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Muscle Damage (muscle + damage)
Selected AbstractsPOPPING SARCOMERE HYPOTHESIS EXPLAINS STRETCH-INDUCED MUSCLE DAMAGECLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2004David L Morgan SUMMARY 1.,Exercise that involves stretching a muscle while active cause microscopic areas of damage, delayed onset muscle soreness and adaptation to withstand subsequent similar exercise. 2.,Longer muscle lengths are associated with greater damage and recent animal experiments show that it is the length relative to optimum that determines the damage. 3.,In humans, walking down stairs, taking two at a time, increases the length of the muscle during the lengthening and increases the delayed onset muscle soreness. 4.,The observed pattern of damage is consistent with explanations based on sarcomere length instabilities. 5.,The pattern of adaptation is consistent with the number of sarcomeres in series in a muscle being modulated by exercise, especially the range of muscle lengths over which eccentric exercise regularly occurs. [source] Mechanisms of stretch-induced muscle damage in normal and dystrophic muscle: role of ionic changesTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005D. G. Allen Muscle damage, characterized by prolonged weakness and delayed onset of stiffness and soreness, is common following contractions in which the muscles are stretched. Stretch-induced damage of this sort is more pronounced in the muscular dystrophies and the profound muscle damage observed in these conditions may involve similar pathways. It has been known for many years that damaged muscles accumulate calcium and that elevating calcium in normal muscles simulates many aspects of muscle damage. The changes in intracellular calcium, sodium and pH following stretched contractions are reviewed and the various pathways which have been proposed to allow ion entry are discussed. One possibility is that TRPC1 (transient receptor potential, canonical), a protein which seems to form both a stretch-activated channel and a store-operated channel, is the main source of Ca2+ entry. The mechanisms by which the changes in intracellular ions contribute to reduced force production, to increased protein breakdown and to increased membrane permeability are considered. A hypothetical scheme for muscle damage which incorporates these ideas is presented. [source] Oestrogen receptor-alpha activation augments post-exercise myoblast proliferationACTA PHYSIOLOGICA, Issue 1 2010A. Thomas Abstract Aim:, Our laboratory has shown that oestrogen acts to augment myoblast (satellite cell) activation, proliferation and total number and that this may occur through an oestrogen receptor (OR)-mediated mechanism. The purpose of this study was to further investigate the mechanism of oestrogen influence on augmentation of post-exercise myoblast numbers through use of a specific OR-, agonist, propyl pyrazole triol (PPT). Methods:, Ovariectomized rats were used (n = 64) and separated into four groups: sham, oestrogen supplemented, agonist supplemented, and a combined oestrogen and agonist supplemented group. These groups were further subdivided into control (unexercised) and exercise groups. Surgical removal of white vastus and soleus muscles was performed 72 h post-exercise. Muscle samples were immunostained for the myoblast markers Pax7 and MyoD. Results:, A significant increase in total (Pax7-positive) and activated (MyoD-positive) myoblasts was found in all groups post-exercise. A further significant augmentation of total and activated myoblasts occurred in oestrogen supplemented, agonist supplemented and the combined oestrogen and agonist supplemented groups post-exercise in white vastus and soleus muscles relative to unsupplemented animals. Conclusion:, These results demonstrate that both oestrogen and the specific OR-, receptor agonist, PPT, can significantly and to similar degrees augment myoblast number and activation following exercise-induced muscle damage. This suggests that oestrogen acts through an OR-mediated mechanism to stimulate myoblast proliferation following exercise, with OR-, playing a primary role. [source] The decrease in electrically evoked force production is delayed by a previous bout of stretch,shortening cycle exerciseACTA PHYSIOLOGICA, Issue 1 2010S. Kamandulis Abstract Aim:, Unaccustomed physical exercise with a large eccentric component is accompanied by muscle damage and impaired contractile function, especially at low stimulation frequencies. A repeated bout of eccentric exercise results in less damage and improved recovery of contractile function. Here we test the hypotheses that (1) a prior stretch,shortening cycle (SSC) exercise protects against impaired muscle function during a subsequent bout of SSC exercise and (2) the protection during exercise is transient and becomes less effective as the exercise progresses. Methods:, Healthy untrained men (n = 7) performed SSC exercise consisting of 100 maximal drop jumps at 30 s intervals. The same exercise was repeated 4 weeks later. Peak quadriceps muscle force evoked by electrical stimulation at 15 (P15) and 50 (P50) Hz was measured before exercise, after 10, 25, 50 and 100 jumps as well as 1 and 24 h after exercise. Results:, P15 and P50 were higher during the initial phase of the repeated bout compared with the first exercise bout, but there was no difference between the bouts at the end of the exercise periods. P15 and P50 were again larger 24 h after the repeated bout. The P15/P50 ratio during exercise was not different between the two bouts, but it was higher after the repeated bout. Conclusion:, A prior bout of SSC exercise temporarily protects against impaired contractile function during a repeated exercise bout. The protection can again be seen after exercise, but the underlying mechanism then seems to be different. [source] Heat shock protein translocation and expression response is attenuated in response to repeated eccentric exerciseACTA PHYSIOLOGICA, Issue 3 2009K. Vissing Abstract Aim:, This study hypothesized that heat shock protein (HSP) translocation and upregulation is more probable to occur after eccentric exercise than after concentric exercise or repeated eccentric exercise. Methods:, Fourteen young, healthy, untrained male subjects completed two bench-stepping exercise bouts with 8 weeks between bouts, and were compared with a control group (n = 6). Muscle biopsies collected from m. vastus lateralis of both legs prior to and at 3 h, 24 h and 7 days after exercise were quantified for mRNA levels and/or for HSP27, ,,-crystallin and inducible HSP70 content in cytosolic and cytoskeletal protein fractions. Results:, The first bout of exercise reduced muscle strength and increased muscle soreness predominantly in the eccentric leg (P < 0.05). These responses were attenuated after the repeated eccentric exercise bout (P < 0.05), suggesting a repeated bout adaptation. Increases in inducible HSP70 and HSP27 protein content in cytoskeletal fractions were observed exclusively after eccentric exercise (P < 0.05). For HSP27, an approx. 10-fold upregulation after first-bout eccentric exercise was attenuated to a an approximately fourfold upregulation after the repeated eccentric exercise bout. mRNA levels for HSP70, HSP27 and ,,-crystallin were upregulated within approximately two to fourfold ranges at time points 3 and 24 h post-exercise (P < 0.05). This upregulation was induced exclusively by eccentric exercise but with a tendency to attenuated expression 3 h after the repeated eccentric exercise bout. Conclusion:, Our results show that HSP translocation and expression responses are induced by muscle damaging exercise, and suggest that such HSP responses are closely related to the extent of muscle damage. [source] Screening for the calstabin-ryanodine receptor complex stabilizers JTV-519 and S-107 in doping control analysisDRUG TESTING AND ANALYSIS, Issue 1 2009Mario Thevis Abstract Recent studies outlined the influence of exercise on the stability of the skeletal muscle calstabin1-ryanodine receptor1-complex, which represents a major Ca2+ release channel. The progressive modification of the type-1 skeletal muscle ryanodine receptor (RyR1) combined with reduced levels of calstabin1 and phosphodiesterase PDE4D3 resulted in a Ca2+ leak that has been a suggested cause of muscle damage and impaired exercise capacity. The use of 1,4-benzothiazepine derivatives such as the drug candidates JTV-519 and S-107 enhanced rebinding of calstabin1 to RyR1 and resulted in significantly improved skeletal muscle function and exercise performance in rodents. Due to the fact that the mechanism of RyR1 remodelling under exercise conditions were proven to be similar in mice and humans, a comparable effect of JTV-519 and S-107 on trained athletes is expected, making the compounds relevant for doping controls. After synthesis of JTV-519, S-107, and a putative desmethylated metabolite of S-107, target compounds were characterized using nuclear magnetic resonance spectroscopy and electrospray ionization (ESI),high-resolution/high-accuracy Orbitrap mass spectrometry. Collision-induced dissociation pathways were suggested based on the determination of elemental compositions of product ions and H/D-exchange experiments. The most diagnostic product ion of JTV-519 was found at m/z 188 (representing the 4-benzyl-1-methyl piperidine residue), and S-107 as well as its desmethylated analog yielded characteristic fragments at m/z 153 and 138 (accounting for 1-methoxy-4-methylsulfanyl-benzene and 4-methoxy-benzenethiol residues, respectively). The analytes were implemented in existing doping control screening procedures based on liquid chromatography, multiple reaction monitoring and simultaneous precursor ion scanning modes using a triple quadrupole mass spectrometer. Validation items such as specificity, recovery (68,92%), lower limit of detection (0.1,0.2 ng/mL), intraday (5.2,18.5%) and interday (8.7,18.8%) precision as well as ion suppression/enhancement effects were determined. Copyright © 2009 John Wiley & Sons, Ltd. [source] Sustained expression of Epstein,Barr virus episomal vector mediated factor VIII in vivo following muscle electroporationHAEMOPHILIA, Issue 3 2006W.-H. MEI Summary., Haemophilia A treatment is an attractive candidate for gene therapy. The aim of haemophilia gene therapy is to obtain long-term therapeutic level of factor VIII (FVIII). We investigated Epstein,Barr virus (EBV)-based episomal vector combined with in vivo electroporation of naked DNA as a safe, efficient and simple method for correcting FVIII deficiency. A combinant FVIII expression EBV-based episomal vector pcDNA3-FVIII-EBVR was constructed and expressed in COS-7 cells. Then the naked plasmid DNA was injected into the quadriceps of mice following the electric pulse stimulation. Our data showed that pcDNA3-FVIII-EBVR expression in transfected COS-7 can maintain stably for at least 60 days and the hFVIII:Ag in plasma in two pcDNA3-FVIII-EBVR groups mice was higher than that in pcDNA-FVIII groups no matter with or without electric pulse stimulation. With the stimulating of electric pulse, the FVIII expression in plasma of recipient mice was increased two- to fourfolds and can be lasted for at least 90 days. No severe muscle damage was detected. So this novel strategy that FVIII expression mediated by EBV episomal vector following muscle electroporation is efficient, safe, simple and economic and may be applicable to clinical usage. [source] Differential activation of stress-responsive signalling proteins associated with altered loading in a rat skeletal muscleJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2005Inho Choi Abstract Skeletal muscle undergoes a significant reduction in tension upon unloading. To explore intracellular signalling mechanisms underlying this phenomenon, we investigated twitch tension, the ratio of actin/myosin filaments, and activities of key signalling molecules in rat soleus muscle during a 3-week hindlimb suspension and 2-week reloading. Twitch tension and myofilament ratio (actin/myosin) gradually decreased during unloading but progressively recovered to initial levels during reloading. To study the involvement of stress-responsive signalling proteins during these changes, the activities of protein kinase C alpha (PKC,) and three mitogen-activated protein kinases (MAPKs),c-Jun NH2 -terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), and p38 MAPK,were examined using immunoblotting and immune complex kinase assays. PKC, phosphorylation correlated positively with the tension (Pearson's r,=,0.97, P,<,0.001) and the myofilament ratio (r,=,0.83, P,<,0.01) over the entire unloading and reloading period. Treatment of the soleus muscle with a PKC activator resulted in a similar paralleled increment in both PKC, phosphorylation and the ,-sarcomeric actin expression. The three MAPKs differed in the pattern of activation in that JNK activity peaked only for the first hours of reloading, whereas ERK and p38 MAPK activities remained elevated during reloading. These results suggest that PKC, may play a pivotal role in converting loading stress to intracellular changes in contractile proteins that determine muscle tension. Differential activation of MAPKs may also help alleviate muscle damage, modulate energy transport and/or regulate the expression of contractile proteins upon altered loading. J. Cell. Biochem. © 2005 Wiley-Liss, Inc. [source] Inflammation-induced leukocyte accumulation in injured skeletal muscle: Role of mast cellsMUSCLE AND NERVE, Issue 6 2008Claude H. Côt, e PhD Abstract Inflammation consequent to muscle damage is characterized by an accumulation of leukocytes. Our aim in this study was to determine whether mast cells can modulate inflammation-induced leukocyte trafficking. One approach consisted of giving rats a mast cell,degranulating agent, CMP 48/80, prior to a protocol of lengthening contractions inducing inflammation without neutrophil accumulation; in parallel, other rats were given the mast cell,stabilizing agent, cromolyn, prior to injecting muscle with bupivacaine, which induces neutrophil accumulation. Damage was evaluated through measurement of contractile force and inflammation using histochemical and immunohistochemichal methods. Stimulation with CMP 48/80 increased the proportion of degranulated mast cells significantly and neutrophil accumulation occurred with lengthening contractions. With bupivacaine, accumulation of neutrophils decreased by 70% when degranulation was inhibited. These results indicate that mast cells are important in the process governing leukocyte trafficking in skeletal muscle trauma and that targeting their inhibition could be an attractive alternative for control of inflammation. Muscle Nerve, 2008 [source] Co-expression of IGF-1 family members with myogenic regulatory factors following acute damaging muscle-lengthening contractions in humansTHE JOURNAL OF PHYSIOLOGY, Issue 22 2008Bryon R. McKay Muscle regeneration following injury is dependent on the ability of muscle satellite cells to activate, proliferate and fuse with damaged fibres. This process is controlled by the myogenic regulatory factors (MRF). Little is known about the temporal relation of the MRF with the expression of known myogenic growth factors (i.e. IGF-1) in humans following muscle damage. Eight subjects (20.6 ± 2.1 years; 81.4 ± 9.8 kg) performed 300 lengthening contractions (180 deg s,1) of their knee extensors in one leg on a dynamometer. Blood and muscle samples were collected before and at 4 (T4), 24 (T24), 72 (T72) and 120 h (T120) post-exercise. Mechano growth factor (MGF), IGF-1Ea and IGF-1Eb mRNA were quantified. Serum IGF-1 did not change over the post-exercise time course. IGF-1Ea and IGF-1Eb mRNA increased ,4- to 6-fold by T72 (P < 0.01) and MGF mRNA expression peaked at T24 (P= 0.005). MyoD mRNA expression increased ,2-fold at T4 (P < 0.05). Myf5 expression peaked at T24 (P < 0.05), while MRF4 and myogenin mRNA expression peaked at T72 (P < 0.05). Myf5 expression strongly correlated with the increase in MGF mRNA (r2= 0.83; P= 0.03), while MRF4 was correlated with both IGF-1Ea and -Eb (r2= 0.90; r2= 0.81, respectively; P < 0.05). Immunofluorescence analysis showed IGF-1 protein expression localized to satellite cells at T24, and to satellite cells and the myofibre at T72 and T120; IGF-1 was not detected at T0 or T4. These results suggest that the temporal response of MGF is probably related to the activation/proliferation phase of the myogenic programme as marked by an increase in both Myf5 and MyoD, while IGF-1Ea and - Eb may be temporally related to differentiation as marked by an increase in MRF4 and myogenin expression following acute muscle damage. [source] Mechanisms of stretch-induced muscle damage in normal and dystrophic muscle: role of ionic changesTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005D. G. Allen Muscle damage, characterized by prolonged weakness and delayed onset of stiffness and soreness, is common following contractions in which the muscles are stretched. Stretch-induced damage of this sort is more pronounced in the muscular dystrophies and the profound muscle damage observed in these conditions may involve similar pathways. It has been known for many years that damaged muscles accumulate calcium and that elevating calcium in normal muscles simulates many aspects of muscle damage. The changes in intracellular calcium, sodium and pH following stretched contractions are reviewed and the various pathways which have been proposed to allow ion entry are discussed. One possibility is that TRPC1 (transient receptor potential, canonical), a protein which seems to form both a stretch-activated channel and a store-operated channel, is the main source of Ca2+ entry. The mechanisms by which the changes in intracellular ions contribute to reduced force production, to increased protein breakdown and to increased membrane permeability are considered. A hypothetical scheme for muscle damage which incorporates these ideas is presented. [source] Succinylcholine and temporal muscle damageANAESTHESIA, Issue 8 2000A. T. Norman [source] ANABOLIC AGENTS FOR IMPROVING MUSCLE REGENERATION AND FUNCTION AFTER INJURYCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2008Gordon S Lynch SUMMARY 1In the present review, we describe how muscles can be injured by external factors, internal factors or during the performance of some actions during sports. In addition, we describe the injury to a muscle that occurs when its blood supply is interrupted, an occurrence common in clinical settings. An overview of muscle regeneration is presented, as well as a discussion of some of the potential complications that can compromise successful muscle repair and lead to impaired function and permanent disability. 2Improving muscle regeneration is important for hastening muscle repair and restoring muscle function and the present review describes ways in which this can be achieved. We describe recent advances in tissue engineering that offer considerable promise for treating muscle damage, but highlight the fact that these techniques require rigorous evaluation before they can become mainstream clinical treatments. 3Growth-promoting agents are purported to increase the size of existing and newly regenerating muscle fibres and, therefore, could be used to improve muscle function if administered at appropriate times during the repair process. The present review provides an update on the efficacy of some growth-promoting agents, including anabolic steroids, insulin-like growth factor-I (IGF-I) and b2 -adrenoceptor agonists, to improve muscle function after injury. Although these approaches have clinical merit, a better understanding of the androgenic, IGF-I and b-adrenoceptor signalling pathways in skeletal muscle is important if we are to devise safe and effective therapies to enhance muscle regeneration and function after injury. [source] SKELETAL MUSCLE FUNCTION: ROLE OF IONIC CHANGES IN FATIGUE, DAMAGE AND DISEASECLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2004DG Allen SUMMARY 1.,Repeated activity of skeletal muscle causes a variety of changes in its properties: muscles become weaker with intense use (fatigue), may feel sore and weak after repeated contractions involving stretch and can degenerate in some disease conditions. The present review considers the role of early ionic changes in the development of each of these conditions. 2.,Single fibre preparations of mouse muscle were used to measure ionic changes following activity induced changes in function. Single fibres were dissected with intact tendons and stimulated to produce force. Fluorescent indicators were microinjected into the fibres to allow simultaneous ionic measurements with determination of mechanical performance. 3.,One theory to explain muscle fatigue is that fatigue is caused by the accumulation of lactic acid, producing an intracellular acidosis that inhibits the myofibrillar proteins. In contrast, we found that during repeated tetani there was little or no pH change, but that failure of calcium release was a major contributor to fatigue. Currently, it is proposed that precipitation of calcium and phosphate in the sarcoplasmic reticulum contributes to the failure of calcium release. 4.,Muscles can be used to shorten and produce force or they can be used to de-accelerate loads (stretched or eccentric contractions). One day after intense exercise involving stretched contractions, muscles are weak, sore and tender, and this damage can take a week to recover. In this condition, sarcomeres are disorganized and there are increases in resting intracellular Ca2+ and Na+. Recently, we demonstrated that the elevation of Na+ occurs through a stretch-activated channel that can be blocked by either gadolinium or streptomycin. Preventing the increase in [Na+]i with gadolinium also prevented part of the muscle weakness after stretched contractions. 5.,Duchenne muscular dystrophy is a lethal degenerative disease of muscles in which the protein dystrophin is absent. Dystrophic muscles are more susceptible to stretch-induced muscle damage and the stretch-activated channel seems to be one pathway for the increases in intracellular Ca2+ and Na+ that are a feature of this disease. We have shown recently that blockers of the stretch-activated channel can minimize some of the short-term damage in muscles from the mdx mouse, which also lacks dystrophin. Currently, we are testing whether blockers of the stretch-activated channels given systemically to mdx mice can protect against some features of the disease. [source] | |||||||||||||