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)

The aim of the present study was to investigate the metabolic base of psychoneurological symptoms, most notably tiredness and loss of concentration ability, appearing after carbohydrate-rich meals and during oral glucose tolerance tests. Such metabolic changes may be the cause of many accidents attributed to the "human factor". Oral glucose tolerance tests (OGTT) were performed in healthy volunteers, divided into symptomatic (n = 21) and symptom-free (n = 15) groups. Since the symptoms arising during OGTT simulate those in alcohol intoxication, a method for clinical examination of alcohol intoxication was used to separate symptom-free from symptomatic subjects. Comparison of blood glucose concentrations during OGTT revealed the symptomatic group to have higher concentrations in blood samples taken 15 min (p less than 0.05), 30 min (p less than 0.01), 45, 60 and 90 min (p less than 0.05) after intake of glucose than those having no symptoms. The symptoms began when the glucose concentration was at maximum, some 38 min (mean value) following the ingestion of glucose. The symptomatic subjects demonstrated a normal assimilation rate of glucose (mean 1.7 %/min) as tested with intravenous glucose tolerance tests and the differences in blood glucose concentrations between the groups is concluded to depend on the rate of absorption of glucose from the intestinal tract. The enterochromaffine cells of the intestinal tract are the site of biosynthesis, storage and release of 5-hydroxytryptamine (5-HT) (serotonin). In whole blood practically all of the 5-HT is of thrombocytic origin. Thrombocytes are thought to be peripheral models of 5-HT neurons in regard to 5-HT uptake, storage release and metabolism. Thrombocytes have a mechanism for 5-HT uptake analogous to the reuptake mechanism for 5-HT in the serotonergic nerve terminals. The whole blood 5-HT changes parallel changes in the 5-HT concentrations of the neurons. In this work 5-HT concentrations were measured during OGTT in whole blood to ascertain the possible relation between 5-HT changes and glucose absorption. For this purpose a reliable, fluorometric method for 5-HT was developed with the following improvements: In whole EDTA-blood the oxidation of 5-HT was prevented with ascorbic acid. The oxidation of hemoglobin iron to ferri-iron was prevented with carbon monoxide, because 5-HT, being a phenol, will otherwise form a complex with ferri-iron. Proteins were precipitated with perchloric acid and the supernatant neutralized before purification of 5-HT by cation exchange.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of 5-hydroxytryptamine (serotonin) in oral glucose intolerance. 658 28

The amino acid imbalance hypothesis should explain the fatigue originating in the brain during sustained exercise or over-training as a branched-chain (BCAA)/aromatic amino acids (AAA) imbalance with increased brain tryptophan uptake and 5-hydroxytryptamine synthesis. The serum amino acid profile was determined in 9 ultra-triathletes before and after completing the 1993 Colmar ultra-triathlon to additionally analyse the extent of this amino acid imbalance during such an extreme prolonged contest lasting more than 23 hours. The summed serum concentration of 25 amino acids decreased by 18% from 3962 +/- 846 to 3255 +/- 694 umol.l-1 likely reflecting a catabolic state of the organism with a decrease in 18 individual amino acids by 9-56%, an increase in cystine (+38%), methionine (+24%), tyrosine (+10%), phenylalanine (+12%), free tryptophan (+74%), and constant glutamine, leucine and total tryptophan levels. Since plasma volume increased by approximately 7.6% with a 3.3 kg body mass decrease in the athletes during the ultra triathlon, a decrease in intra-cellular water with an extra-cellular fluid increase is hypothesized. This decrease in cellular hydration state is seen as a protein-catabolic signal.
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PMID:Serum amino acid concentrations in nine athletes before and after the 1993 Colmar ultra triathlon. 764 5

Pharmacological manipulation of brain serotonergic [5-hydroxytryptamine (5-HT)] activity affects run time to exhaustion in the rat. These effects may be mediated by neurochemical, hormonal, or substrate mechanisms. Groups of rats were decapitated during rest, after 1 h of treadmill running (20 m/min, 5% grade), and at exhaustion. Immediately before exercise rats were injected intraperitoneally with 1 mg/kg of quipazine dimaleate (QD; a 5-HT agonist), 1.5 mg/kg of LY 53857 (LY; a 5-HT antagonist), or the vehicle (V; 0.9% saline). LY increased and QD decreased time to exhaustion (approximately 28 and 32%, respectively; P < 0.05). At fatigue, QD animals had greater plasma glucose, liver glycogen, and muscle glycogen concentrations but lower plasma free fatty acid concentration than did V and LY animals (P < 0.05). In general, plasma corticosterone and catecholamine levels during exercise in QD and LY rats were similar to those in V rats. Brain 5-HT and 5-hydroxyindole-3-acetic acid concentrations were higher at 1 h of exercise than at rest (P < 0.05), and the latter increased even further at fatigue in the midbrain and striatum (P < 0.05). Brain dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were higher at 1 h of exercise (P < 0.05) but were similar to resting levels at fatigue. QD appeared to block the increase in DA and DOPAC at 1 h of exercise, and LY prevented the decrease in DA and DOPAC at fatigue (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuroendocrine and substrate responses to altered brain 5-HT activity during prolonged exercise to fatigue. 836

Postviral fatigue syndrome (PFS) occurs both in epidemics and sporadically. Many of the original epidemics were related to poliomyelitis outbreaks which either preceded or followed them. The core clinical symptoms are always the same: severe fatigue made worse by exercise, myalgia, night sweats, atypical depression and excessive sleep. The other common symptoms include dysequilibrium disorders and irritable bowel syndrome. We have detected enteroviral genome sequences in muscle biopsies from cases of PFS, using specific enteroviral oligonucleotide primers in the polymerase chain reaction (PCR). In addition, whole virus particles can be demonstrated in PCR-positive muscle, using solid-phase immuno-electron microscopy. An increase in the number and size of muscle mitochondria was found in 70% of PFS cases, suggesting an abnormality in metabolic function. Evidence of hypothalamic dysfunction was present, particularly involving 5-hydroxytryptamine metabolism. A putative model of PFS, based on persistent enteroviral infection in laboratory mice, revealed resolving inflammatory lesions in muscle with, however, a marked increase in the production of certain cytokines in the brain. This model may help to explain the pathogenesis of PFS.
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PMID:Enteroviruses and postviral fatigue syndrome. 838 8

Fat oxidation provides a fuel for many tissues and it provides an important signal to decrease glucose utilization and oxidation in muscle and so conserve glucose for essential organs such as the brain. The control of fatty acid oxidation is achieved in part through its plasma concentrations, which may be precisely controlled by the triacylglycerol-fatty acid substrate cycle, which can also, if oxidation is taken into account, be viewed as a branch point in this important pathway. Branch points may provide precision in regulation if one of the fluxes at the branch is low compared with the other flux. Both branch points and substrate cycles are energetically expensive and may account for some of the increases in energy expenditure in conditions of injury, burns, and sepsis and in the postexercise condition. Fatty acids, through effects on plasma free tryptophan concentrations and hence 5-hydroxytryptamine concentrations in the brain, may play a role in central fatigue. Polyunsaturated fatty acids are claimed to have immunosuppressive properties. Work has been done to provide a biochemical analysis of how they might influence some functions of cells of the immune system.
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PMID:The regulatory, informational, and immunomodulatory roles of fat fuels. 847 91

Physical exercise influences the central dopaminergic, noradrenergic and serotonergic systems. A number of studies have examined brain noradrenaline (norepinephrine), serotonin (5-hydroxytryptamine; 5-HT) and dopamine with exercise. Although there are great discrepancies in experimental protocols, the results indicate that there is evidence in favour of changes in synthesis and metabolism of monoamines during exercise. There is a possibility that the interactions between brain neurotransmitters and their specific receptors could play a role in the onset of fatigue during prolonged exercise. The data on the effects of branched chain amino acid (BCAA) supplementation and 'central fatigue' seem to be conflicting, although recent studies suggest that BCAA supplementation has no influence on endurance performance. There are numerous levels at which central neurotransmitters can affect motor behaviour; from sensory perception, and sensory-motor integration, to motor effector mechanisms. However, the crucial point is whether or not the changes in neurotransmitter levels trigger or reflect changes in monoamine release. Until recently most studies were done on homogenised tissue, which gives no indication of the dynamic release of neurotransmitters in the extracellular space of living organisms. Recently, new techniques such as microdialysis are voltammetry were introduced to measure in vivo release of neurotransmitters. Microdialysis can collect virtually any substance from the brain of a freely moving animal with a limited amount of tissue trauma. This method allows measurement of local neurotransmitter release during on-going behavioural changes such as exercise. The results of the first studies using these methods indicate that the release of most neurotransmitters is influenced by exercise. Although the few studies that have been published to date show some discrepancies, we feel that these recently developed and more sophisticated in vivo methods will improve our insight into the relationship between the monoamine and other transmitters during exercise. Continued quantitative and qualitative research needs to be conducted so that a further understanding of the effects of exercise on brain neurotransmission can be gained.
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PMID:Exercise and brain neurotransmission. 857 Oct

Fatigue of voluntary muscular effort is a complex phenomenon. To date, relatively little attention has been placed on the role of the central nervous system (CNS) in fatigue during exercise despite the fact that the unwillingness to generate and maintain adequate CNS drive to the working muscle is the most likely explanation of fatigue for most people during normal activities. Several biological mechanisms have been proposed to explain CNS fatigue. Hypotheses have been developed for several neurotransmitters including serotonin (5-HT; 5-hydroxytryptamine), dopamine, and acetylcholine. The most prominent one involves an increase in 5-HT activity in various brain regions. Good evidence suggests that increases and decreases in brain 5-HT activity during prolonged exercise hasten and delay fatigue, respectively, and nutritional manipulations designed to attenuate brain 5-HT synthesis during prolonged exercise improve endurance performance. Other neuromodulators that may influence fatigue during exercise include cytokines and ammonia. Increases in several cytokines have been associated with reduced exercise tolerance associated with acute viral or bacterial infection. Accumulation of ammonia in the blood and brain during exercise could also negatively effect the CNS function and fatigue. Clearly fatigue during prolonged exercise is influenced by multiple CNS and peripheral factors. Further elucidation of how CNS influences affect fatigue is relevant for achieving optimal muscular performance in athletics as well as everyday life.
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PMID:Possible mechanisms of central nervous system fatigue during exercise. 900 Jan 55

Dexfenfluramine increases serotonergic activity by stimulating serotonin (5-hydroxytryptamine; 5-HT) release into brain synapses, inhibiting its reuptake into presynaptic neurons and by directly stimulating postsynaptic serotonin receptors. On the basis of the serotonin hypothesis of appetite control, these actions would be expected to reduce appetite and, consequently, bodyweight. Studies conducted in animals and in overweight patients with and without associated disorders have confirmed the weight-reducing efficacy and good tolerability of dexfenfluramine. In 3-month clinical studies in obese patients, weight reductions with dexfenfluramine 15mg twice daily combined with dietary support were significantly higher than those achieved with placebo and similar to those with ephedrine/caffeine 20/20mg 3 times daily, sibutramine 10mg once daily and fluoxetine 60 mg/day. Furthermore, dexfenfluramine recipients with non-insulin-dependent diabetes mellitus, hyperlipidaemia or hypertension consistently show improvements in glycaemic control, blood lipid profiles and blood pressure. 12-month trial results indicate that most weight loss occurs in the initial 6 months and appears to be maintained for a further 6 months. Weight regain after withdrawal of treatment in 12-month studies demonstrates that dexfenfluramine is effective in maintaining a stable bodyweight at a lower level than placebo and in limiting food intake over this time period. Commonly reported adverse events with dexfenfluramine include diarrhoea, tiredness, dry mouth and somnolence; these symptoms are generally mild and transient. Approximately 7 and 10% of dexfenfluramine recipients in short and long term studies withdrew because of adverse events. Dexfenfluramine was better tolerated than ephedrine/caffeine and fluoxetine in short term studies. Obesity is a chronic condition that is accompanied by a number of metabolic complications. It is a significant health problem in developed countries, and as a major risk factor for many chronic diseases, including diabetes and cardiovascular disease, the economic burden of this condition is considerable. As with other chronic conditions, there is a role for pharmacological intervention in patients with severe obesity. However, drugs should be considered as only one component of a weight-control programme, since additional lifestyle modification is required to maintain weight loss. The promising data on the long term efficacy and tolerability of dexfenfluramine as well as its favourable effects on risk factors associated with obesity requires confirmation in long term studies. In the meantime, dexfenfluramine should be considered a valuable adjunct to a reduced-calorie diet in the management of severe obesity, particularly in patients with associated disorders and those unsuccessful with conventional weight loss measures. Available data support the use of the drug for up to 1 year to maintain weight loss and thus dexfenfluramine should be considered for long term administration.
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PMID:Dexfenfluramine. An updated review of its therapeutic use in the management of obesity. 911 19

Tryptophan is the precursor of the neurotransmitter 5-hydroxytryptamine (5-HT), known to be involved in sleep and fatigue. In the blood, tryptophan binds to albumin, and that which does not, free tryptophan, competes with branched chain amino acids (BCAA) for entry into the brain. The plasma concentrations of albumin, free tryptophan, total tryptophan, and BCAA were measured before and after major surgery in nine elderly and nine coronary artery bypass graft (CABG) patients. In both the elderly and the CABG patients plasma free tryptophan concentrations were increased after surgery, compared with baseline levels; the plasma free tryptophan/BCAA concentration ratio was also increased significantly after surgery. Plasma albumin concentrations were decreased significantly after surgery in both the elderly and the CABG patients. Plasma BCAA concentrations were not affected by surgery in either group. The effect of exercising to exhaustion on 5-HT and tryptophan were investigated in Nagase analbuminemic rats (NAR). The intrasynaptosomal concentration of tryptophan, 5-hydroxy-tryptophan, and 5-HT was increased by fatigue after exercise. In addition, running time to exhaustion was shortened in NAR. These data suggest that free tryptophan uptake and 5-HT synthesis were enhanced in the nerve terminal. A decrease in plasma albumin may account for the increase in plasma-free tryptophan levels. An increase in plasma free tryptophan, resulting in an enhanced plasma concentration ratio of free tryptophan/BCAA, may lead to a higher 5-HT concentration in some parts of the brain and, consequently, to central fatigue. It is suggested that provision of BCAA as a dietary supplement may counteract the increase in plasma free tryptophan and thus improve the status of some patients after major surgery.
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PMID:Changes in the albumin binding of tryptophan during postoperative recovery: a possible link with central fatigue? 920 93

The aim of the study was to evaluate in a double-blind manner the effect of the long-acting 5-hydroxytryptamine 2 (5-HT2)-receptor blocker Ritanserin on clinical symptoms in patients with fibromyalgia syndrome (FM) and on production of antibodies to serotonin, gangliosides and phospholipids, recently shown to have a high incidence in this disease. Fifty-one female patients with typical FM were included in the 16-week study: 24 received Ritanserin and 27 received a placebo. Antibodies to 5-HT, gangliosides (Gm1) and phospholipids (thromboplastin) were determined by enzyme-linked immunosorbent assay at day 0 and at the end of week 16. The psychological and physical status, including tender points, of the patients was evaluated at day 0 and at the end of weeks 4 and 16. At the end of the study, there was an improvement (p < 0.05) in feeling refreshed in the morning in the Ritanserin-treated group and headache was also significantly improved compared with the placebo group. There was no difference in pain, fatigue, sleep, morning stiffness, anxiety and tender point counts in the Ritanserin and placebo groups. Fifty-one per cent of the 51 patients had at least one of the three antibodies to 5-HT, Gm1 and phospholipids. The incidence and activity of these antibodies were not influenced by Ritanserin or placebo. The observation that Ritanserin has only a small effect on clinical symptoms indicates that disturbances in serotonin metabolism or uptake may be only one factor in the pathogenesis of the disease. The high incidence of a defined autoantibody pattern in FM could again be confirmed in this study. However, it remains speculative whether immunological reactions are, indeed, involved.
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PMID:A randomised double-blind 16-week study of ritanserin in fibromyalgia syndrome: clinical outcome and analysis of autoantibodies to serotonin, gangliosides and phospholipids. 964 2


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