Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report describes how the resistance to fatigue of a muscle fibre relates to the fibre's most important ATP-producing and ATP-consuming reactions. Twelve intact single muscle fibres were dissected from lumbrical muscles of Xenopus laevis. Their resistance to fatigue induced by repeated tetanic stimulation was determined, as well as their succinate dehydrogenase activity and calcium-stimulated myofibrillar ATPase activity. The enzyme activities were determined by means of quantitative histochemistry. It was found that resistance to fatigue correlates with succinate dehydrogenase activity (r = 0.83) and with myofibrillar ATPase activity (r = -0.74). The highest correlation was found between resistance to fatigue and the ratio of succinate dehydrogenase to myofibrillar ATPase activity (r = 0.93). It is concluded that muscular fatigue is closely related to cellular energetics.
 ...
PMID:Resistance to fatigue of single muscle fibres from Xenopus related to succinate dehydrogenase and myofibrillar ATPase activities. 183 77

1. Single muscle fibres were dissected from the toe muscles of Xenopus laevis and microinjected with Fura-2 to measure myoplasmic calcium concentration ([Ca2+]i). Injected fibres were illuminated at 340 and 380 nm and the ratio of the resulting fluorescence at 505 nm (the Fura-2 ratio) was taken as a measure of [Ca2+]i. Fibres were fatigued at 21 degrees C by repeated tetani until developed tension had fallen to 50% of control. 2. Tetanic tension declined monotonically during fatiguing stimulation, whereas the tetanic Fura-2 ratio first increased and then declined. At the 10th tetanus, tension was 87% of control whereas the Fura-2 ratio was 106% of control. At the end of fatiguing stimulation, where tension was around 50% of control, the tetanic Fura-2 ratio was reduced to 71%. The rate of decline of both tension and the Fura-2 ratio after a tetanus slowed during fatigue. During recovery, the tension and the tetanic Fura-2 ratio recovered in parallel. 3. The resting Fura-2 ratio increased throughout fatigue reaching 237% of control when tension had declined to 50%. There was a rapid phase of recovery, complete within 1 min, by which time the resting Fura-2 ratio was 198% of control. Subsequent recovery was slower and took 20-30 min to reach a stable level which was 121% of control. 4. The resting Fura-2 ratio towards the end of fatiguing stimulation was greater than the tetanic Fura-2 ratio in the early part of recovery although there was no detectable increase of resting tension during fatiguing stimulation. This observation suggests that the Ca2+ sensitivity of the contractile proteins was reduced at the end of fatiguing stimulation. 5. Plots of the tetanic tension against tetanic Fura-2 ratios throughout fatiguing stimulation and recovery also suggested that Ca2+ sensitivity was reduced during fatiguing stimulation when compared to recovery. 6. The increases in resting [Ca2+]i caused by raised [K+]o (from 2.5 to 10 mM) and/or by application of 15% CO2 were much less than those produced by fatiguing stimulation. Much of the elevated [Ca2+]i in fatigue could be reversed by application of dantrolene (25 microM). 7. The results suggest that both reduced tetanic [Ca2+]i and reduced Ca2+ sensitivity contribute to the decline of tension during fatigue.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Changes in tetanic and resting [Ca2+]i during fatigue and recovery of single muscle fibres from Xenopus laevis. 184 42

It has been postulated that the staircase response of skeletal muscle is effected by Ca2+-dependent phosphorylation of myosin light chains. Dantrolene inhibits calcium release from the sarcoplasmic reticulum, so treatment with dantrolene should prolong the time required to reach the peak of the staircase response. Furthermore, since it has been postulated that Ca2+ release is attenuated by fatigue, there should be similarities between the staircase of fatigued muscle and staircase in the presence of dantrolene. The left gastrocnemius muscle of anesthetized rats was isolated in situ and connected to an isometric transducer. In the control condition, developed tension increased for approximately 10 s with repetitive stimulation at 10 Hz. The time to reach the peak of staircase was prolonged after a 5 min period of stimulation at 10 Hz or after injection of dantrolene sodium (0.8 mg.kg-1 IV). Other similarities between the dantrolene treated group and the fatigue group include the following: contraction time was shorter in fatigue (12.8 +/- 0.8 ms) and with dantrolene (14.7 +/- 1.3 ms) than in the controls (16.4 +/- 1 ms), and half-relaxation time increased from 5 s (10.8 +/- 9 ms) to 15 s (13.8 +/- 0.8 ms) of staircase in the control but did not increase at this time in the dantrolene or fatigue groups. This study demonstrates that both fatigue and a reduction in Ca2+ release from sarcoplasmic reticulum will prolong the time required to reach the peak of staircase.
 ...
PMID:Skeletal muscle staircase response with fatigue or dantrolene sodium. 184 39

Prolonged activation of skeletal muscle leads to a decline of force production known as fatigue. In this review we outline the ionic and metabolic changes that occur in muscle during prolonged activity and focus on how these changes might lead to reduced force. We discuss two distinct types of fatigue: fatigue due to continuous high-frequency stimulation and fatigue due to repeated tetanic stimulation. The causes of force decline are considered under three categories: 1) reduced Ca2+ release from the sarcoplasmic reticulum, 2) reduced myofibrillar Ca2+ sensitivity, and 3) reduced maximum Ca(2+)-activated tension. Reduced Ca2+ release can be due to impaired action potential propagation in the T tubules, and this is a principal cause of the tension decline with continuous tetanic stimulation. Another type of failing Ca2+ release, which is homogeneous across the fibers, is prominent with repeated tetanic stimulation; the underlying mechanisms of this reduction are not fully understood, although several possibilities emerge. Changes in intracellular metabolites, particularly increased concentration of Pi and reduced pH, lead to reduced Ca2+ sensitivity and reduced maximum tension, which make an important contribution to the force decline, especially with repeated tetanic stimulation.
 ...
PMID:Cellular mechanisms of fatigue in skeletal muscle. 187 66

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.
 ...
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.
 ...
PMID:Differential activation of myofibrils during fatigue in phasic skeletal muscle cells. 830 Aug 50

Hypertension may influence the atherosclerotic process of large arteries via pressure and shear forces. The pressure force dilates and stiffens arteries because of the non-linear elastic behaviour of arterial walls. This partly explains the increased diameter and decreased compliance of the brachial artery in hypertensive subjects compared with normotensive controls. However, pressure lowering by antihypertensive drugs does not always reverse large artery alterations indicating that other mechanisms are involved. Reversal of low compliance obtained with certain antihypertensive drugs is generally concomitant with large artery vasodilation, suggesting that smooth muscle relaxation plays a major role in the compliance response to drugs. Atherosclerosis associated with hypertension also causes additional loss of compliance and creates a vicious circle of sclerosis development by accelerating the biophysical fatigue of bioelastomers. Hypertension may contribute to atherogenesis by means of wall shear stress which is the frictional force exerted by the circulating blood column on the intima of arteries. Since it is likely that atherosis lesions may develop preferentially in low shear conditions, hypertension may promote the haemodynamic conditions of atherogenesis at the blood-wall interface. The response of wall shear to antihypertensive treatment is not unequivocal. For example, the beta-blocker, atenolol, does not change shear whereas carteolol increases shear rate and stress and these effects are closely related to change in platelet-free calcium concentration. This finding is consistent with the effect of shear forces on cell permeability to calcium demonstrated in vitro and points to the crucial role of wall shear as a biophysical signal capable of modifying the endothelial structure and function of arteries.
 ...
PMID:Physiopharmacological approach to mechanical factors of hypertension in the atherosclerotic process. 194 80

Internal fixation of comminuted unstable fractures of the severely osteoporotic proximal femur is sometimes supplemented with polymethyl-methacrylate (PMMA). We here report an in vitro biomechanical evaluation of a biodegradable particulate composite that might be used for similar purposes. The composite includes a matrix phase consisting of a hydrolyzable prepolymer [polypropylene fumarate (PPF)] cross-linked with methacrylate monomer, and a particulate phase consisting of tricalcium phosphate and calcium carbonate. We implanted dynamic hip screws in 22 cadaveric proximal femora and measured the yield load for an oblique force applied to the femoral head. The hip screws were then reinforced with either PMMA or the PPF composite and tested again. On the basis of analysis of variance, the average increases in yield load for PMMA and PPF reinforcement of 1,750 and 1,130 N were statistically significant (p less than 0.00005), suggesting that both materials enhance congruence between implant and bone and thereby increase the projected load-bearing area of the implant. The increase in yield force with PMMA was slightly higher than the increase with PPF (p less than 0.05), but both values after reinforcement were close (3,790 +/- 561 N for PMMA vs. 3,240 +/- 669 N for PPF). If we can demonstrate that appropriate rates of degradation, bony ingrowth, and static and fatigue properties can be achieved in vivo with this system, our data suggest that this PPF composite may have potential as an adjunct to the internal fixation of unstable fractures of the osteoporotic hip.
 ...
PMID:Biomechanical evaluation of a biodegradable composite as an adjunct to internal fixation of proximal femur fractures. 198 49

In order to derive practical health care suggestions, researchers examined the health beliefs, practices, and experiences of Korean women living in the US. The study involved 20 volunteer Koran women from the Chicago metropolitan area, and to avoid communication problems, the interviews were conducted in Korean, later translated into English. The age of the volunteers ranged from 26-32 years; they had been in the US from 1-10 years (the average was 3.3). As far as their beliefs were concerned, the women took a holistic approach to health, emphasizing not only the physical, but also the psychological and the spiritual. As many as 1/2 the women rated their health as below average, which they attributed to problems such as emotional stress and fatigue (the study suggests that this high rate of stress is the product of having to adjust to a new society). Concerning their health practices, only 1 woman regularly had a Pap test and did regular breast self-examination. And while 6 of the women reported that they couldn't drink milk, 18 said they ate well and took prescribed vitamin, iron, and calcium pills. Also, all the women attended prenatal care clinics, and the rate of breastfeeding was 60% -- higher than the national average. Relying on traditional medicine, all 20 women reported eating brown seaweed soup for 20 days after childbirth, and 5 said that they took tonic herbs during the puerperium. These practices sometimes caused conflict at the hospital, and language difficulties also caused problems. The study recommends: 1) developing pamphlets in Korean about the US health care delivery system and community health programs; 2) developing a bilingual pamphlet of medical terms; 3) ensuring that health car workers visit the patients more often to give them more opportunities to ask for assistance; 4) when needed, using family members as interpreters; and 5) having health care workers discuss diet with the patients.
 ...
PMID:Beliefs, practices, and experiences of Korean women in relation to childbirth. 202 35

Impaired diastolic function of the hypertrophied and stiffened left ventricle is a characteristic feature of hypertrophic cardiomyopathy (Figure 1). Altered left ventricular filling dynamics and reduced left ventricular distensibility or increased left ventricular diastolic chamber stiffness are associated with reduced left ventricular stroke volume, increased left ventricular filling pressures and compressive effects on the coronary microcirculation. These factors contribute importantly to the clinical presentation of many patients, including symptoms of fatigue, dyspnea and angina pectoris. Reduced distensibility results both from factors determining the passive elastic properties of the ventricular chamber (including severity of hypertrophy, fibrosis and cellular disarray) and from factors influencing the rate and extent of active left ventricular relaxation (Figure 2). The factors contributing to impaired relaxation in hypertrophic cardiomyopathy are mediated via either inactivation dependent or load-dependent mechanisms. In laboratory animals, compromise of myocardial inactivation results in a persistent increase in intracellular calcium concentration and in prolonged interaction of the contractile proteins. Additionally, there is evidence for an increased number of active receptors for calcium antagonists and, lastly, for myocardial ischemia (Figure 3). Load-dependent mechanisms include diminished wall tension at the opening of the mitral valve, changes in afterload, contractility and coronary flow. Other factors are nonuniform and asynchronous regional ventricular function due to differing increases in thickness of the ventricular walls and ischemia (Figure 4). Calcium channel blockers exert a favorable influence on left ventricular relaxation and filling (Figure 5); verapamil and diltiazem are preferable to nifedipine. Verapamil increases left ventricular stroke volume without an increase in the end-diastolic pressure (Figure 6), reduces regional asynchrony if present, and leads to a more homogeneous regional diastolic filling (Figure 4).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Left ventricular diastolic function in hypertrophic cardiomyopathy. 202 81


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>