Biomedical subjects

N Pivac

Publications and source records attributed to N Pivac.

At least 19 recordsLinked to original sources

PubMed2006

The effects of olanzapine and fluphenazine on plasma cortisol, prolactin and muscle rigidity in schizophrenic patients: a double blind study.

Pharmacotherapy of schizophrenia is associated with the stressful side effects. Muscle rigidity causes distress, discomfort and poor compliance. The aim of the study was to determine the relationship between plasma hormones (cortisol and prolactin/PRL) and muscle rigidity in female schizophrenic patients treated with olanzapine or fluphenazine. In a randomized, double-blind 22-weeks study, 12 patients were treated with olanzapine (5-20 mg/day) and 10 patients received fluphenazine (6-21 mg/day). Treatment with olanzapine moderately decreased, while treatment with fluphenazine significantly increased plasma cortisol levels and muscle rigidity. The marked and moderate increase in plasma PRL levels were found in patients treated with fluphenazine and olanzapine, respectively. The results suggested that olanzapine induced moderate neuroendocrine effects and a reduction in rigidity as compared to fluphenazine treatment.

Adult↗

PubMed2001

Platelet serotonin concentration in dialysis patients with somatic symptoms of depression.

Platelet serotonin (5-HT) concentration was measured in 65 male and 45 female chronic renal patients on hemodialysis (HD) with different somatic symptoms of depression (crying spells, irritability, sleep disturbance, fatigability, loss of appetite, weight loss, somatic preoccupation and loss of libido), to find out the relationship between the severity of symptoms and platelet 5-HT concentration. Male and female patients had significantly lower platelet 5-HT concentration than 62 male and 38 female healthy subjects. Gender-differences in platelet 5-HT values observed in healthy subjects were not found in patients. Platelet 5-HT concentration differed in the groups of patients with the different scores of particular somatic symptoms (loss of appetite and loss of libido), but was similar in patients with other somatic symptoms. There was no relationship between platelet 5-HT concentration and the severity of somatic symptoms, or between platelet 5-HT concentration and age of the patients. Gender-related differences in the occurrence of somatic symptoms were detected in patients with the different degrees of weight loss, somatic preoccupation and loss of libido. Our results suggest that platelet 5-HT concentration could not be used as a biological marker for the severity of somatic symptoms in chronic renal patients on HD.

Adolescent↗

PubMed2000

TCH-346 (Novartis).

TCH-346, an anti-apoptotic compound, is under development by Novartis for the potential treatment of Parkinson's disease (PD) and motor neuron disease [271447,342937]. By September 1999, phase I clinical trials for PD were underway [342937]. The compound was discovered in a screen for molecules with both norepinephrine uptake and MAO inhibiting properties but, although it had anti-apoptotic properties, it did not inhibit MAOA or MAO-B [333136,332004]. The compound increases lifespan in the progressive motorneuropathy mouse model and prevents ischemia in models of ischemia and seizure [288893]. In vivo, it shows neurorescuing and anti-apoptotic properties in PC12 cells and cerebellar granule cells, among others, at concentrations of 0.1 pM to 10 microM, suggesting that its action might prove potentially useful against Alzheimer's and/or Parkinson's disease [332004]. The compound has also shown neurorescuing properties in rat pups after axotomy, rat hippocampal CA1 neurons after transient ischemia/hypoxia and mouse nigral dopaminergic (DA) neurons after treatment with MPTP in doses ranging between 0.0003 and 0.1 mg/kg po or sc, depending on the model [333136]. Data presented by the University of Nijmengen and the Free University of Amsterdam show that TCH-346 improves the behavioral and enzymatic outcome in the rat 6-OH-dopamine model of Parkinson's disease. TCH-346 (0.0014 mg/kg sc bid) prevented abnormal stepping (open field test) and prevented increases in fore and hind-paw retraction time. TCH-346 also improved acquisition in the Morris water maze task and, at doses between 0.0014 and 0.14 mg/kg, prevented reduction in tyrosine hydroxylase immunoreactivity [345259]. Affinity binding studies with TCH-346 showed that GAPDH is the target [294902,283200]. Differential display RT-PCR also showed that protein-isoaspartyl-methyl transferase is induced by the drug [283200].

Journal Article↗

PubMed1999

Platelet serotonin, plasma cortisol, and dexamethasone suppression test in schizophrenic patients.

BACKGROUND: Serotonin (5-HT) regulates hypothalamic-pituitary-adrenal (HPA) axis activity. Abnormal response to the dexamethasone suppression test (DST) and altered platelet 5-HT concentration have been shown in some schizophrenic patients. METHODS: Platelet 5-HT and plasma cortisol concentrations were determined simultaneously in 86 male schizophrenic patients before and after DST. Basal plasma cortisol and platelet 5-HT levels were also determined in 69 healthy male persons. RESULTS: Schizophrenic patients had higher plasma cortisol and platelet 5-HT concentrations than healthy persons. An abnormal escape from dexamethasone suppression was observed in 50% of patients. In these patients predexamethasone cortisol and platelet 5-HT concentrations were higher than in patients with normal DST. CONCLUSIONS: This study demonstrates that schizophrenic patients have the HPA axis dysregulation that could be connected with a disturbance in the 5-HT system.

Adult↗

PubMed1999

Sex differences, season of birth and platelet 5-HT levels in schizophrenic patients.

Similar occurrence of schizophrenia was observed in men and women independent of their season of birth. Platelet 5-HT concentration was determined in 116 healthy control subjects (61 male and 55 female) and 152 patients with schizophrenia (96 male and 56 female). Platelet 5-HT concentration was significantly higher in male than in female healthy persons and schizophrenic patients. Male and female healthy subjects born in different seasons had similar platelet 5-HT concentrations, whereas schizophrenic patients with different birth-seasons had significantly different platelet 5-HT concentrations. The highest platelet 5-HT levels were observed in both male and female schizophrenic patients born in winter when compared to matched healthy controls. Male schizophrenic patients born in winter had higher platelet 5-HT levels than schizophrenic men born in spring and summer. Female schizophrenic patients born in winter had higher platelet 5-HT than schizophrenic women born in all other seasons. These results indicated sex differences in platelet 5-HT levels in healthy persons and schizophrenic patients. The relationship between season of the birth and platelet 5-HT concentration observed only in schizophrenic patients added further support to the presumption that schizophrenia is connected with a disturbance in the central serotoninergic system.

Adolescent↗

PubMed1999

EPHAR 99--Second European Congress of Pharmacology. 3-7 July 1999, Budapest, Hungary.

This meeting was chaired by Dr ES Vizi (Chairman of the Hungarian Pharmacological Society) and was attended by approximately 1600 delegates from 62 countries, including the USA, Canada, Israel, Japan and various parts of Europe. The opening ceremony was honored by the plenary lecture of a Nobel prize winner, Dr J Axelrod. The conference consisted of plenary sessions, 57 symposia and poster sessions. Each day the program included seven morning and seven afternoon symposia, simultaneously held, and a large poster section. The symposia focused on the neurotransmitter receptors as targets for the action of new drugs, new trends in the treatment of diabetes, Alzheimer's and Parkinson's diseases, psychiatric disorders, cardiac and gastrointestinal diseases and neuronal damage. All abstracts (more than 1200) were published in Fundamental and Clinical Pharmacology (1999) 13(Suppl 1). This year's meeting was substantially larger than the first EPHAR congress held in Milan, Italy, in 1995. It was generally well organized and served to introduce new basic and clinical knowledge in pharmacology.

Journal Article↗

PubMed1998

Platelet 5-HT and plasma cortisol concentrations after dexamethasone suppression test in patients with different time course of schizophrenia.

Platelet 5-HT and plasma cortisol concentrations were determined in 59 schizophrenic patients with different time course of illness before and after dexamethasone suppression test (DST). An abnormal DST (nonsuppression) was observed in 51% of patients. In these patients basal cortisol and platelet 5-HT concentrations were higher than in patients with normal DST. After DST, plasma cortisol levels were higher in nonsuppressors with intermittent and intermittent-chronic time course, whereas platelet 5-HT concentrations were increased in nonsuppressors with intermittent-chronic time course. The results suggest that schizophrenic patients have dysregulated hypothalamic-pituitary-adrenal axis as shown by a high rate of DST nonsuppression, and that nonsuppressors showed hypercortisolemia and hyperserotonemia independent of the time course of schizophrenia. No significant association between DST and time course of the illness was found.

Adult↗

PubMed1998

QT interval as a marker of venous reactivity in dialysis patients.

Fourteen patients (7 females and 7 males, mean age 51.9 +/- 11.6 years) were studied to find out whether there is a connection between the QTc interval (a diagnostic tool for evaluating autonomic neuropathy) and venous reactivity in uremics on chronic hemodialysis. The QT interval was measured using standard lead II as reference, corrected for heart rate, and designed QTc. Venous reactivity was measured by the so-called venoconstriction test. Pressure changes inside the vein were obtained by injection of 2 micrograms of noradrenaline, and expressed in venoconstrictive units (VCU). The mean QTc was 445.7 +/- 36.9 ms. The mean venous tone response was 2130.9 +/- 1435.5 VCU. There was a significant correlation between the QTc interval and venous reactivity to catecholamine (r = 0.565, P = 0.03). It is concluded that the QTc interval may be used as a marker of venous tone reactivity, suitable for everyday clinical practice. Furthermore, the magnitude of this reactivity possibly represents either the end-organ or peripheral sympathetic impairment.

Adult↗

PubMed1998

Comparison of chlorthalidone, propranolol and bopindolol in six-month treatment of arterial hypertension.

The aim of this study was to test the hypothesis that prolonged treatment of mild to moderate hypertension with low-dose thiazide diuretics or beta blockers does not induce any of the major untoward biochemical changes, such as hypertriglyceridemia, hypercholesterolemia, hyperuricemia and electrolyte imbalances. The effect of these drugs was analyzed in 100 outpatients (52 males and 48 females) aged 52.0 +/- 7.9 years with mild to moderate hypertension, in a prospective 6-month study. After an appropriate workup, the patients were randomized to either 25 mg chlorthalidone (40 patients), 120 mg propranolol (30 patients), or 2 mg per day bopindolol (30 patients). A significant reduction of approximately 10% in systolic and diastolic blood pressure was recorded in all the groups. At the end of the 6th month, in the chlorthalidone group triglycerides increased to 3.0 +/- 2.1 mmol/l from 2.8 +/- 1.6 mmol/l, while cholesterol after an initial increase to 6.6 +/- 1.6 from 6.4 +/- 1.6 mmol/l returned to the baseline level. Uricemia and serum potassium concentration decreased by 4%. The body weight was reduced to 83.8 +/- 13.4 kg from 86.1 +/- 13.4 kg. There was no change in serum glucose level. In the propranolol group, as expected, heart rate decreased by 20%, but there were no significant changes in glucose and potassium plasma concentration. Triglycerides did not change significantly, while cholesterol, after a small increase, returned to the initial levels. Similar results were obtained in the bopindolol group, apart from the triglycerides, which increased significantly (to 2.5 +/- 1.1 from 2.2 +/- 0.4 mmol/l), probably because of the lower baseline concentration. We conclude that in prolonged treatment, chlorthalidone, propranolol and bopindolol do not induce significant untoward biochemical changes that alone might increase cardiovascular risk.

Adult↗

PubMed1998

Diuretic effects of furosemide infusion versus bolus injection in congestive heart failure.

In a randomized, single-blind, crossover clinical trial, the diuretic efficacy of the same total dose of furosemide (2 x 40 mg) administered in either conventional intravenous bolus injection or continuous infusion was studied in 20 patients (nine males and 11 females), aged 37-75 years, with congestive heart failure. Furosemide infusion, administered first, produced a significantly greater diuresis than the bolus when compared with baseline (86%: 29.6%; p = 0.029). This was followed by a similar increase in 24-h urinary sodium, potassium and chloride excretion, with no significant difference from the bolus effect. The following day, diuretic and saluretic effects of furosemide did not differ significantly between the study groups. Nevertheless, when continuous furosemide infusion was administered first, it produced a greater increase in urinary volume, 24-h urinary sodium, potassium and chloride than when bolus injection was applied the next day. Conversely, when furosemide bolus was administered first, followed by the infusions the next day, the effects were almost equal, regardless of the mode of administration. It is concluded that in the treatment of refractory edema in patients with congestive heart failure, continuous intravenous infusion of furosemide is superior to the conventional intermittent bolus injection, especially if it is administered at the very beginning of the hospital treatment, and presumably is even better with higher dosage and longer infusion time span.

Adult↗

PubMed1997

Hypothalamic-pituitary-adrenal axis function and platelet serotonin concentrations in depressed patients.

Plasma cortisol and platelet serotonin (5-hydroxytryptamine, 5-HT) concentrations were determined in 39 male psychotic and 39 male non-psychotic depressed inpatients, and in 69 male healthy control subjects. Psychotic or non-psychotic depressed patients had higher predexamethasone plasma cortisol levels than found in the control group. After the dexamethasone suppression test (DST), psychotic and non-psychotic depressed patients were subdivided into suppressors and non-suppressors. Psychotic and non-psychotic patients had significantly different platelet 5-HT concentrations among themselves and compared with the control group. However, there was no significant correlation between plasma cortisol levels and platelet 5-HT concentrations. Dexamethasone administration did not affect platelet 5-HT concentrations within subtypes of depressed patients. Abnormal cortisol suppression after the DST occurred more frequently in psychotic than in non-psychotic patients. Platelet 5-HT and plasma cortisol concentrations were decreased in patients with pronounced suicidal behaviour. Our results suggest that plasma cortisol and platelet 5-HT concentrations might serve as independent biological markers for different subtypes of depression.

Adult↗

PubMed1997

Seasonal influence on platelet 5-HT levels in patients with recurrent major depression and schizophrenia.

The influence of seasons on platelet serotonin (5-HT) concentration was determined in 88 unipolar depressed and 117 schizophrenic male inpatients, and 90 normal male controls. Platelet 5-HT concentrations showed moderate, but insignificant intragroup seasonal variations in healthy controls and in the groups of depressed (psychotic and nonpsychotic) and schizophrenic (positive and negative) patients. In spring, platelet 5-HT concentrations were higher in schizophrenic patients than in normal controls or in depressed patients, while in other seasons platelet 5-HT concentrations were not significantly different between the groups. Higher platelet 5-HT concentrations were detected in psychotic when compared to nonpsychotic depressed patients in summer, fall, and winter. Increased platelet 5-HT concentrations observed in schizophrenic patients with positive symptoms clearly separated these patients from patients with negative schizophrenia, especially in spring, summer, and fall. Our results indicate the necessity to match patients with regard to the season of the sampling, and to divide depressed and schizophrenic patients into subtypes.

Adult↗

PubMed1997

Platelet 5-HT levels and hypothalamic-pituitary-adrenal axis activity in schizophrenic patients with positive and negative symptoms.

Hypothalamic-pituitary-adrenal (HPA) axis activity and platelet 5-HT concentrations were determined before dexamethasone suppression test (DST) in 80 male schizophrenic patients with predominantly positive or negative symptoms. Significant differences in platelet 5-HT and no differences in baseline plasma cortisol concentrations among schizophrenic suppressors and nonsuppressors were found. A similar rate of nonsuppression (56% positive and 53% negative schizophrenic patients) was detected. Platelet 5-HT, but not plasma cortisol concentrations, could be used to differentiate positive and negative symptoms of schizophrenia.

Adult↗

PubMed1996

Platelet 5-HT concentrations and suicidal behaviour in recurrent major depression.

Platelet 5-HT concentrations were determined in 84 male and 82 female psychotic and non-psychotic depressed inpatients with various degrees of suicidal behaviour, and in 175 healthy controls. Psychotic patients had higher platelet 5-HT concentrations than non-psychotic depressed patients and healthy controls. A sex difference, i.e., lower platelet 5-HT concentrations in females was found in healthy controls, depressed patients, non-psychotic patients and non-suicidal depressed patients. A negative relationship was shown between platelet 5-HT concentrations and suicidal behaviour. The lowest platelet 5-HT concentrations were associated with the most pronounced suicidal behaviour (with suicidal attempts and with the acts of suicide). The results suggest that the differences in platelet 5-HT concentrations found in depressed patients might be used as a biological marker for suicidal behaviour.

Adolescent↗

PubMed1996

Effects of diazepam on conflict behaviour and on plasma corticosterone levels in male and female rats.

The anxiolytic properties of diazepam and its effects on plasma corticosterone levels were compared in male and female, water deprived rats exposed to the punished (0.8 mA) drinking procedure. The effects of diazepam on unpunished licking, tested under familiar or unfamiliar conditions, and on the lick latency were also studied and a comparison between the two sexes was made. Both punished and unpunished drinking were less in females than in males. In both sexes, a clear anticonflict effect, i.e. a much greater effect on punished than on unpunished drinking, was obtained with 2 and 4 mg/kg, but not with 1 mg/kg, of diazepam i.p. Plasma corticosterone levels were higher in water deprived females than in males. Following the punished and unpunished drinking procedure, plasma corticosterone levels were found to have decreased more in female than in male rats, especially after administration of 1 mg/kg of diazepam. Diazepam had similar anticonflict effects in rats of both sexes but had a greater suppressive effect on the plasma corticosterone levels in female rats. There was no correlation between the anxiolytic effects of diazepam and its effect on the plasma corticosterone levels. When testing was done under unfamiliar conditions, the latency to licking was greater in female than in male rats and diazepam (1, 2 and 4 mg/kg) increased this latency in both sexes. The results suggest sex differences in the neuroendocrine, but not in the anxiolytic, effects of diazepam.

Analysis of Variance↗

PubMed1995

Sex differences in conflict behaviour and in plasma corticosterone levels.

The levels of plasma corticosterone and conflict behaviour were followed in male and female water deprived Wistar rats exposed to the punished (0.2 or 0.8 mA) drinking test. The unpunished drinking, performed under familiar or unfamiliar conditions, and plasma corticosterone levels of these male and female rats were determined. Plasma corticosterone was elevated in water-deprived rats compared to rats under normal conditions. In all cases plasma corticosterone levels were considerably higher in water deprived females than in males. The highest levels in both sexes were obtained following drinking punished with 0.8 mA shocks. While the unpunished drinking did not differ between the two sexes, the punished drinking was significantly lower in females than in males. Although female rats displayed less punished licks and had higher plasma corticosterone levels than males, there was no correlation between the two parameters.

Animals↗

PubMed1995

Vascular effects of chlorthalidone in mild hypertensives.

In a randomized trial with chlorthalidone, 30 hypertensive outpatients of both genders, aged 50.4 +/- 8.6 years, having diastolic blood pressure between 95 and 110 mm HG were divided into 2 groups of 15, after a two-week placebo period. The A group received chlorthalidone in a single dose of 23 mg for one month, and the next month was given a 12.5 mg alternative dose, whereas the B group was given 12.5 mg in the first month and 25 mg in the second. Changes in vascular reactivity were measured by occlusive plethysmography (mercury strain-gauge) at the ends of the placebo period, the first and the second month of therapy. All the observed parameters, i.e. rest flow, peak flow, venous capacity, and maximal venous outflow, were found to have increased with 25 mg chlorthalidone, and similar findings were registered when 12.5 mg of the drug were given. Venous capacity increased significantly in both groups (from 2.6 to 3.2 and from 3.0 to 3.4 ml/100 ml). The peak-flow values augmented significantly only in the group where 25 mg of chlorthalidone were given first (from 18.6 to 23.9 ml/100 ml/min). Both doses had a similar antihypertensive effect, decreasing the mean arterial pressure by some 8% in the upright, sitting, and supine position. It is concluded that the antihypertensive effect of chlorthalidone is, at least partly, due to changes in vascular reactivity; vasodilation is more prominent on the venous side of the circulation. Low-dose chlorthalidone is equipotent as antihypertensive, its side-effects are rare, and the cost of such a therapy is by far the lowest.

Adult↗

PubMed1993

Q-T interval as predictor of serum calcium level.

To assess whether measurement of the electrocardiograhic (ECG) Q-T interval is a useful predictor of total serum calcium concentration, 15 uraemic patients were studied (10 female, five male; age range, 25-60 years). Resting ECGs were interpreted by three independent observers without knowledge of the patients' identity or serum calcium. Three variants of measurement of the Q-T interval were analysed, of which Q-aTc, the interval from the beginning of the Q-wave to the apex of the T-wave, was the most consistent (coefficient of variation, 2.7%). This also provided the best correlation with measured serum calcium concentration (P < 0.001). When compared to biochemical measurements, the predicted serum calcium concentration was within 95% confidence limits in 14 of the 15 patients studied. However, the wide confidence limits of this technique mean that it cannot be recommended in routine clinical practice.

Adult↗