Search PubMed⌕ Search

Biomedical subjects

M Del Zompo

Publications and source records attributed to M Del Zompo.

At least 55 records · Page 3Linked to original sources
PubMed1987

MPTP fails to induce lipid peroxidation in vivo.

It has been speculated that the conversion of MPTP to MPP+ destroys dopaminergic neurons by promoting the generation of hydroxyl radicals and causes lipid peroxidation. The results obtained in the present work indicate that the primary products of lipid peroxidation are not detectable in MPTP treated animals and thus other mechanisms besides lipid peroxidation should be considered to explain the cytotoxicity of this neurotoxin.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Properties of 3H-MPTP binding sites in human blood platelets.

Our study demonstrates that 3H-1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (3H-MPTP) specifically binds to platelet membrane sites in humans. This specific, high affinity and saturable binding has properties similar to those of 3H-MPTP binding to rat and monkey brain, with a higher affinity. Deprenyl, a specific inhibitor of MAO type B enzyme, was the most potent drug in displacing 3H-MPTP from platelet binding sites. Platelets are considered a good model for central aminergic neurons and are very rich with MAO enzymatic activity, exclusively of type B. Our findings support previous evidence indicating a correspondence between 3H-MPTP binding sites and MAO-B enzyme. Moreover the presence of 3H-MPTP binding sites on human platelets suggests the use of this peripheral tissue as a simple model to study at least partially the mechanisms of neurotoxic action of MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

High affinity binding sites for 1-methyl-4-phenyl-pyridinium ion (MPP+) are present in mouse brain.

The possible involvement of 1-methyl-4-phenyl-pyridinium ion (MPP+) in the toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) prompted us to search for and characterize [3H]MPP+ binding sites in the mouse. Our data show that [3H]MPP+ binds saturably and with high affinity to mouse brain membranes. Scatchard analysis resulted in one straight line. The apparent KD was 15 +/- 1 nM and the Bmax 245 +/- 30 fmol/mg protein. The distribution of [3H]MPP+ binding sites shows a regional variation: the hypothalamus having highest binding and the cerebellum the lowest. Several compounds failed to inhibit [3H]MPP+ binding whereas only analogues of MPP+, MPTP and paraquat were able to antagonize this binding to brain. Specific binding with analogous characteristics also occurs in peripheral tissues. Considering the postulated role of MPP+ in MPTP neurotoxicity, further studies on [3H]MPP+ binding sites might be relevant to elucidate the mechanisms of this toxicity.

1-Methyl-4-phenylpyridinium↗
PubMed1986

Involvement of monoamine oxidase enzymes in the action of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, a selective neurotoxin, in the squirrel monkey: binding and biochemical studies.

1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) is a new neurotoxin that causes degeneration of the dopaminergic nigrostriatal neurons and induces a Parkinson-like state in several species, including humans and monkeys. The present study was designed to better characterize the properties of [3H]MPTP binding sites and to evaluate the interaction of MPTP with the oxidation of dopamine by monoamine oxidase (MAO) in an animal species (Saimiri Sciureus) shown to be lesioned by MPTP. Our data confirm the presence of high affinity and saturable binding sites for [3H]MPTP in the squirrel monkey. Specific binding with analogous characteristics also occurs in peripheral tissues. Various substances failed to inhibit the [3H]MPTP binding, whereas only MAO inhibitors (MAOI) were able to antagonize this binding to brain and peripheral tissues. In particular, deprenyl, a selective inhibitor of MAO type B enzyme, was relatively more potent as a displacer of [3H]MPTP from its binding sites both in brain and in peripheral tissues. Our results further suggest a correspondence between [3H]MPTP sites and MAO, particularly MAO-B, in monkey brain. Moreover, our data show that the oxidative deamination of dopamine is inhibited by MPTP in vitro. In conclusion, these data are consistent with the hypothesis of the involvement of MAO in the neurotoxic effects of MPTP, even though further experiments are necessary to better clarify the molecular mechanism of MPTP neurotoxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Primate-rodent 3H-MPTP binding differences, and biotransformation of MPTP to a reactive intermediate in vitro.

Specific binding of 3H-MPTP to brain homogenates is displaced predominantly by MAO-A inhibitor clorgyline in rat, and by MAO-B inhibitor deprenyl in monkey. A covalently bound metabolite is formed by MAO-B in vitro from MPTP, through a reaction almost completely inhibited by physiological concentrations of glutathione and significantly reduced by other sulfhydryl containing compounds. The difference in binding site pharmacological properties may account for the relative resistance of rat to the neurotoxic effect produced by MPTP in primates. The glutathione-prevented metabolic conversion to a reactive intermediate may be important for the mechanism of MPTP neurotoxicity and relevant to idiopathic Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

A reactive metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine is formed in rat brain in vitro by type B monoamine oxidase.

The formation of a reactive intermediate in the oxidative metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) that can covalently bind to monoamine oxidase or other cellular macromolecules has been postulated by several authors. We report here direct in vitro evidence that MPTP is converted by monoamine oxidase, predominantly type B, to a reactive metabolite, which binds irreversibly to proteins in rat brain. Rat brain homogenates were incubated at 37 degrees C with 1-[methyl-3H]MPTP and the perchloric acid precipitates were washed exhaustively with organic solvents and counted for radioactivity. The amount of recovered radioactivity was enzyme-related: it was time- and temperature-dependent and did not occur with preboiled tissue. This metabolic activity required oxygen; it was concentrated in the crude mitochondrial fraction and varied in different brain regions. Pargyline and deprenyl prevented the radioactivity binding, whereas clorgyline was less potent, indicating that monoamine oxidase, predominantly of type B, is the enzyme responsible for the production of the reactive metabolite. Glutathione and, to a lesser extent, cysteine and dithiothreitol, but not ascorbic acid, inhibited the irreversible protein binding, suggesting that sulfhydryl groups may react with the metabolite possibly leading to SH-conjugates. 1-Methyl-4-phenyl-2,3-dihydropyridinium increased the irreversible protein binding, indicating that the reactive metabolite of MPTP may not be identified as the dihydropyridinium compound. This chemically reactive intermediate might play a role in MPTP neurotoxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Therapeutic efficacy of a partial dopamine agonist in drug-free parkinsonian patients.

Terguride, a mixed agonist-antagonist of central dopamine receptors, was administered to eight patients with Parkinson's Disease. The clinical symptomatology of all patients improved significantly. The maximum neurological effect of terguride was noted at the highest daily dose (1.2 mg) after 21 days of treatment in all subjects, with a statistically significant average of 50.6% neurological improvement on the Webster scale in respect to admission. All single scores of the Webster scale decreased significantly: swing of the arms, facial expression, bradikinesia, rigidity and gait, particularly. No significant adverse reactions were observed during treatment. Our study in drug-free parkinsonian patients demonstrated that terguride is able to improve the neurological symptoms similar to DA agonists, but without their typical side effects.

Aged↗
PubMed1985

Cluster headache: clinical efficacy of lithium salts in a haemodialysis treated patient.

Over the last ten years the efficacy of lithium salts in cluster headache has been well demonstrated. Our patient, who had been suffering from cluster headache for approximately 30 years, had been in haemodialysis treatment for the last ten years for chronic renal failure. Moreover, he was affected by heart failure and peptic ulcer. The patient was currently under therapy with Digitalis, Isorbide dinitrate, and ranitidine and was dialyzed three times a week for a total of five hours each time. Neither prophylactic headache therapy nor high doses of analgesic drugs had proved effective. Although this patient was in haemodialysis, lithium treatment was indicated. The administration of lithium carbonate 300 mg during dialysis days and 150 mg during non-dialysis days improved the attacks. Complete recovery from the attacks was obtained when the serum levels of lithium reached the therapeutic range. No side effects were noted.

Cluster Headache↗
PubMed1985

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: correspondence of its binding sites to monoamine oxidase in rat brain, and inhibition of dopamine oxidative deamination in vivo and in vitro.

A saturable, specific, high-affinity binding site for [3H]1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine was found in rat brain homogenates. The CNS regional distribution, the subcellular fractionation, and the displacement by pargyline, clorgyline, and deprenyl suggest that this binding site may correspond to monoamine oxidase. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine inhibited the oxidative deamination of dopamine, both in vivo and in vitro. Striatal levels of 3,4-dihydroxyphenylacetic acid were significantly reduced shortly after intravenous administration, and returned to normal values after a few hours. The in vitro formation of 3,4-dihydroxyphenylacetic acid from dopamine was inhibited by concentrations of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine comparable to those of pargyline.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1984

Peripheral benzodiazepine binding sites in kidney: modifications by diabetes insipidus.

Using [3H] diazepam as ligand, it is possible to distinguish neuronal binding sites from those present on glial elements and in peripheral tissues (non-neuronal). The function of the "non-neuronal" binding sites is still obscure. Preliminary data showed a distribution of [3H] diazepam binding sites in kidney that could suggest a localization along the renal tubules. This is the site at which a renal peptide, arginine-vasopressin (AVP) is supposed to act. In an attempt to examine the function of these "non-neuronal" sites, we studied the [3H] diazepam binding in kidney of Brattleboro rats which lack AVP and present the symptoms of diabetes insipidus. The homozygous Brattleboro rats showed an increase in the apparent number of benzodiazepine binding sites (Bmax) compared to Long-Evans control rats. Replacement of AVP in these animals results in a reversal of the electrolyte alterations of diabetes insipidus and in an increase of the affinity of the [3H] diazepam binding. These findings may indicate a possible relationship between benzodiazepine binding sites and vasopressin action in kidney and may support receptor function of these "non-neuronal" binding sites.

Animals↗
PubMed1984

Linkage between X-chromosome markers and manic-depressive illness. Two Sardinian pedigrees.

Pedigrees of manic-depressive patients in treatment at the Lithium Clinic of the Institute of Clinical Pharmacology, University of Cagliari, were evaluated for linkage between major affective illness and the protan-deutan-glucose-6-phosphate-dehydrogenase region of the X-chromosome. Two informative pedigrees were found, investigated and analyzed for linkage using a multigenerational model and considering age-dependent penetrance. The results are consistent with the hypothesis of X-linkage in major affective illness.

Adolescent↗
PubMed1983

Increased paroxysmal activity of partial seizures in man by apomorphine.

In order to study the role of dopamine (DA) in the regulation of seizure mechanisms in man, a non-emetic dose of apomorphine, a direct stimulant of DA receptors, was administered to eight patients effected by different types of epilepsy. The EEG changes induced by apomorphine administration in comparison to those elicited by promazine or placebo were evaluated in a double blind cross-over study. Similarly to promazine treatment, apomorphine worsened the EEG recordings of some patients. The apomorphine-induced increase in paroxysmal activity was observed in patients affected by partial epilepsy and was not related to the sleep-inducing properties of the drug. This effect is interpreted as being the result of a stimulation of DA autoreceptors, mediating a decrease of dopaminergic activity in the central nervous system. The use of apomorphine as an EEG activating agent is suggested.

Adolescent↗
PubMed1983

Properties of two benzodiazepine binding sites in spinal cord.

Two types of benzodiazepine receptors were demonstrated in spinal cord. Binding to one of these sites (neuronal) was sensitive to the centrally active benzodiazepine, clonazepam, and binding was enhanced both by chloride and GABA. The second site was sensitive to 7-chloro-1,3-dihydro-1-methyl-5-(p-chlorophenyl) 2H-1,4-benzodiazepine-2-one (R05-4864) and thus is similar to the site characteristic of non-neuronal tissue. Binding to the neuronal site was inhibited by the putative glycine antagonist, strychnine, both in spinal cord and brain. This inhibition may account for the reported anti-GABAergic properties of strychnine and does not appear to be related to the glycine receptor.

Animals↗