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Biomedical subjects

G L Piccinin

Publications and source records attributed to G L Piccinin.

At least 19 recordsLinked to original sources

Neuropsychological correlates of L-deprenyl therapy in idiopathic parkinsonism.

1. Monoaminergic neurotransmitter systems are known to play an important role in neuropsychological functions and they are impaired in dementia of DAT and PD. 2. L-deprenyl is a monoamine-enhancing drug which at low doses selectively inhibits MAO-B, an enzyme whose brain activity has been reported to increase in normal aging and neurodegenerative dementing disorders. 3. The authors studied the effects of L-deprenyl, 10 mg/day, on several cognitive domains in idiopathic parkinsonians without dementia. Ten out-patients, treated with levodopa plus DDI, were tested before receiving L-deprenyl and retested six months after they had been treated with the drug. A control group of ten parkinsonian out-patients treated with only levodopa plus DDI, matched for age, educational level, severity and duration of extrapyramidal disease, was tested by the same neuropsychological battery and retested after a comparable time interval. 4. Statistically significant changes were noted in the verbal and visuospatial learning performances of PD patients treated with the combination of L-deprenyl and levodopa.

Aged↗

Alzheimer-type dementia and verbal memory performances: influence of selegiline therapy.

In a double blind randomized crossover trial lasting 6 months selegiline, a selective MAO-B inhibitor, was tested against placebo for activity on verbal memory performances in Alzheimer-type dementia (DAT). Verbal memory was assessed with the Rey-Auditory-Verbal Learning Test at the start of treatment, at the time scheduled for crossover (90 days) and at the end of the trial (180 days). The results suggest that selegiline possesses significant activity on some memory parameters, which seems to depend on an improvement both in information processing abilities and in learning strategies at the moment of acquisition.

Alzheimer Disease↗

L-deprenyl therapy improves verbal memory in amnesic Alzheimer patients.

Altered monoaminergic neurotransmission could play an important role in the cognitive dysfunctions typical of dementia of the Alzheimer type (DAT). DAT is not, however, a homogenous phenomenon inasmuch as two forms are distinguishable: early onset (EO) and late onset (LO). Moreover, focal patterns of neuropsychological deterioration fall into various subgroups. According to our hypothesis, DAT patients, who at the onset of the disease mainly manifest memory disorders, also represent a specific subgroup characterized by impaired cortically projecting catecholaminergic pathways. In a 6-month randomized, double-blind, cross-over study versus placebo we analysed the influence of L-deprenyl on the verbal memory of 19 amnesic EO-DAT patients. Verbal memory was assessed by means of the Rey Auditory Verbal Learning Test. The results obtained show significantly better performances for L-deprenyl treated patients in learning and long-term memory skills. We suggest that L-deprenyl, through selective inhibition of MAO-B and by increasing the activity of the catecholaminergic systems, positively influences cognitive functions and behaviour founded on memory efficiency.

Aged↗

Neuropsychological effects of L-deprenyl in Alzheimer's type dementia.

The monoaminergic neurotransmission defect seen in dementia of the Alzheimer type (DAT) is linked to a known increased activity of type B cerebral monoamine oxidases (MAO-Bs). The use of drugs that are able to block this abnormal activity could therefore be useful in the treatment of some cognitive deficits that characterize DAT. Twenty patients with a clinical diagnosis of DAT and with a slight-moderate mental deterioration were treated with 10 mg/day of L-deprenyl, a selective MAO-B inhibitor, according to a double-blind crossover design vs. placebo. Initial treatment (drug or placebo) was randomly assigned. The patients' cognitive functions were evaluated at baseline and then after 3 and 6 months of treatment with drug or placebo. The patients crossed over treatment after 3 months, without a washout interval. The results of the study show the higher and statistically significant effects of L-deprenyl on memory and attention that seem to be due to an improved function of the monoaminergic systems involved in the process of neuronal degeneration.

Aged↗

[Treatment of progressive supranuclear palsy].

The neuropharmacological and neurochemical features of Progressive Supranuclear Palsy (PSP) are reviewed, together with the results obtained by various therapeutic trials. PSP is a neurodegenerative disease which often causes Parkinsonian symptoms but dopaminomimetic drugs have given rise to poor improvement, in spite of dopamine decrease observed in PSP patients' nigrostriatal region. The uselessness of L-DOPA therapy in PSP patients may explain the numerous failures encountered in PSP patients misdiagnosed as Parkinsonian. On the basis of the recent discovery of striatal dopaminergic receptor abnormalities and of interaction between various neurotransmitters, the authors suggest some possible therapeutic substances that might improve the outcome of the disease.

Aged↗

[Therapy of insomnia].

The authors review the neurochemical and electrophysiological features of insomnia, together with the results obtained by various substances. The literature data show that the benzodiazepines (BZ) should be administered for short periods of time, in order to avoid addiction and withdrawal symptoms. For this reason, the authors suggest that, before starting a therapy with such substances, an accurate clinical evaluation should be made and a good knowledge of the pharmacokinetics of the various BZ is essential.

Anti-Anxiety Agents↗

Effect of subconvulsive doses of bicuculline on the incorporation of radioactive precursors into glycerolipids in rat brain areas.

Bicuculline (either 25 mumol or 12.5 mumol/kg body wt) was administered to rats by intraperitoneal route. Animals treated with 25 mumol/kg experienced convulsions, whereas those receiving 12.5 mumol/kg did not. Controls received saline instead of the drug. Radioactive precursors [2-3H] glycerol and/or [1,2 14C] ethanolamine were injected into cerebral ventriculi simultaneously with bicuculline and the rats were killed 12 min afterwards. Their brains were dissected by hand into four parts (cerebellum, brain stem, hippocampus, cerebral cortex) and the labeling of lipid classes determined after extraction and separation. Although glycerol was incorporated into lipid better than ethanolamine in all areas, the fate of the injected radioactive precursors varied according both to area and treatment. The lowest uptake of radioactivity was in the cerebral cortex and the highest in the brain stem and hippocampus. Moreover, the administration of bicuculline influenced the distribution of radioactivity among lipid classes; these variations, however, were not dependent on the administered doses of bicuculline. We conclude that the effects on glycerolipid metabolism observed in convulsing animals are due to several causes including alterations of systemic parameters (hypertension, hypoxia, etc.). The distribution of glycerol label between phospholipid and neutral lipid is proposed as a biochemical model for the study of convulsive and subconvulsive states.

Animals↗

Frontal lobe dysfunction in Parkinson's disease: prognostic value for dementia?

The purpose of this longitudinal study was to investigate if the presence of frontal motor deficits in parkinsonians without signs of global intellectual impairment may have a predictive value for the development of a progressive dementing process during the course of the illness. An examination of the higher level of motor organization, using skills thought to depend upon the integrity of the frontal regions, was performed by 30 parkinsonian patients who did not present any signs of general intellectual impairment. According to their performance, as compared with controls, they were divided into two subgroups: those with and those without frontal dysfunctions. After a mean period of 4 years, a second neuropsychological examination was carried out to assess any eventual change of mental status. The results suggest that frontal dysfunctions may be observed several years before the appearance of generalized intellectual impairment and may be considered one of the predictive factors for development of dementia in Parkinson's disease. Careful consideration of these defects during examination of motor abilities may be of value in the clinical management of parkinsonian patients.

Aged↗

Incorporation of glycerol and ethanolamine into glycerophospholipid in rat brain areas during bicuculline-induced convulsive seizures.

The effect of bicuculline-induced convulsive seizures on lipid metabolism has been studied in four brain areas (cerebellum, cerebral cortex, hippocampus, and brainstem) using [2-3H]glycerol and [1,2-14C]ethanolamine as radioactive lipid precursors administered simultaneously with bicuculline. Twelve minutes after the administration, the uptake of radioactivity depended both on brain area and treatment, being generally higher in convulsing rats. The uptake of glycerol was influenced to a larger extent than that of ethanolamine and increased during convulsions, but its incorporation into lipids did not. In contrast, the amount of ethanolamine incorporated into lipids increased during bicuculline-induced seizures. The difference in behavior of glycerol and of ethanolamine is also indicated by the decrease of the 3H/14C ratio of phosphatidyl-ethanolamine in various brain areas during convulsions. It is, therefore, evident that the metabolism of the two precursors is affected differently by seizures.

Animals↗

Effect of cytidine on the modification of phospholipid metabolism induced by ischemia.

[1-14C-]Arachidonic acid was injected into the lateral ventricle of the gerbils (meriones unguiculatus) two hours before producing brain ischemia by the bilateral ligation of the carotid arteries. Ten minutes before the carotid ligation a group of animals received an additional intraventricular injection of cold cytidine (2.5 mumol/brain). Control animals with and without cytidine, together with the ischemic group, were decapitated directly into liquid nitrogen ten minutes after carotid ligation or sham surgery. Cytidine is able to both stimulate arachidonic acid incorporation into lipids and noticeably correct the release of this acid from polar lipids induced by ischemia. Based on these findings, it is possible to assume that cytidine exerts an effect on the biosynthesis of phosphoglycerides as well as on their catabolic activities.

Animals↗

Cerebellar metabolism of phosphatidylethanolamine and its water-soluble precursors during bicuculline-induced convulsive seizures.

The incorporation of labeled ethanolamine into phosphatidylethanolamine (PE) and its water-soluble precursors, phosphoethanolamine and CDP-ethanolamine, is measured in rat cerebella during the course of bicuculline-induced convulsive seizures. The labeling of CDP-ethanolamine and phosphoethanolamine diminishes 6 min after the administration of both bicuculline and radioactive ethanolamine whereas that of PE is unaffected in these conditions. Time is very important to this effect; indeed, no differences of the labeling of PE water-soluble precursors can be found in rat cerebellum of normal and convulsing animals 12 min after the administration. The cerebellar pool of CDP-ethanolamine doubles after 6 min of convulsions, which means that unlabeled CDP-ethanolamine forms from a non-radioactive source, such as lipid, may be through the reversal of the ethanolamine phosphotransferase reaction. This effect disappears 12 min after the injection of the convulsant.

Animals↗

Cerebellar metabolism of phosphatidylcholine and its hydrosoluble precursors during bicuculline-induced convulsive seizures.

The cerebellar incorporation of labeled choline into phosphatidylcholine (PC) and its hydrosoluble choline-containing precursors has been examined during the course of bicuculline-induced convulsive seizures. The labeling of phosphocholine and of PC diminished in these conditions whereas that of cytidine-5'-diphosphate choline (CDP-choline) was practically unaffected. Moreover, the cerebellar pools of phosphocholine and CDP-choline increased by 75-100% after 6 min of convulsions; these compounds were formed from lipid through the action of phospholipases or through the reverse action of choline phosphotransferase. From the data reported in this paper it should also be inferred that the cytidylyltransferase reaction was activated. It is therefore concluded that the cerebellar metabolism of PC and its precursors was affected in various ways by the bicuculline-induced convulsive seizures.

Animals↗

Effect of various drugs producing convulsive seizures on rat brain glycerolipid metabolism.

Convulsive seizures were elicited in the rat by the injection of several different drugs (pyridoxal phosphate, bicuculline, penicillin and ouabain). Glycerolipid metabolism was studied after the intraventricular injection of [2-3H]glycerol, which was incorporated into rat brain glycerides. The percentage of total lipid label found in each lipid class (phosphatidylethanolamine, PE; phosphatidylcholine, PC; phosphatidylserine, PS; phosphatidic acid, PA; phosphatidylinositol, PI; diacylglycerol (+ monoacylglycerol), DG and triacylglycerol, TG) depended on the time elapsed from the injection of the labeled precursor. The percent of total lipid radioactivity as PE and PC increased with time (3-60 min), whereas the opposite was true for the radioactivity of DG and PA. The radioactivity of other lipid classes did not appreciably vary between 3 and 60 min from the injection of the labeled glycerol. The intraventricular administration of pyridoxal phosphate together with labeled glycerol decreased the percent of lipid radioactivity as PE and increased that as DG. This 'lipid effect' was detected also after the administration of other convulsants, such as ouabain and penicillin. The intraperitoneal administration of bicuculline affected lipid metabolism in cerebellum.

Animals↗

The effect of cytidine-diphosphate choline (CDP-choline) on brain lipid changes during aging.

Lipid synthesis has been tested in vivo in different brain areas of 12-month-old male rats. Cortex, striatum, brainstem, and subcortex of brain have been examined. The cerebellum was discarded. Mixtures of (2-3H)glycerol and (Me-14C)choline were injected into the lateral ventricle of the brain as lipid precursors, and their incorporation into total lipid, water-soluble intermediates and choline-containing phospholipids was examined 1 hr after isotope injection. In another series of experiments cytidine-5'-diphosphate choline (CDP-choline) was injected intraventricularly to the aged rats 10 min before sacrifice with a simultaneous injection, and radioactivity assays were performed as above. Distribution of radioactivity content of CDP-choline among brain areas 10 min after its administration showed a noticeable enrichment of the nucleotide and water-soluble-related compounds in the examined areas, but to a lesser degree in the cerebral cortex. The incorporation of labelled glycerol, which is severely depressed in aged rats in all four areas [Gaiti et al, 1982, 1983], was increased only in the cortex, and apparently decreased in the other areas. This last result is probably due to a dilution effect brought about by the administered cold CDP-choline upon the (14C)-containing water-soluble metabolites. As a consequence, the (3H)/(14C) ratio in total lipid and in isolated phosphatidylcholine and choline plasmalogen increased after CDP-choline treatment.

Aging↗

The influence of cytidine on the endogenous pool of CDP-choline, CDP-ethanolamine, and CMP of the rat brain.

Cold cytidine was intraventricularly administered into the brain of young rats, and its effect on CDP-choline, CDP-ethanolamine, and CMP pools followed for different time intervals and with various amounts of administered cytidine. The injected nucleoside produces a measureable increase of th concentrations of all three nucleotides. The increase produced by injecting 2.5 mumol of cytidine for brain does not essentially change with higher doses of injected nucleoside, except for CMP, whose increase reaches a maximum with 5 mumol of cytidine. A clear time dependence on cytidine administration was shown. The increases of the three nucleotide concentrations do not show a maximum till 60 min from administration into CMP and CDP-bases and measurably increases their endogenous brain pools. The compound is likely to enter metabolic events connected with phospholipid metabolism in brain.

Animals↗

The effect of pyridoxal phosphate-induced convulsive seizures on rat brain phospholipid metabolism.

The intraventricular injection of pyridoxal phosphate (PLP; 1 mumole/brain) to rats causes convulsive seizures beginning 3 min after injection and lasting for about 20 min. The incorporation of [2-3H] glycerol into rat brain glycerides has been studied to ascertain whether treatment with PLP affects the incorporation of label into various lipid classes. The labeling pattern of glycerides is changed by the administration of PLP. The observed alterations begin a few min after injection, together with the convulsive seizures. 1 h after the injection the pattern of labeling of brain glycerides returns to normal. Different glycerides are differently affected by PLP. This work demonstrates that the labeling of diglyceride increases whereas that of phosphatidylethanolamine decreases following PLP administration.

Animals↗

Characteristic clinical aspects of Parkinson patients with intellectual impairment.

The present study is based on the hypothesis that Parkinson's disease is not a single homogeneous entity and that parkinsonians with intellectual impairment are a distinct subgroup of the parkinsonian population. An assessment of cognitive functions was performed on 70 patients with Parkinson's disease and on 90 control patients. Analysis of their performances led to the division of parkinsonians into two subgroups: with and without neuropsychological impairment. Investigation of the clinical characteristics of the two subgroups showed that parkinsonians who are mentally impaired differ from other parkinsonians in that they present a more marked severity of the extrapyramidal syndrome with predominant bradykinesia and an earlier deteriorating response to levodopa treatment.

Age Factors↗