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

The aim of this study was to investigate if enhanced peripheral ammonia production during exhaustive exercise increases ammonia detoxication in brain mediated by glutamine synthesis, and subsequently influences glutamate and gamma-aminobutyric acid (GABA) levels. This neurotransmitter production is related to the metabolism of glutamine. A group of rats was trained for 6 weeks by treadmill running (TR). They were compared to a group of untrained rats (UN). At the end of training, half of TR and UN rats were submitted to one session of treadmill running until exhaustion (288+/-12 min and 62+/-5 min in TR and UN group, respectively). At exhaustion, running and control rats were sacrificed in order to collect blood and to take samples of the following brain structures: cortex, striatum and cerebellum. Treadmill running until exhaustion induced an increase in blood ammonia by 140% without significant differences between TR and UN groups. Brain ammonia increased in both groups. However, TR group exhibited values 50% higher than those observed in UN group. Brain glutamine was increased at exhaustion in all groups of running rats by 30-75% of basal value whereas the glutamate only decreased in TR rats which were able to run for a longer time. In this group, the GABA level decreased in striatum. These data confirm that enhanced brain ammonia level during exercise stimulates glutamine synthesis as a mechanism of detoxication. After several hours of running, a reduction in brain glutamate levels was observed in all brain structures in trained rats but only in the striatum in untrained animals. The reduced availability of this GABA precursor decreases GABA levels only in the striatum of TR group by 45% of the resting value. These results suggest a relation between cerebral changes in neurotransmitters and excitatory amino acids, such as glutamate and GABA, and central fatigue.
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PMID:Effects of prolonged exercise on brain ammonia and amino acids. 972 Oct 55

Muscle proteins turn over slowly and there are minimal diurnal changes in the size of the muscle protein pool in response to feeding and fasting. Nitrogen balance and tracer studies indicate that protein oxidation and net protein breakdown (degradation--synthesis) is not increased during dynamic exercise at intensities of < or = 70% VO2max. An imbalance between muscle protein synthesis and degradation does exist during one leg knee extensor exercise and during two legged cycling in patients with glycogen phosphorylase deficiency. In these latter cases amino acids liberated from the protein pool are used for synthesis of TCA-cycle intermediates and glutamine. Six amino acids are metabolized in resting muscle: leucine, isoleucine, valine, asparagine, aspartate and glutamate. Only leucine and part of the isoleucine molecule can be converted to acetylCoA and oxidized. The carbon skeleton of the other amino acids is used for synthesis of TCA-cycle intermediates and glutamine. The six amino acids provide the amino groups and the ammonia for synthesis of glutamine and alanine, which are released by muscle in excessive amounts. About half of the glutamine release from muscle originates from glutamate taken up from the blood. 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 and a high TCA cycle flux in the first minutes 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. 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 thus seem to play a central role in the energy metabolism of the exercising muscle.
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PMID:Protein and amino acid metabolism in human muscle. 978 36

Overtraining is of serious concern to long-distance runners and will affect 65% of them at some time in their competitive career. The clinical presentation is nonspecific but the classical symptoms include fatigue, mood disturbances, frequent upper respiratory infections and injury, and a decrease in performance. Dysfunction of the hypothalamic pituitary axis from repeated stress, of a physical or nonphysical nature, represents the most likely pathogenesis of this condition. There is no single biological marker that is diagnostic of an overtrained state; however, several parameters deserve further study. The time to volitional fatigue on a cycle ergometer at an intensity of 110% of the individual anaerobic threshold represents a possible laboratory test. Salivary IgA holds promise as a useful immunoligical marker of the overtrained state and further research is needed to determine the validity of plasma glutamine as a blood marker. The most promising tool at present is a measure of the athlete's mood state, and several psychological tools can be used for this purpose.
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PMID:Markers of excessive exercise. 991 82

The aim of the present study was to compare the effects of exercise at 80% VO2max (resulting in fatigue within 1 h) with more prolonged exercise at a lower work rate (55% VO2max for up to 3 h) on blood neutrophil function and plasma concentrations of cortisol, glutamine and glucose. Eighteen healthy male subjects (mean+/-SD age 22.5+/-3.7 yrs, VO2max 60.1+/-6.6 ml x kg(-1) x min(-1)) cycled on an electrically braked ergometer at 80% VO2max to fatigue (37+/-19 min). On another occasion, separated by at least one week, subjects performed exercise on the same ergometer at 55% VO2max for 3 h or to fatigue, whichever was the sooner. Mean exercise time was 164+/-23 min. The order of the trials was randomised. Both exercise bouts caused significant (p<0.05) elevations of the blood leucocyte count and plasma cortisol concentration and reductions in the in vitro neutrophil degranulation response to bacterial lipopolysaccharide and oxidative burst activity. After exercise at the lower work rate for a longer duration, plasma cortisol concentration was higher, blood leucocyte and neutrophil counts were higher, blood lymphocytes, plasma glucose and indices of neutrophil function were lower than those observed at 80% VO2max. Plasma glutamine only fell significantly during recovery after the more prolonged exercise. We conclude that when exercise is very prolonged, the diminution of innate immune function is greater, or at least as great as that observed after fatiguing exercise at higher work rates. Furthermore, reductions in neutrophil function after exercise at 80% VO2max were not related to changes in the plasma glutamine concentration, although both plasma glutamine and neutrophil function were decreased at 1 and 2.5 h post-exercise in the long duration exercise trial.
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PMID:Effects of exercise intensity, duration and recovery on in vitro neutrophil function in male athletes. 1019 Jul 75

Although current research suggests that individuals involved in either high-intensity resistance or endurance exercise may have an increased need for dietary protein, the available research is either equivocal or negative relative to the ergogenic effects of supplementation with individual amino acids. Although some research suggests that the induction of hyperaminoacidemia via intravenous infusion of a balanced amino acid mixture may induce an increased muscle protein synthesis after exercise, no data support the finding that oral supplementation with amino acids, in contrast to dietary protein, as the source of amino acids is more effective. Some well-controlled studies suggest that aspartate salt supplementation may enhance endurance performance, but other studies do not, meriting additional research. Current data, including results for several well-controlled studies, indicated that supplementation with arginine, ornithine, or lysine, either separately or in combination, does not enhance the effect of exercise stimulation on either hGH or various measures of muscular strength or power in experienced weightlifters. Plasma levels of BCAA and tryptophan may play important roles in the cause of central fatigue during exercise, but the effects of BCAA or tryptophan supplementation do not seem to be effective ergogenics for endurance exercise performance, particularly when compared with carbohydrate supplementation, a more natural choice. Although glutamine supplementation may increase plasma glutamine levels, its effect on enhancement of the immune system and prevention of adverse effects of the overtraining syndrome are equivocal. Glycine, a precursor for creatine, does not seem to possess the ergogenic potential of creatine supplementation. Research with metabolic by-products of amino acid metabolism is in its infancy, and current research findings are equivocal relative to ergogenic applications. In general, physically active individuals are advised to obtain necessary amino acids through consumption of natural, high-quality protein foods.
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PMID:Facts and fallacies of purported ergogenic amino acid supplements. 1041 Aug 46

Although skeletal muscle is capable of oxidizing selected amino acids, exercise in the fed and carbohydrate-replete condition results in only a small increase in amino acid utilization. Nevertheless, it may be important to increase the dietary protein requirements of active individuals. There is ongoing debate as to whether the amino acids for oxidation are derived from the free amino acid pool, from net protein breakdown, or a combination of both. There has been interest in the potential ergogenic benefits of amino acid ingestion; however, BCAA ingestion does not appear to affect fatigue during prolonged exercise, there is little support from controlled studies to recommend glutamine ingestion for enhanced immune function, and although glutamine stimulates muscle glycogen synthesis, its addition to carbohydrate supplements provides no additional benefit over ingestion of carbohydrate alone.
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PMID:Amino acids and endurance exercise. 1125 41

Individual amino acid supplementation affects various types of athletic performance. However, little information on combinations of amino acids is currently available. This study evaluated an amino acid mixture containing L-leucine, L-isoleucine, L-valine, L-arginine, and L-glutamine to 3.6 g of total amino acids per dose. Twenty-three rugby players were given 3.6 g, twice, daily of the amino acid mixture for 90 days (June-August 1994) and blood samples were collected for analyses in September 1993, March 1994, September 1994, and September 1995. After 90 days of supplementation, almost all of the athletes reported improvement in vigor and earlier recovery from fatigue. Significant increases (P<0.05) were observed in hemoglobin, RBC count, hematocrit, and serum iron by amino acid supplementation. Significant increases (P<0.05) were also noted in total cholesterol and low-density lipoprotein along with decreased (P<0.05) alkaline phosphatase. All values reverted to original levels when measured after one year of continued training without supplementation.
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PMID:Amino acid supplementation affects hematological and biochemical parameters in elite rugby players. 1167 7

To probe the effect of glutamine and GABA on metabolism of [U-(13)C]glutamate, cerebellar astrocytes were incubated with [U-(13)C]glutamate (0.5 mM) in the presence and absence of glutamine (2.5 mM) or GABA (0.2 mM). It could be shown that consumption of [U-(13)C]glutamate was decreased in the presence of glutamine and release of labeled aspartate and [1,2,3-(13)C]glutamate decreased as well, whereas the concentrations of these metabolites increased inside the cells. Glutamine decreased energy production from [U-(13)C]glutamate presumably by substituting for glutamate as an energy substrate. No additional effect was seen in the presence of both glutamine and GABA. When cerebellar granule neurons were incubated with [U-(13)C]glutamate (0.25 mM) and GABA (0.05 mM), less [U-(13)C]glutamate was used for energy production than in controls. Because the barbiturate thiopental did not elicit such response (Qu et al., 2000, Neurochem Int 37:207-215) it appears that GABA also has a metabolic function in the glutamatergic cerebellar granule neurons in contrast to the astrocytes.
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PMID:Effect of glutamine and GABA on [U-(13)C]glutamate metabolism in cerebellar astrocytes and granule neurons. 1174 15

During and after maximal exercise there is a 15-30 % decrease in the metabolic uptake ratio (O(2)/[glucose + 1/2 lactate]) and a net lactate uptake by the human brain. This study evaluated if this cerebral metabolic uptake ratio is influenced by the intent to exercise, and whether a change could be explained by substrates other than glucose and lactate. The arterial-internal jugular venous differences (a-v difference) for O(2), glucose and lactate as well as for glutamate, glutamine, alanine, glycerol and free fatty acids were evaluated in 10 healthy human subjects in response to cycling. However, the a-v difference for the amino acids and glycerol did not change significantly, and there was only a minimal increase in the a-v difference for free fatty acids after maximal exercise. After maximal exercise the metabolic uptake ratio of the brain decreased from 6.1 +/- 0.5 (mean +/- S.E.M.) at rest to 3.7 +/- 0.2 in the first minutes of the recovery (P < 0.01). Submaximal exercise did not change the uptake ratio significantly. Yet, in a second experiment, when submaximal exercise required a maximal effort due to partial neuromuscular blockade, the ratio decreased and remained low (4.9 +/- 0.2) in the early recovery (n = 10; P < 0.05). The results indicate that glucose and lactate uptake by the brain are increased out of proportion to O(2) when the brain is activated by exhaustive exercise, and that such metabolic changes are influenced by the will to exercise. We speculate that the uptake ratio for the brain may serve as a metabolic indicator of 'central fatigue'.
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PMID:The intent to exercise influences the cerebral O(2)/carbohydrate uptake ratio in humans. 1195 54

To determine the effect of the major histocompatibility complex on the development of symptoms during acute human parvovirus B19 infection, we compared human leukocyte antigen (HLA) class I and II alleles in 36 patients with symptomatic acute B19 infection with those in >900 control subjects from northwestern England. The frequency of each of HLA-DRB1*01 (P=.016), DRB1*04 (P=.007), and DRB1*07 (P<.0001) alleles was significantly higher in parvovirus B19 patients than in control subjects. In the parvovirus group, 63.9% carried the rheumatoid arthritis-associated shared epitope sequence, compared with 45% of control subjects (odds ratio [OR], 2.2; 95% confidence interval [CI], 0.97-4.8; P=.04), and carriage was associated with fatigue during the acute phase (OR, 4.2; 95% CI, 0.8-23.9; P=.047). All symptomatic parvovirus-associated HLA-DRB1 molecules carry a neutrally charged glutamine at position 10 and a positively charged lysine at position 12 of the first hypervariable region. HLA-B49 was associated with parvovirus infection independently of HLA-DRB1*01, DRB1*04, and DRB1*07.
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PMID:Association of symptomatic acute human parvovirus B19 infection with human leukocyte antigen class I and II alleles. 1219 70


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