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

We hypothesized that muscle fiber bundles produce reactive oxygen intermediates and that reactive oxidant species contribute to muscular fatigue in vitro. Fiber bundles from rat diaphragm were mounted in chambers containing Krebs-Ringer solution. In studies of intracellular oxidant kinetics, bundles were loaded with 2',7'-dichlorofluorescin, a fluorochrome that emits at 520 nm when oxidized; emissions were quantified using a fluorescence microscope. Emissions from unstimulated muscles increased over time (P < 0.001). Accumulation of fluorescence was slowed by addition of catalase (P < 0.001) or superoxide dismutase (P < 0.001) and was accelerated by repetitive muscular contraction (P < 0.05). To determine effects of reactive oxygen intermediates on fatigue, curarized bundles were stimulated to contract isometrically; force was measured. Catalase, superoxide dismutase, and dimethyl sulfoxide were screened for effects on low- and high-frequency fatigue. Antioxidants inhibited low-frequency fatigue [after 5 min of repetitive contractions, force at 30 Hz was 20% greater than control (P < 0.015)] and increased the variability of fatigue at 30 Hz (P < 0.03). Antioxidants did not alter high-frequency (200-Hz) fatigue. We conclude that 1) diaphragm fiber bundles produce reactive oxygen intermediates, including O2-. and H2O2; 2) muscular contraction increases intracellular oxidant levels; and 3) reactive oxygen intermediates promote low-frequency fatigue in this preparation.
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PMID:Reactive oxygen in skeletal muscle. I. Intracellular oxidant kinetics and fatigue in vitro. 147 54

This review addresses current understanding of oxygen radical mechanisms as they relate to the brain during ischemia and reperfusion. The mechanism for radical production remains speculative in large part because of the difficulty of measuring radical species in vivo. Breakdown of lipid membranes during ischemia leads to accumulation of free fatty acids. Decreased energy stores during ischemia result in the accumulation of adenine nucleotides. During reperfusion, metabolism of free fatty acids via the cyclooxygenase pathway and metabolism of adenine nucleotides via the xanthine oxidase pathway are the most likely sources of oxygen radicals. Although leukocytes have been found to accumulate in some models of ischemia and reperfusion, their mechanistic role remains in question. Therapeutic strategies aimed at decreasing brain injury have included administration of radical scavengers at the time of reperfusion. Efficacy of traditional oxygen radical scavengers such as superoxide dismutase and catalase may be limited by their inability to cross the blood-brain barrier. Lipid-soluble antioxidants appear more efficacious because of their ability to cross the blood-brain barrier and because of their presence in membrane structures where peroxidative reactions can be halted.
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PMID:Oxygen radical mechanisms of brain injury following ischemia and reperfusion. 175 40

We used in situ gastrocnemius muscle of anaesthetized dogs to test the hypothesis that O2 radical production during muscle contraction contributes to fatigue. Muscle tension was measured with a force transducer and blood flow was monitored with an electromagnetic flow probe. Muscle contractions were produced by stimulating the nerve for 15 min at 20 Hz, 12 trains/min, and a duty cycle of 0.25. Three groups of seven animals were given an infusion of 0.2 mL.min-1 of either saline, low-dose oxygen radical scavengers (250 IU.mL-1 superoxide dismutase, 640 IU.mL-1 polyethylene glycol (PEG)-catalase, 0.25 mg.mL-1 deferoxamine, and 0.1 mg.mL-1 oxypurinol), or high-dose oxygen radical scavengers (3300 IU.mL-1 superoxide dismutase, 6600 IU.mL-1 PEG-catalase, 2.5 mg.mL-1 deferoxamine, and 0.1 mg.mL-1 oxypurinol). Blood flow and vascular resistance of the gastrocnemius muscle during stimulation did not differ among groups. After 15 min of stimulation, the developed tension (represented as a percentage of initial tension developed) was 66 +/- 7% in the saline treated group, 70 +/- 6% in the low-dose group, and 70 +/- 4% in the high-dose group. The change in tension during recovery was not significant in the control or low-dose groups. However, there was partial recovery in the high-dose group. In conclusion, in this preparation, oxygen radical scavengers did not delay the development of decreased muscle tension.
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PMID:Failure of oxygen radical scavengers to modify fatigue in electrically stimulated muscle. 177 47

It has been shown in previous studies that cell poration (i.e., reversible permeabilization of cell membrane) and cell fusion can be induced by applying a pulse (or pulses) of high-intensity DC (direct current) electric field. Recently we suggested that such electro-poration or electro-fusion can also be accomplished by using an oscillating electric field. The DC field relies solely on the dielectric breakdown of the cell membrane to induce cell fusion. The oscillating field, on the other hand, can produce not only a dielectric breakdown, but also a sonicating motion in the membrane that could result in a structural fatigue. Thus, a combination of a DC field and an oscillating field is expected to enhance the efficiency of cell poration and cell fusion. This study is an experimental test of such an idea. Here, pulses of high-intensity, DC-shifted RF (radio frequency) electric field were used to induce cell poration and cell fusion. The fusion experiments were done on human red blood cells. The poration experiments were done on a fibroblast cell line using a molecular probe (which is a DNA plasmid containing the marker gene chloramphenicol acetyltransferase, CAT) and assayed by a gene transfection technique. It was found that the pulsed RF field is highly efficient in both cell fusion and cell poration. Also, in comparison with electro-poration using a DC field, the RF field results in a higher percentage of cells surviving the exposure to the electric field.
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PMID:Cell poration and cell fusion using an oscillating electric field. 281 30

By creating motility disorders, functional pancreatic insufficiency, inadequate bowel absorptive surface, bacterial overgrowth, or mucosal changes, several disease states and treatments have an adverse impact on the body's ability to digest and/or absorb nutrients adequately. The subjective and objective observations associated with the malabsorption syndrome--fatigue, paresthesia, weight change, alterations in bowel movements, and laboratory abnormalities--are caused by losses of macronutrients, electrolytes, minerals, and vitamins in the stool. The absorption workup consists of tests for fat absorption, bowel integrity, pancreatic function, and bacterial overgrowth, which may be performed alone or in combination to aid in identifying specific absorptive defects. Other diagnostic procedures include abdominal x-rays and CAT scans and intestinal biopsy. A logical, well-planned workup is essential in order to avoid unnecessary and/or costly testing. Nutrition management utilizes parenteral, enteral, and oral feeding in combination with adjunct medical measures for maximizing nutrient absorption and minimizing nutrient losses.
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PMID:Malabsorption in adults: etiology, evaluation, and management. 309 70

In a phase I trial 34 patients with pancreatic cancer were treated with the murine monoclonal antibody (MAb) BW 494 (BI 51.011) directed against a glycoprotein antigen. The patients received repeated doses of MAb over a time period from 5 to 14 days (highest single dose 100 mg, highest cumulative dose 490 mg). During this treatment serum levels of murine IgG increased to 43.4 micrograms/ml. The serum half life of murine IgG ranged from 2 to 3 days. Repeated injections of MAb BW 494 were normally well-tolerated when given within the first 15 days. Two patients presented with fatigue and a neuritis-like syndrome 2 weeks after the last IgG infusion which had resolved spontaneously by the next day. Severe allergic reactions were observed in 3 patients after repeated injections of the MAb. These 3 patients had high levels of human anti-murine antibodies (HAMA). Four weeks after the first application of MAb BW 494, 17/18 patients presented with HAMA (IgG). It could be demonstrated that the anti-murine response was in part anti-idiotypic. At the moment 16/34 patients are eligible for evaluation of tumor response. There was no complete or partial remission; however, 2 patients responded with minor tumor regression up to 32 weeks documented by reduction of liver metastases and primary tumor in CAT scan. Five additional patients presented with a long period of stable disease after immunotherapy (up to 40 weeks). Nine patients had progressive tumor disease in spite of MAb treatment.
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PMID:Immunotherapy of pancreatic cancer with monoclonal antibody BW 494. 316 51

A 32-year-old woman with a contraceptive history of use of combination contraceptives (Oviston, Non-Ovlon) between 1966 and 1979 (with a 1-year interruption), followed by radical hysterectomy in 1979, complained of dull right upper quadrant pain, nausea, vomiting, and fatigue in 1980. Among various diagnostic studies performed only cholecystography and cholangiography demonstrated clear areas in the gallbladder assumed to be stones. Cholecystectomy performed in 1981 showed chronic inflammation of the gallbladder without stones. The undersurface of the liver revealed a greyish tumor (3 cm in diameter). Frozen section demonstrated mature hepatocellular adenoma. Wedge excision of the tumor and cholecystectomy were performed without complications. CAT-scan follow-up showed no residual pathology. Additional literature search reports 58 cases in western European and American journals. Diagnosis of these benign tumors is difficult because the symptoms are vague. The main complication is intraabdominal hemorrhage necessitating emergency lobectomy. Ligation of a branch of the hepatic artery is done in case of inoperability. CAT-scan and ultrasonography with selective angiography are the best procedures to ascertain the diagnosis. Needle biopsy is contraindicated because of the risk of hemorrhage.
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PMID:[Hepatocellular adenoma following long-term intake of ovulation inhibitors]. 630 51

The changes of locomotor activities in rat loaded with swimming exercise were recorded by our newly devised apparatus. In addition, changes of lipid peroxide levels and their related enzyme activities in rat brain, liver as well as blood were studied. The results obtained were as follows: 1. The locomotor activities in rat recorded by the apparatus showed the same patterns as that reported by the other researchers. 2. After the loading of swimming, locomotor activities in rat during the dark period decreased significantly as compared to those of the control. 3. The levels of TBARS (thiobarbituric acid reactive substance), SOD (superoxide dismutase) and GSH-px (glutathione peroxidase) in rat liver elevated after the swimming exercise in the first group, which was sacrificed after loading with one treatment (about 5 hours) exercise of swimming. 4. The level of TBARS in rat brain elevated after the swimming exercise in the second group, which was sacrificed after loading with two treatment exercise of swimming. 5. The level of TBARS in plasma decreased, and GSH-px, GR (glutathione reductase) and catalase in red blood cells elevated in the third group, which was sacrificed after two-hour rest following the loading with two treatment exercise of swimming. It is indicated that our newly devised apparatus is useful for monitoring locomotor activities in rat, and that the fatigue in rat caused by swimming load can be shown in terms of changes in the above activities. The elevation of the level of TBARS during the swimming exercise observed in tissues of the brain and liver may suggest that the lipid peroxidation will reflect a certain state of fatigue in rat.
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PMID:[Changes of locomotor activities, lipid peroxide levels and their related enzyme activities in rat loaded with swimming exercise (author's transl)]. 727 88

Cold injury is a tissue trauma produced by exposure to freezing temperatures and even brief exposure to a severely cold and windy environment. Rewarming of frozen tissue is associated with blood reperfusion and the simultaneous generation of free oxygen radicals. In this review is discussed the current understanding of the mechanism of action of free oxygen radicals as related to cold injury during rewarming. Decreased energy stores during ischaemia lead to the accumulation of adenine nucleotides and liberation of free fatty acids due to the breakdown of lipid membranes. On rewarming, free fatty acids are metabolized via cyclo-oxygenase and adenine nucleotides are metabolized via the xanthine oxidase pathway. These may be the source of free oxygen radicals. Leukocytes may also play a major role in the pathogenesis of cold injury. Oxygen radical scavengers, such as superoxide dismutase and catalase, may help to reduce the cold induced injury but their action is limited due to the inability readily to cross the plasma membrane. Lipid soluble antioxidants are likely to be more effective scavengers because of their presence in membranes where peroxidative reactions can be arrested.
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PMID:The role of free radicals in cold injuries. 760 50

We have previously shown that antioxidant enzymes (superoxide dismutase and catalase) depress contractility of unfatigued diaphragm fiber bundles and inhibit development of acute fatigue. In the present study, we tested for similar effects of N-acetyl-cysteine (NAC), a nonspecific antioxidant approved for clinical use. Diaphragms were excised from deeply anesthetized rats. Fiber bundles were removed, mounted isometrically at 37 degrees C, and stimulated directly using supramaximal current intensity. Studies of unfatigued muscle showed that 10 mM NAC reduced peak twitch stress (P < 0.0001), shortened time to peak twitch stress (P < 0.002), and shifted the stress-frequency curve down and to the right (P < 0.05). Fiber bundles incubated in 0.1-10 mM NAC exhibited a dose-dependent decrease in relative stresses developed during 30-Hz contraction (P < 0.0001) with no change in maximal tetanic (200 Hz) stress. NAC (10 mM) also inhibited acute fatigue. Throughout 10 min of intermittent contraction at 30-40 Hz, treated bundles developed higher stresses than time-matched control bundles (P < 0.0001). NAC concentrations > or = 30 mM were toxic, causing a prompt irreversible decrease in maximal tetanic stress (P < 0.0001). Because NAC effects mimic the effects of other antioxidant agents with different mechanisms of action, we conclude that exogenous antioxidants exert stereotypical effects on contractile function that differ between unfatigued and fatiguing muscle. Unlike antioxidant enzymes, however, NAC has been approved for clinical use and may be used in future studies of human muscle fatigue.
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PMID:N-acetylcysteine depresses contractile function and inhibits fatigue of diaphragm in vitro. 796 Dec 53


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