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Biomedical subjects

F Moroni

Publications and source records attributed to F Moroni.

At least 127 records · Page 7Linked to original sources
PubMed1988

Kynurenic acid is present in the rat brain and its content increases during development and aging processes.

The content of kynurenic acid, a tryptophan (TRP) metabolite which acts as an antagonist of the excitatory amino acid receptors, was measured in the brain, blood, liver and kidney of rats of different ages, using a sensitive and specific method based on ion exchange chromatography and high-performance liquid chromatography (HPLC). In a portion of the cortex of these animals the content of serotonin (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA) and of TRP was also measured using HPLC and electrochemical detection. The brain content of kynurenic acid was extremely low during the first week of life measuring 15 +/- 3 pmol/g protein (mean +/- S.E.M.), was found to be 320 +/- 31 at 3 months and continued to increase reaching levels of 747 +/- 116 at 18 months of age. Aging failed to change kynurenate content in the liver and kidney while blood kynurenate concentration increased from 28 +/- 5 (pmol/ml) in 3 months old rats to 65 +/- 10 in those 18 months old. The accumulation of kynurenate in the brain was not due to an increased availability of TRP to the central nervous system of aged rats. In fact, the cortical content of this amino acid was slightly lower in animals 18 months old than in those 3 months old. These large changes of the brain content of an electrophysiologically active TRP metabolite such as kynurenic acid could help explain the functional differences present in the brain of newborn and aged animals.

Aging↗
PubMed1988

Differential actions of neurotrophic factors on lesion-induced damage of the serotonergic neurons projecting to the hippocampus.

The changes induced by nerve growth factor (NGF) and by GM1-ganglioside administration on serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and tryptophan content and on choline acetyltransferase activity, were studied in the central nervous system of rats undergoing electrolytic damage of a mesencephalic area, located near the nucleus interpeduncularis. This lesion selectively reduced the content of 5-HT and 5-HIAA in the ipsilateral hippocampus. Daily intraperitoneal injection of GM1-ganglioside (30 mg/kg/day for 6-14 days) significantly reduced the injury-induced loss of hippocampal 5-HT and 5-HIAA content. On the contrary NGF, administered at a dose (10 micrograms/rat i.c.v. twice a week for 2 weeks) which was able to increase, in the same animals, the cortical choline acetyltransferase activity, failed to affect the lesion-induced reduction of 5-HT and of 5-HIAA in the hippocampus.

Animals↗
PubMed1988

Decrease in rat cerebral quinolinic acid concentration following chronic hydrocortisone treatment.

The effects of acute or repeated hydrocortisone administration were studied on the content of quinolinic acid (QUIN), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) assessed by mass fragmentography (QUIN) and high-performance liquid chromatography (5-HT and 5-HIAA) in various brain areas of the rat. Acute administration of the steroid did not significantly modify the brain content of these tryptophan metabolites while, when repeatedly administered at doses of 5 or 50 mg/kg i.p., hydrocortisone significantly reduced the cortical content of QUIN (by 28%, P less than 0.05 and 21%, P less than 0.05 respectively) and the utilization of 5-HT (as evaluated from the ratio 5-HIAA/5-HT by 22%, P less than 0.05 at 50 mg/kg). These data confirm that hydrocortisone administration affects tryptophan metabolism in the rat.

Animals↗
PubMed1988

Morphine withdrawal in vitro: potentiation of agonist-dependent polyphosphoinositide breakdown.

Naloxone (10(-5) -10(-9) M) significantly increased the K+ (30 mM)-induced release of [3H[noradrenaline when it was applied to cortical slices taken from morphine-dependent rats but did not change the release of transmitter when applied to slices prepared from non-dependent animals. Therefore, this preparation was considered suitable to study withdrawal-related events and was used to monitor the agonist-induced changes of phospholipase C activity in the withdrawal state. Noradrenaline (1-100 microM) and carbachol (50-500 microM), when applied to cortical slices preincubated with [3H]inositol or with [32P]orthophosphate, dose dependently increased the formation of labeled inositol phosphates or of phosphatidic acid. This confirmed that noradrenaline and carbachol increase phospholipase C activity. This increase was significantly enhanced by naloxone (10(-6) M) when the slices were taken from dependent animals. The results now reported show for the first time in mammalian tissues that opioid withdrawal is associated with changes of phosphoinositide metabolism.

Animals↗
PubMed1988

Identification and measurement of kynurenic acid in the rat brain and other organs.

Kynurenic acid, a biologically active tryptophan metabolite, has been identified and measured in the rat brain and other organs using HPLC and GC/MS. Both the described methods required extraction of the compound in alkaline ethanol and initial purification on Dowex ion-exchange resins. The GC/MS approach used 3-hydroxy-2-naphthoic acid as an internal standard and a derivatization procedure with diazomethane and trifluoroacetic anhydride. The HPLC procedure was performed on a reverse-phase column using a spectrophotometric detector. Both the GC/MS and the HPLC methods had the lowest detection limit in the range of 10 pmol/injection, but the variability of the results was lower when HPLC was used. HPLC analysis showed the content of kynurenic acid to be 14 +/- 2 pmol/g wet wt in the brain, 75 +/- 7 in the heart, 87 +/- 8 in the liver, and 298 +/- 10 in the kidneys. Comparable but variable values were obtained with GC/MS.

Animals↗
PubMed1988

Lesioning and recovery of the serotoninergic hippocampal afferents: differential effects of GM1 ganglioside.

The effects of administration of GM1 ganglioside on the content of 5-HT and of 5-HIAA in the hippocampus after two different types of lesions of the serotoninergic afferents to the hippocampus were studied. The first type of lesion consisted in severing the dorsal hippocampal afferents. This caused a monolateral decrease of the content of 5-HT and of 5-HIAA in the hippocampal by 60 and 38%, respectively. Since a partial spontaneous recovery occurred after 40-60 days, this model has been used in the past to study sprouting phenomena in the 5-HT system. Daily intraperitoneal administration of GM1 ganglioside (30 mg/kg), for up to 60 days, did not modify this partial recovery. The second lesion consisted of electrolytic damage to a mesencephalic area, where scattered 5-HT cells projecting to the hippocampus are known to be located. The content of 5-HT and 5-HIAA in the hippocampus, ipsilateral to this lesion, decreased by 37 and by 26%, respectively. Administration of GM1 ganglioside (30 mg/kg/day for 6-14 days) partially antagonized the decrease of both 5-HT and 5-HIAA induced by the lesion. These data are in agreement with the view that gangliosides may reduce neuronal injury after mechanical lesions, with a mechanism which is probably not related to neuronal sprouting.

Afferent Pathways↗
PubMed1988

Clinical experiences with Ro 15-1788 (anexate) in benzodiazepine and mixed-drug overdoses.

Benzodiazepine overdose is the most common of admission to the Toxicological Unit of the University of Florence. The aim of this study has been to evaluate the efficiency of Ro 15-1788 in benzodiazepine and mixed drug overdoses. The administration of Ro 15-1788 was followed by a quick reversal of central nervous system depression and was more effective in benzodiazepine overdoses than in mixed drug overdoses. The dose was titrated individually and the range 2-10 mg was effective according to the conditions of the patient. In some cases, the comatose state relapsed; further administration of Ro 15-1788 again promptly reversed the condition. On awakening, two patients displayed anxiety and restlessness.

Adult↗
PubMed1988

Excitatory amino acid release from rat hippocampal slices as a consequence of free-radical formation.

The release of D-[3H]aspartate, [3H]noradrenaline, and of endogenous glutamate and aspartate from rat hippocampal slices was significantly increased when the slices were incubated with xanthine oxidase plus xanthine to produce superoxide and hydroxyl free radicals locally. Allopurinol, a specific xanthine oxidase inhibitor, the hydroxyl-radical scavenger D-mannitol, or the superoxide-radical scavenger system formed by superoxide dismutase plus catalase prevented this release. These results suggest that endogenous excitatory amino acids are released consequent to the formation of free radicals. The excess of glutamate and aspartate released by this mechanism could be one of the factors contributing to the death of neurons after anoxic or ischemic injuries.

Allopurinol↗
PubMed1988

Presence of kynurenic acid in the mammalian brain.

Kynurenic acid, a tryptophan metabolite able to antagonize the actions of the excitatory amino acids, has been identified and measured for the first time in the brain of mice, rats, guinea pigs, and humans by using an HPLC method. Its content was 5.8 +/- 0.9 in mouse brain, 17.8 +/- 2.0 in rat brain, 16.2 +/- 1.5 in guinea pig brain, 26.8 +/- 2.9 in rabbit brain, and 150 +/- 30 in human cortex (pmol/g wet wt. mean +/- SE). The regional distribution of this molecule was uneven. In rats, guinea pigs, and rabbits, the brainstem was the area richest in this compound. Tryptophan administration (100-300 mg/kg, i.p.) to rats resulted in a significant increase of the brain content of kynurenic acid. Similarly, 1 h after probenecid administration (200 mg/kg, i.p.), the brain content of kynurenate increased by fourfold, thus suggesting that its turnover rate is relatively fast.

Animals↗
PubMed1988

A new endogenous anxiolytic agent: L-pyroglutamic acid.

By use of a simple anticonflict procedure (Vogel test), it was demonstrated that L-pyroglutamic acid (L-pyrrolidone carboxylic acid [L-PCA]), an amino acid naturally occurring in mammalian tissues and fluids, possesses anxiolytic activity. This tissues and fluids, possesses anxiolytic activity. This effect was stereospecific (D-PCA was inactive) and, in the rat, it was not associated with a decrease in motor activity. Ro 15-1788, a benzodiazepine antagonist, did not modify L-PCA actions. Furthermore, anxiolytic doses of the amino acid did not change the content of 5-hydroxytryptamine (5-HT) or of 5-hydroxyindoleacetic acid (5-HIAA) in the rat cortex and hippocampus. These results suggest that the mechanism of the anxiolytic activity of L-PCA is different from that of the benzodiazepines and of 5-HT1a agonists.

Animals↗
PubMed1988

Morphine withdrawal in cortical slices: suppression by Ca2+-channel inhibitors of abstinence-induced [3H]-noradrenaline release.

1. The effects of morphine withdrawal were evaluated in vitro by monitoring the actions of naloxone on the depolarization-induced release of [3H]-noradrenaline (NA) in cortical slices taken from naïve or dependent rats. The effects of dihydropyridine molecules acting on Ca2+-channels (nimodipine and Bay K 8644) were also studied in this model. 2. Naloxone (10(-8)-10(-5) M) dose-dependently enhanced the K+ induced release of [3H]-NA in slices taken from dependent rats, but failed to modify the [3H]-NA release from 'naïve' slices. 3. The naloxone-induced potentiation of release was significantly reversed by nimodipine (10(-8)-10(-6) M). These doses of nimodipine did not change [3H]-NA release (both basal and K+ induced) in preparations obtained from naïve rats. 4. Bay K 8644 potentiated the K+-induced [3H]-NA release from cortical slices taken from naïve rats to a similar extent as that of naloxone in dependent rats. 5. These results suggest that the naloxone potentiation of the depolarization-induced [3H]-NA release in slices taken from dependent rats may be considered a model of morphine withdrawal in vitro. In this model dihydropyridine Ca2+-channel antagonists suppress morphine-withdrawal effects in a similar manner to observations made in vivo.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Agonists, antagonists and modulators of excitatory amino acid receptors in the guinea-pig myenteric plexus.

1. The receptors for glutamic acid (L-Glu) present in the guinea-pig myenteric plexus-ileal longitudinal muscle preparation have been studied by measuring the muscle contraction induced by numerous putative endogenous agonists acting at these receptors. Furthermore, the actions of different concentrations of antagonists, glycine, Mg2+ and Ca2+ on the ileal contractions induced by L-Glu have been evaluated. 2. The EC50 values of the most common putative endogenous agonists of these receptors were: L-Glu 1.9 X 10(-5) M; L-aspartate 8 X 10(-5) M; quinolinate 5 X 10(-4) M; L-homocysteate 1.4 X 10(-4) M; the dipeptide aspartyl-glutamate 8 X 10(-5) M, while N-acetyl-aspartyl-glutamate was inactive. Among the molecules used to classify excitatory amino acid receptors, N-methyl-D-aspartate (NMDA) was the most potent (EC50 5 X 10(-4) M). Kainic and quisqualic acids were almost completely inactive. 3. The responses to L-Glu were competitively antagonized by 2-amino-5-phosphonovaleric acid. They were, also, prevented by hyoscine (10(-7) M) and by tetrodotoxin (3 X 10(-7) M), suggesting that the L-Glu-induced ileal contraction was in some way dependent upon an action on the myenteric cholinergic neurones. Kynurenic acid was a non-competitive antagonist, gamma-D-glutamyl-taurine (10(-4) M) and aminophosphonobutyric acid (10(-4) M) did not modify the L-Glu-induced contractions. 4. Glycine (10(-5) M) significantly potentiated the effects of glutamate especially when the ionic composition of the superfusion medium contained concentrations of Ca2+ in the range of 0.6-1.2 mM. Strychnine 3 X 10(-5) M did not modify the actions of glycine. 5. The data presented here confirm the presence of NMDA receptors in the guinea-pig myenteric plexus, and show that these receptors, similar to those present in primary neuronal cultures may be modulated by glycine.

Animals↗
PubMed1988

Clinical pharmacokinetics of valproic acid--1988.

Sodium valproate (valproic acid) has been widely used in the last decade and is now considered a relatively safe and effective anticonvulsant agent. Recently, several investigators have proposed its use in the treatment of anxiety, alcoholism and mood disorders, although these indications require further clinical studies. Valproic acid is available in different oral formulations such as solutions, tablets, enteric-coated capsules and slow-release preparations. For most of these formulations bio-availability approaches 100%, while the absorption half-life varies from less than 30 minutes to 3 or 4 hours depending on the type of preparation used. Once absorbed, valproic acid is largely bound to plasma proteins and has a relatively small volume of distribution (0.1 to 0.4 L/kg). Its concentration in CSF is approximately one-tenth that in plasma and is directly correlated with the concentration found in tears. At therapeutic doses, valproic acid half-life varies from 10 to 20 hours in adults, while it is significantly shorter (6 to 9 hours) in children. Valproic acid undergoes extensive liver metabolism. Numerous metabolites have been positively identified and there is reasonable evidence that several of them contribute to its pharmacological and toxic actions. In fact, several valproic acid metabolites have anti-convulsant properties, while many of the side effects it may cause (e.g. those related to hyperammonaemia or liver damage) are most often observed in patients previously treated with phenobarbitone. This could indicate that induction of liver enzymes is responsible for the formation of toxic valproic acid metabolites.

Administration, Oral↗
PubMed1987

Lesioning and recovery of the serotoninergic projections to the hippocampus.

The time course of the changes of the hippocampal 5-hydroxytryptamine (5-HT) system after a lesion of the dorsal afferents to this brain area was studied by measuring the content of 5-HT and of 5-hydroxyindoleacetic acid (5-HIAA) in the dorsal, medial and ventral hippocampus. Furthermore, the binding sites for [3H]5-HT, [3H]ketanserin, [3H]imipramine and [3H]mianserin and a 5-HT-mediated behavior (head-twitch responses) were studied in controls and in animals bearing such a lesion. The contents of 5-HT and of 5-HIAA are higher in the ventral than in the dorsal hippocampus. Seven days after the lesion the 5-HT content decreases by 78% in the dorsal and by 50% in the ventral hippocampus. However, 60 days later, a partial recovery, possibly due to a collateral sprouting, does occur. The ratios between 5-HIAA and 5-HT are also increased 10, 14 and 21 days after the lesion, suggesting an increased utilization of the amine by the remaining neuronal terminals. The Bmax of the recognition sites for [3H]5-HT and [3H]mianserin, but not those for [3H]ketanserin are increased 10 days after the lesion and this increase lasts at least 30 days. Finally, starting 10 days after surgery and lasting for 40 days, a 5-HT-mediated behavior (head-twitch responses) shows supersensitivity. These results suggest that important changes occur in the 5-HT innervation of the hippocampus after a mechanical lesion: among these we showed a slow collateral sprouting, an increased utilization of the amine and a supersensitivity of 5-HT receptors.

Animals↗