Increasing Fatigue LIfe of 09Mn2Si Steel by means of High-Temperature Multistep Helical Rolling

The effect of high temperature helical rolling (HR) on structure and fatigue life of 09Mn2Si pipe steel has been studied. With the use of transmission electron microscopy there was revealed that rolling gives rise to refinement of ferrite grains and cracking (fracturing) of cementite plates within the pearlite phase. The effect manifests itself to the greatest extent in the surface layer where due to the rolling the level of plastic deformation was the highest. Data of microhardness measurements confirms the gradient pattern of strain hardening over the cross section during the HR occurs while the most intensive microhardness increasing take place at the depth of up to 3 mm. According to the mechanical testing results the helical rolling of 09Mn2Si steel gives rise to increasing the level of deforming stress at the yield plateau as well as the proportionality limit with a general decrease in the relative elongation. At the same time, despite the strain hardening resulting from the helical rolling the mechanisms of plastic deformation which manifest themselves in the form of parabolic hardening with a smooth decrease in the flow stress level after neck formation are preserved in the steel. During the cyclic tension the number of cycles prior to failure increases from 2.5 to 3.8 times that depends on the location of specimens' cutting from the rolled rod. The highest improvement in fatigue fracture resistance is registered for specimens cut out from the core of the rolled rods

Increasing Fatigue LIfe of 09Mn2Si Steel by means of High-Temperature Multistep Helical Rolling

The effect of high temperature helical rolling (HR) on structure and fatigue life of 09Mn2Si pipe steel has been studied. With the use of transmission electron microscopy there was revealed that rolling gives rise to refinement of ferrite grains and cracking (fracturing) of cementite plates within the pearlite phase. The effect manifests itself to the greatest extent in the surface layer where due to the rolling the level of plastic deformation was the highest. Data of microhardness measurements confirms the gradient pattern of strain hardening over the cross section during the HR occurs while the most intensive microhardness increasing take place at the depth of up to 3 mm. According to the mechanical testing results the helical rolling of 09Mn2Si steel gives rise to increasing the level of deforming stress at the yield plateau as well as the proportionality limit with a general decrease in the relative elongation. At the same time, despite the strain hardening resulting from the helical rolling the mechanisms of plastic deformation which manifest themselves in the form of parabolic hardening with a smooth decrease in the flow stress level after neck formation are preserved in the steel. During the cyclic tension the number of cycles prior to failure increases from 2.5 to 3.8 times that depends on the location of specimens' cutting from the rolled rod. The highest improvement in fatigue fracture resistance is registered for specimens cut out from the core of the rolled rods

Possibilities for predicting ventricular tachyarrhythmias in patients with heart failure with reduced ejection fraction based on surface electrocardiography. First results from a single-center prospective study

According to current clinical guidelines, the risk of life-threatening ventricular tachyarrhythmias (VTAs) in patients with heart failure (HF) is determined by left ventricular ejection fraction (LVEF). The available clinical and experimental data indicate the imperfection of this one-factor approach, which specifies the need to search for new predictors of VTAs. In this prospective study, we performed a comparative analysis of surface electrocardiographic parameters in HF patients with LVEF ≤35% without syncope or sustained ventricular arrhythmias in history, who were implanted with cardioverter defibrillator as a primary prevention of sudden cardiac death. During the two-year follow-up, the primary endpoint (new-onset persistent VTA episode, or VTA/ventricular fibrillation that required electrotherapy) was recorded in 42 patients (25,5%). The secondary endpoint (an increase in LVEF by 5% or more of the initial level against the background of cardiac resynchronization therapy) was more often recorded in the group of patients without VTAs (41 (33%) vs 4 (9,5%), p=0,005). The studied cohort of patients was characterized by a left axis deviation (72%), LV hypertrophy signs (84%), impaired intra-atrial (P wave duration of 120 (101-120) ms) and intraventricular conduction (QRS duration of 140 (110-180) ms), ventricular electrical systole prolongation (QTcor — 465 (438-504) ms). Differences between the groups divided depending on reaching the primary endpoint in terms of the Cornell product, Cornell voltage index and ICEB, as well as the detection rate of complete left bundle branch block morphology had levels of significance close to critical (p=0,09; p=0,05; p=0,1; p=0,09, respectively). The multivariate predictive model included following factors: Cornell product, Tp-Te/ QRS, P wave duration (diagnostic efficiency of the model was 60%: sensitivity, 61,1%, specificity, 59,6%; p=0,007)

EFFECT OF UROKINASE GENE-KNOCKOUT ON GROWTH OF MELANOMA IN EXPERIMENT

The purpose of the study was to reveal special features of the В16/F10 melanoma growth in urokinase (uPA) gene knockout mice with and without chronic neurogenic pain (CNP). Material and methods. The study included male and female С57ВL/6 mice (n = 102) and C57BL/6-Plautm1.1BugThisPlauGFDhu/GFDhu mice with uPA gene knockout  (n = 48). Mice of the main subgroups underwent subcutaneous transplantation of В16/F10 melanoma 2 weeks after bilateral ligation of sciatic nerves (CNP model); mice of the same strain with standard melanoma transplantation served as controls. Results and discussion. Survival of uPA gene knockout mice did not differ from that of normal animals – 1.5 times higher in females than in males (p < 0.05), with melanoma onset in gene-deficient mice a week earlier. The dynamics of tumor growth had pronounced gender differences: in females, the tumor did not grow and its maximal volume prior to death was 1.0 cm3, while tumors in males were characterized by an active growth with two peaks of volume increase (weeks 2 and 4). Melanoma was weakly metastatic – solitary metastases to the lungs (in females) or no metastases, but pulmonary and heart hemorrhages were noted (in males). CNP decreased the survival of uPA gene knockout females, as well as of normal animals, but did not influence the survival of males; primary tumors in genedeficient mice appeared a few days later than in controls but their growth was more intense, with diminished gender differences. Increased metastasis was manifested by the initiation of metastatic lesions to the lungs and liver in males, with maintained pulmonary hemorrhages, and by increased number of metastatic foci in the lungs together with the appearance of pulmonary hemorrhages in females. Conclusions. The influence of uPA gene knockout on the course of В16/F10 melanoma differs in male and female mice. CNP enhances malignant tumor growth, diminishing gender differences, and activates melanoma metastasis

Интенсивность хемилюминесценции, состояние антиоксидантной системы и окислительная модификация белков плазмы крови при развитии рецидива рака яичников

The state of antioxidant system (the activity of catalase and ceruloplasmine), the intensity of chemiluminescence, and oxidative modification of proteins were studied in blood plasma of 61 patients with ovarian cancer (cystadenocarcinoma) III–IV stage in state of remission and ones with a local recurrent tumor. The dynamics of these indices was analyzed in dependence of recurrent tumor vascularization. The statistically significant changes of the activity of some links of antioxidant system were found, as well as chemiluminescence intensity increase in blood plasma. The level of oxidative modificated protein molecules was raised, the most expressed for products of the main character (530 nm). The dynamics of level of carbonyl derivatives of the neutral and main character (370 and 530 nm) was opposite directed during intensification of recurrent tumour vascularization and increase in speed of blood-groove in a recurrent tumorУ 61 больной раком яичников (цистаденокарцинома) III–IV стадий в состоянии ремиссии и с локальным рецидивом ис- следованы в плазме крови интенсивность хемилюминесценции, состояние ряда звеньев антиоксидантной системы (активность каталазы, церулоплазмина) и уровень окислительной модификации белков общепринятыми спектрофотометрическими методами. Проанализирована динамика изученных показателей в крови больных с рецидивом в зависимости от интенсивности кровотока в рецидивной опухоли. Обнаружено достоверное изменение активности некоторых звеньев антиоксидантной системы, усиление хемилюминесценции плазмы крови. Показано увеличение степени окисленности белковых молекул, наиболее выраженное для продуктов основного характера (530 нм). По мере прогрессирования онкологического процесса при формировании рецидивной опухоли, усилении ее васкуляризации и увеличении скорости кровотока наблюдается противоположно направленная динамика уровня карбонильных производных нейтрального и основного характера (370 и 530 нм

ИЗУЧЕНИЕ ПОВРЕЖДЕННОСТИ ДНК КЛЕТОК КУЛЬТУРЫ HeLa МЕТОДОМ ДНК-КОМЕТ ПРИ КОМБИНИРОВАННОМ ВОЗДЕЙСТВИИ УЛЬТРАЗВУКОМ И 5-ФТОРУРАЦИЛОМ

To understand the mechanism of the effect of 5 % 5-fluorouracil (5-FU) gel used simultaneously with ultrasound (US ) on a tumor in patients with cervical cancer, the level of DNA damage was studied in vitro. We used cervical adenocarcinoma HeLa CC L-2 cells cultured under standard conditions in RPMI-1640 medium with 10 % fetal bovine serum and 50 μg / ml gentamicin. Ultrasound exposure lasted 10 min. (frequency of 0.88 MHz and intensity of 0.2 W / cm2). The 5-FU dose was 0.7 мкМ, with the time of exposure of 24 hours. In 24 hours after starting exposure, the level of DNA damage to the cells of the culture was studied using the comet assay in the alkaline version and evaluated by the % DNA parameter in the comet tail (% TDNA). The statistical significance of the differences was evaluated using the Mann-Whitney U test and Fisher’s exact test. The combined exposure to ultrasound / 5-FU led to a 5.2-fold increase in % TDNA compared to the control culture, % TDNA was 1.9 times higher after exposure to 5-FU alone and 3.0 times higher after exposure to ultrasound alone. In 24 hours after the combined exposure, less than 50 % of the culture cells had a low level of DNA damage (<10 % TDNA), i.e. completed the repair process and could continue to proliferate, and more than 30 % of the culture cells still had a high level of damage (>30 % TDNA) and were probably in the process of apoptosis. Thus, the results of the study showed that the combined effect of ultrasound / 5-FU on the HeLa culture helped to overcome resistance to chemotherapy, having a synergistic effect.Для понимания механизма эффективности локального применения 5 % геля 5-фторурацила (5-ФУ) с одновременным контактным ультразвуковым (УЗ) воздействием на опухоль у больных раком шейки матки в модельных условиях был изучен уровень поврежденности ДНК. Использована культура аденокарциномы шейки матки HeLa CC L-2, культивированная в стандартных условиях в среде RPMI-1640 с добавлением 10 % фетальной сыворотки теленка и 50 мкг/мл гентамицина. Воздействие ультразвуком осуществляли с помощью аппарата УЗТ-1.03У (Россия) в течение 10 мин с частотой 0,88 МГц и интенсивностью 0,2 Вт/см2. Доза 5-ФУ составила 0,7 мкМ, время воздействия 24 ч. Через 24 ч после начала воздействия уровень поврежденности ДНК клеток культуры исследовали методом ДНК-комет (Comet Assay) в щелочном варианте и оценивали по параметру % ДНК в хвосте кометы (% TDNA). Комбинированное воздействие УЗ/5-ФУ приводило к статистически значимому увеличению % TDNA – в 5,2 раза по сравнению с контрольной культурой, при этом % TDNA был в 1,9 раза выше показателя после воздействия только 5-ФУ и в 3,0 раза выше показателя после воздействия УЗ. Через 24 ч после комбинированного воздействия менее 50 % клеток культуры имели низкий уровень поврежденности ДНК (<10 % TDNA), то есть закончили процесс репарации и могли продолжить пролиферацию, а более 30 % клеток культуры все еще имели высокий уровень поврежденности (>30 % TDNA) и, вероятно, находились в процессе апоптоза. Таким образом, комбинированное воздействие УЗ/5-ФУ на культуру HeLa способствовало преодолению резистентности к химиопрепарату, оказывая синергический эффект

DNA damage in circulating leukocytes measured with the comet assay may predict the risk of death

The comet assay or single cell gel electrophoresis, is the most common method used to measure strand breaks and a variety of other DNA lesions in human populations. To estimate the risk of overall mortality, mortality by cause, and cancer incidence associated to DNA damage, a cohort of 2,403 healthy individuals (25,978 person-years) screened in 16 laboratories using the comet assay between 1996 and 2016 was followed-up. Kaplan-Meier analysis indicated a worse overall survival in the medium and high tertile of DNA damage (p < 0.001). The effect of DNA damage on survival was modelled according to Cox proportional hazard regression model. The adjusted hazard ratio (HR) was 1.42 (1.06-1.90) for overall mortality, and 1.94 (1.04-3.59) for diseases of the circulatory system in subjects with the highest tertile of DNA damage. The findings of this study provide epidemiological evidence encouraging the implementation of the comet assay in preventive strategies for non-communicable diseases

Уровень нейротрофинов в головном мозге у мышей с нокаутом гена урокиназы при экспериментальной меланоме и коморбидной патологии

The objective was to evaluate the levels of neurotrophins in the brain of mice with urokinase (uPA) gene knockout, carriers of B16/F10 melanoma developing in presence of comorbid pathology – chronic neurogenic pain (CNP).Methods and materials. The study included female mice of two strains: С57ВL/6 (n=40) and C57BL/6-PlautmI.IBug-ThisPlau6FDhu/GFDhu (n=28). In the main groups, CNP was created by the bilateral sciatic nerve ligation, with В16/F10 melanoma transplanted under the skin of the back 2 weeks after. The comparison groups included sham operated animals with melanoma transplantation, the control groups – sham operated animals and animals with CNP. Mice were decapitated on day 21 of the tumor growth, and the brain levels of brain neurotrophic factor (BDNF); nerve growth factor (NGF), neurotrophins 3 (NT3) and 4 (NT4) were studied by ELISA.Results. The brain of mice with uPA gene knockout demonstrated higher levels of NT3 (by 1.3 times (p=0.0146)), NT4 (by 2.6 times) and NGF-β (by 1.9 times (p=0.0021)) and lower BDNF (by 1.7 times (p=0.0203)), compared to mice without knockout. Cerebral reduction of NGF-β was a nonspecific brain response to CNP and neoplastic growth in female mice, enhanced in the combination of the pathological factors. Greater stimulation of subcutaneous melanoma growth in female mice with uPA knockout under the influence of CNP combined with a 2-fold decrease in levels of NT3 and BDNF in the brain, along with 2.2 times higher cerebral levels of NGF-β, compared to female mice without knockout.Conclusions. In female mice with uPA gene knockout compared to mice without knockout, we revealed background differences and other dynamics of neurotrophin levels in the brain at melanoma growth both alone and in combination with comorbid pathology – CNP.Цель – изучить уровень нейротрофинов в головном мозге мышей с нокаутом гена урокиназы (uPA), носителей меланомы B16/F10, растущей на фоне коморбидной патологии – хронической нейрогенной боли (ХНБ).Методы и материалы. Работа выполнена на самках мышей линий С57ВL/6 (n=40) и C57BL/6-PlautmI.IBugThisPlau6FDhu/GFDhu (n=28). В основных группах моделировали ХНБ двусторонней перевязкой седалищных нервов и через 2 недели под кожу спины перевивали меланому В16/F10. Группы сравнения – ложнооперированные животные с перевивкой меланомы. Контрольные группы – ложнооперированные животные и животные с ХНБ. На 21-е сутки опухолевого роста мышей декапитировали и в головном мозге методом иммуноферментного анализа определяли содержание нейротрофического фактора мозга (BDNF); фактора роста нервов (NGF), нейротрофинов-3 (NT3) и -4 (NT4).Результаты. У мышей с нокаутом по uPA было больше NT3 (в 1,3 раза (р=0,0146)), NT4 (в 2,6 раза) и NGF-β (в 1,9 раза (р=0,0021)) и меньше BDNF (в 1,7 раза (р=0,0203)). Неспецифическим ответом головного мозга самок мышей на ХНБ и неопластический рост являлась церебральная редукция NGF-β, выраженность которой увеличивалась при сочетании патологических факторов. Бóльшая стимуляция подкожного роста меланомы у самок мышей с нокаутом uPA под влиянием ХНБ сочеталась с двухкратным уменьшением содержания NT3 и BDNF в мозге на фоне в 2,2 раза бóльшего, чем у самок без нокаута, церебрального уровня NGF-β.Заключение. У самок мышей с нокаутом гена uPA, в отличие от мышей без нокаута, выявлены фоновые отличия и иная динамика уровней нейротрофинов в головном мозге при росте меланомы в самостоятельном варианте и на фоне коморбидной патологии – ХНБ