Genotypic and phenotypic characteristics of <i>Mycobacterium tuberculosis</i> drug resistance in TB children

Background. Russian Federation is included in the list of 30 countries with the highest burden of tuberculosis, including MDR tuberculosis. The most important part of this problem is the primary MDR/XDR TB in children.The aim: a comparative analysis of the phenotypic and genotypic profile of drug resistance to anti-tuberculosis drugs (ATP) according to whole genome sequencing of M. tuberculosis strains from children.Materials and methods. Whole genome sequencing (WGS) results of 61 M. tuberculosis isolates from children with tuberculosis in 2006–2020 in the Russian Federation were analyzed for anti-TB drug resistance mutations, according to the WHO catalog and were compared with the results of phenotypic drug sensitivity.Results. The M. tuberculosis belonged to two genetic groups: Beijing genotype – 82 % (50/61) dominant Central Asian Russian (31/50) and B0/W148 (16/50) subtypes, and non-Beijing (Ural, S, LAM) – 18 % (11/61). Three isolates belonged to Asian Ancestral subtype (3/50). Of the 61 isolates, only 14.7 % (9/61) were sensitive to antiTB drugs, 49.2 % (30/61) were MDR and 14.7 % (9/61) were pre-XDR. Comparison of the resistance profile (MDR/pre-XDR) with genotype revealed an upward shift for Beijing isolates, in particular Beijing B0/W148 (15/16) subline compared to other Beijing (19/34) (Chi-square with Yates correction = 5.535; p &lt; 0.05) and nonBeijing (5/12) (Chi-square with Yates correction = 6.741; p &lt; 0.05) subtypes. Discrepancies between genotypic and phenotypic drug resistance profiles were found in 11.5 % (7/61) of cases.Conclusions. Based on the analysis of WGS data, the genotypic characteristics of M. tuberculosis and the most complete set of drug resistance mutations were obtained, indicating a significant prevalence in MDR and pre-XDR TB of cases caused by epidemic subtypes of Beijing (B0/W148 and Central Asian Russian). The molecular mechanisms of adaptation of M. tuberculosis to the treatment of anti-TB drugs are not unique for the child population but reflect the general processes of the spread of MDR/XDR in Russia

ИССЛЕДОВАНИЕ ПЕРФУЗИИ ПРИ НАРУШЕНИЯХ ЦЕРЕБРАЛЬНОГО КРОВООБРАЩЕНИЯ. ЧАСТЬ II (ЧАСТНАЯ КТ- И МР-СЕМИОТИКА, ПАТТЕРНЫ ПАТОЛОГИЧЕСКИХ ИЗМЕНЕНИЙ). ОБЗОР

The second part of a review article devoted to a detailed consideration of the issues of diagnostic semiotics of acute disorders of cerebral circulation using CT and MR perfusion study techniques. We consider the physiological aspects of formation of the basic parameters of tissue perfusion: of cerebral blood Șow (CBF), cerebral blood volume (CBV), mean transit time (MTT) and time to peak (TTP) contrast, as well as patterns of pathological changes in these parameters (hypo-, hyper- and aperfusion), developing in various degrees of brain ischemic damage and penumbra areas. It is noted that the improvement of MRI using for tissue classi⠇cation of perfusion-diநusion (PWI/DWI) mismatch has a better chance of primary development due to the fact that it non-radiation exposure and is not connected with the need to introduce a large contrast volume, and with the introduction of non-contrast arterial spin labeled technique (ASL). Variants of events in the dynamics of perfusion as a result of reperfusion therapy. There were discussed the problems limiting the use of perfusion techniques in clinical practice.Вторая часть обзорной статьи посвящена детальному рассмотрению вопросов диагностической семиотики острых нарушений церебрального кровообращения с использованием КТ- и МР-методик перфузионного исследования. Рассмотрены физиологические аспекты формирования основных параметров тканевого кровотока: скорости (CBF), объема кровотока (CBV) и времени транзита (МТТ) и пика (TTP) контрастирования, а также паттерны патологических изменений этих параметров (гипо-, гипер- и аперфузия), развивающиеся в различных по степени ишемического повреждения зонах инфаркта и пенумбры. Отмечается, что совершенствование МРТ с применением для тканевой классификации комплекса перфузионно-диффузионного несоответствия (PWI/DWI mismatch) имеет большие шансы преимущественного развития вследствие того, что лишена лучевой нагрузки и не связана с необходимостью введения большого объема контраста, а с внедрением методики мечения спинов артериальной крови (ASL) – и вовсе без такового. Представлены варианты перфузионных событий в динамике и в результате реперфузионных мероприятий. Обсуждены проблемы, ограничивающие применение перфузионных методик в широкой клинической практике

Hypotensive effect of bi-potassium salt of 1-hexadecyl-2-methylcarbamoylphosphatidic acid in rats with renovascular hypertension

The study describes the synthesis and hypotensive effects of stable platelet activation factor (PAF) precursor 1-hexadecyl-2-m ethylcarbamoyl-phosphatidic acid (HMCP) оn outbred Wistar rats with 1-kidney 1-clip (1K1C) renovascular hypertension. Intravenous injection of 0.1, 0.5, 1 and 5 mg/kg HMCP resulted in a sharp decline of up to 50% of MAP with subsequent restoration to initial level. In some hypertensive 1K1C rats HMCP has a prolonged effect with blood pressure stabilized at 75% of initial level after 30 min post injection. HMCP was toxic at higher doses with a LD50 around 3 mg/kg

Rezul'taty primeneniya preduktala (trimetazidina) u pozhilykh patsientov s refrakternoy stenokardiey, stradayushchikh sakharnym diabetom

Представлены результаты клинического исследования по оценки эффективности добавления триметазидина к монотерапии изосорбида динитратом у пациентов с сахарным диабетом. Указанная терапия позволяла эффективно устранять ишемию миокарда, рефрактерную по отношению к нитропрепаратам. Препарат активно влияет на энергетический метаболизм ишемизированного миокарда, причем - наиболее эффективен в условиях нарушенного углеводного обмена. Отсутствие какой-либо гемодинамической активности значительно улучшает профиль переносимости триметазидина и позволяет считать его идеальным препаратом выбора для лечения пожилых пациентов, предрасположенных к развитию побочных эффектов на фоне традиционной антиангинальной терапии. Метаболический механизм действия, реализующийся на клеточном уровне и не связанный с изменениями гемодинамики, определяет абсолютную аддитивность триметазидина по отношению к традиционным антиангинальным препаратам. Исследование продемонстрировало, что триметазидин можно рекомендовать, в качестве полноценной альтернативы современным методам реваскуляризации миокарда у больных ИБС с такими неблагоприят ными особенностями течения заболевания, как пожилой возраст, наличие СД и рефрактерность стенокардии по отношению к традиционным антиангинальным препаратам

A thermophilic L-lactic acid producer of high optical purity: isolation and identification

Biodegradable polymers, specifically polylactide, are an important part of food packaging and medical devices. Microbiological synthesis uses cheap renewable raw materials and industrial waste to produce a high yield of lactic acid, the monomer of polylactide. This method needs new effective lactic acid producing strains, e.g., thermophilic bacteria. The research involved thermophilic bacterial strains isolated from soil and compost samples. Their ability to produce organic acids and extracellular enzymes was tested using the method of high-performance liquid chromatography (HPLC) and microbiological tests respectively. The real-time polymerase chain reaction method (PCR) detected L-lactate dehydrogenase structural genes of L-lactate dehydrogenase of Bacillaceae. Strain T7.1 was fermented using glucose and yeast extract as carbon and nitrogen sources, respectively. The optical purity of lactic acid was evaluated using quantitative gas chromatography on a chiral column to separate lactate isomers. The molecular genetic analysis of the 16S rRNA gene sequence was applied to identify strain T7.1. The chromatographic analysis proved that 10 out of 13 isolated thermophilic strains were effective lactic acid producers. They demonstrated proteolytic, amylolytic, or cellulase activities. During the fermentation, strain T7.1 produced 81 g/L of lactic acid with a peak productivity at 1.58 g/(L·h). The optical purity of the product exceeded 99.9% L-lactate. The genetic analysis identified strain T7.1 as Weizmannia coagulans (Bacillus coagulans). The research revealed a promising thermophilic producer of optically pure L-lactic acid. Further research is needed to optimize the cultivation conditions, design an effective and cheap nutrient medium, and develop engineering and technological solutions to increase the yield

Skeletal Muscle Resident Progenitor Cells Coexpress Mesenchymal and Myogenic Markers and Are Not Affected by Chronic Heart Failure-Induced Dysregulations

Background and Purpose. In heart failure (HF), metabolic alterations induce skeletal muscle wasting and decrease of exercise capacity and quality of life. The activation of skeletal muscle regeneration potential is a prospective strategy to reduce muscle wasting; therefore, the aim of this project was to determine if functional properties of skeletal muscle mesenchymal progenitor cells (SM-MPC) were affected by HF-induced functional and metabolic dysregulations. Methods. Gastrocnemius muscle biopsy samples were obtained from 3 healthy donors (HD) and 12 HF patients to purify mRNA for further analysis and to isolate SM-MPC. Cells were expanded in vitro and characterized by immunocytochemistry and flow cytometry for expression of mesenchymal (CD105/CD73/CD166/CD146/CD140b/CD140a/VIM) and myogenic (Myf5/CD56/MyoG) markers. Cells were induced to differentiate and were then analyzed by immunostaining and Q-PCR to verify the efficiency of differentiation. The expression of genes that control muscle metabolism and development was compared for HD/HF patients in both muscle biopsy and in vitro-differentiated myotubes. Results. The upregulation of MYH3/MYH8/Myf6 detected in HF skeletal muscle along with metabolic alterations indicates chronic pathological activation of the muscle developmental program. SM-MPC isolated from HD and HF patients represented a mixed population that coexpresses both mesenchymal and myogenic markers and differs from AD-MMSC, BM-MMSC, and IMF-MSC. The functional properties of SM-MPC did not differ between HD and HF patients. Conclusion. In the present work, we demonstrate that the metabolic and functional alterations we detected in skeletal muscle from HF patients do not dramatically affect the functional properties of purified and expanded in vitro SM-MPC. We speculate that skeletal muscle progenitor cells are protected by their niche and under beneficial circumstances could contribute to muscle restoration and prevention and treatment of muscle wasting. The potential new therapeutic strategies of HF-induced skeletal muscle wasting should be targeted on both activation of SM-MPC regeneration potential and improvement of skeletal muscle metabolic status to provide a favorable environment for SM-MPC-driven muscle restoration