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)

It is generally recognized that a decrease in carbohydrate availability can lead to the development of fatigue during prolonged exercise in humans. Administration of glucose or other carbohydrates before or during exercise has been shown to postpone fatigue, conserve muscle glycogen and improve performance. Carbohydrates can be categorised according to their ability to increase blood glucose concentration (known as glycaemic index) and by the extent they stimulate the release of insulin. The glycaemic index is reflected in the rate at which consumed carbohydrate is made available in the blood. Glucose is the only type of carbohydrate that can readily be oxidised by skeletal muscle for energy production. Gastric emptying is the primary factor limiting the rate of carbohydrate delivery to the blood and therefore influences the utilisation of exogenous carbohydrate ingested before or during exercise. Various methods have been used to assess the oxidation of exogenous carbohydrates during exercise. Peak rates of CHO oxidation during exercise have been reported between 0.4 and 1.0 g/min, and the rates of oxidation do not appear to be influenced to a major extent by the use of multiple drinking schedule in comparison with a single bolus schedule. Previous studies also suggest that the ingestion of fructose during exercise does not offer any additional benefits over ingestion of glucose or glucose polymer solutions of similar concentration. The hormones insulin, glucagon and adrenaline together with cortisol and growth hormone play key roles in the regulation of carbohydrate metabolism during exercise. Ingestion of moderately concentrated carbohydrate solutions (4-8%) enhances prolonged exercise performance and is appropriate for optimising energy and fluid delivery without causing adverse effects. The ergogenic effects of carbohydrate ingestion on performance during intermittent exercise such as competitive sports are less well established, although the evidence to date suggests diminished performance when carbohydrate are limiting.
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PMID:Exogenous carbohydrate utilisation: effects on metabolism and exercise performance. 940 48

Many types of drugs are used by athletes to improve performance. This paper reviews the literature on 3 categories of drugs: those that enhance performance as stimulants (amphetamines, ephedrine, and cocaine), those that are used to reduce tremor and heart rate (beta-blockers) and those involved in bodyweight gain or loss (anabolic-androgenic steroids, growth hormone, beta 2-agonists, and diuretics). Limitations of research on these drugs as they relate to performance enhancement are also discussed. The numerous studies that have assessed the effects of amphetamines on performance report equivocal results. This may be due to the large interindividual variability in the response to the drug and the small sample sizes used. Most studies, however, show that some individuals do improve exercise performance when taking amphetamines, which may be attributed to their role in masking fatigue. As a stimulant, ephedrine has not been found to improve performance in the few studies available. More recently, ephedrine has been purported to be effective as a fat burner and used by athletes to maintain or improve muscle mass. Although research on individuals with obesity supports the use of ephedrine for fat loss, no studies have been done on athletes. The few studies of cocaine and exercise suggest that little to no performance gains are incurred from cocaine use. Moreover, the sense of euphoria may provide the illusion of better performance when, in actuality, performance was not improved or was impaired. beta-Blockers have been found to reduce heart rate and tremor and to improve performance in sports that are not physiologically challenging but require accuracy (e.g. pistol shooting). However, there is evidence that some individuals may be high responders to beta-blockers to the extent that their heart rate response is so blunted as to impair performance. Although equivocal, several studies have reported that anabolic-androgenic steroids increase muscle size and strength. However, most studies are not well controlled and use insufficient drug doses. One recent well controlled study did find an increase in muscle mass and strength with supraphysiological doses, and the improvements were greater in participants who were also resistance training. There is little information available on the effects of growth hormone on muscle mass or performance in athletes, although data suggest that growth hormone administration does not increase muscle protein synthesis. beta 2-Agonists, such as clenbuterol and salbutamol, when administered orally appear to improve muscular strength due to their potential role in increasing muscle mass. However, studies have not been done using athletes. Diuretics results in a loss of body water and hence bodyweight that can be advantageous for sports with strict bodyweight classifications. There is insufficient evidence on possible performance decrements in the field that could result from dehydration induced by the diuretics. Overall, the most significant concern in studies of drug use is the large inter-individual variability in responses to a drug. Further studies are needed to understand why some individuals are more responsive than others and to assess whether the responses are consistent for a given individual. Most studies of drug effectiveness have not used athletes. The effectiveness of many drugs may be reduced in highly trained athletes because there is a lower margin for improvement.
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PMID:Drugs and sport. Research findings and limitations. 942 62

Interleukin-6, an inflammatory cytokine, is characterized by pleiotropy and redundancy of action. Apart from its hematologic, immune, and hepatic effects, it has many endocrine and metabolic actions. Specifically, it is a potent stimulator of the hypothalamic-pituitary-adrenal axis and is under the tonic negative control of glucocorticoids. It acutely stimulates the secretion of growth hormone, inhibits thyroid-stimulating hormone secretion, and decreases serum lipid concentrations. Furthermore, it is secreted during stress and is positively controlled by catecholamines. Administration of interleukin-6 results in fever, anorexia, and fatigue. Elevated levels of circulating interleukin-6 have been seen in the steroid withdrawal syndrome and in the severe inflammatory, infectious, and traumatic states potentially associated with the inappropriate secretion of vasopressin. Levels of circulating interleukin-6 are also elevated in several inflammatory diseases, such as rheumatoid arthritis. Interleukin-6 is negatively controlled by estrogens and androgens, and it plays a central role in the pathogenesis of the osteoporosis seen in conditions characterized by increased bone resorption, such as sex-steroid deficiency and hyperparathyroidism. Overproduction of interleukin-6 may contribute to illness during aging and chronic stress. Finally, administration of recombinant human interleukin-6 may serve as a stimulation test for the integrity of the hypothalamic-pituitary-adrenal axis.
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PMID:The pathophysiologic roles of interleukin-6 in human disease. 944 73

The present study evaluates the effects of 2 years of growth hormone (GH) replacement therapy on psychological well-being and cognitive performance in adults with childhood-onset growth hormone deficiency (CO-GHD). A total of 48 GHD adult men (mean age: 27 years) were randomly assigned to one of four treatment groups: placebo treatment, or GH replacement in a dose of 1, 2, or 3 IU/m2, respectively. Placebo treatment was given for 6 months. Psychological assessments were made every 6 months. Assessments included somatic and psychological complaints, depression, fatigue, vigor, tension, state/trait anxiety, iconic memory, short-term memory, long-term memory and perceptual-motor skill. GH treatment was considered physiological if the observed insulin-like growth factor-I (IGF-I) levels were within the normal range. It was considered supraphysiological if serum IGF-I rose to a value exceeding the upper normal limit. During the placebo-controlled phase of the study the changes in memory performance were positively correlated to the GH induced changes in serum IGF-I concentration and, more weakly, to the daily GH substitution dose. At 6 months memory only had improved in the group receiving supraphysiological GH treatment, but not in the group of patients who had a normalization of serum IGF-I. However, after 1 year of treatment a normalization of memory functioning was found in both groups of patients and this was preserved during the 2nd year of treatment. No changes were observed in psychological well-being and perceptual-motor skill. We conclude that GH replacement improves memory function in adults with CO-GHD. It has no effect on psychological well-being or perceptual-motor skill. Supraphysiological treatment accelerates the recovery of memory performance. However, the long-term effects are not different from those achieved with physiological GH replacement.
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PMID:Cognitive changes during growth hormone replacement in adult men. 961 51

Effects of a serotonin re-uptake inhibitor and oral amino acid supplementations on physical and mental performance as well as neuroendocrine variables were investigated. 10 male subjects cycled in four trials until exhaustion. Participants ingested a placebo in trial (T) I, 20 mg paroxetine in T II, 21 g branched-chain amino acids (BCAA) in T III and 20g tyrosine (TYR) in T IV. Heart rate, capillary lactate, plasma insulin, free fatty acids, glucose, serotonin and beta-endorphin did not differ in trials. Plasma ammonia increments during exercise were higher in T III. Plasma BCAA in T III and plasma TYR in T IV were increased after 30 min of exercise according to the supplemented substances. In contrast to all other trials, the ratio of plasma free TRP/BCAA did not increase in T III. Plasma TYR/BCAA was augmented in T IV and decreased in T III after 30 min of exercise, whereas it did not change in T I and II. Plasma prolactin (PRL), growth hormone, cortisol, adrenocorticotropic hormone, norepinephrine and epinephrine increased during all trials. Plasma PRL increments were higher in T IV. Exhaustion was reached earlier in T II. No significant differences were found between other trials. Drive during psychometric testing subsequent to exercise was improved in T III and IV. The results indicate that fatigue during endurance exercise was increased by pharmacological augmentation of the brain serotonergic activity. However, a reduction of 5-HT synthesis via BCAA supplementation did not affect physical fatigue. TYR administration did not alter physical performance either although plasma PRL increments suggest that changes in the monoaminergic system were induced. Precaution is necessary before assuming an ergogenic value of amino acids.
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PMID:Influence of paroxetine, branched-chain amino acids and tyrosine on neuroendocrine system responses and fatigue in humans. 962 32

Poor sleep, daytime fatigue, and loss of cognitive ability exist during all stages of HIV infection, worsening with disease progression. These symptoms contribute to disability and poor quality of life. Data from several research groups support a role of somnogenic inflammatory process peptides elevated in HIV infection, e.g. TNF alpha. Though the literature is in conflict regarding an effect of HIV infection on growth hormone (GH) secretion, GH axis dysregulation and treatment with GH may be important in HIV infection, e.g. in the wasting syndrome. It has long been known that GH varies with changes in sleep. The hypothesis tested in the current study was that the relationship between delta frequency (0.5-4.0 Hz) sleep EEG amplitude (square root of power from frequency analysis) and GH secretion would differ between HIV positive (HIV+) and HIV negative (HIV-) subjects. In 14 subjects (6 HIV+ and 8 HIV-, none with current or past AIDS-defining illness) a linear relationship change across the night's sleep was found in the coupling between delta frequency sleep EEG amplitude and GH secretion. The phase coupling change was in opposite directions in HIV+ versus HIV- subjects. This difference supports the hypothesis that the brain-based coordination of sleep and sleep-related physiology deteriorates early in HIV infection, and that GH dysregulation may contribute to this sleep pathology.
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PMID:Growth hormone, fatigue, poor sleep, and disability in HIV infection. 964 13

Resistance to the anabolic effects of growth hormone (GH) occurs with severe caloric deficit. This study examined whether moderate caloric deficit (50% of daily intake for 7 days) in the adolescent rat exceeds a critical threshold for GH action and whether a combination of GH and insulin-like growth factor I (IGF-I) would have enhanced anabolic effects on the diaphragm (Dia). Five groups of rats (4 wk old) were studied: 1) control (Ctl), 2) nutritionally deprived (ND), 3) ND + GH, 4) ND + IGF-I, and 5) ND + GH + IGF-I. IGF-I was given by continuous infusion (200 microg/day). GH was injected subcutaneously (250 microg every 12 h). Contractile and fatigue properties of the Dia were determined in vitro. Quantitative histochemical methods were used to determine Dia fiber type proportions, cross-sectional areas, and succinate dehydrogenase activities. The body weight of Ctl rats increased 46% compared with 7% in ND animals, whereas that of ND rats receiving growth factors was intermediate. Serum IGF-I levels were reduced 54% in ND animals and maintained with the provision of growth factors. Dia fatigue resistance was improved in ND animals receiving growth factors. There were no differences in Dia contractile properties, fiber type proportions, or succinate dehydrogenase activities across groups. ND resulted in atrophy/growth arrest of all Dia fibers (20-32%) compared with Ctl. Administration of IGF-I and/or GH completely prevented atrophy/growth arrest of all Dia fibers. No additive or synergistic effects were noted. We propose that these growth factors may provide useful short-term adjunctive nutritional support in circumstances in which the provision of optimal nutrition may be delayed or inadequate.
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PMID:IGF-I and/or growth hormone preserve diaphragm fiber size with moderate malnutrition. 965 74

In snoring men improved nasal breathing during sleep has been shown to decrease snoring and morning tiredness. The aim was to evaluate whether improved nasal breathing had any effect on growth hormone (GH) secretion, the nocturnal secretion of GH being associated with deep sleep. Forty-two snoring men, mean age 45 years and mean body mass index 26 kg.m-2, slept every night during one month with the Nozovent nostril dilator. Before and at the end of the test period, we analysed serum insulin-like growth factor 1 (IGF-1), thyrotropin (TSH), free thyroxine (free T4), free 3,5,3'-triiodothyronine (free T3), cortisol and testosterone in blood sampled at 08:00 h. Fifteen of the 37 snoring men who completed the study experienced a reduction in snoring and were less tired in the morning during the test period. In this group, the mean IGF-1 concentration was significantly increased (p < 0.05) after one month. There was no significant difference in mean IGF-1 level between the snorers and a population sample. Likewise, TSH, free T4, free T3, cortisol and testosterone concentrations were within normal limits. Snorers with reduced snoring and morning tiredness due to improved nasal breathing showed an increase in morning IGF-1 concentration which can probably be explained by higher nocturnal GH secretion induced by more deep sleep.
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PMID:Improved nasal breathing in snorers increases nocturnal growth hormone secretion and serum concentrations of insulin-like growth factor 1 subsequently. 992 61

The symptomatology associated with severe growth hormone (GH) deficiency in adult life is a real entity but unfortunately it is also nonspecific with extreme fatigue and obesity dominating the clinical picture. Quality of life (QOL) is a term widely used by clinicians, research scientists and policy-makers, though there is a lack of consensus over its definition. Most of the related literature lists aspects assumed to be components of QOL and most measures are based upon the assumption that QOL is related to the ability to function in certain domains of physical, social and environmental existence such as work, leisure pursuits, socializing, etc. Most published studies on QOL have utilized generic measures of health status which were developed more than 20 years ago, were not designed for clinical trials, and it is debatable whether all the questions are relevant to patients. Only the Nottingham Health Profile has content derived entirely from lay people as opposed to being written by professionals. This has led to the development of QOL measures specific for GH deficiency based on unstructured qualitative interviews (1-2 h), which, unfortunately, have been carried out in a relatively small number of patients. Furthermore, the disease-specific measures of QOL are not truly specific for GH deficiency, as the patient has in almost all cases had a pituitary tumor, undergone surgery and/or radiotherapy and is receiving other hormone therapy for additional pituitary hormone deficits. Should the ideal control population for comparison with the GH-deficient patient cohort be normal subjects or patients with chronic disorders? Placebo-controlled studies of GH therapy indicate a definite placebo effect contributing to the improvement in QOL in GH-deficient adults. QOL is generally stated to be less affected in young adults with childhood-onset GH deficiency compared with patients with adult-onset GH deficiency. How do we know? Do we have disease-specific measures applicable to the adolescent age group? In reality, many centres utilize reduced QOL as an indication for GH replacement. However, heavy reliance is placed on the subjective patient interview rather than objective use of a disease-specific questionnaire. Why? Because there is no questionnaire score (number) available to reflect degree of impairment of QOL at baseline or of improvement in QOL in response to GH therapy.
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PMID:The use of self-rating questionnaires as a quantitative measure of quality of life in adult growth hormone deficiency. 1044 81

Basal concentrations of cortisol (CORT), beta-endorphin (beta EP), growth hormone (GH) and testosterone (T) and their disruption during 32 h of recovery after treadmill exercise were investigated in 4 geldings. Blood samples were collected from resting horses every 20 min between 0600-1000 and 1500-1900 h, and hourly between 1000-1500 h on 3 consecutive days. Treadmill exercise tests comprising 2 min intervals at 30, 50, and 70% VO2max then to fatigue at 100% VO2max were conducted between 1020-1130 h on Day 2. Blood was collected before, during and 15, 30, 60 and 90 min after exercise. Mean (Cav), peak (Cmax) and total (i.e. integrated) (Ctot) concentrations were calculated for CORT, beta EP and GH during the 20 min sampling sessions, and for CORT, beta EP, GH and T between 1000-1300 h on Days 1-3 (incorporating the samples during exercise on Day 2) and 1300-1900 h on Days 1-3. Cav, Cmax and Ctot for CORT, beta EP, GH and T were greater during exercise and recovery than in the same period on Day 1. Cav and Ctot values for plasma T during the 1300-1900 h period were significantly elevated on Day 2 and compared to Day 1 (P < 0.05), but there were no differences between Days 1 and 3 values for these variables. We concluded that plasma T concentration increases in response to maximal exercise in geldings, as does plasma CORT, beta EP and GH. Furthermore, maximal exercise disrupts basal plasma concentrations of CORT, beta EP and GH for up to 24 h and T for 26-32 h post exercise in geldings, therefore reflecting the minimum recovery periods required before evaluating normal, resting levels of these hormones in horses undergoing training.
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PMID:Maximal exercise transiently disrupts hormonal secretory patterns in standardbred geldings. 1065 22


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