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)

The resting membrane potential (RMP), the intracellular free Na+ concentration ([Na+]i) and the intracellular free K+ concentration ([K+]i), were measured with double-barrelled ion-selective microelectrodes in mouse soleus muscles in vitro. In addition, the Na+ contents and K+ contents have been measured with the flame photometric technique. At rest the beta 2-selective adrenoceptor agonist terbutaline (10(-5) M) increased the membrane potential and [K+]i, and decreased [Na+]i when compared with control muscles. During a 5 min stimulation period the muscles, which were incubated with the beta 2-adrenoceptor agonist, showed a smaller depolarization, a smaller decrease in [K+]i and a smaller increase in [Na+]i than stimulated control muscles. This difference was probably associated with an increased rate of Na-K-pumping in the beta 2-adrenoceptor stimulated muscles. The beta 2-agonist treated muscles were more resistant to fatigue than control muscles. This effect was significant with 10(-6) M terbutaline (25 degrees C). A depolarization obtained by increasing [K+]o was shown to reduce the maximal tension. It is postulated, that the K+ shifts, which are responsible for the depolarization during muscle activity, are one of the mechanisms underlying muscle fatigue.
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PMID:The effect of beta 2-adrenoceptor activation on ion-shifts and fatigue in mouse soleus muscles stimulated in vitro. 290 15

Myofibrillar proteins in muscles of the claws and abdomen of lobster, Homarus americanus, and the claws of fiddler crab, Uca pugnax, and land crab, Gecarcinus lateralis, have been analyzed with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Fibers contained numerous isoforms of structural and regulatory proteins in assemblages correlated with fiber type. One fast (F) and two slow (S1 and S2) fibers were identified. All F fibers possessed two isoforms of paramyosin (P1 and P2), while all slow fibers, with the exception of Uca major claw, contained only the P2 variant. S1 and S2 fibers were distinguished by the distribution of a large isoform of troponin-T (T1; Mr = 55,000); S2 fibers in all three species contained T1 in addition to one or two smaller-molecular-weight variants usually associated with S1 fibers. In order to determine whether the slow fibers differed in histochemical properties, land crab claw closer muscle was cryosectioned and stained for myofibrillar ATPase and NADH diaphorase activities. Most S2 fibers had lower ATPase and higher NADH diaphorase activities than S1 fibers, which indicated that S2 fibers had a lower rate of contraction and were more fatigue-resistant than S1 fibers. It is proposed that the S1 and S2 fibers defined by biochemical and histochemical criteria are identical to the slow-twitch and tonic fibers, respectively characterized physiologically.
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PMID:Histochemical and biochemical characterization of two slow fiber types in decapod crustacean muscles. 296 38

Dilated cardiomyopathy, owing to any cause, usually culminates in the clinical syndrome of congestive heart failure. Heart failure is characterized by exertional dyspnea and fatigue, but the precise mechanisms that produce these symptoms are still not clear. Sodium retention occurs early in heart failure, but this disturbance is dynamic in nature and is not always present in the patient. The mechanism of early salt and water retention in heart failure is not defined. Gross edema and ascites occur much later, undoubtedly owing to the convergence of a number of factors. The peripheral adaptations to heart failure include activation of the renin-angiotensin system and the sympathetic nervous system, and the release of AVP. The result is an increase in preload with a resultant increase in stroke volume for some patients, but the price is paid in the form of heightened impedance to ejection and circulatory congestion. The sympathetic nervous system disturbances in heart failure are striking, as disturbances in both circulating and myocardial NE levels are consistently found. Vasorelaxant and natriuretic hormones, as well as certain prostaglandins, may be released in an attempt to offset excessive "compensatory" pressor-sodium retentive mechanisms, but the net result seems to be excessive peripheral vasoconstriction and a downward spiral of deterioration in many patients. One would hope that an unraveling of the complex pathophysiology of heart failure would lead to therapy that would change the natural history of the disease. The results of the first V-HeFT trial give room for cautious optimism in this regard.
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PMID:Pathophysiology of congestive heart failure secondary to congestive and ischemic cardiomyopathy. 304 87

Angiotensin converting enzyme (ACE)-inhibitors combined with diuretics and, if necessary, with calcium antagonists can be used with good success for the treatment of otherwise resistant hypertension. Calcium antagonists are an alternative for physically active hypertensive patients who complain of muscular fatigue during treatment with beta-receptor-blocking agents. The calcium antagonist nifedipine has made the treatment of hypertensive emergencies much easier than with the use of clonidine and particularly sodium nitroprusside. In order to determine the place of ACE-inhibitors and of calcium antagonists in the treatment of hypertension- particularly in comparison with beta-blockers and diuretics- controlled long-term studies on the prognosis of patients with mild to moderate hypertension and on the incidence of side effects would be required.
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PMID:[Have angiotensin-converting enzyme inhibitors improved therapy of hypertension?]. 305 77

In principle, target inactivation analysis provides a means of determining the molecular weights (Mr) and states of aggregation of proteins in native environments where they are functionally active. We applied this irradiation technique to the rat liver microsomal membrane proteins: cytochrome b5, epoxide hydrolase, flavin-containing monooxygenase, NADH-ferricyanide reductase, NADPH-cytochrome P-450 reductase, and seven different forms of cytochrome P-450. Catalytic activities, spectral analysis of prosthetic groups, and sodium dodecyl sulfate-polyacrylamide electrophoresis/peroxidase-coupled immunoblotting were used to estimate apparent Mr values in rat liver microsomal membranes. Except in one case (cytochrome P-450PCN-E), the estimated Mr corresponded most closely to that of a monomer. Purified cytochrome P-450PB-B, NADPH-cytochrome P-450 reductase and epoxide hydrolase were also subjected to target inactivation analysis, and the results also suggested monomeric structures for all three proteins under these conditions. However, previous hydrodynamic and gel-exclusion results clearly indicate that all three of these proteins are oligomeric under these conditions. The discrepancy between target inactivation Mr estimates and hydrodynamic results is attributed to a lack of energy transfer between monomeric units. Thus, while P-450PCN-E may be oligomeric in microsomal membranes, target inactivation analysis does not appear to give conclusive results regarding the states of aggregation of these microsomal proteins.
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PMID:Target inactivation analysis applied to determination of molecular weights of rat liver proteins in the purified state and in microsomal membranes. 311 94

This study tests three hypotheses regarding mechanisms that produce rapid shallow breathing during a severe inspiratory resistive load (IRL): 1) an intact vagal afferent pathway is necessary; 2) diaphragm fatigue contributes to tachypnea; and 3) hypoxia may alter the pattern of respiration. We imposed a severe IRL on pentobarbital sodium-anesthetized dogs, followed by bilateral vagotomy, then by supplemental O2. IRL alone produced rapid shallow breathing associated with hypercapnia and hypoxia. After the vagotomy, the breathing pattern became slow and deep, restoring arterial PCO2 but not arterial PO2 toward the control values. Relief of hypoxia had no effect, and at no time was there any evidence of fatigue of the diaphragm as measured by the response to phrenic nerve stimulation. We conclude that an intact afferent vagal pathway is necessary for the tachypnea resulting from a severe IRL, neither hypoxia nor diaphragm fatigue played a role, and, although we cannot rule out stimulation of vagal afferents, the simplest explanation for the increased frequency in our experiments is increased respiratory drive due to hypercapnia.
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PMID:Vagal afferents, diaphragm fatigue, and inspiratory resistance in anesthetized dogs. 313 22

A case of hyponatremia is presented with water intoxication due to treatment with oxcarbazepine (OxCZ). The patient was admitted because of exceeding dullness and increasing seizures. Low values for serum sodium and osmolality were found. Simultaneously with the reduction in OxCZ, values of sodium and osmolality increased, normalizing on discontinuation of the drug, and the exceeding tiredness as well as the generalized seizures disappeared. Low values of arginine-vasopressin were found, suggesting that the mode of action of OxCZ was directly or indirectly at the level of the kidney.
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PMID:Hyponatremia induced by oxcarbazepine. 314 48

Most hemodialysis is now carried out with a dialysate sodium concentration of 140-145 mEq/L. Higher dialysate sodium has been used, but controversy exists concerning the increased incidence of high blood pressure (HBP), thirst, and weight gain. A double blind prospective study was carried out in five stable men on chronic hemodialysis. Dialysis was performed in random sequence with a dialysate sodium of 145, 150, or 155 mEq/L for 2 months at a time. Vital signs were monitored before, during, and after dialysis, and the presence of symptoms during and between dialyses was documented. There was a significant increase in interdialytic weight gain with increasing dialysate sodium: 145 mEq/L (2.2 kg), 150 mEq/L (2.6 kg), 155 mEq/L (2.9 kg). There was a small, nonsignificant increment in dry weight of 0.5 kg between a dialysate of 145 mEq/L to 155 mEq/L but no increase in the mean arterial blood pressure. There was no difference in the incidence of interdialytic or intradialytic symptoms, including cramps, nausea, or fatigue, nor any change in serum sodium or other routine laboratory data before dialysis. It is concluded that a high dialysate sodium is not associated with an increased incidence of hypertension, symptoms, or a change in serum sodium but is associated with an increase in interdialytic weight gain.
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PMID:A randomized double blind trial of dialysate sodiums of 145 mEq/L, 150 mEq/L, and 155 mEq/L. 319 30

Digoxin could improve diaphragm contractility and fatigability if inhibition of sodium-potassium adenosine triphosphatase enhances calcium influx from extracellular sources, or it could impair contractility and worsen fatigue if it impairs maintenance of the membrane potential. We studied the effects of digoxin on isometric force production, fatigue, and recovery in isolated, directly stimulated, guinea pig and rat diaphragms. Digoxin had no effect on maximal twitch or tetanic tensions compared with control diaphragms in either rat (2 ng/ml to 20 micrograms/ml) or guinea pig (2 ng/ml to 2 micrograms/ml) hemidiaphragms. Digoxin worsened high frequency fatigue and impaired recovery from fatigue in guinea pigs (200 ng/ml to 2 micrograms/ml) but not in rat (2 micrograms/ml) hemidiaphragms. We conclude that digoxin has no effect on diaphragm contractility. Hypopolarization of the membrane potential is the likely cause for the increased fatigability. The difference in responsiveness between species is likely due to insensitivity of rat sodium-potassium adenosine triphosphatase to digoxin.
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PMID:The effect of digoxin on contractility and fatigue of isolated guinea pig and rat hemidiaphragms. 320 78

Residency training may disrupt normal sleep/wake cycles, resulting in mood and performance deficits and alterations in biological rhythms. To characterize such disturbances and determine whether they are associated with an alteration in the day/night pattern of melatonin excretion, measurements were obtained around-the-clock in seven male subjects, each studied in two 48-h sessions. Session 1 was conducted during the week before beginning a residency, and session 2 at 6 months into a first-year surgical residency. The mean time of the end of nocturnal sleep and the timing of the temperature rhythm were both (P less than .01) approximately 2.3 h earlier in session 2 (vs. 1). The sleepiness rhythm and the overall mood score rhythm were also phase-advanced (P less than .05) in session 2. The mean value of mood around-the-clock was significantly worse due to increased anger, tension, confusion, depression, and fatigue in session 2. Vigilance, tested by simple reaction time, did not exhibit a 25-h rhythm and was worse in session 2 with an increase (P less than .05) in mean response latency less than 1 s and an increase (P less than .01) in lapse time (microsleep, greater than 1- s latency). The urinary cortisol rhythm exhibited a raised curve average value (mesor) in session 2 (vs. 1, P less than .05), but no difference was revealed in amplitude or acrophase. Urinary excretion of Na+, K+, and Cl- did not differ between sessions, though the Na+/K+ ratio peaked earlier in session 2 (P less than .05). The urinary 6-sulfatoxymelatonin rhythm did not differ in timing, amplitude, or mesor between sessions. A residency training schedule can be associated with altered timing in rhythms of sleep, sleepiness, temperature, and mood and with deterioration of mood and performance without detectable alteration of the endogenous melatonin pattern as exhibited by the excretion rate of the principal urinary metabolite.
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PMID:Alterations of temperature, sleepiness, mood, and performance in residents are not associated with changes in sulfatoxymelatonin excretion. 322 34


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