Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fatigue and lethargy, common symptoms in uraemia, have been attributed to many factors. To assess possible bioenergetic contributions to this, we examined the forearm muscle of five patients in end-stage renal failure using 31P-magnetic resonance spectroscopy. There was a small increase in the ratio of intracellular inorganic phosphate to ATP in resting muscle, suggesting an increased cytosolic phosphate concentration. During exercise, increased phosphocreatine breakdown was accompanied by rapid intracellular acidification and an increase in calculated lactic acid accumulation in the muscle of the uraemic subjects, suggesting glycolysis dominating over oxidative phosphorylation as a source of ATP. After exercise, the half-time of phosphocreatine (PCr) recovery was longer in the uraemic subjects, suggesting diminished mitochondrial function. The initial rate of PCr resynthesis was not significantly decreased, but when account was taken of the high cytosolic ADP concentration (which drives mitochondrial oxidative ATP synthesis) the calculated maximum oxidative capacity was significantly reduced in the uraemic subjects. Thus there was evidence of mitochondrial dysfunction in uraemia due either to limitation of oxygen supply, reduced mitochondrial content, or an intrinsic mitochondrial defect. This resulted in increased phosphocreatine depletion and increased glycolytic ATP production during exercise and there was partial compensation of the mitochondrial abnormality by increased ADP concentration. In three of these patients studied after elevation of haemoglobin with erythropoeitin (from 8 to 12 g/dl), initial phosphocreatine breakdown and lactic acid accumulation during exercise were normalized, while exercise duration and calculated maximum oxidative capacity remained significantly abnormal. This suggests that anaemia contributes to these metabolic abnormalities but does not fully explain them.
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PMID:Effect of chronic uraemia on skeletal muscle metabolism in man. 838 87

The microcirculatory state (by the method of conjunctival biomicroscopy) and ADP-induced platelet aggregation were examined in 42 patients with atherosclerotic and 34 patients with involutional depression both before and after the treatment which included vasoactive preparations and calcium antagonists. It was determined vascular and intravascular alterations predominance and increase of platelet aggregation in patients with atherosclerotic depression independently of leading syndrome, in patients with involutional depression with anxiety prevalence as well as in patients in stuporous state. The tendency was revealed of such disturbances increasing as for as psychosis was extended. Trental and Cavinton antiplatelet and spasmolytic properties were potentiated by inclusion of Corinfar in complex therapy and that promoted earlier microcirculatory alterations removal as well as aggregatograms and patient mental state normalization.
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PMID:[Changes in the microcirculatory rheological properties of the blood and their correction in patients with atherosclerotic and involutional depressions]. 858 81

The ice worm, Mesenchytraeus solifugus, is among a few metazoan species that survive exclusively in glacier ice/snow. In this study, we demonstrate that ice worm adenylate levels [i.e. adenosine 5'-triphosphate (ATP), ADP and AMP] are maintained at levels well above their mesophilic counterparts, and that their response to temperature change is distinctly opposite, namely, ice worms increase energy levels as temperatures fall. Initially, this response is characterized by a sharp spike in [ATP] and the adenylate energy charge (even at sub-zero temperatures), which is followed by corresponding increases in [ADP] and [AMP] within a few days. These results suggest that ice worms have evolved a compensatory mechanism by which gains in adenylate nucleotides off-set, at least in part, the inherent lethargy and death usually associated with cold temperature.
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PMID:The ice worm, Mesenchytraeus solifugus, elevates adenylate levels at low physiological temperature. 1472 Jun 8

The remarkable time-resolution enhancement by deep lethargic hypothermia (15 degrees C rectal temperature, "cold narcosis," "anesthesia by internal cold") of metabolic events in the rat brain after oxygen deprivation has been exploited to monitor metabolic changes by in vivo (31)P-NMR. A correlation was established between the bioenergetic status of the brain and physiological descriptors of tolerance (survival and revival times) determined in parallel experiments with large series of animals. Spectral peak integrals were transformed into absolute concentrations by comparison to biochemically determined time series of data obtained in freeze-trapping experiments conducted under identical conditions. Serial spectra were used to reconstruct the time-course kinetics of intracellular brain pH and of concentration changes of inorganic phosphate, phosphocreatine, ATP, and ADP. Both the biochemical and NMR time series of data were simultaneously fitted by a set of exponential kinetic equations accounting for relationships imposed by the Lohmann and adenylate kinase reactions. Depletion profiles were then computed for a number of descriptors of brain energy status (energy charge, phosphorylation potential, total adenylate, and primary energy stores expressed as the sum of high-energy phosphate-bond equivalents). The results contribute to the understanding of the role of brain energetics in tolerance to oxygen deprivation.
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PMID:Brain energetics and tolerance to anoxia in deep hypothermia. 1615 18