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Biomedical subjects

V Carlà

Publications and source records attributed to V Carlà.

33 records · Page 2Linked to original sources
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

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↗
PubMed1986

Content of quinolinic acid and of other tryptophan metabolites increases in brain regions of rats used as experimental models of hepatic encephalopathy.

The content of the tryptophan metabolites quinolinic acid (QUIN), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) was measured in various brain areas of rats bearing a portocaval anastomosis (PCA) for 4 weeks, using mass fragmentography or HPLC. In these animals, the content of the excitotoxic compound QUIN increased by 75% in the cortex and 125% in the cerebellum. The content of 5-HT increased by 27% in the brainstem. No changes occurred in other brain areas. On the other hand, the content of 5-HIAA increased by 66% in the cortex, 65% in the caudate, 64% in the hippocampus, 120% in the diencephalon, and 185% in the brainstem. Probenecid administration caused a larger increase of 5-HIAA accumulation in various brain areas of PCA-bearing rats than in those of sham-operated controls. The cortical content of QUIN and 5-HIAA increased after administration of ammonium acetate (7 mmol/kg), whereas an equimolar amount of sodium acetate was inactive. These results confirm that profound changes in the disposition of tryptophan occur in the brains of experimental animals used as models of hepatic encephalopathy. Furthermore, this study adds the excitotoxic compound QUIN to the list of molecules possibly involved in the pathogenesis of this brain disorder.

Acetates↗
PubMed1986

Increase in the content of quinolinic acid in cerebrospinal fluid and frontal cortex of patients with hepatic failure.

Quinolinic acid (QUIN), an excitotoxic tryptophan metabolite, has been identified and measured in human cerebrospinal fluid (CSF) using a mass-fragmentographic method. Furthermore, its content has been evaluated in frontal cortex obtained at autopsy from the cadavers of patients who died after hepatic coma. During the coma, the concentration of QUIN in the CSF was 152 +/- 38 pmol ml-1. In contrast, the concentration in control patients affected by different pathologies was 22 +/- 7 pmol ml-1. In the frontal cortex of patients who died after episodes of hepatic encephalopathy, the content of QUIN was three times higher than in controls (2.6 +/- 0.6 versus 0.80 +/- 0.08 nmol/g wet weight). As a result of these investigations we are now able to extend our previous observations on the increase of QUIN in the brains of rats used as experimental models of hepatic encephalopathy to man. QUIN should therefore be added to the list of compounds possibly involved in the pathogenesis and symptomatology of brain disorders associated with liver failure.

Aged↗
PubMed1984

The excitotoxin quinolinic acid is present and unevenly distributed in the rat brain.

The presence of quinolinic acid (2,3-pyridinedicarboxylic acid, QA) in the rat brain has been demonstrated using a mass-spectrometric method. Distribution studies indicate that this molecule is more concentrated in the cortex (2.1 nmol/g wet weight) than in other brain areas. Tryptophan, a possible QA precursor, administered in large doses, increases the cortical content of QA. The contrary occurs when rats are pretreated with p-chlorophenylalanine, a drug capable of decreasing brain tryptophan concentration. The neurotoxin 5,7-dihydroxytryptamine is inactive. Our findings support the idea that QA merits special attention as a potential transmitter and as an endogenous excitotoxin in brain.

5,7-Dihydroxytryptamine↗
PubMed1984

Pyroglutamic acid administration modifies the electrocorticogram and increases the release of acetylcholine and GABA from the guinea-pig cerebral cortex.

Pyroglutamic acid (1-PCA), a cyclic derivative of glutamic acid, was administered i.p. (7.7 mmol/kg) or intracerebroventricularly (25 - 50 mumol) to freely moving guinea-pigs, provided with semi-permanently implanted epidural cups. The effect of this compound on cortical Acetylcholine (ACh) and GABA outflow, as well as on gross behaviour and electrocorticogram (E.Co.G.) was investigated. 1-PCA increased the release of ACh and GABA from the cortical surface, did not change their cortical content, decreased the spontaneous motor activity and synchronized the E.Co.G.. These results suggest that 1-PCA increases GABA release, possibly by changing amino acid transport through the biological barrier or by acting as antagonist on the receptors for glutamic acid. In turn, the activation of the GABA system increases, as previously demonstrated, the cortical ACh release and causes mild sedation and E.Co.G. synchronization.

Acetylcholine↗
PubMed1981

Hypothermia induced in rabbits by intracerebroventricular taurine: specificity and relationships with central serotonin (5-HT) systems.

The intracerebroventricular (i.c.v.) injection of taurine produced a fall in core temperature, the extent of which was dependent on the thermal gradient between the body and the environment. Concurrently, a sudden rise in ear skin temperature, which was maximal in the cold and negligible at 30 degrees C, was observed. The fever induced by i.v. injection of Escherichia coli endotoxin was antagonized by taurine. High temperatures produced by i.c.v. injection of prostaglandin E1 were also suppressed by taurine. Intracerebroventricular injections of bicuculline and strychnine, but not those of picrotoxin or pentylentetrazol, were able to reduce hypothermia induced by taurine. Intracerebroventricular injection of the taurine reuptake inhibitor guanidinoethyl sulfonate, on the contrary, did enhance the hypothermic response to taurine. Injection (i.c.v.) of serotonin (5-HT) elicited a fall in core temperature which was not accompanied by a rise in ear skin temperature, but was antagonized by the concurrent injection of the 5-HT antagonist methysergide. Pretreating animals with p-chlorophenyl-alanine caused a significant fall of brain 5-HT contents and a reduction of the hypothermic response to taurine. The latter effect was also observed when the animals were i.c.v. pretreated either the methysergide or with the 5-HT reuptake blockers chlorimipramine and Lilly 110140. These findings give support to the hypothesis that taurine-induced hypothermia in rabbits mediated by some taurine sensitive cells and, at least in part, by serotonergic synaptic mechanisms.

Animals↗
PubMed1980

[Preliminary results on the possible role of intestinal peroxidase (EC 1.11.1.7) in the biosynthesis of prostaglandins].

The ability of a partially purified rat ileum peroxidase to synthetize PGE2 and PGF2 alpha from arachidonic acid was researched. The enzyme preparation, when incubated anaerobically with H2O2 and arachidonic acid, produced a compound extractable with ethyl acetate which showed on TLC the same Rf as authentic PGE2. This compound, after elution from the gel, was able to contract the rat strip fundus preparation.

Animals↗
PubMedDate not supplied

Hepatic encephalopathy: lack of changes of gamma-aminobutyric acid content in plasma and cerebrospinal fluid.

The aim of the study was to verify the role of gamma-aminobutyric acid in the pathogenesis of hepatic encephalopathy occurring in cirrhotic patients by attempting to correlate plasma and cerebrospinal fluid content of authentic gamma-aminobutyric acid with the neurological manifestations of hepatic encephalopathy. For this purpose, plasma and cerebrospinal fluid gamma-aminobutyric acid levels were measured by means of mass fragmentography in 17 cirrhotic patients with hepatic encephalopathy and in 6 cirrhotics without neurological symptoms. Moreover, in all patients, a second sample was obtained during the clinical course of hepatic encephalopathy. The mean plasma and cerebrospinal fluid gamma-aminobutyric acid levels were not different in patients with or without hepatic encephalopathy and did not change during the evolution of the neurological symptoms. The lack of changes in the gamma-aminobutyric acid content in plasma and cerebrospinal fluid during hepatic encephalopathy is in contrast with the hypothesized importance of increased entry into the brain of gamma-aminobutyric acid in the pathogenesis of hepatic encephalopathy.

Adult↗