Antagonism of seizures induced by the administration of the endogenous convulsant quinolinic acid into rat brain ventricles.

The effect of pretreatment with drugs on generalized clonic-tonic seizures induced by intracerebroventricular (i.c.v.) administration of the endogenous convulsant quinolinic acid (QUIN, 50 micrograms) was studies in rats. Of the inhibitory amino acids tested, only 1-glycine (50 and 100 micrograms, i.c.v.) diminished the number of animals with seizures while taurine and GABA were ineffective. Of the kynurenine metabolites, only kynurenic acid (50 micrograms, i.c.v.) prevented seizures and lethality. Picolinic acid, nicotinic acid and nicotinamide were ineffective. The standard anticonvulsants phenobarbital, diphenylhydantoin and primidone were effective antagonists of QUIN-induced seizures at doses which did not influence pentylenetetrazol seizures. However, the only drug which completely prevented QUIN-induced seizures was diazepam (10 mg/kg). It also prevented pentylenetetrazol seizures in rats in a four times lower dose. The GABA derivatives sodium hydroxybutyrate and phenibut (beta-phenyl-GABA), which are effective QUIN-antagonists in mice, were found to be ineffective in rats. Species differences between rats and mice in the efficacy of antagonists QUIN are discussed.

[Changes in dexamethasone test indices and reduction in the rate of serotonin absorption by thrombocytes in chronic alcoholics]. / Izmenenie pokazatelei deksametazonovogo tests i snizhenie skorosti pogloshcheniia serotonina trombotsitami u bol'nykh khronicheskim alkogolizmom.

Seventy-one chronic alcoholics with affective disorders were studied for the dexamethason test (DT) and for the rate of platelet serotonin absorption (RPSA) prior to and following the treatment. A considerable part of the patients displayed pathological changes in DT which correlated with the degree of affective symptomatology. The DT may serve as one of the methods for diagnosing affective disturbances in alcoholism. The RPSA was equally depressed in all the patients studied (by about 30% as against the control group) irrespective of the severity of affective symptomatology. The increase in the activity of central serotoninergic processes expressed in a RPSA decrease seems to reflect an underlying basic biochemical pathology of alcoholism rather than disorders in the affective sphere.

Differential diagnosis of anomalous pulmonary venous return. A clinical-roentgenological study.

The paper presents an analysis of the results of clinical and roentgenological examination of 88 patients with anomalous pulmonary venous return (42 females, 46 males), aged 2 weeks to 33 years. This defect has highly diverse anatomical variants. Its most frequent form is partial anomalous drainage (70.5%), while total drainage is much less frequent (29.5%). As regards the return level of the pulmonary veins, the site occurring most frequently is the supracardial one (63%), followed by the cardial (20%), mixed (11%) and infracardial site (6%). The authors compare the findings of X-ray examination with the results of catheterization of the right and left heart, selective angiocardiography (62) and the findings made intraoperatively (82), and assess the value of routine X-ray examination for differential diagnosis of partial and total anomalous pulmonary venous drainage at different return levels.

[Stimulatory effects of intraventricular administration of kynurenines, amino acids, and convulsants: differences between rats and mice]. / Vozbuzhdaiushchie éffekty vvedennykh v zheludochki mozga kinureninov, aminokislot i konvul'santov: razlichiia mezhdu krysami i myshami.

Quinolinic acid appeared to be the only kynurenine metabolite among tested (L- and DL-kynurenine sulfate, kynurenic and nicotinic acids, nicotinamide) which induced locomotor excitation and clonic seizures in rats whereas all of them exerted convulsant action in mice. Excitatory 1-glutamic and 1-aspartic amino acids and inhibitory amino acids GABA, 1-glycine and taurine did not induce either excitation of seizures in rats but did so in mice. Moreover, GABA, 1-glycine and taurine induced obvious sedation, side position and discoordination in rats. Convulsants strychnine sulfate and pentylenetetrazol induced seizures both in rats and in mice. The differences between mice and rats seem to be due to better availability of hippocampus for the intraventricularly administered drugs in mice. Mice seem to be preferable for studies with intraventricularly administered excitatory amino acids including kynurenines, whereas rats are preferable for inhibitory amino acids.

Excitatory effects of kynurenine and its metabolites, amino acids and convulsants administered into brain ventricles: differences between rats and mice.

When introduced intracerebroventricularly, quinolinic acid appeared to be the only kynurenine metabolite among those tested (L- and DL-kynurenine sulfate, kynurenic and nicotinic acids, nicotinamide) which induced locomotor excitement and clonic seizures in rats; in high dosage all exhibited convulsant action in mice. L-Kynurenine sulfate (500 micrograms) induced continuous rotation in rats around a longitudinal axis in one or other direction. It also potentiated the convulsant effect of strychnine sulfate and caffeine. Neither the excitatory amino acids, L-glutamic and L-aspartic acids nor the inhibitory amino acids, GABA, glycine and taurine induced excitement or seizures in rats but did in mice. In rats, GABA, glycine and taurine induced sedation, side position and discoordination. The convulsants, strychnine sulfate and pentylenetetrazole, induced seizures both in rats and mice. Differences between species may derive from the better access of intracerebroventricularly administered drugs to mouse hippocampus. Thus mice may be preferable for studies of this type on excitatory amino acids (including kynurenine pathway metabolites) and rats for those on inhibitory amino acids.

[Changes in hepatic tryptophan pyrrolase activity and plasma 11-hydroxycorticosteroid levels in rats after single and protracted alcohol administration and withdrawal]. / Izmenenie aktivnosti triptofanpirrolazy pecheni i urovnia 11-oksikortikosteroidov plazma krovi krys pri odnokratnom i dlitel'nom prieme étanola i posle ego otmeny.

Single administration of ethanol in doses of 3 and 5 g/kg per os caused a 4--5fold increase in plasma 11-hydroxycorticosteroids after one hour and an approximately 2 fold increase in liver tryptophan pyrrolase activity after 5 hours. Adrenalectomy abolished the effect of ethanol. Prolonged alcoholization of rats with 2--10% solutions of ethanol ad libitum resulted in the decreased tryptophan pyrrolase activity 2 months after the experiment was initiated. This effect seems likely to be accounted for by the inhibition of the synthesis of this enzyme and its activation by steroid hormones. Withdrawal of ethanol after 2-month alcoholization was associated with an appreciable potentiation of tryptophan pyrrolase activity.

[Different effects of kynurenines on rat liver tryptophan pyrrolase activity]. / Razlichnoe vliianie kinureninov na triptofanpirrolaznuiu aktivnost' pecheni krys.

3-Hydroxyanthranilic, quinolinic and nicotinic acids/50 mg/kg, intraperitoneally/increased the content of rat blood plasma 11-hydroxycorticosteroids as well as the activity of liver tryptophane pyrrolase. After administration of anthranili and picolinic acids, elevation in 11-hydroxycorticosteroid content was not followed by an increase in the tryptophane pyrrolase activity. Picolinic acid diminished induction of tryptophane pyrrolase activity by hydroxycortisone and anthranilic acid dicc not affect the induction. Adrenalectomy prevented the increase in tryptophane pyrrolase activity after treatment with nicotinic, quinolinic and 3-hydroxyanthranilic acids. Prolonged augmentation of kynurenines in the organism might be a result of a mediated through corticosteroids increase in the tryptophane pyrrolase activity caused by elevation in the level of 3-hydroxyanthranilic, quinolinic and nicotinic acids.

[Distribution of lithium in the plasma and erythrocytes of frogs following a single injection of different doses of lithium carbonate]. / Raspredelenie litiia v plazme i éritrotsitakh krovi liagushki posle odnokratnogo vvedeniia razlichnykh doz karbonata litiia.

On administration of lithium carbonate to grass frogs (Rana temporaria) in doses of 50-100 mg/kg its concentration in the plasma after 1 hour (2.9 +/- 0.48-8.7 +/- 0.43 mekv/l) far exceeded the therapeutic concentration in man and also in other animal species after administration of the comparable doses of lithium concentration ratio in the erythrocytes and plasma comprising 0.1-0.2. On administration of lithium in doses of 10 and 25 mg/kg its concentration in the plasma corresponded after a lapse of 1,4 and 24 hours to 0.38 +/- 0.03--0.98 +/- 0.03; 0.33 +/- 0.02--0.69 +/- 0.03 and 0.37 +/- 0.01-0.70 +/- 0.02 mekv/l, respectively, while the ratio of concentration in the erythrocytes and plasma was 0.5-0.3. and approximately accorded with the therapeutic values in man. To make a comparison between clinical and experimental findings, obtained in other animal species, it is advisable the lithium carbonate doses not exceeding 25 mg/kg be used.

[Clinical course and diagnosis of congenital heart defects]. / Klinika i diagnostika neopredelenno-sformirovannogo serdtsa.

An indefinitely formed heart is a compound lesion of the cardiovascular system in which an anatomical examination of the atria does not permit any decisive interpretation of the formation of the heart. The disease can be subdivided into two pathological syndromes. The first syndrome includes a partially patent atrioventricular canal with a joint atrium, an absence of the hepatic segment of the inferior vena cava, a partally anomalous drainage of the pulmonary veins, bilobular lungs, abdominal heterotaxy and polysplenism. The second syndrome is characterized by an open atrioventricular canal with a joint atrium or a cor biloculare, an abberant superior vena cava, or varilateral position of the superior and inferior venae cavae, a completely anomalous drainage of the pulmonary veins, transposition of the major vessels with a stenosis or atresia of the pulmonary artery, trilobular lungs, abdominal heterotaxy and asplenism. The leading role in the diagnosis of the pathology belongs to heart catheterization and angiocardiography.

[Effect of lithium on the serotonin and kynurenine paths of tryptophan metabolism]. / Vliianie litiia na serotoninovyi i kinureninovyi puti obmena triptofana.

Lithium carbonate in dosages from 50--100 mg/kg leads to an increase of tryptophanepyrrolase activity in the liver of rats from 50--80%, 5 hours following a single-time intraperitoneal administration and does not exert any influence after 1,3 and 20 hours. The same dosages (50 and 100 mg/kg) of lithium lead to an increase of II-hydroxycorticosteroids in in the blood plasma of rats to 2.5 times and could be prevented by a preliminary administration of dexametasone. A chronic administration of lithium (50 mg/kg) during 10 days did not exert any influence on the triptophanepyrrolase activity and the level of 11-hydroxycorticosteroids in the blood plasma of rats. These data permit of assume that an increase of tryptophanepyrrolase activity by lithium is moderated by an increase of II-hydroxycorticosteroids in the blood.

[Mediation of the lithium increase in rat liver tryptophan pyrrolase activity by 11-hydroxycorticosteroids]. / Oposredovannoe 11-oksikortikosteroidami povyshenie litiem aktivnosti triptofanpirrolazy pecheni krys

After a single intraperitoneal administration lithium carbonate (50 and 100 mg per kg of body weight) caused an increase in the tryptophane pyrrolase activity in rat liver tissue by 50-80% within 5 hrs and did not affect the enzyme within 1, 3 and 20 hrs. Content of lithium was quite unaltered in rat blood serum after administration of lithium carbonate at a dose of 50 mg/kg; it slightly exceeded the therapeutic level at a dose of 100 mg/kg. Addition of the lithium preparation (7-10(-3)-7-10(-5) M) to liver homogenates did not change the tryptophane pyrrolase activity in vitro. The same doses of lithium (50 and 100 mg/kg) caused a 2.5-fold increase in content of 11-hydrocorticosteroids in rat blood plasma; the effect was prevented by previous administration of dexamethasone. In experiments with adrenalectomized rats lithium did not affect the enzymatic activity. Repeated administration of lithium (50 mg/kg) within 10 days did not affect the tryptophane pyrrolase activity and did not alter the content of 11-hydroxycorticosteroids in rat blood plasma. The data obtained suggest that the increase in the tryptophane pyrrolase activity, caused by lithium, is mediated through the elevation in content of 11-hydroxycorticosteroids in blood.

[Effect of lithium on the central serotonin- and adrenergic processes after its chronic administration]. / Vliianie litiia na tsentral'nye serotonin- i adrenergichskie protsessy pri khronicheskom vvedenii

With its chronic administration in a dose of 100 mg/kg lithium carbonate inhibited shaking of the head induced in mice with 5-hydroxytryptophan (5-HTP). This effect did not differ from the action following a single injection of lithium, when the interval between injection of lithium and of 5-HTP was one hour. With the interval lengthened to 24 hours the frequency of shaking diminished only under the effect of chronic administration. At the 5th, 10th and 21st day of a daily administration lithium failed to produce any effect on the hypothermal action of a reserpine-like agent Po 4-1284, but would reduce the protective action of imipramine in a ptosis test. A single injection of lithium made against the background of a chronic injection of water produced an opposite effect, viz. it significantly reduced the protective action of imipramine in hypothermia, but did not affect it with reference to ptosis. Hence, chronic administration of lithium leads to potentiation in its action of the serotonin-negative and central adreno-negative componets and to extenuating the peripheral adreno-negative component.