ИЗУЧЕНИЕ ПРОЦЕССОВ ДИФФУЗИИ ПРИ РАЗРАБОТКЕ ГАЗОГИДРАТНыХ ЗАЛЕЖЕЙ

Вивчена роль процесів дифузії при розробці газогідратних покладів. Проана- лізовані можливі механізми проходження газу крізь пористі середовища. Роз- глянуто вплив броунівського руху частинок при видобуванні газу з природних газогідратів. Изучена роль процессов диффузии при разработке газогидратных залежей. Проанализированы возможные механизмы прохождения газа сквозь порис- тые среды. Рассмотрено влияние броуновского движения частиц при добыче газа из природных газогидратов. The role of diffusion processes in development of gas hydrate deposits is exam- ined. Possible mechanisms of passing of gas through porous media are analyzed. The effect of Brownian motion of particles during the extraction of natural gas from gas hydrates is considered

Balance of inflammatory pathways and interplay of immune cells in the liver during homeostasis and injury

Multiple potentially harmful stimuli challenge the liver, the chief metabolic and detoxifying organ of the human body. Due to its central an atomical location, continuous blood flow from the gastrointestinal tract through the hepatic sinusoids allows the metabolically active hepatocytes, the non-parenchymal cells and the various immune cell populations residing and patrolling in the liver to interact with antigens and microbiological components coming from the intestine. Cytokines are key mediators within the complex interplay of intrahepatic immune cells and hepatocytes, because they can activate effector functions of immune cells as well as hepatocytic intracellular signaling pathways controlling cellular homeostasis. Kupffer cells and liver-infiltrating monocyte-derived macrophages are primary sources of cytokines such as tumor necrosis factor (TNF). The liver is also enriched in natural killer (NK) and natural killer T (NKT) cells, which fulfill functions in pathogen defense, T cell recruitment and modulation of fibrogenic responses. TNF can activate specific intracellular pathways in hepatocytes that influence cell fate in different manners, e.g. pro-apoptotic signals via the caspase cascade, but also survival pathways, namely the nuclear factor (NF)-kappaB pathway. NF-kappaB regulates important functions in liver physiology and pathology. The exact dissection of the contribution of recruited and resident immune cells, their soluble cytokine and chemokine mediators and the intracellular hepatocytic response in liver homeostasis and injury could potentially identify novel targets for the treatment of acute and chronic liver disease, liver fibrosis or cirrhosis

Growth Differentiation Factor-15 Is a Predictor of Mortality in Critically Ill Patients with Sepsis

Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor-β superfamily related to inflammation and macrophage activation. Serum concentrations of GDF-15 can predict poor survival in chronic diseases, but its role in sepsis is obscure. Therefore, we investigated GDF-15 as a prognostic biomarker in critically ill patients. We measured GDF-15 levels in 219 critically ill patients (146 with sepsis, 73 without sepsis) upon admission to the intensive care unit (ICU), in comparison to 66 healthy controls. GDF-15 levels were significantly increased in ICU patients compared to controls. GDF-15 was further increased in sepsis and showed a strong association with organ dysfunction (kidney, liver and lactate) and disease severity (APACHE II and SOFA score). High GDF-15 concentrations at admission independently predicted ICU (HR 3.42; 95% CI 1.33–8.78) and overall mortality (HR 2.02, 95% CI 1.02–3.88) in all ICU critically ill patients as well as in a large subgroup of sepsis patients (ICU mortality: HR 3.16; 95% CI 1.10–9.07; overall mortality: HR 2.62; 95% CI 1.14–6.02). Collectively, serum GDF-15 levels are significantly increased in critically ill patients, associated with sepsis, organ failure, and disease severity. High GDF-15 levels at ICU admission predict short- and long-term mortality risk

Pharmacological Inhibition of the Chemokine CXCL16 Diminishes Liver Macrophage Infiltration and Steatohepatitis in Chronic Hepatic Injury

Non-alcoholic fatty liver disease (NAFLD) is a major cause of morbidity and mortality in developed countries, resulting in steatohepatitis (NASH), fibrosis and eventually cirrhosis. Modulating inflammatory mediators such as chemokines may represent a novel therapeutic strategy for NAFLD. We recently demonstrated that the chemokine receptor CXCR6 promotes hepatic NKT cell accumulation, thereby controlling inflammation in experimental NAFLD. In this study, we first investigated human biopsies (n = 20), confirming that accumulation of inflammatory cells such as macrophages is a hallmark of progressive NAFLD. Moreover, CXCR6 gene expression correlated with the inflammatory activity (ALT levels) in human NAFLD. We then tested the hypothesis that pharmacological inhibition of CXCL16 might hold therapeutic potential in NAFLD, using mouse models of acute carbon tetrachloride (CCl4)- and chronic methionine-choline-deficient (MCD) diet-induced hepatic injury. Neutralizing CXCL16 by i.p. injection of anti-CXCL16 antibody inhibited the early intrahepatic NKT cell accumulation upon acute toxic injury in vivo. Weekly therapeutic anti-CXCL16 administrations during the last 3 weeks of 6 weeks MCD diet significantly decreased the infiltration of inflammatory macrophages into the liver and intrahepatic levels of inflammatory cytokines like TNF or MCP-1. Importantly, anti-CXCL16 treatment significantly reduced fatty liver degeneration upon MCD diet, as assessed by hepatic triglyceride levels, histological steatosis scoring and quantification of lipid droplets. Moreover, injured hepatocytes up-regulated CXCL16 expression, indicating that scavenging functions of CXCL16 might be additionally involved in the pathogenesis of NAFLD. Targeting CXCL16 might therefore represent a promising novel therapeutic approach for liver inflammation and steatohepatitis