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Biomedical subjects

P Monteleone

Publications and source records attributed to P Monteleone.

At least 109 records · Page 6Linked to original sources

Selective damage of neuron perikarya in the medial septum of the rat forebrain: effects on food and water intake, urine output and body weight.

The intraseptal administration of the neurotoxin kainic acid (KA) induced a significant depletion of the neuronal population and glial proliferation in medial septal areas. The behavioral effects induced by this selective destruction of the neurons indigenous to the medial septal areas were investigated. KA produced a marked increase in urine output and a transient reduction in body weight, but failed to affect water and food intake.

Animals↗

Pharmacological activation of the GABAergic system does not affect GH and PRL release in acromegaly.

An extensive hypothalamic neurotransmitter impairment has been proposed in acromegaly. However, at the moment, the hypothalamic GABAergic system has been little investigated in this disorder. Since GABA has been shown to modulate growth hormone (GH) and prolactin (PRL) secretion in human subjects, it seemed reasonable to investigate hypothalamic GABAergic functioning through the assessment of basal GH and PRL responses to pharmacological activation of this system. 800 mg of sodium valproate (SV), a drug with GABA facilitating properties, were administered orally to 7 acromegalic patients and 9 healthy volunteers. Blood samples were collected before and after the drug administration for the measurement of plasma GH and PRL levels. SV induced a clear-cut rise in basal GH and a decrease in basal PRL in healthy subjects, but it did not induce any change in the basal levels of these hormones in acromegalics. These results suggest that the response of GH and PRL to SV in acromegaly is qualitatively different from normal controls.

Acromegaly↗

Combined alpha-adrenergic stimulation results in biphasic response of growth hormone release in man.

Oral clonidine administration or insulin-induced hypoglycemia may enhance GH secretion through alpha 2-adrenergic stimulation in man. To further characterize the role of adrenergic transmission in the regulation of GH release, the effects of combined administration of clonidine and insulin were investigated in 16 normal men randomly assigned to 2 groups. The first group received 0.1 U/kg regular insulin, iv, followed by placebo or clonidine (0.150 mg), orally, on 2 different days, 2 weeks apart. The second group received oral clonidine (0.150 mg), followed by iv placebo or insulin (0.1 U/kg) on 2 different days, 2 weeks apart. Insulin induced a clear-cut increase in plasma GH (F = 79.88; P less than 0.001) that was not affected by placebo, whereas it was significantly inhibited by oral clonidine (P less than 0.001 at 60, 90, and 120 min). Similarly, oral clonidine administration resulted in a clear-cut rise in plasma GH levels (F = 16.44; P less than 0.001) that was significantly reduced by insulin (P less than 0.001, P less than 0.02, and P less than 0.05 at 60, 90, and 120 min, respectively). These results suggest that while moderate activation of the alpha 2-adrenergic system stimulates GH release, further stimulation of the same system may result in inhibition, rather than further activation, of GH secretion.

Adult↗

Evidence for a sex difference in the basal growth hormone response to GABAergic stimulation in humans.

Evidence has been provided supporting the existence of a sex-related difference in the GH secretion following different GH-releasing stimuli. Since pharmacological activation of the endogenous gammaaminobutyric acid (GABA) system results in increased basal GH release in humans, the present study was undertaken to investigate whether a sex difference is present in the GH response to GABAergic stimulation. Sixteen healthy subjects (8 women and 8 men) received orally 10 mg of baclofen, the direct GABAB agonist which freely crosses the blood-brain barrier. Blood samples were collected before (T = -30 and 0) and 30, 60, 90, 120 and 180 min after the drug administration for plasma GH measurements. Following baclofen administration, plasma GH rose in healthy males (F = 19.417, P less than 0.0001), but not in females (F = 1.67, NS). These results suggest that GABA modulation of human GH release is sex-dependent.

Adult↗

Gonadal steroids do not affect basal growth hormone response to naloxone in humans.

Evidence has accumulated that endogenous hypothalamic opioid activity fluctuates through the menstrual cycle depending upon the ovarian steroid milieu. In fact, naloxone, the specific opiate antagonist, is more effective in producing neuroendocrine changes in the late follicular and midluteal phases of the menstrual cycle, when the functional activity of hypothalamic opiate system is high. In order to investigate a possible regulatory function of endogenous opioids on basal growth hormone (GH) secretion in humans, we studied the basal GH response to naloxone (2 mg iv as a bolus) in different phases of the menstrual cycle in ten regularly menstruating women and in eight hypogonadal (postmenopausal) females before and after estrogen treatment. This protocol was carried out to test the hypothesis that estrogens could sensitize basal GH response to opiate receptor blockade. The results do not support this view and suggest that, under basal conditions, hypothalamic opiates have minimal influence on GH secretion in humans.

Adult↗

Impaired growth hormone response to sodium valproate in normal aging.

Evidence has been provided for impaired neurotransmitter functioning in the brain of elderly subjects. In order to assess central GABAergic transmission, the activity of the hypothalamic GABA system may be investigated by basal growth hormone (GH) response to the GABAergic drug sodium valproate (SV). For this purpose 15 healthy men (aged 19-81 years) received orally 800 mg SV or placebo tablets on two different occasions, 1 week apart. Blood samples were collected before and after drug administration for determining GH and SV plasma levels. A clear-cut increase in plasma GH was observed following SV (P less than 0.001 in young persons, P less than 0.005 in old subjects), but in the aged subjects this rise was statistically lower than in the young men (P less than 0.001 at t = 90 min). No difference was observed in basal GH levels and in SV plasma concentrations between elderly and young subjects. delta GH (= maximum post-SV GH level minus baseline GH value) was significantly inversely related to age (r = -0.90, P less than 0.001). These results may suggest an impaired hypothalamic-pituitary responsiveness to a pharmacological challenge enhancing endogenous GABA tone in the elderly.

Adult↗

Is the dexamethasone suppression test predictive of response to specific antidepressant treatment in major depression?

The authors attempt to correlate the response to dexamethasone suppression test (DST) with a clinical response to antidepressant drugs in 68 patients with major depression. Antidepressants that influence noradrenergic or serotonergic transmission with relative different potencies were selected and used in standard doses for 6 weeks. The response was evaluated weekly by raters blind to DST results and to antidepressant medications prescribed. The retrospective analysis failed to correlate DST response with outcome of treatment. Therefore the present results suggest that this laboratory test does not help to identify subgroups of depressed patients responding preferentially to various antidepressant drugs.

Adult↗

Conditional associative learning in drug-free schizophrenic patients.

The performance on spatial and nonspatial associative learning tasks was tested in a sample of male drug-free DSM III-diagnosed schizophrenic patients and in a closely matched normal control group. Schizophrenics showed a worse performance on both versions of the task, but especially on the nonspatial one. A significant correlation was observed between some indices of the nonspatial task and the scores on two subscales (affective flattening and anhedonia) of the scale for the assessment of negative symptoms by Andreasen. These results are consistent with the hypothesis of a dysfunction of dorsolateral prefrontal cortex in schizophrenia and with the postulated linkage between such dysfunction and negative schizophrenic symptomatology.

Adult↗

Pharmacological evidence for a dual GABAergic regulation of growth hormone release in humans.

Effects of sodium valproate, which is believed to act via a gamma-aminobutyric acid mechanism, on basal and exercise-induced rise of growth hormone release have been tested in eighteen healthy volunteers. The exercise test consisted of using a stationary bicycle ergometer at 450 kg/min for 20 min. 600 mg per os of the drug resulted in a significant enhancement in plasma hormonal concentrations, whereas no effects were induced by placebo (p less than 0.005). Conversely, the growth hormone rise stimulated by exercise was markedly inhibited by sodium valproate (p less than 0.001 and p less than 0.01 at time 20, 40 and 60 min respectively). The results of this study are consistent with the hypothesis that a dual GABAergic control of growth hormone secretion is present in man.

Adult↗

Growth hormone response to sodium valproate in chronic schizophrenia.

The hypothesis of a gamma-aminobutyric acid (GABA) involvement in the pathophysiology of schizophrenia has been recently proposed but not confirmed. As GABA has been shown to affect basal growth hormone (GH) secretion in humans, the assessment of plasma GH response to a GABAergic drug, such as sodium valproate (SV), in schizophrenic subjects might be a tool with which to investigate central GABA activity in this illness. For this purpose, we administered orally 800 mg of SV or placebo to 13 chronic schizophrenics and to 10 normal controls, and measured plasma GH levels before and after the drug administration. SV enhanced basal GH secretion in healthy male volunteers, but not in chronic schizophrenics. These results suggest a defect of the endogenous GABA system in chronic schizophrenia. Whether the reduced responsiveness observed represents a primary defect or a secondary alteration of the GABA system in schizophrenia is as yet unknown.

Adult↗

Congenital acute nonlymphoblastic leukemia with translocation (9;18).

Chromosome analysis is becoming an increasingly important tool in the diagnosis and treatment of childhood malignancies. This report illustrates a new translocation t(9;18) in a neonate with congenital acute nonlymphocytic leukemia, which predicted a bone marrow relapse in a normal appearing bone marrow.

Acute Disease↗

Evidence for a GABAergic control of the exercise-induced rise in GH in man.

The effect of the GABAergic drug sodium valproate (SV) on the exercise-induced release of growth hormone (GH) was investigated in 10 healthy males. The exercise test consisted of using a stationary bicycle ergometer at 450 kg/min for 20 min. SV 600 mg blunted the increase in GH induced by the exercise, suggesting GABAergic regulation of GH secretion in man, at least under certain physiological conditions.

Adult↗

Effect of nicotine on drinking and diuresis in septal lesioned rats.

Lesions of septal nuclei in rats enhance water intake and urine outflow. The effects of nicotine tartrate (2.5 mg/kg) on drinking and diuresis were investigated in normal, sham and septal lesioned rats. Nicotine administration resulted in a surprising hyperdipsia and polyuria in lesioned animals, the mean output rose from 38 +/- 1.3 ml (before treatment) to 101.6 +/- 6.1 (during treatment) and water intake increased from 74.2 +/- 1.8 ml to 129.8 +/- 6.4 ml.

Acetylcholine↗

Differential responses in prolactin levels induced by naloxone in humans.

The plasma prolactin (PRL) response to the opiate antagonist naloxone was tested in drug-free healthy volunteers (10 men, 18 regularly menstruating women who were in the late follicular phase of their ovarian cycles, and seven post-menopausal women). Naloxone hydrochloride (2 mg intravenous bolus) and placebo (normal saline) were administered on two different days in a double-blind fashion. Blood samples were collected at -15, 0, 30, 60, 120, 180 and 240 min after the injection. In the women of reproductive age, naloxone reduced plasma PRL concentrations, whereas in the post-menopausal women and the men, naloxone resulted in no significant change. However, in the post-menopausal women treated with estrogen (intramuscular 17-beta-estradiol), the opiate antagonist was able to lower plasma PRL concentrations. Thus, it appears that opiate effects on PRL secretion are influenced by the gonadal steroid environment and that estrogens may play a modulating role.

Adult↗

Failure of the GABAergic drug, sodium valproate, to reduce basal plasma prolactin secretion in chronic schizophrenia.

The psychoneuroendocrinology of schizophrenia derives from the presumption that neurotransmitter or receptor abnormalities in the limbic regions might extend to or influence the hypothalamus, which plays a role in the regulation of prolactin (PRL) secretion from the anterior pituitary gland. Since a GABA disturbance has been recently proposed in the pathogenesis of certain schizophrenic symptoms, and since a tuberoinfundibular-GABA (TI-GABA) system has been shown to modulate PRL secretion in humans, we tested the activity of this system both in controls and in chronic schizophrenic women. For this purpose the GABAergic drug sodium valproate (800 mg) was administered orally to 20 healthy women and 18 chronic schizophrenic women. Plasma PRL levels were measured before and after the drug administration. Sodium valproate decreased PRL concentrations only in the healthy women. Although the hypothesis of a GABA disturbance in schizophrenia at present is only speculative, these results might suggest a defect of the TI-GABA system in chronic schizophrenia.

Adult↗