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)

Until recently, there was no specific therapy available for patients with Gaucher's disease. Since April 1991 a highly purified human placental preparation of glucocerebrosidase (Ceredase, Genzyme) has been available for clinical studies in Germany. Sequential deglycosylation of the native enzyme yields a mannose-terminated preparation that may preferentially bind to the plasma membrane of macrophages. The present report analyzes the first German (and European) long-term results with glucocerebrosidase therapy in five patients with type I Gaucher's disease (four women and one man, aged 29-40 years). All patients suffered from excessive enlargement of the liver and spleen with subsequent pancytopenia and from skeletal complications. Multiple pathological fractures had already occurred in three of the five patients, requiring several surgical procedures. Fatigue and asthenia were present in all patients. The initial dose of glucocerebrosidase was chosen according to the severity of complications in the individual patient (20-50 U/kg given i.v. every 2nd week) and was performed in the five patients for 12-18 months. After a few weeks all patients reported that fatigue and asthenia were markedly reduced. After 12 months, blood counts of erythrocytes, leukocytes and platelets had completely normalized in all but one of the patients. After 4-6 months a significant reduction in the sizes of liver and spleen could be observed in all patients. No further fractures occurred during treatment. Significant side-effects of glucocerebrosidase treatment did not occur. The new glucocerebrosidase preparation offers the first effective drug therapy for patients with Gaucher's disease. Although the treatment proved effective and harmless, it is, at least initially, very expensive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucocerebrosidase for treatment of Gaucher's disease: first German long-term results. 781 9

N-acetylcysteine (NAC) is a nonspecific antioxidant that selectively inhibits acute fatigue of rodent skeletal muscle stimulated at low (but not high) tetanic frequencies and that decreases contractile function of unfatigued muscle in a dose-dependent manner. The present experiments test the hypothesis that NAC pretreatment can inhibit acute muscular fatigue in humans. Healthy volunteers were studied on two occasions each. Subjects were pretreated with NAC 150 mg/kg or 5% dextrose in water by intravenous infusion. The subject then sat in a chair with surface electrodes positioned over the motor point of tibialis anterior, an ankle dorsiflexor of mixed-fiber composition. The muscle was stimulated to contract electrically (40-55 mA, 0.2-ms pulses) and force production was measured. Function of the unfatigued muscle was assessed by measuring the forces produced during maximal voluntary contractions (MVC) of ankle dorsiflexor muscle groups and during electrical stimulation of tibialis anterior at 1, 10, 20, 40, 80, and 120 Hz (protocol 1). Fatigue was produced using repetitive tetanic stimulations at 10 Hz (protocol 1) or 40 Hz (protocol 2); intermittent stimulations subsequently were used to monitor recovery from fatigue. The contralateral leg then was studied using the same protocol. Pretreatment with NAC did not alter the function of unfatigued muscle; MVC performance and the force-frequency relationship of tibialis anterior were unchanged. During fatiguing contractions stimulated at 10 Hz, NAC increased force output by approximately 15% (P < 0.0001), an effect that was evident after 3 min of repetitive contraction (P < 0.0125) and persisted throughout the 30-min protocol. NAC had no effect on fatigue induced using 40 Hz stimuli or on recovery from fatigue. N-acetylcysteine pretreatment can improve performance of human limb muscle during fatiguing exercise, suggesting that oxidative stress plays a causal role in the fatigue process and identifying antioxidant therapy as a novel intervention that may be useful clinically.
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PMID:N-acetylcysteine inhibits muscle fatigue in humans. 798 4

Six subjects participated in a residential study assessing the effects of consuming beverages containing energy derived from ethanol or dextrose on total energy and macronutrient intake. On certain days, subjects had to consume four beverages containing a total of approximately 2400 or 4600 kJ, equivalent to 22% and 42% of energy intake under conditions in which no-beverages were required. Each of four conditions (2400 kJ ethanol, dextrose; 4600 kJ ethanol, dextrose), and a no-beverage control condition was examined for 2 days. Subjects compensated for approximately 37% of the energy contained in the beverages such that total intake increased by 13% under the 2400 kJ conditions and 27% under the 4600 kJ conditions. There was no differential effect of ethanol content on energy intake. Cumulative intake curves indicated that caloric compensation was minimal following the consumption of beverages in the evening. While all of the beverage conditions significantly decreased energy intake derived from carbohydrate, the proportion of energy derived from fat, carbohydrate, and protein without the energy content of the beverages was essentially unaffected by dextrose- or ethanol-containing beverages. These results suggest that the effects of ethanol on intake of other foods can be accounted for by the energy content of ethanol as a beverage and by ethanol consumption in the evening when there is little time for daily caloric compensation, rather than by the pharmacological effects of ethanol.
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PMID:Ethanol as an energy source in humans: comparison with dextrose-containing beverages. 850 71

Three cases are reported of hypoglycemia manifested by profound sinus bradycardia and fatigue, which responded to i.v. dextrose with prompt normalization of the cardiac rhythm. The cases involved 3 different patients and disease processes: a young female who had anorexia nervosa and profound malnutrition; an elderly, nondiabetic male who subsequently experienced a transient ischemic attack: and a patient who had diabetes mellitus managed with chronic, subcutaneous insulin administration. It is vitally important that the emergency physician recognize unusual clinical manifestations of hypoglycemia and fully evaluate such scenarios when hypoglycemia may occur. Untreated, hypoglycemia may result in significant chronic morbidity, and rarely, in death. Bradyarrhythmias--particularly sinus bradycardia--should be added to the list of potential clinical manifestations of hypoglycemia.
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PMID:Hypoglycemia manifested by sinus bradycardia: a report of three cases. 881 87

To evaluate the influence of a high-O2 affinity of the erythrocyte and of flow rate on muscle's ability to extract O2 and develop force, we perfused dog gastrocnemius contracting isometrically at 4 Hz with normal-O2-affinity perfusate or high-O2-affinity perfusate at high and moderate flows (200 and 100 ml . min-1 . 100g-1, respectively). High-O2-affinity perfusate was prepared by incubating human citrate-phosphate-dextrose-stored erythrocytes with buffered saline containing cyanate (4 degrees C, 18 h) and normal-affinity perfusate by storing 2,3-diphosphoglycerate-rejuvenated erythrocytes in the same solution without cyanate. PO2 when blood is half oxygenated was 30.6 Torr for normal perfusate and 18.1 Torr for high-affinity perfusate. During 4-Hz stimulation, the tension developed by the muscle increased incrementally (positive staircase) to reach a peak value after 1.2-1.6 min for the normal perfusate and 0.6-0.7 min for the high-affinity perfusate (P < 0.05). The rate of decline during the early fatigue (measured from the onset of tension decline to 3 min) with high-affinity perfusate was significantly faster than it was with normal perfusate (P < 0.05). These findings suggest that both the staircase effect and the early fatigue are related to O2 availability, which is restricted when erythrocytes have a high O2 affinity. The peak O2 uptake values measured at 3 and 5 min were significantly lower (by 14-24%) with high-affinity perfusate than with normal perfusate at a given level of O2 delivery (arterial O2 content x flow) (P < 0.05). PO2 of venous effluent was proportionally related to peak O2 uptake. The present results indicate that neither blood flow nor O2 delivery is the sole determinant of the muscle's ability to extract O2.
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PMID:Flow-dependent influence of high-O2-affinity erythrocytes on peak VO2 in exercising muscle in situ. 896 44

The aim of this study was to examine whether ingesting water alone, or dextrose (7.5 g x 100 ml(-1)) with electrolytes, or fructose/corn solids (7.5 g x 100 ml(-1)) (400 ml every 20 min) would reduce the perceived exertion associated with 16 km (3 h) walking/running in the heat compared with that perceived during exercise with no fluid intake. Perceived exertion was assessed at 1-h intervals during exercise. Blood samples, required for analysis of blood glucose, plasma sodium, plasma osmolality and plasma volume, were obtained prior to exercise and at 1-h intervals during the exercise; further samples were obtained 1-h intervals for 3 h following the exercise. Drinking fluids at regular intervals reduced the level of perceived exertion. In the test during which no fluid was ingested, body mass decreased by 4.9 (0.4) kg [mean (SEM)], but decreased less with ingestion of either the dextrose/electrolytes or fructose/corn solids solutions, or water alone [1.3 (0.2) kg, 1.6 (0.3) kg and 2.0 (0.1) kg, respectively]. Plasma volume fell by 17% when taking no fluid, but fell less when ingesting fluids. Blood glucose fell significantly (P < 0.01) when taking no fluid and rose to 8.4 (1.3) mmol x l(-1) (P < 0.001) and 6.8 (1.1) mmol x l(-1) (P < 0.01) with ingestion of the dextrose/electrolytes or fructose/corn solids solutions, respectively. Urine output was greater with ingestion of water than with any of the other drinks. Six subjects experienced fatigue during exercise with no fluid and failed to complete the exercise. These results suggest that fatigue was caused by several interacting factors: a fall in blood glucose and plasma volume, dehydration, and neuroglycopenia. Taking fluids during exercise reduced the strain and the rating of perceived exertion; this was better achieved by ingesting a dextrose/electrolytes solution.
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PMID:Dehydration in soldiers during walking/running exercise in the heat and the effects of fluid ingestion during and after exercise. 940 63

Heat-related illnesses cause 240 deaths annually. Although common in athletes, heat-related illnesses also affect the elderly, persons with predisposing medical conditions and those taking a variety of medications. Symptoms range from mild weakness, dizziness and fatigue in cases of heat edema, to syncope, exhaustion and multisystem complications, including coma and death, in cases of heat stroke. Milder heat-related symptoms can be treated with hydration, rest and removal from the hot environment. Heat stroke, a life-threatening problem, must be treated emergently. Prompt recognition is critical since rapid cooling is the cornerstone of treatment and must not be delayed. Fluid resuscitation with dextrose and normal or half-normal saline is also important. These therapies should be instituted while the patient is being stabilized. Heat illness may be prevented by recognizing which individuals are at risk, using appropriate hydration and paying attention to acclimatization and environmental conditions. Preventive care should include drinking plenty of fluids before, during and after activities, gradually increasing the time spent working in the heat and avoiding exertion during the hottest part of the day.
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PMID:Heat-related illnesses. 975 May 42

Ten physically active, untrained, college-aged males (26.4 +/- 5. 8 years old) received creatine (CR, 5 g creatine monohydrate + 3 g dextrose) and placebo (PLA, 7 g dextrose) supplementation four times per day for 5 days in a double-blind, randomized, balanced, crossover design. Performance was assessed during maximal and three repeated submaximal bouts of isometric knee extension and handgrip exercise. CR supplementation significantly increased (p <.05) maximal isometric strength during knee extension but not during handgrip exercise. CR supplementation increased time to fatigue during each of the three bouts of submaximal knee extension and handgrip exercise when compared to the PLA trials. These findings suggest that CR supplementation can increase maximal strength and time to fatigue during isometric exercise. However, the improvements in maximal isometric strength following CR supplementation appear to be restricted to movements performed with a large muscle mass.
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PMID:Creatine supplementation differentially affects maximal isometric strength and time to fatigue in large and small muscle groups. 1036 51

Because the haemoglobin concentration Hb[ during exercise may be at the upper limit of blood viscosity for effective oxygen delivery, we hypothesised that administration of blood would not further enhance oxygen delivery or exercise capacity. Six Thoroughbred geldings were used in 5 incremental treadmill exercise tests over a period of 4 weeks. The first test was performed 6 days prior to phlebotomy, which involved the removal of 20 ml/kg bwt of venous blood. Exercise tests were performed at 1, 8 and 15 days after blood removal. Six days after the 15 day post phlebotomy exercise test, blood from each horse was reinfused and the final test performed 24 h after blood reinfusion. During the 3 weeks following blood collection, the blood, collected into acid citrate dextrose, was stored at 3 degrees C. Each exercise test involved measurements of arterial and mixed venous blood gases, plasma lactate concentrations, heart rate and VO2 using an open flow system. Cardiac output was measured by direct Fick. The removal and reinfusion of blood had significant effects on packed cell volume (PCV) with the lowest PCV value during exercise of 0.57 +/- 0.04 l/l being recorded in the second post phlebotomy test and the highest value of 0.67 +/- 0.04 l/l found after blood reinfusion. There were no significant effects of phlebotomy or blood reinfusion on arterial blood gas values. However, arteriovenous oxygen content difference was significantly altered by phlebotomy and reinfusion. The maximal values during the 3 tests following phlebotomy were significantly lower (P < 0.05) by about 7% than those before phlebotomy and after blood reinfusion, mirroring the alterations in Hb[. There was no significant effect of phlebotomy or blood reinfusion on heart rate but stroke volume was significantly higher (P < 0.01) during the 3 post phlebotomy tests than for the control or blood reinfusion tests. There was no significant effect of phlebotomy or blood reinfusion on either the submaximal or maximal values for VO2. No significant effect of blood removal or reinfusion was found on the treadmill run time to fatigue. We concluded that haemodynamic adjustments following phlebotomy or blood reinfusion maintained oxygen delivery during exercise. No detrimental effects on exercise capacity were found from phlebotomy nor beneficial effects from autologous blood transfusion. However, it should be noted that the extent of change induced in Hb[ was relatively small and with the number of horses in the study, the experimental power was not great.
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PMID:Effects of phlebotomy and autologous blood transfusion on oxygen transport in the racehorse. 1065 39

The aim of this study was to assess, by positron emission tomography (PET), the effect on cerebral functional activity of a new lorazepam-gamma-aminobutyric acid (GABA) conjugate [3-(4-acetamido)-butyrril lorazepam (DDS2700)]. Ten healthy volunteers were studied by PET and [18F]fluoro-deoxy-D-glucose ([18F]FDG) under baseline conditions and following the administration of DDS2700. Regional cerebral blood flow (rCBF) was measured by PET and 15O-water in three additional participants while they performed attentive tasks, before and after drug administration. DDS2700 induced a decrease in the regional cerebral metabolic rate of glucose (rCMRglu) in the thalamus (-17%), cerebellum (-11%) and caudate nucleus (-8%). The observed effects on glucose metabolism were probably related to the subjective sedation and tiredness reported by the participants. During the attentive tasks, rCBF increased in frontal and temporal regions associated with attentional processing of auditory material. These circuits were no longer active after DDS2700 administration, while rCBF increased in cingulate cortex, occipitoparietal regions, pons and cerebellum. These drug-induced activations might be directly related to intervening sleepiness and to the consequent effort in keeping attention focused on the tasks. The effects of DDS2700 on glucose metabolism at rest, and on rCBF during activation conditions, indicate a drug action on cerebral networks involved in alertness, vigilance and attention maintenance. PET assessment by [18F]FDG and water may provide complementary information in pharmacodynamic studies.
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PMID:Acute effect of 3-(4-acetamido)-butyrril-lorazepam (DDS2700) on brain function assessed by PET at rest and during attentive tasks. 1133 50


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