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)

Sarcoplasmic reticulum (SR) Ca(2+)-release channel function is modified by ligands that are generated during about of exercise. We have examined the effects of lactate on Ca(2+)- and caffeine-stimulated Ca2+ release, [3H]ryanodine binding, and single Ca(2+)-release channel activity of SR isolated from rabbit white skeletal muscle. Lactate, at concentrations from 10 to 30 mM, inhibited Ca(2+)- and caffeine-stimulated nodine binding to and inhibited Ca(2+)- and caffeine-stimulated [3H]ryanodine binding to and inhibited Ca(2+)- and caffeine-stimulated Ca2+ release from SR vesicles. Lactate also inhibited caffeine activation of single-channel activity in bilayer reconstitution experiments. These findings suggest that intense muscle activity, which generates high concentrations of lactate, will disrupt excitation-contraction coupling. This may lead to decreases in Ca2+ transients promoting a decline in tension development and contribute to muscle fatigue.
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PMID:Lactate inhibits Ca(2+) -activated Ca(2+)-channel activity from skeletal muscle sarcoplasmic reticulum. 904 23

Currently available as a dietary supplement, the pineal hormone melatonin is portrayed by the media as a formidable weapon against disease and aging. Accordingly, primary health care providers should be cognizant of which of its proposed uses are supported by biomedical research and which are, as yet, unproven. Melatonin entrains circadian rhythms and, thus, can treat jet lag, delayed sleep phase syndrome, and sleep disorders in the blind and in some neurologically impaired children. By virtue of its hypnotic effect, melatonin can mitigate insomnia in the elderly. Reductions in melatonin secretion have been associated with many disorders, including cardiovascular disease, Alzheimer's, diabetes, SIDS, and aging; however, melatonin's role in their etiology and/or pathophysiology is unproven. Preliminary studies suggest a possible adjuvant therapeutic role for melatonin in cancer therapy. Melatonin secretion is reduced by alcohol, caffeine, and some commonly prescribed drugs. Since tolerance, fatigue, and other side effects have been reported, melatonin use on consecutive nights should be avoided and only the lowest effective hypnotic dose should be taken.
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PMID:Melatonin: media hype or therapeutic breakthrough? 905 17

Dexfenfluramine increases serotonergic activity by stimulating serotonin (5-hydroxytryptamine; 5-HT) release into brain synapses, inhibiting its reuptake into presynaptic neurons and by directly stimulating postsynaptic serotonin receptors. On the basis of the serotonin hypothesis of appetite control, these actions would be expected to reduce appetite and, consequently, bodyweight. Studies conducted in animals and in overweight patients with and without associated disorders have confirmed the weight-reducing efficacy and good tolerability of dexfenfluramine. In 3-month clinical studies in obese patients, weight reductions with dexfenfluramine 15mg twice daily combined with dietary support were significantly higher than those achieved with placebo and similar to those with ephedrine/caffeine 20/20mg 3 times daily, sibutramine 10mg once daily and fluoxetine 60 mg/day. Furthermore, dexfenfluramine recipients with non-insulin-dependent diabetes mellitus, hyperlipidaemia or hypertension consistently show improvements in glycaemic control, blood lipid profiles and blood pressure. 12-month trial results indicate that most weight loss occurs in the initial 6 months and appears to be maintained for a further 6 months. Weight regain after withdrawal of treatment in 12-month studies demonstrates that dexfenfluramine is effective in maintaining a stable bodyweight at a lower level than placebo and in limiting food intake over this time period. Commonly reported adverse events with dexfenfluramine include diarrhoea, tiredness, dry mouth and somnolence; these symptoms are generally mild and transient. Approximately 7 and 10% of dexfenfluramine recipients in short and long term studies withdrew because of adverse events. Dexfenfluramine was better tolerated than ephedrine/caffeine and fluoxetine in short term studies. Obesity is a chronic condition that is accompanied by a number of metabolic complications. It is a significant health problem in developed countries, and as a major risk factor for many chronic diseases, including diabetes and cardiovascular disease, the economic burden of this condition is considerable. As with other chronic conditions, there is a role for pharmacological intervention in patients with severe obesity. However, drugs should be considered as only one component of a weight-control programme, since additional lifestyle modification is required to maintain weight loss. The promising data on the long term efficacy and tolerability of dexfenfluramine as well as its favourable effects on risk factors associated with obesity requires confirmation in long term studies. In the meantime, dexfenfluramine should be considered a valuable adjunct to a reduced-calorie diet in the management of severe obesity, particularly in patients with associated disorders and those unsuccessful with conventional weight loss measures. Available data support the use of the drug for up to 1 year to maintain weight loss and thus dexfenfluramine should be considered for long term administration.
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PMID:Dexfenfluramine. An updated review of its therapeutic use in the management of obesity. 911 19

The present study examined the effects of caffeine, as typically ingested through coffee, on ambulatory systolic and diastolic blood pressure (BP), heart rate, and mood. Normotensive coffee drinkers wore a BP monitor for two 24-hr periods, consuming decaffeinated coffee. Each cup was supplemented with 125 mg caffeine or cornstarch. Systolic and diastolic BPs were elevated on the day caffeine was consumed (maximum, 3.6 and 5.6 mm Hg, respectively), most notably shortly after ingestion. Heart rate was higher overnight following caffeine consumption. Negative Affectivity was also increased by caffeine, but Positive Affectivity and tiredness were unaffected.
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PMID:The effects of caffeine on ambulatory blood pressure, heart rate, and mood in coffee drinkers. 913 5

Eight exclusive cola drinkers in Experiment 1 (mean caffeine intake = 157 +/- 74 mg/day) and 16 drinkers of both cola and coffee in Experiment 2 (mean caffeine intake = 579 +/- 201 mg/day) underwent 6 independent, double-blind weekly trials. Each trial began with a randomized cross-over sampling period of 1 day of access to noncaffeinated cola and 1 day of access to caffeinated (33 mg/8 oz) cola. During the subsequent 1- or 2-day test period, participants had unlimited concurrent access to the 2 colas. Reliable caffeine self-administration occurred in 2 of 8 participants in Experiment 1 and in 4 of 16 participants in Experiment 2. Self-reported drowsiness, fatigue, and headache were higher when participants received only placebo colas in Experiment 2, but not Experiment 1. Caffeine self-administration via cola occurs both among people whose primary source of caffeine is cola and among those whose primary source of caffeine is coffee.
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PMID:Caffeine self-administration in humans: 1. Efficacy of cola vehicle. 926 77

This investigation tested the notion that fatiguing stimulation induces intrinsic changes in the contractile apparatus and sarcoplasmic reticulum (SR) and that these changes are initiated by elevated intracellular Ca2+ concentration ([Ca2+]i). Immediately after stimulation of frog semitendinosus muscle, contractile apparatus and SR function were measured. Despite a large decline in tetanic force (Po), maximal Ca2+-activated force (Fmax) of the contractile apparatus was not significantly altered. However, Ca2+ sensitivity was increased. In conjunction, the rate constant of Ca2+ uptake by the SR was diminished, and the caffeine sensitivity of Ca2+ release was decreased. During recovery, Po, contractile apparatus, and SR function each returned to near-initial levels. Exposure of skinned fibers to 0.5 microM free Ca2+ for 5 min depressed both Fmax and Ca2+ sensitivity of the contractile apparatus. In addition, caffeine sensitivity of Ca2+ release was diminished. Results suggest that fatigue induces intrinsic alterations in contractile apparatus and SR function. Changes in contractile apparatus function do not appear to be mediated by increased [Ca2+]i. However, a portion of the change in SR Ca2+ release seems to be due to elevated [Ca2+]i.
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PMID:Contractile apparatus and sarcoplasmic reticulum function: effects of fatigue, recovery, and elevated Ca2+. 926 39

The effects of short-term deprivation of caffeinated beverages on mood, withdrawal symptoms, and psychomotor performance were studied in habitual coffee drinkers. Twenty-four male and female coffee drinkers were tested at midday (1130-1330 h) under two conditions. On one day they consumed caffeinated beverages ad lib prior to testing, and on the other they remained caffeine abstinent. The order of treatments was counterbalanced. Mood and withdrawal symptom reports were collected by questionnaires. Psychomotor performance was tested with a computerized test battery. Caffeinated-beverage deprivation was associated with decreased vigor and increased fatigue and with symptoms including headache. No changes in psychomotor performance were observed. Even short periods of caffeinated-beverage deprivation, equivalent in length to missing regular morning coffee, can produce noticeable unpleasant caffeine-withdrawal symptoms by the middle of the day. These symptoms may be a common side effect of habitual caffeinated beverage consumption.
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PMID:Effects of brief caffeinated-beverage deprivation on mood, symptoms, and psychomotor performance. 926 92

Increasing extracellular K+ concentration ([K+]o) from 4 to 7-14 mM reduced both tetanic force and resting membrane potential (Em) in isolated slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles of the mouse. The tetanic force-[K+]o relationships showed a greater force loss over 8-11 mM [K+]o in soleus than EDL, mainly because the Em was 2-3 mV less negative at each [K+]o in soleus. The tetanic force-resting Em relationships show that force was reduced in two phases: phase 1 (Em < -60 mV), a 20% force decline in which the relationships superimposed in soleus and EDL, and phase 2 (Em -60 to -55 mV), a marked force decline that was steeper in EDL than soleus. Additionally in phase 2, longer stimulation pulses restored tetanic force; the twitch force-stimulation strength relationship was shifted toward higher voltages; caffeine, a myoplasmic Ca2+ concentration elevator, increased maximum force; and twitch force fell abruptly. We suggest that 1) the K(+)-depressed force is due to reduced Ca2+ release resulting from an altered action potential profile (phase 1) and inexcitable fibers due to an increased action potential threshold (phase 2), and 2) K+ contributes to fatigue in both fast- and slow-twitch muscle when it causes depolarization to about -60 mV.
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PMID:Different effects of raised [K+]o on membrane potential and contraction in mouse fast- and slow-twitch muscle. 927 57

1. The effect of a beta-adrenoceptor antagonist, propranolol, was investigated on excitation-contraction coupling in small, intact bundles of soleus muscle fibres from the rat. 2. (+/-)-Propranolol significantly inhibited twitch and tetanic tension with IC50 values of 6.7 microM and 3.5 microM, respectively. 3. (+)-Propranolol (which has 100 times less beta-blocking activity than the (+/-) form) was approximately one third as effective as the (+/-) form at inhibiting isometric tension. 4. (+/-)-Propranolol (20 microM) had no significant effect on the amplitude of caffeine contractures, suggesting that it did not directly inhibit Ca2+ release from the sarcoplasmic reticulum. 5. The resting membrane potential measured after 15 min perfusion with 20 microM (+/-)-propranolol was not significantly different from control. However, this concentration of (+/-)-propranolol significantly reduced both the peak amplitude and the maximum rate of rise of the action potential. Both effects were only partially reversible after extensive washing. 6. (+/-)-Propranolol perfusion caused a modest reduction in the amplitude of sub-maximal K+ contractures at concentrations (5 microM) that markedly depressed tetanic tension. 7. The results indicate that (+/-)-propranolol can decrease isometric tension independently of beta-receptor occupation by (i) reducing the amplitude and rate of rise of the action potential and (ii) by directly inhibiting excitation-contraction coupling. The relatively low IC50 for the 'membrane-stabilizing' action of propranolol on tetanic tension (3.5 microM), combined with the ability of the drug to accumulate gradually in biological membranes, may contribute to a peripheral component of the tremorolytic and fatigue-inducing actions of propranolol on skeletal muscle.
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PMID:Inhibitory effects of (+/-)-propranolol on excitation-contraction coupling in isolated soleus muscles of the rat. 935 2

The effects of short-term caffeine deprivation on mood, withdrawal symptoms and psychomotor performance were studied in habitual coffee drinkers. Thirty-one male and female coffee drinkers were tested twice at midday (1130 to 1330 h) 4 h after double-blind administration of 250 mg of caffeine or placebo. Mood and withdrawal symptoms reports were collected by questionnaires. Psychomotor performance was tested with a brief computerized test battery, and causal blood pressure was measured. Caffeine deprivation was associated with decreased vigor and increased fatigue and with symptoms including sleepiness and yawning. Blood pressure was lower by 5-6 mm Hg. No changes in psychomotor performance were observed. Even short periods of caffeine deprivation, equivalent in length to missing regular morning coffee, can produce noticeable unpleasant caffeine withdrawal symptoms in habitual coffee drinkers. Such symptoms may be common side effects of habitual caffeine consumption that contribute to the maintenance of this behavior.
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PMID:Caffeine withdrawal symptoms following brief caffeine deprivation. 940 12


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