USE OF SEQUENCING METHODS FOR SPECIES IDENTIFICATION EXEMPLIFIED BY PHYLOGENETIC RELATIONSHIPS WITHIN GENUS HEDYSARUM L.

At the moment, a relevant objective in pharmacognosy, is the use of all kinds of the DNA analysis methods for identifying plant materials, detecting counterfeits, genetically modified crops and products.The aim of the research is to study the possibility of using molecular genetic research methods in the analysis of the genus Hedysarum L., for the identification of medicinal plant materials. This article presents the results of the application of molecular genetic research methods in the analysis of the genus Hedysarum L. in the flora of the North Caucasus.Materials and methods. The study material was the samples of the genus Hedysarum L. species collected in the North Caucasus: Hedysarum caucasicum M. Bieb. (in the fruiting phase in the territory of the Karachay-Cherkess Republic); Hedysarum grandiflorum Pall. (in the fruiting phase in the Volgograd region); Hedysarum daghestanicum Rupr. ex Boiss. (in the flowering phase in the Republic of Dagestan). Sequencing of the ITS1-5.8S-ITS2 marker region of gene 5.8S by the RNA ribosome was carried out according to the Sanger method on the AbiPrism 3130 genetic analyzer at the laboratory of biosystematics and cytology of Komarov Botanical Institute of the Russian Academy of Sciences.Results. Based on a comparative study of the marker region of the nuclear ribosomal gene 5.8S rRNA, marker nucleotide substitutions of Hedysarum caucasicum M. Bieb., Hedysarum daghestanicum Rupr. ex Boiss., Hedysarum grandiflorum Pall, have been identified. The most probable secondary structure of 5.8S rRNA has been constructed. It has been shown that based on the analysis performed, it is possible to predict additional raw material sources of mangiferin and other groups of xanthones using the molecular data exemplified by the Obscura section.Conclusion. Based on the data obtained, it can be concluded that the morphological classification of the genus Hedysarum L. can be confirmed within the Obscura section.

CLINICAL AND ECONOMIC JUSTIFICATION OF SOFTWARE SCREENING PERFORMANCE OF COLORECTAL CANCER AT THE REGION LEVEL

The aim of the study is to assess the clinical and economic effectiveness of the practical implementation results of programmed screening for colorectal cancer (CRC) in the Primorsky Territory using clinical and economic research methods.Materials and methods. In the study, the following kinds of data were used: the statistical data from the regional clinic’s cancer registry on the structure of the morbidity and average life expectancy of CRC patients in the Primorsky Territory; the data on the cost of screening studies and the stages of anticancer therapy in accordance with the “Territorial Tariff Agreement on Payment for Medical Care (Medical Services) in the System of Compulsory Health Insurance in the Territory of Primorsky Krai”, 2021. Two methods of clinical and economic analysis with the corresponding calculation formulas have been applied. The cost of medical interventions were estimated in accordance with the screening standards and clinical guidelines for the treatment of malignant neoplasms of the colon and rectum, approved by the Scientific and Practical Council of the Ministry of Health of the Russian Federation, 2020.Results. The evidence-based substantiation of screening clinical effects has been obtained: the structure redistribution of colorectal cancer incidence towards the prevalence of early forms by 16.81%; the average increase in the life expectancy of patients with the studied disease is 12.8 months. A natural consequence of these events is the predicted decrease in the mortality rate from CRC in the territory of the subject in the subsequent years. The economic justification of CRC screening software which guarantees a significant saving in health care resources amounting to 23% compared to an alternative strategy, has been demonstrated. It can influence the management decisions on the further strategy of the mass introduction of this medical technology.Conclusion. Currently, CRC screening is the most effective way to reduce morbidity and mortality from this disease. The predominance of the early diagnosis of the disease is extrapolated to significant savings in public health care. A promising direction for further research in the field of CRC screening is the study of its long-term effects, in particular, a detailed clinical and economic analysis of the diagnostics effectiveness and the elimination of premalignant neoplasms.

STUDY OF CLINICAL AND PATHOGENETIC EFFECTS OF ANTI-VIRAL DRUG BASED ON FAVIPIRAVIR IN COMORBID PATIENTS WITH COVID-19 AT THE OUTPATIENT STAGE OF TREATMENT

In many ways, arterial hypertension and obesity determine the likelihood of a severe course and lethal outcomes in COVID-19. This fact justifies the expediency of an early use of drugs with a direct antiviral action, the analysis of their efficacy not only in the acute, but also in the postcovid period.The aim of the research was to analyze the outpatient cards and case histories of the COVID-19 patients to study the effect of the early (up to the 5th day after the onset of the first symptoms of the disease) use of the drug based on favipiravir, on the frequency of patients’ hospitalizations with arterial hypertension and obesity, as well as to determine the cytokine status characteristics of this patient category in the postcovid period.Materials and methods. “An open prospective comparative study of the “Areplivir®” (favipiravir) efficacy in the debut of COVID-19 in comorbid patients” was carried out in the Republic of Mordovia (the analysis of the hospitalizations frequency and blood levels of M-CSF, EPO in 218 patients, in terms of the use of the antiviral preparation).Results. According to the results of the analysis, it was found out that, despite the presence of comorbid conditions that increase the risk of developing a severe course of COVID-19, i.e. obesity and essential arterial hypertension, in the group of patients taking favipiravir, the need for hospitalization was twice as low (p < 0.05), in relation to the comparison group. The analysis of the cytokine status revealed that in the postcovid period, in the group that took the drug based on favipiravir at the outpatient stage, the average level of M-CSF was significantly lower (p> 0.05), and EPO was higher (p> 0.05) than in the patients from the group “without antiviral drugs at the outpatient stage”. Indirectly, according to the previously obtained data, that acts as a potential marker for reducing the risk of long-term cardiovascular complications of COVID-19.Conclusion. This study showed that an early prescription of favipiravir contributes to a decrease in the rate of COVID-19 patients’ hospitalization even against the background of concomitant hypertension and obesity, due to a decrease in the likelihood of moderate and severe courses of the disease, and also leads to an earlier objective and subjective recovery. The results demonstrated a high potential benefit of an early favipiravir use in the novel coronavirus infection and in the prevention of postcovid complications.

ANALYSIS OF THE PERSONNEL’S CONSISTENT READINESS FOR CHANGES AS ILLUSTRATED BY THE EXAMPLE OF AN EXPORT-ORIENTED BIOTECHNOLOGICAL ENTERPRISE

The biotechnology industry is currently one of the most dynamically developing sectors of the pharmaceutical industry, that is why it requires improvement in the personnel management system aimed at increasing the flexibility and adaptability of the organization.The aim of the research is to determine the degree of readiness of the organization’s employees for innovations as illustrated by the example of an export-oriented enterprise.Materials and methods. The source information was collected from the employees of the biotechnological enterprise through a questionnaire survey. The representative sample included 588 respondents. The statistical processing of data was carried out using the specialized software IBM SPSS STATISTICS (IBM, USA, 2017). The consistent readiness of the organization’s employees for innovations was determined using I.O. Zagashev’s methods. To assess the reliability of the psychological test, an internal consistency model with Cronbach’s alpha was applied. Statistical hypotheses were tested by comparing the central tendencies of two independent samples using Student’s t-test and the Mann–Whitney nonparametric test.Results. The distribution results of key motivating factors for personnel showed that motivating factors such as an adequate salary and sustainable employment took the leading positions. However, the assessment of the employees’ consistent readiness for innovations according to I.O. Zagashev’s methods shows a high degree of the personnel’s readiness for changes due to positive emotional perception of any innovations.Conclusion. The results obtained make it possible to arrive at the conclusion that the established team favorably responds to all innovations, and is ready to support them in the future being aware of the organization’s desire for innovations. In the future, the results will be used to determine the required management functions and goals and to develop the personnel management strategy in the context of the knowledge transfer, technology and export policy of the pharmaceutical enterprise.

DEVELOPMENT OF PERORAL HYPOLIPIDEMIC FORMULATION BASED ON SULFATED ARABINOGALACTAN IN THE FORM OF POTASSIUM SALT

An original heparinoid, sulfated arabinogalactan in the form of potassium salt, possessing anticoagulant and hypolipidemic activities, has been developed at the A.E. Favorsky Irkutsk Institute of Chemistry Siberian Branch of the Russian Academy of Sciences.The aim was to develop solid peroral dose forms (capsules and film-coated tablets) for the prevention and treatment of atherosclerotic lesion of blood vessels on the basis of potassium salt of sulfated arabinogalactan which would be suitable for further clinical trials of these forms.Materials and methods. The following materials were used in the work: sulfated arabinogalactan in the form of potassium salt, obtained at the A.E. Favorsky Irkutsk Institute of Chemistry Siberian Branch of the Russian Academy of Sciences; Ludipress®; AEROSIL® 200 Pharma; calcium stearate; Aquacoat ECD. The powder mixtures were briquetted followed by tableting and application of the finished film coating Aquacoat ECD, and encapsulation in hard gelatin capsules.Results. Composition and technological characteristics of capsules and film-coated tablets were determined using physico-chemical and technological properties of sulfated arabinogalactan in the form of potassium salt. Technological parameters and quality indicators were determined for the solid pharmaceutical dose forms in accordance with the requirements of the State Pharmacopoeia of the Russian Federation of the XIVth edition. Conclusion. The optimum compositions and technology for the preparation of capsules and film-coated tablets based on potassium salt of sulfated arabinogalactan for the prevention and treatment of atherosclerotic lesion of blood vessels, were developed. The data obtained were used for the regulatory documentation design.

A FEW REPRESENTATIVES OF ASTEROIDAE (ASTERACEAE) SUBFAMILY AND GERANIUM (GERANIACEAE) GENUS IN THE BAIKAL REGION (REVIEW

The aim of the article was to analyze the state of knowledge of the following plants: Heteropappus altaicus (Willd.) Novopokr., Solidago dahurica L., Leucanthemum vulgare Lam., Tripleurospermum inodorum (L.), Antennaria dioica (L.) Gaertn., Leontopodium conglobatum (Turcz.) Hand.-Mazz. and Geranium eriostemon Fischer., G. pratense L., G. wlassowianum Fisch. ex Link. (Geraniaceae).Materials and methods. To compile the review, the information from the following scientific open and available literature sources placed in scientific libraries of institutions, in electronic databases and search systems, was used: floristic summaries “Flora of Siberia”; “Flora of Central Siberia”; Electronic library of the Siberian branch of the Russian Academy of Sciences; Elibrary; PubMed; Scopus; CyberLeninka, Google Academy; The Plant List, Global Compositae Checklist. The search carried out, was based on the publications for the period of 2009-2020, on the information requests for names of families and subfamilies, names of plant species, biologically active compounds in English, Latin and Russian.Results. A comparative analysis of morphological characters, common species names and the synonyms for the listed species, has been carried out. The studied objects are characterized by the presence of polyphenolic compounds and substances of a triterpene structure, in particular, flavonoids, hydroxycinnamic acids, tannides. In addition, the representatives of the Asteroideae subfamily (Asteraceae) show the accumulation of essential oils, and the representatives of the Geranium genus (geranium) show the accumulation of anthocyanins. The spectrum of the pharmacological activity includes anti-inflammatory, choleretic, antimicrobial, antispasmodic and other types of effects.Conclusion. The presented review makes it possible to arrive at the conclusion about a certain knowledge level of the regional representatives of the Asteroideae subfamily and the Geranium genus. This determines the prospects of these plant objects for further pharmacognostic and pharmacological research and the creation of drugs on their basis – the sources of polyphenolic compounds.

EFFECT OF GLYPROLINES ON THE LEVEL OF APOPTOTIC AND NEUROTROPHIC FACTORS UNDER CONDITIONS OF “SOCIAL” STRESS

The aim of the article was to study the effect of glyproline neuropeptide compounds Thr–Lys–Pro–Arg–Pro–Gly–Pro (Selank), Pro–Gly–Pro and Pro–Gly–Pro–Leu, on the level of apoptotic factors (caspase-3, caspase-8, the tumor necrosis factor) and neurotrophic factors (the nerve growth factor and the brain neurotrophic factor) in the blood serum of white rats under the experimental modeling of “social” stress.Materials and methods. The experimental studies were carried out on 90 nonlinear white male rats aged 6 months. By the type of behavior, in the process of “social” stress modeling, all the rats were divided into “aggressors” and “victims”. In the study, the following experimental groups (n=10) were formed: control individuals; groups of the rats exposed to stress for 20 days; groups of the animals treated intraperitoneally at the dose of 100 μg/kg/day, starting from the 1st day of the stress factor exposure, with a course of 20 days of glyproline compounds Thr–Lys–Pro–Arg–Pro–Gly–Pro (Selank), Pro–Gly–Pro and Pro–Gly–Pro–Leu. The effect of the compounds on the level of apoptotic and neurotrophic factors was assessed by determining the level of caspase-3, caspase-8, the tumor necrosis factor, the nerve growth factor and the brain neurotrophic factor of white rat blood serum by enzyme immunoassay.Results. According to the results of the study, it was found out that under the conditions of “social” stress, there was an increase in the apoptotic processes accompanied by an increase in the level of caspase-3, caspase-8, TNF-α in the blood serum of white rats, as well as a decrease in the concentration of neurotrophic factors – BDNF and NGF. The administration of giproline compounds against the background of stress, contributed to the restoration of the studied indicators level, which is most likely due to the presence of antiapoptotic and neuroprotective effects in giprolines due to the inhibition of the caspase-dependent cascade of apoptosis reactions, as well as the induction of the synthesis of neurotrophic factors with the antiapoptotic activity.Conclusion. Thus, the administration of glyproline neuropeptide compounds Thr–Lys–Pro–Arg–Pro–Gly–Pro (Selank), Pro–Gly–Pro and Pro–Gly–Pro–Leu under stress conditions, contributes to the restoration of the initiating and effector caspases level, as well as of neurotrophic factors. As a result of the experiment, an anti-apoptotic effect is observed due to the inhibition of the caspase-dependent cascade of reactions, as well as a stress-protective effect is observed due to the restoration of the brain neurotrophic factors level.

HEAT SHOCK PROTEIN HSP70: PREREQUISITES FOR USE AS A MEDICINAL PRODUCT

Heat shock protein Hsp70 is one of the main cytoprotection components under the action of various external stimuli. The analysis of the literature data shows that nowadays, the researches’ overwhelming evidence has proven the role of Hsp70 as a biological target for the drug development; however, the ideas about its use as a drug are often multidirectional.The aim of the article is to analyze and generalize the literature data on the features of the physiological functions of heat shock protein Hsp 70, and indicate the possibilities of its use for the pharmacological correction of various pathological conditions.Materials and methods. In the process of selecting material for writing this review article, such databases as Google Patents, Science Research Portal, Google Scholar, ScienceDirect, CiteSeer, Publications, ResearchIndex, Ingenta, PubMed, KEGG, etc. were used The following words and word combinations were selected as markers for identifying the literature: Hsp70, Hsp70 stroke, Hsp70 neuroprotection, Hsp70 cytoprotection, recombinant drugs.Results. In this review, the pharmacology of one of the key members of this family, Hsp70, was focused on. The literary analysis confirms that this molecule is an endogenous regulator of many physiological processes and demonstrates tissue protective effects in modeling ischemic, neurodegenerative and inflammatory processes. The use of recombinant exogenous Hsp70 mimics the endogenous function of the protein, indicating the absence of a number of typical limitations characteristic of pharmacotherapy with high molecular weight compounds, such as immunogenicity, a rapid degradation by proteases, or a low penetration of histohematogenous barriers.Conclusion. Thus, Hsp70 may become a promising agent for clinical trials as a drug for the treatment of patients with neurological, immunological, and cardiovascular profiles.

TYPE 2 DIABETES MELLITUS’S DECOMPENSATED FORM: ON THE PROBLEM OF EFFECTIVE PHARMACOTHERAPY IN REAL CLINICAL PRACTICE

The aim of this retrospective study was to analyze the pharmacotherapy regimens of the decompensated form of type 2 diabetes mellitus (DM2) and to evaluate its effectiveness, its compliance with clinical recommendations.Materials and methods: A retrospective analysis of 54 medical cards of patients with decompensated DM2 was conducted. The 1st group (n=24; 44%) included the patients who had a decrease in glycated hemoglobin (HbA1c) by 50% or more in 3 months after hypoglycemic therapy; and the 2nd group (n=30; 56%) – the patients whose HbA1c level decreased by less than 50%.Results. A HbA1c level was 10.4% in the 1st group and 13.2% in the 2nd group (р<0.001). However, the target levels of venous blood plasma glucose and HbA1c were not achieved in any of the patient groups. The total number of the drugs prescribed to the patients ranged from 4 (in 25% (n=6) and 10% (n=3) cases in the 1st and the 2nd groups, respectively) to 8 (in 12.5% (n=3) and 20% (n=6) cases in the 1st and the 2nd, groups, respectively). However, in a number of cases some violations of clinical recommendations were recorded: the prescription to the obese patients of insulin drugs, the administration of sulfonylureas derivatives to patients with a history of cardiovascular diseases of the atherosclerotic origin, but modern hypoglycemic drugs with proven benefits in reducing cardiovascular risks were rarely prescribed.Conclusion. The tactics of pharmacotherapy in the patients with a decompensated form of DM2 does not fully comply with the approved clinical guidelines, which requires the effectiveness of treatment optimization of this medically and socially significant pathology.