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Biomedical subjects

D Marazziti

Publications and source records attributed to D Marazziti.

At least 19 recordsLinked to original sources
PubMed2001

Decreased platelet [3H]paroxetine binding sites in suicide attempters.

Research to date would suggest the possible involvement of the serotonin (5-HT) system in the pathophysiology of suicide. With this study, we aimed to investigate the platelet 5-HT transporter, by means of the specific binding of tritiated paroxetine ([3H]Par), in a sample of 20 suicide attempters recruited at a first-aid service, as compared with healthy control subjects and psychiatric patients with no current or previous history of suicide attempt. The results, showing a decreased number of [3H]Par binding sites in suicide attempters, would suggest the involvement of the presynaptic 5-HT transporter in self-aggressive behavior.

Adolescent↗
PubMed2001

Simultaneous analysis of clozapine, clomipramine and their metabolites by reversed-phase liquid chromatography.

1. The authors present here a sensitive and rapid reversed-phase liquid chromatographic method which enables the simultaneous analysis in plasma of two different drugs and their metabolites: the atypical neuroleptic clozapine and the tricyclic antidepressant clomipramine. 2. Samples and the internal standard (dibenzepine) were extracted through automated solid-phase procedure, evaporated dryness and injected into the chromatograph. Mobile phase was a mixture of water and acetonitrile (63:37, v:v) containing TEMED and triethylamine. The total chromatographic time was of 14 min and analyte peaks were detected by means of an ultraviolet spectrophotometer preset at 254 nm. 3. Results revealed an assay sensitivity of 5 microg/L for clozapine or norclozapine and of 10 microg/L for clomipramine and desmethylclomipramine. Recoveries for these drugs and their metabolites were more than 60% and their coefficient of variation (within day and day-to-day) ranged from 1.3 % to 2.5 %. In spiked plasma, within day and day-to-day coefficients of variability (CV) were less than 5%. The simultaneous evaluation of these two drugs with adequate sensitivity and precision makes it particularly useful for therapeutic drug monitoring during mono- or polypharmacotherapy.

Antidepressive Agents, Tricyclic↗
PubMed2001

Distribution of [3H]GR65630 binding in human brain postmortem.

We investigated the distribution of serotonin (5-HT) receptors of type 3 (5-HT3) in human brain areas, by means of the the specific binding of [3H]GR65630. The brains were obtained during autoptic sessions from 6 subjects. Human brain membranes and the binding of [3H]GR65630 were carried out according to standardized methods. The highest density (Bmax +/- SD, fmol/mg protein) of [3H]GR65630 binding sites was found in area postrema (13.1+/-9.7), followed at a statistically lower level, by nucleus tractus solitarius (6.7+/-3.4), nervus vagus (5.5+/-2.1), striatum (4.8+/-2.4) with a progressive decrease in amygdala, olivar nuclei, hippocampus, olfactory bulbus and prefrontal cortex, and then by the other cortical areas and the cerebellum, where no binding was detected. These observations extend previous findings on the distribution of 5-HT3 receptors and confirm interspecies variations that might explain the heterogeneous properties of 5-HT3 receptors in different animals.

Aged↗
PubMed2001

Citalopram in refractory obsessive-compulsive disorder: an open study.

This study aimed to evaluate the effect of citalopram in patients with refractory obsessive-compulsive disorder (OCD) which had not responded to previous antiobsessional treatments. Eighteen patients were selected for this study: they had been suffering from OCD, according to DSM-IV criteria, for at least 2 years and had various comorbid disorders. All had been treated with serotonin reuptake inhibitors at adequate dosages for at least 6 months, but had failed to respond. Consequently, they were shifted to citalopram, titrated up to the dose of 40 mg, within 2 weeks. After 4 months of this regimen, 14 out of the total of 18 patients had shown a reduction in OC symptoms, as assessed by the decrease in the Yale-Brown Obsessive Compulsive Scale total score; no relevant side-effects were reported, except for a mild nausea in four patients within the first few days of treatment, which quickly disappeared. The use of citalopram would appear to be an useful strategy in refractory OCD cases.

Adolescent↗
PubMed2001

No correlation between aggression and platelet (3)H-paroxetine binding in obsessive-compulsive disorder patients.

Different findings suggest that the serotonin (5-HT) system may be involved in both the regulation of aggression and the pathophysiology of obsessive-compulsive disorder (OCD). Our study aimed to evaluate the aggressive features of a group of OCD patients and to explore possible correlations with a serotonergic marker, namely platelet 5-HT transporter. Psychopathological and biological patterns were compared with those of a group of healthy controls and those of patients with major depression. Twenty-one patients affected by OCD, 21 by depression and 21 healthy controls were included in the study. Aggressive features were measured by means of the Buss and Durkee Hostility Inventory (BDHI). The platelet 5-HT transporter was evaluated by means of the (3)H-paroxetine binding parameters (maximum binding capacity, B(max) and dissociation constant, K(d)). The OCD patients showed a total score on the BDHI not significantly different from that of healthy controls and lower than that of depressed patients. The factor profile was similar in the 3 groups, but higher in the depressed patients. The irritability, resentment, guilt, negativism and suspiciousness factors were significantly more pronounced in depressed patients. Some sex-related difference in single factors were also observed. The B(max) of (3)H-paroxetine binding was lower in OCD patients than in depressives or healthy controls. OCD patients were more similar to healthy controls than to depressed patients with regard to aggressive features measured by means of the BDHI. This suggests that aggression in OCD is a complex phenomenon that probably requires specific instruments of evaluation.

Adolescent↗
PubMed2001

mRNA expression of serotonin receptors of type 2C and 5A in human resting lymphocytes.

We investigated the presence of mRNA for serotonin receptors of type 2C (5-HT(2C)) in resting lymphocytes by means of RT-PCR and Southern blotting analyses, given their possible role in the pathophysiology of anxiety and eating disorders. At the same time, we explored also the presence of the specific mRNA for 5-HT(5A) receptors, a novel subtype for which still no functional data exist. Healthy subjects and patients with obsessive-compulsive or bipolar disorders were included in the study. The results showed the presence of the specific mRNAs for both 5-HT(2C) and 5-HT(5A) receptors in resting lymphocytes of the three groups of subjects. An additional band was also observed after the amplification of the 5-HT(5A) cDNA in each sample. These findings, while revealing the presence of 5-HT(2C) and 5-HT(5A) receptor mRNAs in an easily available tissue, can be considered preliminary for future quantitative analyses in patients with different psychiatric conditions.

Adult↗
PubMed2001

Pharmacological characterization of the serotonin transporter in young and elderly subjects.

The potency of some tricyclics (imipramine and clomipramine) and selective 5-HT reuptake inhibitors (fluoxetine, paroxetine, and citalopram) in displacing the [(3)H]paroxetine binding to platelet membranes was measured in young and elderly subjects of both sexes. The results showed that the most potent compound in all subjects was paroxetine, followed by clomipramine, citalopram, fluoxetine, and imipramine, with no differences between male and female subjects. All drugs, except paroxetine and clomipramine, showed significantly lower pKi values in the elderly subjects of both sexes. These findings would suggest that although the pharmacological profile of the 5-HT transporter is not modified qualitatively by age, quantitative changes in its affinity do perhaps occur which would justify more careful studies on this topic in order to get optimal dosages of drugs acting at this level.

Adult↗
PubMed2001

Correlation between platelet alpha(2)-adrenoreceptors and symptom severity in major depression.

BACKGROUND: Abnormalities in different parameters of the norepinephrine system have been widely described in major depression. The presence of alpha(2)-adrenoreceptors in blood platelets, similar to those in the brain, prompted us to evaluate them in depressed patients, as compared with healthy controls. METHODS: Fifteen outpatients affected by major depression, according to DSM IV criteria, and 15 comparable healthy control subjects, were included in the study. The alpha(2)-adrenoreceptors were measured by means of the specific binding of [(3)H]rauwolscine, a highly selective antagonist for this receptor subtype. The severity of depression was assessed by means of the Hamilton Rating Scale for Depression (HRSD). RESULTS: The results did not show any difference in [(3)H]rauwolscine binding parameters (B(max) and K(d)) between patients and controls. However, in the patients, a significant and positive correlation between B(max), which measures the density of the receptors, and HRSD total score was detected. CONCLUSIONS: Therefore, although no change in alpha(2)-adrenoreceptors seems to occur in major depression, the density of these receptors would seem to be related to the severity of depressive symptoms.

Adult↗
PubMed2000

Gender and age-related variation in adenylyl cyclase activity in the human prefrontal cortex, hippocampus and dorsal raphe nuclei.

The influence of gender and age on adenylyl cyclase activity was investigated, through a Dowex-alumina double step chromatographic procedure, in the prefrontal cortex, hippocampus and dorsal raphe nuclei obtained from autopsy cadavers. Results showed that forskolin-stimulated enzyme activity in raphe nuclei was greater in men than in women; a region-dependent rank order of basal, forskolin-induced adenylyl cyclase activity and percentage forskolin-stimulation was observed in women only. Lastly, basal values correlated positively with forskolin-stimulated adenylyl cyclase activity in all areas except the prefrontal cortex of the male subjects. Positive significant correlations were also found between both forskolin-stimulated enzyme activity and percentage forskolin stimulation and aging in the prefrontal cortex. Overall, the findings suggest that sex and/or age-related differences in brain adenylyl cyclase vary from one cerebral region to the other.

Adenylyl Cyclases↗
PubMed2000

Lack of stereoselectivity of 8-hydroxy-2(di-N-propylamino)tetralin-mediated inhibition of forskolin-stimulated adenylyl cyclase activity in human pre- and post-synaptic brain regions.

The stereoselectivity of the serotonin1A (5-HT1A) receptor compound 8-hydroxy-2(di-N-propylamino)tetralin (8-OH-DPAT) on forskolin-stimulated adenylyl cyclase activity was investigated in membranes from human 5-HT pre-synaptic (raphe nuclei) and post-synaptic (hippocampus and prefrontal cortex) regions of autopsy brains. After sample incubation with agonists and antagonists, results showed that both the racemic mixture of 8-OH-DPAT or its (+) and (-) enantiomers behaved as full agonists in the tested brain regions. Enantiomer potency (EC50, nM) and efficacy (percentage of maximal inhibition, %) values were similar in all regions under investigation. However, some inter and intra-region variations in racemic 8-OH-DPAT potency and efficacy have been observed. In particular, the potency of racemic 8-OH-DPAT was higher in the prefrontal cortex and raphe nuclei than in the hippocampus, where it was in fact lower than either single enantiomers. Agonist effects were competitively reversed by 5-HT1A antagonists, although once again a different profile was revealed in the hippocampus. The data underscores the lack of stereospecificity of 8-OH-DPAT-mediated inhibition of adenylyl cyclase activity in either pre- or post-synaptic human brain regions. Moreover, such results have significant implication, as they support the notion that human 5-HT1A receptors might vary from one brain region to the other.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Increased density of the platelet serotonin transporter in autism.

BACKGROUND: Various data have shown the involvement of serotonin (5-HT) in autism. The presence of the 5-HT transporter in platelets, similar to the same structure located in presynaptic serotonergic neurons, has produced a series of studies aimed at assessing its functionality in this disorder, but the ensuing findings are quite controversial. For this reason, we investigated the 5-HT transporter by means of the specific binding of [3H]-Paroxetine ([3H]-Par), which is currently considered the first-choice ligand for labeling it, in platelets of 20 autistic children and adolescents, as compared with healthy control subjects. METHODS: Twenty children and adolescents of both sexes suffering from autism according to DSM IV criteria were included in the study and compared with a similar group of healthy control subjects. Platelet membranes and the binding of [3H]-Par were carried out according to standardized protocols. RESULTS: The results showed a significantly higher density of [3H]-Par binding sites in autistic children than in healthy control subjects. CONCLUSIONS: These findings support the presence of a serotonergic dysfunction in autism and would suggest that the 5-HT transporter may have a specific role in this disorder, also in the light of its recently proposed role in brain development.

Adolescent↗
PubMed2000

Risperidone augmentation in refractory obsessive-compulsive disorder: an open-label study.

Risperidone, an atypical neuroleptic, has been proposed for augmentation strategies in resistant obsessive-compulsive disorder (OCD). We report the results of an open-label trial on the use of the combination of serotonin reuptake inhibitors (SRIs) with risperidone in 20 refractory OCD outpatients. All patients had been suffering from OCD, according to DSM-IV criteria, for at least 2 years and had various comorbid disorders. All had been treated with a SRI at adequate dosages for at least 6 months, but had failed to respond. Therefore, risperidone was added and the dosage titrated up to the mean dose of 3 mg/day over 8 weeks. After 2 months of this regimen, all patients had shown a reduction in obsessive-compulsive symptoms, as assessed by the decrease in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) total score, particularly those with a lifetime comorbidity with bipolar disorder; only three patients reported mild sedation and postural hypotension, two mild extrapyramidal side-effects (tremors and akatysia) and two an increased appetite. All these effects were well tolerated and no patient halted the treatment. The addition of risperidone would appear to be a useful strategy for augmenting SRI effectiveness in refractory OCD patients.

Adult↗
PubMed2000

Simultaneous plasma level analysis of clomipramine, N-desmethylclomipramine, and fluvoxamine by reversed-phase liquid chromatography.

A simple reversed-phase liquid chromatographic method enabling the simultaneous analysis in plasma of the tricyclic antidepressant clomipramine, its demethylated metabolite, and the selective serotonin reuptake inhibitor fluvoxamine, was developed. The drugs and dibenzepine, the internal standard, were extracted from 1 mL plasma through an automated solid-phase procedure, eluted in a total chromatographic time of approximately 14 min and detected by means of an ultraviolet spectrophotometer preset at 254 nm. An assay sensitivity of 10 microg/L was observed for all analytes. Recoveries for these drugs and their metabolites ranged between 65% and 98% and their coefficient of variation (within-day and day-to-day) between 1.9% and 2.9%. In spiked plasma, within-day and day-to-day imprecision data were less than 5%. The simultaneous determination of clomipramine, N-desmethylclomipramine, and fluvoxamine with adequate sensitivity and accuracy may be useful for the monitoring of drug treatment in depression and obsessive-compulsive disorder, where combinations of such drugs are employed.

Adult↗
PubMed2000

Increased inhibitory activity of protein kinase C on the serotonin transporter in OCD.

Different observations show a reduced functionality of the serotonin (5-HT) transporter in obsessive-compulsive disorder (OCD) that might be due to a disturbance of its regulation at intracellular level. Protein kinase C (PKC) has been reported to provoke a decrease in the number of the 5-HT transporter proteins. Therefore, we investigated whether OCD patients differed from control subjects in the effect of PKC upon the 5-HT transporter, after stimulation of this enzyme with 4beta-12-tetradecanoylphorbol 13-acetate (beta-TPA). Fifteen patients affected by OCD, according to DSM-IV criteria, were compared with a similar group of healthy subjects. The determination of 5-HT uptake was carried out according to the method of Arora and Meltzer with slight modifications. At baseline, OCD patients showed a significant decrease in the maximal velocity (V(max)) of 5-HT uptake, as compared with control subjects, with no change in the Michaelis-Menten constant (K(m)). The activation of PKC with beta-TPA provoked a significant decrease in V(max) values in both groups, but the effect was significantly more robust in OCD patients who, in turn, also showed also an increase in K(m) values. These findings could indicate the presence of hyperactivity of PKC in OCD that could be the result of increased activity of the phosphatidylinositol pathway. In addition, this suggests new potential therapeutic targets in OCD.

Adolescent↗
PubMed1999

Platelet [3H]paroxetine binding in patients with OCD-related disorders.

The recently introduced notion of clinical conditions being related one to another, the spectrum concept, permits the testing of the involvement of serotonergic systems in a broad range of disorders tentatively linked to obsessive-compulsive disorder (OCD) for which no pathophysiological hypotheses yet exist. We therefore compared the binding of [3H]paroxetine ([3H]Par), a ligand that specifically labels the serotonin (5-HT) transporter, in platelets of drug-free outpatients suffering from various OCD-related disorders with binding in platelets of OCD patients and healthy subjects. Diagnoses were made according to DSM-IV criteria. The most frequent diagnosis was that of body dysmorphic disorder, followed by impulse control disorder, kleptomania, Tourette's syndrome and trichotillomania. Platelet membranes and [3H]Par binding were studied according to standardized protocols. The results, showing a similarly decreased density of [3H]Par binding sites in both patient groups as compared with healthy subjects, suggest the presence of a shared abnormality at the level of the presynaptic 5-HT transporter, probably linked to a common dimension yet to be identified.

Adolescent↗
PubMed1999

Immunological alterations in adult obsessive-compulsive disorder.

BACKGROUND: Some recent findings suggest the involvement of autoimmune mechanisms in childhood onset of obsessive-compulsive disorder (OCD), on the basis of a parallel drawn with Sydenham's chorea, a manifestation of rheumatic fever. A monoclonal antibody called D8/D17 characterizing a B-lymphocyte antigen, present in almost all patients with rheumatic fever, has been found also in children affected by OCD, Tourette syndrome, and chronic tics to a greater degree than in healthy control subjects. The few observations of disturbances of some immunologic parameters in adult OCD patients, prompted the authors to investigate and compare subsets of peripheral immunological cells for differences in adult patients with OCD and healthy control subjects. METHODS: Twenty patients suffering from OCD, with no comorbidity for other psychiatric disorders, were compared with a similar group of healthy control subjects. The immune subsets were measured by flow cytometry. RESULTS: The CD8+ lymphocytes were significantly increased and CD4+ lymphocytes significantly decreased in OCD patients, while the other cells did not differ between the two groups. No correlation was found between immunologic and clinical parameters. CONCLUSIONS: These data indicate that patients with adult OCD showed increased CD8+, i.e., suppressor T lymphocytes, and decreased CD4+, which identify helper T lymphocytes, as compared with a similar group of healthy control subjects. The findings appear peculiar to patients with OCD and are suggestive of an immunologic imbalance, which might be related to the stress deriving from the frustrating situation determined by the disorder itself.

Adolescent↗