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Relevance. Despite the fact that the pharmacological effect of drugs is well known and studied, unfortunately, it is impossible to predict the development of drug allergies, since the individual characteristics of the body's reactivity are of great importance in its development. The goal is to analyze the clinical situation of the development of drug allergies to illustrate the importance of the role of biotransformation and the chemical structure of drugs in its diagnosis.Methods. The study was carried out on the patient after signing informed consent and included anamnesis, physical examination, skin prick tests with inhalant allergens, installation of a peripheral venous catheter, and provocative testing.Results. prick tests with: 0.9 % NaCl solution (negative control), histamine solution (10 mg/ml) (positive control), amoxicillin + clavulanic acid (100 mg + 20 mg), ampicillin (100 mg/ml), cephalexin (50 mg/ml) — positive results, ceftazidime (20 mg/ml), clarithromycin (20 mg/ml) — negative results; intravenous tests with: 0.9 % NaCl solution (negative control), ceftazidime (2 mg/ml), clarithromycin (0.01 mg/ml) — negative results; oral PDT with cefuroxime (cumulative dose — 250 mg), josamycin (cumulative dose — 1000 mg) — negative results. As a result of skin testing, LA for the amino group of beta-lactams was confirmed; No data have been obtained for LA on the beta-lactam ring, clavulanic acid, or macrolides.

INTRODUCTION. Small interfering RNAs (siRNAs) are among the most promising types of therapeutic nucleic acids aiming at the inhibition of pathogenetically relevant gene expression through the RNA interference mechanism. However, the limited bioavailability and immunogenicity of siRNAs and imperfect delivery systems hinder the clinical potential and applicability of siRNA medicinal products.AIM. This study aimed to summarise recent advances in the development of siRNA medicinal products and the corresponding delivery systems, review clinical trial results, and outline future development prospects for these medicinal products.DISCUSSION. This article covers the molecular mechanisms underlying RNA interference, the considerations for siRNA development, and the techniques for effective siRNA delivery. The article dwells upon various systems for nucleic acid delivery to targeted cells. The most promising delivery systems are non-viral systems, including liposomes, exosomes, nanoparticles, polymers, cell-penetrating peptides, and GalNAc ligands. Their main advantages include their ease of complexation with nucleic acids, modification and functionalization potential, favourable safety profile, ability to cross biological barriers, and tropism to target tissues. The article summarises the information that has accumulated over the past few years in clinical trials of siRNA medicinal products for a range of conditions, including metabolic disorders, infections, and cancers, as well as hereditary, ophthalmic, renal, and hepatic diseases. Special attention is paid to siRNA medicinal products undergoing clinical trials (over 10 products) and approved for clinical use (6 products, including MIR 19, the first authorised Russian siRNA medicinal product).CONCLUSION. Ultimately, siRNA medicinal products are a promising tool for personalised medicine, exhibiting therapeutic potential for a wide range of pathological conditions. Further studies of siRNA medicinal products should aim at improving siRNA production technology to increase their bioavailability and half-life period. In addition, these studies should aim at enhancing delivery systems for these products to mitigate toxicity risks and maximise efficacy.

The article discusses the possibilities of functional diagnostics of the respiratory function of the lungs in patients with bronchial asthma and chronic obstructive pulmonary disease. Functional diagnostic methods such as capnometry, spirometry, assessment of lung diffusivity and multiple breath nitrogen washout can be used not only to assess airway dysfunction, but also to monitor the course of the disease. There is a need for further development of methods for studying the respiratory function of the lungs and, if possible, their introduction into everyday clinical practice. The purpose of this review was the possibility of diagnostic tests to assess the ventilation and gas exchange function of the lungs in patients with bronchial asthma and chronic obstructive pulmonary disease.

Objective: to characterize a group of patients with fixed drug erythema (FDE) caused by fluconazole to determine the sensitivity and specificity of the local provocative application test (LPAT) and to evaluate cross-allergenic reactivity with other antifungal drugs of the azole group.Materials and methods: a prospective study was conducted in the period from 2012 to 2022. 347 patients with delayed drug hypersensitivity (DDH) were consulted, FDE could be suspected in 86 patients (24.8%), of which 23 patients were caused by fluconazole (26.8%). We included patients with suspected fluconazole FDE (n=23). LPAT with fluconazole was performed in 12 patients, drug provocation test (DPT) with ketoconazole – 17, DPT with itraconazole – 15, DPT with fluconazole – 1.Results: the ratio of men and women was 1:6.3, the average age was 30.39±10.23 years. In 1 patient, the diagnosis of FDE caused by fluconazole was withdrawn. Number of reactions: 1 – in 2 patients (9.1%), more than one reaction – in 20 (90.9%). 4 patients (18.2%) had atopy. Sensitivity of LPAT for diagnosing DDH in FDE caused by fluconazole was 41.7%, specificity – 100%, false-negative rate – 58.3%, positive predictive value – 100%. DPT with ketoconazole, itraconazole was negative in 100% of cases.Conclusions: the results obtained allow us to conclude that FDE caused by fluconazole in the vast majority of cases developed in women aged 19 to 30 years. Since patients with FDE caused by fluconazole tolerate ketoconazole and itraconazole well, it is highly likely that they can switch from fluconazole to one of these drugs. LPAT should be used for diagnosing FDE caused by fluconazole, since it was absolutely safe for the patient and allowed avoiding DPT in 42% of patients. Importantly that the timely and correct diagnosis in more than 90% of cases, it was possible to prevent the development of a repeated reaction to fluconazole.

Obesity, type 2 diabetes mellitus and cardiovascular diseases associated with these conditions remain one of the largest global health problems. According to statistics, at least 90 % of patients with type 2 diabetes mellitus are obese or at least overweight (BMI > 25). Very often, the cause of death in this cohort of patients is the development of a cardiovascular catastrophe. Currently, there is a gradual rejection of the exclusively glucose-centric concept of type 2 diabetes mellitus therapy in favor of an organoprotective one. In this article, we examined the possibility of using various groups of incretinomimetics (DPP-4 inhibitors and GLP-1 agonists) in the primary prevention of cardiovascular diseases in patients with type 2 diabetes mellitus in perimenopause, and comparing their effects with traditional metformin therapy.The aim of the study was to evaluate the effect of non – insulin antidiabetic drugs from the class of incretinomimetics on risk factors for the development of cardiovascular diseases in patients with type 2 diabetes mellitus in perimenopause.Object and methods. A dynamic examination of three groups of patients was carried out. The first group (n = 22) received therapy with the GLP-1 agonist semaglutide, the second group (n = 30) metformin therapy and the third (n = 19) with the DPP-4 inhibitor linagliptin. All patients, in addition to general clinical examination, assessment of the dynamics of weight loss and insulin resistance, underwent a dynamic study of triglyceride levels, low – density lipoprotein cholesterol, as well as markers of general inflammation – C-reactive protein and interleukin-6.Results. The results of the study showed that semaglutide and metformin were equally effective in reducing body weight, but metformin and linagliptin did not significantly affect the level of atherogenic fractions of the lipidogram, unlike semaglutide. Nevertheless, both semaglutide, linagliptin, and metformin reduced the level of markers of general inflammation.Conclusions. The results of the study allow us to discern a certain cardioprotective potential not only in agonists of GLP-1, but also in representatives of the class of DPP-4 inhibitors, which requires further research.

Therapeutic monoclonal antibodies (mAbs), which are developed to treat many pathologies, including cancer, autoimmune and infectious diseases, are one of the fastest growing classes of medicinal products. Given the large number of mAbs in the pipeline and continued interest from pharmaceutical companies, the mAb market is expected to continue to grow in the coming years. To maximise both the therapeutic benefit and the safety of medicinal products in this class, it is essential that their pharmacological properties be carefully characterised and understood.The aim of the study was to analyse literature data on approaches to studying the pharmacokinetics of mAbs. This review presents data on the main physicochemical and pharmacological properties of mAbs and compares them with small molecules. The article describes the influence of various factors on mAb pharmacokinetics.For example, such factors include the method of administration, hydrophilicity, and charge of the mAb, individual characteristics of the patient (body weight, plasma albumin levels, genetic characteristics, etc.), and concurrent administration of other medicinal products. The authors evaluated the role of intra- and inter-individual variability of pharmacokinetic parameters. The rapid development of this group of medicinal products and the emergence of new promising molecules are indicative of the need to study the pharmacokinetics and pharmacodynamics of mAbs in detail and to maximise both the therapeutic benefit and the safety of the medicinal products in this class.

Introduction. Promising sources of biologically active compounds (BAS) are extracts obtained from various morphological parts of plants of the numerous genus Astragalus L. One of the main groups of BAS isolated from plants of this genus are flavonoids, saponins, and polysaccharides. Sufficiently studied are Astragalus membranaceus (Fisch.) Bunge) and Astragalus mongholicus Bge., whose extracts have a wide range of pharmacological activity. Expansion of the nomenclature of medicinal plant materials and the study of BAS groups that determine the main pharmacological effects are topical studies in pharmacognosy. From this point of view, little-studied species of Astragalus (Astragalus henningii (Stev.) Klok., Astragalus testiculatus Pall., Astragalus varius S.G. Gmel., Astragalus dasyanthus Pall.), massively growing in the Volga region, are of interest.Aim. Isolation and identification of 5 aglycones of flavonoids in hydrolysates of water-alcohol extracts from Astragalus herb: A. henningii, A. testiculatus, A.varius, A. dasyanthus by HPLC/UV.Materials and methods. The objects of the study were the herb of four types of Astragalus (A. henningii, A. testiculatus, A.varius, A. dasyanthus), harvested during the period of mass flowering in the Saratov region and dried to an air-dry state. To study the composition of phenolic compounds, extraction was carried out with 70 % ethanol in the ratio of raw material : extracting agent 1 : 10 by infusion for 7 days. Acid hydrolysis was carried out with hydrochloric acid 37 % with heating for 40 min. The resulting hydrolysates were analyzed on an Agilent 1260 chromatograph (Agilent Technologies, USA) with a diode array detector, manual sample injection (Agilent G1328C manual injector, Agilent Technologies, USA) and an Agilent OpenLab CDS chromatographic data collection and processing system using an individually selected elution gradient of the mobile phase (0.1 % solution of orthophosphoric acids/acetonitrile). Compounds in the hydrolysates were identified by the retention times and UV spectra of a mixture of reference standards (RS) of quercetin, isorhamnetin, luteolin, kaempferol, and apigenin.Results and discussion. An elution gradient was selected for one time determination of 5 aglycones of flavonoids with a single analysis time of 13 minutes. These conditions made it possible to identify compounds in the hydrolyzates of water-alcohol extracts of four types of Astragalus. Luteolin, quercetin and apigenin were found in hydrolyzates of A. henningii, A. testiculatus and A. varius; isorhamnetin and kaempferol were found in A. henningii and A. varius. None of the analyzed aglycones was found in the A. dasyanthus hydrolyzate.Conclusion. After preliminary selection of the optimal conditions for the chromatographic separation of a mixture of 5 aglycones of flavonoids, hydrolysates of four types of Astragalus were analyzed. The data obtained indicate the prospects for further study of the chemical composition of Astragalus and confirm the expediency of their use for obtaining of new herbal remedies.

Autoimmune polyendocrine syndromes (APS) are a group of syndromes characterized by autoimmune damage of two or more endocrine glands, leading most often to their hypofunction. Often these syndromes are combined with various organ-specific non-endocrine diseases of an autoimmune nature. Currently, 4 types of APS are distinguished: APS 1, APS 2, APS 3, APS 4. APS 1 is a monogenic autosomal recessive disease based on a violation of the structure of the AIRE gene. The classic signs of APS 1 are: chronic candidiasis of the skin and mucous membranes, primary hypoparathyroidism and autoimmune primary chronic adrenal insufficiency. Moreover, clinical features of APS 1 can include primary hypogonadism, primary hypothyroidism with a history of autoimmune thyroiditis and type 1 diabetes. Among non-endocrine pathology, other autoimmune diseases may occur during patient’s life: alopecia, vitiligo, pernicious anemia, malabsorption syndrome, autoimmune hepatitis, enamel abnormality, ectodermal dysplasia, isolated IgA deficiency, bronchial asthma, glomerulonephritis. APS 2 is a multifactorial pathology caused by mutation of genes and the influence of the environment. Two of the most common clinical options of type 2 APS are identified: Schmidt – chronic primary adrenal insufficiency in combination with chronic autoimmune thyroiditis or Graves disease and Carpenter – chronic adrenal insufficiency syndrome in combination with type 1 diabetes. APS 3 and 4 differ from APS 2 only in combinations of components – endocrine and non-endocrine diseases. They lack chronic primary adrenal insufficiency and chronic primary hypoparathyroidism. In addition, rare genetic pathologies occurring with polyglandular syndrome are known, such as Kearns-Seir syndrome, IPEX syndrome, POEMS syndrome, Tungsten syndrome, etc. Diagnosis of APS is difficult due to the variety of clinical symptoms and the difficulty of differential diagnosis. APS is characterized by the incorporation of new autoimmune components during long period of time, which makes it difficult to diagnose a variant of the syndrome. If the autoimmune damage of an endocrine gland appears, other components of APS should be excluded at the latent stage. Currently, there are no effective methods to block auto-aggression. Therapy of numerous endocrine and non-endocrine dysfunctions in APS consists of the treatment of particular components of the syndrome.

The methods for quantitative determination of thiamine in blood plasma by means of LC-MS method providing studies of bioequivalence are developed in this paper.

RETRACTED ARTICLEThis article reviews the methodological basic procedures of the allergenic extracts standardization protocols used for the allergen-specific immunotherapy in the world nowadays. The comparative analysis of the normative documents regulating the basic technological stages of allergenic extracts production was carried out. The data concerning the production and quality control of this biological drugs group was generalized. It is shown that the method of tandem mass spectrometry of high resolution combined with high performance liquid chromatography could be advantageously employed in the study area.

Spina bifida is a developmental defect of the spinal cord and / or spine that results from abnormal closure of the embryonic neural tube. Many factors have been described to determine the risks of developing this pathology, but the incidence of the defect is still high. 61 % of patients with Spina bifida have neurogenic bladder dysfunction based on intravesical hypertension, which contributes to reverse urethral flow and bladder-uretero-renal reflux associated with chronic inflammatory and obstructive urinary tract disease. In 25–50 % of patients with Spina bifida, urological pathology is complicated by the development of chronic kidney disease, which significantly reduces the quality of life of these patients. In some types of Spina bifida, urological symptoms may be prominent or even isolated and may indicate the presence of the malformation. Therefore, early diagnosis of Spina bifida and timely prophylactic and therapeutic measures are of particular importance.

Based on the results of Monte Carlo calculations of the spatial energy distributions of photons in iron from point isotropic and planar mononirectional monoenergy sources with energies of 10-50 MeV, the air Kerma attenuation multiplicities and dose accumulation factors of the material under consideration are determined.. The calculations take into account the contribution of the fluorescence, annihilation radiation and bremsstrahlung. The independence of the accumulation factors from the angular distribution of the source radiation is shown, and the independence of the attenuation multiplicities from the angular distribution of the source radiation and the weak dependence on its energy in the energy range 30-50 MeV is also shown. The corrections for the barrier protection are determined and their independence from the thickness of the protection and the photon energy of the source is noted. The obtained information allows to reduce the errors of the results of calculations of the thickness of anti-radiation protection of electronic accelerators at high energies, using developed engineering methods of calculation. The obtained information can also be used in calculations of protection against brake radiation of electronic accelerators by engineering methods.

The relationship between dissolution and bioavailability is an example of the interdependency between the quality of a medicinal product and its safety and efficacy. The uniqueness of thioctic acid is that it can exist in an oxidised and a reduced form, showing lipophilic (lipoic acid) and hydrophilic (dihydrolipoic acid) properties. Bioavailability studies of thioctic acid are necessary to evaluate the expected therapeutic effect and mitigate side effects of the medicinal product.The aim of the study was to carry out equivalence dissolution testing to compare the release of thioctic acid from medicinal products produced by several manufacturers.Materials and methods: the study used a reference medicinal product and three multisource medicinal products by different manufacturers; more specifically, film-coated tablets containing 600 mg of thioctic acid. The experiment was carried out in dissolution media at pH of 6.8±0.05 and 1.2±0.05. Statistical analysis was performed by calculating the average amounts of the substance dissolved, the standard deviation (SD), and the relative standard deviation (RSD, %) using Microsoft Office Excel 2007.Results: The authors chose the testing conditions (dissolution media pH values of 6.8±0.05 and 1.2±0.05) taking into account the nature and characteristics of thioctic acid. The comparison of thioctic acid release profiles based on the calculation of the similarity factor (f2) showed that the dissolution profiles of multisource medicinal products 2 and 3 at pH 6.8 were equivalent to that of the reference medicinal product (more than 85% of the active pharmaceutical ingredient released within 15 minutes) and the dissolution profile of multisource medicinal product 1 was not equivalent to it (with f2 of 28).Conclusions: the established differences in the rate and degree of active ingredient release from the studied medicinal products may indicate possible differences in their pharmacological effectiveness in vivo.

Secretory phospholipases A2 (sPLA2) represent a large superfamily of enzymes with a molecular weight of 14-19 kDa, including 15 groups and more than 30 isoforms belonging to four types: secretory (sPLA2), cytosolic (cPLA2), calcium-independent (iPLA2) and lipoprotein-associated phospholipase A2 (LP-PLA2, PAF-AH). Eleven species of secretory sPLA2s (IB, IIA, IIC, IID, IIE, IIF, III, V, X, XIIA, and XIIB) have been found in mammals, performing versatile functions and participating in the pathogenesis of a wide range of diseases. On the one hand, sPLA2 may promote elimination of damaged, apoptotic cells by hydrolyzing membrane phospholipids, and exerts a strong bactericidal and antiviral properties, including pronounced effects against antibiotic-resistant strains of microorganisms. In this regard, the use of sPLA2 may represent a new strategy for the treatment of bacterial and viral infections. Moreover, due to the action of sPLA2 on its substrates, a number of biologically active molecules (arachidonic, lysophosphatidic acids, lysophospholipids, fatty acids, prostaglandins, leukotrienes, thromboxanes) are formed, which provide strong inflammatory, detergent, coagulating effects and increase vascular permeability. This pro-inflammatory role of sPLA2 may explain its increase levels and activity in cardiovascular, respiratory, autoimmune, metabolic, oncological, bacterial and viral disorders. The review article presents a classification of sPLA2 isoforms, their substrates, regulatory factors, biological significance, and mechanisms of their strong bactericidal, virucidal, and pro-inflammatory activity in the heart and lung disorders, autoimmune, metabolic, bacterial, and viral diseases. In particular, the mechanisms of the selective action of sPLA2 against Gram-positive and Gram-negative microorganisms are discussed. We consider diagnostic and prognostic significance, correlations between elevated levels and activity of sPLA2 and distinct clinical symptoms, severity and outcome in the patients with coronary heart disease (CAD), acute myocardial infarction (AMI), atherosclerosis, acute inflammatory lung injury (ALI), respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, bronchial asthma, bacterial infections, septicemia and viral (COVID-19) infections. The opportunity of using sPLA2 as a biomarker of the severity and outcome of patients with chronic obstructive pulmonary disease, bacterial infections, sepsis and viral infections, including COVID-19, is also considered.

Relevance of the study: The quantification of endogenous substances is an important task in experimental and clinical pharmacology. In the case of working with endogenous compounds, certain difficulties arise. The main one is the impossibility of obtaining the same biomatrix without endogenous compounds for use as standard solutions in the construction of calibration curves. Purpose: The aim of our study was to develop a mathematical methodology for calculating the concentration of endogenous compounds in biological objects measured by chromatography, which allows us to obtain a statistically reliable interval estimation of the concentration of endogenous compounds. Materials and methods: To implement the computational part of the proposed algorithm, the Mathcad engineering calculation program version 15.0 from PTC (Parametric Technology Corporation) is used, which operates under the family of Windows operating systems (XP, 7, Vista, 8). Main results: A mathematical methodology has been developed for calculating the concentration of endogenous compounds in biological objects measured by chromatography, which allows one to obtain a statistically reliable interval estimate of the concentration of endogenous compounds. A feature of this technique is the use of an exclusively analyzed bioobject for quantitative determination of endogenous substances, without the use of so-called “pure” bioobjects for calibration curves, as well as expensive deuterated analogs of markers – substrates of CYP450 isoenzymes and their metabolites. This allows you to maintain the original biomatrix effect when removing the chromatogram. A statistical apparatus is also used to eliminate possible gross errors. To confirm the reliability of the developed method of quantitative determination, the convergence of the results obtained by this method using deuterated standards is established. Conclusions: A mathematical methodology has been developed for calculating the concentration of endogenous compounds in biological objects measured by chromatography, which allows one to obtain a statistically reliable interval estimate of the concentration of endogenous compounds. A feature of this technique is the use of only the analyzed bioobject for quantitative determination of endogenous substances, which allows you to maintain the original biomatrix effect when removing the chromatogram.

Nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid, can have a dose-dependent nephrotoxic effect. The study of the pharmacokinetics of acetylsalicylic acid products will contribute to timely detection and correction of side effects caused by this medicinal product.The aim of the study was to evaluate potential nephrotoxic effects following a single oral administration of 75 mg of acetylsalicylic acid, based on the analysis of the pharmacokinetic parameters.Materials and methods: the study involved 24 healthy volunteers who received 75 mg of acetylsalicylic acid (tablets) once orally. The measurement of the active metabolite of acetylsalicylic acid—salicylic acid—in blood plasma was performed by HPLC/MS using an Agilent 1200 liquid chromatography system coupled to an Agilent 6140 tandem mass spectrometer. Agilent Eclipse XDB-C18 column (4.6 mm×150 mm; 5.0 μm) was used for chromatographic separation. The test procedure used in the study was validated. The results obtained were used to calculate the pharmacokinetic parameters: Cmax (maximum concentration), Tmax (time to maximum concentration), T1/2 (half-life of the drug), AUC0-t (area under the pharmacokinetic curve from 0 to the last time point of the curve), AUC0-∞ (total area under the pharmacokinetic curve from 0 to ∞), MRT (mean residence time of the drug in the blood), Kel (elimination rate constant), Cl/F (total clearance), Vd/F (apparent volume of distribution). The Statistics (22.0.0.0) software was used for statistical processing of the results.Results: T1/2 of salicylic acid in blood plasma was determined to be 1.6 ± 0.5 h, Cmax was 4523.0 ± 725.0 ng/mL, and Tmax was 0.98 ± 0.4 h. AUC0–t was equal to 16183.0 ± 3823.0 ng×h/m, Vd/F was 12.0 ± 3.1 L/kg, and MRT was 2.9 ± 0.6 h.Conclusions: the analysis of the pharmacokinetic parameters demonstrated a high absorption rate, intensive distribution, and moderate elimination rate of salicylic acid (the main metabolite of acetylsalicylic acid), indicating a low risk of nephrotoxic effects associated with the studied dose of the drug.

Hypothyroidism belongs to widespread endocrine diseases. Disorders in the functions of various organs and systems causes difficulties in timely revealing of this diagnosis. The article analyzes the syndromes with which this pathology has to be differentiated. The algorithm of laboratory and instrumental diagnostics and treatment principles are presented.

The review article contains up-to-date information on the etiology, pathogenesis, clinical features, and genetic diagnosis of chronic adrenal insufficiency in children and adolescents. Diseases associated with hypocorticism are described. Diagnostic methods and treatment tactics are presented.

The review article describes the current data on the etiology, pathogenesis, clinical features, genetic diagnosis, and treatment tactics for hypoaldosteronism in children and adolescents. Phenotypic signs typical for this syndrome are described.

Antipsychotics are a first-line treatment for psychotic disorders. The cytochrome P450 isoenzymes CYP3A4/5 and CYP2D6 metabolize most antipsychotics. The activity of these isoenzymes in children changes with maturation, so it is different from that in adults. Objective: to study the associations of CYP3A and CYP2D6 isoenzyme activity parameters with the efficacy and safety of antipsychotics in adolescents with an acute psychotic episode. Patients and methods. The investigation enrolled 53 adolescents with an acute psychotic episode who took antipsychotics. The observation period lasted 14 days. The CGAS, PANSS, UKU SERS, SAS, and BARS scales were used to evaluate the efficiency and safety of the therapy on day 14. The activity of CYP3A and CYP2D6 isoenzymes was measured by determining the metabolic ratios of the concentrations of endogenous substrates of the isoenzymes and their metabolites in a morning urine sample on days 1 and 14 of the study. The activity of CYP3A was assessed by the 6-beta hydroxycortisol/cortisol ratio; that of CYP2D6 was measured by the 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline/pinoline ratio. The influence of carriage of polymorphic variants CYP2D6*4,*9,*10, CYP3A4*22, CYP3A5*3 on the activity of isoenzymes was excluded by removing their carriers from the analysis. Results and discussion. The investigators revealed an association of certain antipsychotic-induced undesirable symptoms with CYP3A and CYP2D6 activity parameters. On day 1, a lower CYP2D6 activity was initially observed in patients with tremor (0.54 [0.34; 1.34] vs 1.25 [0.91; 1.75]; p=0.023). Also, patients with any documented adverse reaction (ARs) to therapy had initially a decreased CYP3A activity (1.2 [0.85; 2.29] vs 2.55 [1.44; 4.83]; p=0.047) and an enhanced CYP3A activity during therapy (the activity difference between day 14 and day 1 was 0.28 [-0.28; 2.32] vs -1.3 [-3.47; 0.66]; p=0.042). Conclusion. The initially reduced activity of CYP2D6 and CYP3A isoenzymes is a significant predictor of antipsychotic-induced ARs in adolescents with an acute psychotic episode. The predictive role of CYP2D6 and CYP3A activity levels in the efficacy of antipsychotics has not been confirmed.

The paper is devoted to solving the problem of sustainable development of Russian organizations and their groups. In the face of a decline in key performance indicators of enterprises of various sectors of the Russian economy, growing signs of insolvency, the consideration of this problem is an extremely timely scientific event. There were applied the following steps to solve the problem: system analysis, the method of scientific abstractions, economic and mathematical modeling. Also, there have been analyzed the existing scientific-conceptual apparatus of the theory of efficiency and the tools used for its management. As a result, a new category has been proposed — “integrated strategic performances”, a number of economic and mathematical models, the chain of decisions based on binary choice. They had been tested for the purpose of predicting insolvency (bankruptcy) in small and medium-sized companies. Experimental work has confirmed the high accuracy of insolvency (bankruptcy) prediction, the ability to use the proposed analytical tools to manage the effectiveness of sustainable development of companies, as well as their groups, to create artificial intelligence in the field of organization management. The interest and the possibility of using innovations in their activities by such institutions like state institutions which are responsible for the development of small and mediumsized businesses, the Ministry of Finance of the republics, financial and municipal authorities departments was also confirmed; tax and law enforcement agencies, etc.

The aim of the article is to clarify the basics of the digitalization strategy of the competitive businesses and identify features of the institutional environment that ensure the development of cryptocurrency as a new asset (IT product) of the modern economy, analyze the methods of implementing the cryptocurrency business models. The relevance of the research paper is determined by the need to develop a competitive Russian cryptocurrency (including the cryptoruble) with the growing private, state and cross-national cryptocurrencies. The scientific novelty of the study implies clarifying the informal and formal rules of the institutional environment and related methods ensuring the development of a competitive cryptocurrency. The authors consider the following methods to implement the institutional features of the cryptocurrencies business model development: logic and blockchain algorithm that establish trust and collaboration between cryptocurrency developers; logic and blockchain consensus algorithm ensuring that all the parties of the blockchain network come to a common agreement (consensus); logic and blockchain algorithms that form cryptocurrency transactions and control its turnover by generating blocks of cryptocurrencies, by forming the structure of blocks and transactions of cryptocurrencies, by storing cryptocurrencies’ keys and providing security, by mining (forging) cryptocurrency, etс.The results of the study provide a basis for identifying the institutional features and the corresponding methods providing a competitive cryptocurrency development with a detailed analysis of the blockchain consensus algorithms that ensure the competitiveness of the cryptocurrency. The conclusions show that the most promising are the hybrid consensus algorithms which may include both the logic of two or more known algorithms and the original logic of a new algorithm. The authors recommend defining the logic of the blockchain consensus algorithm as a priority when developing a cryptocurrency to ensure reliability of the transactions in the blockchain network, thus increasing the competitiveness of the cryptocurrency.

Goal. To develop a mathematical and imitation model of the electric drive of the railroad switch as a two- and three-mass electromechanical system based on DC and AC motors as the main executive element of railway automation. The modelling is based on the parameters of the SP-6m switches as the main modification of the executive element of the Ukrainian domestic railways automation system. Methodology. The authors have presented the mechanical part of the railroad switch as a three-mass construction scheme with serial connection of elastic masses. Special attention is paid to the character of the movement of the switch point tongues, when describing them in the form of two- and three- mass kinematic schemes, as well as to the mechanical state of the traction and connections as nodes, which are most sensitive to the negative effects of some modes of the railroad switch. Results. A simulation mathematical model of SP-6m switch for AC and DC motors, which allows to study the influence of various factors, has been developed and tested at the stand of the Automation Laboratory of the Ukrainian State University of Railway Transport, Kharkiv. The deviation in the basic parameters of the switch translation process is less than 5 %. Originality. For the first time a mathematical model of an electric drive of the railroad switch is developed, which takes into account elastic relations and load characteristics as an object of controlling the speed of movement of switch point tongues. Practical significance. We have created a mathematical model of the electric drive of the railroad switch which allows to examine the influence of various factors, including the influence of the environment on the operation of the switch.

Mortality in athletes in 50% of cases is due to cardiovascular disorders, among which a significant role belongs to cardiac arrhythmias, in particular, atrial fibrillation (AF). Therefore, understanding of risk factors for AF in this group of patients is of great importance. In this review, we summarize recent experimental and clinical data on the links between physical activity, arterial hypertension, obesity, disorders of carbohydrate metabolism and AF.

To certify gas mixtures in the range of low (10-3-10-8 g/m3) mercury concentrations, we have proposed and tested a traceable method for measuring the mass concentration of mercury in gaseous media by inductively coupled plasma mass spectrometry (ICP/MS). The proposed method is based on a scheme that provides for the mass spectrometer calibration for saturated vapors (physical constant) of pure metallic mercury, dosed directly into the carrier gas stream - argon. The undoubted advantage of this method is its applicability to various gases and gas mixtures, which allows you to simulate any matrix medium that affects the measurement results of mercury content when analyzed by other methods. On this basis, «Methods of measuring the mass concentration of mercury in binary gas mixtures by ICP/MS» were developed and certified. The measurement range of mercury mass concentration is from 0,03 to 1000 pg/m3, the relative expanded uncertainty of measurements U- 4 %.

The article considers modern data on etiology, pathogenesis, clinical picture, genetic diagnostics of hypoparathyroidism in adolescents and children. The syndromes flowing with the clinical picture of this disease are described. The methods of examination and modern recommendations for treatment are presented.

The review article presents current data on water-electrolyte balance in healthy and pathological state. The diseases and conditions which occur in insipidary syndrome are described. The features of the clinical picture, diagnostic methods and treatment principles are considered.

The review article presents current data on water-electrolyte balance in healthy and pathological state. The diseases and conditions which occur in insipidary syndrome are described. The features of the clinical picture, diagnostic methods and treatment principles are considered.

In the survey article, modern data on etiology, pathogenesis, clinics, genetics and diagnostics of pheochromocytomas/ paragangliomas are analyzed. It also presents methods of instrumental examination and current recommendations for treatment.

The review article presents current data on water-electrolyte balance in healthy and pathological state. The diseases and conditions which occur in insipidary syndrome are described. The features of the clinical picture, diagnostic methods and treatment principles are considered.

The study of the state of carbohydrate and lipid metabolism in 47 children and adolescents with type 1 diabetes mellitus showed a progressive decrease in residual insulin secretion and insulin-binding activity of lymphocytes against the background of metabolic disorders of fatty acids, which are risk factors for severe course of the disease with the rapid development of hypoxia and other diabetic complications, including functional disorders in the digestive system.

In the survey article, modern data on etiology, pathogenesis, clinics, genetics and diagnostics of pheochromocytomas/ paragangliomas are analyzed. It also presents methods of instrumental examination and current recommendations for treatment.

The article presents a modern analysis of the family forms of the syndrome of multiple endocrine neoplasia in children and adolescents in foreign and domestic literature. Genetic mutations and characteristic phenotypic manifestations, diagnostic methods, approaches to prevention and treatment are described.

Alfacalcidol is an active synthetic preparation of vitamin D, characterized by high bioavailability and broad pharmacological properties. The article substantiates the possibility of widespread use of alfacalcidol in children and adolescents with osteoporosis of endocrine genesis.

The review of current «cocktail» phenotyping methods for biotransformation activity determination enabling simultaneous characterization of main cytochrome P450 isoforms activity was made. Furthermore, the possibility of their application in clinical practice in order to correct administered drugs dosage for the purpose of minimizing drug adverse reactions appearance risk was assessed.

A sensitive method for quantification of pinoline and its metabolite in human plasma using solid phase extraction and high performance liquid chromatography with mass-spectrometry was developed. Analytical range was 250-1500 pg/ml both for pinoline and for 6-hydroxy-1,2,3,4-tetrahydro-β-carboline. The developed method may be used to determine the current status of CYP2D6 activity.

Simultaneous quantification method of assaying main CYP isoforms substrates-markers and their metabolites in urine using HPLC-MS/MS was developed to determine activity of following isoforms: caffeine/paraxanthine for CYP1A2, losartane/E-3174 for CYP2C9, cortisole/6-β-hydroxycortisole for CYP3A4 and pinoline/6-hydroxy-1,2,3,4-tetrahydro-β-carboline for CYP2D6. Carbamazepine was used as internal standart. Urine was used as biological object, samples were prepared by extraction with ethyl acetate : hexane : diethyl ether (50:35:15) mixture continued with pH correction of urine sample using borate buffer (pH=9,4) and following extraction with ethyl acetate : hexane mixture (50:50). Method was successfully validated and can be put in clinical practice for CYP isoforms activity determination.

The article discusses the issue of increasing the efficiency of the Russian steel industry taking into consideration the requirements of the concept of sustainable development. To solve this problem the author reviews the practices of metal scrap collection and recycling at the leading enterprises of the North America, Europe and the forecast of metal recycling development in the world economy up to the year 2050. This part of the survey shows that technologies of metal scrap and other types of industrial waste recycling could result in considerable economy of different types of resources. The great benefit of using metal scrap recycling technologies by the companies in the United States and the European Union is new jobs creation and improvement of environmental conditions. Taking into account the mentioned benefits of using recycling technologies in steel industry the author analyzes the forecast information and concludes that the further development of steel industry may lead to two times increase in metal scrap collection and recycling by the middle of the XXI century. Companies of the Chinese People Republic, countries members of NAFTA and Japan will prevail in the regional structure of metal scrap consumption. The article also states that the system of metal scrap collection and recycling in the Russian Federation will have to be recreated on the qualitatively new foundation. The most important distinctive feature of a new system still under creation from the former one is that before all the enterprises engaged into metal scrap collection had made part of a single concern and operated as a branch of steel industry. In this regard the Russian Federation faces the problem of re-creation of institutional foundation of metal scrap collection and recycling as well as creation of mechanisms to manage this industry efficiently. This in turn will require the development of legal, regulatory, organizational, economic and scientific support.

Methods used to control the quality of peptide products depend on the level of development of analytical and bioorganic chemistry, and the level of instrumentation. Peptide identification is a difficult task and largely depends on the complexity of its structure. There does not exist a comprehensive and simple test, except for NMR, which, however, is rather expensive and time-consuming and involves complex data interpretations. Moreover, it does not allow for unambiguous determination of the peptide purity and formula (amino acid composition, sequence, chirality of amino acid residues). For this reason, a combination of methods is often used, including amino acid analysis, TLC/HPLC and mass spectrometry, and, less frequently, sequencing. Current international practice of peptide analysis is to use HPLC in combination with mass spectrometric, mainly tandem (HPLC-MS/MS), detection. According to literature sources the amino acid sequence of linear peptides can be analysed using various enzymes and subsequent identification of proteolysis products by mass spectrometry. This article presents approaches to the development of test methods for analysis of purity and identification testing of a small interfering RNA-based novel medicinal product, which will help standardise and control the quality of the production process.

The article presents the analysis of the current situation and observed trends in the global and Russian iron and steel industry. Based on those, several conclusions are made, specifically, that currently the growth in consumption of steel in the world is declining, but there is considerable overproduction of it. Based on the described findings the author describes the long-term prognosis of possible scenarios of development of the Russian steel industry, which is the basis of recommendations to improve the sector’s development strategy in the Russian Federation until 2030. In particular, it is proposed to prepare a transformation scenario, which is a feature of the management of sustainable development of ferrous metallurgy in the conditions of a possible reduction in demand for products, not only in the foreign, but also domestic markets. To do this, it is recommended to include indicators characterizing the economic, social and environmental performance activities into the government policy documents, governing the development of the steel industry. Also, it is recommended to consider the effectiveness of an integrated strategic and its derivatives as the most important innovation of system performance management tool for the activity of Russian metallurgical enterprises and groups.

Acute respiratory viral infection (ARVI) is one of the most common causes of morbidity in Russia. The incidence rate is high regardless of age or social group [1]. Sore throat is the most common symptom during ARVI, prevalence rate is 95%[2]. Symptomatic treatment of ARVI requires the use of various drugs, including drugs for pain in the throat. Such preparations are widely represented on the market, while they have a different form and different composition. One of the most popular are sprays containing benzydamine hydrochloride. Professional associations recommend using Benzydamine hydrochloridewhile sore throat, also in paediatric practice [3].In connection with a large number of generics, the issue of standardization of such sprays is topical. To compare the range of the actual concentration of the active substance in interchangeable preparations with different trade names, a comparative determination of the concentrations of benzydamine hydrochloride in sprays of 4 trade names was carried out in 6 different series in each. The quantitative determination was carried out by HPLC with a UV detector. As a result, the active substance concentration ranges were determined in 6 batches of the preparation of each trade name, and the coefficient of variation of concentrations was calculated and conclusions were made on the difference in the indicated indices among preparations of various manufacturers.

Development and improvement of biotechnological drugs currently more relevant than ever. Drugs obtained by means of biotechnology, have a number of positive qualities. Biotechnology allows you to create such products, which are currently impossible to synthesize by chemical means, in addition, the production of drugs using biotechnology meets the standards of quality, efficacy and safety and, more importantly, economically. Biotech drugs are used for treatment of infectious, autoimmune, cancer, are used to prevent, thereby finding wide application in medicine.

The present article highlights the issues of standardization of diagnostic and therapeutic allergen extracts used for allergen-specific immunotherapy (ASIT) in Russia and abroad. Quality evaluation methods for finished immunobiologicals (allergens) in accordance with the regulatory documents and using biological, immunochemical and advanced physical and chemical analytical techniques (in vitro and in vivo diagnosis) have been considered. Basic standardization strategies for allergenic preparations (determination of total allergenic activity, biological activity, the content of major allergens) have been presented. Two systems of allergen standardization (allergen units and biological units) have been introduced. The potential for use of high-performance liquid chromatography combined with mass spectrometry (HPLC-MS) as the most promising method for the standardization of allergen extracts has been considered. The advantages and disadvantages of the mentioned method for the standardization of allergens has been described. The method of chromatographic analysis of the total extract of drooping birch pollen, developed by the experts of the Chair of Pharmaceutical and Toxicological Chemistry of the I. M. Sechenov First Moscow State Medical University, has been given as an example.

Perindopril is a prodrug which is converted to an active metabolite perindoprilat in the human organism. The present study led to the development of a fast and easily reproducible procedure for simultaneous detection of perinoprilat and its metabolite in plasma using HPLC with mass-spectrometric detector (LC-MS). Detection of the target substance was performed using atmospheric pressure electrospray ionization (API-ES) techniques in negative polarity in two modes: SIM1, ion, m/z=368,10 for perindopril and SIM2, ion, m/z=339,30 for perindoprilat. Retention time of perindopril was about 2,4 min, for perindoprilat - about 1,4 min. Sample processing was performed using solid-phase extraction. The method’s limit of quantification was equal to 1 ng/ml for perindopril and 1 ng/ml for perindoprilat. The developed procedure was used to analyse pharmacokinetics and bioequivalence of medicines containing 8 mg of perindopril. Values of all calculated pharmacokinetic parameters had no statistically meaningful differences. Confidence intervals obtained fall within bioequivalence criterion (80-125% for AUC and 75-133% for Сmax и Cmax/AUC). The medicines under analysis were found to be bioequivalent.

The article presents relevant information on the features of cytochrome P450 isoenzyme CYP2D6 functioning. 20-25% of drugs are metabolized by the action of CYP2D6. Determination of its activity allows for adjusting pharmacotherapy to increase the efficacy and safety of a drug or a combination of drugs. Cytochrome P450 isoenzymes genotyping and phenotyping methods allow for choosing the dosage and dosing regimen for patients on an individual basis. This article describes the genetic characteristics affecting CYP2D6. CYP2D6 polymorphism has a significant impact on pharmacokinetics and metabolism of a drug. This may lead to side effects, or decrease the pharmacological action of the drug. The article covers the cases of change in clinical response to receiving β-blockers (metoprolol), antidepressants (venlafaxine) and opioids (codeine). These changes occurred in the presence of certain CYP2D6 alleles which speed up or slow down the metabolism. It also provides information on drug-drug interactions involving inhibition of cytochrome P450 isoenzyme CYP2D6. Genotyping methods are used to determine the potential activity of CYP2D6. Dose adjustment is carried out basing on the results obtained. The current isoenzyme status is defined by phenotyping methods. CYP2D6 activity can be evaluated by determining the ratio of the substrate and its metabolite using HPLC. Pinoline, which is metabolized to 6-hydroxy-1,2,3,4-tetrahydro-β-carboline, is the endogenous substrate for estimating the activity of CYP2D6.

One of the common issues of modern medicine is the risk of adverse drug effects when administering certain medicines. The causes of these effects may be various, but they mostly occur because of increased or decreased activity of xenobiotic-metabolizing enzymes, based on cytochrome P450 isoenzyme system (also known as CYP). For the date there is a number of different ways to determine the activity of the mentioned system in specific patient. The authors have studied the basic methods of determining the activity of drug-metabolizing enzymes and the approaches to their introduction into clinical practice, as well as the prospects of using them for the purpose of personalization of pharmacy and pharmacotherapy rationalization.

The article reports the results of the study which investigated the pharmacokinetics of mono- and multi-component ibuprofen-containing drugs following single oral administration to healthy volunteers. Plasma concentration of ibuprofen was determined by HPLC with spectrophotometric detection. The main pharmacokinetic parameters - Cmax, Tmax, AUC0-t, AUC0-¥, MRT, Kel, TЅ - were calculated after single oral administration of the tested drugs. The pharmacokinetics of Ibuprofen/mono and Ibuprofen (pitofenone+fenpiverinium bromide) after single administration did not demonstrate any statistically significant differences, while the combination drug Ibuprofen/paracetamol did have statistically significant differences in pharmacokinetics as compared to the monocomponent Ibuprofen drug.

The article reviews existing methods of determining CYP3A4 isoenzyme activity. The authors assess the significance of CYP3A4 activity determination and the applicability of these methods in clinical practice to adjust drugs doses and minimize risks of adverse reactions. The article demonstrates the possibility of developing a method for simultaneous determination of several CYP3A4 substrates which is necessary to rule out potential errors arising upon introduction of other P450 cytochrome enzymes into metabolism of some endogenous substrate. It is suggested that blood should no longer be used as a biological object in the study in order to decrease the method’s invasiveness.

Introduction, Purpose. One of the major tasks in the system of the country economic safety support is the monitoring the economy status provided by the Russian Federation Strategy of Economic Safety Support until 2030. At the same time the surveillance system over the economy status and dynamics of Russia in order to make the administrative decisions for safety as organizational information and technical system and institute in the outline of public administration does not exist now. In this regard putting the problem concerning the working out the system of monitoring is the relevant scientific and application-oriented task. Methods. In order to settle the stated task in the article the systems analysis, vital approach to a research of organizational systems, macroeconomic were used. Results. Defining the concept of monitoring in the sphere of an economic safety as the continuous regulated process is offered; the monitoring purpose as an involvement in support of economy stability, minimization of internal and external environment uncertainties is formulated. The main objectives and data domains of monitoring, its generalized information model are defined. The concept of vulnerability in the system of support of an economic safety is introduced. The task of creating the institutional infrastructure of monitoring, scientific and methodical, staffing, regulated and other types of its support is set. Discussion. The results of the research can be used in organizing the project of creation the monitoring system, deployment of methodical researches.

Results of pharmacokinetic study of a new dipeptide anxiolytic GB-115 in rats, rabbits and volunteers were presented. After oral drug administration significant differences were found. For example, a dose-independent parameter - the elimination rate constant was decreased: rat < human < rabbit. By contrast the half-life of GB-115 was increased: rat