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Biomedical subjects

D Marazziti

Publications and source records attributed to D Marazziti.

At least 73 records · Page 4Linked to original sources

Presence of serotonin1A (5-HT1A) receptor mRNA without binding of [3H]-8-OH-DPAT in peripheral blood mononuclear cells.

The authors investigated the presence of serotonin receptor type 1A (5-HT1A) as labeled by the specific ligand 3H-8 hydroxy-2-(di-N-propylamino)tetralin (3H-8-OH-DPAT) in saturation experiments, and the expression of the mRNA encoding them, in human peripheral blood mononuclear cells (PBMC). In situ hybridization experiments were performed as well. The results, showing that the binding of [3H]-8-OH-DPAT to lymphocyte membranes increased linearly up to 100 nM without reaching saturation, may indicate that the 3H-8-OH-DPAT was not specifically labeling the 5-HT1A receptor. By contrast, the expression studies revealed 5-HT1A mRNA in PBMC. These findings suggest that, despite the presence of mRNA, 5-HT1A receptors are not expressed in PBMC, at least in healthy controls.

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

Platelet markers in suicide attempters.

1. The authors measured 3H-imipramine (3H-IMI) binding and serotonin (5HT) uptake parameters as well as sulphotransferase activity in platelets of suicide attempters. 2. Platelet 3H-IMI binding sites and 5HT uptake are related to similar sites and processes present in the brain, and sulphotransferase (ST) is an enzyme involved in the catabolism of cathecholamines. 3. The results showed the presence of a decreased density of both 3H-IMI binding and of 5HT uptake sites, with no change in ST activity in suicide attempters, as compared with healthy controls. 4. The reduced 3H-IMI binding and 5HT uptake may be related to a hypofunction of presynaptic serotonergic mechanisms which might be altered in suicidal behavior.

Adolescent↗

Effectiveness of the combination verapamil and chlorpromazine in the treatment of severe manic or mixed patients.

1. The authors investigated the possible antimanic properties of a Calcium channel blocker, Verapamil, in 15 in-patients admitted consecutively to the female psychiatric ward at Pisa University for a manic episode. 2. The results showed that most of the patients presented a global improvement of the manic symptoms and, in some cases, even a complete clinical remission. 3. Although it was necessary to add chlorpromazine for the severe conditions of several patients, verapamil appeared to speed the positive outcome and to lead to a faster resolution of the symptoms. In addition, the association of verapamil and chlorpromazine did not produce any relevant side-effect. These preliminary findings thus indicate that verapamil by itself does not seem to be sufficient in the treatment of a severe affective episode, but it may constitute an alternative to lithium salts in association with neuroleptics.

Adolescent↗

Phenomenology and neurobiology of cocaine withdrawal: are they related?

1. The presence of mood disturbances and platelet 3H-imipramine binding, a putative peripheral serotonergic marker, were evaluated in a group of 27 cocaine users three days after drug withdrawal. 2. Parameters of cocaine use and the linkage between cocaine withdrawal and "post-cocaine depression" were also investigated. In a subgroup of 10 patients, both psychopathological and biological measurements were repeated after 5 or 6 weeks. 3. Interpretation of the data by Pearson's analysis showed a statistically significant and positive correlation between Hamilton Rating Scale for Depression (HAM-D) scores and period of use. A trend towards a negative correlation, which however did not reach the statistical significance, was found between 3H-Imipramine binding and period of cocaine use, number of days of abstinence and HAM-D scores 4. When compared with normal volunteers at baseline, patients had significantly lower Bmax and Kd values which returned towards normal values after 5 or 6 weeks of cocaine withdrawal. 5. These results indicate the presence of a decreased platelet imipramine binding during cocaine withdrawal which may be due to the effect of the drug or alternatively, a result of concomitant depression which may be primary or secondary in origin. The decreased imipramine binding is a reversible phenomenon, since it increases with the time, in parallel with the improvement of depressive symptoms.

Adult↗

Imipramine binding as a predictor of fluoxetine response in depressed patients.

We evaluated platelet 3H-imipramine (3H-IMI) binding parameters (Bmax and Kd) at baseline (t0) and 2 months after (t1) treatment with fluoxetine in a group of outpatients affected by a major depressive episode, according to DSM-IIIR criteria. The possible relationships between biological parameters and the Hamilton Rating Scale for Depression (HRSD) total score were examined. The results confirmed previous reports that depressed patients possessed a lower density (Bmax) of platelet 3H-IMI binding sites than healthy controls, but the Bmax tended to decrease with fluoxetine. In addition, we observed a negative correlation between Bmax values at t0 and the HRSD total scores at t1 indicating that the patients who responded better to fluoxetine were those with a lower Bmax at t0. Future studies will substantiate this preliminary observation on the possible usefulness of platelet 3H-IMI binding as a predictor of pharmacological response.

Adult↗

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↗

Human platelet sulfotransferase shows seasonal rhythms.

Our study aimed to investigate the possible presence of seasonal changes in platelet phenolsulfotransferase (ST) in a group of 20 healthy, drug-free subjects of both sexes between 24 and 37 years of age. Blood samples were taken four times a year in the period immediately following the equinoxes and the solstices. The results showed that both Sts underwent seasonal changes: the lowest values were found in autumn and in winter, and the highest in the summer. A positive correlation between the two STs and the length of the photoperiod was observed in winter whereas in the spring we detected a negative correlation between the TL ST and the photoperiod length. Future studies should clarify whether platelet ST of patients with mood disorders shows a similar seasonality.

Adult↗

Localization and gene expression of serotonin 1A (5HT1A) receptors in human brain postmortem.

We investigated the binding parameters, i.e. the maximum binding capacity (Bmax) and the dissociation constant (Kd), of [3H]8-hydroxy-2-(di-N-propylamino)tetralin ([3H]8-OH-DPAT) labeling the serotonin receptor of the 1A type (5HT1A), and the distribution of the mRNA encoding it in some human brain areas obtained from autoptic samples. The results showed that the Bmax was significantly higher in the hippocampus than in the prefrontal cortex and the striatum, while the Kd had the inverse, although not significant, pattern. The expression study revealed that 5HT1A mRNA distribution in the hippocampus and prefrontal cortex was consistent with the data of the [3H]8-OH-DPAT binding. A different result was obtained in the striatum where no 5HT1A mRNA expression was detected, despite the measurement of specific [3H]8-OH-DPAT binding. These findings underline the different nature of [3H]8-OH-DPAT binding sites in different brain areas and the need for further studies on 5HT receptor gene expression in human brain.

Aged↗

Solubilization and characterization of [3H]imipramine and [3H]paroxetine binding sites from calf striatum.

The serotonin (5-HT) transporter from calf striatum cerebral membranes was solubilized with digitonin and characterized by gel exclusion chromatography. [3H]Imipramine and [3H]paroxetine were utilized as markers for labeling it. 3H-imipramine labels a high- and a low-affinity site on striatum membranes, whereas it binds to a single high-affinity site on the solubilized fraction. [3H]Paroxetine binds with the same affinity to a single site on both membranes and solubilized preparations. After gel exclusion chromatography of the solubilizate both [3H]imipramine and [3H]paroxetine bind on an identical fraction of 205 kDa molecular weight, with a similar maximum number of binding sites (Bmax). Our results suggest that both 3H-imipramine and [3H]paroxetine bind to a common site on the 5-HT transporter.

Animals↗

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↗

Changes in peripheral benzodiazepine receptors in patients with panic disorder and obsessive-compulsive disorder.

Peripheral benzodiazepine (BDZ) receptors were investigated through the binding of the specific ligand 3H-PK-11195 to platelet membranes, in 17 patients suffering from panic disorder (PD) and in 16 patients affected by obsessive-compulsive disorder (OCD). The results, showing that the density (Bmax) of peripheral BDZ receptors was significantly lower in patients with PD than in controls or OC patients, suggest that the number of platelet BDZ receptors varies with different anxiety disorders and that perhaps this marker may be beneficial in differentiating some subtypes of these disorders.

Adolescent↗

Platelet serotonergic markers and aggressive behaviour in healthy subjects.

The availability of peripheral markers of the serotonergic system, which appears to play a major role in aggressive behaviour, prompted us to investigate in healthy subjects the possible correlations between platelet 3H-imipramine (3H-IMI) binding or mono-amine-oxidase (MAO) activity and aggression as measured by the Italian version (QTA) of the Buss and Durkee Inventory. The results showed the presence of significant and positive correlations between MAO activity and QTA total scores and the scales of negativism and verbal aggression, and no correlation between 3H-IMI binding parameters and QTA. These findings seem to suggest that perhaps the MAO activity is more linked to the dimension of aggression than is IMI binding.

Adult↗

Age-related changes in peripheral benzodiazepine receptors of human platelets.

Using 3H-PK 11195 as radioligand, the number and affinity of peripheral benzodiazepine receptors in platelets of 15 elderly healthy subjects were compared to those of 15 young subjects. The results showed that the dissociation constant (Kd) was significantly higher in the elderly than in the young subjects, while the density of binding sites did not differ. These findings suggest that the age-related changes in peripheral benzodiazepine receptors may be coupled with secondary changes in their hypothesized functions.

Adult↗

Social class and mood disorders: clinical features.

We examined clinical features in 877 in- and outpatients affected by depression who were enrolled in psychopharmacological trials, subdivided according to Hollingshead's method into five social classes. The results showed that social class correlated significantly with the subtypes of mood disorders, with bipolar disorder being more frequent amongst the upper than the lower social classes. Furthermore, as already reported in other countries, social class appeared to influence the psychopathological pattern of depressive symptoms: somatization and anxiety were more frequent amongst the lower social classes, while psychic and cognitive symptoms were more common amongst the upper classes.

Adult↗

A single electroconvulsive treatment affects platelet serotonin uptake in bipolar I patients.

We evaluated serotonin (5HT) uptake parameters in platelets of a group of bipolar I patients in both a depressive phase and a mixed state, before (t0) and after (t1) the first electroconvulsive treatment (ECT). The results showed the presence of significant changes in the number of the carrier proteins for 5HT at t1, which in most cases preceded the clinical improvement. Although other mechanisms are certainly involved, these data suggest that ECT may influence the 5HT transport through platelet membranes.

Adult↗

Psychological stress and body temperature changes in humans.

We investigated the possible changes in body temperature, heart frequency, and blood pressure in 22 residents sitting for the yearly exam at the Specialty School of Psychiatry at Pisa University. All subjects were then evaluated 2 or 3 weeks later, in calm situations. In a subgroup, a specific plasmatic diazepam binding inhibitor (BBIA), previously described, was also measured. The results showed that all subjects underwent significant stress-related changes in the parameters studied, which suggest the involvement of different mechanisms in preexam stress.

Adult↗

Peripheral markers of serotonin and dopamine function in obsessive-compulsive disorder.

In an attempt to clarify the possible role of a serotonergic and dopaminergic dysfunction in obsessive-compulsive disorder (OCD), we measured platelet 3H-imipramine (3H-IMI) binding, serotonin uptake, and platelet sulfotransferase activity in 17 drug-free OCD patients and an equal number of healthy controls. Serotonin uptake and 3H-IMI binding sites in platelets have been shown to constitute peripheral markers of those present in presynaptic serotonergic neurons. Sulfotransferase, an enzyme involved in the catabolism of phenolic compounds and of cathecholamines such as dopamine, has similar kinetic characteristics in brain and platelets. Our results showed a lower number of 3H-IMI binding sites and a higher level of sulfotransferase activity in OCD patients compared with those in controls. These preliminary results suggest involvement of both the serotonin and dopamine systems in OCD.

Adult↗