New forecasting model of a lethality at a cirrhosis of a liver of a virus and alcoholic etiology

With the purpose of building of the new prognostic model including only quantitative variables, absent in model Child—Pugh, and allowing to define the individual forecast at sick of a cirrhosis of a liver (CL) of a virus and alcoholic etiology, it is lead uniinstantly prospective research of 249 sick CL virus (В, С, B+C), and an alcoholic etiology. Age of patients from 17 till 75 years (Me=50 years), 114 men and 135 women. For the season of observation (from 10 days till 57 months) 119 patients have died. Comparison on indexes of a biochemical analysis of a blood, a haemogram and a portal hemodynamic between the died and persisted patients on the seasons 1,3.6 and 12 months is lead. As a result of carrying out logistical regression analysis with including the received prognostic factors (leukocytosis, anemia, lymphopenia, aspartate aminotransferase - AST, creatinine), the prognostic model including nuclear heating plant and a creatinine is received: e(b0+b1*AST+b2*creatinine)/(1+e(b0+b1*AST+b2*creatinine)), where P - probability of offensive of a lethal outcome; e - the mathematical constant peer 2,72; AST - mmol/l; creatinine – mmol/1. A constant b0 and regressions quotients b, and b2 for each prognostic season (1, 3 and 6 months) are sizes constants. The new model is comparable on prognostic accuracy to model Child-Pugh, but follow- p allows to define the individual forecast of offensive of a lethal outcome within 1. 3 and 6 months at sick CL.Цель. Создание новой прогностической модели, не включающей переменные, содержащиеся в модели Чайлда-Пью и позволяющей определять индивидуальный прогноз больных циррозом печени (ЦП), а не последовательность наступления летальных случаев в популяции больных ЦП, определяемую моделью Чайлда-Пью. Материал и методы. Проведено обсервационное одномоментное проспективное исследование 249 больных ЦП вирусной (В, С), алкогольной и алкогольно-вирусной этиологии. Возраст от 17 до 75 лет (Ме=50 лет), 114 мужчин и 135 женщин. За период наблюдения (от 10 дней до 57 недель) умерли 119 пациентов. Проведено сравнение по показателям биохимического анализа крови, гемограммы и портальной гемодинамики между умершими и выжившими больными по периодам 1,3,6 и 12 месяцев. Результаты В результате проведения логистического регрессионного анализа с включением полученных прогностических факторов (лейкоцитоз, анемия, лимфопения, ACT, креатикин), получена прогностическая модель, включающая ACT и креа-тинин- Р = e(b0+b1*АСТ+b2*креатинин)/(1+e(b0+b1*AСT+b2*креатинин)), где Р — вероятность наступления летального исхода; е — математическая константа, равная 2,72; b0 — константа регрессионного уравнения; b, — регрессионный коэффициент для ACT; b2 — регрессионный коэффициент для креатинина; ACT — Ед/л; креатинин - мкмоль/л. Процент успешной классификации случаев — 75%, 83,6% и 92,3% для 6, 3 и 1 месяца соответственно. У модели Чайлда-Пью — 74,4%, 85,1% и 92% соответственно. Выводы Новая модель сопоставима по прогностической точности с моделью Чайлда-Пью, но позволяет определять индивидуальный прогноз наступления летального исхода в течение 1, 3 и 6 месяцев у больных ЦП

СВЯЗЬ МЕЖДУ РЕГУЛИРУЮЩИМИ БЕЛКАМИ АУТОФАГИИ M-TOR И BECLIN-1 И ПАРАМЕТРАМИ ЛИМФОГЕННОГО МЕТАСТАЗИРОВАНИЯ ПРИ КОЛОРЕКТАЛЬНОМ РАКЕ

Currently the impact of autophagy on carcinogenesis remains understudied. On the one hand, autophagy acts as a tumor suppressor, as it activates degradation of oncoproteins,  toxic proteins, and damaged cell organelles, that may be aggressive and lead to DNA  damage. On the other hand, autophagy may promote tumor cell survival under hypoxia and  in the presence of reactive oxygen species, which occurs primarily due to blocking of  apoptosis mechanisms, raising the chances for maintaining tumor clone dynamics.  Autophagy regulation is a complicated and multi-stage process. The main regulator here is a  signaling pathway that activates serine/threonine protein kinase m-TOR (the mammalian  target of rapamycin). Data on the impact of autophagic proteins ATG5, LC3A, LC3B, and  Beclin-1 on malignant cell survival as well as on tumor growth and progression have been  reported in literature. However, studies aimed at seeking possible relationships between autophagy and pathogenetic mechanisms of carcinogenesis are of great interest.The aim of the study is to investigate a relationship between the expression parameters of  autophagy regulatory proteins m-TOR and Beclin-1 and the features of lymphogenic metastasis in colorectal cancer.Materials and methods. The study included 105 patients with T1-4N0-3M0 colorectal cancer treated in the Thoracic and Abdominal Department of Cancer Research Institute of  Tomsk Research Medical Center from 2012 to 2015. The average age of patients was  59.7±4.3 years. Morphological verification of the diagnosis was performed on the biopsy  samples of primary tumor tissue. Staging of colorectal cancer was determined according to  the TNM classification of malignant tumors (2002).Results. Analysis of the frequency of lymphogenic metastasis depending on the presence or absence of m-Tor and Beclin-1 expression in tumor cell cytoplasm revealed a statistically significant link between these variables.Conclusion. The obtained findings clearly exhibit that deceleration or loss of autophagic  activity in the tumor is accompanied by implementation of lymphogenic dissemination, which is a predictor of an unfavorable outcome of the disease.На сегодняшний день влияние процессов аутофагии на канцерогенез остается не до конца изученным. С  одной стороны, аутофагия является опухолевым супрессором за счет активации разрушения онкогенных  протеинов, токсичных белков и дефектных органелл, которые могут обладать агрессивными свойствами и  способствовать повреждению ДНК клетки. C другой стороны, аутофагия может способствовать выживанию  опухолевых клеток в условиях гипоксии и присутствия активных форм кислорода, что происходит  преимущественно за счет блокировки механизмов апоптоза, увеличивая шансы на поддержание циркуляции  опухолевого клона. Регуляция аутофагии является сложным, многоэтапным и комплексным  процессом. Основным его регулятором является сигнальный путь, который активирует белок  протеинкиназосерин-треониновой специфичности m-Tor (мишень рапамицина у млекопитающих). В  литературе имеются данные о влиянии белков аутофагии ATG5, LC3A и LC3B, Beclin-1 на способность  злокачественно трансформированных клеток к выживанию, а также на развитие опухоли и ее прогрессирование. Крайне актуальными являются исследования, направленные на поиск возможных взаимосвязей между процессами аутофагии и патогенетическими механизмами канцерогенеза.Цель исследования – изучить взаимосвязь экспрессионных параметров белков-регуляторов аутофагии m-TOR и Beclin-1 с параметрами лимфогенного метастазирования при колоректальном раке.Материал и методы. В исследование были включены 105 пациентов с колоректальным раком T1–4N0–3M0,находившихся на лечении в отделении торако-абдоминальной онкологии НИИ онкологии Томского НИМЦ в  период с 2012 по 2015 г. Средний возраст больных составил 59,7±4,3 года. Морфологическая верификация  диагноза колоректального рака проводилась на биопсийном материале фрагментов ткани первичной  опухоли. Распространенность онкологического заболевания определялась согласно международной классификации по системе TNM (2002).Результаты. Анализ частоты лимфогенного метастазирования в зависимости от наличия или отсутствия  экспрессии белков m-Tor и Beclin-1 в цитоплазме опухолевых клеток выявил статистически значимую связь между этими параметрами.Заключение. Полученные данные отчетливо демонстрируют тот факт, что снижение или утрата активности  процессов аутофагии в опухоли сопровождается реализацией механизмов лимфогенной диссеминации, которая является предиктором неблагоприятного прогноза заболевания

Magnetic Field Structures in a Facular Region Observed by THEMIS and Hinode

The main objective of this paper is to build and compare vector magnetic maps obtained by two spectral polarimeters, i.e. THEMIS/MTR and Hinode SOT/SP, using two inversion codes (UNNOFIT and MELANIE) based on the Milne-Eddington solar atmosphere model. To this end, we used observations of a facular region within active region NOAA 10996 on 23 May 2008, and found consistent results concerning the field strength, azimuth and inclination distributions. Because SOT/SP is free from the seeing effect and has better spatial resolution, we were able to resolve small magnetic polarities with sizes of 1" to 2", and we could detect strong horizontal magnetic fields, which converge or diverge in negative or positive facular polarities. These findings support models which suggest the existence of small vertical flux tube bundles in faculae. A new method is proposed to get the relative formation heights of the multi-lines observed by MTR assuming the validity of a flux tube model for the faculae. We found that the Fe 1 6302.5 \AA line forms at a greater atmospheric height than the Fe 1 5250.2 \AA line.Comment: 20 pages, 9 figures, 3 tables, accepted for publication in Solar Physic

Acoustic Power Absorption and its Relation with Vector Magnetic Field of a Sunspot

The distribution of acoustic power over sunspots shows an enhanced absorption near the umbra--penumbra boundary. Earlier studies revealed that the region of enhanced absorption coincides with the region of strongest transverse potential field. The aim of this paper is to (i) utilize the high-resolution vector magnetograms derived using Hinode SOT/SP observations and study the relationship between the vector magnetic field and power absorption and (ii) study the variation of power absorption in sunspot penumbrae due to the presence of spine-like radial structures. It is found that (i) both potential and observed transverse fields peak at a similar radial distance from the center of the sunspot, and (ii) the magnitude of the transverse field, derived from Hinode observations, is much larger than the potential transverse field derived from SOHO/MDI longitudinal field observations. In the penumbra, the radial structures called spines (intra-spines) have stronger (weaker) field strength and are more vertical (horizontal). The absorption of acoustic power in the spine and intra-spine shows different behaviour with the absorption being larger in the spine as compared to the intra-spine.Comment: 18 pages, 7 figures, In Press Solar Physics, Topical Issue on Helio-and-Astroseismolog

Hypothesis: are neoplastic macrophages/microglia present in glioblastoma multiforme?

Most malignant brain tumours contain various numbers of cells with characteristics of activated or dysmorphic macrophages/microglia. These cells are generally considered part of the tumour stroma and are often described as TAM (tumour-associated macrophages). These types of cells are thought to either enhance or inhibit brain tumour progression. Recent evidence indicates that neoplastic cells with macrophage characteristics are found in numerous metastatic cancers of non-CNS (central nervous system) origin. Evidence is presented here suggesting that subpopulations of cells within human gliomas, specifically GBM (glioblastoma multiforme), are neoplastic macrophages/microglia. These cells are thought to arise following mitochondrial damage in fusion hybrids between neoplastic stem cells and macrophages/microglia

The effect of silver-containing sorbent on red blood cells during hemosorption: an <i>in vitro</i> study

The aim of the study was to investigate the influence of the original porous silver–containing sorbent on the morphofunctional parameters of red blood cells during in vitro hemoperfusion. Material and methods. Donor blood was perfused through glass columns filled with a sorbent based on porous aluminum oxide, polydimethylsiloxane and silver nanoclusters and a sorbent without silver. The effect of a silver-containing sorbent on the change in morphofunctional parameters of red blood cells after perfusion through sorbents was determined by scanning flow cytometry. Results and their discussion. Due to the uniformity of the distribution of silver (0.1 %) over the sorbent granules, the parameters of the porous structure – the specific surface area and pore volume – practically do not change compared to the sorbent without silver. Morphological parameters of original donor blood and after hemoperfusion are within the norm. The functional parameters are also normal, although the introduction of silver in to the sorbent slightly increases the number of active band 3 (B3) proteins on erythrocyte membranes, both in comparison with the donor red cell mass as a control and in comparison with the sorbent without silver. There is also an increase in the ultimate extensibility of the erythrocyte membrane compared to the original blood (2.2 times) and the sorbent without silver (1.4 times). Conclusions. A sorbent modified with silver and a sorbent without silver does not have a damaging toxic effect on the morphofunctional parameters of blood under perfusion conditions. The mechanisms affecting the indicators of the ultimate extensibility of the erythrocyte membrane after blood perfusion through a silver-containing sorbent require further research

РОЛЬ ПРОЦЕССОВ АУТОФАГИИ И АНГИОГЕНЕЗА ПРИ КОЛОРЕКТАЛЬНОМ РАКЕ

The purpose of the study was a review of available data on the role of autophagy and angiogenesis in the development, progression and prognosis of colorectal cancer. Material and methods. Databases searched were Medline, Cochrane Library and Elibrary. Of 340 studies, 48 were used to write a systematic review. Results. To date, there is a variety of prognostic markers used in the study of pathogenesis, diagnosis and treatment of colorectal cancer. The review describes the molecular mechanisms of the participation of various proteins of autophagy and angiogenesis in the pathogenesis and progression of colorectal cancer, and the potential importance of their use in clinical practice is presented. Conclusion. Many of the existing markers can be used not only in assessing the prognosis, but also sensitivity to chemotherapy. However, the contradictory results of studies with respect to certain proteins require further study, validation, and subsequent introduction into practice. Цель исследования – обобщение имеющихся данных о роли аутофагии и ангиогенеза в развитии, прогрессировании и оценке прогноза колоректального рака. Материал и методы. Поиск соответствующих источников производился в системах Medline, Cochrane Library, Elibrary. Из 340 найденных исследований 48 были использованы для написания систематического обзора. Результаты. На данный момент существует многообразие прогностических маркеров, используемых при изучении патогенеза, диагностике и лечении колоректального рака. В обзоре рассмотрены молекулярные механизмы участия различных белков аутофагии и ангиогенеза в патогенезе и прогрессировании коло- ректального рака, представлено потенциальное значение использования их в клинической практике. Заключение. Многие из существующих маркеров могут быть использованы при оценке не только прогноза, но и чувствительности к химиотерапии. Однако противоречивые результаты исследований в отношении некоторых белков требуют дальнейшего изучения, их валидации с последующим внедрением в практику.

Prognostic value of doppler sonography of the hepatic blood flow at sick of the cirrhosis of the liver

The purpose of work: to develop informative prognostic parameters of Doppler sonography a hepatic blood flow at sick of a cirrhosis of a liver (CL) of a virus and alcoholic etiology. Stuff and methods. It is lead uniinstantly prospective research of 88 sick CL virus (В, С, B+C) and alcoholic etiology in the age of from 30 years up to 71 years (Me=49,5 years), 33 men and 55 women. For 2 years of observation 37 patients have died. Are compared indexes of Doppler sonography a portal hemodynamic between the died and persisted patients on the seasons 6 ,1 2 ,1 8 and 24 months. Results: are formulated prognostic rules. Rule 1 (the forecast for 6 months): at VpeakHA (peak speed of a blood flow in a hepatic artery) > 103 sm/sec, probability of a lethality — 28,9%, and at VpeakHA 103 sm/sec, probability of a lethality — 73,3%, and at VpeaKHA 395 ml/min, probability of a lethality — 71,4%, and at VvolSMV 95sm/sec, probability of a lethality — 92 %, and at VpeaKHA 340 ml/min, probability of a lethality — 90,9%, and at VvolSMV 103 см/сек, вероятность летальности — 28,9%, а при VпикПА 103 см/сек, вероятность летальности — 73,3%, а при \/пикПА 395 мл/мин, вероятность летальности — 71,4%, а при Vo6B6B 95 см/сек, вероятность летальности — 92%, а при УпикПА 340 мл/мин, вероятность летальности — 90,9%, а при Vo6BБB < 340 мл/мин, вероятность отсутствия летальности — 47,3%. Выводь: ультразвуковая допплерография является информативной методикой прогноза у больных ЦП для периодов 6,18 и 24 мес

Estimation of acute toxicity of a drug based on the complex of lithium citrate, polymethylsiloxane, aluminum oxide

Research Institute of Clinical and Experimental Lymphology has developed an innovative drug based on a complex of lithium citrate, polymethylsiloxane and aluminum oxide (LOAP). Lithium-based drugs are effective in treating bipolar disorders. However, the toxic effects of lithium cause a “narrow therapeutic window”, which limits its clinical use. The creation of the drug LOAP was aimed at creating a prolonged form with a slow release of lithium to reduce toxic properties and use lithium citrate as an active pharmacological agent. At the moment, the lithium complex has no analogues. The purpose of the study was to study the parameters of acute toxicity of the LOAP. Material and methods. When studying acute toxicity, drugs were administered once intragastrically to mice and rats at doses of 12000, 10000, and 5000 mg/kg. Results. A single administration of drugs intragastrically through a probe in the maximum possible doses to mice and rats did not cause the death of animals and did not cause a locally irritating effect on the gastric mucosa. LOAP can be assigned to hazard class 4 (GOST 12.1.007-76)

Cell fusions in mammals

Cell fusions are important to fertilization, placentation, development of skeletal muscle and bone, calcium homeostasis and the immune defense system. Additionally, cell fusions participate in tissue repair and may be important to cancer development and progression. A large number of factors appear to regulate cell fusions, including receptors and ligands, membrane domain organizing proteins, proteases, signaling molecules and fusogenic proteins forming alpha-helical bundles that bring membranes close together. The syncytin family of proteins represent true fusogens and the founding member, syncytin-1, has been documented to be involved in fusions between placental trophoblasts, between cancer cells and between cancer cells and host cells. We review the literature with emphasis on the syncytin family and propose that syncytins may represent universal fusogens in primates and rodents, which work together with a number of other proteins to regulate the cell fusion machinery