MICROBIOLOGICAL STUDY OF A PERSPECTIVE HEPATOPROTECTIVE AGENT BASED ON DRY EXTRACT FROM PRUNUS DOMESTICA FRUITS

One of the main directions of improving the concept of treatment of diseases of the gastrointestinal tract and liver, which is accompanied by dysfunction of the hepatobiliary system and intestines, was the search and development of herbal remedies with hepatoprotective effect with a laxative effect and concomitant prebiotic activity. Aim of the research: to study the antimicrobial and prebiotic properties of the studied phytosubstance obtained from the fruits of Prunus domestica. Materials and methods. The study of the antimicrobial activity of the test sample of plum fruit extract with fibers was performed in vitro by the method of multiple serial dilutions. The reference strains of the following microorganisms were used as the microbiological model: S.aureus-ATCC-25923, E.сoli-ATCC-25922, P. aéruginosa-ATCC-27853, B. subtilis-ATCC-6633, C.albicans-ATCC-885653. The determination of the prebiotic properties of the studied sample was carried out by the method of cultivation of bacteria Bifidobacterium bifidum No. 1 and L. rhamnosus R0011 ND on nutrient media, which included the composition of plum fruit with fibers. Results. Studies on the antimicrobial activity of plum fruit extract with fibers showed that the studied phytosubstance does not reveal antagonistic properties both with respect to gram-positive and gram-negative bacteria, as well as in the case of Candida fungi. The results of studies on the study of the prebiotic properties of the studied extract confirmed the improvement of the main physiological parameters of the culture of bifidobacteria strain Bifidobacterium bifidum No. 1 and the strain lactobacillus L. rhamnosus R0011 ND when the fruit plums with fibers were added to the culture medium. Conclusions. The conducted studies allowed to establish the prebiotic properties of the studied extract of plum fruits with fibers, which proves the promise of its use in complex therapy schemes for gastrointestinal pathology

PROGNOSTIC ASSESSMENT OF STRESS-RELATED FACTORS IN HEALTHCARE WORKERS DURING THE COVID-19 PANDEMIC

Introduction: The COVID-19 pandemic is an extraordinary challenge for all countries and affects the psychological wellbeing of healthcare professionals working with people suffering from COVID-19 and puts them at a high risk of mental health problems. The aim of the study was to identify stress-related factors that affect the mental health of healthcare workers during the COVID-19 pandemic in Ukraine. Subjects and methods: A total of 1098 Ukrainian healthcare workers were surveyed using an online questionnaire consisting of questions relating to a) socio-demographic characteristics; b) perceptions of the COVID-19 related situation; and c) stress and protective factors. Respondents were divided into two groups, depending on whether they provided care to the patients with COVID-19 or not. Results: Of the 1087 healthcare workers, 863 (79.4%) were found to have anxiety / fear caused by the COVID-19. No significant difference was detected between professionals who did and did not provide personal assistance to patients with COVID-19 concerning anxiety / fear related to COVID-19 (p=0.0776). Based on logistic regression model (χ2(6)=263.70, p=0.000) the most significant predictive factors for anxiety / fear caused by the COVID-19 were factors related to safety and risk perception (the risk of getting infected, dying, infecting loved ones, perception of the threat of the epidemic spread), information factors (constant news about COVID-19), as well as factors related to the organisation of care (lack of staff in health care facilities). Conclusions: Negative risk perception, high consumption of COVID-19 news, and shortage of staff in health care facilities were significant predictors of anxiety / fear caused by the COVID-19

Сучасні технології дослідження геному мікобактерій

Molecular technologies play a leading role in the laboratory diagnosis of tuberculosis and mycobacteriosis. The successes in studying the genome of Mycobacterium have contributed to significant progress in understanding the evolution, variability, and genetic diversity of pathogens, as well as the development of diagnostic technologies, including research into resistance to anti-tuberculosis drugs. The aim of this research is to conduct a comparative study of the spectrum of modern technologies for studying the genomes of mycobacteria and their impact on the efficiency of the laboratory diagnosis of tuberculosis. Materials and methods: a search for sources of information was carried out in the PubMed, Medline, Web of Science, and Google Scholar databases. Materials related to the technology of molecular diagnosis of tuberculosis and mycobacteriosis and for determining the susceptibility of pathogens to anti-tuberculosis drugs were selected. Results: it was determined that the modern methods for studying the genome of mycobacteria include amplification technologies (PCR analysis), hybridization, restriction, spoligotyping, sequencing, and their various combinations. The main methods are standard and modified protocols of PCR (RAPD-PCR, AP-PCR, rep-PCR, Real-time PCR, Inverse PCR, TB-LAMP, HIP, LM-PCR). Genomic Restriction Analysis can be used in studies of MTBC and NTM strains (RFLP, AFLP analysis, MIRU-VNTR genotyping). The most effective method for genome analysis is WGS. Complex methods that utilize a combination of molecular technologies allow for the direct detection of mycobacteria in clinical samples. Conclusions: the widespread application of genomic technologies in the study of mycobacteria will contribute to the effective implementation of the global WHO strategy for the prevention, treatment, and control of tuberculosis and mycobacteriosisМолекулярні технології займають провідне місце в лабораторній діагностиці туберкульозу та мікобактеріозів. Успіхи досліджень генома представників роду Mycobacterium призвели до значного прогресу в розумінні еволюції, мінливості та генетичного різноманіття патогенів, а також розвитку діагностичних технологій, включаючи дослідження стійкості до протитуберкульозних препаратів. Мета роботи: провести порівняльного дослідження спектру сучасних технологій вивчення геномів мікобактерій та їх впливу на ефективність лабораторної діагностики туберкульозу. Матеріали та методи: пошук джерел інформації здійснювався в базах даних PubMed, Medline, Web of Science, Google Scholar. Відібрано матеріали щодо технології молекулярної діагностики туберкульозу та мікобактеріозів та визначення чутливості збудників до протитуберкульозних препаратів. Результати: встановлено, що сучасні методи дослідження геному мікобактерій включають технології ампліфікації (ПЛР-аналіз), гібридизації, рестрикції, споліготипування, секвенування та їх різні комбінації. До основних методів належать стандартні та модифіковані протоколи ПЛР (RAPD-PCR, AP-PCR, rep-PCR, Real-time PCR, Inverse PCR, TB-LAMP, HIP, LM-PCR). Геномний рестрикційний аналіз може бути застосований при дослідженні штамів MTBC і NTM (RFLP, AFLP аналіз, генотипування MIRU-VNTR). Найефективнішим методом аналізу геному є WGS. Комплексні методи, які використовують комбінацію молекулярних технологій, дозволяють безпосередньо виявляти мікобактерії в клінічних зразках. Висновки: широке застосування технологій дослідження геному при вивченні мікобактерій сприятиме ефективній реалізації глобальної стратегії ВООЗ щодо профілактики, лікування та боротьби з туберкульозом і мікобактеріозам

Investigation of the influence of dry extracts of bupleurum aureum and Salsola collina L. on the antimicrobial effect of co-trimoxazole

Scientific data on the pharmacodynamics of dry extracts of Bupleurum aureum and Salsola collina L. based on the results of studying the antimicrobial effect and the similar effect of co-trimoxazole when they are used together have been supplemented. The investigated phytoextracts do not show antimicrobial properties, but they do not change the antimicrobial effect of co-trimoxazole when they are used in combination. The aim of the study was to experimentally investigate the antimicrobial effect of extracts of Bupleurum aureum and Salsola collina L. and establish the possible antagonistic effect of these extracts on the antimicrobial drug co-trimoxazole when used together. Materials and methods. The research was conducted in May 2016. Screening of the antimicrobial effect of extracts of Bupleurum aureum and Salsola collina L. and establishing of the possible antagonistic effect of these extracts on the antimicrobial drug co-trimoxazole when they are used together was carried out in the laboratory of the Department of Microbiology of the National Pharmaceutical University, which has a certificate of attestation 045/14 dated 28.10.2014. For determination of antimicrobial activity, the agar diffusion method ("well" method), which is based on the ability of medicinal substances to penetrate the agar layer, was used. A set of reference strains of microorganisms was used: S. aureus ATCC 6538, E. coli ATCC 8739, P. aeruginosa ATCC 9027, B. subtilis ATCC 6633, C. albicans ATCC 10231. Petri dishes were filled with two layers of solid nutrient medium. The lower layer - 10 ml of melted "cold" AGV agar (medium No. 3), the upper layer - nutrient medium for the corresponding test strain. After cooling the lower layer of agar, three thin-walled steel cylinders (inner diameter - 6.0±0.1 mm, height - 10.0±0.1 mm) were placed on it at an equal distance from each other and from the edge of the cup. The top layer was poured around the cylinders - 13.5 ml of agar, melted and cooled to 45-48°С, mixed with the seed dose of the test microorganism (1.5 ml of microbial suspension, the concentration corresponding to the type of microorganism). After cooling the upper layer of agar, the cylinders were removed with sterile tweezers and 0.25-0.3 ml of the studied drug was added to the resulting wells. The results were recorded after 24 h by measuring the zone of growth inhibition, including the diameter of the wells. Measurements were made with an accuracy of 1 mm, while focusing on the complete absence of visible growth. The obtained data were analyzed using the methods of variational statistics. The significance level is p<0.05. The studied plant extracts of Bupleurum aureum (aqueous and alcoholic) and Salsola collina L. (aqueous and alcoholic) were used in doses of 0.005 mg/ml and 0.01 mg/ml, which corresponded to doses of 5 mg/kg and 10 mg/kg. Experimental data were also processed by parametric (Newman-Keuls) and non-parametric (Mann-Whitney) methods of variational statistics, using the Statistica 6.0 statistical software package; differences were considered statistically significant at p<0.05. Results. At the final stage, the determination of the antimicrobial effect of water and alcohol extracts of Bupleurum aureum and Salsola collina L. at doses of 1 mg/ml and 5 mg/ml was carried out, and the effect of BAS of these extracts on the antimicrobial effect of co-trimoxazole when used together was determined. In the course of the study, it has been established, that the addition of the above-mentioned extracts to the co-trimoxazole formulation does not affect its initial antimicrobial properties. Conclusion. Today, drug-induced liver injury remains one of the most important problems of hepatology and pediatrics, pharmacological science pays a lot of attention to the search for new effective and harmless drugs with a hepatoprotective effect, and the improvement of existing drugs is primarily aimed at increasing their specificity and reducing side effects related to the pharmacological properties of the drug. Currently, there is increasing interest in medicinal plants as a source of various biologically active substances (BAS), which provide a wide spectrum of pharmacological action of the agent, which allows to immediately affect various links of the pathogenesis of liver diseases. The analysis of scientific sources made it possible to establish that medicinal products of plant origin, thanks to BAS, possess polymodality of effects and reveal a versatile complex effect on the course of pathological processes in the body. Most drugs are characterized by good tolerability, absence of withdrawal syndrome and toxicity to parenchymal organs. Medicinal plants are used not only as monopreparations, but also in combination with synthetic drugs and as raw materials for obtaining BA

The Search for New Antibacterial Agents among 1,2,3-Triazole Functionalized Ciprofloxacin and Norfloxacin Hybrids: Synthesis, Docking Studies, and Biological Activity Evaluation

Among all modern antibiotics, fluoroquinolones are well known for their broad spectrums of activity and efficiency toward microorganisms and viruses. However, antibiotic resistance is still a problem, which has encouraged medicinal chemists to modify the initial structures in order to combat resistant strains. Our current work is aimed at synthesizing novel hybrid derivatives of ciprofloxacin and norfloxacin and applying docking studies and biological activity evaluations in order to find active promising molecules. We succeeded in the development of a synthetic method towards 1,2,3-triazole-substituted ciprofloxacin and norfloxacin derivatives. The structure and purity of the obtained compounds were confirmed by 1H NMR, 13C NMR, 19F NMR, LC/MS, UV-, IR- spectroscopy. Docking studies, together with in vitro research against Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6633, Pseudomonas aeruginosa ATCC 27853, Candida albicans NCTC 885-653 revealed compounds in which activity exceeded the initial molecules

The Search for New Antibacterial Agents among 1,2,3-Triazole Functionalized Ciprofloxacin and Norfloxacin Hybrids: Synthesis, Docking Studies, and Biological Activity Evaluation

Among all modern antibiotics, fluoroquinolones are well known for their broad spectrums of activity and efficiency toward microorganisms and viruses. However, antibiotic resistance is still a problem, which has encouraged medicinal chemists to modify the initial structures in order to combat resistant strains. Our current work is aimed at synthesizing novel hybrid derivatives of ciprofloxacin and norfloxacin and applying docking studies and biological activity evaluations in order to find active promising molecules. We succeeded in the development of a synthetic method towards 1,2,3-triazole-substituted ciprofloxacin and norfloxacin derivatives. The structure and purity of the obtained compounds were confirmed by 1H NMR, 13C NMR, 19F NMR, LC/MS, UV-, IR- spectroscopy. Docking studies, together with in vitro research against Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6633, Pseudomonas aeruginosa ATCC 27853, Candida albicans NCTC 885-653 revealed compounds in which activity exceeded the initial molecules

Структурна модифікація ципрофлоксацину та норфлоксацину з метою пошуку нових антибіотиків задля подолання резистентності до них

The aim of the work. Among all the representatives of four generations of fluoroquinolones ciprofloxacin (CIPRO) and norfloxacin (NOR) remain widely used and prescribed antibiotics in clinical practice. However, the problem of resistance towards them is gradually increasing. Thus, our investigation is dedicated to chemical modification of C-7 position of Ciprofloxacin and Norfloxacin ring as a promising solution to combat antibiotic resistance and open a pathway towards convenient synthesis of new fluoroquinolones derivatives. Materials and methods. The subjects of the research were N-piperazine-substituted ciprofloxacin and norfloxacin. The methods of molecular docking and organic synthesis were applied in the study. The structures of the obtained compounds were confirmed by 1H NMR, 13C NMR, 19F NMR, LC/MS, IR, UV spectroscopy. The antimicrobial activity was measured by the method of double serial dilutions against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Bacillus subtilis (ATCC 6633), Pseudomonas aeruginosa (ATCC 27853), Candida albicans (NCTC 885-653) and diffusion in agar method against clinical strains. The results. 7-(4-(2-Cyanoacetyl)piperazin-1-yl)-1-R-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acids were synthesized and their structures were confirmed. The obtained compounds showed the antibacterial activity on the reference level for double dilution method and exceeded control for “well” method. Conclusions. The current investigation revealed the promising route for the expanding of the existing fluoroquinolones diversity. Pharmacodynamics and pharmacokinetics changes could be achieved by chemical modifications of C-7 position of the initial ring. Further research utilizing the obtained compounds as starting ones opens a promising way to novel active molecules synthesis and combating the problem of antibiotic resistanceЦель. Среди существующих представителей четырех поколений фторхинолонов ципрофлоксацин (CIPRO) и норфлоксацин (NOR) остаются широко используемыми в клинической практике антибиотиками. Однако постепенно растет проблема резистентности к ним. Данное исследование посвящено химической модификации положения C-7 ципрофлоксацина и норфлоксацина как перспективному подходу к борьбе с устойчивостью к антибиотикам и поиску новых методик для синтеза производных фторхинолонов. Материалы и методы. Предметами исследования были ципрофлоксацин и норфлоксацин. В исследовании использовались методы молекулярного докинга и органического синтеза. Структуры полученных соединений были установлены методами 1Н ЯМР, 13С ЯМР, 19F ЯМР, ЖХ/МС, ИК, УФ-спектроскопии. Антимикробную активность измеряли методом двойных серийных разведений против Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Bacillus subtilis (ATCC 6633), Pseudomonas aeruginosa (ATCC 27853), Candida albicans (NCTC 885-653) и методом диффузии в агар против клинических штаммов. Результаты. Синтезированы 7-(4-(2-цианоацетил)пиперазин-1-ил)-1-R-6-фтор-4-оксо-1,4-дигидрохинолин-3-карбоновые кислоты и доказана их структура. Полученные соединения продемонстрировали антибактериальную активность на уровне контроля для метода двойных серийных разведений и превысили контроль в методе диффузии в агар. Выводы. Проведенное исследование показало перспективный путь расширения существующего многообразия фторхинолонов. Фармакодинамические и фармакокинетические изменения могут быть достигнуты путем химических модификаций положение C-7 известных молекул. Дальнейшие исследования с использованием полученных соединений в качестве исходных открывают перспективный путь к синтезу новых активных молекул и борьбы с проблемой устойчивости к антибиотикам.Мета роботи. Серед існуючих представників чотирьох поколінь фторхінолонів ципрофлоксацин (CIPRO) та норфлоксацин (NOR) залишаються широко використовуваними в клінічній практиці антибіотиками. Однак поступово зростає проблема резистентності до них. Дане дослідження присвячене хімічній модифікації положення C-7 ципрофлоксацину та норфлоксацину як перспективному підходу до боротьби зі стійкістю до антибіотиків та пошуку нових методик задля синтезу похідних фторхінолонів. Матеріали та методи. Предметами дослідження були ципрофлоксацин та норфлоксацин. У дослідженні були застосовані методи молекулярного докінгу та органічного синтезу. Структури отриманих сполук були доведені методами 1Н ЯМР, 13С ЯМР, 19F ЯМР, РХ/МС, ІЧ, УФ-спектроскопії. Антимікробну активність вимірювали методом подвійних серійних розведень проти Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Bacillus subtilis (ATCC 6633), Pseudomonas aeruginosa (ATCC 27853), Candida albicans (NCTC 885-653) та методом дифузії в агар проти клінічних штамів. Результати. Синтезовано 7-(4-(2-ціаноацетил)піперазин-1-іл)-1-R-6-фтор-4-оксо-1,4-дигідрохінолін-3-карбонові кислоти та доведено їх структуру. Отримані сполуки продемонстрували антибактеріальну активність на рівні контролю для методу подвійних серійних розведень та перевищили контроль у методі дифузії в агар. Висновки. Проведене дослідження виявило перспективний шлях розширення існуючого різноманіття фторхінолонів. Фармакодинамічні та фармакокінетичні зміни можуть бути досягнуті шляхом хімічних модифікацій положення C-7 відомих молекул. Подальші дослідження з використанням отриманих сполук як вихідних відкривають перспективний шлях до синтезу нових активних молекул та боротьби з проблемою стійкості до антибіотикі

Structural Modification of Ciprofloxacin and Norfloxacin for Searching New Antibiotics to Combat Drug-resistant Bacteria

The aim of the work. Among all the representatives of four generations of fluoroquinolones ciprofloxacin (CIPRO) and norfloxacin (NOR) remain widely used and prescribed antibiotics in clinical practice. However, the problem of resistance towards them is gradually increasing. Thus, our investigation is dedicated to chemical modification of C-7 position of Ciprofloxacin and Norfloxacin ring as a promising solution to combat antibiotic resistance and open a pathway towards convenient synthesis of new fluoroquinolones derivatives. Materials and methods. The subjects of the research were N-piperazine-substituted ciprofloxacin and norfloxacin. The methods of molecular docking and organic synthesis were applied in the study. The structures of the obtained compounds were confirmed by 1H NMR, 13C NMR, 19F NMR, LC/MS, IR, UV spectroscopy. The antimicrobial activity was measured by the method of double serial dilutions against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Bacillus subtilis (ATCC 6633), Pseudomonas aeruginosa (ATCC 27853), Candida albicans (NCTC 885-653) and diffusion in agar method against clinical strains. The results. 7-(4-(2-Cyanoacetyl)piperazin-1-yl)-1-R-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acids were synthesized and their structures were confirmed. The obtained compounds showed the antibacterial activity on the reference level for double dilution method and exceeded control for “well” method. Conclusions. The current investigation revealed the promising route for the expanding of the existing fluoroquinolones diversity. Pharmacodynamics and pharmacokinetics changes could be achieved by chemical modifications of C-7 position of the initial ring. Further research utilizing the obtained compounds as starting ones opens a promising way to novel active molecules synthesis and combating the problem of antibiotic resistanc

Abstracts of The Second Eurasian RISK-2020 Conference and Symposium

This abstract book contains abstracts of the various research ideas presented at The Second Eurasian RISK-2020 Conference and Symposium.The RISK-2020 Conference and Symposium served as a perfect venue for practitioners, engineers, researchers, scientists, managers and decision-makers from all over the world to exchange ideas and technology about the latest innovation developments dealing with risk minimization