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)

We have examined the influence of electrical stimulation on caffeine-induced tension generation during contracture testing used to diagnose malignant hyperthermia. The cumulative contracture response to caffeine was compared in pairs of morphologically comparable muscle bundles obtained from the same patient. Only one of the two bundles was stimulated electrically during the test. Statistically significant differences in tension were found at caffeine concentrations greater than or equal to 4 mmol litre-1, the tension developed being invariably larger in the unstimulated fascicles. These results suggest that electrical stimulation results in suppression of the dose-dependent, caffeine-induced contracture. This effect could be a result of the potentiation of twitch tension by caffeine, muscle fatigue, or both. Overall, the observed differences did not alter the in vitro diagnosis of malignant hyperthermia.
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PMID:In vitro diagnosis of malignant hyperthermia: influence of electrical stimulation on the contracture response to caffeine. 163 10

The efficacy and safety of oral sumatriptan as a 100-mg dispersible tablet was compared with oral Cafergot (2 mg ergotamine tartrate, 200 mg caffeine) in a multicentre, randomized, double-blind, double-dummy, parallel-group trial. In the trial, 580 patients were treated from 47 investigating centres in nine European countries. Sumatriptan was significantly more effective than Cafergot at reducing the intensity of headache from severe or moderate to mild or none; 66% (145/220) of those treated with sumatriptan improved in this way by 2 h, compared with 48% (118/246) of those treated with Cafergot (p less than 0.001). The onset of headache resolution was more rapid with sumatriptan, whereas recurrence of migraine headache within 48 h was lower with Cafergot. Sumatriptan was also significantly more effective at reducing the incidence of nausea (p less than 0.001), vomiting (p less than 0.01) and photophobia/phonophobia (p less than 0.001) 2 h after treatment, and fewer patients on sumatriptan (24%) than on Cafergot (44%, p less than 0.001) required other medication after 2 h. The overall incidence of patients reporting adverse events was 45% after sumatriptan and 39% after Cafergot; the difference was not significant. The most commonly reported events in the sumatriptan-treated patients were malaise or fatigue and bad taste; these were generally mild and transient. Nausea and/or vomiting, abdominal discomfort, and dizziness or vertigo were reported by a greater proportion of Cafergot-treated patients. It is concluded that oral sumatriptan was well tolerated and is a more effective acute treatment for migraine than Cafergot.
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PMID:A randomized, double-blind comparison of sumatriptan and Cafergot in the acute treatment of migraine. The Multinational Oral Sumatriptan and Cafergot Comparative Study Group. 165 39

Caffeine is one of the most widely consumed drugs in the world. There is a strong belief that caffeine is an ergogenic aid to sports performance. Although much evidence suggests that caffeine may improve endurance exercise performance, questions still remain with regard to its effects on neuromuscular function and brief, high-intensity exercise performance. At the cellular level, caffeine stimulates the central nervous system (CNS), enhances neuromuscular transmission and improves skeletal muscle contractility. The former two effects seem to have facilitative effects on activities which require quick reactions and rapid movements. This is evident in that simple and choice reaction and movement times are reduced following ingestion of small quantities of caffeine. It appears, however, that the caffeine-induced increases in muscle contractility seen in vitro do not translate into improved strength, in vivo. Acute caffeine ingestion does not seem to increase maximal voluntary contractions or maximal power output nor delay fatigue. Thus use of caffeine to improve performance in activities requiring strength and short-term endurance seems unwarrented. Further research is needed before clear conclusions can be draw regarding caffeine's effects on neuromuscular function and high-intensity exercise performance.
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PMID:Caffeine, neuromuscular function and high-intensity exercise performance. 166 90

Drug use among athletes has become a recognised problem in sports. Athletes may use drugs for therapeutic indications, for recreational or social reasons, as ergogenic aids or to mask the presence of other drugs during drug testing. Stimulants were some of the first drugs used and studied as ergogenic aids. Amphetamines may increase time to exhaustion by masking the physiological response to fatigue. Caffeine may improve utilisation of fatty acids as a fuel source thereby sparing muscle glycogen. Cocaine and other sympathomimetic drugs have little or no effect on athletic performance. Anabolic steroids appear to have the potential to increase lean muscle mass and strength under certain conditions. Human growth hormone may also be used for an anabolic effect, but data on this effect are lacking. Erythropoietin may represent a pharmacological alternative to blood doping by increasing red blood cell mass. The use of narcotic analgesics is not necessarily ergogenic but can be harmful if used to allow participation of an athlete with a severe injury. According to the American College of Sports Medicine alcohol does not possess an ergogenic effect. However, it may be used to reduce anxiety or tremor prior to competition. Marijuana does not increase strength. Tobacco products may produce psychomotor effects or control appetite which may be beneficial to some athletes. Other drugs used by athletes include beta-blocking agents, diuretics, and a variety of nutritional supplements. In addition, diuretics and probenecid may be taken to mask drug contents in the urine. Whether the ergogenic effects are real or perceived, the potential for adverse effects exists for all of these drugs. Potential health complications represent a serious risk to an otherwise healthy population. Further research on the long term health risks in athletes taking ergogenic drugs is needed.
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PMID:Enhancement of athletic performance with drugs. An overview. 168 20

1. The purpose of this investigation was to determine if alterations in extracellular calcium (Ca2+) influx by the dihydropyridine derivatives Bay K 8644 and nifedipine affected skeletal muscle fatigue. 2. Tetanic contractions (80 Hz, 100 msec) of frog sartorius muscles were evoked every sec for 3 min. Muscles were fatigued in normal Ringer's solution (NR), in NR containing 1 microM nifedipine of 10 microM Bay K 8644 or in low Ca2+ Ringer's. 3. In each case, the experimental conditions increased the rate and magnitude of fatigue. Rate constants of fatigue obtained during Bay K 8644, nifedipine and low Ca2+ conditions (-.0122 +/- .0016, -.0397 +/- 0022 and 0.0169 +/- .0064 sec-1, respectively) were significantly greater than NR (-.0104 +/- .0006 sec-1, p less than .05). In addition, tetanic forces developed at the end of the stimulation period under the experimental conditions (3.90 +/- 0.81, 1.21 +/- 1.40 and 2.04 +/- 1.10% of initial) were significantly less than NR (7.18 +/- 1.27%, p less than .05). 4. Caffeine contracture forces (10 mM) evoked immediately after stimulation were not significantly different between conditions. 5. These results suggest that alterations in sarcolemmal Ca2+ exchange has some influence on the fatigue process.
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PMID:Dihydropyridine effects on skeletal muscle fatigue. 172 73

Measurements of the intracellular free concentration of Ca2+ ([Ca2+]i) were performed during fatiguing stimulation of intact, single muscle fibers, which were dissected from a mouse foot muscle and loaded with fura-2. Fatigue, which was produced by repeated 100-Hz tetani, generally occurred in three phases. Initially, tension declined rapidly to approximately 90% of the original tension (0.9 Po) and during this period the tetanic [Ca2+]i increased significantly (phase 1). Then followed a lengthy period of almost stable tension production and tetanic [Ca2+]i (phase 2). Finally, both the tetanic [Ca2+]i and tension fell relatively fast (phase 3). The resting [Ca2+]i rose continuously throughout the stimulation period. A 10-s rest period during phase 3 resulted in a significant increase of both tetanic [Ca2+]i and tension, whereas a 10-s pause during phase 2 did not have any marked effect. Application of caffeine under control conditions and early during phase 2 resulted in a substantial increase of the tetanic [Ca2+]i but no marked tension increase, whereas caffeine applied at the end of fatiguing stimulation (tension depressed to approximately 0.3 Po) gave a marked increase of both tetanic [Ca2+]i and tension. The tetanic [Ca2+]i for a given tension was generally higher during fatiguing stimulation than under control conditions. Fatigue developed more rapidly in fibers exposed to cyanide. In these fibers there was no increase of tetanic [Ca2+]i during phase 1 and the increase of the resting [Ca2+]i during fatiguing stimulation was markedly larger. The present results indicate that fatigue produced by repeated tetani is caused by a combination of reduced maximum tension-generating capacity, reduced myofibrillar Ca2+ sensitivity, and reduced Ca2+ release from the sarcoplasmic reticulum. The depression of maximum tension-generating capacity develops early during fatiguing stimulation and it is of greatest importance for the force decline at early stages of fatigue. As fatigue gets more severe, reduced Ca2+ sensitivity and reduced Ca2+ release become quantitatively more important for the tension decline.
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PMID:Changes of myoplasmic calcium concentration during fatigue in single mouse muscle fibers. 176 71

1. Single, intact muscle fibres from the flexor brevis foot muscle of the mouse have been fatigued at 25 degrees C by 350 ms, 70 Hz stimulation trains, initially delivered every 3.8 s and then at stepwise decreasing intervals until tension was down to about 30% of the original (Po). Rested fibres generated a specific force of 372 +/- 8.4 kPa (mean +/- S.E.M., n = 25). 2. Endurance, defined as time to attain 0.5 Po, varied from 2.5 to 24 min, with the majority of fibres falling in the range 4-8 min, corresponding to 70-160 tetani. In all fibres where it was followed, tension recovery after cessation of stimulation was 90% or better. 3. Tetanic force declined in a characteristic way during fatiguing stimulation: initially tension fell to about 0.85 Po during eight to fourteen tetani (phase 1), then followed a long period of nearly steady tension generation (phase 2) and finally there was a rapid force decline (phase 3). 4. Caffeine (15 or 25 mM) caused a slight potentiation of tetanic force in the rested state (4.7 +/- 0.9%, n = 21) and slowed relaxation. No change in resting tension was seen with caffeine at concentrations up to 25 mM. 5. Caffeine (15-25 mM) caused a rapid and dramatic increase in tetanic force when applied to severely fatigued fibres: force output rose from 29.8 +/- 1.5 to 82.5 +/- 1.2% (n = 13) of Po. During phase 2 force potentiation with caffeine was much smaller. 6. A 10 s pause resulted in a large, transient force increase when imposed during phase 3 but had little effect on force production during phase 2. 7. Intracellular acidosis, induced by superfusion with Tyrode solution gassed with 30% CO2 instead of the normal 5% (extracellular pH 6.5 vs. 7.3), resulted in a fall in tetanic tension to about 0.85 Po (n = 7). This depression could to some extent be counteracted by 15 mM-caffeine, which brought tension back to about 0.90 Po. 8. It is concluded that there are at least two mechanisms for force decline during fatiguing stimulation: one which manifests itself early and is likely to be related to cross-bridge function and another representing deficient Ca2+ handling which becomes prominent at a later stage. For severe fatigue (0.3 Po) the latter mechanism is dominant.
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PMID:Force decline due to fatigue and intracellular acidification in isolated fibres from mouse skeletal muscle. 190 15

In fatigued muscles the T-system is swollen; thus the action potential may fail to travel along the T-system or the T-tubule terminal cisternae signal may fail to bring about TC Ca2+ release. This would lead to a decrease in the number of myofibrils activated and in force development, but if fatigue is the result of a generalized process, all the myofibrils would be affected equally leading to a lower activation of all of them. We have investigated this possibility in isolated twitch muscle fibres by giving them repetitive tetanic stimulations until fatigue developed. The behaviour of myofibrils was followed with cinemicrophotography. Before fatigue, no lack of shortening of myofibrils could be found. During fatigue groups of myofibrils became wavy. When exposed to caffeine, the wavy myofibrils disappeared and tension similar to the control developed. The tension-caffeine concentration relationship was shifted to the left after development of fatigue. In low Na+ solution fatigue developed faster and after reintroducing normal Ringer, tension recovered substantially. K-contractures were smaller during fatigue. These results indicate that in this type of fatigue, a step in the EC coupling chain of events is involved in its development.
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PMID:Differential activation of myofibrils during fatigue in phasic skeletal muscle cells. 830 Aug 50

1. Nifedipine (1.5-3.0 x 10(-5) M) potentiated the (sub)tetanic tension during 10-50 Hz indirect or direct stimulation of the rat diaphragm preparation; the twitch contractions were not potentiated. 2. The effect was antagonized in high Ca2+ (5-10 x normal) solutions. 3. A comparison with the twitch potentiators caffeine (1.0 x 10(-3) M), quinine (1.4 x 10(-5) M) and phenytoin (2.0 x 10(-5) M), showed that only phenytoin, a putative Ca-antagonist, caused a nifedipine-like frequency-dependent potentiation, indicating a Ca-antagonistic rather than an unspecific effect. 4. A similar (sub)tetanic potentiation was found in a K(+)-free solution. 5. The slow development of the potentiation during repetitive stimulation is in accordance with an effect on the slow Ca channels known to be present in mammalian skeletal muscle. 6. A delay of the fatigue-inducing accumulation of K+ in the T tubules, which may occur during a nifedipine-induced reduction of a Ca2(+)-stimulated K+ efflux, as well as in a K(+)-free solution, may explain the effect.
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PMID:Selective potentiation of subtetanic and tetanic contractions by the calcium-channel antagonist nifedipine in the rat diaphragm preparation. 205 26

Twenty-two coffee drinkers (three to seven cups per day) underwent repeated double-blind trials to test for caffeine self-administration, withdrawal, and adverse effects. Each trial consisted first of a randomized crossover period of 1 day of decaffeinated coffee and 1 day of caffeinated coffee (100 mg) to assess withdrawal and adverse effects of caffeine. Next, subjects were given 2 days of concurrent access to the two coffees. The relative use of the two coffees was used to assess caffeine self-administration. Reliable caffeine self-administration occurred in three of 10 subjects in study 1 and seven of 12 subjects in study 2. Withdrawal symptoms were headaches, drowsiness, and fatigue. The major adverse effect from self-administration was tremulousness. The occurrence of headaches on substitution of decaffeinated coffee prospectively predicted subsequent self-administration of caffeine. These results indicate that some coffee drinkers exhibit signs of a caffeine dependence, ie, they self-administer coffee for the effects of caffeine, have withdrawal symptoms on cessation, and experience adverse effects.
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PMID:Caffeine self-administration, withdrawal, and adverse effects among coffee drinkers. 206 91


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