Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study's purpose was to examine the influence of an altered activity level, via artificial rearing, on the contractile properties, myosin heavy chain phenotypes (MHC), and muscle fiber sizes of the developing rat tongue retractor musculature. Artificially reared rat pups were fed through a gastric cannula, eliminating nutritive suckling from postnatal day 4 to postnatal day 14. Rat pups were observed immediately following artificial rearing (postnatal day 14) and after a 1-mo resumption of function (postnatal day 42). The contractile characteristics of the tongue retractor musculature were measured in response to stimulation of the hypoglossal nerve. At postnatal day 14, artificially reared rat pups demonstrated significantly longer twitch half-decay times, lower fusion frequencies, and a marked decrease in fatigue resistance. These contractile speed and fatigue characteristics were fully recovered following a 1-mo resumption of function. MHC phenotypes of the styloglossus muscle (a tongue retractor) were determined by gel electrophoresis. At postnatal day 14, artificial rearing had not altered the MHC phenotype or muscle fiber sizes of the styloglossus muscle. However, following a 1-mo resumption of function artificially reared rat pups demonstrated a small but significant increase in MHCIIa expression and decrease in MHCIIb expression compared with dam-reared rats. These results support artificial rearing as a useful model for altering the activity level of the tongue and suggest that normal suckling behavior is necessary for the normal postnatal development of the tongue retractor musculature. This may also be the case for premature infants necessarily fed artificially.
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PMID:Effect of artificial rearing on the contractile properties and myosin heavy chain isoforms of developing rat tongue musculature. 1284 5

Capillary proliferation occurs during compensatory hypertrophy. We investigated whether the expression of vascular endothelial growth factor (VEGF) is elevated at the onset of hypertrophy when capillary proliferation is minimal, and whether muscle damage as assessed by muscle force deficits, may occur at the onset of hypertrophy. To investigate this, we induced in 9-month-old rats, under isoflurane anesthesia, hypertrophy of the left plantaris muscle by denervation of the gastrocnemius and soleus muscles. Capillarization was investigated in both the deep (oxidative) and the superficial (glycolytic) regions of the plantaris muscle. After 2 weeks, muscle mass had increased by 16% (p< 0.01), which was not accompanied by increases in fiber size. The maximal tetanic force (P(0)) and specific tension (P(0).g(-1) or P(0).cm(2)) and twitch characteristics were unaltered, and fatigue resistance of the overloaded muscle was improved (p< 0.05). However, the myosin heavy chain composition was unaltered. Capillary proliferation was not yet evident, but VEGF mRNA and protein levels were elevated 1.5- and 8-fold, respectively (p< 0.05). We concluded that the normal specific tension and the elevated VEGF expression after 2 weeks of overload indicate (1) an absence of or minimal muscle damage at this early time point, and (2) that elevated VEGF expression precedes and is involved in capillary proliferation that occurs during the later stages of compensatory hypertrophy.
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PMID:Vascular endothelial growth factor, capillarization, and function of the rat plantaris muscle at the onset of hypertrophy. 1452 79

Muscle has an intrinsic ability to adapt to different types of work by changing fibre type and muscle mass. This process involves quantitative and qualitative changes in gene expression including those of the myosin heavy chain (MyHC) isogenes that encode different types of molecular motors. Increased expression of slow MyHC and of metabolic genes result in increased fatigue resistance. Recently, there has been some insight into how oxidative metabolism, as well as slow myosin expression, is regulated and the role of calcium in initiating switches in gene expression. In relation to muscle mass and power output it has been appreciated that local as well as systemic factors are important. Our group have cloned three types of IGF-I in human muscle which are derived from the IGF-I gene by alternative splicing. The expression of one of these that appears to be an autocrine/paracrine splice variant is only detectable after mechanical stimulation (MGF) and a systemic type (IGF-IEa) that is produced by the liver and other tissue including muscle. As the result of a reading frame shift, the MGF peptide has a different C terminal sequence to IGF-IEa. Interestingly, the MGF C terminal peptide has been found to act as a separate growth factor and to initially activate mononluceated myoblasts (satellite cells). MGF also responds to different signals and has different expression kinetics to IGF-IEa. The mechanotransduction mechanism for this signalling may directly or indirectly involve the dystrophin complex as dystrophic muscle, unlike normal muscle, is unable to express MGF in response to overload. Also the ability to express MGF has been found to decline markedly during ageing. The deficiency in expressing MGF and activating satellite cells in dystrophic and aged muscles may explain why muscle mass is not maintained in these situations. However, in normal muscle MGF appears to initiate local muscle repair with its over expression resulting in hypertrophy.
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PMID:Gene expression in muscle in response to exercise. 1460 23

In humans, progressive resistance exercise is recognized for its ability to induce skeletal muscle hypertrophy. In an attempt to develop an animal model which mimics human progressive resistance exercise, Sprague-Dawley rats were trained to climb a 1.1-m vertical (80 degree incline) ladder with weights secured to their tail. The rats were trained once every 3 days for 8 weeks. Each training session consisted of 4-9 (6.02 +/- 0.23) climbs requiring 8-12 dynamic movements per climb. Based on performance, the weight carried during each session was progressively increased. Over the course of 8 weeks, the maximal amount of weight the rats could carry increased 287%, p </= 0.001. The improved training performance was associated with a 23% absolute increase in the weight of the flexor hallucis longus (FHL), with a concomitant 24% increase in both total and myofibrillar protein, p</= 0.001. Peak tetanic tension (Po) of the FHL increased 20%, p </= 0.001, while specific tetanic tension (SPo) was not altered. No change in twitch tension (Pt) was observed, which resulted in a 22% decrease in specific twitch tension (SPt) p </= 0.01. Despite a decrease in resistance to fatigue, p </= 0.05, myosin heavy chain composition, ATP, ADP, creatine, and creatine phosphate concentrations of the FHL were not altered. The results of this study describe an animal model that mimics many of the training parameters and physiological adaptations observed with human progressive resistance exercise.
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PMID:Physiological hypertrophy of the FHL muscle following 8 weeks of progressive resistance exercise in the rat. 1500 1

Some rodent species show rhythmic bouts of vibrissal protractions and retractions, referred to as whisking, that are among the fastest movements performed by mammals. To better understand the muscular basis of whisking, we compared (1) whisker movements of two whisking species (mouse, rat) and a non-whisking species (guinea pig), (2) the muscle fiber composition of intrinsic whisker muscles of whisking and a non-whisking species, and (3) the muscle fiber composition of intrinsic whisker muscles and of selected skeletal muscles. Using high-speed videography, we found that mice, rats, and guinea pigs can generate fast and large-amplitude whisker movements. Guinea pigs do not show bouts of fast, strictly rhythmic whisker movements, and the average speed of their whisker movements is much lower than in mice and rats. Analysis of mRNA expression of myosin heavy chain isoforms, myofibrillar ATPase staining, and antibody labeling indicate that in all three species intrinsic whisker muscles are composed predominantly of type 2B muscle fibers. Intrinsic whisker muscles of mice consisted of type 2B (> or =90%) and type 2D fibers. In rats we observed, in addition to type 2B/2D fibers, approximately 10% of slow type 1 fibers, and in guinea pigs we observed approximately 3% of slow type 1 fibers and 20% of type 2A fibers. Type 2B fibers have high levels of anaerobic glycolytic enzymes providing a rapid source of ATP and high maximum velocity of contraction but are less fatigue resistant than other muscle fiber types. The high percentage of type 2B fibers distinguishes the intrinsic whisker musculature from skeletal muscles and may have evolved for fast scanning of the sensory environment.
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PMID:Fiber types of the intrinsic whisker muscle and whisking behavior. 1505 18

Resistance exercise can result in both potentiating and fatiguing responses. These responses can acutely affect performance, which may affect subsequent exercise sessions in the same day. The purpose of this investigation was to study the acute neuromuscular responses to two high intensity training sessions in the same day. Twelve recreationally trained males performed two training sessions, each involving ten sets of five repetitions in the speed squat exercise. For the initial session (HIT-1), the barbell load was constant at 70% one repetition maximum, whereas during the second session (HIT-2), barbell load decreased if movement velocity decreased. Neuromuscular performance testing consisted of unilateral isometric knee extensor actions performed prior to the training day (PRE) and following each testing session. Prior to the sessions, subjects provided a muscle biopsy for myosin heavy chain analysis. Peak force was impaired 16.9 (9.5)% (P approximately 0.00; d=1.62) following HIT-1 and 19.9 (18.4)% (P approximately 0.00; d=1.94) following HIT-2. Initial rate of force development was depressed from PRE following HIT-1 (P approximately 0.00; d=1.74) and HIT-2 (P approximately 0.00; d=2.18); however, this was dependent on muscle fiber composition. Significant correlations existed between the change score for initial rate of force development from HIT-1 to HIT-2 and myosin heavy chain I (r= -0.60; P=0.04) and IIa (r=0.69; P=0.01) expression. Impaired neuromuscular performance following HIT-1 may occur due to low frequency fatigue. For individuals with predominantly myosin heavy chain IIa, HIT-2 appeared to induce post-activation potentiation, resulting in restoration of the initial rate of force development.
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PMID:Neuromuscular fatigue and potentiation following two successive high intensity resistance exercise sessions. 1518 85

Recruitment determines the profile of fibre-type-specific genes expressed across the range of muscle fibres associated with slow, fast fatigue-resistant and fast fatiguable motor units. Downstream signalling pathways activated by neural signalling and mechanical load have been the focus of intensive research in past years. It is now known that Ca(2+)-dependent calcineurin-nuclear factor of activated T cells and insulin-like growth factor 1 pathways and their downstream mediators contribute to these adaptive responses. These pathways regulate gene expression through muscle-specific (myocyte-enhancing factor 2, myoblast determination protein) and non-specific (nuclear factor of activated T cell 2, GATA-2) transcription factors. Transcriptional signals activated with increased contractile activity result in altered expression of fibre-type specific genes, including the myosin heavy chain isoforms and oxidative and glycolytic enzymes and a net change in muscle fibre-type composition. In contrast, transcriptional signals activated by increased load bearing result in hypertrophy or a growth response, a component of which involves satellite cell recruitment and fusion with existing adult myofibres. Calcineurin has been identified as a key mediator in the hypertrophic response, and the current challenge has been to determine the downstream target genes of this pathway. Exciting new data have emerged, showing that myostatin, a negative regulator of muscle growth, and utrophin, a cytoskeletal protein important in maintaining membrane integrity, are downstream targets of calcineurin signalling. Increased understanding of these mediators of muscle growth may provide strategies for the development of effective therapeutics to counter muscle weakness and muscular dystrophy.
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PMID:Calcineurin and skeletal muscle growth. 1529 53

Skeletal muscles are composed of fibres of different types, each type being identified by the isoform of myosin heavy chain which is expressed as slow 1, fast 2A, fast 2X, and fast 2B. Slow fibres are resistant to fatigue due to their highly oxidative metabolism whereas 2X and 2B fibres are easily fatiguable and fast 2A fibres exhibit intermediate fatigue resistance. Slow fibres and fast fibres are present in equal proportions in the adult human diaphragm while intercostal muscles contain a higher proportion of fast fibres. A small fibre size, abundance of capillaries, and a high aerobic oxidative enzyme activity are typical features of diaphragm fibres and give them the resistance to fatigue required by their continuous activity. Because of their fibre composition, intercostal muscles are less resistant to fatigue. The structural and functional characteristics of respiratory muscle fibres are not fixed, however, and can be modified in response to several physiological and pathological conditions such as training (adaptation to changes in respiratory load), adaptation to hypoxia, age related changes, and changes associated with respiratory diseases. The properties of respiratory muscle fibres can also be modified by pharmacological agents such as beta2 agonists and corticosteroids used for the treatment of respiratory diseases.
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PMID:Respiratory muscle fibres: specialisation and plasticity. 1533 61

Patients with obstructive sleep apnea (OSA) often exhibit fatigued or inefficient upper airway dilator and constrictor muscles; an upper airway dilator, the geniohyoid (GH) muscle, is a particular example. Intermittent hypoxia (IH) is a frequent concomitant of OSA, and it may trigger muscle fiber composition changes that are characteristic of a fatigable nature. We examined effects of short-term IH on diaphragmatic and GH muscle fiber composition and fatigue properties by exposing 24 rats to alternating 10.3% O(2)-balance N(2) and room air every 480 s (240 s duty cycle) for a total duration of 5, 10, 15, 20, or 30 h. Sternohyoid fiber composition was also examined. Control animals were exposed to room air on the same schedule. Single-fiber analyses showed that GH muscle fiber types changed completely from myosin heavy chain (MHC) type 2A to MHC type 2B after 10 h of exposure, and the conversion was maintained for at least 30 h. Sternohyoid muscle fibers showed a delayed transition from MHC type 2A/2B to MHC type 2B. In contrast, major fiber types of the diaphragm were not significantly altered. The GH muscles showed similar tension-frequency relationships in all groups, but an increased fatigability developed, proportional to the duration of IH treatment. We conclude that short-term IH exposure alters GH muscle composition and physical properties toward more fatigable, fast-twitch types and that it may account for the fatigable upper airway fiber types found in sleep-disturbed breathing.
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PMID:Geniohyoid muscle properties and myosin heavy chain composition are altered after short-term intermittent hypoxic exposure. 1555 11

We have analysed the rate and ultimate extent of muscle functional recovery after snake venom-induced myotoxicity, as well as the relationships between functional, biochemical and structural indices of recovery. We also compared the effects of various injuries leading to muscle necrosis, loss of innervation/vasculature and/or precursors of muscle cells (pmc). We found that several parameters of rat soleus muscle such as maximal isometric force, slow myosin heavy chain, and citrate synthase, were fully and rapidly restored within 6 weeks after treatment with snake Notechis scutatus venom (im, 2 microg/muscle). In contrast, some muscle contractile properties (degree of tetanic fusion, fatigue resistance...) were not fully recovered even by 12 weeks after venom treatment. However, when compared to other injuries, recovery 3 weeks after venom treatment, was better than that observed after severing the terminal nerve and accompanying vessels and after cryodamage known to kill pmc. In conclusion, our studies demonstrate that-contrary to what is commonly believed -- muscle treated by myotoxic agent does not recover rapidly and fully. However, the degree or rate of muscle recovery after snake venom treatment was much better when compared to other types of injury. In addition, histological and biochemical parameters cannot be used as such to easily predict functional recovery following injury.
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PMID:Functional, cellular and molecular aspects of skeletal muscle recovery after injury induced by snake venom from Notechis scutatus scutatus. 1580 29


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