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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent reports have demonstrated that superoxide is released by the contracting diaphragm. Moreover, extracellular scavengers of superoxide (i.e., exogenously administered superoxide dismutase) reduce diaphragm fatigue rate, arguing that superoxide released from contracting muscles may have functionally significant effects. The mechanism by which free radical formation and release occurs has not, however, been determined, and all past studies of this phenomenon have been conducted at a single muscle length (the length of maximum force generation, Lo) and at a single level of carbon dioxide. The purpose of the present study was twofold: (1) to examine the effect of blockade of two free radical-generating pathways (i.e., to block cyclooxygenase with indomethacin and xanthine oxidase with oxypurinol) on superoxide release by the contracting diaphragm, and (2) to examine the effect of altering muscle length, carbon dioxide levels, and stimulation frequency on superoxide release during contraction. Studies were performed using an isolated, arterially perfused, rat diaphragm preparation in which superoxide release was assessed in real time by measuring arteriovenous cytochrome c reduction gradients across this muscle. We found that superoxide release during contraction was: (1) not altered by indomethacin administration, (2) partially reduced by oxypurinol administration, (3) reduced by decreasing muscle length, (4) reduced by increasing carbon dioxide concentrations, and (5) reduced by decreasing stimulation frequency. The first two findings indicate that xanthine oxidase pathways contribute to free radical formation under these circumstances but cyclooxygenase does not. The last three findings suggest that these common physiologic alterations have significant effects on free radical release by contracting muscle.
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PMID:Modulation of release of reactive oxygen species by the contracting diaphragm. 1071 39

Muscular exercise results in an increased production of radicals and other forms of reactive oxygen species (ROS). Recent evidence suggests that radicals and other ROS are an underlying aetiology in exercise-induced disturbances in muscle redox status. These exercise-induced redox disturbances in skeletal muscle are postulated to contribute to both muscle fatigue and/or exercise-induced muscle injury. To defend against ROS, muscle cells contain complex cellular defence mechanisms to reduce the risk of oxidative injury. Two major classes (enzymic and non-enzymic) of endogenous protective mechanisms work together to reduce the harmful effects of oxidants in the cell. Primary antioxidant enzymes include superoxide dismutase (EC 1.15.1.1; SOD), GSH peroxidase (EC 1.11.1.9; GPX), and catalase (EC 1.11.1.6); these enzymes are responsible for removing superoxide radicals, H2O2 and organic hydroperoxides, and H2O2 respectively. Important non-enzymic antioxidants include vitamins E and C, beta-carotene, GSH and ubiquinones. Vitamin E, beta-carotene and ubiquinone are located in lipid regions of the cell, whereas GSH and vitamin C are in aqueous compartments of the cell. Regular endurance training promotes an increase in both total SOD and GPX activity in actively-recruited skeletal muscles. High-intensity exercise training has been shown to be generally superior to low-intensity exercise in the upregulation of muscle SOD and GPX activities. Also, training-induced upregulation of antioxidant enzymes is limited to highly-oxidative skeletal muscles. The effects of endurance training on non-enzymic antioxidants remain a relatively uninvestigated area.
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PMID:Analysis of cellular responses to free radicals: focus on exercise and skeletal muscle. 1081 71

These experiments tested the hypothesis that in vitro diaphragmatic fatigue resistance is enhanced in animals treated with glucocorticoids. Female Sprague-Dawley rats (4 months old) were randomly assigned to a control (N =12) or glucocorticoid treatment group (N =12). Treatment animals were injected daily for 8 days with prednisolone (5 mg kg(-1)); control animals were injected with the same volume of the vehicle. Twenty-four hours after the last injection, the following in vitro diaphragmatic contractile properties were examined in costal diaphragm strips: maximal twitch (P(t)) half time to peak tension (1/2 TPT), half relaxation time (1/2 RT), force-frequency relationship, and the rate of fatigue development. Diaphragmatic fatigue was assessed by monitoring the decrease in force production (measured as percent of initial force) over a 60-min contractile period. The in vitro fatigue protocol incorporated a supramaximal stimulus delivered at 30 Hz every 2 s with a train duration of 250 ms (duty cycle 12.5%). Citrate synthase (CS), superoxide dismutase (SOD), and water content of the costal diaphragm were also determined. Glucocorticoid administration induced an 18.9% (P<0.05) decrease in animal body weight when compared to the control. Similar weight losses also occurred in the diaphragm with a decrease (P<0.05) in mass of 16.5% compared to the control. Furthermore, prednisolone treatment resulted in a significant reduction in the cross-sectional area (CSA) of type IIb fibres with no change in the CSA area of type I and IIa fibres. 1/2 TPT and 1/2 RT were significantly prolonged (P<0.05) in the glucocorticoid treated rats whereas the force-frequency curve was unaltered (P>0.05). Fatigue resistance was greater in the glucocorticoid group (P<0.05); the relative force production differed between groups at the end of 1 min of contractions and remained different throughout the 60-min fatigue protocol. Citrate synthase, SOD, and water content were not different between groups. These experiments support the hypothesis that costal diaphragm strips of glucocorticoid-treated rats possess a greater resistance to fatigue. We postulate that this fatigue resistance is due to glucocorticoid-induced changes muscle fibre type composition.
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PMID:Glucocorticoid-induced alterations in the rate of diaphragmatic fatigue. 1086 Jun 36

Three groups of NZW rabbits were studied to examine the role of free radical scavengers in preventing diaphragm injury produced by inspiratory resistive load (IRL): control, IRL, and scavenger groups. An IRL (Pao: 45-55 cm H2O) was applied to the IRL and the scavenger groups on Day 1. Free radical scavengers (polyethylene glycol superoxide dismutase, N-acetylcysteine, and mannitol) were given (intravenously) to the scavenger group both before and after the IRL. All rabbits were killed on Day 3 to collect diaphragms. Point counting H&E-stained diaphragm x-sections indicated that abnormal diaphragm muscle in the IRL group was significantly greater than control (p < 0.01). However, it was significantly lower in the scavenger group than the IRL group (p < 0.05) and it did not differ from control. In vitro diaphragm physiological studies found that the twitch tension (p < 0.05) and maximal tension (p < 0.01) in the IRL group were significantly lower than control. The maximal tensions (p < 0.05) in the scavenger group were lower than control. After the fatigue protocol, diaphragmatic contractility in the scavenger group was similar to control and was better maintained compared with the IRL group. We conclude that free radical scavengers can prevent the development of diaphragm injury as evidenced by histology but the protection of diaphragm function is limited.
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PMID:Free radical scavengers and diaphragm injury following inspiratory resistive loading. 1167 24

OBJECTIVE: To explore the possible mechanisms for the occurrence of diaphragm fatigue induced by diaphragm pacing. METHODS: The phrenic nerve of 8 dogs were exposed and subjected to stimulation with electric pulses emitted by a diaphragm pacemaker to induce diaphragm fatigue models, and the contents of ATP, ADP, AMP and AXP in the diaphragm muscles before and after diaphragm pacing were determined by high-performance liquid chromatography (HPLC). The contents of SOD and MDA were also measured and the morphological alteration of the mitochondria observed with transmission electron microscope. RESULTS: The contents of ATP, ADP, AXP and SOD were found significantly lower but MDA was higher during fatigue than those in normal conditions, while AMP content manifested no obvious change. Some mitochondria in the diaphragm muscles swelled and in a few cases, vacuolar degeneration was observed. CONCLUSIONS: The exhaustion and synthesis disturbance of ATP may explain the generation of diaphragm fatigue, and the reduction of dynamophore and ultrastructural injuries of the cells induced by oxygen free radicals may also contribute to this result.
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PMID:Changes in adenine nucleotide, SOD and MDA contents and mitochondria ulteractructure during diaphragm fatigue in dogs induced by diaphragm pacing. 1242 86

Chronic fatigue syndrome (CFS) is an illness characterized by persistent and relapsing fatigue, often accompanied by numerous symptoms involving various body systems. The etiology of CFS remains unclear; however, a number of studies have shown that oxidative stress may be involved in its pathogenesis. In the present study, a mouse model of CFS was used in which mice were forced to swim for one 6-minute session on each day for 15 days and the immobility period was recorded. There was a significant increase in immobility period in saline-treated mice on successive days. Intraperitoneal treatment with the potent antioxidants carvedilol (5 mg/kg) and melatonin (5 mg/kg) produced a significant reduction in immobility period. Similar results were observed with herbal preparations administered orally: Withania somnifera (100 mg/kg), quercetin (50 mg/kg), and St. John's wort (Hypericum perforatum L., 10 mg/kg). Biochemical analysis revealed that chronic swimming significantly induced lipid peroxidation and decreased glutathione (GSH) levels in the brains of mice. The rats also showed decreased levels of antioxidant defense enzymes, superoxide dismutase (SOD), and catalase. Co-administration of antioxidants carvedilol, melatonin, W. somnifera, quercetin or St. John's wort significantly reduced lipid peroxidation and restored the GSH levels decreased by chronic swimming in mice. Further, the treatment increased levels of SOD in the forebrain and of catalase. The findings strongly suggest that oxidative stress plays a significant role in the pathophysiology of CFS and that antioxidants could be useful in the treatment of CFS.
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PMID:Effect of natural and synthetic antioxidants in a mouse model of chronic fatigue syndrome. 1263 96

Skeletal muscle arterioles from obese Zucker rats (OZR) exhibit oxidant stress-based alterations in reactivity, enhanced alpha-adrenergic constriction, and reduced distensibility vs. microvessels of lean Zucker rats (LZR). The present study determined the impact of these alterations for perfusion and performance of in situ skeletal muscle during periods of elevated metabolic demand. During bouts of isometric tetanic contractions, fatigue of in situ gastrocnemius muscle of OZR was increased vs. LZR; this was associated with impaired active hyperemia. In OZR, vasoactive responses of skeletal muscle arterioles from the contralateral gracilis muscle were impaired, due in part to elevated oxidant tone; reactivity was improved after treatment with polyethylene glycol-superoxide dismutase (PEGSOD). Arterioles of OZR also exhibited increased alpha-adrenergic sensitivity, which was abolished by treatment with phentolamine (10-5 M). Intravenous infusion of phentolamine (10 mg/kg) or PEG-SOD (2,000 U/kg) in OZR altered neither fatigue rates nor active hyperemia from untreated levels; however, combined infusion improved performance and hyperemia, although not to levels in LZR. Microvessel density in the contralateral gastrocnemius muscle, determined via histological analyses, was reduced by approximately 25% in OZR vs. LZR, while individual arterioles from the contralateral gracilis muscle demonstrated reduced distensibility. These data suggest that altered arteriolar reactivity contributes to reduced muscle performance and active hyperemia in OZR. Further, despite pharmacological improvements in arteriolar reactivity, reduced skeletal muscle microvessel density and arteriolar distensibility also contribute substantially to reduced active hyperemia and potentially to impaired muscle performance.
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PMID:Impaired skeletal muscle perfusion in obese Zucker rats. 1285 17

Chronic renal failure (CRF) is associated with oxidative stress that promotes production of reactive oxygen species. L-Carnitine is a cofactor required for transport of long-chain fatty acids into the mitochondrial matrix. Recent research has shown that some clinical conditions (i.e., anorexia, chronic fatigue, coronary heart disease, diphtheria, hypoglycemia, and male infertility) benefit from exogenous supplementation of L-carnitine. The aim of this study was to examine the role of L-carnitine in protecting the aorta, heart, corpus cavernosum, and kidney tissues against oxidative damage in a rat model of CRF. Male Wistar albino rats were randomly assigned to either the CRF group or the sham-operated control group, which had received saline or L-carnitine (500 mg/kg, i.p.) for 4 weeks. CRF was evaluated by BUN and serum creatinine measurements. Aorta and corporeal tissues were used for contractility studies or stored along with heart and kidney tissues for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels. Plasma MDA, GSH levels and erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were also studied. In the CRF group, the contraction and the relaxation of aorta and corpus cavernosum samples decreased significantly compared with controls and were partially reversed by L-carnitine treatment. In the CRF group, there were significant increases in tissue MDA with marked reductions in GSH levels in all tissues and plasma compared with controls. In the plasma SOD, CAT and GSH-Px activities were also reduced. All these effects were reversed by L-carnitine as well. The increase in MDA level and the concomitant decrease in GSH level of tissues and plasma and also suppression of the antioxidant enzyme activities in plasma demonstrate that oxidative mechanisms are involved in CRF-induced tissue damage. L-carnitine, possibly via its free radical scavenging and antioxidant properties, ameliorates oxidative organ injury and CRF-induced dysfunction of the aorta and corpus cavernosum. These results suggest that L-carnitine supplementation may have some benefit in CRF patients.
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PMID:L-carnitine ameliorates oxidative damage due to chronic renal failure in rats. 1507 58

Ground-based analogs of spaceflight are an important means of studying physiologic and nutritional changes associated with space travel, and the NASA Extreme Environment Mission Operations V (NEEMO) is such an analog. To determine whether saturation diving has nutrition-related effects similar to those of spaceflight, we conducted a clinical nutritional assessment of the NEEMO crew (4 men, 2 women) before, during, and after their 14-d saturation dive. Blood and urine samples were collected before, during, and after the dive. The foods consumed by the crew were typical of the spaceflight food system. A number of physiologic changes were observed, during and after the dive, that are also commonly observed during spaceflight. Hemoglobin and hematocrit were lower (P < 0.05) after the dive. Transferrin receptors were significantly lower immediately after the dive. Serum ferritin increased significantly during the dive. There was also evidence indicating that oxidative damage and stress increased during the dive. Glutathione peroxidase and superoxide dismutase decreased during and after the dive (P < 0.05). Decreased leptin during the dive (P < 0.05) may have been related to the increased stress. Subjects had decreased energy intake and weight loss during the dive, similar to what is observed during spaceflight. Together, these similarities to spaceflight provide a model to use in further defining the physiologic effects of spaceflight and investigating potential countermeasures.
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PMID:Nutritional status changes in humans during a 14-day saturation dive: the NASA Extreme Environment Mission Operations V project. 1522 67

Low-density lipoproteins (LDL) are very sensitive to oxidative processes initiated by oxygen free radicals, known to be produced in large quantities during intense physical exercise. Oxidatively modified lipoprotein particles (oxLDL) are strongly atherogenic and immunogenic, as a consequence specific autoantibodies (oLAB) against oxLDL are produced by the immune system. This study was designed to evaluate the oLAB titres in professional soccer players and to find out whether the immune response to oxidative modification of LDL correlates with the antioxidant status of individual players. Eleven players volunteered to participate in an incremental treadmill running exercise to volitional fatigue twice (in October and January) during the competitive season. Venous blood samples were withdrawn before and 3 min after the cessation of the test. Serum levels of oLAB were measured by ELISA (Biomedica). Blood samples were analyzed for glutathione peroxidase, reduced glutathione, superoxide dismutase, catalase and glutathione reductase. The activity of creatine kinase (CK) and concentrations of malondialdehyde (MDA), vitamin E and retinol were determined in plasma. From 11 subjects only in 4 players, in both graded running tests, the oLAB titres were low (< 200 mU.ml(-1)). The remaining athletes presented elevated oLAB (800-1400 mU.ml(-1)). Significantly lower activities of catalase and glutathione reductase and lower concentration of alpha-tocopherol were recorded in the 2nd trial. When the data were arranged according to the oLAB titres no significant between-group differences were found in either pre- and post-test activities of antioxidant enzymes or in concentrations of antioxidants. However, significantly higher CK activities and a tendency towards more elevated plasma MDA concentrations were observed in subjects with higher oLAB levels. It seems justified to presume that high titres of antibodies against oxLDL, as evidenced in most of the players, could be accounted for by their higher in vivo susceptibility of LDL to structural modification under conditions of intensive training-induced oxidative stress, despite their apparently normal antioxidant status.
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PMID:Evaluation of autoantibodies against oxidized LDL (oLAB) and blood antioxidant status in professional soccer players. 1564 38


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