Estimations of electron-positron pair production at high-intensity laser interaction with high-Z targets

Electron-positron pairs' generation occuring in the interaction of $10^{18}$-$10^{20}$~W/cm$^2$ laser radiation with high-Z targets are examined. Computational results are presented for the pair production and the positron yield from the target with allowance for the contribution of pair production processes due to electrons and bremsstrahlung photons. Monte-Carlo simulations using the PRIZMA code confirm the estimates obtained. The possible positron yield from high-Z targets irradiated by picosecond lasers of power $10^2$-$10^3$~TW is estimated to be $10^9$-$10^{11}$

STRUCTURAL TRANSFORMATIONS IN AXILLARY AND MESENTERIC LYMPH NODES IN CHEMOTHERAPY AND SURGICAL TREATMENT OF EXPERIMENTAL MAMMARY TUMOR

Was conducted histological study axillary and mesenteric lymph nodes in breast cancer induced by intramammary administration of N-methyl-N-nitrosourea, chemotherapy according to the CMF scheme (cyclophosphamide, methotrexate, 5-fluorouracil), operative removal of breast tumors (6.5 months from the beginning of the experiment). The results of the study. At chemotherapy of breast cancer, compared with the group with breast cancer without treatment, there was a decrease in the number of tumor cells in the axillary lymph nodes in comparison with mesenteric lymph nodes. The decrease in the area of the paracortical zone and the area of secondary lymphoid nodes remain in the axillary lymph nodes, in comparison with breast cancer without treatment. The reduction of the paracortical zone square remains in mesenteric lymph nodes. The area of lymphoid nodules with germinative centers decreases. The number of postcapillary venules with high endothelium and the number of macrophages in structural zones grow down. In the axillary lymph nodes after surgical treatment of breast cancer and chemotherapy in comparison with the treatment of breast cancer only with cytostatics, there is decrease in the area of the paracortical zone (with an increase in the number of small lymphocytes) and medullare cords. The area of lymphoid nodules with germinative and without germinative centers increases. In mesenteric lymph nodes, drainage function is reduced, increased the area of the paracortical zone, reduced the areas of lymphoid nodules with germinative centers and medullare cords (increased proliferative activity of cells), macrophage reaction in the cortical substance was revealed. Conclusion. The severity of structural transformations in cytoarchitectonics of the axillary and mesenteric lymph nodes depends on the treatment method

EFFECT OF ERYTHROPOIETIN ON CYTOKINE PRODUCTION BY STEM CELLS

Erythropoietin (EPO) is mainly used to stimulate erythropoiesis. Its cytoprotective effects upon other cells of the human body and animals were recently shown, in particular, anti-apoptotic effect was observed. EPO effect upon the cells is mediated by interaction with erythropoietin receptor, with a complex forming a heterodimeric bond with β-common chain (CD131). In the present work, we studied the changes in erythropoietin receptor expression, and production spectrum of biologically active molecules in bone marrow mononuclear cells (BM-MNC) of patients with coronary heart disease. The flow cytometric assays showed that short-term incubation of BM-MNC with erythropoietin caused increased expression of the erythropoietin receptors on hematopoietic stem cells and tended to reduce the number of endothelial progenitor cells carrying the erythropoietin receptors. Solid-phase enzyme immunoassay in conditioned media from BM-MNC revealed that long-term (72 hours) exposure of BM-MNC to erythropoietin promoted increased production of IL-1β, PDGF-AB, and Epo, if compared to the basal production level (p < 0.05). Short-term incubation of BM-MNC with erythropoietin (60 minutes) caused a significant increase in the IL-1β, PDGF-AB and CXCL-12 / SDF-1α production levels, as well as significant reduction in the IL-10 production levels compared to the basal levels (p < 0.05)

Effect of erythropoietin on bone marrow mononuclear cells

Stem/progenitor cells are considered an alternative method of heart failure therapy by promoting regeneration of damaged myocardium in myocardial infarction. Effectiveness of cell therapy depends on the population composition and functional activity of the cell graft, and, in turn, it depends on the conditions of microenvironment. Cultivation of stem/progenitor cells with erythropoietin stimulates proliferative potential causing in vitro resistance to hypoxia, and in vivo stimulation of angiogenesis. We aimed for assessing effects of erythropoietin upon hematopoietic cells. We studied some effects of short-term incubation of bone marrow mononuclear cells (BM-MNCs) in patients with coronary heart disease (CHD) with erythropoietin upon cellular phenotype, cell cycle, apoptosis and their proliferative potential. BM-MNCs were isolated from bone marrow aspirate from patients with CHD in a density gradient, then incubated for 60 minutes with erythropoietin (33.4 IU/ml). Using flow cytometric assay of the total BM-MNCs pool, we have shown there endothelial progenitor cells at different stages of maturation and differentiation, mesenchymal stem cells are. Their total number did not exceed 30%. Short-term incubation of BM-MNCs with erythropoietin reduces expression of CD184 “homing receptor” molecules on CD34+ cells, and causes increase of CD184 on CD31+ cells in the BM-MNCs pool (p < 0.05). In addition, erythropoietin has been shown to cause a delay of CD34+ cells in the resting phase (G0G1), reduce a proportion of cells in the synthetic phase (S) and mitosis (G2/M) (p<0.05), and does not affect apoptosis, as shown by Annexin V-FITC Apoptosis Detection Kit. Erythropoietin had no significant effects on expression on BM-MNCs surface molecules involved in providing adhesion, such as CD18, CD29, CD44, CD49a, CD54, CD62E, CD146, and CD202b. MTT-method has shown that the short-term preincubation of BM-MNCs with erythropoietin contributed to a significant decrease in proliferative activity of BM-MNCs (p < 0.05). However, there was a tendency towards increased resistance of erythropoietin-pretreated BM-MNCs to oxidative stress induced by hydrogen peroxide. We have also revealed a correlation between the numbers of endothelial progenitor cells at different stages of differentiation, and numbers of hematopoietic stem cells in the total BM-MNCs pool. The number of CD34+/CD133+, CD34- / CD31+, CD45+/EpoR+, and CD34+/EpoR+ in BM-MNCs pool are dependent on the age of patients. Hence, a short-term incubation of BM-MNCs with erythropoietin promotes the cells to be retained in resting phase of the cell cycle, thus, in turn, helping to reduce proliferative potential of BM-MNCs

CORRELATION BETWEEN CYTOKINE CONTENT IN LYMPH OF THORACIC LYMPH DUCT AND MESENTERIC LYMPH NODE STRUCTURAL TRANSFORMATIONS IN EXPERIMENTAL MAMMARY TUMOR AND CHEMOTHERAPY

The aim of the study was to fulfill correlation analysis of morphometry of the mesenteric lymph nodes and the concentration of cytokines in the lymph of the thoracic duct in breast cancer induced by intramammary administration of N-methyl-N-nitrosourea, chemotherapy according to the CMF scheme (cyclophosphamide, methotrexate, 5-fluorouracil). The results of the study. At breast cancer revealed positive correlation: in the germinative centers and medullary cords of cytokine IL-5 with mitotically dividing cells, chemokines MIP-1α with average lymphocytes, in the germinative centers of immunoblasts with cytokine GRO/KC, in the paracortical zone chemokine MCP-1 with macrophages, reticular cells with IL-6 and M-CSF, in the medullary sinuses chemokine GRO/KC with small lymphocytes and mature plasma cells (number which decreases). All this may indicate the activity of the local immune response in the lymph nodes aimed on the antitumor protection. After chemotherapy of breast cancer, compared with breast cancer without treatment, revealed positive relationship, which may indicate increased immunomodulatory and antitumor actions of cytokines: correlation of interferon IFNγ with small lymphocytes (number which increased) and macrophages in the germinative centers and mitotically dividing cells in the medullary cords, correlation in the germinative centers of immunoblasts with MIP-1α and increased of number small lymphocytes in T-dependent zone lymph nodes, correlation in medullary cords of interleukin IL-17 with mature plasma cells (number which increased) , correlation of interleukin IL-18 with mature plasma cells in medullary sinuses. Conclusion. Study of the correlation of the concentration of cytokines in the lymph of the thoracic duct with structural changes in the mesenteric lymph nodes revealed dependencies aimed at increasing the immunomodulating and antitumor effects of cytokines

Spatio-temporal dynamics and plastic flow of vortices in superconductors with periodic arrays of pinning sites

We present simulations of flux-gradient-driven superconducting rigid vortices interacting with square and triangular arrays of columnar pinning sites in an increasing external magnetic field. These simulations allow us to quantitatively relate spatio-temporal microscopic information of the vortex lattice with typically measured macroscopic quantities, such as the magnetization $M(H)$. The flux lattice does not become completely commensurate with the pinning sites throughout the sample at the magnetization matching peaks, but forms a commensurate lattice in a region close to the edge of the sample. Matching fields related to unstable vortex configurations do not produce peaks in $M(H)$. We observe a variety of evolving complex flux profiles, including flat terraces or plateaus separated by winding current-carrying strings and, near the peaks in $M(H)$, plateaus only in certain regions, which move through the sample as the field increases

Особенности субпопуляционного состава дендритных клеток у больных ревматоидным артритом

Rheumatoid arthritis (RA) is one of the most common rheumatic diseases. Dendritic cells (DCs) as the main antigen-presenting cells play an important role in the pathogenesis of RA. There are two major DC populations: myeloid and plasmacytoid DCs (mDCs and pDCs). B cells as antibody-producing cells also play an important role in the pathogenesis of RA. The probability of achieving low disease activity and clinical and laboratory remission has been proven to be maximal in the very early period of the disease and in the patients who have not been previously prescribed disease-modifying antirheumatic drugs (DMARDs). In this connection, it is necessary to elaborate additional criteria and biomarkers for early RA.Objective: to investigate the subpopulation composition of DCs in patients with early-stage RA.Patients and methods. The investigation enrolled 60patients with RA who met the 2010 ACR/EULAR and the 1987ACR criteria. The patients with RA were divided into two groups: 1) 30patients with early RA (the disease duration was not more than 1 year); 2) 30 patients with advanced RA. A control group consisted of 30 patients with osteoarthritis (OA) who met the ACR criteria. All the patients with RA were treated with DMARDs. The patients with early RA had not previously received DMARDs; after being included in the study, they were prescribed methotrexate 15-20 mg/week. The patients with advanced RA took methotrexate 15-25 mg/week (n=24), sulfasalazine 2 g/day (n=5), or leflunomide 20 mg/day (n=1).At the first stage, the levels of different subpopulations of DCs and B lymphocytes were studied in the patients with early RA before initiation of therapy and in those with advanced RA and in the control persons. At the following stage, the time course of changes was investigated in the subpopulation composition of DCs and B lymphocytes during therapy.Results and discussion. The subpopulations of peripheral blood DCs in early RA were characterized. A subpopulation of mDCs was shown to dominate in the patients with early RA versus those with advanced RA or osteoarthritis (OA). In addition, the patients with RA showed a high B lymphocyte level. It was noted that there was no significant differences in the level of pDCs between RA and OA patients and there was an inverse relationship between the relative peripheral blood level of pDC and disease activity, which confirms the immunosuppressive role of pDCs in the pathogenesis of RA. The levels of mDCs and B lymphocytes during DMARD therapy were ascertained to significantly decrease to those seen in healthy donors.Conclusion. Thus, the findings suggest that the number of mDCs and B lymphocytes increases in patients with early RA, unlike those with OA. In addition, the change in the number of mDCs and B cells during therapy is associated with the dynamics of disease activity and may suppose that mDCs are a target for the action of DMARDs.Ревматоидный артрит (РА) является одним из наиболее распространенных ревматических заболеваний. Дендритные клетки (ДК) играют важную роль в патогенезе РА как основные антиген-презентирующие клетки. Выделяют две основные популяции ДК: миелоидные (мДК) и плазмоцитоидные (пДК). Также важную роль в патогенезе РА играют В-клетки как клетки-антителопродуценты. Доказано, что вероятность достижения низкой активности и клинико-лабораторной ремиссии максимальна в самом раннем периоде заболевания и у тех пациентов, которым базисные противовоспалительные препараты (БПВП) ранее не назначали. В связи с этим необходима разработка дополнительных критериев, а также биомаркеров раннего РА.Цель исследования — изучить субпопуляционный состав ДК у больных РА на ранних стадиях заболевания.Пациенты и методы. В исследование включено 60 пациентов с РА, соответствующих критериям ACR/EULAR 2010 г. и ACR 1987 г. Пациенты с РА были разделены на две группы: в 1-ю группу вошли больные с ранним РА (длительность заболевания не более 1 года, n=30), во 2-ю — с развернутым РА (n=30). Контрольную группу составили 30 пациентов с остеоартритом (ОА), соответствующих критериям ACR. Всем пациентам с РА проводили терапию БПВП. Пациенты с ранним РА ранее не получали БПВП, после включения в исследование им был назначен метотрексат 15—20 мг/нед. Пациенты с развернутым РА получали метотрексат по 15—25мг/нед (n=24), сульфасалазин 2 г/сут (n=5) или лефлуномид 20мг/сут (n=1).На первом этапе проведено исследование уровня различных субпопуляций ДК, а также В-лимфоцитов у пациентов с ранней стадией РА до начала терапии, а также у пациентов с развернутым РА и в контрольной группе. На следующем этапе была изучена динамика субпопуляционного состава ДК и В-лимфоцитов на фоне терапии.Результаты и обсуждение. Охарактеризованы субпопуляции ДК периферической крови при раннем РА. Показано, что у пациентов с ранним РА, в отличие от пациентов с развернутым РА и остеоартритом (ОА), наблюдается доминирование субпопуляции мДК. Кроме того, пациенты с РА характеризуются высоким уровнем В-лимфоцитов. Отмечено отсутствие значимых различий в уровне пДК между пациентами с РА и ОА, также выявлена обратная связь между относительным содержанием пДК в периферической крови и активностью заболевания, что подтверждает иммуносупрессивную роль пДК в патогенезе РА. Установлено значимое снижение содержания мДК и В-лимфоцитов на фоне терапии БПВП до уровня здоровых доноров.Выводы. Таким образом, полученные данные свидетельствуют об увеличении числа мДК и В-лимфоцитов у пациентов с ранним РА в отличие от пациентов с ОА. Кроме того, изменение количества мДК и В-клеток на фоне терапии ассоциировано с динамикой активности заболевания и позволяет предположить, что мДК являются мишенью для воздействия БПВП

Клинико-функциональная оценка интрамиокардиальной имплантации аутологичных клеток костного мозга, обработанных эритропоэтином, в хирургии ИБС (6-месячные результаты)

Aim. Clinical and functional evaluation of the implantation of autologous bone marrow cells treated with erythropoietin in laser channels during coronary bypass grafting in patients with end-stage coronary lesion.Materials and methods. 60 patients with coronary artery disease with diffuse and (or) distal right coronary artery disease were randomized into two groups: patients of group 1 (n = 30) underwent coronary bypass grafting, implantation of autologous bone marrow cells treated with erythropoietin in laser channels, patients of the 2nd group (n = 30) were operated with coronary bypass grafting of the left coronary artery system. Assessment of the clinical status, myocardial perfusion and contractility was performed initially, 6 months after the operation.Results. Six months after the operation, there was a more pronounced decrease in angina pectoris (CCS) in the main group compared to the control group, also we revealed a 6-minute walk test scores improvement. Based on two-stage scintigraphy (Tc99) in the main group before the surgical treatment, a rest perfusion defect was 8.5% [3.5, 18.5], a stress-induced perfusion defect – 7.0% [6.0, 12, 3]. In the control group, the rest defect was 9.1% [5.6, 12.4], the stress-induced perfusion defect was 7.3% [6.1, 8.7]. 6 months after surgery rest perfusion defect at the indirect revascularization group was 6.0% [2.5, 16.5] (p = 0.008), a stress-induced defect was 4.0% [1.5, 6.3] (p = 0.05). In the control group, the rest defect was 8.7% [5.3, 10.3], the stress-induced perfusion defect was 6.8% [5.3, 9.1] (p = 0.21). The results of scintigraphy with MIBG showed a left ventricle innervation defect (PID) significant decrease in the main group: initially 15.4% [14.2, 16.3], after 6 months 11.7% [9.3, 13, 2] (p = 0.045). In the control group, there was an unreliable decrease in PID: initially 14.3% [10.2, 17.3], after 6 months 13.8% [9.1, 14.2] (p = 0.14).Conclusion. Our preliminary results revealed more pronounced effect of the new indirect revascularization method expressed as in myocardial perfusion improve, myocardial sympathetic innervation restoration and clinical status improvement in comparison with control group.Цель. Клинико-функциональная оценка эффекта применения трансмиокардиальной лазерной реваскуляризации в сочетании с имплантацией прекондиционированных эритропоэтином клеток аутологичного костного мозга в хирургии ишемической болезни сердца.Материалы и методы. Больные ИБС с диффузным и(или) дистальным поражением правой коронарной артерии (n = 60) рандомизированы на две группы: пациентам 1-й группы (n = 30) выполнено коронарное шунтирование, c имплантацией прекондиционированных эритропоэтином клеток аутологичного костного мозга в область нижней стенки левого желудочка, пациентам 2-й группы (группа контроля, n = 30) выполнено коронарное шунтирование системы левой коронарной артерии. Оценка клинического статуса, перфузии и сократительной способности миокарда выполнена исходно, через 6 месяцев после операции.Результаты. Через 6 месяцев после операции выявлено более выраженное снижение функционального класса (ФК) стенокардии (ССS) в основной группе по сравнению с группой контроля, улучшение показателей теста 6-минутной ходьбы. По результатам двухэтапной сцинтиграфии миокарда с технетрилом (Тс99) М в основной группе до хирургического лечения отмечен стойкий дефект перфузии 8,5% [3,5; 18,5], стресс-индуцированный дефект перфузии 7,0% [6,0; 12,3]. В контрольной группе – стабильный дефект 9,1% [5,6; 12,4], стресс-индуцированный дефект перфузии 7,3% [6,1; 8,7]. Через 6 месяцев в основной группе стойкий дефект перфузии составил 6,0% [2,5; 16,5] (p = 0,008), стресс-индуцированный дефект – до 4,0% [1,5; 6,3] (p = 0,05). В контрольной группе – стабильный дефект 8,7% [5,3; 10,3], стресс-индуцированный дефект перфузии 6,8% [5,3; 9,1] (р = 0,21). Результаты сцинтиграфии с МIBG демонстрируют значимое уменьшение площади дефекта иннервации (ПДИ) в сегментах нижней стенки левого желудочка в основной группе: исходно 15,4% [14,2; 16,3], через 6 месяцев 11,7% [9,3; 13,2] (р = 0,045). В контрольной группе выявлено недостоверное уменьшение ПДИ: исходно 14,3% [10,2; 17,3], через 6 месяцев 13,8% [9,1; 14,2] (р = 0,14).Заключение. Исследование продемонстрировало улучшение перфузии в зоне непрямой реваскуляризации, восстановление симпатической иннервации миокарда, лучшие показатели ФК (CCS), теста 6-минутной ходьбы у пациентов в основной группе

УРОВНИ ГОРМОНОВ, микроРНК И ЦИТОКИНОВ В ЛИМФЕ В НОРМЕ И ПРИ РАКЕ МОЛОЧНОЙ ЖЕЛЕЗЫ В ЭКСПЕРИМЕНТЕ

The involvement of hormones, microRNAs and cytokines in breast cancer pathogenesis has been well established. Lymph picks up secretory products of breast cancer cells. The purpose of the study was to evaluate the levels of hormones, microRNAs and cytokines in lymph. Wistar rats were injected with N-methyl-N-nitrosourea to induce breast cancer. The rats were subjected to either surgery alone or chemotherapy alone (cyclophosphamide, methotrexate and 5-fluorouracil). In some animals, surgery was followed by chemotherapy. The levels of follicle-stimulating hormone (FSH), prolactin, luteinizing hormone (LH), estradiol (E2) and thyroglobulin (TG), microRNA-21, microRNA-221, microRNA-222, microRNA-429 and 24 cytokines were determined. Chemotherapy was shown to result in the reduction in the levels of prolactin, thyroglobulin, FSH and estradiol. In rats with breast cancer, the expression levels of microRNA-21, microRNA-221 and microRNA-222 were increased, and the expression levels of microRNA-429 were decreased. In breast cancer rats, the levels of most cytokines were found to be increased. Correlations between the levels of cytokines, hormones, and microRNAs in lymph were identified. Differences in the expression levels of cytokines, hormones, and microRNAs in lymph with respect to treatment option were detected.Цель исследования – оценка уровней гормонов, микроРНК и цитокинов в лимфе.Материал и методы. Экспериментальный рак молочной железы индуцировали введением N-метил-N-нитрозомочевины у крыс Wistar. Часть животных подвергалась только оперативному вмешательству или только химиотерапии (циклофосфан, метотрексат, 5-фторурацил). У части животных сочетали оперативное вмешательство с последующим курсом ХТ. В лимфе исследовали содержание фолликулостимулирующего гормона (ФСГ), пролактина, лютеинизирующего гормона (ЛГ), эстрадиола (Е2) и тириоглобулина (ТГ), микроРНК-21, микроРНК-221, микроРНК-222, микроРНК-429 и 24 цитокинов.Результаты. Показано, что на фоне ХТ снижаются уровни пролактина, тиреоглобулина, ФСГ и эстрадиола. В группе животных с РМЖ увеличены уровни экспрессии микроРНК-21, микроРНК-221, микроРНК-222 и снижены уровни экспрессии микроРНК-429. При РМЖ в лимфе увеличены уровни большинства цитокинов. Между уровнями в лимфе цитокинов, гормонов и микроРНК определены взаимосвязи. В лимфе выявляются различные уровни цитокинов, гормонов и микроРНК с учетом вида проведенного лечения