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Vol 24, No 8 (2021)


Lung fibrosis in COVID-19 survivors: histone deacetylase inhibitors as a promising therapeutic strategy

Aitbaev K.A., Murkamilov I.T., Murkamilova H.A., Fomin V.V., Kudaibergenova I.O., Yusupov F.A.


Over the past twenty years, the world has witnessed several viral epidemics such as the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), influenza A subtype H1N1 virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and more recently the novel SARS-CoV coronavirus 2, which caused the disease COVID-19. The latest epidemic proved to be the most destructive and claimed more than 2 million lives. Today's efforts to combat COVID-19 are focused on controlling the spread of the coronavirus and identifying effective treatment options. Meanwhile, an analysis of data regarding the long-term clinical consequences of previous coronavirus infections (SARS-CoV and MERS-CoV) shows that with the removal of the virus from the body, the pathological process in many cases does not end and can develop into long-term lung damage, in particular, fibrous interstitial disease or pulmonary fibrosis. Thus, pulmonary fibrosis can become an ongoing problem in patients recovering from COVID-19. Therefore, it is necessary now to determine the strategy of preventive measures both to counteract the development of pulmonary fibrosis in patients with COVID-19 during inpatient treatment, and to prevent its occurrence and progression in the long term. Although anti-fibrotic drugs such as pirfeni-done and nintedanib have been shown to be effective in reducing the rate of deterioration in lung function, their results have not significantly improved patient recovery. In addition, the use of these drugs has been associated with serious side effects. In this regard, the purpose of this article is to consider the use of histone deacetylase inhibitors (HDACs) as an alternative epigenetic therapy strategy to prevent the development or progression of pulmonary fibrosis in recovered SARS-CoV-2 patients.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(8):3-12
pages 3-12 views

Development of an algorithm for formation of a plasma donor base for producing a standard sample of anti-D antibody

Vildanova N.S., Kormshchikova E.S., Butina E.V., Poponina E.A., Yovdiy A.V., Sherstnev F.S., Vorobiev K.A., Paramonov I.V., Kudasheva E.Y., Tarasov A.N.


Relevance. The potency of raw materials, intermediate products and the finished preparation of human anti-D immunoglobulin must be determined in international units. The application of the international standard for anti-D immunoglobulin in the Russian Federation has difficulties associated with the duration of delivery and the need to comply with increased requirements for the conditions of transportation of biological thermolabile substances. In this regard, there is a need for the development of a domestic standard sample for the content of anti-D antibodies and its certification in international units. An integral step in obtaining this standard is the creation of a raw material base, taking into account the requirements for the content of anti-D antibodies in the immune blood plasma of donors. The aim of the study. To develop an algorithm for the selection of plasma donors for the production of a domestic standard sample for the anti-D antibodies content. Material and methods. The data of the information system of transfusiology for the period from january 2015 to december 2020 were analyzed about 510 donors with identified anti-erythrocyte antibodies. Immunohematological tests were performed by gel centrifugation using reagents and a set of equipment manufactured by Bio-Rad Laboratories (Switzerland). The concentration of anti-D antibodies in the blood plasma of donors was calculated in relation to the 2nd WHO international standard for anti-D immunoglobulin, NIBSC 01/572 (Great Britain). Results. It is proposed to use blood plasma of persons naturally immunized to the D-antigen as a substance for the production of a standard sample. As a result of the analysis of the requirements for the analytical range of methods for determining the potency of human anti-D immunoglobulin, it was established that the content of anti-D antibodies in the production pool of plasma for obtaining a standard sample should be at least 3.75 IU/ml. The selection of donors begins with the formation from the transfusion information system of list person with Rh-negative affiliation and identified anti-erythrocyte antibodies based on the results of a medical examination. Potential donors of anti-D plasma sent for immunohematological examination for determine the specificity of antierythrocyte antibodies and the content of anti-D antibodies. The presence of specific antibodies to the D-antigen is the basis for including information about the donor in the forming database. Conclusions. The necessity of creating a domestic standard sample for the content of anti-D antibodies has been proved. An algorithm for the formation of a raw material base for the production of a domestic standard sample has been developed. Using the formulated selection principles, a donor base was created, including 22 women (as of December 2020), in whose plasma the anti-D antibodies content is in the range from 0.1 to 28.5 IU/ml.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(8):13-20
pages 13-20 views

Assessment of the hepatotoxic potential of organot in compounds containing 2,6-di-tert-butylphenol fragme

Dodokhova M.A., Safronenko A.V., Kotieva I.M., Milaeva E.R., Shpakovsky D.B., Makarenko Y.M., Trepel V.G., Alkhuseyn-Kulyaginova M.S.


The article is devoted to the in vivo study of the effect of organotin compounds containing 2,6-di-tert-butylphenol fragment on liver mor- pho-functional state. The aim of this study was to evaluate the biochemical and histological changes in the liver with a single intragastric administration of bis (3,5-di-tert-butyl-4-hydroxyphenylthiolate) dimethyltin (Me3) and (3,5-di-tert-butyl-4-hydroxyphenylthiolate) triphenyltin (Me5) to Wistar rats (female) at the maximum tolerated dose (MTD) of 2000 mg/kg and 750 mg/kg, respectively. It was found that the introduction of Me3 and Me5 do not cause significant structural changes in liver, and the disorders are of a functional nature. The results of this work allow us to conclude that the hepatotoxicity of organotin compounds containing 2,6-di-tert-butylphenol is low, which opens up broad prospects for studying these compounds as candidates for antitumor drugs
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(8):21-27
pages 21-27 views

The influence of dry extract Potentilla alba L. on the generative function of female rats

Babenko A.N., Krepkova L.V., Dmitrieva O.P., Lemyaseva S.V., Borovkova M.V., Kuzina O.S.


Relevance. Currently, thyroid diseases have a high social significance, which is determined by a significant increase in their prevalence, large financial costs for diagnosis and treatment. In this regard, the active search for new medicines with a thyroprotective effect continues. Of particular interest are medicinal plants that serve as a source of biologically active substances that affect the main mechanisms of the development of the disease. Such plants include Potentilla alba L., from the roots and rhizomes of which, in the Research institute of medicinal and aromatic plants, a dry extract with a thyrotropic effect was obtained. Due to the fact that one of the mandatory stages of preclinical studies of new pharmacological substances is the study of their effect on the generative function of laboratory animals, it was relevant to study the effect of the dry extract Potentilla alba L. on the ability of female rats to conceive. The aim of the study was to study the effect of the dry extract on the generative function of female experimental rats and their offspring in the pre - and postnatal period of development. Material and Methods. The choice of methods for studying the effect of the dry extract Potentilla alba L. on the generative function of female rats was determined by the requirements set out in the "Guidelines for conducting preclinical studies of medicines". Experiments were performed on male and female Wistar rats weighing 180-200 g (female) and 200-240 g (male). In this study, the test extract was introduced to female rats in the stomach for 15 days at doses of 25 and 125 mg/kg. After the end of the introduction period, the experimental females were mated with intact males. The control animals were intact females and males crossed with each other. The resulting pregnant females were divided into two groups. In the first group of female rats on the 20th day of pregnancy, the number of corpus luteum, positions of implantation, resorptions, live and dead fetuses was calculated, pre-and post-implantation death was calculated; the fetuses were subjected to external examination. From female rats of the other group, offspring were obtained, in which the dynamics of changes in body weight and death before the end of the feeding period (21 days) were taken into account, the rate of maturation of sensory-motor reflexes was determined, and the functional state of the central nervous system was studied according to oriented reactions in the "open field" test. Results. As a result of the experiment, it was found that the introduction of dry extract Potentilla alba L. to female rats in the tested doses before mating with intact males did not affect their ability to conceive. The studied extract did not have a negative effect on the ante - and postnatal development of the offspring of female rats that received the extract before mating with intact males. Conclusion. The dry extract Potentilla alba L. with prolonged introduction into the stomach of female rats in doses exceeding the therapeutic 5 and 15 times, did not affect their generative function and indicators of physical development of the offspring.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(8):28-33
pages 28-33 views

Scientifically based approach to selection of drug components for treatment of wounds of different genesis

Pyatigorskaya N.V., Kargin V.S., Brkich G.E.


In modern conditions, increasing production and expanding the range of medicines, including those for external use, is inextricably linked with an increase in their quality. The existing dosage forms for external use, despite their widespread use in the pharmacotherapy of various diseases, do not fully meet modern requirements. This dictates the urgent need to create new drugs for external use. Of particular importance are the increased requirements for drugs for the treatment of wounds of various origins, which, along with the wound healing effect, should provide a pronounced osmotic effect in the wound, stimulate the growth of granulation and have a positive effect on the formation of local factors of immunological activity. Such a range of properties can be achieved only by creating combined drugs containing components with certain desired properties in combination with a scientifically grounded composition of excipients that actively affect the release, absorption, biotransformation and, ultimately, a more pronounced pharmacological effect of active substances. Considerable attention is paid to the problems of choosing a drug for external use for the treatment of external diseases in the literature. However, the results of treatment of patients leave much to be desired. The solution to this problem lies in the creation of new antimicrobial drugs, based on the search and selection of modern components for the pharmaceutical development of a therapeutically effective drug. The aim of the work is to conduct an information and analytical search for the selection of components for the pharmaceutical development of a drug for the treatment of wounds of various origins. As a result of a consistent analysis of the available literature data on polymeric drugs for the treatment of wounds, the search for potential components of a long-acting drug based on chitosan for the treatment of wounds of various origins was carried out. For the pharmaceutical development of a drug for the treatment of wound infection and stimulation of healing, it is possible to use enzymes immobilized in the structure of the carrier-chitosan as an active substance.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(8):34-41
pages 34-41 views

Evaluation of the variability of some phenolic compounds in the dagestan samples of Teucrium chamaedrys L.

Vagabova F.A., Radjabov G.K., Musaev A.M., Islamova F.I.


For the first time, the results of the total content of some phenolic compounds of 70% water-ethanol extracts of the aboveground part of the Teucrium chamaedrys L. and the assessment of their variability depending on the altitude factor in the natural conditions of Dagestan are presented. The material for the study was collected during the flowering phase in 2013. The content of flavonoids and anthocyanins was determined by spectrophotometric method on SF-56. Total antioxidants - amperometric method. The content of accumulation of phenolic compounds in the aboveground part of T. chamaedrys varies in the range of 2.02-3.06% (the sum of flavonoids); 0.31-0.43 % (the sum of anthocyanins); 4.35-9.64 mg/g (the sum of antioxidants), depending on the population. The influence of the altitude factor on the accumulation of phenolic compounds showed a multi-vector direction, with a significant positive relationship between the altitude above sea level and the content of total antioxidants. In addition, a direct correlation was found between the content of flavonoids and antioxidants, which indicates the key role of flavonoids in the antioxidant status of T. chamaedrys. Statistical methods of analysis made it possible to reveal a greater difference in the variability of the content of phenolic compounds by populations than within populations. Based on the classification matrix, it was possible to divide all samples into separate isolated populations. The results obtained can be used both in the theoretical aspect (revealing the mechanisms of variability of biochemical parameters from abiotic factors), and in the applied meaning.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(8):42-48
pages 42-48 views

Theoretical aspects of the creation and pharmaceutical analysis of ointment combinations of antifungal and anti-inflammatory drugs with Tizol gel

Anisimova T.G.


New forms of drugs for local delivery are emerging and used in modern pharmaceutical and medical practice. Aqua complex of titanium glycerosolvate "Tizol" is a substance for local delivery of drugs. The development of glycerohydrogel and its properties are promising for the creation of two- and three-component formulations of anti-inflammatory and antifungal compositions of titanium-containing ointments. The synergy of the pharmacological properties of the Tizol gel and the active ingredients increase compliance and faster recovery. The review of literature sources covers the analysis of the pharmacological application and the possibility of complexation of the Tizol gel with antiphlogistic and antifungal drugs. The combinations are presented for manufacture at the pharmacy. The directions of practical use in medicine and pharmacy of new combinations are described in the article. The expansion of the therapeutic use of metami-zole sodium and itraconazoleis shown when creating combinations of ointments. The development of new combinations of ointments involves qualitative and quantitative analyzes that are used in manufacturing, preclinical and clinical trials. The review presents some methods for identifying active substances with sensitivity intervals for general reactions. Available instrumental and simple classical chemical methods of analysis are used for the quantitative analysis of drugs in the proposed two- and three-component ointments. The conditions of the experiments refer to the author's developments. Analysis of literature data made it possible to study and substantiate the necessity and possibility of creating new anti-inflammatory and antifungal combinations of ointments with Tizol gel. Newer ointments may be effective and safe competitors to topical finished drug products. The new combinations will be widely used in medicine and pharmacy. The presented information about the author's own experimental work in the development of quantitative and qualitative analyzes of new drug compositions shows the prospect of further scientific research in the field of pharmaceutical analysis, preclinical trials.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(8):49-55
pages 49-55 views

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