Evaluation of the antibacterial activity of the preparation benzydamine hydrochloride

Introduction. With an increase in the level of acquired antibiotic resistance of pathogens, treatment becomes more complicated and slows down, especially in infections associated with biofilms. There is a growing need for the development and use of new antibacterial drugs with specific antimicrobial activity.Aim. To study the antimicrobial action and the dynamics of the formation of resistance to benzydamine hydrochloride from a various infection agents. Materials and methods. To obtain biofilms, microorganisms were cultivated in flat-bottomed culture plates. Planktonic cells were obtained by suspending and reseeding single colonies of the daily culture into flat-bottomed culture plates. To determine the antimicrobial activity of the studied preparations, two-fold dilutions were prepared and added to the wells of the plate with a bacterial culture. The dynamics of the formation of resistance to benzydamine hydrochloride was studied by passaging the cultures in a liquid nutrient medium with increasing concentrations of the antiseptic by a twofold step. After 2–3 days of incubation from a test tube with the maximum concentration of the drug, in which bacterial growth was observed, the bacteria were transferred to new ones with higher concentrations of the drug.Results. It was shown that benzydamine hydrochloride showed a high level of activity against bacteria M. catarrhalis and yeast-like fungi C. albicans. A slightly lower activity of the drug was noted for bacteria of the species S. aureus and E. coli, however, within the limits of the therapeutic concentration of the drug in finished dosage forms. Benzydamine hydrochloride had a significantly higher level of antibacterial activity against pre-formed biofilms compared to drugs such as chlorhexidine and hexetidine. An analysis of the dynamics of the formation of resistance to the drug benzydamine hydrochloride in microorganisms of various species showed that the possibility of developing resistance to benzydamine hydrochloride is extremely small. The process of adaptation was observed only in E. coli. The studied strains of the species S. aureus, C. albicans, and M. catarrhalis did not acquire resistance to the test drug.Conclusion. Benzydamine hydrochloride can be effectively used against a wide range of pathogens of ENT infections, as it has been shown to have a significantly higher level of antibacterial activity against pre-formed biofilms, various types of bacteria and yeast-like fungi and an extremely low level of resistance compared to other antiseptic drugs

Кандидемия у онкологических больных: фенотипические и молекулярно-генетические характеристики резистентности к противогрибковым лекарственным средствам, гены факторов патогенности Candida spp.

Relevance. The global trend of rapid increase in resistance to antifungal drugs due to multiple factors, dictates the need for continuous monitoring of taxonomic structure and susceptibility of nosocomial pathogens, causing invasive fungal infections, for permanent correction of the optimal prevention and treatment strategies.Purpose: to determine antifungal susceptibility of the main yeast pathogens in candidemia in cancer patients, as well as to determine resistance genes and pathogenic factor genes.Material and Methods. Eighty-two strains of Candida spp. isolated from blood of cancer patients from 2015 to 2021 were analyzed. Minimum inhibitory concentrations of fuconazole, voriconazole, posaconazole, anidulafungin and micafungin were determined by a gradient method (E-test, BioMerieux, France). The EUCAST and CLSI criteria were used for MIC value assessment. The genes, associated with pathogenicity factors, and resistance to antifungal drugs were identifed.Results. Our study results based on EUCAST 2020, v.10.0 criteria showed that triazoles, especially fuconazole, were the least effective drugs in empirical therapy for invasive candidiasis (including candidemia). Resistance of Candida spp. fuconazole was superior to that of voriconazole (47.2 % vs 23.2 %, respectively, p<0.01) and posaconazole (47.2 % vs 30.4 %, respectively, p><0.05). The highest in vitro activity was observed in echinocandins, and anidulafungin was 2 times more active than micafungin (4.1 % of resistant strains vs 11.4 %, respectively), with no statistically signifcant difference (p>0.05). The ERG11 and FKS1 genes associated with resistance to antifungal drugs were detected in 28.6 % of Candida spp. strains. The ERG11 gene was detected in 8.6 % of cases, exclusively in Candida albicans strains. The FKS1 gene was identifed in 20.0 % of strains (85.7 % of them were C. parapsilosis, 7.1 % each were C. tropicalis and C. glabrata). Pathogenic factor genes were identifed in 78.6 % of C. albicans and in 79.1 % of C. parapsilosis strains.Conclusion. Molecular genetic methods for the detection of Candida spp strains carrying resistance genes to antifungal drugs, and the determination of pathogenicity factors are promising trends in searching for biomarkers. They facilitate interpretation of results of microbiological study to assess the ability of Candida spp. strains to develop invasive mycoses.Актуальность. Мировая тенденция стремительного увеличения уровня резистентности к противогрибковым препаратам, которая связана со многими факторами, диктует необходимость постоянного мониторинга таксономической структуры нозокомиальных возбудителей инвазивных грибковых инфекций и их чувствительности к антифунгальным лекарственным средствам с целью постоянной коррекции наиболее оптимальной тактики профилактики и лечения инвазивных грибковых инфекций.Цель исследования – определение чувствительности к антифунгальным препаратам основных возбудителей при кандидемии у онкологических больных, а также определение генов резистентности и факторов патогенности.Материал и методы. Проанализировано 82 штамма Candida spp., выделенных из крови онкологических больных в течение 2015–21 гг. Определение минимальных ингибирующих концентраций флуконазола, вориконазола, позаконазола, анидулафунгина и микафунгина выполняли градиентным методом (Е-тест, BioMerieux, France). Для оценки значений МИК использовали критерии EUCAST и CLSI. Определены гены, ассоциированные с факторами патогенности и резистентности к противогрибковым лекарственным средствам.Результаты. По результатам нашего исследования (критерии EUCAST) в качестве эмпирической терапии инвазивного кандидоза (в т. ч. кандидемии) наименее эффективными препаратами являются триазолы, особенно флуконазол, к которому статистически значимо чаще штаммы Candida spp. резистентны по сравнению с вориконазолом (47,2 % против 23,2 %, p<0,01) и позаконазолом (47,2 % против 30,4 %, p><0,05). Наибольшая активность in vitro отмечается у препаратов группы эхинокандинов, причем анидулафунгин в 2 раза активнее микафунгина (4,1 % резистентных штаммов против 11,4 %), но статистически значимой разницы при этом не выявлено. Гены ERG11 и FKS1, ассоциированные с резистентностью к противогрибковым препаратам, были выявлены у 28,6 % штаммов Candida spp.. Ген ERG11 детектирован в 8,6 % случаев, причем только у штаммов Candida albicans. Ген FKS1 определен у 20,0 % штаммов (85,7 % – C. parapsilosis, по 7,1 % – C. tropicalis и C. glabrata). Гены факторов патогенности определены у 78,6 % штаммов C. albicans и у 79,1 % изолятов C. parapsilosis. Заключение. Молекулярно-генетические методы выявления штаммов Candida spp., несущих гены резистентности к антифунгальным препаратам, определение факторов патогенности –><  0,01) и позаконазолом (47,2 % против 30,4 %, p<0,05). Наибольшая активность in vitro отмечается у препаратов группы эхинокандинов, причем анидулафунгин в 2 раза активнее микафунгина (4,1 % резистентных штаммов против 11,4 %), но статистически значимой разницы при этом не выявлено. Гены ERG11 и FKS1, ассоциированные с резистентностью к противогрибковым препаратам, были выявлены у 28,6 % штаммов Candida spp.. Ген ERG11 детектирован в 8,6 % случаев, причем только у штаммов Candida albicans. Ген FKS1 определен у 20,0 % штаммов (85,7 % – C. parapsilosis, по 7,1 % – C. tropicalis и C. glabrata). Гены факторов патогенности определены у 78,6 % штаммов C. albicans и у 79,1 % изолятов C. parapsilosis. Заключение. Молекулярно-генетические методы выявления штаммов Candida spp., несущих гены резистентности к антифунгальным препаратам, определение факторов патогенности –>< 0,05). Наибольшая активность in vitro отмечается у препаратов группы эхинокандинов, причем анидулафунгин в 2 раза активнее микафунгина (4,1 % резистентных штаммов против 11,4 %), но статистически значимой разницы при этом не выявлено. Гены ERG11 и FKS1, ассоциированные с резистентностью к противогрибковым препаратам, были выявлены у 28,6 % штаммов Candida spp.. Ген ERG11 детектирован в 8,6 % случаев, причем только у штаммов Candida albicans. Ген FKS1 определен у 20,0 % штаммов (85,7 % – C. parapsilosis, по 7,1 % – C. tropicalis и C. glabrata). Гены факторов патогенности определены у 78,6 % штаммов C. albicans и у 79,1 % изолятов C. parapsilosis.Заключение. Молекулярно-генетические методы выявления штаммов Candida spp., несущих гены резистентности к антифунгальным препаратам, определение факторов патогенности – это перспективные направления для поиска биомаркеров, облегчающих сложную задачу трактовки результатов микробиологического исследования по оценке способности штаммов Candida spp. к развитию инвазивных микозов

On the Issue of the Berber Written Tradition

The article is devoted to the study of the linguistic tradition of the Berbers, who are the indigenous people of North Africa. The Berbers have maintained a rich tradition of spoken language. At the turn of the 20th ‑21st centuries, against the backdrop of the intensification of the movement for self‑determination, their cultural and linguistic rights, the Berbers launched a large‑scale activity aimed at restoring the national written language. The author suggested that the need to develop standardized writing was partly due to the desire of the Berbers to consolidate the official status of their language in the Constitution. The author notes that the aggravation of the so‑called “Berber question” at the end of the 20th century spurred the interest of scientists and researchers in the Berber written heritage. Most of the surviving handwritten documents make Berber texts (mostly religious), recorded using the Arabic alphabet between the 15th and early 20th centuries. The study of conditions for their creation and fields of their application shows that these texts played a significant role in the dissemination of religious and scientific knowledge among the Berbers. It is concluded that despite the use of the predominantly oral form of the language, the Berbers managed to create a unique written tradition. The article discusses in detail the main problems of the study of Berber manuscripts, among which: the requirement from the researcher of serious pre‑knowledge in various fields; the problem of accessibility of texts stored in private collections; the need to develop unified approaches to the description of Berber manuscripts, their digitization and other important arrangements to ensure the availability of documents for the scientific‑research community. Particular attention is paid to the history of the creation of the first collections of Berber manuscripts and their cataloging. The author has also highlighted the work of scientists, who made a qualitative contribution to the study of the Berber manuscripts, most of which have not yet been discovered and carry significant potential aimed at pre‑ serving and enhancing the Berber cultural and historical heritage

Does the wall thickness of the left atrial appendage and its isthmus depend on their macroscopic characteristics?

Knowledge in interrelations between gross anatomy of the left atrial appendage (LAA) and thickness of the walls of LAA and periauricular area enables decreasing operational risks in LAA ostium occluding and «Cox-Maze» surgery for atrial fibrillation. The aim of the study was to identify significant interrelations between the macroscopic characteristics of the LAA (size, shape, number of lobes) and the parameters of the wall thickness of the LAA and its isthmus. Material and methods. The study includes 50 heart specimens of patients died from non-cardiac diseases. We examined 60 anatomical sections from 30 hearts by means Olympus SZX2-ZB10 microscope, and histological slices from 20 hearts. Results. The layers of the LAA wall were thinner than those in the isthmus. The thickness of LAA walls did not show direct correlation with the external dimensions of LAA. We found inverse correlation (Rs = – 0.4, p < 0,05) between the thickness of the myocardium, endocardium and some external sizes of LAA. The wall thickness of «chicken wing», «cauliflower» and «arrowhead» was the same. The wall of single-lobe LAA was thinner than that of two-lobed LAA (p = 0.036). The LAA isthmus wall was thinner (p = 0.03) in hearts with «cauliflower» LAA compared to hearts with LAA resembled a «chicken wing». Differences in wall thickness in LAA of various shapes were due to the degree of subepicardial fatty tissue development. Intracardiac operations should be done with the utmost care in patients with «cauliflower» LAA and single-lobe LAA to avoid damage of the LAA and periauricular area. Conclusions. The research found clinically significant interrelations between the LAA wall thickness and the number of its lobes as well as between the LAA isthmus wall thickness and LAA shape variants

Early-late genes of the ecdysone cascade as models for transcriptional studies

<p>The <i>DHR3</i> and <i>Hr4</i> early-late genes of the ecdysone cascade are described as models for transcriptional studies in <i>Drosophila</i> cells. In a set of experiments, it became clear that these genes are a convenient and versatile system for research into the physiological conditions upon 20-hydroxyecdysone induction. <i>DHR3</i> and <i>Hr4</i> gene transcription is characterized by fast activation kinetics, which enables transcriptional studies without the influence of indirect effects. A limited number of activated genes (only 73 genes are induced one hour after treatment) promote the selectivity of transcriptional studies via 20-hydroxyecdysone induction. <i>DHR3</i> and <i>Hr4</i> gene expression is dose dependent, is completely controlled by the hormone titer and decreases within hours of 20-hydroxyecdysone withdrawal. The <i>DHR3</i> and <i>Hr4</i> gene promoters become functional within 20 minutes after induction, which makes them useful tools for investigation if the early activation process. Their transcription is controlled by the RNA polymerase II pausing mechanism, which is widespread in the genome of <i>Drosophila melanogaster</i> but is still underinvestigated. Uniform expression activation of the <i>DHR3</i> and <i>Hr4</i> genes in a cell population was confirmed at both the RNA and protein levels. Homogeneity of the transcription response makes DHR3/Hr4 system valuable for investigation of the protein dynamics during transcription induction.</p