Genes of susceptibility to early neurodegenerative changes in the rat retina and brain: analysis by means of congenic strains

Contains the lists of RNO1 genes which are located within examined regions of rat chromosome 1 (Additional file 2: Tables S1, S2, S3, S4 and S5) (XLSX 349 kb

Mononuclear Mn(II), Co(II), and Cu(II) pivalates

Mononuclear Mn(II), Co(II), and Cu(II) pivalates were synthesized for the first time. They were isolated as salts with a composition NBu 4[MPiv3], where Piv is the pivalate anion. In the structure of the [MnPiv3] and [CoPiv3] coordination units, the environment of the central atom was found to be close to a trigonal prism. In [CuPiv3], the distorted square environment of Cu is formed by one bidentate O,O′-Piv and two monodentate Piv's; the second O atoms of monodentate Piv's tend to occupy the positions close to the apical positions of the elongated octahedron. An X-ray diffraction study of NBu 4[CoPiv3] and NBu4[CuPiv3] crystals showed strong disordering of the O atoms of the coordinated carboxylate groups at room temperature, which was suppressed when NBu4[CoPiv 3] was cooled to 85 K and NBu4[CuPiv3] to 30 K. In the synthesis of NBu4[CoPiv3] and NBu 4[CuPiv3], new compounds, namely, tetranuclear (NBu 4)2[Co4Piv8(AcO)2(H 2O)4] and (NBu4)2[Cu 4Piv8(AcO)2(H2O)2], respectively, formed along with the major product. © 2014 Elsevier Ltd. All rights reserved

Hyaluronidase pharmacological properties and clinical application in ophthalmology

Corneal diseases are the fourth leading cause of blindness in the world, accounting for approximately 5 % of cases. Existing methods of treatment in more than 30 % of cases do not have a full therapeutic effect and when the process is stopped, they end with a persistent violation of corneal transparency, a decrease or complete loss of visual functions. The lack of effective means that evidence-based restore corneal transparency determines the relevance of the search for modern drugs and ways to deliver them, the possibilities of enhancing the therapeutic effect. The possibilities of using hyaluronidase preparations in ophthalmology are considered based on the study of its biological and pharmacological properties. Enzyme catalyzes the breakdown of acid mucopolysaccharides including hyaluronic acid by cleavage of the glycosidic bond β(1→4), the biological effect is determined by the molecular weight of the resulting fragments: high-molecular fragments have antiangiogenic properties, increased ability to bind fibrinogen, anti-inflammatory and immunosuppressive effects, and low-molecular fragments have pro-inflammatory activity and promote angiogenesis. The barrier function of the cornea is provided by the features of its anatomical structure, while the features of its regeneration with the formation of turbidity are accompanied by overexpression and migration to the stroma of cytokines TGF-β and PDGF, activation of myofibroblasts and the formation of a fibroproliferative response. The high anti-inflammatory, immunomodulatory, regenerative and antifibrotic activity of hyaluronidase, the possibility of its effect on a complex pathophysiological cascade of destructive processes and minimization of the scarring process stimulate more extensive experimental and clinical studies on the development of new methods of treating ophthalmic diseases using hyaluronidase drugs

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

Redox-induced change in the ligand coordination mode

© 2014 American Chemical Society. The reaction of cobalt(II) pivalate with a spin-labeled Schiff base (HL1) in organic solvents formed trinuclear complex [Co3(Piv)2L1 2L2 2]·Solv (Solv is Me2CO and/or C7H16 and CH3CN) containing both nitroxide L1 and the product of its single-electron reduction, nitrone L2. The formation of [Co3(Piv)2L1 2L2 2] was a consequence of an unusual phenomenon, which we called "redox-induced change in the ligand coordination mode". A reduction of L1 to L2 led to a change in the set of donor atoms and even in the size of the metallocycle. This phenomenon was also found for mononuclear [CrL1 2L2] and [FeL1 2L2]·Me2CO

Screening of West Siberian patients with primary congenital glaucoma for CYP1B1 gene mutations

Primary congenital glaucoma (PСG) is a visual organ pathology that leads to progressive blindness and poor vision in children. Its main cause is an anomaly of the anterior chamber angle. Most cases of PСG are sporadic, but familial cases with an autosomal recessive (predominantly) and autosomal dominant (rare) type of inheritance have been described. Congenital glaucoma is a rare condition (1 case per 10,000–20,000 newborns), but its prevalence is substantially higher (up to 1 case per 250 newborns) in countries where consanguineous marriages are common. Mutations in the CYP1B1 gene, which encodes cytochrome P450 1B1, are the most common cause of autosomal recessive primary congenital glaucoma. This enzyme is known to be involved in retinoic acid metabolism and is necessary for normal eye development. The aim of this work was to assess the polymorphism of the CYP1B1 gene among West Siberian patients with primary congenital glaucoma. Direct automatic Sanger sequencing of exons and adjacent splicing sites of the CYP1B1 gene was carried out in 28 people with the PCG phenotype from a West Siberian region. As a result, in the sample of the white population we examined, pathogenic variants previously described in other ethnic groups were revealed: E387K (rs55989760), R444* (rs377049098), R444Q (rs72549376), and P437L (rs56175199), as well as novel single-nucleotide deletion p.F114Lfs*38 in the CYP1B1 gene. The latter can cause a frame shift, changed amino acid composition, and a formation of truncated in the protein. None of the detected mutations were found in the control sample of ophthalmologically examined individuals without PCG (100 people). Variants R444* (rs377049098) and R444Q (rs72549376) were not found in the general population sample either (576 randomly selected West Siberia residents). All the detected mutations caused the development of the autosomal recessive form of primary congenital glaucoma. The most severe clinical phenotype was observed in carriers of mutations in codon 444 of the gene. Consequently, in children with signs of increased intraocular pressure, molecular genetic analysis of the CYP1B1 gene is advisable for early diagnosis and timely initiation of PCG therapy

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