Biomedical subjects

E Urbańska

Publications and source records attributed to E Urbańska.

5 recordsLinked to original sources

PubMed1994

Increased brain quinolinic acid production in mice infected with a hamster neurotropic measles virus.

In order to examine the status of quinolinic acid (QUIN) metabolism in a model of delayed excitotoxic neurodegeneration, the de novo production of QUIN from 3-hydroxyanthranilic acid was assessed in brain homogenates and brain slices of mice injected with hamster neurotropic measles virus. In the hippocampus, which presents exclusive nerve cell loss in this model, the activity of 3-hydroxyanthranilic acid oxygenase, an astrocytic enzyme responsible for the biosynthesis of QUIN, was increased 3.3-fold by 7 days after virus inoculation. Less dramatic increases were observed in the cerebral cortex and the striatum, while cerebellar enzyme activity was not different from control values. In the same brain homogenates, no changes occurred in the activities of kynurenine aminotransferase, the biosynthetic enzyme of the neuroprotectant kynurenic acid, and of the astrocytic marker glutamine synthetase. At 7 days postinoculation, hippocampal slices from virus-treated animals, when exposed to 3-hydroxyanthranilic acid, produced 18 times more QUIN than slices from control animals. Notably, a significant increase was also seen 3 days postinoculation, i.e., at a time when astrocytes had started to proliferate but prior to the onset of neurodegeneration (Eur. J. Neurosci. 3:66-71, 1991). These data suggest that astrocyte-derived QUIN may play a causative role in the occurrence of hippocampal nerve cell loss in measles virus-infected mice.

3-Hydroxyanthranilate 3,4-Dioxygenase↗

PubMed1993

[Polycythemia].

On the basis of own material, the authors discuss the epidemiology, clinical picture, and results of treatment of newborns with polycythaemia. An analysis shows that the blood hyperviscosity syndrome is an underestimated cause of many pathological signs in newborns.

Blood Viscosity↗

PubMed1992

Antiparkinsonian drugs memantine and trihexyphenidyl potentiate the anticonvulsant activity of valproate against maximal electroshock-induced seizures.

Memantine increased the threshold for electroconvulsions, when administered at 1.0-6.0 mg/kg (i.p.) and given in subthreshold doses of 0.0156, 0.0625, 0.125 and 0.5 mg/kg (i.p.) potentiated the protective efficacy of valproate, against maximal electroshock (50 mA)-induced seizures in mice, lowering the ED50 from 235 to 197, 172, 164 and 130 mg/kg, respectively. Trihexyphenidyl, applied in doses of 30 and 50 mg/kg (i.p.), did not influence the electroconvulsive threshold per se but when combined with valproate, strongly enhanced its anticonvulsant activity against maximal electroshock-induced seizures lowering the ED50 from 206 to 103 and 46 mg/kg, respectively. The chimney test and retention testing in mice revealed that administration of memantine at 0.5 mg/kg (i.p.) or trihexyphenidyl at 30 mg/kg (i.p.) together with valproate in doses of 130 or 103 mg/kg (i.p.), respectively, resulted in motor impairment and caused impairment of long-term memory, similar to the effects of valproate alone, when applied at its ED50 against maximal electroshock. Neither memantine nor trihexyphenidyl altered the total level of valproate in plasma. It may be concluded that the potentiation of the anticonvulsant activity of valproate, by memantine and trihexyphenidyl, is not associated with a pharmacokinetic interaction.

Animals↗

PubMed1991

Influence of MK-801 on the anticonvulsant activity of antiepileptics.

MK-801 (a potent non-competitive antagonist of N-methyl-D-aspartic acid-mediated events) in subcutaneous doses of 0.1 and 0.2 mg/kg increased the threshold for electroconvulsions and in doses of 0.0031 and 0.0125 mg/kg enhanced the protective activity of valproate against maximal electroshock-induced convulsions in mice. Valproate-induced side-effects (evaluated by means of dark-avoidance acquisition and retention testing and the chimney test) at its ED50 against maximal electroshock (i.e. 268 mg/kg) were pronounced whereas they were absent in the case of a combined treatment with MK-801 (0.0125 mg/kg) and valproate (91 mg/kg). This treatment provided 50% protection against maximal electroshock-induced seizures. Moreover, MK-801 (0.0125 and 0.05 mg/kg) potentiated the anticonvulsant action of phenobarbital, reducing phenobarbital-induced motor impairment totally at 0.05 mg/kg, but did not influence the protection offered by carbamazepine and diphenylhydantoin at 0.05 mg/kg. The N-methyl-D-aspartic acid antagonist did not affect the total plasma levels of either valproate or phenobarbital (as measured by immunofluorescence), so a pharmacokinetic interaction, in terms of total plasma levels at least, is unlikely to be involved in the observed effects. The finding that the combined treatment of MK-801 with valproate or phenobarbital, apart from the distinct potentiation of their anticonvulsant activities, is devoid of side-effects should be carefully considered.

Animals↗

PubMed1991

Aminooxyacetic acid produces excitotoxic lesions in the rat striatum.

The neuropathological, biochemical, and behavioral effects of intrastriatal injection of aminooxyacetic acid (AOAA), a non-specific transaminase inhibitor, were examined in rats. AOAA, 0.1-1 mumol, produced neuronal damage when injected into the striatum of adult rats but failed to damage the striatum of 6-d-old or decorticated rats. AOAA-induced (0.25 mumol-1 mumol) striatal lesions in adult rats displayed excitotoxic characteristics and could be prevented by the N-methyl-D-aspartate (NMDA) receptor antagonists (-)-2-amino-7-phosphono-heptanoate (AP7; 0.25 mumol) or kynurenate (KYNA; 0.5 mumol), but not by the non-NMDA antagonist 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline (NBQX; 0.25 mumol). AOAA produced a dose-dependent reduction in striatal L-glutamate decarboxylase activity, as measured 14 d following intrastriatal injection, which could also be prevented by AP7 or KYNA, but not by NBQX. These findings suggest that AOAA-induced lesions are preferentially mediated by activation of the NMDA subtype of excitatory amino acid receptors. Behavioral studies revealed that the cataleptic response to haloperidol, 2 mg/kg, was decreased whereas the cataleptic response to arecoline, 15 mg/kg, and morphine, 15 mg/kg, was potentiated in AOAA lesioned animals 14 d following bilateral intrastriatal injections of AOAA, 0.25 and 1 mumol. In rats which received unilateral intrastriatal injection of AOAA, 0.1-1 mumol, apomorphine, 0.5 mg/kg, induced circling towards the lesioned side. Rats which received AP7, 0.25 mumol, or KYNA, 0.5 mumol, coadministered with AOAA, 0.25 mumol, behaved as vehicle-treated controls, while those which received NBQX, 0.25 mumol, and AOAA, 0.25 mumol, had behavioral patterns similar to those subjected to AOAA alone.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗