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

Cholestasis contributes to the genesis of fatigue through several mechanisms. Among these mechanisms, affected serotonergic neurotransmission is important in the pathogenesis of central fatigue. Previously, elevated levels of 5-hydroxyindole acetic acid (5-HIAA), the metabolite of 5-hydroxytryptamine (5-HT) and increased 5-HT(2) receptor density were demonstrated in the anterior hypothalamus and in the hippocampus of bile duct resected rats (BDR), respectively. The aim of this paper is to demonstrate evoked 5-HT release in selected brain regions like anterior hypothalamus and hippocampal CA1 regions of cholestatic rats using BDR rats as an experimental model for cholestasis. In this study, we analyzed the K+ evoked 5-HT and its metabolite 5-HIAA levels by using HPLC with electrochemical detection in the microdialysis samples collected from anterior hypothalamic and hippocampal CA1 regions of sham-operated and BDR rats (n = 6). The ratios of [5-HIAA] to [5-HT] following perfusion with 100 mM K+ artificial cerebrospinal fluid was used for the comparison of the evoked release of 5-HT. Locomotor activity was used to assess the signs of cholestasis associated fatigue in the BDR rats. The vertical and horizontal activity counts within 15 min were found to be decreased in the BDR rats compared to sham-operated rats (p < 0.05). Besides, the number of fecal boli (an index of emotionality) was also significantly fewer in the cholestatic rats (p < 0.05). No significant difference between the sham-operated and the BDR rats was detected in the basal 5-HT and 5-HIAA levels of anterior hypothalamus. K+ stimulation yielded a more profound increase in the [5-HIAA]/[5-HT] in the BDR rats (p < 0.05). The basal levels of 5-HT in CA1 region of the BDR rats was found to be lower than that of sham-operated group (p < 0.05), but no significant difference was observed in terms of evoked 5-HT release in both sham-operated and BDR rats. These findings imply the presence of affected serotonergic system in cholestasis.
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PMID:5-hydroxytryptamine release in the anterior hypothalamic and the hippocampal areas of cholestatic rats. 1618 17

The primary aims of this paper were to examine the effect of heat stress on working memory, choice reaction time and mood state, and to investigate the relationship between heat induced changes in plasma concentrations of selected neurotransmitters and hormones, and cognition. Heat stress resulted in a deterioration of performance on a central executive task (random movement generation) but not on verbal and spatial recall, and choice reaction time tasks. Perceptions of vigour decreased and fatigue increased following exposure to heat stress. Plasma concentrations of cortisol and 5-hydroxytryptamine significantly increased following exposure to heat. Regression analyses showed that percent body mass loss and change from baseline (Delta) concentrations of cortisol, post-exposure to heat, were significant predictors of Delta random movement generation and Delta fatigue. A secondary purpose was to examine the effect of recovery on cognition and mood. Following recovery, the performance of the central executive task was poorer than pre-treatment. Mood states, catecholamines and 5-hydroxytryptamine concentrations returned to pre-treatment values, but cortisol fell to a level significantly lower. Regression correlations showed that Delta adrenaline and Delta scores, post-recovery, on the central executive task were significantly correlated. Delta noradrenaline correlated significantly with Delta fatigue. It was concluded that heat stress results in deterioration in the performance of central executive tasks and perceptions of mood state, and that this can be predicted by changes in body mass loss and plasma concentrations of the hormones cortisol and adrenaline.
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PMID:Heat stress, plasma concentrations of adrenaline, noradrenaline, 5-hydroxytryptamine and cortisol, mood state and cognitive performance. 1630 71

The anterior pituitary hormone prolactin (PRL), measured in the peripheral blood circulation, reflects alterations in central brain 5-hydroxytryptamine (serotonin) and dopaminergic activity and is used as a marker of 'central fatigue' during active heat exposure. Significant correlations have consistently been found between PRL and core temperature (T(CORE)) during prolonged exercise. There has been no investigation into the relationship between PRL and other key thermoregulatory variables during exercise, such as weighted mean skin (T(SK)) and mean body temperature (T(B)), heat storage (HS), thermal gradient (T(GRAD)), heart rate (HR) and skin blood flow (cutaneous vascular conductance, CVC). Therefore, the aim of this study was to ascertain if a significant relationship exists between PRL and these thermoregulatory variables during prolonged exercise. Nine active male subjects conducted three trials of approximately 60% VO(2peak) at 70-80 rpm for 45 min on a semi-recumbent cycle ergometer at three different ambient temperatures [6 degrees C (Cold), 18 degrees C (Neutral) and 30 degrees C (Hot)] to elicit varying levels of thermoregulatory stress during exercise. Significant differences existed in T(SK), T(B), HS, T(GRAD) and CVC across the environmental conditions (p < 0.001). Core temperature (T(CORE)), HR and PRL were significantly elevated only in Hot (p < 0.05). Moderate correlations were found for T(CORE), T(SK), T(B), HS, T(GRAD), HR and CVC with post-exercise PRL (rho = 0.358-0.749). The end-of-exercise <38.0 degrees C T(CORE) responses were not (rho = -0.129, p > 0.05) but the >38.0 degrees C T(CORE) responses were (rho = 0.845, p < 0.001) significantly related to their corresponding PRL responses. The significant relationships between PRL release and T(SK), T(B), HS, T(GRAD), HR and CVC have extended previous research on T(CORE) and PRL release and indicate an association between these thermoregulatory variables, as well as T(CORE), and serotonergic/dopaminergic activity during prolonged exercise.
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PMID:Exercise thermoregulation and hyperprolactinaemia. 1633 20

An account of the tryptophan (Trp)-5-hydroxytryptamine (5-HT)-central fatigue theory is provided and an explanation of how oral administration of BCAAs can decrease fatigue on the basis of this theory is given. The rate-limiting step in the synthesis of 5-HT is the transport of Trp across the blood-brain barrier. This transport is influenced by the fraction of Trp available for transport into the brain and the concentration of the other large neutral amino acids, including the BCAAs, which are transported via the same carrier system. During endurance exercise, there is an uptake of Trp by the brain, suggesting that this may increase the synthesis and release of 5-HT in the brain. Oral intake of BCAAs may reduce this uptake and also brain 5-HT synthesis and release, thereby delaying fatigue. Other hypotheses for the effect of BCAAs on central fatigue are included.
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PMID:Branched-chain amino acids and central fatigue. 1636 97

Several factors have been identified to cause peripheral fatigue during exercise, whereas the mechanisms behind central fatigue are less well known. Changes in the brain 5-hydroxytryptamine (5-HT) level is one factor that has been suggested to cause fatigue. The rate-limiting step in the synthesis of 5-HT is the transport of tryptophan across the blood-brain barrier. This transport is influenced by the fraction of tryptophan available for transport into the brain and the concentration of the other large neutral amino acids, including the BCAAs (leucine, isoleucine, and valine), which are transported via the same carrier system. Studies in human subjects have shown that the plasma ratio of free tryptophan (unbound to albumin)/BCAAs increases and that tryptophan is taken up by the brain during endurance exercise, suggesting that this may increase the synthesis of 5-HT in the brain. Ingestion of BCAAs increases their concentration in plasma. This may reduce the uptake of tryptophan by the brain and also 5-HT synthesis and thereby delay fatigue. Accordingly, when BCAAs were supplied to human subjects during a standardized cycle ergometer exercise their ratings of perceived exertion and mental fatigue were reduced, and, during a competitive 30-km cross-country race, their performance on different cognitive tests was improved after the race. In some situations the intake of BCAAs also improves physical performance. The results also suggest that ingestion of carbohydrates during exercise delays a possible effect of BCAAs on fatigue since the brain's uptake of tryptophan is reduced.
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PMID:A role for branched-chain amino acids in reducing central fatigue. 1642 44

In this article we discuss studies showing that rats are able to regulate their intake of BCAA depending on the level of exercise, and that they will choose a solution of BCAA over water during times of intense exercise. We found that the voluntary intake of a solution made of BCAA, L-arginine and L-glutamine positively correlated with the timing and volume of exercise during the dark (active) period of the circadian rhythm. In the second behavioral protocol in which rats were fed BCAA fortified diet (2.0%, wt:wt), we observed voluntarily increased volume of physical activity beginning from d 4 of feeding on. In the second, neuro-behavioral, part of the study we measured the brain content of 5-hydroxytryptamine (5-HT) as well as plasma amino acid profiles in well-trained exercising rats to test a hypothesis that BCAA may alleviate central aspects of fatigue. A solution made of BCAA, L-arginine, and L-glutamine applied before running elevated the BCAA/tryptophan plasma ratio at the end of and after running, and decreased 5-HT release in the lateral hypothalamus and amygdala after running, when compared with the controls. The exercise-related shift in the fluid preference toward a BCAA-based solution suggests an ergogenic benefit. The forced-running study shows the lateral hypothalamus and possibly amygdala might be the critical brain regions implied in the central effects of a BCAA-based solution.
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PMID:Exercise-dependent preference for a mixture of branched-chain amino acids and homeostatic control of brain serotonin in exercising rats. 1642 45

Acanthopanax senticosus Harms (AS) is classified into the family of Araliaceae. The plant has been used as an analeptic aid, which improves weakened physical status and strength. Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter and tryptophan hydroxylase (TPH) catalyzes the rate-f the raphe nuclei. These are associated with "central fatigue hypotheses" in the brain. In the present study, the effects of Acanthopanax senticosus on the time to exhaustion by treadmill exercise and on 5-HT synthesis and TPH expression in the dorsal raphe were investigated by immunohistochemistry. In the present results, Acanthopanax senticosus increased the time to exhaustion by treadmill running and it suppressed the exercise-induced increase of 5-HT synthesis and TPH expression. Acanthopanax senticosus was effective as caffeine for increasing the exhaustion time in treadmill running and for reducing the exercise-induced increase of 5-HT synthesis and TPH expression in the dorsal raphe. The present study shows that Acanthopanax senticosus reduces fatigue during exercise by the inhibition of exercise-induced 5-HT synthesis and TPH expression in the dorsal raphe.
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PMID:Effect of Acanthopanax senticosus on 5-hydroxytryptamine synthesis and tryptophan hydroxylase expression in the dorsal raphe of exercised rats. 1782 16

Since the publication of the serotonin hypothesis, numerous theories involving the accumulation or depletion of different substances in the brain have been proposed to explain central fatigue. Although the theoretical rationale for the "serotonin-fatigue hypothesis" is clear, several seemingly well-conducted studies have failed to support a significant role for 5-hydroxytryptamine in the development of fatigue. As brain function appears to be dependent upon the interaction of a number of systems, it is unlikely that a single neurotransmitter system is responsible for central fatigue. Several other mechanisms are involved, with evidence supporting a role for the brain catecholamines. Fatigue is therefore probably an integrated phenomenon, with complex interaction among central and peripheral factors. When prolonged and excessive training happens, concurrent with other stressors and insufficient recovery, performance decrements can result in chronic maladaptations that can lead to the overtraining syndrome (OTS). The mechanism of the OTS could be difficult to examine in detail, perhaps because the stress caused by excessive training load, in combination with other stressors, might trigger different "defence mechanisms" such as the immunological, neuroendocrine, and other physiological systems that all interact and probably therefore cannot be pinpointed as the "sole" cause of the OTS. It might be that, as in other syndromes, the psychoneuroimmunology (study of brain-behavior-immune interrelationships) might shed a light on the possible mechanisms of the OTS, but until there is a definite diagnostic tool, it is of utmost importance to standardize measures that are now thought to provide a good inventory of the training status of the athlete. It is very important to emphasize the need to distinguish the OTS from overreaching and other potential causes of temporary underperformance such as anemia, acute infection, muscle damage, and insufficient carbohydrate intake.
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PMID:Brain neurotransmitters in fatigue and overtraining. 1805 10

Chronic fatigue syndrome (CFS) is a debilitating disorder of unknown etiology with no known lesions, diagnostic markers or therapeutic intervention. The pathophysiology of CFS remains elusive, although abnormalities in the central nervous system (CNS) have been implicated, particularly hyperactivity of the serotonergic (5-hydroxytryptamine; 5-HT) system and hypoactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Since alterations in 5-HT signaling can lead to physiologic and behavioral changes, a genetic evaluation of the 5-HT system was undertaken to identify serotonergic markers associated with CFS and potential mechanisms for CNS abnormality. A total of 77 polymorphisms in genes related to serotonin synthesis (TPH2), signaling (HTR1A, HTR1E, HTR2A, HTR2B, HTR2C, HTR3A, HTR3B, HTR4, HTR5A, HTR6, and HTR7), transport (SLC6A4), and catabolism (MAOA) were examined in 137 clinically evaluated subjects (40 CFS, 55 with insufficient fatigue, and 42 non-fatigued, NF, controls) derived from a population-based CFS surveillance study in Wichita, Kansas. Of the polymorphisms examined, three markers (-1438G/A, C102T, and rs1923884) all located in the 5-HT receptor subtype HTR2A were associated with CFS when compared to NF controls. Additionally, consistent associations were observed between HTR2A variants and quantitative measures of disability and fatigue in all subjects. The most compelling of these associations was with the A allele of -1438G/A (rs6311) which is suggested to have increased promoter activity in functional studies. Further, in silico analysis revealed that the -1438 A allele creates a consensus binding site for Th1/E47, a transcription factor implicated in the development of the nervous system. Electrophoretic mobility shift assay supports allele-specific binding of E47 to the A allele but not the G allele at this locus. These data indicate that sequence variation in HTR2A, potentially resulting in its enhanced activity, may be involved in the pathophysiology of CFS.
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PMID:Genetic evaluation of the serotonergic system in chronic fatigue syndrome. 1807 67

Frovatriptan is an orally active 5-hydroxytryptamine (5-HT) receptor agonist which binds with high affinity to 5-HT(1B) and 5-HT(1D) receptors. Earlier clinical trials demonstrated that frovatriptan 2.5 mg is significantly more effective than placebo in the acute management of migraine and its associated symptoms. More recently, frovatriptan was shown to be effective in the management of menstrual migraine. The incidence of menstrual migraine in subjects receiving frovatriptan 2.5 mg twice daily during the six day perimenstrual period was 41% compared with 67% with placebo. Frovatriptan treatment is generally well tolerated. The most commonly reported adverse effects were dizziness, paresthesia, dry mouth, and fatigue. Pharmacologic studies demonstrated that frovatriptan is cerebroselective. Its selectivity for cerebral vessels lessens the potential for undesirable peripheral effects. Frovatriptan has a terminal deposition half-life of approximately 26 hours, which appears to be independent of age, gender, and renal function. This imparts that frovatriptan may be particularly well suited to patients with prolonged migraines and those who suffer migraine recurrence. Frovatriptan does not alter cytochrome P450 (CYP450) isoenzymes, as such it is unlikely to affect the metabolism of other drugs. No dosage adjustments are necessary based on age, renal, or mild to moderate hepatic impairment. Apart from its efficacy in the acute management of migraine, frovatriptan is an effective agent when used as either acute therapy or as intermittent prophylaxis therapy of menstrual migraines, particularly in women who do not respond to conventional therapies.
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PMID:Frovatriptan: a review of pharmacology, pharmacokinetics and clinical potential in the treatment of menstrual migraine. 1836 Jun 5


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