8 research outputs found

    Dependence of Chemical Etching rate of PTR-glasses on Terms of Photo-thermo-induced Crystallization

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    Etching kinetics of virgin photo-thermo-refractive glass and glassceramics (after photo-thermo-induced crystallization process at various terms) in aqueous hydrofluoric acid based solution has been investigated for the first time. It has been shown that the etching rate of the glassceramic is increasing with increasing of nanocrystalls number and size. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/3540

    New mutations in genes associated with cefiderocol resistance in a clinical isolate of Pseudomonas aeruginosa

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    Objective. To assess the effects of chromosomal mutations on emergence of cefiderocol resistance among Pseudomonas aeruginosa clinical isolates. Materials and Methods. Study design purported to compare the characteristics of phenotypic antibiotic resistance and chromosomal mutations of P. aeruginosa strains of a common origin possessing different resistance levels to cefiderocol. Two P. aeruginosa isolates from the sputum of a patient with cystic fibrosis who had not previously received cefiderocol were analyzed. Species identification was performed using an MALDI-TOF MS instrument and whole genome sequencing (WGS) data obtained from the MGISEQ-2000 platform. Antibiotic resistance was estimated based on minimum inhibitory concentration (MIC) testing. Plasmid-borne resistance genes and mutations in chromosomal genes associated with cefiderocol resistance were revealed based on WGS data. Results. Both P. aeruginosa isolates had the same antibiotic MIC values excluding meropenem and cefiderocol MIC values. Cefiderocol MICs were significantly different between the two strains corresponding to the resistant clinical category for one isolate and to the susceptible category for another one. Both strains belonged to 2554 sequence type. Eight potentially significant mutations in iron-uptake genes and genes associated with beta-lactam resistance were detected in the genome of the cefiderocol-resistant isolate, which were absent in the cefiderocol-susceptible strain. Cefiderocol resistant isolate harbored frameshift mutations in pirA, pirR and piv and nonsynonymous mutations in pfeA, cirA, iutA, pbpА and pchD. Conclusions. Cefiderocol resistance can emerge among P. aeruginosa isolates which were not exposed to cefiderocol as the phenomenon of cross-resistance. Resistance to cefiderocol can be conferred not by a single mutation, but by a combination of chromosomal gene alterations

    Распространенность металло-β-лактамаз и эффлюкс-механизмов у карбапенемрезистентных госпитальных штаммов Pseudomonas aeruginosa, выделенных в г. Москве в 2012–2015 гг.

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    Background. Pseudomonas aeruginosa, the major nosocomial opportunistic pathogen, is an important cause of infectious morbidity and mortality among immunocompromised patients.Objective. To establish the role of metallo-β-lactamases (MBL) and efflux-mediated mechanisms in conferring carbapenem resistance in nosocomial isolates of P. aeruginosa.Methods. We analyzed carbapenem nonsusceptible nosocomial P. aeruginosa isolates obtained from pediatric and adult patients at three hospitals in Moscow in 2012–2015. Carbapenem susceptibility was assessed using the E-test. In addition, minimal inhibitory concentrations (MICs) of meropenem were tested by the broth microdilution method. The presence of MBL was determined using the EDTA-mediated suppression test. Efflux-dependent resistance was measured using an assay based on MIC modification by an ionophore carbonyl cyanide 3-chlorophenyl hydrazine (CCCP).Results. A total of 54 carbapenem nonsusceptible P. aeruginosa isolates was examined. The presence of an MBL was detected in 37 (69%) isolates, 29 (54%) isolates had efflux-mediated resistance. In 10 (19%) isolates neither MBL nor efflux activity was found. Five out of 6 isolates (83%) with highly active efflux were MBL-positive. Among isolates with low efflux activity, 74% (17/23) possessed MBL, whereas in isolates with no efflux the rate of MBL-positivity was 60% (15/25).Conclusion. The prevalence of MBL- and efflux-mediated carbapenem resistance in nosocomial P. aeruginosa is high. Moreover, our results reveal that several resistance mechanisms may combine at the isolate level. These data may contribute to the development of novel strategies in combating carbapenem resistance.Обоснование. Синегнойная палочка — Pseudomonas aeruginosa — входит в число наиболее актуальных возбудителей оппортунистических инфекций, являясь одной из главных причин госпитальной заболеваемости.Цель: проанализировать роль металло-β-лактамаз (МБЛ) и эффлюкс-механизмов в формировании карбапенемрезистентности у госпитальных штаммов P. aeruginosa.Методы. В качестве объектов исследования были использованы 54 изолята P. aeruginosa от детей и взрослых пациентов из трех госпиталей города Москвы, полученных в течение 2012–2015 гг. Для всех штаммов были определены минимальные подавляющие концентрации (МПК) меропенема. Все отобранные штаммы были протестированы на наличие МБЛ путем подавления их активности этилендиаминтетрауксусной кислотой. Оценка активности эффлюкс-систем производилась на основе определения степени подавления МПК под влиянием ингибитора эффлюкса карбонил-цианид-3-хлорфенилгидразона.Результаты. Было выявлено 69% (37/54) МБЛ-продуцирующих штаммов [МБЛ(+)], значимость эффлюкс-механизмов в формировании карбапенемрезистентности подтверждена у 54% (29/54) штаммов. В 19% (10/54) карбапенемрезистентных изолятов P. aeruginosa не обнаружено ни МБЛ, ни активности эффлюкс-систем. Распространенность МБЛ положительно коррелировала (rS =0,068) с активностью эффлюкса: среди бактерий с отсутствием эффлюкс-активности было 60% МБЛ(+)-штаммов, среди изолятов с умеренным эффлюксом — 74%, а в популяции с гиперэкспрессией эффлюкса 83% штаммов обладали МБЛ.Заключение. Полученные результаты иллюстрируют широкую распространенность важнейших механизмов карбапенемрезистентности — МБЛ- и эффлюкс-активности — и доказывают существование сложных сочетаний различных форм устойчивости у одного и того же штамма. Полученная информация может быть полезной для создания лечебно-профилактических методов борьбы с карбапенемрезистентностью

    ИЗБИРАТЕЛЬНОЕ ВЛИЯНИЕ ЛЕГОЧНОГО СУРФАКТАНТА НА РАЗНЫЕ СУБПОПУЛЯЦИИ АЛЬВЕОЛЯРНЫХ МАКРОФАГОВ ПРИ ТУБЕРКУЛЕЗЕ

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    Pulmonary surfactant is necessary component for maintenance of high level of phagocytic activity of alveolar macrophages. Tuberculosis inflammation reduces the production of surfactant by type II cells and phagocytic activity of alveolar macrophages. The effects of exogenous pulmonary surfactant on the ultrastructural changes of various subpopulations of alveolar macrophages were studied by TEM-method. For investigations the bronchial alveolar lavage fluid from guinea pigs infected of M. tuberculosis and treated by isoniazid or isoniazid + exogenous pulmonary surfactant were used. It was shown that isoniazid + exogenous pulmonary surfactant normalizes the heterogeneous population of alveolar macrophages providing stimulating effects on their maturation and phagocytic activity more effectively than isoniazid therapy. Исследовано влияние экзогенного легочного сурфактанта на ультраструктуру различных субпопуляций альвеолярных макрофагов в условиях химиотерапии экспериментального туберкулеза легких морских свинок. Показано, что введение животным экзогенного природного сурфактанта дополнительно к химиотерапии нормализует гетерогенный состав альвеолярных макрофагов, оказывая стимулирующий эффект на их созревание и фагоцитарную активность. На культуре моноцитарных клеток человека линии ТНР-1 продемонстрировано, что экзогенный сурфактант также способствует появлению в культуре более зрелых по своей морфологии и фагоцитарной активности макрофагальных клеток.

    Synthetic prions with novel strain-specified properties

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    Prions are infectious proteins that possess multiple self-propagating structures. The information for strains and structural specific barriers appears to be contained exclusively in the folding of the pathological isoform, PrP(Sc). Many recent studies determined that de novo prion strains could be generated in vitro from the structural conversion of recombinant (rec) prion protein (PrP) into amyloidal structures. Our aim was to elucidate the conformational diversity of pathological recPrP amyloids and their biological activities, as well as to gain novel insights in characterizing molecular events involved in mammalian prion conversion and propagation. To this end we generated infectious materials that possess different conformational structures. Our methodology for the prion conversion of recPrP required only purified rec full-length mouse (Mo) PrP and common chemicals. Neither infected brain extracts nor amplified PrP(Sc) were used. Following two different in vitro protocols recMoPrP converted to amyloid fibrils without any seeding factor. Mouse hypothalamic GT1 and neuroblastoma N2a cell lines were infected with these amyloid preparations as fast screening methodology to characterize the infectious materials. Remarkably, a large number of amyloid preparations were able to induce the conformational change of endogenous PrPC to harbor several distinctive proteinase-resistant PrP forms. One such preparation was characterized in vivo habouring a synthetic prion with novel strain specified neuropathological and biochemical properties
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