Search PubMed⌕ Search

Biomedical subjects

R F Villa

Publications and source records attributed to R F Villa.

At least 73 records · Page 4Linked to original sources
PubMed1984

Role of drugs in recovery of metabolic function of rat brain following severe hypoglycemia.

Severe hypoglycemia with isoelectric EEG induced extensive deterioration of the energy state and gross alteration of amino acid contents on the rat cerebral and cerebellar cortex. During recovery, tissue glucose concentration returned to normal, while both lactate and pyruvate concentrations increased to above normal. In the recovery period, the ATP concentration increased but the adenine nucleotide pool remained reduced, even if the ADP and AMP contents were close to normal. Phosphocreatine was restored to normal concentration with reciprocal changes in creatine content. During recovery there was a rise in glutamate and glutamine concentrations, gamma-aminobutyrate content returning to normal value. Ammonia and aspartate decreased below normal, while alanine increased above normal. The effect of some pharmacological agents on the posthypoglycemic recovery was tested: (a) Ergot alkaloids (dihydroergocristine, dihydroergocriptine, dihydroergocornine); (b) Vinca minor alkaloids (vincamine TPS, (-) eburnamonine); (c) Rauwolfia serpentina alkaloids (reserpine, raubasine); (d) synthetic agent (piracetam). During the posthypoglycemic recovery, these different agents exhibited different, or even contrasting, interferences on glycolytic metabolites, amino acids and energy-rich phosphates. The metabolic alterations in the cerebellar cortex were qualitatively of the same character of those in neocortex. However, the metabolic alterations were less extensive and more sensitive to drug action.

Amino Acids↗
PubMed1984

Effect of aging on cerebral cortex energy metabolism in hypoglycemia and posthypoglycemic recovery.

Severe hypoglycemia, causing the cessation of spontaneous EEG, induced in cerebral cortex of rats of different ages, causes gross energy failure and extensive derangement of both carbohydrate and amino acid contents. During posthypoglycemic recovery of adult rats, there was moderate restitution of energy metabolism and both ATP concentration and adenine nucleotide pool remained still reduced, even if the creatine phosphate and ADP contents were close to normal. During recovery of adult rats there was a rise in glutamate and glutamine concentrations and the perturbated aspartate and gamma-aminobutyrate cerebral contents normalized. Ammonia content decreased to normal, while alanine content was markedly elevated. Aging does not affect the cerebral metabolic derangements occurring in severe hypoglycemia, but rather the metabolic changes that the brain tend to reverse during the posthypoglycemic restitution. In fact, there was lower restitution of the contents of cerebral cortical metabolites of "mature" and "senescent" rats in comparison with "adult" ones. Particularly, in older brains the contents of many amino acids and adenylate nucleotides remained largely abnormal.

Adenine Nucleotides↗
PubMed1984

Effect of ischaemia and pharmacological treatment on enzyme activities of cortical mitochondria and synaptosomes.

Changes in the maximal rate of some enzymatic activities related to energy transduction (lactate dehydrogenase; citrate synthetase and malate dehydrogenase; total NADH-cytochrome c reductase and cytochrome oxidase) and others such as glutamate dehydrogenase and acetylcholine esterase were assayed both in the purified mitochondrial fraction and in the crude synaptosomal fraction from the cerebral cortex of rats. The evaluations were performed before and after a postdecapitative normothermic ischaemia of 5, 10, 20 and 40 min duration. The ischaemic damage resulted in a decrease in the activity of mitochondrial malate dehydrogenase and total NADH-cytochrome c reductase, and of synaptosomal acetylcholine esterase. The biochemical evaluations were performed also after an intraperitoneal pretreatment with vincamine TPS, trimetazidine DC and suloctidil (50 mg/kg). These drugs induced different changes in enzyme activities as a function of the duration of ischaemia. These various interferences are discussed with regard to the possible mode of action of the drugs.

Acetylcholinesterase↗
PubMed1984

Effect of hypoxia and pharmacological treatment on some enzyme activities in dog brain areas.

The effects of nicergoline on changes in enzymatic activities induced by hypoxia and post-hypoxic recovery were studied in various brain areas of young-adult and mature Beagle dogs. In different fractions (homogenate in toto, purified mitochondria, crude synaptosomes, SM1 and SM2 synaptic mitochondria) the maximal rate (Vmax) was investigated of the more representative enzymatic activities of: a) glycolysis, b) Krebs' cycle, c) electron transfer chain, d) amino acid and acetylcholine metabolism, e) lysosomal function. The physiopathological conditions caused alterations in different enzymatic activities depending on the area and subfraction investigated. Nicergoline tended to antagonize some of these alterations. Its action was mainly on non-synaptic mitochondria by a "braking" effect on some key enzyme activities of mitochondrial metabolism (i.e. citrate synthase, cytochrome oxidase and glutamate dehydrogenase) which suggests a sparing action in the brain.

Aging↗
PubMed1984

Cerebral and cerebellar metabolic changes induced by drugs during the recovery period after profound hypoglycemia.

On rat cerebral and cerebellar cortex, severe hypoglycemia with isoelectric EEG induced extensive deterioration of the energy state and gross alteration of amino acid contents. During recovery, tissue glucose concentration returned to normal, while the rate of glycogen synthesis was slow, both lactate and pyruvate concentrations increasing to above normal. In the recovery period, the ATP concentration increased but the adenine nucleotide pool remained reduced, even if the ADP and AMP contents were close to normal. Phosphocreatine was restored to normal concentrations with reciprocal changes in creatine content. During recovery there was a rise in glutamate and glutamine concentrations, gamma-aminobutyrate content returning to normal value. Ammonia and aspartate decreased below normal, while alanine increased above normal. The effect of some drugs on the post-hypoglycemic recovery was tested: (a) Ergot alkaloids (dihydroergocristine, dihydroergocriptine, dihydroergocornine); (b) Vinca minor alkaloids (vincamine TPS, (--)-eburnamonine); (c) Rauwolfia serpentina alkaloids (reserpine, raubasine); (d) synthetic agent (piracetam). During the post-hypoglycemic recovery, these different agents exhibited different, or even contrasting, interferences on glycolytic metabolites, amino acids and energy-rich phosphates. The metabolic alterations in the cerebellar cortex were qualitatively of the same character of those in neocortex. However the metabolic alterations were less extensive and more sensitive to drug action.

Adenine Nucleotides↗
PubMed1984

Recovery period after profound hypoglycemia. Influence of some metabolic modulators on the cerebral endogenous substrate utilization.

The content of "energy-rich" phosphates was markedly decreased in rat cerebral cortex after 20 min of severe hypoglycemia, followed by partial restitution during the recovery period. The adenine nucleotide pool remained reduced even if the energy charge returned to normal. During hypoglycemia the non-glucose endogenous substrates were provided by glycolytic intermediates, by Krebs' cycle intermediates and by related amino acids. Other substrates for brain oxidation were provided by the breakdown of phospholipids and fatty acids. After a 20 min period of post-hypoglycemic recovery, partial restoration of carbohydrates and amino acids occurred, the amino acid pool size being still reduced. The alterations in phospholipids and fatty acids persisted, while there was a tendency towards normalization of the free fatty acid cerebral content. During the post-hypoglycemic recovery, treatment with some specific metabolic modulators (i.e., uridine, L-acetylcarnitine, hopantenate, 6-amino-nicotinamide) suggests the possibility of an alternative cerebral substrate utilization due to the modulation of the cerebral biochemical machinery. Thus, increased carbohydrate utilization by hopantenate was consistent with decreased lipid breakdown, while increased carbohydrate utilization by uridine was concomitant with decreased amino acid degradation. On the other hand, decreased cerebral carbohydrate utilization by 6-aminonicotinamide was concomitant with increased lipid and amino acid breakdown. Furthermore, the increased loss of cerebral phospholipids and fatty acids by L-acetylcarnitine occurred in the presence of a large glucose availability and was concomitant with an extensive reduction on cerebral glycolytic flux.

Amino Acids↗
PubMed1983

Rat cortex synaptic and nonsynaptic mitochondria: enzymatic characterization and pharmacological effects of naftidrofuryl.

In order to investigate the in vivo pharmacological effects of the drug naftidrofuryl, we prepared populations of synaptic and nonsynaptic mitochondria from rat brain cortex. In these different mitochondrial populations the activities of citrate synthase, malate dehydrogenase, total NADH cytochrome c reductase, cytochrome oxidase, and glutamate dehydrogenase were evaluated. Except for glutamate dehydrogenase, the specific activities of the enzymes evaluated in the "free" mitochondrial fraction were higher than those observed in the "synaptic" SM1 and SM2 mitochondrial fractions, the difference between SM1 and SM2 fractions being significant. The in vivo administration of naftidrofuryl induced few and different changes in the various mitochondrial populations.

Animals↗
PubMed1983

Changes induced by ischemia on some cerebral enzymatic activities related to energy transduction and amino acid metabolism.

The maximal rate of some cerebral enzymatic activities related to energy transduction (hexokinase; phosphofructokinase; lactate dehydrogenase; citrate synthase; malate dehydrogenase; total NADH-cytochrome c reductase; cytochrome oxidase), amino acid metabolism (glutamate decarboxylase; glutamate dehydrogenase) and cholinergic metabolism (acetylcholine esterase) were tested in the cerebral cortex and in sub-cortical area of rats. The evaluations were performed both in the homogenate in toto and in the crude mitochondrial fraction, before and after a postdecapitative normothermic ischemia of 5, 10, 20, and 40 min duration. The results are discussed also with respect to the pharmacological pretreatment with two biological substances which may modulate amino acid (L-alanine) and phospholipid metabolism (CDP-choline). The analysis of the present data suggests the occurrence in brain tissue of a variety of interrelated factors implicated in the ischemia-induced changes of the maximal rate of the enzymatic activities related to the energy transduction. These include: (a) rearrangement of the enzymatic activities because of the changed metabolic and chemico-physical condition; (b) decrease in the activity of enzymes related to the electron transfer chain and glycolysis; (c) changes in enzymes related to mitochondrial membranes. The effects of in vivo administration of alanine or CDP-choline, even if significant, are not consistent throughout the time period studied.

Amino Acids↗
PubMed1983

Synaptic and non-synaptic mitochondria from rat cerebral cortex. Characterization and effect of pharmacological treatment on some enzyme activities related to energy transduction.

By a cellular subfractionation technique, synaptic and non-synaptic mitochondria from a single rat cerebral cortex were obtained. In these different mitochondrial populations the activity of citrate synthase, malate dehydrogenase, total NADH-cytochrome c reductase, cytochrome oxidase and glutamate dehydrogenase were evaluated. Except for glutamate dehydrogenase, the enzyme specific activities evaluated in the "free" mitochondrial fraction were higher than those evaluated in the "synaptic" SM1 and SM2 mitochondrial fractions, the differences between SM1 and SM2 fractions being significant. The effect of the in vivo administration of naftidrofuryl given at different doses and at different times was studied. The treatment induced few but different changes in the various mitochondrial populations.

Animals↗
PubMed1982

Influence of age upon the cerebral metabolic changes induced by acute hypoxia on the synaptosomes from dog brain.

The synaptosomal fraction obtained from the motor area of the cerebral cortex of normocapnic, normoxic or hypoxic "young adult," "mature" and "senescent" beagle dogs is incubated and analyzed for : ATP, ADP, AMP, creatine phosphate, pyruvate and lactate. The data are compared with those obtained from the whole controlateral cortical motor area, by the surface freezing technique. After hypoxic hypoxia /15 min; PaO2 = 17-19 mm Hg), the metabolite contents and ratios are differently affected by ageing when the evaluations are performed in the incubated synaptosomal preparation or in the controlateral whole cerebral tissue. In fact, ageing does not affect so much the cerebral changes that occur in the overall energetic state during the hypoxic assault in vivo, but rather those that the synaptosomes remember the tend to reverse during the subsequent incubation in vitro. The protective action of several drugs on the synaptosomal phosphorylation state is tested. Phenobarbital shows a quite broad, age-independent spectrum of action. (-)Eburnamonine and dihydroergocristine exhibits a more limited, age-dependent effectiveness, but are devoid of anesthetic action. Papaverine proves unable to affect the tested biochemical parameters.

Adenine Nucleotides↗
PubMed1982

Drug action on the metabolic changes induced by acute hypoxia on synaptosomes from the cerebral cortex.

The synaptosomal fractions obtained from the motor area of the cerebral cortex of normocapnic, normoxic, or hypoxic, untreated beagle dogs and of pentobarbital (Nembutal)- or cytidine diphosphate (CDP)-choline-treated dogs were incubated and analyzed for ATP, ADP, AMP, creatine phosphate, pyruvate, and lactate. The data were compared with data obtained by the surface freezing technique from the whole contralateral cortical area. The in vivo intracarotid perfusion of the drug differentially affected the content of the metabolites and their ratio. This occurred whether the evaluations were performed in the incubated synaptosomal preparations or in whole cerebral tissue, both during normoxia and after hypoxia (15 min; PaO2 = 17-19 mm Hg). Thus, intracarotid perfusion of nembutal increased the synaptosomal phosphorylation state both in normoxic and in hypoxic animals, whereas the effect on the metabolism of the contralateral cortical motor area as a whole was in all cases less than that observed in the synaptosomal fraction. Perfusion with CDP-choline increased synaptosomal phosphorylation after the hypoxic condition, but had no effect in normoxia or on the whole cortical tissue of the motor area. The possibility of obtaining a cerebral sparing action by utilizing molecules devoid of anesthetic action is suggested.

Acute Disease↗
PubMed1981

Metabolic changes induced by acute hypoxia on the synaptosomes from dog brain.

Synaptosomal preparations from the motor area of the cerebral cortex of normocapnic, normoxic or hypoxic untreated beagle dogs and phenobarbital-, papaverine-, and (-) eburnamonine-treated dogs were incubated for 10 min at 24 degrees C and analyzed for ATP, ADP, AMP creatine phosphate, pyruvate, and lactate. The data were compared with those obtained from the whole controlateral cortical motor area, by the surface-freezing technique. Both during normoxia and after hypoxic hypoxia (15 min, at PaO2 equal to 17-19 mm Hg) the metabolite contents and ratios were very different in the incubated synaptosomal preparations and in the whole cerebral tissues. As concerns the drug treatment, papaverine was always inactive, while (1) eburnamonine increased the synaptosomal phosphorylation state in hypoxic dogs, being ineffective on the glycolytic metabolites evaluated. Phenobarbital increased the synaptosomal phosphorylation state both in normoxic and in hypoxic animals, and was effective also on the glycolytic metabolites studied.

Adenine Nucleotides↗
PubMed1981

Brain enzymes and ischemia.

Changes in the maximal rate of some cerebral enzymatic activities related to 400ene transduction and neurotransmission (lactate dehydrogenase; citrate synthase and malate dehydrogenase; total NADH-cytochrome c reductase and cytochrome oxidase; glutamate dehydrogenase; acetylcholine esterase) were assayed both in the crude or purified mitochondrial fraction and in the crude synaptosomal fraction from rat whole brain or cerebral cortex. The evaluations were performed in rats before and after a postdecapitative normothermic ischemia of 5, 10, 20 and 40 min duration. Modification observed in some of these activities wer discussed for comparison with other experimental results from different researchers. At present no definite conclusions can be drawn, but certainly the observed modifications in activity of enzymes are not passive but expression of deranged metabolism of ischemic neurons.

Acetylcholinesterase↗
PubMed1981

Cerebral enzymatic activities during chronic hyperammonemia and treatment with S-adenosyl-L-methionine, adenosine and methionine in the rat.

The effect of the chronic intramuscular administration of some agents related to the S-adenosyl-L-methionine system on the hyperammonemia syndrome was evaluated. This experimental syndrome was induced in the rat by intraperitoneal administration of high doses of ammonium acetate (33, 100 and 300 mg/kg/day, 6 days a week for 80 days) followed by the assay of the activities of some cerebral enzymes involved in energy transduction. The enzymatic activities studied in the homogenate and in the mitochondrial fractions of brain tissue were: lactate dehydrogenase, citrate synthase, malate dehydrogenase, total NADH-cytochrome c reductase and cytochrome oxidase. All three doses of ammonium acetate induced significant modifications in the cerebral enzymatic activities. These doses reduced the activity of the total NADH-cytochrome c reductase both in the homogenate and in the mitochondrial fraction. On the other hand the activity of malate dehydrogenase was reduced limited to the two lower doses in the homogenate only. The simultaneous daily treatment (i.m.) with equimolar doses of substances involved in the S-adenosyl-L-methionine system (adenosine, methionine and S-adenosyl-L-methionine) did not cause any significant modification of the cerebral enzymatic activities associated with the administration of ammonium acetate at the three dose levels, thus confirming our previous results.

Adenosine↗
PubMed1981

Effect of vincamine on some enzymatic activities from various areas of the beagle dog cerebral cortex.

The effect of a chronic (3 months) treatment with vincamine on the enzymatic activities related to energy transduction was studied on several areas of the cerebral cortex of dog brain. About enzymatic activities of the four different cortical areas, in controls, no difference was observed between the enzymatic activities evaluated in the crude mitochondrial fraction, with regard to both the tricarboxylic acid cycle (citrate synthase, malate dehydrogenase) and the electron transport chain (total NADH-cytochrome c reductase, cytochrome oxidase). On the contrary, in the homogenate, lactate dehydrogenase, malate dehydrogenase and acetylcholine esterase showed different maximal activities. In the crude mitochondrial fraction the intravenous treatment with the three different doses of vincamine failed to cause any significant change as compared to controls. On the contrary, with regard to the enzymatic activities evaluated in the homogenate in toto, the analysis of variance revealed an effect on cytochrome oxidase at the dose of 3 mg/kg intravenously.

Animals↗