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Background. Molecular structures combining a phosphorus-containing counterpart and non-polar radicals are employed in design of pro-drugs as structural and functional groups necessary for transportation of drugs through cellular barriers. It is assumed that the carrier itself does not exhibit biological activity. However, the “organic phosphate – alkyl radical” complex may possess its own metabolic and pharmacological properties even in the absence of a drug moiety.The aim. To study the effect of fluorinated alkyl phosphates on the growth of bacterial test cultures in an agar medium and to identify conjugated metabolic markers using UV/visible spectroscopy.Materials and methods. The effect of six organyl phosphates on the growth of five types of bacteria under aerobic conditions was evaluated by the method of wells in an agar medium. For solutions containing cell metabolites of Pseudomonas aeruginosa, the absorption spectra were recorded at 250–280 nm. The principal component analysis (PCA) was used for multivariate comparative analysis of the spectra. Results. The studied organyl phosphates bearing the ethyl and propyl radicals are potential temporary carriers of the drug moiety, since they are capable of penetrating through cellular barriers. However, the fluorinated compounds exhibit bactericidal properties, the degree of which depends on the arrangement of fluorine atoms in the radical. The most active compounds are those exhaustively halogenated at the terminal carbon atom of the ethyl radical (-СН2-СF3), while non-fluorinated organyl phosphate is the least active. UV/visible spectra of P. aeruginosa cultivation products, according to PCA data, contain patterns reflecting the metabolic effects mediated by these structural features of the radicals.Conclusion. In terms of practical application of the studied compounds, the activity of a proantibiotic based on organyl phosphate with a non-fluorinated ethyl(propyl) radical will be determined only by the specificity of the drug moiety. Exactly the same molecule, but exhaustively fluorinated at the terminal carbon atom of the alkyl radical, is likely to be characterized by lower specificity and higher activity under the additive (or synergistic) action of metabolically active groups.

Aim: To determine the differences in the frequencies of polymorphic variants at the rs4244285(*2), rs4986893 (*3), rs12248560 (*17), loci of the CYP2C19 gene, and the rs2305948 locus of the VEGFR-2...

Cysteamine (2-aminoethanethiol) undergoes oxidative cross-coupling with secondary phosphine sulfides and phosphine selenides under mild conditions (room temperature, 2–5 h, CCl4/Et3N) to give products of monocoupling at the amino group (ethylchalcogenophosphinic amides with free SH functions) and dicoupling (l-chalcogenophosphorylamino-2-chalcogenothioethanes) in 72–85% total yield. Under similar conditions, stirring an equimolar mixture of bis(2-phenylethyl)phosphine sulfide (or selenide), 1-butylamine, and 1-butanethiol leads to the chemoselective formation of the corresponding chalcogenophosphinic amides in high yield.

Oligomers of cholesterol vinyl ether (CVE) with methyl vinyl sulfide synthesized in the presence of cationic catalyst ВF3 OEt2 in up to 81% yield (Mn up to 5700) demonstrate optical activity exceeding that of CVE homopolymer, which is probably due to both conformational effects of the oligomer chain and chirality induction during the polymerization.

Oligomers of cholesterol vinyl ether with methyl vinyl sulfide were synthesized in up to 81% yield (Mn up to 5700) by cationic copolymerization of the indicated monomers in the presence of BF3 ‧ OEt2. The oligomers demonstrate optical activity exceeding that of cholesterol vinyl ether homopolymer.

Cationic copolymerization of cholesterol vinyl ether with N-allenylpyrrolidone yielded co-oligomers with molecular mass of 1200-2100. The polymerization of N-allenylpyrrolidone involves both 1,2- and 2,3-positions of the allenyl substituent to give four types of units as a result of prototropic isomerization of the initially formed structures. In the developed method, the composition of co-oligomers can be controlled and, hence, their hydrophilic/hydrophobic balance, solubility, and membranotropic properties can also be controlled to change the potential biological activity of the products.

Zinc(II) and cobalt(II) complexes of N-allylimidazole, bis(N-allylimidazole)zinc diacetate (1) and bis(N-allylimidazole)cobalt dichloride (2), have been prepared and characterized by X-ray crystallography, NMR, FTIR spectroscopy, microanalysis and melting point. The single crystal X-ray diffraction analysis confirms that compounds 1 and 2 are monomeric with tetra-coordinate zinc and cobalt centers. Complexes 1 and 2 have been tested using four in vivo models of acute hypoxia of different genesis (hypobaric, hemic, histotoxic, hypoxia with hypercapnia). Complex 1 reveals a moderate effect against the hemic and histotoxic hypoxia, and a high effect against the hypobaric hypoxia and hypoxia with hypercapnia, while complex 2 demonstrates a high antihypoxic activity in all the studied models.

The directed synthesis of new pharmacophoric molecules is one of the urgent tasks of organic chemistry. A special place in this area is occupied by vital nitrogen-containing heterocycles and their derivatives, on the basis of which new promising precursors of drugs are created. For example, pyridinium salts are part of such well-known drugs as pyridoxine, mexidol and metadoxine. Phosphorus-containing pyridine derivatives, among which compounds with cytotoxic and antimicrobial properties have been identified, are also being actively studied now. Thus, the development of convenient approaches for obtaining new functional phosphorus-containing pyridine derivatives is an important and timely task. Special attention is paid to synthetic methods that correspond to the PASE (pot, atom and step economy) paradigm. Using this approach, we have synthesized hydrochlorides and tosylates of 4-bis(2-phenylethyl)chalcogenophosphoryl-pyridine, not described previously, by practically quantitative interaction of the available 4-bis(2-phenylethyl)chalcogenophosphorylpyridines with hydrochloric or 4-methylbenzenesulfonic acids at room temperature or slight heating (40-45 °C). The reaction proceeds regioselectively on the nitrogen atom of the base pyridine. The second reaction center in the 4-bis(2-phenylethyl)chalcogenophosphorylpyridine molecule, chalcogenophosphoryl group, does not participate in the studied process, even when using an excess of hydrochloric acid. The starting 4-bis(2-phenylethyl)chalcogenophosphorylpyridines are easily obtained on the basis of the original reaction of pyridine with secondary phosphine chalcogenides with the assistance of electron-deficient acetylenes. Using the example of microorganisms of different taxonomic groups: Bacillus subtilis B-406, Enterococcus durans B-603, Penicillium citreo-viride F-1777, Escherichia coli B-1238, we have found that the target hydrochlorides and tosylates of 4-bis(2-phenylethyl)chalcogenophosphorylpyridine exhibit pronounced antimicrobial activity against non-spore gram-positive microorganisms.

Aim . To study the associations of allelic variants of the CYP2C19 gene with atherosclerotic lesions of the coronary arteries in patients with acute coronary syndrome (ACS) in the North of Siberia (Surgut) and in large cities of the Siberian Federal Okrug (SFO). Material and methods . During the study 296 patients with ACS were examined at admission to cardiology hospitals in large cities of the North (Surgut, 114 patients) and SFO (Irkutsk and Kemerovo, 182 patients). All patients underwent coronary angiography and genetic research (identification of CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles). Results . In patients with ACS living in the North of Russia allelic variant CYP2C19*17 (*17/*17) is positively associated with the severity of lesion of left coronary artery (LCA) ( χ 2 =9,81; p=0,002), as well as with at least 50% stenosis, more than 70% lesion of the proximal or middle part of the three main arteries, or more than 50% lesion of LCA trunk ( χ 2 =6,52; p=0,011), and previous myocardial infarction ( χ 2 =8,15; p=0,004). Among patients with ACS living in cities of the Siberian Federal Okrug, the allelic variant CYP2C19*17 (*17/*17) is directly associated with diabetes mellitus ( χ 2 =5,48; p=0,019) and less than 45% left ventricular ejection fraction ( χ 2 =4,20; p=0,040). Regression analysis showed that in patients with ACS living in the northern region of Russia, only the allelic variant CYP2C19*17 (*17/*17) correlated with at least 50% stenosis of LCA trunk (Exp (B): 11,623, 95% CI: 1,893; 71,342; p=0,008). It did not correlate with the male sex, age, smoking and diabetes (p>0,05). Conclusion . The results show the presence of direct associations of CYP2C19*17 alleles with prognostically unfavorable coronary atherosclerosis in ACS patients living in the North of Siberia.

Relevance: despite the improvement of surgical techniques, the number of postoperative complications in surgical interventions on the trachea remains high. One of the ways to improve the results of treatment is the development and study of new surgical interventions. Aim: The work is devoted to the study of the topographic and anatomical features of the structure of the rat trachea Materials and methods: The study was performed using rats of the Wistar line and was approved by a local ethical committee. Methods of descriptive anatomy and morphology were used. Results: the obtained results made it possible to reveal features of the topographic-anatomical structure of the rat trachea: the presence of hyaline cartilages in the form of a ring; grown-up cartilaginous rings forming the fusion of the X, Y, W forms; in the submucosal layer of the trachea there are multiple clusters of mucoses associated with lymphatic tissue; pronounced venous traheoidesis plexus; developed, dense adventitia of the trachea. In rats, the epithelial transition from a multilayer flat non-coronary to a single-stranded thief-synchoid occurs below the vocal cords. According to the histological structure, the rat trachea wall is close to the human trachea, has adventitia, a cartilaginous framework, a submucosal osseous and a mucous membrane. Conclusion: these features of the structure of the trachea of ​​Wistar rats allow them to be used to model pathology of the trachea and to develop surgical interventions.

The narrowing of the lumen of the trachea due to cicatricial stenoses of the trachea is one of the urgent problems of the modern surgery. The processes taking place in the trachea and lungs lead to a change in the state of the immune system. Assessment of the dynamics of indices of nonspecific resistance is one of the methods for assessing the severity of the course of the disease. We studied the indices of nonspecific resistance of the organism in narrowing the lumen of the trachea in an experiment in the early postoperative period. The study was carried out on the basis of the scientific department of experimental surgery with the vivarium of Irkutsk Scientific Centre of Surgery and Traumatology, on 24 white male Wistar rats with a body weight of 300–350 g. We simulated narrowing the lumen of the trachea by placing a silicone tube in the lumen of the trachea for 14 days. The parameters of phagocytosis, the state of phagocytic activity of blood neutrophils, spontaneous NBT-test, induced NBT- test were studied. The animals were withdrawn from the experiment on the 3rd, 7th and 14th day. We revealed that as a result of narrowing of the lumen of the trachea with the original procedure, the nonspecific resistance of the organism was violated with inhibition of the phagocytic activity of leukocytes. There was inhibition of phagocytic activity of leukocytes and depletion of the functional reserve of leukocytes.

Aim. To evaluate the level of circulating free nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) in hypertensive patients with high cardiovascular risk.Material and methods. The study included 70 patients, of which 51 were patients with hypertension (HTN) and 19 were healthy. The study of the level of circulating free nDNA and mtDNA was carried out using quantitative polymerase chain reaction (PCR). Additionally, demographic data, comorbidities, risk factors, heredity, results of complete blood count and biochemical blood tests, electrocardiography and echocardiography were analyzed.Results. The level of nDNA in HN patients was significantly higher than in healthy patients: Me (LQ; UQ) — 227 (110; 370) copies/mL and 88 (62; 116) copies/ml, respectively (pConclusion. The level of circulating free DNA in hypertensive patients with very high cardiovascular risk is significantly increased, and therefore this parameter can be a cardiovascular risk marker.

Aim. To systematize information about levels of evidence of studies devoted to surgical pathology of spleen. Material and Methods . Medical literature in various search systems was analyzed (PubMed search system, The Cochrane Library, academic electronic library eLibrary.ru) using the following keywords: spleen diseases, hyposplenism, hypersplenism, abscess, cyst, echinococcus, parasitic cyst, spleen trauma, spleen rupture, non-surgical treatment. The search results were correlated with ICD-10 according to evidence-based value. Results. Analysis included 36 publications, including 6 literature overviews with meta-analysis, 12 prospective studies and 18 retrospective studies. Evidence was found that preservation of spleen tissue with arterial blood supply rather than autotransplantation prevents development of postsplenectomy hyposplenism. Conservative tactics in spleen pathology benefits from endovascular blood circulation reduction, radiofrequency ablation and minimally invasive surgery. Vaccination prior to splenectomy and preventive antibiotic therapy after splenectomy reduce the lifetime risk of peracute infection. Non-surgical treatment of damage is a standard maneuver. Conclusion. Evidence-based medicine of spleen diseases remains rare. Possibly, because of this, the reduced quality of life after splenectomy vs. conservative operations has not been proven for the majority of conditions. Further carefully planned studies will be able to test this hypothesis in relation to surgical spleen pathology.

We studied capabilities of confocal laser scanning microscopy in the analysis of lipid droplets volume and of quantity of functional mitochondria and reactive oxygen species production in liver cells for early diagnosis of cytochemical disturbances at dyslipoproteinemia (16 days of experiment). The results showed the increase of lipid droplets volume in hepatocytes, decrease of functional mitochondria and increase of reactive oxygen species production. We evaluated the potential of real-time PCR method in the analysis of mitochondrial DNA of blood plasma at early stages of dyslipoproteinemia and in experimental infarction. On the background of registered blood lipid metabolism disorders and structural and functional changes in liver cells, we determined the tendency to three-time increase in concentration of circulating cell-free mtDNA on the 16th day of dyslipoproteinemia as compared to the control data. We used a model of myocardial infarction to show statistically significant increase in the level of circulating cell-free blood mtDNA from 48 hours after adrenaline injection and we found that this level maintained up to 144 hours after adrenaline injection. Obtained data can serve as a basis for creation of technologies for diagnostic monitoring of atherosclerosis and myocardial infarction severity.

The device for cell encapsulation makes it possible to fabricate microcapsules of a preset size with even smooth surface, without defects or adhesion to each other, with viable cells inside the capsule. The cells were derived from newborn piglet pancreases.

Organic superbase DBU, 1,8-diazabicyclo[5.4.0]undec-7-ene, readily annulated with aromatic cyanopropargylic alcohols nder mild conditions (CH2Cl2, 20–25 °C, 30 min) to afford new cyanomethylideneperhydro[1,3]oxazolo[2’,3’:2,3]pyrimido-,2-a]azepines.

For the first time [4+2]-cycloaddition reactions were carried out between furfuryl vinyl ethers and typical dienophiles and heterodienes proceeding in uncatalyzed conditions and resulting in previously unknown heterocyclic systems containing either free vinyloxy groups or furfuryl substituents. With maleic anhydride and maleimide furfuryl vinyl ethers afforded 1-(vinyloxyalkyl)tricyclodec-8-ene-3,5-diones in up to 72% yields, and with N-benzylideneaniline or acrolein the corresponding functionally substituted tetrahydroquinolines (yield up to 65%) or 3,4-dihydropyrans (yield 23–50%) were obtained.

This review analyzes methods of measuring hemostasis parameters and the characteristics of medical technologies used for assessment of the coagulation and thrombocyte-vessel components of hemostasis. The optimum means and are of decisive importance in selecting the correct method for monitoring measures of hemostasis during anticoagulant and antiaggregant treatment, which is particularly important in clinical practice as a tool for he prophylaxis of thrombosis. Particular attention is paid to measuring devices used at point-of-care locations or at the bedside as a contemporary trend to portability and simplification of the use of instruments.

Genetics of arterial hypertension is broadly discussed as of one of multifactorial diseases. Invention of an algoritm for risk stratification based upon genetic parameters, gives chance to select groups of higher essential hypertension (EH) risk with the aim of primary prevention. One of such prototypes was assessed, that inculdes 11 genetic markers, in 30 patients with known clinical parameters; 19 of those were with EH and 11 normotonics. Individual impact is assessed of each marker and comparison done for total risk in patients. As a result, there were no differences found in individual risk for patients with and without EH by 11 markers, between subgroups. There was protective effect found for the allele С rs1799998 of gene CYP11B2 (OR 0,247; CI=[0,081-0,754], p=0,01).

HGF is one of the factors taking part in regeneration and recovery of liver after injury. The article is dedicated to the study of influence of single HGF intake on the indices of non-specific immune response in rats after 70% liver resection in the early postoperative period. Research was conducted on 42 six-months white male Wistar rats of 250–300 g. It was revealed that level of segmentonuclear neutrophils and lymphocytes in the group with HGF intake stand at normal level on the 2nd day and normalizes to the 11th day that testifies to the decrease of inflammatory response. Increased level of leukocytes and monocytes is registered in the group with HGF intake. Also integrity of non-specific resistance in the early postoperative period on the 2nd day is registered. Suppression of phagocytosis indices with preservation of functional activity of phagocytes was registered to the 11th day.

Polyquaternization reactions of bis[2-(4-pyridyl)ethyl]phenylethylphosphine oxide and tris[2-(4-pyridyl)ethyl]phosphine oxide with 1,4-dibromobutane were implemented for the first time to give linear (water-soluble) and cross-linked (limitedly water swelling), respectively, representatives of new phosphorus- and nitrogen-containing ionenes. The synthesized linear ionenes react with heparin and polyacrylic acid yielding water-insoluble polyelectrolyte complexes.

Changes in the level of blood cell-free circulating mitochondrial DNA were examined during experimental adrenaline-induced myocardial injury in rats. The amount of mitochondrial DNA in the blood was significantly elevated at 48 and 72 h after subcutaneous injection of adrenaline solution, and it was accompanied by development of multiple small-focal myocardial ischemia. This suggests that the measured level of blood cell-free circulating mitochondrial DNA might be used as a biomarker of acute myocardial ischemia.

The history of creation and the main aspects of work of the Department of Biomedical Research and Technology of the Irkutsk Scientific Center for the first 5 years is described. Selected as a methodological framework, the concept of translational medicine has provided, on the one hand, a wide range of research, on the other hand it brought the fundamental research to clinical testing on the basis of Hospital of the Irkutsk Scientific Center of the SB RAS. The materials included in the presented collection were announced.

Purpose of the study. To rate prognostic properties of changes in mitochondrial DNA concentration in the blood plasma of patients with chronic cerebral ischemia and ischemic heart disease in relation to the disease and the effectiveness of the therapy. Materials and methods. The study involved patients suffering from coronary heart disease (CHD) and chronic cerebral ischemia (CCI) with stable and unstable atherosclerotic plaques, who have signed informed consent to the data processing within the framework of scientific research. The patients were admitted to the hospital for examination and treatment of CHD and CCI in Cardiology and Neurology Unit of the Hospital of ISC SB RAS. The subjects underwent laboratory and instrumental examination and analysis of the level of free circulating serum mitochondrial DNA by real-time PCR (copies/ml). The examination results considered as satisfactory were compared with the mtDNA levels before and after the treatment. Results. The average value of the mtDNA levels before and after the treatment in patients of neurological and cardiological profile were significantly different: 1 093 686 copies/ml vs 418 046 copies/ml, respectively (p = 0.02). Unlike women, men mtDNA levels statistically significantly (p = 0.03) decreased after the treatment. We revealed statistically significant differences in mtDNA level indicators before and after the treatment, depending on the definition of the series (p = 0.0010) for rank test Kruskal – Wallis test. The results of the proposed research will help to identify prognostic factors of destabilization of cell damage and plaques in endothelial dysfunction, atherosclerosis and its complications, to conduct clinical test of the method for predicting and diagnostics of cellular damage in chronic ischemia on a background of atherosclerosis.

Aim: to reveal the association of gene CYP2C19 polymorphisms and efficacy and safety endpoints of clopidogrel therapy in patients with acute coronary syndrome. Materials and methods. A total of 431 patients with acute coronary syndrome undergoing coronary stent placement was studied. CYP2C19 polymorphisms (*2, *3, *17) were evaluated, platelet aggregation with ADP and efficacy and safety for 30 days after coronary stent placement was studied. Results. Within the selected patients there was no significant association between carriage of at least one allele of the CYP2C19*2, and/or CYP2C19*3 and paradoxical response to clopidogrel. Significant association between carriage of allele CYP2C19*17 and the presence of bleeding was detected. The algorithm for selection of individual drug therapy for patients receiving clopidogrel therapy was developed. Conclusion. The results can be extremely important for decision-making about the strategy of dual antiplatelet therapy and the tactics of choice of drugs.

Purpose of the study. To test the functional associations of polymorphic variants of genes in the regulation of blood pressure and vascular tone in employees of the ISC SB RAS. Materials and methods. The study involved patients, employees of the ISC SB RAS, being under care of the outpatient clinic of the Hospital of the ISC SB RAS. During routine laboratory testing the patients were taken 2 ml of blood for genetic analysis and further molecular genetic study on “Hypertension”, “Endothelial dysfunction”, “Pharmacogenetics”, “Inflammatory response” panels. Results. In the analysis of 12 genes coding for key proteins of hormonal enzyme blood pressure regulation systems, polymorphism of CYP11B2 showed statistically significant correlation with the presence of arterial hypertension, which makes its further study promising. The presence of allele C showed protective significance in relation to the development of hypertension with OR = 0,247. When checking associations of functional polymorphic variants of genes, the products of which are involved in the regulation of vascular tone, with hypertension in patients younger than 50 years old we found association of T/T rs5443GNB3 genotype with the debut of hypertensive disease under the age of 50. The data obtained allow the doctor to choose the most personalized and effective safe drug from certain groups, as well as its dose for employees having passed molecular genetic testing. These data can reveal predisposition to the most widespread and socially significant diseases in the surveyed subjects and provide specific personalized recommendations for the prevention of these diseases.

Secondary phosphine selenides reacted as selenating agents with benzoylphenylacetylene in wet acetonitrile (70–72°C) to give bis(2-benzoyl-1-phenylvinyl) selenide in up to 43% yield.

Contexte Les anticoagulants reduisent le risque de complications thromboemboliques veineuses apres traumatisme isole du membre inferieur.

Using methods of nuclear medicine in experiment, we studied pathophysiologic mechanisms of bacteriemia in disseminated peritonitis in various laboratory animals. The results give grounds to consider regularities revealed to be universal.

Aim. To reveal the association of gene polymorphism CYP2С19*2 and recurrent early stent thrombosis in coronary vessels, and paradoxal response to clopidogrel intake in patients — the inhabitants of Siberian Region — after acute coronary syndrome. Material and methods. Totally 105 patients studied, hospitalized for stenting of coronary arteries in acute coronary syndrome, never received clopidogrel previously. The polymorphism of studied СУР2С19: *2, *3, *17 alleles, as assessment of platelet aggregation with ADP before and after clopidogrel intake, as of endpoints on safety and efficacy during 30 days (thrombotic complications, bleeding). Results. Within the selected patients there was no any significant association of any CYP2С19*2 and/or CYP2С19*3 alleles and paradoxic laboratory reaction. There was significant association of the CYP2C19*17 gene carriage and bleedings. When comparing the groups of patients having or not having complications related to clopidogrel (thrombotic or bleedings), there was significant difference in residual platelet aggregation. Conclusion. The results of the study might be strongly significant for the decisions making on double antiplatelet therapy and on the tactics of drugs preference.

Based on an analysis of results of treatment of 184 patients the authors make a conclusion that staged surgical correction is an expedient method for traumas of the abdomen and acute intestinal obstruction with necrosis of the bowel.

Целью исследования была проверка гипотезы о том, что развертывание в регионе специализированной помощи пострадавшим с сочетанной травмой существенно улучшает результаты лечения по сравнению с таковыми при оказании квалифицированной помощи. В рамках разработанного ранее авторами протокола мониторинга сочетанной травмы (МОСТ) обследованы региональные центры Сибирского федерального округа - Барнаул (специализированная помощь пострадавшим), Иркутск и Улан-Удэ (оба - квалифицированная помощь). Проведен сравнительный анализ распределения пострадавших по полу, возрасту, механизму травмы, ведущему повреждению, тяжести повреждений, летальности. Исследованы эпидемиологические характеристики сочетанной травмы. Наибольшая заболеваемость отмечена в Иркутске - 165 на 100 000 населения, наибольшая смертность - также в Иркутске (58,6 на 100 000). Выявлено, что общая летальность при сочетанной травме, госпитальная летальность, а также летальность при крайне тяжелых повреждениях в Барнауле была статистически значимо ниже, чем в Иркутске и Улан-Уде. Таким образом, развертывание специализированной помощи пострадавшим позволило существенно снизить летальность, что является основным критерием эффективности оказываемой помощи.