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The results of the atomic absorption analysis of the elemental status of pigs of Kemerovo breed are presented. The studies were carried out in pig farm in Kuzbass. Organ samples from pigs were taken immediately after slaughter and analyzed at the Analytical Center for Collective Use of the Sobolev Institute of Geology and Mineralogy (ACCU Sobolev IGM SB RAS) by atomic absorption spectrometry with flame and electrothermal atomization using SOLAAR M6 spectrometer (USA) according to State Standard 26929-94 “Raw food and food products. Cadmium levels in bristles (W=0.94, p>0.05) and kidneys (W=0.92, p>0.05) were characterized by normal distribution. In the breeding zone of the Kemerovo breed, the content of heavy metals in soil, water and feed was studied, which did not exceed the MPC. The mean cadmium levels in the kidneys and spleen were within the standard intervals established for pigs. Cadmium levels in the spleen and bristle were characterized by a smaller interquartile range relative to the kidneys. The obtained data on the concentration of cadmium in the organs and bristles of pigs of the Kemerovo breed can be used for the intravital assessment of the interior of animals.

The article substantiates the relevance of the study of the Soviet experience in the development of industrial and labor potential in order to use it in modern conditions; revealed objectively existing signs inherent in the socio­economic situation in Russia both in the Soviet period and at the present time; a historiographic analysis of the history of the economic development of the USSR was carried out; the practice of creating in education system that made it possible to achieve the goals of industrialization and socio­economic development of the USSR was studied. The study was conducted by the team of authors of the federal state budgetary educational institution of higher education «State University of Management» as part of the execution of the state task of the Ministry of Science and Higher Education of the Russian Federation No. 075­03–2022–156 / 6 dated 09.21. Economic and Industrial Potential of the Russian State under the Technological Blockade and Western Sanctions: Soviet Experience and Modern Solutions.

The article presents the generalized results of a survey of universities as part of the regular labor market monitoring conducted by the Council for Professional Qualifications in the field of HR management. The survey data made it possible to draw a number of conclusions about the current state and quality of training in the field of HR management (current educational programs, forms and level of interaction between universities and employers, the demand for graduates and the compliance of their qualifications with the requirements of employers and professional standards), to identify the most significant problems and their causes, as well as assess the prospects (including the future of professional and public accreditation of educational programs, independent assessment of the qualifications of graduates, as well as the feasibility of maintaining HR management as an independent area of professional training) and the conditions for their implementation.

An important task of mechanics of synthetic fishing twisted rope and string products and braided cords is to create a fundamental basis for describing their fracture processes during deformation in operation, i.e. to develop a framework for fracture mechanics (building models and algorithms for calculating structures and technological processes at large plastic deformations, taking into account fracture). There is considered the necessity of developing and introducing the simple and at the same time effective criteria of destruction, allowing to estimate reliably the conditions of safe operation of twisted rope and string products, threaded products and braided cords and especially the structures of industrial fishing gear. Determination of stress concentrations, is an obvious task in connection with the creation of new fishing trawls, purse seines and grips with complex shape-changing geometry. This problem is actual for many branches of industry, including transport and machine-building, where at the designing stage it is necessary to take into account possible emergency situations caused by intensive dynamic effects in twisted rope and string, threaded products and braided cords. Components and structures of twisted rope and string products, threaded products and braided cords should withstand the specified loads in a wide range of loading rates. In particular, the theory allows to solve nonlinear problems, taking into account changes in geometry of deformable twisted rope and string products, threaded products and braided cords, as well as to obtain analytical solutions of various problems.

To date, there is no registered injectable dosage form of levocarnitine for veterinary use on the territory of the Russian Federation. Based on the above, the purpose of our work was to conduct preclinical studies of L-carnitine of subchronic toxicity for veterinary use in laboratory animals. Experiments to test the toxicity were performed on outbred rats in October 2021 at the vivarium of St. Petersburg State University of Veterinary Medicine. The study involved females weighing 190210 grams, purchased from RAPPOLOVO Laboratory Animal Nursery. To study subchronic toxicity via subcutaneous injection, L-carnitine was administered in 2 dose levels. The doses were determined based on the results of the acute toxicity experiment: 1/5 and 1/10 of the maximum tolerated dose. The first experimental group (n=10) received the drug subcutaneously at a dose of 0.08 mg/kg (1/5 of 2000 mg/kg). The second experimental group (n = 10) received the drug subcutaneously at a dose of 0.04 mg/kg (1/10 of 2000 mg/kg). The control group (n = 10) received sodium chloride 0.09 % subcutaneously at a dose of 1/5 of 2000 mg/kg. The drug was administered subcutaneously daily for 42 days. Killing and blood sampling from the second half of the animals was carried out after assessing the recovery period (10 days after drug cancellation). As a result of studies of subchronic toxicity of subcutaneously administered L-carnitine for veterinary use in laboratory animals, it was found that the dosage of 1/5 of the maximum tolerated, and the dosage of 1/10 of the maximum tolerated, do not cause external signs of toxicosis and death of rats. No significant changes in the hematological parameters of blood of animals from the experimental and control groups were found.

The article describes the case of Daria D., 23 years old, who has been using various drugs (LSD, marijuana, mephedrone) for a number of years and independently abandoned using drags with the transition to the use of microdoses of red fly agaric (Amanita Muskaria). Her mental and addictive status is analyzed. It is concluded that, despite the systematic use of drugs, there are no grounds for making Darya D. a psychiatric or addiction diagnosis.

Abstract The development of CAR-T specific therapy made a revolution in modern oncology. Despite the pronounced therapeutic effects, this novel approach displayed several crucial limitations caused by the complications in pharmacokinetics and pharmacodynamics controls. The presence of the several severe medical complications of CAR-T therapy initiated a set of attempts aimed to regulate their activity in vivo. We propose to apply the barnase-barstar system to control the cytotoxic antitumor activity of CAR-T cells. To menage the regulation targeting effect of the system we propose to use barstar-modified CAR-T cells together with barnase-based molecules. Barnase was fused with designed ankyrin repeat proteins (DARPins) specific to tumor antigens HER2 (human epidermal growth factor receptor 2) The application of the system demonstrates the pronounced regulatory effects of CAR-T targeting.

In the article, the authors conducted a comprehensive study of the interior, including biochemical, physiological, physicochemical, cytogenetic, and other indicators in sheep of the Romanov breed of Western Siberia. For the study, blood serum samples were taken from 10 rams-producers and 30 lambs at four months. Conventional methods took blood samples. Analyses were performed in the biochemistry laboratory of Novosibirsk State Agrarian University using the technique of competitive enzyme immunoassay with the reagent kit “SteroidIFAtestosterone” for the quantitative determination of testosterone concentration in blood serum. In the sheep breeding area, the authors constantly monitored the content of heavy metals in water, soil, feed, organs, and tissues. The concentration of chemical elements did not exceed the permissible exposure limit. Enzyme-linked immunosorbent assay was performed on a Thermo Scientific Multiskan FC analyzer. The authors performed statistical processing of experimental data using standard methods of descriptive statistics, the statistical programming language, or the RStudio data analysis environment (using the functions DescrStats, Summary, Sd, Read. Table, Write. Table, Aes). The authors established the influence of the age of ontogenesis on the testosterone content in Romanov rams. Presented figure with two variation curves with high transgression. The average testosterone level was 1.8 times higher in lambs (0.774 mmol/l) than in lambs. Testosterone concentration was characterized by high phenotypic variability. The authors have identified reference intervals for testosterone in blood serum depending on environmental conditions in sheep of the Romanov breed of Western Siberia.

Results of the evaluation of copper levels in the liver, kidneys, lungs, and spleen of Landrace pigs are presented. Studies were performed on clinically healthy six-month-old animals bred in a large pig farm in Altai Krai. Animal housing conditions were standard, typical for meat-fattening feeding was used. The authors performed an elemental analysis of samples of parenchymal organs using atomic absorption spectrometry with flame and electrothermal atomization. The data were processed using Microsoft Office Excel and the R programming language in the RStudio data analysis environment version 2022.07.2+576 (RStudio, PBC). It was found that the distribution in the case of copper accumulation in the kidneys and lungs was different from usual, and the dispersions were not homogeneous. Based on the mean value and median, the authors established an increasing ranked series of the copper content in the organs: spleen < lungs < kidneys < liver, in numerical terms: 1: 1.1: 6.4: 7.5. Median copper values in the liver, kidneys, lungs, and spleen were 6.25; 5.02; 0.88; and 0.83 mg/ kg, respectively. More excellent uniformity is characteristic of copper accumulation in the lungs and spleen. Using the Kraskell-Wallis criterion, we found that the collection of copper varies significantly in the organs under study (H = 80.03, df = 3, p < 0.0001). Pairwise comparison showed significant differences for pairs: “liver - lungs” (p < 0.0001), “kidneys - lungs” (p < 0.0001), “liver - spleen” (p < 0.0001), “kidneys - spleen” (p < 0.0001). Cluster analysis revealed two groups: “lungs - spleen” and “liver - kidneys,” which differ significantly in the level of copper accumulation. The data obtained can be used to calculate the corresponding standard values of the copper content in the liver, kidneys, lungs, and spleen of Landrace pigs under the conditions of Western Siberia.

The object of this study is contemporary Russian-Latin American relations. The influence of the current international context related to the crisis around Ukraine on Russia's strategic partnerships (SP) with a number of Latin American states is considered in detail. The first part reveals the specifics of this relationship format. The second part analyzes the dynamics of the dialogue with Argentina, Brazil, Bolivia, Venezuela, Cuba, Nicaragua, Peru and Ecuador, depending on the depth of the impact on them of the confrontation between Russia and the West after the start of the Russian special military operation in Ukraine. In conclusion, the work highlights similarities and differences in the lines of conduct of Russia's Latin American strategic partners in today's conflicting international political conditions. This study is one of the first attempts to comprehend the effects of the Ukrainian crisis on the state and possible future of strategic partnerships between Russia and nations of the LAC region. A new look at the issue, involving systematic approach and case study method, which allows analyzing and including each national example of bilateral strategic partnership in the broader context of the dialogue between the Russian Federation and Latin America, determines the author's contribution. Main conclusions are as follows. First, although the reaction of Russia's strategic partners to the Ukrainian crisis and its global consequences varies, their common desire to maintain the momentum of mutually beneficial cooperation with Russia is noticeable. Secondly, within strategic partnerships, one can single out a material and symbolic components, and it is on the second that the complication of the international context has hit the hardest. Finally, the current situation clearly requires Russia to revise its Latin American strategy, the first step of which could just be a rethinking of the SP format.

The aim: Pharmacoeconomic substantiation and marketing research of immunoprotective phytopreparations in Ukraine to substantiate rational pharmacotherapy of the effectiveness of immunomodulatory drugs of plant origin and pharmaceutical care of patients to strengthen individual immunity. Materials and methods: Research materials - data from the State Register of Medicinal Products of Ukraine; information content of the Public Health Center of the Ministry of Health of Ukraine; data of the State Register of Wholesale Prices for medicines declared in Ukraine under the international non-proprietary or common name as of 01.01.2023. Research methods: theoretical analysis of scientific sources, systematic, retrospective, descriptive and frequency analysis of information resources of databases; pharmacoeconomic analysis, marketing analysis of positioning in the pharmaceutical market of Ukraine to substantiate rational pharmacotherapy and the effectiveness of immunomodulatory drugs of plant origin to strengthen individual immunity. Results: Theoretical analysis and pharmacoeconomic substantiation of rational pharmacotherapy of efficiency of application of drugs of immunomodulatory action of plant origin and pharmaceutical care for strengthening of individual immunity of patients is carried out. The algorithm of pharmacoeconomic analysis of the use of immunomodulatory phytopreparations to ensure rational pharmacotherapy and pharmaceutical care of outpatients is substantiated. To substantiate the availability of effective immunomodulatory phytopreparations for patients, marketing research on the use of immunomodulatory phytopreparations in Ukraine has been conducted. Conclusions: The theoretical analysis shows that the use of immunomodulatory drugs of plant origin is appropriate in rational pharmacotherapy to strengthen the individual immunity of patients, which is especially relevant in an exacerbation of the epidemic situation caused by the spread of infectious diseases of viral origin. An algorithm of pharmacoeconomic substantiation has been developed, which provides an opportunity to confirm the therapeutic efficacy and pharmacoeconomic feasibility of immunomodulatory phytopreparations for rational pharmacotherapy and pharmaceutical care of patients. The results of marketing research provide an opportunity to determine the availability (positioning and price range) for patients of effective immunomodulatory phytopreparations in Ukraine and outline the prospects for pharmaceutical development and registration on the pharmaceutical market of Ukraine of new effective immunomodulatory drugs of plant origin.

Performance of external longitudinal and transverse forces developed in the course of towing the trawl systems, namely, the tension and compression forces of cables, ropes and yarns of the rope-net gears in commercial fishing of the longitudinal modulus of elasticity and the transverse modulus of elasticity in the cordage products. Physical and mechanical properties of the synthetic nylon threads, ropes and nylon cords, from which most trawl systems are made, are considered. Analysis of the physical and mechanical properties of synthetic rope products and cords based on the specified parameters for possible static and dynamic loads is proposed. Algorithms for calculating the physical and mechanical properties of threads, ropes and nylon cords are proposed under the condition of constant volume and mass. Method of calculating physical and mechanical properties of the nylon threads and ropes under the condition of uncertainty gives an error not exceeding 0.4% in calculating the relative elongation δε, but the maximum error δμ in calculating Poisson's ratio μ reaches 7.12%. This proves that the formula for calculating the Poisson's ratio μ for anisotropic bodies does not allow estimating this ratio at low loads and constant volume.

One of the new linguocreative practices of organizing the city space as a cultural text is analyzed. The game discourse of polycode texts is considered, which combine elements of different semiotic systems: signs of traffic rules, supplemented by visualized symbolic allusions and quotations, collectively referring to the motifs of famous works of art. The constructive principles of modeling the associative context of polycode posters placed in the Literary Quarter of Yekaterinburg are characterized. The universality of the generation of game texts of any semiotic nature on the basis of an operational technique that creates the effects of associative deducibility and associative integration is substantiated. The novelty of the study is related to the description of the algorithm for creating and deciphering a game polycode text of this type, identifying the factors and strategies for reading it by the addressee. The dynamic component of the semantic diversity of the analyzed texts is experimentally verified, taking into account the respondents’ recognition of the prototypes of the game transform, reflection on the connection between its visual and verbal components, and the ability to derive allusive implicatures. Particular attention is paid to the analysis of game transform decoding strategies in the light of the mechanisms of linguocreative thinking based on the switching of associative stereotypes in the language game register.

There is a paradox when protective IgG antibodies to the SARS-CoV-2 virus are detected only in a part of patients who have contracted COVID-19. At the same time, some persons who were in contact with the infected, but did not get sick with COVID-19 (without disease symptoms, PCR negative), still produce IgG antibodies to the SARS-CoV-2 virus. The presence of IgG to the SARS-CoV-2 virus correlates with a changed immune response when infected with seasonal viral diseases - in particular, the ability to produce protective antibodies decreases. All this determines the different clinical course of the disease and the features of the patient’s post-COVID conditions (PCC). To study various immune responses of patients and asymptomatic carriers of COVID-19, 414 people were examined. The novelty of the study is that, for the first time, not only the levels of protective IgG antibody titers to the SARS-CoV-2 virus were determined, but also their correlation with the markers of lymphocyte activation CD25, CD54 (ICAM-1) and CD95 in patients who did not suffer from COVID- 19, got sick with COVID-19 and just had a heart attack. Research has scientific and practical goals, including the search for new therapeutic opportunities. Our attention was drawn to the domestic multitarget immunotherapy drug Mercurid (RP UA6098/01/01). Its ability to control T-lymphocyte activation molecules and modulate their activity was studied. The therapeutic efficiency of Mercurid was 75.6 %.

The article deals with modern problems of perception and implementation of the basic principle of therule of law through correlation with the constitutional and legal concept of parliamentarism, proposed as alever to improve the efficiency of lawmaking procedures and the formation of an internally stable and fairstate mechanism. Attention is drawn to the practical difficulties of comparing the terms under consideration,associated with different national perceptions of the concept of the rule of law; with the debatable definitionof the justice of the law; with the presence of an often subtle difference between the legal force of a law anda by-law; with the intrusion of the judiciary and executive power into the prerogatives of the legislator; withthe processes of globalization, putting supranational bodies above parliaments; with chaos, inconsistency,irrationality and a significant amount of legal norms, as well as a variety of areas of legal regulation in themodern state. At the same time, the article notes positive trends in the convergence of legal structures ofthe rule of law and parliamentarism, associated with the emergence of legal levers to ensure the reality ofthe rule of law (law), including constitutional justice, supranational bodies; awareness of the inextricablerelationship between the rule of law and the implementation of human rights, the separation of powers,the accessibility and fairness of the court, the responsibility of the authorities; posing the question of theeffectiveness of legislation.

The article is devoted to the analysis of current trends in the field of clinical psychiatry. Using the example of borderline personality disorder, in which verbal hallucinations are observed, the problem of qualifying psychotic symptoms in non-psychotic disorders is discussed. The question is raised that such phenomena can be considered either as diagnostic errors or as a new psychiatric reality.

BACKGROUND: Food allergy is an actual problem in pediatric practice. In recent decades, there has been an increase in the prevalence of food allergies, as well as an increase in the number of severe cases. AIM: To assess the prevalence of food allergy and the role of hereditary and environmental factors in food allergy development in children according to epidemiological cohorts and cross-sectional studies. MATERIALS AND METHODS: A systematic review of epidemiological cohorts and cross-sectional studies published between January 1, 2000 and December 31, 2021, was conducted This review investigated the developmental factors and prevalence of food allergy. RESULTS: This review made it possible to generalize and systematize the accumulated worldwide scientific data on food allergy. An analysis of epidemiological studies revealed a significant prevalence of food allergy, which reflected the natural course of the disease; the highest rates were found among young children, and by school age, the prevalence of symptoms and confirmed food allergy is gradually decreasing. Based on epidemiological data, the main risk factors for food allergy are hereditary predisposition and environmental factors that modify the microbial environment. CONCLUSION: It is necessary to further study the genetic markers of food allergy, as well as the role of microbiotic factors in the implementation of hereditary predisposition to allergic diseases.

The authors presented the haematological blood parameters of Romanov breed sheep and their association with genotypes according to the β-lactoglobulin locus. Blood plays a significant role in the body as metabolism is carried out. It delivers nutrients and oxygen to the cells of the body organs and removes metabolic waste products and carbon dioxide. The intensity of the metabolic processes can be judged from haematological data. Since blood enzymes, their activity, metabolic levels, and biochemical adaptation are encoded in their genes, the authors believe that the biochemical composition of blood in animals is, to a certain extent, related to their breeding and productive qualities. Identifying patterns of relationship and influence of genetic factors in breeds of different animals is one of the main tasks in the study of breeding features and further improvement and control of breed peculiarities of animals. For our analysis, 40 blood samples were taken from Romanov breed sheep for haematological tests, DNA extraction and PCR. DNA technology in conjunction with other factors should be used to improve the breeding process and the productive traits of the breeds. The haematological status of sheep has been examined on a PCE-90VET (HTI, USA) haematological analyser. The clinical and haematological parameters of Romanov breed sheep of different genotypes indicate high adaptation plasticity and a high level of metabolic processes occurring in the body of animals. The authors found that homozygous β-Lg A/A sheep had 1.5 times the number of leukocytes in the blood compared to heterozygous β-Lg A/B animals.

The aim: To estimate type 2 diabetes mellitus (T2DM) prevalence in patients who came for a consultation to the private practice cardiologist. Materials and methods: 97 patients with cardiovascular diseases (СVD), visited a cardiologist in private medical center, were included (mean age 49,5 (42,8; 58,3) years, 43 (44.3 %) males) and T2DM prevalence was estimated. Results: 84 (86.6 %) patients had arterial hypertension, 19 patients (19.6 %) had coronary artery disease. Mean body mass index was 29,4 (25,2; 33,4) kg/m2. Waist circumference above recommended was observed in 78.4 %. 30 рatients (30.9 %) were overweight, 44.3 % had abdominal obesity. Almost all patients had atherogenic dyslipidemia. Total T2DM prevalence was 19.6 %, including cases of first-diagnosed diabetes (17.5 %). Conclusions: T2DM and prediabetes prevalence in our sample of patients with CVD was higer than described for the general population. Рatients with cardiovascular diseases require careful assessment of diabetes risk factors for its timely detection and for possiblу improving the outcomes.

The impact of Taldan crushed stone plant and wastes formed in process of its activity on the environment is considered. About 2.9 million tons of siftings of rock grinding were accumulated in dump massifs with a total area of 600 hectares. Therefore, elimination of accumulated harm to the environment that has arisen over many years of operation of Taldan crushed stone plant is the actual task. One of the technological solutions of liquidation of objects of accumulated harm to the environment based on physicochemical impact on wastes is stabilization or artificial stone formation. Drawing of siftings of rock in soil concrete compositions (artificial stone materials) allows to solve complex of acute environmental problems due to their largetonnage direct use. The use of siftings of rock in road building will contribute to the rational and cost-effective use of natural mineral raw materials, since this process will not entail an increase in the costs of its extraction and processing. A set of modern methods (atomic-emission spectrometry with inductively coupled plasma, scanning electron microscopy, X-ray phase analysis, infrared spectroscopy) were used to study the chemical, phase composition and properties of siftings of rock to substantiate the possibility of its utilization in the composition of soil concrete. It is shown that the introduction of an 8 wt. % of mineral binder and polymer stabilizing additive Element (1, 5, 10 wt. %) allows to get soil concrete with a mark of strength М100.

The possibility of utilization of overburden rocks of the Chernovsky brown coal and Baleysko-Taseevsky gold occurrences (Trans-Baikal Region) in the road construction industry is studied. Polymeric additives Cryogelite and StabOL were chosen as stabilizing additives in the compositions of road-building composites. The initial mineral samples were examined by methods of atomic emission spectrometry with inductively coupled plasma, powder diffraction, and infrared spectroscopy. It was found that the introduction to formulation of composites with use of overburden rocks of 8 wt. % Portland cement and 10 wt. % fly ash, as well as stabilizing additives Cryogelit (Chernovskoe occurrence) and StabOL (Baleysko-Taseevskoe occurrence), allows to obtain samples with strength grade M40 and frost resistance grade F15. The biotesting method proved that the obtained composites do not have an acute toxic effect on test objects and are safe for the environment and human health.

Objective. To study the influence biopreparations, different in origin and mechanisms of action, on the yield and oil content in oil flax seeds under arid conditions against the background of artificial and natural moistening. Methods. Field, biochemical, calculation and statistical. Results. It has been found that in the conditions of natural moistening of the Southern Steppe of Ukraine, the use of such preparations ass Azofosforin, Ekofosforin, Binoc TK and Bio-gel on oil flax crops, according to the recommendations for seed treatment and sowing in the “herringbone” phase, increases oil yield due to increase in seed yield and, in most cases, the oil content of the seeds. The efficiency of individual preparations was determined by the weather conditions of the growing season. The predominant effect of organic fertilizer Bio-gel on the yield was found, while microbial preparations had a positive effect on both the yield and oil content in flax seeds. The use of Ekofosforin and Binoc TK for seed inoculation increases yields by 0.22 and 0.11 t/ha, and oil content — by 0.5 and 0.4 percentage points, respectively. Double application of the Azofosforin increases the conditional fat yield by 31 % via increasing seed yield by 0.11 t/ha. The use of microbiological preparations and organic fertilizers for seed treatment before sowing and for foliar fertilization in the cultivation of oil flax of Vira variety has a positive effect on yield, oil content in seeds, which increases fat yield by 11.0–57.9 %. Conclusion. The use of biopreparations in the technology of growing oil flax is a basic element of obtaining products for food and medical use. The highest yield (0.99 t/ha) and the highest fat yield (428 kg/ha) in the experiment is provided by pre-sowing seed treatment with organic fertilizer Bio-gel at a dose of 1.5 L/ha. The highest oil content (43.0 %) is provided by foliar treatment of plants with Azofosforin. The use of microbiological preparations Ekofosforin, Binoc TK and Azofosforin for seed treatment increases the yield by 0.08–0.22 t/ha and oil yield by 11.1–12.9 %.

Ganglioside GD2 is a well-established target expressed on multiple solid tumors, many of which are characterized by low treatment efficiency. Antibody-drug conjugates (ADCs) have demonstrated marked success in a number of solid tumors, and GD2-directed drug conjugates may also hold strong therapeutic potential. In a recent study, we showed that ADCs based on the approved antibody dinutuximab and the drugs monomethyl auristatin E (MMAE) or F (MMAF) manifested potent and selective cytotoxicity in a panel of tumor cell lines and strongly inhibited solid tumor growth in GD2-positive mouse cancer models. Here, we employed two different GD2-binding moieties–minibodies and scFv fragments that carry variable antibody domains identical to those of dinutuximab, and site-directly conjugated them to MMAE or MMAF by thiol-maleimide chemistry with drug-to-antibody ratios (DAR) of 2 and 1, respectively. Specific binding of the antibody fragment-drug conjugates (FDCs) to GD2 was confirmed in direct ELISA, flow cytometry, and confocal microscopy. Selective cytotoxic and cytostatic effects of the conjugates were observed in GD2-positive but not GD2-negative neuroblastoma and melanoma cell lines. Minibody-based FDCs demonstrated more pronounced cytotoxic effects and stronger antigen binding compared to scFv-based FDCs. The developed molecules may offer considerable practical benefit, since antibody fragment-drug conjugates are capable of enhancing therapeutic efficacy of ADCs by improving their pharmacokinetic characteristics and reducing side effects.

Pancreatic cancer (PC) is one of the most aggressive malignancies. A combination of targeted therapies could increase the therapeutic efficacy in tumors with heterogeneous target expression. Overexpression of the human epidermal growth factor receptor type 3 (HER3) and the epithelial cell adhesion molecule (EpCAM) in up to 40% and 30% of PCs, respectively, is associated with poor prognosis and highlights the relevance of these targets. Designed ankyrin repeat protein (DARPin) Ec1 fused with the low immunogenic bacterial toxin LoPE provides specific and potent cytotoxicity against EpCAM-expressing cancer cells. Here, we investigated whether the co-targeting of HER3 using the monoclonal antibody seribantumab (MM-121) and of EpCAM using Ec1–LoPE would improve the therapeutic efficacy in comparison to the individual agents. Radiolabeled 99mTc(CO)3-Ec1–LoPE showed specific binding with rapid internalization in EpCAM-expressing PC cells. MM-121 did not interfere with the binding of Ec1–LoPE to EpCAM. Evaluation of cytotoxicity indicated synergism between Ec1–LoPE and MM-121 in vitro. An experimental therapy study using Ec1–LoPE and MM-121 in mice bearing EpCAM- and HER3-expressing BxPC3 xenografts demonstrated the feasibility of the therapy. Further development of the co-targeting approach using HER3 and EpCAM could therefore be justified.

The design and search for new selective inhibitors of CAII with a better pharmacological profile, which would cause minimal electrolyte disturbances in the body, remains an urgent problem of medical chemistry and pharmacology today. It is important that the discovered new classes of inhibitors do not always contain the main “pharmacophoric” function (sulfamide), which is characteristic of “classic” drugs (Acetazolamide, Methazolamide, Ethoxzolamide, Dorzolamide and others), but are derivatives of phenols, polyamines, coumarins/thiocoumarins, ureas, thioureas, hydroxamates, etc. These molecules also bind in the active site of the enzyme, but do not interact directly with the catalytic zinc ion or interact through zinc-coordinated water molecules/hydroxide ion. However, this leads to an increase in their selectivity and, as a result, pharmacological action. Continuing the search for compounds that affect urination, we were interested in aroylhydrazones of esters of quinone oxime. Firstly, they are characterized by certain structural features (dynamic and geometric isomerism); secondly, they exhibit redox properties; thirdly, the presence of aromatic fragments makes it possible to create a voluminous combinatorial library for analysis. These compounds are ligands in complexation reactions, and an additional increase in the number of hydrogen acceptors in the molecule due to structural modification will improve ligand-enzymatic interactions with carbonic anhydrase (CAII) and, as a result, reveal new promising diuretics. The aim – design and search for potential diuretics (CA II inhibitors) among aroylhydrazones of esters of quinone oxime using in silico, traditional synthesis and in vivo methodologies. Methods of organic synthesis, physico-chemical methods of analysis of organic compounds (NMR1H-spectroscopy, elemental analysis). Prediction of affinity to the biological target, prediction of toxicity and lipophilicity of the combinatorial library of benzohydrazides O-aroyl esters of quinone oxime using computer services. The study of compounds affecting the excretory function of rat kidneys was carried out according to the generally accepted method of E.B.Berkhin with water load. The investigation of the probable mechanism was carried out using flexible molecular docking, as an approach to search for molecules that have affinity for human carbonic anhydrase type II (CAII). Macromolecular data of the crystal structure of CAII (PDB ID – 3HS4) were downloaded from the Protein Data Bank (PDB). The design was developed and the search for diuretic agents among benzohydrazides of O-aroyl esters of quinone oximes was developed using in silico methods (prediction of affinity, lipophilicity, toxicity and enzyme-ligand interactions), traditional organic synthesis, and in vivo methods (effect on excretory function of rat kidneys). The synthesis of benzohydrazides of O-aroyl esters of quinone oxime was carried out by the interaction of aroylhydrazines with 4-[(aroylimino)]cyclohexa-2,5-dien-1-ones. The structure of the synthesized compounds was confirmed by elemental analysis and1H NMR spectra. Studies of the effect of synthesized compounds on the excretory function of rat kidneys allowed us to identify a number of promising compounds among aroylhydrazones of quinonexime esters, which increase daily diuresis by 54.2-352.8% compared to the control group. At the same time, it was established that the most active was N'-(4-[(2-chlorobenzoyloxy)imino]cyclohexa-2,5-dien-1-ylidene)-3-nitrobenzohydrazide, which increased daily diuresis by 352.8% in comparison with the control group, while exceeding the effect of “Hydrochlorothiazide” (170.8%). The developed and implemented strategy for the search for diuretics among benzohydrazides of O-aroylesters of quinone oxime allowed the identification of an effective compound, which in terms of diuretic effect exceeds the comparison drug “Hydrochlorothiazide”. Visualization of the molecular docking of the active compounds showed that their geometry makes it difficult to place them in the pocket of the active site of CA II, but the pronounced diuretic effect can also be associated with their ability to form coordination bonds with the zinc cation. The obtained results justify the further targeted search for potential diuretics among this class of compounds for a more detailed understanding and study of the mechanism of action.

The article presents the results of research on the influence of agrotechnical techniques on the formation of legume-cereal agrophytocenoses. The research method includes conducting a field experiment on the experimental field of North-West Research Institute of Milk and Grassland Agriculture in the Vologda region. The soil of the experimental site is drained, medium cultivated, sod-podzolic, medium loam. The following varieties have been chosen for carrying out the experiment: Permskiy mestnyy red clover, Dymkovskiy red clover, Vega 87 variegated alfalfa, Sverdlovskaya 37 meadow fescue, Losinka reed fes-cue, Leningradskaya 204 timothy, SibNIISKHOZ 189 awnless brome, VIK 66 pasture ryegrass. As a re-sult of research in 2017–2019, it was found that the share of sown grass species was high regardless of the species composition and method of sowing and ranged from 82.9 to 98.5%. The content of weed vegeta-tion was 1.4–2.0 times higher in grass stands sown under the cover of barley compared to those sown without cover. The yield of grasses was affected by the composition of agrophytocenoses and the number of bites. On average, for two years of use, a grass mixture of the third option was distinguished, including red clover, timothy and reed fescue. It significantly exceeded the yield of the control variant by 0.39 t/ha of dry matter. The method of sowing did not affect the yield of herbage. When you get three grass mow-ing, protein collection increases by 8–24%, and its content in the plant mass — by 20–32% compared to double mowing. Scope – agricultural enterprises of the European North of the Russian Federation.

Chemokines are involved in the humoral regulation of body homeostasis. Changes in the blood level of chemokines were found in cancer, atherosclerosis, diabetes, and other systemic diseases. It is essential to distinguish the effects of co-morbid pathologies and cancer on the level of chemokines in the blood. We aimed to analyze, by multiplex cytometry, the levels of chemokines in the blood of healthy young volunteers as well as of intact mice and mice with CT26 colon and Pan02 pancreatic tumors. Two types of chemokines were identified both in human and murine plasmas: homeostatic ones, which were found in high concentrations (>100 pg/mL), and inducible ones, which can be undetectable or determined at very low levels (0–100 pg/mL). There was a high variability in the chemokine levels, both in healthy humans and mice. To analyze chemokine levels during tumor growth, C57BL/6 and BALB/c were inoculated with Pan02 or CT26 tumor cells, accordingly. The tumors significantly differed in the growth and the mortality of mice. However, the blood chemokine levels did not change in tumor-bearing mice until the very late stages. Taken collectively, blood chemokine level is highly variable and reflects in situ homeostasis. Care should be taken when considering chemokines as prognostic parameters or therapeutic targets in cancer.

Purpose. The aim is to estimate the content of pro- and anti-inflammatory cytokines (IL-1β, IL-8, IL-10, MCP-1, ICAM-1, VEGF) in tear of patients with advanced proliferative diabetic retinopathy and complicated primary cataract after phacoemulsification surgery and IOL implantation with vitreoretinal surgery accomplished at once in comparison with vitreoretinal surgery only. Material and methods. 34 cases of surgery treatment of patients with PDR and complicated primary cataract were enrolled. This patients were divided into two groups depending on the treatment tactics. In the 1st group patients were subjected to a two–step surgical procedure: vitreoretinal surgery (VRS) with silicone oil tamponade performed as the 1st step in their treatment; followed by the 2nd step, phacoemulsification surgery and silicone oil removal, and the IOL implantation, respectively. In the 2nd group phacoemulsification performed simultaneously with vitreoretinal surgery: phacoemulsification, IOL implantation, vitreoretinal surgery with silicone oil tamponade. The second step differed in the removal of silicone oil from the vitreous cavity. On the 2nd day after the 1st step surgery and before surgical treatment the tear samples of the patients of both groups have been examined. Results. A concentration of the following cytokines: IL-8, MCP-1, ICAM-1 in the 2nd group was 2,5-5 times higher than in the 1st group. Conclusion. The research revealed that the patients with advanced PDR are accurately determined by the increased concentration of IL-8, MCP-1, ICAM-1 in tear after phacoemulsification surgery and IOL implantation with vitreoretinal surgery accomplished at once in comparison with vitreoretinal surgery only. Keywords: cytokines, diabetic retinopathy, cataract, vitreoretinal surgery.

The authors have studied the genetic value of producers of the aboriginal Kulunda finewool sheep breed based on various analysis methods of the productivity of their progeny. The data on 574 offspring (daughters) received from 16 rams-producers of the “Steptoe” breeding farm of Altai Krai were used in the research. The genotypes of ram progeny were evaluated by the productivity of the rams at one year of age. In assessing the fathers, the number of effective daughters needed to confirm a sufficient number of offspring was calculated. Water, soil, and feed were tested for heavy metals content in the sheep breeding area, which did not exceed the MPC (Maximum Permissible Concentration). The breeding indices of the progeny ranged from 114 to 1562. The live weight of the rams was 120 kg. The live weight of the daughters was 50.0 kg. The sheep (daughters) had a wool gain of 5.7 kilograms per ewe. The authors established a high homogeneity of the genotypes of rams producers in terms of the live weight of daughters. The genetic variability of the fathers was 3.2%. According to productivity indices, the rams-producers (#4452, 26133, 3611, 0125 and 44244) occupied the first five ranks. The effect of the genotypes of ram producers on the daughters’ live weight and wool hair gain was established. The ranking data showed the advantage of daughters in several traits obtained from prepotent producers. The authors suggest that ram sires no. 3611, 0125, 26133 and 44244 should be used extensively to improve breeding efficiency. The authors also applied the Hozo method in the absence of normal distribution of traits. In other cases, data processing by methods of variation statistics was used.

Objective. To establish the influence of soil treatment methods on the number of earthworms and microbial biomass in dark-chestnut heavy loam soil with observance of the following crop rotation: soybean – winter wheat – corn; verify the hypothesis of the negative influence of traditional soil treatment technologies on the number of earthworms. Methods. Analytical, field, laboratory, system analysis, statistical. Results. During the studies conducted in 2018–2021 at Askanian State Agricultural Experimental Station of the Institute of Irrigated Agriculture of the NAAS, the positive influence of zero soil treatment technologies on the studied parameters versus with traditional technologies was established. A 2.5-fold increase in the number of earthworms and a 1.1-fold increase in microbial biomass was reported with zero soil treatment technologies. The interaction between soil treatment factors and cover crops in the structure of crop rotation was 23.7 %. Soil treatment technologies had a negligible influence on the size of microbial biomass — at the level of 1.4 %. The significance of the action of cover crops in crop rotation was 10.0 %. The experiment also showed a higher number of earthworms in the soil with zero soil treatment technologies with cover crops and traditional technologies for control, due to better live environment and favourable conditions for reproduction and distribution of the population depending on soil treatment technologies. Changes in the density of the soil layer 0–30 cm were within the measurement error (for zero soil treatment technologies the studied parameter was 1.23 g/cm3, for traditional — 1.24 g/cm3). Compaction of 0–20 cm soil layer with zero and traditional soil treatment technologies was reported. The content of soil organic matter by the years of studies under zero soil treatment technologies increased to 3.0 %, which is 1.2 times higher than with traditional technologies. Conclusion. Under the conditions of stationary field experiment the positive influence of zero soil treatment technologies on early changes of biological properties of soil, which were characterized by increase in number of earthworms and size of microbial biomass, has been established. The positive influence of cover crops on soil quality was determined, which was characterized by signs of biota activation in the 0–30 cm layer and improvement of biological and physical properties of the soil.

The purpose of the article is to study the features of the development of digitalization in the management system of the logistics complex. The transport complex serving important sectors of the economy is considered, with special emphasis on the development of the unified transport system of the Republic of Kazakhstan, modernization and efficiency improvement of all its elements in the resolutions of the Government of the Republic of Kazakhstan and other state documents. It was also noted that the transport sector of the republic plays a special role in ensuring the further dynamic and sustainable development of the economy of Kazakhstan, the implementation of the state strategy for its integration into the world economy. The development of the transport sector should take into account the current state and prospects of economic development, as well as the best international practices in the development of transport and logistics systems. Hence, the high relevance of solving issues aimed at the development of transport and logistics, which led to the importance of choosing the author's research and research in this area as a real sector of the economy of Kazakhstan. In this article, the authors considered the stages of implementation of the state program “Digital Kazakhstan” on the basis of the basic principles, identified goals and objectives. The system nature of the design work of the intelligent transport system is shown. The solution of tasks for the implementation of the program “Roadmap for the formation of the food belt of Astana for 2017-2018” is justified. Based on the results of a study of the transport sector in the context of the modern development of the economy of the Republic of Kazakhstan, the authors identified problematic issues and made appropriate conclusions.

Purpose. To compare and evaluate long-term results of two-stage surgical treatment of patients with advanced proliferative diabetic retinopathy and complicated incipient cataract. Material and methods. 73 patients with advanced proliferative diabetic retinopathy and complicated incipient cataract performed by vitrectomy from 2016 to 2020 were analyzed. In the 1st group patients were subjected to a two-step surgical procedure: vitreoretinal surgery with silicone oil tamponade performed as the 1st step in their treatment; followed by the 2d step, phacoemulsification surgery and silicone oil removal, and the IOL implantation, respectively. In the 2d group phacoemulsification performed simultaneously with vitreoretinal surgery: phacoemulsification, IOL implantation, vitreoretinal surgery with silicone oil tamponade. The second step differed in the removal of silicone oil from the vitreous cavity. Results. Visual functions improved in 88.8% of cases in group 1, and in 51.3% in group 2. Conclusion. Outcomes of the studies suggest that it is more viable to perform phacoemulsification surgery sometime later along with silicone oil removal on PDR patients with complicated primary cataract. This sequence of treatment procedure ensures a more gentle approach to the anatomic structures of the eye during the first stage (vitreoretinal surgery) and contributes to the reduction in the number of intraoperative and postoperative complications. Key words: diabetic retinopathy, cataract, vitreoretinal surgery.

To assess the impact of summer heat waves on key parameters of oxidative stress in patients with coronary heart disease.We included 30 male patients aged 5213 years with stable angina pectoris of IIIII functional class with at least one coronary artery stenosis proved by angiography (ischemic group) in comparison with 10 male patients aged 487 years with no angiographic sings of significant coronary stenosis and without angina manifestation (non-ischemic group). The following parameters were studied: activity of superoxide dismutase (Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), the level of malondialdehyde (MDA) and MDA-modified low-density lipoproteins (MDA-LDL). The analysis of indicators was performed at normal average daily temperature (daytime temperature not higher than 20С) and after a heat wave (daytime temperature above 27C for more than 2 consecutive days).Our study revealed the decrease of CAT and GSH-Px activities with increased activity of Cu,Zn-SOD in both groups after the heat wave. At the same time we observed accumulation of MDA and increased MDA-LDL level in both groups. Initially ischemic patients showed significantly increased level of CAT and GSH-Px activity compared to the non-ischemic group, while it was no difference in activity of Cu,Zn-SOD and MDA and MDA-LDL level. We observed significant reduce of Cu,Zn-SOD activity in ischemic patients compared to non-ischemic group with no significant differences in all other studied parameters of oxidative stress after heat wave.Changes in the key parameters of oxidative stress in patients with ischemic heart disease during summer heat waves are comparable to those in patients without ischemia, however significantly greater inhibition of GSH-Px activity and significantly lower increase in Cu,Zn-SOD activity was noted. These results may indicate misregulation of free radical processes in patients with ischemic heart decease.Цель. Исследовать изменение ключевых параметров окислительного стресса у больных с ишемической болезнью сердца (ИБС) при волнах летней жары. Материалы и методы. В исследование включены 30 мужчин (5213 лет) со стабильным клиническим течением ИБС и стенокардией напряжения IIIII функционального класса. Группу сравнения составили 10 мужчин (487 лет) с ангиографически доказанным отсутствием значимого поражения коронарного русла без проявлений стенокардии. Биохимические исследования включали: измерение активности эритроцитарных антиоксидантных ферментов (супероксиддисмутазы Cu,Zn-SOD, каталазы CAT, глутатионпероксидазы GSH-Px) и содержание продуктов свободнорадикального окисления (малонового диальдегида МДА и МДА-модифицированных липопротеидов низкой плотности МДА-ЛПНП). Анализ биохимических показателей проводили при нормальной среднесуточной температуре окружающей среды (дневная температура не выше 20С) и после волны жары (дневная температура не менее 27C на протяжении более 2 сут). Результаты. В обеих исследованных группах в ответ на тепловой стресс при волне жары отмечено снижение активности CAT и GSH-Px при увеличении активности Cu,Zn-SOD. Одновременно наблюдали увеличение уровня МДА и снижение уровня МДА-ЛПНП. Исходно в группе с ИБС выявлен достоверно повышенный уровень активности CAT и GSH-Px в сопоставлении с группой сравнения, тогда как по активности Cu,Zn-SOD, содержанию МДА и МДА-ЛПНП достоверных отличий не выявлено. После волны летней жары наблюдали существенное снижение активности Cu,Zn-SOD у больных с ИБС, тогда как достоверных межгрупповых различий всех других исследованных параметров окислительного стресса не отмечено. Заключение. Изменения ключевых параметров окислительного стресса в крови пациентов с ИБС при волнах летней жары в целом сопоставимы с таковыми в группе сравнения (без стенокардии с ангиографически доказанным отсутствием значимого поражения коронарного русла), однако при практически идентичном росте уровня МДА у пациентов этих групп отмечено значительно большее ингибирование активности GSH-Px при значительно меньшем увеличении активности Cu,Zn-SOD у больных с ИБС, что может свидетельствовать о большем нарушении регуляции свободнорадикальных процессов у этих пациентов.

In the publication, O.V. Konovalova, V.I. Fedorova, A.P. Dvoretskaya presented letters 1931-1932 of the leader and theoretician of the party of socialists-revolutionaries V.M. Chernov to a prominent figure of the party O.S. Minor and a representative of Harbin socialists-revolutionaries organization M. I. Klyaver regarding the split of the Foreign delegation of the socialists-revolutionaries. They are preserved in the collection of VM. Chernov of the International Archives and Collections at the International Institute of Social History in Amsterdam. The presented letters help to clarify VM. Chernov’s position on the key issues of the history of the SR party during the Russian revolution, Civil War, and emigration of the 1920s, and also shed light on the deep reasons for the split of the ZD AKP.

The characteristic of bulls-producers of red breeds of OAO Barnaulskoe breeding enterprise on the quality of sperm and its resistance to cryopreservation are presented. The breeding enterprise has examined samples of water, soil, feed for the content of heavy metals. In the studied samples, no excess of the LOC was found. The research results were processed on a PC using population statistics methods. Angler bulls produced the largest amount of ejaculates unsuitable for cryopreservation. It is 20.6%. According to this indicator, they surpassed the producers of red Danish and red steppe breeds by 4.1-7.8%. The animals of the latter breed showed the smallest amount (1.7%) of ejaculates rejected after defrost. In Angler bulls, this indicator was 5.95%, in red Danish bulls it was 2.95%, which is 3.52 and 1.75 times higher than in red steppe breeders (P established between individual bulls of the red steppe breed in the number of ejaculates rejected before cryopreservation (2.84-22.29%) and after defrost (0-7.09%). The differences between breeds in the frequency of rejected ejaculates before freezing and after cryopreservation indicate a certain role of heredity in the resistance of animals for these indicators. Spearman’s rank correlation coefficient between these traits was 0.312. It indicates the possibility of preliminary assessment and selection of bulls according to the first indicator. But the final assessment of the bull-producers can be made by the frequency of rejected ejaculates after thawing. We propose to consider the issue of additional accounting in breeding programs for the resistance of the seed of bulls-producers to cryopreservation.

This research is devoted to the variability of linear and weight growth of Sander lucioperca (Stizostedion lucioperca) in the Novosibirsk water-storage basin. The presented work is part of a comprehensive research of Sander lucioperca phenotypic pool of the Novosibirsk water-storage basin. 43 individuals have been selected for the analysis aged 3,0–4,5 years in the period October-November 2019. Measurements of Sander lucioperca have been carried out according to the “Manual for the study of fi sh”, the fi sh has been weighed on a technical scale VLKT-500 with an accuracy of 1 g. The fi rst time the linear and some aspects of the weight growth of Sander lucioperca in the Novosibirsk water-storage basin have been described in the paper, since the growth directly depends on the development and is one of its components. The biological characteristics and features of Sander lucioperca have been analyzed. For the development of the population of Sander lucioperca as well as other fi sh species one of the main biotic factors is the feed supply. The availability of feed for hydrobionts is determined by the quantity, quality and availability of feed in the reservoir, since the feed supply has a signifi cant impact on the biological parameters of fi sh. The ecological situation of the Novosibirsk water-storage basin has been studied. The obtained data on Sander lucioperca measurements can be used as average population values. Increasing the parameters of the assessment of living organisms makes it possible to more accurately assess the conformation of animals. A high level of correlation (r=0,878) between the linear and weight growth of Sander lucioperca has been established, and a regression equation describing the change in length as a function of live weight (y = 9,5853 x + 39,1164) has been calculated. There is a tendency to decrease the number of Sander lucioperca in the Novosibirsk water-storage basin.

Antioxidant and anti-ischemic properties of the pharmacological agonist of galanin receptor GalR2 WTLNSAGYLLGPβAH (Gal) and its C-terminal fragment, dipeptide carnosine (βAH), were studied in the model of regional ischemia and reperfusion of the rat heart in vivo in the dose range of 0.5-5.0 mg/kg and Cu²⁺-induced free radical oxidation of low density lipoproteins (LDL) of human plasma in vitro for peptide concentrations of 0.01 mM and 0.1 mM. Gal was obtained by automatic solid phase synthesis using the Fmoc methodology; its structure was characterized by 1H-NMR spectroscopy and MALDI-TOF mass spectrometry. Intravenous administration of the optimal dose of Gal (1 mg/kg) to rats after ischemia was more effective than carnosine in reducing of the myocardial infarct size and the activity of creatine kinase-MB and lactate dehydrogenase in blood plasma at the end of reperfusion. It also improved the metabolic state of the reperfused myocardium and reduced the formation of peroxidation products during reperfusion. Gal reduced more effectively the formation of adducts of hydroxyl radicals in the interstitium of the area at risk (AAR) of the rat heart than carnosine. Carnosine at a dose of 1 mg/kg more effectively increased the activity of catalase and glutathione peroxidase in the AAR by the end of reperfusion compared to Gal. In a model of Cu²⁺-initiated oxidation of human plasma LDL 0.1 mM carnosine demonstrated a significantly more pronounced reduction in the formation of lipid radicals compared to Gal. The results show that Gal can be considered as a promising agent that reduces myocardial injury during reperfusion and oxidative stress.Antioksidantnye i protivoishemicheskie svoĭstva farmakologicheskogo agonista retseptorov galanina WTLNSAGYLLGPβAH (Gal) i ego S-kontsevogo fragmenta dipeptida karnozina (βAH) izucheny na modeli regional'noĭ ishemii i reperfuzii serdtsa krysy in vivo v diapazone doz 0,5-5,0 mg/kg i Cu²⁺-indutsirovannogo svobodnoradikal'nogo okisleniia lipoproteinov nizkoĭ plotnosti (LNP) plazmy cheloveka in vitro dlia kontsentratsiĭ peptidov 0,01 mM i 0,1 mM. Gal poluchen avtomaticheskim tverdofaznym sintezom s ispol'zovaniem Fmoc-metodologii; ego struktura okharakterizovana s pomoshch'iu 1N-IaMR-spektroskopii i MALDI-TOF mass-spektrometrii. Vnutrivennoe vvedenie krysam optimal'noĭ dozy Gal (1mg/kg) posle ishemii v bol'sheĭ stepeni, chem v sluchae karnozina, umen'shalo razmery infarkta miokarda i snizhalo aktivnost' kreatinkinazy-MV i laktatdegidrogenazy v plazme krovi v kontse reperfuzii, uluchshalo metabolicheskoe sostoianie reperfuziruemogo miokarda i umen'shalo obrazovanie produktov perekisnogo okisleniia pri reperfuzii. Gal umen'shal obrazovanie adduktov gidroksil'nykh radikalov v interstitsii zony riska (ZR) v dostoverno bol'sheĭ stepeni, chem karnozin. Karnozin v doze 1 mg/kg bolee éffektivno uvelichival aktivnost' katalazy i glutationperoksidazy v ZR levogo zheludochka serdtsa krysy k kontsu reperfuzii po sravneniiu s Gal. V modeli Cu²⁺-initsiirovannogo okisleniia LNP plazmy krovi cheloveka 0,1 mM karnozin prodemonstriroval dostoverno bolee vyrazhennoe umen'shenie obrazovaniia lipidnykh radikalov po sravneniiu s Gal. Rezul'taty pokazyvaiut, chto Gal mozhno rassmatrivat' v kachestve perspektivnogo sredstva, snizhaiushchego povrezhdeniia serdtsa pri reperfuzii i okislitel'nom stresse.

To analyze creatine phosphokinase as a predictor of destructive cholecystitis.We analyzed 105 patients with various clinical variants of acute calculous cholecystitis (catarrhal, phlegmonous, gangrenous), and comparable age, gender and comorbidities. The study included patients with gallstone disease and gallbladder inflammation aged 30-7 years who underwent laparoscopic cholecystectomy, open cholecystectomy, cholecystectomy through mini-laparotomy. We excluded patients with gallstone disease complicated by mechanical jaundice aged under 30 years and over 70 years old. Control group consisted of 35 patients with exacerbation of chronic calculous cholecystitis. Creatinine phosphokinase (CPK) was analyzed at admission by standard kinetic colorimetric method in all patients with suspected acute cholecystitis. Statistical analysis of data was carried out using the SPSS Statistics 7.0 software in compliance with the principles of statistical analysis adopted for research in biology and medicine.CPK level was 257.7±27.9 U/L (Analysis of serum creatine phosphokinase can be included in the algorithm of preoperative examination to study the prospects of this approach for predicting severity of acute cholecystitis.Острый холецистит — одна из наиболее часто встречающихся болезней абдоминальной неотложной хирургии. Высокая летальность как на интраоперационном, так и на послеоперационном этапе при остром холецистите указывает на несвоевременную диагностику осложнений и запоздалое лечение. Рассматривается роль одного из ферментов аутолиза в прогнозировании риска деструктивных процессов в стенке желчного пузыря.Изучить в качестве предиктора риска развития деструктивного холецистита фермент аутолиза креатинфосфокиназу.Проведено одномоментное исследование среди 105 пациентов с различными клиническими вариантами острого калькулезного холецистита (катаральный, флегмонозный, гангренозный), сопоставимых по возрасту, полу и сопутствующим заболеваниям. Критерии включения в группу исследования: пациенты, страдающие желчнокаменной болезнью с воспалительными изменениями в желчном пузыре в возрасте от 30 до 70 лет, оперированные по стандартной методике лапароскопической холецистэктомии или лапаротомии с холецистэктомией. Критерии исключения из группы исследования: пациенты, страдающие желчнокаменной болезнью, осложненной механической желтухой, в возрасте младше 30 лет и старше 70 лет. Группу клинического сравнения составили 35 пациентов, страдающих хроническим калькулезным холециститом. Всем пациентам с подозрением на острый холецистит определяли активность креатининфосфокиназы стандартным кинетическим колориметрическим методом.У пациентов с острым калькулезным холециститом уровень креатининфосфокиназы составил 257,7±27,9 ЕД/л (Определение уровня креатинфосфокиназы в периферической крови может быть включено в алгоритм дооперационного обследования с целью изучения перспективности использования для прогнозирования тяжести течения острого холецистита.