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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent investigations from our and other laboratories indicate that glycogen is a carbon-chain precursor in muscle for the synthesis of TCA cycle intermediates and glutamine. During intense exercise and in conditions of a relative lack of energy (hypoxia, trauma, sepsis) the metabolism of branched-chain amino acids (BCAA) is accelerated in muscle. In the primary BCAA aminotransferase reaction 2-oxoglutarate is used as amino-group acceptor (putting a carbon-drain on the TCA cycle) under formation of glutamate. Glutamate will subsequently react with ammonia, generated in the AMP deaminase reaction or by deamination of amino acids, under formation of glutamine in a reaction catalysed by glutamine synthetase (glutamate + ammonia + ATP--> glutamine + ADP). Muscle glycogen stores may be smaller or less available at high altitude. It is hypothesized that this will lead to premature fatigue (due to both a lack of fuel and of TCA cycle carbon-precursor) and to a reduction in the synthesis rate of glutamine. A chronic reduction in the synthesis rate of glutamine during a long term stay at high altitude on its turn may lead to gut atrophy, bacterial translocation, endotoxemia, muscle protein catabolism and a weakened immune status.
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PMID:Amino acid metabolism, muscular fatigue and muscle wasting. Speculations on adaptations at high altitude. 148 45

Fatigue is a common adverse effect of cancer and its therapy. However, the specific mechanisms underlying cancer fatigue are unclear. One physiologic mechanism may involve changes in skeletal muscle protein stores or metabolite concentration. A reduction in skeletal muscle protein stores may result from endogenous tumor necrosis factor (TNF) or from TNF administered as antineoplastic therapy. This muscle wasting would require patients to exert an unusually high amount of effort to generate adequate contractile force during exercise performance or during extended periods of sitting or standing. This additional effort could result in the onset of fatigue. Additionally, cancer fatigue may develop or become exacerbated during exercise as a consequence of changes in the concentration of skeletal muscle metabolites. These biochemical alterations may interfere with force that is produced by the muscle contractile proteins. These physiologic changes may play a role in the decision to include exercise in the rehabilitation plans of patients with cancer. They also may affect ideas about fatigue.
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PMID:Fatigue mechanisms in patients with cancer: effects of tumor necrosis factor and exercise on skeletal muscle. 159 64

The chronic "unloading" of the neuromuscular system during spaceflight has detrimental functional and morphological effects. Changes in the metabolic and mechanical properties of the musculature can be attributed largely to the loss of muscle protein and the alteration in the relative proportion of the proteins in skeletal muscle, particularly in the muscles that have an antigravity function under normal loading conditions. These adaptations could result in decrements in the performance of routine or specialized motor tasks, both of which may be critical for survival in an altered gravitational field, i.e., during spaceflight and during return to 1 G. For example, the loss in extensor muscle mass requires a higher percentage of recruitment of the motor pools for any specific motor task. Thus, a faster rate of fatigue will occur in the activated muscles. These consequences emphasize the importance of developing techniques for minimizing muscle loss during spaceflight, at least in preparation for the return to 1 G after spaceflight. New insights into the complexity and the interactive elements that contribute to the neuromuscular adaptations to space have been gained from studies of the role of exercise and/or growth factors as countermeasures of atrophy. The present chapter illustrates the inevitable interactive effects of neural and muscular systems in adapting to space. It also describes the considerable progress that has been made toward the goal of minimizing the functional impact of the stimuli that induce the neuromuscular adaptations to space.
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PMID:Neuromuscular adaptation to actual and simulated weightlessness. 775 53

Seventeen patients undergoing elective open cholecystectomy were given conventional total parenteral nutrition either with (nine patients) or without (eight) glutamine supplementation of 20 g/day for 3 days after surgery and thereafter ordinary food for the following 27 days. Muscle protein synthesis, as assessed by the total concentration of ribosomes, decreased in control patients on day 3 following surgery and remained low on days 10, 20 and 30 (P < 0.05). In patients who received glutamine the total ribosome concentration was maintained on the third day after operation. Concurrently, the subjective feeling of fatigue increased on days 3 and 10 after surgery and the nitrogen balance was negative after operation in both groups, without any difference related to glutamine supplementation. Intravenous glutamine after surgery counteracts a decline in muscle protein synthesis only for as long as it is provided.
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PMID:Long-term effects of postoperative total parenteral nutrition supplemented with glycylglutamine on subjective fatigue and muscle protein synthesis. 782 Apr 92

Eccentric muscle contractions generate delayed onset muscle soreness (DOMS), possibly as a result of the high tensions involved causing muscle damage. Muscle function, serum indicators of muscle damage, and DOMS were investigated throughout a training regimen that involved a 40-min eccentric walk down a 25% gradient on a treadmill at 6.4 km/h once a week for 8 wk. Serum creatine kinase and myoglobin concentrations were used as indicators of muscle damage, and both demonstrated a delayed increase after the exercise protocol. The muscles that contracted eccentrically exhibited low-frequency fatigue, as well as decreases in muscle fatigability and maximal voluntary contraction force, which were greatest immediately postexercise. Although the results show that training reduces DOMS, the serum muscle protein response, and muscle function impairment, the time courses of these adaptations are different. It is suggested that the function of the muscle can be impaired without apparent muscle damage.
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PMID:Effect of training on eccentric exercise-induced muscle damage. 828 2

Muscle may suffer from a number of diseases or disorders, some being fatal to humans and animals. Their management or treatment depends on correct diagnosis. Although no single method may be used to identify all diseases, recognition depends on the following diagnostic procedures: (1) history and clinical examination, (2) blood biochemistry, (3) electromyography, (4) muscle biopsy, (5) nuclear magnetic resonance, (6) measurement of muscle cross-sectional area, (7) tests of muscle function, (8) provocation tests, and (9) studies on protein turnover. One or all of these procedures may prove helpful in diagnosis, but even then identification of the disorder may not be possible. Nevertheless, each of these procedures can provide useful information. Among the most common diseases in muscle are the muscular dystrophies, in which the newly identified muscle protein dystrophin is either absent or present at less than normal amounts in both Duchenne and Becker's muscular dystrophy. Although the identification of dystrophin represents a major breakthrough, treatment has not progressed to the experimental stage. Other major diseases of muscle include the inflammatory myopathies and neuropathies. Atrophy and hypertrophy of muscle and the relationship of aging, exercise, and fatigue all add to our understanding of the behavior of normal and abnormal muscle. Some other interesting related diseases and disorders of muscle include myasthenia gravis, muscular dysgenesis, and myclonus. Disorders of energy metabolism include those caused by abnormal glycolysis (Von Gierke's, Pompe's, Cori-Forbes, Andersen's, McArdle's, Hers', and Tauri's diseases) and by the acquired diseases of glycolysis (disorders of mitochondrial oxidation). Still other diseases associated with abnormal energy metabolism include lipid-related disorders (carnitine and carnitine palmitoyl-transferase deficiencies) and myotonic syndromes (myotonia congenita, paramyotonia congenita, hypokalemic and hyperkalemic periodic paralysis, and malignant hyperexia). Diseases of the connective tissues discussed include those of nutritional origin (scurvy, lathyrism, starvation, and protein deficiency), the genetic diseases (dermatosparaxis, Ehlers-Danlos syndrome, osteogenesis imperfecta, Marfan syndrome, homocystinuria, alcaptonuria, epidermolysis bullosa, rheumatoid arthritis in humans, polyarthritis in swine, Aleutian disease of mink, and the several types of systemic lupus erythematosus) and the acquired diseases of connective tissues (abnormal calcification, systemic sclerosis, interstitial lung disease, hepatic fibrosis, and carcinomas of the connective tissues). Several of the diseases of connective tissues may prove to be useful models for determining the relationship of collagen to meat tenderness and its other physical properties. Several other promising models for studying the nutrition-related disorders and the quality-related characteristics of meat are also reviewed.
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PMID:Diseases and disorders of muscle. 839 47

The dystrophin-deficient, X-linked dystrophic mouse (mdx) was used to evaluate the efficacy of prednisolone treatment. A test protocol was used to take advantage of the quantifiable weakness and disability as well as molecular genetic defect shared with the X-linked Duchenne muscular dystrophy (DMD). Whole-body weakness and fatigue were determined by non-invasive force-transducer physiographic and variable-speed treadmill techniques, respectively. Other measurements included hind-limb muscle protein, calcium, and histomorphology. Subcutaneously-administered prednisolone elicited significant improvements in whole body strength throughout a two-month test period. Increases in strength were also accompanied by measurable increments in running endurance. In fact, prednisolone treatment appeared to protect mdx mice from the stressful effect of continuous running as determined by strength and muscle fiber diameter. Test results from this study support the limited therapeutic benefit observed previously in DMD patients treated with the glucocorticoid.
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PMID:Strength and endurance in the therapeutic evaluation of prednisolone-treated MDX mice. 843 32

The purpose of this study was to investigate whether exercise could induce calpain activation by altering the Ca2+ required for half-maximal activity (pCa50) and/or susceptibility of digestible muscle protein substrates. Rats (225 g) were assigned to control, exercise (25 m/min, 0% grade), and 24-h recovery groups. Exercise resulted in a generalized 48 +/- 18% loss of muscle glycogen and a twofold increase in plasma creatine kinase levels (P < or = 0.05). Exercise increased total caseinolysis of diethylaminoethyl Sepharose-prepared low (u) and high (m) Ca2+ calpain isoforms by 22 and 30%, respectively (P < or = 0.05). The pCa50 of u- and m-calpain with exercise increased from 5.98 +/- 0.12 to 6.20 +/- 0.15 (P > or = 0.05) and from 3.63 +/- 0.10 to 3.90 +/- 0.16 (P > or = 0.05), respectively. In vitro, calpain-mediated degradation/disappearance rates (i.e., percentage of protein degraded in 10 min) for control tropomyosin and alpha-actinin were 69 and 30% compared with 92 and 61% after exercise (P < or = 0.05). The results of this study confirm that level running increases total nonlysosomal Ca2+ specific protease activity, which may promote exercise-induced muscle damage or fatigue.
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PMID:Skeletal muscle calcium-activated neutral protease (calpain) with exercise. 848 81

1. Chronic fatigue syndrome is characterized by muscle fatigue and pain at rest, symptoms which are usually exacerbated with exercise. Although various studies have shown minor, non-specific morphological and biochemical changes in muscle of patients with chronic fatigue syndrome, no consistent defect has been identified. Some have suggested that an enteroviral infection in muscle may cause the chronic muscle fatigue seen in patients with chronic fatigue syndrome, with acute infection directly and irreversibly impairing mitochondrial function, and persistent infection depressing muscle protein synthesis and metabolism. 2. To clarify the involvement of enterovirus infection in chronic fatigue syndrome, muscle biopsies from a group of patients with chronic fatigue syndrome were examined for the presence of enteroviral RNA by reverse transcriptase-polymerase chain reaction techniques in relation to functional studies of muscle mitochondria and the muscle RNA/DNA ratio. 3. Fifty-eight percent of patients reported an uncharacterized 'viral infection' before the onset of their illness, but none of the muscle samples from 34 patients contained detectable amounts of enteroviral RNA. Muscle tissue had a general reduction in the RNA/DNA ratio and mitochondrial enzyme activities with no specific abnormality in the activity of enzymes encoded partially on the mitochondrial genome (cytochrome-c oxidase) or nuclear genome (citrate synthase, succinate reductase). 4. These data provide no evidence of an enteroviral infection in muscle of patients with chronic fatigue syndrome, although this does not exclude a role of enterovirus in initiating the disease process. The general reduction in RNA/DNA ratio and mitochondrial enzyme activities is consistent with a general reduction in habitual activity.
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PMID:Investigation by polymerase chain reaction of enteroviral infection in patients with chronic fatigue syndrome. 877 36

The combination of abnormally low plasma cystine and glutamine levels, low natural killer (NK) cell activity, skeletal muscle wasting or muscle fatigue, and increased rates of urea production defines a complex of abnormalities that is tentatively called "low CG syndrome." These symptoms are found in patients with HIV infection, cancer, major injuries, sepsis, Crohn's disease, ulcerative colitis, chronic fatigue syndrome, and to some extent in overtrained athletes. The coincidence of these symptoms in diseases of different etiological origin suggests a causal relationship. The low NK cell activity in most cases is not life-threatening, but may be disastrous in HIV infection because it may compromise the initially stable balance between the immune system and virus, and trigger disease progression. This hypothesis is supported by the coincidence observed between the decrease of CD4+ T cells and a decrease in the plasma cystine level. In addition, recent studies revealed important clues about the role of cysteine and glutathione in the development of skeletal muscle wasting. Evidence suggests that 1) the cystine level is regulated primarily by the normal postabsorptive skeletal muscle protein catabolism, 2) the cystine level itself is a physiological regulator of nitrogen balance and body cell mass, 3) the cyst(e)ine-mediated regulatory circuit is compromised in various catabolic conditions, including old age, and 4) cysteine supplementation may be a useful therapy if combined with disease-specific treatments such as antiviral therapy in HIV infection.
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PMID:Role of cysteine and glutathione in HIV infection and other diseases associated with muscle wasting and immunological dysfunction. 936 43


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