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Biomedical subjects

M Maj

Publications and source records attributed to M Maj.

At least 19 recordsLinked to original sources

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

Activity, peroxide compound formation, and heme d synthesis in Escherichia coli HPII catalase.

Wild-type Escherichia coli HPII catalase (heme d containing) has 15% the activity of beef liver enzyme per heme. The rate constant for compound I formation with H2O2 is 1.3 x 10(6) M(-1) s(-1). HPII compound I reacts with H2O2 to form O2 with a rate constant of 1.8 x 10(6) M(-1) s(-1). Forty percent of HPII hemes are in the compound I state during turnover. Compound I is reduced by ethanol and formate at rates of 5 and 13 M(-1) s(-1) (pH 7.0), respectively. Incubation of HPII compound I with ferrocyanide and ascorbate does not form a compound II species. Mutation of His128 to alanine or asparagine gives inactive protoheme proteins. Mutation of Asn201 gives partially active heme d forms. Asn201Ala has 24%, Asn201Asp 10%, and Asn201Gln 0.4% of wild-type activity. Asn201His contains protoheme when isolated and converts this via protoheme compound I to a heme d species. Both distal heme cavity residues His128 and Asn201 are implicated in catalytic activity, compound I formation, and in situ heme d biosynthesis. HPII Asn201, like the corresponding residue in protoheme catalases, may promote H+ transfer to His128 imidazole, facilitating (i) peroxide anion binding to heme and (ii) stabilization of a transition state for heterolytic cleavage of the O-O bond.

Animals

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

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

Reaction of E. coli catalase HPII with cyanide as ligand and as inhibitor.

Cyanide forms an inhibitory complex with the haem d-containing E. coli catalase HPII, spectrally similar to the cyanide complex of beef liver enzyme but with absorption bands shifted 90 nm towards the red end of the spectrum. Both the Kd and Ki values are approximately 7 microM in the wild-type enzyme. The cyanide reaction is slow, with a bimolecular 'on' constant approx. 2000 x smaller than that of eukaryotic enzyme, and an 'off' constant diminished by a similar amount. Catalases with a mutated distal histidine (H128) fail to bind cyanide at cyanide concentrations below 50 mM. Catalases with a mutated distal asparagine (N201) show only small changes in cyanide affinity from the wild type. The major fraction of HPII N201A has a Kd approximately 40 microM, and a minor fraction has a lower cyanide affinity; the major fraction of HPII N201Q has a Kd approximately 15 microM. The Kd and Ki for HPII N201D is approximately 8 microM, essentially identical with that of the wild type but N201D appears to bind cyanide somewhat more rapidly than does wild-type enzyme. The HPII mutant N201H can be obtained in both haem d and protohaem forms; it exhibits two types of cyanide binding behaviour. In its protohaem form it binds cyanide poorly (Kd > or = 0.25 mM). After peroxide treatment converts t into haem d or a closely related species it binds cyanide with a much higher affinity (Kd approximately 15 microM). Cyanide binding to HPII requires a distal histidine to provide hydrogen-bonding stability, but not a distal asparagine. Rates of cyanide binding and release are controlled by haem group accessibility through the channel leading to the outside. In HPII N201H channel opening may depend upon oxidation of the haem from the starting protohaem to the final haem d form.

Animals

Multilead quantitative EEG profile of clozapine in resting and vigilance-controlled conditions.

Clozapine is the prototype of a new class of drugs, referred to as 'atypical antipsychotics'. As a matter of fact, the antipsychotic activity of the drug was not predicted by the first studies with quantitative electroencephalography (QEEG), which actually reported an antidepressant pattern. All previous QEEG studies carried out in healthy subjects used a maximum of four leads, exploring only the posterior quadrants of the scalp. The present article reports findings of a multilead QEEG study carried out in 16 healthy men under resting and vigilance-controlled conditions. Increases in slow (delta, theta, and alpha1) and decreases in fast (alpha2 and beta) activities were found, corresponding to changes described for chlorpromazine-type antipsychotics. These results are compared with those of earlier studies. It is suggested that changes in the beta frequency range vary across subjects, whereas changes in slow and alpha activity are more consistent and critical for defining the QEEG profile of the drug.

Adult

Late non-response to lithium prophylaxis in bipolar patients: prevalence and predictors.

65 bipolar patients who had shown a complete response to lithium prophylaxis over a 5-year period were followed up for a further period of 5 years. 12.7% of them had at least two affective episodes during the latter period, despite persistently adequate compliance. These late non-responders, as compared with stable responders, had a significantly higher number of previous affective episodes and hospitalizations and a significantly longer duration of illness. It is suggested that the main determinant of late non-response is the 'driving force' of the illness, finally overwhelming the prophylactic effect of lithium.

Adult

Effect of treatment duration on plasma levels of clozapine and N-desmethylclozapine in men and women.

Plasma levels of clozapine and its major metabolites, N-desmethylclozapine and clozapine-N-oxide, were measured in 18 schizophrenic patients at different times (4, 6 and 24 weeks) during the course of treatment with multiple doses of the drug, by using high performance liquid chromatography (HPLC) with UV detection. Plasma levels of clozapine and N-desmethylclozapine were significantly higher in females than in males after 4 and 6 weeks, but not after 24 weeks, of treatment. No sex difference was found at any time with respect to plasma levels of clozapine-N-oxide.

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

A new questionnaire assessing coping strategies in relatives of patients with schizophrenia: development and factor analysis.

This paper describes the development and validation of a questionnaire assessing the coping strategies adopted by relatives of patients with schizophrenia. The final version of the questionnaire includes 27 items, grouped into seven subscales (information, positive communication, social interests, coercion, avoidance, resignation and patient's social involvement), the intra-rater reliability of which ranges from 0.46 to 0.76. Cronbach's alpha coefficient, which tests the content validity of the subscales, ranges from 0.68 to 0.83. Factor analysis identifies three factors (problem-oriented coping strategies, emotionally focused strategies, and maintenance of social interests in association with patient's avoidance), accounting for 70.9% of the total variance. This questionnaire may be particularly useful for targeting and monitoring psychoeducational interventions in the families of patients with schizophrenia.

Adaptation, Psychological

Influence of moclobemide on cognitive functions of nine depressed patients: pilot trial with neurophysiological and neuropsychological indices.

Quantitative electroencephalogram (QEEG) changes induced by the acute administration of moclobemide (200 mg) in patients with major depression include a transient increase in theta-activity, a slight augmentation of alpha-activity and a sustained increase in beta-activity. This QEEG profile distinguishes moclobemide from sedative antidepressants. A 42-day treatment with 400 mg/day of the drug produces a significant decrease in the late positive-complex peak latency of the event-related potentials, suggesting a positive effect on attention and cognitive functions.

Adult

Measuring the potency of pulp mill effluents for induction of hepatic mixed-function oxygenase activity in fish.

A bioassay protocol was optimized for measuring the potency of effluents or waterborne chemicals for inducing mixed-function oxygenase (MFO) activity of rainbow trout (Oncorhynchus mykiss). Measurements of ethoxyresorufin O-deethylase (EROD) can be made with an established endpoint assay using large volumes of reagents and tissue. However, a new kinetic microplate assay offers significant savings in time, reagents, and sample volumes. Data are distributed lognormally and must be log transformed before statistical analyses. EROD activity increases with exposure time to pulp mill effluent, and a 4-d exposure provides a near-maximal response. Optimum fish size conforms to standard practices in fish toxicology; loading rates should not exceed 1 g of fish per liter of test solution per day. Feed should be withheld from test fish 48 h before testing to reduce the variance of measured activity, and anaesthetizing fish with MS-222 does not affect their response to MFO inducers. Pulp mill effluents do not lose their potency during 2-3 wk of exposure at temperatures ranging from -20 to 13 degrees C, whether stored in plastic or glass. Steel containers were associated with slight losses in potency. Bioassays of MFO induction in fish exposed to liquid effluents are practical and conform to standard practice for testing the lethality of waterbone chemicals. The results are sufficiently precise that differences among means based on live fish per treatment can be discriminated statistically when activity changes by threefold or more.

Analysis of Variance