Features of Physical Development of Schoolchildren in the Conditions of Specialized Training

The article presents a comparative analysis of physical development of 13-year-olds and cadet basic profile of teaching in urban schools in the parameters of somatometry and visiometry characterizing physical development, functional state, adaptation of the heart and body to current training loads. Coming of puberty is marked by intense growth of the body with heterochronous changes in the proportions and dimensions of its muscular skeletal system and the structure of internal organs. During this period, the role of mechanisms for self-regulation of heart activity and, in general, autonomous regulation of the functions of the cardiovascular system increases. At the initial stage in adolescents the manifestation of tachycardia and cardiac type of self-regulation of blood circulation increases. It is accompanied with deterioration in inotropic function of the myocardium against the background of a pronounced effect of sympatotonia and vagotonia on the systolic function of the myocardium

Признаки поражения пищевода у детей со склеродермией по данным маноимпедансометрии: исследование серии случаев

Background. Currently, scleroderma is a rather rare disease, including among children. Despite the growing interest of investigators in this pathology, the problem of diagnosing oesophageal affection in various forms of systemic sclerosis remains under-investigated since endoscopic data does not provide a complete picture of the oesophageal function. Currently, mano-impedancemetry (MIP) is the leading method in Europe for determining the oesophageal function, including in children with scleroderma; in the Russian Federation, it is used only in adults. Proper and timely evaluation of the oesophageal motility state will allow not only to expand our understanding of the disease pathogenesis but also to determine the efficacy of the initiated therapy and to give practice suggestions in terms of treatment tactics in the early stages of the disease. Our aim was to determine the possibilities of mano-impedancemetry for diagnosing oesophageal affection in juvenile scleroderma. Patients and Methods. The study included children with juvenile scleroderma taken to the department of rheumatology and dermatology from June to August 2016. To identify oesophageal function disorders, all patients underwent high-resolution manometry in combination with impedancemetry. Results. A decrease in the distal oesophageal contraction amplitude in more than 30% of “wet” swallows was found in 2 of 7 children with juvenile systemic scleroderma and in one of 6 children with juvenile focal scleroderma. All 13 patients had peristaltic waves in the distal oesophagus with an amplitude of <30 mm Hg. They had interrupted peristalsis, in which the peristaltic wave did not go through the entire length of the oesophagus; one of these patients showed a simultaneous contraction with an amplitude of <30 mm Hg. All children (n=13) showed a positive correlation (r= 0.021) between the systemic disease and impaired motility (р=0.021). Conclusion. Despite the clinical and laboratory methods for diagnosing scleroderma, the data of oesophageal mano-impedancemetry is an important criterion, primarily for the differential diagnosis of systemic and focal scleroderma, and assists in the early initiation of therapy for oesophageal motility disorders.Marina Ju. Stepanyan, Ekaterina I. Alexeeva, Elena V. Komarova confirmed the absence of a reportable conflict of interest.Ekaterina I. Alexeeva — receiving research grants from Pfizer, Roche, Centocor, Novartis.Nikolay N. Murashkin — receiving research funding from pharmaceutical companies Jansen, Eli Lilly. Receiving fees for scientific advice from Galderma, Pierre Fabre, Bayer, Astellas, Libriderm.Актуальность. В настоящее время склеродермия остается достаточно редким, в том числе среди детей, заболеванием. Тем не менее интерес исследователей к данной патологии возрастает, поскольку диагностика поражения пищевода при различных формах системного склероза достаточно проблематична, а результаты эндоскопического исследования не отображают полной картины функции пищевода. На современном этапе метод маноимпедансометрии для определения функции пищевода, в том числе у детей со склеродермией, является ведущим в Европе, однако на территории Российской Федерации применяется только у взрослых. Правильная и своевременная оценка моторного состояния пищевода позволит не только расширить наши представления о патогенезе заболевания, но и определить эффективность начатой терапии и выработать практические рекомендации относительно тактики лечения уже на ранних этапах развития заболевания. Цель исследования — определить возможности маноимпедансометрии для диагностики поражений пищевода при ювенильной склеродермии. Методы. В исследование включены 13 детей с ювенильной склеродермией, госпитализированных в отделения ревматологии и дерматологии в период с июня по август 2016 г. Всем пациентам с целью выявления функциональных нарушений пищевода выполнена манометрия высокого разрешения в сочетании с импедансометрией. Результаты. Снижение амплитуды сокращений в дистальном отделе пищевода более чем в 30% «влажных» глотков обнаружено у 2 из 7 детей с ювенильной системной склеродермией и у 1 из 6 с ювенильной очаговой склеродермией. У всех пациентов выявлены перистальтические волны в дистальном отделе пищевода амплитудой <30 мм рт.ст., а также непроведенная перистальтика, при которой перистальтическая волна не проходит всю длину пищевода; у 1/13 — одновременное сокращение с амплитудой <30 мм рт.ст. У всех детей выявлена положительная корреляция между системным вариантом заболевания и нарушением перистальтики (р=0,021). Заключение. Благодаря методу маноимпедансометрии верифицируются моторные нарушения пищевода, что обеспечивает пациенту своевременную и соответствующую медицинскую помощь.Е.И. Алексеева — получение грантов на проведение исследований от компаний Pfizer, Roche, Centocor, Novartis.М.Ю. Степанян, Е.В. Комарова подтвердили отсутствие конфликта интересов, о котором необходимо сообщить.Н.Н. Мурашкин — получение исследовательских грантов от фармацевтических компаний Jansen, Eli Lilly. Получение гонораров за научное консультирование от компаний Galderma, Pierre Fabre, Bayer, Astellas, Libriderm

ОСОБЕННОСТИ ПАТОМОРФОЗА ПРИ СОНОДИНАМИЧЕСКОЙ ХИМИОТЕРАПИИ НА ЭТАПАХ ЛУЧЕВОГО ЛЕЧЕНИЯ РАКА СЛИЗИСТОЙ ОБОЛОЧКИ ПОЛОСТИ РТА

Abstract.Morphological response of the tumor was investigated after sonodynamic chemotherapy during distal gamma-therapy (DGT) in patients with cancer of the oral cavity. Sixty-one patients were divided into two groups: group 1 (n=31) received DGT and local ultrasound treatment (0,88 MHz±0,33% and I=1,0Вm/cm2) with 5 mg of platidiam  and group 2 (n=30) received only DGT. Biopsies were investigated by standard morphological and immunohistochemical analysis after achieving total dose of radiation 40 Gy. In the main group the mass of stroma increased 1,9 times after starting of treatment and 1,6 times in comparison with the control group, mitotic activity of the cells decreased 3,9 and 1,9 times respectively, and index of parenchymal damage was 2,4 times higher in the main group than in the control. There was fibrosis and focuses of cells with “cells – shadows” with dystrophic changes of the nucleus and cytoplasma.There was a high index of Ki-67 proliferating activity (60-75%) and high apoptotic index (50-65%) of all cell layers.  The rate of Ki-67 and gene p53 decreased 1,3 and 1,5 times respectively after treatment. In specimens of the main group basal layer cells expressed Ki-67 and p53 in 10-15% of area and didn’t differ from normal values. The rate of KI-67 and expression of p53 gene decreased 7.1 and 6.5 after treatment. Sonodynamic chemotherapy contributes to the suppression of the biological aggressiveness of the tumor, provides a much more pronounced antitumor effect compared to the effect of ionizing radiation alone.Исследовали  морфологический  ответ опухоли на воздействие,  включающее проведение  сонодинамической химиотерапии при дистанционной гамматерапии (ДГТ) рака  слизистой  оболочки  полости  рта (РСПР). 61 больной РПСР были разделены  на основную (31 больному  при ДГТ проводилась   локально  на очаг  опухоли 5 мг платидиама  с помощью  ультразвукового  воздействия  частотой  0,88 МГц±0,33%, и I=1,0Вm/см2) и контрольную (30 больным, сопоставимым по клиническим параметрам,  проводилась  только аналогичная ДГТ) группы. До лечения и после планового перерыва на дозе 40 Гр исследовались  биоптаты опухолей по стандартным морфологическим и иммуногистохимическим методикам. В основной группе доля стромы опухоли увеличилась в 1,9 раз, чем до лечения и в 1,6 раз против контроля, митотическая активность клеток снизилась  в 3,9 и 1,9 раз соответственно, а индекс повреждения паренхимы был выше в 2,4 раза чем в контрольной. Определялся  выраженный фиброз,  наблюдались фокусы клеток, представленные  «клетками — тенями», с выраженными дистрофическими изменениями ядра и цитоплазмыВ контрольной группе было отмечено  сохранение  высокого индекса  пролиферации  Ki-67 (60–75%)  и высокий апоптотический индекс (50–65%)  всех клеточных слоев опухоли. Уровень маркера  Ki-67 и экспрессия мутагенного гена р53 по сравнению с исходными данными снизилась лишь в 1,3 и в 1,5 раз соответственно. В образцах опухоли основной группы клетки базального слоя плоского эпителия вокруг опухоли экспрессировали  Ki-67, p53 в 10–15%  площади и не отличались от нормальных показателей. Уровень маркера  Ki-67 и экспрессия мутагенного гена р53 по сравнению с исходными данными снизились в 7,1 и 6,5 раз соответственно. Таким образом,  сонодинамическая химиотерапия способствует подавлению биологической агрессивности опухоли, обеспечивает существенно более выраженный противоопухолевый эффект по сравнению с действием только ионизирующего излучения

Symptoms of Oesophageal Affection in Children With Scleroderma According to Mano-Impedancemetry: A Case Series

Background. Currently, scleroderma is a rather rare disease, including among children. Despite the growing interest of investigators in this pathology, the problem of diagnosing oesophageal affection in various forms of systemic sclerosis remains under-investigated since endoscopic data does not provide a complete picture of the oesophageal function. Currently, mano-impedancemetry (MIP) is the leading method in Europe for determining the oesophageal function, including in children with scleroderma; in the Russian Federation, it is used only in adults. Proper and timely evaluation of the oesophageal motility state will allow not only to expand our understanding of the disease pathogenesis but also to determine the efficacy of the initiated therapy and to give practice suggestions in terms of treatment tactics in the early stages of the disease. Our aim was to determine the possibilities of mano-impedancemetry for diagnosing oesophageal affection in juvenile scleroderma. Patients and Methods. The study included children with juvenile scleroderma taken to the department of rheumatology and dermatology from June to August 2016. To identify oesophageal function disorders, all patients underwent high-resolution manometry in combination with impedancemetry. Results. A decrease in the distal oesophageal contraction amplitude in more than 30% of “wet” swallows was found in 2 of 7 children with juvenile systemic scleroderma and in one of 6 children with juvenile focal scleroderma. All 13 patients had peristaltic waves in the distal oesophagus with an amplitude of <30 mm Hg. They had interrupted peristalsis, in which the peristaltic wave did not go through the entire length of the oesophagus; one of these patients showed a simultaneous contraction with an amplitude of <30 mm Hg. All children (n=13) showed a positive correlation (r= 0.021) between the systemic disease and impaired motility (р=0.021). Conclusion. Despite the clinical and laboratory methods for diagnosing scleroderma, the data of oesophageal mano-impedancemetry is an important criterion, primarily for the differential diagnosis of systemic and focal scleroderma, and assists in the early initiation of therapy for oesophageal motility disorders.Marina Ju. Stepanyan, Ekaterina I. Alexeeva, Elena V. Komarova confirmed the absence of a reportable conflict of interest.Ekaterina I. Alexeeva — receiving research grants from Pfizer, Roche, Centocor, Novartis.Nikolay N. Murashkin — receiving research funding from pharmaceutical companies Jansen, Eli Lilly. Receiving fees for scientific advice from Galderma, Pierre Fabre, Bayer, Astellas, Libriderm

Simultaneous Probing of Metabolism and Oxygenation of Tumors In Vivo Using FLIM of NAD(P)H and PLIM of a New Polymeric Ir(III) Oxygen Sensor

Tumor cells are well adapted to grow in conditions of variable oxygen supply and hypoxia by switching between different metabolic pathways. However, the regulatory effect of oxygen on metabolism and its contribution to the metabolic heterogeneity of tumors have not been fully explored. In this study, we develop a methodology for the simultaneous analysis of cellular metabolic status, using the fluorescence lifetime imaging microscopy (FLIM) of metabolic cofactor NAD(P)H, and oxygen level, using the phosphorescence lifetime imaging (PLIM) of a new polymeric Ir(III)-based sensor (PIr3) in tumors in vivo. The sensor, derived from a polynorbornene and cyclometalated iridium(III) complex, exhibits the oxygen-dependent quenching of phosphorescence with a 40% longer lifetime in degassed compared to aerated solutions. In vitro, hypoxia resulted in a correlative increase in PIr3 phosphorescence lifetime and free (glycolytic) NAD(P)H fraction in cells. In vivo, mouse tumors demonstrated a high degree of cellular-level heterogeneity of both metabolic and oxygen states, and a lower dependence of metabolism on oxygen than cells in vitro. The small tumors were hypoxic, while the advanced tumors contained areas of normoxia and hypoxia, which was consistent with the pimonidazole assay and angiographic imaging. Dual FLIM/PLIM metabolic/oxygen imaging will be valuable in preclinical investigations into the effects of hypoxia on metabolic aspects of tumor progression and treatment response

Conformational features of lactate dehydrogenase: Temperature effect in presence of small molecules, mathematical model

The aim. To study the conformational changes of lactate dehydrogenase under the influence of different concentrations of intermediates (pyruvate, oxaloacetate) in the temperature gradient with the subsequent building of a mathematical model. Materials and methods. Thermolability of lactate dehydrogenase was studied using the method of differential scanning fluorimetry to determine the change in endogenous fluorescence of tryptophan and tyrosine under the conditions of stable concentration of lactate dehydrogenase and changing concentrations of pyruvate and oxaloacetate. Further, a mathematical model was developed for a more in-depth consideration of the behavior of the catalytic protein. Results. We found that pyruvate and oxaloacetate in low concentrations have a thermostabilizing effect on lactate dehydrogenase conformation; the effect of pyruvate is statistically more significant in comparison with oxaloacetate (p < 0.05). The studied ligands in high concentrations reduce the thermal stability of lactate dehydrogenase. Conclusion. Understanding the role of small molecules in the regulation of biological and catalytic processes has long remained in the background of scientific interest, but today the work in this direction is reaching a new level. The data obtained indicate the possibility of small molecules acting as ligands when interacting with enzymes. © 2020 Siberian State Medical University. All rights reserved

Red Light-Emitting Water-Soluble Luminescent Iridium-Containing Polynorbornenes: Synthesis, Characterization and Oxygen Sensing Properties in Biological Tissues In Vivo

New water-soluble polynorbornenes P1–P4 containing oligoether, amino acid groups and luminophoric complexes of iridium(III) were synthesized by ring-opening metathesis polymerization. The polymeric products in organic solvents and in water demonstrate intense photoluminescence in the red spectral region. The polymers P1 and P3 with 1-phenylisoquinoline cyclometalating ligands in iridium fragments reveal 4–6 fold higher emission quantum yields in solutions than those of P2 and P4 that contain iridium complexes with 1-(thien-2-yl)isoquinoline cyclometalating ligands. The emission parameters of P1–P4 in degassed solutions essentially differ from those in the aerated solutions showing oxygen-dependent quenching of phosphorescence. Biological testing of P1 and P3 demonstrates that the polymers do not penetrate into live cultured cancer cells and normal skin fibroblasts and do not possess cytotoxicity within the concentrations and time ranges reasonable for biological studies. In vivo, the polymers display longer phosphorescence lifetimes in mouse tumors than in muscle, as measured using phosphorescence lifetime imaging (PLIM), which correlates with tumor hypoxia. Therefore, preliminary evaluation of the synthesized polymers shows their suitability for noninvasive in vivo assessments of oxygen levels in biological tissues

Development of DNA aptamers for visualization of glial brain tumors and detection of circulating tumor cells

Here, we present DNA aptamers capable of specific binding to glial tumor cells in vitro, ex vivo, and in vivo for visualization diagnostics of central nervous system tumors. We selected the aptamers binding specifically to the postoperative human glial primary tumors and not to the healthy brain cells and meningioma, using a modified process of systematic evolution of ligands by exponential enrichment to cells; sequenced and analyzed ssDNA pools using bioinformatic tools and identified the best aptamers by their binding abilities; determined three-dimensional structures of lead aptamers (Gli-55 and Gli-233) with small-angle X-ray scattering and molecular modeling; isolated and identified molecular target proteins of the aptamers by mass spectrometry; the potential binding sites of Gli-233 to the target protein and the role of post-translational modifications were verified by molecular dynamics simulations. The anti-glioma aptamers Gli-233 and Gli-55 were used to detect circulating tumor cells in liquid biopsies. These aptamers were used for in situ, ex vivo tissue staining, histopathological analyses, and fluorescence-guided tumor and PET/CT tumor visualization in mice with xenotransplanted human astrocytoma. The aptamers did not show in vivo toxicity in the preclinical animal study. This study demonstrates the potential applications of aptamers for precise diagnostics and fluorescence-guided surgery of brain tumors.peerReviewe