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Biomedical subjects

P Monteleone

Publications and source records attributed to P Monteleone.

At least 19 recordsLinked to original sources

Plasma prolactin response to D-fenfluramine is blunted in bulimic patients with frequent binge episodes.

BACKGROUND: Abnormalities of brain serotonin (5-HT) transmission have been implicated in the pathophysiology of bulimia nervosa (BN), but no conclusive data have yet been provided. The purpose of this study was to assess 5-HT transmission via the measurement of the prolactin (PRL) response to the specific 5-HT releasing agent D-fenfluramine (D-FEN) in both patients with BN and comparison subjects. METHODS: According to a double-blind placebo-controlled design, plasma PRL response to D-FEN was measured in 14 drug-free bulimics and 14 matched healthy controls. In both patients and controls, eating-related psychopathology, depressive and obsessive-compulsive symptoms, and aggressiveness were measured by rating scales. RESULTS: Baseline plasma levels of PRL and 17 beta-oestradiol were significantly reduced in bulimic patients, whereas basal plasma levels of cortisol did not significantly differ from healthy controls. PRL response to D-FEN was not different between patients and controls as groups, but it was significantly blunted in bulimics with high frequency bingeing (> or = 2 binge episodes per day; N = 7) as compared to both those with low frequency bingeing (< or = 1 binge episode per day; N = 7) and matched controls. A significant negative correlation emerged between the frequency of binge episodes and the hormone response to D-FEN. Moreover, although patients scored higher than healthy subjects on rating scales assessing depressive and obsessive-compulsive symptoms and aggressiveness, no significant correlation was found between these measures and the PRL response to D-FEN. CONCLUSIONS: These results support the idea that serotonin transmission is impaired in bulimic patients with frequent binge episodes.

Adult

Effect of fluoxetine on the plasma concentrations of clozapine and its major metabolites in patients with schizophrenia.

The effect of fluoxetine on the plasma concentrations of clozapine and its major metabolites was studied in 10 schizophrenic patients with residual negative symptoms. Patients stabilized on clozapine therapy (200-450 mg/day) received additional fluoxetine (20 mg/day) for eight consecutive weeks. During fluoxetine administration, mean plasma concentrations of clozapine, norclozapine and clozapine N-oxide increased significantly by 58%, 36% and 38%, respectively. There was no difference in negative symptomatology, as measured by the Scale for Assessment of Negative Symptoms, and the drug combination was generally well tolerated. The concomitant elevation in plasma levels of clozapine and its major metabolites suggests that fluoxetine inhibits the metabolism of clozapine by affecting pathways other than N-demethylation and N-oxidation. Close monitoring of clinical response and, possibly, plasma clozapine levels is recommended whenever fluoxetine is given to patients stabilized on clozapine therapy.

Adult

Full-syndrome, partial-syndrome and subclinical eating disorders: an epidemiological study of female students in Southern Italy.

We screened a sample of 919 female students, aged 13-19 years, by means of the EDI 2 and GHQ-28 questionnaires. Those students identified as being at risk for an eating disorder (281 subjects) underwent a psychiatric interview. We found 2 cases of full-syndrome anorexia nervosa (0.2%), 21 cases of full-syndrome bulimia nervosa (2.3%) and 2 cases of full-syndrome binge-eating disorder (0.2%). Moreover, 35 girls (3.8%) met the criteria for partial-syndrome and 98 girls (10.7%) fulfilled the criteria for subclinical eating disorders. Subjects with partial-syndrome and subclinical eating disorders had higher scores than those with no diagnosis, but lower scores than students with full-syndrome eating disorders, on both the EDI 2 and GHQ-28 questionnaires. A follow-up of subjects with partial-syndrome and subclinical eating disorders is now in progress.

Adolescent

Decreased blood levels of tumor necrosis factor-alpha in patients with obsessive-compulsive disorder.

To investigate immune system function in obsessive-compulsive disorder (OCD) we measured plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) in 14 drug-free obsessive-compulsive patients and 14 matched healthy controls. No significant differences were observed between patients and controls in plasma levels of IL-1 beta and IL-6, whereas plasma levels of TNF-alpha were significantly lower (p = 0.001) in the former. Blood levels of prolactin did not differ between the two groups, whereas plasma cortisol concentrations were significantly higher in patients than in healthy subjects (p = 0.02). No significant correlation was found between immune parameters, on the one hand, and endocrine or psychopathological measures on the other. These results suggest that OCD is associated with a decreased production in TNF-alpha, but normal synthesis of IL-1 beta and IL-6.

Adult

Prolactin response to d-fenfluramine is blunted in people with anorexia nervosa.

BACKGROUND: Several studies have explored serotonin (5-HT) transmission in people with anorexia nervosa, but their results have been inconsistent. METHOD: According to a double-blind placebo-controlled design, plasma prolactin response to the specific serotonergic probed d-fenfluramine was investigated in 10 under weight and two normal-weight women with anorexia, and in 12 age-matched healthy females. Eating-related psychopathology, depressive and obsessive--compulsive symptoms, and aggressiveness were measured by appropriate rating scales. RESULTS: Compared with healthy control subjects, the women with anorexia showed reduced baseline prolactin and oestrogen levels and increased basal cortisol concentrations. The prolactin response to d-fenfluramine was blunted and did not correlate with psychopathological measures. CONCLUSIONS: These results support a dysfunction of 5-HT transmission in anorexia nervosa. This dysfunction does not seem to be related to concomitant depressive or obsessive--compulsive symptoms or to the level of aggressiveness of the patients.

Adolescent

Plasma prolactin response to d-fenfluramine in obsessive-compulsive patients before and after fluvoxamine treatment.

The prolactin (PRL) responses to oral d-fenfluramine (30 mg) and placebo were assessed in 13 patients with obsessive-compulsive disorder (OCD) and in matched healthy subjects. After the neuroendocrine test, all patients were treated with fluvoxamine maleate (150-300 mg/day). At the end of the 10th week of treatment, 10 patients underwent again the neuroendocrine assessment. In drug-free patients, the PRL response to d-fenfluramine was significantly lower than in the comparison group. After 10-week fluvoxamine treatment, the PRL response to the serotonergic agent normalized. These findings suggest that, at least at the neuroendocrine level, central serotonergic responsivity is reduced in drug-free OCD patients, and that long-term fluvoxamine administration is associated with its normalization.

Adolescent

Effect of chronic clozapine administration on [3H]MK801-binding sites in the rat brain: a side-preference action in cortical areas.

We studied modifications in [3H]MK801-binding sites in the rat brain after chronic clozapine. We found a 20-30% reduction of [3H]MK801-binding sites in the anterior cingulate, frontoparietal motor and frontoparietal somatosensory cortices on the left side but none on the right. We also demonstrated a 20% bilateral increase of N-methyl-D-aspartate (NMDA) receptors in the dentate gyrus of the hippocampus. No changes were found in the prefrontal cortex, caudate-putamen, nucleus accumbens, hippocampus or olfactory tubercle.

Animals

Plasma levels of interleukin-6 and tumor necrosis factor alpha in chronic schizophrenia: effects of clozapine treatment.

Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) were assessed in 17 chronic schizophrenic patients who had been drug-free for 3 weeks and in 17 age- and sex-matched healthy subjects. Plasma concentrations of both cytokines were measured again in 12 patients after a 10-week treatment with clozapine. Compared with healthy controls, drug-free schizophrenic patients exhibited similar plasma IL-6 concentrations, but significantly higher levels of TNF alpha. After clozapine treatment, blood concentrations of TNF alpha fell to normal levels. These preliminary data support an immune activation in drug-free schizophrenic patients and an effect of clozapine on immune parameters.

Adult

Suppression of nocturnal plasma melatonin levels by evening administration of sodium valproate in healthy humans.

To investigate the role of gamma-aminobutyric acid (GABA) in the modulation of human melatonin production, we studied the effects of the acute administration of the GABAergic drug, sodium valproate (VAL), on nocturnal blood melatonin levels in healthy subjects. To this purpose, 4 healthy men and 3 healthy women, aged 24-33 years, underwent three experimental sessions in which they received orally 400 mg VAL, 800 mg VAL, or placebo, in random order, according to a double-blind design. The drug administration was done at 19:00 hours; thereafter, blood samples were collected over the night, in dark conditions with the help of a red light. As compared to placebo, VAL, at the dosage of both 400 and 800 mg, significantly suppressed nocturnal blood melatonin levels, the higher dose being slightly more effective than the lower one. The maximum suppression coincided with the highest plasma levels of valproic acid. These findings support the view that endogenous GABA may participate in the modulation of the activity of the human pineal gland.

Adult

Differences between morning and afternoon hormonal responses to D-fenfluramine in healthy humans.

The prolactin (PRL) and cortisol responses to oral D-fenfluramine (30 mg) and placebo were measured in seven healthy subjects (two women and five men) in the morning and in the afternoon. As compared to placebo, D-fenfluramine significantly increased plasma PRL levels in both the morning and the afternoon, with no significant circadian difference. On the contrary, D-fenfluramine significantly enhanced plasma cortisol levels in the afternoon, but not in the morning. These data suggest that the time of the day at which the D-fenfluramine challenge test is carried out may be an important variable in determining the glucocorticoid response to the 5-HT releasing agent in humans.

Adult

Cortisol response to d-fenfluramine in patients with obsessive-compulsive disorder and in healthy subjects: evidence for a gender-related effect.

In order to evaluate serotonergic function in obsessive-compulsive disorder (OCD), plasma cortisol response to d-fenfluramine (30 mg p.o.) was examined in 20 drug-free obsessive-compulsive patients (10 males and 10 females) and in 20 age- and sex-matched healthy subjects, under double-blind, placebo-controlled conditions. We found that: (a) baseline plasma cortisol secretion was significantly increased in patients with OCD; (b) in healthy subjects, the cortisol response to d-fenfluramine was evident in women, but no in men; (c) plasma cortisol response to the serotonergic challenge did not differ between patients and controls, but it was significantly reduced in female patients as compared to healthy women. These results demonstrate a hyperactivity of the hypothalamo-pituitary-adrenal axis in obsessive-compulsive patients and suggest a dysfunction of 5-HT transmission in female patients.

Administration, Oral

Decreased nocturnal secretion of melatonin in drug-free schizophrenics: no change after subchronic treatment with antipsychotics.

To evaluate the biosynthetic activity of the pineal gland in schizophrenia, the circadian rhythm of plasma melatonin was investigated in 9 drug-free chronic schizophrenics and in matched healthy subjects. In 7 of the patients, the 24-hour secretory pattern of the pineal hormone was reassessed after 10 weeks of treatment with antipsychotic drugs. In drug-free schizophrenics, the nocturnal increase in plasma melatonin levels was significantly blunted as compared to healthy subjects (p < 0.0001). Chronic treatment with antipsychotic drugs significantly improved psychotic symptomatology, but did not change the secretory pattern of melatonin. These data show that the biosynthetic activity of the pineal gland is impaired in chronic schizophrenia and that successful treatment with antipsychotic drugs does not go parallel with changes in the production of melatonin.

Adult

Prolactin response to d-fenfluramine in obsessive-compulsive patients, and outcome of fluvoxamine treatment.

BACKGROUND: Although several studies have directly explored serotonin (5-HT) transmission in patients with obsessive-compulsive disorder (OCD), their results have been inconsistent and their clinical relevance is doubtful. METHOD: According to a double-blind placebo-controlled design, plasma prolactin (PRL) response to a specific serotonergic probe, d-fenfluramine, was measured in 20 drug-free obsessive-compulsive patients and in 20 matched healthy controls. After the neuroendocrine test, 15 patients completed a 10-week treatment with fluvoxamine. Psychopathological assessment was performed before and after therapy. RESULTS: PRL response in OCD patients was blunted under the drug-free condition; correlated inversely with pretreatment ratings of obsessive-compulsive and depressive symptomatology; and correlated inversely with the improvement in obsessive-compulsive score observed after fluvoxamine treatment. CONCLUSIONS: These results support the idea of a dysfunction of 5-HT transmission in OCD, and suggest that the greater this impairment, the better the response to drugs which selectively block the reuptake of 5-HT.

Adolescent

Sigma receptor modulation of noradrenergic-stimulated pineal melatonin biosynthesis in rats.

Because sigma receptors are richly concentrated in the rat pineal gland, the present study was performed to investigate their possible role in the modulation of melatonin production. To this purpose, we assessed in vivo the effects of the sigma-receptor ligands 1,3-di(2-tolyl)guanidine and (+)-N-allylnormetazocine on the rat pineal gland activity during either the daytime or the nighttime. Compared with vehicle, 1,3-di(2-tolyl)guanidine and (+)-N-allylnormetazocine potentiated the enhancement of N-acetyltransferase activity and pineal melatonin content induced by isoproterenol administration during the daytime, whereas they did not affect the diurnal basal biosynthetic activity of the gland. Conversely, at night, 1,3-di(2-tolyl)guanidine and (+)-N-allylnormetazocine enhanced significantly the physiological increases in both pineal N-acetyltransferase activity and melatonin levels. This enhancement was prevented by pretreatment with rimcazole, a specific sigma-receptor antagonist. These findings suggest that, in rats, the activation of pineal sigma-receptor sites does not affect the biosynthetic activity of the pineal gland during daytime, whereas it potentiates the production of melatonin when the gland is noradrenergically stimulated either by isoproterenol administration or by the endogenously released norepinephrine at nighttime.

Animals

Does bright light suppress nocturnal melatonin secretion more in women than men?

Sex differences in the sensitivity of the human pineal gland to the suppressant effect of bright light on melatonin synthesis were studied in 6 healthy men and women. Blood samples were collected in two randomly ordered sessions: in one, subjects rested supine in bed, in the dark, from 21.00 to 7.00 h; in the other session, they were exposed to bright light (2,000 lux) from 2.00 to 4.00 h. In the dark condition, no significant differences were observed between men and women in either the timing or the absolute values of melatonin plasma levels, whereas after bright light exposure, the suppression of plasma melatonin was a 40% greater in women than in men. These findings suggest that, in humans, there is a sex difference in the nocturnal sensitivity of the pineal to light.

Adult

Effects of single and repeated electroconvulsive shock on isoproterenol-stimulated pineal N-acetyltransferase activity and melatonin production in rats.

The response of the pineal gland to acute isoproterenol administration represents a useful tool to investigate beta 1-adrenoceptor function, because the production of melatonin and the activity of its main synthesizing enzyme, N-acetyltransferase (NAT), are regulated by beta 1-adrenergic receptors. In the present study, rats underwent single electroconvulsive shock (ECS) administration (0.80 mA, 0.5 s, at midday), chronic ECS treatment (0.80 mA, 0.5 s, once daily for 8 days), or sham treatments. On the day after the last ECS or sham ECS, animals were injected with isoproterenol hydrochloride (1 mg.kg-1 SC) or volume-matched saline at 1600 h. After single ECS, isoproterenol injection induced a clear-cut increase in both pineal NAT activity and melatonin levels with no significant differences between ECS-treated rats and the sham-treated ones. In rats chronically treated with ECS, the isoproterenol-induced increases in both pineal NAT activity and melatonin content were significantly lower than in sham-treated animals (p < 0.001 for NAT activity; p < 0.005 for melatonin levels; Turkey's test). These data show that the pinealocyte beta-adrenoceptor function is reduced by chronic, but not acute ECS administration, and that this change is not due to the nonspecific stress effect of animal handling or to the acute effects of the last of a series of ECS.

Acetyltransferases

Effects of gonadectomy and temperature on the N-acetyltransferase activity in the harderian gland of the green frog Rana esculenta.

Since, in the Harderian gland (HG) of the hamster, the N-acetyltransferase (NAT), the specific enzyme involved in the biosynthesis of melatonin, exhibits a sexual dimorphism, in the present study, we investigated whether such a dimorphism is present also in the HG of the green frog Rana esculenta. In intact frogs, no significant differences emerged between males and females in the HG NAT activity under both cold (10 degrees C) and warm (22 degrees C) temperature conditions. In female frogs, the HG NAT activity was significantly decreased by both gonadectomy (P < 0.001) and warm temperature (P < 0.001), the two effects being not additive. In male animals, neither gonadectomy nor temperature alone significantly affected the activity of the NAT enzyme in the HG. However, gonadectomized male frogs exposed to warm temperature exhibited a significant drop in the HG NAT activity (P < 0.005). These data show that, in Rana esculenta, although no sexual dimorphism exists in the HG NAT activity, a sex difference is evident in the modulation of the enzyme activity by gonads and temperature, the female frogs being more sensitive to the impairing effects of both gonadectomy and higher temperature.

Animals

Plasma melatonin and cortisol circadian patterns in patients with obsessive-compulsive disorder before and after fluoxetine treatment.

The circadian rhythms of melatonin and cortisol were evaluated in seven outpatients with obsessive-compulsive disorder (OCD) before and after 8 weeks of fluoxetine treatment (20 mg/day in the first 2 weeks, and 40 mg/day afterwards), and in seven healthy subjects matched to patients on age, sex and season of testing. The results confirm our previous findings of a decreased 24-h production of melatonin (p < .05; two-way ANOVA with repeated measures) and of an increased circadian secretion of cortisol (p < .01) in OCD patients with respect to matched controls, and show, for the first time, that these hormonal alterations do not significantly change after 2 months of fluoxetine administration, in spite of a good clinical improvement. These data suggest that the normalization of the biochemical changes underlying the altered endocrine parameters in obsessive-compulsive patients is not necessary for effective therapy or clinical remission.

Adult