Pub Date : 2021-05-17DOI: 10.19163/2307-9266-2020-8-6-456-464
N. Porseva, A. Soloninina, O. Dvorskaya
Prevention of non-medical use of drugs is the most important task of the state anti-drug policy of the Russian Federation, the effectiveness of which can largely be due to the professional awareness of pharmaceutical specialists, their compliance with the established regulations for the dispensing of drugs, and proper pharmaceutical advice.The aim. The research of pharmaceutical specialists’ information awareness on the matters of drug abuse.Material and methods. The study was based on the analysis of the regulatory legal acts of the Russian Federation governing the procedure for prescribing and dispensing drugs, instructions for the medical use of the drugs used for the purpose of abuse. In the course of the study, a systematic approach has been applied. It includes methods of structural-logical, cluster and content analyses, methods of generalization and grouping. The study of pharmaceutical specialists’ information awareness on the matters of drug abuse was carried out using a random sample survey using a specially developed questionnaire: 396 employees of pharmacy organizations of various forms of property from the Perm Territory, the Chelyabinsk and Kirov regions, the Udmurt and Chuvash Republics, the Komi Republic, were questioned in the period from 2017 to 2019. The questionnaire included 35 questions, structured in 4 blocks. The first block included questions on education, position, work experience of the respondents, the second - questions on identifying knowledge on the range of drugs used for abuse, and categories of consumers of such drugs. The third block contained questions on the regulation and compliance with the procedure for dispensing drugs. The fourth block of the questionnaire was intended to establish the methods and sources of obtaining information on the abuse of the drugs sold by specialists of pharmacy organizations.Results. On the basis of the analysis carried out, an insufficient level of knowledge by specialists of the regulatory legal acts governing the trade of drugs, the range of drugs used for the purpose of abuse, and the categories of their consumers have been established. The violation of the rules for dispensing drugs has been revealed, as well as the lack of systematic sources of information on drug abuse.Conclusion. The need to develop a training program for pharmaceutical specialists on the prophylaxis and prevention of drug abuse has been established. In order to work out additional competencies in the prevention of non-medical use of drugs and improve the quality of pharmaceutical consulting, it is necessary to conduct appropriate educational activities.
{"title":"STUDY OF PHARMACEUTICAL SPECIALISTS’ INFORMATION AWARENESS ON THE MATTERS OF DRUG ABUSE","authors":"N. Porseva, A. Soloninina, O. Dvorskaya","doi":"10.19163/2307-9266-2020-8-6-456-464","DOIUrl":"https://doi.org/10.19163/2307-9266-2020-8-6-456-464","url":null,"abstract":"Prevention of non-medical use of drugs is the most important task of the state anti-drug policy of the Russian Federation, the effectiveness of which can largely be due to the professional awareness of pharmaceutical specialists, their compliance with the established regulations for the dispensing of drugs, and proper pharmaceutical advice.The aim. The research of pharmaceutical specialists’ information awareness on the matters of drug abuse.Material and methods. The study was based on the analysis of the regulatory legal acts of the Russian Federation governing the procedure for prescribing and dispensing drugs, instructions for the medical use of the drugs used for the purpose of abuse. In the course of the study, a systematic approach has been applied. It includes methods of structural-logical, cluster and content analyses, methods of generalization and grouping. The study of pharmaceutical specialists’ information awareness on the matters of drug abuse was carried out using a random sample survey using a specially developed questionnaire: 396 employees of pharmacy organizations of various forms of property from the Perm Territory, the Chelyabinsk and Kirov regions, the Udmurt and Chuvash Republics, the Komi Republic, were questioned in the period from 2017 to 2019. The questionnaire included 35 questions, structured in 4 blocks. The first block included questions on education, position, work experience of the respondents, the second - questions on identifying knowledge on the range of drugs used for abuse, and categories of consumers of such drugs. The third block contained questions on the regulation and compliance with the procedure for dispensing drugs. The fourth block of the questionnaire was intended to establish the methods and sources of obtaining information on the abuse of the drugs sold by specialists of pharmacy organizations.Results. On the basis of the analysis carried out, an insufficient level of knowledge by specialists of the regulatory legal acts governing the trade of drugs, the range of drugs used for the purpose of abuse, and the categories of their consumers have been established. The violation of the rules for dispensing drugs has been revealed, as well as the lack of systematic sources of information on drug abuse.Conclusion. The need to develop a training program for pharmaceutical specialists on the prophylaxis and prevention of drug abuse has been established. In order to work out additional competencies in the prevention of non-medical use of drugs and improve the quality of pharmaceutical consulting, it is necessary to conduct appropriate educational activities.","PeriodicalId":20025,"journal":{"name":"Pharmacy & Pharmacology","volume":"10 1","pages":"456-464"},"PeriodicalIF":0.0,"publicationDate":"2021-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84910288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-17DOI: 10.19163/2307-9266-2020-8-6-380-391
V. Petrov, A. Amosov, A. Gerasimenko, O. Shatalova, A. V. Ponomareva, A. N. Akinchits, I. S. Kulakova, V. S. Gorbatenko
The development of a "cytokine storm", characteristic of severe COVID-19 forms, can be defined as a state of uncontrolled release of a large number of inflammatory mediators.The attachment of SARS-CoV-2 S-glycoprotein to angiotensin-converting enzyme 2 is considered a process that triggers complex molecular interactions that lead to hyperinflammation. In its turn, it is realized through several systems: renin-angiotensin-aldosterone, kallikrein-kinin and a complement system. Knowledge of these mechanisms suggests potential therapeutic interventions that can be targeted by existing therapeutic agents to counter the cytokine storm and treat the acute respiratory distress syndrome associated with COVID-19.The aim of the review article is to summarize the currently known data on the molecular processes underlying the uncontrolled "cytokine storm" in the patients with severe COVID-19, and possible options for their pharmacological correction.Materials and methods. The data base was represented by such systems as Medline, Cochrane Central Register of Controlled Trials, Scopus, Web of Science Core Collection, Cochrane Library, ClinicalTrials.gov, Elibrary, Google-Academy. A search was carried out for the following keywords and combinations: COVID-19, renin-angiotensin-aldosterone system, bradykinin, complement system, hyaluronic acid, pharmacotherapy.Results. The development of a "cytokine storm" in COVID-19 is mediated by pathogenetic changes in the body in response to the penetration of SARS-CoV-2 into the cell. In the RAAS, suppression of ACE2 leads to a decrease in its ability to degrade ATII, which, on the one hand, leads to a decrease in the amount of AT1-7, and, on the other hand, to the effect of ATII on AT1R with the subsequent development of vasoconstriction and lung damage. The disturbances in the kallikrein-kinin system are associated, on the one hand, with the increased expression of kallikrein and an increase in the formation of bradykinin and its metabolite des-Arg 9-bradykinin. On the other hand, the disturbances are associated with the suppression of the expression of the C1-esterase inhibitor which prevents the formation of kallikrein, and impaired inactivation of des-Arg 9-bradykinin under the action of ACE 2. The nucleocapsid protein SARS-CoV-2 triggers the activation of the complement system through the lectin pathway. It leads to the production of anaphylatoxins C3a and C5a, which stimulate the synthesis of pro-inflammatory cytokines. Proinflammatory cytokines are potent inducers of the HAS 2 gene in the endothelium, which encodes the membrane enzymes of hyaluronate synthase. The sweating of the fluid into the alveoli caused by the "bradykinin storm" in combination with the overproduction of hyaluronic acid, which accumulates water 1000 times its own mass, can lead to the formation of a dense jelly-like substance that prevents gas exchange.Conclusion. Promising areas of pharmacotherapy for "cytokine storm" are associated with its i
“细胞因子风暴”的发展是严重COVID-19形式的特征，可以定义为大量炎症介质不受控制地释放的状态。SARS-CoV-2 s -糖蛋白附着在血管紧张素转换酶2上被认为是一个触发复杂分子相互作用的过程，导致过度炎症。反过来，它是通过几个系统实现的:肾素-血管紧张素-醛固酮，钾化钾素-激肽和补体系统。对这些机制的了解表明，现有治疗剂可以靶向潜在的治疗干预措施，以对抗细胞因子风暴并治疗与COVID-19相关的急性呼吸窘迫综合征。这篇综述文章的目的是总结目前已知的关于严重COVID-19患者中不受控制的“细胞因子风暴”的分子过程的数据，以及可能的药物纠正方案。材料和方法。数据库由Medline、Cochrane Central Register of Controlled Trials、Scopus、Web of Science Core Collection、Cochrane Library、ClinicalTrials.gov、Library、Google-Academy等系统代表。检索以下关键词及组合:COVID-19、肾素-血管紧张素-醛固酮系统、缓激肽、补体系统、透明质酸、药物治疗。在COVID-19中，“细胞因子风暴”的发展是由机体对SARS-CoV-2渗透进入细胞的病理变化介导的。在RAAS中，ACE2的抑制导致其降解ATII的能力下降，这一方面导致AT1-7的量减少，另一方面导致ATII对AT1R的影响，随后发展为血管收缩和肺损伤。缓激肽-激肽系统的紊乱一方面与缓激肽表达增加和缓激肽及其代谢物- arg - 9-缓激肽形成增加有关。另一方面，这些干扰与c1 -酯酶抑制剂的表达抑制有关，c1 -酯酶抑制剂阻止了钾化激酶的形成，并在ACE 2的作用下破坏了des-Arg - 9-缓激肽的失活。核衣壳蛋白SARS-CoV-2通过凝集素途径触发补体系统的激活。它导致过敏毒素C3a和C5a的产生，刺激促炎细胞因子的合成。促炎细胞因子是内皮细胞中编码透明质酸合酶膜酶的ha2基因的有效诱导剂。由“缓激肽风暴”引起的液体出汗进入肺泡，再加上透明质酸的过量产生，积累了1000倍于自身质量的水，可以导致形成致密的果冻状物质，阻碍气体交换。“细胞因子风暴”的药物治疗有希望的领域与它对上述系统功能障碍的影响有关。然而，大多数治疗新冠病毒的药物的有效性和安全性都需要通过精心设计的临床试验来研究。
{"title":"MECHANISMS OF CYTOKINE STORM DEVELOPMENT IN COVID-19 AND NEW POTENTIAL TARGETS OF PHARMACOTHERAPY","authors":"V. Petrov, A. Amosov, A. Gerasimenko, O. Shatalova, A. V. Ponomareva, A. N. Akinchits, I. S. Kulakova, V. S. Gorbatenko","doi":"10.19163/2307-9266-2020-8-6-380-391","DOIUrl":"https://doi.org/10.19163/2307-9266-2020-8-6-380-391","url":null,"abstract":"The development of a \"cytokine storm\", characteristic of severe COVID-19 forms, can be defined as a state of uncontrolled release of a large number of inflammatory mediators.The attachment of SARS-CoV-2 S-glycoprotein to angiotensin-converting enzyme 2 is considered a process that triggers complex molecular interactions that lead to hyperinflammation. In its turn, it is realized through several systems: renin-angiotensin-aldosterone, kallikrein-kinin and a complement system. Knowledge of these mechanisms suggests potential therapeutic interventions that can be targeted by existing therapeutic agents to counter the cytokine storm and treat the acute respiratory distress syndrome associated with COVID-19.The aim of the review article is to summarize the currently known data on the molecular processes underlying the uncontrolled \"cytokine storm\" in the patients with severe COVID-19, and possible options for their pharmacological correction.Materials and methods. The data base was represented by such systems as Medline, Cochrane Central Register of Controlled Trials, Scopus, Web of Science Core Collection, Cochrane Library, ClinicalTrials.gov, Elibrary, Google-Academy. A search was carried out for the following keywords and combinations: COVID-19, renin-angiotensin-aldosterone system, bradykinin, complement system, hyaluronic acid, pharmacotherapy.Results. The development of a \"cytokine storm\" in COVID-19 is mediated by pathogenetic changes in the body in response to the penetration of SARS-CoV-2 into the cell. In the RAAS, suppression of ACE2 leads to a decrease in its ability to degrade ATII, which, on the one hand, leads to a decrease in the amount of AT1-7, and, on the other hand, to the effect of ATII on AT1R with the subsequent development of vasoconstriction and lung damage. The disturbances in the kallikrein-kinin system are associated, on the one hand, with the increased expression of kallikrein and an increase in the formation of bradykinin and its metabolite des-Arg 9-bradykinin. On the other hand, the disturbances are associated with the suppression of the expression of the C1-esterase inhibitor which prevents the formation of kallikrein, and impaired inactivation of des-Arg 9-bradykinin under the action of ACE 2. The nucleocapsid protein SARS-CoV-2 triggers the activation of the complement system through the lectin pathway. It leads to the production of anaphylatoxins C3a and C5a, which stimulate the synthesis of pro-inflammatory cytokines. Proinflammatory cytokines are potent inducers of the HAS 2 gene in the endothelium, which encodes the membrane enzymes of hyaluronate synthase. The sweating of the fluid into the alveoli caused by the \"bradykinin storm\" in combination with the overproduction of hyaluronic acid, which accumulates water 1000 times its own mass, can lead to the formation of a dense jelly-like substance that prevents gas exchange.Conclusion. Promising areas of pharmacotherapy for \"cytokine storm\" are associated with its i","PeriodicalId":20025,"journal":{"name":"Pharmacy & Pharmacology","volume":"1 1","pages":"380-391"},"PeriodicalIF":0.0,"publicationDate":"2021-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87547427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-17DOI: 10.19163/2307-9266-2020-8-6-446-455
E. Oganesyan, S. S. Shatokhin
42 derivatives of chalcone, flavanone and flavone having a phloroglucinic type of ring “A” and containing the same electron-donating substituents on ring “B”, have been studied. Flavonoids with the phloroglucinic type of ring “A” are the most common in nature, which is due to the peculiarities of biogenetic formation with the participation of malonyl and acetyl fragments.The aim of the article is to determine the effect of the hydroxy group in position 6' of chalcones and in position 5 of flavanones and flavones on bond numbers (Nµ), free valence indices (Fµ), Mulliken charges (a.e), electron density, unsaturation indices (IUA) of the carbon atoms C-1 → C-6 → C-7 → C-8.Materials and methods. The calculations of the listed above parameters with the use of the semi-empirical method PM7 (WinMopac 2016 program) have been carried out on a workstation with an Intel Xeon E5-1620 3.5 GHz processor, 20 GB of RAM.Results. The quantum-chemical characteristics of the considered derivatives having a phloroglucinic type of the “A” ring, indicate that the OH group in position 6' of chalcones (in the corresponding flavanones and flavones in position 5) has different effects: a slight increase occurs in chalcones negative charge (a.e.) and electron density, the bond numbers take different values, which depends on the position and number of substituents on the ring "B". In flavanones, Nµ practically remains at the same level of 3.822-3.829. For flavones, the binding numbers Nµ for C-8 are in the range of 3.700-3.706, and the Mulliken charges are in the range from -0.4120 to -0.4356. For position-substituted C-3 (6anone and 7anone), the charges are -0.4436 and -0.4479, respectively. The charge on C-7 of chalcones is negative for compounds 4x, 5x, 10x and 13x from -0.0204 to -0.0470. The remaining derivatives of the chalcone, as well as the corresponding flavanones and flavones, are characterized by a positive value of a.e. on C-7. Based on the bond numbers (Nµ), free valency indices (Fµ) have been found for the carbon atoms of the cinnamoyl fragment C-1 → C-6 → C-7 → C-8. When comparing the obtained data, it was found out that for chalcones on C-1 → C-8 atoms, the values of the free valence indices are in the range of 0.900-0.980 for compounds 12x, 13x, where Fµ> 1. For flavanones on C-1, C-3, and C-5 atoms (compounds 12anone and 13anone), the free valence indices are in the range of 0.984-1.024, and for the remaining atoms the value of Fµ is approximately the same as that of chalcones. On the C-8 atoms of all the derivatives, as well as on C-1, C-3 and C-5 (compounds 12one, 13one), Fµ ≥ 1.0. It can be assumed that at values of Fµ = 0.850-0.955 for all the analyzed compounds, coupling reactions on the double bond are possible, and if Fµ ≥1, the coupling will take place according to the free radical mechanism. The data obtained indicate that the OH group in position 6’ for the chalcone and 5 for the flavanones, does not significantly effect the Mulliken charge (a.e)
{"title":"USE OF QUANTUM-CHEMICAL PARAMETERS FOR FORECASTING ANTIRADICAL (HO·) ACTIVITY OF RELATED STRUCTURES CONTAINING A CINNAMIC MOLD FRAGMENT. III. CHALCONES, FLAVANONES AND FLAVONES WITH PHLOROGLUCINIC TYPE OF RING “A”","authors":"E. Oganesyan, S. S. Shatokhin","doi":"10.19163/2307-9266-2020-8-6-446-455","DOIUrl":"https://doi.org/10.19163/2307-9266-2020-8-6-446-455","url":null,"abstract":"42 derivatives of chalcone, flavanone and flavone having a phloroglucinic type of ring “A” and containing the same electron-donating substituents on ring “B”, have been studied. Flavonoids with the phloroglucinic type of ring “A” are the most common in nature, which is due to the peculiarities of biogenetic formation with the participation of malonyl and acetyl fragments.The aim of the article is to determine the effect of the hydroxy group in position 6' of chalcones and in position 5 of flavanones and flavones on bond numbers (Nµ), free valence indices (Fµ), Mulliken charges (a.e), electron density, unsaturation indices (IUA) of the carbon atoms C-1 → C-6 → C-7 → C-8.Materials and methods. The calculations of the listed above parameters with the use of the semi-empirical method PM7 (WinMopac 2016 program) have been carried out on a workstation with an Intel Xeon E5-1620 3.5 GHz processor, 20 GB of RAM.Results. The quantum-chemical characteristics of the considered derivatives having a phloroglucinic type of the “A” ring, indicate that the OH group in position 6' of chalcones (in the corresponding flavanones and flavones in position 5) has different effects: a slight increase occurs in chalcones negative charge (a.e.) and electron density, the bond numbers take different values, which depends on the position and number of substituents on the ring \"B\". In flavanones, Nµ practically remains at the same level of 3.822-3.829. For flavones, the binding numbers Nµ for C-8 are in the range of 3.700-3.706, and the Mulliken charges are in the range from -0.4120 to -0.4356. For position-substituted C-3 (6anone and 7anone), the charges are -0.4436 and -0.4479, respectively. The charge on C-7 of chalcones is negative for compounds 4x, 5x, 10x and 13x from -0.0204 to -0.0470. The remaining derivatives of the chalcone, as well as the corresponding flavanones and flavones, are characterized by a positive value of a.e. on C-7. Based on the bond numbers (Nµ), free valency indices (Fµ) have been found for the carbon atoms of the cinnamoyl fragment C-1 → C-6 → C-7 → C-8. When comparing the obtained data, it was found out that for chalcones on C-1 → C-8 atoms, the values of the free valence indices are in the range of 0.900-0.980 for compounds 12x, 13x, where Fµ> 1. For flavanones on C-1, C-3, and C-5 atoms (compounds 12anone and 13anone), the free valence indices are in the range of 0.984-1.024, and for the remaining atoms the value of Fµ is approximately the same as that of chalcones. On the C-8 atoms of all the derivatives, as well as on C-1, C-3 and C-5 (compounds 12one, 13one), Fµ ≥ 1.0. It can be assumed that at values of Fµ = 0.850-0.955 for all the analyzed compounds, coupling reactions on the double bond are possible, and if Fµ ≥1, the coupling will take place according to the free radical mechanism. The data obtained indicate that the OH group in position 6’ for the chalcone and 5 for the flavanones, does not significantly effect the Mulliken charge (a.e)","PeriodicalId":20025,"journal":{"name":"Pharmacy & Pharmacology","volume":"18 1","pages":"446-455"},"PeriodicalIF":0.0,"publicationDate":"2021-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73423551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-17DOI: 10.19163/2307-9266-2020-8-6-416-425
P. A. Golubinskaya, M. V. Sarycheva, A. Dolzhikov, V. Bondarev, M. Stefanova, V. Soldatov, S. Nadezhdin, M. V. Korokin, M. Pokrovsky, Yuriy E. Burda
The therapeutic effect of multipotent mesenchymal stem cells has been proven on various disease models. One of the mechanisms is the paracrine effect of the cells on the surrounding tissues.The aim. To investigate the secretome effectiveness of the multipotent mesenchymal stem cells in the treatment of adjuvant arthritis and contact-allergic dermatitis in Wistar rats.Materials and methods. Adjuvant arthritis was simulated in 26 female rats by the administration of Freund's complete adjuvant and then treated with the administration of 100 µl of multipotent mesenchymal stem cell secretome or saline. Contact-allergic dermatitis was modeled on 30 female rats by applying 200 μl of an oil solution of dinitrofluorobenzene to the skin on days 1, 5 and 6. Then the rats were treated with fluocinolone ointment (a positive control), baby cream (a negative control), baby cream with a secretome of native multipotent mesenchymal stem cells or from the cells processed with dexamethasone.Results. Judging by the indicators of the longitudinal and transverse dimensions of the paws in rats and a histological examination, the secretome did not have any anti-inflammatory effect on adjuvant arthritis. A cream with a secret from multipotent mesenchymal stem cells processed with dexamethasone, was the most effective on the model of contact-allergic dermatitis: the clinical improvement occurred on the 2nd day. The secretome from native multipotent mesenchymal stem cells and fluocinolone had a therapeutic effect on the 3rd day of application, the negative control - on the 4th day. The lymphocytic infiltration coefficient was significantly lower (p <0.05) in all the cases compared to the negative control (2.8 ± 0.1). However, the lowest infiltration was observed when the cream with secretome from native (1.75 ± 0,1) and dexamethasone-stimulated (1.76 ± 0.1) multipotent mesenchymal stem cells was being used.Conclusion. The cream with the secretome of multipotent mesenchymal stem cells suppresses lymphocytic infiltration more strongly than the highly active topical glucocorticosteroid - fluocinolone - on the model of contact-allergic dermatitis, which is a classic local delayed-type hypersensitivity reaction. However, a further study of the therapeutic effect of the secretome on models of systemic inflammatory diseases is required after its preliminary purification from large-molecular proteins.
{"title":"APPLICATION OF MULTIPOTENT MESENCHYMAL STEM CELL SECRETOME IN THE TREATMENT OF ADJUVANT ARTHRITIS AND CONTACT-ALLERGIC DERMATITIS IN ANIMAL MODELS","authors":"P. A. Golubinskaya, M. V. Sarycheva, A. Dolzhikov, V. Bondarev, M. Stefanova, V. Soldatov, S. Nadezhdin, M. V. Korokin, M. Pokrovsky, Yuriy E. Burda","doi":"10.19163/2307-9266-2020-8-6-416-425","DOIUrl":"https://doi.org/10.19163/2307-9266-2020-8-6-416-425","url":null,"abstract":"The therapeutic effect of multipotent mesenchymal stem cells has been proven on various disease models. One of the mechanisms is the paracrine effect of the cells on the surrounding tissues.The aim. To investigate the secretome effectiveness of the multipotent mesenchymal stem cells in the treatment of adjuvant arthritis and contact-allergic dermatitis in Wistar rats.Materials and methods. Adjuvant arthritis was simulated in 26 female rats by the administration of Freund's complete adjuvant and then treated with the administration of 100 µl of multipotent mesenchymal stem cell secretome or saline. Contact-allergic dermatitis was modeled on 30 female rats by applying 200 μl of an oil solution of dinitrofluorobenzene to the skin on days 1, 5 and 6. Then the rats were treated with fluocinolone ointment (a positive control), baby cream (a negative control), baby cream with a secretome of native multipotent mesenchymal stem cells or from the cells processed with dexamethasone.Results. Judging by the indicators of the longitudinal and transverse dimensions of the paws in rats and a histological examination, the secretome did not have any anti-inflammatory effect on adjuvant arthritis. A cream with a secret from multipotent mesenchymal stem cells processed with dexamethasone, was the most effective on the model of contact-allergic dermatitis: the clinical improvement occurred on the 2nd day. The secretome from native multipotent mesenchymal stem cells and fluocinolone had a therapeutic effect on the 3rd day of application, the negative control - on the 4th day. The lymphocytic infiltration coefficient was significantly lower (p <0.05) in all the cases compared to the negative control (2.8 ± 0.1). However, the lowest infiltration was observed when the cream with secretome from native (1.75 ± 0,1) and dexamethasone-stimulated (1.76 ± 0.1) multipotent mesenchymal stem cells was being used.Conclusion. The cream with the secretome of multipotent mesenchymal stem cells suppresses lymphocytic infiltration more strongly than the highly active topical glucocorticosteroid - fluocinolone - on the model of contact-allergic dermatitis, which is a classic local delayed-type hypersensitivity reaction. However, a further study of the therapeutic effect of the secretome on models of systemic inflammatory diseases is required after its preliminary purification from large-molecular proteins.","PeriodicalId":20025,"journal":{"name":"Pharmacy & Pharmacology","volume":"1 1","pages":"416-425"},"PeriodicalIF":0.0,"publicationDate":"2021-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83497717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-17DOI: 10.19163/2307-9266-2020-8-6-476-480
Mohammad Rizki Fadhil Pratama, S. Siswandono
The aim. The number of runs in the docking process with AutoDock 4 is known to play an important role in the validity of the results obtained. The greater the number of runs it is often associated with the more valid docking results. However, it is not known exactly how the most ideal runs in the docking process with AutoDock 4. This study aims to determine the effect of the number of runs docking processes with AutoDock 4 on the validity of the docking results.Materials and methods. The method used is the redocking process with AutoDock 4.2.6. The receptor used is an estrogen receptor with ligand reference estradiol (PDB ID 1GWR). Variations were made on the number of runs from 10 to 100 in multiples of 10. The parameters observed were RMSD, free energy of binding, inhibition constants, amino acid residues, and the number of hydrogen bonds.Results. All experiments produce identical bond free energy, where the maximum difference in inhibition constant is only 0.06 nM. The lowest RMSD is indicated by the number of runs of 60, with a RMSD value of 0.942. There is no linear relationship between the number of runs and RMSD, with R in the linear equation of 0.4607.Conclusion. Overall, the number of runs does not show a significant contribution to the validity of the results of docking with AutoDock 4. However, these results have only been proven with the receptors used.
的目标。在AutoDock 4的对接过程中运行的次数对于所获得结果的有效性起着重要的作用。运行次数越多，通常与更有效的对接结果相关联。然而，目前还不清楚最理想的对接过程是如何与AutoDock 4运行的。本研究旨在确定AutoDock 4的对接过程运行次数对对接结果有效性的影响。材料和方法。使用的方法是AutoDock 4.2.6的重新对接过程。使用的受体是雌激素受体与配体参比雌二醇(PDB ID 1GWR)。运行次数从10到100，以10的倍数变化。观察的参数有RMSD、结合自由能、抑制常数、氨基酸残基和氢键数。所有实验均得到相同的键自由能，其中抑制常数的最大差异仅为0.06 nM。最低RMSD由60次运行数表示，RMSD值为0.942。试验次数与RMSD之间不存在线性关系，R在0.4607的线性方程中。总体而言，运行次数对AutoDock 4对接结果的有效性没有显着贡献。然而，这些结果仅在使用受体的情况下得到证实。
{"title":"NUMBER OF RUNS VARIATIONS ON AUTODOCK 4 DO NOT HAVE A SIGNIFICANT EFFECT ON RMSD FROM DOCKING RESULTS","authors":"Mohammad Rizki Fadhil Pratama, S. Siswandono","doi":"10.19163/2307-9266-2020-8-6-476-480","DOIUrl":"https://doi.org/10.19163/2307-9266-2020-8-6-476-480","url":null,"abstract":"The aim. The number of runs in the docking process with AutoDock 4 is known to play an important role in the validity of the results obtained. The greater the number of runs it is often associated with the more valid docking results. However, it is not known exactly how the most ideal runs in the docking process with AutoDock 4. This study aims to determine the effect of the number of runs docking processes with AutoDock 4 on the validity of the docking results.Materials and methods. The method used is the redocking process with AutoDock 4.2.6. The receptor used is an estrogen receptor with ligand reference estradiol (PDB ID 1GWR). Variations were made on the number of runs from 10 to 100 in multiples of 10. The parameters observed were RMSD, free energy of binding, inhibition constants, amino acid residues, and the number of hydrogen bonds.Results. All experiments produce identical bond free energy, where the maximum difference in inhibition constant is only 0.06 nM. The lowest RMSD is indicated by the number of runs of 60, with a RMSD value of 0.942. There is no linear relationship between the number of runs and RMSD, with R in the linear equation of 0.4607.Conclusion. Overall, the number of runs does not show a significant contribution to the validity of the results of docking with AutoDock 4. However, these results have only been proven with the receptors used.","PeriodicalId":20025,"journal":{"name":"Pharmacy & Pharmacology","volume":"83 1","pages":"476-480"},"PeriodicalIF":0.0,"publicationDate":"2021-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85311044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-17DOI: 10.19163/2307-9266-2020-8-6-436-445
E. Orlova, I. Dorfman, M. Orlov, M. Abdullaev
The aim. To evaluate the economic efficiency and the choice of the vaccination strategy in the respiratory pneumococcal infection risk groups among the adult population of the Astrakhan region.Materials and methods. The data for the period of 2015 - 2018 were analyzed on the number of registered diseases in the patients living in the service area of the medical organizations (Form No. 12, Federal State Statistics Service Orders No. 591, dated 27 November, 2015; No. 679, dated 22 November, 2019). The following working directives were studied: the base medical examination documentation submitted by medical institutions (Form No. 030/y “Dispensary Monitoring Checklist”; lists of the persons subjected to medical observation in the reporting year; Orders of the Ministry of Health of the Russian Federation: No. 1344, dated 12 December, 2012; No. 173n, dated 29 March, 2019). Statistical materials of the territorial fund for compulsory medical insurance of the Astrakhan region on the payment of medical care to 12,970 patients who had had pneumonia in 2015-2018, were analyzed. The financial support of vaccination based on the results of tenders for the procurement of pneumococcal vaccines organized by the regional Ministry of Health, was considered. The calculations were carried out in accordance with the guidelines of “Cost-effectiveness of vaccine prophylaxis” (Methodological guidelines 3.3.1878-04, dated 04.03.2004).Results. The prospective calculation of the vaccination cost showed that the benefits of vaccination with pneumococcal conjugate vaccine Prevenar13 (PCV13) and pneumococcal polyvalent vaccine Pneumovax 23 (PPV23) with a 95% vaccination coverage, are recorded after 2 years. The economic benefit of vaccination by reducing the possible number of pneumonias at the end of 2028 will be 968.2 million rubles.Conclusion. The economic feasibility of vaccine prophylaxis of the adult contingent with an increased risk of developing pneumococcal infection has been established. The sequential strategy of PCV13 and PPV23 application provides the most effective localization of pneumococcal infection. The research results should be widely introduced into the long-term plans for vaccination and healthcare practice in the Astrakhan region.
{"title":"PHARMACOECONOMIC EVALUATION OF ANTI-PNEUMOCOCCAL VACCINATION IN RISK GROUPS FOR THE PREVENTION OF COMMUNITY-ACQUIRED PNEUMONIA AMONG ADULTS IN THE ASTRAKHAN REGION","authors":"E. Orlova, I. Dorfman, M. Orlov, M. Abdullaev","doi":"10.19163/2307-9266-2020-8-6-436-445","DOIUrl":"https://doi.org/10.19163/2307-9266-2020-8-6-436-445","url":null,"abstract":"The aim. To evaluate the economic efficiency and the choice of the vaccination strategy in the respiratory pneumococcal infection risk groups among the adult population of the Astrakhan region.Materials and methods. The data for the period of 2015 - 2018 were analyzed on the number of registered diseases in the patients living in the service area of the medical organizations (Form No. 12, Federal State Statistics Service Orders No. 591, dated 27 November, 2015; No. 679, dated 22 November, 2019). The following working directives were studied: the base medical examination documentation submitted by medical institutions (Form No. 030/y “Dispensary Monitoring Checklist”; lists of the persons subjected to medical observation in the reporting year; Orders of the Ministry of Health of the Russian Federation: No. 1344, dated 12 December, 2012; No. 173n, dated 29 March, 2019). Statistical materials of the territorial fund for compulsory medical insurance of the Astrakhan region on the payment of medical care to 12,970 patients who had had pneumonia in 2015-2018, were analyzed. The financial support of vaccination based on the results of tenders for the procurement of pneumococcal vaccines organized by the regional Ministry of Health, was considered. The calculations were carried out in accordance with the guidelines of “Cost-effectiveness of vaccine prophylaxis” (Methodological guidelines 3.3.1878-04, dated 04.03.2004).Results. The prospective calculation of the vaccination cost showed that the benefits of vaccination with pneumococcal conjugate vaccine Prevenar13 (PCV13) and pneumococcal polyvalent vaccine Pneumovax 23 (PPV23) with a 95% vaccination coverage, are recorded after 2 years. The economic benefit of vaccination by reducing the possible number of pneumonias at the end of 2028 will be 968.2 million rubles.Conclusion. The economic feasibility of vaccine prophylaxis of the adult contingent with an increased risk of developing pneumococcal infection has been established. The sequential strategy of PCV13 and PPV23 application provides the most effective localization of pneumococcal infection. The research results should be widely introduced into the long-term plans for vaccination and healthcare practice in the Astrakhan region.","PeriodicalId":20025,"journal":{"name":"Pharmacy & Pharmacology","volume":"1 1","pages":"436-445"},"PeriodicalIF":0.0,"publicationDate":"2021-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77640278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-17DOI: 10.19163/2307-9266-2020-8-6-465-475
I. Narkevich, O. D. Nemyatykh, K. A. Kovaleva, L. Ratova, I. Trushnikova, E. N. Parizhskaya, A. Konradi
The aim of this study is to assess the life quality of patients with stable coronary artery disease after angioplasty and stenting of coronary arteries at the post-hospital stage.Materials and methods. Methods of the sociological analysis (questionnaire surveys) and methods of mathematical statistics (descriptive statistics, time series method, factor and variance analyses) were used at different stages of the prospective observational study. The research materials were as follows:1458 electronic patient records with a stable coronary heart disease (SCHD) after angioplasty and stenting of coronary arteries (ASCA); 620 questionnaires filled in by patients before the surgery, 1, 6, 12 months after discharge. The statistical analysis was performed using the IBM SPSS Statistics software.Results. The results of a comprehensive survey make it possible for us to assert that during the studied period, stable good healths of cardiac surgery patients with ASCA were maintained. Within the framework of the EQ-5D-5L questionnaire, it was revealed that more than 50% of patients have no physiological problems. The results of the SAQ analysis demonstrate that 58% of the patients feel better, and more than 34% of the patients do not have shortness of breath 1 year after the surgery. A statistically significant improvement in their healths was established according to a visual analogue scale relatively to the annual observation mark (62.82 ± 20.95), which corresponds to the high results assessment of the medical technology use. At the same time, 53% of the patients notify that the treatment results meet their own expectations.Conclusion. The proposed calculation of the integrated index of patients’ treatment efficiency demonstrated by the patients with stable coronary heart disease after angioplasty and stenting of the coronary arteries is based on the results of the factor analysis. This calculation can be used to assess the efficiency of pharmacotherapy in the framework of a value-oriented approach to the treatment of a number of other pathologies.
{"title":"LIFE QUALITY ASSESSMENT OF PATIENTS WITH STABLE CORONARY ARTERY DISEASE AFTER MYOCARDIAL REVASCULARIZATION","authors":"I. Narkevich, O. D. Nemyatykh, K. A. Kovaleva, L. Ratova, I. Trushnikova, E. N. Parizhskaya, A. Konradi","doi":"10.19163/2307-9266-2020-8-6-465-475","DOIUrl":"https://doi.org/10.19163/2307-9266-2020-8-6-465-475","url":null,"abstract":"The aim of this study is to assess the life quality of patients with stable coronary artery disease after angioplasty and stenting of coronary arteries at the post-hospital stage.Materials and methods. Methods of the sociological analysis (questionnaire surveys) and methods of mathematical statistics (descriptive statistics, time series method, factor and variance analyses) were used at different stages of the prospective observational study. The research materials were as follows:1458 electronic patient records with a stable coronary heart disease (SCHD) after angioplasty and stenting of coronary arteries (ASCA); 620 questionnaires filled in by patients before the surgery, 1, 6, 12 months after discharge. The statistical analysis was performed using the IBM SPSS Statistics software.Results. The results of a comprehensive survey make it possible for us to assert that during the studied period, stable good healths of cardiac surgery patients with ASCA were maintained. Within the framework of the EQ-5D-5L questionnaire, it was revealed that more than 50% of patients have no physiological problems. The results of the SAQ analysis demonstrate that 58% of the patients feel better, and more than 34% of the patients do not have shortness of breath 1 year after the surgery. A statistically significant improvement in their healths was established according to a visual analogue scale relatively to the annual observation mark (62.82 ± 20.95), which corresponds to the high results assessment of the medical technology use. At the same time, 53% of the patients notify that the treatment results meet their own expectations.Conclusion. The proposed calculation of the integrated index of patients’ treatment efficiency demonstrated by the patients with stable coronary heart disease after angioplasty and stenting of the coronary arteries is based on the results of the factor analysis. This calculation can be used to assess the efficiency of pharmacotherapy in the framework of a value-oriented approach to the treatment of a number of other pathologies.","PeriodicalId":20025,"journal":{"name":"Pharmacy & Pharmacology","volume":"31 1","pages":"465-475"},"PeriodicalIF":0.0,"publicationDate":"2021-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78837769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-17DOI: 10.19163/2307-9266-2020-8-6-417-435
D. Kurkin, E. Morkovin, N. Osadchenko, D. A. Bakulin, E. Abrosimova, M. Dubrovina, N. Kovalev, Y. Gorbunova, I. Tyurenkov
The aim of the study is an experimental confirmation of the use of a new combination of biologically active substances with tonic and antioxidant effects. This combination contains acetylcysteine in its composition to reduce the severity of psychoneurological consequences of alcohol intoxication.Materials and methods. The study was conducted on male Wistar rats. The post-intoxication state was simulated by a single injection of ethanol (3 g/kg, intraperitoneally). Half an hour after awakening, the rats were divided into groups, which were injected with saline, acetylcysteine (1 g/kg), taurine (20 mg/kg), caffeine ( 20 mg/kg), succinic acid (100 mg/kg), lipoic acid (100 mg/kg), pyridoxine (400 mg/kg), or a combination of acetylcysteine with all these substances taken in a twice lower dose (except taurine). Before the treatment and 3 hours after it, the degree of neurological disorders was fixed according to the Combs and D'Alecy scale, in the Open Field test and the Adhesion test. Then the animals were euthanized to assess the level of glutathione, triglycerides and malondialdehyde (MDA) in liver homogenates, to determine the activity of enzymatic antioxidant systems and serum aminotransferases.Results. In the animals injected with alcohol, there were evident signs of neuropsychiatric disorders, manifested in a low motor activity and a decrease in fine motor skills. This state did not change after an oral administration of saline. After the administration of acetylcysteine, taurine, caffeine, succinic and lipoic acids, pyridoxine and, to a greater extent, their compositions, the compensation of neuropsychiatric disorders and improvement of fine motor skills were notified. In the liver of these animals, the levels of glutathione, MDA, triglycerides, and the activity of antioxidant defense enzymes corresponded to the physiological norm.Conclusion. The introduction of a combination of acetylcysteine with taurine, caffeine, pyridoxine, lipoic and succinic acids after an acute alcohol intoxication, to a greater extent than each of the substances separately, contributes to the function retention of the antioxidant system of hepatocytes. Besides, it reduces the level of their dystrophic changes and leads to a decrease in the severity of psychoneurological disturbances in the experimental animals.
{"title":"CORRECTION OF PSYCHONEUROLOGICAL SIGNS OF ACUTE ALCOHOL INTOXICATION IN RATS WITH A NEW ACETYLCYSTEINE-BASED COMPOSITION","authors":"D. Kurkin, E. Morkovin, N. Osadchenko, D. A. Bakulin, E. Abrosimova, M. Dubrovina, N. Kovalev, Y. Gorbunova, I. Tyurenkov","doi":"10.19163/2307-9266-2020-8-6-417-435","DOIUrl":"https://doi.org/10.19163/2307-9266-2020-8-6-417-435","url":null,"abstract":"The aim of the study is an experimental confirmation of the use of a new combination of biologically active substances with tonic and antioxidant effects. This combination contains acetylcysteine in its composition to reduce the severity of psychoneurological consequences of alcohol intoxication.Materials and methods. The study was conducted on male Wistar rats. The post-intoxication state was simulated by a single injection of ethanol (3 g/kg, intraperitoneally). Half an hour after awakening, the rats were divided into groups, which were injected with saline, acetylcysteine (1 g/kg), taurine (20 mg/kg), caffeine ( 20 mg/kg), succinic acid (100 mg/kg), lipoic acid (100 mg/kg), pyridoxine (400 mg/kg), or a combination of acetylcysteine with all these substances taken in a twice lower dose (except taurine). Before the treatment and 3 hours after it, the degree of neurological disorders was fixed according to the Combs and D'Alecy scale, in the Open Field test and the Adhesion test. Then the animals were euthanized to assess the level of glutathione, triglycerides and malondialdehyde (MDA) in liver homogenates, to determine the activity of enzymatic antioxidant systems and serum aminotransferases.Results. In the animals injected with alcohol, there were evident signs of neuropsychiatric disorders, manifested in a low motor activity and a decrease in fine motor skills. This state did not change after an oral administration of saline. After the administration of acetylcysteine, taurine, caffeine, succinic and lipoic acids, pyridoxine and, to a greater extent, their compositions, the compensation of neuropsychiatric disorders and improvement of fine motor skills were notified. In the liver of these animals, the levels of glutathione, MDA, triglycerides, and the activity of antioxidant defense enzymes corresponded to the physiological norm.Conclusion. The introduction of a combination of acetylcysteine with taurine, caffeine, pyridoxine, lipoic and succinic acids after an acute alcohol intoxication, to a greater extent than each of the substances separately, contributes to the function retention of the antioxidant system of hepatocytes. Besides, it reduces the level of their dystrophic changes and leads to a decrease in the severity of psychoneurological disturbances in the experimental animals.","PeriodicalId":20025,"journal":{"name":"Pharmacy & Pharmacology","volume":"111 1","pages":"426-435"},"PeriodicalIF":0.0,"publicationDate":"2021-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87039001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-17DOI: 10.19163/2307-9266-2020-8-6-405-415
E. Stepanova, I. Remezova, A. M. Shevchenko, A. Morozov, V. K. Maltseva
Micronized purified flavonoid fraction (MPFF) is the original phlebotropic drug. Its marketed form (Detralex®) consists of 90% diosmin and 10% of other flavonoids. Calculated as hesperidin, it is the most widely used drug today. Diosmin and hesperidin, which are parts of the majority of venoactive drugs, are sparingly water-soluble compounds, and this feature can effect on their clinical efficacy. One of the ways to increase the solubility of these compounds leading to an increase in bioavailability, is the micronization of the active ingredients.The aim of the investigation is a comparative determination of the dynamics and dissolution efficiency of the drugs containing bioflavonoid fractions in the dissolution test, as well as the analysis of the micronization degree and its impact on technology and biopharmaceutical parameters.Materials and methods. A biopharmaceutical release profile was determined using HPLC. Disintegration, characteristics of the shape and size of the tablets’ particles were determined according to the methods of the State Pharmacopoeia of the XIV-th edition.Results. The objects created with the use of diosmin and hesperidin, have been considered in detail. The role of technological solutions in relation to the corresponding dosage forms is notified. Detailed biopharmaceutical characteristics have been established with a choice of HPLC-based release control methodology. All the drugs in this group have a low water solubility leading to the maximum bioavailability for Detralex® which is about 1.26%; and no more than 0.2% for other analyzed models.Conclusion. Detralex® dominates among the analyzed objects (tablets) in terms of the release rate. With regard to the overall quantitative indicators of release, the actual numbers are quite low, which is associated with the poor water solubility of the active substances.
{"title":"PHLEBOPROTECTORS BASED ON FLAVONOIDS: DOSAGE FORMS, BIOPHARMACEUTICAL CHARACTERISTICS, TECHNOLOGICAL FEATURES","authors":"E. Stepanova, I. Remezova, A. M. Shevchenko, A. Morozov, V. K. Maltseva","doi":"10.19163/2307-9266-2020-8-6-405-415","DOIUrl":"https://doi.org/10.19163/2307-9266-2020-8-6-405-415","url":null,"abstract":"Micronized purified flavonoid fraction (MPFF) is the original phlebotropic drug. Its marketed form (Detralex®) consists of 90% diosmin and 10% of other flavonoids. Calculated as hesperidin, it is the most widely used drug today. Diosmin and hesperidin, which are parts of the majority of venoactive drugs, are sparingly water-soluble compounds, and this feature can effect on their clinical efficacy. One of the ways to increase the solubility of these compounds leading to an increase in bioavailability, is the micronization of the active ingredients.The aim of the investigation is a comparative determination of the dynamics and dissolution efficiency of the drugs containing bioflavonoid fractions in the dissolution test, as well as the analysis of the micronization degree and its impact on technology and biopharmaceutical parameters.Materials and methods. A biopharmaceutical release profile was determined using HPLC. Disintegration, characteristics of the shape and size of the tablets’ particles were determined according to the methods of the State Pharmacopoeia of the XIV-th edition.Results. The objects created with the use of diosmin and hesperidin, have been considered in detail. The role of technological solutions in relation to the corresponding dosage forms is notified. Detailed biopharmaceutical characteristics have been established with a choice of HPLC-based release control methodology. All the drugs in this group have a low water solubility leading to the maximum bioavailability for Detralex® which is about 1.26%; and no more than 0.2% for other analyzed models.Conclusion. Detralex® dominates among the analyzed objects (tablets) in terms of the release rate. With regard to the overall quantitative indicators of release, the actual numbers are quite low, which is associated with the poor water solubility of the active substances.","PeriodicalId":20025,"journal":{"name":"Pharmacy & Pharmacology","volume":"5 1","pages":"405-415"},"PeriodicalIF":0.0,"publicationDate":"2021-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80077654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-17DOI: 10.19163/2307-9266-2020-8-6-392-404
B. Kantemirova, E. Orlova, O. S. Polunina, E. Chernysheva, M. Abdullaev, D. Sychev
Cardiovascular diseases (CVDs) are the leading cause of disability and mortality worldwide. Increased thrombosis is the trigger point for the development of various CVDs and their complications, and therefore, therapy with P2Y12-receptor inhibitors is always pathogenetically justified and vital. However, according to the various data, 10-25% of patients treated with clopidogrel have “resistance” to antiplatelet therapy. The causes for the formation of resistance are still not clear. There is no generally accepted, standard methodology for determining resistance to antiplatelet agents. In addition, there are no methodological approaches to identify the patients with resistance to antiplatelet drugs, and standardized schemes for correcting a low sensitivity to these drugs.The aim of this review was to summarize the available results of foreign and domestic studies devoted to the investigation of the effectiveness and safety problems of antiplatelet drugs administration from the point of view of the genetic predisposition to changes in their metabolism.Materials and methods. For the review, the following information from scientific literature represented in open and accessible sources for the period of 1996-2020, was used: pharmgkb.org, PubMed, Scopus, Web of Science Core Collection, Elibrary. Search queries – “Genetic features+antiplatelet therapy+ethnic groups”, “CYP2C19+clopidogrel+antiplatelet therapy effectiveness”; “Stent retrombosis+CYP2C19 polymorphism+ residual platelet reactivity” and “CYP2C19 polymorphism+ethnic groups+clopidogrel resistance” in both Russian and English equivalents. All these data are placed in electronic databases.Results. Currently, the problem of the resistance formation to antiplatelet drugs is studied insufficiently. The best thought-out issue is the research of the effect of the polymorphic alleles carriage of the CYP2C19 gene on the residual platelet reactivity in the patients administrated with dual antiplatelet treatment, including clopidogrel. In general, the analysis of open literature sources indicates the presence of a statistically significant association between the carrier of slow alleles of the CYP2C19 gene and the residual platelet reactivity, clinically manifested by thrombosis and adverse cardiovascular events. The occurrence frequency of polymorphic carriage of the CYP2C19 gene varies in different ethnic groups, so it cannot be extrapolated to individual subjects, peculiar in the ethnic diversity.Conclusion. To develop preventive and predictive measures aimed at overcoming resistance to antiplatelet agents, as well as working out methodological approaches to personalized prescribtion of this group drugs, a further investigation with the expansion of the search for causes and the study of the other genes participation of the cytochrome P450 system, is required.
心血管疾病(cvd)是全世界致残和死亡的主要原因。血栓形成增加是各种心血管疾病及其并发症发展的触发点，因此，使用p2y12受体抑制剂治疗总是病理合理且至关重要。然而，根据各种数据，10-25%接受氯吡格雷治疗的患者对抗血小板治疗有“抵抗”。形成阻力的原因尚不清楚。目前尚无普遍接受的标准方法来测定抗血小板药物的耐药性。此外，目前还没有方法学方法来识别抗血小板药物耐药患者，也没有标准化的方案来纠正对这些药物的低敏感性。本文综述了国内外从抗血小板药物代谢改变的遗传易感角度探讨抗血小板药物给药有效性和安全性问题的研究结果。材料和方法。本综述使用了1996-2020年期间在开放和可访问资源中代表的科学文献的以下信息:pharmgkb.org, PubMed, Scopus, Web of Science Core Collection, library。搜索查询-“基因特征+抗血小板治疗+族群”，“CYP2C19+氯吡格雷+抗血小板治疗效果”;“支架后栓塞+CYP2C19多态性+残留血小板反应性”和“CYP2C19多态性+民族+氯吡格雷耐药”的俄文和英文等效文献。所有这些数据都存放在电子数据库中。目前，对抗血小板药物耐药形成的研究还不够充分。考虑得最好的问题是研究携带CYP2C19基因多态性等位基因对包括氯吡格雷在内的双重抗血小板治疗患者残留血小板反应性的影响。总的来说，通过对公开文献来源的分析，CYP2C19基因慢等位基因携带者与血小板残留反应性之间存在统计学意义上的相关性，临床表现为血栓形成和心血管不良事件。CYP2C19基因多态性携带的发生频率在不同民族中存在差异，不能推断为个体，具有民族多样性的特点。为了制定针对抗血小板药物耐药的预防和预测措施，以及制定该类药物个性化处方的方法学方法，需要进一步研究细胞色素P450系统的病因和其他基因参与的研究。
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