Strains of Trichoderma spp., producing L-lysine-a-oxidase, prospective in chemotherapy of malignant tumors, were studied. The best results of the enzyme biosynthesis were observed on the wheat bran medium. When grown on the media with various pH levels, the strains showed different spectra of the L-aminooxidase activity. The highest activity of the strains was recorded with respect to destruction of L-lysine. The lysine-producing organism Brevibacterium sp. induced L-lysine-a-oxidase activity in Trichoderma spp.

Investigation of the activity of supra- and supra (e)-dependent dehydrogenases of the Staphylococcus epidermidis strains isolated from the pharynx mucous membrane of healthy subjects showed that the level of the substrate exchange between the tricarbonic acid cycle and the amino acid metabolism reactions, as well as the intensity of the glycolysis terminal reactions and the glutathione reductase activity depended on the bacteria susceptibility to cefotaxime.

The preliminary studies mainly revealed comparable inhibition activities of 3-oxime of betulonic acid, 3^-O-acetyl-28-O-hemiph-thalate of betulin and 3,28-dioxime of betulin against reproduction of influenza viruses A (H1N1), A (H7N1), A (H3N2) and B, as well as against the strains of influenza virus A (H1N1) with intrinsic resistance to rimantadine and A (H7N1) with acquired resistance to the drug. The level of the activity depended on the system used for the virus reproduction. The highest level was observed under conditions providing higher permissibivity, i.e. in the chick embryo fibroblast cell culture for A (H7N1) and in fragments of chick embryo chorioallantoic membranes (for all the viruses). In the experiments with virus A/FPV/Rostock/34 (H7N1) in the chick embryo fibroblast cell culture the average effective concentrations (EC₅₀) of the triterpene compounds were 10.4-17.5 mcM in comparison to EC₅₀ of rimantadine (0.014 mcM). The use of every of the compounds in combination with rimantadine resulted in a 2-16 times decrease of their EC₅₀ and correction of the concentration-effect relation of rimantadine. However, when rimantadine was used alone within the higher range of the nontoxic concentrations (11.6-57.6 mcM). its antiviral properties were significantly less pronounced. As a result the virus titer difference in comparison to the control within the above range of the rimantadine concentrations increased from < 1 to > 2.35 lg PPU/ml and the relations of the maximal tolerance concentrations of the compounds to their EC₅₀ increased 1.7-15.9 times.

Population analysis of 20 batumin susceptible staphylococcal strains, isolated from clinical materials allowed to detect resistant clones only in 3 strains. The frequency of batumin resistant variants isolation was low and depended on the antibiotic concentration. Resistance to batumin in 5 clinical strains and in 1 reference strain of Staphylococcus aureus ATCC 6538 P (209P) developed under laboratory conditions and induced significant phenotypic and chemotaxonomic changes in the pathogen. The variants, resistant to batumin, had the same degree of virulence for mice as the initial susceptible strain. The batumin resistant variants of S.aureus were unstable and on the medium without batumin completely restored their initial phenotype.

«Empty» liposomes and ceftriaxone (CT)-entrapped liposomes were developed. Lipids of natural origin, i. e. soybean phosphatidyl choline (PhCh) and cholesterol were used for the design. The conditions for production of the CT-entrapped liposomes were optimized to provide the maximum content of the antibiotic in the liposomes. The effect of the «empty» liposomes and the antibiotic-entrapped liposomes on healing of skin wounds was studied on rats. The wound on the skin surface of the rat back was purulent due to contamination with E.coli (10⁹ cells/ml). The treatment with the antibiotic solution, «empty» liposomes or CT-entrapped liposomes was started in 48 hours. The use of the PhCh «empty» liposomes promoted more rapid healing of the wound vs. the control or the treatment with CT aqueous solution. The treatmen of the wound with the CT-entrapped PhCh liposomes provided 2 times more rapid healing vs. the control or the use of the CT aqueous solution.

Significant and reliable activity of panavir was shown in experiments on mice intramuscularly infected with the rabies virus. The animal protection depended on the dose of panavir and the treatment scheme. The reliable protection (30-45% of the mice, p<0.05-0.01) was observed only after the panavir intramuscular injection to the site of the virus inoculation (the infection atrium), but not after the systemic (intraperitoneal) administration. High titers of the virus-neutralizing antibodies (7.92-10.45 IU/ml), comparable to the antibody titers in the combined suspensions of the brain tissues (6.01 - 10.45% IU/ml), were detected in the combined sera of the survived animals treated with panavir. For the first time a quantitative method for determination of the virus-neutralizing antibody levels in IU/ml was used (the FAVN test, the gold standard for comparative evaluation of the level of the vaccinal and infective antirabies immunity).

Activity of levofloxacin, lomefloxacin and moxifloxacin against 20 FI⁺ and 20 FI^- strains of Yersinia pestis was studied. It was shown that the strains were highly susceptible to the fluoroquinolones. In the experiments on mice subcutaneously infected with suspension of strains 231 FI⁺ and 231 FI^- of Y.pestis in a dose of about 1000 LD₅₀ (10⁴ microbial cells) the ED₅₀ of levofloxacin and moxifloxacin was 5.5-14.0 mg/kg independent of the infective culture phenotype and that of lomefloxacin was 18.5 mg/kg. Estimation of the impact of the pathogen infective dose value on the results of the experimental plague treatment with the therapeutic dose equivalent to the human one showed high efficacy of the fluoroquinolones (efficacy index of 10⁴). The treatment for 7 days provided 90-100-percent survival of the animals. The prophylactive use of lomefloxacin (in 5 hours - 5 days) was less efficient (70-80% of the survivals) in the animals infected with the antigen-changed (FI^-) variant of the pathogen. Levofloxacin and moxifloxacin provided 90-100-percent survival of the animals treated for a course of 5 days independent of the pathogen phenotype. The study demonstrated that the use of levofloxacin, lomefloxacin and moxifloxacin was prospective for the prophylaxis and therapy of experimental plague.

Biological properties of influenza viruses A (H1N1), that were the cause of the infection in humans in April - May 2009, and the action of the Russian antivirals on their reproduction were studied in vitro. The nucleotide sequence in the viruses was determined and followed by detection of the mutations responsible for resistance to the antiinfluenza drugs. The experiments showned that arbidol and ribavirin had a selective inhibitory action on reproduction of the viruses in the MDCK cell culture while rimantadine had no affect on their reproduction. The data were confirmed by the results of the genome analysis in influenza viruses A/California/04/2009(H1N1), A/California/07/2009(H1N1) and A/Moscow/01/2009(H1N1)swl, that revealed no replacements defining the resistance to arbidol while the viruses contained a mutation in position 31 of М2 protein, responsible for the resistance to adamantans.

The clinical and laboratory efficacy of the treatment of children with pyelonephritis with addition of cycloferon, an inductor of early interferon of types 1 and 2, to the main therapy was studied. The mechanism of the cycloferon action was described. The clinical and laboratory remission within a year was observed in 64.3% of the patients treated with addition of cycloferon vs. 47.1% of the patients under the main therapy without the cycloferon addition. The number of the relapses lowered to 7.1% vs. 20.6% of the episodes in the control group. The minimal risk of the disease exacerbation (0.37) in the patients treated with cycloferon and the relative risk of the unfavourable outcomes among the patients under the therapy with addition of cycloferon (0.5967<1) were determined.

The therapeutic efficacy of Viferon, a recombinant human interferon alpha-2b (rectal suppositoria) was studied in the therapy of relapsing herpesvirus infection in women. The clinical efficacy of the drug was recorded in 90% of the patients. The analysis of the remote results of the treatment made it possible to conclude that the Viferon suppositoria had an antirelapsing activity.

Characteristics of the clinical process of staphylococcal endocarditis in 115 inpatients and the adequacy of various regimens for their antibiotic therapy within a period of 10 years were analysed. Four clinical criteria for prognosis of staphylococcal endocarditis were determined: intravenous narcomania, splenomegalia, leukocytosis and hemorrhagic skin eruption. The analysis of the Russian and foreign findings showed that the use of betalactams (oxacillin, the 1^st and 3^rd generation cephalosporins) and lincomycin provided the adequate therapy resulting in eradication of the pathogen in case of oxacillin resistant staphylococci, whereas the use of ciprofloxacin and vancomycin was inexpedient. In case of MRSA it was recommended to use vancomycin and in case of endocarditis due to S.aureus with intermediate resistance to vancomycin (VISA, MIC > 0.5 mcg/ml) the use of line-zolid was recommended.

From the clinicoeconomic viewpoints the treatment of community-acquired pneumonia in patients without risk factors under hospital conditions with aminopenicillins was more appropriate, whereas for the treatment of patients with risk factors the following scheme of antibiotic therapy was advantageous: a beta-lactam (cefotaxime/ceftriaxone) in combination with a macrolide (azithromycin). The recommended therapy provided statistically lower percentage of negative pneumonia processes and decreased the treatment expenditures.

Nuclear receptors are transcription factors that are essential in embryonic development, cellular differentiation, metabolism . Ligand-regulated nuclear PXR receptor responds to diverse arrays of chemically distinct ligands , xenobiotics, drugs and regulates expression of the genes involved in xenobiotic and drug metabolism. The structural basis of the receptor provides interaction with a variety of ligands which are agonists or antagonists. Nuclear receptors researches are important for design of metabolism regulating drugs and in drug interaction studies.