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

Mood changes following ingestion of dextroamphetamine (D-AMP) or methylphenidate (MPH) were examined in 40 narcoleptic patients. The Profile of Mood Status (POMS) and eight additional adjectives describing feelings were used to quantify changes in mood before taking stimulant medication and approximately 90 minutes after ingestion of medication. No significant differences were found between the effects of the two stimulants. When the data from D-AMP and MPH were combined, significantly higher ratings on the POMS factor of Vigour-Activity and the adjectives of 'confident', 'talkative' and 'competitive' were found. Lower ratings after medication were noted for the POMS factors of Fatigue-Inertia, Depression-Dejection and Confusion-Bewilderment (all P < 0.001). These effects are similar to those previously reported in normal subjects as well as in certain other patient populations. The findings indicate a possible therapeutic role of stimulant medication not only for the treatment of excessive sleepiness but also for improving affect, motor and mental vigour, and aspects of cognition.
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PMID:Acute mood improvement after dextroamphetamine and methylphenidate in narcolepsy. 1060 64

The aim was to investigate metabolic response in muscle during submaximal treadmill exercise to fatigue, with a special emphasis on adenine nucleotide degradation products such as inosine monophosphate (IMP) in muscle and hypoxanthine, xanthine and uric acid in plasma. Five Standardbred trotters performed treadmill exercise on 2 occasions, once at 7 m/s and once at 10 m/s. Venous blood samples were taken at rest, during exercise and at the end of exercise. Muscle biopsies were taken before and after exercise and muscle temperature was measured before and after exercise. Running time differed among horses and was 48-58 min at 7 m/s and 10-15.5 min at 10 m/s. Both lactate and uric acid concentrations in plasma showed a gradual increase during exercise at both 7 and 10 m/s. At the end of exercise, values for uric acid were higher and values for lactate lower at 7 m/s compared with at 10 m/s. No marked changes were seen in plasma concentrations of hypoxanthine or xanthine with exercise. Muscle glycogen decreased after exercise at both 7 and 10 m/s with a marked depletion seen in some fibres. Muscle lactate concentrations increased after exercise at both 7 m/s and at 10 m/s. No significant changes were seen in adenosine triphosphate (ATP), ADP and AMP concentrations, whereas IMP concentrations increased after exercise at both 7 m/s and at 10 m/s. The results of this study indicate that AMP deamination occurs with submaximal exercise and that development of fatigue may be related to adenine nucleotide degradation in muscle.
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PMID:Muscle adenine nucleotide degradation during submaximal treadmill exercise to fatigue. 1065 72

The aim was to study metabolic response and locomotion pattern in Standardbred trotters during incremental treadmill exercise performed by increasing speed by 1 m/s in 1 min steps (start 7 m/s) until the onset of fatigue. The test protocol included determination of oxygen uptake, heart rate (HR), stride length (SL) and stride frequency (SF). Venous blood samples were collected at rest, at the end of each exercise step and after 30 min of recovery. Muscle biopsies were taken at rest and post exercise and muscle temperature was measured after exercise. As horses fatigued at different speed steps (9-11 m/s), variation was seen in running time (180-300 s), oxygen uptake (109-170 ml/kg bwt min), HR (200-225 beats/min), SL (4.4-5.7 m) and SF (116-130 strides/min) at the last speed step. Increased mean plasma lactate concentration (20.5 mmol/l) was seen at onset of fatigue and increased mean uric acid concentration after 30 min of recovery (112.8 mumol/l). After exercise, a decrease was seen in muscle ATP (7.1 mmol/kg d.w.), creatine phosphate (43.9 mmol/kg d.w.) and glycogen (160 mmol/kg d.w.), and an increase was seen in ADP (0.3 mmol/kg d.w.), AMP (0.18 mmol/kg d.w.), IMP (5.8 mmol/kg d.w.) and lactate (100.8 mmol/kg d.w.). At onset of fatigue, muscle temperature varied from 39.9-41.4 degrees C. Running time correlated with SL (r = 0.86), with an increase in IMP (r = 0.79) and AMP (r = 0.70) post exercise and with plasma uric acid concentration (r = 0.74) at 30 min of recovery. SF correlated negatively with the increase in ADP after exercise (r = 0.85). The results of this study indicate that running time during incremental treadmill exercise until the onset of fatigue is related to locomotion pattern and to a marked degree of anaerobic metabolism, especially adenine nucleotide degradation.
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PMID:Incremental treadmill exercise until onset of fatigue and its relationship to metabolic response and locomotion pattern. 1065 79

We investigated the effects, and the mechanism of the effects, of isoproterenol on diaphragmatic contractility and fatigue in septic peritonitis in vitro. Ninety-six rats were divided into two groups of 48. One group (CLP group) was treated with cecal ligation and perforation (CLP) and the other (sham group) was treated with laparotomy. The left hemidiaphragm was removed at 16 h after the operation. We assessed the diaphragmatic contractility by twitch characteristics and force-frequency curves in vitro. Diaphragm fatigue was induced by rhythmically stimulating strips to contract at 60/ min (20 Hz, 0.33-s trains, 1 train/s) over a 4-min period. Force-frequency curves were determined before and after fatigue. Isoproterenol (10(-9), 10(-8), and 10(-7) M), a beta-adrenoceptor agonist, was cumulatively administered to the organ bath. Isoproterenol significantly increased diaphragmatic contractility. There were no significant changes in diaphragmatic contractility in the sham group. Isoproterenol (10(-7) M) significantly accelerated diaphragmatic recovery of fatigue and increased cAMP levels both in the sham group and the CLP group. Propranolol (10(-7) M), a general beta-adrenoceptor blocker, completely abolished the positive inotropic effect of isoproterenol (10(-7) M) and increased cAMP levels in the CLP group. Dibutyryl cAMP (10(-3) M), a derivative of cyclic AMP, mimicked the effects of isoproterenol in the CLP group. These results suggest that isoproterenol increases diaphragmatic contractility and accelerates diaphragmatic recovery of fatigue in septic peritonitis by activating the adenylate cyclase system.
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PMID:Effects of isoproterenol on diaphragmatic contractility in septic peritonitis. 1067 83

The aim of the present study was to investigate the effect of creatine (Cr) supplementation on muscle metabolic response in connection with a maximal treadmill exercise test, known to cause a marked anaerobic metabolic response and adenine nucleotide degradation. First, 6 Standardbred trotters performed a standardised maximal exercise test until fatigue (baseline test). The test used was an inclined incremental treadmill test in which the speed was increased by 1 m/s, starting at 7 m/s, every 60 s until the horse could no longer keep pace with the treadmill. After this baseline test, the horses were separated into 2 equal groups. One half received a dose of 25 g creatine monohydrate twice daily, and the other group were given the same dose of lactose (placebo). The supplementation period was 6.5 days, after which the maximal treadmill exercise test was performed again. A washout period of 14 days was allowed before treatments were switched between groups and a new supplementation period started. After this second supplementation period a new maximal exercise test was performed. After supplementation with creatine or placebo, horses were stopped after performing the same number of speed steps and duration of exercise as they had in the baseline test. Blood samples for analysis of plasma lactate, creatine (Cr), creatinine, hypoxanthine, xanthine and uric acid concentrations were collected at rest, during each speed step and during recovery. The total blood volume (TBV) was also determined. Muscle biopsies for analysis of muscle metabolites (adenosine triphosphate [ATP], adenosine diphosphate [ADP], adenosine monophosphate [AMP], inosine monophosphate [IMP], creatine phosphate [CP], lactate [La] and glycogen) were taken at rest, immediately post exercise and after 15 min recovery. The results showed no significant increase in plasma Cr or muscle total creatine concentration (TCr) after supplementation with Cr. At the end of exercise ATP and CP concentrations had decreased and IMP and lactate concentrations increased in muscle in all groups. Plasma lactate concentration increased during exercise and recovery and plasma uric acid concentration increased during recovery in all groups. No influence could be found in TBV after supplementation with creatine. These results show that creatine supplementation in the dosage used in this study had no influence on muscle metabolic response or TBV.
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PMID:Effect of creatine supplementation on muscle metabolic response to a maximal treadmill exercise test in Standardbred horses. 1109 28

This study was designed to investigate the effects on single skeletal muscle fibers of a novel thienylhydrazone, referred to as LASSBio-294, which is a bioisoster of pyridazinone compounds that inhibit the cyclic AMP-specific phosphodiesterase (PDE) 4. Twitch and fatigue were analyzed in single skeletal muscle fibers isolated from either the semitendinous or the tibialis anterior muscles dissected from the frog Rana pipiens. LASSBio-294 (12.5-100 microM) increased twitch tension, accelerated the maximal rate of tension decay during relaxation, and had very little effect in the maximal rate of tension development of muscle fibers directly stimulated at < or =30 Hz. The positive inotropic effect of LASSBio-294 developed slowly, reaching its maximum at 40 min and was inversely proportional to the frequency of stimulation, becoming negligible at 60 and 90 Hz. The concentration-response relationship for LASSBio-294-induced potentiation of twitch tension was bell-shaped, with maximal effect occurring at 25 microM. In addition, LASSBio-294 reduced development of fatigue induced by tetanic stimulation of the muscle fibers and reduced the time needed for 80% prefatigue tension recovery after fatigue had developed to 50% of the maximal pretetanic force. These effects of LASSBio-294 can be fully explained by stimulation of the sarcoplasmic reticulum Ca2+ pump and could be ascribed to an increase in cellular levels of cyclic AMP due to PDE inhibition. The novel thienylhydrazone LASSBio-294 may be useful for treatment of patients suffering from conditions in which muscle fatigue is a debilitating symptom (e.g., chronic heart failure).
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PMID:A novel thienylhydrazone, (2-thienylidene)3,4-methylenedioxybenzoylhydrazine, increases inotropism and decreases fatigue of skeletal muscle. 1160 67

Glycolytic flux in white muscle can be increased several-hundredfold by exercise. Phosphofructokinase (PFK; EC 2.7.1.11) is a key regulatory enzyme of glycolysis, but how its activity in muscle is controlled is not fully understood. In order not to neglect integrative aspects of metabolic regulation, we have studied in frogs (Rana temporaria) a physiological form of muscle work (swimming) that can be triggered like a reflex. We analysed swimming to fatigue in well rested frogs, recovery from exercise, and repeated exercise after 2 h of recovery. At various times, gastrocnemius muscles were tested for glycolytic intermediates and effectors of PFK. All metabolites responded similarly to the two periods of exercise, with the notable exception of fructose 2,6-bisphosphate (F2,6P(2)), which we proved to be a most potent activator of frog muscle PFK. The first bout of exercise triggered a more than 10-fold increase in F2,6P(2); PFK activity and the content of F2,6P(2) in muscle were well correlated. F2,6P(2) decreased to pre-exercise levels in fatigued frogs and it virtually disappeared during recovery. Varying by a factor of 70, F2,6P(2) was the most dynamic of all metabolites in muscle. Even more surprisingly, F2,6P(2) did not respond at all to a second bout of exercise. Other activators of PFK, such as Pi, AMP and ADP, are increased as a consequence of increased ATP turnover in contracting muscle cells. This does not apply to F2,6P(2) which is likely to respond to extracellular signals and could be involved in mechanisms by which muscle metabolism is integrated into the metabolism of the whole body. Whether this phenomenon exists in vertebrates other than the frog, and maybe even in humans, and how the content of F2,6P(2)in muscle is controlled are intriguing open questions.
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PMID:Different modes of activating phosphofructokinase, a key regulatory enzyme of glycolysis, in working vertebrate muscle. 1202 62

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

Objective. To observe the effect of sustained +Gx exposure on contractility of rat diaphragm and explore its mechanism. Method. Forty-two male Wistar rats were randomly divided into control group (underwent +1 Gx exposure, n=21) and experiment group (underwent +15 Gx for 3 min, n=21). The tension of rat diaphragm in vivo, contents of nucleoside phosphates and lactic acid in diaphragm and ultrastructure of diaphragm were measured and observed respectively. Result. 1) Compared with pre- +Gx, low-frequency tension of diaphragm of experiment group decreased significantly (P<0.01), whereas high-frequency tension did not significantly decrease after +Gx (P>0.05). As to the control group, however, the tension of diaphragm tested at a wide range of frequencies was almost unchanged (P>0.05). 2) Compared with control group, ATP decreased (P<0.01), while ADP and lactic acid contents in diaphragm increased significantly (P<0.05 and P<0.01) after +Gx in experiment group. In addition, ratios of ADP/AMP and AMP/ATP increased significantly (P<0.01). 3) After +Gx exposure, hypoxic changes in ultrastructure of rat diaphragm occurred in experiment group, but not in control group. Conclusion. Sustained +Gx exposure could cause diaphragm muscle fatigue, which was possibly due to changes in energy metabolism and ultrastructure of rat diaphragm induced by hypoxia under +Gx stress.
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PMID:[Effects of +Gx stress on contractility of rat diaphragm and its mechanism]. 1244 37

The pathogenesis of neurological sequelae in glutaric aciduria I (GA I) is still unclear. Some evidence exists for compromised energy generation in the brain of patients with GA I resulting in 'slow-onset' excitotoxicity. Previously, we have shown a reduced activity of the mitochondrial ATPsynthase in cultured mixed cortex cells from neonatal rats incubated with 2-4mM 3-hydroxyglutarate (3-OH glut) for 24h. In the present study we measured cellular contents of high energy phosphate compounds (creatinephosphate CP, ATP, and ADP) in this model after a 24h incubation period with 2-4mM glutarate (glut) or 3-OH glut. 3-OH glut specifically led to a reduction of CP content in a dose-dependent manner, whereas concentrations of ATP, ADP, and AMP remained unchanged. The drop in CP-concentration could be prevented by preincubation with the non-competitive NMDA-receptor antagonist MK 801 or coincubation with 1mM creatine. NMDA-receptor associated ion channels may be opened due to a lack of energy inside the neurons caused by a reduction of CP. This is followed by membrane depolarization which could impair electrogenic creatine transport into the cell.
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PMID:Glutaric aciduria I: creatine supplementation restores creatinephosphate levels in mixed cortex cells from rat incubated with 3-hydroxyglutarate. 1261 82


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