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 age and gender related differences in serum amino acid concentrations have been assessed in 72 (23-92 years) medically screened healthy men and women who were divided into three male and three female groups according to age. Free-time physical activity and food intake were analysed from the 5-day diaries. The subjects were instructed to eat according to their normal dietary habits and to avoid any clinical complementary nutritional products or other products that could increase protein or energy intake. The blood samples (5 ml) taken from the antecubital vein after an over-night fast were analysed for their amino acid contents by chromatography. In total nutrient intake of energy (P < 0.001), protein (P < 0.001), alcohol (P < 0.05), water (P < 0.01), sodium (P < 0.001) and fiber P < 0.001) decreased significantly with age. The concentration of total amino acids (P < 0.01), essential amino acids (P < 0.001), non-essential amino acids (P < 0.05) and branched-chain amino acids (P < 0.05) decreased, whereas citrulline (P < 0.001) and cysteine (P < 0.001) were the only amino acids, which increased with aging. In addition, men had significantly higher concentrations than women of essential amino acids (P < 0.001), branched-chain amino acids (P < 0.001), and 10 of the 22 individual amino acids assayed (P < 0.01). Women had significantly higher concentrations of aspartate (P < 0.05), glycine (P < 0.01), serine (P < 0.001) and taurine (P < 0.01) than men. It is concluded that the decrease in serum total amino acid concentration is associated with decreased energy and protein intake with aging and men have higher essential amino acid concentration in serum than women.
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PMID:Serum amino acid concentrations in aging men and women. 1276 4

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

The production of reactive oxygen species in skeletal muscle is linked with muscle fatigue. This study investigated the effects of the antioxidant compound N-acetylcysteine (NAC) on muscle cysteine, cystine, and glutathione and on time to fatigue during prolonged, submaximal exercise in endurance athletes. Eight men completed a double-blind, crossover study, receiving NAC or placebo before and during cycling for 45 min at 71% peak oxygen consumption (VO2 peak) and then to fatigue at 92% VO2 peak. NAC was intravenously infused at 125 mg.kg(-1).h(-1) for 15 min and then at 25 mg.kg(-1).h(-1) for 20 min before and throughout exercise. Arterialized venous blood was analyzed for NAC, glutathione status, and cysteine concentration. A vastus lateralis biopsy was taken preinfusion, at 45 min of exercise, and at fatigue and was analyzed for NAC, total glutathione (TGSH), reduced glutathione (GSH), cysteine, and cystine. Time to fatigue at 92% VO2 peak was reproducible in preliminary trials (coefficient of variation 5.6 +/- 0.6%) and with NAC was enhanced by 26.3 +/- 9.1% (NAC 6.4 +/- 0.6 min vs. Con 5.3 +/- 0.7 min; P <0.05). NAC increased muscle total and reduced NAC at both 45 min and fatigue (P <0.005). Muscle cysteine and cystine were unchanged during Con, but were elevated above preinfusion levels with NAC (P <0.001). Muscle TGSH (P <0.05) declined and muscle GSH tended to decline (P=0.06) during exercise. Both were greater with NAC (P <0.05). Neither exercise nor NAC affected whole blood TGSH. Whereas blood GSH was decreased and calculated oxidized glutathione increased with exercise (P <0.05), both were unaffected by NAC. In conclusion, NAC improved performance in well-trained individuals, with enhanced muscle cysteine and GSH availability a likely mechanism.
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PMID:N-acetylcysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance-trained individuals. 1519 75

Fatigue of hand and forearm muscle groups can limit task performance by astronauts wearing space suits. Countermeasures to delay fatigue would therefore be useful to the space program. N-acetylcysteine (NAC) has been shown to inhibit fatigue during other tasks so we tested its effects during handgrip exercise. Volunteers practiced isometric handgrip maneuvers until performance was reproducible over three successive sessions (baseline). Performance then was retested after ingesting NAC (150 mg.kg(-1)) or saline. Drug administration increased NAC and cysteine blood levels (P < 0.001). Performance of sustained maximal efforts was unaffected. During repetitive submaximal efforts, NAC delayed fatigue (130% baseline) and inhibited glutathione oxidation. Saline did not alter glutathione status or performance of sustained maneuvers; repetitive task performance was increased by 15% (P < 0.05), a placebo effect. These data indicate that NAC supports glutathione homeostasis in exercising humans and may delay muscle fatigue during repetitive handgrip exercise. Our findings support oxidative stress as a causal factor in human muscle fatigue and argue for larger translational studies to define NAC effects on human performance.
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PMID:Effects of N-acetylcysteine on glutathione oxidation and fatigue during handgrip exercise. 1602 22

There is now some evidence that chronic fatigue syndrome (CFS) is accompanied by signs of oxidative stress and by a decreased antioxidant status. The aim of the present study was to examine whether CFS is accompanied by an immune response to neoepitopes of a variety of modified lipids and proteins indicating damage caused by oxidative and nitrosative stress. Toward this end we examined serum antibodies to fatty acids (oleic, palmitic and myristic acid), by-products of lipid peroxidation, i.e. azelaic acid and malondialdehyde (MDA), acetylcholine, S-farnesyl-L-cysteine, and N-oxide modified amino-acids in 14 patients with CFS, 14 subjects with partial CFS and 11 normal controls. We found that the prevalences and mean values for the serum IgM levels directed against oleic, palmitic and myristic acid, MDA, azelaic acid, S-farnesyl-L-cysteine, and the N-oxide derivates, nitro-tyrosine, nitro-phenylalanine, nitro-arginine, nitro-tryptophan, and nitro-cysteinyl were significantly greater in CFS patients than in normal controls, whereas patients with partial CFS took up an intermediate position. There were significant and positive correlations between the serum IgM levels directed against fatty acids, MDA and azelaic acid and the above N-oxide-derivates and the severity of illness (as measured by the FibroFatigue scale) and symptoms, such as aches and pain, muscular tension and fatigue. The results show that CFS is characterized by an IgM-related immune response directed against disrupted lipid membrane components, by-products of lipid peroxidation, S-farnesyl-L-cysteine, and NO-modified amino-acids, which are normally not detected by the immune system but due to oxidative and nitrosative damage have become immunogenic.
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PMID:Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins. 1715 17

To investigate the relation between plasma amino acid levels and mental fatigue, we measured the plasma concentrations of 20 amino acids in 9 healthy volunteers before and after a fatigue-inducing mental task session for 8 hr. As fatigue-inducing mental tasks, the subjects performed an advanced trail making test, a Japanese KANA pick up test, and a mirror drawing test. As a control, 8-hr relaxation session was performed in the same subjects at an interval of 4 weeks. Immediately after the fatigue session, the plasma levels of branched-chain amino acids, tyrosine, cysteine, methionine, lysine, and arginine were below those after a relaxation session. The values for other blood parameters including total protein, albumin, glucose, and total cholesterol did not show any differences between the 2 sessions. These results indicate that mental fatigue may be characterized by a decrease in the plasma level of these amino acids.
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PMID:Mental fatigue-induced decrease in levels of several plasma amino acids. 1716 Mar 70

There is now some evidence that chronic fatigue syndrome is accompanied by an activation of the inflammatory response system and by increased oxidative and nitrosative stress. Nuclear factor kappa beta (NFkappabeta) is the major upstream, intracellular mechanism which regulates inflammatory and oxidative stress mediators. In order to examine the role of NFkappabeta in the pathophysiology of CFS, this study examines the production of NFkappabeta p50 in unstimulated, 10 ng/mL TNF-alpha (tumor necrosis factor alpha) and 50 ng/mL PMA (phorbolmyristate acetate) stimulated peripheral blood lymphocytes of 18 unmedicated patients with CFS and 18 age-sex matched controls. The unstimulated (F=19.4, df=1/34, p=0.0002), TNF-alpha-(F=14.0, df=1/34, p=0.0009) and PMA-(F=7.9, df=1/34, p=0.008) stimulated production of NFkappabeta were significantly higher in CFS patients than in controls. There were significant and positive correlations between the production of NFkappabeta and the severity of illness as measured with the FibroFatigue scale and with symptoms, such as aches and pain, muscular tension, fatigue, irritability, sadness, and the subjective feeling of infection. The results show that an intracellular inflammatory response in the white blood cells plays an important role in the pathophysiology of CFS and that previous findings on increased oxidative stress and inflammation in CFS may be attributed to an increased production of NFkappabeta. The results suggest that the symptoms of CFS, such as fatigue, muscular tension, depressive symptoms and the feeling of infection reflect a genuine inflammatory response in those patients. It is suggested that CFS patients should be treated with antioxidants, which inhibit the production of NFkappabeta, such as curcumin, N-Acetyl-Cysteine, quercitin, silimarin, lipoic acid and omega-3 fatty acids.
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PMID:Not in the mind of neurasthenic lazybones but in the cell nucleus: patients with chronic fatigue syndrome have increased production of nuclear factor kappa beta. 1769 79

Obstructive sleep apnoea is characterised by intermittent hypoxia due to recurrent obstructions of the pharyngeal airway during sleep. We have shown that chronic intermittent hypoxia impairs respiratory muscle function and CNS control of upper airway patency. In this study, we tested the hypothesis that disruption of an endogenous antioxidant defence system exacerbates the effects of intermittent hypoxia on upper airway muscle contractile function. Thirty-two male Wistar rats were placed in restrainers with their heads in hoods in which the ambient oxygen concentration could be modified by controlling the gas supply to the hoods. Sixteen rats were exposed to alternating equal periods of hypoxia and normoxia, twice per minute, 8 hours per day for 1 week. The remaining 16 animals were exposed to normoxia continuously under identical experimental conditions. In both groups, half the animals received daily injections of buthionine sulfoxamine (BSO), an inhibitor of the rate-limiting enzyme in glutathione synthesis. The other half received daily vehicle injections. At the end of the 1-week treatment period, the sternohyoid muscles were removed and fatigue characteristics were determined in vitro. Intermittent hypoxia was associated with a decrease in sternohyoid muscle endurance, an effect that was exacerbated by treatment with BSO. In separate experiments, daily treatment with the antioxidant N-acetyl cysteine blocked the deleterious effects of intermittent hypoxia on respiratory muscle function. We suggest that oxidative stress contributes to impaired upper airway muscle endurance in our animal model and that endogenous glutathione may be especially important in limiting free radical-induced muscle dysfunction. Our results may have particular relevance to respiratory disorders associated with recurrent hypoxia, such as the sleep apnoea/hypopnoea syndrome.
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PMID:Oxidative stress impairs upper airway muscle endurance in an animal model of sleep-disordered breathing. 1808 17

Blastocystis is a ubiquitous enteric protozoan found in the intestinal tracts of humans and a wide range of animals. Evidence accumulated over the last decade suggests association of Blastocystis with gastrointestinal disorders involving diarrhea, abdominal pain, constipation, nausea, and fatigue. Clinical and experimental studies have associated Blastocystis with intestinal inflammation, and it has been shown that Blastocystis has potential to modulate the host immune response. Blastocystis is also reported to be an opportunistic pathogen in immunosuppressed patients, especially those suffering from AIDS. However, nothing is known about the parasitic virulence factors and early events following host-parasite interactions. In the present study, we investigated the molecular mechanism by which Blastocystis activates interleukin-8 (IL-8) gene expression in human colonic epithelial T84 cells. We demonstrate for the first time that cysteine proteases of Blastocystis ratti WR1, a zoonotic isolate, can activate IL-8 gene expression in human colonic epithelial cells. Furthermore, we show that NF-kappaB activation is involved in the production of IL-8. In addition, our findings show that treatment with the antiprotozoal drug metronidazole can avert IL-8 production induced by B. ratti WR1. We also show for the first time that the central vacuole of Blastocystis may function as a reservoir for cysteine proteases. Our findings will contribute to an understanding of the pathobiology of a poorly studied parasite whose public health importance is increasingly recognized.
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PMID:Blastocystis ratti contains cysteine proteases that mediate interleukin-8 response from human intestinal epithelial cells in an NF-kappaB-dependent manner. 1815 86

Fatiguing exercise promotes oxidation of intracellular thiols, notably glutathione. Interventions that oppose or reverse thiol oxidation can inhibit fatigue. The reduced cysteine donor l-2-oxothiazolidine-4-carboxylate (OTC) supports glutathione synthesis and is approved for use in humans but has not been evaluated for effects on skeletal muscle. We tested the hypotheses that OTC would 1) increase reduced glutathione (GSH) levels and decrease oxidized glutathione, and 2) inhibit functional indexes of fatigue. Diaphragm fiber bundles from adult male ICR mice were incubated for 1 or 2 h at 37 degrees C with buffer (control, C) or OTC (10 mM). N-acetylcysteine (NAC; 10 mM) was used as a positive control. We measured GSH metabolites and fatigue characteristics. We found that muscle GSH content was increased after 1-h incubation with OTC or NAC but was not altered after 2-h incubation. One-hour treatment with OTC or NAC slowed the decline in force with repetitive stimulation [mean (SD) fatigue index at 300 s: OTC = 34 +/- 6% vs. C = 50 +/- 8%, P < 0.05; NAC = 55 +/- 4% vs. C = 65 +/- 8%, P < 0.05] as did the 2-h OTC treatment (OTC = 38 +/- 9% vs. C = 51 +/- 9%, P < 0.05). These results demonstrate that OTC modulates the muscle GSH pool and opposes fatigue under the current experimental conditions.
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PMID:L-2-Oxothiazolidine-4-carboxylate reverses glutathione oxidation and delays fatigue of skeletal muscle in vitro. 1940 60


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