Pub Date : 2023-06-30DOI: 10.18413/rrpharmacology.9.10034
T. N. Povetyeva, O. Afanasyeva, L. Zibareva, Y. Nesterova, N. I. Suslov, P. V. Kulpin, Gleb N. Zyuz`kov, S. Krylova, Olesya V. Vsyakikh
Introduction: This article studies the wound healing activity of the flavonoid schaftoside – apigenin -6-C-β-D glucopyranosyl 8-C-α-L arabinopyranoside (C26H28O14) isolated from the above-ground part of Lyсhnis chalcedonica L. Materials and Methods: The experiments were carried out on sexually mature mongrel male CD-1 mice. The wound healing effect of schaftoside was studied on a model of a plane skin wound. Schaftoside was applied externally (topically) in the form of an aqueous solution using a pipette of 100 mcl per wound at concentrations of 0.1 uG/mL, 1.5 uG/mL, 3.0 uG/mL, one time per day during the entire period of wound healing from the first day after the wound had been induced until its complete epithelialization. Aloe juice (100 mcL per wound) was used as a positive control. A solvent (water) – 100 mcL per wound – was applied to control animals. Results and Discussion: The results of our study on the model of a plane skin wound showed that the compound schaftoside isolated from Lyсhnis chalcedonica, when applied externally (topically) at concentrations of 0.1 uG/mL, 1.5 uG/mL, 3.0 uG/mL, contributes to a significant reduction in the size of plane skin wounds, comparable to the action of aloe juice (the comparison drug). The wound healing effect is more pronounced at the first, second, and third weeks of the healing process, i.e. at the stage of inflammation, proliferation, and activation of the repair process. Under the influence of schaftoside at a concentration of 3.0 uG/mL, a more complete epithelialization was recorded than in the group where the comparison drug (aloe juice) was applied. Conclusion: Our study for the first time shows a pronounced wound healing effect from aqueous solution of the flavonoid schaftoside from Lyсhnis chalcedonica on the model of a plane skin wound in mice. Graphical Abstract
{"title":"Investigation of wound healing activity of the flavonoid schaftoside isolated from Lychnis chalcedonica","authors":"T. N. Povetyeva, O. Afanasyeva, L. Zibareva, Y. Nesterova, N. I. Suslov, P. V. Kulpin, Gleb N. Zyuz`kov, S. Krylova, Olesya V. Vsyakikh","doi":"10.18413/rrpharmacology.9.10034","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10034","url":null,"abstract":"Introduction: This article studies the wound healing activity of the flavonoid schaftoside – apigenin -6-C-β-D glucopyranosyl 8-C-α-L arabinopyranoside (C26H28O14) isolated from the above-ground part of Lyсhnis chalcedonica L.\u0000Materials and Methods: The experiments were carried out on sexually mature mongrel male CD-1 mice. The wound healing effect of schaftoside was studied on a model of a plane skin wound. Schaftoside was applied externally (topically) in the form of an aqueous solution using a pipette of 100 mcl per wound at concentrations of 0.1 uG/mL, 1.5 uG/mL, 3.0 uG/mL, one time per day during the entire period of wound healing from the first day after the wound had been induced until its complete epithelialization. Aloe juice (100 mcL per wound) was used as a positive control. A solvent (water) – 100 mcL per wound – was applied to control animals.\u0000Results and Discussion: The results of our study on the model of a plane skin wound showed that the compound schaftoside isolated from Lyсhnis chalcedonica, when applied externally (topically) at concentrations of 0.1 uG/mL, 1.5 uG/mL, 3.0 uG/mL, contributes to a significant reduction in the size of plane skin wounds, comparable to the action of aloe juice (the comparison drug). The wound healing effect is more pronounced at the first, second, and third weeks of the healing process, i.e. at the stage of inflammation, proliferation, and activation of the repair process. Under the influence of schaftoside at a concentration of 3.0 uG/mL, a more complete epithelialization was recorded than in the group where the comparison drug (aloe juice) was applied.\u0000Conclusion: Our study for the first time shows a pronounced wound healing effect from aqueous solution of the flavonoid schaftoside from Lyсhnis chalcedonica on the model of a plane skin wound in mice.\u0000Graphical Abstract\u0000","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45206062","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 : 2023-06-19DOI: 10.18413/rrpharmacology.9.10032
А.С. Нетребенко
Введение. В связи с высокой социально-экономической значимостью острого повреждения почек, на повестке ученого сообщества остро стоит вопрос о методах диагностики и лечения данной патологии. В ряде исследований уже были выявлены цитопротективные эффекты пептида, имитирующего α-спираль B эритропоэтина, и инфликсимаба при моделировании ишемически-реперфузионного повреждения печени, миокарда, нервной ткани. Целью данного исследования явилось изучение ренопротективных эффектов сочетанного применения pHBSP и инфликсимаба при ишемически-реперфузионном повреждении почек. Материалы и методы. Эксперимент проводился на 230 белых лабораторных крысах-самцах линии Wistar. Животным вводили pHBSP и инфликсимаб. Под наркозом выполняли унилатеральную нефрэктомию справа и накладывали зажим на контралатеральную почечную ножку. Через 5 минут, 24 и 72 часа после реперфузии проводили функциональные пробы и изымали образцы тканей для лабораторных исследований. Результаты и их обсуждение. Полученные результаты подтверждают наличие дозозависимых ренопротективных свойств у пептида, имитирующего α-спираль B эритропоэтина, и инфликсимаба. Нефропротективные эффекты сочетанного применения pHBSP в дозе 25 мкг/кг и инфликсимаба в дозе 10 мг/кг значительно превосходили действие данных препаратов в монорежиме. Об этом свидетельствует нормализация функции почечных канальцев, достоверный рост уровня микроциркуляции, отсутствие деструктивных изменений при патоморфологическом исследовании, а также снижение экспрессии TNF-α на 54% и IL-1β на 65% в сравнении с группой ишемии-реперфузии по данным иммуногистохимии. Подтверждена важная роль АТФ-зависимых калиевых каналов в реализации ренопротективных свойств pHBSP. Выводы. Подтверждено наличие ренопротективных свойств у пептида, имитирующего α-спираль Bэритропоэтина, и инфликсимаба, а также обосновано превосходство их сочетанного использования с целью коррекции морфофункциональных нарушений при моделировании ишемически-реперфузионной травмы почек благодаря мультимодальному воздействию на патогенетические процессы. Графическая аннотация
{"title":"Коррекция ишемических и реперфузионных повреждений почек при сочетанном применении инфликсимаба и пептида, имитирующего α-спираль B эритропоэтина","authors":"А.С. Нетребенко","doi":"10.18413/rrpharmacology.9.10032","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10032","url":null,"abstract":"Введение. В связи с высокой социально-экономической значимостью острого повреждения почек, на повестке ученого сообщества остро стоит вопрос о методах диагностики и лечения данной патологии. В ряде исследований уже были выявлены цитопротективные эффекты пептида, имитирующего α-спираль B эритропоэтина, и инфликсимаба при моделировании ишемически-реперфузионного повреждения печени, миокарда, нервной ткани. Целью данного исследования явилось изучение ренопротективных эффектов сочетанного применения pHBSP и инфликсимаба при ишемически-реперфузионном повреждении почек.\u0000Материалы и методы. Эксперимент проводился на 230 белых лабораторных крысах-самцах линии Wistar. Животным вводили pHBSP и инфликсимаб. Под наркозом выполняли унилатеральную нефрэктомию справа и накладывали зажим на контралатеральную почечную ножку. Через 5 минут, 24 и 72 часа после реперфузии проводили функциональные пробы и изымали образцы тканей для лабораторных исследований.\u0000Результаты и их обсуждение. Полученные результаты подтверждают наличие дозозависимых ренопротективных свойств у пептида, имитирующего α-спираль B эритропоэтина, и инфликсимаба. Нефропротективные эффекты сочетанного применения pHBSP в дозе 25 мкг/кг и инфликсимаба в дозе 10 мг/кг значительно превосходили действие данных препаратов в монорежиме. Об этом свидетельствует нормализация функции почечных канальцев, достоверный рост уровня микроциркуляции, отсутствие деструктивных изменений при патоморфологическом исследовании, а также снижение экспрессии TNF-α на 54% и IL-1β на 65% в сравнении с группой ишемии-реперфузии по данным иммуногистохимии. Подтверждена важная роль АТФ-зависимых калиевых каналов в реализации ренопротективных свойств pHBSP.\u0000 Выводы. Подтверждено наличие ренопротективных свойств у пептида, имитирующего α-спираль Bэритропоэтина, и инфликсимаба, а также обосновано превосходство их сочетанного использования с целью коррекции морфофункциональных нарушений при моделировании ишемически-реперфузионной травмы почек благодаря мультимодальному воздействию на патогенетические процессы.\u0000Графическая аннотация","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48842526","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 : 2023-06-19DOI: 10.18413/rrpharmacology.9.10031
M. I. Sari, I. Putra, D. W. Wijaya
Introduction: Coronavirus disease 2019 (COVID-19) was first reported in 2019 and has since become a health concern due to its rapid spread and high mortality rate. With the discovery of vaccines, there has been a reduction in disease occurrence, transmission, mortality, and morbidity in a population. However, with the emergence of newvariants, the available vaccines show varying efficiencies depending on the population and variants, while the present drugs may lose their effectiveness, hence the urgent need to explore effective therapies. Mesenchymal stemcells (MSCs) have been widely studied for their anti-inflammatory and immunomodulatory effects as COVID-19treatment and shown their potential to improve the condition of COVID-19 patients. This systematic review aims to assess the therapeutic potential of MSCs as anti-inflammatory and immunomodulatory agent in COVID-19. Materials and Methods: A literature search is performed on PubMed, ScienceDirect, ProQuest, and Google Scholar and potentially relevant studies to review, based on the inclusion and exclusion criteria we have determined.We identified 14,090 publications from our search and excluded duplicates as well as irrelevant studies from title,abstract, and full-text screening. Data extraction and analysis were then performed in the 20 eligible studies. Results and Discussion: Results show that MSCs improve immune system dysregulation throughimmunomodulatory and anti-inflammatory effects, through reducing blood C-reactive protein (CRP) and IL-6 levels. Conclusion: We conclude that MSC is one of the promising treatments in COVID-19 regardless of variants. Graphical Abstract
{"title":"The therapeutic potential of mesenchymal stem cells in COVID-19: Present and future","authors":"M. I. Sari, I. Putra, D. W. Wijaya","doi":"10.18413/rrpharmacology.9.10031","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10031","url":null,"abstract":"Introduction: Coronavirus disease 2019 (COVID-19) was first reported in 2019 and has since become a health concern due to its rapid spread and high mortality rate. With the discovery of vaccines, there has been a reduction in disease occurrence, transmission, mortality, and morbidity in a population. However, with the emergence of newvariants, the available vaccines show varying efficiencies depending on the population and variants, while the present drugs may lose their effectiveness, hence the urgent need to explore effective therapies. Mesenchymal stemcells (MSCs) have been widely studied for their anti-inflammatory and immunomodulatory effects as COVID-19treatment and shown their potential to improve the condition of COVID-19 patients. This systematic review aims to assess the therapeutic potential of MSCs as anti-inflammatory and immunomodulatory agent in COVID-19.\u0000Materials and Methods: A literature search is performed on PubMed, ScienceDirect, ProQuest, and Google Scholar and potentially relevant studies to review, based on the inclusion and exclusion criteria we have determined.We identified 14,090 publications from our search and excluded duplicates as well as irrelevant studies from title,abstract, and full-text screening. Data extraction and analysis were then performed in the 20 eligible studies.\u0000Results and Discussion: Results show that MSCs improve immune system dysregulation throughimmunomodulatory and anti-inflammatory effects, through reducing blood C-reactive protein (CRP) and IL-6 levels.\u0000Conclusion: We conclude that MSC is one of the promising treatments in COVID-19 regardless of variants.\u0000Graphical Abstract","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41777114","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 : 2023-06-07DOI: 10.18413/rrpharmacology.9.10029
I. V. Bibik, E. Bibik, K. Frolov, Sergey G. Krivokolysk, V. Dotsenko, A. Pankov
Introduction: It is revelant to solve the problem of anesthesia based on the research of new highly effective and safe medicines. Among modern studies, the preparation of heterocyclic compounds starting from cyanothioacetamide with analgesic and anti-inflammatory activities is of considerable interest. Materials and Methods: болевой синдром Results: It is shown that all the studied 1,4-dihydropyridines and condensed thieno[2,3-b]pyridines and reveal analgesic activity of varying degrees of severity, based on the values of the criterion Anat. Discussion: It was found that the most pronounced analgesic activity was shown by three studied samples: compounds AZ-023, AZ-331 and AZ-383. The complex criterion of analgesic activity of Anat for animals receiving a sample AZ-023 was 50.1, exceeding the indicator in the comparison group by 42 times. The values of this criterion in animals that had received samples AZ-331 and AZ-383 were the highest, namely 64.3 and 68.4, which is 53 and 57 times higher than that of sodium metamizole, respectively. Conclusion: The obtained results and the advantage of the studied samples over the reference drug determine the expediency of further preclinical studies and a detailed study of their acute and chronic toxicity, as well as hepato-, nephro-, hemato- and gastrotoxicity. Graphical Abstract
{"title":"Empirical determination of the degree of analgesic activity of some new 3-aminothieno[2,3-b]pyridines and 1,4-dihydropyridines based on a complex criterion","authors":"I. V. Bibik, E. Bibik, K. Frolov, Sergey G. Krivokolysk, V. Dotsenko, A. Pankov","doi":"10.18413/rrpharmacology.9.10029","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10029","url":null,"abstract":"Introduction: It is revelant to solve the problem of anesthesia based on the research of new highly effective and safe medicines. Among modern studies, the preparation of heterocyclic compounds starting from cyanothioacetamide with analgesic and anti-inflammatory activities is of considerable interest.\u0000Materials and Methods: болевой синдром\u0000Results: It is shown that all the studied 1,4-dihydropyridines and condensed thieno[2,3-b]pyridines and reveal analgesic activity of varying degrees of severity, based on the values of the criterion Anat.\u0000Discussion: It was found that the most pronounced analgesic activity was shown by three studied samples: compounds AZ-023, AZ-331 and AZ-383. The complex criterion of analgesic activity of Anat for animals receiving a sample AZ-023 was 50.1, exceeding the indicator in the comparison group by 42 times. The values of this criterion in animals that had received samples AZ-331 and AZ-383 were the highest, namely 64.3 and 68.4, which is 53 and 57 times higher than that of sodium metamizole, respectively.\u0000Conclusion: The obtained results and the advantage of the studied samples over the reference drug determine the expediency of further preclinical studies and a detailed study of their acute and chronic toxicity, as well as hepato-, nephro-, hemato- and gastrotoxicity.\u0000Graphical Abstract\u0000","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43198366","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 : 2023-06-06DOI: 10.18413/rrpharmacology.9.10028
Dhafir Masheta, Shafq Al-azzawi
Introduction: Tumor-homing peptides have gained great attention as tools for the development of non-invasive and targeting drug delivery systems (DDS) to minimize drug systemic toxicity and enhance bioavailability. This study aims to improve antitumor targeting in prostate cancer via uploading a drug to a DDS comprised of a cell penetrating peptide decorated with a tumor-homing peptide, PL3. Material and Methods: The DDS was constructed via solid-phase peptide synthesis and then characterized via mass spectrum and high performance liquid chromatography. A cell viability assessment to evaluate its cytotoxicity on both tumor (prostate cancer cells) and normal cells was conducted, while a confocal laser scanning microscope and flow-cytometer were employed to investigate internalization. To inspect the effectiveness of the drug-loaded DDS, a biochemical enzyme inhibition assay on the target enzyme dihydrofolate reductase (DHFR) was performed. Results and Discussion: The findings supported the succeeded synthesis and loading of the drug into this carrier system and demonstrated its high efficacy in cytotoxic effect and inhibiting DHFR with considerable cellular uptake in prostate cancer cells. Conclusion: The drug was delivered to the target prostate cancer cells by the PL3-functionalized DDS, limiting its localization to tumor cells rather than normal cells. Therefore, the study results highlighted the significance of the DDS in tumor therapy interventions. Graphical Abstact
{"title":"Improving antitumor targeting via using PL3 homing peptide and cell-penetrating peptide","authors":"Dhafir Masheta, Shafq Al-azzawi","doi":"10.18413/rrpharmacology.9.10028","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10028","url":null,"abstract":"Introduction: Tumor-homing peptides have gained great attention as tools for the development of non-invasive and targeting drug delivery systems (DDS) to minimize drug systemic toxicity and enhance bioavailability. This study aims to improve antitumor targeting in prostate cancer via uploading a drug to a DDS comprised of a cell penetrating peptide decorated with a tumor-homing peptide, PL3.\u0000Material and Methods: The DDS was constructed via solid-phase peptide synthesis and then characterized via mass spectrum and high performance liquid chromatography. A cell viability assessment to evaluate its cytotoxicity on both tumor (prostate cancer cells) and normal cells was conducted, while a confocal laser scanning microscope and flow-cytometer were employed to investigate internalization. To inspect the effectiveness of the drug-loaded DDS, a biochemical enzyme inhibition assay on the target enzyme dihydrofolate reductase (DHFR) was performed. \u0000Results and Discussion: The findings supported the succeeded synthesis and loading of the drug into this carrier system and demonstrated its high efficacy in cytotoxic effect and inhibiting DHFR with considerable cellular uptake in prostate cancer cells.\u0000Conclusion: The drug was delivered to the target prostate cancer cells by the PL3-functionalized DDS, limiting its localization to tumor cells rather than normal cells. Therefore, the study results highlighted the significance of the DDS in tumor therapy interventions.\u0000Graphical Abstact","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45611153","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 : 2023-06-01DOI: 10.18413/rrpharmacology.9.10027
Владимир И. Петров, Иван С. Аникеев, Татьяна Е. Зайчикова, Андрей В. Стрыгин, Анна М. Доценко
Введение: Снижение смертности пациентов с сепсисом, принимающие пиперациллин, возможно при получении ими длительной инфузии, что улучшает воздействие противомикробных препаратов. Однако такая терапия пиперациллином требует проведения терапевтического лекарственного мониторинга, применение новейшего аналитического оборудования и разработанных методик количественного определения пиперациллина. Материалы и методы: Для приготовления маточных и стандартных растворов пипирецилинаиспользовались сухие навески соответствующих сертифицированных стандартов пипирецилина. Разделение компонентов проводили с использованием ВЭЖХ системы Agilent 1260 с бинарным насосом и термостатируемым автосемплером. Анализируемые вещества детектировали с помощью гибридной масс-спектрометрической системы Sciex QTRAP 5500. Валидация разработанного метода проводилась в соответствии с правилами проведения исследований биоэквивалентности лекарственных препаратов в рамках Евразийского экономического союза; 2016. – Астана. Результаты и их обсуждения: Ионы-«предшественники» пиперациллина соответствовали частицам m/z 518,2. Наиболее интенсивными ионами-«продуктами», зарегистрированными при фрагментации протонированных молекул в ячейке соударений, были частицы m/z 143,1, m/z 115,0. При валидации разработанного метода были установлены основные валидационные параметры: линейность, точность, правильность, чувствительность (нижний предел количественного определения). Заключение: Подтвержденный аналитический диапазон методики составил 0,5–100 мкг/мл в плазме крови. Полученный аналитический диапазон позволяет применять разработанную методику для проведения аналитической части исследований фармакокинетики пиперацилина. Графическая аннотация
{"title":"Разработка и валидация количественного ВЭЖХ-МС/МС метода определения пиперациллина в плазме крови","authors":"Владимир И. Петров, Иван С. Аникеев, Татьяна Е. Зайчикова, Андрей В. Стрыгин, Анна М. Доценко","doi":"10.18413/rrpharmacology.9.10027","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10027","url":null,"abstract":"Введение: Снижение смертности пациентов с сепсисом, принимающие пиперациллин, возможно при получении ими длительной инфузии, что улучшает воздействие противомикробных препаратов. Однако такая терапия пиперациллином требует проведения терапевтического лекарственного мониторинга, применение новейшего аналитического оборудования и разработанных методик количественного определения пиперациллина. \u0000Материалы и методы: Для приготовления маточных и стандартных растворов пипирецилинаиспользовались сухие навески соответствующих сертифицированных стандартов пипирецилина. Разделение компонентов проводили с использованием ВЭЖХ системы Agilent 1260 с бинарным насосом и термостатируемым автосемплером. Анализируемые вещества детектировали с помощью гибридной масс-спектрометрической системы Sciex QTRAP 5500. Валидация разработанного метода проводилась в соответствии с правилами проведения исследований биоэквивалентности лекарственных препаратов в рамках Евразийского экономического союза; 2016. – Астана. \u0000Результаты и их обсуждения: Ионы-«предшественники» пиперациллина соответствовали частицам m/z 518,2. Наиболее интенсивными ионами-«продуктами», зарегистрированными при фрагментации протонированных молекул в ячейке соударений, были частицы m/z 143,1, m/z 115,0. При валидации разработанного метода были установлены основные валидационные параметры: линейность, точность, правильность, чувствительность (нижний предел количественного определения). \u0000Заключение: Подтвержденный аналитический диапазон методики составил 0,5–100 мкг/мл в плазме крови. Полученный аналитический диапазон позволяет применять разработанную методику для проведения аналитической части исследований фармакокинетики пиперацилина. \u0000Графическая аннотация \u0000","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47038690","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 : 2023-05-27DOI: 10.18413/rrpharmacology.9.10026
Anna V. Zagrebelnaya, L. Korokina, T. Malorodova, Olesya V. Shcheblykina, T. Avtina, Anton A. Bolgov, E. Malyutina, V. Simonov, Vladislav A. Travkin, Artem А. Dmitriev, Amonullo A. Aripov, Dmitry V. Shcheblykin
Introduction: The purpose of this work is to review the main pathogenetic mechanisms of the development of PH, as well as modern established methods of treatment of various types of PH and to consider new, most relevant and promising possibilities of therapy for this pathology. Etiology, pathogenesis and epidemiology: In the modern structure of diseases, pulmonary hypertension plays a significant role, affecting about 1% of the population. However, each of its five main groups has its own characteristics. The causes of pulmonary hypertension can be a polyetiological violation of the processes of endotheliocyte apoptosis and angiogenesis, passive transmission of increased pressure from the left heart to the small circulatory system, chronic hypoxia, leading to vascular remodeling, and many others. In general, it is worth noting that, despite the multiplicity of etiological factors, the main pathogenetic link in the development of pulmonary hypertension is endothelial dysfunction. Treatment and promising areas of research: This article discusses the main established approaches to the treatment of pulmonary hypertension: general recommendations for patients, drugs used as supportive nonspecific therapy, as well as specific conservative and radical methods of treatment. In addition, the main modern directions of scientific research in the field of treatment of pulmonary hypertension are described. Such promising methods as the use of stem cells, gene therapy and epigenetic drugs are considered. Conclusion: Despite active research and many different drugs intended for the treatment of pulmonary hypertension, this pathological condition remains an urgent health problem. Thus, the search for new points of application of therapy and fundamentally new methods of treatment of pulmonary hypertension remains relevant to this day.
{"title":"Pulmonary hypertension: modern methods of treatment and ways of their long-term development.","authors":"Anna V. Zagrebelnaya, L. Korokina, T. Malorodova, Olesya V. Shcheblykina, T. Avtina, Anton A. Bolgov, E. Malyutina, V. Simonov, Vladislav A. Travkin, Artem А. Dmitriev, Amonullo A. Aripov, Dmitry V. Shcheblykin","doi":"10.18413/rrpharmacology.9.10026","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10026","url":null,"abstract":"Introduction: The purpose of this work is to review the main pathogenetic mechanisms of the development of PH, as well as modern established methods of treatment of various types of PH and to consider new, most relevant and promising possibilities of therapy for this pathology.\u0000Etiology, pathogenesis and epidemiology: In the modern structure of diseases, pulmonary hypertension plays a significant role, affecting about 1% of the population. However, each of its five main groups has its own characteristics. The causes of pulmonary hypertension can be a polyetiological violation of the processes of endotheliocyte apoptosis and angiogenesis, passive transmission of increased pressure from the left heart to the small circulatory system, chronic hypoxia, leading to vascular remodeling, and many others. In general, it is worth noting that, despite the multiplicity of etiological factors, the main pathogenetic link in the development of pulmonary hypertension is endothelial dysfunction.\u0000Treatment and promising areas of research: This article discusses the main established approaches to the treatment of pulmonary hypertension: general recommendations for patients, drugs used as supportive nonspecific therapy, as well as specific conservative and radical methods of treatment. In addition, the main modern directions of scientific research in the field of treatment of pulmonary hypertension are described. Such promising methods as the use of stem cells, gene therapy and epigenetic drugs are considered.\u0000Conclusion: Despite active research and many different drugs intended for the treatment of pulmonary hypertension, this pathological condition remains an urgent health problem. Thus, the search for new points of application of therapy and fundamentally new methods of treatment of pulmonary hypertension remains relevant to this day.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48417238","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 : 2023-05-17DOI: 10.18413/rrpharmacology.9.10024
T. Berezhnova, V. V. Shishkina, D. Esaulenko, Yelena A. Lunyova, Yelena S. Goryushkina, Angelina A. Abramyan, Kseniya S. Dyadina, Anastasia I. Chechelnitsky, Tatiana V. Samoilenko
Introduction: Glucocorticosteroid therapy is the basic therapeutic option for rheumatoid arthritis; however, long-term treatment with low and medium doses is associated with the development of negative side effects. As reported, oxidative stress is crucial in the pathogenesis of rheumatoid arthritis. Therefore, pharmacotherapy that combines application of methylprednisolone pulse therapy and an aqueous molecular hydrogen solution seems to be a reasonable treatment option in these cases. Materials and Methods: The study of the effectiveness of combined pharmacotherapy for rheumatoid arthritis was carried out on mature male rats. Rheumatoid arthritis was simulated by introducing bovine type II collagen into the right knee joint. Animals of the 1st – control – group received placebo; animals of the 2nd group received molecular hydrogen-enriched water intragastrically; animals of the 3rd group received methylprednisolone solution intravenously by catheterization of the tail vein, and animals of the 4th group received water enriched with molecular hydrogenintragastrically and methylprednisolone solution intravenously. After withdrawal of animals from the experiment, microsections of their joint tissues were analysed histologically and biomarkers of the joint inflammation were detected immunohistochemically. Results and Discussion: Morphological analysis of microsections taken from animals of the 4th group evidenced effectiveness of the combined therapy based on quantitative estimation of the inflammatory biomarker expression. Dynamic polarization of M1/M2 macrophage was manifested with high quality in animals of this group. Conclusion: The search for new therapeutic options for rheumatoid arthritis is expanded due to major antioxidant substances that can reduce duration of treatment, while ensuring positive dynamics of the course of the disease. Graphical abstract:
{"title":"Combined use of pulse therapy and molecular hydrogen in rats with experimental rheumatoid arthritis: Clinical and histological evaluation of therapeutic effectiveness","authors":"T. Berezhnova, V. V. Shishkina, D. Esaulenko, Yelena A. Lunyova, Yelena S. Goryushkina, Angelina A. Abramyan, Kseniya S. Dyadina, Anastasia I. Chechelnitsky, Tatiana V. Samoilenko","doi":"10.18413/rrpharmacology.9.10024","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10024","url":null,"abstract":"Introduction: Glucocorticosteroid therapy is the basic therapeutic option for rheumatoid arthritis; however, long-term treatment with low and medium doses is associated with the development of negative side effects. As reported, oxidative stress is crucial in the pathogenesis of rheumatoid arthritis. Therefore, pharmacotherapy that combines application of methylprednisolone pulse therapy and an aqueous molecular hydrogen solution seems to be a reasonable treatment option in these cases. \u0000Materials and Methods: The study of the effectiveness of combined pharmacotherapy for rheumatoid arthritis was carried out on mature male rats. Rheumatoid arthritis was simulated by introducing bovine type II collagen into the right knee joint. Animals of the 1st – control – group received placebo; animals of the 2nd group received molecular hydrogen-enriched water intragastrically; animals of the 3rd group received methylprednisolone solution intravenously by catheterization of the tail vein, and animals of the 4th group received water enriched with molecular hydrogenintragastrically and methylprednisolone solution intravenously. After withdrawal of animals from the experiment, microsections of their joint tissues were analysed histologically and biomarkers of the joint inflammation were detected immunohistochemically. \u0000Results and Discussion: Morphological analysis of microsections taken from animals of the 4th group evidenced effectiveness of the combined therapy based on quantitative estimation of the inflammatory biomarker expression. Dynamic polarization of M1/M2 macrophage was manifested with high quality in animals of this group. \u0000Conclusion: The search for new therapeutic options for rheumatoid arthritis is expanded due to major antioxidant substances that can reduce duration of treatment, while ensuring positive dynamics of the course of the disease. \u0000Graphical abstract:","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45542201","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 : 2023-05-17DOI: 10.18413/rrpharmacology.9.10023
L. V. Mikhailova, Y. Belousova, E. Moiseeva, Alina A. Tsapkova, N. Gazatova, Alexandra R. Plotnikova, Danila G. Rudev, Svetlana A. Doktorova, V. Rafalskiy
Introduction: After the COVID-19 pandemic, public healthcare has faced a new problem, the persistence of symptoms, the most significant of which is undue fatigue. The definition of coronavirus infection as an endothelial disease suggests a possible relationship between asthenic syndrome and endothelial dysfunction. Aim: to evaluate endothelial function in patients after COVID-19 before and after treatment with combination drug of ethylmethylhydroxyperidine succinate (EMHPS)/vitamin B6. Materials and Methods: A prospective study included 33 participants, 82% women and 18% men aged 22 to 68 years after COVID-19. There were two site visits made in the course of the study and a 4-week treatment course between the visits. Results: After the treatment, the index of endothelium-dependent vasodilation increased in women and decreased in men. The differences were statistically insignificant. The number of subjects with a normal level of endothelium-dependent vasodilation increased from 7 to 11 after the treatment. The index of vascular wall stiffness corresponded to the mean age of the examined participants and did not statistically change, although women tended to decrease stiffness and men to increase it. The initial level of nitric oxide was lower in women and statistically significantly increased after treatment, while it remained unchanged in men. Discission: The study confirms a prolonged course of the post-covid. We assume that the virus destroys endothelial cells.Endothelial dysfunction is known to be associated with an increased cardiovascular risk. Conclusion: The indicators of endothelial function changed in patients after treatment with the drug. It is necessary to perform endothelial function studies in more patients after COVID-19. Graphical Abstract
{"title":"Dynamics of endothelial function indexes in patients with post-Covid syndrome using a combination drug of ethylmethylhydroxyperidine succinate/vitamin B6","authors":"L. V. Mikhailova, Y. Belousova, E. Moiseeva, Alina A. Tsapkova, N. Gazatova, Alexandra R. Plotnikova, Danila G. Rudev, Svetlana A. Doktorova, V. Rafalskiy","doi":"10.18413/rrpharmacology.9.10023","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10023","url":null,"abstract":"Introduction: After the COVID-19 pandemic, public healthcare has faced a new problem, the persistence of symptoms, the most significant of which is undue fatigue. The definition of coronavirus infection as an endothelial disease suggests a possible relationship between asthenic syndrome and endothelial dysfunction. \u0000Aim: to evaluate endothelial function in patients after COVID-19 before and after treatment with combination drug of ethylmethylhydroxyperidine succinate (EMHPS)/vitamin B6. \u0000Materials and Methods: A prospective study included 33 participants, 82% women and 18% men aged 22 to 68 years after COVID-19. There were two site visits made in the course of the study and a 4-week treatment course between the visits. \u0000Results: After the treatment, the index of endothelium-dependent vasodilation increased in women and decreased in men. The differences were statistically insignificant. The number of subjects with a normal level of endothelium-dependent vasodilation increased from 7 to 11 after the treatment. The index of vascular wall stiffness corresponded to the mean age of the examined participants and did not statistically change, although women tended to decrease stiffness and men to increase it. The initial level of nitric oxide was lower in women and statistically significantly increased after treatment, while it remained unchanged in men. \u0000Discission: The study confirms a prolonged course of the post-covid. We assume that the virus destroys endothelial cells.Endothelial dysfunction is known to be associated with an increased cardiovascular risk. \u0000Conclusion: The indicators of endothelial function changed in patients after treatment with the drug. It is necessary to perform endothelial function studies in more patients after COVID-19. \u0000Graphical Abstract \u0000","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46270014","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 : 2023-05-04DOI: 10.18413/rrpharmacology.9.10022
S. A. Alekhin, E. N. Bezhina, D. P. Nazarenko, L. V. Druzhikin
Introduction: Mesenteric thrombosis is a severe pathology with necrotization of intestinal tissues and death of the patient. The development of effective pharmacotherapy is an important task facing researchers. Materials and Methods: All studies were performed on 42 female white rats of the Wistar line, weighing 250±25 g. Segmental mesenteric thrombosis was reproduced by ligation of three segmental arteries in the area of the ileum. The volume of necrosis was determined by the triphenyl tetrazolium method. Results and Discussion: We have studied for the first time the effect of the arginase inhibitor L-norvaline on the volume of small intestine necrotized tissues in a model of acute segmental mesenteric thrombosis in rats. The study revealed a decrease in the volume of necrotic tissues from 32.39±0.47% to 23.84±0.39%, and the administration of glibenclamide did not cause complete cancellation of the L-norvaline action and led to a decrease in the volume of necrosis to 29.69±0.42%. Conclusion: Arginase inhibitor L-norvaline has protective effect in intestinal ischemia Graphical Abstract
{"title":"First discovered positive effect of L-norvaline on the volume of small intestine tissues necrosis in a model of segmental mesenteric thrombosis in rats","authors":"S. A. Alekhin, E. N. Bezhina, D. P. Nazarenko, L. V. Druzhikin","doi":"10.18413/rrpharmacology.9.10022","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10022","url":null,"abstract":"Introduction: Mesenteric thrombosis is a severe pathology with necrotization of intestinal tissues and death of the patient. The development of effective pharmacotherapy is an important task facing researchers. \u0000Materials and Methods: All studies were performed on 42 female white rats of the Wistar line, weighing 250±25 g. Segmental mesenteric thrombosis was reproduced by ligation of three segmental arteries in the area of the ileum. The volume of necrosis was determined by the triphenyl tetrazolium method. \u0000Results and Discussion: We have studied for the first time the effect of the arginase inhibitor L-norvaline on the volume of small intestine necrotized tissues in a model of acute segmental mesenteric thrombosis in rats. The study revealed a decrease in the volume of necrotic tissues from 32.39±0.47% to 23.84±0.39%, and the administration of glibenclamide did not cause complete cancellation of the L-norvaline action and led to a decrease in the volume of necrosis to 29.69±0.42%. \u0000Conclusion: Arginase inhibitor L-norvaline has protective effect in intestinal ischemia \u0000Graphical Abstract \u0000","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43046986","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}
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