No abstract

Introduction. Glucocorticoids are the important component of combined chemotherapy of blood cancer. Therapeutic effects of glucocorticoids is realized via activation of glucocorticoid receptor transrepression, the development of side effects is associated with transactivation. We demonstrated earlier that compound belonging the class of selective glucocorticoid receptor agonists, CpdA, selectively induced transrepression in blood cancer cells. CpdA represents a mixture of two enantiomers, which can differ in interaction with the receptor. Aim. The main aim of present study was to synthesize CpdA enantiomers and to evaluate their biological properties. Materials and methods. Synthesis was carried out based on Sharpless dihydroxylation; anti-tumor activity in vitro was evaluated by antiproliferative and pro-apoptotic effects. Ligand properties were estimated by PCR-analysis of glucocorticoid- and NF-kB-dependent genes expression. Results and conclusions. We demonstrated that CpdA enantiomers revealed anti-tumor activity in vitro and did not induce transactivation. Moreover, S-enantiomer of CpdA in the most tests demonstrated more pronounced activity and is more perspective molecule for future studies in vivo.

Relevance. Despite more than 50 years of successful experience with pertussis immunization, pertussis remains an important public health problem. WHO estimated 16 million people worldwide are infected per year, a significant number of whom are children under 1 year of age. In the last 10 years a significant increase in the incidence of whooping cough has been observed in many countries with a high immunization coverage level. In Russia, specific prevention of whooping cough, is held since 1959. Specific prevention of whooping cough has led to considerable improvement of an epidemiological situation and has shown its social and economic importance for maintenance of sanitary and epidemiologic wellbeing on this infection in Russia. Goal. Study the structure of population B. pertussis circulating in Russia in dynamics of whooping cough epidemic process. Materials and methods Studied 573 B. pertussis strains allocated from patients with whooping cough in 1948 - 2015 used multilocus sequence typing (MAST). Isolates divided in five groups: 1948 - 1969 - 37 strains, isolated in the vaccination period and the first ten years of mass childhood immunization; 1970 - 1989 - 63 strains; 1990 - 2005 - 203 strains (from G.N. Gabrichevsky Institute of Epidemiology and Microbiology collection); 2006 - 2012 - 185 strains; 2013 - 2015 - 85 strains. Genotyping of strains was carried out according to the scheme MAST2 on the basis of a sequence of fragments of genes of ptxP-fim3-prn. Results of sequencing-typing were computed in the CromasLite program, identification of alleles and sequencing types carried out on EMBL/GenBank. Results. Formation of population of B.pertussis strains during more than 50 years went on the way of consecutive change of vaccinal genotype strains with strains of new nonvaccinal genotypes. Conclusions. Modern population of the causative agent of whooping cough is presented by the strains of genotype 322 and 329 possessing high virulence and causing heavier clinical course of disease.

Recently immune checkpoint inhibitors amazingly changed the landscape of cancer therapy worldwide. The number of immune checkpoint molecules in clinical practice is constantly increasing. There are some monoclonal antibodies recently registered in the Russian Federation: anti-PD1 antibodies (nivolumab, pembrolizumab), anti-PD-L1 (atezolizumab, durvalumab), anti-CTLA-4 (ipilimumab). Immune-mediated endocrinopathies are some of the most common complications of immunotherapy. According to the results of clinical studies, the incidence of serious endocrine immuno-mediated adverse events with anti-PD1 monoclonal antibodies is low (3.5–8%). The use of anti-CTLA4 antibodies, combined regimens, and the use of immunotherapy after chemoradiotherapy significantly increase the incidence of serious adverse events to 30%. In clinical practice of N.N. Blokhin Cancer Research Center among 245 non-small cell lung cancer and hepatocellular carcinoma patients treated with immunotherapy, 22 (8,9%) developed an immune-mediated endocrinopathy. Most patients developed adverse events of 1–2 degrees, in two patients – 3 degrees, requiring discontinuation of treatment. The aim of this article was to provide useful information and recommendations regarding the management of common immuno-related endocrine adverse events (including hypothyroidism, hyperthyroidism, pituitary, adrenal insufficiency) for clinical oncologists.

Резюме. Цель исследования: оценка эффективности применения молекулярно-генетической диагностики при обследовании контактных лиц в очагах коклюшной инфекции. Материалы и методы. Под наблюдением находилось 4930 человек из 8 общеобразовательных учреждений г. Москвы и Московской области в период с 2012 по 2015 гг. Изучено 430 проб клинического материала. В исследование были включены учащиеся 1-9, 11 классов и работники образования различных категорий. Исследования проводили согласно методическим рекомендациям МР 3.1.2.0072-13. Экстракцию ДНК B. pertussis из исследуемых образцов проводили с помощью тест-системы «АмплиПрайм ® ДНК-сорб-АМ». Выявление специфических фрагментов генома возбудителя коклюша осуществляли методом ПЦР-РТ с помощью тест-системы «Амп лиСенс ® Bordetella multi-FL» и методом ПЦР при изотермальных условиях с оригинальной комбинацией праймеров. Результаты. Из обследуемых контактных лиц в очагах коклюшной инфекции в 80,9% были дети и 19,1%-взрослые. В трех из восьми образовательных учреждений ранее были выявлены случаи коклюша у 7 детей в возрасте 7, 9, 11 и 15 лет. Диагноз коклюша у них был подтвержден в одном случае с помощью бактериологического метода и в шести случаяхс помощью серологических методов (ИФА и РНГА). Обнаружено 33 положительных ДНК-образца (7,7% от общего числа проб). ДНК-положительные образцы выделены от 18 учащихся и 15 работников образовательных учреждений. Среди учащихся положительные образцы в основном обнаружены у учеников 4-х классов в возрасте 10-11 лет. Среди работников образовательных учреждений ДНК-положительные образцы в большинстве (33,3%) случаев выделены от педагогов, а также от медицинского персонала и работников столовой. В двух очагах, где ранее были установлены источники инфекции, обнаружено 15 ДНК-положительных образцов, при этом у троих обследованных с ДНК-позитивными пробами наблюдались клинические проявления. В тех оча-Адрес для переписки: