Vol 23, No 4 (2024)

Objective. Analysis of the results of scientific research on the effectiveness of fingolimod (FTY720), a modulator of sphingosine-1-phosphate receptors. Methods. Collection, systematization and comparative evaluation of literature data and the results of our own research on the experimental and clinical study of fingolimod, a non-specific modulator of sphingosine-1-phosphate receptors. Results. The review article presents current evidence on the sphingomyelin cycle of intracellular metabolism of sphingolipids; localization and functioning of five isoforms of the sphingosine-1-phosphate receptor. The current information about the first non-selective modulator of sphingosine-1-phosphate receptors, fingolimod, is described in detail. According to the literature, the protective effect of fingolimod has been shown in the treatment of multiple sclerosis and cerebrovascular pathologies. According to the results of our own research, the differentiated effect of fingolimod on non-respiratory lung functions in autoimmune (experimental autoimmune encephalomyelitis, antiphospholipid syndrome) and vascular (cerebral ischemia, intracerebral hemorrhage) pathology of the brain has been shown. Conclusion. Fingolimod, as a non-selective modulator of sphingosine-1-phosphate receptors, has a wide spectrum of action in various pathologies, including autoimmune ones. The widespread use of sphingosine-1-phosphate receptors in the mammalian body and their involvement in the implementation of many biological processes open up great prospects for studying the potential therapeutic possibilities of fingolimod and other modulators of sphingosine-1-phosphate receptors.

Objective. Study of the pharmacological effect of melaxen on the pro- and anti-inflammatory cytokines content of in the colonic wall in mice with experimental ulcerative colitis. Methods. Ulcerative colitis was simulated by replacing drinking water with a 5% solution of dextran sodium sulfate in boiled water for 5 days. Animals were removed from the experiment on the 5th, 7th and 28th days. Melaxen was administered intragastrically at a dose of 0.5 mg/kg body weight in a volume of 0.3 ml once a day for 7 days from the onset of ulcerative colitis simulation. The reference drug sulfasalazine was administered intragastrically in a volume of 0.3 ml at a dose of 200 mg/kg body weight for 7 days. The content of IL-1β, IL-4, IL-6, IL-10, IL-17 in the homogenate of the medial colon was determined by ELISA. Results. An increase in the IL-1β, IL-6 and IL-17 concentration was found on the 5th-7th days of disease development in mice with ulcerative colitis compared to the naïve group. The IL-4 content decreased on the 5th-7th days of the experiment, while the IL-10 concentration, on the contrary, increased. The IL-6 concentration was significantly higher than in naïve mice on the 28th day. The melaxen administration caused a decrease in IL-1β by 36.6 and 40.4%, IL-6 by 43.2% (only on day 5), IL-17 by 45.6 and 42.6%. A further decrease in the IL-1β and IL-6 concentration was shown on the 28th day. The melaxen administration caused an increase in the anti-inflammatory IL-4 and IL-10 concentrations on the 5th-7th days compared to the control group. No effect of melaxen on the content of anti-inflammatory cytokines has been established in chronic colitis. The pharmacological effect of melaxen is higher than sulfasalazine one. Conclusion. The corrective melaxen effect on the inflammatory cytokines production is apparently associated with the suppression of the Th1 lymphocytes activity.

Objective. To highlight the most pressing issues of the use of local anesthetics in dental practice. Methods. Based on domestic and international scientific publications, information is provided on clinical pharmacology and the possibilities of using local anesthetics in dental practice. Results. With local injection anesthesia, pain sensitivity is blocked at the site of injection of the anesthetic (infiltration anesthesia), as well as in the area of innervation of this nerve or part of it (conduction or regional anesthesia). Local anesthetics reduce or completely eliminate the flow of pain impulses from the site of intervention into the central nervous system by acting on sensitive nerve endings or fibers. Conclusions. Local anesthesia is the most widely used method of anesthesia in dental practice. This type of anesthesia is indicated in all cases when performing dental interventions accompanied by a painful reaction. It is contraindicated only in one case - if the patient is intolerant of local anesthetic.

Objective. Evaluation of the effectiveness of the rehabilitation program offered to patients with CHF based on the dynamics of the integral indicator of quality of life and body composition indicators. Methods. An open randomized controlled experimental study involved 120 patients with CHF and different body composition (isolated disorders of the fat and muscle components, sarcopenic obesity, weight loss and sarcopenia), randomly distributed into 2 groups: experimental and control. Within six months, patients from the experimental group, in addition to standard treatment methods, underwent the proposed rehabilitation program, which includes a diet with protein intake of at least 1 g / kg of body weight, as well as a set of physical exercises selected individually taking into account the condition of the patient's muscular component and respiratory gymnastics. The patients underwent bioimpedance measurements to assess their body composition. The MLHFQ questionnaire was used to assess the quality of life, highlighting three aspects: disease, palliative status and social adaptation. Results. Statistically significant differences in muscle mass, IMM/BMI, and quality of life indicators were found in patients of the experimental group before and after rehabilitation. Negative dynamics of indicators was also found in patients who are not undergoing cardiac rehabilitation. Conclusion. Cardiorehabilitation can be used in the provision of palliative care as a tool that improves the body composition of patients with CHF, as well as their quality of life.

Objective. To study the state of disability, assess the dynamics and structure of overall and primary disability of the attached child population during the period of 2020-2022. Methods. Calculation of relative and absolute values, mathematical and statistical analysis of data using tabular and graphical methods with the use of built-in programs was performed. Results. It was found that over the last three years, there has been a tendency for an increase in overall disability rates (by 1.1 times) and primary disability among children (by 1.4 times). In the structure of overall disability, children aged 10-14 years (33.1%) and 5-9 years (30.7%) represent the largest share. Conclusion. The greatest increase in overall disability was noted in the adolescent age group - by 30.4%, and in primary disability - among children aged 0 to 4 years (by 55.9%) and 5 to 9 years (by 25.4%). Gender differences were identified: the rates of overall and primary disability among boys were higher than among girls by 1.2 and 1.4 times, respectively.

Objective. Present a clinical case of a rare orphan disease using the example of Noah-Laksova syndrome, identified by characteristic phenotypic features. Methods. Based on literature data, the work describes in detail the latest scientific research on the results of studying Noah-Laksova syndrome. An analysis was carried out of the anamnestic data of the clinical case described in the article, materials from the inpatient chart, and the results of clinical and additional studies. Results. A case of a severe rare disease leading to the death of the patient is described. A diagnostic search algorithm is demonstrated. The characteristic phenotypic features and clinical manifestations of the syndrome are given. Due to the progression and improvement of medical care in neonatal practice, an increase in the life expectancy of patients with Noah-Laksova syndrome has been noted. Conclusion. The clinical example presented in the article shows the possibilities of diagnosing a rare orphan disease without genetic verification. In this case, the diagnosis of Noah-Laksova syndrome was made on the basis of striking and specific phenotypic features.

Objective. Analysis of the effectiveness of dental devices and technologies that prevent cold damage to teeth. Methods. Collection and analysis of literature data and the results of our own research on the study of dental resistance to cold influences and the development of dental devices and technologies that prevent cold damage to teeth. Results. Inhaling cold air with an open mouth at low ambient temperature threatens tooth damage, which is accompanied by toothache and ends with mechanical damage to the teeth due to the crystallization of water, which is part of their tissues. The risk of tooth damage increases with an increase in frost, wind, snowfall and the duration of inhaling cold air with an open mouth. The pathogenesis of cold injuries of teeth and a list of modern devices and technologies aimed at preventing cold lesions of teeth are considered. The essence of various technologies and their effectiveness in conditions of exposure to cold air on teeth are discussed. The features of thermal insulation of healthy teeth, as well as teeth with braces installed on them, are noted. Conclusion. The use of special decorative thermal insulation stickers on teeth provides thermal insulation of teeth when inhaling frosty air and prevents cold injuries to teeth. The introduction of such dental devices into everyday practice in order to prevent cold damage to tooth enamel and the development of cold toothache in polar explorers, oil workers, gas workers and other specialists working outdoors in winter in conditions of northern latitudes, the Arctic, Antarctica and/or highlands, as well as in military personnel when performing combat missions and athletes Those involved in winter sports seem to be an important medical and social task.

Objective. To develop microsurgical simulation model in a microneurosurgical laboratory for resident training. Methods. The first stage was isolation of the neurovascular bundle of the chicken thigh, the second stage was microneurosurgical training itself (end-to-end and end-to-side anastomoses of an artery, end-to-end nerve anastomosis, end-to-side anastomosis of a vein). All manipulations were performed under microscope (4-timemagnification) using microsurgical techniques. The following factors were considered: tightness, patency, the need for additional sutures and their number. End-to-end anastomoses were performed on the artery, vein and nerve, as well as end-to-side anastomosis between the artery and vein. A total of 15 arterial and 15 venous anastomoses were performed. Results. during their residency training in the specialty "neurosurgery" residents sequentially performed isolation of a neurovascular bundle on the chicken thigh followed by stitching end-to-end arterial anastomosis and end-to-side arteriovenous anastomosis, as well as end-to-end nerve suture under a microscope using microsurgical technique. At the end, the technique has improved, the speed of anastomosis performance has increased alongside with the accuracy and quality of work, and the tightness of vascular microanastomosis has also grown. Conclusions. Simulation training on a chicken thigh is a useful tool for developing microsurgical skills during residency training in the specialty "neurosurgery".

Objective. To discover additional radiomic IDH status predictors in adult-type diffuse gliomas that can be potentially applicable under conditions of primary diagnosis. Methods. Retrospective comparative statistical analysis of radiomic features extracted from 46 brain MRI in adult-type diffuse gliomas with known IDH status using HistogramMatching, ScaleIntensity preprocessing techniques and LevelTracing, GrowingFromSeeds segmentation tools. Results. The most effective combination of preprocessing/segmentation tools has been established - ScaleIntensity and LevelTracing, respectively. 5 reliable radiomic IDH status predictors revealing ROIs’ textural heterogeneity at the voxel level were identified. Conclusion. The possibility of developing a statistically reliable multiparametric IDH status predictive model based on traditional MRI data has been proved under conditions of small and technically heterogeneous sample. Presumably the use of relatively unified preprocessing methods and operator-dependent segmentation tools is preferred. The revealed radiomic features probably illustrate the degree of tumors’ morphological heterogeneity. Machine learning principles are planned to be introduced into the process of the predictive model creation.

Objective. To systematize the literature data on the pathogenesis and diagnostics of cerebral hemodynamic disorders occurring in acute cerebrovascular accident (CVA) of the hemorrhagic type. Methods. Analysis of data from domestic and foreign studies devoted to the pathogenesis and diagnostics of cerebral hemodynamic disorders occurring in acute cerebrovascular accident of the hemorrhagic type. Results. One of the most significant complications of the hemorrhagic type of CVA is the development of delayed cerebral ischemia, the main pathogenesis link of which is spasm of the cerebral main arteries, which also extends to the microcirculation system. The severity of irreversible complications of hemorrhagic stroke and their consequences are determined by hemodynamic disorders at the level of the microcirculatory bed vessels that provide transcapillary exchange and maintain tissue homeostasis. The state of cerebral microcirculation in pathological conditions can be maintained for some time due to the mechanisms of self-regulation of cerebral circulation. However, if the compensatory reserve of the autoregulation system is exhausted, the system will lose the ability to maintain the constancy of cerebral hemodynamics in conditions of acute intracranial hemorrhage. At the same time, an important contribution to the pathogenesis is made by hemoglobin biodegradation and the formation of free radicals, which trigger a complex of contractions of cerebral artery smooth muscle cells and a violation of vasodilatory activity due to prostacyclin/thromboxane A2 imbalance or oxyhemoglobin-induced inhibition of acetylcholine-mediated vasodilation. Proliferative vasculopathy, immunoreactive and inflammatory processes have also been postulated as possible mechanisms of vasospasm, microthrombosis and the development of delayed cerebral ischemia. Delayed cerebral ischemia can progress to cerebral infarction, which determines disability and high mortality. The problem of non-invasive assessment of the state of cerebral microcirculation remains unresolved, since currently the methods of studying peripheral circulation, developed primarily to assess microcirculation in the skin, do not allow non-invasively obtaining information about the state of cerebral microcirculation, which makes the problem of developing a set of indirect criteria of cerebral microhemodynamics relevant. Conclusion. To date, there is no combined diagnostic method that includes an assessment of structural changes in brain tissue and the state of microcirculation, which is necessary for the temporal and spatial assessment of disorders in the hemorrhagic type of stroke, as well as for establishing the pathophysiological cascade of vasospasm development.

Objective. Research on the development and validation of a technique for the quantitative determination of flavonoids in granules of Alfredia cernua L. polyextract. Methodology. Granules of polyextract of Alfredia cernua L. were used in the studies. For the quantitative determination of the sum of flavonoids we chose the method of differential spectrophotometry based on the determination of the products of the complexation reaction with aluminum (III) chloride. The method for quantitative determination of the sum of flavonoids in the herb Alfredia cernua L. was taken as a basis. Validation of the method was carried out according to the indicators provided by the State Pharmacopoeia of the 15th edition. Results. Granules of polyextract from the lower leaves of Alfredia cernua L., which have a nootropic effect, were used as an object of research. The flavonoid complex of Alfredia polyextract was studied and the predominance of isoquercitrin was revealed, which determines the cerebroprotective and nootropic effects of Alfredia cernua preparations. Differential spectrophotometry at an analytical wavelength of 410 nm was proposed as a technique for quantitative analysis. Calculations of the quantitative content of the sum of flavonoids were carried out in terms of isoquercitrin. The flavonoid sum content of alfredia polyextract granules was (10.59±0.33) mg in 1 sachet packet. Validation of the quantification methodology was carried out. The average acceptability value (the average percentage of openability adjusted by 100%) is in the range of 97-102%, the average percentage of openability was 99.93%, and the relative standard deviation does not exceed 3%, which corresponds to the RSD value optimal for this method of analysis. Studies were conducted on the internal laboratory repeatability (precision) and stability of the technique when working on devices of different brands. At the same time, comparable results were obtained. The mean acceptability value (mean opening percentage adjusted to 100%) ranged from 97-102%, the mean opening percentage was 99.93%, and the relative standard deviation did not exceed 3%, which corresponds to the RSD value optimal for this method of analysis. Intra-laboratory repeatability (precision) and stability of the methodology when operated on different brands of instruments were investigated. Comparable results were obtained. Conclusions. We have developed techniques for qualitative and quantitative analysis of Alfredia cernua L. polyextract granules. For qualitative analysis of flavonoid complex and isoquercitrin, we propose to use cyanidin assay and TLC technique. Differential UV-spectrophotometry, based on the determination of the reaction products of complexation of flavonoids with aluminium (III) chloride at an analytical wavelength of 410 nm, was proposed for the quantitative analysis of the amount of flavonoids in the pellets of polyextract of Alfredia cernua L. The results of the studies showed that the developed methodology for the quantitative determination of flavonoids in terms of isoquercitrin in the preparation of Alfredia cernua L. meets the requirements of GF 15 edition.

Objective. It is to develop methods of quantifying the amount of flavanoids in red-stemmed buckwheat grass. To make research for the selection of optimal parameters for the extraction of the ground part of raw materials in order to obtain extracts with a high content of biologically active substances. Methods. The object of the study is the red-stemmed buckwheat grass. Various extractants were used in the extraction process (purified water and ethyl alcohol 40%, 70% and 95%). Confirmation of the presence of flavonoids in the raw materials was carried out according to State Pharmacopoeia XV. Results. Qualitative reactions have shown that all extracts of red-stem buckwheat contain flavonoids. It was found that aluminum chloride leads to a bathochromic shift in the electronic absorption spectrum of red-stem buckwheat extracts with an absorption maximum similar to a solution of SS rutin (410 nm). Therefore, we selected rutin as the standard sample. It was found that the most effective extractant is ethyl alcohol with a concentration of 40%. Also it was found that the maximum extraction of flavonoids from the raw material takes place within 30 minutes. After statistical processing of data from five parallel measurements, it was revealed that the content of the sum of flavonoids, in terms of rutin, is 9.32-10.71%. Conclusion. The presence of flavonoids in red-stem buckwheat grass has been proven using qualitative reactions. It was revealed that the content of flavonoids in the raw materials of raw materials, when using various extractants, varies in the range from 1.72 to 10.71%. Optimal parameters have been established (extractant - ethyl alcohol 40%, the ratio of "raw material - extractant" is 1:25; extraction time is 30 minutes) for maximum extraction of flavonoids from the red-stemmed buckwheat herb. A method for quantifying the sum of flavonoids in terms of rutin has been developed.

Objective. Study of morphological and anatomical features of species of the genus Yarrow ( Achillea L.) using modern microscopic and statistical methods for inclusion in pharmacopoeial article 2.5.0101.18 ‘Yarrow herb’ of the State Pharmacopoeia of the Russian Federation. Methods. The above-ground part (herb) of species of the genus Yarrow growing in the Samara region and other regions of the Russian Federation - common yarrow ( Achillea millefolium L.), cartilaginous yarrow ( Achillea cartilaginea Ledeb. ex Rchb.), noble yarrow ( Achillea nobilis L.) - was studied. Raw materials were collected during the period of mass flowering of the plant 2021-2023. Light and polarising microscopy were chosen as research methods. Conclusion. As a result of the morphological-anatomical analysis, statistical processing was carried out and parameters of the following traits were determined: Number of flowers in the elementary inflorescence basket: the average number of flowers in the elementary inflorescence basket should be not less than 12 and not more than 15; Length and width of leaf spikes: length from the centre of the base to the apex of the spike varies from 62.9±0.1 µm to 63.4±0.1 µm, width at the base of the spike varies from 54.6±0.2 µm to 55.0±0.2 µm, shape wedge-shaped.

Objective. The purpose of this work is to establish the requirements for authenticity, the indicators of grinding, the content of impurities and the quantitative determination of biologically active compounds for a new plant raw material - the herb Erodium cicutarium . Methods. The establishment of quality indicators and testing of medicinal plant raw materials was carried out on the basis of the requirements of the general pharmacopoeia articles included in the State Pharmacopoeia of the XV edition, namely the requirements of sections 1.5.3. Methods of analysis of medicinal plant raw materials, medicinal products of plant origin and Section 1.2.2.2. Testing for the maximum content of impurities. The quantitative determination method was developed on the basis of the spectrophotometric method, the spectral characteristics were evaluated on the SF-2000 spectrophotometer (Russia) in cuvettes with a layer thickness of 10 mm. Results. Studies have been conducted on the standardization of whole, crushed and powdered raw materials - the herb Erodium cicutarium . Authenticity indicators have been developed, including morphological, anatomical and diagnostic signs, as well as qualitative reactions confirming the presence of tannins and flavonoids. The normative indicators included in the section «Tests» are proposed: humidity for whole and crushed raw materials - no more than 11%, for powder - no more than 10%, total ash - no more than 4%, ash insoluble in hydrochloric acid - no more than 1%, the content of foreign impurities: browned and yellowed parts of raw materials - no more than 3%, organic impurities - no more than 1%, mineral - no more than 0,5%, the grinding of raw materials - according to the results of sieve analysis, depending on the type of raw material. The quantitative analysis of active substances is proposed to be carried out by spectorophotometry under selected optimal conditions, as a result of which norms for the quantitative content of flavonoids are proposed. Conclusion. The results obtained are the basis of the draft pharmacopoeia article, and the possibility of expanding the range of herbal preparations.

Objective. Exploring methods to stimulate the development of drugs to treat unsatisfactory medical experiences. Methods. Information-analytical methods, methods of analysis and synthesis, logical methods, dividing the general into parts, extrapolation. Results. The stages of development of new medical technologies using regenerative medicine drugs have been identified. The main problem in the production of such drugs is small batches, which leads to high costs. The second problem in bringing ATMP to the market is the small number of patients and difficulties in conducting clinical trials. To solve the problem of conducting clinical trials, as well as the availability of new medical technologies, professional communities have created patient registries by disease profile, and are conducting long-term planning of clinical trials within the framework of registration and post-registration studies. The design and patient inclusion criteria are formulated in advance at an early stage of development through consultation with regulatory authorities. The EMA and FDA have reached an agreement to conduct joint scientific consultations on the development of gene and cell therapy drugs. At the current stage, the main problems that hinder progress in the development of new technologies of gene and cell therapy are being solved - high cost, unaffordable for a number of healthcare systems; restrictions on the number of subjects in clinical trials, leading to problems with the evidence base, technology transfer and production scaling. The next trend in the development of the HTLP market is the approval of expanded indications for use. Conclusion. High-tech drugs require complex regulation and separate requirements for the development and use of these drugs. The modern vector of scaling production and development processes requires specific approaches to managing the risks of using VTLP. From a commercial point of view, allogeneic drugs are more effective. Autologous drugs are necessary to solve personalized therapeutic problems. In the near future, global convergence of regulation of the circulation of drugs for regenerative medicine is expected, which is necessary to consolidate efforts to increase its availability and safety.