The experimental study is devoted to the identification of possible psychomodulatory and anxiolytic effects of ACTH(4- 7)-Pro-Gly-Pro and ACTH(6-9)-Pro-Gly-Pro under conditions of thyroid hyperfunction. Material and methods. The experiment was performed on white male rats, which were divided into groups: I – control; II – rats with hyperthyroidism model, III and IV – animals receiving ACTH(4-7)-Pro-Gly-Pro (Semax) and ACTH(6-9)-Pro-Gly-Pro at doses of 174 and 178 μg/kg/day, respectively, for 21 days against the background of hyperthyroidism. The development of experimental hyperthyroidism in animals was induced by administration of an aqueous solution of potassium iodide at a dose of 75 µg/kg by intragastric gavage, daily for 3 weeks. Behavioural activity was assessed using psychopharmacological tests “Lattice” and “Light-Dark box” in standard modification. Results and discussion. Under conditions of experimental hyperthyroidism in the “Lattice” test, changes in psychomotor behaviour of animals were observed in the form of suppression of orienteering and exploratory activity, namely, a decrease in the number of stands and exploratory “peeks” downwards. In the test “Light-Dark box” against the background of thyroid hyperfunction, an increase in the level of anxiety was observed, manifested in a decrease in the time spent in the light compartment, the number of transitions between compartments and racks, as well as an increase in the number of assessments of “risk” – “looking out” of the compartment. The studied substances ACTH(4-7)-Pro-Gly-Pro and ACTH(6-9)-Pro-Gly-Pro in conditions of experimental hyperthyroidism promoted the correction of the above-mentioned behavioural disorders, eliminating the anxiety-depressive state of laboratory animals. Conclusions. When studying the effect of ACTH(4-7)-Pro-Gly-Pro and ACTH(6-9)-Pro-Gly-Pro substances under conditions of experimental hyperthyroidism on behavioural activity of white rats in the tests “Lattice” and “Light-Dark box” it was revealed that the studied peptide compounds exhibit psychomodulatory and anxiolytic effects, correcting behavioural reactions.

Aim. To evaluate the usage of antihypertensive drugs (AHDs) and their combinations in participants aged 35 to74 years with arterial hypertension (AH) in the population-based study ESSE-RF3.Material and methods. Representative samples of the population aged 35 to 74 years from 15 regions of Russia (n=28731) with a response rate over 70% were examined in the ESSE-RF3 study. Therapy received by 9944 participants with AH (with systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg, or when the subject was taking AHDs) was analyzed. Information about AHDs intake (brand name of the drug) was recorded by questionnaire and coded according to International Nonproprietary Names by classes. Statistical analysis was performed using the open-source R 4.1 environment. Comparison of discrete indicators between groups was performed using Fisher’s exact test. The significance level for all tested hypotheses was taken as.05. The study was approved by the Ethics Committee of FGBI “NMRC TPM” of the Ministry of Health of the Russian Federation, each participant signed an informed consent.Results. Among the patients receiving therapy for AH, angiotensin-converting enzyme inhibitors (ACEIs) were used by 38.8% of participants, angiotensin receptor blockers (ARBs) — 31.6%, betablockers (BBs) — 29.0%, сalcium channel blockers (CCBs) — 21.5%, diuretics — 18.6%, 1.1% — outdated AHDs; 8.6% — other groups of drugs. Monotherapy was used by 53.1% of patients, 33.1% of participants received two, and 13.9% received three AHDs. Among participants taking two or more AHDs (including single-pill combinations (SPC)), males most often received the combination of BB+ ACEI and females — BB+ARBs. SPC AHDs were used by 10.3% of those receiving therapy (males: 9.8%, females: 10.6%). Among SPCs, the top three combinations were CCBs + ACEIs (28%), diuretics + ACEIs (27.5%), and diuretics + ARBs (24.4%).Conclusion. The population study ESSE-RF3, based on the survey of a representative sample of the Russian population aged 35-74 years, showed that more than a half of participants with AH receiving therapy were used the monotherapy, only every tenth of those treated received SPC. The problem of insufficient patients’ literacy was indicated — about 1% of patients received outdated AGPs. In addition, 8.6% of patients used non-AHDs for the treatment of AH. For improving the control of AH treatment, it is necessary to increase the adherence of patients to the prescribed therapy and more strict adherence of doctors to the published guidelines for AH treatment.

Pharmacogenetics aims to investigate the correlation between patient genetic characteristics and the efficacy of pharmaceutical agents, while concurrently evaluating the risks of adverse reactions. This field of research necessitates the application of complex statistical analysis methodologies, and artificial intelligence (AI) capabilities are increasingly being leveraged for such analyses. AI represents an advanced technology employed to automate the execution of tasks that traditionally demand substantial human intellectual effort. A review of scientific literature on the application of machine learning models in pharmacogenetic research has demonstrated that AI is a highly sophisticated and flexible tool capable of facilitating the widespread implementation of pharmacogenetics in clinical practice. A promising area for the application of AI in pharmacogenetics involves the integration of this technology into tasks related to the analysis, detection, prediction, and support of pharmacogenetic information and decision-making systems. The utilization of deep learning technologies has the potential to expand the understanding of drug pharmacodynamics, indications, and contraindications, which may potentially lead to the updating of educational and methodological literature on pharmacology and substantially advance the quality of patient pharmacotherapy. However, the implementation of AI technologies may be hindered by factors such as a shortage of qualified personnel, ethical disagreements, and complexities in legal regulation of this domain. Nonetheless, the application of AI technologies in pharmacogenetic research demonstrates high effectiveness and expediency, despite the existing challenges.

Опыт применения таргетных препаратов у детей с муковисцидозом в Астраханской области О. А. Башкина, Д

One of the main biological characteristics of SARS-CoV-2 is its remarkable ability to adapt to new environmental conditions. Accelerated evolution of the COVID-19 pathogen complicates anti-epidemic measures, including the need to update the antigenic composition of vaccines and maintain current vaccination measures, complicates the prognosis of the infection course, and reduces the efficacy of drugs based on monoclonal antibodies and specific antiviral inhibitors. Under these conditions, the search for new approaches to monitoring clinically and epidemiologically significant variants of the virus that escape the factors of humoral immunity, as well as to the accelerated development of relevant immunobiological preparations, becomes important. This in turn requires the use of approaches to assess the serological properties of new variants, such as neutralization reactions using live infectious virus or immunochemical methods with limited antigen detection. Immuno-PCR (iPCR) is a method which is lacked majority of virus neutralization reaction and immunochemical methods (ELISA and LFT) disadvantages. The iPCR method has many modifications aimed at increasing specificity while reducing background amplification, simplifying staging, and multiplexing. Taking into account the high sensitivity of iPCR, it is possible not only to measure the exact amount of antigen, but also to use the diagnostics in the minimum quantities available, for example, in clinical samples. This fact makes iPCR method high-promising in personalized medicine field. Key words: SARS-CoV-2, coronavirus evolution, immuno-PCR, humoral immunity

Currently, the problem of diagnosis and treatment of diseases associated with disorders of the angiogenesis process, as well as regenerative processes, is acute. Factors regulating the processes of angiogenesis in allergic diseases, including atopic dermatitis, play a key role in maintaining chronic inflammation and can have a significant impact on the course of the disease. Materials and methods: The study is analytical cross-sectional and presented by a comprehensive examination of 140 patients with AtD aged 2 to 12 years (median age 4.2 years), divided into 2 groups: 70 children with an established diagnosis of AtD; 70 children with atopic dermatitis infected with herpes simplex virus (AtD+HVI). The control group consisted of 70 somatically healthy children. A special laboratory examination included the determination of specific IgM and/or IgG class antibodies to herpes simplex virus type 1-2 antigens by enzyme immunoassay (ELISA); determination of the DNA of the studied herpesviruses in blood samples by polymerase chain reaction; determination of vascular endothelial growth factor A (VEGF-A) in the blood plasma of patients by ELISA. The results of our own research: A statistically significant (p <0.001) increase in the level of vascular endothelial growth factor A in blood serum was found in children with AtD compared with the control group. Against the background of infection with the herpes simplex virus, an increase in the level of vascular endothelial growth factor A in blood serum was revealed compared with patients with atopic dermatitis (p < 0.001). There was also a statistically significant increase in serum VEGF-A levels in patients with AtD (p < 0.001) and AtD+HVI (p < 0.001) with an increase in the severity of AtD. This was confirmed by the results of a correlation analysis that revealed the relationship between the level of VEGF-A and the severity of clinical symptoms of the disease.The addition of herpesvirus infection to AtD worsens the clinical symptoms of this disease.

To compare blood creatinine levels in children with constitutionally exogenous obesity and in children without obesity. Materials and methods of research. The analysis of serum creatinine levels (Jaffe colorimetric method) was carried out in 162 children with constitutionally exogenous obesity, including overweight children, grade 1–4 obesity and 178 children of the control group who were treated in the Department of endocrinology of the Regional Children's Clinical Hospital of Astrakhan in the age range from one and a half to 17 years. The study period was more than 10 years. The criterion for exclusion from the study was the absence of concomitant pathology of the urinary system. The results and their discussion. When comparing serum creatinine levels in two groups of children (obese and non-obese), a significant increase was found in the group of children with constitutionally exogenous obesity. Thus, creatinine in the blood ≥ 120.0 mmol/l was recorded in 25 children out of 162 examined with constitutionally exogenous obesity and in 3 children out of 178 without obesity (χ 2 = 19.43; p < 0.00001). The highest serum creatinine levels were recorded in children with obesity of 1–2 degrees. Conclusion. Constitutionally exogenous obesity is associated with chronic impairment of nitrogen excretion function of the kidneys.

The study of genes regulating the function of cytokines is an important aspect in the pathogenesis of bronchial asthma, predicting its severity and control. And also, as a result, the implementation of therapeutic approaches for this disease. Interleukin genes have a high degree of polymorphism. The aim of the work was to establish the significance of the effect of polymorphisms of the interleukin genes IL-4 590TC (rs2243250), IL-4RA I50V (rs2243250), TNF-alpha 308AG (rs1800629) on the phenotypic manifestations of the disease. a control group of children consisting of 90 people, patients with bronchial asthma of varying severity – 86 children. The identification of genetic polymorphisms was carried out by PCR. Statistical processing was carried out using the nonparametric chi-square criterion method with the analysis of conjugacy tables. The predictor significance of the homozygous variant of GG and the TNF-alpha allele G rs1800629 in severe disease, as well as the homozygous AG genotype with moderate severity of the disease. Studies of cytokine gene polymorphism in AD contribute to the study of the molecular genetic basis of AD formation and can be used to personalize therapy.

В рамках поиска новых антибактериальных препаратов проанализированы иммунотропные свойства производных хиназолин-4-она. Результаты проведенных экспериментов свидетельствуют о наличии иммунокорригирующей активности изучаемых соединений, что проявлялось коррекцией показателей белой крови и фагоцитарной активности нейтрофилов в условиях генерализованной стафилококковой инфекции. (N-(4-Метоксифенил)-2-[4-оксо-3(4H)-хиназолинил]ацетамид и 3-[2-оксо-2-(4-фенилпиперазин-1-ил)этил]хиназолин-4(3H)-он) при внутрибрюшинном введении 1 раз в сутки в течение 10 дней в дозе 500 мг/кг в условиях генерализованной стафилококковой инфекции у мышей вызывают увеличение фагоцитарного индекса в 1,4 и 1,7 раза (p < 0,05) и фагоцитарного числа в 1,5 и 1,3 раза (p < 0,01), по сравнению с группой животных, не получавших фармакологическую поддержку. Эти вещества нормализуют показатели белой крови, путем снижения общего количества лейкоцитов в среднем в 1,5 раза (p < 0,05), палочкоядерных нейтрофилов — в 1,8 и 1,4 раза (p < 0,01), лимфоцитов — в среднем в 1,5 раза (p < 0,01), а также увеличения сегментоядерных нейтрофилов в 1,7 и 1,3 раза (p < 0,01). Полученные результаты являются причиной проведения детальных исследований влияния производных хиназолин-4(3Н)-она на клеточное, гуморальное и макрофагально-фагоцитарное звенья иммунитета.

An analysis of the literature data on the role of the cardiotrophin-1 protein in chronic heart failure was carried out. Articles were selected and analyzed in PubMed, ScienceDirect, ProQuest, GoogleScholar, Cochrane, Medline, AMED, EMBASE, CINHAL, SportDiscus, Scopus and PEDro databases. The search for articles was carried out using the keywords: «Heart failure», «Biological markers», «Cardiotrophin-1», «Galectin-3», «Myocardium» and their combinations. Inclusion criteria were publication date from 2017 to 2022, clinical studies, meta-analyses and systematic reviews, randomized controlled trials, availability of the full text in the public domain or the abstract. Exclusion criteria: abstracts, monographs, textbooks, publication date before 2017, inconsistency with the research topic. A total of 80 publications were found. The review included 18 publications from 2017 to 2022 that corresponded to the topic and purpose of the study and were significant for revealing the subject of the study. Information is presented on the role of cardiotrophin-1 in chronic heart failure. Cardiotrophin-1 is activated in cardiac fibroblasts and cardiomyocytes in response to mechanical, humoral, metabolic and hypoxic stress. This biomarker is abundantly expressed in cardiac tissue and its overexpression is mainly stimulated by ventricular stretch/pressure, which promotes myocardial hypertrophy. Experimental administration of cardiotrophin-1 leads to fibrosis and myocardial remodeling, which indicates its role as a diagnostic biomarker in these pathologies and chronic heart failure in general.

Aim. To systematize modern scientific research that studies the role of monocytic chemoattractant in the development and progression of various diseases. Key points. At present, the interest of the scientific community in the issues of the pathoge-netic role of the monocyte-macrophage link of the cytokine spectrum in the development of a number of pathological changes in the body has increased. Conclusion. The monocyte chemoattractant is one of the key components of endothelial dysfunction and possibly can be presented as a biological marker of various diseases, which will greatly assist in early diagnosis and organization of the treatment process accordingly. Keywords: monocyte chemoattractant, nervous system, children

РезюмеАктуальность: На сегодняшний день бактериальные инфекции, вызванные микроорганизмами характеризуются устойчивостью к антибиотикам, что является одной из ведущих причин затяжного течения инфекционно-воспалительных заболеваний или же генерализации процесса, протекающего с развитием системной воспалительной реакции Тяжесть инфекционной патологии обусловлена гиперпродукцией провоспалительных цитокинов, что может привести к развитию, так называемого, «цитокинового шторма» с последующим развитием полиорганной недостаточности.Для преодоления этой проблемы были приложены значительные усилия, в том числе и разработка новых эффективных антимикробных препаратов, способных оказывать иммунорегуляторный эффект.В настоящее время пиримидиновые гетероциклические соединения рассматриваются как перспективная группа веществ для использования их в качестве основы для лекарственных препаратов.Цель исследования: Оценка уровня про-и противовоспалительных цитокинов в условиях экспериментальной генерализованной стафилококковой инфекции под влиянием производного пиримидина -3-(2-Фенил-2-оксоэтил)-хиназолин-4(3Н)-она.Материалы и методы: Влияние производного пиримидина на уровень про-и противовоспалительных цитокинов оценивали на модели генерализованной инфекции, вызванной внутрибрюшинным введением мышам Staphylococcus aureus.Мыши 5-недельного возраста (самцы, 40 особей) были разделены на группы (n=10): контроль I -животные, получавшие внутрибрюшинно эквиобъем воды для инъекций; контроль II -инфицированные стафилококком мыши, не получавшие лечения; две опытные группы -мыши, получавшие внутрибрюшинно цефтриаксон в средней терапевтической дозе -50 мг/кг и 3-(2-Фенил-2-оксоэтил)хиназолин-4(3Н)-она в дозе 21 мг/кг в течение 7 дней.Уровень цитокинов в сыворотке крови определяли методом иммуноферментного анализа

The review characterizes the role of the basic targets of antibacterial agents: efflux pumps, enzymes (DNA gyrases as a subclass of topoisomerases, homoserine transacetylase, various classes of sortases, aromatase, lipoteichoic synthase, polyketide synthase, pantothenate synthetase, acetyl-CoA carboxylase, sensory histidine kinase, kinase, cyclooxygenase, etc.), penicillin-binding protein, quorum sensing systems, and adhesins in significant biochemical processes of pathogen maintenance and virulence manifestation. It has been demonstrated that a chemical can exhibit the antimicrobial effect when it binds to protein molecules responsible for pathogenicity of a microorganism. The role of quinazolinone derivatives exhibiting high reactivity and stability in chemical processes and characterized by a wide spectrum of pharmacological activity, including antimicrobial activity with respect to various Gram-positive and Gram-negative bacteria, has been determined. It has been shown that structural changes induced by introducing various substituents contribute to a change in the degree of hydrophilicity and, as a result, determine a different degree of penetration of the drug through the cell membrane, the ability to form intermediate complex compounds stabilized by a system of hydrogen bonds, as well as by van der Waals and stacking interactions, with enzymatic targets, receptor regulatory proteins, and signaling systems of pathogen cells. The results of mathematical modeling of the mechanism of action of the compounds synthesized by the authors of the article are discussed. The possibility of creating a pharmaceutical with a pronounced antimicrobial activity by combining the quinazolinone core with various heterocyclic derivatives is assessed. The considered regularities are of practical importance for the researchers in the field of medicinal chemistry, organic synthesis, biotechnology, clinical pharmacology, and pharmaceutical chemistry and technology, whose efforts are aimed at designing a new drug.

Микробиота кишечника человека, представляя собой уникальную совокупность метаболически активных микроорганизмов, играет важную роль в регуляции широкого спектра физиологических процессов, в том числе функционировании нейроиммуноэндокринной системы посредством нейрональных, иммунных и метаболических взаимодействий, играющих роль в патогенезе нейродегенеративных

Introduction: This study was devoted to the experimental study of the effect of Semax (Met-Glu-His-Phe-Pro-Gly-Pro) on the level of pro- and anti-inflammatory cytokines (IL-1β, IL-4, IL-6, TNF-α, TGF-β1) in conditions of "social" stress Aim of the study: to study the effect of Semax on the level of pro- and anti-inflammatory cytokines (IL-1β, IL-4, IL-6, TNF-α, TGF-β1) under conditions of “social” stress. Materials and methods: White nonlinear rats (males, 6–8 months of age) were used as experimental animals. The animals were divided into groups: 1 – the control group (n=10); 2 – animals exposed to "social" stress (20 days) (n=10 aggressors/10 victims); 3 – rats exposed to "social" stress and receiving Semax intraperitoneally at a dose of 100 μg / kg / day (20 days) (n=10 aggressors/10 victims). Sensory contact was chosen as an experimental model of "social" stress. The level of cytokines (IL-1β, IL-4, IL-6, TNF-α, TGF-β1) was determined by the method of enzyme-linked immunosorbent assay. Results: Currently, within the framework of the development of a direction to study the functioning of the unified cytokine network of the body, there is a need for a detailed analysis of changes in the production of individual cytokines during various pathophysiological reactions, including stressful effects. The experimental "social" stress is accompanied by an increase in the production of IL-1β, IL-6, TNF-α, TGF-β1, which allowed us to consider stress as the main inducer of the production of cytokines of the family of proinflammatory interleukins and various growth factors. It was previously thought that inflammation and the immune response are the only factors capable of causing the production of most cytokines. In recent years, scientific works have appeared in which stress occupies an important place among the inducers of cytokine production. This fact has been confirmed by our experiments. Experimental "social" stress is accompanied by changes in the production of IL-1β, IL-4, IL-6, TNF-α, TGF-β1, which allowed us to consider stress as the main inducer of the production of proinflammatory cytokines and growth factors. Conclusion: Evaluation of the effect of Semax on the level of cytokines under conditions of "social" stress showed that the effect of Semax is aimed at restoring the level of the studied cytokines in the group of stressed animals.

Изучено влияние экстракта травы Астрагала лисьего (Astragalus vulpinus Willd.) на активность окислительной модификации липидов и белков в сыворотке крови белых крыс в условиях информационного стресса. Информационный стресс моделировали формированием пищедобывательного поведения в многоальтернативном лабиринте. Процессы липидной пероксидации оценивали при спектрофотометрическом измерении в сыворотке крови диеновых конъюгатов, исходного уровня ТБК-реактивных продуктов, скоростей спонтанного и индуцированного аскорбатом и ионами железа перекисного окисления липидов. Для определения степени перекисного окисления белков в сыворотке крови применяли метод, основанный на реакции взаимодействия окисленных аминокислотных остатков белков с 2,4-динитрофенилгидразоном. О состоянии антиоксидантной защиты судили по активности каталазы и супероксиддисмутазы. Установлено, что экстракт травы Астрагала лисьего проявляет выраженные стресс-протекторные, антиоксидантные и антирадикальные свойства в отношении показателей липидной пероксидации и окислительной модификации белков, а также каталазной и супероксиддисмутазной активности в сыворотке крови белых крыс в условиях информационного стресса.

This review presents data on endothelial dysfunction and the mechanisms of its development in coro-navirus disease. The possible pathology of the urinary system and its frequency in children against the background of COVID-19, which is mainly due to endothelial dysfunction, is described. Displayed studies on the frequency of urinary tract infections in children and adolescents during a pandemic, which depended on the level of quarantine measures, which in turn affect the neuro-psychological causes of bladder dysfunction, limited timely access to medical care, etc. A systematic review of stud-ies published in English from 2000 to 2019 was performed (with predominant inclusion (84,6 %) of data for the last 2 years) using PubMed, ScienceDirect, ProQuest, GoogleScholar, Cochrane, Medline, AMED databases., EMBASE, CINHAL, SportDiscus, Scopus and PEDro. The review included review articles, meta-analyses, qualitative studies, retrospective and prospective studies.