Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brain tryptophan is low in fibromyalgia. Intake of protein rich in large neutral amino acids is reported to lower brain tryptophan. This study was undertaken to assess whether any reduction of such proteins by exclusion of animal protein from the diet reduced pain and morbidity in fibromyalgia patients. It was an open, randomized controlled trial. 37 subjects with fibromyalgia were enrolled in the vegetarian diet and 41 in the amitriptyline groups. The outcome was assessed with the help of frequencies of fatigue, insomnia & non-restorative sleep, pain score on a 10-point VAS and tender point count. Fatigue, insomnia and non-restorative sleep were present in 41, 26 and 32 subjects before and in 3, 0 and 0 subjects respectively at six weeks of treatment in the amitriptyline group. The pain score and tender point count were 6.2 +/- 1.9 & 16.1 +/- 2.3 before and 2.3 +/- 1.3 & 6.4 +/- 3.0 after treatment. All these differences were significant (P < 0.001). In the vegetarian diet group, fatigue, insomnia and non-restorative sleep were present in 36, 24 and 27 subjects before and in 34, 29 and 29 subjects at six weeks of treatment. The pain score and tender point count were 5.7 +/- 1.8 and 15.7 +/- 2.4 before and 5.0 +/- 1.8 & 14.7 +/- 3.6 after treatment. All these differences were insignificant except that in the pain score. The decrease in the pain score, though significant, was much smaller than that in the amitriptyline group. So, it may be concluded that vegetarian diet is a poor option in the treatment of fibromyalgia.
 ...
PMID:Vegetarian diet in the treatment of fibromyalgia. 1150 70

As shown in the first part of this review, well equilibrated neurotransmission in which 5-HT plays a dominant role is important for proper neuromodulation and adjustment of neuronal network elements. Adequate 5-HT system function supports regulation of intercommunicative neuronal transmission in the brain, which optimizes behavioral neuromodulation during and after different forms of exertions, thereby preventing transient dysregulation. Impairment of neuromodulation and neuronal network in the brain with transient dysfunctions or permanent substantial deficits at manifestation of various types of depression results from prevalent impairment of 5-HT neurotransmission and its central interaction with other neurotransmitter systems. Exercise-induced increase of free tryptophan (TRP) in blood occurs due to liberation from albumin, which is caused by adrenergically induced lipolysis of free fatty acids and results in higher free TRP uptake into the brain. Consecutively enhanced serotonin (5-HT) biosynthesis does not per se initiate mood impairment or central fatigue. It is suggested that in overtrained athletes central fatigue, mental deficiency and behavioral alterations with depressive mood are probably not primarily caused by metabolic and neuromuscular alterations. The primary trigger of these transient behavioural alterations might instead be initiated by a central exhaustive exercise stress which elicits impairment of complex neuromodulation, also afflicting the interaction of central neurotransmitters or hypothalamic neuropeptides and releasing factors. In a consecutive correction of the variation, the implication of the serotonergic system on the central neuromodular disturbance might improve or prevent the progressive course both in transient and in permanent mental disorders. However, an unsuccessful attempt to improve the depressive symptomatology leads mostly to an overproportional exaggeration of the behavioral changes.
 ...
PMID:Physiology and pathophysiology of the serotonergic system and its implications on mental and physical performance. Part II. 1159 Apr 75

Several lines of evidence suggest that central serotoninergic neurons may mediate fatigue signals during prolonged exercise. In this study we examined the effects of diet and ambient temperature on peripheral modulators and indices of serotoninergic function and their relationship to exercise performance. Six well-trained cyclists participated, in randomised order, in two diet and exercise regimens each lasting 8 days and comprising four cycle tests to exhaustion at 70 % of maximum oxygen uptake. On days 1 and 5, subjects exercised to exhaustion to deplete muscle glycogen. For 3 days after the first depletion trial a diet providing 10 % of energy in the form of carbohydrate (CHO) was consumed (low CHO), and for 3 days after the second depletion trial a diet providing 80 % (high CHO) of energy as CHO was consumed, and each diet was followed by a performance trial at the same ambient temperature, either 10 degrees C or 30 degrees C (days 4 and 8). This schedule was repeated after 1 week, but performance trials were carried out at the other ambient temperature. In the cold, cycling time increased (P < 0.01) from 89.2 (78.0-129.5) min (median (range)) in the low CHO trial to 158.2 (116.9-165.6) min in the high CHO trial. In the heat, cycling time increased from 44.0 (31.8-51.4) min in the low CHO trial to 53.2 (50.2-82.2) min on the high CHO trial (P = 0.02). The serum prolactin (Prl) concentration was higher at exhaustion during the two trials in the heat than in the two trials in the cold. Serum Prl levels were unrelated to the purported peripheral modulators of serotoninergic function (plasma concentrations of total tryptophan (Trp), free Trp, branched-chain amino acids (BCAAs), free Trp/BCAA ratio and total Trp/BCAA ratio) but were significantly related to the rectal temperatures measured during the two trials in the heat. This finding provides indirect evidence that the serotoninergic system may be involved in fatigue during exercise under conditions of heat stress.
 ...
PMID:Hyperprolactinaemia during prolonged exercise in the heat: evidence for a centrally mediated component of fatigue in trained cyclists. 1185 66

The relationship between brain glucose and serotonin is still unclear and no direct evidence of an action of brain glucose on serotonergic metabolism in central fatigue phenomena has been shown yet. In order to determine whether or not brain glucose could influence the brain 5-hydroxytryptamine (5-HT) system, we have monitored in microdialysis the effects of a direct injection of glucose in rat brain hippocampus on serotonergic metabolism [i.e. 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and tryptophan (TRP)], during high intensive treadmill running. The injection was performed just before and after exercise. We have shown that glucose induced a decrease of brain 5-HT levels to a minimum of 73.0 +/- 3.5% of baseline after the first injection (P < 0.01) and to 68.5 +/- 5.5% of baseline after the second injection (P < 0.01) and consequently prevented the exercise-induced 5-HT enhanced levels. We have observed the same phenomenon concerning the 5-HIAA, but brain TRP levels were not decreased by the injections. In conclusion, this study demonstrates that brain glucose can act on serotonergic metabolism and thus can prevent exercise-induced increase of 5-HT levels. The results also suggest that extracellular brain glucose does not act on the synthesis way of 5-HT, but probably on the release/reuptake system.
 ...
PMID:Evidence that brain glucose availability influences exercise-enhanced extracellular 5-HT level in hippocampus: a microdialysis study in exercising rats. 1219 20

Administration of the cytokines interferon-alpha and interleukin-2 is used for the treatment of various disorders, such as hepatitis C and various forms of cancer. The most serious side-effects are symptoms associated with depression, including fatigue, increased sleepiness, irritability, loss of appetite as well as cognitive changes. However, great differences exist in the prevalence of the development of depressive symptoms across studies. Differences in doses and duration of therapy may be sources of variation as well as individual differences of patients, such as a history of psychiatric illness. In addition, sensitization effects may contribute to differential responses of patients to the administration of cytokines. In animals administration of pro-inflammatory cytokines induces a pattern of behavioural alterations called 'sickness behaviour' which resembles the vegetative symptoms of depression in humans. Changes in serotonin (5-HT) receptors and in levels of 5-HT and its precursor tryptophan in depressed people support a role for 5-HT in the development of depression. In addition, evidence exists for a dysregulation of the noradrenergic system and a hyperactive hypothalamic-pituitary-adrenal (HPA) axis in depression. Some mechanisms exist which make it possible for cytokines to cross the blood-brain barrier. Pro-inflammatory cytokines such as IL-1beta, IFN-alpha, IFN-gamma and TNF-alpha affect the 5-HT metabolism directly and/or indirectly by stimulating the enzyme indoleamine 2,3-dioxygenase which leads to a peripheral depletion of tryptophan. IL-1, IL-2 and TNF-alpha influence noradrenergic activity and IL-1, IL-6 and TNF-alpha are found to be potent stimulators of the HPA axis. Altogether, administration of cytokines may induce alterations in the brain resembling those found in depressed patients, which leads to the hypothesis that cytokines induce depression by their influence on the 5-HT, noradrenergic and HPA system.
 ...
PMID:The psychoneuroimmuno-pathophysiology of cytokine-induced depression in humans. 1246 36

It has been reported that exercise increases brain tryptophan (TRP), which is related to exhaustive fatigue. To study this further, the effect of increased TRP availability on the central nervous system (CNS) with regard to mechanical efficiency, oxygen consumption (VO(2)) and run-time to exhaustion was studied in normal untrained rats. Each rat was anesthetized with thiopental (30 mg/kg ip b. wt.) and fitted with a chronic guiding cannula attached to the right lateral cerebral ventricle 1 week prior to the experiments. Immediately before exercise, the rats were randomly injected through these cannulae with 2.0 microl of 0.15 M NaCl (n=6) or 20.3 microM L-TRP solution (n=6). Exercise consisted of running on a treadmill at 18 m min(-1) and 5% inclination until exhaustion. TRP-treated rats presented a decrease in their mechanical efficiency (21.25+/-0.84%, TRP group vs. 24.31+/-0.98%, saline-treated group; P< or =.05), and increased VO(2) at exhaustion (40.3+/-1.6 ml kg(-1) min(-1), TRP group vs. 36.0+/-0.8 ml kg(-1) min(-1), saline group; P< or =.05), indicating that the metabolic cost of exercise was higher in the former group. In addition, a highly significant reduction was also observed in run-time to exhaustion of TRP animals compared to those of the saline-treated group (15.2+/-1.52 min, TRP group vs. 50.6+/-5.4 min, saline group; P< or =.0001). It can be deduced from the data that intracerebroventricular TRP injection in rats increases O(2) consumption and reduces mechanical efficiency during exercise, diminishing running performance.
 ...
PMID:Evidence that tryptophan reduces mechanical efficiency and running performance in rats. 1247 55

Considerable evidence points towards a prominent role for central nervous system (CNS) mechanisms in the pathogenesis of chronic fatigue syndrome (CFS), a disorder characterized chiefly by persistent, often debilitating, fatigue. We wished to characterize circulating profiles of putative amino acid modulators of CNS 5-hydroxytryptamine (5-HT; serotoninergic) and dopaminergic function in CFS patients at rest, as well as during symptom-limited exercise and subsequent recovery. Groups of 12 CFS patients and 11 age- and sex-matched sedentary controls, with similar physical activity histories, underwent ramp-incremental exercise to the limit of tolerance. Plasma amino acid concentrations, oxygen uptake and ratings of perceived exertion were measured at rest, and during exercise and recovery. Peak oxygen uptake was significantly lower in the CFS patients compared with controls. Rating of perceived exertion in the patients was higher at all time points measured, including at rest, relative to controls. Levels of free tryptophan (free Trp), the rate-limiting 5-HT precursor, were significantly higher in CFS patients at exhaustion and during recovery, whereas concentrations of branched-chain amino acids (BCAA) and large neutral amino acids (LNAA) were lower in CFS patients at exhaustion, and for LNAA also during recovery. Consequently, the [free Trp]/[BCAA] and [free Trp]/[LNAA] ratios were significantly higher in CFS patients, except at rest. On the other hand, levels of tyrosine, the rate-limiting dopaminergic precursor, were significantly lower at all time points in the CFS patients. The significant differences observed in a number of key putative CNS 5-HT and dopaminergic modulators, coupled with the exacerbated perception of effort, provide further evidence for a potentially significant role for CNS mechanisms in the pathogenesis of CFS.
 ...
PMID:Chronic fatigue syndrome: new evidence for a central fatigue disorder. 1270 66

Free tryptophan (Trp), which is augmented by liberated free fatty acids (FFA) from adipose tissue, can induce mental fatigue via serotonin during exercise. Since an attenuation in FFA has been observed with omega-3 fatty acid (n-3fa) use, our purpose was to examine the effect of n-3fa supplementation on free Trp availability and exercise fatigue. Ten recreationally trained men ( n=5) and women ( n=5), with maximal oxygen consumption (VO(2max))of 51.6 (3.0) and 44.3 (1.4) ml kg(-1) min(-1), respectively, were studied on two occasions following an overnight fast, before and after n-3fa supplementation (4 g day(-1) for 4 weeks). The exercise trials consisted of a 75-min treadmill run at 60% VO(2max) followed immediately by a high-intensity incremental bout to fatigue. Measurements included exercise monitors, plasma volume (PV), triglycerides (TG), FFA, glycerol, lactate, and glucose. Free Trp and branched-chain amino acids (BCAA) were measured and correlated with time to fatigue; all blood variables were corrected for PV. Free Trp, lactate, glucose, FFA, and glycerol were not significantly different between trials, but TG ( P<0.001) and the free Trp/BCAA ratio were significantly lower after n-3fa use [1.76 (0.18)x10(-2) microg ml(-1)] versus before supplementation [2.17 (0.22), P=0.033]. There was a non-significant increase in time to fatigue after supplementation [10.2 (0.3) min] versus before n-3fa use [9.7 (0.2), P=0.068], and a tendency for higher BCAA levels after supplementation, P=0.068. However, neither free Trp nor the free Trp/BCAA ratio significantly predicted time to fatigue. In conclusion, n-3fa supplementation did not diminish free Trp concentrations or significantly improve endurance performance during a maximal bout of exercise.
 ...
PMID:Effect of n-3 fatty acids on free tryptophan and exercise fatigue. 1505 85

During long-distance exercise, branched-chain amino acid (BCAA) catabolism could lead to an increase in the blood tryptophan/BCAA ratio and an early onset of 'central fatigue'. Based on these considerations, we studied the modifications of blood serum BCAA and tryptophan (Try) levels in 30 endurance horses competing in rides varying in distance from 20 to 72 km. From all horses, blood samples were drawn just before and just after the end of the ride. Samples were analysed for their leucine (Leu), valine (Val), isoleucine (Iso) and Try levels. Data were processed by anova, using sampling moment and ride as factors, and by LSD post hoc test. Significant differences were recorded among the different distance rides for Leu, Val, Iso, Try, Try/BCAA ratio; the same trend was recorded between samples taken at the start and the end of the race for Val and Leu. The main effect observed was an increase of BCAA levels for all rides, except the 72-km ride; for Try, a significant increase was present in all races, except the 50-km ride. The Try/BCAA ratio decreased in 20- and 50-km races and increased in the others. These data confirm that long-distance exercise involves a mobilization of BCAA. The utilization of BCAA seems to be important in prolonged exercise: in the 72-km ride, we observed a decrease in BCAA blood serum levels, while a major role of Try was indicated by its increase, resulting in a rise of the Try/BCAA ratio.
 ...
PMID:Blood serum branched chain amino acids and tryptophan modifications in horses competing in long-distance rides of different length. 1505 43

The level of tryptophan and 5-hydroxyindoleacetic acid were measured in the brain (striatum) of rats on tryptophan-deficient diet and tryptophan-enriched diet. We measured concentrations of tryptophan and 5-hydroxyindoleacetic acid in striatum by using microdialysis and HPLC methods. The extracellular level of tryptophan and 5-hydroxyindoleacetic acid concentration in the striatum of a tryptophan-reduced rats was decreased by about 50% compared with a tryptophan-enriched diet. In the tryptophan-reduced condition, the rats an increased the running time of more than 100 min, compared with those on a tryptophan-enriched diet. These results suggest the tryptophan and 5-hydroxytryptamine in the central nervous system are involved in fatigue.
 ...
PMID:The effect of tryptophan deficiency in the brain on rat fatigue levels: a rat model of fatigue reduction. 1520 70


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>