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PubMed2006

Strength and fatigability of selected muscles in upper limb: assessing muscle imbalance relevant to tennis elbow.

PURPOSE: The aetiology of tennis elbow has remained uncertain for more than a century. To examine muscle imbalance as a possible pathophysiological factor requires a reliable method of assessment. This paper describes the development of such a method and its performance in healthy subjects. We propose a combination of surface and fine-wire EMG of shoulder and forearm muscles and wrist strength measurements as a reliable tool for assessing muscle imbalance relevant to the pathophysiology of tennis elbow. METHODS: Six healthy volunteers participated. EMG data were acquired at 50% maximal voluntary isometric contraction from five forearm muscles during grip and three shoulder muscles during external rotation and abduction, and analysed using normalized median frequency slope as a fatigue index. Wrist extension/flexion strength was measured using a purpose-built dynamometer. RESULTS: Significant negative slope of median frequency was found for all muscles, with good reproducibility, and no significant difference in slope between the different muscles of the shoulder and the wrist. (Amplitude slope showed high variability and was therefore unsuitable for this purpose.) Wrist flexion was 27+/-8% stronger than extension (mean+/-SEM, p=0.006). CONCLUSION: This is a reliable method for measuring muscle fatigue in forearm and shoulder. EMG and wrist strength studies together can be used for assessing and identifying the muscle balance in the wrist-forearm-shoulder chain.

Adult↗
PubMed2006

Inspiratory muscles experience fatigue faster than the calf muscles during treadmill marching.

The possibility that respiratory muscles may fatigue during extreme physical activity and thereby become a limiting factor leading to exhaustion is debated in the literature. The aim of this study was to determine whether treadmill marching exercise induces respiratory muscle fatigue, and to compare the extent and rate of respiratory muscle fatigue to those of the calf musculature. To identify muscle fatigue, surface electromyographic (EMG) signals of the inspiratory (sternomastoid, external intercostals), expiratory (rectus abdominis and external oblique) and calf (gastrocnemius lateralis) muscles were measured during a treadmill march of 2 km at a constant velocity of 8 km/h. The extent of fatigue was assessed by determining the increase in root-mean-square (RMS) of EMG over time, and the rate of fatigue was assessed from the slope of the EMG RMS versus time curve. Results indicated that (i) the inspiratory and calf muscles are the ones experiencing the most dominant fatigue during treadmill marching, (ii) the rate of fatigue of each muscle group was monotonic between the initial and terminal phases of exercise, and (iii) the inspiratory muscles fatigue significantly faster than the calf at the terminal phase of exercise, and are likely to fatigue faster during the initial exercise as well. Accordingly, this study supports the hypothesis that fatigue of the inspiratory muscles may be a limiting factor during exercise.

Adult↗
PubMed2005

Embryonic deregulation of muscle stress signaling pathways leads to altered postnatal stem cell behavior and a failure in postnatal muscle growth.

PW1 is a mediator of p53 and TNFalpha signaling pathways previously identified in a screen to isolate muscle stem cell regulators. We generated transgenic mice carrying a C-terminal deleted form of PW1 (DeltaPW1) which blocks p53-mediated cell death and TNFalpha-mediated NFkappaB activation fused to the myogenin promoter. Embryonic/fetal muscle development appears normal during transgene expression, however, postnatal transgenic pups display severe phenotypes including runtism, reduced muscle mass and fiber diameters resembling atrophy. Atrogin-1, a marker of skeletal muscle atrophy, is expressed postnatally in transgenic mice. Electron microscopic analyses of transgenic muscle reveal a marked decrease in quiescent muscle satellite cells suggesting a deregulation of postnatal stem cells. Furthermore, transgenic primary myoblasts show a resistance to the effects of TNFalpha upon differentiation. Taken together, our data support a role for PW1 and related stress pathways in mediating skeletal muscle stem cell behavior which in turn is critical for postnatal muscle growth and homeostasis. In addition, these data reveal that postnatal stem cell behavior is likely specified during early muscle development.

Animals↗
PubMed2000

Skeletal muscle function and fibre types: the relationship between occlusal function and the phenotype of jaw-closing muscles in human.

Mammalian skeletal muscle cells are composed of repeated sarcomeric units containing thick and thin filaments of myosin and actin, respectively. Excitation of the myosin ATPase enzyme is possible only with presence of Mg-ATP and Ca(2+). Skeletal muscle fibres may be classified into several types according to the isoform of myosin they contain. Nine isoforms of myosin heavy chain are known to exist in mammalian skeletal muscle including type I, IIA, IIB, IIX, IIM, alpha, neonatal, embryonic, and extra-ocular. Healthy adult human limb skeletal muscle contains type I, IIA, IIB, and IIX myosin heavy chains. The jaw-closing muscles of most carnivores and primates have tissue-specific expression of the type IIM or 'type II masticatory' myosin heavy chain. Adult human jaw-closing muscles, however, do not contain IIM myosin. Rather, they express type I, IIA, IIX (as in human limb muscle), and myosins typically expressed in developing or cardiac muscle. The morphology of human jaw-closing muscle fibres is also unusual in that the type II fibres are of smaller diameter that type I fibres, except in cases of increased function and hypertrophy. This paper describes the relationship of fibre types and motor unit function to changes in human occlusion and masticatory activity. Refereed Scientific Paper

Adult↗
PubMed2004

Skeletal muscle atrophy leads to loss and dysfunction of muscle precursor cells.

Atrophy of skeletal muscle leads to decreases in myofiber size and nuclear number; however, the effects of atrophic conditions on muscle precursor cells (MPC) are largely unknown. MPC lie outside myofibers and represent the main source of additional myonuclei necessary for muscle growth and repair. In the present study, we examined the properties of MPC after hindlimb suspension (HS)-induced atrophy and subsequent recovery of the mouse hindlimb muscles. We demonstrated that the number of MPC in atrophied muscles was decreased. RT-PCR analysis of cells isolated from atrophied muscles indicated that several mRNA characteristic of the myogenic program in MPC were absent. Cells isolated from atrophied muscles failed to properly proliferate and undergo differentiation into multinucleated myotubes. Thus atrophy led to a decrease in MPC and caused dysfunction in those MPC that remained. Upon regrowth of the atrophied muscles, these deleterious effects were reversed. Our data suggest that preventing loss or dysfunction of MPC may be a new pharmacological target during muscle atrophy.

Animals↗
PubMed2000

MRF-4 exhibits fiber type- and muscle-specific pattern of expression in postnatal rat muscle.

The crucial role played by the myogenic regulatory factors (MRFs) in the development of skeletal muscle has been well characterized. The continued expression of these factors in skeletal muscle of the postnatal animal has led to the suggestion that they may play a role in the regulation of muscle fiber phenotype. The few studies that have examined the expression of MRF-4 in postnatal muscle have been carried out at the whole muscle level. These studies demonstrated that this factor is expressed at a higher level than any other MRF but suggested that this was not affected by muscle phenotype. In this study, the expression of the MRF-4 transcript has been examined at the cellular level by in situ hybridization. It was observed that in the mixed fiber type muscle the gastrocnemius, MRF-4 was preferentially expressed in slow muscle fibers, but in the slow postural soleus, no fiber type specificity was observed. These observations suggest that MRF-4 may play a role in the regulation of muscle fiber phenotype in the postnatal animal.

Animals↗
PubMed2004

Inhibition of ryanodine receptor 1 in fast skeletal muscle fibers induces a fast-to-slow muscle fiber type transition.

Skeletal muscle fiber type is regulated by innervation-induced cell signaling including calcium release mechanisms that lead to transcriptional activation of fiber type-specific genes. Avian fast pectoralis major (PM) and slow medial adductor (MA) muscles differentially control expression of the slow myosin heavy chain 2 (slow MyHC2) gene. We report here that slow MyHC2 gene expression in fast PM muscle fibers is repressed by endogenous activity of the ryanodine receptor 1 (RyR1). Inhibition of RyR1 with ryanodine led to expression of the slow MyHC2 gene in innervated PM muscle fibers in vitro. Administration of ryanodine to innervated PM muscle fibers also decreased protein kinase C (PKC) activity, the reduction of which is necessary for slow MyHC2 gene expression in both PM and MA muscle fibers. Furthermore, RyR1 inhibition increased slow MyHC2 promoter activity in innervated PM muscle fibers and enhanced transcriptional activities of nuclear factor of activated T cells (NFAT) and myocyte enhancer factor 2 (MEF2), as well as their interactions with their respective binding sites of the slow MyHC2 promoter. These results indicate that RyR1 activity in innervated fast PM muscle fibers contributes to the cell type-specific repression of slow muscle specific genes.

Animals↗
PubMed1987

Developing muscle spindles in the mouse masseter muscle studied by electron microscopy.

The morphogenesis of the muscle spindles of the masseter muscle was investigated by electron microscopy. The mice used in this study were those from the 16-day-old fetuses to the four-day-old young, and the three-month-old adult ICR mice. At the time of observation the formation of the masseter muscle spindle had already started in the 16-day-old fetus. In the 17-day-old fetus, the sensory nerve terminated not only in the myotube but also in the myoblast in which no myofilaments were yet formed. From the observations on the 16-day-old and 17-day-old fetuses, it is suggested that the myotubes of the intrafusal muscle fibers are formed by the fusion of the myocytes already containing the myofilaments. The gamma motor end-plate appeared two days later than the sensory nerve terminal formation in the muscle spindle. The initial inner capsule of the spindle was observed in the four-day-old young. The cell without the myofilaments appeared amidst the cluster of the intrafusal muscle fibers in the three-day-old young. It is considered that this cell may be the origin of the inner capsule cell. The periaxial space formation and the myelination of the masseteric nerve fiber occurred in the four-day-old young. The formation of the postsynaptic folds was observed in the extrafusal muscle fiber at the same stage. Thus, the muscle spindles, nerve fibers and the extrafusal muscle fibers showed a remarkable development at the same time in this early postnatal stage.

Animals↗
PubMed1980

Number and distribution of muscle spindles in the masticatory muscles of the rat.

The frequency and distribution of muscle spindles in the muscles of mastication of the rat have been studied. The average number of spindles found was 110 in the masseter, 75 in the temporalis and 25 in the medial pterygoid muscle, the spindles being predominantly in the medial parts of these muscles. No muscle spindles were found in the lateral pterygoid or posterior digastric muscle, and only isolated spindles were found in a few of the anterior digastric muscles. These differences between the jaw-closing and the jaw-opening muscles are intriguing and ask for further investigation of the role of the muscle spindles in mastication.

Animals↗
PubMed1983

Is a crossover to the contralateral side by nerve transplants a satisfactory source for reinnervation of a muscle transplant? An experimental study in the rectus femoris muscle of the rabbit.

In ten rabbits the nerve branch to the left rectus femoris muscle was prolonged to the contralateral side by a nerve graft. Three months later the distal end of the transplant was connected to the transsected nerve branch to the right rectus femoris muscle. Nerve biopsies were taken from the muscle nerve, the nerve graft at the time of grafting and from the distal end of the nerve graft immediately before nerve suture in the second operation. Six months after the second operation the final assessment of muscle function and of the histology of the muscle and of the muscle nerve was performed. The functional results of the rectus femoris muscle reinnervated by a crossover nerve graft ranged between 6% and 56% of a normal standard muscle and seemed to be insufficient to justify a clinical use for muscle transplant reinnervation in the extremities. The histological findings also confirmed the basic possibility of elongating a motor nerve by nerve grafts, but the second nerve suture, the interposition of a long nerve graft, and the obviously changed reflex system probably caused a moderate and unpredictable muscle function.

Animals↗
PubMed2006

Altered muscle activation patterns in symptomatic women during pelvic floor muscle contraction and Valsalva manouevre.

AIMS: To investigate the muscle activation patterns of the abdomino-pelvic region used by incontinent women during a pelvic floor muscle (PFM) contraction and a Valsalva manouevre compared to healthy, asymptomatic subjects. METHODS: Thirteen incontinent (symptomatic) women, identified using ultrasound to be consistently depressing the bladder base during PFM contraction, and thirteen continent women (asymptomatic) able to perform an elevating PFM contraction were assessed using surface electromyography (EMG) of the PFM, abdominal and chest wall muscles and vaginal and intra-abdominal pressure (IAP) measurements during PFM contraction and Valsalva under ultrasound surveillance. RESULTS: There were no differences between groups in age, parity or BMI. There was a difference in muscle activation patterns between groups (P = 0.001). During PFM contraction the PFM were less active and the abdominal and chest wall muscles were more active in the symptomatic group. During Valsalva, the PFM and EO were more active in the symptomatic group but there was no difference in the activation of the other muscles between groups. There was a significant interaction (group x pressure) for change in IAP (P = 0.047) but no significant interaction for change in vaginal pressure (VP) (P = 0.324). CONCLUSIONS: The symptomatic women displayed altered muscle activation patterns when compared to the asymptomatic group. The symptomatic women were unable to perform a voluntary PFM contraction using a localized muscle strategy, instead activating all the muscles of the abdomino-pelvic cavity. The potential for muscle substitution strategies reinforces the need for close attention to specificity when prescribing PFM exercise programs.

Adult↗
PubMed2005

Indomethacin preserves muscle mass and reduces levels of E3 ligases and TNF receptor type 1 in the gastrocnemius muscle of tumor-bearing mice.

Tumor-induced skeletal muscle wasting involves tumor necrosis factor (TNF) and the ubiquitin-proteasome pathway of muscle protein degradation. In this study, growth of the colon-26 adenocarcinoma in mice was associated with diminished gastrocnemius muscle mass and increased muscle levels of actin, ubiquitin-conjugated proteins, free ubiquitin, E3 ubiquitin ligases, and the type 1 TNF receptor (TNFR1). Indomethacin at 1 or 5 mg/kg/day reduced tumor growth and muscle levels of TNFR1. However, only the 5 mg dose of indomethacin reduced muscle wasting and muscle levels of the E3 ligases and actin. These data suggest that the beneficial effects of indomethacin in the treatment of tumor-induced skeletal muscle wasting may involve inhibition of TNF- and ubiquitin-mediated pathways of muscle protein degradation. These data also demonstrate that E3 ligases, which are involved in disuse atrophy, also are associated with tumor-induced skeletal muscle wasting.

Adenocarcinoma↗
PubMed1993

Developmental regulation of the Drosophila tropomyosin II gene in different muscles is controlled by muscle-type-specific intron enhancer elements and distal and proximal promoter control elements.

Transcriptional control of the Drosophila tropomyosin II gene muscle promoter has been investigated by expressing TmII promoter lacZ reporter gene constructs in P-element-mediated transformed flies. A TmII/lacZ reporter gene containing 243 bp of upstream sequence, the first exon, the first intron, and 72 bp of the second exon was expressed in all muscles of embryos, larvae, and adults. Deletion of upstream sequences between -243 and -22 bp only reduced the levels of transgene expression in muscle while deletion of the intron eliminated expression. Analysis of deletions within the first intron indicated that a 454-bp muscle enhancer region, from +167 to +621, was required for high levels of transgene expression in all larval and adult muscles. When this region was deleted low levels of expression still occurred in larval and adult somatic and visceral muscles; however, there was no detectable expression in adult indirect flight and jump muscles. The 454-bp muscle enhancer region was also able to drive muscle-specific expression when placed upstream of a heterologous hsp70 promoter; however, three subfragments of the 454-bp region were unable to drive expression of the hsp70 promoter, suggesting that this region may contain multiple interacting cis-acting elements. Interestingly, the 454-bp region was inactive when placed upstream of a TmII promoter construct containing upstream DNA and most of the first exon but was active when additional exon and intron DNA was included, indicating that additional promoter elements are located in this region. Thus TmII transcription is controlled by multiple muscle type-specific cis-acting control elements and upstream and downstream promoter control elements.

Animals↗
PubMed1997

Ectopic expression of MEF2 in the epidermis induces epidermal expression of muscle genes and abnormal muscle development in Drosophila.

Myocyte-specific enhancer-binding factor 2 (MEF2) is a myogenic regulatory factor in vertebrates and Drosophila. Whereas the role of MEF2 in regulating vertebrate myogenesis and muscle genes has been extensively studied, little is known of the role of MEF2 in regulating Drosophila myogenesis. We have shown in a recent analysis of the regulation of the Drosophila Tropomyosin I (TmI) gene in transgenic flies that MEF2 is a positive regulator of TmI expression in the somatic body-wall muscles of embryos, larvae, and adults. To understand further the role of MEF2 in myogenesis and test the role of MEF2 in regulating TmI expression, we have used the yeast GAL4/UAS system to generate embryos in which MEF2 is ectopically expressed in tissues where it is not normally expressed or embryos in which MEF2 is overexpressed in the mesoderm and muscles. We observe that ectopic expression of MEF2 in the epidermis and the ventral midline cells in embryos activates the expression of TmI and other muscle genes in these tissues and that this activation is stage-dependent suggesting a requirement for additional factors. Furthermore, ectopic expression of MEF2 in the epidermis results in a decrease in the expression of signaling molecules in the epidermis and a failure of the embryo to properly form body-wall muscles. These results indicate that MEF2 can function out of context in the epidermis to induce the expression of muscle genes and interfere with a requirement for the epidermis in muscle development. We also find that the level of MEF2 in the mesoderm and/or muscles in embryos is critical to body-wall muscle formation; however, no effect is observed on the development of the visceral muscle or dorsal vessel.

Animals↗
PubMed1999

Expression of matrix metalloproteinases 2 and 9 in regenerating skeletal muscle: a study in experimentally injured and mdx muscles.

Matrix metalloproteinases (MMPs) cooperatively degrade all components of the extracellular matrix (ECM). Remodeling of ECM during skeletal muscle degeneration and regeneration suggests a tight regulation of matrix-degrading activity during muscle regeneration. In this study, we investigated the expression of MMP-2 and MMP-9, in normal muscles and their regulation during regeneration process. We further investigated their secretion by C2C12 myogenic cell line. Two models of muscle degeneration-regeneration were used: (1) normal muscles in which necrosis was experimentally induced by cardiotoxin injection; (2) mdx muscles which exhibit recurrent signs of focal myofiber necrosis followed by successful regeneration. MMPs were studied by zymography; their free activity was quantified using 3H-labeled gelatin substrate and mRNA expression was followed by Northern hybridization. Muscle degeneration-regeneration was analyzed by conventional morphological methods and in situ hybridization was performed on muscle sections to identify the cells expressing these MMPs. Results show that MMP-2, but not MMP-9 expression, is constitutive in normal muscles. Upon injury, the active form of MMP-2 is transiently increased, whereas MMP-9 is induced within 24 h and remains present for several days. Quantitative assays of free gelatinolytic activity show a progressive and steady increase that culminates at 7 days postinjury and slowly returns to normal levels. In adult mdx mice, both pro and active forms of MMP-2 and MMP-9 are expressed. Northern blot results support these findings. Zymography of C2C12-conditioned medium shows that myogenic cells produce MMP-2. By in situ hybridization we localized MMP-9 mRNA in inflammatory cells and putative activated satellite cells in injured muscles. Our data allow the correlation of the differential expression of pro and/or active forms of MMP-2 and MMP-9 with different stages of the degeneration-regeneration process: MMP-9 expression is related to the inflammatory response and probably to the activation of satellite cells, whereas MMP-2 activation is concomitant with the regeneration of new myofibers.

Animals↗
PubMed2003

Muscle reoxygenation rate after isometric exercise at various intensities in relation to muscle oxidative capacity.

The purpose of this study was to determine whether the reoxygenation rate (Reoxy-rate) immediately after static exercise at various submaximal intensities would be related to muscle oxidative capacity. Seven healthy male subjects performed isometric handgrip exercise for 10 sec at 30%, 60% and 90% of maximal voluntary contraction (MVC). The Reoxy-rate and muscle oxygen consumption during exercise (muscle VO2EX) were monitored by near infrared continuous wave spectroscopy (NIRcws). The muscle oxidative capacity was evaluated by the time constant for phosphocreatine resynthesis (PCrTc) using 31-phosphorus magnetic resonance spectroscopy (31P-MRS). The Peak blood flow of brachial artery after exercise (BABFpeak) was measured using Doppler ultrasound. There was no correlation between PCrTc and Reoxy-rate at 30% and 60% MVC. In contrast, Reoxy-rate at 90% MVC was positively correlated to PCrTC (r = 0.825, p < 0.05). The muscle VO2EX increased 5.9, 8.8 and 12.6-fold of the resting on average at 30%, 60% and 90% MVC, respectively, and the muscle VO2EX at 90% MVC was significantly higher than that at 30% and 60% MVC. On the other hand, BABFpeak increased only just 1.9, 2.4 and 2.7-fold of the resting on average at 30%, 60% and 90% MVC, respectively (Fig. 4). These results suggest that the higher oxidative capacity muscle shows slower muscle reoxygenation after 10 sec isometric exercise at 90% MVC because the Reoxy-rate after this type of exercise may be influenced more by muscle VO2 than by O2 supply. In contrast, 60% MVC and lower exercise intensities may not be severe enough to influence the muscle VO2 dependent Reoxy-rate.

Exercise↗
PubMed1992

Enhancement of muscle regeneration in the rat gastrocnemius muscle by low energy laser irradiation.

The effect of low-energy laser (He-Ne) irradiation on the rate of skeletal muscle regeneration after partial excision of the rat gastrocnemius muscle was studied using quantitative histological morphometric methods. The injured zones of the experimental rats were subjected to direct He-Ne laser (632.8 nm wavelength) irradiation (6.0 mW for 2.3 min) immediately following injury and once daily thereafter for 5 days. Muscles that were injured as above and subjected to red or room light irradiation served as a control group. The volume fraction (percent of total volume of injured zone) of the mononucleated cells in the injured zone decreased gradually with time after injury, but more rapidly in the laser irradiated muscles than in the control. At 3 days post-injury the myotubes in the laser-irradiated muscles populated a significantly higher percentage (13.9 +/- 1.1%) of the injured area than in the control muscles (7.8 +/- 1.0%). The volume fraction of the young myofibers in the laser irradiated muscles exceeded 30.6 +/- 2.2% and 49.6 +/- 5.6% at 8 and 11 days post-injury, respectively, while in control muscles these structures comprised only 9.6 +/- 1.0% and 27.2 +/- 3.8% of the injured zone at 8 and 11 days after injury, respectively. It is concluded that He-Ne laser irradiation during the regeneration process promotes muscle maturation in the injured zone following partial excision of the rat gastrocnemius muscle.

Animals↗
PubMed1990

Multifocal innervation and muscle length. A morphological study on the role of myo-myonal junctions, fiber branching and multiple innervation in muscles of different size and shape.

The dependence of the inner organisation and innervation of a skeletal muscle on its size was studied at the level of single muscle fiber architecture and motor endplate topography in muscles of different size, all of them lacking a tendinous scaffolding. The muscles evaluated in this study were: Mm. sternomastoideus, gracilis and latissimus dorsi of the rat and the M. sternocephalicus of the horse. In these muscles a subdivision into two or more 'innervation-compartments' becomes obvious in fascicles reaching a certain length. This provides the possibility of an almost synchronous activation of the entire muscle by its nerve. At the level of single muscle fiber elements, large numbers of myo-myonal junctions were discernible in many sites. However, unequivocal multiple innervation was found, with several end-plates per single muscle fiber, without the interposition of any junctional structure. Myo-myonal junctions, combined with a characteristic branching pattern of many muscle fibers, and scattered innervation sites, obviously play an important role in the architecture of fan-like muscles lacking a tendinous scaffolding.

Animals↗