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Biomedical subjects

U Bonuccelli

Publications and source records attributed to U Bonuccelli.

At least 109 records · Page 6Linked to original sources
PubMed1987

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice is enhanced by ethanol or acetaldehyde.

Persistent neurochemical changes consistent with parkinsonism have been reported in brains of mice treated with repeated high doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We now report that ethanol or acetaldehyde potentiate MPTP-induced damage to mouse striatum. One hour after the combined treatments (ethanol and MPTP or acetaldehyde and MPTP), the animals exhibited a marked and long-lasting catatonic posture and then returned gradually to apparently normal locomotion. Seven days after MPTP administration, depletion of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in mouse striatum were further potentiated in the group of animals treated with ethanol. This effect was more evident when the treatment was repeated twice and was dose-dependent. Acetaldehyde was more potent than ethanol in enhancing MPTP neurotoxicity. A single exposure to acetaldehyde before and during MPTP treatment produced a very consistent fall of DA, DOPAC and HVA but not serotonin (5HT) or 5-hydroxyindoleacetic acid (5HIAA) in the striatum. This suggests that ethanol effects on MPTP neurotoxicity might be related to acetaldehyde formation.

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

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↗
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

Effects of carbamazepine on prolactin secretion in normal subjects and in epileptic subjects.

The effects of carbamazepine (CBZ) on spontaneous secretion of prolactin (PRL) and after stimulation with thyrotropin releasing hormone (TRH) were evaluated. Volunteer subjects after acute CBZ administration, and epileptic subjects with complex partial seizures chronically treated with CBZ, were examined. In an epileptic group, CBZ did not change TRH stimulatory effect on PRL secretion. No appreciable changes of PRL spontaneous secretion were observed, and only a small increase of sleep-entrained values with preservation of the normal secretory circadian rhythm was noted, both in normal subjects and in epileptic subjects. This result could be explained by a serotoninergic activity of PRL changes produced by CBZ in these various conditions agrees with the absence of published reports of CBZ side effects associated with hyperprolactinemia.

Adult↗
PubMed1984

Evaluation of a new radioimmunological assay for the determination of the B subunit of creatine kinase enzyme.

We used a new radioimmunological (RIA) kit for the assay of B subunit of creatine kinase enzyme (CK). This RIA system uses a specific antisera against the B subunit as ligant, human CK-BB labelled with 125I as tracer, and purified human CK-BB isoenzyme as standard. The mean (+/- SD) sensitivity obtained was 0.25 +/- 0.16 ng/tube and the between assay variability was about 9-10%. Serum levels of 113 normal subjects was not normally distributed. The 95% of values was found below 5 ng/ml. This new RIA is usefull in clinical practice when serum levels of CK-BB isoenzyme must be determined. This method is quickly and it is characterized by a good degree of precision, but the CK-MB isoenzyme cross-reacts for about 40% in this RIA system. Therefore, for the clinical diagnosis by means of this RIA it is necessary to rule out the concomitant elevations of serum CK-MB values.

Creatine Kinase↗
PubMed1983

Gynecomastia in epileptics treated with phenobarbital, phenytoin and fluoresone: two case reports.

Gynecomastia developed in two epileptic patients some months after the addition of oral fluoresone 750 mg daily to the phenobarbital and phenytoin already being administered. The common systemic diseases that may give rise to gynecomastia were excluded. One of the patients presented hyperprolactinemia and a raised estrogen/androgen ratio but the hormone levels were not raised in the other. The onset of symptoms after fluorescence in both cases is highly suggestive, although the pathogenetic mechanism is not clear.

Adult↗
PubMed1980

Phenobarbital prophylaxis of post traumatic epilepsy.

Phenobarbital (PB) was tested for its efficacy in averting post-traumatic epilepsy (PTE) in patients with non-missile head injuries. The protocol envisaged the administration of PB throughout a period of two years in randomly assigned doses ranging from 0.5 to 1.5 and from 1.6 to 2.5 mg/kg/day. The study included neurologic examination, EEG and plasma PB levels. Ninety patients, 83 of whom with serious head injury followed the prescribed treatment for the entire period. Two adult patients manifested seizures 5 and 10 months after the trauma. They were being treated with doses over 1.5 mg/kg/day. Another patient had a seizure six months after the end of the prophylaxis. Low doses of PB and monitoring permitted a reduction of side effects. The low incidence of PTE indicates that PB has an efficient prophylactic effect. The results also show that a low dosage has a favourable effect.

Adolescent↗
PubMed1979

Circadian rhythm in gonadotropin secretion in children with constitutional stature delay.

Plasma levels of luteinizing and follicle-stimulating hormones were measured for 24 hours in six subjects affected by constitutional stature delay associated with sexual maturation delay. The children in pubertal stage exhibited fluctuating plasma concentrations of these hormones which significantly increased during sleep, as in healthy pubertal subjects. Thus in this type of delayed puberty, the synchronization of augmented gonadotropin secretion with sleep develops later in chronologic age but it is strongly related to bone age.

Adolescent↗
PubMedDate not supplied

Myopathic involvement in two cases of Hallervorden-Spatz disease.

Muscle biopsy was performed in two patients with Hallervorden-Spatz disease and increased serum creatine kinase levels. Morphological analysis showed myopathic signs such as subsarcolemmal accumulation of myeloid structures, dense bodies and debris, endomysial macrophage activation, focal necrosis and fiber splitting. We emphasize the finding of muscle involvement in Hallervorden-Spatz disease, like in other forms of neuroacanthocytosis.

Adolescent↗
PubMedDate not supplied

Unbalanced progesterone and estradiol secretion in catamenial epilepsy.

Ten women with a documented history of catamenial epilepsy underwent a hormonal study to evaluate hypophyseal-gonadal function. Baseline values of luteinizing hormone, follicle-stimulating hormone and prolactin were similar in catamenial seizure patients and in control groups throughout a complete menstrual cycle. Stimulated secretions of the same hypophyseal hormones in catamenial seizure patients overlapped those of the controls. The luteal secretion ratio of progesterone to estradiol was significantly reduced in catamenial seizure patients versus normal controls. In a subgroup of catamenial seizure patients on antiepileptic therapy, luteal progesterone levels were remarkably decreased compared to normal and epileptic controls. These results indicate that catamenial epilepsy is characterized by an imbalance in ovarian steroid secretion and emphasize the need for an endocrinological assessment in these patients.

Adolescent↗
PubMedDate not supplied

Flunarizine in migraine prophylaxis: predictive factors for a positive response.

The efficacy of flunarizine in migraine prophylaxis is confirmed in both open and controlled trials. However, it is unknown what factors may influence a good response to prophylaxis with flunarizine. The aim of this study was to determine the possible predictive factors for therapeutic responsiveness to 3 months' treatment with flunarizine. One-hundred headache patients treated with flunarizine were evaluated. We considered "responders" those patients who recorded a reduction in migraine frequency of 75% after treatment. Statistical analysis revealed four factors which might influence therapeutic responsiveness in our patients. Positive factors were a family history (p<0.01) and high intensity of pain (p<0.01); negative factors were frequent attacks (p<0.01) and a history of analgesic abuse (p<0.001). Patients with no previous history of analgesic abuse, low frequency of attacks at baseline, higher levels of migraine pain, and positive family history constitute the prototype of flunarizine long-term treatment responders.

Adolescent↗
PubMedDate not supplied

Pharmacokinetics and pharmacodynamics of L-Dopa after acute and 6-week tolcapone administration in patients with Parkinson's disease.

Tolcapone, a central and peripheral catechol O-methyltransferase (COMT) inhibitor, reduces the conversion of L-Dopa into 3-O-methyl-Dopa (3-OMD), thus leading to more stable and sustained L-Dopa plasma levels. This study was designed to evaluate the effects of acute and 6-week tolcapone administration on L-Dopa pharmacokinetics and pharmacodynamics in Parkinson's disease (PD) patients with predictable motor fluctuations. Tapping test, walking time, and tremor, as well as L-Dopa and 3-OMD plasma levels, were assessed before and for 5 hours after the administration of a single L-Dopa dose, alone or in combination with 200 mg tolcapone, in seven patients with PD. This clinical and pharmacokinetic study was repeated after 6 weeks of tolcapone therapy (200 mg three times daily). It was observed that tolcapone, after both acute and chronic administration, prolonged the motor improvement induced by L-Dopa. As a result, at week 6 of tolcapone therapy, the daily hours spent "off" were significantly decreased. Tolcapone significantly increased the area under the curve of L-Dopa plasma levels by slowing down the elimination of L-Dopa from plasma, whereas the maximal concentration of L-Dopa was not modified. 3-OMD levels decreased significantly after acute tolcapone administration, and after 6 weeks of tolcapone therapy, they were approximately one sixth of pre-tolcapone values. The data confirm that tolcapone decreases L-Dopa clearance and prolongs motor response in PD patients with motor fluctuations, and that this effect is maintained after 6 weeks of tolcapone therapy.

Antiparkinson Agents↗
PubMedDate not supplied

Diurnal motor variations to repeated doses of levodopa in Parkinson's disease.

Patients with Parkinson's disease (PD) in long-term levodopa therapy often complain of worsening of motor symptoms in the afternoon and evening. The pathophysiology of this phenomenon is not known. We evaluated the motor response to repeated doses of levodopa during a 12-hour period in 52 parkinsonian patients (19 de novo, 20 stable, and 13 wearing-off). On the day of the study, all patients received standard doses of levodopa/carbidopa at 8:00 a.m., 12:00 noon, and 4:00 p.m. Motor measurements such as tapping test, walking time, and tremor score, and blood samples for levodopa and 3-O-methyldopa (3OMD) plasma analysis, were performed hourly. Mean motor scores and pharmacokinetic data, evaluated for a period of 3 hours after each levodopa dose, were compared. In de novo patients, we did not observe diurnal changes in motor score, whereas a progressive daytime worsening was visible in stable and wearing-off patients. No significant difference in levodopa pharmacokinetics after each levodopa dose was observed within each patient group, whereas 3OMD plasma levels significant increased with repeated levodopa administrations. However, no significant correlation between motor scores and 3OMD plasma levels was observed, suggesting that the diminishing motor response to afternoon and evening doses of levodopa in patients in long-term levodopa therapy does not relate to the pharmacokinetics of the drug. It is possible that this phenomenon may be an expression of the occurrence of tolerance to repeated doses of levodopa.

Administration, Oral↗
PubMedDate not supplied

Mexiletine in the treatment of torticollis and generalized dystonia.

Mexiletine is an antiarrhythmic drug that has been reported to exert antidystonic properties. We performed an open-label study to collect further evidence of the antidystonic effect of mexiletine in spasmodic torticollis (ST) and to evaluate its possible use in generalized dystonia. We administered mexiletine to six patients with dystonia (three with generalized dystonia and three with ST) who had failed to respond to previous pharmacotherapy. The drug was started at a dose of 200 mg/d by mouth and increased up to a maximum dose of 800 mg/d. Patients were evaluated at regular intervals over a 6-week period with use of the Fahn & Marsden Dystonia Scale and the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and videotaped. At the end of the trial, the videotapes were reviewed and scored by a blind observer. Patients were then followed for at least 1 year and evaluated every 3 months at the dose reached during the study period. No adverse effects were reported in five patients; in one patient, dizziness developed at the dosage of 800 mg/d, requiring a reduction of the dose. At the end of a 6-week period, a significant improvement in the rating scale for dystonia and in videotape ratings was observed after mexiletine treatment (p < 0.01). Our data indicate that mexiletine is a useful drug in dystonia treatment.

Adult↗
PubMedDate not supplied

SSRIs do not worsen Parkinson's disease: evidence from an open-label, prospective study.

Selective serotonin reuptake inhibitors (SSRIs) have been reported to be useful in the treatment of depression in patients with Parkinson's disease (PD). However, a few reports have suggested that SSRIs may worsen parkinsonian motor symptomatology and extrapyramidal side effects have been reported in depressed patients treated with SSRIs. So far, no prospective trial comparing the effects of different SSRIs in depressed patients with PD has been performed. The aim of the present study was to assess the effects of four SSRIs (citalopram, fluoxetine, fluvoxamine, and sertraline) on motor performance and their efficacy on depression in a group of patients with PD. Sixty-two consecutive nondemented, nonfluctuating, depressed patients with PD were included in four treatment groups (15 patiens received citalopram, 16 fluoxetine, 16 fluvoxamine, and 15 sertraline). The evaluation of extrapyramidal and depressive symptomatology was performed with use of the Unified Parkinson's Disease Rating Scale (UPDRS), Beck Depression Inventory, and Hamilton Depression Rating Scale at baseline and after 1, 3, and 6 months. Fifty-two patients completed the study. UPDRS scores were not significantly modified by the add-on therapy with each of the SSRIs studied. A significant improvement in depressive symptoms from baseline to the end of the trial was obtained with all SSRIs (Beck and Hamilton scores improving; p < 0.05 according to an analysis of variance). Our findings suggest that SSRIs do not significantly worsen extrapyramidal symptomatology and may ameliorate depression in patients with PD.

Aged↗