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 skeletal muscle has the capacity to respond adaptively to increased use. This observation could open up the feasibility of constructing pumping chambers to support or even replace cardiac work. We investigated the changes in enzyme activity due to chronic stimulation in an animal skeletal muscle. In 5 adult sheep the psoas muscle of one side was electrically stimulated through the muscle nerves, with an implantable stimulation unit for 5 weeks. The activity of the hexokinase (E.C.2.7.1.1.), lactate dehydrogenase (E.C.1.1.1.27), malate dehydrogenase (E.C.1.1.1.37), creatine kinase (E.C.2.7.3.2.) choline acetyltransferase and the contents of adenosine triphosphate and adenosine diphosphate were determined in bioptic specimen. The use of only 15 Hertz as a stimulation frequency led to a transformation of an originally fast-twitch muscle into a slow-twitch muscle with reduced susceptibility to fatigue. These results indicate a potential role of the skeletal muscle as an ideal myocardial substitute with the ability to perform hemodynamic work.
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PMID:[Biochemical changes in skeletal muscles after chronic indirect stimulation]. 260 58

isometric tension and maximum velocity of shortening of frog sartorious and biceps muscles were measured at varying pH and compared with the values obtained for muscles treated with DNFB. Both To and Vmax exhibited increase with increase in pH above neutral pH upto pH 9, and decreased as the pH was decreased up to 5. Muscle treated with DNFB at pH 7 showed about 30% decrement but these too improved at pH 9 to almost 105% and 130% respectively compared to untreated muscle at pH 7. Using the number of short duration tetanic contractions, which reduce To and Vmax by half, as an index for the onset of fatigue, high pH was found to have a positive effect in both normal and DNFB-treated muscle. Thus, the crucial factor for onset of fatigue is not a fall in ATP level but acidification and treatment with high pH Ringer's solution partially annuls the effect of acidosis, arising either naturally or from DNFB treatment. One additional role of creatine kinase activity to that of ATP regeneration is suggested to be the maintenance of neutral pH in the sarcoplasm.
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PMID:Effect of extracellular pH and DNFB treatment on the mechanical performance of frog skeletal muscle. 262 70

A review of metabolic pathways is presented, which are involved in muscular energy production during hypoxia according to recent experimental findings. By means of own exercise examinations the course of reactions providing ATP anaerobically in the muscles of limbs with poor circulation is analysed. Therefore, the arteriovenous differences in the concentrations of lactate, pyruvate, ammonia, hypoxanthine and alanine in the femoral blood of patients with stage II AOD were determined. In addition, the intracellular phosphorus compounds ATP, PCr and Pi as well as the tissue pH were measured noninvasively in the calf muscles using 31P magnetic resonance spectroscopy. The results give evidence for marked activation of the creatine kinase reaction, of glycolysis, of the myokinase reaction and of the purine nucleotide cycle in the ischaemic musculature at loads of short duration, which are in total sufficient to maintain the concentration of ATP even during claudication pain. In spite of salvage pathways like alanine formation, the end products of these "emergency reactions", Pi, H+ and NH4+, accumulate and exert deleterious cytotoxic effects, which are thought to be responsible for rapid muscle fatigue and claudication pain in PAOD.
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PMID:[Regulation of ischemic muscle metabolism in peripheral arterial occlusive disease]. 267 1

The values obtained from the measurement of serum creatine phosphokinase (SCPK) in 70 cases of chronic cor pulmonale in exacerbation and 72 cases in remission were compared with the normal value as measured in 160 healthy adults at the same period. The results showed that the normal value of SCPK was 46.50 +/- 12.71 u/L in male, while 32.51 +/- 10.8 u/L in female. The differences of the values of SCPK in male and female are highly significant statistically (P less than 0.001). Although the values of SCPK were within normal limits (M +/- 2SD) in most patients with chronic cor pulmonale (72.38-84.10%) in this paper, the values of SCPK of some of them (13.60-22.36%) were higher than normal. But in a few of the patients in exacerbation (2.27-5.26%) the SCPK values were lower than normal. The increased activity of SCPK in patients with chronic cor pulmonale may be related to the vigorous movement of the respiratory muscles. While the level of SCPK decreased to extremely low degree may indicate that the respiratory muscles may be excessively fatigue. So we suggest that the levels of SCPK which are markedly higher or lower than normal could be served as an reference index for the excessive activity or fatigue of the respiratory muscles respectively in chronic cor pulmonale.
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PMID:[The clinical significance of serum creatine phosphokinase measurement in patients with chronic cor pulmonale]. 279 44

Fatigue of isolated gastrocnemius muscles from R. pipiens leads to a marked increase in the proportion of phosphofructokinase bound to the particulate fraction and a decrease in the binding of lactate dehydrogenase, pyruvate kinase, creatine phosphokinase and glyceraldehyde-3-phosphate dehydrogenase. Only the proportion of aldolase bound to the particulate fraction was unaffected by fatigue. This pattern was unchanged when fatigued muscles were extracted at pH 6.5 rather than 7.5. Thus, muscle fatigue leads to opposite changes in the binding of the glycolytic enzymes.
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PMID:The effect of fatigue on the binding of glycolytic enzymes in the isolated gastrocnemius of Rana pipiens. 280 95

A 15-year-old girl with a four-month history of cardiac failure from undetermined cause was admitted to the hospital with weakness, fatigue, and weight loss. During her hospitalization she was found to have abused diet aids, laxatives, and cathartics. Although an electrocardiogram revealed nonspecific T-wave abnormalities and laboratory studies showed supranormal enzyme test results for creatine kinase and lactate dehydrogenase, no definite explanation of the cardiomyopathy was forthcoming. Ipecac abuse leading to cardiomyopathy was suspected early in the hospitalization. HPLC analysis of a urine sample showed emetine, a principle component of ipecac, the presence of which was later confirmed by more-specific HPLC analysis with photodiode array detection.
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PMID:Emetine identified in urine by HPLC, with fluorescence and ultraviolet/diode array detection, in a patient with cardiomyopathy. 292 Apr 26

A 9-year-old boy who complained of fatigue, myalgias, and progressive weakness was found to have a markedly elevated serum creatine phosphokinase (CPK). He developed polyuria with polydipsia and was noted to be hypertensive and severely hypokalemic. Treatment with potassium and spironolactone alleviated his signs and symptoms and normalized the blood pressure and CPK. Initial studies revealed low plasma renin activity that did not increase with change from supine to upright position. Plasma aldosterone was consistently elevated in the supine position, decreased with upright posture, and was not suppressed by administration of dexamethasone. Plasma 18-hydroxycorticosterone also was elevated. Enhanced computerized tomography (CT) revealed a mass in the left adrenal that had not been seen on the initial unenhanced scan. Adrenal vein catheterization confirmed elevated plasma aldosterone on that side. Adrenalectomy was performed, and a well-encapsulated adenoma was found at examination of the surgical specimen. Postoperatively, suppression of plasma renin activity continued for many months without signs of aldosterone deficiency.
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PMID:Aldosterone-producing adenoma presenting with hypokalemic myopathy. Case report and review. 329 4

It is estimated that there are approximately six million patient-years of clinical experience with fenofibrate among physicians outside of the United States. A review of the European literature and unpublished studies supplied by the manufacturer (Laboratoires Fournier, Dijon, France) has been compiled with the data recently reported from a double-blind, placebo-controlled study completed in the United States. In general, fenofibrate has been found to reduce serum triglyceride levels by 30 to 60 percent in patients with type II B and IV hyperlipoproteinemia. Serum cholesterol levels were also reduced by 20 to 25 percent in this group of hypertriglyceridemic patients. A similar reduction in serum cholesterol levels was also found in type II A patients (normal triglyceride levels). Low-density lipoprotein levels were usually reduced in those patients with elevated levels and high-density lipoprotein levels increased when baseline levels were low. Fenofibrate also produced a 10 to 28 percent reduction in uric acid that was sustained for years. The incidence of unwanted effects ranged from 2 to 15 percent in the open trials lasting from a few months up to six years. Gastrointestinal problems (abdominal discomfort, diarrhea, and constipation) are most common, occurring in approximately 5 percent of patients. Reports including fatigue, headache, loss of libido, impotence, dizziness, and insomnia were grouped as neurologic and occurred with a total incidence of 3 to 4 percent. In about 1 percent of patients, muscle tenderness developed, often accompanied by elevated creatine phosphokinase levels. These and the gastrointestinal problems occurred with a similar frequency in the placebo-treated cohort in controlled studies. In approximately 2 percent of patients, a skin rash developed, an incidence that appears significantly higher than that of placebo control groups. Liver changes in rodents have included marked peroxisome proliferation and increased hepatic carcinomas with very high doses. In humans, only a small increase in incidence of elevated levels of serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase seems to be present and is not clearly different from that of the control groups. Alkaline phosphatase, gamma-glutamyl transferase, and bilirubin levels are often decreased with no known undesirable effects. Investigations into the lithogenicity of bile indicated a significant increase in five studies. However, there has been no evidence of a significant rise in the incidence of cholelithiasis in the clinical trials completed to date.
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PMID:Comparative toxicity and safety profile of fenofibrate and other fibric acid derivatives. 331 50

Lactic acid is formed and accumulated in the muscle under conditions of high energy demand, rapid fluctuations of the energy requirement and insufficient supply of O2. During intense exercise sustained to fatigue muscle pH decreases to about 6.4-6.6. Force generation does not appear to be limited by the high H+ ion concentration per se but is more related to the PCr level. Phosphofructokinase may be inhibited by high H+ concentration but the inhibition is adequately overcome by increases in the activators AMP and ADP. A high concentration of H+ will decrease PCr by a direct effect on the creatine kinase equilibrium and indirectly by an increase in ADP. The effect of acidosis on glycolysis and on the PCr level will result in a decreased rate of ADP rephosphorylation, and it is suggested that ADP increases transiently above the steady-state level in the contracting muscle fibre. It is further suggested that the function of Na-K-ATPase is impaired by the increase of ADP resulting in an altered ionic balance over the muscle cell membrane. Muscle fatigue is thus considered to be due to an insufficient rate of ADP rephosphorylation resulting in a block in the activation process or in the excitation/contraction coupling.
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PMID:Muscle fatigue and lactic acid accumulation. 347 Oct 61

We conducted a trial of a murine monoclonal antimelanoma antibody-ricin A chain immunotoxin (XOMAZYME-MEL) in 22 patients with metastatic malignant melanoma. The dose of immunotoxin administered ranged from 0.01 mg/kg daily for 5 days to 1 mg/kg daily for 4 days (total dose: 3.2 to 300 mg). Side effects observed in most patients were a transient fall in serum albumin with an associated fall in serum protein, weight gain, and fluid shifts resulting in edema. In addition, patients experienced mild to moderate malaise, fatigue, myalgia, decrease in appetite, and fevers. There was a transient decrease in voltage on electrocardiograms without clinical symptoms, change in serial echocardiograms or elevation of creatine phosphokinase MB isozyme levels. Symptoms consistent with mild allergic reactions were observed in three patients. The side effects were related to the dose of immunotoxin administered and were generally transient and reversible. Encouraging clinical results were observed, even after a single course of a low dose of immunotoxin. In addition, localization of antibody and A chain to sites of metastatic disease was demonstrated by immunoperoxidase staining of biopsy specimens. Additional studies are being conducted to continue the evaluation of safety and efficacy of immunotoxin therapy for malignancy.
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PMID:Therapy of patients with malignant melanoma using a monoclonal antimelanoma antibody-ricin A chain immunotoxin. 349 66


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