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

Care of patients with cancer can be enhanced by continued involvement of the primary care physician. The physician's role may include informing the patient of the diagnosis, helping with decisions about treatment, providing psychological support, treating intercurrent disease, continuing patient-appropriate preventive care, and recognizing and managing or comanaging complications of cancer and cancer therapies. Adverse effects of therapy and cancer-related symptoms include nausea, febrile neutropenia, pain, fatigue, depression, and emotional distress. 5-Hydroxytryptamine antagonists are effective in controlling acute nausea associated with chemotherapy. Febrile neutropenia requires systematic evaluation and early empiric antibiotics while awaiting culture results. Cancer-related pain, depression, and fatigue often are underdiagnosed and undertreated. Use of brief screening tools for assessing fatigue and emotional distress can improve management of these symptoms. Exercise prescription, activity management, and psychosocial interventions are useful in treating cancer-related fatigue. The physician must be alert for signs and symptoms of cancer-related emergencies like spinal cord compression, hypercalcemia, tumor lysis syndrome, pericardial tamponade, and superior vena cava syndrome.
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PMID:Primary care of the patient with cancer. 1747 4

Cancer-related fatigue (CRF) is one of the most prevalent symptoms patients with cancer experience, both during and after treatment. CRF is pervasive and affects patients' quality of life considerably. It is important, therefore, to understand the underlying pathophysiology of CRF in order to develop useful strategies for prevention and treatment. At present, the etiology of CRF is poorly understood and the relative contributions of the neoplastic disease, various forms of cancer therapy, and comorbid conditions (e.g., anemia, cachexia, sleep disorders, depression) remain unclear. In any individual, the etiology of CRF probably involves the dysregulation of several physiological and biochemical systems. Mechanisms proposed as underlying CRF include 5-HT neurotransmitter dysregulation, vagal afferent activation, alterations in muscle and ATP metabolism, hypothalamic-pituitary-adrenal axis dysfunction, circadian rhythm disruption, and cytokine dysregulation. Currently, these hypotheses are largely based on evidence from other conditions in which fatigue is a characteristic, in particular chronic fatigue syndrome and exercise-induced fatigue. The mechanisms that lead to fatigue in these conditions provide a theoretical basis for future research into the complex etiology of this distressing and debilitating symptom. An understanding of relevant mechanisms may offer potential routes for its prevention and treatment in patients with cancer.Disclosure of potential conflicts of interest is found at the end of this article.
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PMID:Mechanisms of cancer-related fatigue. 1757 53

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

Previous studies suggest an important role for serotonergic (5-HT) modulation of the acoustic startle reflex (ASR) and prepulse inhibition (PPI). Acute challenge of brain serotonin by means of tryptophan depletion test (TDT) represents an established human challenge tool for temporary reduction of tryptophan (-TRP) levels and central nervous serotonin. Under these experimental conditions, PPI was found attenuated in males, but greater biochemical effects of TDT in the central nervous system of females are known. Therefore, in order to explore influence of 5-HT on various standard startle parameters in females, 16 young healthy females participated in a double-blind, cross-over TDT study. Acoustic stimuli were presented in 15 pulse-alone trials (100 dB, 40 ms) randomly followed by 25 pulse-alone or prepulse (70 dB, 30 ms; 120 ms interval) trials alongside electromyographic eyeblink recordings and mood state assessments. During 81% depletion of free plasma TRP, mean ASR magnitudes were significantly reduced compared to control (+TRP) condition while there were no differences in habituation or PPI nor did startle parameters correlate with mood states. Changes of plasma TRP and mood states correlated in tendency negatively in (-TRP) for depression and positively in (+TRP) for fatigue. In conclusion, this first study of startle parameters after TDT in a homogenous female population demonstrates that depletion of brain 5-HT in women only influences ASR.
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PMID:Effects of experimental acute tryptophan depletion on acoustic startle response in females. 1790 1

The serotonin neurotransmitter system, including the 5-HT(3) receptor, has been implicated in the genesis of fatigue in patients with liver disease. Therefore, we examined the possible role of 5-HT(3) receptors in cholestasis-associated fatigue. Rats were either bile duct resected (BDR) or sham resected and studied 10 days postsurgery. A significant decrease in hypothalamic 5-HT(3) receptor expression was detected by immunohistochemistry and Western blot in BDR vs sham rats, coupled with increased hypothalamic serotonin turnover identified by an elevated 5-hydroxyindoleacetic acid (5-HIAA) to 5-HT ratio in BDR vs sham rats. To examine fatigue-like behaviour, an activity meter was used. BDR rats exhibited significantly lower locomotor activity than did sham animals. Subcutaneous injection of the 5-HT(3) receptor antagonist tropisetron (0.1 mg kg(-1)) resulted in significantly increased locomotor activity in BDR rats compared to the activity in saline-treated controls, but was without effect in sham rats. However, a 10-fold higher dose of tropisetron significantly increased locomotor activity in both BDR and sham rats compared to saline-injected controls. These findings indicate that cholestasis in the rat is associated with increased hypothalamic serotonin turnover, decreased hypothalamic 5-HT(3) receptor expression, and enhanced sensitivity to locomotor activation induced by 5-HT(3) receptor antagonism, thereby implicating the 5-HT(3) receptor system in cholestasis associated fatigue.
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PMID:Downregulated hypothalamic 5-HT3 receptor expression and enhanced 5-HT3 receptor antagonist-mediated improvement in fatigue-like behaviour in cholestatic rats. 1791 12

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

This review examines the pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA). Stimulants that increase alertness/reduce fatigue or activate the cardiovascular system can include drugs like ephedrine available in many over-the-counter medicines. Others such as amphetamines, cocaine and hallucinogenic drugs, available on prescription or illegally, can modify mood. A total of 62 stimulants (61 chemical entities) are listed in the WADA List, prohibited in competition. Athletes may have stimulants in their body for one of three main reasons: inadvertent consumption in a propriety medicine; deliberate consumption for misuse as a recreational drug and deliberate consumption to enhance performance. The majority of stimulants on the list act on the monoaminergic systems: adrenergic (sympathetic, transmitter noradrenaline), dopaminergic (transmitter dopamine) and serotonergic (transmitter serotonin, 5-HT). Sympathomimetic describes agents, which mimic sympathetic responses, and dopaminomimetic and serotoninomimetic can be used to describe actions on the dopamine and serotonin systems. However, many agents act to mimic more than one of these monoamines, so that a collective term of monoaminomimetic may be useful. Monoaminomimietic actions of stimulants can include blockade of re-uptake of neurotransmitter, indirect release of neurotransmitter, direct activation of monoaminergic receptors. Many of the stimulants are amphetamines or amphetamine derivatives, including agents with abuse potential as recreational drugs. A number of agents are metabolized to amphetamine or metamphetamine. In addition to the monoaminomimetic agents, a small number of agents with different modes of action are on the list. A number of commonly used stimulants are not considered as Prohibited Substances.
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PMID:Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA). 1850 Mar 82

It is clear that the cause of fatigue is complex, influenced by both events occurring in the periphery and the central nervous system (CNS). It has been suggested that exercise-induced changes in serotonin (5-HT), dopamine (DA), and noradrenaline (NA) concentrations contribute to the onset of fatigue during prolonged exercise. Serotonin has been linked to fatigue because of its documented role in sleep, feelings of lethargy and drowsiness, and loss of motivation, whereas increased DA and NA neurotransmission favors feelings of motivation, arousal, and reward. 5-HT has been shown to increase during acute exercise in running rats and to remain high at the point of fatigue. DA release is also elevated during exercise but appears to fall at exhaustion, a response that may be important in the fatigue process. The rates of 5-HT and DA/NA synthesis largely depend on the peripheral availability of the amino acids tryptophan (TRP) and tyrosine (TYR), with increased brain delivery increasing serotonergic and DA/NA activity, respectively. TRP, TYR, and the branched-chained amino acids (BCAAs) use the same transporter to pass through the blood-brain barrier, meaning that the plasma concentration ratio of these amino acids is thought to be a very important marker of neurotransmitter synthesis. Pharmacological manipulation of these neurotransmitter systems has provided support for an important role of the CNS in the development of fatigue. Work conducted over the last 20 y has focused on the possibility that manipulation of neurotransmitter precursors may delay the onset of fatigue. Although there is evidence that BCAA (to limit 5-HT synthesis) and TYR (to elevate brain DA/NA) ingestion can influence perceived exertion and some measures of mental performance, the results of several apparently well-controlled laboratory studies have yet to demonstrate a clear positive effect on exercise capacity or performance. There is good evidence that brain neurotransmitters can play a role in the development of fatigue during prolonged exercise, but nutritional manipulation of these systems through the provision of amino acids has proven largely unsuccessful.
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PMID:Amino acids and the brain: do they play a role in "central fatigue"? 1857 73

1. Serotonin is a neurotransmitter that modulates several functions, such as food intake, energy expenditure, motor activity, mood and sleep. Acute exhaustive endurance exercise increases the synthesis, concentration and metabolism of serotonin in the brain. This phenomenon could be responsible for central fatigue after prolonged and exhaustive exercise. However, the effect of chronic exhaustive training on serotonin is not known. The present study was conducted to examine the effect of exhaustive endurance training on performance and serotonin concentrations in the hypothalamus of trained rats. 2. Rats were divided into three groups: sedentary rats (SED), moderately trained rats (MOD) and exhaustively trained rats (EXT), with an increase of 200% in the load carried during the final week of training. 3. Hypothalamic serotonin concentrations were similar between the SED and MOD groups, but were higher in the EXT group (P < 0.05). Performance was lower in the EXT group compared with the MOD group (P < 0.05). 4. Thus, the present study demonstrates that exhaustive training increases serotonin concentrations in the hypothalamus, together with decreased endurance performance after inadequate recovery time. However, the mechanism underlying these changes remains unknown.
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PMID:Effect of endurance training on hypothalamic serotonin concentration and performance. 1922 Mar 27

The original central fatigue hypothesis suggested that fatigue during prolonged exercise might be due to higher 5-HT activity. Therefore, we examined the effects of acute administration of a selective 5-HT reuptake inhibitor (SSRI) on performance and thermoregulation. Eleven healthy trained male cyclists completed four experimental trials (two in 18 degrees C, two in 30 degrees C) in a double-blind randomised crossover design. Subjects ingested either a placebo (PLA: lactose 2 x 10 mg) or citalopram (CITAL 2 x 10 mg) on the evening before and the morning of the trial. Subjects cycled for 60 min at 55% W(max), immediately followed by a time trial (TT) to measure performance. The significance level was set at P < 0.05. Acute SSRI did not significantly change performance on the TT (18 degrees C P = 0.518; 30 degrees C P = 0.112). During recovery at 30 degrees C, core temperature was significantly lower in the CITAL trial (P < 0.012). At 30 degrees C heart rate was significantly lower after exercise in CITAL (P = 0.013). CITAL significantly increased cortisol concentrations at rest (P = 0.016), after the TT (P = 0.006) and after 15-min recovery (P = 0.041) at 30 degrees C. 5-HT reuptake inhibition did not cause significant reductions in performance. Core temperature was significantly lower only after the time trial in heat after CITAL administration. The present work failed to prove whether or not 5-HT has an exclusive role in the onset of centrally mediated fatigue during prolonged exercise in both normal and high ambient temperature.
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PMID:Time trial performance in normal and high ambient temperature: is there a role for 5-HT? 1953 65


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