The DNA constructions with nucleotide sequences of human genes of NAT1 and NAT2 and promoter-enhancedregion of a mice albumin gene were created. The coding parts of NAT1 and NAT2 genes were amplified from a matrix of genomic human DNA with use of NAT1-Not and NAT1-Xho oligonucleotides in case of NAT1 and NAT2-Not and NAT2-Xho in case of NAT2 . Plasmids of pSI-NAT1 and pSI-NAT2 split by BamHI and EcoRV endonuclease (the site of a restriction of EcoRV was entered in enAlb-F oligonucleotide). Synthesis of the oligonucleotide primers and detection of human genes expression and the created transgene animals with the use of specific oligonucleotide primers was carried out in parallel. At the following stages allocation of DNA/RNA from blood plasma test, amplification of genomic DNA, identification of PCR products was carried out by method of a horizontal electrophoresis. Existence in gel of DNA strip corresponding size testified to existence in a sample of a required gene. Transgene mice (F0) with the designs integrated into their genome including nucleotide sequences of genes of human NAT1 and NAT2 under the albumin gene mice promoter were generated. Total effectiveness of a transgenesis for NAT1 gene is 1,1% and for NAT2 - 0,6%. The analysis of integration of transgenes in various descendants (F1) organs and tissues of primary transgene mice (F0) showed that human genes NAT1 and NAT2 was found in the cells of all three germinal leaves.

In work on the basis of experimental research, a comparative analysis of ultrasonic vocalizations of rabbits in a state of rest and during exposure to low-frequency rhythmic electrical stimulation (electric sleep) was carried out. The rest characterized typical two-peak shape of the ultrasonic signal: first peak of USV with greater power spectral density occurs in the frequency range of 20-25 kHz, while the second peak - in the range of 33-38 kHz. In the state of the ability to generate rabbit`s ultrasound electric sleep stored as ultrasonic waveform is similar to that of the rest. Low-frequency repetitive stimulation leads to a shift of the first peak of ultrasonic vocalizations in frequency and a slight decrease of the power spectral density of the second peak.

We have estimated a perspective of the microinjection (MI) for isolation from blastocysts inbred mouse cells of the innercell mass (ICM) and trophoblast (TB) - sources of new stem cell lines of embryonic origin. It is shown that microinjection into the cavity of the blastocyst 10nl Witten’s medium and/or vital dyes (0.03% trypan blue and 0.1% phenol red) leads to damage of not more than 4-5% of the cells. In the process there are visible changes in the morphology of the blastocyst, which are almost completely leveled out during the first 24 h of incubation in the Witten’s medium. It was revealed that microinjection procedure doesn’t affect the subsequent development of the injected blastocyst to stage of primary colonies formation in vitro as a single population of interacting innercell mass and trophoblast. It’s also shown that the mechanical puncture of shiny shell (zona pellucida) and osmotic shock from the introduction of excessive amounts of fluid into the internal blastocyst cavity contribute to blastocyst outputting from zona pellucida and to colony formation (for NMRI and SHK cell lines up to 93 and 78 to 47 and 44% in control, respectively). Thus, microinjection small volumes of medium balanced by salt composition and/or solutions of vital dyes (less than 10 nl) can serve a sauxiliary method to increase the efficiency of isolation of primary colonies from inbred mice blastocysts with different genotype and to create new experimental models for biomedical research.

The influence of rhythmic transcranial electrical stimulation of brain structures on the dynamics of processes of the functional state regeneration of the nervous, cardiovascular and respiratory systems after 6-hour physical activity in healthy volunteers was studied. It is shown that the application of methods of rhythmic transcranial electro-stimulation of the brain to restore functional status in individuals with determinate physical fatigue ensures the formation of positive dynamics of the subjective state indicators, the Central nervous, cardiovascular and muscular systems, and physiological reserves.

Selective, sensitive and reproducible method for the quantitative determination of amitriptyline and clomipramine in human serum by reversed-phase high performance liquid chromatography with tandem mass spectrometry (HPLC-MS / MS) using both electrospray (ESI) and chemical ionization at atmospheric pressure (APCI) was developed. Sample preparation was performed by protein precipitation with acetonitrile. Detection was performed in positive ionization mode by monitoring of multiple reactions (MRM). Quantification was performed using promethazine as internal standard. The analytical range of the method is 5-1000 ng / ml for each drug. This technique can be used for therapeutic drug monitoring.

An attempt to develop an approach to QSAR-modeling properties of coordination compounds was made. Using complexes of vanadium as an example the difficulties in predicting the value of half-lethal dose (LD₅₀) using modern chemoinformatical programs were shown. It was found that small samples require a correction factor linking the predicted and experimental value of LD₅₀. A correlation between the value of the distribution coefficient "n-octanol / water" (logP) of ligands and complexes’ LD₅₀ values was shown on a large sample of compounds.

The method to induce superovulation in mice-donors, including the synchronization of sexual cycles of the female donor by pre-infusion to males through the partition, which allows you to get to determine time up to 17 zygotes per donor with highly visible pronucleus, suitable for introduction in them of genetically engineered structures was improved. Linear fragments of plasmid gene-engineering constructions comprising the nucleotide sequence of the human NAT1 and NAT2 genes under the promoter of the mouse albumin ( hNAT1 и hNAT2 ), microinjection into the male pronucleus of zygotes collected from the female F1 hybrid mice (CBA/lac * C57BL/6). In the preparation of the female recipients were also used taking prereplanting female recipients to vasectomy penis males through the partition, which contributed to the stimulation of the process of folliculogenesis and synchronization of sexual cycles in females-recipients. It is possible to obtain a greater number of female pseudoharmonic-recipients with copulation wads to determine time, which is one of the criteria of usefulness of the animal recipient and the possibility of successful transplantation of the embryos to it, microinjection genetically engineered constructs. Based on these techniques, developed variant of a modified technology for producing transgenic mice with the genes NAT1 and human NAT2 .

The study was performed as a retrospective analysis of the results of previous studies on preclinical researches of new chemical compounds promising as a means of improving efficiency. We analyzed the control group of animals received in the course of the kinezohydrodinamic study, forced swimming test with a load, test on rota-rod with rats, running on a treadmill to failure with mini-pigs. It is shown that the influence of the factor "season" for all analyzed parameters was statistically significant. The most important it was for the index test on rota-rod, endurance and maximum swimming speed in kinezohydrodinamic study. Moderate importance of seasonality factor has been set for the index average swimming speed, performance indicators and fatigue in kinezohydrodinamic study. Seasonality hardly has any effect on the time limit of swimming animals with load and mini-pigs running on a treadmill to failure. Thus, the more extreme impact test animal, the less significant is the seasonal factor. The results need to be considered when planning preclinical studies aimed at assessing the physical performance of animals.

The work is dedicated to the generation of resistant lines of transgenic mice with human genes NAT1 and NAT2. The initial lines for generation of transgenic mice with human genes NAT1 and NAT2 used hybrid mice CBA/lac x C57BL/6. Using the method of microinjection of gene constructs into the pronucleus first transgenic mouse were obtained first generation of mice with the human gene NAT1 and NAT2 . F1 and F2 generation of transgenic animals are interbred with non-transgenic animals of the opposite gender. The resulting offspring, after checking for the presence of gene are bred without genetic contamination. Inbreeding was carried out on mice of the third generation. Upon receipt of each new generation of transgenic animals were check for the presence of human genes NAT1 and NAT2 by real-time PCR. For this created a system of four species-specific PCR primers and fluorescent probes for Real-Time PCR human genes Nat1 and Nat2 in transgenic animals. The number of population of transgenic animals obtained by the 6th generation of the animal with the human gene NAT1 - 860 mice, and the number of animals with a human gene NAT2 - 680 mice.

In the article test research results of influence of new agents from raw materials of fawn`s antlers on biosynthetic processes in rats skeletal muscles cells in conditions of long physical activity are described. The trial was led patented technique, which includes histologic, histochemical and morphometric researches. The most changes in structure and skeletal muscles cytolergy of test animals relatively similar to the control group are recorded in the application of funds from the genitals of males, tendons, tails, embryos punt. The obtained data make assertions about the ability of new agents from raw materials of fawn`s antlers to stimulate biosynthetic activity in rats skeletal muscles cells and to exhibit significant the tonic activity.

The ability of nickel-titanium implants with nanosized surface layers modified by titanium and carbon to support the regenerative process and to resist to the complex organism influences. Investigation of the biocompatibility and bioresistance of the TiNi implants was carried out on 32 outbred white mice. It was found that all implants were biocompatible and did not make a negative impact on histotypic cellular differentiation in the area of the defect at the end of 14 days. The identified traces of nickel in the blood plasma of experimental animals showed high bioactivity of the initial TiNi implants with unmodified surfaces. Application of TiNi -diamond-like carbon coatings on the surfaces of the implants reduced the bioactivity of the material and provided valuable reparative tissue regeneration.

The ability of nickel-titanium implants with nanosized surface layers modified by titanium and carbon to support the regenerative process and to resist to the complex organism influences. Investigation of the biocompatibility and bioresistance of the TiNi implants was carried out on 32 outbred white mice. It was found that all implants were biocompatible and did not make a negative impact on histotypic cellular differentiation in the area of the defect at the end of 14 days. The identified traces of nickel in the blood plasma of experimental animals showed high bioactivity of the initial TiNi implants with unmodified surfaces. Application of TiNi -diamond-like carbon coatings on the surfaces of the implants reduced the bioactivity of the material and provided valuable reparative tissue regeneration.

The study of comparative pharmacokinetics of preparations containing rosuvastatin, 20 mg was carried out. Determination of the rosuvastatin concentration in the blood plasma of volunteers was performed by HPLC with mass spectrometric detection. Conditions for the chromatographic separation, conditions of extraction and quantitative determination of the plasma rosuvastatin levels were selected. For the study preparations to calculate the main pharmacokinetic parameters: AUC_0-∞, C_max, T_max, C_max/AUC. 90% confidence interval for the log-transformed values AUC_0-∞ was 81,5-106,0 and C_max - 86,3-106,1. The study concluded compared bioequivalence of drugs.