1,721,106 research outputs found

    Effets du vieillissement et de divers agents pharmacologiques sur le métabolisme énergétique cérébral au cours de la récupération post-hypoglycémique chez le rat

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    Severe acute hypoglycaemia with isoelectric electroencephalogram induces a major deterioration of the energy state and amino acid contents of the brain. During post-hypoglycaemia recovery of adult animals, brain glucose concentrations return to normal values, whereas glycogen turnover remains low as aspartate and pyruvate concentrations increase. ATP levels rise, but the adenine-nucleotide pool remains small despite return to normal of ADP and AMP. Brain phosphocreatine levels return to normal values, with reciprocal changes in creatine content. In adult rats one also notes during recovery an increase in brain glutamine and glutamate, whereas the gamma-aminobutyrate returns to normal. Finally, ammonium and aspartate remain below, and alanine remains above normal values. Aging has no effect on cerebral metabolic disturbances induced by hypoglycaemia, but it influences the cerebral metabolic restoration processes that develop during post-hypoglycaemia recovery. The restitution of cerebral metabolites is weaker in mature and senescent rats than in adult rats. In the oldest rats, in particular, the concentrations of most of the amino acids and of adenyl nucleotides remain largely abnormal. The effects of dihydroergocristine, erbunamonine, raubasine, almitrine and of the almitrine-raubasine combination on post-hypoglycaemia recovery were evaluated in adult, mature and senescent rats. During recovery these pharmacological agents exert different effects on glycolytic metabolites, amino acids and energy-rich phosphate

    Influence du vieillissement sur le métabolisme énergétique cérébral pendant la récupération post-hypoglycémique chez le rat - application pharmacologique

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    Influence of aging on cerebral energetic metabolism was evaluated during and after severe hypoglycemia in rats respectively 20 (adults), 60 (matures) or 100 (senescents) week-old. Cerebral content of carbohydrates, amino-acids, ammonia, ATP, ADP, AMP, creatine phosphate and creatine was analysed after 20 min insulin induced hypoglycemia and after 20 min hypoglycemic recovery induced by glucose infusion. In the rats of different ages tested, effect of raubasine (0.85 mg X kg-1 i.p. and i.v.), almitrine (2.68 mg X kg-1 i.p. and i.v.) and association almitrine plus raubasine (at the same doses) on post-hypoglycemic recovery was tested. Aging does not affect the cerebral metabolic disorders occurring in severe hypoglycemia, but rather the metabolic changes during the post-hypoglycemic restitution. In fact there is lower restitution of the concentrations of cerebral cortical metabolites in older rats: the concentrations of many amino-acids and adenylate nucleotides remains largely abnormal. Compared with saline treated post-hypoglycemic rats, raubasine decreases by 15 to 20\% cerebral glucose and pyruvate contents in "adults" and "matures" rats and by 10 to 15\% glutamate content in rat of different ages tested. Almitrine decreases by 20\% cerebral glucose concentration in "matures" and "senescent" rats. In this latter group, almitrine decreases lactate and ammonium contents and increases by 23\% glutamine level. In rats of all ages that were submitted to 20 min insulin induced hypoglycemia followed by 20 min glucose induced post-hypoglycemic recovery, the association almitrine plus raubasine decreases by 20 to 30\% cerebral glucose, pyruvate and lactate contents and decreases by 15\% glutamate. In older brains the association almitrine plus raubasine decreases by 50\% cerebral content in ammonium and concomitantly induces an equivalent increase in glutamine content. The effect of the combination almitrine plus raubasine is characterized by an increase in rate of metabolic recovery process in all ages teste

    Effects of hypoxia and pharmacological treatment on enzyme activities in skeletal muscle of rats of different ages

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    The activities of enzymes related to energy metabolism in the gastrocnemius and soleus muscles in young-adult (4 months), mature (12 months), and senescent (24 months) rats were compared after continuous (72 consecutive h) exposure to normobaric hypoxia or normoxia after the vasodilator naftidrofuryl or saline solution had been given intraperitoneally for 30 consecutive days. The maximum rats (Vmax) of the following enzyme activities in the crude extract and/or the crude mitochondrial fraction of each muscle specimen were evaluated for: the anaerobic glycolytic pathway (hexokinase, phosphofructokinase, pyruvate kinase, and lactate dehydrogenase), the tricarboxylic acid cycle (citrate synthase, and malate dehydrogenase), the electron transfer chain (cytochrome oxidase), and the NAD+/NADH redox state (total NADH cytochrome c reductase). The significance of differences between the enzyme activities at different ages or under different experimental conditions in the two tissue preparations of the two muscles were determined by ANOVA. MCA and ETA2 were used to evaluate the net effects of the experimental conditions. First, aging did not seem to affect the soleus and gastrocnemius muscles in the same way. In the gastrocnemius muscle, the major changes were seen in enzymes of the glycolytic pathway, in the crude extracts. In the soleus muscle, the more striking changes in enzyme activities as a function of aging were found in the crude mitochondrial fraction. We also found that hypoxia caused more important changes in 12-month-old rats than in those of other ages (especially the enzyme activities of the gastrocnemius muscle). Naftidrofuryl modified the effects of hypoxia only sometimes and further investigations are necessary before we can draw any conclusions about the pharmacological activity of naftidrofuryl in hypoxi

    Relationships between gamma-aminobutyrate and succinate cycles during and after cerebral ischemia

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    Some metabolites (glycogen, glucose, glucose-6-phosphate, pyruvate, lactate, citrate, alpha-ketoglutarate, succinate, fumarate, malate, glutamate, aspartate, gamma-aminobutyrate, glutamine, alanine, NH+4) were measured in rat cerebral cortex after 5 minutes of complete compression ischemia, as well as after 5, 15, or 30 minutes of recirculation following 5 minutes of ischemia. Complete ischemia induced a drop of glycolytic substrates and intermediates, consistent with the increase of lactate, succinate, alanine, and gamma-aminobutyrate, and with the decrease of malate, fumarate, and alpha-ketoglutarate. These events may be regarded as an expression of the activation of the gamma-aminobutyrate cycle and of the succinate cycle, where succinate itself, in the absence of O2, acts as a terminal electron acceptor. During post-ischemic recovery, cerebral parameters tended to normalize, except for the further increase of alanine and the still higher than normal content of both succinate and gamma-aminobutyrate, as an expression of the possible activation of the gamma-glutamyl and gamma-aminobutyrate cycles during recover

    In vitro action of uridine diphosphate glucose (UDPG) on phrenic diaphragm preparations

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    The action of uridine-5'-diphosphoglucose (UDPG) on the contractile response of the phrenic diaphragm preparation from guinea pig was investigated. UDPG activity was assayed on the preparation at rest or during the exercise; in this case indirect electrical stimulation of phrenic diaphragm preparation or direct stimulation of denervated or curarized muscle were employed. Krebs' solutions adequately modified with regard to glucose concentration were used. The effect of UDPG on the neuromuscular junction was also investigated by recording miniature end plate potentials. An effect of the drug on neuromuscular transmission and on glucose metabolism could be demonstrate
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