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Muscle Injury (muscle + injury)

Distribution by Scientific Domains

Medical Sciences	84%
Life Sciences	15%

Selected Abstracts

Improvement of muscle healing through enhancement of muscle regeneration and prevention of fibrosis

MUSCLE AND NERVE, Issue 3 2003
Kenji Sato MD
Abstract Skeletal muscle is able to repair itself through regeneration. However, an injured muscle often does not fully recover its strength because complete muscle regeneration is hindered by the development of fibrosis. Biological approaches to improve muscle healing by enhancing muscle regeneration and reducing the formation of fibrosis are being investigated. Previously, we have determined that insulin-like growth factor,1 (IGF-1) can improve muscle regeneration in injured muscle. We also have investigated the use of an antifibrotic agent, decorin, to reduce muscle fibrosis following injury. The aim of this study was to combine these two therapeutic methods in an attempt to develop a new biological approach to promote efficient healing and recovery of strength after muscle injuries. Our findings indicate that further improvement in the healing of muscle lacerations is attained histologically by the combined administration of IGF-1 to enhance muscle regeneration and decorin to reduce the formation of fibrosis. This improvement was not associated with improved responses to physiological testing, at least at the time-points tested in this study. Muscle Nerve 28: 365,372, 2003 [source]

Definitive engagement of cytotoxic CD8 T cells in C protein,induced myositis, a murine model of polymyositis

ARTHRITIS & RHEUMATISM, Issue 10 2010
Takahiko Sugihara
Objective To substantiate a pathogenic role of cytotoxic CD8 T cells in the development of a murine polymyositis model, C protein,induced myositis (CIM). Methods Beta2 -microglobulin,null mutant, perforin-null mutant, and wild-type (WT) C57BL/6 mice were immunized with skeletal muscle C protein fragments to provoke CIM. Regional lymph node CD8 or CD4 T cells stimulated with C protein,pulsed dendritic cells were transferred adoptively to naive mice. Inflammation and damage of the muscle tissues were evaluated histologically. Results The incidence of myositis development was significantly lower in ,2 -microglobulin,null and perforin-null mutant mice compared with WT mice. Inflammation was less severe in mutant mice, and the incidence of muscle injury was reduced significantly. Adoptive transfer of lymph node T cells from mice with CIM induced myositis in naive recipient mice. The CD8 T cell,induced muscle injuries were significantly more severe than the CD4 T cell,induced muscle injuries. Conclusion Perforin-mediated cytotoxicity by CD8 T cells is definitively responsible for muscle injury in CIM. [source]

In vitro effects of lidocaine on the contractility of equine jejunal smooth muscle challenged by ischaemia-reperfusion injury

EQUINE VETERINARY JOURNAL, Issue 1 2010
M. GUSCHLBAUER
Summary Reasons for performing study: Post operative ileus (POI) in horses is a severe complication after colic surgery. A commonly used prokinetic drug is lidocaine, which has been shown to have stimulatory effects on intestinal motility. The cellular mechanisms through which lidocaine affects smooth muscle activity are not yet known. Objectives: To examine the effects of lidocaine on smooth muscle in vitro and identify mechanisms by which it may affect the contractility of intestinal smooth muscle. Hypothesis: Ischaemia and reperfusion associated with intestinal strangulation can cause smooth muscle injury. Consequently, muscle cell functionality and contractile performance is decreased. Lidocaine can improve basic cell functions and thereby muscle cell contractility especially in ischaemia-reperfusion-challenged smooth muscle. Methods: To examine the effects of lidocaine on smooth muscle function directly, isometric force performance was measured in vitro in noninjured and in vivo ischaemia-reperfusion injured smooth muscle tissues. Dose-dependent response of lidocaine was measured in both samples. To assess membrane permeability as a marker of basic cell function, release of creatine kinase (CK) was measured by in vitro incubations. Results: Lidocaine-stimulated contractility of ischaemia-reperfusion injured smooth muscle was more pronounced than that of noninjured smooth muscle. A 3-phasic dose-dependency was observed with an initial recovery of contractility especially in ischaemia-reperfusion injured smooth muscle followed by a plateau phase where contractility was maintained over a broad concentration range. CK release was decreased by lidocaine. Conclusion: Lidocaine may improve smooth muscle contractility and basic cell function by cellular repair mechanisms which are still unknown. Improving contractility of smooth muscle after ischaemia-reperfusion injury is essential in recovery of propulsive intestinal motility. Potential relevance: Characterisation of the cellular mechanisms of effects of lidocaine, especially on ischaemia-reperfusion injured smooth muscle, may lead to improved treatment strategies for horses with POI. [source]

D-2-Hydroxyglutaric acid inhibits creatine kinase activity from cardiac and skeletal muscle of young rats

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2003
C. G. Da Silva
Abstract Background, Tissue accumulation of high amounts of D-2-hydroxyglutaric acid (DGA) is the biochemical hallmark of the inherited neurometabolic disorder D-2-hydroxyglutaric aciduria (DHGA). Patients affected by this disease usually present hypotonia, muscular weakness, hypothrophy and cardiomyopathy, besides severe neurological findings. However, the underlying mechanisms of muscle injury in this disorder are virtually unknown. Materials and methods, In the present study we have evaluated the in vitro role of DGA, at concentrations ranging from 0·25 to 5·0 mm, on total, cytosolic and mitochondrial creatine kinase activities from skeletal and cardiac muscle of 30-day-old Wistar rats. We also tested the effects of various antioxidants on the effects elicited by DGA. Results, We first verified that total creatine kinase (CK) activity from homogenates was significantly inhibited by DGA (22,24% inhibition) in skeletal and cardiac muscle, and that this activity was approximately threefold higher in skeletal muscle than in cardiac muscle. We also observed that CK activities from mitochondrial (Mi-CK) and cytosolic (Cy-CK) preparations from skeletal muscle and cardiac muscle were also inhibited (12,35% inhibition) by DGA at concentrations as low as 0·25 mm, with the effect being more pronounced in cardiac muscle preparations. Finally, we verified that the DGA-inhibitory effect was fully prevented by preincubation of the homogenates with reduced glutathione and cysteine, suggesting that this effect is possibly mediated by modification of essential thiol groups of the enzyme. Furthermore, ,-tocopherol, melatonin and the inhibitor of nitric oxide synthase L-NAME were unable to prevent this effect, indicating that the most common reactive oxygen and nitrogen species were not involved in the inhibition of CK provoked by DGA. Conclusion, Considering the importance of creatine kinase activity for cellular energy homeostasis, our results suggest that inhibition of this enzyme by increased levels of DGA might be an important mechanism involved in the myopathy and cardiomyopathy of patients affected by DHGA. [source]

Effect of anti-inflammatory and antioxidant drugs on the long-term repair of severely injured mouse skeletal muscle

EXPERIMENTAL PHYSIOLOGY, Issue 4 2005
A. Vignaud
Non-steroidal anti-inflammatory drugs are frequently prescribed after skeletal muscle injury. It is not known whether this type of medication can interfere with muscle repair, although inflammatory response is thought to play an important role in this process. Tibialis anterior muscles of mice were injured by myotoxic agent (snake venom) or crushed. Then, animals were treated daily for 10,14 days with different types of non-steroidal anti-inflammatory and antioxidant drugs. The long-term repair was studied 10,42 days after injury by analysing the recovery of in situ muscle force production, size of regenerating muscle cells and expression of myosin heavy chain. Our results show that diclofenac, diferuloylmethane (curcumin), dimethylthiourea or pyrrolidine dithiocarbamate treatment did not significantly affect muscle recovery after myotoxic injury (P > 0.05). Similarly, diferuloylmethane, dimethyl sulphoxide or indomethacin administration did not markedly change muscle repair after crush injury. However, we noted that high doses (> 2 mg kg,1) of diferuloylmethane or indomethacin increased lethality and reduced muscle repair after crush injury. In conclusion, non-steroidal anti-inflammatory and antioxidant drugs did not exhibit long-term detrimental effects on muscle recovery after injury, except at lethal doses. [source]

Skeletal muscle fiber type conversion during the repair of mouse soleus: Potential implications for muscle healing after injury

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 11 2007
Tetsuya Matsuura
Abstract We used a mouse model of cardiotoxin injury to examine fiber type conversion during muscle repair. We evaluated the soleus muscles of 37 wild-type mice at 2, 4, 8, and 12 weeks after injury. We also used antibodies (fMHC and sMHC) against fast and slow myosin heavy chain to classify the myofibers into three categories: fast-, slow-, and mixed (hybrid)-type myofibers (myofibers expressing both fMHC and sMHC). Our results revealed an increase in the percentage of slow-type myofibers and a decrease in the percentage of fast-type myofibers during the repair process. The percentage of hybrid-type myofibers increased 2 weeks after injury, then gradually decreased over the following 6 weeks. Similarly, our analysis of centronucleated myofibers showed an increase in the percentage of slow-type myofibers and decreases in the percentages of fast- and hybrid-type myofibers. We also investigated the relationship between myofiber type conversion and peroxisome proliferator-activated receptor-, coactivator-1, (PGC-1,). The expression of both PGC-1, protein, which is expressed in both the nucleus and the cytoplasm of regenerating myofibers, and sMHC protein increased with time after cardiotoxin injection, but we observed no significant differential expression of fMHC protein in regenerating muscle fibers during muscle repair. PGC-1,-positive myofibers underwent fast to slow myofiber type conversion during the repair process. These results suggest that PGC-1, contributes to myofiber type conversion after muscle injury and that this phenomenon could influence the recovery of the injured muscle. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1534,1540, 2007 [source]

Review article: the gastrointestinal complications of myositis

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2010
E. C. EBERT
Aliment Pharmacol Ther,31, 359,365 Summary Background, The inflammatory myopathies are a group of acquired diseases characterized by a proximal myopathy caused by an inflammatory infiltrate of the skeletal muscle. The three major diseases are dermatomyositis, polymyositis and inclusion body myositis. Aims, To review the gastrointestinal manifestations of myositis. Methods, Over 110 articles in the English literature were reviewed. Results, Dysphagia to solids and liquids occurs in patients with myositis. The pharyngo-oesophageal muscle tone is lost and therefore patients develop nasal speech, hoarseness, nasal regurgitation and aspiration pneumonia. There is tongue weakness, flaccid vocal cords, poor palatal motion and pooling of secretions in the distended hypopharynx. Proximal oesophageal skeletal muscle dysfunction is demonstrated by manometry with low amplitude/absent pharyngeal contractions and decreased upper oesophageal sphincter pressures. Patients exhibit markedly elevated creatine kinase and lactate dehydrogenase levels consistent with muscle injury. Myositis can be associated with inflammatory bowel disease, coeliac disease and interferon treatment of hepatitis C. Corticosteroids and other immunosuppressive drugs comprise the mainstay of treatment. Inclusion body myositis responds poorly to these agents and therefore a myotomy is usually indicated. Conclusion, Myositis mainly involves the skeletal muscles in the upper oesophagus with dysphagia, along with proximal muscle weakness. [source]

Annexin expression in inflammatory myopathies

MUSCLE AND NERVE, Issue 1 2004
Stefan Probst-Cousin MD
Abstract The pathogenesis of the inflammatory myopathies is still unclear, making their treatment largely empirical. Improved understanding of the molecular mechanisms of inflammatory muscle injury may, however, lead to the development of more specific immunotherapies. To elucidate a possible pathogenic contribution of calcium-binding proteins such as the annexins, we immunohistochemically investigated muscle biopsy specimens from patients with dermatomyositis (10 cases), polymyositis (9 cases), and inclusion-body myositis (4 cases), compared to control cases comprising sarcoid myopathy (3 cases), Duchenne muscular dystrophy (DMD; 4 cases), and normal muscle (3 cases). We found expression of annexins A1, A2, A4, and A6 in the vascular endothelium of all cases. Myofibers expressed annexins A5, A6, and A7 diffusely and weakly in the cytosol, whereas annexins A5 and A7 were also particularly localized to the sarcolemma. In the inflammatory myopathies, in areas of myonecrosis in DMD, and in granulomatous lesions of sarcoid myopathy, reactivity of annexins A1, A2, A4, A5, and A6 was observed in macrophages and T-lymphocytes. Whereas the latter annexins appear to be nonspecific indicators of activation, annexin A1 upregulation may represent endogenous anti-inflammatory mechanisms that merit further investigation. Muscle Nerve 30: 102,110, 2004 [source]

Inflammatory myopathies: Clinical, diagnostic and therapeutic aspects

MUSCLE AND NERVE, Issue 4 2003
Frank L. Mastaglia MD
Abstract The three major forms of immune-mediated inflammatory myopathy are dermatomyositis (DM), polymyositis (PM), and inclusion-body myositis (IBM). They each have distinctive clinical and histopathologic features that allow the clinician to reach a specific diagnosis in most cases. Magnetic resonance imaging is sometimes helpful, particularly if the diagnosis of IBM is suspected but has not been formally evaluated. Myositis-specific antibodies are not helpful diagnostically but may be of prognostic value; most antibodies have low sensitivity. Muscle biopsy is mandatory to confirm the diagnosis of an inflammatory myopathy and to allow unusual varieties such as eosinophilic, granulomatous, and parasitic myositis, and macrophagic myofasciitis, to be recognized. The treatment of the inflammatory myopathies remains largely empirical and relies upon the use of corticosteroids, immunosuppressive agents, and intravenous immunoglobulin, all of which have nonselective effects on the immune system. Further controlled clinical trials are required to evaluate the relative efficacy of the available therapeutic modalities particularly in combinations, and of newer immunosuppressive agents (mycophenolate mofetil and tacrolimus) and cytokine-based therapies for the treatment of resistant cases of DM, PM, and IBM. Improved understanding of the molecular mechanisms of muscle injury in the inflammatory myopathies should lead to the development of more specific forms of immunotherapy for these conditions. Muscle Nerve 27:407,425, 2003 [source]

Definitive engagement of cytotoxic CD8 T cells in C protein,induced myositis, a murine model of polymyositis

Muscle resident macrophages control the immune cell reaction in a mouse model of notexin-induced myoinjury

ARTHRITIS & RHEUMATISM, Issue 1 2010
Madly Brigitte
Objective Skeletal muscle may be the site of a variety of poorly understood immune reactions, particularly after myofiber injury, which is typically observed in inflammatory myopathies. This study was undertaken to explore both the cell dynamics and functions of resident macrophages and dendritic cells (DCs) in damaged muscle, using a mouse model of notexin-induced myoinjury to study innate immune cell reactions. Methods The myeloid cell reaction to notexin-induced myoinjury was analyzed by microscopy and flow cytometry. Bone marrow (BM) transplantation studies were used to discriminate resident from exudate monocyte/macrophages. Functional tests included cytokine screening and an alloantigenic mixed leukocyte reaction to assess the antigen-presenting cell (APC) function. Selective resident macrophage depletion was obtained by injection of diphtheria toxin (DT) into CD11b,DT receptor,transgenic mice transplanted with DT-insensitive BM. Results The connective tissue surrounding mouse muscle/fascicle tissue (the epimysium/perimysium) after deep muscle injury displayed a resident macrophage population of CD11b+F4/80+CD11c,Ly-6C,CX3CR1, cells, which concentrated first in the epimysium. These resident macrophages were being used by leukocytes as a centripetal migration pathway, and were found to selectively release 2 chemokines, cytokine-induced neutrophil chemoattractant and monocyte chemoattractant protein 1, and to crucially contribute to massive recruitment of neutrophils and monocytes from the blood. Early epimysial inflammation consisted of a predominance of Ly-6ChighCX3CR1lowCD11c, cells that were progressively substituted by Ly-6ClowCX3CR1high cells displaying an intermediate, rather than high, level of CD11c expression. These CD11cintermediate cells were derived from circulating CCR2+ monocytes, functionally behaved as immature APCs in the absence of alloantigenic challenge, and migrated to draining lymph nodes while acquiring the phenotype of mature DCs (CD11c+Ia+CD80+ cells, corresponding to an inflammatory DC phenotype). Conclusion The results in this mouse model show that resident macrophages in the muscle epimysium/perimysium orchestrate the innate immune response to myoinjury, which is linked to adaptive immunity through the formation of inflammatory DCs. [source]

Expression of the dermatomyositis autoantigen Mi-2 in regenerating muscle

ARTHRITIS & RHEUMATISM, Issue 12 2009
Andrew L. Mammen
Objective Autoantibodies against the chromatin remodeler Mi-2 are found in a distinct subset of patients with dermatomyositis (DM). Previous quantitative immunoblotting experiments demonstrated that Mi-2 protein levels are up-regulated in DM muscle. This study was undertaken to define the population of cells expressing high levels of Mi-2 in DM muscle and to explore the regulation and functional role of Mi-2 during muscle regeneration. Methods The expression of Mi-2 was analyzed by immunofluorescence microscopy in human muscle biopsy specimens. In an experimental mouse model, cardiotoxin was used to induce muscle injury and repair, and expression of Mi-2 during muscle regeneration was studied in this model by immunofluorescence and immunoblotting analyses. In addition, a cell culture system of muscle differentiation was utilized to artificially modulate Mi-2 levels during proliferation and differentiation of myoblasts. Results In human DM muscle tissue, increased Mi-2 expression was found preferentially in the myofibers within fascicles affected by perifascicular atrophy, particularly in the centralized nuclei of small perifascicular muscle fibers expressing markers of regeneration. In injured mouse muscle tissue, Mi-2 levels were dramatically and persistently up-regulated during muscle regeneration in vivo. Premature silencing of Mi-2 with RNA interference in vitro resulted in accelerated myoblast differentiation. Conclusion Expression of Mi-2 is markedly up-regulated during muscle regeneration in a mouse model of muscle injury and repair. It is also up-regulated in human DM myofibers expressing markers of regeneration. Results of the in vitro studies indicate that this protein may play a role in modulating the kinetics of myoblast differentiation. Our findings thus suggest that high levels of Mi-2 expression in muscle biopsy tissue from patients with DM reflect the presence of incompletely differentiated muscle cells. [source]

Muscle strain injuries of the hindlimb in eight horses: diagnostic imaging, management and outcomes

AUSTRALIAN VETERINARY JOURNAL, Issue 8 2010
EA Walmsley
Objective To describe the clinical presentation, ultrasound findings, management and outcome in horses with muscle tear injuries of the hindlimbs. Design Retrospective case series Procedure Medical records of eight horses were reviewed and information on signalment, history, presenting complaint, physical examination findings and further diagnostic tests were recorded. Diagnosis of muscle injury was determined by the presence of abnormal ultrasound findings, compared with the contralateral limb, and, when required, nuclear scintigraphy. Follow-up information was obtained via telephone interviews with owners, trainers and referring veterinarians. Results Muscle tears causing lameness were identified in the middle gluteal (3), semitendinosus (1), semimembranosus (2) and gracilis (2) muscles. Tears were classified by ultrasound imaging as partial (6) or complete (2). The degree of lameness did not appear to be indicative of the extent of injury or of completion of healing. Long-term follow-up was available for seven horses and the outcome was favourable in six cases. Conclusions and clinical relevance Ultrasonography is useful in the diagnosis and assessment of moderate to severe muscle strain injuries. The prognosis appears to be favourable in most cases, although recurrence of injury and lameness can delay the return to athletic activity and an inferior outcome with persistent gait abnormality may occur. [source]