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Biomedical subjects

M Nikolova

Publications and source records attributed to M Nikolova.

At least 55 records · Page 3Linked to original sources

Study on the anti-hypoxic effect of cinnarizine and its interaction with prostacyclin.

The anti-hypoxic effect of cinnarizine was studied using the following experimental methods: hypobaric and anoxic hypoxia in mice, complete ischemia by decapitation in mice and hemic hypoxia in rats. Papaverine, xanthinol nicotinate and naftidrofuryl were used as reference drugs. In hypobaric and anoxic hypoxia the interaction of cinnarizine with the effect of prostacyclin (PGI2) was investigated. Cinnarizine showed an anti-hypoxic effect in all the methods used. It was more effective in hypobaric and anoxic hypoxia, in incomplete ischemia by decapitation, and less effective in hemic hypoxia. Cinnarizine potentiated the effect of PGI2 shifting the anti-hypoxic dose-response curve of PGI2 to the left. Suggestions as to the possible mechanism of anti-hypoxic action of cinnarizine are made.

Animals↗

Anti-hypoxic effect of piracetam and its interaction with prostacyclin.

The anti-hypoxic effect of piracetam was studied using the following experimental methods: hypobaric and anoxic hypoxia in mice, complete ischemia by decapitation in mice, incomplete ischemia by bilateral carotid occlusion in rats and hemic hypoxia in rats. Cinnarizine and vinpocetine were used as reference drugs. In hypobaric hypoxia, anoxic hypoxia, and complete ischemia by decapitation the interaction of piracetam with the effect of prostacyclin (PGI2) was investigated. Piracetam showed anti-hypoxic effect in all the methods used. Its effect was greater than that of cinnarizine and similar to that of vinpocetine. Piracetam potentiated the effect of PGI2 shifting the anti-hypoxic dose-response curve of PGI2 to the left.

Animals↗

Anti-hypoxic effect of centrally and systemically administered prostacyclin (PGI2).

Prostacyclin (PGI2) induced a dose-dependent prolongation of survival time of mice subjected to hypoxic and anoxic hypoxia, when administered either intracerebroventricularly (i.c.v., 0.001-10 micrograms/mouse), intravenously (i.v., 0.5-500 micrograms/kg) or intraperitoneally (i.p., 50-500 micrograms/kg). The effects of a single dose of 50 micrograms/kg i.v. or i.p. and of 1 microgram/mouse i.c.v. persisted for about 30 min. The anti-hypoxic effect of PGI2 is most likely due to an action upon the CNS.

Animals↗

Effect of piracetam in models of experimental inflammation.

The effect of piracetam has been studied in experimental models of the inflammatory process--the models of rat's paw oedema and intraperitoneal formalin ascites for the exudative phase and the cotton pellet model for the proliferative phase. Piracetam restricts the development of the exudative and proliferative phases of the inflammatory process. The degree of this reduction in the models used is similar to that observed after treatment with known antiinflammatory drugs. On the basis of data in the literature, the effects observed are explained by the action of piracetam upon cell-membrane permeability and the oxidation-reduction processes in the cell.

Animals↗

Piracetam and brain excitability. An electrophysiological study in cats.

The effect of piracetam on the excitability of the brain has been examined in cats by electrophysiological approaches: spontaneous electrocorticogram (ECoG), visual evoked potentials (VEPs) and their recovery cycles in some brain structures (visual and associative cortex, lateral geniculate body, centrum medianum thalami and mesencephalic reticular formation). Piracetam (100 mg/kg i.v.) increased the spectral power of ECoG and particularly in the associative cortex for the frequency bands of 10-12 and 19-22 Hz. Piracetam decreased the early components and facilitated the late components of VEPs predominantly in the associative cortex. Changes were found in the recovery cycles too, namely, facilitation and shortening of recovery in all structures studied except in lateral geniculate body. The data suggest that piracetam acts as a non-specific activator on the excitability thus optimizing the functional state of the brain.

Animals↗

Effect of aligeron and cinnarizine in models of general and local depression of the cortical bioelectrical activity in cats.

The effect of aligeron (5 mg/kg i.v.) and cinnarizine (10 mg/kg i.v.) on general and local depression of cortical bioelectrical activity was studied in acute experiments on cats. Asphyxic anoxia and hypoventilation hypoxia were used as models of general depression. Local depressions were caused by topical application of potassium chloride (KCl) and adenosine-5'-monophosphate (AMP) on the cortex. In hypoventilation hypoxia aligeron and cinnarizine increased cortical resistance to hypoxia and accelerated the recovery of cortical bioelectrical activity. In KCl- and AMP-induced depressions the drugs showed a protective effect manifested in a decrease of the degree and duration of the depression. In asphyxic anoxia their effect was insignificant.

Animals↗

Anti-hypoxic effect of indomethacin and its interaction with prostacyclin.

The anti-hypoxic effect of indomethacin (1-10 mg/kg) was studied using the following experimental methods: asphyxic anoxia in cats, hypobaric and anoxic hypoxia in mice, incomplete ischemia by bilateral carotid occlusion and hemic hypoxia in rats. In hypobaric and anoxic hypoxia the interaction of indomethacin with the effect of prostacyclin (PCl2) was investigated. Indomethacin showed an anti-hypoxic effect in all the methods used: it enhanced anoxia resistance index in asphyxic anoxia and significantly increased survival of rats and mice subjected to experimental hypoxia. Indomethacin potentiated the effect of PGl2, shifting the anti-hypoxic dose-response curve of PGl2 to the left. The possible mechanism of action of indomethacin in relation to cyclo-oxygenase inhibition is discussed.

Animals↗

[Resistance of different breeds of laying poultry to Marek's disease virus].

Investigated were a total of 447 two-day-old chicks of lines 5-A, ia-73' ll and lS of the Leghorn breed divided into 2 groups: controls--99 males and females, and test ones--348 infected at the age of 2 days via intraabdominal injection with 0.4 cm3 heparinized blood each, containing 5000 PFU per dose of the Marek's disease virus (CT-1 isolate). Both linear and sexual variations were found in the resistance of the birds. Most resistant proved to be the 5-A chicks of both sexes, and most susceptible--those of the lS line. No essential differences were observed in the response of the initial lines of broiler birds and the lines of laying birds raised in this country at the intraabdominal infection with the same virus. It was established that the birds of lines 5-A and 6-E of the Canadian Leghorn breed were close in terms of resistance with the birds of lines 66 and 77 of the Cornish breed, while those of the Leghorn lines ll and lS were resembling by resistance the birds of lines 88 and 89 of the White Plymouth Rock broilers which were more susceptible to Marek's disease. It is stated that the cockerels and poults of the ia-73 synthetic line, newly developed in this country, show essentially varying resistance most probably associated with insufficient consolidation.

Animals↗

Study on the anti-hypoxic effect of some drugs used in the pharmacotherapy of cerebrovascular disease.

The anti-hypoxic effect of some agents used in the pharmacotherapy of cerebrovascular disease was studied using the following methods: incomplete ischemia by bilateral carotid ligation in rats, anoxic hypoxia by inhalation of argon in mice, and hemic hypoxia induced by injection of sodium nitrite (120 mg/kg s.c.) in rats. The following drugs were studied: piracetam, orotic acid, centrophenoxine, pentobarbital, vincamine, vinpocetine, cinnarizine, aligeron, xanthinol nicotinate and papaverine. The most pronounced anti-hypoxic effect was shown primarily with the metabolic acting drugs, such as orotic acid, centrophenoxine, piracetam and pentobarbital, followed by the preparations with combined metabolic and vasoactive properties (vincamine and vinpocetine). The predominantly vasoactive drugs were less effective in anoxic hypoxia, but showed more pronounced effect in incomplete ischemia.

Animals↗

Effect of piracetam in some models of general and local depression of the cortical bioelectrical activity in cats.

The effect of piracetam (100 mg/kg i.v.) on general and local depression of the cortical bioelectrical activity was studied in acute experiments on cats. Asphyxic anoxia and hypoventilation hypoxia were used as models of general depression. Local depressions were caused by topical application of potassium chloride (KCl), adenosine monophosphate (AMP) and pentobarbital on the cortex. In the models of general depression piracetam increased cortical resistance to hypoxia and accelerated the recovery of the cortical bioelectrical activity. In KCl- and AMP-induced depressions piracetam diminished their degree and duration and completely protected the cortex against pentobarbital-caused depression.

Adenosine Monophosphate↗

1,4-Benzodiazepines. VIII - Central depressive activity and spasmolytic action of isoquino-[2,1-d] [1,4] benzodiazepines. Structure-activity relationships.

The pharmacological activity of four new groups of isoquino [2,1-d] ((1,4]benzodiazepines, i.e. the 6-oxo-12,13-dimethoxy-5H-7H--9,10-dihydroisoquino [2,1-d] [1,4]benzodiazepinium bromides (I); 5,9,10,14b--tetrahydroisoquino [2,1-d] [1,4]benzodiazepin-7H-6-ones (II); 6-phenyl-12,13--dimethoxy-7,9,10,14b-tetrahydroisoquino [2,1-d] [1,4]benzodiazepines (III) and 6-phenyl-12,13-dimethoxy-7H-9,10-dihydroisoquino [2,1-d] [1,4]benzodiazepinium bromides (IV) was studied. All the compounds studied are biologically active. They show a depressive effect on the central nervous system, which is most pronounced in (II). It was established that the presence of alkyl substituents in the position-7 of the structure (II) as well as the chlorine atom in position-2 resulted in an increase of activity. Most of these compounds possess a mild or strong antinociceptive effect. Some of them exhibited an antireserpine activity as well. The spasmolytic effect of (IV) was strong while the rest of the compounds exerted a very weak spasmolytic effect. All the compounds tested on the autonomous nervous system possess the characteristics of weak sympathomimetics.

Animals↗

[Relationship between the genetic polymorphism of alkaline phosphatase and the resistance of broiler poultry to Marek's disease virus].

Studied was the polymorphism of alkaline phosphatase in blood plasma samples taken from 507 poulets and cocks of lines 66 and 77 of the Cornish breed, and lines 88 and 99 of the White Plymouth Rock breed. The birds were divided into three groups to test their resistance to Marek's disease: (1) controls, (2) infected with the virus of Marek's disease with 3 subgroups--resistant birds, slightly susceptible ones, and strongly susceptible ones, and (3) contacts, with two subgroups--survivals and birds that died. The blood plasma alkaline phosphatase was determined through horizontal electrophoresis on a starch gel, employing the method of Gahne. It was found that the alkaline phosphatase genetype FF frequency was lower with lines 66 and 77 than with line 88 and especially with line 99 of the White Plymouth Rock breed which proved most susceptible to the virus of Marek's disease. In the homozygotic alkaline phosphatase genetype SS none of the investigated lines showed any mortality. The resistance of broiler birds to Marek's disease was governed by the Akps allele, while the susceptibility was governed by the Akpf one. The former could be used as a genetic marker in the selection of initial lines of broiler birds by resistance, and the latter could be used as a marker in the selection by susceptibility.

Alkaline Phosphatase↗

Anti-hypoxic effect of prostacyclin.

The anti-hypoxic effect of prostacyclin (PGI2) was studied using the following methods: hypoventilation hypoxia and hypovolemic oligemia in cats and hypobaric hypoxia and complete ischemia by decapitation in mice. In experiments on cats PGI2 (250 ng/kg/min i.v.) led to an improvement of hypoxia-impaired EEG activity. In hypobaric hypoxia, PGI2 at all doses applied (50-500 micrograms/kg) led to a significant increase in the survival time (from 67.5% to 196%). In complete ischemia by decapitation, PGI2 at doses from 50 to 500 micrograms/kg significantly prolonged the gasping movements (from 7.8% to 20.6%). Different mechanisms of the anti-hypoxic effect of PGI2 are discussed. The effect observed would be potentially beneficial in hypoxic and ischemic states.

Animals↗

Experimental electroencephalographic study on orotic acid.

Proceeding from the data obtained concerning the effects of orotic acid on excitability processes in CNS and our neuropharmacological investigations, we studied its effects on cerebral bioelectrical activity in acute experiments with "encéphale isolé" and in intact animals with chronically implanted electrodes, at single and 10-day treatment periods in a setting where the spontaneous activity and that evoked by visual and sound stimulation were recorded. At a dose of 100 mg/kg i.v. orotic acid significantly increased the theta wave range and showed a tendency towards increasing the beta waves, preserving, at a somewhat lower level (in comparison with control animals), the reactions to visual and sound stimulation. Comparison with the neuropharmacological studies is good reason to conclude that orotic acid stabilizes the cortical neuronal function; it does not influence the ascendent activating reticular formation, but probably inhibits the descending polysynaptic pathways. It is suggested that besides its metabolic effect orotic acid also has an effect on brain vessels.

Acoustic Stimulation↗

Effect of orotic acid on the excitability processes in central nervous system and on cerebral circulation in cats.

The influence of orotic acid on cortical excitability processes and cerebral circulation was studied in acute experiments in cats. The effect on CNS excitability was assessed by examination of the cortical visual-evoked potentials and the recovery cycles. The flash-evoked responses were recorded from visual cortex (VC), associative cortex (AsC) and auditory cortex (AuC). The recovery cycles were determined as the ratio of the average response to the test stimulus and those to the conditioning stimulus depending on the interstimulus interval duration. For investigation of cerebral circulation the method of local cerebral rheoencephalography (REG) was used. The following REG parameters were assessed: amplitude, anacrotic sections of the curve and its relative part, and duration of the wave. The arterial blood pressure was monitored continuously. Orotic acid administration (50 mg/kg i.v.) induced a significant increase in the amplitude of the primary response from VC and AsC. Significant shortening of the peak latency of the second wave of the response in the VC was also observed. The recovery cycles examination showed a facilitation of the test response. The changes observed indicate an increase of excitability processes in the CNS. The REG changes after orotic acid indicate a cerebrovascular resistance decrease and increase in cerebral blood volume. It is assumed that increased cortical activity by orotic acid may lead to an improvement of cerebral circulation.

Animals↗