Новая модель дормантности Mycobacterium tuberculosis in vitro

The article describes a new in vitro dormancy model of M. tuberculosis based on cultivation with deprivation of four components of the standard medium of Mediumbrook 7H9. The modeling method and characteristics of the obtained dormant phenotype of M. tuberculosis are described in detail, and fields for potential application of the model are proposed.В статье представлена новая invitro модель дормантности M. tuberculosis, основанная на культивировании в условиях депривации четырех компонентов стандартной питательной среды Middlebrook 7H9. Детально описаны способ моделирования, характеристики полученного дормантного фенотипа M. tuberculosis, предложены области потенциального применения модели

Новосибирскому научно-исследовательскому институту туберкулеза 75 лет

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Современные методы профилактики ототоксичности аминогликозидов у больных туберкулезом легких

Contemporary publications on possible pharmaceutical treatment of ototoxic effect of aminoglycosides have been analyzed. In this respect, substances with the antioxidant effect seem to be the most promising. Their use in therapeutic doses is not accompanied by adverse reactions, and they do not interfere with the antibacterial effect of anti-tuberculosis drugs. Currently, the mechanisms of the otoprotective action of various antioxidants are being studied.Проведен анализ современной литературы о возможности медикаментозной коррекции ототоксических эффектов аминогликозидов. Наиболее перспективными в данном аспекте представляются вещества с антиоксидантным действием. Их применение в терапевтических дозах не сопровождается нежелательными побочными эффектами, они не влияют на антибактериальное действие противотуберкулезных препаратов. В настоящее время изучаются механизмы отопротекторного действия различных антиоксидантов

A new in vitro dormancy model of <i>Mycobacterium tuberculosis</i>

The article describes a new in vitro dormancy model of M. tuberculosis based on cultivation with deprivation of four components of the standard medium of Mediumbrook 7H9. The modeling method and characteristics of the obtained dormant phenotype of M. tuberculosis are described in detail, and fields for potential application of the model are proposed

Formation of macrophage phenotupe in inflammatory and fibrogenic response: The role of mevalonate pathway and nuclear receptors LXR

Free cholesterol (Ch) and its oxidative derivatives, oxysterols (OS), are often accumulated in macrophages during chronic inflammation and atherogenesis. The effects of Ch and OS on the balance of pro- and anti-inflammatory cytokines in inflammatory response and the role of mevalonate pathway in the effects of these sterols are studied poorly. Both Ch and OS are able to affect mevalonate pathway activity and activity of nuclear hormonal receptors LXR. However the roles of LXR and mevalonate pathway in Ch and OS effects on macrophage polarization are unknown. We studied the effects of Ch, OS, atorvastatin, and mevalonic acid on the LPS-induced TNF-α, IL-10 and TGF-β1 production in macrophage cell culture. The study was carried out in murine peritoneal macrophages preincubated for 4 h with Ch (5 μg/mL), 25-hydroxycholesterol (25-OH-Ch) (5 μg/mL), 7-keto-Ch (5 μg/mL), farnesol (10 μM), or atorvastatin (5 μmol/mL) in the presence or absence of 1 mM of mevalonate. The cells were further incubated in the presence or absence of E. coli 0111:B4 lipopolysaccharide (LPS) for 24 h, and cytokine concentrations in incubation media were determined. Macrophages preincubation with Ch, 25-OH-Ch, or atorvastatin decreased LPS-induced TNF-α production in cell cultures, while supplementation of preincubation medium with mevalonic acid abrogated the effects of atorvastatin and Ch. The Ch, 25-OH-Ch, 7-keto-Ch and atorvastatin significantly reduced IL-10 production by LPS–stimulated macrophages, while farnesol had no effect. Supplementation of Ch or atorvastatin-containing preincubation medium with mevalonate restored IL-10 production. The TGF-β1 production was significantly enhanced by the presence of Ch or atorvastatin in preincubation medium as compared to the control level in non-treated macrophages, while 25-OH-Ch or farnesol decreased profoundly TGF-β1 production. Mevalonate abrogated the effect of Ch or atorvastatin but not of 25-OH-Ch or farnesol. These results allow to conclude, that the presence of Ch in micro-environment of inflammatory macrophages promotes anti-inflammatory and fibrogenic macrophage response; the latter is connected, at least in part, with the deficiency of mevalonate pathway intermediates, particularly to the deficiency of farnesol. At the same time hydroxysterols suppress both pro- and anti-inflammatory macrophage response independently of the impact of these compounds on mevalonate pathway. Apparently, pharmacological interference in the process of farnesylation could be a new approach to the control of chronic inflammation, including atherogenesis

TRANSPLANTATION OF AUTOLOGOUS MESENCHYMAL STEM CELLS IN THE EXPERIMENTAL MYCOBACTERIAL INFECTION: IMPACT OF CONDITIONING

The use of mesenchymal stem cells (MSC) in immune therapy of drug resistant tuberculosis is to be experimentally justified. The impact of non-conditioned and poly(A:U)-conditioned MSC on the course of BCG-infection in mice has been studied. It has been proved that double administration of MSC to mice of BALB/c line in 11 and 12.5 weeks after infection with BCG caused significant reduction of granulomas formation and activated the mycobacterial growth. On the contrary the similar administration of MSC with poly(A:U) conditioning significantly inhibited the mycobacterial growth and provided no effect on granulomas formation. Non-conditioned MSC manifested immune suppression properties, and poly(A:U) conditioning caused their pro-inflammatory polarization in vitro. It has been concluded that MSC therapy of mycobacterial infection can be effective in case of targeted formation of pro-inflammatory immune-phenotype of MSC

METHODS OF MULTIDIMENSIONAL STATISTIC PROCESSING OF DATA APPLIED TO FIND REGULARITIES IN THE COURSE OF TUBERCULOSIS IN SIBERIAN AND FAR EASTERN FEDERAL DISTRICTS

The article presents results of multi-dimensional analysis of 83 rates, calculated on the basis of federal and sectoral reports on tuberculosis in 21 regions of Siberian and Far Eastern Federal Districts, which were collected from 2006 to 2016. For statistic processing of data, a distance matrix was used with its consecutive analysis by principal coordinates analysis, which allowed detecting the closest correlations between rates. It has been proved that main factors of successful tuberculosis control are the following: improvement of the organizational quality of treatment and diagnostics, provision with qualified medical personnel, early detection through expansion of coverage of population with fluorography screening. The principal coordinates method also allowed performing a multilateral evaluation of epidemic situation in all regions and defining the ones with the most favorable tuberculosis situation