Assessment of the DNA damage level in peripheral blood leukocytes of mice treated orally with Rapitalam in acute and therapeutic doses

Centre there was performed experimental research, which carried out the identification and quantitative assessment of alkali-labile sites and DNA strand breaks in leukocytes of peripheral blood of male mice treated with Rapitalam. The method is based on the assessment of the integrity of DNA in leukocytes of the whole blood of animals. Rapitalam was administered to animals orally according to 2 schemes: a single acute dose (413 mg/kg, which corresponds to 1/5 LD50 dose) and once daily in a therapeutic dose (3 mg/kg) for 4 day

Peculiarities of polyneuropathy in the peripheral t-cell lymphoma with cytostatics

This paper presents data on the occurrence and form of polyneuropathy in the peripheral T-cell lymphoma, and its main pathogenesis elements. Here the toxic effects of cytotoxic drugs and their role in the impairment of the nervous system have been describe

Zero modes, beta functions and IR/UV interplay in higher-loop QED

We analyze the relation between the short-distance behavior of quantum field theory and the strong-field limit of the background field formalism, for QED effective Lagrangians in self-dual backgrounds, at both one and two loop. The self-duality of the background leads to zero modes in the case of spinor QED, and these zero modes must be taken into account before comparing the perturbative beta function coefficients and the coefficients of the strong-field limit of the effective Lagrangian. At one-loop this is familiar from instanton physics, but we find that at two-loop the role of the zero modes, and the interplay between IR and UV effects in the renormalization, is quite different. Our analysis is motivated in part by the remarkable simplicity of the two-loop QED effective Lagrangians for a self-dual constant background, and we also present here a new independent derivation of these two-loop results.Comment: 15 pages, revtex

Behavioral and social risk factors for metabolically unhealthy obesity: data form a 12-year prospective study in the Russian population

Aim. To study the contribution of behavioral and social risk factors to the development of metabolically unhealthy obesity (MUO) according to a prospective study in the Russian population.Material and methods. From the HAPPIE project, 3197 people aged 45-69 years with a body mass index ≥30 kg/m2 were selected, who had all the necessary parameters for obesity phenotype determination. The prospective analysis included the first (2003-2005) and third screenings (2015-2017). A subsample was formed (n=1275; 276 men — 22%, 999 women — 78%). The mean follow-up period was 12,4 years. IDF criteria (2005) were taken for analysis.Results. Men with a metabolically healthy obesity (MHO) phenotype most often have a secondary and higher education, while women with MHO — vocational and secondary education. In women, secondary education was most often noted. Among persons with obesity, both men and women are more often not single, while having MUO as follows: 56,8% and 34,2%, respectively. Men and women have a low-intensity activity, regardless of the obesity phenotype. The prevalence of smoking in the present time does not differ in the MHO and MUO groups. Metabolically healthy women consume more alcohol than those with MUO. In men with sedentary lifestyle and fasting hyperglycemia, the risk of MUO over a 12-year follow-up period was significantly higher. In women, the risk of conversion from MHO to MUO is increased when blood pressure (BP) is ≥130/85 mmHg.Conclusion. In the Russian population, the risk of MUO in men increases with a level of physical activity <3 h/week and a blood glucose level ≥6,1 mmol/l; in women, only BP ≥130/85 mm Hg contributes to the development of MUO

Current regulatory requirements for non-clinical evaluation of prophylactic vaccines

Vaccines are subject to specific regulatory requirements for the evaluation of their quality, safety, and efficacy. In 2005, the World Health Organisation (WHO), as the main international organisation coordinating measures to combat infectious disease outbreaks, began developing documents on the evaluation of vaccine quality, safety, and efficacy. The world’s leading regulatory authorities (FDA, EMA, etc.) have also issued recommendations for conducting non-clinical studies of vaccines.The aim of this study was a critical review of the regulatory requirements established by foreign national and international regulatory authorities for non-clinical evaluation of the safety and efficacy of vaccines.According to the study results, since the 2000s, the WHO and the world’s leading regulatory authorities have produced more than 40 regulatory documents describing certain aspects of non-clinical studies of the safety and efficacy of vaccines. These documents can be divided into two groups: the first group addresses non-clinical studies of vaccines in general, and the second one dwells upon the evaluation of the quality, safety, and efficacy of specific types of vaccines. For the Russian guidelines on non-clinical evaluation of the quality, safety, and efficacy of immunobiologicals, the latest revision dates back to 2013 and does not provide any information on new medicinal products. Currently, work is underway to prepare the regulatory framework for medicines, including vaccines, in the Member States of the Eurasian Economic Union (EAEU). This review of regulatory documents on non-clinical safety and efficacy studies of vaccines may be useful in drafting harmonised guidelines for the relevant groups of vaccines in the EAEU. It may also be of use to developers, manufacturers, and researchers involved in the creation and non-clinical study of vaccines

Challenges in development and authorisation of gene therapy products

There are a lot of diseases known today, which are caused by genetic abnormalities. Advances in genetics and biotechnology brought about gene editing technologies that can produce almost any gene, which ultimately led to the emergence of a new class of medicines - gene therapy products (GTPs). The aim of the study was to analyse international experience in development and authorisation of GTPs. The review highlights the challenges in GTP development, related to the search for an optimal approach to therapeutic gene delivery to the target cells. Viral vectors were shown to be a promising gene delivery system, with adenovirus (AV) and adeno-associated virus (AAV) based products demonstrating the highest efficacy and safety. The paper reviews current approaches to gene editing that allow modification of AVs and AAVs to improve GTP efficacy and safety. These modifications are carried out with the aim of, e.g., including a large therapeutic gene into a viral vector, decreasing viral protein expression levels, and decreasing viral vector immunogenicity. The review summarises GTP authorisation procedures in the USA and the European Union, including data on FDA and EMA subcommittees and departments entrusted with advisory functions. The paper mentions that there is one Russian-produced GTP authorised in the Russian Federation, and some other GTPs are in the pipeline. Therefore, the Russian regulatory framework and the Eurasian regulations and recommendations should be updated in order to accommodate for GTP development and authorisation

Fe/Co Alloys for the Catalytic Chemical Vapor Deposition Synthesis of Single- and Double-Walled Carbon Nanotubes (CNTs). 1. The CNT−Fe/Co−MgO System

Mg0.90FexCoyO (x + y ) 0.1) solid solutions were synthesized by the ureic combustion route. Upon reduction at 1000 °C in H2-CH4 of these powders, Fe/Co alloy nanoparticles are formed, which are involved in the formation of carbon nanotubes, which are mostly single and double walled, with an average diameter close to 2.5 nm. Characterizations of the materials are performed using 57Fe Mo¨ssbauer spectroscopy and electron microscopy, and a well-established macroscopic method, based on specific-surface-area measurements, was applied to quantify the carbon quality and the nanotubes quantity. A detailed investigation of the Fe/Co alloys’ formation and composition is reported. An increasing fraction of Co2+ ions hinders the dissolution of iron in the MgO lattice and favors the formation of MgFe2O4-like particles in the oxide powders. Upon reduction, these particles form R-Fe/Co particles with a size and composition (close to Fe0.50Co0.50) adequate for the increased production of carbon nanotubes. However, larger particles are also produced resulting in the formation of undesirable carbon species. The highest CNT quantity and carbon quality are eventually obtained upon reduction of the iron-free Mg0.90Co0.10O solid solution, in the absence of clusters of metal ions in the starting material. Introduction Catalyti

ПАТОГЕНЕТИЧЕСКИЕ АСПЕКТЫ ВЗАИМОСВЯЗИ ИНФЕКЦИОННЫХ ЗАБОЛЕВАНИЙ РОТОВОЙ ПОЛОСТИ С РАЗВИТИЕМ И ПРОГРЕССИРОВАНИЕМ АТЕРОСКЛЕРОЗА И ВОЗМОЖНОСТИ ИХ КОМПЛЕКСНОЙ ПРОФИЛАКТИКИ

The article contains the modern literature data about impact of various infectious agents on the development and progression of atherosclerotic disease. The data are demonstrated the role of various infectious diseases, including periodontal diseases, in the development of biological degradation and destabilization of atherosclerotic plaques. The article questions of organization of primary prevention of cardiovascular disease based on the screening assessment by stomatologist the oral sanitary status. Necessary to carry out sanitation of chronic infection foci of the mouth on the basis of existing children’s health centers. The children’s health centers have a set of dental equipment, with which can perform a screening diagnosis of dental caries, periodontal diseases, non-carious lesions, diseases of the mucous membranes, and conduct preventive oral sanitation. The duties of dental hygienists is teaching children of different age groups to the rules of oral care, demonstration of skills, brushing teeth, information about the importance of prevention of dental caries and periodontal disease, as it is not only important for the preservation of the teeth, but also may prevent the development of ardiovasculardisease adulthood.В статье приводится обзор современной литературы о влиянии различных инфекционных агентов на развитие и прогрессирование атеросклероза. В частности, приводятся данные о роли некоторых возбудителей заболеваний периодонта в деструкции и дестабилизации капсулы атеросклеротических бляшек. Рассматриваются вопросы организации первичной профилактики сердечно-сосудистых заболеваний, основанной на скрининговой оценке гигиенического состояния полости рта и своевременной санации очагов инфекции на базе действующих детских центров здоровья. Детские центры здоровья оснащены комплектом стоматологического оборудования, что позволяет в режиме скринингового тестирования осуществлять диагностику кариеса зубов, болезней пародонта, некариозных поражений, болезней слизистой оболочки и проводить превентивную санацию ротовой полости. В обязанности стоматолога-гигиениста входит обучение детей разных возрастных групп правилам ухода за полостью рта, демонстрация навыков чистки зубов, информирование о важности профилактики кариеса зубов и заболеваний пародонта, так как это имеет не только важное значение для сохранения зубов, но и может предотвратить развитие сердечно-сосудистых заболеваний во взрослом возрасте