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Biomedical subjects

D Marazziti

Publications and source records attributed to D Marazziti.

At least 55 records · Page 3Linked to original sources
PubMed1998

Presence and characterization of the serotonin transporter in human resting lymphocytes.

Although evidence exists of the presence of a serotonin (5-HT) reuptake system in lymphocytes, no information is available on the pharmacological characterization of this structure. Our study aimed to investigate this matter, therefore, by means of the binding of [3H]-paroxetine ([3H]PAR), a selective 5-HT reuptake inhibitor (SSRI), which is considered the ligand of choice for binding studies. Lymphocytes were obtained from a pool of 20 healthy subjects who volunteered for the study. The results showed the presence of a specific and saturable [3H]PAR binding to lymphocyte membranes, with a Hill number close to unity indicative of the presence of one site only. The most potent drugs inhibiting [3H]PAR binding were SSRIs (paroxetine, fluoxetine, citalopram) followed by clomipramine, imipramine, and 5-HT, whereas haloperidol, mazindol, and nomifensine had a negligible effect. These findings suggest that [3H]-PAR in human resting lymphocytes specifically labels the 5-HT transporter.

Adolescent↗
PubMed1998

Gender-related seasonality of human platelet phenolsulfotransferase activity.

This study focused on the investigation of the possible effect of gender and season on the activity of the thermolabile and thermostable forms of platelet phenolsulfotransferase (PST) in a group of 23 healthy, drug-free volunteers of both sexes. The results showed a different seasonal profile of PST activity in men and women: in men, PST seasonal rhythms revealed a shallow profile with higher values in both the spring and summer than in the autumn. Conversely, in women, the PST seasonality showed a profile consisting overall of a main peak in the summer. Also, significant gender-dependent correlations were found between the photoperiod length and PST values. Our findings should stimulate further investigation into gender-dependent molecular mechanisms underlying the regulation of the metabolism of endogenous and xenobiotic agents, such as monoamines and phenols, which are the substrates of PST.

Adult↗
PubMed1998

Prevalence of psychiatric disorders in thyroid diseased patients.

Several studies have underlined the high prevalence of psychiatric symptoms and disorders in thyroid diseases. The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes, by means of a standardized instrument, i.e., the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised, Upjohn Version (SCID-UP-R). The results showed higher rates of panic disorder, simple phobia, obsessive-compulsive disorder, major depressive disorder, bipolar disorder and cyclothymia in thyroid patients than in the general population. These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities.

Adult↗
PubMed1997

Cloning of GPR37, a gene located on chromosome 7 encoding a putative G-protein-coupled peptide receptor, from a human frontal brain EST library.

A cDNA sequence encoding a putative peptide-specific G-protein-coupled receptor (GPR37) was isolated from a set of human brain frontal lobe expressed sequence tags. The GPR37 cDNA predicts a single open reading frame coding for a 613-amino-acid protein with seven hydrophobic transmembrane domains. The GPR37 genomic sequence was mapped to chromosome 7q31, and it was isolated upon screening of a chromosome 7-specific genomic library. The GPR37 gene spans more than 25 kb and contains two exons and a single intron which interrupts the GPR37 cDNA within the sequence encoding the presumed third transmembrane domain. Northern blot analysis with GPR37 probes revealed a main 3.8-kb mRNA and a less abundant 8-kb mRNA, both expressed in human brain tissues, particularly in corpus callosum, medulla, putamen, and caudate nucleus. The lowest level of expression was detected in cerebellum. The 3.8-kb mRNA is also less abundantly expressed in liver and placenta. Although the ligand for the putative GPR37 receptor has not been identified, its deduced amino acid sequence shows a high degree of homology (approximately 40% in the transmembrane regions) with most mammalian peptide-specific G-protein-coupled receptors and particularly with the human endothelin-B, bombesin-BB1, and bombesin-BB2 receptors.

Adult↗
PubMed1997

Apparent absence of aging and gender effects on serotonin 1A receptors in human neocortex and hippocampus.

The effects of gender, aging and gender x age on the binding of the 5-HT1A receptor high-affinity agonist [3H]8-hydroxy-2(di-N-propylamino)tetralin ([3H]8-OH-DPAT), were evaluated and compared in tissues of human prefrontal, temporal, parietal, occipital cortex and hippocampus obtained from 21 autopsy subjects. The results revealed no variation with age or gender in either the [3H]8-OH-DPAT maximum binding capacity (Bmax) or dissociation constant (Kd) values. On the other hand, when separate correlations to subject ages were performed for men and women, aging effects on [3H]8-OH-DPAT Bmax and Kd were detected: in men, a significant age-dependent decrease in Kd values was observed in the occipital cortex; in women, the Bmax significantly decreased with aging in the parietal cortex and hippocampus, while increasing in occipito-cortical membranes. Overall, the present study reveals that, although neither gender nor aging 'per se' seem to modify the 5-HT1A receptor binding, gender may reveal region-specific aging effects, i.e. on receptor affinity in men and receptor density in women. Such findings should stimulate further investigation on the hypothesized existence of gender x age-related cross-connections between serotonergic system and hypothalamus-pituitary-gonadal circuits.

Adult↗
PubMed1997

Further characterisation of [3H]8-hydroxy-2-(di-N-propylamino)tetralin binding sites in human brain postmortem.

The saturation parameters and the pharmacological characteristics of the binding of the serotonin 1A (5-HT1A) receptor agonist [3H]8-hydroxy-2-(di-N-propylamino)tetralin ([3H]8-OH-DPAT), as well as the effects of nucleotides and divalent cations (Mg2+, Mn2+) on it, were compared in some human postmortem brain regions: the main cortical areas, hippocampus and striatum. [3H]8-OH-DPAT labelled a single population of recognition sites with the highest maximal capacity (Bmax) in the hippocampus and the lowest affinity in the striatum. Among the various cortical areas, the frontal cortex exhibited the highest Bmax. The pharmacological profile of the [3H]8-OH-DPAT binding sites was consistent with the labelling of the 5-HT1A receptor in the hippocampus and cortex, whereas the striatal site shared strong similarity to the presynaptic serotonin transporter. Modulation of [3H]8-OH-DPAT binding by divalent cations and nucleotides was detectable and stable in autopsy brains. In particular, nucleotide effects were area-dependent: guanosine thiotriphosphate (GTP gamma S) reduced [3H]8-OH-DPAT binding to the same extent in the hippocampus and frontal cortex, while having no effect in the striatum. Divalent cation effects depended also upon the brain area: in the striatum, they inhibited [3H]8-OH-DPAT binding, while stimulating it in the hippocampus and, with less extent, in the frontal cortex. In summary, these findings suggest that the [3H]8-OH-DPAT binding and its modulatory parameters in human brain tissues seem to show similarities but also some differences with respect to those determined in the rat brain. Furthermore, postmortem stability of GTP and divalent cation sensitive 5-HT1A receptors underlines the need for further studies on the regulatory and functional properties of this receptor in the human brain.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

[3H]ketanserin binding in human brain postmortem.

This study aimed at comparing the binding characteristics of [3H]ketanserin, a high-affinity serotonin 2A (5-HT2A) receptor antagonist, in the prefrontal cortex, hippocampus and striatum of human brain post-mortem. The results indicated the presence of a single population of binding sites in all the regions investigated, with no statistical difference in maximum binding capacity (B(max)) or dissociation constant (K(d)) values. The pharmacological profile of [3H]ketanserin binding was consistent with the labeling of the 5-HT2A receptor, since it revealed a competing drug potency ranking of ketanserin = spiperone > clozapine = haloperidol > methysergide > mesulergine > 5-HT. In conclusion, the 5-HT2A receptor, as labeled by [3H]ketanserin, would seem to consist of a homogenous population of binding sites and to be equally distributed in human prefronto-cortical, limbic and extrapyramidal structures.

Autopsy↗
PubMed1997

Changes in platelet markers of obsessive-compulsive patients during a double-blind trial of fluvoxamine versus clomipramine.

Abnormalities of platelet serotonin (5-HT) transporter, which are supposed to reflect similar dysfunctions in the central nervous system (CNS), have been reported in obsessive-compulsive disorder (OCD). Other platelet parameters altered in OCD are represented by phenolsulfotransferase (PST) activity, an enzyme involved in the catabolism of catecholic neuro-transmitters, and peripheral benzodiazepine receptors. Since no information is available on the behavior of these putative markers during antiobsessive treatments, the aim of the present study was to measure and compare 3H-imipramine (3H-IMI) binding, which labels the 5-HT transporter, PST activity, and 3H-PK 11,195 binding, which labels peripheral benzodiazepine receptors, in a group of 18 patients with obsessive-compulsive disorder (OCD) before and after a treatment with fluvoxamine versus clomipramine. The results showed that at baseline the patients had a decreased number of 3H-IMI binding sites, which correlated negatively with the Y-BOCS total score, an increased PST activity and no difference in 3H-PK 11,195 binding, as compared with healthy volunteers. After eight weeks of treatment with either clomipramine or fluvoxamine, which was effective in all patients, the number of 3H-IMI binding sites increased significantly toward normal values, while the PST showed no change. These findings suggest that the reduction in 3H-IMI binding sites in OCD may be related to the severity of the illness and possibly to a positive response to serotonin re-uptake inhibitors, and might be considered as a state-dependent marker, whereas the PST activity would seem to be a trait of the illness.

Adult↗
PubMed1997

A double-blind study of fluvoxamine and clomipramine in the treatment of obsessive-compulsive disorder.

A double-blind trial was carried out to assess the efficacy and safety of fluvoxamine, a selective serotonin reuptake inhibitor, in comparison with clomipramine, a classical tricyclic antidepressant, in the treatment of obsessive-compulsive disorder. A total of 26 individuals with obsessive-compulsive disorder and with no comorbid disorders at baseline were included in the study. The obsessive-compulsive disorder symptom severity was rated using the Yale-Brown Obsessive-Compulsive Scale and the Clinical Global Impression Scale. The primary efficacy measures indicated an equal improvement in the two groups (38% in the patients taking fluvoxamine and 40% in those taking clomipramine, as compared with baseline values), but onset was faster in the clomipramine group. Side effects, in particular anticholinergic side effects, were more prominent in the clomipramine group. The present double-blind trial confirms an equal efficacy of clomipramine and fluvoxamine in obsessive-compulsive patients. Although clomipramine had a faster onset, fluvoxamine was better tolerated, so that it seems more suitable for long-term treatment of obsessive-compulsive patients.

Adolescent↗
PubMed1997

Platelet serotonin transporter in coeliac disease.

We investigated a peripheral serotonergic marker, i.e. platelet tritiated imipramine (3H-IMI) binding sites, which are part of the 5-HT transporter complex similar to that present in the brain, in 20 patients affected by coeliac disease (CD), as compared with 20 healthy controls. Platelet membranes and 3H-IMI binding were carried out according to a standardized protocol. The results showed that coeliac patients had significantly lower 3H-IMI binding sites than controls. This finding would suggest the presence of a dysfunction at the level of the 5-HT transporter that might underline the psychic disturbances frequently observed in coeliac patients.

Adolescent↗
PubMed1996

Platelet sulfotransferase in different psychiatric disorders.

The aim of our study was to measure and compare platelet phenolsulfotransferase (PST) activity in patients affected by different psychiatric disorders and in healthy volunteers. The results showed that the activity of both of the two forms of PST was significantly higher in 30 patients with obsessive-compulsive disorder and in 25 manic patients than in 20 healthy volunteers. On the contrary, normal values were found in 11 dysthymic patients, 12 bipolar depressives, and 14 patients with panic disorder, whereas lower values were found in 12 unipolar depressives and 30 patients with migraine. It would therefore seem that different neuropsychiatric disorders are associated with different levels of PST activity.

Adult↗
PubMed1996

Comparative anatomical distribution of serotonin 1A, 1D alpha and 2A receptor mRNAs in human brain postmortem.

The distribution of messenger ribonucleic acids (mRNA) for serotonin (5-HT) receptors of 1A, 2A and 1D alpha type (5-HT1A, 5-HT2A, and 5-HT1D alpha) was examined and compared in autoptic human brain by means of in-situ hybridization using cRNA probes, in those areas with the highest density of the receptors, as observed with binding techniques. The results showed that the 5-HT1A receptor mRNA was abundantly expressed in the layers II-VI of all cortical areas under examination, but the highest expression was found in the hippocampus, particularly in the granular cells of the dentate gyrus and in the pyramidal cell layer of the Hammon's horn. The 5-HT2A receptor mRNA was mainly present in the layers III-V of the cortex, with regional differences which were particularly marked in the striate area where the layer IV was specifically labeled. On the other hand, in the hippocampus, 5-HT2A receptor mRNA was restricted to the pyramidal cell layer of the CA1 field of the Hammon's horn. No expression of both 5-HT2A and 5-HT1D alpha receptors was detected in the caudate nucleus and in putamen where only a light labeling by means of the 5-HT1A receptor probe was detected. The 5-HT1D alpha receptor mRNA was found only in the CA3 field of the Hammon's horn. These findings confirm that 5-HT receptors are widely distributed in the brain, but that the different subtypes possess a selective localization in different neuronal populations which, in turn, may express one or more receptors. The regional differences may represent the anatomical substrate of different serotonergic functions and dysfunctions.

Adult↗
PubMed1996

The serotonin transporter from human brain: purification and partial characterization.

The serotonin (5-HT) transporter from human striatum was solubilized by digitonin and purified by affinity chromatography. The native protein-detergent complex had a molecular mass of 205 kDa, as estimated by gel-exclusion chromatography of the eluates obtained from affinity chromatography. The purified 5-HT transporter migrated as a single band of 67 kDa in SDS-PAGE. To clarify the spatial relationships between the binding sites of the tricyclic antidepressants, as [3H]-imipramine, and of the selective serotonin reuptake inhibitors, as [3H]-paroxetine, on the 5'HT transporter, both radioligands were used to label it in the purification steps. [3H]-paroxetine bound with the same affinity to a single high-affinity site on both membrane and purified preparations. [3H]-imipramine labeled a high- and a low-affinity site on parent membranes, whereas it bound to a single high-affinity site on the purified extract. Tricyclic antidepressants, selective serotonin reuptake inhibitors and 5-HT itself displaced [3H]-paroxetine and [3H-]imipramine from their high-affinity binding sites on both the membrane-bound and the purified 5-HT transporter in a monophasic fashion with Hill coefficients close to unity. Furthermore, both [3H]-paroxetine and [3H]-imipramine displayed a similar maximum binding capacity on an identical protein of 205 kDa. Our results suggest overlapping binding sites for tricyclic antidepressants, selective serotonin reuptake inhibitors and 5-HT on the 5-HT transporter.

Antidepressive Agents, Tricyclic↗
PubMed1996

Benzodiazepine binding inhibitory activity: new supportive findings on its presence in psychiatric patients and further biochemical analyses.

The authors investigated the presence of a serum activity inhibiting the specific binding of 3H-flunitrazepam (which labels the central benzodiazepine receptors) (BBIA) in patients with different psychiatric disorders and analyzed it by means of high performance liquid chromatography (HPLC) analysis. The results showed that the lowest activity was present in healthy controls who were not different from patients with schizophrenia and obsessive-compulsive disorder. On the contrary, the BBIA values of these 3 groups of patients were significantly lower than those found in patients with bipolar disorder in various phases (depressive, mixed or manic), in unipolar depressives and in patients with panic and delusional disorders. The HPLC analysis of the serum extracts revealed the presence of 3 peaks of activity which were differently distributed in the patients and in the healthy controls, peak 3 being totally absent in the last group and mainly represented in bipolar depressives. The GABA ratio values showed that peaks 1 and 2 behave as agonists while peak 3 behaves as an inverse agonist. The mass fragmentography of the different peaks is in progress.

Adult↗
PubMed1996

Decreased platelet 3H-paroxetine binding in obsessive-compulsive patients.

The similarities between the serotonin (5-HT) transporter in both human platelets and human brain permit us to investigate this structure in patients with different psychiatric disorders. Several reports have shown abnormalities of the 5-HT transporter, by means of the measurement of the 5-HT uptake or of the 3H-imipramine binding, in platelets of patients with obsessive-compulsive disorder (OCD). The availability of the ligand 3H-paroxetine, a selective 5-HT reuptake inhibitor, to label the 5-HT transporter, promoted us to evaluate the binding of 3H-paroxetine in platelets of 18 drug-free patients with OCD. The results, showing that the patients had a lower number of 3H-paroxetine sites, which is inversely correlated with the Yale Brown Obsessive-Compulsive Scale total score, than a similar group of controls, add supporting evidence to the involvement of 5-HT in OCD. In addition, the decreased functionality of the 5-HT transporter seems to be linked to the severity of OC symptoms.

Adolescent↗
PubMed1996

Platelet abnormalities in aggressive subjects with mental deficiency.

Platelet 3H-imipramine (3H-IMI) binding and platelet sulfotransferase (ST) activity, taken as markers of the serotonin (5-HT) and sulfated neurotransmitters (tyramine, dopamine, serotonin, noradrenaline), respectively, were evaluated in 14 severely aggressive subjects institutionalized since childhood for mental retardation and in an equal number of healthy controls. The results showed the presence of a lower number of 3H-IMI binding sites and a higher ST activity in the patients as compared with controls. These data provide supporting evidence for the hypothesis of an abnormality of the 5-HT system and suggest possible dysfunctions of dopamine and sulfated amines in aggressive behavior, at least as reflected by platelet markers.

Adult↗