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Biomedical subjects

U Scapagnini

Publications and source records attributed to U Scapagnini.

180 records · Page 10Linked to original sources
PubMedDate not supplied

Modulating effects of the synthetic thymic dipeptide pidotimod on the immune system in the aging rat.

We have investigated the in vivo and in vitro effect of pidotimod, a synthetic thymic-derived drug, on the immune response in young (2 month-old), and aging (24 month-old) Sprague-Dawley rats. We studied the effect of different doses of pidotimod on the responsiveness of both cultured peripheral blood lymphocytes and splenocytes to mitogenic stimuli, as well as on interleukin-2 production by peripheral blood lymphocytes after stimulation with interleukin-1 and phytohemagglutinin. Treatment with pidotimod in vivo as well as in vitro resulted in an increase of tritiated thymidine incorporation in both mitogen-stimulated lymphocytes and splenocytes from 24 month-old rats. Production of IL-2 from lymphocytes of 24 month-old rats was significantly increased in groups of animals treated with pidotimod. On the other hand, treatment with pidotimod did not influence the responsiveness of 2 month-old rat lymphocytes to mitogens, nor affected IL-2 production. Our results suggest a possible specific modulatory activity of pidotimod on the aging immune system.

Adjuvants, Immunologic↗
PubMedDate not supplied

Effects of CDP-choline administration on receptor-stimulated inositol phospholipid hydrolysis in brain slices and neuronal cultures.

Repeated addition of CDP-choline (100 microM, once a day since the 2nd day of maturation in culture) to corticostriatal neurons led to an increased basal hydrolysis of inositol phospholipids, as revealed by an enhanced formation of [3H]inositolmonophosphate ([3H]InsP) in the presence of 10 mM Li+. This increase was prevented by the muscarinic receptor antagonist, atropine, or by tetrodotoxin, but not by other receptor antagonists, such as L-2-amino-4-phosphonobutanoate (L-AP4), prazosin or ketanserin. The increase in inositol phospholipid hydrolysis induced by repeated addition of CDP-choline was obliterated when cultures were incubated in the presence of the muscarinic receptor agonist, carbamylcholine. CDP-choline had no effect on inositol phospholipid hydrolysis in cultured cerebellar neurons, which are devoid of cholinergic cells. The basal hydrolysis of inositol phospholipids was also increased in hippocampal slices prepared from rats repeatedly injected with CDP-choline (200 mg/kg, i.p. for 15 days). As observed in cultured cortico-striatal neurons, this increase was prevented by atropine and was masked in the presence of carabamylcholine. Taken collectively, these data indicate that repeated exposure to exogenous CDP-choline increases polyphosphoinositide turnover, an effect that results from an increased availability of acetylcholine acting on muscarinic receptors.

Acetylcholine↗
PubMedDate not supplied

Excitatory amino acids and neuronal plasticity: modulation of AMPA receptors as a novel substrate for the action of nootropic drugs.

The nootropic drug, aniracetam, behaves as a positive modulator of AMPA-sensitive glutamate receptors in a variety of systems, including intact brain tissue, amphibian oocytes injected with rat brain mRNA, and cultured neurons. In electrophysiological studies, aniracetam both increases the peak amplitude and reduces the rate of decay of the ion current generated by AMPA or quisqualate. In cultured neurons, aniracetam (as well as oxiracetam and piracetam) enhances the stimulation of 45Ca2+ influx produced by AMPA but not that produced by kainate or NMDA. In addition, aniracetam (as other nootropic drugs) increases the maximal density of low affinity binding sites for [3H]AMPA in crude synaptic membranes. Positive modulation of AMPA receptors by aniracetam provides a novel molecular substrate which explains the clinical efficacy of nootropic drugs as memory and cognition enhancers.

Amino Acids↗
PubMedDate not supplied

Repeated injections of piracetam improve spatial learning and increase the stimulation of inositol phospholipid hydrolysis by excitatory amino acids in aged rats.

Repeated injections of piracetam (400 mg/kg, i.p. once a day for 15 days) to 16-month old rats led to an improved performance on an 8-arm radial maze, used as a test for spatial learning. This effect was accompanied by a greater ability of excitatory amino acids (ibotenate and glutamate) to stimulate [3H]inositol-monophosphate formation in hippocampal slices incubated in the presence of 10 mM Li+. Repeated administration of piracetam did not induce changes in excitatory amino acid-stimulated polyphosphoinositide hydrolysis in hippocampal slices prepared from 2-month old animals.

Animals↗
PubMedDate not supplied

Nerve growth factor inhibits some acute experimental inflammations.

Nerve growth factor (NGF) displays an inhibitory effect on peritoneal dye leakage in mice and on some types of acute inflammation in rats, i.e. acetic acid peritonitis and paw oedema induced by carrageenin, serotonin and dextran. Activity was only present in a restricted dose range, either after subcutaneous (1-8 micrograms/kg) or subplantar (0.5-5 micrograms) injection, and was characterized by a rapid onset of response. In the carrageenin test, NGF administered s.c. was more potent than indomethacin (INDO) and betamethasone (BTM); in addition, while the activity of INDO and BTM was observed only 2-3 hr after carrageenin challenge, the response of NGF developed within 1 hr, suggesting that NGF inhibits the early phase of the oedema. NGF exhibited a different action than BTM and INDO also in serotonin and dextran paw oedema. NGF (0.008 mg/kg s.c.) inhibited the serotonin oedema as early as 15 min and reached its maximum at 1 hr, whereas BTM (0.8 mg/kg) required at least 3 hr to attain the same effect. Serotonin oedema was not inhibited by INDO (even at 16 mg/kg) up to 0.25-6 hr, proving that this model of inflammation is insensitive to the inhibitors of prostaglandin synthesis. When given subplantary, NGF reduced dextran oedema, whereas BTM and INDO were ineffective. Pretreatment with specific anti-NGF antibodies abolished all the above effects of NGF, but did not modify the anti-inflammatory activity of BTM and INDO. NGF was less effective in reducing the exudate volume on carrageenin pleurisy and did not prevent cell migration. Tested in vitro, NGF showed no direct scavenging effect on superoxide radicals. These findings suggest that NGF may be involved in some types of acute inflammation by reducing vascular permeability.

Acetates↗
PubMedDate not supplied

Behavioral effects of deprenyl in aged rats.

The effects of an inhibitor of MAO-B, deprenyl, have been studied in aged male rats. Subcutaneous (s.c.) injection of deprenyl was followed by a facilitated acquisition of active avoidance behavior and a facilitated retention of passive avoidance response in a dose-dependent manner. Ambulation and rearing of aged rats in an open field were increased by deprenyl. No effect was found on grooming behavior. Apomorphine-induced stereotypies were potentiated and haloperidol-induced catalepsy was inhibited by deprenyl. Some elements of sexual behavior, i.e. latency to mounting and intromission and frequency of mounts and intromissions, were improved by deprenyl. Furthermore, deprenyl reduced the immobility of aged rats in a "despair" test, suggesting an antidepressant activity. Deprenyl seems to be effective in correcting some of the behavioral deficits of aged animals. Its behavioral effects can be related to the inhibition of cerebral MAO-B.

Age Factors↗
PubMedDate not supplied

Characterization of the antinociceptive effects of a ganglioside derivative in rodents.

The results of a broad pharmacological screening on a natural mixture of gangliosides (GA) and an inner ester (AGF1) are reported. Up to relatively high doses, GA and AGF1 did not affect general behavior and neurologic functions and were devoided of diuretic, antipyretic, ulcerogenic, antireserpine, antiapomorphine, anticholinergic and anticonvulsivant actions. Both compounds interfere specifically with some induced conditions of inflammation and pain, but AGF1 shows a stronger action in reducing phenylquinone writhing than GA which appears to possess a more pronounced anti-inflammatory activity. In the rat paw oedema the anti-inflammatory effect of GA and AGF1 developed 1 hr after carrageenin and reached its maximum at 2 hr, suggesting that an inhibition of the serotonin and kinin phases might be partly responsible. Therefore, it would seem that the anti-inflammatory action of gangliosides is not exerted by an inhibition of the prostaglandin (PG) system. This assumption is supported by the finding that GA and AGF1 did not influence yeast-induced hyperthermia nor produced ulcerogenic effects in fasted rats. Subcutaneous administration of AGF1 is less potent than indomethacin (2 times) in reducing phenylquinone writhings, but more effective than GA (6 times), codeine (9 times) and acetylsalicylic acid (187 times). After i.c.v. administration the anti-writhing activity of AGF1 was far more potent than that of all the other compounds. The neuronal substrate involved in the AGF1 antinociception is unknown at this time. The comparative study with GA suggests a dissociation between the anti-inflammatory activity and the antinociceptive response. The lack of analgesia in the hot plate test and the naloxone insensitive anti-writhing effect of AGF1 in mice indicate that a central opioid mechanism is not involved in the antinociceptive action. Furthermore, the negativity of the neurogenic plasma extravasation test seems to exclude also an interaction with peripheral opiate receptors. It is suggested that the antinociceptive action of AGF1 has both a peripheral and a central component via an interference with peripheral exsudative phenomena and the central serotonergic tonus.

Analgesics↗
PubMedDate not supplied

Pyroglutamic acid improves learning and memory capacities in old rats.

The effects of the arginine salt of pyroglutamic acid (2-oxo-pyrrolidone carboxylic acid, PCA) on learning and memory capacities of old rats were studied in a subchronic treatment schedule (i.p. injection of 0.1 and 1 g/kg/day for 15 days). The acquisition and extinction of active avoidance behaviour were studied in a pole-jumping test situation. The retention of passive avoidance response was examined in a step-through passive avoidance task. PCA facilitated the rate of acquisition of pole-jumping response, and inhibited the extinction of the response. The dose of 1 g/kg was more potent than 0.1 g/kg in this respect. Also in the passive avoidance task, the treatment with PCA was followed by an improvement of avoidance retention. These results indicate that PCA is a behaviourally active compound in that it improves learning and memory capacities in old rat.

Aging↗
PubMedDate not supplied

Effects of flunarizine on experimentally-induced convulsions in animals.

D,L-allylglycine-induced seizures in rats were antagonized by flunarizine and other antiepileptic drugs. In this respect, the spectrum of flunarizine appears to be similar to that of diphenylhydantoin. A behavioral analysis of the effects of various drugs on amygdaloid kindled rats showed that flunarizine exerts anticonvulsive effects in this model with an ED50 of 42.8 mg/kg. Furthermore, flunarizine (1, 5, 25 and 50 mg/kg i.p.) reduced seizure parameters in rats injected with strychnine or pentetrazol. In this case, flunarizine reduced seizure intensity and increased the percentage of survival. In another study on genetically epileptic beagles, flunarizine significantly affected the REM and deep slow-wave sleep latencies.

Allylglycine↗
PubMedDate not supplied

Behavioral effects of perinatal administration of antidepressant drugs in the rat.

The monoamine reuptake blockers, imipramine, desipramine, and chlorimipramine, and the monoamine-oxidase inhibitors, iproniazid and isocarboxazid, were administered to pregnant rats (acutely at day 15 of pregnancy, or subchronically from day 10 of pregnancy to the delivery) or to newborn pups (from day 1 to day 5 of life). Prenatal acute injection of the antidepressant drugs failed to modify the development of neonatal reflexes of the rat pups and their adult behavior. Prenatal subchronic administration of the antidepressant drugs was followed by an increase in the number of pups showing neonatal reflexes, but also by an inhibition of the open field behavior and the acquisition of active avoidance responses tested in adulthood. In this respect, monoamine-oxidase inhibitors appeared to be more potent than monoamine reuptake blockers. Furthermore, neonatal administration of all the antidepressant drugs caused an inhibition of the acquisition of active avoidance responses tested in adulthood, but only the monoamine-oxidase inhibitor, isocarboxazid, significantly inhibited also the open field behavior of adult rats. Neither prenatal nor neonatal administration of the antidepressant drugs affected sexual activity of adult rats. The present results suggest that only a prolonged treatment with antidepressant drugs can affect neonatal or adult behavior of the rat, probably through an interference with central monoamine neurotransmission.

Animals↗
PubMedDate not supplied

Neuroendocrine effects of bromperidol.

In the present study we have considered the influence of various antipsychotic drugs (mostly butyrophenones) on some neuroendocrine axes (hypothalamic-hypophyseal-gonadal, hypothalamic-hypophyseal-thyroidal and hypothalamic-hypophyseal-prolactin axes). The antagonistic activity of bromperidol on DA receptors regulating the hypothalamic LH-RH release was compared in vitro to that of haloperidol. To support the possible inhibitory role of DA neurons on HHTA activity, we have evaluated the capacity of bromperidol to remove the apomorphine induced blockade of cold stress-stimulated TSH release. Finally, to evaluate the influence of the drug on prolactin release, bromperidol was compared with haloperidol and pimozide in adult male rats. The results obtained show that bromperidol is able to antagonize as well as haloperidol the DA-induced LH-RH release. The butyrophenone partially remove, in contrast to pimozide, the inhibitory effect of L-DOPA and apomorphine on TSH release. In in vivo and in vitro experiements the antidopaminergic action of bromperidol, evaluated by PRL release, can be considered intermediate between pimozide and haloperidol.

Apomorphine↗
PubMedDate not supplied

Excitatory amino acids and neurotoxicity.

In the past three decades evidence indicating a role for excitatory amino acids in determining certain neurological disorders has been accumulated. Although the mechanisms underlying the neuronal damage induced by glutamate are not yet fully understood, many intracellular processes are thought to contribute to the development of excitotoxic injury, acting in combination to determine cell death. In this article we report the leading hypotheses in the understanding of excitatory amino acid-induced toxicity, which focus on the role of Ca2+ and Ca(2+)-activated processes, for example the activation of Ca(2+)-dependent enzymes such as kinases, lipases and proteases and the formation of the messenger molecule nitric oxide for the production of free radicals, in the development of neuronal damage. The possible implications for excitotoxicity of second messenger systems generated by glutamate acting on the metabotropic receptor subtypes will also be discussed.

Brain↗
PubMedDate not supplied

Dihydroergocryptine protects from acute experimental allergic encephalomyelitis in the rat.

The effect of dihydroergocryptine, a natural alkaloid derivative which exhibits D2 dopaminomimetic properties, has been studied in Lewis female rats with experimentally induced allergic encephalomyelitis. A chronic treatment with dihydroergocryptine started two days before immunization, induced a dramatic reduction of prolactin levels accompanied by a marked amelioration of neurological signs. In addition, the proliferative activity of splenic lymphocytes induced by the mitogen Concanavalin-A (Con-A) was reduced in dihydroergocryptine-treated animals. It is suggested that this effect is related to the ability of dihydroergocryptine to lower prolactin concentrations or also, partially, to a neuroprotective action of this drug.

Animals↗
PubMedDate not supplied

Antidegenerative effects of Mg(2+)-valproate in cultured cerebellar neurons.

We have investigated in the present study the effect of Mg(2+)-valproate on necrotic degeneration induced by an excitotoxic insult in primary culture of cerebellar neurons, that is an homogeneous population of glutamatergic neurons. Mg(2+)-valproate protected cultures against glutamate-induced neurotoxicity, acting as an indirect N-methyl-D-aspartate (NMDA) receptor antagonist, thus reducing free radical formation and affecting the biochemical parameters (i.e. 45Ca(2+)-influx, cyclic GMP formation, inositol phospholipid hydrolysis and protein kinase C translocation) that undergo modifications following NMDA receptor activation in cerebellar granule cells.

Animals↗