Coagulation Disorders in Infective Endocarditis: Role of Pathogens, Biomarkers, Antithrombotic Therapy (Systematic Review)

The issue of antithrombotic therapy in patients with infective endocarditis has been studied for over 75 years. During that time studying of pathogenesis of the disease and its embolic complications, lead to the introduction of the concept of “immunothrombosis”. That mechanism allows infective agents (mostly bacteria) to be cloaked from the immune system and to multiply freely, leading to growth of vegetation, thus resulting in higher chance of fragmentation. Small-scale experimental and clinical studies on the correction of hemostatic disorders in infective endocarditis, that were performed in 20th century, didn’t show any significant results, that could affect clinical practice. However, reinterpretation of available data on coagulative system will allow to have elements of hemostasis as an application point in treating infective endocarditis. The article will discuss latest insights on the role of hemostasis system in pathophysisology of infective endocarditis, its effects on the development of the embolic complications, perspectives for diagnostics and treatment

Cytogenomic Profile of Uterine Leiomyoma: In Vivo vs. In Vitro Comparison

We performed a comparative cytogenomic analysis of cultured and uncultured uterine leiomyoma (UL) samples. The experimental approach included karyotyping, aCGH, verification of the detected chromosomal abnormalities by metaphase and interphase FISH, MED12 mutation analysis and telomere measurement by Q-FISH. An abnormal karyotype was detected in 12 out of 32 cultured UL samples. In five karyotypically abnormal ULs, MED12 mutations were found. The chromosomal abnormalities in ULs were present mostly by complex rearrangements, including chromothripsis. In both karyotypically normal and abnormal ULs, telomeres were ~40% shorter than in the corresponding myometrium, being possibly prerequisite to chromosomal rearrangements. The uncultured samples of six karyotypically abnormal ULs were checked for the detected chromosomal abnormalities through interphase FISH with individually designed DNA probe sets. All chromosomal abnormalities detected in cultured ULs were found in corresponding uncultured samples. In all tumors, clonal spectra were present by the karyotypically abnormal cell clone/clones which coexisted with karyotypically normal ones, suggesting that chromosomal abnormalities acted as drivers, rather than triggers, of the neoplastic process. In vitro propagation did not cause any changes in the spectrum of the cell clones, but altered their ratio compared to uncultured sample. The alterations were unique for every UL. Compared to its uncultured counterpart, the frequency of chromosomally abnormal cells in the cultured sample was higher in some ULs and lower in others. To summarize, ULs are characterized by both inter- and intratumor genetic heterogeneity. Regardless of its MED12 status, a tumor may be comprised of clones with and without chromosomal abnormalities. In contrast to the clonal spectrum, which is unique and constant for each UL, the clonal frequency demonstrates up or down shifts under in vitro conditions, most probably determined by the unequal ability of cells with different genetic aberrations to exist outside the body

НАТРИЙ-КАЛИЙ-ХЛОР-КОТРАНСПОРТ В РЕГУЛЯЦИИ МИОГЕННОГО ТОНУСА СОСУДОВ

The article discusses the data on the functioning of Na+,K+,2Cl– cotransport – the carrier providing electroneutral symport of sodium, potassium and chloride, as well as molecular mechanisms of the regulation and physiological significance of this carrier. We analyzed the novel data on involvement of ubiquitous isoform of Na+,K+,2Cl–cotransporter (NKCC1) in regulation of vascular smooth muscle contraction, and role of this carrier in the regulation of cell volume and intracellular chloride concentration.В статье рассматриваются принципы функционирования Na+,K+,2Cl–-котранспорта – трансмембранного ионного переносчика, осуществляющего электронейтральный симпорт натрия, калия и хлора, молекулярные механизмы его регуляции и физиологическое значение. Приводятся новые данные о роли универсальной изоформы Na+,K+,2Cl–-котранспортера (NKCC1) в регуляции сокращения гладких мышц сосудов, объема клеток и внутриклеточной концентрации хлора

Ubiquitous [Na+]i/[K+]i-Sensitive Transcriptome in Mammalian Cells: Evidence for Ca2+i-Independent Excitation-Transcription Coupling

Stimulus-dependent elevation of intracellular Ca2+ ([Ca2+]i) affects the expression of numerous genes – a phenomenon known as excitation-transcription coupling. Recently, we found that increases in [Na+]i trigger c-Fos expression via a novel Ca2+i-independent pathway. In the present study, we identified ubiquitous and tissue-specific [Na+]i/[K+]i-sensitive transcriptomes by comparative analysis of differentially expressed genes in vascular smooth muscle cells from rat aorta (RVSMC), the human adenocarcinoma cell line HeLa, and human umbilical vein endothelial cells (HUVEC). To augment [Na+]i and reduce [K+]i, cells were treated for 3 hrs with the Na+,K+-ATPase inhibitor ouabain or placed for the same time in the K+-free medium. Employing Affymetrix-based technology, we detected changes in expression levels of 684, 737 and 1839 transcripts in HeLa, HUVEC and RVSMC, respectively, that were highly correlated between two treatments (p<0.0001; R2>0.62). Among these Na+i/K+i-sensitive genes, 80 transcripts were common for all three types of cells. To establish if changes in gene expression are dependent on increases in [Ca2+]i, we performed identical experiments in Ca2+-free media supplemented with extracellular and intracellular Ca2+ chelators. Surprisingly, this procedure elevated rather than decreased the number of ubiquitous and cell-type specific Na+i/K+i-sensitive genes. Among the ubiquitous Na+i/K+i-sensitive genes whose expression was regulated independently of the presence of Ca2+ chelators by more than 3-fold, we discovered several transcription factors (Fos, Jun, Hes1, Nfkbia), interleukin-6, protein phosphatase 1 regulatory subunit, dual specificity phosphatase (Dusp8), prostaglandin-endoperoxide synthase 2, cyclin L1, whereas expression of metallopeptidase Adamts1, adrenomedulin, Dups1, Dusp10 and Dusp16 was detected exclusively in Ca2+-depleted cells. Overall, our findings indicate that Ca2+i-independent mechanisms of excitation-transcription coupling are involved in transcriptomic alterations triggered by elevation of the [Na+]i/[K+]i ratio. There results likely have profound implications for normal and pathological regulation of mammalian cells, including sustained excitation of neuronal cells, intensive exercise and ischemia-triggered disorders

Topographical and Biological Evidence Revealed FTY720-Mediated Anergy-Polarization of Mouse Bone Marrow-Derived Dendritic Cells In Vitro

Abnormal inflammations are central therapeutic targets in numerous infectious and autoimmune diseases. Dendritic cells (DCs) are involved in these inflammations, serving as both antigen presenters and proinflammatory cytokine providers. As an immuno-suppressor applied to the therapies of multiple sclerosis and allograft transplantation, fingolimod (FTY720) was shown to affect DC migration and its crosstalk with T cells. We posit FTY720 can induce an anergy-polarized phenotype switch on DCs in vitro, especially upon endotoxic activation. A lipopolysaccharide (LPS)-induced mouse bone marrow-derived dendritic cell (BMDC) activation model was employed to test FTY720-induced phenotypic changes on immature and mature DCs. Specifically, methods for morphology, nanostructure, cytokine production, phagocytosis, endocytosis and specific antigen presentation studies were used. FTY720 induced significant alterations of surface markers, as well as decline of shape indices, cell volume, surface roughness in LPS-activated mature BMDCs. These phenotypic, morphological and topographical changes were accompanied by FTY720-mediated down-regulation of proinflammatory cytokines, including IL-6, TNF-α, IL-12 and MCP-1. Together with suppressed nitric oxide (NO) production and CCR7 transcription in FTY720-treated BMDCs with or without LPS activation, an inhibitory mechanism of NO and cytokine reciprocal activation was suggested. This implication was supported by the impaired phagocytotic, endocytotic and specific antigen presentation abilities observed in the FTY720-treated BMDCs. In conclusion, we demonstrated FTY720 can induce anergy-polarization in both immature and LPS-activated mature BMDCs. A possible mechanism is FTY720-mediated reciprocal suppression on the intrinsic activation pathway and cytokine production with endpoint exhibitions on phagocytosis, endocytosis, antigen presentation as well as cellular morphology and topography

PREBIOTICS IN NUTRITION OF CHILDREN OF EARLY AGE

Abstract. Proper nutrition is the key factor of growth and development of the child. Early artificial feeding and irrational introduction of complementary food is one of the problems of infants leading to development of functional disorders of the gastrointestinal tract, impaired immunological protection and manifestation of atopic diseases. We described the effects of the main pre-biotic components of functional nutrition in children of early age. Also we demonstrated the importance of prebiotics for the formation of intestinal microflora, including the development of local mucosal homeostasis due to immunomodulatory action

Influence of pregnancy and birth factors on the development of acute kidney injury in premature infants

The Objective of this article is to assess the influence of the factors of pregnancy, childbirth and the early neonatal period on the development of acute kidney damage in premature newborns with very low and extremely low body weight. In addition, this disease significantly affects the prognosis and quality of life of the child. In addition, acute kidney damage significantly increases mortality among patients of the intensive care unit for newborns. There has been established a connection between acute hypoxia in childbirth, extremely low body weight at birth, intrauterine infection and III severity on the NTISS scale with the development of acute kidney damage in the early neonatal period. Early detection of this condition requires a comprehensive study of the mechanisms of its development and possible risk factors

Iron-Phosphate Ceramics for Solidification of Mixed Low-Level Waste

A method of immobilizing mixed low-level waste is provided which uses low cost materials and has a relatively long hardening period. The method includes: forming a mixture of iron oxide powders having ratios, in mass %, of FeO: Fe{sub 2}O{sub 3}: Fe{sub 3}O{sub 4} equal to 25-40: 40-10: 35-50, or weighing a definite amount of magnitite powder. Metallurgical cinder can also be used as the source of iron oxides. A solution of the orthophosphoric acid, or a solution of the orthophosphoric acid and ferric oxide, is formed and a powder phase of low-level waste and the mixture of iron oxide powders or cinder (or magnetite powder) is also formed. The acid solution is mixed with the powder phase to form a slurry with the ratio of components (mass %) of waste: iron oxide powders or magnitite: acid solution = 30-60: 15-10: 55-30. The slurry is blended to form a homogeneous mixture which is cured at room temperature to form the final product