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Biomedical subjects

S Stancheva

Publications and source records attributed to S Stancheva.

12 recordsLinked to original sources

Behavioral effects of stem-leaves extract from panax ginseng C.A. Meyer.

The behavioral effects of extracts from ginseng stem and leaves (GL), standardized with respect to the total saponines, and from ginseng roots (G115), standardized with respect to the content of ginsenosides were examined in experiments on rats with undisturbed memory and in rats with experimentally-impaired memory (electroconvulsive shock) using the methods for active avoidance (shuttle-box) and passive avoidance (step-down, step-through), the water-maze method and the method for studying exploratory behavior. On multiple administration G115 exerted favorable effects on learning and memory and on the higher nervous activity as a whole. These effects greatly varied with the dose and administration schedules, with the rat strain, with the rat's ability to perform adequately in any particular learning task, and with the behavioral method. The extract from the overground part of ginseng (GL) had, in the majority of cases, an effect weaker than that of G115 or was without effect at all. Based on previous and present results, we discuss the role of the changes in brain biogenic monoamines induced by the extracts for their mechanism of action.

Amnesia

Memory effects of a group of newly-synthesized pyrrolidine derivatives with putative nootropic effect.

The original pyrrolidine derivatives with putative nootropic effect: para-chloro-phenoxyacetyl-2-pyrrolidinone (Mf-P), 1-adamantanyl-2-pyrrolidinone (A-P), 2-oxo-1-pyrrolidine-3,7-dimethylxanthine (A-T) and para-benzoyl-1,4-dipyrrolidinone (p-P), were studied. Toxicological screening performed on mice demonstrated the low toxicity of the compounds. Five- or seven-day oral administration of the substances to rats in a dose of 100 mg/kg weight facilitated the learning process and improved the memory of the rats with most of the conditioned-reflex methods used. Application of Mf-P to 2- and 24-month-old rats for 8 days induced changes in the levels of some biogenic monoamines in the brain structures studied. The results obtained, as well as the results of other studies in this laboratory, show that the pyrrolidine derivatives studied, which can be considered to be original new aniracetam analogues, improve the memory process. This effect varies strongly depending on the regime of application of the compounds studied, on the memory capacity of the experimental animals and on the experimental method used. The changes in the brain neurotransmission induced by the substances studied play an essential role in their mechanism of action.

Animals

Effect of angiotensin II on the Vogel conflict paradigm and on the content of dopamine and noradrenaline in rat brain.

Experiments on male rats were conducted to test the effect of the octapeptide angiotensin II (AT II), introduced intracerebroventricularly (i.c.v.), on a conflict paradigm (drink-foot shock conflict procedure) and on the levels of dopamine and noradrenaline in the hypothalamus and hippocampus during that test. AT II was found to cause substantial reduction of the number of punished responses (biphasically and dose-dependently: the lower dose (0.1 microgram) and the high dose (5 micrograms) have a stronger effect than the moderate doses), which implies a proconflict or anxiomimetic effect. At the same time AT II (1 microgram) caused a substantial reduction of the dopamine level in the hypothalamus and hippocampus. The explanation of the AT II-induced changes in the conflict behaviour (anxiogenic action) is sought in its interaction with the AT II receptors (binding sites) in the brain structures (hypothalamus, hippocampus, etc.), participating in that behaviour, as well as in its modulating effect on the DA-ergic transmission in these structures.

Angiotensin II

Effect of adafenoxate on different rat brain structures monoamine oxidase activity in vitro.

1. The effect of the nootropic drug adafenoxate on monoamine oxidase (MAO) activity in rat brain cortex, striatum, hypothalamus and hippocampus has been studied using the following substrates: tyramine (total MAO), serotonin (MAO A) and beta-phenylethylamine (MAO B). 2. In a series of increased concentrations (from 5 x 10(-4) up to 1 x 10(-5) M) adafenoxate inhibits total MAO, MAO A and MAO B in the brain structures studied. 3. The adafenoxate IC50 values obtained illustrate its inhibitory properties and its lack of selectivity toward MAO in the brain structures isolated. 4. The results of our research prove the participation of MAO in the mechanisms through which adafenoxate affects the brain monoaminergic systems and realises its central effects.

Animals

Effects of chronic diazepam and medazepam treatment on the level of biogenic monoamines in different rat brain areas.

Studies were made of the effect of 19-day administration of diazepam (1 mg.kg-1, i.p.) and medazepam (5 mg.kg-1, i.p.) on the level of biogenic monoamines in different rat brain areas: cerebral cortex, striatum, hippocampus, and hypothalamus. The noradrenaline (NA), dopamine (DA) and serotonin (5-HT) levels were determined. After chronic treatment with diazepam no alterations in the NA content in the cortex, striatum and hypothalamus were found. Medazepam increased the NA level in the cortex, striatum, and hippocampus without changing it in the hypothalamus. Repeated administration of diazepam or medazepam led to an increase in the DA level in the striatum. Both benzodiazepines provoked a significant increase in the hippocampal 5-HT level, which could be attributed to the antianxiety effect of these drugs.

Animals

Ontogenetic development of 3,5-adenosine monophosphate phosphodiesterase in guinea pig and rat ileum.

The postnatal development of phosphodiesterases with low and high Michaelis constants in guinea pig and rat ileum was studied. The tow types of phosphodiesterases were found to increase their activity post partum, and this increase was particulary pronounced in the rat. The rise in the enzyme activity took place mainly at the expense of the increase of the phosphodiesterase with high Km. In addition to the quantitative differences in the phosphodiesterase activity of yound and adult animals, considerable age differences were also observed in the sensitivity of the enzyme to inhibitors and activators. These data can contribute to the explanation of the differences in the action of some drugs influencing the phosphodiesterase in young and adult organisms.

3',5'-Cyclic-AMP Phosphodiesterases

[Effect of ionizing radiation on cerebral phosphodiesterase].

The authors examined the influence of x-ray irradiation on phosphodiesterase system in the brain of rats and the sensitivity of the enzyme to inhibitors (caffeine, theophyline, thyopental) and activators (imidozol). The animals (Wistar with weights of 150--200 gm/were irradiated singly with a dose of 737 r. Phosphodiesterase activity (PD) was determined by the method of Filburn and Carn (1972) at two substrate concentrations (1 and 100 microM). X-ray irradiation did not change PD with high Km, while the enzyme with low Km was reduced significantly and transitionaly. Caffeine, theophyline and thyopental inhibited more PD with low Km in the irradiated rats in comparison with the control nonirradiated rats. The activating effect of imidazol on PD with low Km was more marked in irradiated rats. These data could be interpreted in the light of the molecular mechanisms, determining the altered action of some drugs after x-ray irradiation.

Animals

A rapid and sensitive assay for monoamine oxidase activity.

Based on the Berthelot reaction, a new sensitive and rapid procedure for monoamine oxidase (MAO) determination with substrate tyramine has been developed. The saturation with oxygen and the separation of ammonia from the substrate were omitted. At the end of incubation the samples were deproteinized with ethanol and consecutive centrifugation. The newly-formed ammonia is converted into the coloured compound indophenol, using the procedure of Fenton (1962). The indophenol concentration, respectively NH3 is determined by spectrophotometry at 625 nm, and calculated by comparison with a set of standard amounts of NH3. The enzyme activity is expressed as nanomoles ammonia, formed by 1 mg protein for 1 min. The method was tested for studying the relationship between the enzyme activity, time of incubation and protein concentration, as well as the effect of pargyline. The kinetics of MAO, using both liver and brain mitochondria as enzyme material was also studied. Considering the specificity, simplicity, versatility and rapid performance, the new method showed several advantages in comparison with the other known methods for MAO determination.

Animals

Studies on the phosphodiesterase in various organs of rats and guinea-pigs of different ages and different sex.

The method of Butcher and Sutherland is used to determine the phosphodiesterase activity of various organ homogenates from rats and guinea-pigs of different age and sex. The different rat organs manifest great differences in their phosphodiesterase activity. Especially high phosphodiesterase activity is found in the adrenal gland and in the brain cortex. Sex is not found to be related to definite differences in the activity of the enzyme. In some organs age differences are established both in the phosphodiesterase activity and in the degree of its inhibition or activation by inhibitors and stimulators of the enzyme. It is assumed that in some organs age conditions changes not only in the general phosphodiesterase activity, but also in the ratio between its isoenzymes.

Age Factors

[Changes in the concentration of biogenic monoamines in different brain regions under the influence of centrophenoxine (experiments on rats)].

The authors administered 50 mg/body weight of centrophenoxine in white rats i.p. for five susseccive days. The content of serotonine in the cerebral cortex, brain stem and cerebellum increased statistically significant in the rats, injected with centrophenoxine. The levels of noradrenaline and dopamine in the brain stem were raised also significantly. Centrophenoxine did not alter the content of cyclic AMP and the activity of phosphodiesterase in the cerebral cortex and brain stem. These data gave foundation to the authors to suggest that in the mechanism of action of centrophenoxine a significant role is given to the changes, induced by this preparation in the content of biogenic amines in the brain stem.

Animals

Differential inhibition of phosphodiesterase according to the organ origin of the enzyme.

Essential differences in the degree of papaverine [5 x 10(-5) M]- and theophylline [1 x 10(-3) M]-induced inhibition of cyclic nucleotide phosphodiesterase (PDE) were found in homogenates from different structures of the CNS as well as from different organs of male albino rats. Both inhibitors of PDE showed a mosaic pattern of their inhibitory effects on the enzyme activity of the brain structures tested. Papaverine inhibited PDE by 36 percent in the spinal cord, 53 percent in the cerebellum, 56 percent in the cortex, and 75 percent in the brain stem. Theophylline inhibited PDE least in the cerebellum (26 percent ) and most markedly in the brain stem (68 percent). Still larger differences were observed in the inhibitory action of papaverine and theophylline on PDE of the organs tested (e.g., papaverine inhibited PDE by 6 percent in the heart and 73 percent in the spleen; theophylline inhibited PDE by 26 percent in the adrenals and by 72 percent in the heart. The mosaic sensitivity of PDE in different organs and brain structures to papaverine and theophylline was considered as an expression of isoenzyme heterogeneity.

Animals