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Changes in the iron content are among the most common metabolic diseases with a number of possible pathophysiological consequences for various body functions. The phenomenon accompanying these situations is the change in cholesterol homeostasis with possible extension to bile acids (BA), ie major executive and regulatory molecules in the metabolism of endobiotics, what can play an important role in associated organ dysfunctions. Since there was only a minimal amount of information in this area, the aim of this work was to evaluate the effect of iron overload and deficiency on the processes involved in BA turnover with the identification of involved molecular mechanisms. The first assessed field was the evaluation of iron deficiency (ID) using a suitable rat model, where ID was induced by a specific diet. This has demonstrated a significant inducing effect on both classical and alternative pathways for BA synthesis from cholesterol. Together with the induction of cholesterol biliary secretion in ID group it led to statistically significant decrease of plasma cholesterol concentrations. The subsequent BA-dependent choleretic effect was induced by their increased liver disposition, without affecting the expression of corresponding transporters, as verified by the kinetic study with 3 H-taurocholate....

Kristýna Hofmanová Effect of soluble endoglin on cholesterol metabolism in the liver of high-fat diet-fed transgenic mice Diploma thesis Charles University, Faculty of Pharmacy in Hradec Králové Pharmacy Background: Increased plasma concentrations of soluble endoglin (sENG) are observed in metabolic deseases like diabetes mellitus type 2 or hypercholesterolemia. It has already been shown that sEng influence the cholesterol metabolism i healthy mice fed standard laboratory diet. However, the effect of sENG on cholesterol metabolism in combination with high fat diet (HFD) is not known yet. The aim of this diploma thesis was to elucidate the influece of the sENG on the meabolism of cholesterol in the liver of transgenic mice (Sol-Eng+ ), with liver demaged by NASH (Non-alcoholic steatohepatitis) induced by HFD. Methods: Three months old male mice (Sol-Eng+ ) with high plasma levels of sENG on the basis of the CBAxC57BL/6J and control "wild-type" mice with unspecified levels of soluble endoglin (n=8, in each group) we used in this study. The animals were divided into groups acording of the level of soluble endoglin and the type of diet: "wild-type" fed for six moths with standard laboratory diet (WTchow); "wild-type" with high fat diet (WTHFD) and high- plasma sENG group fed HFD for six months...

Charles University Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Student: Marie Šimková Supervisor: Mgr. Alena Prašnická Title of diploma thesis: Alternation of bile production due to iron depletion Introduction: Liver has an irreplaceable role in the production and secretion of bile. This body fluid serves as the main excretion way of some endogenous and exogenous substances. Another liver property is the ability to store substances essential for correct functions of the body, e.g. iron. It has been shown that iron could have an impact on the bile production and secretion. Aim: The aim of this diploma thesis was to discover an impact of iron depletion on the bile synthesis and metabolism, especially on bile acids, and the way it affects transporters expression. Methods: Male Wistar rats (n=6 in each group, 250 ± 20 g) were divided into two groups: control group (Chow diet) fed with standard diet and iron depletion group (ID), fed with iron depletion diet for 21 days. To investigate the changes in bile flow, the bile had been collected for 120 min during in vivo clearance study. The analysis of the changes in expression of bile transporters and enzymes responsible for de novo bile acid synthesis was performed at the mRNA (qRT-PCR) and protein (Western blot)...

Author: Nikola Jozefčeková Title: Endoglin and liver Form: Diploma Thesis University: Charles University, Faculty of Pharmacy in Hradec Králové Degree: Pharmacy This diploma thesis concludes the available information about endoglin, its isoforms in the liver and its impact on the liver during various pathological conditions. In the first part of the thesis describes morphology and physiology of the liver, its structure, histology and metabolic functions. Second part contains an information about endoglin, its isoforms and role in TGF-β signaling complex, expression of endoglin and regulation of the expression. In the third part are described liver diseases during which is expression of endoglin changed. This part deals with the significance of endoglin as a diagnostic and prognostic marker. Endoglin (CD105, TGF-β receptor III) is a homodimeric transmembrane glycoprotein and a membrane co-receptor TGF-β with high expression in endothelial cells. Endoglin plays an important role in the vascular development. Endoglin is involved in the processes of angiogenesis, vascular homeostasis and TGF-β signalization. It affects activity of TGF-βRII, ALK1 and ALK5 receptors. Due to the interactions with TGF-β complex, modulation of activity of ALK receptors and Smads, endoglin controls fibrotic and anti-...

Charles University Department of Biological and Medical Sciences Candidate: Konstantinos Bountalis Supervisor: prof. PharmDr. Petr Nachtigal, Ph.D. Title of diploma thesis: Soluble endoglin effects on endothelial dysfunction markers in mice Endothelial dysfunction is associated with modification of endothelial cells amount failing to maintain vascular homeostasis and result in variable pathological inflammatory states as well as in progression of vascular damage. Particularly its state is characterized by high expression of cell adhesion molecules, reduction of vasodilation and accumulation of cholesterol molecules. The purpose of this study is to detect soluble endoglin effects on the expression of VCAM-1 and ICAM-1 in aorta in mice. The experiment was accomplished utilizing specific immunohistochemical methods for the detection of expression of selected adhesion molecules. High fat diet administration resulted in development of mild hypercholesterolemia in mice in both groups. High levels of soluble endoglin however did not significantly affect the expression of VCAM-1 and ICAM-1 in aortic endothelium when compared to mice with low levels of soluble endoglin. The results of this study did not show pro-inflammatory effects of soluble endoglin in aorta in mice.

Zuzana Slámová Diagnostics of exanthematic childhood diseases Bachelor thesis Charles University, Faculty of Pharmacy in Hradec Králové Health bioanalytics Background: The aim of the bachelor thesis was to determine the morbidity, incidence and prevalence of selected exanthematic childhood diseases (measles, scarlet fever, rubella, fourth disease, fifth disease and chickenpox) in the period 2013 - 2016 at the Department of Clinical Microbiology and Immunology of Regional Hospital Liberec, a. s. including a comparison with occurance of diseases in the whole Czech Republic. Methods: The methodical part was focused on the methods which are the basis of specific analyzers at the Department of Clinical Microbiology and Immunology of the Regional Hospital Liberec, a. s. These methods are ELISA, CLIA, KFR, PCR and cultivation. Analyzers used to diagnose antibodies against selected diseases are Alegria® (ORGENTEC), LIAISON® XL (DiaSorin) and Chorus Trio (DIESSE). For the direct quick detection of the disease was used quantitative PCR (qPCR) method on the CFX96 Touch ™ Real-Time PCR Detection System (BioRad). Detection of bacterial agents was performed by cultivation. Results: The results were processed over the period 2013 - 2016 from data provided by the Department of Clinical Microbiology and Immunology...