BENZ- AND HETARENE-ANNULATED AZEPINES FROM DONOR-ACCEPTOR CYCLOPROPANES

This work was supported by Russian Science Foundation (grant № 18-13-00449

Probiotic activity of <i>Bacillus subtilis</i> metabolites in experimentally induced dysbiosis in mice

Scientific relevance. A promising option for dysbiosis correction is the use of metabiotics, products based on metabolites of probiotic microorganisms. During fermentation, Bacillus subtilis bacteria (strains 3H and 1719) produce metabolites that exhibit probiotic properties in vitro. These observations in vitro motivate an in vivo investigation of B. subtilis metabolite effects on colonic mucosal microbiota in mice in experimentally induced dysbiosis and an assessment of the potential of B. subtilis metabolites as metabiotics.Aim. The authors aimed to compare the probiotic activity of B. subtilis 3H and B. subtilis 1719 metabolites and a commercial metabiotic in antibiotic-induced dysbiosis in mice.Materials and methods. The authors induced experimental dysbiosis in BALB/c mice weighing 18–20 g by intraperitoneal injection of gentamicin. For subsequent correction, the test groups received sorbent-bound B. subtilis metabolites, and the comparison group received a commercial metabiotic containing B. subtilis metabolites (VKPM B-2335(3)3) via intragastric injection for 21 days. The quantitative and qualitative analysis of colonic mucosal microbiota included microbial culturing and colony identification by MALDI-TOF mass spectrometry.Results. Antibiotic-induced colonic dysbiosis in mice manifested itself as a decrease in the dominant microbiota and an increase in opportunistic pathogens. After 7 days of metabolite administration, the Lactobacillus population returned to normal in all treatment groups. The mice that received B. subtilis 3H metabolites showed the best results: their Lactobacillus spp. composition corresponded to that of intact animals. The content of Lac+ Escherichia coli returned to 100% in all treatment groups. After 21 days of metabolite administration, the authors observed the elimination of bacteria (Rodentibacter spp., Aerococcus spp.) and fungi (Trichosporon spp., Kazachstania spp.) in the B. subtilis 3H group; Trichosporon spp. (no effect on Kazachstania spp.) in the B. subtilis 1719 group; and Enterococcus spp., Kazachstania spp., and Trichosporon spp. (no effect on Rodentibacter spp. and Aerococcus spp.) in the commercial metabiotic group.Conclusions. Metabolites of B. subtilis strains 3H and 1719 help to restore the diversity and abundance of colonic microbiota in antibiotic-induced dysbiosis. The differences observed in microbiota re-establishment in the treatment groups indicate that there is interstrain variability in the probiotic activity of B. subtilis metabolites

Microbiological assessment of the effectiveness of standard therapy in atopic dermatitis

Background. Atopic dermatitis is an inflammatory skin disease characterized by recurrent lesions and intense pruritus. Nowadays there is a stepwise approach to the treatment of atopic dermatitis, which is defined by disease intensity and complications such as secondary skin infections. However, the current management of atopic dermatitis may not always lead to the expected outcome due to not only immune dysregulation of both adaptive and innate immunity but also imbalance of the skin microbiome. Aims. The aim of the study was to evaluate changes in the composition of the skin microbiome in both lesional and non-lesional skin in patients with atopic dermatitis during standard treatment. Materials and methods. Twenty patients with atopic dermatitis and twenty six healthy controls over 18 years old were included into the study. All microbiome samples were obtained from lesional and non-lesional skin sites of atopic dermatitis patients before and after therapy. Whereas samples from healthy controls were taken once from a flexor surface of the elbow. Species identification of clinical isolates were identified using MALDI Biotyper Sirius (Bruker Daltonics). Results. At baseline, the prevalence of S. aureus colonization among patients with atopic dermatitis was 34.20% in lesional skin and 32.50% in non-lesional skin. After treatment, there was a significant decrease in the prevalence of S. aureus carriage in both lesional and non-lesional skin areas (р 0.05). However, no significant difference was observed in the proportion of all other staphylococci (р 0.1). Interestingly, S. aureus was not found in healthy controls. Conclusions. The results of the study demonstrated the effectiveness of standard therapy for managing patients with atopic dermatitis as it had a positive impact on the skin microbial community and showed a decrease in S. aureus proportion after the treatment

Problematic aspects of participation of pharmacists in the system of pharmacovigilance in Russia

In article results pharmacoepidemiology researches on studying of knowledge of pharmacists (n=187) on safety issues medicinal and pharmacovigilance are resulted. 28 % of pharmacists have adverse drug reactions to medicines in the practice, however submit spontaneous messages only 5 % of respondents. Princi pal causes of low activity of pharmacists - a lack of time for drawing up of reports and low level of knowledge in the field of safety of medical products. 89 % of pharmacists need educational programs on pharmacovigilanc

Исследование пробиотической активности метаболитов бактерий Bacillus subtilis при экспериментальном дисбиозе у мышей

Scientific relevance. A promising option for dysbiosis correction is the use of metabiotics, products based on metabolites of probiotic microorganisms. During fermentation, Bacillus subtilis bacteria (strains 3H and 1719) produce metabolites that exhibit probiotic properties in vitro. These observations in vitro motivate an in vivo investigation of B. subtilis metabolite effects on colonic mucosal microbiota in mice in experimentally induced dysbiosis and an assessment  of the potential of B. subtilis metabolites as metabiotics.Aim. The authors aimed to compare the probiotic activity of B. subtilis 3H and B. subtilis 1719 metabolites and a commercial metabiotic in antibiotic-induced dysbiosis in mice.Materials and methods. The authors induced experimental dysbiosis in BALB/c mice weighing 18–20 g by intraperitoneal injection of gentamicin. For subsequent correction, the test groups received sorbent-bound B. subtilis metabolites, and the comparison group received a commercial metabiotic containing B. subtilis metabolites (VKPM B-2335(3)3) via intragastric injection   for 21 days. The quantitative and qualitative analysis of colonic mucosal microbiota included microbial culturing and colony identification by MALDI-TOF mass spectrometry.Results. Antibiotic-induced colonic dysbiosis in mice manifested itself as a decrease in the dominant microbiota and an increase in opportunistic pathogens. After 7 days of metabolite administration, the Lactobacillus population returned to normal in all treatment groups. The mice that received B. subtilis 3H metabolites showed the best results: their Lactobacillus spp. composition corresponded to that of intact animals. The content of Lac+ Escherichia coli returned to 100%   in all treatment groups. After 21  days  of  metabolite  administration,  the  authors  observed the elimination of bacteria (Rodentibacter spp., Aerococcus spp.) and fungi (Trichosporon spp., Kazachstania spp.) in the B. subtilis 3H group; Trichosporon spp. (no effect on Kazachstania spp.) in the B. subtilis 1719 group; and Enterococcus spp., Kazachstania spp., and Trichosporon spp. (no effect on Rodentibacter spp. and Aerococcus spp.) in the commercial metabiotic group.Conclusions. Metabolites of B. subtilis strains 3H and 1719 help to restore the diversity and abundance of  colonic  microbiota  in  antibiotic-induced  dysbiosis.  The differences  observed in microbiota re-establishment in the treatment groups indicate that there is interstrain variability in the probiotic activity of B. subtilis metabolites.Актуальность. Перспективные средства для коррекции дисбиоза — метабиотики, препараты на основе метаболитов пробиотических микроорганизмов. В опытах in vitro бактерии Bacillus subtilis (штаммы 3H и 1719) в процессе культивирования синтезируют метаболиты, обладающие пробиотическими свойствами. Представляет интерес исследование влияния данных метаболитов in vivo на мукозную микробиоту толстого кишечника в условиях экспериментального дисбиоза (у мышей) и оценка возможности их применения в качестве метабиотиков в медицине.Цель. Изучить пробиотическую активность метаболитов бактерий B. subtilis 3H и B. subtilis 1719 в сравнении с показателями коммерческого метабиотика при антибиотик-ассоциированном дисбиозе у мышей.Материалы и методы. Работа проводилась на мышах линии BALB/c, массой 18–20 г. Экспериментальный дисбиоз моделировали при помощи внутрибрюшинного введения гентамицина. Для коррекции развившихся нарушений животным опытных групп в течение 21  сут  интрагастрально вводили  метаболиты  штаммов B. subtilis, иммобилизованные на сорбенте, а в группе сравнения — коммерческий метабиотик, содержащий метаболиты штамма B. subtilis ВКПМ № В-2335(3)3. Мукозную микробиоту толстого кишечника мышей качественно и количественно оценивали посредством бактериологического метода. Выросшие колонии микроорганизмов идентифицировали при помощи масс-спектрометрии MALDI-TOF.Результаты. Экспериментальный антибиотик-ассоциированный дисбиоз толстого  кишечника мышей проявился в снижении количества доминантной микробиоты и росте условно-патогенных микроорганизмов. Введение исследуемых метаболитов в течение 7 сут привело во всех опытных группах к нормализации содержания бактерий Lactobacillus; наилучшие показатели выявлены у животных, которым вводили штамм B. subtilis 3H, видовой состав лактобацилл соответствовал интактным мышам. Восстановление содержания лактозопозитивной кишечной палочки (E. coli lac+) достигло 100%. После 21 сут  применения метаболитов B. subtilis 3H зафиксирована элиминация бактерий Rodentibacter spp., Aerococcus spp., грибов Trichosporon spp., Kazachstania spp. Метаболиты штамма B. subtilis 1719 способствовали элиминации  грибов  Trichosporon spp.,  однако  не  влияли   на   количество Kazachstania spp. При введении коммерческого метабиотика выявлена элиминация Enterococcus spp., Kazachstania spp. и  Trichosporon spp.,  при  этом не  отмечено воздействия на Rodentibacter spp. и Aerococcus spp.Выводы. Метаболиты штаммов B. subtilis 3H и 1719 способствовали восстановлению качественного и количественного состава микробиоценоза толстого кишечника в условиях антибиотик-ассоциированного дисбиоза у мышей. Выявленные различия в процессах нормализации микробиоценоза в разных группах животных указывают на вариативность специфической активности бактерий B. subtilis

Fighting Putin and the Kremlin’s grip in neo-authoritarian Russia: the experience of liberal journalists

Slavtcheva-Petkova, V. (2017). Fighting Putin and the Kremlin’s grip in neo-authoritarian Russia: the experience of liberal journalists. Journalism. Copyright © [2017]. Reprinted by permission of SAGE Publications.Russia is one of the most dangerous countries for journalists and the conflict with Ukraine and Russia’s involvement in Syria present even further challenges for the future of Russian journalism. In addition to the financial pressures, physical attacks, abductions and harassment, liberal journalists now face an increasing threat to the democratising role they see themselves as playing. President Vladimir Putin’s soaring popularity and the elaborate range of tactics used to suppress press freedom are forcing liberal media to rethink their mission(s) and identity(ies). This paper presents empirical evidence on the range of tactics used by Russian authorities as well as the coping strategies adopted by journalists. The study shows that some Russian media and journalists demonstrate a great degree of resilience in their efforts to expose wrongdoings and hold the powerful to account. The article questions the applicability of Western-centric normative media system theories because it shows that the breadth, depth, and mechanisms of control in modern-day Russia are very different from the ones used during Soviet times, and yet, Russian media and society do not appear to be on a linear journey from authoritarianism to democracy. The article presents the findings of a semi-ethnographic study of some of Russia’s most influential liberal news outlets – Novaya Gazeta, Radio Echo of Moscow and Radio Free Europe/Liberty. The study was conducted in May 2014 in the midst of the conflict with Ukraine. It involved observations of editorial meetings, documentary analysis and interviews with editors, deputy editors and journalists

Anger and disgust shape judgments of social sanctions across cultures, especially in high individual autonomy societies

Data availability; The datasets analyzed during the current study are available in the Center for Open Science repository, https://osf.io/djnfg/.Supplementary Information is available online at: https://link.springer.com/article/10.1038/s41598-024-55815-x#Sec17 .When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions.This research was funded by the Swedish Foundation for Humanities and Social Sciences (Riksbankens Jubileumsfond) [P17-0030:1]. The contribution of J.W was supported by CAS Youth Innovation Promotion Association and fundings from the Institute of Psychology, Chinese Academy of Sciences (Y5CX052003 and E2CX3315CX). The contributions of M.H and S.G. for the Czech part of research was supported by a Grant 23-061770S of the Czech Science Foundation and by RVO: 68081740 of the Institute of Psychology, Czech Academy of Sciences. Open access funding provided by Linköping University

Endothelial dysfunction and its correction with perindopril therapy in patients with coronary heart disease

Aim. To investigate endothelial dysfunction (ED) in patients with coronary heart disease (CHD), stable effort angina, Functional Class (FC) I-III, as well as to study perindopril potential in ED correction.Material and methods. The study included 37 CHD patients (22 men, 15 women; mean age 62,2+5,3 years) with FC I-II (n=22) and FC III angina (n=15). The control group included 16 healthy individuals. Fndothelium-dependent vasodilatation (FDVD) of brachial artery (BA) was assessed in reactive hyperemia test at baseline and after 6 weeks of perindopril therapy (8 mg/d); in controls, FDVD was assessed at baseline only.Results. At baseline, ED was observed in 79 % of CHD patients: in 42 %, as an inadequate vasodilatation effect (&lt; 10 % from the baseline), and in other 37 %, as no BA diameter increase or vasoconstriction. ED was more prevalent in individuals with FC III angina (93 %) than in participants with FC I-II angina (69 %). Perindopril therapy was associated with increased numbers of patients with vasodilatation &gt; 10 % (+9 %)or&lt;10 % (+3,5 %), while the number of participants with vasoconstriction reduced by 12,5 %. The number of ED participants reduced by 26 % and 8 % for FC I-II and FC III, respectively. Among those with FC I-II angina, perindopril treatment was associated with significant increase in BA diameter (+9,8 %; p&lt;0,05), linear and volumic blood flow velocity (from 15,0+1,9 to 41,5+2,1 cm/s (p&lt;0,05) and from 2,1+0,5 to 6,9+0,5 ml/s (p&lt;0,05), respectively).Conclusion. Adding perindopril (8 mg/d) to standard anti-ischemic therapy was associated with reduced ED, which could be regarded as a vasoprotective perindopril effect

INDUCTION OF SECONDARY BACTERIAL PNEUMONIA IN MICE INFECTED WITH PANDEMIC AND LABORATORY STRAINS OF THE H1N1 INFLUENZA VIRUS

Aim. In this study we developed and characterized a mouse model of secondary S. aureus and S. pneumoniae pneumonia following influenza virus infection with H1N1 pandemic and laboratory strains and their reassortment. Materials and methods. BALB/с mice were infected intranasally with A/California/04/2009/(H1N1 pndm), A/Puerto Rico/8/34 or their reassortment NIBRG-121xp followed by different strains of S. аureus и S. pneumoniae. The pathogenicity of infection was assessed by mouse survival and weight change, viral titre and bacterial count in the lungs. Results. It was shown that the infection of mice with three strains of the H1N1 influenza virus with a comparable level of pathogenicity leads to a different severity of secondary bacterial infection. The mouse adapted A/California/04/2009 pandemic strain possessed the greatest ability to alter antibacterial immunity. Conclusion. An experimental model of post-influenza bacterial pneumonia utilizing three strains of the H1N1 influenza virus and various strains of S. aureus or S. pneumoniae was established. The ability of viruses to provoke bacterial superinfection of different severity is characterized