New opportunities in the treatment of asthenic symptoms after a new coronavirus infection

Introduction. Asthenia is an urgent problem during the pandemic of new coronavirus infection (COVID-19) because of its high frequency regardless of the severity of the disease.The purpose of this subanalysis of data from the multicenter controlled randomized clinical trial TONUS was to evaluate the efficacy and safety of meldonium therapy for аsthenia in COVID-19 survivors.Materials and methods. A total of 880 patients with asthenia who underwent COVID-19 within the last 6 months were included in the analysis. The efficacy of asthenia therapy was assessed by the MFI-20 scale, Schulte tables, and the General Clinical Impression (CGI) scale. All patients were previously randomized in two parallel branches of the TONUS study, including patients without concomitant disease in TONUS-1 (who received meldonium 500 mg/day for 14 days in the main group) and patients with cardiovascular or cerebrovascular disease in TONUS-2, who received meldonium at a dose of 1000 mg/day for 42 days in the main group. In both arms of the study, the drugs in the comparison groups were multivitamin complexes.Results. For the TONUS-1 groups.In the group of patients receiving meldonium compared with the control group (p < 0.001): total MFI-20 score decreased and was 31 (25; 40); MFI-20 –35 (–46; 23); performance value –5 (–11; –2) seconds; proportion of patients with significant improvement (by CGI-I) by the end of follow-up was 92.8%. For TONUS-2 groups.In the group of patients receiving meldonium compared with the control group (p < 0.001): total MFI-20 score decreased to 35 (27; 44); MFI-20 –34 (–46; –21), performance value –5 (–11; –2), proportion of patients with significant improvement (by CGI-I) by end of follow-up – 90.8%.Conclusion. Significant positive dynamics and regression of asthenia were noted in the groups of patients receiving meldonium in comparison with the control groups

Effect of the Predecessor and the Nitrogen Rate on Productivity and Essential Oil Content of Coriander (Coriandrum sativum L.) in Southeast Bulgaria

Received: May 31st, 2022 ; Accepted: August 13th, 2022 ; Published: September 19th, 2022 ; Correspondence: [email protected] (Coriandrum sativum L.) is one of the most important essential oil crops on a global scale. Coriander productivity is determined by the genotype, the environmental factors, as well the agronomic practices. A field experiment was conducted in Southeast Bulgaria during three vegetation seasons (2015, 2016, and 2017). The present study aimed at analysing the influence of two crop predecessors (winter wheat and sunflower) and four nitrogen (N) levels (0, 40, 80, and 120 kg ha-1 ). Productivity elements, seed yield, and seed essential oil content of coriander (cv. Mesten drebnoploden) were under evaluation. The results obtained showed that winter wheat was a more suitable predecessor of coriander in comparison to sunflower. The highest results regarding the number of umbels per plant, the umbel’s diameter, the number of umbellets per umbel, the number of seeds per umbel, the seed weight per plant, the 1,000 seed mass, as well as the seed yield for the rate of 80 kg ha-1 of N were recorded. The highest essential oil content after applying 120 kg ha-1 of N was established. Increasing the N level from 0 to 120 kg ha-1 led to a positive and significant effect on essential oil yield. No significant differences between the N rates of 80 and 120 kg ha-1 were recorded. The received results contributed for the evaluatation of the optimum nitrogen level, as well as for the determination of a more suitable predecessor of coriander in order to obtain the highest yield of better quality in the region of Southeast Bulgaria

Peculiarities of the Conjugative pSa Plasmid Transfer from <I>Escherichia coli</I> into <I>Francisella tularensis</I>

per a recipient cell). pSa′ plasmid molds several topological shapes with variable electrophoretic mobility in E. coli C600, while in tularemia microbe, this plasmid has only one shape. After the transfer of the plasmid from E. coli cells into F. tularensis cells each individual clone of tularemia microbe possesses a plasmid which differs in its electrophoretic mobility from plasmids of other clones

Role of SNP markers on chromosome 10 in the pathogenesis of atrial fibrillation

Atrial fibrillation (AF) is one of the most common tachyarrhythmias, contributing to both environmental and genetic factors, a clear understanding of which can be extremely important for determining management tactics and predicting the disease course. The article provides a brief overview of studies on genetic predictors of AF, in particular, SNP markers found on chromosome 10. Establishing a relationship between the identified SNPs on chromosome 10 and functional genes, changes in the structure or regulation of which can affect the development of AF, opens the veil of understanding how these SNPs affect the pathogenesis of AF

EVALUATION OF SUITABILITY OF METHODS FOR TESTING BLOOD PROTEIN HYDROLYSATES FOR THEIR BIOLOGICAL ACTIVITY AND TOXICITY

The use of high quality nutrient media comprising protein hydrolysates as the main components for maintaining their nutrient value is a critical prerequisite for appropriate fnal product preparation in FMD vaccine biotechnology. The incoming control of raw materials, in particular testing blood protein hydrolysates of different batches for their quality, is of considerable importance. Currently, there are different methods for the determination of hydrolysate efcacy using cell cultures and unicellular organisms as test systems. We used suspended baby hamster kidney (ВНК-21) cell line as a model for testing blood protein hydrolysates in the raw materials intended for FMD vaccine production for their biological activity and toxicity. The validation of the proposed method was carried out to confrm the reliability of the test results obtained. The following main validation characteristics were determined through testing 560 blood protein hydrolysate samples: trueness, specifcity, sensitivity, as well as precision under repeatability and reproducibility conditions. The validation results for the proposed method demonstrated high reliability (Fisher’s criterion – 0.021; ≤0.050) and full compliance with acceptance criteria

Quantification of the initial levels of calciprotein particles as a screening marker of mineral homeostasis in patients with cardiovascular disease and in patients with chronic kidney disease

Aim. To evaluate the initial concentration of calciprotein particles (CPPs), which are scavengers of excessive calcium and phosphate, in patients with cardiovascular disease and in patients with chronic kidney disease as compared with the healthy volunteers.Material and methods. The study included 308 individuals as follows: 1) 88 participants of the PURE study without hemodynamically relevant carotid athero scle rosis and symptomatic coronary atherosclerosis; 2) 88 patients with cere brovascular disease (CVD) who required carotid endarterectomy; 3) 88 pa tients with coronary artery disease (CAD) who required percutaneous coronary intervention or coronary artery bypass graft surgery; 4) 63 patients with stage 5 chronic kidney disease (CKD). We measured following mineral homeostasis parameters: total and ionized calcium, phosphate, total protein, albumin, and fetuin-A. Then, we determined a baseline serum CPP concentration by flow cytometry using a fluorescent-labeled bisphosphonate OsteoSense 680EX. Results. In comparison with other patients, healthy volunteers had the highest serum CPP concentration (249 CPPs/µL), indicating the retained ability to compensate mineral homeostasis disturbances by aggregation of excessive calcium and pho sphate with acidic proteins (mineral chaperones). Reduced serum CPP concentration in patients with CVD (170 CPPs/µL), CAD (139 CPPs/µL), and stage 5 CKD (193-203 CPPs/µL) showed impaired aggregation of excessive serum calcium and phosphate, which was also reflected by an increased level of blood ionized calcium.Conclusion. Patients with CVD, CAD, and stage 5 CKD have lower serum CPP concentration than healthy individuals. In combination with elevated ionized calcium and reduced albumin, this suggests the depletion of calcium binding buffers in the serum of patients with cardiovascular and renal diseases

Antiseptics: from the past to the presence

This article is dedicated to historical aspect of the use of antiseptics, and it contains data from the modern scientific literature about the interactions between antiseptics and pathogens in biofilms.В статье рассмотрен исторический аспект применения антисептиков, а также приведены данные из современной научной литературы о взаимодействии антисептиков и патогенов в составе биопленок

Оценка экспрессии провоспалительных цитокинов в гладкомышечных клетках коронарной артерии, экспонированных мутагеном алкилирующего механизма действия

Background. It is known that DNA damage in smooth muscle cells can trigger their clonal expansion and transformation into foam cells. Thus, the study of the molecular genetic mechanisms of the vascular smooth muscle cells response to genotoxic exposure is important and relevant in the context of an in-depth understanding of atherogenesis.Aim. To study mRNA level and concentration of proinflammatory cytokines IL6 and IL8 in the human coronary artery smooth muscle cells exposed to alkylating mutagen.Methods. Gene expression signature of studied cytokines in the human coronary artery smooth muscle cells was accessed by quantitative polymerase chain reaction in the two timepoints – immediately after six-hour exposure to mitomycin C (point 1) and after six-hour exposure to mitomycin C followed by 24 hours of cells being cultivated on mitomycin C-free cell growth medium (point 2). Smooth muscle cells cultured according to the above scheme without genotoxin were used as controls. HPRT1, GAPDH and B2M were used as the reference genes. Gene expression level was calculated by ΔCt method. IL6 and IL8 concentration was evaluated in the culture media in points 1 and 2 by enzyme-linked immunosorbent assay. Statistical analysis was performed in GraphPad Prism 9 software.Results. Immediately after mutagenic exposure (point 1) we discovered no significant changes in the expression level of IL6 and IL8 in the mitomycin C exposed smooth muscle cells compared to controls. Removal of mutagen increased expression of IL6 and IL8 in the experimental group (0,36- and 0,67-fold, respectively). At the same time, we discovered no significant differences in the studied cytokines concentration in the culture medium of mutagen-exposed cells compared to the nonexposed controls.Conclusion. Genotoxic stress in human coronary artery smooth muscle cells exposed to alkylating mutagen (mitomycin C) leads to differential expression but not secretion of proinflammatory cytokines IL6 and IL8. Thus, exposure of smooth muscle cells to mitomycin C do not trigger their proinflammatory phenotype. Актуальность. Известно, что повреждение ДНК гладкомышечных клеток может быть триггером их клональной экспансии и трансформации в пенистые клетки. Таким образом, изучение молекулярно-генетических механизмов ответа гладкомышечных клеток сосудов на генотоксическое воздействие представляется важным и актуальным в контексте углубленного понимания механизмов атерогенеза.Цель. Изучить характер изменения уровня мРНК и концентрации провоспалительных цитокинов IL6 и IL8 в гладкомышечных клетках коронарной артерии человека, культивируемых в условиях генотоксической нагрузки.Материалы и методы. Уровень генной экспрессии изучаемых цитокинов в гладкомышечных клетках коронарной артерии человека оценивали с помощью количественной полимеразной цепной реакции в двух временных точках – непосредственно после 6 ч экспозиции клеток митомицином С (точка 1) и после 6 ч экспозиции мутагеном с последующими 24 ч культивирования клеток в чистой культуральной среде (точка 2). Контролем служили гладкомышечные клетки, культивированные по вышеуказанной схеме без генотоксической нагрузки. В качестве референсных генов использовали HPRT1, GAPDH и B2M. Уровень экспрессии генов интереса рассчитывали по методу ΔCt. Концентрацию IL6 и IL8 в культуральной среде определяли с помощью иммуноферментного анализа в точках 1 и 2. Статистический анализ полученных результатов проводили в программе GraphPad Prism 9.Результаты. Непосредственно после мутагенного воздействия (точка 1) не выявлено изменения уровня экспрессии генов IL6 и IL8 в гладкомышечных клетках, экспонированных митомицином С, по сравнению с неэкспонированным контролем. После удаления из культур мутагена в экспериментальной группе отмечено снижение уровня мРНК генов IL6 и IL8 по сравнению с контролем (кратность изменения экспрессии составила 0,36 и 0,67 соответственно). При этом достоверных различий концентрации изученных цитокинов в культуральной среде гладкомышечных клеток, экспонированных митомицином С, по сравнению с контролем не выявлено.Заключение. Генотоксический стресс в гладкомышечных клетках коронарной артерии человека, вызванный алкилирующим мутагеном митомицином С, приводит к изменению профиля генной экспрессии, но не концентрации провоспалительных цитокинов IL6 и IL8. Таким образом, воздействие митомицина С на гладкомышечные клетки не приводит к формированию ими провоспалительного фенотипа

Современные аспекты поражения центральной нервной системы у больных ВИЧ-инфекцией (обзор литературы)

The literature review highlights modern ideas about the pathogenesis, pathomorphology, and clinical manifestations of central nervous system damage in patients with HIV infection, and also touches on the problems of diagnosis and treatment of these opportunistic infections. Particular attention should be paid to patients with severe immunodeficiency (CD4+T-lymphocyte count &lt; 200 cl/ml) due to the high risk of secondary diseases of the central nervous system. Along with the etiological verification of opportunistic diseases of the central nervous system, magnetic resonance imaging of the brain is important at the initial stage of diagnosis, with the help of which it is possible to identify changes in the brain substance characteristic of certain pathogens. In addition to the basic etiotropic therapy of opportunistic infections in HIV patients, effective antiretroviral therapy and its index of penetration into the central nervous system play a crucial role.В обзоре литературы освещаются современные представления о патогенезе, патоморфологии, клинических проявлениях поражения центральной нервной системы у больных ВИЧ-инфекцией, а также затрагиваются проблемы диагностики и лечения данных оппортунистических инфекций. Особое внимание следует уделять пациентам с тяжелым иммунодефицитом (количество CD4+Т-лимфоцитов ≤ 200 кл/мкл) в связи с высоким риском развития вторичных заболеваний центральной нервной системы. Наряду с этиологической верификацией оппортунистических заболеваний центральной нервной системы, важное значение на начальном этапе диагностики имеет магнитно-резонансная томография головного мозга, с помощью которой можно выявить характерные для определенных возбудителей изменения в веществе головного мозга. Помимо базовой этиотропной терапии оппортунистических инфекций, у больных ВИЧ-инфекцией решающую роль играют эффективная антиретровирусная терапия и ее индекс проникновения в центральную нервную систему

Вакцинация против новой коронавирусной инфекции пациентов с отягощенным сердечно-сосудистым и аутоиммунным анамнезом

The review article is devoted to a discussion of the issues of vaccination against a new coronavirus infection in patients with cardiovascular and autoimmune diseases. Presented at the time of this writing are data on domestic vaccines safety in the Russian Federation: combined vector vaccines “Gam-COVID-Vac” and “Gam-COVID-Vac-Lyo”, peptide-based vaccine “EpiVacCorona”, concentrated, purified and inactivated whole-virion “KoviVac” vaccine, and a standalone vaccine/booster shot “Sputnik Light”. The analysis of the main contraindication applicable to the vaccines in different categories of patients has been carried out. A number of consensus documents published by Russian and foreign professional medical associations and communities on the issues of vaccination of patients with cardiovascular and autoimmune diseases are considered in detail.Обзорная статья посвящена обсуждению вопросов вакцинопрофилактики новой коронавирусной инфекции (COVID-19) у пациентов с сердечно-сосудистыми и аутоиммунными заболеваниями. Представлены актуальные на момент написания статьи данные по вопросам безопасности зарегистрированных в Российской Федерации отечественных вакцин: комбинированных векторных вакцин «Гам-КОВИД-Вак» и «Гам-КОВИД-Вак-Лио», вакцины на основе пептидных антигенов «ЭпиВакКорона», вакцины коронавирусной инактивированной цельновирионной концентрированной очищенной «КовиВак» и вакцины для профилактики COVID-19 «Спутник Лайт». Проведен анализ основных ограничений к вакцинации данными препаратами у различных категорий больных. Подробно рассмотрен ряд консенсусных документов, опубликованных российскими и зарубежными профессиональными медицинскими ассоциациями и сообществами, по вопросам вакцинации пациентов с сердечно-сосудистыми и аутоиммунными заболеваниями