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

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

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)

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

Патология периферического кровообращения при хронической сердечной недостаточности

In the mechanisms of chronic heart failure (CHF) the key role traditionally given to a violation of intracardiac haemocirculation. Thus, in the guidelines for the evaluation and management of chronic heart failure in the adult, experts of the American College of Cardiology and the American Heart Association (2001-2013) define CHF as «a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood». Usually rightly believe that than the expression of inotropic and/or lusitropic failure of the appropriate ventricle in patients with CHF, the generally lower of him quality of life and a worse prognosis. However, the severity of the clinical manifestations of heart failure, on the one hand, and reducing the level of satisfaction with life - on the other, is not always depends only on the state of intracardiac hemodynamics. The authors of the review have analyzed papers published on the problem of the pathology of the peripheral circulation in CHF. Consistently examines the role of peripheral vascular remodeling and increased arterial stiffness, endothelial dysfunction of major and resistance arteries, as well as pathology of microcirculation. It has been shown that the development and progression of heart failure is accompanied by a deterioration in the peripheral circulation due to the remodeling of arteries muscular-elastic type and veins with a reduction in vascular dilatation reserve, increase of regional vascular resistance and venous tone, disturbances of tissue transcapillary exchange of oxygen and activate of procoagulant properties of blood. The significance of the effects of vasoconstrictor neurohormonal systems and inflammation in mechanisms of disorders of peripheral circulation in patients with CHF, particularly associated with the metabolic syndrome, have discussed.В механизмах развития хронической сердечной недостаточности (ХСН) ключевая роль традиционно отводится нарушению внутрисердечной гемоциркуляции. Так, в рекомендациях по оценке и лечению ХСН у взрослых эксперты Американской коллегии кардиологов и Американской ассоциации сердца (2001-2013 гг.) определяют ХСН как «сложный клинический синдром, который может быть вызван любым структурным или функциональным заболеванием сердца, нарушающим способность желудочка наполняться кровью или изгонять ее». Обычно справедливо полагают, что чем выраженнее инотропная и (или) люситропная несостоятельность соответствующего желудочка у пациента с ХСН, тем в целом ниже у него качество жизни и хуже прогноз. Вместе с тем степень выраженности клинических проявлений ХСН, с одной стороны, и снижение уровня удовлетворенности жизнью – с другой, далеко не всегда зависят только от состояния внутрисердечной гемодинамики. Авторы обзора анализируют работы, опубликованные по проблеме патологии периферического кровообращения при ХСН. Последовательно рассматривается роль ремоделирования периферических сосудов и увеличения жесткости артерий, дисфункции эндотелия крупных и резистивных артерий, а также патологии микроциркуляции.Показано, что развитие и прогрессирование ХСН сопровождается ухудшением периферического кровообращения за счет ремоделирования артерий мышечно-эластического типа и вен со снижением сосудистого дилатационного резерва, повышения как регионального сосудистого сопротивления, так и венозного тонуса, нарушения тканевого транскапиллярного обмена кислорода и активации прокоагулянтных свойств крови. Обсуждается значение вазоконстрикторных эффектов нейрогуморальных систем и воспаления в механизмах нарушения периферического кровообращения у пациентов с ХСН, особенно ассоциированной с метаболическим синдромом.

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

Effect of Cu-, Zn-containing complex based on a porous matrix on fibroblast proliferation, apoptosis, necrosis and nitric oxide production

A comparative study of the effect of a matrix based on porous aluminum and a silicon organic polymer polydimethylsiloxane (PDMS) (А12O3@PDMS) and a matrix complex with copper and zinc sorbed on its surface (Cu@Zn- А12O3@PDMS) on the functional properties of fibroblasts has been carried out. Material and methods. The effect of the Cu@Zn- А12O3@PDMS complex and the matrix on the cell proliferative potential (MTT test), apoptosis, necrosis and the production of stable nitric oxide (NO) metabolites were studied in an in vitro experiment with a human embryo fibroblast cell line (HEF-15). Results. The compared samples of Cu@Zn-A12O3@PDMS and Al2O3@PDMS are similar in their physico-chemical properties. Study of HEF-15 functional potential indicates a higher level of cell proliferation and ability to produce NO after contact with the complex. There was no significant increase in apoptosis and necrosis of HEF-15 in the presence of samples of the complex and the carrier. Conclusion. The absence of a significant negative effect of the tested samples on the functional status of cells of the FEH-15 line (proliferation, apoptosis, necrosis, NO secretion) in vitro allows the use of the Cu@Zn-A12O3@PDMS complex for further analysis of its safety in experimental models of skin defects in animals

The effect of a complex of melatonin, aluminum oxide and polymethylsiloxane on the cellular composition of the mice spleen kept in round-the-clock lighting conditions

It is known that the circadian rhythm of melatonin production depends on the intensity of illumination. Violation of the light regime leads to suppression of melatonin synthesis and the development of desynchronosis, which increases the risk of developing a number of pathologies. In this regard, it is relevant to search for opportunities to restore disturbed circadian rhythms and, especially, to correct immune dysfunctions that occur in these situations.The aim of this study was to examine the effect of a complex of melatonin, aluminum oxide and polymethylsiloxane on the lymphocytes of the spleen of mice kept under round-the-clock lighting.Materials and methods. Mice of the C57Bl/6J line were kept under round-the-clock lighting for 14 days, against which they were intragastrically injected with distilled water, aluminum oxide with polydimethylsiloxane, melatonin and a complex of melatonin, aluminum oxide and polymethylsiloxane (a new drug developed by the Research Institute of Clinical and Experimental Lymphology – Branch of the Federal Research Center Institute of Cytology and Genetics SB RAS; Patent of Russian Federation No. 2577580, 2016), represented by a complex of porous material (aluminum oxide with polydimethylsiloxane) and melatonin, immobilized in the pores, from which it is gradually released in a liquid medium. Intact animals kept under the light regime of ST 12/12 and under round-the-clock lighting served as a control. Immunophenotyping of spleen B- and T-lymphocytes was performed on a flow cytofluorimeter with monoclonal antibodies APC CD3 and FITC CD19. For studying the distribution of cells by stages of the cell cycle in splenocytes, the amount of intracellular DNA was measured by the level of inclusion of propidium iodide.Results. Flow cytometry of the distribution of B- and T-lymphocytes of the spleen in male mice of the C57Bl/6J line kept under round-the-clock lighting conditions (KO 24/0 h) revealed a decrease in the percentage of B-lymphocytes and an increase in the number of T-lymphocytes, compared with animals kept under standard lighting conditions (the light/dark photoperiod – 14/10 hours). The ratio of CD19+/CD3+ lymphocytes of the spleen in mice under the conditions of KO significantly decreases (1.5 times) compared to intact animals (p ≤ 0.001). The administration of pure and modified melatonin (Complex M) to animals kept under round-the-clock lighting conditions has an equally pronounced normalizing effect on the cellular composition of B- (CD19) and T- (CD3) lymphocytes of the spleen, bringing the values of the studied parameters to the control values of the intact animals (p ≤ 0.001) Round-the-clock lighting affects the proliferative potential of splenocytes, reducing the number of cells in the G2/M phase, compared with animals treated with melatonin (p ≤ 0.050). The introduction of melatonin leads to an increase in the percentage of cells in the G2/M phase relative to the placebo group (p ≤ 0.050). In the group of mice treated with Complex M, the greatest increase in cells at the S + G2/M phases and the highest percentage of cells at the G2/M phase were revealed compared to the placebo control group (p ≤ 0.050).Conclusion. The complex of melatonin, aluminum oxide and polymethylsiloxane has additional immunotropic properties in relation to the modifier molecule, which, apparently, are due to the joint immunostimulating effect of melatonin and the lymphostimulating effect of the sorbent. Melatonin in the composition of the complex shows its properties more stably

Pathology of the peripheral circulation in chronic heart failure

In the mechanisms of chronic heart failure (CHF) the key role traditionally given to a violation of intracardiac haemocirculation. Thus, in the guidelines for the evaluation and management of chronic heart failure in the adult, experts of the American College of Cardiology and the American Heart Association (2001-2013) define CHF as «a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood». Usually rightly believe that than the expression of inotropic and/or lusitropic failure of the appropriate ventricle in patients with CHF, the generally lower of him quality of life and a worse prognosis. However, the severity of the clinical manifestations of heart failure, on the one hand, and reducing the level of satisfaction with life - on the other, is not always depends only on the state of intracardiac hemodynamics. The authors of the review have analyzed papers published on the problem of the pathology of the peripheral circulation in CHF. Consistently examines the role of peripheral vascular remodeling and increased arterial stiffness, endothelial dysfunction of major and resistance arteries, as well as pathology of microcirculation. It has been shown that the development and progression of heart failure is accompanied by a deterioration in the peripheral circulation due to the remodeling of arteries muscular-elastic type and veins with a reduction in vascular dilatation reserve, increase of regional vascular resistance and venous tone, disturbances of tissue transcapillary exchange of oxygen and activate of procoagulant properties of blood. The significance of the effects of vasoconstrictor neurohormonal systems and inflammation in mechanisms of disorders of peripheral circulation in patients with CHF, particularly associated with the metabolic syndrome, have discussed