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 cytotoxicity of hydroquinone (HQ) and several of its metabolites was studied using freshly isolated proximal tubular (PT) kidney cells from rats. Incubations were conducted for periods of up to 4 h at 37 degrees C, with cytotoxicity measured either as increased leakage of lactate dehydrogenase or as a decreased energy status, as determined by decreased ratios of adenosine triphosphate (ATP) to adenosine diphosphate (ADP). Incubation atmospheres consisted of either 95% O(2)/5% CO(2), to promote cell viability in vitro, or 5% O(2)/5% CO(2)/90% N(2). Preliminary studies with bovine serum albumin (BSA) added to the incubation media indicated a lack of toxicity for HQ or its metabolites. For the tests discussed in this report, incubations were performed without the addition of BSA. Under 95% O(2) atmospheres, PT cells from male Fischer F344 rats were significantly more sensitive to HQ than those from male Sprague-Dawley (SD) rats, with decreases in ATP to ADP ratios seen as early as 0.5 h at a concentration of 0.5 mM. When incubations were performed under a 5% O(2) atmosphere, 2-(cysteine-S-yl)hydroquinone (Cys-HQ) and HQ toxicities were observed later (3-4 h) in the incubation period, occurred at higher concentrations, were similar in magnitude for the two strains, and were greater for Cys-HQ than for HQ. These results show that variations in oxygen tension can dramatically influence the toxicity of HQ and its metabolites. The specific compounds tested that were cytotoxic at a physiologically relevant oxygen tension (5%) were (in decreasing order of potency): Cys-HQ > 2-(glutathion-S-yl)hydroquinone > HQ. These results support an association of toxicity with metabolism through the glutathione pathway, with ultimate toxicity associated with the cysteinyl conjugate. Biochemical characteristics of PT cells from these two strains suggest a significantly greater capacity of cells from the SD rat to respond to oxidative stress.
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PMID:The effect of oxygen tension on the cytotoxicity of hydroquinone and selected hydroquinone metabolites to isolated rat renal proximal tubular cells. 1508 69

Associations between fatigability and biochemical properties within motor unit (MU) types were explored in two hindlimb muscles of the adult rat. Type FF MUs in extensor digitorum longus and type S units in soleus were subjected either to a moderate (type FF) or severe (type S) 6-min, fatigue-inducing stimulation protocol. For both MU types, the range of values for their fatigability was considerably greater than the ranges in the activity levels of three enzymes in the units' constituent muscle fibers (MFs). These enzymes represented major energy-yielding pathways: adenylokinase, for high-energy phosphate metabolism; lactate dehydrogenase, for anaerobic glycolysis; and malate dehydrogenase, for oxidative metabolism. There were also relatively weak associations between the fatigue indices of the MUs and the activity levels of the three enzymes. Thus, this work supports previous conclusions that the force decline exhibited by MUs during electrically evoked contractions depends on both MF biochemistry and other intracellular mechanisms. Electromyographic measurements suggested that these other mechanisms are distal to the intramuscular branches of the axon in type FF units, and distal to excitation-contraction coupling in type S units.
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PMID:Fatigue of rat hindlimb motor units: biochemical-physiological associations. 1538 17

Stimulation of healthy granulocyte donors allows the collection of therapeutic doses of granulocytes. The stimulation with G-CSF alone was compared with G-CSF plus dexamethasone. Blood samples were drawn at baseline, at leukapheresis, and at follow-up visit. Donors answered a questionnaire to evaluate side effects of the stimulation regimen. The combination of G-CSF and dexamethasone resulted in higher WBC count than G-CSF alone (39.4 +/- 7.8 vs. 34.8 +/- 8.3/nl). Glucose (136 +/- 45 mg/dl) and lactate dehydrogenase (195 +/- 38) increased significantly after stimulation with G-CSF plus dexamethasone but returned to baseline levels at the follow-up visit. Generally, stimulation was well tolerated by the donors. A higher rate of mild bone pain and headache was experienced in donors stimulated with G-CSF plus dexamethasone than in donors receiving G-CSF alone. Fatigue and myalgia were reported at similar rates in both groups. A high proportion of the donors stated that they would accept a further stimulation and granulocyte donation. At the follow-up visit, blood counts and chemistry had returned to normal values.
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PMID:Donor tolerance and results of stimulation with G-CSF alone or in combination with dexamethasone for the collection of granulocytes. 1549 56

Gamisipjundaebo-tang (GSDBT) has been used for the purpose of development of physical strength. In the present study, we investigated the immune enhancing effect induced by GSDBT. We investigated the anti-immobility effect of GSDBT via a forced-swimming test and blood biochemical parameters related to fatigue, glucose, blood urea nitrogen, lactic dehydrogenase, creatine kinase, and total protein. GSDBT (0.1 and 1 g/kg) was orally administered to mice for 14 days. After 7 and 14 days, as assessed through a forced-swimming test, immobility time was decreased in the GSDBT-administrated group (0.1 and 1 g/kg) in comparison with the control group. In addition, after 8 days, the contents of glucose and lactate dehydrogenase in the blood serum were increased, and contents of blood urea nitrogen were decreased in the GSDBT-administrated group. After 15 days, the contents of glucose were increased, and the contents of lactate dehydrogenase and blood urea nitrogen were decreased in the GSDBT-administrated group. However, it had no effect on the elevation of creatine kinase and total protein level. We also investigated the effect of GSDBT on the production of cytokines in human T-cell line, MOLT-4 cells, and splenocytes. GSDBT significantly increased interferon (IFN)-gamma and interleukin (IL)-2 levels compared with the media control but did not affect IL-4. GSDBT increased the protein expression of IFN-gamma in MOLT-4 cells. These results suggest that GSDBT may be useful in immune function improvement and may also have antifatigue properties.
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PMID:Decrease of immobility behavior in forced-swimming test and immune system enhancing effect of traditional medicine Gamisipjundaebo-tang. 1550

Because the clinical significance of von Willebrand factor (vWF), a marker of endothelial injury, has not been well studied in adult patients with dermatomyositis (DM), we evaluated whether plasma vWF levels are useful as an index of disease activity in these patients. We measured plasma vWF antigen levels in 11 patients with active adult DM, 13 patients with inactive DM, and 18 healthy subjects using an enzyme-linked immunosorbent assay. The association of vWF level with clinical condition and muscle-derived enzyme leakage among DM patients was examined using analysis of covariance and logistic regression analysis. Furthermore, we studied the effects of treatment on the vWF antigen level. The mean vWF antigen level was significantly higher in active DM patients than in inactive DM patients and healthy subjects. Higher vWF levels were associated with clinical symptoms, such as general fatigue, fever, and muscle weakness. They were also associated with the levels of aspartate aminotransferase, alanine aminotransferase, and aldolase, but not with those of lactate dehydrogenase and creatine kinase (CK). vWF antigen was correlated with muscle enzymes except for CK. The plasma vWF levels in six patients with active DM significantly decreased after successful corticosteroid treatment. Plasma vWF level may be considered a useful marker of disease activity in adult DM patients.
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PMID:Clinical significance of von Willebrand factor in patients with adult dermatomyositis. 1556 94

We hypothesized that patients with chronic obstructive pulmonary disease developing contractile fatigue of the quadriceps during cycle exercise may have characteristic metabolic and muscle features that could increase their susceptibility to fatigue, thus differentiating them from those who do not develop fatigue. We examined, in 32 patients, the fiber-type proportion, enzymatic activities, and capillary density in the vastus lateralis and the arterial blood lactate level during constant work-rate cycling exercise. Contractile fatigue was defined as a postexercise fall in quadriceps twitch force greater than 15% of resting values. Twenty-two patients developed contractile fatigue after exercise. No significant differences were found between fatiguers and non-fatiguers for the endurance time, fiber-type proportion, and oxidative enzyme activities. The lactate dehydrogenase activity was significantly higher (p < 0.05) and muscle capillarization significantly reduced in fatiguers (p < 0.05). Compared with non-fatiguers, the arterial lactate level during exercise was significantly higher in fatiguers (p < 0.001). A significant relationship was found between the fall in quadriceps twitch force and lactate dehydrogenase activity, capillary/fiber ratio, and blood lactate level. We conclude that changes in muscle enzymatic profile and capillarization with a greater reliance on glycolytic metabolism during exercise are associated with contractile fatigue in patients with chronic obstructive pulmonary disease.
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PMID:Contractile fatigue, muscle morphometry, and blood lactate in chronic obstructive pulmonary disease. 1573 55

The purpose of this study was to determine the efficacy of resistance exercise in reversing skeletal muscle myopathy in heart transplant recipients. Myopathy, engendered by both heart failure and immunosuppression with glucocorticoids, is a post-transplant complication. The sequelae of myopathic disease includes fiber-type shifts and deficits in aerobic metabolic capability. We randomly assigned patients to either 6 months of resistance exercise (training group; n = 8) or a control (control group; n = 7) group. Exercise was initiated at 2 months after transplant. Biopsy of the right vastus lateralis was performed before and after the 6-month intervention. Myosin heavy chain (MHC) composition was assessed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Biochemical assays were performed to determine citrate synthase, 3-hydroxyacyl-CoA-dehydrogenase, and lactate dehydrogenase activity. There were no group differences (p >or=0.05) in MHC composition and enzymatic reserve at baseline. Improvements in the training group for citrate cynthase (+40%), 3-hydroxyacyl-CoA-dehydrogenase (+10%), and lactate dehydrogenase activity (+48%) were significantly greater (p <or=0.05) than in the control group (+10%, -15%, and +20%, respectively). Oxidative type 1 MHC isoform concentration increased significantly in the training group (+73%, p <or=0.05) but decreased in the control group (-28%; p <or=0.05). Glycolytic type 2x MHC isoform increased significantly (17%; p <or=0.05) in the control group but decreased (-33%; p <or=0.05) in the training group. This is the first study to demonstrate that resistance training elicits myofibrillar shifts from less oxidative type II fibers to more oxidative fatigue-resistant type I fibers in heart transplant recipients. Resistance exercise initiated early in the post-transplant period is efficacious in changing skeletal muscle phenotype through increases in enzymatic reserve and shifts in fiber morphology.
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PMID:Effect of resistance exercise on skeletal muscle myopathy in heart transplant recipients. 1587 92

We report an instructive case of diffuse large B-cell lymphoma presenting as acute heart failure. A 69-year-old human immunodeficiency virus-negative man was admitted to our hospital for general fatigue. A computed tomographic scan of the chest and abdomen showed pericardial effusion, but there was no evidence of tumor masses, lymph node enlargement, or hepatosplenomegaly. During the chemotherapy, increased lactate dehydrogenase and pleural effusion appeared. The tumor cells in the effusion showed positivity for CD5, CD19, CD20, kappa chain, and Bcl-2 and negativity for CD10 and CD23. The chromosomes showed t(8;14)(q24;q32) with c-myc/immunoglobulin (Ig)H rearrangement, and the MIB-1 index was not high (60%). Neither human herpes virus 8 nor Epstein-Barr virus DNA was detected in the cells by polymerase chain reaction. The response to chemotherapy was very poor, and the patient died 4 months after the diagnosis. A spectrum of the symptoms of CD5+ lymphoma encompasses pericardial effusion and also can accompany c-myc/IgH rearrangement.
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PMID:CD5+ diffuse large B-cell lymphoma with c-myc/IgH rearrangement presenting as primary effusion lymphoma. 1591 62

Lactic acid is considered the end product of glycolysis and is a major cause of muscle fatigue. However, the lactate dehydrogenase (LDH) reaction is bidirectional: Lactate can be oxidized to pyruvate and used as a substrate for the Krebs cycle. Therefore, our hypothesis was that lactate sustains the contractile function of rat extraocular muscles during periods of increased activity. The study used extraocular and extensor digitorum longus (EDL) muscles from adult Sprague-Dawley rats to determine LDH isoform expression, total LDH activity, and contractile function in vitro. To evaluate the role of lactate on fatigue, we tested the effect of cinnamate, a blocker of lactate transport, and exogenous lactate on fatigue resistance. Cinnamate accelerated fatigue in the extraocular muscles: Endurance and residual force decreased significantly. Conversely, cinnamate did not affect the endurance or residual force of EDL muscles. Replacing glucose with exogenous lactate increased EDL fatigability but had no effect on the extraocular muscles. However, the extraocular muscles fatigued faster when exposed to exogenous lactate combined with cinnamate. The LDH-A and LDH-C isoforms were expressed at lower levels in extraocular muscle; LDH-B was equally abundant in the EDL and extraocular muscles. Total LDH activity in the extraocular muscles was only approximately 32% of the level in EDL. These results support the hypothesis that lactate sustains the contractile performance of the extraocular muscles.
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PMID:Lactate is a metabolic substrate that sustains extraocular muscle function. 1632 56

A 67-year-old woman presented with impaired general performance, suffering from fatigue, dyspnea on exertion, and paresthesia of the finger tips. The laboratory findings showed increased white blood cells at 11.37 x 10(3)cells/microl with 26.5% abnormal cells, low haemoglobin and, elevated creatinine, although serum lactate dehydrogenase and calcium levels were normal. Serum immunofixation was positive for monoclonal IgM-kappa paraprotein. Total serum protein and the IgM component were elevated. X-ray examination of the skeleton was normal. Bone marrow aspiration showed 59.5% infiltration of abnormal cells that were characterized by typical mature plasmacytoid morphology. Abnormal cells expressed surface CD20, surface CD138, and cytoplasmic IgM, but not surface CD56 nor surface IgM by flow cytometric immunophenotyping with CD38 gating. Immunohistochemistry showed surface CD38, surface CD20, and cytoplasmic IgM. The clinical findings led to the diagnosis of the IgM Plasma cell leukemia (PCL). The patient received multi-agent chemotherapy (VAD and EDAP with rituximab). The clinical symptoms disappeared, leading to the tumor load reduction. To the best of our knowledge, this is the first report of successful treatment of multi-agent chemotherapy with rituximab for IgM PCL.
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PMID:Successful treatment of multi-agent chemotherapy with rituximab for IgM plasma cell leukemia. 1654 Jan 68


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