26 research outputs found
Organization of students’ self-guided work in biomedical departments of medical university using distant learning technology
The aim of the investigation to substantiate and analyze the practical implementation of using distance learning technologies (DLT) for managing the formation of basic knowledge during students’ individual work in the Department of Histology, Cytology and Embryology, Human Anatomy and Biological Chemistry. Methods. The methods involve analysis of an individual students’ work. Results. Questionnaires showed that the use of distance learning technologies during preparation for the practical classes allows to achieve the same result for most students as in the traditional forms of preparing (without DLT), to reach a significant saving of time. Respondents note the increased meaningfulness of individual work; the appearance of motivation to study the practical material; an increase of educational efficiency on the stage of extracurricular study due to the operative removal of arising question during the consulting process; as well as satisfaction with this form of education. Under control of knowledge and skills during practical classes, the increasing of students’ performance quality was noted. Scientific novelty. Using a basic knowledge standard of medicine; regulated methodical support for individual work and the introduction of DLT in the medical and biological departments of the university provides the continuity of teaching and fundamental knowledge integration, the formation of professional competencies of students. Practical significance. The demand of theoretical subjects’ content for students of 4–6 courses and the possibility of distance access for appropriate educational resources of biomedical departments would achieve a real interdisciplinary integration and support the necessary level of basic knowledge of young specialists in relation to a specific professional activityЦель статьи – обосновать и проанализировать практическую реализацию использования дистанционных обучающих технологий (ДОТ) для управления процессом формирования фундаментальных знаний во время внеаудиторной самостоятельной работы студентов на кафедрах гистологии, цитологии и эмбриологии, анатомии человека и биологической химии.Методики исследования: анализ практики организации самостоятельной работы студентов. Результаты. Анкетирование показало: использование дистанционных обучающих технологий при подготовке к практическим занятиям позволяет большинству студентов для достижения того же результата, что и при традиционных формах подготовки (без применения ДОТ), добиваться существенной экономии времени. Респонденты отмечают возросшую осмысленность самостоятельной работы, появление мотивации к изучению учебного материала, повышение эффективности обучения на этапе внеаудиторной подготовки благодаря оперативному устранению возникающих вопросов в процессе консультирования. При контроле знаний и умений на практических занятиях отмечено существенное повышение качественной успеваемости студентов. Научная новизна. Использование стандарта фундаментальных знаний медицины, регламентированное методическое сопровождение самостоятельной работы и внедрение дистанционных обучающих технологий на медико-биологических кафедрах университета обеспечивают преемственность преподавания и успешное формирование профессиональных компетенций у студентов. Практическая значимость. Дистанционный доступ к образовательным ресурсам медико-биологических кафедр позволяет достигнуть реальной междисциплинарной интеграции и поддерживать необходимый уровень фундаментальных знаний у молодых специалистов с учетом их конкретной специализаци
Применение метформина – целевая метаболическая терапия в онкологии
It is well known that metformin is widely used for the treatment of type II diabetes mellitus. However, in numerous epidemiological studies it was shown that patients taking metformin were less likely to have cancer of different localization and had better survival prognosis. Many researchers consider metformin to be a targeted metabolic drug that has many goals: it acts on mitochondria, affects intracellular signaling, blocks channels, inhibits the formation of endothelial and platelet growth factors, reduces the level of vitamins involved in the synthesis of nucleotides and amino acids, etc. It has also been established that metformin belongs to the group of “metabostemness” drugs, that is, it acts on cancer stem cells, blocking their division. We conducted a survey study that highlights the most important mechanisms and fields of application of metformin. The study of the use of this drug in oncology will make it possible to understand the pathogenetic targets of metabolic therapy and the prevention of cancer. Общеизвестно широкое применение метформина для лечения сахарного диабета II типа. Однако в многочисленных эпидемиологических исследованиях было показано, что больные, принимавшие метформин, реже болели раком различной локализации и имели лучший прогноз по выживаемости. Многие исследователи считают метформин таргетным метаболическим препаратом, который имеет множество целей: действует на митохондрии, влияет на внутриклеточный сигналинг, блокирует каналы, тормозит образование эндотелиального и тромбоцитарного факторов роста, снижает уровень витаминов, вовлеченных в синтез нуклеотидов и аминокислот и пр. Также установлено, что метформин относится к группе «метабостемных» препаратов, то есть действует на раковые стволовые клетки, блокируя их деление. Нами проведено обзорное исследование, которое освещает важнейшие механизмы и области применения метформина. Изучение применения данного препарата в онкологии позволит понять патогенетические мишени метаболической терапии и профилактики онкопатологий.
Expression level of androgen receptors in tumor tissue and its prognostic significance in primary operable luminal breast cancer without overexpression of Her2/neu in postmenopausal women
Aim. To evaluate the expression level and prognostic significance of androgen in primary operable luminal breast cancer without overexpression of Her2/neu in postmenopausal women.
Methods. We analyzed treatment outcomes of 60 cases of primary operable (T1-2N0M0) luminal breast cancer without overexpression of Her2/neu in postmenopausal women. The follow-up period was 5 years. All cases were divided by immunohistochemical method into luminal A (20 females) and luminal B (40 patients) subtypes. Along with the standard panel of immunohistochemical markers, expression of nuclear androgen receptors was measured in tumor tissues of all patients. Depending on the expression levels, patients with luminal A and B subtypes were divided into three groups: (1) with high, (2) moderate and (3) low or negative expression.
Results. Mean levels of androgen receptor expression in the nuclei of tumor cells in patients with luminal A subtype (57.3±5.9%) were higher than those of luminal B subtype (21.4±4.04%) by 62.7% (Mann-Whitney test, р=0.0026). In patients with luminal A subtype, the maximal accumulation of androgen receptors in the nuclei of tumor cells was 2.7 times higher (р=0.0023) than in patients with luminal B subtype. All cases diagnosed with the disease progression were characterized by low or negative level of nuclear androgen receptor expression.
Conclusion. Negative and low levels of androgen receptor expression in tumor tissues of postmenopausal patients with luminal primary operable breast cancer without overexpression of Her2/neu might be an independent factor associated with poor prognosis
Метаболизм триптофана при различном эффекте иммунотерапии немелкоклеточного рака легкого ингибиторами PD-1 / PD-L1
Introduction. In the structure of cancer incidence, lung cancer ranks first among men. In order to study the molecular mechanisms of the initiation and progression of lung cancer, it is necessary to study not only the tumor cells themselves, but also the features of the systemic tryptophan metabolism. Tryptophan catabolites, being to a large extent product of the metabolic activity of the intestinal microbiota, can affect the effectiveness of immunotherapy with checkpoint inhibitors. The kynurenine pathway of tryptophan metabolism is intensified in the body of cancer patients; its products have a pro-oncogenic and immunosuppressive effect, which may hinder the effectiveness of immunotherapy.Objective – to study the dynamics of changes in various metabolites of tryptophan metabolism in the blood serum and feces of patients with non-small cell lung cancer with various effects of immunotherapy with inhibitors of PD-1 (programmed cell death receptor 1) / PD-L1 (programmed cell death receptor 1 ligand).Materials and methods. The study included blood serum and stool samples obtained from 20 patients with non-small cell lung cancer treated with PD-1 / PD-L1 inhibitors. Using high-performance liquid chromatography with mass spectrometric analysis, the levels of 13 tryptophan metabolites were assessed in patients with various effects of immunotherapy. The significance of differences between the samples was assessed using a nonparametric method according to the Mann – Whitney test. They were considered statistically significant at p <0.05.Results. In fecal analyzes of patients in whom a positive effect of immunotherapy was observed, baseline levels of 5-hydroxyindole acetate and quinolinic acid were lower than in patients with tumor progression. Positive clinical dynamics was accompanied by a decrease in the content of indole-3-lactate, kynurenine and indole-3-carboxaldehyde in the feces of patients. In the serum of patients with a positive response, the initial content of 5-hydroxyindole acetate, indole-3-acetate, indole-3-butyrate and quinoline acid was lower than in patients with progression of non-small cell lung cancer. A positive response to immunotherapy was characterized by an increase in the levels of indole-3-butyrate and indole-3-propionate, and a negative response was not accompanied by statistically significant changes in the studied tryptophan metabolites.Conclusion. Profiling tryptophan metabolites in feces and serum of patients with non-small cell lung cancer can be used to predict the effectiveness of immunotherapy with PD-1 / PD-L1 inhibitors.Введение. В структуре онкологической заболеваемости рак легкого занимает 1-е место среди мужчин. С целью изучения молекулярных механизмов инициации и прогрессирования рака легких необходимо исследовать не только сами опухолевые клетки, но и особенности системного метаболизма триптофана. Катаболиты триптофана, будучи в большой степени продуктами метаболической активности микробиоты кишечника, могут влиять на эффективность проведения иммунотерапии ингибиторами контрольных точек. Кинурениновый путь метаболизма триптофана интенсифицируется в организме онкологических пациентов, его продукты имеют проонкогенное и иммуносупрессивное действие, что может препятствовать эффективности иммунотерапии.Цель исследования – изучение динамики изменений различных метаболитов триптофанового обмена в сыворотке крови и кале больных немелкоклеточным раком легкого при различных эффектах иммунотерапии ингибиторами PD-1 (рецептора программируемой клеточной гибели 1) / PD-L1 (лиганда рецептора программируемой клеточной гибели 1).Материалы и методы. В исследование были включены образцы сыворотки крови и кала, полученные от 20 больных немелкоклеточным раком легкого, получавших ингибиторы PD-1 / PD-L1. С помощью высокоэффективной жидкостной хроматографии с масс-спектрометрическим анализом проведена оценка уровней 13 метаболитов триптофана у больных с различными эффектами иммунотерапии. Достоверность различий между выборками оценивали с помощью непараметрического метода по критерию Манна–Уитни. Они считались статистически значимыми при р <0,05.Результаты. В анализах кала пациентов, у которых наблюдали положительный эффект от иммунотерапии, исходные уровни 5-гидроксииндолацетата и хинолиновой кислоты были ниже, чем у больных с прогрессированием опухоли. Положительная клиническая динамика сопровождалась снижением содержания индол-3-лактата, кинуренина и индол-3-карбоксальдегида в анализах кала больных. В сыворотке пациентов с положительным ответом исходное содержание 5-гидроксииндолацетата, индол-3-ацетата, индол-3-бутирата и хинолиновой кислоты оказалось ниже, чем у пациентов с прогрессированием немелкоклеточного рака легкого. Положительный ответ на иммунотерапию характеризовался повышением уровней индол-3-бутирата и индол-3-пропионата, а отрицательный – не сопровождался статистически значимыми изменениями исследованных триптофановых метаболитов.Заключение. Профилирование метаболитов триптофана в кале и сыворотке больных немелкоклеточным раком легкого может быть использовано для прогнозирования эффективности иммунотерапии ингибиторами PD-1 / PD-L1
«Кинурениновый переключатель» и ожирение
Aim. To assess the concentrations of bacterial and eukaryotic metabolites mainly involved in indole, kynurenine, and serotonin pathways of tryptophan metabolism in a cohort of patients with obesity. Materials and methods. Using high-performance liquid chromatography with mass spectrometric detection, the concentrations of several serum metabolites, such as kynurenine, kynurenic acid, anthranilic acid, xanthurenic acid, quinolinic acid, 5-hydroxyindole-3-acetate, tryptamine, serotonin, indole-3-lactate, indole-3-acetate, indole-3- butyrate, indole-3-carboxaldehyde, indole-3-acrylate, and indole-3-propionate, were analyzed in a cohort of obese patients compared with healthy volunteers.Results. It was found that serum levels of tryptophan metabolites of microbial and eukaryotic origin were significantly increased in obese patients. Therefore, the concentration of kynurenine in the blood serum in obese patients was 2,413 ± 855 nmol / l, while in healthy volunteers of the same age group, the level of kynurenine in the blood serum was 2,122 ± 863 nmol / l. In obese patients, two acids formed due to kynurenine metabolism; the concentrations of kynurenic and quinolinic acids were increased in the blood serum. The concentration of kynurenic acid in the blood serum in obese patients was 21.1 ± 9.26 nmol / l, and in healthy patients, it was 16.8 ± 8.37 nmol / l. At the same time, the level of quinolinic acid in the blood serum in obese patients was 73.1 ± 54.4 nmol / l and in healthy volunteers – 56.8 ± 34.1 nmol / l. Normally, the level of quinolinic acid is 3.4 times higher than the concentration of kynurenic acid, and in case of obesity, there is a comparable increase in these acids in the blood serum.From indole derivatives, mainly of microbial origin, the concentrations of indole-3-lactate, indole-3-butyrate, and indole-3-acetate were significantly increased in the blood serum of obese patients. In obese patients, the serum concentration of 5-hydroxyindole-3-acetate was elevated to 74.6 ± 75.8 nmol / l (in healthy volunteers – 59.4 ± 36.6 nmol / l); indole-3-lactate – to 523 ± 251 nmol / l (in healthy volunteers – 433 ± 208 nmol / l); indole-3-acetate – to 1,633 ± 1,166 nmol / l (in healthy volunteers – 1,186 ± 826 nmol / l); and indole-3-butyrate – to 4.61 ± 3.31 nmol / l (in healthy volunteers – 3.85 ± 2.51 nmol / l).Conclusion. In case of obesity, the utilization of tryptophan was intensified by both the microbiota population and the macroorganism. It was found that obese patients had higher concentrations of kynurenine, quinolinic and kynurenic acids, indole-3-acetate, indole-3-lactate, indole-3-butyrate, and 5-hydroxyindole-3-acetate. Apparently, against the background of increased production of proinflammatory cytokines by adipocytes in obese patients, the “kynurenine switch” was activated which contributed to subsequent overproduction of tryptophan metabolites involved in the immune function of the macroorganism. Цель. Изучить содержание метаболитов бактериального и эукариотического происхождения индольного, кинуренинового и серотонинового путей обмена триптофана у пациентов с ожирением.Материалы и методы. Методом высокоэффективной жидкостной хроматографии с масс-спектрометрическим детектированием изучили концентрации сывороточных метаболитов: кинуренина, кинуреновой кислоты, антраниловой кислоты, ксантуреновой кислоты, хинолиновой кислоты, 5-гидросииндол-3-ацетата, триптамина, серотонина, индол-3-лактата, индол-3-ацетата, индол-3-бутирата, индол-3-карбоксальдегида, индол-3-акрилата, индол-3-пропионата у пациентов с ожирением в сравнении с группой здоровых добровольцев.Результаты. Установлено, что у пациентов с ожирением в сыворотке крови статистически значимо повышен уровень метаболитов триптофанового обмена микробиотического и эукариотического происхождения. Концентрация кинуренина в сыворотке крови у больных с ожирением составляла 2 413 ± 855 нмоль/л, тогда как у здоровых добровольцев такой же возрастной группы – 2 122 ± 863 нмоль/л. Также у пациентов с ожирением в сыворотке крови были повышены две кислоты, которые образуются в результате метаболизма кинуренина – кинуреновая и хинолиновая. Концентрация кинуреновой кислоты в сыворотке крови у пациентов с ожирением составляла 21,1 ± 9,26 нмоль/л, а у здоровых 16,8 ± 8,37 нмоль/л соответственно. Тогда как концентрация хинолиновой кислоты в сыворотке крови при ожирении – 73,1 ± 54,4 нмоль/л, а у здоровых добровольцев – 56,8 ± 34,1 нмоль/л. В норме концентрация хинолиновой кислоты в 3,4 раза выше, чем концентрация кинуреновой кислоты, а при ожирении происходит сопоставимое их повышение. Из производных индола, которые имеют преимущественно микробиотическое происхождение, в сыворотке крови пациентов с ожирением статистически значимо повышена концентрация индол-3-лактата, индол-3-бутирата и индол-3-ацетата. У пациентов с ожирением концентрация в сыворотке крови метаболита серотонина – 5-гидроксииндол-3-ацетата – была повышена и составляла 74,6 ± 75,8 нмоль/л (у здоровых добровольцев – 59,4 ± 36,6 нмоль/л); индол-3-лактата – 523 ± 251 нмоль/л (у здоровых добровольцев 433 ± 208 нмоль/л); индол-3-ацетата – 1 633 ± 1166 нмоль/л (у здоровых добровольцев 1 186 ± 826 нмоль/л); индол-3-бутирата – 4,61 ± 3,31 нмоль/л (у здоровых добровольцев 3,85 ± 2,51 нмоль/л).Заключение. При ожирении происходит интенсификация утилизации триптофана как микробиотической популяцией кишечника, так и макроорганизмом. Установлено, что больные с ожирением имеют более высокие концентрации кинуренина, хинолиновой и кинуреновой кислот, индол-3-ацетата, индол-3-лактата, индол-3-бутирата и 5-гидроксииндол-3-ацетата. Видимо, на фоне гиперпродукции провоспалительных цитокинов адипоцитами у пациентов с ожирением срабатывает «кинурениновый переключатель», что и обеспечивает гиперпродукцию метаболитов триптофанового обмена, которые вовлечены в иммунологическую функцию макроорганизма.
Seabirds enhance coral reef productivity and functioning in the absence of invasive rats
Biotic connectivity between ecosystems can provide major transport of organic matter and nutrients, influencing ecosystem structure and productivity1, yet the implications are poorly understood owing to human disruptions of natural flows2. When abundant, seabirds feeding in the open ocean transport large quantities of nutrients onto islands, enhancing the productivity of island fauna and flora3,4. Whether leaching of these nutrients back into the sea influences the productivity, structure and functioning of adjacent coral reef ecosystems is not known. Here we address this question using a rare natural experiment in the Chagos Archipelago, in which some islands are rat-infested and others are rat-free. We found that seabird densities and nitrogen deposition rates are 760 and 251 times higher, respectively, on islands where humans have not introduced rats. Consequently, rat-free islands had substantially higher nitrogen stable isotope (δ15N) values in soils and shrubs, reflecting pelagic nutrient sources. These higher values of δ15N were also apparent in macroalgae, filter-feeding sponges, turf algae and fish on adjacent coral reefs. Herbivorous damselfish on reefs adjacent to the rat-free islands grew faster, and fish communities had higher biomass across trophic feeding groups, with 48% greater overall biomass. Rates of two critical ecosystem functions, grazing and bioerosion, were 3.2 and 3.8 times higher, respectively, adjacent to rat-free islands. Collectively, these results reveal how rat introductions disrupt nutrient flows among pelagic, island and coral reef ecosystems. Thus, rat eradication on oceanic islands should be a high conservation priority as it is likely to benefit terrestrial ecosystems and enhance coral reef productivity and functioning by restoring seabird-derived nutrient subsidies from large areas of ocean
T9
Metformin is a antidiabetic drug with anticancer properties. However, the mechanism action by which metformin affects various cancer cells still unknown. It is known that tumor growth is accompanied by changes in the metabolic cascade that includes overproduction of lactate and adenosine. The adenosine is released into the extracellular environment and regulates differentiation, proliferation, and angiogenesis of tumor mass. We found that lactate is activator of key enzyme of adenosine metabolism – adenosine deaminase (ADA).
Aim: The aim of our study was to investigate the catabolism of adenosine in the tumor while taking metformin.
Materials and methods: In this study we investigated the level of adenosine, inosine, hypoxanthine and ADA activity in 15 women aged 46–76 years, with breast cancer (BC) T2-4N1M0 (cancer tissues) during treatment with metformin, 1000 mg per day for 3 months. Control group – 15 women aged 46–76 years, with stage T2-4N1M0 breast cancer (cancer tissues) without metformin therapy.
Statistical analysis was performed using the license package StatSoft. Statistica 12.0.
Results: ADA activity during treatment with metformin was 2-fold increased: 12.1 ± 2.49 nmol/min*mg in comparison with 4.77 ± 0.943 nmol/min*mg. Concentration of catabolic products of adenosine degradation was increased before metformin therapy. Inosine level was 0.121 ± 0.041 micro mol/g tissue (BC tissues from women without metformin 0.042 ± 0.015 micro mol/g tissue). Hypoxanthine 2.45 ± 0.428 micro mol/g tissue (in comparison with 0.711 ± 0.269 micro mol/g tissue). Whereas, adenosine level in BC after metformin therapy was 0.226 ± 0.148 micro mol/g tissue (in comparison with 0.186 ± 0.056 micro mol/g tissue), that were not significantly different.
Conclusion: Thus, we have found that metformin significantly increases the rate of catabolism of adenosine, and this in turn reduces the inhibitory effect on the tumor microenvironment cytotoxic cells. Therefore, our data for the first time provide novel evidence for a mechanism that the anticancer activities of metformin are due to adenosine metabolism regulation
PDGF ENZYMATIC ACTIVITY IN PATIENTS WITH DELAYED FRACTURE CONSOLIDATION
Introduction. Techniques that use growth factors to improve bone fragment consolidation and to treat the inflammatory and degenerative diseases of the musculoskeletal system have become very popular. Many researchers are actively searching for personification of this therapy and the reasons for delayed consolidation. The purpose of the study – to identify the biomarker for delayed bone consolidation.Materials and Methods. The study groups consisted of patients with high-energy tibia open fractures with normal (group 1) and with delayed (2nd group) consolidation of bone fragments. The enzymatic activity of platelet-derived growth factor (PDGF) in blood serum was studied after 7 days and in 1, 3 and 6 months after bone fragments reduction. Spectrophotometric technique (Specord-200) was used.Results. In patients with normal consolidation of bone fragments, the enzymatic activity of PDGF was statistically significantly higher in comparison with the group with delayed healing. At the same time, the highest activity was reported on day 7, and by third month it was becoming lower.Conclusion. Bone healing depends on PDGF enzymatic activity, besides significant differences on various stages of healing were observed. Further study the reasons for the PDGF enzymatic deficiency and its correction are of a great interest for reducing the timing of consolidation