Polyphosphate Ester-Type Transporters Improve Antimicrobial Properties of Oxytetracycline.

Prolonged use of antibiotics can cause toxicity in human and animal cells and lead to the development of antibiotic resistance. The development of drug delivery systems for enhanced antibacterial properties of antibiotics could reduce toxic effects and minimize the development of resistance. The aim of this study was to evaluate the effectiveness of oxytetracycline in complexes with new polyphosphate ester-type transporters and to investigate the antimicrobial effect of these complexes on , , and growth in vitro.

Identification and Quantification by NMR Spectroscopy of the 22 and 22 Epimers in Budesonide Pharmaceutical Forms.

The authors developed four variants of the qNMR technique (H or C nucleus, DMSO-d6 or CDCl solvent) for identification and quantification by NMR of 22 and 22 epimers in budesonide active pharmaceutical ingredient and budesonide drugs (sprays, capsules, tablets). The choice of the qNMR technique version depends on the drug excipients. The correlation of H and C spectra signals to molecules of different budesonide epimers was carried out on the basis of a comprehensive analysis of experimental spectral NMR data (H-H gCOSY, H-C gHSQC, H-C gHMBC, H-H ROESY).

Development and Validation of 2-Azaspiro [4,5] Decan-3-One (Impurity A) in Gabapentin Determination Method Using qNMR Spectroscopy.

The authors developed a H qNMR test procedure for identification and quantification of impurity A present in gabapentin active pharmaceutical ingredient (API) and gabapentin products. The validation studies helped to determine the limit of quantitation and assess linearity, accuracy, repeatability, intermediate precision, specificity, and robustness of the procedure. Spike-and-recovery assays were used to calculate standard deviations, coefficients of variation, confidence intervals, bias, Fisher's test, and Student's -test for assay results.

Aggregation of Influenza A Virus Nuclear Export Protein.

Influenza A virus nuclear export protein (NEP) plays an important role in the viral life cycle. Recombinant NEP proteins containing (His)-tag at either N- or C-terminus were obtained by heterologous expression in Escherichia coli cells and their high propensity for aggregation was demonstrated. Dynamic light scattering technique was used to study the kinetics and properties of NEP aggregation in solutions under different conditions (pH, ionic strength, presence of low-molecular-weight additives and organic solvents).

[Impact of Radioactive Elements on Microbial Complexes in Cryogenic Soils of Yakutia].

It has been found that microorganisms in cryogenic soils of Yakutia are resistant to the long-term impact of cesium and thorium. The number of microorganisms in the studied ecological-trophic groups does not depend on the concentrations of radioactive elements. Differences in the number of microorganisms are determined by the physicochemical conditions that are created in different horizons of the soils studied.

[The study of aberrant methylation in blood leukocytes of liquidators of the Chernobyl accident].

The study of aberrant methylation of CpG islands in the promoter regions of genes (P16/CDKN2A, P14/ARF, RASSF1A, GSTP1) in blood leukocytes of liquidators of the Chernobyl accident (n = 83, 38-76 years of age) and control subjects of two groups (n = 48, age ≤ 35 and n = 65, age > 35) was carried out using methylation-sensitive restriction endonuclease analysis followed by PCR. The total number of AciI sites in the analyzed fragments ranged from 2 to 7 for different genes. Only 1 subject (2.

[Microbial communities of frozen soils of the Tuimaada Valley in Central Sakha].

This study determined the characteristic features of microbial communities inhabiting frozen soils of Central Sakha. All groups of microorganisms were present in high numbers comparable with the microbial densities in steppe soils of Transbaikalia; their distribution along soil profiles followed a specific pattern with no decrease in abundance with depth. In summer, the dominant groups of the microbial pool were actinomycetes and oligonitrophilic bacteria, while in autumn it was heterotrophic bacteria.

[The estimation method of compounds opiate activity based on universal three-dimensional model of the nonselective opiate pharmacophore].

Created by means alternative strategy of structural similarity search universal three-dimensional model of the nonselective opiate pharmacophore and the estimation method of agonistic and antagonistic properties of opiate receptors ligands based on its were described. The examples of the present method use are given for opiate activity estimation of compounds essentially distinguished on the structure from opiates and traditional opioids.

[Monoclonal antibodies to rubella virus glycoprotein E1].

Aim: To obtain monoclonal antibodies (MCAs) to glycoprotein E1 of rubella virus, to assess their immunochemical characteristics and ability to use fluorescent MCA for rapid identification of rubella virus.

Materials And Methods: Rubella virus strain C-74 (Moscow), vaccine strains "Orlov" (Saint-Petersburg), Wistar RA 27/3 (USA) as well as strain Judith (Germany) were used. Viral antigens were obtained using diploid cells L-68 and cell lines VNK-21-F and Vero E6.

[Investigation of detoxification polymorphisms genes, methylenetetrahydrofolate-reductase (MTHFR) and P53 in the radiosensitive human cells].

The genes of detoxication, MTHFR and p53 were studied in Down' and Ehlers-Danlos syndrome cells. The frequency GSTM1(0/0) genotype in Down syndrome patients was in 1.5 times higher than in control cells (p < 0.

[The effect of polymorphism of genes of xenobiotics detoxication on the frequencies of spontaneous and induced chromosome aberrations in human lymphocytes].

Here presented the data on the frequencies of chromosome aberrations in lymphocytes of peripheral blood of 97 volunteers depending on genotypes by genes of xenobiotics detoxication before and after gamma-irradiation with dose of 1 Gy in vitro. The frequencies of aberrations were estimated by analyzing not less than 500-1000 metaphases per person. The data of cytogenetic analysis were compared with the results of PCR-genotyping of loci GSTM1, GSTT1, GSTP1, CYP1A1, CYP2D6, NAT2, and MTHFR.

[Protection of radiosensitive human cells against the action of heavy metals by antimutagens and adapting factors: association with genetic and protein polymorphisms].

Cells of a diploid line obtained from embryos with the Down's syndrome, known to be unable to repair gamma-induced DNA damage, were treated with natural (garlic extract, retinol) and synthetic (crown compound) antimutagens and with adapting factors (heat shock, low CdCl2 concentrations, 10(-8) M). The protective effect was evaluated by registering DNA breaks and cell survival, and the protection coefficients were calculated. The most effective results were obtained with the use of the garlic extract and retinol.

[Gene polymorphisms in patients with Down's syndrome].

Polymorphisms of glutation-S-transferase (GSTM1, GSTT1 GSTP1) and methylentetrahydrofolate reductase (MTHFR) genes have been studied in DNA from blood lymphocytes of 18 patients with Down's syndrome and 61 controls. Frequencies of normal alleles of GST genotypes were lower in patients as compared to the controls. A DNA analysis of 11 patients and 17 controls revealed the presence of mutations in region 246-250 of exon 7 of the p53 gene in 4 patients.

[The course and treatment and efficiency of surgical treatment for disseminated pulmonary tuberculosis].

Chemotherapy for disseminated tuberculosis by the schemes regulated by the Order "On Improvement of Tuberculosis-Controlling Measures in the Russian Federation" issued by the Ministry of Health of the Russian Federation under No. 109 on March 21, 2003, leads to the regression of intoxication syndrome and the normalization of general blood analysis parameters in most patients, provides bacterial excretion cessation in 72.7% of the patients and decay cavity closure in 53.

[The analysis of mutations at mini- and microsatellite DNA loci in the family members of a group of occupationally exposed to tritium and tritium oxide plant workers].

Mini/microsatellite (MNS/MCS) loci are efficient tools in solving basic and applied problems in different spheres of biology and medicine due to their unique characteristics - a high frequency of tandem repeats in combination with their wide variability. Specifically, they have been found use as potential markers of genetic effects of ionizing radiation on animals and on human. However there is no general agreement as to the influence of irradiation on the frequency of mutations in hypervariable repetitive DNA sequences up to now.

[The course of generalized tuberculosis in a northern region].

The course of generalized tuberculosis in a northern region is mainly characterized by its subacute onset; moreover, the symptoms of intoxication and the bronchopulmonary manifestations of the disease are observed practically in all patients. Socially dysadapted individuals are most susceptible to this disease. Even if patients with generalized tuberculosis have significant symptoms of the diseases, only a few of them resort to a health care facility within a month after their occurrence.

[Genotype dependence of cytogenetic and epidemiological characteristics in the liquidators of the accident at the ChNPP].

The dependence of the level of unstable chromosome aberrations and nononcological diseases on the genotype in 57 liquidators of the ChNPP accident was studied. Candidate genes presumably affecting radiosensitivity were highly polymorphic loci of xenobiotic detoxication genes (glutathione-S-transferases GSTM1, GSTT1, GSTP1) and the 5,10-methylenetetrahydrofolate reductase gene (MTHFR) involved in DNA methylation and synthesis. An increased frequency (0.

[Transgenerational genomic instability in children of liquidators of the accident at the ChNPP (cytogenetic and immunogenetic characteristics)].

A complex of cytogenetic and of immunogenetic study of the state of the lymphocyte genomes in the liquidators of the ChNPP accident and their unirradiated children has been carried out for the first time. Increased frequencies of the chromosome aberrations, of gene mutations (TCR mutations) and of predictors of apoptosis (cells with CD95+ immunophenotype) have been revealed in both generations. The analysis of correlations between the parameters under study has demonstrated distinctive features characteristic of induction of genomic instability in the organism of unirradiated children as compared to their fathers--liquidators directly exposed to radiation.

Polymorphism of detoxification genes and cell resistance to mutagens in patients with Ehlers-Danlos syndrome.

Study of polymorphism in 3 genes of the glutathione S-transferase family (GSTM1, GSTT1, and GSTP1) in children with Ehlers-Danlos syndrome whose cells were defective in repair of gamma-induced DNA damages revealed accumulation of GSTM1(+) genotypes compared to children of the control group. Generation of reactive oxygen species by neutrophils from patients with this syndrome was higher than in healthy donors. Our results indicate that glutathione S-transferase genes are involved in the resistance to mutagenic agents and demonstrate medical and genetic peculiarities of patients with Ehlers-Danlos syndrome.

[State-of-the-art pharmacotherapy of juvenile arthritis].

The review of state-of-the-art stage of pharmacotherapy of juvenile arthritis is represented. Main principles and features of the use of antirheumatic remedies in children are given with the accent to age limitations. Detailed characteristic used drugs and treatment schemes and also recommendations for prevention and monitoring of collateral reactions are given.

[The problem of the transgeneration phenomenon of genome instability in sick children of different age groups after the accident at the Chernobyl Nuclear Power Plant].

A complex genetic examination of children which belong to two cohorts and their parents were carried out. The first cohort included children and constantly living on territories contaminated with radionuclides (Novozybkov district, Bryansk region). They were subdivided in groups according to the ontogenetic age periods of development of their parents at the time of the Chernobyl accident.

[Genetic polymorphism of glutathione-S-transferases and inhibition of DNA repair].

A complex investigation of different cell defence systems, such as: DNA repair, antioxidant system (SOD), xenobiotic detoxification system (glutathione-S-transferases M1 and T1), radioadaptive response (RAR) in lymphocytes of patients with hereditary disease of connective tissue (Elers-Danlose syndrome) was carried out. The frequency of genotype GSTM1 (0/0) in children with Elers-Danlose syndrome (23%) is lower as compared to the control group (44%). The lymphocytes of children with Elers-Danlose syndrome were characterized by reduced ability to repair gamma-induced damage of DNA.

[The problem of induced genome instability as the basis of the increased morbidity in children exposed to low-intensity radiation at low doses].

The main results of the complex examination of the genome instability are presented in children constantly living on territories contaminated with radionuclides as a result of the accident at the CNPP (Novozybkov district, Bryansk region, 16-18 Ci/km2, 137Cs) and in children exposed to low-intensity radiation at different stages of ontogenetic development: children exposed to postnatal irradiation in 1986 (born before the accident), children exposed to intrauterine irradiation during the accident in 1986, children of irradiated parents born after the accident in 1987-1992 and in 1994-2000. In all examined groups of irradiated children increased frequencies of certain radiation-induced chromosome aberrations were observed as well as a reduced activity of unscheduled synthesis of genomic DNA in lymphocytes and peculiarities in individual heterozygosity of genes encoding structural and enzymatic proteins of blood. An increased radiosensitivity of lymphocyte genomes to testing in vitro irradiation and peculiarities in the dynamics of the frequencies of chromosome aberrations and sister chromatid exchanges in 3 cell generations were revealed in children from the contaminated areas.

[Association of pulmonary tuberculosis morbidity with local earth's crustal fractures on the territory of a contemporary industrial town].

The purpose of the present study was to examine the association of the incidence and severity of primary pulmonary tuberculosis with the anomalies of physical factors (geomagnetic field, gamma-radiation, radon emanation) above the local earth's crustal fractures (LECF) on the territory of Surgut. Analyzing the findings indicated the significant prevalence of both the rates of total primary morbidity of pulmonary tuberculosis and its exudative forms and the predominance of bacterial isolating patients among the residents in the area of LECF versus the continuum. Antituberculosis therapeutic-and-prophylactic measures should be planned, by taking into account the regional features of the state of anomalous physical fields.