PubMed Health⌕ Search

Biomedical subjects

U Bonuccelli

Publications and source records attributed to U Bonuccelli.

At least 73 records · Page 4Linked to original sources
PubMed1996

Identification and determination of 3,4-dihydroxyphenylacetaldehyde, the dopamine metabolite in in vivo dialysate from rat striatum.

3,4-Dihydroxyphenylacetic acid (DOPAC) is commonly considered to be the main dopamine (DA) metabolite produced by monoamine oxidase (MAO); however, the initial product of DA oxidation is 3,4-dihydroxyphenylacetaldehyde (DOPALD). Owing to technical difficulties in detecting DOPALD from a biological matrix, no studies have so far been performed to measure brain levels of this aldehyde in vivo. In this work, using transstriatal microdialysis in freely moving rats, we identified DOPALD by HPLC coupled to a coulometric detector. In chromatograms obtained from microdialysis samples, DOPALD appeared as a peak with a retention time coincident with that of the standards obtained via enzymatic and chemical synthesis. On the other hand, DOPALD was undetectable ex vivo from rat striatal homogenates. This discrepancy is probably due to the preferential extraneuronal localization together with the high reactivity of the aldehyde, which is rapidly removed by the dialysis probe, whereas the ex vivo procedure allows its condensation and enzymatic conversion. Measurement of DOPALD levels as a routine procedure might represent a reliable tool to evaluate DA oxidative metabolism directly, in vivo. Moreover, parallel detection of DOPALD and DOPAC levels in brain dialysate may make it possible to distinguish between the activity of MAO and aldehyde dehydrogenase. DOPALD, like many endogenous aldehydes, has been shown to be toxic to the cell in which it is formed. Therefore, in vivo measurement of DOPALD levels could highlight new aspects in the molecular mechanisms underlying both acute neurological insults and neurodegenerative diseases.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Disappearance of skin lipofuscin storage and marked clinical improvement in adult onset coeliac disease and severe vitamin E deficiency after chronic vitamin E megatherapy.

A case of adult onset coeliac disease with IgA and severe vitamin E deficiencies, associated with cerebellar impairment and peripheral neuropathy, is described. Nerve conduction velocities, BAERs and SEP were altered. Brain nMR showed cortical atrophy mainly in the frontal and parietal regions. At ultrastructural examination, nerve biopsy showed a severe nerve fiber loss with presence of lipofuscin. Lipofuscin has been also found in skin and muscle biopsy. Duodenal biopsy showed villar atrophy with criptae hypoplasia. IgA, Apo A1 lipoprotein and cholesterol were decreased. Serum level of vitamin E was not detectable and its amount did not increase after an oral loading (2 g bolus). Parenteral vitamin E administration (900 mg/day) was able to normalize the plasma values only after 6 months of chronic administration of the drug in coincidence with a significant improvement of clinical and neurophysiological signs, and disappearance of lipofuscin storage in the skin biopsy.

Brain Diseases, Metabolic↗
PubMed1995

White matter hyperintensities in Parkinson's disease. Clinical correlations.

OBJECTIVES: To verify recent preliminary data indicating that white matter hyperintensities on magnetic resonance imaging are more abundant in patients with Parkinson's disease (PD) than in healthy subjects and to examine possible correlation between these abnormalities and clinical features of PD. DESIGN: Magnetic resonance imaging data on patients with PD and normal subjects were compared as to frequency, extent, and topographic location of white matter hyperintensities; moreover, in the PD group, we studied the possible correlation of white matter hyperintensities with clinical features such as severity, disease duration, and therapy. SETTING: The outpatient clinic of the Institute of Clinical Neurology and the Neuroradiology Unit of the University of Pisa (Italy). PATIENTS: We studied 102 nondemented patients with idiopathic PD and 68 sex- and age-matched healthy controls, all screened for absence of cerebrovascular risk factors. OUTCOME MEASURES: White matter hyperintensities were classified as periventricular hyperintensities and deep hyperintensities. Frequency, extent, and topographic location of both periventricular and deep hyperintensities were evaluated. The clinical parameters examined were disease duration, treatment type, and disease severity (using Hoehn and Yahr staging and the Unified Parkinson's Disease Rating Scale), as well as disease progression index (ratio between Hoehn and Yahr stage and disease duration). RESULTS: The frequency and the extent of periventricular hyperintensities were significantly higher in patients with PD than in healthy subjects. Moreover, within the PD group, the patients who had periventricular hyperintensities had significantly shorter disease duration and greater disease severity, ie, a higher disease progression index, than those who did not. CONCLUSION: These data suggest that periventricular hyperintensities may represent a marker for a clinical subtype of PD characterized by a more rapid neurodegenerative process.

Aged↗
PubMed1995

Transcranial Doppler ultrasound in migraine and tension-type headache after apomorphine administration: double-blind crossover versus placebo study.

The effect of the dopaminergic agonist apomorphine on blood velocity in the middle cerebral artery has been studied in patients with migraine, tension-type headaches, and healthy subjects by means of transcranial Doppler monitoring. Following the administration of apomorphine, systolic velocity and mean velocity significantly increased and pulsatility index significantly decreased in migraineurs compared to placebo and to the other groups of subjects. These changes were dose-dependent and showed a time-curved compatible with the pharmacokinetic profile of the drug. The different effect of apomorphine in migraineurs compared with controls and tension-type headache patients implies that migraineurs have increased sensitivity to dopaminergic stimuli and suggests that transcranial Doppler monitoring after apomorphine administration could be a useful tool in the evaluation of migraineurs.

Adult↗
PubMed1995

Headache, panic disorder and depression: comorbidity or a spectrum?

Past epidemiological and clinical research has identified depression as the most common psychiatric disorder associated with headache. The present study carried out in a neurology headache clinic showed that the major associations were with current anxiety disorders, especially panic and related conditions. These findings were particularly true of the subgroup of migraine with aura; in the relatively few patients with mood disorders, depression was nearly always comorbid with panic or other anxiety disorders. Past history of depression was mainly a characteristic of the tension headache group. These data are compatible with the hypothesis that migraine, especially that with aura, panic disorder and some forms of depressive illness are part of the same spectrum.

Adolescent↗
PubMed1995

A crossover, controlled study comparing pergolide with bromocriptine as an adjunct to levodopa for the treatment of Parkinson's disease.

A single-blind, crossover study was carried out to compare the efficacy and safety of pergolide against that of bromocriptine in 57 patients with Parkinson's disease who showed a declining response to levodopa therapy. Patients were randomly assigned to receive either bromocriptine followed by pergolide, or pergolide followed by bromocriptine. Both drugs were administered for 12 weeks. Patients were assessed by a clinician blinded to treatment assignment using the New York University Parkinson's Disease Scale. The average daily dose of pergolide was 2.3 +/- 0.8 mg and of bromocriptine 24.2 +/- 8.4 mg. Addition of pergolide or bromocriptine resulted in a significant improvement in total scores when compared with the previous treatment of levodopa alone (pergolide, p = 0.0001; bromocriptine, p = 0.0005). Pergolide was more effective than bromocriptine in daily living scores (p = 0.02) and motor scores (p = 0.038). No differences in the incidence of dyskinesias, dystonias, or psychosis were observed between groups. Fewer adverse events were recorded in the pergolide group, and most patients and physicians preferred pergolide to bromocriptine. Pergolide as adjunctive therapy to levodopa was more effective than bromocriptine in this short-term trial.

Aged↗
PubMed1995

Dihydroergocryptine in the treatment of Parkinson's disease.

In the last 20 years dopamine agonists have been considered more and more helpful as primary therapy for Parkinson's disease (PD). Recently the neuroprotective activity and the therapeutic efficacy of a new ergot derivative, alpha-dihydroergocryptine (DHEC), has been highlighted. In the present work we resume the experimental and clinical data reported about this drug. The rationale for dopamine (DA) agonists as primary therapy for Parkinson's disease (PD) is based on the possibility to delay the onset of long term I-dopa syndrome (LTS) (King, 1992); moreover DA agonists seem to exert a neuroprotective effect on substantia nigra neurons. In fact, they stimulate DA receptors bypassing the degenerating nigrostriatal neurons and their metabolic machinery (Lieberman, 1992; Olanow, 1992); more recently, some studies have shown that these drugs have a direct protective effect too (Felten et al., 1992; Yoshikawa et al., 1994). In this minireview we resume the data reported about neuroprotective activity and therapeutic efficacy of a new ergot derivative, alpha-dihydroergocryptine (DHEC).

Antiparkinson Agents↗
PubMed1995

Cabergoline improves motor disability without modifying L-dopa plasma levels in fluctuating Parkinson's disease patients.

Studies on the influence of some dopamine agonists, particularly bromocriptine, on the pharmacokinetics of L-dopa have furnished contrasting results. Thus, any possible pharmacokinetic interaction should be taken into consideration when adding a new dopamine agonist to L-dopa treatment. In 12 Parkinson's disease (PD) patients with motor fluctuations, cabergoline was added in an 8-week study to their usual L-dopa/carbidopa therapy. Cabergoline was administered once a day at increasing doses of 0.5, 1, 2, and 3mg/day for a period of one week per dose, and 4mg/day for three weeks. Motor performance was assessed weekly evaluating the motor examination of the Unified Parkinson's Disease Rating Scale (UPDRS) and the patients' diaries of daily on-off time. Blood levels of both L-dopa and 3-O-methyldopa (3-OMD) were assayed by HPLC in two different days, over an 8-hour period, before initiating cabergoline and at the end of the study. The results of this study confirm that cabergoline is effective in the management of PD motor fluctuations without modifying L-dopa and 3-OMD pharmacokinetics.

Analysis of Variance↗
PubMed1994

Motor expression of kainic acid seizures is attenuated by dopamine depletion in mice.

We studied the effect of striatal dopamine depletion induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice on kainic acid (KA) evoked seizures. MPTP, 36 mg/kgp i.p. for 3 days, caused an 80% drop of striatal dopamine. Animals pretreated with MPTP, plus controls treated with saline, were challenged with five different convulsant doses of KA (3, 6, 12, 18 and 36 mg/kg i.p.). The seizures were monitored by electrographic recording and behavioral observation. MPTP pretreatment greatly attenuated the severity of the convulsions and the mortality induced by KA. The effect was mostly evident at the intermediate and at the high doses of KA. Surprisingly, no differences between the MPTP and control groups were found on the intensity and time course of the electrical seizures. Increment doses of KA resulted in a more severe electrographic seizure pattern in both the saline and the MPTP pretreated groups. Our data suggest that the dopamine depletion induced by MPTP does not alter the genesis of KA induced seizures, but may alter the function of cerebral structures involved in the control of seizure motor expression.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

Pergolide compared with bromocriptine in Parkinson's disease: a multicenter, crossover, controlled study.

We compared the efficacy and safety of pergolide and bromocriptine in 57 patients with Parkinson's disease (PD) with a declining response to levodopa therapy in a single-blind, crossover study. Patients were placed randomly on the sequence bromocriptine-pergolide (12 + 12 weeks) or vice versa. Regular evaluations using the New York University Parkinson's Disease Scale were performed by a clinician blinded to treatment assignment. Patients' and clinicians' impressions also were recorded. The average daily dose of pergolide was 2.3 +/0- 0.8 mg, and that of bromocriptine was 24.2 +/- 8.4 mg. Significantly greater efficacy was demonstrated by both drugs as adjunctive therapy to levodopa compared with previous treatment of levodopa alone (pergolide, p = 0.0001; bromocriptine, p = 0.0005; Wilcoxon t test). Pergolide was more effective than bromocriptine in daily living scores (p = 0.020) and motor scores (p = 0.038). No difference in dyskinesias, dystonias, and psychosis was observed. Adverse events were more frequent in bromocriptine-treated patients. Most patients and physicians preferred pergolide to bromocriptine. Pergolide as adjunctive therapy to levodopa was more effective than bromocriptine in this short-term trial.

Aged↗
PubMed1994

Platelet 3H-imipramine binding and sulphotransferase activity in primary headache.

We investigated platelet 3H-imipramine (3H-IMI) binding, a putative peripheral serotonergic marker, and the activity of sulphotransferase (ST), an enzyme involved in the catabolism of catecholamines and phenolic compounds, in 14 patients suffering from migraine without aura (MWoA) and in 10 with tension-type headache (TH), as compared with a group of controls. The possible relationships between the biological parameters and clinical features were also examined. The results showed that the two groups of patients had a lower number of 3H-IMI binding sites and a lower activity of the thermolabile form of ST, which acts preferentially on monoamine substrates, than the healthy controls, with no intergroup differences. Significant correlations between psychopathological rating scales and characteristics of the illness were observed in the patients with TH. The decreased number of platelet 3H-IMI binding sites is suggestive of a presynaptic serotonergic dysfunction and confirms the involvement of 5HT in primary headaches. The reduced ST activity might produce changes in the level of sulphated biogenic amines, including dopamine and tyramine, which might have an additional role in the pathophysiology of some aspects of primary headache.

Adolescent↗
PubMed1994

White matter MRI hyperintensities in a hundred and twenty-nine consecutive migraine patients.

The most frequently reported abnormal MRI finding in migraine is the presence of high signal white matter foci (WMF) on long TR images. Recently, WMF have been distinguished in periventricular WMF (PVF), when contiguous to ventricles, and deep WMF (DF), when far from these. DF, but not PVF, appear positively correlated with cerebrovascular risk factors and are called leukoaraiosis. In this study the MRI examination was performed in 129 consecutive migraine patients (83 of them had migraine without aura and 46 migraine with aura). In 19.3% of the migraineurs studied we observed WMF on T2 weighted images strictly localized in the deep white matter (DF). No PVF were observed. These findings were independent of the type of migraine and did not correlate with age, sex, disease duration, or frequency of attacks. The presence in a subgroup of migraineurs of leukoaraiosis (DF), for which a vascular genesis has been hypothesized, suggests that migraine could represent, a cerebrovascular risk factor in these patients.

Adult↗
PubMed1994

Clozapine in Huntington's chorea.

In an open-label trial, we evaluated the efficacy of clozapine on abnormal involuntary movements in five patients with Huntington's chorea. We administered clozapine at increasing doses of 25, 50, and 150 mg/d for 3 weeks. Subjective self-evaluation of all patients reported reduction of chorea and improvement of daily living activities. At the end of the trial, all patients requested to continue with clozapine. Objective evaluation with the Abnormal Involuntary Movements Scale demonstrated in all patients moderate-to-marked reduction of abnormal involuntary movements without any significant side effects; the improvement was dose-dependent and markedly decreased 1 week after drug withdrawal.

Clozapine↗
PubMed1993

Apomorphine test for dopaminergic responsiveness: a dose assessment study.

The clinical diagnosis of idiopathic Parkinson's disease (IPD) remains difficult and is supported by a favorable response to levodopa, while failure to respond represents an exclusion criterion. Recently, the response to subcutaneous apomorphine has been suggested as a tool in predicting levodopa responsiveness in parkinsonian syndromes. We administered apomorphine at doses of 10, 50, and 100 micrograms/kg subcutaneously against placebo over two consecutive days in 37 patients with parkinsonism and evaluated the motor response for 90 min after each dose. Subsequently, we compared the motor response with the follow-up response to levodopa therapy and to a final diagnosis. Twenty-seven patients of 37 showed a positive response to apomorphine, and 10 had a negative response. All positive responses to the apomorphine test were obtained with 50 or 100 micrograms/kg doses. Because of the high frequency of side effects with the dose of 100 micrograms/kg, 50 micrograms/kg seems more useful. After an adequate period of levodopa/carbidopa therapy (12-month follow-up), 29 patients improved; 25 of these had demonstrated a positive response to the apomorphine test. The final diagnosis of IPD, made on the basis of an exhaustive clinical and neuroradiological evaluation and on the response to chronic levodopa therapy, was in good agreement with the response to the apomorphine test (predictivity of diagnosis, 86.4%). Our data indicate that subcutaneous apomorphine at the dose of 50 micrograms/kg is a useful tool in the differential diagnosis of parkinsonian syndromes.

Aged↗
PubMed1993

Effect of metadoxine on striatal dopamine levels in C57 black mice.

In the present study, we examined the effect of metadoxine on striatal levels of dopamine, 5-hydroxytryptamine (5-HT) and their metabolites in male C57 Black mice. Striatal content was assayed after systemic administration of metadoxine ranging from 1 micrograms kg-1 to 500 mg kg-1. Striatal dopamine increased 1 h after treatment with metadoxine (150 mg kg-1), but the most notable effect was obtained 24 h after the drug administration. At this time a plateau was reached; the two major metabolites of dopamine showed the same trend. Seven days after metadoxine administration, striatal dopamine approached the control values. Over the same time intervals, striatal 5-HT increased to a lesser extent and 5-hydroxy-indoleacetic acid did not differ significantly from controls. Striatal dopamine increased significantly at a dose of 250 micrograms kg-1 up to a dose of 1 mg kg-1 metadoxine; no further increment was observed between 1 and 500 mg kg-1 metadoxine. Administration of each component at doses equimolar to 1 mg metadoxine showed that pyridoxine produced only a mild increase in striatal dopamine compared with controls. We suggest that the metadoxine-induced striatal dopamine increase is obtained by increasing synthesis of dopamine.

Animals↗
PubMed1992

Apomorphine in malignant syndrome due to levodopa withdrawal.

We report a case of neuroleptic malignant syndrome (NMS) following abrupt reduction of chronic levodopa treatment in a 71 year old female parkinsonian patient. The NMS resolved within 24 hours of the addition of apomorphine to levodopa therapy.

Aged↗