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Aim. Systematization of data on antibiotic resistance of Helicobacter pylori in Russia over the past 10 years. Methods. A search for studies were carried out in electronic databases MEDLINE/PubMed, EMBASE, Cochrane, Russian Science Citation Index. We analyzed the papers published over the past 10 years (2011 to 2020). In the final analysis, publications were selected from periodical peer-reviewed foreign and Russian publications, in which validated tests for assessing the microorganism resistance were used with detailed descriptive statistics, which allows the obtained data to be included in the meta-analysis. Results. The final analysis included 11 studies (808 isolates). H. pylori resistance to clarithromycin was 10.39% (95% confidence interval CI 7.10314.219), metronidazole 33.95% (95% CI 15.32955.639), amoxicillin 1.35% (95% CI 0.281 3.202), levofloxacin 20.0% (95% CI 12.63728.574), tetracycline 0.98% (95% CI 0.3532.163). Double clarithromycin-metronidazole resistance was reported in 2.7% (95% CI 1.1364.345). Conclusion. This meta-analysis is the first analytical work that allows objectifying the current structure of H. pylori antibiotic resistance in the Russian Federation. The data obtained in the analysis of publications over the past 10 years indicate a low resistance of the microorganism to clarithromycin (less than the regulated threshold of 15%), which allows us to consider the triple regimen of eradication therapy as a first-line therapy in our country.

Inducible character of resistance to tetracycline, chloramphenicol and ampicillin was investigated in 20 strains of Vibrio cholera non-O1/non-O139 serogroups isolated from inhabitants of Uzbekistan in 1990 (10 strains, ctx+) and in 2001 (5 strains, ctx-) and from inhabitants of Kalmykiya within 2003-2005 (5 strains, ctx-). Eight of the 20 isolates showed not only capacity for induction of the antibiotic resistance, but also its possible self transfer to Escherichia coli and reverse crosses in El Tor V.cholerae P-5879. It was shown that the effect of the antibacterial on the isolates phenotypic susceptibility could increase the resistance markers expression, when the genomes contained sites responsible for their expression, that required constant bacteriological control of the treatment efficacy and the use of the isolates antibioticograms for early replace of the inefficient drug by the efficient one. The prevalence of V.cholerae O1 and non-O1/non-O13 serogroups with multiple resistance to the antibacterial and the genetic potency for the antibiotic resistance development in the pathogen made difficult the choice of efficient drugs for prophylaxis and treatment of diseases caused by V.cholerae.

The article Is devoted to the study of biological properties of antibiotic-resistant bacteria Propionibacterium acnes and their sensitivity to antibacterial cationic peptides varnerin and hominin. P.acnes Ac-1450 strain resistant to rifampicin and tetracycline were obtained by selection. With the help of the Kirby-Bauer disk diffusion test, it is shown that the acquisition of resistance to these antibiotics is accompanied by a decrease in the sensitivity of bacteria to a number of other antibacterial drugs. As a result of the determination of the minimum inhibitory concentrations of cationic peptides, it has been established that the sensitivity of antibiotic-resistant P.acnes strains to varnerin and hominin is maintained at the sensitivity level of the parent strain. Antibiotic-resistant bacteria show a more pronounced ability for adhesion and biofilm formation in comparison with the bacteria of the parent strain, however, the formation of biofilms can be effectively suppressed by staphylococcins. Analysis of the curves of the formation intensity of P.acnes biofilms, depending on the content of peptides in the medium, made it possible to establish concentrations that inhibit the growth of biofilms by 50%. Despite the fact that the values obtained were 5-12 times higher than the MIC values for planktonic culture of P.acnes, staphylococcins are promising drugs for combating infections caused by propionic bacteria.

The effect of chloramphenicol and tetracycline, as inhibitors of protein synthesis, on electrophysical properties of Escherichia coli K-12 cells was investigated. Significant changes in the orientation spectra (OS) of the cell suspensions incubated with various concentrations of chloramphenicol were observed only at the first five frequencies of the electric field (10-1000 kHz). When the cells were exposed to chloramphenicol (1.5 mcg/ml) or tetracycline (1.7 mcg/ml), no changes in the OS were recorded. Significant changes in the electrooptic signal were observed, when the K-12 cells were simultaneously incubated with chloramphenicol (1.5 mcg/ml) and tetracycline (1.7 mcg/ml), that could be due to the synergistic action of the antibiotics. Therefore, the electrooptic analysis provided registration of higher antibacterial effect with the simultaneous use of chloramphenicol and tetracycline. Additional control experiments with the cell culture on the LB nutrient medium containing chloramphenicol and tetracycline were performed. The results suggested that the use of electrophysical methods for investigation of antibiotics effect on microorganisms was rather efficient.

In patients under artificial lung ventilation (ALV) there is often observed development of severe ventilator-associated pneumonia (VAP) due to polyresistant hospital pathogens. It should be noted that in the patient described here with the initial diagnosis of community-acquired pneumonia rapidly subjected to prolonged ALV the previous antibacterial therapy by broad spectrum drugs significantly increased the risk of contamination just by multiresistant nosocomial strains, which hampered the starting therapy of nosocomial pneumonia either when there were not available or sometimes there were available microbial cultures. When the treatment of severe pneumonias caused by multiresistant hospital flora resistant to carbapenems is actual, in the alternative therapy it could be used tigecycline, a tetracycline from the group of glycylcyclines. A case of successful treatment of nosocomial VAP by tigecycline based on the results of the bronchoalveolar lavage (BAL) culture is described. The case is of interest because tigecycline was used as off label.

A total of 399 Neisseria gonorrhoeae clinical isolates collected in different regions of the Russian Federation in 20152017 were analyzed for tetracycline susceptibility and genetic markers of resistance. Drug susceptibility testing was performed by serial dilution method in agar and minimum inhibitory concentration (MIC) was measured according to the Russian “Guidelines for microbial susceptibility testing for antibacterial agents No. 4.2.1890-04”. Tetracycline resistance determinants were studied by using hydrogel microarray with immobilized oligonucleotide probes able to identify a series of chromosomal mutations and detect plasmid tetM gene. Different resistance determinants were found in 193 isolates (48.4%). Mutation in codon 57 in the rpsJ gene (41.2%) was most common that decreases tetracycline affinity to ribosome 30S subunit, mainly due to Val57Met substitution both as a point mutation as well as in combination with others. Mutations in the rpsJ gene were found in strains with the intermediate tetracycline susceptibility. Mutations in the porB gene (lower tetracycline influx) held the se cond place in prevalence pattern (23.1%); the Gly120Lys substitution usually led to emergence of tetracycline resistance either as a point mutation or in combination with other substitutions. Substitutions of Gly120 for other residues (Asp, Asn, and Thr) and Ala121 for Asp, Asn, and Gly had much less effect on resistance level. The –35 delA deletion in the promoter region of mtrR gene (increased expression of MtrC-MtrD-MtrE efflux pump) was observed in 11.3% strains. The tetM gene was found in 27 strains including 17 American and 10 Dutch type tetM determinants. Evolutionary tree was constructed for the tetM genes with the estimation of their homology with similar genes in genera Streptococcus, Enterococcus and Mycoplasma. Mutations in chromosomal genes resulted in increase of tetracycline MIC up to 2–4 mg/L; 4 mg/L MIC was observed in case of simultaneous presence of several mutations. Strains bearing tetM gene-containing plasmid showed extremely high resistance level: MIC ≥ 8 mg/L (64 mg/L for the two samples). Thus, long-lasting withdrawal of tetracycline use for treatment of gonococcal infections in Russia (since 2003) resulted in decreased percentage of resistant strains (including strains with intermediate susceptibility) from 75% down to 45.4%. However, currently tetracycline resistance in Russia remains elevated that is explained by the presence of different resistance determinants in the half of isolates under study.

The simple and available technique of determination of tetracycline in the form of colored complex with iron(III) ions and B12 vitamin in the form of the colored thiocyanate complex of cobalt(II) after a chemical mineralization of cyanocobalamin is offered. The analytes were separated from the accompanying components by sorption to polyurethane foam based on ethers. The conditions of sorption separation and measurement of analytical signal of these substances are optimized. The obtained results are in satisfactory agreement with data declared by the manufacturer. The adequacy of proposed approach is confirmed by results of indirect X-ray fluorescence analysis of tetracycline drug substance and injection solution B12 vitamin (cyanocobalamin).

Despite great scientific progress in the sphere of hepatoprotectors development during recent years, the issues of hepatocytes protection and regeneration is relevant enough. In this aspect derivatives of heterocyclic systems are of great interest, in particular, of 1,2,4-triazole. The aim is histological study of the compound of potassium 2-((4-amino-5-(morpholinomethyl)-4H-1,2,4-triazol-3-yl)thio)acetate (PKR-173) corrective influence on the chickens liver under tetracycline hepatitis condition. Materials and methods. As an object of research potassium 2-((4-amino-5- (morpholinomethyl)-4H-1,2,4-triazol-3-yl)thio) acetate was used which is a water-soluble compound. Histological examination was carried out of the intact chickens liver (intact control); of the chickens after tetracycline administration (control pathology); of the chickens which before the administration of tetracycline were administrated PKR-173 compound or thiotriazoline. All chickens were administrated tetracycline per os in the doze of 500 mg/kg for 5 days. PKR-173 compound and thiotriazoline were administrated per os for 3 days before tetracycline in doze of 150 mg/kg and 50 mg/kg respectively. Results. It has been noted that preventive administration of PKR-173 compound for chickens aged 7–18 days visually prevented the development of nonspecific morphological changes which are characteristic of acute moderately severe drug-induced bird’s liver injury. Compound PKR-173 contributed the organ histostructure normalization, prevented dystrophy manifestations, significantly reduced necrosis of hepatocytes and inflammatory reaction in the perivenular zone of triad system. Comparative drug thiotriazoline prevented hepatocytes dystrophy manifestation, in the vast majority of chickens contributed to hepatic plates structure restoration and inflammatory response reduction. In order to confirm the visual data according to the task, a semi-quantitative assessment of the PKR-173 and thiotriazoline corrective effect on chickens liver parenchyma morphological state was carried out. Conclusions. Analysis of the pathological process quantitative characteristics, which developed in the chicken liver after tetracycline administration and corrective influence of the investigated drugs on it, has shown that the PKR-173 compound significantly reduced the manifestations of all the pathological features detected for testing compared to control pathology. The PKR-173 compound is probably not inferior to comparative drug thiotriazoline by normalizing effect on the organ histostructure restoration and antidystrophic action intensity. The PKR-173 compound significantly outperforms the comparative thiotriazoline for anti-necrotic and anti-inflammatory effects.

At present all new medicinal products and cosmetics that absorb medium-wavelength UVB, long-wavelength UVA, or visible light in the range 290–700 nm need to be tested for potential phototoxicity. phototoxicity is evaluated by both in vitro and in vivo methods. There are guidelines for in vitro phototoxicity evaluation, however, there are no formally validated protocols for in vivo phototoxicity evaluation. The purpose of this study was to test an economically viable and informative method for in vivo evaluation of tetracycline and ketorolac phototoxicity using outbred rats. Two medicinal products potentially capable of causing clinically established phototoxic reactions were used in this study: tetracycline (tablets, 200 mg/kg and 300 mg/kg) and ketorolac (gel, 13.4 mg/kg, 26.8 mg/kg and 40.3 mg/kg). The medicines were administered in both single and multiple doses. Ultraviolet irradiator OUFK-03 (OOO «Solnyshko», Russia) was used as a light source. The UV exposure (5 J/cm2 and 15 J/cm2) was performed once 1 h after medicine administration. The skin reaction was evaluated 30 minutes and 24 hours after irradiation and then daily for 2 weeks. As a result, the following optimal parameters were determined for in vivo evaluation of phototoxic reactions caused by the medicines: radiation intensity — 15 J/cm2 for single systemic administration and 5 J/cm2 for single topical (dermal) administration; recommended period of skin reaction evaluation for outbred rats is not less than 7 days.

A food product is a multicomponent system containing proteins, fats, carbohydrates. Determination of antibiotics in this case is complicated by the influence of interfering components of different nature. Methods for determining antibiotics (chloramphenicol and tetracycline) in foods with multicomponent matrices (lipid-protein, lipid-carbohydrate) have been proposed. Techniques include antibiotics extraction using various solvents, purification of extracts and concentration of antibiotics using natural sorbents (activated carbon and silica-alumina), followed by eluting of certain components with ethanol and analyzing by high performance liquid chromatography (HPLC) with UV detection. The content of antibiotics was determined in products purchased in retail stores in Vladivostok: lime honey produced in the farms of the Primorsky Territory and the Republic of Bashkortostan, hawthorn honey produced in the farms of the Republic of Bashkortostan, and chicken liver produced in the poultry farms of the Primorsky Territory. The extraction degrees of chloramphenicol and tetracycline from honey and chloramphenicol from chicken liver have been determined by the «added-found» method. The extraction degree of chloramphenicol from honey was 90%, from chicken liver - 78%. The extraction degree of tetracycline from honey samples was 82%. The content of chloramphenicol and tetracycline in some honey samples and chloramphenicol in chicken liver samples purchased in the retail network was determined. Tetracycline and chloramphenicol were found in 2 samples of lime honey with antibiotics content of 0.052 and 0.020 mg/kg, respectively. Chicken liver samples contained from 0.007 to 0.01 mg/kg of chloramphenicol.

The literature review tells about current views on the clinical and molecular aspects of antibiotic resistance of Helicobacter pylori (H. pylori). Today, the growing number of H. pylori strains resistant to the first-line regimens is considered to be the main reason of treatment failure. In the total global population, incidence of drug-resistant strains of H. pylori varies greatly across different geographic areas and correlates with the total frequency of antibiotics intake by the corresponding population. Latest global consensus recommendations regulate a differential choice strategy in selecting eradication therapy. The choice should take into account the level of resistance of H. pylori to clarithromycin, as this type of resistance has greatest clinical significance.

Aim: Systematization of data on antibiotic resistance of Helicobacter pylori in Russia over the past 10 years., Methods: A search for studies were carried out in electronic databases MEDLINE/PubMed, EMBASE, Cochrane, Russian Science Citation Index. We analyzed the papers published over the past 10 years (2011 to 2020). In the final analysis, publications were selected from periodical peer-reviewed foreign and Russian publications, in which validated tests for assessing the microorganism resistance were used with detailed descriptive statistics, which allows the obtained data to be included in the meta-analysis., Results: The final analysis included 11 studies (808 isolates). H. pylori resistance to clarithromycin was 10.39% (95% confidence interval CI 7.10314.219), metronidazole 33.95% (95% CI 15.32955.639), amoxicillin 1.35% (95% CI 0.281 3.202), levofloxacin 20.0% (95% CI 12.63728.574), tetracycline 0.98% (95% CI 0.3532.163). Double clarithromycin-metronidazole resistance was reported in 2.7% (95% CI 1.1364.345)., Conclusion: This meta-analysis is the first analytical work that allows objectifying the current structure of H. pylori antibiotic resistance in the Russian Federation. The data obtained in the analysis of publications over the past 10 years indicate a low resistance of the microorganism to clarithromycin (less than the regulated threshold of 15%), which allows us to consider the triple regimen of eradication therapy as a first-line therapy in our country.

A synthetic genetic chain was created-a two-promoter integrator, the activity of the output signal of which is high only with the high activity of two promoters at the input of the chain. The integrator is shown to work by the example of cancer-specific promoters of the human survivin and telomerase genes that can be used for specific transcription of target genes in tumor cells. To create the integrator, we used the well-known TET-ON 3G transactivator, regulated by doxycycline.

The effect of Hypecoum erectum L. extract on the morphofunctional condition of the liver in rats with experimental tetracycline-associated hepatitis was studied. The experiment included 40 albino rats Wistar. The animals treated with tetracycline hydrochloride (1.0 g/kg body weight) were exposed to the extract in a dose of 50 mg/kg for 5 days. On the 7th day of the experiment the following indices were determined: malonic dialdehyde concentration, catalase activity, the levels of ATP, pyruvate and lactate in the liver homogenate, as well as the blood levels of reduced glutathione. The liver pathomorphological investigation was applied. The H. erectum extract was shown to inhibit lipid peroxidation, to increase the activity of the host endogenous antioxidant system, to normalize the hepatocyte energy provision and to limit the liver degeneration.

In experiments on albino rats with toxic hepatitis due to their exposure to tetracycline hydrochloride it was shown that a course of therapeutic and preventive administration of Dig-da-shi-tan decoction had a strong hepatoprotective effect. Antioxidative, membrane integrative, cholagogic and antiinflammatory activities of the remedy were revealed.

The granulated dry extract from Gentianopsis barbata (Froel) Ma in a dose of 0.1 g/kg produced a pronounced therapeutic effect in rats with experimental toxic (tetrachloromethane) and drug-induced (tetracycline) hepatitis. The gentian extract improved the bile production and secretion functions of liver, normalized the protein, lipid, and pigment metabolism, and increased the antioxidant system activity in the test animals.

Fatty tetracycline-induced steatosis is shown to reduce levels of mitochondrial and microsomal cytochromes. A decrease of microsomal cytochromes in the liver of hypoxia-resistant animals was similar to that of hypoxia-sensitive ones. This decrease was different for hypoxia-resistant and hypoxia-sensitive animals: for the former only cytochrome a declined, in the latter case cytochromes c+, c1 and a.

A series of plasmids with tetracycline resistance genes (Tcr-operon) subjected to transcription from chloramphenicol acetyl transferase promoter (Cmr-promoter) have been constructed on the basis of plasmid pBR325, AprCmrTcr. For this purpose, a 0.8 Md fragment in pBR325 DNA bordered by unique EcoRI and HindIII restriction sites was cut out and structural genes of Tcr-operon were fused to the cat gene nucleotides corresponding to Cmr-promoter and first 72 amino acids of cat (alton, Vapnek, 1979; Marcoli et al., 1980). These plasmids with molecular weight amounting to 3 Md confer AprTcr phenotype to host cells. Tetracycline resistance can be eliminated completely by the deletion of a) Cmr-promoter; b) part of the first Tcr-operon gene.

A study was made of the efficacy of trypan blue, acridine orange, tetracycline and oxytetracycline for detection of tumour cells injected into the blood stream of rats. The cells were identified in the mesenteric microvessels by intravital microscopy. Fluorescence of fluorochromized cells was observed in the blue-violet (lambda max = 400 nm) and ultra-violet (lambda max = 365 nm) irradiation of the fluorescent lamp and in the laser irradiation (lambda = 337 nm). The cells stained with acridine orange had a higher fluorescence intensity and a more distinct structure than those labelled with tetracyclines. Identification of cells with trypan blue was more difficult. The fluorescent method of determination is rather simple and permits to indentify tumour cells directly in the blood stream.

The studies provided development of a new method consisting of placing 2 filter paper strips each impregnated with an antibiotic (2 antibiotics are used out of 3: levomycetin, tetracycline and streptomycin) under a layer of Ploskirev's medium with sodium sulfacyl. The antibiotics are chosen proceeding from the predominance in the given area of Shigella resistant to some of the above antibiotics. The method simplifies and makes more economic the tests, provides higher frequency of Shigella isolation as compared to the procedure with the routine Ploskirev's medium or gradient dishes, has almost the same isolation frequency as with the use of 2 plates (with and without antibiotic). The method is recommended for wide use in practice.

The Ploskirev medium with addition of tetracycline in an amount of 10 mu/ml was used for increasing the isolation frequency of dysenteric bacteria. 102 faeces samples from children with acute dysentery were tested. It was shown that the Ploskirev medium with tetracycline was elective and its use is advisable for isolation of antibiotic resistant Shigella.

Tetracycline was used as a fluorescent test-antibiotic for Ca2+ ions in rat liver mitochondria. Incubation of the isolated mitochondria under anaerobic conditions at 20 degrees C resulted in a rapid (in 30-min) loss by the mitochondria of the property to accumulate Ca2+. Disturbances of the mitochondrial Ca2+-accumulating property during the survival of the liver developed much more slowly (it took over 2 hours) and were not monotonous; the maximal values were recorded during the 5th-10th and the 60th minutes of survival.

The specificity of integration of chloramphenicol resistance transposon (Tn9) into Vibrio El Tor chromosome was studied. As shown by the isolation of auxotrophs offerring various nitritional requirements, Tn9 displayed fairly low specificity in its interaction with the chromosome. When inserted into cholera vibrio chromosome, Tn9 induced secondary rearrangements of genetic material. Nutritional requirements were identified for the polyauxotrophic clones which resulted from the mutations in chromosome region adjacent to the insertion sites of Tn9 and Tn10. Based on these observations a preliminary map was constructed for certain regions of V. eltor chromosome.