MicroRNA level in patients with stable coronary artery disease with borderline coronary artery stenosis

Aim. To assess the level of microRNA (miR) -21, -22, -126, -221 in patients with coronary artery disease (CAD) with borderline coronary artery stenosis depending on comorbidities and sex.Material and methods. We examined 37 patients with class 1-3 stable CAD aged 49-59 years with borderline (40-70%) coronary artery stenosis. The relative level of miRNA was determined using real-time polymerase chain reaction. Statistical analysis was performed using the non-parametric Mann-Whitney U-test. P<0,05 were considered statistically significant. Results. The miR-221 level was higher in the group of patients with stable CAD with borderline coronary artery stenosis with a metabolically unhealthy obesity (MUO) phenotype, but without diabetes (p=0,042). The level of miR-22 and miR-126 was higher in the group of patients with stable CAD phenotype with borderline stenosis and diabetes (p=0,007 and p=0,034, respectively). The analysis of miR levels in stable CAD patients depending on sex, without taking into account the phenotype, found that miR-21 and miR-221 values were higher in men (p=0,021 and p=0,014, respectively). The study of the sex characteristics of miR content in relation to different phenotypes revealed an increase of miR22 levels in men with MUO and diabetes (p=0,048) and an increase of miR-126 levels in women with concomitant diabetes in the comparison both with patients without MUO and diabetes (p=0,018), as well as with MUO and without diabetes (p=0,007). Conclusion. The study of the miRNA level in patients with CAD with borderline coronary artery stenosis is of great interest and reflects a promising direction in diagnosis based on comorbid pathology. Keywords: miRNA, obesity phenotypes, coronary artery disease, borderline coronary artery stenosis. Relationships and Activities: none. 1Novosibirsk State Medical University, Novosibirsk; 2Federal Research Center of Fundamental and Translational Medicine, Novosibirsk; 3E.N. Meshalkin National Medical Research Center, Novosibirsk, Russia.><0,05 were considered statistically significant.Results. The miR-221 level was higher in the group of patients with stable CAD with borderline coronary artery stenosis with a metabolically unhealthy obesity (MUO) phenotype, but without diabetes (p=0,042). The level of miR-22 and miR-126 was higher in the group of patients with stable CAD phenotype with borderline stenosis and diabetes (p=0,007 and p=0,034, respectively). The analysis of miR levels in stable CAD patients depending on sex, without taking into account the phenotype, found that miR-21 and miR-221 values were higher in men (p=0,021 and p=0,014, respectively). The study of the sex characteristics of miR content in relation to different phenotypes revealed an increase of miR22 levels in men with MUO and diabetes (p=0,048) and an increase of miR-126 levels in women with concomitant diabetes in the comparison both with patients without MUO and diabetes (p=0,018), as well as with MUO and without diabetes (p=0,007).Conclusion. The study of the miRNA level in patients with CAD with borderline coronary artery stenosis is of great interest and reflects a promising direction in diagnosis based on comorbid pathology

Стандартные образцы антибактерильных веществ утвержденного типа: принцип разработки

The authors of the publication have described the basic principles of the procedure of defining metrological characteristics of certified reference materials (hereinafter referred to as CRMs) of antibacterial substances that are being developed. CRMs of antibacterial substances are intended for certification of measurement procedures and accuracy control of measurement results. CRMs can be used for graduation, calibration of measuring instruments if their metrological and technical characteristics comply with the procedures of graduation and calibration of measuring instruments, as well as determination of antibiotic sensitivity of pathogenic microorganisms and authenticity of active substances in pharmaceutical drugs.Авторами работы изложены основные принципы процедуры установления метрологических характеристик, разрабатываемых стандартных образцов антибактериальных веществ утвержденного типа. Стандартные образцы антибактериальных веществ утвержденного типа предназначены для аттестации методик измерений и контроля точности результатов измерений. Стандартные образцы могут быть использованы для градуировки, калибровки средств измерений при соответствии метрологических и технических характеристик стандартного образца требованиям методик градуировки, калибровки средств измерений, а также определения чувствительности патогенных микроорганизмов к антибиотикам и подлинности действующего вещества в лекарственных средствах

Risk Factors of Portal Vein Thrombosis in Patients with Different Child-Pugh Classes Liver Cirrhosis

Aim: to evaluate the frequency of portal vein thrombosis (PVT) and build predictive models of the development of PVT for patients with liver cirrhosis (LC) of A and B/C classes by Child-Pugh.Materials and methods. Research design is a case-control. The Case group included 130 patients with newly diagnosed PVT not caused by invasive hepatocellular carcinoma (HCC); 29 patients were assigned to class A, 101 patients were assigned to class B/C. From the database of cirrhotic patients without PVT 60 Controls for class A and 205 for B/C were selected using sratified randomization by sex, age and etiology of cirrhosis. The Mann-Whitney U-test and Pearson's chi-squared test were used to compare the groups. Odds ratios (OR) and 95 % confidence intervals (95 % CI) were calculated. Logistic regression models are constructed with the separation of the sample into training and test (0.7; 0.3). The operational characteristics of the models were calculated on the test sample; ROC analysis was carried out, the area under the ROC curve (AUC) was calculated.Results. The overall frequency of PVT was 4.1 % (95 % CI 2.7-5.8 %) in class A and 10.4 % (95 % CI 8.5-12.5 %) class B/C. Patients with class A and B/C PVT differed from the corresponding controls by more severe portal hypertension: the frequency of bleeding / number of interventions on varices compared with the control were 41/45 % vs. 7/8 % (p < 0.001) for class A and 25.7/30.7 % vs. 16.1/16.1 % (p < 0.05) for class B/C, ascites frequency was 24 % vs. 8 % (p < 0.05) for class A and 89.1 % vs. 68.3 % (p < 0.001) for class B/C. The cutoff by the portal vein diameter was the same for both classes — 13.4 mm; the spleen length was similar and amounted 17.5 mm for class A, 17.1 mm for class B/C. Patients with PVT differed from the corresponding controls by neutrophil-to-lymphocyte ratio: class A 2.33 (1.82; 3.61) vs. 1.76 (1.37; 2.20), p < 0.01, class B/C 2.49 (1.93; 3.34) vs. 2.15 (1.49; 3.26), p < 0.05. Patients of class B/C had a higher incidence of newly diagnosed malignant tumors - 23.8% (primarily HCC that does not invade the portal vein), compared with control and cases of class A - 6.3 % and 3 % (p < 0.05), respectively. The best model for class A included variceal bleeding, ascites, portal vein diameter, absolute number of neutrophils, for class B — ascites, spleen length, portal vein diameter, malignant tumors / local factors; sensitivity, specificity, accuracy and AUC were 79.3 %, 90 %, 86.5 %, 0.897 and 73.3 %, 68.3 %, 69.9 %, 0.789, respectively.Conclusion. Independently of the Child-Pugh class of LC, the main risk factor for PVT is severe portal hypertension

Стандартный образец тилозина тартрата

To date, antibiotics are often used in the treatment of infectious diseases in medicine and veterinary medicine, as well as growth promoters in animal husbandry. The uncontrolled use of antibiotics leads to antibiotic residues in food products that are easily transmitted to humans through food chains. Due to these undesirable effects, as well as in connection with the circulation of substandard and counterfeit medicinal products, it is necessary to control the quality of medicinal products, as well as monitor the food safety of animal products by determining the content of drug residues using reference materials (RMs).The aim of this research was to develop a CRM for the composition of tylosin tartrate.In the course of the research, a method for preparing the initial RM was tested and successfully implemented, a critical analysis of methods for measuring the content of tylosin tartrate was carried out, and the choice of the HPLC method as the main method for quantitative determination of the certified value of the measured quantity (mass fraction of tylosin) was justified. The disadvantages of the microbiological method and the titrimetry method as alternative methods were shown. In accordance with RMG 93–2015 and GOST ISO Guide 35–2015, the standard uncertainty of the RM certified value from the characterization method, heterogeneity and instability of the material was estimated. The expanded uncertainty of the certified value was calculated. The result of the work performed was the approval of a new type of the CRM for the composition of tylosin tartrate GSO 11632 2020.Normalized metrological characteristics: the mass fraction of tylosin is 800–1100 µg/mg, the relative expanded uncertainty at k = 2, P= 0.95 is 6%. The CRM is stored in sealed ampoules separately from food and feed in a dry and dark place at a temperature from plus 4 °C to minus 18 °C, the shelf life of the CRM is 4 years.The practical significance of the results obtained makes it possible to expand the possibility of certification of measurement methods and control of the accuracy of the measurement results of the mass fraction of tylosin in veterinary medicinal products, food and food raw materials, animal feed, and environmental objects. The CRM can also be used to identify tylosin in medicinal products and to determine the susceptibility of pathogens to tylosin.Достаточно часто в современном мире применяют антибиотики для лечения инфекционных заболеваний в медицине и ветеринарии, а также в качестве стимуляторов роста в животноводстве. Бесконтрольное применение антибиотиков приводит к появлению остатков антибиотиков в пищевых продуктах, которые легко передаются человеку по пищевым цепочкам. Из-за этих нежелательных эффектов и в связи с оборотом недоброкачественных и контрафактных лекарственных препаратов необходимо контролировать качество лекарственных препаратов, а также проводить мониторинг пищевой безопасности продукции животноводства путем определения содержания остатков лекарственных препаратов в ней посредством применения стандартных образцов (СО).Целью настоящего исследования стала разработка СО утвержденного типа состава тилозина тартрата.В ходе выполнения исследования апробирована и успешно реализована методика подготовки исходного материала СО, проведен критический анализ методов измерений содержания тилозина тартрата, обоснован выбор метода ВЭЖХ в качестве основного метода количественного определения аттестованного значения измеряемой величины (массовой доли тилозина). Показаны недостатки микробиологического метода и метода титриметрии, рассмотренных в качестве альтернативных методов. В соответствии с РМГ 93–2015 и ГОСТ ISO Guide 35–2015 оценена стандартная неопределенность аттестованного значения СО от метода характеризации, от неоднородности и от нестабильности материала. Рассчитана расширенная неопределенность аттестованного значения. Результатом выполненных работ явилось утверждение нового типа СО состава тилозина тартрата ГСО 11632–2020.Нормированные метрологические характеристики: массовая доля тилозина 800–1100 мкг/мг, относительная расширенная неопределенность при k = 2, Р= 0,95 равна 6%. СО хранится в запаянных ампулах, отдельно от продуктов питания и кормов, в сухом, защищенном от света месте при температуре от +4 °С до -18 °С, срок годности СО 4 года.Практическая значимость полученных результатов позволяет расширить возможность аттестации методик измерений и контроля точности результатов измерений массовой доли тилозина в лекарственных средствах ветеринарного применения, в продуктах питания и продовольственном сырье, кормах для животных, объектах окружающей среды. СО может также использоваться для определения подлинности тилозина в лекарственных средствах и определения чувствительности патогенных микроорганизмов к тилозину

Cholinergic Deficit Induced by Central Administration of 192IgG-Saporin Is Associated With Activation of Microglia and Cell Loss in the Dorsal Hippocampus of Rats

Alzheimer’s disease (AD) is associated with degeneration of cholinergic neurons in the basal forebrain. Administration of the immunotoxin 192IgG-saporin to rats, an animal model of AD, leads to degeneration of cholinergic neurons in the medial septal area. In the present study, cholinergic cell death was induced by intracerebroventricular administration of 192IgG-saporin. One and a half months after injection, we studied the histopathology of the hippocampus and the responses of microglia and astrocytes using immunohistochemistry and neuroglial gene expression. We found that treatment with 192IgG-saporin resulted in neuronal loss in the CA3 field of the hippocampus. Microglial proliferation was observed in the dentate gyrus of the dorsal hippocampus and white matter. Massive proliferation and activation of microglia in the white matter was associated with strong activation of astrocytes. However, the expression of microglial marker genes significantly increased only in the dorsal hippocampus, not the ventral hippocampus. These effects were not related to non-specific action of 192IgG-saporin because of the absence of the Nerve growth factor receptor in the hippocampus. Additionally, 192IgG-saporin treatment also induced a decrease in the expression of genes that are associated with transport functions of brain vascular cells (Slc22a8, Ptprb, Sdpr), again in the dorsal hippocampus but not in the ventral hippocampus. Taken together, our data suggest that cholinergic degeneration in the medial septal area induced by intracerebroventricular administration of 192IgG-saporin results in an increase in the number of microglial cells and neuron degeneration in the dorsal hippocampus

Right to Health in the International Legal System of Human Rights at the Universal and Regional Levels

INTRODUCTION. The individual's right to health is a set of natural and positive legal frameworks that govern a person’s life activity, individual and family wellbeing, enforcement of health guarantees by the statesparticipants of universal and regional treaties of the field under question. The formation of this right stems from biological characteristics of each person, socio-economic conditions, environment, access to health and sanitation services, national health-care system progress, existence of vulnerable groups of population. Goals of the UN Sustainable Development Agenda 2030 (UN General Assembly resolution 70/1) include such essential aspects of the right to health as ending poverty and hunger in all its forms everywhere; promote food security and healthy lifestyle; the well-being of all individuals at any age; ensure availability and sustainable management of water and sanitation for all; protection and restoration of water-related ecosystems; enhancement of the States capacity to prevent and reduce national and global health risks. According to the position of the World Health Organization (WHO) the right to health imposes on the States a legal obligation to ensure timely access to adequate levels of high-quality health care, clean and safe drinking water, sanitation, adequate nutrition, shelter, health-related information and education, gender equality. As a result, the considerable amount of attention is paid to the analysis of the content of general and specific international instruments at the universal level and the international legal specificities of enshrining and maintaining an individual's right to health. The text also places the emphasis on its normative framing in the law of the Council of Europe and the European Union, reflecting the decisions and rulings of the European Court of Human Rights (ECHR).MATERIALS AND METHODS. The legal framework of the study is based on universal international treaties of the UN system, regional regulations of the Council of Europe and the EU, legal position of the UN specialized agencies, the International Committee of the Red Cross (ICRC) and the ECHR. The scientific works of domestic and foreign authors related to the study of the right to health are used as a theoretical foundation. The research uses general scientific and special cognitive techniques wherein legal analysis and synthesis, systemic, formal-legal, comparative-legal, historical-legal and dialectical methods are applied.RESEARCH RESULTS. The research indicates that the modern international legal concept of the right to health is being developed at the universal and regional level. Furthermore, specific international legal guarantees for the protection of this right are emerging for special groups such as women and children, refugees, stateless persons and migrant workers, protected persons, the wounded and the sick – all persons affected by international armed conflicts. There is a certain trend in Council of Europe and EU law towards an extended interpretation of the human right to health responding to new challenges to the realization that right, concerning bioethics, human genome editing, and the effects of nuclear testing and environmental pollution.DISCUSSION AND CONCLUSIONS. Following a review of the content and implementation of the right to health in the universal and regional international legal systems for the human rights and freedoms protection, the authors suggest its incorporation in a group of personal rights, social benefits provided by the state, and simultaneously in a collective right to development pertaining to the population as a whole. The universal international legal institutions establishing special rights for vulnerable groups will continue to be applied by member states in the context of a situational response to the global needs of families, women and children, international migration, armed conflicts, environmental conditions, and bioethical issues. The authors encourage the complement of the European system of human rights protection with an additional protocol to the Council of Europe Convention for the Protection of Human Rights and Fundamental Freedoms of 1950, involving the right to health security

Biodiversity and epidemic potential of Chiropteran coronaviruses (<i>Nidovirales: Coronaviridae</i>)

Aim. The aim of this review is a comprehensive analysis of current literature data on coronaviruses identified in bats.Discussion. Coronaviruses (Coronaviridae) constitute the most extensive family of viruses of the order Nidovirales. Coronaviruses have a wide range of hosts, including mammals (Alphacoronavirus, Betacoronavirus, Deltacoronavirus, Gammacoronavirus) and birds (Deltacoronavirus, Gammacoronavirus), amphibians (Alphaletovirus) and are pathogens of respiratory, intestinal, cardiovascular. Until the beginning of this century, only etiological agents of mild and moderate respiratory diseases were known among pathogenic coronaviruses for humans. In the 21st century, new highly pathogenic coronaviruses were discovered that caused outbreaks of severe pneumonia with high mortality: the severe acute respiratory syndrome coronavirus (Severe acute respiratory syndrome‐related coronavirus, SARS‐CoV; 2002‐2003, southern provinces of China), the Middle East respiratory coronavirus Syndrome (Middle East respiratory syndrome‐related coronavirus, MERS‐CoV; 2012, western part of Saudi Arabia) and type 2 acute respiratory syndrome coronavirus (Severe acute respiratory syndrome‐related coronavirus 2, SARS‐CoV‐2; 2019 ‐..., the eastern part of central China). The natural reservoirs of SARS‐CoV, SARS‐CoV‐2 and MERS‐CoV are bats (Chiroptera). Coronaviruses circulating in bat populations are not only phylogenetically close to the currently known especially dangerous human viruses but probably have epidemic potential that can be realized in the future.Conclusion. This review presents current data on coronaviruses of bats: taxonomic status, spectrum of potential hosts, distribution. The ecological features of coronaviruses of bats are considered in the context of their epidemiological significance. The origin of pathogenic human coronaviruses is discussed