Recovery Of Skeletal Muscle Function Research Articles

Atrophy signaling pathways in respiratory and limb muscles of guinea pigs exposed to chronic cigarette smoke: role of soluble guanylate cyclase stimulation.

Skeletal muscle dysfunction in chronic obstructive pulmonary disease (COPD) is characterized by a significant reduction in muscle strength and endurance. Preclinical studies show that stimulation of the soluble guanylate cyclase (sGC)-cGMP pathway attenuates muscle mass loss and prevents cigarette smoke-induced oxidative stress, indicating that pharmacological activation of the guanylyl cyclase pathway in COPD may provide a beneficial therapeutic strategy that reaches beyond the lung. In this study, conducted in an animal model of COPD, we first set out to assess the effect of cigarette smoke (CS) on biomarkers of muscle fatigue, such as protein degradation and its transcriptional regulation, in two types of muscles with different energy demands, i.e., the diaphragm and the gastrocnemius muscle of the limbs. Second, we evaluated the administration of an sGC stimulator on these markers to study the potential efficacy of such treatment in the recovery of skeletal muscle function. Exposure to CS led to weight loss, which was associated in the gastrocnemius with increased levels of proteolytic markers of muscle atrophy (MURF-1, Atrogin-1, proteasome C8 subunit 20 s, and total protein ubiquitination), whereas the size of fast-twitch muscle fibers decreased significantly. Long-term treatment with the sGC stimulator BAY 41-2272 resulted in a significant reduction in gastrocnemius levels of the aforementioned proteolytic markers, concomitant with a weight recovery and increased cGMP levels. Remarkably, levels of some of the analyzed biomarkers differed between respiratory and limb muscles. In conclusion, targeting sGC might exert beneficial effects on muscle alterations in patients with COPD.

SS31 Ameliorates Oxidative Stress via the Restoration of Autophagic Flux to Protect Aged Mice From Hind Limb Ischemia.

BackgroundOxidative stress and impaired autophagic flux play important roles in the development of peripheral artery disease (PAD). SS31 is considered an important antioxidant peptide and autophagy regulator. We aimed to investigate the role of SS31 in PAD myopathy and its possible mechanism both in vivo and in vitro.MethodsA hind limb ischemia (HLI) model was established with old C57BL/6 (14-month-old) mice. Mice in the SS31 group were intraperitoneally injected with SS31 (3 mg/kg) for 4 weeks. We examined skeletal muscle function and histomorphology, autophagy-related protein levels and reactive oxygen species (ROS) content. For the in vitro experiments, after C2C12 myotubes were treated with CoCl2, SS31, and chloroquine (CQ) or rapamycin (RAPA), we measured ROS content, autophagy-related protein levels and antioxidant enzyme expression.ResultsSS31 treatment effectively enhanced the recovery of skeletal muscle function, alleviated skeletal muscle injury and suppressed mitochondrial ROS production in ischemic limbs. SS31 reduced apoptosis and oxidative stress, and SS31 restored impaired autophagic flux by inhibiting the AKT-mTOR pathway. In vitro studies showed that SS31 restored autophagic flux and improved oxidative stress in C2C12 cells. Moreover, phosphorylated AKT (p-AKT) and phosphorylated mTOR (p-mTOR) levels were reduced.ConclusionThese experiments indicated that SS31 can inhibit oxidative stress by restoring autophagic flux to reverse hypoxia-induced injury in vivo and in vitro.

Phytoecdysteroids Accelerate Recovery of Skeletal Muscle Function Following in vivo Eccentric Contraction-Induced Injury in Adult and Old Mice.

Background: Eccentric muscle contractions are commonly used in exercise regimens, as well as in rehabilitation as a treatment against muscle atrophy and weakness. If repeated multiple times, eccentric contractions may result in skeletal muscle injury and loss of function. Skeletal muscle possesses the remarkable ability to repair and regenerate after an injury or damage; however, this ability is impaired with aging. Phytoecdysteroids are natural plant steroids that possess medicinal, pharmacological, and biological properties, with no adverse side effects in mammals. Previous research has demonstrated that administration of phytoecdysteroids, such as 20-hydroxyecdysone (20E), leads to an increase in protein synthesis signaling and skeletal muscle strength.Methods: To investigate whether 20E enhances skeletal muscle recovery from eccentric contraction-induced damage, adult (7–8 mo) and old (26–27 mo) mice were subjected to injurious eccentric contractions (EC), followed by 20E or placebo (PLA) supplementation for 7 days. Contractile function via torque-frequency relationships (TF) was measured three times in each mouse: pre- and post-EC, as well as after the 7-day recovery period. Mice were anesthetized with isoflurane and then electrically-stimulated isometric contractions were performed to obtain in vivo muscle function of the anterior crural muscle group before injury (pre), followed by 150 EC, and then again post-injury (post). Following recovery from anesthesia, mice received either 20E (50 mg•kg−1 BW) or PLA by oral gavage. Mice were gavaged daily for 6 days and on day 7, the TF relationship was reassessed (7-day).Results: EC resulted in significant reductions of muscle function post-injury, regardless of age or treatment condition (p < 0.001). 20E supplementation completely recovered muscle function after 7 days in both adult and old mice (pre vs. 7-day; p > 0.05), while PLA muscle function remained reduced (pre vs. 7-day; p < 0.01). In addition, histological markers of muscle damage appear lower in damaged muscle from 20E-treated mice after the 7-day recovery period, compared to PLA.Conclusions: Taken together, these findings demonstrate that 20E fully recovers skeletal muscle function in both adult and old mice just 7 days after eccentric contraction-induced damage. However, the underlying mechanics by which 20E contributes to the accelerated recovery from muscle damage warrant further investigation.

Reducing NF-κB Signaling Nutritionally is Associated with Expedited Recovery of Skeletal Muscle Function After Damage.

ContextThe early events regulating the remodeling program following skeletal muscle damage are poorly understood.ObjectiveThe objective of this study was to determine the association between myofibrillar protein synthesis (myoPS) and nuclear factor-kappa B (NF-κB) signaling by nutritionally accelerating the recovery of muscle function following damage.Design, Setting, Participants, and InterventionsHealthy males and females consumed daily postexercise and prebed protein-polyphenol (PP; n = 9; 4 females) or isocaloric maltodextrin placebo (PLA; n = 9; 3 females) drinks (parallel design) 6 days before and 3 days after 300 unilateral eccentric contractions of the quadriceps during complete dietary control.Main Outcome MeasuresMuscle function was assessed daily, and skeletal muscle biopsies were taken after 24, 27, and 36 hours for measurements of myoPS rates using deuterated water, and gene ontology and NF-κB signaling analysis using a quantitative reverse transcription PCR (RT-qPCR) gene array.ResultsEccentric contractions impaired muscle function for 48 hours in PLA intervention, but just for 24 hours in PP intervention (P = 0.047). Eccentric quadricep contractions increased myoPS compared with the control leg during postexercise (24–27 hours; 0.14 ± 0.01 vs 0.11 ± 0.01%·h-1, respectively; P = 0.075) and overnight periods (27–36 hours; 0.10 ± 0.01 vs 0.07 ± 0.01%·h-1, respectively; P = 0.020), but was not further increased by PP drinks (P > 0.05). Protein-polyphenol drinks decreased postexercise and overnight muscle IL1R1 (PLA = 2.8 ± 0.4, PP = 1.1 ± 0.4 and PLA = 1.9 ± 0.4, PP = 0.3 ± 0.4 log2 fold-change, respectively) and IL1RL1 (PLA = 4.9 ± 0.7, PP = 1.6 ± 0.8 and PLA = 3.7 ± 0.6, PP = 0.7 ± 0.7 log2 fold-change, respectively) messenger RNA expression (P < 0.05) and downstream NF-κB signaling compared with PLA.ConclusionProtein-polyphenol drink ingestion likely accelerates recovery of muscle function by attenuating inflammatory NF-κB transcriptional signaling, possibly to reduce aberrant tissue degradation rather than increase myoPS rates.

Impaired phagocytic function in CX3CR1+ tissue-resident skeletal muscle macrophages prevents muscle recovery after influenza A virus-induced pneumonia in old mice.

Skeletal muscle dysfunction in survivors of pneumonia disproportionately affects older individuals in whom it causes substantial morbidity. We found that skeletal muscle recovery was impaired in old compared with young mice after influenza A virus‐induced pneumonia. In young mice, recovery of muscle loss was associated with expansion of tissue‐resident skeletal muscle macrophages and downregulation of MHC II expression, followed by a proliferation of muscle satellite cells. These findings were absent in old mice and in mice deficient in Cx3cr1. Transcriptomic profiling of tissue‐resident skeletal muscle macrophages from old compared with young mice showed downregulation of pathways associated with phagocytosis and proteostasis, and persistent upregulation of inflammatory pathways. Consistently, skeletal muscle macrophages from old mice failed to downregulate MHCII expression during recovery from influenza A virus‐induced pneumonia and showed impaired phagocytic function in vitro. Like old animals, mice deficient in the phagocytic receptor Mertk showed no macrophage expansion, MHCII downregulation, or satellite cell proliferation and failed to recover skeletal muscle function after influenza A pneumonia. Our data suggest that a loss of phagocytic function in a CX3CR1+ tissue‐resident skeletal muscle macrophage population in old mice precludes satellite cell proliferation and recovery of skeletal muscle function after influenza A pneumonia.

Exercise and Muscle Atrophy.

The incidence of muscle atrophy is increasing with each passing year, which imposes a huge burden on the quality of life of patients. It is a public health issue that causes a growing concern around the world. Exercise is one of the key strategies to prevent and treat various diseases. Appropriate exercise is conducive to compensatory muscle hypertrophy, to improve muscle strength and elasticity, and to train muscle coordination, which is also beneficial to the recovery of skeletal muscle function and the regeneration of muscle cells. Sequelae of paralysis of patients with limb dyskinesia caused by muscle atrophy will be significantly alleviated after regular exercise therapy. Furthermore, exercise therapy can slow down or even reverse muscle atrophy. This article aims to introduce the characteristics of muscle atrophy and summarize the role and mechanism of exercise in the treatment of muscle atrophy in the existing studies, in order to further explore the mechanism of exercise to protect muscle atrophy and provide protection for patients with muscular atrophy.

Post-exercise And Pre-sleep Protein-polyphenol Supplementation Improves Recovery Following Muscle-damaging Eccentric Exercise: Preliminary Findings.

PURPOSE: Eccentric contraction (EC) induced muscle damage is characterised by weakened force production, increased soreness and elevated plasma creatine kinase (CK). Recovery rate is likely to be dependent on muscle remodelling, which may be influenced by dietary protein and polyphenol availability. We investigated if consuming protein-polyphenol drinks post-exercise and before bed improved recovery of knee extensor function and reduced soreness following a bout of EC. METHODS: In a randomised, parallel groups, placebo controlled double blind design, 18 healthy males and females (22 ± 1 y; BMI: 24.0 ± 0.9 kg·m-2 (± SEM)) consumed a controlled isocaloric diet (1.2 g·kg-1 protein) for 7 days before and after a single bout of 300 maximal unilateral quadriceps EC, in combination with either post-exercise (20 g whey, casein and pea protein blend and 650 mg pomegranate extract) and pre-bed (20 g casein protein and 480 mg tart cherry extract) drinks (Beachbody LLC) (PRO; n = 9; 4 females), or isocaloric maltodextrin placebos (PLA; n = 9; 3 females). Total isokinetic work over 30 maximal knee extensions (TW), peak isometric torque (PT) and muscle soreness (visual analogue scale (VAS) and pressure pain threshold (PPT)) were measured relative to the contralateral control limb (%con) before and every 24 h for 7 d following EC, as was CK. Data were analysed using two-way ANOVAs. RESULTS: EC caused a maximum decline in TW in PLA after 48 h to 68 ± 6 %con (P < 0.001) which remained below baseline until 120 h (P < 0.05). Conversely, TW in PRO was reduced at 24 h only (to 89 ± 5 %con; P < 0.05) and was restored thereafter. PT decreased following EC (P < 0.001) and was significantly lower in PLA compared with PRO at 48 h (69 ± 5 vs 107 ± 13 %con, respectively) and 96 h (76 ± 7 vs 110 ± 14 %con, respectively). Muscle soreness in both groups peaked within 72 h of EC (P < 0.05), but vastus medialis PPT was attenuated at 72 h in PRO compared to PLA (102 ± 3 vs 88 ± 3 %con, respectively; P < 0.05). Plasma CK rose > 30-fold from 96 to 120 h (P < 0.01), and was similar between groups (P > 0.05). CONCLUSION: Consumption of commercially available post-exercise and before bed protein-polyphenol beverages accelerated recovery of skeletal muscle function following EC-induced muscle damage, potentially due to improved protein turnover and remodelling. Supported by a Beachbody LLC (USA) grant.

Relevance of nutritional support and early rehabilitation in hospitalized patients with COPD.

Exacerbation of COPD is associated with a worsening of lung function and symptoms, and a serious loss in functional status and health related quality of life. It also represents the major cause for emergency hospitalization in COPD patients which places the patient at risk for developing further muscle weakness. Actually, loss of muscle function developed fast and continued to decrease over time during hospitalization and may be further compromised when disease deterioration would require the use of ventilator support. Exacerbations have long term consequences on physical performance, physical activity and health-related quality of life as recovery of skeletal muscle function is slow and incomplete and may even be compromised in case of re-exacerbation. Factors such as bed rest, reduced physical activity, hypoxia, inflammation, drug treatment and negative protein balance due to insufficient dietary intake and increased resting energy expenditure are all potential contributors to skeletal muscle weakness during exacerbation. Because low levels of physical activity and poor physical performance are predictor of hospital re-admission and are associated with lower survival in these patients, interventions to prevent the additional loss of muscle function during exacerbation or to hasten functional recovery have been recently explored. This review focuses on the knowledge regarding the potential benefit of early rehabilitation and nutritional supplementation as modifiable factors susceptible to ameliorate muscle weakness during exacerbation in hospitalized COPD patients.

Angiotensin‐(1‐7) Treatment Aids in the Recovery of Skeletal Muscle Function After Acute Injury in Rats

IntroductionPathologic fibrosis is a major impedance to the recovery of muscle function after injury, and is augmented in the elderly population. Angiotensin‐(1‐7) [Ang‐(1‐7)] is an endogenous, 7‐amino acid peptide hormone of the renin‐angiotensin system, which has been shown to reduce fibrosis in the heart, lung and kidney. The objective of this research was to examine the effect of Ang‐(1‐7) treatment on the recovery of muscle function in older rats after compression injury.MethodsCompression injury was induced in the hind limbs of 12 month old male Lewis rats as previously described1. Ang‐(1‐7) was delivered at a dose of 24 μg/kg/hr by an osmotic pump implanted immediately after injury. Muscle function was measured via peroneal nerve stimulation. The tibialis anterior (TA) muscles were collected at day 14 after injury and processed for histological analyses and quantitative PCR (qPCR) analyses.ResultsOur data showed that treatment with Ang‐(1‐7) significantly increased muscle function 7 and 14 days after injury. However, we did not find any significant changes in fibrosis with Ang‐(1‐7) treatment.ConclusionsOur data suggests that Ang‐(1‐7) may be acting directly on the muscle tissue and/or the local microenvironment in order to promote restoration of muscle function.Support or Funding InformationSupported by pilot funding from the Wake Forest Baptist Health Hypertension and Vascular Research Center

GDF11 Treatment Attenuates the Recovery of Skeletal Muscle Function After Injury in Older Rats.

Loss of skeletal muscle mass and function results in loss of mobility for elderly patients. Novel therapies that can protect and/or restore muscle function during aging would have profound effects on the quality of life for this population. Growth differentiation factor 11 (GDF11) has been proposed as a "youthful" circulating factor that can restore cardiac, neural, and skeletal muscle functions in aging animals. However, conflicting data has been recently published that casts doubt on these assertions. We used a complex rat model of skeletal muscle injury that physiologically mimics injuries seen in patients; to investigate the ability of GDF11 and to enhance skeletal muscle regeneration after injury in older rats. Our data showed that GDF11 treatment resulted in a significant increase in tissue fibrosis, accompanied by attenuated functional recovery, as compared to animals treated with vehicle alone. GDF11 impaired the recovery of skeletal muscle function in older rats after injury.

Recovery Of Skeletal Muscle Function Is Not Augmented By Acute Resveratrol Supplementation After Injury

PURPOSE: Skeletal muscle function is significantly reduced after injury. Here, we attempted to hasten functional recovery of injured mouse tibalis anterior muscles with dietary resveratrol, a bioactive plant polyphenol. Importantly, resveratrol has been shown to promote differentiation of muscle cells in culture; however, its impact on muscle regeneration has not been adequately explored. METHODS: Mice were fed standard rodent chow with or without resveratrol (0.05%, w/w) 30 days prior to barium chloride-induced muscle injury. Experimental diets persisted throughout the recovery process and isometric torque of the anterior crural muscles and cross-sectional area of the regenerating tibialis anterior were analyzed at one, two, and three weeks following injury. RESULTS: Maximal isometric torque was reduced by 80 and 23% one and two weeks following injury in untreated mice, respectively. By three weeks, maximal isometric torque was not different from baseline indicating muscle function had recovered. Isometric torque and cross-sectional area of regenerating fibers were not different at any time point during recovery in resveratrol treated mice. CONCLUSION: Acute, low-dose resveratrol supplementation did not enhance functional or structural recovery of regenerating skeletal muscle after barium chloride-induced injury. Further research is likely required that explores different resveratrol dosing strategies and their effects on skeletal muscle regenerative processes.

Recovery of skeletal muscle function following injury is not augmented by acute resveratrol supplementation

Background and Aim: Skeletal muscle function is significantly reduced following traumatic muscle injury and complete recovery can take several weeks. Pharmacological agents like nonsteroidal anti-inflammatory drugs have been used to minimize pain and inflammation associated with muscle injury. However, their safety and efficacy to improve muscle repair have been challenged. To that end, safer and more effective treatment options remain to be identified. Accordingly, resveratrol use has numerous health benefits in clinical population. Further, resveratrol has been shown to promote myoblast differentiation in 0 vitro , which suggests it could be used to improve skeletal muscle regeneration in vivo. Methods: Experimental mice received resveratrol supplementation (0.05% wt/wt) 4 weeks prior to injury, which persisted throughout recovery. Muscle injury was induced by injecting a diluted barium chloride solution into the tibialis anterior (TA). Isometric tetanic and twitch torque of the anterior crural muscles were measured prior to the injury and 7, 14, or 21 days postinjury. Results: Resveratrol supplementation had no effect on preinjury isometric tetanic and twitch torque of the anterior crural muscles. Seven days after injury, tetanic torque production was reduced by 80% compared to preinjury values. Functional and structural recovery steadily improved at 14 days and was completed 21 days after injury. However, resveratrol treatment had no beneficial effects on isometric torque or regenerated fiber area. Conclusion: Acute, low-dose resveratrol supplementation did not improve functional or structural recovery of regenerating mouse TA after injury. Further research is likely required that explores alternate resveratrol dosing strategies and their effects on skeletal muscle repair processes.

Skeletal muscle functional recovery in the hyperlipidemic murine model of human vascular disease

Skeletal muscle functional recovery in the hyperlipidemic murine model of human vascular disease

Skeletal Muscle Force and Functional Exercise Tolerance Before and After Lung Transplantation: A Cohort Study

We investigated the impact of lung transplantation and outpatient pulmonary rehabilitation after lung transplantation on skeletal muscle function and exercise tolerance. Skeletal muscle force (Quadriceps force, QF), exercise tolerance (six minute walking distance, 6MWD) and lung function were assessed in 36 patients before and after lung transplantation. Seventeen male and 19 female patients (age 57 +/- 4) showed skeletal muscle weakness before the transplantation. A further 32 +/- 21% reduction was seen 1.2 (interquartile range 0.9 to 2.0) months after LTX. The number of days on the intensive care unit was significantly related to the observed deterioration in muscle force after LTX. At this time point 6MWD was comparable to pre-LTX. Rehabilitation started 37 (IQR 29 to 61) days after LTX. 6MWD and QF improved significantly (140 +/- 91 m, and 35 +/- 48%, respectively; p < 0.05) with rehabilitation. QF remained below pre-LTX values. The evolution of the 6MWD with the transplantation and the subsequent rehabilitation was less in female compared to male subjects. We conclude that muscle strength deteriorates after lung transplantation, particularly in patients with long ICU stay. Outpatient pulmonary rehabilitation is feasible after lung transplantation and leads to recovery of skeletal muscle function. In female patients this recovery is significantly less compared to male recipients.

The Effect of PEGylated Fibrin Injection On The Recovery Of Skeletal Muscle Function Following Ischemia‐Reperfusion Injury.

Ischemia/Reperfusion (I/R) injury can cause irreversible damage to muscle tissue. PEGylated Fibrin is an inert substance which can be used to deliver growth factors to improve regeneration in such irreversibly damaged muscle. In this study we evaluated the effect of PEGylated Fibrin injection on the recovery of skeletal muscles following the application of 4‐hour pneumatic tourniquets. There was no significant difference in force recovery between injection and non‐injection groups for the In Vivo force assessment (p=0.19), the In Situ force assessment (p=0.12) and the Specific tetanic tension of the muscle tissue (p=0.51). Histological assessment of the muscles did not reveal any significant differences between the injected and non‐injected muscle. While fibrin injection is known to induce an inflammatory response, it did not appear to affect recovery of function in these muscles. These results indicate that PEGylated fibrin gel has no detrimental effect on muscle tissue when injected, making it an appropriate material to deliver growth factors into skeletal muscle. This work was funded in part by the U.S. Army Medical Research and Material Command grant DAMD W81XWH‐06‐1‐0540 to RPF.

Delayed Recovery Of Skeletal Muscle Function In Dysferlin- deficient Mice Following Large-strain Lengthening Contractions

The mechanisms underlying skeletal muscle injuries caused by forceful lengthening (eccentric) contractions are poorly understood. Previously, we have found in rats that recovery from a single, large-strain lengthening contraction is independent of myogenesis, but dependent on a membrane repair process thought to involve dysferlin. PURPOSE: To test the hypothesis that recovery of function following large-strain lengthening contractions is inhibited in mice lacking dysferlin. METHODS: Wild type (WT, n = 3), male, C57Bl/6J mice and dysferlin-deficient A/J (n = 3) mice, 12–14 wks of age, were used as per IACUC approved protocols. Lengthening contractions were induced by superimposing 90°-170° of plantarflexion at 900°/s onto tetanic contractions of the dorsiflexors. Eight contractions (1 contraction/ 3 min) were used to produce a reproducible and significant loss of torque. We measured dorsiflexor torque before, immediately after, and at 1.5, 3, 5, 7, 14, and 21 d after injury. Fluorescein dextran (F-dx; 10 kDa) injected intraperitoneally, and plasma creatine kinase (CK) activity, were used to assess membrane damage. RESULTS: Repeated measures ANO VA with time and genotype as independent variables, and torque (% of pre-injury) as the dependent variable, followed by Tukey-Kramer post-hoc analysis were performed. On the day of injury, torque was 55 ± 4% in WT and 37 ± 1% in A/J of their respective pre-injury levels. Whereas A/J did not recover completely 21 d after injury (73 ± 1 %), WT completely recovered function 7 d after injury (100 ± 2 %). Membrane damage, measured as F-dx positive fibers, increased from 2 ± 0.5 % before injury to 26 ± 4% immediately after injury in WT, and remained high (29 ± 2%) at the end of the 7-d recovery period. In A/J, F-dx positive fibers increased from 12 ± 4 % to 43 ± 3 %, but decreased to 35 ± 4%, 7 d later. CONCLUSIONS: Dysferlin is necessary for normal recovery from injury by large-strain lengthening contractions. The presence of F-dx in WT fibers 7 d after injury suggests survival of those fibers. In contrast, the decrease in F-dx positive fibers in dysferlin-deficient TAs over time suggests that a population of injured fibers were lost, perhaps due to necrosis. The replacement of this population of fibers may require myogenesis, explaining the longer period of recovery in dysferlin-deficient A/J mice.

Resistance Training Improves Muscle Function and Body Composition in Patients With Hyperthyroidism

Bousquet-Santos K, Vaisman M, Barreto ND, Cruz-Filho RA, Salvador BA, Frontera WR, Nobrega AC. Resistance training improves muscle function and body composition in patients with hyperthyroidism. Objective To evaluate the effect of resistance training on skeletal muscle performance and body composition in patients with medically treated hyperthyroidism. Design Nonrandomized controlled trial. Setting Large public tertiary hospital. Participants Sixteen sedentary patients with recent clinical diagnosis and laboratory confirmation of hyperthyroidism (7 men, 9 women; age, 38±11y; weight, 58.4±2.6kg; height, 1.6±0.3m) were assigned to the control group (medical therapy; n=9) or training group (medical therapy associated with resistance training; n=7). An age- and sex-matched healthy group served as controls (3 men, 5 women; age, 40±3y; weight, 68.4±4.3kg; height, 1.6±0.3m). Intervention Resistance training twice a week for 16 weeks. Main Outcome Measures Peak muscular strength (by dynamometry and 1 repetition maximum method) and endurance (30% of peak force) for 7 movements and anthropometric measurements. Results The hyperthyroid patients as a group had lower baseline overall strength values when compared with healthy subjects (200.3±16.0kg vs 274.9±21.8kg, respectively; P=.006). Overall absolute increases in strength (49kg vs 91kg, P<.05) and endurance (78.5×10 2kg/s vs 176.9×10 2kg/s, P<.05) were higher in the training group compared with the control group. Body weight increased in both groups, but the sum of muscular circumference increased only in the training group (training group, 92.6±3.3cm vs 97.1±3.8cm; control group, 94.6±2.2cm vs 94.4±2.1cm; P<.05), with no change in the sum of skinfolds. Conclusions Resistance training accelerates the recovery of skeletal muscle function and promotes weight gain based on muscle mass improvement in patients with medically treated hyperthyroidism.

How muscles recover from paresis and atrophy after intramuscular injection of botulinum toxin A: Study in juvenile rats

Botulinum toxin A (BoNT-A) is a potent biological toxin widely used for the management of skeletal muscle spasticity or dynamic joint contracture. Intramuscular injection of BoNT-A causes muscle denervation, paresis, and atrophy. This clinical effect of botulinum toxin A lasts 3 to 6 months, and injected muscle eventually regains muscle mass and recovers muscle function. The goal of the present study was to characterize the molecular and cellular mechanisms leading to neuromuscular junction (NMJ) regeneration and skeletal muscle functional recovery after BoNT-A injection. Fifty-six 1-month-old Sprague-Dawley rats were used. Botulinum toxin A was injected into the left gastrocnemius muscle at a dosage of 6 units/kg body weight. An equivalent volume of saline was injected into the right gastrocnemius muscle to serve as control. The gastrocnemius muscle samples were harvested from both hind limbs at 3 days, 7 days, 15 days, 30 days, 60 days, 90 days, 180 days, and 360 days after administration of toxin. In addition, the gastrocnemius muscles from 1-month-old rats with no injections were harvested to serve as uninjected control group. Muscle samples were processed and mRNA was extracted. Real-time polymerase chain reaction (PCR) and gene microarray technology were used to identify key molecules involved in NMJ stabilization and muscle functional recovery. More than 28,000 rat genes were analyzed and approximately 9000 genes are expressed in the rat gastrocnemius muscle. Seven days following BoNT-A injection, 105 genes were upregulated and 59 genes were downregulated. Key molecules involved in neuromuscular junction (NMJ) stabilization and muscle functional recovery were identified and their time course of gene expression following BoNT-A injection were characterized. This animal study demonstrates that following intramuscular injection of BoNT-A, there is a sequence of cellular events that eventually leads to NMJ stabilization, remodeling, and myogenesis and muscle functional recovery. This recovery process is divided into two stages (aneural and neural) and that the IGF-1 signaling pathway play a central role in the process.

Microscopic changes at the neuromuscular junction in free muscle transfer.

Free muscle transfers do not generate the same force after transfer as that at the original sites. Light and electron microscopy were used to study serially during 30 weeks the changes at the neuromuscular junction after free muscle transfer of the gracilis muscle in the adult Wistar rat. Under light microscopy, after staining with acetylthiocholine the neuromuscular junction showed changes of degeneration with withdrawal of the innervating axon terminal followed by regeneration and reconstitution of the neuromuscular junction. The newly formed neuromuscular junction still lacked the structural detail seen in the control neuromuscular junction, even after 30 weeks. With the electron microscope, mitochondrial swelling and clumping of the synaptic vesicles were followed by withdrawal of the axon terminal from the muscle membrane on denervation. The infolding of the muscle membrane at the neuromuscular junction became less prominent. With reinnervation the ultrastructure of the junction was only partially reestablished with poorly reconstituted primary and secondary folds of the muscle membrane 30 weeks after the transfer. Failure of complete reformation of the ultrastructure of the neuromuscular junction may provide another explanation for failure of full recovery of skeletal muscle function after free muscle transfer.

RESISTANCE TRAINING IMPROVES SKELETAL MUSCLE FUNCTION IN HYPERTHYROIDISM

Hyperthyroidism is associated with general muscle atrophy and weakness, compromising the patient's quality of life. Although resistance training improves muscle function in subjects with several chronic diseases, its impact in hyperthyroidism is still unknown. PURPOSE: To determine the effect of resistance training on the recovery of skeletal muscle function of patients with hyperthyroidism. METHODS: Patients from the university hospital with the clinical diagnosis and laboratory confirmation of Graves' disease (age: 49 ± 5yr) were submitted, before treatment and 4 months later, to anthropometric measurements (height, weigth, skinfolds and circumferences) and determination of muscular peak strength and endurance (sustaining 30% of peak force). Five movements were evaluated: handgrip by dynamometry, and knee extension, knee flexion, ankle plantar flexion, and supine benchpress by 1-RM (one repetition maximum). After the first evaluation, the patients were assigned to one of two groups: 1) Control (C: standard drug treatment; n = 11) and 2) Training (T: drug treatment plus individualized progressive resistance training twice/week; n = 7). RESULTS: Body weight increased in both groups (p < 0.05), while sum of circunferences increased only in T (p < 0.05) with no change in the sum of skinfolds (p > 0.05). Contrasting to some improvements in force and endurance in C group, all movements presented higher results for both peak force and endurance in T (p < 0.05). Overall absolute increase in strength (C: 46 kg vs T: 91 kg; p = 0.001) and endurance (C: 6634 kg·s vs T: 17688 kg·s; p = 0.022) were higher in T. CONCLUSION: Resistance training seems to increase muscle mass and facilitates the recovery of muscle performance in patients with hyperthyroidism undergoing pharmacological treatment. These results suggest that resistance training may improve the quality of life of those patients and, therefore, should have practical implications in the clinical setting.