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Muscle Atrophy (muscle + atrophy)
Selected AbstractsMolecular mechanisms activating muscle protein degradation in chronic kidney disease and other catabolic conditionsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2005J. Du Abstract Muscle atrophy is a prominent feature of chronic kidney disease (CKD) and is frequent in other catabolic conditions. Results from animal models of these conditions as well as patients indicate that atrophy is mainly owing to accelerated muscle proteolysis in the ubiquitin-proteasome (Ub-P'some) proteolytic system. The Ub-P'some system, however, rapidly degrades actin or myosin but cannot breakdown actomyosin or myofibrils. Consequently, another protease must initially cleave the complex structure of muscle. We identified caspase-3 as an initial and potentially rate-limiting proteolytic step that cleaves actomyosin/myofibrils to produce substrates degraded by the Ub-P'some system. In rodent models of CKD and other catabolic conditions, we find that caspase-3 is activated and cleaves actomyosin to actin, myosin and their fragments. This initial proteolytic step in muscle leaves a characteristic footprint, a 14-kDa actin band, providing a potential diagnostic tool to detect muscle catabolism. We also found that stimulation of caspase-3 activity depends on inhibition of IRS-1-associated phosphatidylinositol 3-kinase (PI3K) activity; inhibiting PI3K in muscle cells also leads to expression of a critical E3-ubiquitin-conjugating enzyme involved in muscle protein breakdown: atrogin-1/MAFbx. Thus, protein breakdown by caspase-3 and the ubiquitin-proteasome system in muscle are stimulated by the same signal: a low PI3K activity. These responses could yield therapeutic strategies to block muscle atrophy. [source] Inflammatory myositis in systemic sclerosis: a South Australian perspectiveINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2005T. Y.-T. Abstract Background:, Muscle atrophy and weakness occurs commonly in patients with systemic sclerosis, especially late in the course of the disease. However, profound proximal muscle weakness secondary to myositis is an infrequent finding. Aim:, To determine the frequency and disease characteristics of patients with myositis in our cohort of systemic sclerosis patients. Methods:, A retrospective case note review of the clinical course of all patients enrolled on the South Australian scleroderma register, a population-based register of 374 living and 234 deceased patients with systemic sclerosis, last updated to the end of December 2002. Results:, Twenty patients with myositis were identified, the majority with diffuse cutaneous systemic sclerosis and overlap syndromes. The calculated frequency of this complication was 3.3% in our population-based cohort. All patients suffered profound proximal muscle weakness complicated by functional impairment. Other clinical features included weakness of cervical musculature (15%), dyspnoea (10%) and dysphagia (10%). Creatine kinase level was elevated in 80% of the patients, with the mean peak creatine kinase level of 1129 U/L. When further investigations were undertaken, 80% of patients demonstrated myopathic changes on electromyography and 92% of patients were found to have histological findings characteristic of an inflammatory process. Positive antinuclear antibodies were identified in all patients, including two with anti-PM-Scl autoantibodies. Conclusion:, Myositis is an infrequent clinical feature in patients with systemic sclerosis. Profound proximal weakness in association with elevated creatine kinase levels and myopathic changes on electromyography should alert the clinician to this complication. The presence of anti-PM-Scl autoantibodies in association with overlap syndromes may have a more favourable prognostic significance. [source] Neuromuscular Electrical Stimulation As a Possible Means to Prevent Muscle Tissue Wasting in Artificially Ventilated and Sedated Patients in the Intensive Care Unit: A Pilot StudyNEUROMODULATION, Issue 4 2010Raf L.J. Meesen PhD Objective:, The aim of this study was to explore if electrical stimulation could prevent muscle atrophy. Material and Methods:, Patients were hospitalized for postoperative coronary artery bypass graftin, chronic obstructive pulmonary disease, ventilatory failure, or acute cerebro-vascular accident, and were divided into an intervention group or a control group. The intervention group underwent daily 30 minute training with an intermittent neuromuscular electrical stimulation applied to the right quadriceps muscle. Heart rate, respiration rate, systolic and diastolic blood pressure, and oxygen saturation were monitored before, during, and after electrical stimulation. Circumference of both thighs was measured. Results:, The intervention resulted in a significant reduction of muscle atrophy in the stimulated as compared with the non-stimulated limb (p < 0.05), without making any impact on cardiovascular, respiratory and, hemodynamic characteristics. Conclusions:, Muscle atrophy is prevented by intermittent neuromuscular electrical stimulation while this intervention showed no obvious impact on the cardio-respiratory conditions of the patients. [source] Differentiation rather than aging of muscle stem cells abolishes their telomerase activityBIOTECHNOLOGY PROGRESS, Issue 4 2009Matthew S. O'Connor Abstract A general feature of stem cells is the ability to routinely proliferate to build, maintain, and repair organ systems. Accordingly, embryonic and germline, as well as some adult stem cells, produce the telomerase enzyme at various levels of expression. Our results show that, while muscle is a largely postmitotic tissue, the muscle stem cells (satellite cells) that maintain this biological system throughout adult life do indeed display robust telomerase activity. Conversely, primary myoblasts (the immediate progeny of satellite cells) quickly and dramatically downregulate telomerase activity. This work thus suggests that satellite cells, and early transient myoblasts, may be more promising therapeutic candidates for regenerative medicine than traditionally utilized myoblast cultures. Muscle atrophy accompanies human aging, and satellite cells endogenous to aged muscle can be triggered to regenerate old tissue by exogenous molecular cues. Therefore, we also examined whether these aged muscle stem cells would produce tissue that is "young" with respect to telomere maintenance. Interestingly, this work shows that the telomerase activity in muscle stem cells is largely retained into old age wintin inbred "long" telomere mice and in wild-derived short telomere mouse strains, and that age-specific telomere shortening is undetectable in the old differentiated muscle fibers of either strain. Summarily, this work establishes that young and old muscle stem cells, but not necessarily their progeny, myoblasts, are likely to produce tissue with normal telomere maintenance when used in molecular and regenerative medicine approaches for tissue repair. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source] The adaptive responses in several mediators linked with hypertrophy and atrophy of skeletal muscle after lower limb unloading in humansACTA PHYSIOLOGICA, Issue 2 2009K. Sakuma Abstract Aim:, To determine the adaptive changes in several molecules regulating muscle hypertrophy and atrophy after unloading, we examined whether unilateral lower limb suspension changes the mRNA and protein levels of SRF-linked (RhoA, RhoGDI, STARS and SRF), myostatin-linked (myostatin, Smad2, Smad3 and FLRG) and Foxo-linked (P-Akt, Foxo1, Foxo3a and Atrogin-1) mediators. Methods:, A single lower limb of each of eight healthy men was suspended for 20 days. Biopsy specimens were obtained from the vastus lateralis muscle pre- and post-suspension. Results:, The volume of the vastus lateralis muscle was significantly decreased after unloading. The amount of RhoA, RhoGDI or SRF protein in the muscle was not significantly changed post-suspension. An RT-PCR semiquantitative analysis showed increased levels of myostatin mRNA but not Smad2, Smad3 or FLRG mRNA. Unloading did not elicit significant changes in the amount of p-Smad3 or myostatin protein in the muscle. The amount of p-Akt protein was markedly reduced in the unloaded muscle. Lower limb suspension did not influence the expression pattern of Foxo1, Foxo3a or Atrogin-1. Conclusion:, Unloading inducing a mild degree of muscle atrophy may decrease p-Akt and increase myostatin but not SRF-linked mediators. [source] Changes in capillary luminal diameter in rat soleus muscle after hind-limb suspensionACTA PHYSIOLOGICA, Issue 4 2000Kano This study examined the time course change of the capillary luminal diameter and the number of capillaries in the rat soleus muscle during hind-limb suspension. Male Wistar rats were divided into 1 and 3 weeks of hind-limb suspension (HS) groups (HS-1 and HS-3). The HS groups were compared with age-matched control groups. All morphometric parameters with respect to capillary and muscle fibre cross-sectional area were determined in perfusion-fixed soleus muscles. After 1 and 3 weeks of hind-limb suspension, the mean muscle fibre cross-sectional area was significantly decreased in HS-1 (,32.0%) and HS-3 (,59.3%) compared with age-matched control groups. Despite a lower capillary-to-fibre ratio (HS-1, ,19.3%; HS-3, ,21.2%), the capillary density was unchanged in HS-1 and significantly increased in HS-3 compared with age-matched control groups. The mean capillary luminal diameter was significantly smaller in HS-1 (,19.9%) and HS-3 (,21.9%) than in the age-matched control groups. The capillary-to-fibre perimeter ratio which indicates the capillary surface area available for gas exchange between blood and tissue did not significantly differ between control groups and HS groups. In conclusion, the morphometrical adaptations in rat soleus with the suspension involved changes in both the capillary luminal diameter and number of capillaries, and the change in capillary surface area was proportional to the degree of muscle atrophy in HS groups. [source] Storage-associated artefact in equine muscle biopsy samplesEQUINE VETERINARY JOURNAL, Issue 1 2009R. L. Stanley Summary Reasons for performing study: Muscle biopsy is increasingly used in equine veterinary practice for investigating exertional, inflammatory or immune mediated myopathies and unexplained muscle atrophy. Although formalin-fixed samples are often used, for complete evaluation, fresh-frozen tissue is required. Freezing muscle in veterinary practice is impractical: samples sent to specialist laboratories for processing are therefore susceptible to delays, potentially leading to artefact and compromising histological interpretation. Hypothesis: Altered temperature, duration and hydration status influence the severity of storage-induced artefact in equine muscle. Methods: Skeletal muscle obtained immediately post euthanasia was divided into 6 independent samples from each of 8 horses. One sample per horse was frozen immediately in isopentane precooled in liquid nitrogen. Additional samples were stored in conditions designed to mimic possible situations encountered in practice, including increased storage times, temperature and hydration status. Following storage, stored samples were frozen as before. Cryosections were stained using haematoxylin and eosin and ranked for artefact on 2 occasions by 2 blinded observers. The best samples were processed subsequently with a panel of routine stains and immunolabelled for collagen V to enable the measurement of minimum fibre diameters. Results: Both prolonged storage and increased hydration resulted in more storage-associated artefact. Samples stored for 24 h chilled on dry gauze were ranked higher than those stored on damp gauze; however, a panel of routinely-used histochemical staining techniques was unaffected by chilled 24 h storage. There was no significant effect of storage on mean fibre diameter; however, both chilled dry and damp storage for 24 h caused a significant increase in fibre-size variability. Conclusion and potential relevance: Caution should be exercised when interpreting fibre size profiles in shipped samples. Equine muscle biopsy samples are optimally shipped in dry gauze, sealed in plastic containers and shipped on ice packs to be processed within 24 h and can thus be interpreted by the receiving laboratory with minimal artefact. [source] Molecular mechanisms activating muscle protein degradation in chronic kidney disease and other catabolic conditionsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2005J. Du Abstract Muscle atrophy is a prominent feature of chronic kidney disease (CKD) and is frequent in other catabolic conditions. Results from animal models of these conditions as well as patients indicate that atrophy is mainly owing to accelerated muscle proteolysis in the ubiquitin-proteasome (Ub-P'some) proteolytic system. The Ub-P'some system, however, rapidly degrades actin or myosin but cannot breakdown actomyosin or myofibrils. Consequently, another protease must initially cleave the complex structure of muscle. We identified caspase-3 as an initial and potentially rate-limiting proteolytic step that cleaves actomyosin/myofibrils to produce substrates degraded by the Ub-P'some system. In rodent models of CKD and other catabolic conditions, we find that caspase-3 is activated and cleaves actomyosin to actin, myosin and their fragments. This initial proteolytic step in muscle leaves a characteristic footprint, a 14-kDa actin band, providing a potential diagnostic tool to detect muscle catabolism. We also found that stimulation of caspase-3 activity depends on inhibition of IRS-1-associated phosphatidylinositol 3-kinase (PI3K) activity; inhibiting PI3K in muscle cells also leads to expression of a critical E3-ubiquitin-conjugating enzyme involved in muscle protein breakdown: atrogin-1/MAFbx. Thus, protein breakdown by caspase-3 and the ubiquitin-proteasome system in muscle are stimulated by the same signal: a low PI3K activity. These responses could yield therapeutic strategies to block muscle atrophy. [source] The mammalian exercise pressor reflex in health and diseaseEXPERIMENTAL PHYSIOLOGY, Issue 1 2006Scott A. Smith The exercise pressor reflex (a peripheral neural reflex originating in skeletal muscle) contributes significantly to the regulation of the cardiovascular system during exercise. Exercise-induced signals that comprise the afferent arm of the reflex are generated by activation of mechanically (muscle mechanoreflex) and chemically sensitive (muscle metaboreflex) skeletal muscle receptors. Activation of these receptors and their associated afferent fibres reflexively adjusts sympathetic and parasympathetic nerve activity during exercise. In heart failure, the cardiovascular response to exercise is augmented. Owing to the peripheral skeletal myopathy that develops in heart failure (e.g. muscle atrophy, decreased peripheral blood flow, fibre-type transformation and reduced oxidative capacity), the exercise pressor reflex has been implicated as a possible mechanism by which the cardiovascular response to physical activity is exaggerated in this disease. Accumulating evidence supports this conclusion. This review therefore focuses on the role of the exercise pressor reflex in regulating the cardiovascular system during exercise in both health and disease. Updates on our current understanding of the exercise pressor reflex neural pathway as well as experimental models used to study this reflex are presented. In addition, special emphasis is placed on the changes in exercise pressor reflex activity that develop in heart failure, including the contributions of the muscle mechanoreflex and metaboreflex to this pressor reflex dysfunction. [source] The molecular chaperone HSP47 rapidly senses gravitational changes in myoblastsGENES TO CELLS, Issue 11 2006Asami Oguro Skeletal muscle unloading induced by spaceflight or bed rest leads to muscle atrophy. It is unclear how muscle atrophy is caused and how muscles respond to microgravity. We addressed the response of collagen and its chaperone system to gravitational forces. We show here that expression of HSP47, a collagen-specific molecular chaperone, responds to gravitational changes, including microgravity and hypergravity in vitro and in vivo. By using the method hindlimb suspension of rats, which mimics microgravity conditions, we demonstrated that the expression of Hsp47 mRNA decreased within 1 day and the mRNA levels of collagen types I and IV were subsequently reduced. In contrast, hypergravity stimulated HSP47 expression. HSP47 and collagen types I and IV were localized intracellularly in the endoplasmic reticulum and/or Golgi apparatus of myoblasts, as expected. Intriguingly, Hsp47 mRNA levels in cultured myoblasts increased significantly with hypergravity treatment at 40G for 2 h, and decreased with microgravity treatment at almost 0G for 1,2 h. Collagen mRNA levels were also altered, although changes were slower and less pronounced compared with those for HSP47. The gravity-regulated HSP47 may play a role in the maintenance of the extracellular matrix by modulating collagen production at the primary stage of adaptation. [source] Pathogenesis of haemophilic synovitis: clinical aspectsHAEMOPHILIA, Issue 2007W. K. HOOTS Summary., Arthropathy remains a major cause of morbidity in patients with haemophilia. Frequent bleeding into the joints leads to joint damage with resultant contractures, joint deformities and arthritis. This in turn leads to muscle atrophy, limited physical activity, osteoporosis and disability. Even though several studies of prophylactic factor replacement for persons with severe haemophilia demonstrate improved joint function, this therapy is still not readily available to most people with haemophilia around the world and a universal treatment protocol has not been used. In this article, we discuss key issues in the treatment of severe haemophilia: the optimal timing of initiation and termination of therapy, dosing options and goals of therapy. The options for countries where prophylaxis is not readily available are also discussed. Most studies are small and not randomized making consensus treatment recommendations difficult to formulate. Randomized, clinical trials are needed to provide the answers regarding the optimal treatment of patients with severe haemophilia. [source] Testosterone Supplementation Therapy for Older Men: Potential Benefits and RisksJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 1 2003David A. Gruenewald MD Serum testosterone levels decline gradually and progressively with aging in men. Many manifestations associated with aging in men, including muscle atrophy and weakness, osteoporosis, reduced sexual functioning, and increased fat mass, are similar to changes associated with testosterone deficiency in young men. These similarities suggest that testosterone supplementation may prevent or reverse the effects of aging. A MEDLINE search was performed to identify studies of testosterone supplementation therapy in older men. A structured, qualitative review was performed of placebo-controlled trials that included men aged 60 and older and evaluated one or more physical, cognitive, affective, functional, or quality-of-life outcomes. Studies focusing on patients with severe systemic diseases and hormone deficiencies related to specific diseases were excluded. In healthy older men with low-normal to mildly decreased testosterone levels, testosterone supplementation increased lean body mass and decreased fat mass. Upper and lower body strength, functional performance, sexual functioning, and mood were improved or unchanged with testosterone replacement. Variable effects on cognitive function were reported, with improvements in some cognitive domains (e.g., spatial, working, and verbal memory). Testosterone supplementation improved exercise-induced coronary ischemia in men with coronary heart disease, whereas angina pectoris was improved or unchanged. In a few studies, men with low testosterone levels were more likely to experience improvements in lumbar bone mineral density, self-perceived functional status, libido, erectile function, and exercise-induced coronary ischemia with testosterone replacement than men with less marked testosterone deficiency. No major unfavorable effects on lipids were reported, but hematocrit and prostate specific antigen levels often increased. Based on these results, testosterone supplementation cannot be recommended at this time for older men with normal or low-normal testosterone levels and no clinical manifestations of hypogonadism. However, testosterone replacement may be warranted in older men with markedly decreased testosterone levels, regardless of symptoms, and in men with mildly decreased testosterone levels and symptoms or signs suggesting hypogonadism. The long-term safety and efficacy of testosterone supplementation remain uncertain. Establishment of evidence-based indications will depend on further demonstrations of favorable clinical outcomes and symptomatic, functional, and quality-of-life benefits in carefully performed, long-term, randomized, placebo-controlled clinical trials. J Am Geriatr Soc 51:101,115, 2003. [source] Amyotrophic lateral sclerosis: all roads lead to RomeJOURNAL OF NEUROCHEMISTRY, Issue 5 2007Jose-Luis Gonzalez de Aguilar Abstract Amyotrophic lateral sclerosis (ALS) is the most frequent adult-onset motor neuron disease characterized by degeneration of upper and lower motor neurons, generalized weakness and muscle atrophy. Most cases of ALS appear sporadically but some forms of the disease result from mutations in the gene encoding the antioxidant enzyme Cu/Zn superoxide dismutase (SOD1). Several other mutated genes have also been found to predispose to ALS including, among others, one that encodes the regulator of axonal retrograde transport dynactin. As all roads lead to the proverbial Rome, we discuss here how distinct molecular pathways may converge to the same final result that is motor neuron death. We critically review the basic research on SOD1-linked ALS to propose a pioneering model of a ,systemic' form of the disease, causally involving multiple cell types, either neuronal or non-neuronal. Contrasting this, we also postulate that other neuron-specific defects, as those triggered by dynactin dysfunction, may account for a primary motor neuron disease that would represent ,pure' neuronal forms of ALS. Identifying different disease subtypes is an unavoidable step toward the understanding of the physiopathology of ALS and will hopefully help to design specific treatments for each subset of patients. [source] Lower leg muscle atrophy in ankle osteoarthritisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 12 2006Victor Valderrabano Abstract The aim of this study was to determine changes in the lower leg muscles associated with ankle osteoarthritis. Fifteen unilateral ankle osteoarthritis patients and fifteen age-gender-matched normal subjects were assessed with clinical [osteoarthritis latency time, pain, alignment, AOFAS ankle score, ankle range of motion (ROM), calf circumference], radiological (ankle osteoarthritis grading), and muscular-physiological parameters [isometric maximal voluntary ankle torque, surface electromyography of the anterior tibial (AT), medial gastrocnemius (MG), soleus (SO), and peroneus longus (PL) muscle]. The osteoarthritis patients had increased pain (6.8 points) and reduced AOFAS score (33.7 points) compared to the control group. Compared to the contralateral healthy leg, the arthritic leg showed reduced mean dorsi-/plantar flexion ROM (16.0°), reduced mean calf circumference (2.1 cm), smaller mean dorsiflexion (16.4 Nm) and plantar flexion (15.8 Nm) torques, lower mean electromyography frequency for all muscles (AT ,22.6 Hz; MG ,27.3 Hz; SO ,25.9 Hz; PL ,28.5 Hz), and lower mean electromyography intensity in the AT [,28.0,×,103 (µv)2], MG [,13.3,×,103 (µv)2], and PL [,12.8,×,103 (µv)2]. SO mean electromyography intensity was not significantly changed [+2.0,×,103 (µv)2]. Unilateral ankle osteoarthritis is associated with atrophic changes of the lower leg muscles. This study supports previous observations on muscle dysfunction in knee osteoarthritis. © 2006 Orthopaedic Research Society. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] Acute botulinum toxin-induced muscle weakness in the anterior cruciate ligament-deficient rabbitJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2005David Longino Abstract We established botulinum type-A toxin (BTX-A) injections as a powerful tool to cause knee extensor weakness in New Zealand White (NZW) rabbits. The purpose of this study was to determine if BTX-A induced quadriceps weakness causes muscle dysfunction beyond that caused by anterior cruciate ligament (ACL) transection in the knee of NZW rabbits. Twenty animals were randomly divided into four study groups (n = 5 each); uninjected controls, BTX-A injection alone, ACL transection alone, BTX-A injection and ACL transection combined. Isometric knee extensor torque, quadriceps muscle mass, and vertical and anterior,posterior ground reaction forces were measured four weeks post single (BTX-A and ACL), unilateral intervention. Muscle weakness, muscle atrophy and decrease in ground reaction forces were all significantly greater for the experimental compared to the untreated contralateral legs. BTX-A injection produced a greater deficit in quadriceps mass and knee extensor torque than ACL transection alone, but produced smaller deficits in the ground reaction forces. ACL transection superimposed on BTX-A injection did not change either knee extensor torque production or muscle mass. Together these results suggest that BTX-A injection causes great force and muscle mass deficits, and affects functional gait in a significant manner, but it has no measurable functional effect when superimposed on ACL transection, at least not in the acute protocol tested here. Hopefully, BTX-A injection for acutely enhancing the degree of muscle weakness in otherwise untreated animals, or in experimental models of osteoarthritis, will help in investigating the role of muscle weakness in joint degeneration. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Early reattachment does not reverse atrophy and fat accumulation of the supraspinatus,an experimental study in rabbitsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2003Hans K. Uhthoff Abstract Introduction: Reattachment of the supraspinatus (SSP) tendon after spontaneous rupture leads to improved shoulder function. Whether this improvement of function is due to a reversal of muscle atrophy and fat accumulation known to occur after SSP rupture is still debated. Our previous study of late reattachment of SSP (12 weeks) failed to confirm a reversal of muscle atrophy and of fat accumulation. Purpose: To find out whether earlier reattachment (6 weeks) reverses atrophy and fat accumulation of the SSP. Material and methods: Reattachment group: in seven rabbits unilateral supraspinatus detachment, reattachment after 6 weeks and killing 6 weeks later. Detachment group: in seven rabbits unilateral supraspinatus detachment and killing 12 weeks later. The contralateral shoulders served as controls (n = 14). Determination of the supraspinatus constituents: muscle, extra- and intramuscular fat in volume and cross-sectional area. Results: Muscle tissue in the reattachment group (8.6 ml ± 1 s.d. = 0.6) and in the detachment group (8.9 ml ± 0.9) were less than in control supraspinati (10.2 ml ± 0.9, both p < 0.05). Extra- and intramuscular fat in the reattachment group (8.7% ± 3.2) was greater than in both, the detachment group (4.6% ± 3.5), and control supraspinati (2.8% ± 1.7, both p < 0.05). Conclusion: In the rabbit, reattachment of the SSP at 6 weeks did neither reverse muscle atrophy nor fat accumulation during the ensuing 6 weeks. However, earlier reattachment (6 weeks) when compared with later reattachment (12 weeks) prevented an increase in fat accumulation. On the other hand, the delay before reattaching the tendon did not lead to an increase in muscle atrophy. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] A Neurologic Syndrome in Golden Retrievers Presenting as a Sensory Ataxic NeuropathyJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 6 2007K. Hultin Jäderlund Background: A sensory ataxic neuropathy has been observed in Swedish Golden Retrievers recently. Animals: Twenty-one affected Golden Retrievers. Methods: Clinical and neurologic status, electrophysiologic, and pathologic status as well as pedigree analyses were evaluated. Results: Clinical signs had an insidious onset between 2 and 8 months of age and a slowly progressive course. Affected dogs were ataxic and dysmetric. They had abnormal postural reactions and decreased spinal reflexes but no apparent muscle atrophy. Clinical pathology, radiography, and electrophysiology of motor systems were all within reference values. Sensory nerve conduction results of affected dogs were significantly different from those of a group of control dogs. Necropsy revealed a chronic progressive central and peripheral sensorimotor axonopathy; the proprioceptive pathways were most severely affected. Conclusions and Clinical Importance: This disease in these Golden Retrievers is distinct from other canine breed-related neurodegenerative diseases or hereditary neurodegenerative diseases described in humans. Pedigree analyses indicated a hereditary background, but the mode of inheritance could not be established. [source] Time-dependent expression of myostatin RNA transcript and protein in gastrocnemius muscle of mice after sciatic nerve resectionMICROSURGERY, Issue 5 2007Chenxin Shao M.D. Myostatin, a member of the transforming growth factor-, (TGF-,) superfamily, has been identified as a negative regulator of skeletal muscle mass. To provide more data on the role of myostatin in denervation-induced muscle atrophy, we examined the time-dependent changes in myostatin mRNA and protein as well as Smad2 and phospho-Smad2 protein levels in the denervated gastrocnemius muscle of mice after sciatic neurectomy, using quantitative real-time RT-PCR and Western blotting, respectively. We conducted morphometric analyses to measure the wet weight ratio of the denervated muscle (the operated side/contralateral nonoperated side) and the cross-sectional area of muscle fibers, and observed the morphology of denervated muscle. The experimental results showed that in the early stage of denervation, the levels of myostatin mRNA and protein in the denervated gastrocnemius muscle increased instantly, reaching a peak at day 3 and day 7 after sciatic neurectomy, respectively, when compared with the normal values. In addition, the phospho-Smad2 protein was observed to have a similar expression profile to that of the myostatin mRNA. The present study perhaps opens a new window into myostatin modulation in muscle atrophy due to denervation. © 2007 Wiley-Liss, Inc. Microsurgery, 2007. [source] Muscle biopsy substantiates long-term MRI alterations one year after a single dose of botulinum toxin injected into the lateral gastrocnemius muscle of healthy volunteers,MOVEMENT DISORDERS, Issue 10 2009A. Sebastian Schroeder MD Abstract Despite numerous clinical and experimental studies on botulinum toxin type A (BoNT/A), long-term alterations of muscle texture and fine structure following BoNT/A treatment have thus far not been studied in normal human skeletal muscle. After obtaining institutional review board approval, we performed a prospective, placebo-controlled, double-blinded follow-up study on two healthy adults using magnetic resonance imaging (MRI) and muscle biopsy to visualize long-term alterations after a single BoNT/A injection into the lateral head of the gastrocnemius muscle. MRI disclosed a high-signal-intensity pattern in short tau inversion recovery sequences, and a reduction of the cross-sectional area in the BoNT/A-injected, but not in the saline-injected contralateral control muscle (at 6 to 9 months in volunteer A: 73%, in B: 62%; at 12 months in A: 88%, and in B: 78%). Enzyme histochemistry, 12 months after injection, confirmed neurogenic atrophy of muscle fibers only in the BoNT/A-injected muscle. Electron microscopy revealed additional degenerative changes at the neuromuscular junction. The data confirm that MRI is a suitable tool to monitor the long-term effect of BoNT/A on skeletal muscle. Neurogenic muscle atrophy following a single BoNT/A injection should be taken into consideration when repeated BoNT/A injections into the same muscles are proposed. © 2009 Movement Disorder Society [source] Muscle ultrasound in neuromuscular disordersMUSCLE AND NERVE, Issue 6 2008Sigrid Pillen MD Abstract Muscle ultrasound is a useful tool in the diagnosis of neuromuscular disorders, as these disorders result in muscle atrophy and intramuscular fibrosis and fatty infiltration, which can be visualized with ultrasound. Several prospective studies have reported high sensitivities and specificities in the detection of neuromuscular disorders. Although not investigated in large series of patients, different neuromuscular disorders tend to show specific changes on muscle ultrasound, which can be helpful in differential diagnosis. For example, Duchenne muscular dystrophy results in a severe, homogeneous increase of muscle echo intensity with normal muscle thickness, whereas spinal muscular atrophy shows an inhomogeneous increase of echo intensity with severe atrophy. A major advantage of muscle ultrasound, compared to other imaging techniques, is its ability to visualize muscle movements, such as muscle contractions and fasciculations. This study reviews the possibilities and limitations of ultrasound in muscle imaging and its value as a diagnostic tool in neuromuscular disorders. Muscle Nerve, 2008 [source] Dissociated small hand muscle atrophy in amyotrophic lateral sclerosis: Frequency, extent, and specificityMUSCLE AND NERVE, Issue 4 2008Satoshi Kuwabara MD Abstract Previous studies suggest that in amyotrophic lateral sclerosis (ALS) the abductor pollicis brevis (APB) and first dorsal interosseous (FDI) are more severely involved than abductor digiti minimi (ADM). To elucidate the pattern, frequency, extent, and specificity of such dissociated muscle atrophy in ALS, compound muscle action potentials recorded from APB, FDI, and ADM were analyzed in 77 ALS patients, 171 normal controls, and 196 disease controls. Compared with normal controls, ALS patients had a reduced APB/ADM amplitude ratio (P < 0.001) and FDI/ADM ratio (P < 0.001), whereas patients with other anterior horn diseases showed similar APB/ADM and FDI/ADM ratios to normal values. Decreased APB/ADM ratio was found in 41% of ALS patients, 5% of normal controls, and 4% of disease controls. Prominent muscle atrophy in APB and FDI, with relatively preserved ADM, appears to be specific to ALS. Dissociated hand muscle atrophy presumably reflects part of the pathophysiology and supports the diagnosis of ALS. Muscle Nerve, 2008 [source] Neuromuscular electrical stimulation in neurorehabilitation,MUSCLE AND NERVE, Issue 5 2007Lynne R. Sheffler MD Abstract This review provides a comprehensive overview of the clinical uses of neuromuscular electrical stimulation (NMES) for functional and therapeutic applications in subjects with spinal cord injury or stroke. Functional applications refer to the use of NMES to activate paralyzed muscles in precise sequence and magnitude to directly accomplish functional tasks. In therapeutic applications, NMES may lead to a specific effect that enhances function, but does not directly provide function. The specific neuroprosthetic or "functional" applications reviewed in this article include upper- and lower-limb motor movement for self-care tasks and mobility, respectively, bladder function, and respiratory control. Specific therapeutic applications include motor relearning, reduction of hemiplegic shoulder pain, muscle strengthening, prevention of muscle atrophy, prophylaxis of deep venous thrombosis, improvement of tissue oxygenation and peripheral hemodynamic functioning, and cardiopulmonary conditioning. Perspectives on future developments and clinical applications of NMES are presented. Muscle Nerve, 2007 [source] Novel dysferlin mutations and characteristic muscle atrophy in late-onset Miyoshi myopathyMUSCLE AND NERVE, Issue 5 2004Naoki Suzuki MD Abstract Miyoshi myopathy is characterized by weakness of the calf muscles during early adulthood. We report a case of late-onset Miyoshi myopathy presenting at 48 years of age, with novel mutations in the dysferlin gene. Muscle computed tomography clearly revealed severe atrophy in the soleus and medial gastrocnemius muscles. Even older patients with atrophy in the posterior compartment of the distal lower extremities and a relatively high serum creatine kinase level should be examined for the dysferlin gene. Muscle Nerve 29: 721,723, 2004 [source] Disease progression in amyotrophic lateral sclerosis: Predictors of survivalMUSCLE AND NERVE, Issue 5 2002T. Magnus MD Abstract Predicting the rate of disease progression has become important as trials of new medical treatments for amyotrophic lateral sclerosis (ALS) are planned. Bulbar onset, early impairment of forced vital capacity, and older age have all been associated with shorter survival. We performed a retrospective study to compare survival factors with disease progression in a German ALS population. We analyzed disease progression in 155 patients at intervals of 4 months over a period of 3 years. To evaluate disease progression, the ALS functional rating scale (ALS-FRS), forced vital capacity (FVC%), and a Medical Research Council (MRC) compound score based on a nine-step modified MRC scale were used. We compared age (<55 years vs. ,55 years), different sites of disease onset (bulbar vs. limb), and gender to the rate of disease progression and performed survival analyses. No overall significant difference could be detected when analyzing these subgroups with regard to disease progression. By contrast, significantly longer survival was observed in the younger age group (56 months vs. 38 months, P < 0.0001) and in patients with limb-onset disease (51 months vs. 37 months, P = 0.0002). Using Cox analyses values we found that the declines of ALS-FRS, FVC%, and MRC compound score were predictive of survival (P < 0.0001, P = 0.002, and P = 0.003, respectively). Future studies are needed to clarify whether nonspecific factors including muscle atrophy, dysphagia, and coexisting diseases influence prediction of survival in ALS patients. A more precise set of predictors may help to better stratify patient subgroups for future treatment trials. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25:000,000, 2002 [source] Regeneration of peripheral nerves after clenbuterol treatment in a rat modelMUSCLE AND NERVE, Issue 12 2001Onno Frerichs MD Abstract Clenbuterol is known to act as a neuroprotective substance in the central nervous system, and also reduces muscle atrophy after denervation. The aim of this study was to evaluate its influence on peripheral nerve regeneration. The rat sciatic nerve model was used in four groups (n = 8 per group). After complete nerve transection and microsurgical coaptation, two groups received a daily oral dose of 100 ,g/kg clenbuterol and two served as controls. Regeneration was assessed clinically, histologically, and morphometrically after 4 and 6 weeks. The weight ratios of calf muscles were calculated. Histological examination showed significantly increased axon counts in the clenbuterol group and a better degree of myelination. Muscle weight ratios of the clenbuterol group were significantly increased after 6 weeks, and the animals showed improved function of the hindlimb. Thus, therapy with 100 ,g/kg clenbuterol daily after coaptation of a sciatic nerve showed a positive influence on clinical, histological, and morphometrical parameters in the rat model. The underlying mechanism remains unclear. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1687,1691, 2001 [source] Neuromuscular Electrical Stimulation As a Possible Means to Prevent Muscle Tissue Wasting in Artificially Ventilated and Sedated Patients in the Intensive Care Unit: A Pilot StudyNEUROMODULATION, Issue 4 2010Raf L.J. Meesen PhD Objective:, The aim of this study was to explore if electrical stimulation could prevent muscle atrophy. Material and Methods:, Patients were hospitalized for postoperative coronary artery bypass graftin, chronic obstructive pulmonary disease, ventilatory failure, or acute cerebro-vascular accident, and were divided into an intervention group or a control group. The intervention group underwent daily 30 minute training with an intermittent neuromuscular electrical stimulation applied to the right quadriceps muscle. Heart rate, respiration rate, systolic and diastolic blood pressure, and oxygen saturation were monitored before, during, and after electrical stimulation. Circumference of both thighs was measured. Results:, The intervention resulted in a significant reduction of muscle atrophy in the stimulated as compared with the non-stimulated limb (p < 0.05), without making any impact on cardiovascular, respiratory and, hemodynamic characteristics. Conclusions:, Muscle atrophy is prevented by intermittent neuromuscular electrical stimulation while this intervention showed no obvious impact on the cardio-respiratory conditions of the patients. [source] Pathogenesis and molecular targeted therapy of spinal and bulbar muscular atrophyNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 2 2007H. Adachi Spinal and bulbar muscular atrophy (SBMA) or Kennedy's disease is a motor neurone disease characterized by muscle atrophy, weakness, contraction fasciculations and bulbar involvement. SBMA mainly affects males, while females are usually asymptomatic. SBMA is caused by expansion of a polyglutamine (polyQ)-encoding CAG trinucleotide repeat in the androgen receptor (AR) gene. AR belongs to the heat shock protein 90 (Hsp90) client protein family. The histopathologic hallmarks of SBMA are diffuse nuclear accumulation and nuclear inclusions of the mutant AR with expanded polyQ in residual motor neurones in the brainstem and spinal cord as well as in some other visceral organs. There is increasing evidence that the ligand of AR and molecular chaperones play a crucial role in the pathogenesis of SBMA. The success of androgen deprivation therapy in SBMA mouse models has been translated into clinical trials. In addition, elucidation of its pathophysiology using animal models has led to the development of disease-modifying drugs, that is, Hsp90 inhibitor and Hsp inducer, which inhibit the pathogenic process of neuronal degeneration. SBMA is a slowly progressive disease by nature. The degree of nuclear accumulation of mutant AR in scrotal skin epithelial cells was correlated with that in spinal motor neurones in autopsy specimens; therefore, the results of scrotal skin biopsy may be used to assess the efficacy of therapeutic trials. Clinical and pathological parameters that reflect the pathogenic process of SBMA should be extensively investigated. [source] Cardiac ankyrin repeat protein is preferentially induced in atrophic myofibers of congenital myopathy and spinal muscular atrophyPATHOLOGY INTERNATIONAL, Issue 10 2003Chisato Nakada Cardiac ankyrin repeat protein (CARP), which is structurally characterized by the presence of four ankyrin repeat motifs in its central region, is believed to be localized in the nucleus and to participate in the regulation of cardiac-specific gene expression in cardiomyocytes. However, we recently found that CARP was induced in skeletal muscle by denervation, leading us to speculate that CARP may be induced under some pathological conditions. In the present study, we immunohistochemically analyzed the expression of CARP in 11 cases of spinal muscular atrophy (SMA) and 14 cases of congenital myopathy. In SMA, CARP was expressed selectively in severely atrophic myofibers, suggesting that CARP expression may reflect the status of muscle atrophy. Furthermore, in the congenital myopathies, the expression patterns of CARP were distinct among the subtypes, which included nemaline myopathy, myotubular myopathy, central core disease, and congenital fiber type disproportion. Although CARP was preferentially expressed in severely damaged myofibers in nemaline myopathy, it was not detected in central core disease. These findings suggest that immunohistochemical evaluation of CARP may be helpful in the diagnosis of SMA and the congenital myopathies. [source] The prion protein in human neuromuscular diseasesTHE JOURNAL OF PATHOLOGY, Issue 3 2004Gábor G Kovács Abstract The basis of human prion diseases affecting the nervous system is accumulation of a disease-associated conformer (PrPSc) of the normal cellular prion protein (PrPC). Earlier studies demonstrated increased expression of PrPC in inclusion body myositis (IBM), dermato-, and polymyositis, as well as neurogenic muscle atrophy. To define the spectrum and reliability of PrPC immunoreactivity, its expression was examined systematically in a series of pathologically characterized muscular disorders by means of immunohistochemistry, confocal laser microscopy, and immunogold electron microscopy. Anti-PrPC immunolabelling of rimmed vacuoles was observed in IBM, inclusions of myofibrillary myopathy, targets, regenerating, and atrophic fibres, mononuclear cells, in addition to ragged red fibres in mitochondrial myopathies, and focal sarcolemmal immunostaining in non-diseased controls. Quantitative analysis demonstrated that, in neurogenic muscle lesions, anti-PrPC staining detects a significantly broader spectrum of fibres than anti-vimentin or anti-NCAM. In dystrophic muscle, PrPC expression was mainly restricted to regenerating fibres. In IBM, PrPC expression was not confined to rimmed vacuoles or vacuolated fibres and only a small percentage (7.1%) of rimmed vacuoles were PrPC positive. Ultrastructurally, PrPC was observed in the cytoplasm of lymphocytes, in the myofibrillar network of targets, and in rimmed vacuoles. Knowledge of disease circumstances with altered expression of PrPC is important in the setting of a potentially increased chance for extraneural PrPC,PrPSc conversion. In addition, our observations suggest that PrPC may have a general stress,response effect in various neuromuscular disorders. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Regulation of STARS and its downstream targets suggest a novel pathway involved in human skeletal muscle hypertrophy and atrophyTHE JOURNAL OF PHYSIOLOGY, Issue 8 2009Séverine Lamon Skeletal muscle atrophy is a severe consequence of ageing, neurological disorders and chronic disease. Identifying the intracellular signalling pathways controlling changes in skeletal muscle size and function is vital for the future development of potential therapeutic interventions. Striated activator of Rho signalling (STARS), an actin-binding protein, has been implicated in rodent cardiac hypertrophy; however its role in human skeletal muscle has not been determined. This study aimed to establish if STARS, as well as its downstream signalling targets, RhoA, myocardin-related transcription factors A and B (MRTF-A/B) and serum response factor (SRF), were increased and decreased respectively, in human quadriceps muscle biopsies taken after 8 weeks of both hypertrophy-stimulating resistance training and atrophy-stimulating de-training. The mRNA levels of the SRF target genes involved in muscle structure, function and growth, such as ,-actin, myosin heavy chain IIa (MHCIIa) and insulin-like growth factor-1 (IGF-1), were also measured. Following resistance training, STARS, MRTF-A, MRTF-B, SRF, ,-actin, MHCIIa and IGF-1 mRNA, as well as RhoA and nuclear SRF protein levels were all significantly increased by between 1.25- and 3.6-fold. Following the de-training period all measured targets, except for RhoA, which remained elevated, returned to base-line. Our results show that the STARS signalling pathway is responsive to changes in skeletal muscle loading and appears to play a role in both human skeletal muscle hypertrophy and atrophy. [source] | |||||||||||||||||||||||||||||||