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

There are at least 5 metabolic causes of fatigue, a decrease in the phosphocreatine level in muscle, proton accumulation in muscle, depletion of the glycogen store in muscle, hypoglycaemia and an increase in the plasma concentration ratio of free tryptophan/branched-chain amino acids. Proton accumulation may be a common cause of fatigue in most forms of exercise and may be an important factor in fatigue in those persons who are chronically physically inactive and also in the elderly: thus, the aerobic capacity markedly decreases under these conditions, so that ATP must be synthesized by the much less efficient anaerobic system. A marked increase in the plasma fatty acid level, which may occur when liver glycogen store is depleted and when hypoglycaemia results, or during intermittent exercise when the rate of fatty acid oxidation may not match the mobilisation of fatty acids, could be involved indirectly in fatigue. This is because such an increase in the plasma level of fatty acids raises the free plasma concentration of tryptophan, which can increase the entry of tryptophan into the brain, which will increase the brain level of 5-hydroxytryptamine: there is evidence that the latter may be involved in central fatigue. In this case, provision of branched-chain amino acids in order to maintain the resting plasma concentration ratio of free tryptophan/branched-chain amino acids should delay fatigue--there is prima facie evidence in support of this hypothesis. This hypothesis may have considerable clinical importance.
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PMID:Physical and mental fatigue: metabolic mechanisms and importance of plasma amino acids. 136 Mar 9

Brain serotonin (5-hydroxytryptamine, 5-HT) has been suggested to be involved in central fatigue during prolonged exercise. Changes in the ratio of plasma free tryptophan (free Trp) to branched-chain amino acids (BCAA) are associated with altered brain 5-HT synthesis. The purposes of this study were to describe systematically the effects of prolonged exercise on changes in plasma free Trp and BCAA and to examine the effects of carbohydrate (CHO) feedings on these same variables. Eight well-trained men [VO2max = 57.8 (SE 4.1) ml kg-1 min-1] cycled for up to 255 min at a power output corresponding to VO2 at lactate threshold (approximately 68% VO2max) on three occasions separated by at least 1 week. Subjects drank 5 ml kg-1 body wt-1 of either a water placebo, or a liquid beverage containing a moderate (6% CHO) or high (12% CHO) concentration of carbohydrate beginning at min 14 of exercise and every 30 min thereafter. Exercise time to fatigue was shorter in subjects receiving placebo [190 (SE 4) min] as compared to 6% CHO [235 (SE 10) min] and 12% CHO [234 (SE 9) min] (P < 0.05). Glucose and insulin decreased in the placebo group, and free Trp, free-Trp/BCAA, and free fatty acids increased approximately five- to sevenfold (P < 0.05). These changes were attenuated in a dose-related manner by the carbohydrate drinks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of carbohydrate feedings on plasma free tryptophan and branched-chain amino acids during prolonged cycling. 148 39

Previous studies have shown that sustained exercise in human subjects causes an increase in the plasma concentration ratio of free tryptophan: other large neutral amino acids [including the branched-chain amino acids (BCAA)]. This should favour the transport of tryptophan into the brain and also the synthesis of 5-hydroxytryptamine, which is thought to contribute to fatigue during prolonged exercise. A mixture of the three BCAA was given to subjects during a 30-km cross-country race or a marathon (42.2 km) and the effects on mental and physical performances were measured. The mental performance, measured as the performance in the Stroop Colour and Word Test (CWT), was improved after, as compared to before the 30-km cross-country race when a BCAA supplement was given during the race, whereas the CWT scores were similar before and after in the placebo group. The running performance in the marathon was improved for the "slower" runners (3.05 h-3.30 h) when BCAA was taken during the race; however, there was no significant effect on the performance in the "faster" runners (less than 3.05 h). The results showed that both mental and physical performance was improved by an intake of BCAA during exercise. In addition, the effects of exercise on the plasma concentration of the aromatic amino acids were altered when a BCAA supplement was given during the marathon.
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PMID:Administration of branched-chain amino acids during sustained exercise--effects on performance and on plasma concentration of some amino acids. 174 9

The current treatments available for migraine are reviewed and may be classified into four basic types. (a) Identification and elimination of migraine trigger factors, which include stress, emotions, fatigue, certain foods and beverages, and certain medications such as oestrogen therapy. (b) Symptomatic treatment of individual attacks. This includes various non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin and paracetamol, and ergotamine, dihydroergotamine and phenothiazines. Morphinomimetics, which are often given for migraine, should really be avoided. (c) Prophylactic treatment which is particularly recommended for patients averaging two or more severe migraine attacks per month. Useful drugs include: beta-adrenergic receptor blockers as first choice, e.g. propranolol, timolol, nadolol and metoprolol; 5-hydroxytryptamine blockers, e.g. pizotifen and methysergide; calcium channel blockers; dihydroergotamine; and NSAIDs. (d) Non-drug treatment which is best combined with identification and elimination of trigger factors, and the use of various relaxation techniques. These four treatment types are covered in some detail, however it is clear that none of them is ideal and side-effects present a problem. Clearly, the continued research and development of novel and specific drugs for migraine is vital.
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PMID:A review of current drugs for migraine. 204 28

The effects on fusimotor discharge rate of algesic agents (bradykinin, potassium chloride, histamine, 5-hydroxytryptamine) and lactic acid, applied by close arterial injection into triceps surae muscles, were investigated in decerebrate cats. Fusimotor discharge was recorded from filaments dissected free from otherwise intact nerves to the triceps muscles. The substances applied induced an increase in discharge rate of spontaneously active gamma fusimotor neurones as well as a recruitment of previously silent ones. Skeletomotor discharges and/or muscle tension changes occurred only occasionally. The increase in fusimotor discharge rate was not always completely abolished by severing the nerves to triceps. What remained was a short-lasting burst at the very onset of blood-pressure fall. It was concluded that the increase in fusimotor discharge rate was mainly, but not solely, elicited reflexly by discharges from Group III and/or IV muscle afferents sensitive to algesic agents. An elevated fusimotor activity might be expected to accompany muscle inflammation and/or trauma when these agents are liberated in muscle tissue. The increase in fusimotor discharge rate elicited by lactic acid injections indicates that the fusimotor system might also be involved in neural processes of muscular fatigue.
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PMID:Reflex effects on gamma fusimotor neurones of chemically induced discharges in small-diameter muscle afferents in decerebrate cats. 220 80

In both trained and untrained rats, exercise increased the plasma concentration ratio of aromatic amino acids to branched-chain amino acids which might favour entry of the aromatic amino acids into the brain. Exercise in trained rats did not change the brain concentration of 5-hydroxytryptamine but increased that of 5-hydroxyindole acetic acid. Exercise in the untrained rat increased the concentration of brain tryptophan and that of 5-hydroxytryptamine but that of 5-hydroxyindole acetic acid was unchanged. The increased concentration of 5-hydroxytryptamine in untrained rats might be involved in central fatigue.
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PMID:Effect of sustained exercise on concentrations of plasma aromatic and branched-chain amino acids and brain amines. 242 44

Sustained exercise to fatigue elicits no major differences either in plasma amino acid levels or in brain 5-hydroxytryptamine (5-HT) metabolism between sedentary and endurance-trained animals. Furthermore, 11 weeks of endurance training did not influence the maximal activity of the enzyme monoamine oxidase in the brain areas which were studied. In both sedentary and endurance-trained rats, sustained running to fatigue caused an increase in the plasma concentration ratio of free tryptophan/other large neutral amino acids and an increase in the concentration of tryptophan in the six brain areas that were studied. The increase was similar in the different regions of the brain and averaged 36%. Exercise caused an increase in the levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the brain stem (14 and 44% respectively) and hypothalamus (16 and 17% respectively) and an increase in the level of 5-HIAA in the hippocampus (21%) and striatum (28%). Exercise also caused an increase in the level of dopamine in the brain stem (56%) and hypothalamus (46%) and of nor adrenaline in the striatum (59%). Since the levels of 5-HT and dopamine were both increased in the brain stem and hypothalamus, it is possible that these changes may play important roles in the central effects of exercise, including both physical and mental fatigue and effects on mood.
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PMID:Effect of sustained exercise on plasma amino acid concentrations and on 5-hydroxytryptamine metabolism in six different brain regions in the rat. 247 2

1. The action and interaction of noradrenaline (NA), 5-hydroxytryptamine (5-HT) and the sympathetic innervation was studied in the isolated taenia of the guinea-pig caecum.2. Addition of 5-HT led to a contraction of the taenia while addition of NA or perivascular nerve stimulation resulted in relaxation. Responses to 5-HT or perivascular nerve stimulation were abolished by tetrodotoxin. Tetrodotoxin did not affect responses to applied NA. Hexamethonium and hyoscine converted the 5-HT response to a relaxation and augmented the relaxation which followed low frequency perivascular nerve stimulation. Hexamethonium and hyoscine did not affect the dose-response relationship for NA.3. Fatigue of mechanical responses of the taenia to perivascular nerve stimulation was accelerated when nerves were stimulated in the presence of 5-HT or alpha-methyl-p-tyrosine (alpha-MPT). These two agents were additive in this action.4. Reserpine, 6-hydroxydopamine and alpha-MPT all reduced the NA content of the taenia. However, only after 6-hydroxydopamine could adrenergic activity be related to NA content.5. Segments of taenia were incubated with either tritiated NA or 5-HT. An increased rate of release of radioactivity followed perivascular nerve stimulation after incubation with either substance. This release did not occur when tissue was taken from animals given reserpine or 6-hydroxydopamine.6. It is concluded that 5-HT activates neural elements exclusively while NA has a direct effect on smooth muscle. 5-HT can apparently be taken up by adrenergic axons, and appears to enter the releasable neurotransmitter pool. Since none of the actions characteristic of 5-HT are seen when it is released by adrenergic axons as a false neurotransmitter, the released amine probably fails to reach neuronal receptors for 5-HT.
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PMID:Studies of the interaction of 5-hydroxytryptamine and the perivascular innervation of the guinea-pig caecum. 434 28

The human dorsal hand vein, exhausted in vivo (tachyphylaxis) by repeated inoculations of 5-hydroxytryptamine, recovers its capacity to contract in response to the 5HT when naloxone (per se ineffective) is inoculated into the same vein. It would seem, therefore, that in the 5HT tachyphylactic mechanism a role could be played by the progressive excitation of a local opioid modulator apparatus (silent in basal condition); naloxone's capacity for neutralizing the vein's fatigue could be indirect evidence of this. This postulation of an opioid role in the tachyphylactic mechanism differs from the conventional thesis, which explains tachyphylaxis as a progressive exhaustion of NA released from the sympathetic neuron by 5HT (see Table 1). Tachyphylaxis is poor, delayed or absent in migraine sufferers; this anomaly is present even in the period between attacks. The anomaly of inverted tachyphylaxis appears amplified during attacks. The loss or inversion of 5HT-tachyphylaxis is constantly observed in heroin addicts during acute abstinence. The fact that the clinical phenomena of acute heroin abstinence are comparable with those of a migraine attack could be a matter for further investigation.
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PMID:Is acute tolerance to 5-hydroxytryptamine opioid dependent? Its absence in migraine sufferers. 631 1

1 Antidepressant drugs produce significant changes in human brain function as reflected in the quantitatively analysed EEG. Two main types of pharmaco-EEG profiles may be differentiated: a thymeretic (desipramine-like) profile characterised mainly by an alpha increase suggesting activating properties and a thymoleptic (imipramine- or amitriptyline-like) profile showing a concomitant increase of slow and fast activities and a decrease in alpha activity indicating also sedative qualities. A small number of compounds exhibit still different profiles. 2 Aside from determining the type of EEG changes, the pharmaco-EEG method seems to be of value in determining time and dose efficacy relations at the target organ, the human brain. Moreover, the relationships between pharmacodynamics and pharmacokinetics may be determined. 3 Fluvoxamine, a selective 5-hydroxytryptamine (5-HT) re-uptake inhibitor from the new class of 2-aminoethyloximethers of aralkylketones, produced a typical thymoleptic pharmaco-EEG profile after oral doses of 75 mg in a double-blind placebo-controlled study involving 10 healthy volunteers. Fluvoxamine (75 mg) induced less augmentation of slow activity than 75 mg imipramine, indicating less sedative properties of fluvoxamine than imipramine. 4 After 75 mg fluvoxamine psychometric tests demonstrated a tendency towards an improvement in attention, concentration, psychomotor activity, after-effect and mood and a significant increase in critical flicker fusion frequency as compared with placebo. Comparison with the reference drug, 75 mg imipramine, revealed a significant superiority of fluvoxamine regarding concentration, psychomotor activity, tapping, reaction time, mood and affectivity. 5 Side-effects (mostly tiredness) were seen in five out of 10 subjects after 75 mg fluvoxamine and in eight out of 10 subjects after 75 mg imipramine. There were no clinically relevant changes in pulse, systolic and diastolic blood pressure.
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PMID:Pharmaco-EEG profiles of antidepressants. Pharmacodynamic studies with fluvoxamine. 640 99


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