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F Dagani

Publications and source records attributed to F Dagani.

49 records · Page 3Linked to original sources

[Cerebral enzymatic activities related to energy transduction processes. A model for the evaluation of pharmacological changes in the brain of the adult rat].

A test model of studying the effects of chronic pharmacological treatment on cerebral metabolism related to energy transduction was developed. The most useful biochemical parameters were the cerebral enzymatic activities related to the glycolytic pathway (lactate dehydrogenase), the Krebs' cycle (citrate synthetase and malate dehydrogenase) and the electron transfer chain (total NADH-cytochrome c reductase and cytochrome oxidase). The model is based on the natural growth-dependent changes occurring in the rat during aging (from 10 to 60 weeks of life). As test drug, 10-methoxy-1,6-dimethyl-ergoline-8 beta-methanol-(5-bromonicotinate) (nicergoline, Sermion) was administered daily for three periods of 16 weeks each (10-26, or 28-44, or 44-60 weeks of life) by two different administration routes (oral and i.p.), and at two different dose levels: oral 1 or 4, i.p. 0.25 or 1 mg/kg. Biochemical data were obtained blindly after 4, 8, 12 and 16 weeks of treatment. The drug tested exerted different effects which were dependent on the various administration periods and the administration routes. No dose-effect relationship was established.

Animals↗

Acute model for the estimation of the cerebral energy state during or after hypoxia and complete or incomplete ischaemia.

The behaviour of fuels (glycogen, glucose), of glycolytic pathway intermediates (glucose-6-phosphate, pyruvate) and end-product (lactate), as well as the pool of labile phosphates (ATP, ADP, AMP, creatine phosphate) and the energy charge of the brain were studied in the motor area of the cerebral cortex of beagle dogs in hypovolaemic hypotension. These parameters were evaluated after acute hypoxia (obtained by altering the composition of the inhalation mixture), after acute hypoxia plus incomplete ischaemia, after acute hypoxia plus complete ischaemia, during post-hypoxic recovery (3, 15 or 30 min after the restoration of normal ventilation), during post-hypoxic recovery and recirculation. A comparative examination of the different conditions showed that the most dramatic fall in the cerebral energy state took place in hypoxia plus complete ischaemia followed, in the order, by hypoxia plus incomplete ischaemia and simple hypoxia. However, reversal was most difficult in hypoxia plus incomplete ischaemia. The different situations are discussed in this paper with regard to the changes taking place in cerebral biochemical events.

Adenosine Diphosphate↗

Effect of (-)eburnamonine, papaverine and UDP-glucose on cerebral energy state during and after experimental hypoxia and ischaemia in beagle dog.

The effect of (-)eburnamonine, papaverine and UDP-glucose intracarotid perfusion has been evaluated in the brain of beagle dogs during various conditions of cerebral damage (hypoxia, hypoxia plus incomplete ischaemia, hypoxia plus complete ischaemia), and after 3, 15 or 30 min of the post-hypoxic recovery and recirculation. The behaviour of fuels (glycogen, glucose), of glycolytic pathway intermediates (glucose-6-phosphate, pyruvate) and end-product (lactate), of the pool of labile phosphates (ATP, ADP, AMP, creatine phosphate) and the energy charge potential of the brain were evaluated in the motor area of the cerebral cortex. The different pharmacological effects of (-)eburnamonine, papaverine and UDP-glucose are discussed with regard to the biochemical changes taking place during the physiopathological conditions tested.

Adenosine Diphosphate↗

Drug action on cerebral energy state during and after various hypoxic conditions.

The behaviour of fuels (glycogen, glucose), of glycolytic pathway intermediates (glucose-6-phosphate, pyruvate) and end-product (lactate), as well as the pool of labile phosphates (ATP, ADP, AMP, creatine phosphate) and the energy charge of the brain were studied in the motor area of the cerebral cortex of beagle dogs. These parameters were evaluated both after various hypoxic conditions (hypoxic hypoxia, hypoxia plus complete or incomplete ischemia) and after 3, 15 or 30 min of post-hypoxic recovery and recirculation. The effect of some drugs (papaverine, UDP-glucose, (-)eburnamonine, suloctidil) following intracarotid perfusion has been evaluated in the various quoted experimental conditions. The tested drugs proved unable to improve the deranged brain metabolism under all the hypoxic conditions. On the contrary, an activating effect of suloctidil and (-)eburnamonine could be observed during the recovery after both hypoxia and hypoxia plus complete ischemia, papaverine being ineffective and UDP-glucose increasing the glycogen synthesis. The drugs proved unable to induce a restitution of the altered brain metabolism after hypoxia plus incomplete ischemia.

Adenosine Triphosphate↗

The mitochondrial electron transfer alteration as a factor involved in the brain aging.

The tissutal concentrations of reduced glutathione (GSH) and the contents of some key components in the electron transfer chain (namely ubiquinone, cytochromes b, c1, c, and aa3) of the intraterminal mitochondria are measured in the forebrains from 20-, 60-, or 100-week-old Wistar rats. Moreover, in 60-week-old rats, the biochemical analyses are performed also 18 h after the induction of a peroxidative stress by cyclohexene-1-one. The rats have been i.p. pretreated for 8 weeks (7 days/week) with agents acting on macrocirculation (papaverine), carbohydrate metabolism (hopanthenate), lipid metabolism (phosphatidylcholine), energy transduction (theniloxazine), and dopaminergic system (dihydroergocriptine). Brain aging is characterized by the decrease in both GSH and mitochondrial cytochrome aa3, without changes in ubiquinone and cytochrome b populations. In the same way, the peroxidative stress induced by cyclohexene-1-one causes both a GSH depletion and an imbalance among the concentrations of the mitochondrial electron transfer carriers. Only cytochrome aa3 retains all the partially-reduced oxygen intermediates tightly bound to its active sites. Therefore, it is possible to hypothesize that an electron leakage at the level of the auto-oxidizing chain components (i.e., cytochrome b and ubiquinone populations) increases the release of activated oxygen species (superoxide radical, hydroxyl radical). The treatment with the quoted pharmacological tools suggests that GSH and mitochondrial electron transfer carriers are functionally linked, but not interdependent one another.

Aging↗

Effect of phenobarbital on cerebral energy state and metabolism. Enzymatic activities.

The changes induced by phenobarbital in cerebral enzymatic activities of the Krebs' cycle (citrate synthase, malate dehydrogenase) and electron transfer chain (total NADH-cytochrome c reductase and cytochrome oxidase) were studied. In addition, the activity of lactate dehydrogenase of acetylcholine esterase and of glutamate dehydrogenase was also studied. These enzymatic activities were evaluated in the homogenate in toto and in a crude mitochondrial fraction from rat brain. The modifications in some of these activities indicate that several new metabolic situations occur in brain tissue after phenobarbital treatment.

Animals↗

Glutamate metabolism, release, and quantal transmission at central excitatory synapses: implications for neural plasticity.

Glutamate is thought to act as a neurotransmitter at several excitatory synapses in the brain. Available knowledge reveals complex intercompartmental dynamics of glutamate, which is synthesized, accumulated and released by presynaptic elements, activates postsynaptic receptors, and is eventually re-uptaken and interconverted to glutamine by the participation of surrounding glial cells. The postsynaptic reactions to physiological release of glutamate during neurotransmission are considered in relation to the quantal approach, which is revealing unsuspected complexity in central synaptic mechanisms. This issue is particularly important in view of its implications in the study of long-term synaptic modifications.

Animals↗

Enzymes related to energy metabolism in human gliomas.

The evaluation of the specific activity of some enzymes related to energy transduction was performed in 7 fresh samples of malignant gliomas and in 4 samples of normal brain tissue. Compared with normal brain tissue, the hexokinase, phosphofructokinase and citrate synthase activities are lower; the lactate dehydrogenase and succinate dehydrogenase are unchanged, while glucose-6-phosphate dehydrogenase and NADP+-isocitrate dehydrogenase activities are higher in gliomas.

Brain Neoplasms↗