metalloproteinases (MMPs) are crucial to the development and maintenance of healthy tissue and are mainly involved in extracellular matrix (ECM) remodeling of skeletal muscle. This study evaluated the effects of chronic allergic airway inflammation (CAAI), induced by ovalbumin, and aerobic training in the MMPs activity in mouse diaphragm muscle. Thirty mice were divided into 6 groups: 1) control; 2) ovalbumin; 3) treadmill trained at 50% of maximum speed; 4) ovalbumin and trained at 50%; 5) trained at 75%; 6) ovalbumin and trained at 75%. CAAI did not after MMPs activities in diaphragm muscle. Nevertheless, both treadmill aerobic trainings, associated with CAAI increased the MMP-2 and -1 activities. Furthermore, MMP-9 was not detected in any group. Together, these findings suggest an ECM remodeling in diaphragm muscle of asthmatic mice submitted to physical training. This result may be useful for a better understanding of functional significance of changes in the MMPs activity in response to physical training in asthma.

MHC class I and II expression in juvenile dermatomyositis skeletal muscle

Objective To assess MHC I and II expressions in muscle fibres of juvenile dermatomyositis (JDM) and compare with the expression in polymyositis (PM), dermatomyositis (DM) and dystrophy. Patients and methods Forty-eight JDM patients and 17 controls (8 PM, 5 DM and 4 dystrophy) were studied. The mean age at disease onset was 7.1 +/- 3.0 years and the mean duration of weakness before biopsy was 9.4 +/- 12.9 months. Routine histochemistry and immunohistochemistry (StreptABComplex/HRP) for MHC I and II (Dakopatts) were performed on serial frozen muscle sections in all patients. Mann-Whitney, Kruskal Wallis, chi-square and Fisher`s exact statistical methods were used. Results MHC I expression was positive in 47 (97.9%) JDM cases. This expression was observed independent of time of disease corticotherapy previous to muscle biopsy and to the grading of inflammation observed in clinical, laboratorial and histological parameters. The expression of MHC I was similar on JDM, PM and DM, and lower in dystrophy. On the other hand, MHC II expression was positive in just 28.2% of JDM cases was correlated to histological features as inflammatory infiltrate, increased connective tissue and VAS for global degree of abnormality (p < 0.05). MCH II expression was similar in DM/PM and lower in JDM and dystrophy, and it was based on the frequency of positive staining rather than to the degree of the MCH II expression. Conclusions MHC I expression in muscle fibres is a premature and late marker of JDM patient independent to corticotherapy, and MHC II expression was lower in JDM than in PM and DM.