Objective - to analyze the results of treatment for patients with ulcerative gastroduodenal bleeding (UGDB) from large and giant chronic ulcers to clarify the tactics of surgical treatment of this category of patients. Materials and methods. A study was conducted on the treatment results of 140 patients with UGDB out of 518 patients who were inpatient treatment at the Saint-Petersburg I. I. Dzhanelidze Research Institute of Emergency Medicine in 2018-2021. The main objectives of the examination of patients with UGDB were: clinical assessment of the patient's condition, identification of the source of bleeding, determination of the severity of blood loss and the risk of recurrence. The risk stratification of recurrent bleeding and adverse outcome was assessed according to the T.A. Rockall scale (1996). The study included elderly patients (average age was 66.8±7.3 years) with high comorbidity (Charlson2 comorbidity index 6.8±2.3) and blood loss of more than 30% of the circulating blood volume. Results. The overall mortality rate in the study group (n-140) was 15.1%. Among patients with severe and extremely severe blood loss, it was significantly higher - 20.8%. Recurrence of bleeding after TAE was noted in 13.3% of cases, after surgical treatment in 3.3% of cases and in 20% of cases in patients undergoing conservative therapy.Conclusion. Despite the changed paradigm of care for patients with UGDB towards conservative therapy, according to the literature, according to the data obtained, we came to the conclusion that in the group of patients with large and giant ulcers, the effectiveness of endoscopic hemostasis is reduced due to the size of the ulcerative defect and the comorbid background. This is evidenced by the high proportion of patients with recurrent bleeding after endoscopic hemostasis. Therefore, for this group of patients, it is necessary to adhere to certain algorithms that are based on assessing the risks of recurrent bleeding and an individual approach to choosing treatment tactics based on the severity of the patient's condition, while respecting the principle: treat not the disease, but the patient.

Objective - to study stress-induced changes in the population of the wall microbiome of the colon of wistar rats and their correction with an analog of the adrenocorticotropic hormone ACTH_6-9-PGP. Materials and methods. The experiments were performed on male Wistar rats (n = 45) weighing 280-300 g. The experimental animals were divided into 5 groups (n=9 in each): 1 - control: non-stressed rats were injected with saline solution, 2 - saline administration to stressed animals, 3-5 - administration of ACTH6-9-PGP to stressed rats in doses of 5, 50 and 500 μg/kg from the 15^th to the 28^th day of the experiment. The method of L.I. Kafarskaya and V.M. Korshunov was used to assess the state of the wall microbiota. The genus/species of the isolated microorganisms was determined on a Maldi Biotyper Microflex mass spectrometer (Bruker, USA). The relative mean and frequency of occurrence of microorganisms were evaluated. Results. 28-day restraint stress leads to the development of qualitative changes in the composition of the wall microbiota of the colon of rats in the form of a decrease in the relative average and frequency of occurrence of obligate microorganisms (Lactobacillus spp., Bifidobacterium spp., E.coli with normal enzymatic activity, Enterococcus spp.) and an increase in the proportion and frequency of opportunistic pathogens (Enterobacter spp., Proteus spp., Klebsiella spp., Morganella spp., Staphylococcus (coagulase-negative), S. aureus, Candida spp.). The use of the melanocortin analog ACTH_6-9-PGP corrected the above-mentioned stress-induced changes in the microbiological landscape of the colon. Conclusion. Thus, the synthetic analogue of melanocortins ACTH_6-9-PGP is a promising molecule for the development of pathogenetically based approaches to the correction of stress-induced disorders in the body.

Objective - to establish the correlations between the content of macro- and microelements and the parameters of the cardiovascular system with different types of self-regulation of the circulatory system in males in Magadan. Materials and methods. A total of 57 teenagers (average age 16.2±0.75 years) of students of the Magadan Polytechnic College and the Magadan Youth Sports School were randomly sampled in 2019. Cardiohemodynamic parameters were measured in adolescents in a sitting position at rest using the method of volumetric compression oscillometry. The laboratory part of the study was performed at Micronutrients LLC (Moscow) using atomic emission spectrometry and mass spectrometry with inductively coupled argon plasma. Hair samples from the occipital part of the head were used to assess the microelement status of the body. The content of 25 chemical elements was determined. Results. It has been established that the highest values of such functional indicators of the cardiovascular system as systolic blood pressure, diastolic blood pressure, stroke volume, stroke index, volumetric ejection velocity, left ventricular contraction power and vascular system compliance are typical for people with vascular TSC. The lowest values are typical for people with cardiac TSC. Adolescents with cardiovascular TSC occupy an intermediate position in terms of indicators. The analysis of the average group indicators of the content of macro- and microelements in adolescent hair showed significant differences between such trace chemical elements as potassium (K), sodium (Na), copper (Cu), chromium (Cr), vanadium (V). The highest content of these elements is observed in the group with cardiovascular TSC, while in the group with vascular TSC their concentration is minimal. Correlation analysis of the trace element composition revealed 17 significant relationships between the indicators in individuals with vascular type TSC, and 14 relationships in individuals with cardiovascular type TSC. There were no significant correlations in the group with cardiac type TSC. Conclusion. As a result of our study, significant direct and inverse correlations were established between the content of macro- and microelements and the types of circulatory self-regulation in adolescents in Magadan. The total number of correlations indicates a high sensitivity of the cardiovascular system of vascular TSC to an imbalance of macro- and microelements, which indicates the most stable functioning of the cardiovascular system in adolescents with this type of TSC.

Objective - to study the histological structure, chemical and elemental composition of the tibial regenerate after 60-day exposure to tartrazine at different times of bone healing, as well as to establish the possible effectiveness of sodium selenite. Materials and methods. The experiment was carried out on ninety mature white male rats. For 60 days, rats were daily intragastrically injected with 1 ml of saline solution (Fiz+Def group) or a similar volume of tartrazine solution at a dose of 750 mg/kg in isolation (T750+Def group) or combined with intramuscular administration of selenase (T750Sel+Def group). On the day 61 of the experiment, a tibial fracture was simulated by applying a through defect. The histological structure of bone regenerate was studied by light microscopy and morphometry. The content of water, organic, and mineral substances in the regenerate was determined by the weight method. The content of calcium, magnesium, and zinc in bone ash was determined by atomic absorption spectrometry. Results. In the T750+Def group, the most pronounced changes relative to the Fiz+Def group were recorded on the 15th and 24th days of the experiment. The area of the regenerate granulation tissue was higher by 118,06% and 84,89%, the area of woven bone, lamellar bone was lower by 28,79% and 24,13%. The water content was higher by 4,50% and 12,91%, the organic matter content - by 7,00% and 7,49%, calcium content - by 6,67% and 5,89%, zinc content - by 16,04% and 10,56%. In the T750Sel+Def group, the parameter values rose to the control values faster than in the T750+Def group. An increase in the area of woven and lamellar bones was found by 23,37% and 24,90% on 24th day, the content of calcium and zinc - by 7,14%, 10,13% and 5,35%, 10,35% on 15th and 24th days. Conclusion. Sixty-day exposure to tartrazine at a dose of 750 mg/kg changes the histological structure, chemical, and elemental composition of the regenerate at different times of its formation, and the introduction of selenase with it reduces their severity.

Objective - to study the dynamics of blood cytokine profile parameters in patients with psoriatic arthritis and metabolic syndrome during complex treatment with tofacinib and various types of physiotherapy. Materials and methods. The study involved 230 patients with psoriatic arthritis with signs of metabolic syndrome (mean age 55.3±7.0 years; 111 men and 119 women). The patients were divided into five groups: the first group received standard drug therapy (Ct), the second group received Ct and tofacitinib (Top+Ct), the third is Ct and plantar laser blood irradiation (NLOC+Ct), the fourth is Ct and phototherapy (Ft+Ct), the fifth is combined treatment (Top+NLK+Ft+Ct). The content of IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, IL-17, IL-18, IL-23, TNF-α and INF-γ in the blood serum of patients was determined by enzyme immunoassay before treatment, as well as 3 and 6 months after its start. Results. It was found that standard treatment did not cause significant changes in all the studied parameters at all follow-up periods. In the remaining groups, 3 months after the start of treatment, there was a significant decrease in blood levels of IL-1b, IL-2, IL-6, IL-8, IL-13, IL-17, IL-18, IL-23, TNF-α, INF-γ against the background of increased levels of IL-4 and IL-10 were most pronounced in the group of Top+NLC+Ft+Ct. In this group, cytokine levels significantly differed from those of other types of treatment at all follow-up periods. This fact may indicate a summation of the effects of different types of therapeutic effects when exposed to different pathogenetic links of the disease. At the same time, no significant differences were found in all groups of patients when comparing their indicators 3 and 6 months after the start of treatment, which indicates that there were no significant changes in their dynamics during this period. Conclusion. The use of standard treatment alone in patients with psoriatic arthritis with metabolic syndrome did not change the blood levels of the studied pro-inflammatory and anti-inflammatory cytokines 3 and 6 months after the start of treatment. The use of additional medicinal (tofacitinib) and non-medicinal (laser therapy, phototherapy) effects against the background of standard therapy caused significant changes in the studied parameters at all follow-up periods, with the most pronounced effect in a subgroup of patients with complex use along with standard treatment of tofacitinib, laser therapy and phototherapy.

Modern studies confirm the fundamental role of macro- and microelements in the formation of biological activity of medicinal plants. Medicinal plants such as knotweed ( Polygonum aviculare L.), yarrow common ( Achillea millefolium L.), wormwood bitter ( Artemisia absinthium L.), motherwort five-lobed ( Leonurus quinquelobatus Gilib.) are widely used as traditional, and in traditional medicine, while being able to accumulate both vital and toxic elements. Objective - to conduct a comparative elemental analysis of medicinal herbs harvested in the natural phytocenosis of the Voronezh region. Materials and methods. Plant herbs are harvested in the phenophase of flowering on the territory of the Voronezh State Biosphere Reserve (environmentally friendly zone). In parallel with grass harvesting, soil samples were taken from the upper horizon (0-20 cm). The elemental composition of medicinal herbs and soil after preliminary sample preparation by the method of acid and microwave decomposition was determined by the method of mass spectrometry with inductively coupled plasma on the ELAN-DRC spectrometer in accordance with the methodological instructions of MUK 4.1.1483-03. Results. 59 elements were quantified. All studied plants are active batteries of phosphorus, potassium, zinc and copper, which is emphasized by their vital importance in plant physiology. Yarrow and wormwood of bitter grass have high selectivity in mineral nutrition - they actively accumulate essential elements, and block the flow of the rest, which characterizes their metabolism as highly specialized. Highlanders of bird and motherwort five-lobed grass are characterized by lower selectivity in the accumulation of elements, absorb elements with a wider front, which can be an adaptation to unstable conditions or rapid growth. The identified features for hyperaccumulation of copper by wormwood, cobalt and nickel motherwort, five-lobed, lithium yarrow create a specific mineral profile that can modulate the activity of enzymes involved in the synthesis of alkaloids, terpenoids, flavonoids, i.e. directly affect the pharmacological potential of the raw material. Conclusion. The studies carried out confirm the rich and safe macro- and microelement profile of medicinal herbs of natural phytocenosis of the Central Black Earth Region. However, growing on the same soil, medicinal plants form a completely different elemental composition of the aerial part, reflecting their adaptation strategies and potential opportunities for use in medicine and nutritionology.

The low penetrating ability of antiviral drugs with acyclovir through the skin barrier is one of the reasons for their limited effectiveness. Therefore, new dosage forms with improved bioavailability, such as ointments based on tizol gel, are becoming a promising area of pharmaceutical development. A prerequisite for the creation and introduction of new drugs into medical practice is the availability of validated quality control methods. Objective - to develop a spectrophotometric method for the quantitative determination of acyclovir in the ointment "Acyclozol", made on tizol gel. Materials and methods. The analysis was performed using acyclovir substance, tizol gel, Aciclozol ointment (0.5 g of antiviral agent in 9.5 g of tizol gel). To carry out the research, spectrophotometry in the ultraviolet region was used using an SF-2000 spectrophotometer. The validation of the methodology was carried out in accordance with the State Pharmacopoeia of the Russian Federation XV edition, OFS.1.1.0012. Results. During the registration of acyclovir absorption spectra, it was found that the spectrophotometric determination of the antiviral agent should be carried out at a wavelength of 253 nm. The linear relationship between acyclovir concentration and optical density has been confirmed. The equation of the calibration graph is calculated. The content of acyclovir in the mild dosage form of "Acyclozol" is in the range of 0.4897-0.5375 g. The relative error of the analysis is not more than ± 1.87%. The proposed method of quantitative analysis of acyclovir is valid in terms of parameters - specificity, accuracy, precision and linearity in the analytical field. Conclusion. Using UV spectrophotometry, a method for estimating the quantitative content of acyclovir in a new antiviral ointment based on tizol gel has been developed and validated.

As part of the study, a method was developed for the synthesis of new benzimidazole derivatives modified with a fragment of spatially hindered phenol. The key step in the synthesis was the condensation reaction of 2,6-di-tert-butyl-p-benzoquinonimine with a number of aromatic and aliphatic aldehydes, which made it possible to obtain the desired compounds - 2,6-di-tert-butyl-4-[2-(R)-3H-benzimidazol-1-yl]-phenols. Identification and confirmation of the structure of the synthesized substances were carried out using a set of physicochemical methods, including elemental analysis, IR and ¹H-NMR spectroscopy. Assessment of antioxidant properties in vitro showed that a number of the obtained compounds have pronounced activity, and some of them have shown higher efficiency compared to reference substances - ubiquinone and dibunol. Objective - purposeful synthesis of a number of 2,6-di-tert-butyl-4-[2(R)-3H-benzimidazol-1-yl]-phenol derivatives using an improved procedure and subsequent comprehensive assessment of their antioxidant potential. Materials and methods. Synthesis of hybrid structures based on benzimidazole and shielded phenol was carried out using a modified method based on classical organic synthesis approaches. Elucidation of structure and identity of all target compounds were performed using a complex of analytical methods including IR, NMR ¹H spectroscopy and elemental analysis. The antioxidant activity of the synthesized samples was studied in a model system based on corn oil rich in a complex of saturated and unsaturated fatty acids. Lipid peroxidation in this system was induced both physically (UV irradiation) and chemically using the Fenton system (H₂O₂/Fe²⁺) as a free radical producer. For comparative analysis under identical conditions, the antiradical activity of the reference compounds ubiquinone and butylated hydroxytoluene was studied. The latter is the active ingredient of the drug dibunol and is a classic example of shielded phenol. Results. Antioxidant properties were studied in vitro for synthesized benzimidazole derivatives modified by introduction of spatially hindered phenol fragment. The results indicate a significant antioxidant effect exceeding that of the reference compounds (ubiquinone and dibunol). A number of leading compounds with maximum activity have been identified. Conclusion. The promise of 2,6-di-tert-butyl-4-[2-(R)-3H-benzimidazol-1-yl] phenols is due to their pronounced antioxidant activity, which opens up opportunities for studying a number of pharmacological effects mediated by it.