Pub Date : 2024-01-15DOI: 10.37489/0235-2990-2023-68-9-10-25-33
V. Gostev, O. Kalinogorskaya, O. Sulian, P. Chulkova, J. Sopova, M. Velizhanina, V. Y. Pleshkov, V. Ageevets, S. V. Sidorenko
Гентамицин является одним из компонентов комбинированной терапии инфекционных эндокардитов, вызванных Staphylococcus aureus, включая метициллинорезистентные штаммы (methicillin-resistant S.aureus, MRSA). Цель исследования — анализ влияния десяти 6-часовых циклов воздействия высоких концентраций (16 мкг/мл) гентамицина in vitro на изменение фенотипа и генотипа аминогликозидочувствительных штаммов S.aureus, относящихся к четырём сиквенс-типам: ST5 (ATCC 29213), ST8, ST97 и ST22 (MRSA). Для всех штаммов, кроме ATCC 29213, после селекции отмечалось увеличение МПК гентамицина до 8–64 мкг/мл. Один штамм (SA0937) диссоциировал на три морфотипа, включая мелкоколониевый вариант (small colony variant, SCV). Вариант производного штамма SA0937 с колониями нормального размера характеризовался ассоциированной устойчивостью к даптомицину за счёт мутации P314L в MprF. Формирование устойчивости не сопровождалось изменением скорости роста, кроме морфотипа SCV. Для штамма ATCC 29213 после селекции отмечалось появление толерантности, проявляющейся в увеличении эффективного киллинга до 14 ч в 24-часовом time-killing эксперименте с концентрацией антибиотика 16 мкг/мл. У штамма ATCC 29213 выявлены мутации в пептидил т-РНК гидролазе (Pth). У трёх штаммов были обнаружены делеции в гене atpG, входящим в состав АТФ-синтазного комплекса. У остальных производных штаммов были выявлены делеции и мутации в генах метаболизма менахинона hepS, menA и трансляционном факторе элонгации G (fusA). Таким образом, использование гентамицина сопряжено с возможным быстрым формированием устойчивости и толерантности, не связанными с приобретением генов аминогликозид-модифицирующих ферментов. Выявление SCV ассоциировано с неблагоприятными клиническими исходами. При использовании комбинированной терапии необходимо учитывать, что существует возможность формирования устойчивости к даптомицину на фоне селекции гентамицином.
{"title":"The Effect of Shock Gentamicin Concentrations on the Formation of Resistance and Small Colony Variants in Staphylococcus aureus","authors":"V. Gostev, O. Kalinogorskaya, O. Sulian, P. Chulkova, J. Sopova, M. Velizhanina, V. Y. Pleshkov, V. Ageevets, S. V. Sidorenko","doi":"10.37489/0235-2990-2023-68-9-10-25-33","DOIUrl":"https://doi.org/10.37489/0235-2990-2023-68-9-10-25-33","url":null,"abstract":"Гентамицин является одним из компонентов комбинированной терапии инфекционных эндокардитов, вызванных Staphylococcus aureus, включая метициллинорезистентные штаммы (methicillin-resistant S.aureus, MRSA). Цель исследования — анализ влияния десяти 6-часовых циклов воздействия высоких концентраций (16 мкг/мл) гентамицина in vitro на изменение фенотипа и генотипа аминогликозидочувствительных штаммов S.aureus, относящихся к четырём сиквенс-типам: ST5 (ATCC 29213), ST8, ST97 и ST22 (MRSA). Для всех штаммов, кроме ATCC 29213, после селекции отмечалось увеличение МПК гентамицина до 8–64 мкг/мл. Один штамм (SA0937) диссоциировал на три морфотипа, включая мелкоколониевый вариант (small colony variant, SCV). Вариант производного штамма SA0937 с колониями нормального размера характеризовался ассоциированной устойчивостью к даптомицину за счёт мутации P314L в MprF. Формирование устойчивости не сопровождалось изменением скорости роста, кроме морфотипа SCV. Для штамма ATCC 29213 после селекции отмечалось появление толерантности, проявляющейся в увеличении эффективного киллинга до 14 ч в 24-часовом time-killing эксперименте с концентрацией антибиотика 16 мкг/мл. У штамма ATCC 29213 выявлены мутации в пептидил т-РНК гидролазе (Pth). У трёх штаммов были обнаружены делеции в гене atpG, входящим в состав АТФ-синтазного комплекса. У остальных производных штаммов были выявлены делеции и мутации в генах метаболизма менахинона hepS, menA и трансляционном факторе элонгации G (fusA). Таким образом, использование гентамицина сопряжено с возможным быстрым формированием устойчивости и толерантности, не связанными с приобретением генов аминогликозид-модифицирующих ферментов. Выявление SCV ассоциировано с неблагоприятными клиническими исходами. При использовании комбинированной терапии необходимо учитывать, что существует возможность формирования устойчивости к даптомицину на фоне селекции гентамицином.","PeriodicalId":8471,"journal":{"name":"Antibiotics and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139622624","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 : 2024-01-15DOI: 10.37489/0235-2990-2023-68-9-10-34-41
D. N. Razgulyaeva, A. M. Klabukov, A. V. Galochkina, A. V. Garshinina, O. N. Zhuravskaya, I. I. Gavrilova, V. A. Manakhov, N. Nesterova, A. Shtro, E. F. Panarin
Background. The modern healthcare system is constantly improving and introducing new measures to protect the population from viral diseases, but the experience of the COVID-19 pandemic has shown that infections cannot always be controlled on global scale. In this regard, the development of new broad-spectrum antiviral drugs is more relevant than ever.The aim of the study was to investigate the antiviral activity and cytotoxicity of copolymers of sodium styrene sulfonate and vinyl monomers of various chemical structures, as well as to identify promising polymers for the development of new antiviral agents.Materials and methods. 14 copolymers of sodium styrene sulfonate (NaSS) with various functional comonomers were synthesized. Three viruses with different reproduction strategies and transmission methods — respiratory syncytial virus, influenza virus, and herpes virus — were selected for the assessment of antiviral activity.Results. The screening identified copolymers that showed high activity against all three viruses. It was found that the introduction of various functional groups into the structure of NaSS did not decrease antiviral activity, but significantly reduced cytotoxicity. The molecular weight has also shown a noticeable effect on the activity. Different sensitivity of viruses and cells to the studied polymers was revealed, likely due to the structural features of the virus shell and cell wall.Conclusions. The results demonstrate the potential of sodium styrene sulfonate copolymers as a model for developing a broad-spectrum antiviral drug.
{"title":"Evaluation of the Antiviral Activity of Drugs from the Group of Polymer Electrolyte Derivatives against a Wide Range of Viruses","authors":"D. N. Razgulyaeva, A. M. Klabukov, A. V. Galochkina, A. V. Garshinina, O. N. Zhuravskaya, I. I. Gavrilova, V. A. Manakhov, N. Nesterova, A. Shtro, E. F. Panarin","doi":"10.37489/0235-2990-2023-68-9-10-34-41","DOIUrl":"https://doi.org/10.37489/0235-2990-2023-68-9-10-34-41","url":null,"abstract":"Background. The modern healthcare system is constantly improving and introducing new measures to protect the population from viral diseases, but the experience of the COVID-19 pandemic has shown that infections cannot always be controlled on global scale. In this regard, the development of new broad-spectrum antiviral drugs is more relevant than ever.The aim of the study was to investigate the antiviral activity and cytotoxicity of copolymers of sodium styrene sulfonate and vinyl monomers of various chemical structures, as well as to identify promising polymers for the development of new antiviral agents.Materials and methods. 14 copolymers of sodium styrene sulfonate (NaSS) with various functional comonomers were synthesized. Three viruses with different reproduction strategies and transmission methods — respiratory syncytial virus, influenza virus, and herpes virus — were selected for the assessment of antiviral activity.Results. The screening identified copolymers that showed high activity against all three viruses. It was found that the introduction of various functional groups into the structure of NaSS did not decrease antiviral activity, but significantly reduced cytotoxicity. The molecular weight has also shown a noticeable effect on the activity. Different sensitivity of viruses and cells to the studied polymers was revealed, likely due to the structural features of the virus shell and cell wall.Conclusions. The results demonstrate the potential of sodium styrene sulfonate copolymers as a model for developing a broad-spectrum antiviral drug.","PeriodicalId":8471,"journal":{"name":"Antibiotics and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139529351","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 : 2024-01-15DOI: 10.37489/0235-2990-2023-68-9-10-42-45
V. Evteev, I. S. Semenova, N. Bunyatyan, A. Prokofiev, V. G. Kukes
The created cell line of human proximal renal tubules RPTEC/TERT1 showed maximum compliance with primary human RPTEC, which makes it optimal for use in studies of the nephrotoxic properties of xenobiotics. Transepithelial resistance measurement (TEER) is a valuable non-invasive method that can be used to quantify the integrity of the cell barrier at various stages of cell growth and differentiation, as well as to predict the toxicity and permeability of drugs.The aim of the study was to examine the dynamics of changes in transepithelial resistance in the model of the RPTEC/TERT1 cell line during incubation with drugs with nephrotoxic effects.Material and methods. The human proximal renal tubule cell line RPTEC/TERT was obtained from the ATCC cell culture bank. Cells at passage 14 were used in the experiment. The following drugs were studied: cisplatin: 2.5 mcg/ml; vancomycin: 50 mcg/ml; doripenem — 20mcg/ml; cefepim — 150mcg/ml. 4–5 repetitions were performed for each concentration of the drug in the experiment. THEER measurements were carried out 4–5 times for each well.Results. Cisplatin, vancomycin, doripenem, and cefepim in the concentrations used do not show a cytotoxic effect on the RPTEC cell line according to TEER dynamics.
{"title":"Study of Antibacterial Drugs’ Nephrotoxicity in the RPTEC Cell Line","authors":"V. Evteev, I. S. Semenova, N. Bunyatyan, A. Prokofiev, V. G. Kukes","doi":"10.37489/0235-2990-2023-68-9-10-42-45","DOIUrl":"https://doi.org/10.37489/0235-2990-2023-68-9-10-42-45","url":null,"abstract":"The created cell line of human proximal renal tubules RPTEC/TERT1 showed maximum compliance with primary human RPTEC, which makes it optimal for use in studies of the nephrotoxic properties of xenobiotics. Transepithelial resistance measurement (TEER) is a valuable non-invasive method that can be used to quantify the integrity of the cell barrier at various stages of cell growth and differentiation, as well as to predict the toxicity and permeability of drugs.The aim of the study was to examine the dynamics of changes in transepithelial resistance in the model of the RPTEC/TERT1 cell line during incubation with drugs with nephrotoxic effects.Material and methods. The human proximal renal tubule cell line RPTEC/TERT was obtained from the ATCC cell culture bank. Cells at passage 14 were used in the experiment. The following drugs were studied: cisplatin: 2.5 mcg/ml; vancomycin: 50 mcg/ml; doripenem — 20mcg/ml; cefepim — 150mcg/ml. 4–5 repetitions were performed for each concentration of the drug in the experiment. THEER measurements were carried out 4–5 times for each well.Results. Cisplatin, vancomycin, doripenem, and cefepim in the concentrations used do not show a cytotoxic effect on the RPTEC cell line according to TEER dynamics. ","PeriodicalId":8471,"journal":{"name":"Antibiotics and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139621467","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 : 2023-07-18DOI: 10.37489/0235-2990-2023-68-3-4-11-18
O. N. Sineva, V. Sadykova, O. P. Bychkova, T. D. Ivankova, K. V. Malysheva, N. Markelova
Due to the emergence of antibiotic resistance in pathogenic microorganisms, it is urgent to search for producers of new antimicrobial metabolites. Actinomycetes are gram-positive mycelial bacteria that produce a large number of antibiotics used in medicine and the agro-industrial complex. Currently, researchers are focused on the search for actinomycetes in ecological niches such as freshwater and marine reservoirs, zones with extreme natural conditions (permafrost soils, glaciers, desert, saline soils, etc.). In this study, cultures of marine actinomycetes were restored after 15 years of storage under vaseline oil. It was shown that all strains retained viability and antibiotic activity at a high level. Based on the results of 16S rRNA gene sequence analysis, the species were identified as: Streptomyces sampsonii 6N, Streptomyces sampsonii 8N, Streptomyces sampsonii 521N, Streptomyces halstedii 22N, Streptomyces brevispora 12N, Streptomyces hirsutus 23N, Streptomyces niveus 14N, Nocardiopsis alba 24N, Nocardiopsis alba 73N, Nocardiopsis alba 85N, Nocardiopsis alba 106N, Nocardiopsis alborubida 722N, Nocardiopsis umidischolae 755N, Nocardiopsis umidischolae 763N. These strains of actinobacteria possessed significant antibiotic activity against the following pathogens: Micrococcus luteus ATCC 9341, Staphylococcus aureus INA 00985, Bacillus subtilis ATCC 6633, Staphylococcus aureus INA 00761 (MRSA — Staphylococcus aureus), Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Pectobacterium carotovorum VKM-B1247, Saccharomyces cerevisiae INA 01042, Candida albicans ATCC 14053, Aspergillus niger ATCC 16404, Aspergillus fumigatus CPB F -37, Fusarium solani VKPM F-890, Fusarium oxysporum VKPM F-148. Therefore, this study evaluated the marine actinomycetes can be potential producers of the novel antibiotics.
{"title":"Antibiotic Potential of Marine Actinomycetes of the Genera Streptomyces and Nocardiopsis","authors":"O. N. Sineva, V. Sadykova, O. P. Bychkova, T. D. Ivankova, K. V. Malysheva, N. Markelova","doi":"10.37489/0235-2990-2023-68-3-4-11-18","DOIUrl":"https://doi.org/10.37489/0235-2990-2023-68-3-4-11-18","url":null,"abstract":"Due to the emergence of antibiotic resistance in pathogenic microorganisms, it is urgent to search for producers of new antimicrobial metabolites. Actinomycetes are gram-positive mycelial bacteria that produce a large number of antibiotics used in medicine and the agro-industrial complex. Currently, researchers are focused on the search for actinomycetes in ecological niches such as freshwater and marine reservoirs, zones with extreme natural conditions (permafrost soils, glaciers, desert, saline soils, etc.). In this study, cultures of marine actinomycetes were restored after 15 years of storage under vaseline oil. It was shown that all strains retained viability and antibiotic activity at a high level. Based on the results of 16S rRNA gene sequence analysis, the species were identified as: Streptomyces sampsonii 6N, Streptomyces sampsonii 8N, Streptomyces sampsonii 521N, Streptomyces halstedii 22N, Streptomyces brevispora 12N, Streptomyces hirsutus 23N, Streptomyces niveus 14N, Nocardiopsis alba 24N, Nocardiopsis alba 73N, Nocardiopsis alba 85N, Nocardiopsis alba 106N, Nocardiopsis alborubida 722N, Nocardiopsis umidischolae 755N, Nocardiopsis umidischolae 763N. These strains of actinobacteria possessed significant antibiotic activity against the following pathogens: Micrococcus luteus ATCC 9341, Staphylococcus aureus INA 00985, Bacillus subtilis ATCC 6633, Staphylococcus aureus INA 00761 (MRSA — Staphylococcus aureus), Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Pectobacterium carotovorum VKM-B1247, Saccharomyces cerevisiae INA 01042, Candida albicans ATCC 14053, Aspergillus niger ATCC 16404, Aspergillus fumigatus CPB F -37, Fusarium solani VKPM F-890, Fusarium oxysporum VKPM F-148. Therefore, this study evaluated the marine actinomycetes can be potential producers of the novel antibiotics.","PeriodicalId":8471,"journal":{"name":"Antibiotics and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80912780","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 : 2023-07-18DOI: 10.37489/0235-2990-2023-68-3-4-30-34
N. M. Gabitova, A. A. Tsibizova, A. Ozerov, M. Samotrueva
The study is devoted to the study of acute toxicity of a new quinazoline compound — 3-[2-Oxo-2-(4-phenylpiperazine-1-yl)ethyl]quinazoline-4(3H)-one (VMA-10-21), promising as an antimicrobial agent active against opportunistic microorganisms. Purpose. Assessment of acute toxicity of the quinazoline derivative 3-[2-oxo-2-(4-phenylpiperazine-1yl)ethyl] quinazoline-4(3h)-oh, exhibiting antimicrobial activity. Material and methods. All experiments were carried out on non-linear mature female rats with a body weight of 180–190 g. Female individuals were in the diestrus stage. The rats were divided into groups (n=6) by a random sample, there were 4 individuals in each group and were kept in cages for a week before the experiment, getting used to laboratory conditions: animals receiving intragastric equiobjection of distilled water (control); experimental animals treated with the compound VMA-10-21 at doses of 1000, 2000; 5000 mg/kg (the doses were selected based on the fact that the study of the toxicity of pyrimidine derivatives with a similar chemical structure showed their relative safety and the absence of lethality from a dose of 500 mg/kg). Results. Assessment of acute toxicity of the quinazoline derivative 3-[2-oxo-2-(4-phenylpiperazine-1yl)ethyl]quinazoline-4(3h)-oh with intragastric administration showed that this compound belongs to class 5 toxicity and is low-toxic according to. Under these conditions, and for LD₅₀, the maximum dose is 5000 mg/kg. However, despite the results obtained, when this compound was administered at a dose of 5000 mg/kg, changes in hemoglobin, the number of leukocytes and platelets, as well as total protein were observed, which may indicate the possible development of pathological changes in the hematopoietic and hepatobiliary systems. Conclusion. Thus, the quinazoline derivative 3-[2-oxo-2-(4-phenylpiperazine-1yl)ethyl]quinazoline-4(3h)-oh with intragastric administration is low-toxic and belongs to the 5th class of toxicity, and therefore the maximum dose is 5000 mg/kg for LD₅₀. However, given the fact that there are changes in hematological and biochemical parameters, this compound needs to be studied in detail under the conditions of course effects on the body of animals.
{"title":"Assessment of Acute Toxicity of Quinazoline Derivative 3-[2-oxo-2-(4-Phenylpiperazine-1-yl)Ethyl]quinazoline-4(3h)-oh Active against Opportunistic Microorganisms","authors":"N. M. Gabitova, A. A. Tsibizova, A. Ozerov, M. Samotrueva","doi":"10.37489/0235-2990-2023-68-3-4-30-34","DOIUrl":"https://doi.org/10.37489/0235-2990-2023-68-3-4-30-34","url":null,"abstract":"The study is devoted to the study of acute toxicity of a new quinazoline compound — 3-[2-Oxo-2-(4-phenylpiperazine-1-yl)ethyl]quinazoline-4(3H)-one (VMA-10-21), promising as an antimicrobial agent active against opportunistic microorganisms. Purpose. Assessment of acute toxicity of the quinazoline derivative 3-[2-oxo-2-(4-phenylpiperazine-1yl)ethyl] quinazoline-4(3h)-oh, exhibiting antimicrobial activity. Material and methods. All experiments were carried out on non-linear mature female rats with a body weight of 180–190 g. Female individuals were in the diestrus stage. The rats were divided into groups (n=6) by a random sample, there were 4 individuals in each group and were kept in cages for a week before the experiment, getting used to laboratory conditions: animals receiving intragastric equiobjection of distilled water (control); experimental animals treated with the compound VMA-10-21 at doses of 1000, 2000; 5000 mg/kg (the doses were selected based on the fact that the study of the toxicity of pyrimidine derivatives with a similar chemical structure showed their relative safety and the absence of lethality from a dose of 500 mg/kg). Results. Assessment of acute toxicity of the quinazoline derivative 3-[2-oxo-2-(4-phenylpiperazine-1yl)ethyl]quinazoline-4(3h)-oh with intragastric administration showed that this compound belongs to class 5 toxicity and is low-toxic according to. Under these conditions, and for LD₅₀, the maximum dose is 5000 mg/kg. However, despite the results obtained, when this compound was administered at a dose of 5000 mg/kg, changes in hemoglobin, the number of leukocytes and platelets, as well as total protein were observed, which may indicate the possible development of pathological changes in the hematopoietic and hepatobiliary systems. Conclusion. Thus, the quinazoline derivative 3-[2-oxo-2-(4-phenylpiperazine-1yl)ethyl]quinazoline-4(3h)-oh with intragastric administration is low-toxic and belongs to the 5th class of toxicity, and therefore the maximum dose is 5000 mg/kg for LD₅₀. However, given the fact that there are changes in hematological and biochemical parameters, this compound needs to be studied in detail under the conditions of course effects on the body of animals.","PeriodicalId":8471,"journal":{"name":"Antibiotics and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89792356","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 : 2023-07-18DOI: 10.37489/0235-2990-2023-68-3-4-4-10
V. Zarubaev, V. S. Smirnov, T. A. Kudryavtseva, S. Petlenko, A. V. Slita, H. Minh, V. Zaplutanov
Introduction. The requirements of modern clinical guidelines for the treatment of respiratory viral infections suggest the possibility of identifying a specific viral pathogen. In this regard, the search for drugs with selective activity against respiratory syncytial virus and parainfluenza virus is relevant. The purpose of the work is to study the antiviral activity of the drug Cytovir®-3 in vitro in relation to the cytopathogenic effect of respiratory viruses (parainfluenza virus and respiratory syncytial virus). Material and methods. The antiviral effect of Cytovir®-3 in comparison with Umifenovir against parainfluenza virus and respiratory syncytial virus was studied on Vero cell culture. Drugs were administered 1 hour before (prophylactic regimen) and 1 hour after (treatment regimen) infection of the cell culture with respiratory viruses. The working range of concentrations of the studied drugs was calculated based on the values of 50% cytotoxic concentration calculated based on the results of a quantitative microtetrazole test. Results and discussion. The drug Cytovir®-3 in two schemes of application (therapeutic or prophylactic) showed its antiviral efficacy in vitro against respiratory syncytial virus and parainfluenza virus due in the non-toxic range (0–794 µg/ml). At the same time, the suppressive effect of the drug Cytovir®-3 against the parainfluenza virus begins at lower concentrations of the drug with its early (preventive) introduction into cell culture (250 mcg/ml). Conclusion. Antiviral activity of Cytovir®-3 has been proven in vitro against parainfluenza virus and respiratory syncytial virus. At the same time, in all series of experiments, Cytovir®-3 had a higher index of selectivity of antiviral action than that of the comparison drug Umifenovir.
{"title":"Study of the Mechanism of Antiviral Activity of Cytovir®-3 Against Respiratory Viruses In Vitro","authors":"V. Zarubaev, V. S. Smirnov, T. A. Kudryavtseva, S. Petlenko, A. V. Slita, H. Minh, V. Zaplutanov","doi":"10.37489/0235-2990-2023-68-3-4-4-10","DOIUrl":"https://doi.org/10.37489/0235-2990-2023-68-3-4-4-10","url":null,"abstract":"Introduction. The requirements of modern clinical guidelines for the treatment of respiratory viral infections suggest the possibility of identifying a specific viral pathogen. In this regard, the search for drugs with selective activity against respiratory syncytial virus and parainfluenza virus is relevant. The purpose of the work is to study the antiviral activity of the drug Cytovir®-3 in vitro in relation to the cytopathogenic effect of respiratory viruses (parainfluenza virus and respiratory syncytial virus). Material and methods. The antiviral effect of Cytovir®-3 in comparison with Umifenovir against parainfluenza virus and respiratory syncytial virus was studied on Vero cell culture. Drugs were administered 1 hour before (prophylactic regimen) and 1 hour after (treatment regimen) infection of the cell culture with respiratory viruses. The working range of concentrations of the studied drugs was calculated based on the values of 50% cytotoxic concentration calculated based on the results of a quantitative microtetrazole test. Results and discussion. The drug Cytovir®-3 in two schemes of application (therapeutic or prophylactic) showed its antiviral efficacy in vitro against respiratory syncytial virus and parainfluenza virus due in the non-toxic range (0–794 µg/ml). At the same time, the suppressive effect of the drug Cytovir®-3 against the parainfluenza virus begins at lower concentrations of the drug with its early (preventive) introduction into cell culture (250 mcg/ml). Conclusion. Antiviral activity of Cytovir®-3 has been proven in vitro against parainfluenza virus and respiratory syncytial virus. At the same time, in all series of experiments, Cytovir®-3 had a higher index of selectivity of antiviral action than that of the comparison drug Umifenovir.","PeriodicalId":8471,"journal":{"name":"Antibiotics and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75311053","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 : 2023-07-18DOI: 10.37489/0235-2990-2023-68-3-4-19-24
R. Begunov, D. Egorov, A. V. Chetvertakova, L. I. Savina, A. Zubishina
Background. Antibiotic resistance of bacteria is a serious concern for modern medicine. The search for new compounds with a pronounced antibacterial effect is an urgent task of pharmaceutical chemistry. The aim of the study was to assess nfluence of the structure of benzimidazole and its derivatives the ability to inhibit the growth of gram-positive bacteria Bacillus subtilis. Materials and methods. Antibacterial activity of diazaheterocycles was evaluated by the method of serial dilutions. Сoncentrations from 0,06 to 1000 µg/l were used. Тhe minimum inhibitory concentration (MIC) of benzimidazole derivatives against Bacillus subtilis BKM B-407 was determined. The antibacterial effect of the studied halogen- and nitrobenzimidazoles was compared with the antimicrobial activity of benzimidazole. Results. The antimicrobial activity of the 12 benzimidazole derivatives was established. 2-trifluoromethylbenzimidazoles containing halogen atoms in the phenylene fragment had the most pronounced inhibitory effect. The dihalogenated derivatives exhibited greater antibacterial activity than the compounds with one halogen atom in the benzene ring. 5,6-dibromo-2-(trifluoromethyl)benzimidazole was the most active compound with an MIC of 0.49 µg/mL, comparable to the commercial antibiotic tetracycline. The antibacterial activity of erythromycin is a half that of this substance. Conclusions. Polyhalogen derivatives of benzimidazole are promising compounds for the development of new antimicrobial drugs against Gram-positive bacteria.
{"title":"Antibacterial Activity of the Halogen- and Nitro Derivatives of Benzimidazole Against Bacillus Subtilis","authors":"R. Begunov, D. Egorov, A. V. Chetvertakova, L. I. Savina, A. Zubishina","doi":"10.37489/0235-2990-2023-68-3-4-19-24","DOIUrl":"https://doi.org/10.37489/0235-2990-2023-68-3-4-19-24","url":null,"abstract":"Background. Antibiotic resistance of bacteria is a serious concern for modern medicine. The search for new compounds with a pronounced antibacterial effect is an urgent task of pharmaceutical chemistry. The aim of the study was to assess nfluence of the structure of benzimidazole and its derivatives the ability to inhibit the growth of gram-positive bacteria Bacillus subtilis. Materials and methods. Antibacterial activity of diazaheterocycles was evaluated by the method of serial dilutions. Сoncentrations from 0,06 to 1000 µg/l were used. Тhe minimum inhibitory concentration (MIC) of benzimidazole derivatives against Bacillus subtilis BKM B-407 was determined. The antibacterial effect of the studied halogen- and nitrobenzimidazoles was compared with the antimicrobial activity of benzimidazole. Results. The antimicrobial activity of the 12 benzimidazole derivatives was established. 2-trifluoromethylbenzimidazoles containing halogen atoms in the phenylene fragment had the most pronounced inhibitory effect. The dihalogenated derivatives exhibited greater antibacterial activity than the compounds with one halogen atom in the benzene ring. 5,6-dibromo-2-(trifluoromethyl)benzimidazole was the most active compound with an MIC of 0.49 µg/mL, comparable to the commercial antibiotic tetracycline. The antibacterial activity of erythromycin is a half that of this substance. Conclusions. Polyhalogen derivatives of benzimidazole are promising compounds for the development of new antimicrobial drugs against Gram-positive bacteria.","PeriodicalId":8471,"journal":{"name":"Antibiotics and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87370183","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 : 2023-07-18DOI: 10.37489/0235-2990-2023-68-3-4-46-51
Z. A. Kambachokova, Z. A. Akhkubekova, R. Aramisova, D. E. Altudova, L. A. Kagazheva, M. A. Shokueva, A. A. Kambachokova, A. B. Kankulova, A. M. Urusbiev, Yusufzai Abdul Vadzhid, I. A. Kochesokova
The research studied the clinical and laboratory characteristics of COVID-19 patients against the background of cardiovascular diseases. A high prevalence of cardiovascular diseases (CVD) was revealed among COVID-19 patients: arterial hypertension (93.4%), chronic heart failure (60.9%), cardiac arrhythmias (40.1%), coronary heart disease (21.9%). A reliable correlation was established between the timing of hospitalization from the onset of the disease and the severity of the infection, mortality was higher in persons hospitalized on the 5–7 day of the disease (59.8%). Patients with CVD are significantly more likely to develop complications, as well as higher deaths (11.53% vs. 4.30%). Pulmonary embolism (44%), acute respiratory distress syndrome (22%), acute kidney injury (20.6%) prevailed in the structure of causes of death. Gender differences in the course and outcomes of COVID-19 were found: the severity of the course and mortality rates were higher among males. According to clinical and laboratory indicators, patients with diseases of the cardiovascular system had a more severe course and a high degree of immuno-inflammatory reactions compared with the group of patients without a premorbid background. Upon admission to the hospital, patients with COVID-19 and CVD were significantly more likely to have a lesion of the pulmonary parenchyma of CT 3 and CT 4 (P<0.05), whereas in the group without concomitant cardiac pathology, lung lesion corresponded to CT 1 (P<0.05); CT of the lungs in dynamics showed differences in the study groups: in patients with COVID-19 and CVD, CT 3 was recorded significantly more often, and in the comparison group — CT 1 (45% vs. 10%, (P<0.05)).
本研究以心血管疾病为背景，研究新冠肺炎患者的临床和实验室特征。新冠肺炎患者心血管疾病(CVD)患病率较高:动脉高血压(93.4%)、慢性心力衰竭(60.9%)、心律失常(40.1%)、冠心病(21.9%)。发病后的住院时间与感染的严重程度之间存在可靠的相关性，在发病后5-7天住院的患者死亡率较高(59.8%)。心血管疾病患者更容易出现并发症，死亡率也更高(11.53% vs. 4.30%)。肺栓塞(44%)、急性呼吸窘迫综合征(22%)、急性肾损伤(20.6%)在死因结构中占主导地位。发现了COVID-19病程和结局的性别差异:男性病程的严重程度和死亡率更高。根据临床和实验室指标，与无病前背景的患者相比，心血管系统疾病患者病程更严重，免疫炎症反应程度更高。入院时，合并CVD的患者更容易出现CT 3、CT 4肺实质病变(P<0.05)，而未合并心脏病变组肺部病变对应CT 1 (P<0.05);两组间肺动态CT显示差异:在合并COVID-19和CVD的患者中，CT 3的记录频率明显高于对照组(45% vs. 10%， P<0.05)。
{"title":"Clinical and Laboratory Characteristics of Patients with COVID-19 on the Background of Cardiovascular Diseases","authors":"Z. A. Kambachokova, Z. A. Akhkubekova, R. Aramisova, D. E. Altudova, L. A. Kagazheva, M. A. Shokueva, A. A. Kambachokova, A. B. Kankulova, A. M. Urusbiev, Yusufzai Abdul Vadzhid, I. A. Kochesokova","doi":"10.37489/0235-2990-2023-68-3-4-46-51","DOIUrl":"https://doi.org/10.37489/0235-2990-2023-68-3-4-46-51","url":null,"abstract":"The research studied the clinical and laboratory characteristics of COVID-19 patients against the background of cardiovascular diseases. A high prevalence of cardiovascular diseases (CVD) was revealed among COVID-19 patients: arterial hypertension (93.4%), chronic heart failure (60.9%), cardiac arrhythmias (40.1%), coronary heart disease (21.9%). A reliable correlation was established between the timing of hospitalization from the onset of the disease and the severity of the infection, mortality was higher in persons hospitalized on the 5–7 day of the disease (59.8%). Patients with CVD are significantly more likely to develop complications, as well as higher deaths (11.53% vs. 4.30%). Pulmonary embolism (44%), acute respiratory distress syndrome (22%), acute kidney injury (20.6%) prevailed in the structure of causes of death. Gender differences in the course and outcomes of COVID-19 were found: the severity of the course and mortality rates were higher among males. According to clinical and laboratory indicators, patients with diseases of the cardiovascular system had a more severe course and a high degree of immuno-inflammatory reactions compared with the group of patients without a premorbid background. Upon admission to the hospital, patients with COVID-19 and CVD were significantly more likely to have a lesion of the pulmonary parenchyma of CT 3 and CT 4 (P<0.05), whereas in the group without concomitant cardiac pathology, lung lesion corresponded to CT 1 (P<0.05); CT of the lungs in dynamics showed differences in the study groups: in patients with COVID-19 and CVD, CT 3 was recorded significantly more often, and in the comparison group — CT 1 (45% vs. 10%, (P<0.05)).","PeriodicalId":8471,"journal":{"name":"Antibiotics and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81470572","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 : 2023-07-18DOI: 10.37489/0235-2990-2023-68-3-4-25-29
T. Kuznetsova, T. Smolina, L. A. Ivanushko, E. V. Persiyanova, A. Silchenko, N. Besednova
Objectives. No sulfated polysaccharides (fucoidans) has been declared as the pharmaceutical substances, adjuvants, etc., which is associated with the problems of obtaining the structurally characterized and homogeneous samples or their oligomeric fractions that retain high biological activity. The highly purified fucoidan with regular reproducible structural characteristics (F1) was obtained by enzymatic hydrolysis of native fucoidan (F2). Aim. The comparative study of fucoidans from the brown alga Fucus evanescens (F1 and F2) effects on the effector functions of innate and adaptive immunity cells loaded with ovalbumin (OVA) in vitro and in vivo. Material and methods. Fucoidan F1 — the enzymatically modified product of native fucoidan; F2 — the native fucoidan. The fucoidans effects on the expression level of the main immunophenotypic markers of innate and adaptive immunity (neutrophils, monocytes, natural killers, lymphocytes) cells in vitro were studied by methods of flow cytometry. The fucoidans effects on the production of serum OVA-specific antibodies (IgG, IgG1, IgG2а) and cytokines (IFNγ, IL-2, IL-10, IL-12) were detected in BALB/c mice immunized with OVA. Results. The tested fucoidans activate the effector functions of innate and adaptive immunity cells loaded with OVA in vitro and act as adjuvants, stimulating both Th1 (IgG2а, INFγ, IL-2) and Th2 (IgG1, IL-10) immune response to OVA in vivo. Conclusions. The immunoadjuvant effect of the enzymatically modified fucoidan (F1) on effector functions of innate and adaptive immunity cells are comparable to those of the native fucoidan (F2). The findings determine the possibility of F1 use as an adjuvant for a wide range of prophylactic and therapeutic vaccines.
{"title":"In vitro and in vivo Immunoadjuvant Effects of the Enzymatically Modified Fucoidan","authors":"T. Kuznetsova, T. Smolina, L. A. Ivanushko, E. V. Persiyanova, A. Silchenko, N. Besednova","doi":"10.37489/0235-2990-2023-68-3-4-25-29","DOIUrl":"https://doi.org/10.37489/0235-2990-2023-68-3-4-25-29","url":null,"abstract":"Objectives. No sulfated polysaccharides (fucoidans) has been declared as the pharmaceutical substances, adjuvants, etc., which is associated with the problems of obtaining the structurally characterized and homogeneous samples or their oligomeric fractions that retain high biological activity. The highly purified fucoidan with regular reproducible structural characteristics (F1) was obtained by enzymatic hydrolysis of native fucoidan (F2). Aim. The comparative study of fucoidans from the brown alga Fucus evanescens (F1 and F2) effects on the effector functions of innate and adaptive immunity cells loaded with ovalbumin (OVA) in vitro and in vivo. Material and methods. Fucoidan F1 — the enzymatically modified product of native fucoidan; F2 — the native fucoidan. The fucoidans effects on the expression level of the main immunophenotypic markers of innate and adaptive immunity (neutrophils, monocytes, natural killers, lymphocytes) cells in vitro were studied by methods of flow cytometry. The fucoidans effects on the production of serum OVA-specific antibodies (IgG, IgG1, IgG2а) and cytokines (IFNγ, IL-2, IL-10, IL-12) were detected in BALB/c mice immunized with OVA. Results. The tested fucoidans activate the effector functions of innate and adaptive immunity cells loaded with OVA in vitro and act as adjuvants, stimulating both Th1 (IgG2а, INFγ, IL-2) and Th2 (IgG1, IL-10) immune response to OVA in vivo. Conclusions. The immunoadjuvant effect of the enzymatically modified fucoidan (F1) on effector functions of innate and adaptive immunity cells are comparable to those of the native fucoidan (F2). The findings determine the possibility of F1 use as an adjuvant for a wide range of prophylactic and therapeutic vaccines.","PeriodicalId":8471,"journal":{"name":"Antibiotics and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84357376","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 : 2023-07-18DOI: 10.37489/0235-2990-2023-68-3-4-52-65
Y. Gomon, A. Kolbin, A. M. Fahrutdinova, T. A. Usmanova, F. Sultanova, Y. Balykina
Aim. Evaluation of the effectiveness of anti-interleukin drugs used in the pathogenetic therapy of COVID-19 in relation to the relative risks of 28-day mortality and the odds ratio of 14-day improvement of symptoms of the disease. Materials and methods. A systematic review of publications concerning the evaluation of the effectiveness of these drugs recommended for use as COVID-19 pathogenetic therapy, with meta-analysis and indirect comparison of the data obtained, was carried out. Results. The meta-analysis included 15 randomized and 8 non-randomized studies. In direct comparison of anti-interleukin drugs with controls, it was demonstrated that only tocilizumab and anakinra surpass standard therapy in terms of the relative risk of 28-day mortality (RR 0.85 [95% CI 0.74; 0.97] and 0.5 [95% CI 0.32; 0.80], respectively). Statistically reliable data were also obtained in favor of the effectiveness of levilimab in comparison with standard therapy according to the criterion of «improvement by the 14th day of the disease», which was 2.29 [1.31; 4.01]. With an indirect comparison of tocilizumab and anakinra, the latter showed greater effectiveness in reducing the 28-day mortality rate: the RR was 1.2 [95% CI 1.16; 1.25], P=0.0001. Conclusion. The meta-analysis of the results of the systematic review demonstrated the effectiveness of tocilizumab and anakinra in relation to the 28-day mortality rate, and levilimab in relation to the indicator «Improvement by the 14th day of the disease».
的目标。评价抗白细胞介素药物用于COVID-19病理治疗的有效性与28天死亡率相对风险和14天疾病症状改善的优势比材料和方法。对推荐用于COVID-19病原学治疗的这些药物有效性评价的出版物进行了系统综述，并对获得的数据进行了荟萃分析和间接比较。结果。荟萃分析包括15项随机研究和8项非随机研究。在直接比较抗白细胞介素药物与对照组时，证明只有托珠单抗和阿那金在28天死亡率的相对风险方面优于标准治疗(RR 0.85 [95% CI 0.74;0.97]和0.5 [95% CI 0.32;分别为0.80])。根据“疾病第14天改善”的标准，与标准治疗相比，也获得了统计学上可靠的数据，支持利伐单抗的有效性，为2.29 [1.31;4.01]。通过间接比较tocilizumab和anakinra，后者在降低28天死亡率方面表现出更大的有效性:RR为1.2 [95% CI 1.16;1.25], P = 0.0001。结论。系统评价结果的荟萃分析显示tocilizumab和anakinra在28天死亡率方面的有效性，以及levilimab在“疾病第14天改善”指标方面的有效性。
{"title":"A Systematic Review with Meta-Analysis and Indirect Comparison of the Effectiveness of COVID-19 Anti-Interleukin Therapy","authors":"Y. Gomon, A. Kolbin, A. M. Fahrutdinova, T. A. Usmanova, F. Sultanova, Y. Balykina","doi":"10.37489/0235-2990-2023-68-3-4-52-65","DOIUrl":"https://doi.org/10.37489/0235-2990-2023-68-3-4-52-65","url":null,"abstract":"Aim. Evaluation of the effectiveness of anti-interleukin drugs used in the pathogenetic therapy of COVID-19 in relation to the relative risks of 28-day mortality and the odds ratio of 14-day improvement of symptoms of the disease. Materials and methods. A systematic review of publications concerning the evaluation of the effectiveness of these drugs recommended for use as COVID-19 pathogenetic therapy, with meta-analysis and indirect comparison of the data obtained, was carried out. Results. The meta-analysis included 15 randomized and 8 non-randomized studies. In direct comparison of anti-interleukin drugs with controls, it was demonstrated that only tocilizumab and anakinra surpass standard therapy in terms of the relative risk of 28-day mortality (RR 0.85 [95% CI 0.74; 0.97] and 0.5 [95% CI 0.32; 0.80], respectively). Statistically reliable data were also obtained in favor of the effectiveness of levilimab in comparison with standard therapy according to the criterion of «improvement by the 14th day of the disease», which was 2.29 [1.31; 4.01]. With an indirect comparison of tocilizumab and anakinra, the latter showed greater effectiveness in reducing the 28-day mortality rate: the RR was 1.2 [95% CI 1.16; 1.25], P=0.0001. Conclusion. The meta-analysis of the results of the systematic review demonstrated the effectiveness of tocilizumab and anakinra in relation to the 28-day mortality rate, and levilimab in relation to the indicator «Improvement by the 14th day of the disease».","PeriodicalId":8471,"journal":{"name":"Antibiotics and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81795868","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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