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

Intensive activity of muscles causes a decline in performance, known as fatigue, that is thought to be caused by the effects of metabolic changes on either the contractile machinery or the activation processes. The concentration of inorganic phosphate (P(i)) in the myoplasm ([P(i)](myo)) increases substantially during fatigue and affects both the myofibrillar proteins and the activation processes. It is known that a failure of sarcoplasmic reticulum (SR) Ca(2+) release contributes to fatigue and in this review we consider how raised [P(i)](myo) contributes to this process. Initial evidence came from the observation that increasing [P(i)](myo) causes reduced SR Ca(2+) release in both skinned and intact fibres. In fatigued muscles the store of releasable Ca(2+) in the SR declines mirroring the decline in SR Ca(2+) release. In muscle fibres with inoperative creatine kinase the rise of [P(i)](myo) is absent during fatigue and the failure of SR Ca(2+) release is delayed. These results can all be explained if inorganic phosphate can move from the myoplasm into the SR during fatigue and cause precipitation of CaP(i) within the SR. The relevance of this mechanism in different types of fatigue in humans is considered.
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PMID:Role of phosphate and calcium stores in muscle fatigue. 1169 62

The ability to perform well in activities that require muscular and cardiorespiratory endurance is a trait influenced, in a considerable part, by the genetic make-up of individuals. Early studies of performance and recent scans of the human genome have pointed at various candidate genes responsible for the heterogeneity of these phenotypes within the population. Among these are the genes for the various creatine kinase (CK) isoenzyme subunits. CK and phosphocreatine (PCr) form an important metabolic system for temporal and spatial energy buffering in cells with large variations in energy demand. The different CK isoenzyme subunits (CK-M and CK-B) are differentially expressed in the tissues of the body. Although CK-M is the predominant form in both skeletal and cardiac muscle, CK-B is expressed to a greater extent in heart than in skeletal muscle. Studies in humans and mice have shown that the expression of CK-B messenger RNA (mRNA) and the abundance and activity of the CK-MB dimer increase in response to cardiorespiratory endurance training. Increases in muscle tissue CK-B content can be energetically favourable because of its lower Michaelis constant (Km) for ADP. The activity of the mitochondrial isoform of CK (Scmit-CK) has also been significantly and positively correlated to oxidative capacity and to CK-MB activity in muscle. In mice where the CK-M gene has been knocked out, significant increases in fatigue resistance together with cellular adaptations increasing aerobic capacity have been observed. These observations have led to the notion that this enzyme may be responsible for fatigue under normal circumstances, most likely because of the local cell compartment increase in inorganic phosphate concentration. Studies where the Scmit-CK gene was knocked out have helped demonstrate that this isoenzyme is very important for the stimulation of aerobic respiration. Human studies of CK-M gene sequence variation have shown a significant association between a polymorphism, distinguished by the NcoI restriction enzyme, and an increase in cardiorespiratory endurance as indexed by maximal oxygen uptake following 20 weeks of training. In conclusion, there is now evidence at the tissue, cell and molecular level indicating that the CK-PCr system plays an important role in determining the phenotypes of muscular and cardiorespiratory endurance. It is envisioned that newer technologies will help determine how the genetic variability of these genes (and many others) impact on performance and health-related phenotypes.
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PMID:Role of creatine kinase isoenzymes on muscular and cardiorespiratory endurance: genetic and molecular evidence. 1170 1

This article describes three cases of undiagnosed hypothyroidism in a developed stage which manifest themselves with myopathic syndrome (myalgia, muscular fatigue, and higher serum levels of creatine kinase, aminotranferases, and lactate dehydrogenase) without the "classic" symptoms of hypothyroidism. In addition, two of the three patients were receiving hypolipidemic drugs for secondary hyperlipoproteinemia, which could have affected the development of the myopathy. Emphasis is placed on the description of atypical symptoms of hypothyroidism and the necessity of endocrinological examination in each case of myopathy with indefinite etiology.
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PMID:[Myopathy syndrome in undiagnosed hypothyroidism]. 1171 70

A 50-year-old man had been well until three months earlier, when he felt general fatigue, and cutaneous rash with itching. Thereafter a general muscular weakness developed and the patient could not walk for a month. Four weeks before referral to our hospital, he had high fever and could not role over in the bed. On admission, the patient was able to walk. He had no skin rash. Neurologically, he showed mild weakness in proximal muscles. Hematologic examination showed mild eosinophilia and serum creatine kinase was mildly elevated. Needle electromyogram revealed a diffuse myogenic pattern in extremities. Eosinophilic myositis was diagnosed by a biopsy of the left calf muscle showing mild infiltration of eosinophilis which was identified using antibodies against eosinophilic granule protein.
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PMID:[A case of eosinophilic myositis proven by immunohistochemistry using antibodies against eosinophilic granule protein]. 1180 47

Force declines when muscles are used repeatedly and intensively and a variety of intracellular mechanisms appear to contribute to this muscle fatigue. Intracellular calcium release declines during fatigue and has been shown to contribute to the reduction in force. Three new approaches have helped to define the role of calcium stores to this decline in calcium release. Skinned fibre experiments show that when intracellular phosphate is increased the amount of Ca2+ released from the sarcoplasmic reticulum (SR) declines. Intact fibre experiments show that the size of the calcium store declines during fatigue and recovers on rest. Intact muscles which lack the enzyme creatine kinase, do not exhibit the usual rise of phosphate during fatigue and, under these conditions, the decline of Ca2+ release is absent or delayed. These results can be explained by the "calcium phosphate precipitation" hypothesis. This proposes that if phosphate in the myoplasm rises, it enters the SR and binds to Ca2+ as Ca2+ phosphate. The resultant reduction in free Ca2+ within the SR contributes to the reduced Ca2+ release during fatigue.
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PMID:Muscle fatigue: the role of intracellular calcium stores. 1188 Jun 93

Exercise generates free radicals only when it is exhaustive. Free radicals are involved in tissue damage caused by exercise. Antioxidant vitamins (vitamin C and E) and other antioxidants such as coenzyme Q, and N-acetyl cysteine prevent muscle damage and decrease muscle fatigue. The main aim of this paper was to test the possible protective effect of two new antioxidants, cyanoside chloride and chromocarbe diethylamine, on the oxidative stress generated by exhaustive exercise. The antioxidants were given to rats daily (50 mg/kg) in drinking water for 30 days. Blood oxidized glutathione/ reduced glutathione ratio, and plasma malondialdehyde levels were determined as indexes of oxidative stress. Plasma creatine kinase, alanine-aminotransferase and lactate dehydrogenase activities were used as markers of muscle damage. Both cyanoside chloride and chromocarbe diethylamine were more effective than vitamin C in the prevention of glutathione oxidation in blood. Furthermore, cyanoside chloride and chromocarbe diethylamine partially prevented muscle damage. Chromocarbe diethylamine was the most effective compound in the prevention of exercise-induced lipid peroxidation (malondialdehyde) in plasma.
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PMID:Cyanoside chloride and chromocarbe diethylamine are more effective than vitamin C against exercise-induced oxidative stress. 1188 79

The firefly luciferin/luciferase reaction was utilized to monitor intracellular ATP concentration ([ATP](i)). Single fibres of mouse skeletal muscle were dissected and injected with luciferase. Luciferin was added to the perfusate and light emission from the fibres was monitored as an indication of [ATP](i). Inhibition of oxidative phosphorylation with cyanide and anaerobic glycolysis with iodoacetate caused light emission to fall to zero within 10 min and the fibres developed a rigor contraction. Inhibition of creatine kinase with 2,4-dinitro-1-fluorobenzene produced a small transient fall in light emission in association with each tetanus. Muscle fibres were fatigued by repeated tetani and 5/12 fibres showed a fall in light emission in the late phase of fatigue. If fibres were allowed to recover from fatigue in the absence of glucose and then restimulated in the absence of glucose they fatigued much more rapidly. However, such fibres showed no obvious change in light emission. We conclude that the luciferin/luciferase system can be used to monitor [ATP](i) in functioning single skeletal muscle cells. A depletion of global [ATP](i) is not observed in all fatiguing fibres and cannot be the sole cause of the final phase of fatigue.
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PMID:Intracellular ATP measured with luciferin/luciferase in isolated single mouse skeletal muscle fibres. 1188 83

During prolonged exercise, changes in the ionic milieu in and surrounding the muscle fibers may lead to fatigue or damage of the muscle and thereby impair performance. In 10 male subjects, we investigated the effects of 100 km running on muscle and plasma electrolyte contents, muscle Na+ -K+ pump content, and plasma concentrations of creatine kinase (CK) and lactate dehydrogenase (LDH). After completion of a 100-km run, significant increases were found in plasma K+ (from 4.0 +/- 0.1 to 5.5 +/- 0.2 mM, P < 0.001), muscle Na+ -K+ pump content (from 334 +/- 11 to 378 +/- 17 pmol/g, P < 0.05), and total muscle Ca2+ content (from 0.84 +/- 0.03 to 1.02 +/- 0.04 micromol/g, P < 0.001). There was also a large increase in the plasma levels of the muscle-specific enzymes CK and LDH, which reached peak values at the end of the run and lasted several days after the run, indicating that a significant degree of muscle membrane leakage was present. The simultaneous occurrence of raised cellular Ca2+ content and muscle membrane leakage supports the theory that Ca2+ plays a role in the initiation of degenerative processes in muscles after severe exercise.
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PMID:Membrane leakage and increased content of Na+ -K+ pumps and Ca2+ in human muscle after a 100-km run. 1196 Sep 39

Increased serum creatine kinase level is a marker of neuromuscular disorders. When combined with exercise intolerance, muscle cramps, fatigue, myoglobinuria, or muscle weakness, metabolic myopathies of a variety of causes should be considered. We encountered an adolescent male with a persistently high serum creatine kinase level and chronic fatigue who was found to have combined partial defects of carnitine palmitoyltransferase II and mitochondrial complex I. Metabolic myopathy may present with chronic fatigue and a persistently high serum creatine kinase level but without muscle weakness and may be attributable to combined enzyme defects.
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PMID:Combined partial deficiencies of carnitine palmitoyltransferase II and mitochondrial complex I presenting as increased serum creatine kinase level. 1208 89

Two cases, mother and her son, suffering from acute poisoning with Tricholoma equestre were described. They had eaten 100-300 grams of this wild mushroom during nine consecutive meals. About 48 hours after the last meal containing the mushroom they developed fatigue, muscle weakness and myalgia, loss of appetite, mild nausea, profuse sweating. Maximal serum creatine kinase activity was 18,150 U/L in the mother and 48,136 U/L in the son. Maximal serum levels of aspartate aminotransferase and alanine aminotransferase were 802 U/L and 446 U/L, respectively, in the mother and 2002 U/L and 454 U/L, respectively, in the son. All routine biochemical tests were within normal range. No other causes of rhabdomyolysis such as parasitic, viral, immune diseases, trauma or exposure to medications were found. All the above mentioned symptoms and biochemical abnormalities disappeared within 23 days of hospitalization. Our observation confirms the results of Bedry and co-workers that Tricholoma equestre contains a toxin, which can cause rhabdomyolysis.
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PMID:Acute poisoning with Tricholoma equestre. 1218 17


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