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)

Plasma levels of glucose, insulin, the insulin-like growth factor (IGF-I and -II) and IGFBP-1 were determined in four young healthy males performing cycle exercise to fatigue while being fed either placebo (trial C) or glucose polymer solution (trial G). There was a significant decline in glucose and insulin from rest to fatigue in C (P < 0.01 and P < 0.05, respectively), but not in G. IGF-I or IGF-II levels did not change significantly in either of the trials. IGFBP-1 levels increased 12-fold in C (11.4 +/- 1.6 ng/ml at rest to 136.5 +/- 19.7 ng/ml at fatigue P < 0.01), and 5.6-fold in G (11.0 +/- 2.3 ng/ml to 62.2 +/- 15 ng/ml, P < 0.05). In C a significant negative correlation was found between IGFBP-1 and glucose (r = 0.69, P < 0.01) and IGFBP-1 and insulin (r = -0.612, P < 0.05) in C, but not in G. These results suggest that during prolonged exercise factors other than insulin or glucose may regulate IGFBP-1 and that IGFBP-1 may serve a role other than to prevent the hypoglycaemic action of the IGFs.
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PMID:Changes in circulating insulin-like growth factor-binding protein-1 (IGFBP-1) during prolonged exercise: effect of carbohydrate feeding. 752 18

In order to test the possibility for rapid responses of blood hormone levels in short-term supramaximal exercises, serum concentrations of corticotropin (ACTH), cortisol (C), total testosterone (tT), free testosterone (fT), growth hormone (GH), thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3), prolactin (PRL), insulin-like growth factor (IGF-I), and sex hormone-binding globulin (SHBG) were determined by RIA procedures in blood samples obtained before and immediately after a 60-s period of consecutive vertical jumps (Bosco test). The study subjects were 16 Italian professional soccer players. Immediately after exercise, significant increases (p < 0.05) were found in the concentrations of ACTH (by 39%), C (by 14%), TSH (by 20%), fT3 (by 28%), fT4 (by 30%), tT (by 12%), fT (by 13%), and SHBG (by 21%). Significant changes were not detected in the blood levels of GH, IGF-I and PRL. Most pronounced testosterone responses were typical for persons of high jumping performance (the increase of serum tT correlated with average power output, r = 0.61 and jumping height, r = 0.66). The larger the drop in power output during 60-s jumping, the higher was the thyroid response: the difference in jumping height between the first and last 15-s period correlated with increases in TSH (r = 0.52) and in fT4, (r = 0.55). In conclusion, the obtained results indicate that in intense exercise, causing the rapid development of fatigue, rapid increases in serum levels of hormones of the pituitary-adrenocortical, pituitary-gonadal and pituitary-thyroid systems occur.
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PMID:Hormonal responses in strenuous jumping effort. 874 23

Octreotide is a somatostatin analogue: a long-acting release (LAR) formulation of octreotide is designed for once-monthly intramuscular administration. As with native somatostatin, octreotide LAR exerts potent inhibitory effects on the secretion of growth hormone and on various peptides of the gastroenteropancreatic endocrine system. When patients with acromegaly who show a positive response to treatment with subcutaneous octreotide 300 to 600 micrograms/day are switched to octreotide LAR 20 or 30 mg, the resulting decrease in growth hormone levels is stable and sustained. Reductions in growth hormone levels to < 5 micrograms/L for about 4 weeks are seen in 86 to 100% of patients, to < 2 to 2.5 micrograms/L in 39 to 75% and to < 1 microgram/L in 24 to 40%. Levels of insulin-like growth factor-1 (IGF-1) decrease in parallel and are often normalised with repeated drug treatment. There is no evidence of tachyphylaxis with long term therapy (up to 34 months). Treatment with octreotide LAR improves facial appearance and soft tissue thickening, and eliminates or reduces the incidence of symptoms such as headache, fatigue, arthralgia and excessive perspiration. Tumour shrinkage has been noted in some, but not all, patients receiving octreotide LAR, although this has not been widely evaluated in clinical studies. Overall, octreotide LAR is well tolerated, and the mild to moderate gastrointestinal events experienced by up to 50% of patients are of short duration and often subside with continued drug administration. The incidence of gallbladder abnormalities (sediment, sludge, microlithiasis and gallstones) increases in patients receiving long term therapy with subcutaneous octreotide, although most patients remain asymptomatic. The incidence of gallbladder abnormalities in patients receiving octreotide LAR compares favourably with that during subcutaneous administration. Glycaemic control is not usually altered during octreotide LAR treatment. In summary, octreotide continues to be the principal pharmacological option for most patients with acromegaly. Octreotide LAR offers the convenience of once-monthly administration compared with daily subcutaneous drug administration. In addition, the good efficacy and tolerability profile of octreotide LAR should enhance patient compliance and acceptability of octreotide therapy and contribute to an improvement in patient quality of life.
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PMID:Octreotide long-acting release (LAR). A review of its pharmacological properties and therapeutic use in the management of acromegaly. 909 66

Previous studies have demonstrated that full recovery from weight loss may take months or years. The present investigation examined short-term recovery (5 wks "post") of physical performance (muscular strength, muscular power, vertical jump), body composition, metabolic hormones (testosterone, luteinizing hormone, sex hormone binding globulin, insulin-like growth factor-1, triiodothyronine, thyroxine, thyroid binding globulin, and thyroid-stimulating hormone) and metabolic markers (transferrin, ferritin, prealbumin, glycerol, nonesterified fatty acids, high-density lipoproteins, and lactate) in 10 healthy young men after an 8-week Army course with an energy deficit (1000 kcal/d) and loss of body mass (-12%). Subjects ate ad libitum after the course ended ("post"). Body composition was determined by dual-energy X-ray absorptiometry; strength from a simulated power clean, power from body mass and jump height, and metabolic hormones were measured in morning-fasted blood by radioimmunoassay. With the exception of transferrin and glycerol, all study parameters were significantly (p<.05) altered by the training course. At 5 weeks post fat-free mass along with all physical performance measures returned to initial levels; however, fat mass had significantly (p<.05) increased over initial levels. Also, with the exception of lactate, all measured hormones and markers were close to initial levels and within normal ranges. Reported complications during recovery included sleep irregularities, diarrhea, loss of motivation and feelings of fatigue. While the long range effect of this energy deprivation experience is uncertain, these data do suggest that severe weight loss does not result in lasting alterations of the contractile and metabolic properties of skeletal muscle in young, lean, healthy men.
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PMID:Physical performance and metabolic recovery among lean, healthy men following a prolonged energy deficit. 929 70

Symptomatic treatment of multiple sclerosis (MS) includes a diverse range of drugs intended to relieve the specific symptoms with which a patient may present at a particular point in the progression of the disease. These drugs, not specifically designed for the treatment of MS, may include antispastic agents (e.g. baclofen), drugs to reduce tremor (e.g. clonazepam), anticholinergics (e.g. oxybutynin) which relieve urinary symptoms, anti-epileptics (e.g. carbamazepine) to control neuralgia, stimulants to reduce fatigue (e.g. amantadine), and antidepressants (e.g. fluoxetine) to treat depression. The treatment of acute relapses or exacerbations is dominated by corticosteroids such as methylprednisolone. The most active area of current investigation is the development of drugs which will inhibit the progression of the disease process itself, and in this category the beta- and alpha-interferons are the most effective drugs currently available, although many new treatments are currently in trials, including immunoglobulin, copolymer-1. bovine myelin, T-cell receptor (TCR) peptide vaccines, platelet activating factor (PAF) antagonists, matrix metallo-proteinase inhibitors, campath-1, and insulin-like growth factor (IGF).
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PMID:Recent developments in drug therapy for multiple sclerosis. 1033 20

Fibromyalgia (FM) is a painful syndrome of nonarticular origin, characterized by fatigue and widespread musculoskeletal pain, tiredness, and sleep disturbances, without any other objective findings on examination. Interestingly, some of the clinical features of FM resemble the ones described in the adult GH-deficiency syndrome. Furthermore, insulin-like growth factor (IGF)-1 levels are frequently reduced in patients with FM. To gain further insight into the mechanisms leading to dysregulation of the GH-IGF-1 axis in these patients, we assessed 24-h spontaneous GH secretion, GH responses to GHRH, and IGF-1 and IGF binding protein (BP)-3 levels before and after 4 days treatment with human (h)GH. We found that, in comparison with controls, patients with FM exhibited a marked decrease in spontaneous GH secretion as assessed by mean GH secretion (2.5 +/- 0.4 microg/L in controls vs. 1.2 +/- 0.1 microg/L in FM, P < 0.05), pulse height (4.7 +/- 0.8 microg/L in controls vs. 2.5 +/- 0.3 microg/L in FM, P < 0.05), and pulse area (4.7 +/- 1 min/mg x L in controls vs. 2.3 +/- 0.3 min/mg x L in FM, P < 0.05). In contrast, GH responses to GHRH (100 microg, i.v.) were similar in controls (mean peak, 13.5 +/- 2.5 microg/L) and in patients with FM (12.2 +/- 3 microg/L). Finally, treatment with hGH (2 IU, s.c. daily), over 4 days, led to a clear-cut increase in plasma IGF-1 and IGFBP-3 levels in patients with FM. In conclusion, our data show that patients with FM exhibited a marked decrease in spontaneous GH secretion, but normal pituitary responsiveness to exogenously administered GHRH, thus suggesting the existence of an alteration at the hypothalamic level in the neuroendocrine control of GH in these patients. Furthermore, our finding of increased IGF-1 and IGFBP-3 levels after GH treatment, over 4 days, opens up the possibility of testing the therapeutic potential of hGH in patients with FM.
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PMID:The growth hormone (GH)-releasing hormone-GH-insulin-like growth factor-1 axis in patients with fibromyalgia syndrome. 1048 13

In any given population of free-living individuals 65 years of age and older, a substantial proportion (in the range of 6% to 25%) suffers from many of the elements of the syndrome of frailty. Although the syndrome is complex and still lacks a standard definition, there is a growing consensus about the signs and symptoms as well as the pattern of biological correlates that characterize this disorder. Patients who are afflicted with frailty typically exhibit loss of muscle strength, fatigue easily, are physically inactive, and have a slow-and often unsteady-gait, with an increased risk (and fear) of falling. They are likely to have a poor appetite and to have undergone a recent, unintentional loss of weight. Frail individuals are more likely than the nonfrail to experience impaired cognition and depression. They die sooner. Frailty, of course, is frequently complicated by a variety of coexistent illnesses. Among the biological correlates of frailty are sarcopenia (now readily measurable by dual-energy x-ray absorptiometry [DXA]), osteopenia (with an increased susceptibility to fracture), and activation of the inflammatory and coagulation systems, with a rise in inflammatory cytokines and several markers of coagulopathy. Age-dependent changes in a number of hormones also appear to promote the development of frailty in the elderly, particularly via their effects on muscle mass and strength, bone density, and by contributing to activation of the catabolic cytokines. In particular, serum levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) decline progressively during aging, and an association between reduction in the levels of these hormones and the involution of advancing age has been proposed. It is not yet known whether, in comparison with their nonfrail counterparts, frail individuals consistently manifest larger reductions in GH and IGF-1 (and other anabolic hormones). More research is needed before it will be known whether the benefits of administering GH to the frail elderly will outweigh the disadvantages. The poor appetite and weight loss that occur in many frail individuals are likely to be accompanied by a degree of visceral protein depletion (with its attendant morbidity), which can be estimated by making serial measurements of indicators of visceral protein status such as transthyretin (TTR), retinol-binding protein (RBP), and albumin. One characteristic of the frailty syndrome that distinguishes it from the effects of aging per se is the potential reversibility of many of its features. Progressive resistance training is feasible for many elderly individuals-even the oldest old-and, by increasing muscle mass and strength, can ameliorate or reverse important aspects of physical frailty. To the extent that visceral protein depletion has been caused by an inadequate intake of calories and protein, consumption of a more adequate diet can result in betterment of the frail patient's nutritional status, as determined by clinical improvement and favorable changes in TTR, RBP, and albumin.
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PMID:Frailty in the elderly: contributions of sarcopenia and visceral protein depletion. 1457 59

Octreotide long-acting release (LAR) is a somatostatin analogue designed for once monthly intramuscular injection. As with endogenous somatostatin, octreotide LAR inhibits secretion of growth hormone (GH) as well as various other peptide hormones. In the treatment of acromegaly, octreotide LAR effectively controlled the secretion of GH and insulin-like growth factor-1 (IGF-1) in about 55-70% of patients (n > 100) who had previously been treated with somatostatin analogues, a similar degree of control to that observed with subcutaneous octreotide and lanreotide slow release (SR). Progressive control of serum levels of GH and IGF-1 was achieved with octreotide LAR in clinical studies of up to 4 years' duration. In addition, primary therapy with octreotide LAR provided effective control of GH and IGF-1 secretion, particularly in patients with a pretreatment GH level <20 microg/L. The percentage of patients achieving a target serum GH level of <2-2.5 micro g/L or normal IGF-1 levels was significantly greater with octreotide LAR 10, 20 or 30 mg every 28 days than with lanreotide SR 30 mg every 7-14 days in a large (n = 125) sequential, 6-month study, but was not significantly different between treatment groups in a small, randomised, nonblind, parallel group study of previously untreated patients. The volume of pituitary tumour shrinkage achieved with octreotide LAR or lanreotide SR was also similar ( approximate, equals 33% after 24 months). Acromegaly symptoms, such as headache, increased perspiration, paraesthesia, fatigue and osteoarthralgia were improved during treatment with octreotide LAR or lanreotide SR. Overall, octreotide LAR is generally well tolerated by most patients. The incidence of gastrointestinal symptoms is about 30% but, in most cases, events are transient and mild to moderate. Gallbladder abnormalities (sediment, sludge, microlithiasis and gallstones) can occur, but only 1% have become symptomatic to date. The prevalence of biliary abnormalities did not change after switching from subcutaneous octreotide, or from lanreotide SR, to octreotide LAR. Glucose metabolism can be affected by octreotide LAR in some patients; about 15% become hyperglycaemic, usually mild in severity. In summary, octreotide LAR controls GH and IGF-1 secretion in about 55-70% of patients with acromegaly. Octreotide LAR is administered intramuscularly every 28 days, offering improved patient compliance and convenience over three-times-daily subcutaneous octreotide. Long-term therapy provides progressive control of serum GH and IGF-1 levels, and is generally well tolerated by most patients. Thus, for the medical management of acromegaly, octreotide LAR is an effective, well tolerated and convenient treatment option.
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PMID:Octreotide long-acting release (LAR): a review of its use in the management of acromegaly. 1460 59

Some of the physiological changes associated with the taper and their relationship with athletic performance are now known. Since the 1980s a number of studies have examined various physiological responses associated with the cardiorespiratory, metabolic, hormonal, neuromuscular and immunological systems during the pre-event taper across a number of sports. Changes in the cardiorespiratory system may include an increase in maximal oxygen uptake, but this is not a necessary prerequisite for taper-induced gains in performance. Oxygen uptake at a given submaximal exercise intensity can decrease during the taper, but this response is more likely to occur in less-skilled athletes. Resting, maximal and submaximal heart rates do not change, unless athletes show clear signs of overreaching before the taper. Blood pressure, cardiac dimensions and ventilatory function are generally stable, but submaximal ventilation may decrease. Possible haematological changes include increased blood and red cell volume, haemoglobin, haematocrit, reticulocytes and haptoglobin, and decreased red cell distribution width. These changes in the taper suggest a positive balance between haemolysis and erythropoiesis, likely to contribute to performance gains. Metabolic changes during the taper include: a reduced daily energy expenditure; slightly reduced or stable respiratory exchange ratio; increased peak blood lactate concentration; and decreased or unchanged blood lactate at submaximal intensities. Blood ammonia concentrations show inconsistent trends, muscle glycogen concentration increases progressively and calcium retention mechanisms seem to be triggered during the taper. Reduced blood creatine kinase concentrations suggest recovery from training stress and muscle damage, but other biochemical markers of training stress and performance capacity are largely unaffected by the taper. Hormonal markers such as testosterone, cortisol, testosterone : cortisol ratio, 24-hour urinary cortisol : cortisone ratio, plasma and urinary catecholamines, growth hormone and insulin-like growth factor-1 are sometimes affected and changes can correlate with changes in an athlete's performance capacity. From a neuromuscular perspective, the taper usually results in markedly increased muscular strength and power, often associated with performance gains at the muscular and whole body level. Oxidative enzyme activities can increase, along with positive changes in single muscle fibre size, metabolic properties and contractile properties. Limited research on the influence of the taper on athletes' immune status indicates that small changes in immune cells, immunoglobulins and cytokines are unlikely to compromise overall immunological protection. The pre-event taper may also be characterised by psychological changes in the athlete, including a reduction in total mood disturbance and somatic complaints, improved somatic relaxation and self-assessed physical conditioning scores, reduced perception of effort and improved quality of sleep. These changes are often associated with improved post-taper performances. Mathematical models indicate that the physiological changes associated with the taper are the result of a restoration of previously impaired physiological capacities (fatigue and adaptation model), and the capacity to tolerate training and respond effectively to training undertaken during the taper (variable dose-response model). Finally, it is important to note that some or all of the described physiological and psychological changes associated with the taper occur simultaneously, which underpins the integrative nature of relationships between these changes and performance enhancement.
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PMID:Physiological changes associated with the pre-event taper in athletes. 1548 4

Studies in vitro show important interactions among vitamin A, lactoferrin, and insulin-like growth factor (IGF) binding proteins (IGFBP) and, thus, the IGF system. As a consequence, mammary gland epithelial cell proliferation and apoptosis during the bovine dry period and potential milk yield may be affected. We have studied effects of feeding vitamin A (550,000 IU/ d) that exceed daily requirements about 8-fold for up to 2 mo to dairy cows during the dry period on concentrations of retinol and its metabolites in plasma and milk, milk lactoferrin, plasma and milk IGF-I and IGFBP-3, lactoferrin and IGF-I mRNA levels in mammary gland tissue, mammary gland apoptosis, and 100-d milk yield in the ensuing lactation. In the group supplemented with vitamin A, the peripartal decrease of plasma retinol was delayed and attenuated, and colostral retinol plus retinylester concentration was enhanced, but colostral beta-carotene concentration decreased. The retinoic acid isomer 9,13-dicis retinoic acid that coeluted with 13-cis retinoic acid, was the predominant circulating retinoic acid and was higher in GrA than the control group. Plasma IGFBP-3 concentrations were positively correlated with plasma retinol concentrations (r = 0.51), but there were no group differences. Numbers of apoptotic epithelial cells in mammary epithelium were higher at drying off and parturition than in the middle of the dry period, coinciding with high concentrations of IGF-I and lactoferrin in mammary secretions. At parturition, numbers of apoptotic cells in mammary gland biopsies in cows supplemented with vitamin A were higher than in control cows. In conclusion, supplementation of dairy cows during the dry period with high amounts of vitamin A did not significantly modify concentrations of lactoferrin, IGFBP-3, and IGF-I in plasma and in mammary secretions, but slightly decreased energy-corrected 100-d milk yield and milk fat yield, possibly because of enhanced apoptic rates of mammary cells.
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PMID:Effects of an enhanced vitamin A intake during the dry period on retinoids, lactoferrin, IGF system, mammary gland epithelial cell apoptosis, and subsequent lactation in dairy cows. 1582 72


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