Metalloproteinase was discovered by Gross and Lapierre in 1962 for the first time. Since then, more than 20 enzymes of this family have been characterized, and their functions have been studied in detail. Metalloproteinases take part in blood pressure regulation, the cell matrix extension and remodeling, anesthesia, multiple sclerosis, blood coagulation, wound healing, tumor transformation and metastasis, etc. This review covers structure of matrix metalloproteinases, their mechanism of action, as well as MMP's endogenous and exogenous inhibitors. A special place is occupied by analysis of approaches to matrix metalloproteinases synthetic inhibitors and their activity. This review demonstrates the perspectivity of new selective matrix metalloproteinase inhibitors design.

Resume. To study the features of an atrium depolarization on the dynamics of the cardioelectric field on the body surface at rats with an alcoholic cardiomyopathy. The cardioelectric field on the body surface of rats with an alcoholic cardiomyopathy was investigated during an atrium depolarization by the method of multiple synchronous cardioelectrotopography. In experimental and control animals, reflecting atrial depolarization, is formed before the appearance of the P„ wave on the ECG, inversion of the body surface potential mapping (BSMP) regions occurs before the beginning of the ascending phase of the P„ wave. In rats of the experimental group, it is shown an increase in the heart rate, the total duration of atrial depolarization, the period of the ascending and descending phases of the P„ wave on the ECG; later (relative to the peak of the R_M-wave) inversion of the BSMP regions and the beginning of the P_II wave by comparison with the control animals. The duration of inversion in experimental rats significantly increased compared with the control. Alcoholic cardiomyopathy leads to significant changes in the spatial and temporal parameters of the cardioelectric field at the initial stages of atrium depolarization, an increase in the non-uniformity of depolarization and a high risk of atrial arrhythmias.

Resume. Methods. Acute subendocardial myocardial ischemia in anesthetized rats (urethane 1300 mg/kg, i.p.) was caused by isoproterenol (20 |jg/kg/ min, i.v.). Endothelial dysfunction was induced, causing hyperhomocysteinemia in rats (methionine 3 g/kg intragastrically 1 time per day for 7 days). The aim. To study on the subendocardial ischemia model in rats the peculiarities of the anti-ischemic action of p-FOX inhibitor trimetazidine and trihydrochloride N¹-(2,3,4-trimethoxybenzyl)-N²-{2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethanediamine constructed on the basis of its structure (compound ALM-802) under conditions of endothelial dysfunction. Results. It was shown that in rats with an intact vascular bed and the reference drug trimetazidine (30 mg/kg, i.v.) and the compound ALM-802 (2 mg/kg, i.v.) demonstrated pronounced anti-ischemic activity, while in animals with endothelial dysfunction only the compound ALM-802 was effective. Conclusion. Endothelial dysfunction prevents the implementation of the trimetazidine anti-ischemic action, but does not affect on the compound ALM-802 effect. When studying the anti-ischemic properties of new pharmacological substances, it is advisable to carry out a certain part of the experiments in model experiments that reproduce endothelial dysfunction.

Ovcharova AN, Safronova OV, Polyakova LL All-Russian Research Institute of Physiology, Biochemistry and Nutrition of animals - branch of Federal state budgetary scientific institution "Federal Research Center Livestock - AUIAB Academician LK Ernst", Borovsk, Kaluga region, Russian Federation Resume. For the correction and prevention of microflora disorders are widely used microbial preparations - probiotics, which have a positive effect on the composition of the intestinal microflora, the immune system of animals. Lactobacilli play a special role in the formation of normal microflora. In 2009. in the laboratory of biotechnology of microorganisms vniifbip was made Association of four strains of lactobacilli: Lactobacillus casei LBR 1/90 (VCM-2780D), Lactobacillus paracasei LBR 5/90 (VCM-2781D), Lactobacillus rhamnosus LBR 33/90 (VCM-11277), Lactobacillus rhamnosus LBR 44/90 (VCM-11278), isolated from the digestive tract of Calves, called tetralactobacterin (TLB). The strains included in probiotics are non-pathogenic and have a wide range of antagonistic activity against bacteria of the genera Staphylococcus, Streptococcus, Escherichia and Salmonella. The aim of this work was to study the effect of tetrasaccharide on nonspecific immunity and physiological parameters of rabbits.

Resume. Pigs in many developed countries have long attracted attention as a biological model. In world practice using specially derived for diurnal breeds of pigs and mini-pigs (khorolskii, herfordshire, etc.). Widely used in experiments and native breeds of pigs - in the United States - Yuka-Tang and American-Essex. In Europe, the largest mini-pig farm is located in Germany. where the gottingen breed is bred. Pigs are emotionally unstable animals with low resistance to stress. In this regard, as a biomedical model of research on pigs allows to check the long-term use of drugs and their aftereffect. The aim of the work is to test a non -invasive anti-stress drug lithium ascorbate to reduce the negative impact of spontaneous stress factors arising in pigs. The experiment was conducted on 5 groups of Irish Landrace pigs (4 experimental and 1 control) with 10 heads each in the period from 2 months to 7 months of age. Animals of 1, 2, 3 and 4 experimental groups were daily fed lithium ascorbate in the form of powder at a dose of 10, 5, 2 and 0.5 mg/kg of live weight, respectively, throughout the fattening period. Before placing the animals in experience and 6 months of age, samples were taken of blood. Adrenaline, norepinephrine, cortisol and progesterone, Malon dialdehyde, thiol-disulfide ratio, superoxide dismutase activity were determined in the blood plasma. On the basis of the conducted researches it is possible to make the conclusion that as a result of influence of stressors arising in the course of a standard production cycle of cultivation of pigs there is a strengthening of activity of system of biological active centers of pigs owing to what the level of the General reactivity of an organism raises. Experimental data on the complex of endocrinological and biochemical parameters indicate that lithium ascorbate in fattening pigs has a positive effect on antioxidant status. The revealed effects of lithium ascorbate indicate the prospects for the development of new effective ways to increase stress resistance, nonspecific resistance.

Resume. Effects of GML-1 compound on activity of isoforms CYP2C9 and CYP1A2 of cytochrome P450 using marker drugs losartane and caffeine in experiments on rats were studied. GML-1 in a dose 10 mg/kg of 10 times higher than the maximum effective anxiolytic dose 1 mg / kg (intraperitoneal administration) did not produce changes of the studied isoforms activity. Study of duration of GML-1 in a dose 10 mg/kg administration on the CYP2C9 activity changing was shown that 3 and 4 days administration of the drug did not affect neither inhibiting nor inducing effect of CYP2C9 isoform.

He technique of quantitative determination of a new compound GIZH-298 in the rat blood plasma was developed and validated. Analysis was performed by HPLC-UV. The method was linear in the range of 100-5000 ng/ml. Recovery of GIZH-298 was 86,88 %. Limit of detection was 100 ng/ml.

Resume. The study of acute and chronic toxicity of the finished dosage form (SFF) GSB-106, the active substance of which is the substituted dimeric peptide, hexamethylenediamine bis (N-monosuccinyl-L-seryl-L-lysine), which has antidepressant and neuroprotective activity. GSB-106, administered in the maximum allowable volumes and concentrations in a single intragastric and intraperitoneal administration to males and females of outbred white mice in the maximum possible doses, which made up, respectively, 120 mg / kg of the active substance (12 g / kg tablet weight) and 40 mg / kg of active substance (4 g / kg tablet weight) did not cause the death of animals. GSB-106 in doses of 1 mg / kg of the active substance (0.1 g / kg of the tablet mass) and 10 mg / kg of the active substance (1 g / kg of the tablet mass) with daily oral and intragastric administration during the month to females and male rats and rabbits did not affect the recorded integral indicators. The toxic effects of GSB-106 were not observed in clinical, laboratory, pathological and histological studies performed in a generally accepted volume.

Resume. The paper presents the data of preclinical studies of the acute and chronic toxicity of the finished dosage form of the compound GK-2, which has neuroprotective properties. It has been established that GK-2 does not cause the death of animals after a single intravenous administration in the maximum allowable volumes to outbred white mice and rats of both sexes. The average lethal doses of HA-2 were determined for intraperitoneal administration. In experiments on mice in females, the LD50 was 15.4 (14.5-16.4) g / kg. In males, the LD50 is 15.7 (14.6-16.9) g / kg. In experiments on rats in females and males, the LD50 was 6.9 (4.5-10.6) g / kg. Daily intravenous administration of the finished dosage form to purebred white rats and rabbits of the chinchilla breed of both sexes for one month at a dose corresponding to therapeutic - 1 mg / kg (in terms of active substance) and exceeding it ten times - 10 mg / kg (in terms of active substance) allowed to establish that GK-2 does not affect the integral indicators. The exceptions were reduced body weight gain and a dose-dependent decrease in feed and water intake in female rats of the experimental groups. In clinical, laboratory, pathological and histological studies performed in accordance with the general protocol, the toxic effects of GK-2 have not been established.

The study of acute toxicity and allergenity glycopeptides lactic acid bacteria in mice and rabbits. At the present level of physical, chemical and biological pollution of the environment, domestic and farm animals in no less, if not more than people, suffer from secondary induced immunodeficiency - an imbalance in the normal functioning of the immune system. This leads to a significant reduction in the overall resistance of the animal to various diseases of a viral and bacterial nature. The normal functioning of the animal's immune system can be restored with the help of immunomodulators, the active principle of which is the glycopeptide synthesized from natural components - a universal structural fragment of the lactic acid bacteria cell membrane that interacts with the immune system of the animal organism.