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

Oxygen transport to and substrate turnover in leg muscle were studied at rest and during light and heavy upright bicycle exercise in two brothers with a hereditary hemoglobinopathy associated with high oxygen affinity (P50 = 13 mmHg). Femoral venous oxygen tension was below normal and femoral venous oxygen saturation above normal at rest and during exercise. Thus, the arterial-femoral venous oxygen saturation difference was decreased. Despite a compensatory increase in hemoglobin concentration, the arterial-femoral venous oxygen content difference tended to be below normal at heavy exercise. Approximately 25% of the oxygen was delivered via the abnormal hemoglobin at relative heavy exercise. Arterial lactate levels, lactate release, and muscle lactate concentration were not increased at any level of exercise. Glucose, alanine, pyruvate, and glycerol turnover were essentially normal, but the glycogen and creatine phosphate stores were abnormally depleted at the termination of heavy exercise. The exercise electrocardiogram (ECG) was normal, indicating that myocardial oxygenation was adequate. Muscle-surface oxygen pressure fields were normal at rest (not investigated during exercise). It is concluded that the high oxygen affinity of the hemoglobin in our two subjects did not lead to heart or skeletal muscle hypoxia during heavy exercise, as judged from the ECG and from the leg lactate turnover. Despite the lack of evidence for muscle hypoxia, the subjects experienced leg muscle fatigue and the creatine phosphate and glycogen stores were depleted more than normally.
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PMID:Tissue oxygenation and muscular substrate turnover in two subjects with high hemoglobin oxygen affinity. 663 May 12

This laboratory previously described an L1210 leukemia cell line (MTXrA) selected for resistance to methotrexate by virtue of impaired transport due to a functional defect in the translocation process. We now report on the sequence analysis of cDNAs encoding the reduced folate carrier from this line and identify a single mutation that results in the substitution of a proline for an alanine in a highly conserved transmembrane region of the protein. Transfection of the parental reduced folate carrier into MTXrA cells resulted in a cell line which exhibited a complete restoration of methotrexate uptake and an enhanced sensitivity to methotrexate. Northern analysis and specific [3H]MTX cell surface binding indicated that expression of the reduced folate carrier was elevated approximately 5-fold in the transfectant compared to parental and MTXrA cells. The MTX influx properties of the transfectant cell line were identical to those of the well characterized reduced folate carrier from parental L1210 cells in terms of: 1) patterns of sensitivity to competing folates, 2) sensitivity to the organic anion sulfobromophthalein, 3) lack of energy dependence, and 4) capacity for trans-stimulation. We also provide new data which suggests that the nucleotide sequence 5' of the predicted ATG initiation codon may encode additional protein information in the form of a leader sequence. Finally, we demonstrate that the MTXrA line has both the mutant and the parental reduced folate carrier alleles but that expression appears to be restricted to the mutant allele. Thus, the methotrexate transport phenotype and resultant drug resistance in this cell line result from genetic/regulatory events at both alleles.
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PMID:Characterization of a mutation in the reduced folate carrier in a transport defective L1210 murine leukemia cell line. 755 35

Our objective was to assess the effects of increased propionate supply on gut and liver function in lactating cows. Four multicatheterized, primiparous cows (30.4 +/- .5 kg/d of milk) were fed for ad libitum intake a diet of 50% alfalfa hay and 50% concentrate (20.6 +/- 1.9 kg/d of DM, 226 +/- 21 MJ/d of metabolizable energy, and 611 +/- 56 g/d of N). Each cow received intramesenteric infusions of NaCl (control) or Na-propionate (150 mmol/h of a 2.5 M solution) in a reversal design. After 72 h of infusion, blood flow (by indicator dilution) and net flux (venoarterial differences multiplied by blood flow) were measured across portal-drained viscera and the liver. Energy supply from feed consumed and from infusion was similar between treatments. Energy that was excreted as milk decreased with propionate infusion. Propionate infusion increased arterial concentration of propionate; decreased absorption of acetate, butyrate, and valerate; and decreased hepatic removal of L-lactate, butyrate, valerate, NEFA, and oxygen. Propionate infusion decreased splanchnic release of glucose and increased splanchnic release of acetate and alanine. Net flux of urea, BHBA, insulin, or glucagon was unaffected by treatments. Our data show a link between a greater proportion of energy supplied as propionate and decreased energy excreted as milk. This response was associated with decreased net removal of glucogenic and ketogenic substrates by the liver and increased supply of acetate for use by peripheral tissues.
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PMID:Effect of mesenteric vein infusion of propionate on splanchnic metabolism in primiparous Holstein cows. 781 5

The similarity of eosinophilia-myalgia syndrome (EMS) and toxic-oil syndrome (TOS) to systemic sclerosis and diffuse fasciitis with eosinophilia (DFE) highlights the potential for environmental agents to induce autoimmune disease. Further, a candidate etiologic agent for EMS, 3-(phenylamino)alanine, is chemically similar to the aniline derivative identified in samples of oil implicated in TOS, 3-(N-phenylamino)-1,2-propanediol, suggesting pathogenic overlap. The late-stage manifestations of EMS and TOS are muscle cramping, arthralgia, severe fatigue, and cognitive impairment. This review focuses on the divergent and parallel findings in EMS, TOS, and DFE. The formation of the Environmentally Associated Connective Tissue Disease Study Group within the American College of Rheumatology will provide a forum for the development of registries to study suspected toxin-induced disorders.
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PMID:Eosinophilia-myalgia syndrome, toxic-oil syndrome, and diffuse fasciitis with eosinophilia. 857 79

Spermatozoa are highly specialized cells, and they offer advantages for studying several basic aspects of metabolic control such as the role of adenosine triphosphate-(ATP)-homeostasis for cell function, the mechanisms of fatigue and metabolic depression, the metabolic channelling through the cytoplasm and the organization and regulation of glycolytic enzymes. Spermatozoa of four species with different reproductive modes are introduced and the first results are presented: Spermatozoa of the marine worm Arenicola marina are well adapted to external fertilization in sea water with fluctuating oxygen tension: they are motile for several hours in oxygen-free sea water, even when the ATP level is dramatically reduced. Anaerobic ATP production occurs by alanine, acetate and propionate fermentation probably by the same pathways known from somatic cells of this species. Under aerobic conditions the phosphagen system might function like a shuttle for energy-rich phosphate from mitochondria to the dynein-ATPases. Storage of turkey and carp spermatozoa for several hours without exogenous substrates and oxygen results in the degradation of phosphocreatine and ATP to inorganic phosphate and adenosine monophosphate (AMP), respectively. Despite low energy charges, stored spermatozoa of both species are capable of progressive movements. In carp spermatozoa fatigue of motility is not accompanied by the dramatic acidosis one discusses as an important effect in muscle fatigue. Energy metabolism of boar spermatozoa is typically based on glycolysis consuming extracellular carbohydrates and producing lactate and protons. The sperm seem to tolerate low intracellular pH (< 6.5). The lack of a phosphagen system (no energy shuttle from mitochondria to the distal dynein-ATPases) is probably compensated by a high glycolytic ATP-production in the mitochondria-free piece of the flagellum.
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PMID:Spermatozoa: models for studying regulatory aspects of energy metabolism. 864 86

Chronic fatigue syndrome (CFS/ME) is a debilitating fatigue illness that has an unknown etiology. We studied 20 chronic fatigue syndrome (CFS) patients, who complied with the Oxford and American CDC definitions, and 45 non-CFS subjects. Participants completed questionnaires, were clinically examined, and had first morning urine specimens collected, which were screened by gas chromatography-mass spectrometry for changes in metabolite excretion. Multivariate analysis of the urinary metabolite profiles differed significantly in the CFS patients compared to the non-CFS patients (P < 0.004). The CFS patients had increases in aminohydroxy-N-methylpyrrolidine (P < 0.00003, referred to as chronic fatigue symptom urinary marker 1, or CFSUM1), tyrosine (P < 0.02), beta-alanine (P < 0.02), aconitic acid (P < 0.05), and succinic acid (P < 0.05) and reductions in an unidentified urinary metabolite, CFSUM2 (P < 0.0007), alanine (P < 0.005), and glutamic acid (P < 0.02). CFSUM1, beta-alanine, and CFSUM2 were found by discriminant function analysis to be the first, second, and third most important metabolites, respectively for discriminating between CFS and non-CFS subjects. The abundances of CFSUM1 and beta-alanine were positively correlated with symptom incidence (P < 0.01 and P < 0.001, respectively), symptom severity, core CFS symptoms, and SCL-90-R somatization (P < 0.00001), suggesting a molecular basis for CFS.
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PMID:Preliminary determination of a molecular basis of chronic fatigue syndrome. 873 84

Muscle phosphofructokinase deficiency (PFKD) is characterized by exercise intolerance due to the enzymatic block in muscle glycolysis. Glucose infusion increases exertional fatigue in these patients, probably by decreasing the availability of free fatty acids (FFA) and ketones, which play a crucial role in ATP production during exercise in PFKD. This suggests that a lower than normal hepatic glucose production would be appropriate during exercise in PFKD. To investigate glucoregulation in PFKD, we measured glucose turnover and hormonal and metabolic responses to 20 minutes of cycle exercise at near maximal effort in three patients with PFKD and in healthy matched controls studied at the same absolute (A, 15 to 30 Watts) and relative (R, 35 to 80 Watts, matched heart rates) work load as the patients. During exercise, mean glucose production was higher in all patients versus controls (30 +/- 4 versus A: 18 +/- 2 and R: 20 +/- 1 mumol.min-1.kg-1). Mean glucose utilization during exercise was similar in patients and controls working at the same relative work load and higher than in controls at the low work load. Exercise-induced increases in arterialized blood were higher in all patients for glucose, FFA, growth hormone, glucagon, and norepinephrine. Plasma alanine and lactate always decreased during exercise in patients and consistently increased in controls. In conclusion, an enhanced neuroendocrine response and a paradoxically exaggerated mobilization of glucose occurs during exercise in PFKD. The responses are probably initiated by neural feedback elicited by disturbances in local muscle metabolism. The responses promote delivery of oxidizable fat to muscle, but at the expense of accumulation and futile cycling of glucose.
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PMID:Paradoxically enhanced glucose production during exercise in humans with blocked glycolysis caused by muscle phosphofructokinase deficiency. 879 77

Fatigue of night duty workers in different divisions of a newspaper office was investigated by physiological methods such as the Blinker, Flicker and grip methods. The relationship between fatigue and hematological parameters such as hemoglobin (Hb), the hematocrit (Ht), serum-free amino acid levels, and indices of liver function such as the GOT and GPT levels were also examined. The composing and press room workers mainly complained of the subjective symptom of muscle fatigue, while workers in the photo-engraving and editorial departments mainly complained of mental fatigue. The overall rate of fatigue in the newspaper office was about 38.1%, but varied from one division to another, being especially high in the photo-engraving and editorial departments. The subjects with fatigue had low levels of serum GOT and GPT and high levels of serum-gluconeogenic amino acids, such as aspartic acid, glutamic acid, prolin, glycine, and alanine. These altered levels of serum-free amino acids and GOT and GPT seemed to be due to increased secretion of adrenal corticoid hormone caused by the stress of fatigue.
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PMID:Studies on fatigue of night duty workers at a newspaper office. 885 78

This review considers four experimental models for studying the dynamics of ammonia and amino acid metabolism in skeletal muscle: the rat hindlimb, the isolated dog gastrocnemius, the leg extensor for humans, and the traditional approach of humans performing two-legged exercise. The rat hindlimb is well suited for studying intense exercise with fast-twitch white fibers, but it is poorly suited for studying prolonged exercise because of rapid fatigue of major portions of the muscle and the restrictions of taking multiple blood samples. The traditional human model is limited because of the inability to quantify accurately the active muscle mass and to determine the true blood flow to the entire active tissue. Despite species differences and the various limitations of the paradigms, there are numerous consistencies in the literature. For example, human muscle and the canine gastrocnemius demonstrate similar magnitudes of efflux of ammonia, glutamine, and alanine (when indexed for the active mass) during prolonged exercise. Muscle has a large ammonia producing capacity during either intense or prolonged exercise. In prolonged exercise this is accompanied by similar productions of alanine and glutamine as well as a large uptake of glutamate. Despite the latter, the intramuscular glutamate concentration rapidly declines by more than 50% and remains constant throughout the exercise period. The leg extensor model and the canine gastrocnemius offer the greatest opportunities to quantify these responses during prolonged exercise.
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PMID:Ammonia and amino acid metabolism in skeletal muscle: human, rodent and canine models. 947 42

Six amino acids are metabolized in resting muscle. They are leucine, isoleucine, valine, asparagine, aspartate, and glutamate. These amino acids provide the amino groups and probably the ammonia required for synthesis of glutamine and alanine, which are released in excessive amounts in the postabsorptive state and during ingestion of a protein-containing meal. Only leucine and part of the isolecine molecule can be oxidized in muscle as they are converted to acetyl-CoA. The other carbon skeletons are used solely for de novo synthesis of TCA-cycle intermediates and glutamine. The carbon atoms of the released alanine originate primarily from glycolysis of blood glucose and from muscle glycogen (about half each in resting conditions). After consumption of a protein-containing meal, BCAA and glutamate are taken up by muscle and their carbon skeletons are used for de novo synthesis of glutamine. About half of the glutamine released from muscle originates from glutamate taken up from the blood, both after overnight starvation, after prolonged starvation, and after consumption of a mixed meal. Glutamine produced by muscle is an important fuel and regulator of DNA and RNA synthesis in mucosal cells and immune system cells, and fulfils several other important functions in human metabolism. The alanine aminotransferase reaction functions to establish and maintain high concentrations of TCA-cycle intermediates in muscle during the first 10 min of exercise. The increase in concentration of TCA-cycle intermediates probably is needed to increase the flux of the TCA-cycle and meet the increased energy demand of exercise. A gradual increase in leucine oxidation subsequently leads to a carbon drain on the TCA-cycle in glycogen-depleted muscles, and may thus reduce the maximal flux in the TCA-cycle and lead to fatigue. Deamination of amino acids and glutamine synthesis present alternative anaplerotic mechanisms in glycogen-depleted muscles, but only allow exercise at 40-50% of Wmax. One-leg exercise leads to the net breakdown of muscle protein. The liberated amino acids are used for synthesis of TCA-cycle intermediates and glutamine. Today, the importance of this process in endurance exercise in the field (running or cycling) in athletes who ingest carbohydrates is not clear. It is proposed that the maximal flux in the TCA-cycle is reduced in glycogen-depleted muscles due to insufficient TCA-cycle anaplerosis, and that this presents a limitation for the maximal rate of fatty acid oxidation. Interactions between the amino acid pool and the TCA-cycle are suggested to play a central role in the energy metabolism of the exercising muscle.
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PMID:Muscle amino acid metabolism at rest and during exercise: role in human physiology and metabolism. 969 93


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