[Intestinal microbiota and chronic heart failure: association and targets of influence of therapy.].

The increasing prevalence of chronic heart failure (CHF) among older people is a global problem. Despite the success of treatment, the mortality rate of these patients remains high, resulting in the need to search for new mechanisms of the development and progression of cardiovascular system pathologies, as well as to develop innovative branches of therapy. Considerable recent interest has been directed towards studying changes in the composition of the intestinal microbiota in people with age, its role in development, as well as potential directions for the prevention of cardiovascular diseases and their complications.

[Features of gastroesophageal reflux disease in elderly patients (literature review).].

In recent years, there has been an increase in the incidence of gastroesophageal reflux disease (GERD) in the elderly not only in our country, but also worldwide. In this regard, the issues of early diagnosis and development of an individualized approach to the treatment of this disease are of particular relevance. When addressing these issues, it is necessary to take into account a number of features in patients of older age groups, which include polymorbidity and polypharmacotherapy in combination with anatomical, physiological and functional age-related changes.

Experimental modeling of preclinical and clinical stages of Parkinson's disease.

Degeneration of dopaminergic (DAergic) neurons of the nigrostriatal system is the key stage in the pathogenesis of Parkinson's disease. The first symptoms of this disease are observed after degeneration of 70-80% neurons, which occurs over 20-30 years. The clinical stage of Parkinson's disease begins after this period.

[Possible role of serotonin 5-HT2 receptors in mechanism of afobazole anxiolytic action: neurochemical study of inter-line differences in mice].

Effects of separate and combined introduction of afobazole and SB-200646A (highly selective 5-HT2B/2C receptor antagonist) on the content of monoamines and their metabolites in brain structures of mice of C57/Bl/6 and BALB/C lines have been studied using neurochemical methods and high-performance liquid chromatography (HPLC). Afobazole (5 mg/kg, i.p.

[Levetiracetam modifies the pattern of audiogenic locomotive response in Wistar and Krushinsky-Molodkina strain rats].

The novel antiepileptic drug levetiracetam (keppra, 80 mg/kg, i.p.) produces a pronounced anticonvulsant effect on all parameters of the audiogenic locomotion response in Wistar rats, leading to the prevention of acoustic seizures approximately in 50% animals.

[Modeling of preclinical and early clinical stages of Parkinson's disease].

The first symptoms of Parkinson's disease manifest 20-30 years after the disease onset when the most dopaminergic neurons degenerated. Therefore, it is necessary to work out preclinical diagnostics and preventive treatment of this disease. Modeling of preclinical and early stages of Parkinson's disease was conducted in mice using 1-methyl-4-phenyl-1,2,3,6-tetrahydropiridine (MPTP).

[Experimental modeling of functional deficiency of the nigrostriatal dopaminergic system in mice].

The dopaminergic nigrostriatal system is a key component of regulation of the motor behaviour. Cell bodies of dopaminergic DA-ergic neurons are located in the compact zone of the substantia nigra, and their axons are projected along the nigrostriatal tract to the striatum. This study was aimed to develop an experimental model of the functional insufficiency of the DA-ergic neurons of the nigrostriatal system without any manifestation of movement disorders, i.

[Development of central and peripheral serotonin-producing systems in rats in ontogenesis].

The work deals with study of development of central and peripheral serotonin-producing systems in rat ontogenesis before and after formation of the blood-brain barrier. By the method of highly efficient liquid chromatography it has been shown that the serotonin level in peripheral blood before formation of the blood-brain barrier (in fetuses and neonatal rats) is sufficiently high for realization of physiological effect on target cells and organs. At the period of formation of the blood-brain barrier the serotonin level in brain sharply rises, whereas the serotonin concentration and amount in plasma and duodenum increase insignificantly.

[Effects of heptapeptide selank on the content of monoamines and their metabolites in the brain of BALB/C and C57Bl/6 mice: a comparative study].

The effect of heptapeptide selank on the content of neurotransmitter monoamines and its metabolites in the brain structures of BALB/C and C57Bl/6 line mice under conditions of the open-field test were studied. Significant interstrain differences in the content of norepinephrine (NE), dopamine (DA), serotonin (5-HT) as well as in the levels of their metabolites in hippocampus, hypothalamus, striatum and frontal cortex of C57Bl/6 and BALB/C mice were demonstrated. In particular, the content of 5-HT and its metabolite 5-oxyindolacetic acid (5-HIAA) in hippocampus of BALB/C mice (with passive stress response) was higher than in the same structure of C57Bl/6 (stress-susceptible) animals.

[The investigation of cataleptic muscle tonus changes in rats after audiogenic seizures].

The duration and severity of cataleptic freezing after audiogenic seizures were investigated in rats of several genotypes with different predisposition to audiogenic epilepsy. These genotypes were the Krushinsky-Molodkina strain (KM--the audiogenic seizure prone strain), the Wistar and two new substrains selected from hybrids KM x Wistar for high ("4") and low ("0") audiogenic seizure susceptibility. The drug injections, which modulated the audiogenic fit severity, induced the changes in catalepsy too.

[Anticonvulsant effects of levetiracetam on audiogenic epileptiform siezures in Krushinsky-Molodkina rats].

The new antiepileptic drug levetiracetam (LVT) at doses of 40 and 80 mg/kg exhibits a pronounced anticonvulsant effect, influencing all the parameters of audiogenic epileptiform seizures (AES) in Krushinsky-Molodkina (KM) rats. The latent period of the motor reaction was increased 3-15 times compared to control, and the intensity of single convulsive episodes was significantly decreased. Changes were also detected in the profile of the first stage of motor activity, and the "two-wave" reaction was observed in 50-80% of animals.

[Neuronal and neurochemical mechanisms underlying the effect of a novel antiepileptic drug levetiracetam].

Published data on the mechanisms involved in the action of levetiracetam (LVT, 2S-(oxo-1-pyrrolidinyl)butanoic acid amide), a widely used agent for the adjunctive therapy of partial epilepsy of different genesis, have been analyzed. A unique profile of the anticonvulsant action of LVT was already revealed at the screening stage: this agent was not effective in the traditional tests, but it demonstrated a pronounced protective effect in kindling models and in the experiments on mice sensitive to the audiogenic convulsions. Now it is commonly accepted that the LVT mode of action is different from that of the other known antiepileptic drugs.

Dopamine synthesis by non-dopaminergic neurons in the arcuate nucleus of rat fetuses.

The aim of the present work was to verify the hypothesis that non-dopaminergic neurons expressing individual complementary dopamine synthesis enzymes can perform the co-located synthesis of dopamine. According to this hypothesis, neurons expressing tyrosine hydroxylase use L-tyrosine for the synthesis of L-dihydroxyphenylalanine (L-DOPA), which then enters neurons expressing aromatic amino acid decarboxylase, which converts L-DOPA to dopamine. Experiments were performed using the mediobasal hypothalamus of rat fetuses, which mostly contains single-enzyme neurons (>99%) and occasional double-enzyme neurons (<1%).

[Allosteric modulators of AMPA type glutamate receptors a novel gubclass of physiologically active substances].

Properties of AMPA type glutamate receptors widely presented within mammalian central nervous system are reviewed. AMPA receptors belong to ionotropic subclass of glutamate receptors and participate in fast excitatory glutamatergic transmission in the brain. Molecular structure of AMPA receptors consists of several subunits (GluRA1-GluRA4), which display various sensitivity to receptor ligands.

[Dopamine synthesis by non-dopaminergic neurons of the rat fetus arquate nucleus].

Our hypothesis was tested in respect to dopamine synthesis by non-dopaminergic neurons expressing individual complementary enzymes of the DA synthetic pathway. According to the hypothesis, L-dihydroxyphenylalanine (L-DOPA) synthesised in tyrosine hydroxylase(TH)-expressing neurons for conversion to dopamine. The mediobasal hypothalamus of rats on the 21st embryonic day was used as an experimental model.

[The interstrain differences in the effects of D-amphetamine and raclopride on dorsal striatum dopaminergic system in KM and Wistar rats (microdialysis study)].

The levels of dopamine (DA) was determined by intracerebral microdialysis in vivo in KM rats selected for high audiogenic epilepsy, and in Wistar rats selected for nonsusceptibility to loud sound. The basal level of dopamine was 25% higher in the KM rats (P < 0.05).

Dizocilpine blocks the effects of delta sleep-inducing peptide-induced suppression of c-fos gene expression in the paraventricular nucleus of the hypothalamus in rats.

The characteristics of the actions of the non-competitive blocker of NMDA receptors dizocilpine on the expression of the early c-fos gene in the paraventricular nuclei of the hypothalamus were studied in rats with different predicted susceptibilities to emotional stress in conditions of treatment with delta sleep-inducing peptide. The results showed that prior treatment with dizocilpine blocked reductions in c-fos expression induced by delta sleep peptide.

[Semax potentiates effects of D-amphetamine on the level of extracellular dopamine in the Sprague-Dawley rat striatum and on the locomotor activity of C57BL/6 mice].

The synthetic peptide semax (a fragment of ACTH 4-7 Pro-Gly-Pro) enhances the release of extracell dopamine (DA) induced by D-amphetamine (5 mg/kg) in the striatum of Spraig-Dowley (SD) rats and increases the locomotor activity stimulated by D-amphetamine (2 mg/kg) in C57/BL6 mice. The basal content of DA, 3,4-dihydroxyphenylacetic acid (DHPAA), and homovanillic acid (HVA) in dialysate of SD rats was 0.5-1.

[Effects of antagonists of the various subtypes of dopamine receptors on the locomotor activity of C57BL mice induced by psychostimulators].

The involvement of dopamine receptors of various subtypes in the mechanisms of locomotor hyperactivity caused by single administration of psychostimulants d-amphetamine and syndnocarb was studied in C57BL mice. Administered in a dose not influencing the spontaneous locomotor activity, SCH23390 and raclopride--selective antagonists of the D1 and D2 subtypes of dopamine receptors, respectively--abolished the hyperactivity induced by d-amphetamine, while not significantly changing the effect of sydnocarb. On the contrary, clozapine--antagonist of the D4 subtype of dopamine receptors--failed to reduce the stimulant action of d-amphetamine, but significantly decreased the effect of sydnocarb under the same experimental conditions.

Role of nitric oxide and lipid peroxidation in pathophysiological mechanisms of audiogenic seizures in GEP Rats and DBA/2 mice.

We evaluated the role of nitric oxide and lipid peroxidation in the pathophysiological mechanisms of seizures in genetically epilepsy prone (GEP) rats and DBA/2 mice with genetically determined audiogenic epilepsy. In rats and mice acoustic stimulation led to locomotor activation followed by clonic-tonic seizures. The contents of nitric oxide and lipid peroxidation products at the peak of seizures markedly surpassed the control level.

[Antipsychotic agents: from phenothiazines to atypical neuroleptics of the second generation].

The paper addresses evolution of the problem of creation, characterization of the pharmacological properties, and elucidation of the mechanisms of action of antipsychotic drugs (neuroleptics)--one of the most important classes of modern psychotropic drugs. The appearance of these drugs marked the onset of a new era in psychiatry, the era of psychopharmacology. Special attention is devoted to the investigations in this direction at the Institute of Pharmacology, which were headed by V.

[Combined effect of amphetamine and midantan on the dopaminergic transmission in the striatum of freely moving rats].

The combined action of midantane (amantadine, a noncompetitive NMDA receptor antagonist used as an antiparkinsonian drug) and amphetamine (a psychostimulant) on the extracellular level of dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) was studied in the striatum of freely moving Wistar rats. After the administration of amphetamine (AMPH) in a dose of 10 mg/kg (i.p.

Behavioral analysis of the consequences of chronic blockade of NMDA-type glutamate receptors in the early postnatal period in rats.

Considering data on the possible glutamatergic nature of the pathogenesis of schizophrenia, we attempted to model cognitive derangements in animals by chronic blockade of NMDA glutamate receptors. Wistar rats received daily s.c.