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Hazardous substances leasing from plastic bottles
Najmanová, Iveta ; Vopršalová, Marie (advisor) ; Pourová, Jana (referee)
v anglickém jazyce Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Iveta Najmanová Supervisor: PharmDr. Marie Vopršálová, CSc. Title of diploma thesis: Hazardous substances that are released from plastic bottles This master thesis focuses on hazardous substances that are released from plastic bottles. Attention is paid especially to bisphenol A and antimony and their effects after oral administration. Given the fact that these substances are harmful to humans, most of the information about their effects was observed in epidemiological studies or studies conducted on laboratory animals and human tissues. The thesis documents the toxicological effects on the body, especially of bisphenol A. To a lesser extent and primarily because of the limited number of studies on this topic, it deals with the influence of antimony. This is a search thesis and the data are the sum of bibliographic records on the subject.
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The effect of polyphenolic substances on vascular smooth muscle
Najmanová, Iveta ; Mladěnka, Přemysl (advisor) ; Tůmová, Lenka (referee) ; Klimas, Ján (referee)
[Sem zadejte text.] Abstract Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Iveta Najmanová, MCs First Supervisor: Assoc. Prof. Přemysl Mladěnka, Pharm.D., Ph.D. Second Supervisor: Marie Vopršalová, Pharm.D., Ph.D. Title of Doctoral Thesis: The effect of polyphenolic substances on vascular smooth muscle Polyphenolic substances are one of the most abundant secondary plant metabolites. Many substances from simple phenols with one benzene core to the polymeric compounds belong to these groups. Two groups, coumarins and flavonoids, were selected for this dissertation. The aim of this thesis was to analyse their effect on vascular smooth muscle in in vitro and in vivo conditions. In the case of coumarins, the aim was reached by writing of a review article. The effect of flavonoids, including their metabolites was experimentaly tested and some of the results have already been published. The first step in my research was to perform a screening of metabolites of quercetin, the most occuring flavonol in the human diet, and compare their vasorelaxant potential. Experiments were performed on isolated rat thoracic aorta. During the testing, the most effective metabolite was definitely 3-(3-hydroxyphenyl)propionic acid (3-HPPA), which was at least one order...
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Effect of long-term exposure to soluble endoglin on the expression of adhesion molecules on endothelial cells
Tuschlová, Dominika ; Najmanová, Iveta (advisor) ; Vicen, Matej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Title of Diploma Thesis: Effect of long-term exposure to soluble endoglin on the expression of adhesion molecules on endothelial cells Author of Diploma Thesis: Dominika Tuschlová Supervisor of Diploma Thesis: PharmDr. Iveta Najmanová, Ph.D. Background: The aim of this thesis was to find out the effect of long-term exposure to soluble endoglin (sEng) on the expression of adhesion molecules on endothelial cells (ICAM-1, VCAM-1, P-selectin). We have worked with a control and experimental group of mice on a standard diet, with different levels of sEng. Methods: Genetically modified female mice from the CBAxC57BL/6J strain with high production of human sEng were used for analysis. These mice formed an experimental group, while mice with a low level of sEng formed a control group. They were 12 months old females. We used biochemical analysis to determine the level of total cholesterol and triacylglycerols (TAG). Levels of sVCAM-1 markers in all mice studied were determined by ELISA. The expression of the adhesion molecules ICAM-1, VCAM-1 and P-selectin was monitored and evaluated by Western blotting, where the structural protein GAPDH was used as a control. Results: Biochemical analysis did not show a...
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Hepatocyte ROCK1 kinase activity incites liver inflammation in murine non-alcoholic fatty liver disease
Dohnálková, Ester ; Nachtigal, Petr (advisor) ; Najmanová, Iveta (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Biological and Medical Sciences Candidate: Mgr. Ester Dohnalkova Consultant: prof. PharmDr. Petr Nachtigal, Ph.D. Title of Thesis: Hepatocyte ROCK1 kinase activity incites liver inflammation in murine non- alcoholic fatty liver disease Background: Rho-associated protein kinase 1 (ROCK1) activity has been previously implicated in lipotoxicity-induced extracellular vesicle (EV) release from hepatocytes. In turn, lipotoxic hepatocyte-derived EVs incite inflammatory response in monocytes and macrophages. In addition, we previously found that activated ROCK1 is a distinct histologic feature of inflammatory stage of murine and human nonalcoholic fatty liver disease (NAFLD). However, it is currently unknown whether activated ROCK1 may directly contribute to NAFLD pathogenesis. Therefore, we aimed to examine the effect of hepatocyte ROCK1 kinase activity on the development of inflammation in a model of murine NAFLD. Methods: To assess the role of ROCK1 in NAFLD, we have adopted an in vivo gain-of-function approach. C57BL/6J mice were injected with either: a) vehicle; b) adeno-associated virus, serotype 8 (AAV8)-packaged, TBG-driven constitutively active ROCK1 (CA-ROCK1) construct; or c) AAV8-packaged, TBG-driven kinase-dead...
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Soluble endoglin effects on membrane endoglin signaling in mouse aorta.
Doležálková, Petra ; Nachtigal, Petr (advisor) ; Najmanová, Iveta (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Author: Petra Doležálková Supervisor: prof. PharmDr. Petr Nachtigal, Ph.D. Diploma Thesis Soluble endoglin effects on membrane endoglin signaling in mouse aorta. Background: The aim of this study was to observe and evaluate the influence of the long- term (12 months) effect of high levels of soluble endoglin on membrane endoglin signalization in the mouse aorta. Specifically, we observed and compared the expression of proteins endoglin, eNOS, and pSmad2/3 in control and a test Sol-Eng+ group of mice. Methods: Two groups of 12-months-old mice with a difference in the level of soluble endoglin were used in this study. Both groups were originated in the same line of transgenic mouse strain CBAxC57BL/6J and fed with ordinary laboratory diet. Western blot technique was used to analyse the expression of individual proteins endoglin, eNOS, and pSmad2/3. The concentration of human soluble endoglin and soluble form of VCAM-1 molecule was evaluated by ELISA analysis. Total cholesterol levels and triglycerides in the plasma were detected by biochemical analysis. Results: Western Blot analysis showed no statistically significant differences in the expression of the membrane endoglin, eNOS enzyme and pSmad2/3...
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Pharmacokinetics of flavanols
Sobolová, Dominika ; Mladěnka, Přemysl (advisor) ; Najmanová, Iveta (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Dominika Sobolová Supervisor: Assoc. Prof. Přemysl Mladěnka, Pharm.D., Ph.D. Title of diploma thesis: Pharmacokinetics of flavanols This work is focusing on summarizing available information about the fate of flavanols in the organism. It is necessary to know the pharmacokinetics to explain their biological effects. In contrast to other flavonoids, they occur in the form of aglycones in plant foods. Galoylation, polymerization and optical isomerism have an important influence on the pharmacokinetics. Partial absorption of monomers begins in the small intestine after oral ingestion. In addition to the liver, the extensive metabolic changes take place even in the enterocytes. The resulting metabolites enter the circulation or they are effluxed back into the intestinal lumen, especially in the case of (epi)catechin sulfates. Epicatechin and catechin are present almost exclusively as glucuronides, sulfates or methylated compounds in the plasma. On the contrary, free unconjugated forms prevail within the gallates. The extent of their absorption is lower. They are excreted via biliary excretion, while other catechins are quickly eliminated by the kidneys in urine. The bioavailability of the parent...
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Antibiotic resistance in Staphylococcus aureus
Švábová, Tereza ; Vejsová, Marcela (advisor) ; Najmanová, Iveta (referee)
Author: Tereza Švábová Title: Resistance to antibiotics in Staphylococcus aureus Bachelor thesis Charles University in Prague, Faculty of Pharmacy, Hradec Králové Field of study: Medical Laboratory Background: The bachelor thesis aims at dealing with Staphylococcus aureus, describing its basic properties, laboratory diagnostics, antigenic structure and the diseases what it causes. Describe types and mechanisms of resistence, antibiotic therapy including mechanisms of antibiotic action. More attention is paid to the strains of MRSA (Methicillin resistant Staphylococcus aureus), because this is one of the biggest problems associated with resistance. Main findings: In the period before to the discovery of antibiotics, invasive infections caused by S. aureus were mostly fatal. With the introduction of antibiotics into practice, the problem of resistance has multiplied. The occurrence of MRSA was the largest in 2009 at - 14.6% in the Czech Republic. In 2014, the occurrence of MRSA was 13%, and 2 years later, there was again a slight increase - 13.9% in 2016 (ECDC, 2018). The selection of antibiotic and the method of antibiotic treatment of infections depend on the clinical condition of the patient, the agent of the disease including its sensitivity, the underlying disease and the properties of the...
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The effect of polyphenolic substances on vascular smooth muscle
Najmanová, Iveta ; Mladěnka, Přemysl (advisor) ; Tůmová, Lenka (referee) ; Klimas, Ján (referee)
[Sem zadejte text.] Abstract Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Iveta Najmanová, MCs First Supervisor: Assoc. Prof. Přemysl Mladěnka, Pharm.D., Ph.D. Second Supervisor: Marie Vopršalová, Pharm.D., Ph.D. Title of Doctoral Thesis: The effect of polyphenolic substances on vascular smooth muscle Polyphenolic substances are one of the most abundant secondary plant metabolites. Many substances from simple phenols with one benzene core to the polymeric compounds belong to these groups. Two groups, coumarins and flavonoids, were selected for this dissertation. The aim of this thesis was to analyse their effect on vascular smooth muscle in in vitro and in vivo conditions. In the case of coumarins, the aim was reached by writing of a review article. The effect of flavonoids, including their metabolites was experimentaly tested and some of the results have already been published. The first step in my research was to perform a screening of metabolites of quercetin, the most occuring flavonol in the human diet, and compare their vasorelaxant potential. Experiments were performed on isolated rat thoracic aorta. During the testing, the most effective metabolite was definitely 3-(3-hydroxyphenyl)propionic acid (3-HPPA), which was at least one order...
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The importance of membrane and soluble endoglin in atherosclerosis.
Mphetang, Constance Bontle ; Nachtigal, Petr (advisor) ; Najmanová, Iveta (referee)
This thesis is about the importance of membrane and soluble endoglin (sEng) in atherosclerosis, both the development and the progression of the state. Atherosclerosis poses a major risk factor for heart diseases and stroke, which renders it a serious health issue. The role of endoglin in atherosclerosis is yet to be defined and this will be discussed below. Endoglin expression was discovered in atherosclerotic vessels predominantly in the endothelial and smooth muscle cells both in experimental animals and humans. This discovery suggests that endoglin plays a role in atherogenesis and stabilization of atherosclerotic plaques. In addition to atherosclerosis, high levels of soluble endoglin were also discovered in cases where hypercholesterolemia and myocardial infarction were observed and were also related to TGF-β signalling inhibition in the walls of the affected vessels. Additionally, statins reasonably lowered soluble endoglin levels and facilitated its expression in the aorta of mice, resulting in a decrease in the atherosclerotic effects and complications. Furthermore, patients with familial hypercholesterolemia underwent extracorporeal eliminations which helped significantly reduce the levels of soluble endoglin. In conclusion, knowing the levels of soluble endoglin and what that indicates in...
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