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 effect of dibutyryl 3',5'-cyclic monophosphate (D-cAMP) on the neuromuscular transmission was studied in a patient with myasthenia gravis during anesthesia. D-cAMP caused a slight increase in single twitch tension, and an initial transient decrease in tension which resulted from the trains of 2 Hz stimuli disappeared after D-cAMP. The finding of the present study suggests that D-cAMP has an anti-fatigue effect in patients with myasthenia gravis.
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PMID:Effect of dibutyryl cyclic AMP on neuromuscular transmission in myasthenia gravis. 18 50

Three fractions of rat adenosine-3',5'-monophosphate-dependent protein kinase were isolated, partially purified in buffer concentration gradient at normal state and after long-term physical loading and studied. It is found that first two fractions of protein kinases at normal state and after intensive muscular work have similar activities with and without cAMP, apparent Km values for ATP and total histone and half-maximal stimulation by cyclic AMP, but they differed from the third fraction. There are differences in some kinetic parameters and in the cyclic AMP stimulated activities between protein kinases after physical loading. The data obtained suggest the existence of at least two kinases in rat skeletal muscle. The isoenzymes differ in their activities during fatigue.
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PMID:[Several properties of 3':5'-AMP-dependent skeletal muscle protein kinases in normal rats and following physical exertion to fatigue]. 21 65

The relationship between variations in diaphragmatic contractility and corresponding changes in total tissue levels of 45Ca and adenosine 3',5'-cyclic monophosphate (cAMP) was examined. The contractile performance of perfused contracting rat diaphragms was manipulated with theophylline (10(-4) M), induced fatigue, or both. The increased contractility associated with theophylline was related to significant increases in 45Ca levels without changes in cAMP levels. Fatigue-diminished contractility was associated with increases in both 45Ca and cAMP levels. The increased 45Ca and cAMP levels associated with fatigue persisted, even in the presence of theophylline. Calcium channel blockade with 10(-4) M verapamil blocked the positive inotropic influence of theophylline as well as the theophylline-associated increase in 45Ca levels. Verapamil had no effect on either the fatigue-associated decreases in contractility or the fatigue-enhanced 45Ca uptake. The results of this study strongly suggest that the enhanced contractility associated with theophylline is related to its influence on cellular calcium metabolism. The elevated level of isotopic calcium measured in fatigued muscle probably represents calcium sequestered in the sarcoplasmic reticulum, the result of cAMP-enhanced Ca-adenosine triphosphatase activity.
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PMID:Theophylline, fatigue, and diaphragm contractility: cellular levels of 45Ca and cAMP. 165 Jul 69

The mechanosensory neuron that innervates the anteronotopleural bristle of Drosophila melanogaster responds with a burst of action potentials to deflection of the bristle towards the body wall. The decay of the firing rate upon sustained deflection is typical of a slowly adapting mechanosensory neuron. Upon repeated monotonous stimulation, the response decreases and the kinetics of adaptation change; the response recovers after rest. This sensory fatigue depends on the duration of the stimuli and the rate of stimulation. Two mutants, rutabaga (rut) and dunce (dnc), which are defective in learning and in the activity of the cAMP cascade, show altered kinetics of sensory fatigue. In rut, which has a reduced cAMP synthesis, the mechanosensory neuron fatigues less rapidly, whereas in dnc, characterized by a reduced cAMP hydrolysis, the neuron fatigues more rapidly than in wild-type flies. The data suggest that the cAMP cascade plays a role in the mechanism of sensory fatigue. Our study shows, for the first time, the effect of memory mutations on functional properties of an identified neuron which subserves a modifiable behavior. The experimental system described here could also be useful for neurogenetic dissection of mechanosensory transduction.
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PMID:Adaptation and fatigue of a mechanosensory neuron in wild-type Drosophila and in memory mutants. 215 60

We have investigated the effect of systemic treatment with drugs that affect the cAMP cascade on the sensory response and sensory fatigue in an identified mechanosensory neuron of Drosophila. Forskolin, an activator of adenylate cyclase, decreases the sensory response of the neuron. H7, an inhibitor of protein kinase, inhibits sensory fatigue. Octopaminergic ligands facilitate sensory fatigue. These results, together with our previous neurogenetic analysis of sensory fatigue in Drosophila (Corfas and Dudai 1990), corroborate the hypothesis that the cAMP cascade is involved in the generation and modulation of sensory fatigue.
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PMID:Pharmacological evidence for the involvement of the cAMP cascade in sensory fatigue in Drosophila. 217 30

A 40-year old female was admitted with complaints of general fatigue and dyspnoea brought on by effort. There were edema on the face, a diffuse and slightly hard goiter on the neck and non-pitting edema in the lower legs. Laboratory findings showed low levels of serum T3 (0.37 ng/ml) and T4 (2.0 micrograms/dl), a very high level of serum TSH (549.8 microU/l), positive thyroid test (x 400) and positive microsome test (x 102,400). The chest roentgenogram showed an enlargement (CTR 62%) of the cardiac silhouette in the shape an ice bag, and the electrocardiogram revealed low QRS voltage with T-wave flattening in all leads. Remarkable pericardial effusion was shown on the two-dimensional echocardiogram. Judging from the indications of hypothyroidism, positive antithyroid antibody and pericardial effusion. This patient was diagnosed as having myxedema heart due to chronic thyroiditis. The levels of plasma alpha-hANP did not elevate so much as the levels in normal controls after right atrial (RA) pacing, although mean right atrial pressure was higher than in normal controls after RA pacing. The levels of plasma alpha-hANP after RA pacing in euthyroid state were higher than those in hypothyroid state. The levels of plasma alpha-hANP after RA pacing became higher after the administration of ATP or db-cAMP both in euthyroid and hypothyroid states. These results indicate that the impaired alpha-hANP secretion in myxedema heart is improved by the administration of thyroxine, ATP or db-cAMP.
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PMID:[A case of myxedema heart showing the improvement of impaired alpha-hANP secretion by administration of ATP and dibutyryl cAMP]. 217 40

The roles of cAMP and inorganic phosphate (Pi) in the regulation of muscle glycogenolysis during exercise have been investigated in humans using the needle biopsy technique. The fraction of phosphorylase a in resting muscle was as a mean 23%, but the rate of glycogenolysis was extremely low. Epinephrine infusion increased cAMP in muscle by 3-fold and transformed 80% of phosphorylase to the a form. Despite this, the rate of glycogenolysis was only 5-10% of the maximum rate of phosphorylase a (Vmax a) determined in vitro. Isometric exercise for 25 s at 66% MVC or electrical stimulation for 50 s at 20 Hz transformed about 53% and 80% of phosphorylase in the a form. The rate of glycogenolysis ranged between 50-90 mmol.kg-1.dm.min-1 and was close to Vmax of phosphorylase a determined in vitro. No significant difference in the rate of glycogenolysis in muscle was observed after isometric exercise to fatigue without and with epinephrine infusion, respectively. Apparently the rate of glycogenolysis in muscle is not solely related to the fraction of phosphorylase in the a form. Several factors could be responsible for allosteric and/or substrate regulation. The results in the present studies can be explained on the basis of substrate regulation of phosphorylase activity, provided that Pi is present in a limiting amount at the active site of phosphorylase in muscle at rest. It is concluded that transformation of phosphorylase b to a is important but alone is not adequate for a high activity and thus for a high rate of glycogenolysis in muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of cyclic AMP and inorganic phosphate in the regulation of muscle glycogenolysis during exercise. 285 69

Hepatocytes from rats deprived of food for 48 h synthesized glucose and urea from glutamine at a rate which, at pH 7.3, was markedly stimulated (175-250%) by dibutyryl cAMP, phenylephrine, and norepinephrine, in agreement with previous investigators. These effectors also stimulated respiration, elevating ATP production by the amount required for the increase in glucose and urea synthesis. Both the basal and stimulated rates were strongly pH dependent with maxima in the region of pH 7.2-7.6 (urea synthesis) and 7.2-7.5 (glucose synthesis) and declined rapidly on either side of these pH values. The inhibitions at acid and alkaline pH were neither due to lack of energy nor to limitation in glutamine uptake. The intracellular concentrations of aspartate, glutamate, and glutamine were lower at pH 6.7 than at pH 7.3 and were differently affected by dibutyryl cAMP and phenylephrine at the two pH values investigated. When calcium was omitted from the suspending medium, the basal rates of glucose and urea production were decreased as was stimulation by the effectors, phenylephrine completely, and the others partially. The stimulations by phenylephrine and dibutyryl cAMP were additive under all conditions tested. The pattern of metabolite changes indicates that although both effectors stimulated glutaminase and increased supply of aspartate to the argininosuccinate synthetase, dibutyryl cAMP gave greater activation of glutaminase whereas the adrenergic agonists gave greater stimulation of later steps on the biosynthetic pathways. It may be physiologically important than at acid pH both ureagenesis and gluconeogenesis are severely suppressed and cannot be effectively stimulated by the major hormonal regulators of these pathways.
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PMID:pH dependence of hormonal regulation of gluconeogenesis and urea synthesis from glutamine in suspensions of hepatocytes. 298 Dec 10

A health survey was conducted on 199 workers engaged in dividing and packaging pyrethroids. The subjects were exposed to fenvalerate at 0.012-0.055 mg/m3 and deltamethrin at 0.005-0.012 mg/m3 in the air with simultaneous skin contact for 0.5-4.5 months. Burning sensations and tightness or numbness on the face appeared in two thirds of the subjects and one third had sniffs and sneezes. Abnormal facial sensations, dizziness, fatigue, and miliary red papules on the skin were more evident in summer than in winter. Neither abnormalities in other organs or systems nor symptoms or signs of acute pyrethroid poisoning were found by interviews, examinations, and laboratory tests. There was no significant difference in plasma levels of NA, cAMP, and cGMP between the examined subjects and the control group. The urine concentration of fenvalerate in the study group ranged from 1.02 to 18.6 micrograms/l; deltamethrin in the urine was present in trace amounts.
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PMID:Effects of pyrethroid insecticides on subjects engaged in packaging pyrethroids. 341 21

The regulation of glycogen phosphorylase and glycogen breakdown in human skeletal muscle has been investigated using the needle biopsy technique. Preliminary studies showed that the activity of phosphorylase in vitro was dependent upon the concentration of inorganic phosphate (Pi) used in the assay system. The Km of phosphorylase a for Pi was found to be 26.2 mmol/l, and that of (a+b) (assayed in the presence of saturating AMP) was 6.8 mmol/l. Because of the difference in Km the apparent percentage of a to (a+b) activity varies with the Pi concentration used in the assay system. Phosphorylase a and (a+b) activities were therefore adjusted to saturating Pi concentrations. The ratio of the activities in this case is independent of the Pi concentration and constitutes a minimal estimate of the fraction of phosphorylase molecules in the a form. The fraction of phosphorylase in the a form in resting muscle was as a mean 22%. Despite nearly a quarter of the phosphorylase being in the a form glycogenolytic activity is extremely low. It is proposed that the concentration of Pi at the active site of the enzyme is low compared to the Km for this of either form of the enzyme, and is limiting to activity. A Pi concentration in resting muscle of 1-3 mmol/l was calculated. During epinephrine infusion at rest 90% of the phosphorylase was transformed to the a form but only a moderate increase in the glycogenolytic rate occurred. This rate approximated to 5-10% of the maximum rate of the enzyme (Vmaxa). During prolonged epinephrine infusion the glycogenolytic rate decreased despite the continuance of 90% or more of the phosphorylase in the a form. In contrast to epinephrine infusion prolonged ischemia resulted in a decrease in the mole fraction of phosphorylase a and simultaneously in an increase of the glycogenolytic rate. During isometric and dynamic exercise there was a rapid transformation of phosphorylase b to a paralleled by pronounced increase in the rate of glycogen breakdown. The increased rate of glycogenolysis during isometric exercise was close to the Vmax of phosphorylase a in vivo. When either form of exercise was continued to fatigue/exhaustion, a re-transformation of phosphorylase a to b was observed. During dynamic exercise cAMP in the muscle increased two fold. This increase was blocked by the prior administration of propranolol.+
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PMID:The regulation of glycogen phosphorylase and glycogen breakdown in human skeletal muscle. 613 34


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