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Biomedical subjects

U Scapagnini

Publications and source records attributed to U Scapagnini.

At least 19 recordsLinked to original sources
PubMed1992

Thyrotropin releasing hormone (TRH) and its analog, RGH-2202, accelerate maturation of cerebellar neurons in vitro.

We have studied the "trophic" action of thyrotropin releasing hormone (TRH) in cultured cerebellar granule cells, a pure and homogeneous population of glutamatergic neurons. As an index of neuronal maturation, we have measured the uptake of D-[3H]aspartate (a non-metabolizable analog of glutamate) at different days of maturation in vitro (DIV). In control cultures, D-[3H]Aspartate increased linearly during maturation reaching plateau values between 7 and 9 DIV; daily addition of TRH tartrate (TRH-t) or RGH-2202 (a TRH analog) accelerated in a concentration-dependent manner the maturation profile of D-[3H]aspartate uptake. This effect was more pronounced for RGH-2202: in cultures treated daily with RGH-2202, D-[3H]aspartate uptake was fully expressed after 3 DIV. Neither TRH-t nor RGH-2202 significantly increased D-[3H]aspartate uptake in mature cells, excluding a direct action on the glutamate transport system. Both compounds specifically potentiated the increase in [3H]inositol monophosphate formation (but not the stimulation of 45Ca2+ influx) induced by N-methyl-D-aspartate (NMDA) receptor agonists, without affecting the stimulation of inositol phospholipid hydrolysis by quisqualate or carbamylcholine. We suggest that, in cultured cerebellar granule cells, TRH and RGH-2202 enhance the trophic action of endogenous glutamate by amplifying some of the intracellular events that follow the influx of extracellular Ca2+ through NMDA-gated ion channels.

Analysis of Variance↗
PubMed1992

Ipriflavone inhibits phosphoinositide hydrolysis and Ca2+ uptake in the osteoblast-like UMR-106 cells.

The mechanism of action of ipriflavone, an isoflavone derivative, was studied in the osteoblastic-like UMR-106 cell line. Ipriflavone affected both phosphoinositide hydrolysis and 45Ca2+ uptake. A repeated treatment of UMR-106 cells (once a day, for 3 days) with ipriflavone decreased, in a concentration-dependent manner, [3H]inositol monophosphate accumulation. This effect was also achieved after single addition of high concentrations of ipriflavone or 100 nM [Asu1,7]eel-calcitonin, a semi-synthetic analog of eel calcitonin. When repeatedly added to UMR-106 cells, 17 beta-estradiol produced a marked inhibition of [3H]inositol monophosphate accumulation, an effect which appeared significant only at a concentration of 1 microM and which was accompanied by a reduced incorporation of [3H]inositol into membrane phospholipids. A repeated treatment with ipriflavone reduced 45Ca2+ uptake as well. This effect was observed also after a single addition of [Asu1,7]eel-calcitonin but not following single or repeated treatment with 17 beta-estradiol. The present data indicate the osteoblast as a direct and specific target for ipriflavone and suggest that this compound may share intracellular transducing mechanisms with other antiosteoporotic hormones such as estrogen and calcitonin.

Calcitonin↗
PubMed1992

Psychoneuroendocrinoimmunology: the basis for a novel therapeutic approach in aging.

Along with the nervous and the endocrine systems, the immune system is one of the three major integrative systems in higher organisms. Growing evidence demonstrates an intimate relationship between the immune system and the endocrine and nervous systems: The psychoneuroendocrine system can influence the immune response and thereby the capacity of the organism to cope with illness, and the immune system can have an impact on neuroendocrine function. Such cross-talk among systems is dependent upon feedback loops working to maintain homeostatic equilibrium.

Adrenocorticotropic Hormone↗
PubMed1992

Ubiquinone protects cultured neurons against spontaneous and excitotoxin-induced degeneration.

Ubiquinone is an endogenous quinone with pharmacological actions mainly related to its antioxidant properties. Here we report that ubiquinone protects cultured cerebellar granule cells against glutamate-induced neurotoxicity. In control cultures at 9 days of maturation in vitro (DIV), a 30-min exposure to 100 microM glutamate induced neuronal degeneration, as reflected by the great percentage (greater than 90%) of cells labeled with propidium iodide 24 h after the exposure. Glutamate-induced neuronal death was dramatically reduced in cultures treated daily with ubiquinone since the second DIV. In these cultures, glutamate failed to induce a "delayed" increase in the influx of 45Ca2+, an established parameter of excitotoxicity. Similarly, repeated addition of ubiquinone attenuated in a concentration-dependent manner the age-dependent degeneration of granule cells that is due to the toxic action of the endogenous glutamate progressively released into the medium. These results suggest that ubiquinone may be a useful drug in the therapy of acute and chronic neurodegenerative diseases related to hyperactivity of excitatory amino acid neurotransmission.

Animals↗
PubMed1992

Nootropic drugs positively modulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-sensitive glutamate receptors in neuronal cultures.

Micromolar concentrations of piracetam, aniracetam, and oxiracetam enhanced alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-stimulated 45Ca2+ influx in primary cultures of cerebellar granule cells. Nootropic drugs increased the efficacy but not the potency of AMPA and their action persisted in the presence of the voltage-sensitive calcium channel blocker nifedipine. Potentiation by oxiracetam was specific for AMPA receptor-mediated signal transduction, as the drug changed neither the stimulation of 45Ca2+ influx by kainate or N-methyl-D-aspartate nor the activation of inositol phospholipid hydrolysis elicited by quisqualate or (+-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid. Piracetam, aniracetam, and oxiracetam increased the maximal density of the specific binding sites for [3H]AMPA in synaptic membranes from rat cerebral cortex. Taken collectively, these results support the view that nootropic drugs act as positive modulators of AMPA-sensitive glutamate receptors in neurons.

Animals↗
PubMed1992

Anti-inflammatory action of AGF44, a ganglioside ester derivative.

Gangliosides (GA) have been shown to promote axonal sprouting and growth of injured peripheral nerves, and enhance functional biochemical and morphologic recovery after CNS damage. Moreover, it has recently been shown that the natural ganglioside mixture (GM1 + GD1a + GD1b + GT1b) from bovine brain is endowed with powerful anti-inflammatory activity in rodents. Here we report that the novel semisynthetic ganglioside derivative AGF44, the isopropyl ester of monosialoganglioside GM1, displays a potent anti-inflammatory activity when orally or topically administered in various models of acute inflammation. AGF44 was effective (0.5-5 mg/kg p.o. or 0.5% gel topical application) in reducing rat paw oedema induced by either carrageenin, histamine, bradykinin, serotonin, nystatin or kaolin. Moreover, crossed confrontation with the effects elicited by other anti-inflammatory agents revealed that AGE44 seems to act through a different pathway than NSAIDs, steroids or antihistaminic/antiserotoninic agents.

Administration, Oral↗
PubMed1979

Chronic degeneration of aminergic nerve endings and blood-aqueous barrier.

Chemical sympathectomy of the anterior segment of the eye was performed in rabbits with 6-hydroxydopamine (6-OHDA) intravitreously injected. The response of the pupillary diameter (PD) and intraocular pressure (IOP) to NE, E and Isoproterenol was determined through instillation of the drugs in the pretreated and control eyes. The results were as follows: 1) Both PD and IOP at different intervals of time from the injection show a sharp decrease in the treated eye. 2) About four weeks after the injection, the instillation of NE and E increases the PD only in the 6-OHDA pretreated eyes, while IP administration is not effective on both control and pretreated eyes. 3) The instillation of the three drugs, while decreasing IOP in the control eyes, does not modify the already low IOP in the pretreated eyes. The authors suggest the presence of a postdenervation supersensitivity affecting only the alpha receptors, since the beta stimulant IP is inactive in both treated and untreated eyes.

Animals↗
PubMed1979

Lack of evidence for an inhibitory role played by tuberoinfundibular dopaminergic neurons on TSH secretion in the rat.

The role of dopamine (DA) in the control of thyroid stimulating hormone (TSH) secretion in basal or cold stimulated conditions was investigated by using pharmacological or neurosurgical tools. The intraventricular injection of DA (5 micrograms/animal) or the subcutaneus (s.c.) injection of a dopaminomimetic agent failed to induce changes of TSH plasma levels in normal or in cold stimulated conditions. The same results were obtained by intraperitoneal (i.p.) administration of haloperidol, a blocker of dopaminergic receptors. The complete deafferentation of hypothalamus, which causes degeneration of norepinephrinergic nerve endings and leaves the DA tuberoinfundibular system unaffected, prevented the TSH release evoked by cold exposure. alpha-Methyl-p-tyrosine (alpha-MpT) (250 mg/kg i.p.), which causes a remarkable reduction of DA in the median eminence (ME) of deafferented animals, was unable to restore the TSH response to cold. Collectively these results seem to suggest that DA does not play a significative role in the control of TSH secretion in the rat.

Animals↗
PubMed1979

Crop-sac response after systemic and intraventricular administration of neuroleptic drugs.

Present experiments were aimed at studying in pigeons the effects of some neuroleptic agents given systemically or into the 3rd cerebral ventricle on PRL secretion and following morphological changes of the crop-sac mucosa both by classical histological methods and scanning electron microscopy. In addition, such changes were also evaluated on the basis of a semiquantitative method using a 1-4 rating scale. 3- or 5-day systemic treatment with reserpine, haloperidol and (ł/-)-sulpiride produced an intense crop-sac response consisting of a marked epithelial hyperplasia and presence of milk-like material. Similarly, a much lower dose of haloperidol, clozapine, and the two enantiomers of sulpiride given into the 3rd cerebral ventricle for 3 consecutive days produced a marked crop-sac response. The l-sulpiride was more active in comparison to the d-enantiomer. In conclusion, present experiments show that, similarly to mammals, in pigeons neuroleptic drugs are able to stimulate prolactin secretion and suggest that these effects are mediated through an action at the hypothalamic and/or pituitary level by removing a tonic dopaminergic inhibition.

Animals↗
PubMed1979

Effect of bromocriptine (CB-154) on oestrogen-induced prolactin release.

In order to study the interaction between oestrogens and bromocriptine on PRL release, we evaluated the ability of bromocriptine (CB-154) to counteract the oestrogen-induced PRL release in four hyperprolactinaemic amenorrhoeic women. Bromocriptine acutely administered induced a similar percentage of PRL decrease in the same patient before and after oestrogen administration. When bromocriptine was chronically administered, contemporary oestrogen injection did not affect PRL release. These results show that bromocriptine is able to block the release of PRL induced by oestrogens, suggesting an interaction between oestrogens and DA-mimetic compounds on PRL release.

Adult↗
PubMed1978

Prevention of compensatory ovarian hypertrophy by local treatment of the ovary with 6-OHDA.

The possible role of a neural mechanism involved in the development of compensatory ovarian hypertrophy has been studied. A new technique, the use of a special plastic capsule, has been developed to allow chronic local treatment of the ovary. Local treatment of one of the ovaries with 6-hydroxydopamine (6-OHDA) resulted in a weight increase in the other ovary. In the unilaterally ovariectomized rat the local application of 6-OHDA on the ovary blocked the development of compensatory ovarian hypertrophy. Local treatment of the ovary with dopamine (DA) did not interfere with the compensatory ovarian growth of the other ovary. Data suggest that intact adrenergic afferent and efferent neural elements of the ovary are required for the development of compensatory ovarian hypertrophy.

Animals↗
PubMed1978

Serotoninergic involvement in the regulation of circadian rhythms of hypothalamic-pituitary adrenal and prolactin axis.

A detailed review of their own experiments and of data existing in the literature regarding the role played by 5HT in the control of circadian rhythms of HHAA and HHPA is given by the AA. In rats, a positive correlation between 5-HT content in the limbic system and plasma corticosterone circadian rhythm has been shown to exist by means of pharmacological and neurosurgical approaches. Lesions of the raphe area result in an abolition of diurnal periodicity of plasma steroids similar to that obtained after inhibition of 5-HT synthesis by means of PCPA. A modification of the amplitude of the plasma corticosterone circadian variations also occurs after more selective destruction of some nuclei (n. centralis superior and n. raphe dorsalis) which reduced 5-HT concentration both in the hypothalamus and the hippocampus. Isolation of the mediobasal hypothalamus by a frontal cut posterior to the optic chiasma abolishes the diurnal fluctuation of plasma corticosterone, indicating that the suprachiasmatic nucleus is a focal site for the 5-HT regulation of the phasic activity of the HHAA. Evidence in favour of 5-HT mechanisms in the limbic area as the biological clock regulating the circadian variations of the adrenal axis is also provided. Restoration of the diurnal rhythm of plasma corticosterone after its abolition could be explained with the existence of a small functional pool of brain 5-HT or with the development of receptor supersensitivity. Pharmacological and surgical manipulation on central 5-HT neurons suggest the existence of two distinct serotoninergic mechanisms, a limbic one and an intrahypothalamic one, which play a modulatory role in the circadian variations of plasma PRL. Also in this case, adaptive accessory brain structures can take over in restoring the circadian hormones periodicity in conditions of impairment of the main serotoninergic mechanisms.

5,6-Dihydroxytryptamine↗
PubMed1977

Thyrotropin and prolactin response to intraspinal TRH administration in man.

The effect of intraspinal (i.s.) TRH administration of Prolactin (Prl) and thyrotropin stimulating hormone (TSH) serum levels was studied in order to verify the existence of a ventricular route in man for releasing factor delivery to the anterior pituitary, which has been previously reported in rats. Ten young male subjects were given 200 microgram thyrotropin releasing hormone (TRH) i.s. injections and Prl and TSH were measured by radioimmunoassay (RIA) before and at various times after TRH administration. In the same subjects, an i.v. TRH test was also performed. After i.s. TRH, a prompt Prl increase (peak values at 10-30 min and return to baseline within 150 min) and a delayed increase (3-5 h following TRH injection) were observed in 7 and 5 subjects respectively, while an early elevation in serum TSH occurred in 6 subjects and a late one in other 6. In two subjects, a biphasic response of both tropins was present. Prl and TSH response to i.v. TRH was within the normal range in all cases; no late rise of the 2 hormones was observed. A kinetic experiment with 125I-TRH was also carried out to elucidate the mode of i.s. vs i.v. TRH action. These results confirm in man data reported in animals which suggest that TRH can be transported from the cerebrospinal fluid (CSF) to the portal system and the hypophysis.

Humans↗
PubMed1977

The role of central noradrenergic neurons in the control of thyrotropin secretion in the rat.

To investigate the role played by hypothalamic noradrenaline (NE) in the regulation of TRH-TSH release during tonic and cold activated conditions, drugs and surgical procedures able to interfere with central NE tonus were utilized. The time course of the effect of alpha-methyl-para-tyrosine (alpha-MpT) on basal TSH secretion was followed. The tyrosine hydroxylase (TH) inhibitor was unable to modify TSH plasma levels, whereas NE hypothalamic content decreased beginning with the third hour. The acute release of TSH evoked by cold exposure (CE) was prevented by pretreatment with alpha-MpT 1 h before; when alpha-MpT was followed 40 min later by clonidine, a central noradrenergic stimulating agent, TSH response to cold, previously blocked by the TH inhibitor was restored. Intraventricular injection of 10 micrograms of clonidine hydrochloride in unstimulated rats caused a significant rise of basal TSH levels 3, but not 10 min after the administration. Complex deafferentation of the medial basal hypothalamus (MBH), which destroys all the NE fibers afferent to this area, caused no change of thyrotropin secretion in basal conditions. Deafferented animals did not show any acute increase of TSH in response to CE. The results of this study provide evidence that NE may be the catecholamine (CA) mediating the rise in TSH following CE and that the direct stimulation of central NE receptors can evoke a massive TSH release from the anterior pituitary gland also in basal conditions.

Animals↗
PubMed1977

Decrease of prolactin by methysergide in amenorrheic hyperprolactinemic women.

The effect of methysergide (MES), a serotoninergic antagonist on prolactin (PRL) blood levels was studied in five hyperprolactinemic amenorrheic women. The drug was administered for five days at a daily dosage of 11.2 mg. MES decreased significantly the PRL blood levels in all subjects (p less than 0.01). Since the MES has been shown to have antiserotoninergic effects and since serotonin has been thought to be involved in the control of PRL release, the effects of MES in lowering PRL might be due to a decrease of serotonin tone.

Adolescent↗