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Morphological characteristic of alterations in the striatum induced by neurodegenerative process in the brain
Němečková, Ivana
("Morphological characteristics of alterations in the striatum induced by neurodegenerative process in the brain") Huntington's disease (HD) is an inherited neurodegenerative disorder. Although the cause of HD, i.e. the production of the mutant form of unstable protein huntingtin (mhtt) which contains 40 and more CAG repeats is known, the effective therapy is not yet available. Therefore, the use of animal models is crucial for the study of the pathogenesis of this fatal disorder. To date, there is no suitable experimental model simulating the neurodegenerative process (NDP) developing in the striatum of the human HD brain. Most of rodent models of HD fall into two broad categories - the neurotoxic lesions and genetically engineered models. The primary aim of our study was a comprehensive morphological description of the development of NDP of HD phenotype in the striatum of the rat brain. We compared the progression of NDP in the lesion induced by intrastriatal injection of quinolinic acid (QA) and in rats transgenic for HD. The groups of male rats surviving for 3, 6-7, 14 days, 1, 3, 6, 9 and 12 months after the QA lesion were compared with 2-, 6-, 12-, 18-, 22-24-month-old tgHD rats and age-matched control (intact) counterparts in both groups. The primary morphological feature of the NDP of HD...
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Copper reducin properties of a series of xanthe-3-ones
Kopková, Nikola ; Mladěnka, Přemysl (advisor) ; Němečková, Ivana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Candidate: Nikola Kopková, MSc Consultant: Assoc. Prof. Přemysl Mladěnka, PharmD., Ph.D. Title of diploma thesis: Copper reducing properties of a series of xanthen-3-ones Key words: copper, reduction, xanthene-3-one, homeostasis Copper is present as a trace element in all tissues and is essential in cellular respiration, in the biosynthesis of neurotransmitters, for the scavening of reactive oxygen species, and is also a cofactor for various enzymes. Disruption of homeostasis can lead to liver and CNS damage, and tumor formation. Typical examples of an imbalance in copper homeostasis represents Wilson and Menkes disease. Xanthene derivatives are biologically active compounds with a possible broad therapeutic spectrum. Some of these derivatives have antitumor, antipyretic, immunomodulatory, antioxidant and other positive biological activities. The aim of this work was to determine whether 2,6,7-trihydroxyxanthen-3-one derivatives have the ability to reduce cupric ions and possibly to detect the effect of various substituents on this ability. As a methodology, a spectrophotometric method based on bathocuproindisulfonic acid as an indicator was used. Ten compounds were tested at different pH values. All...
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Effect of glucose treatment on endoglin and biomarkers of endothelial dysfunction in endothelial cells
Adamcová, Adriana ; Nachtigal, Petr (advisor) ; Němečková, Ivana (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Title of Diploma Thesis: Effect of glucose treatment on endoglin and biomarkers of endothelial dysfunction in endothelial cells Author: Adriana Adamcová Supervisor of Diploma Thesis: prof. PharmDr. Petr Nachtigal, Ph.D. Background: The aim of this thesis was to evaluate the expression of endoglin and biomarkers of endothelial dysfunction (eNOS, VCAM-1) in aortic endothelial cells exposed to oscillating glucose. Methods: Human aortic endothelial cells (HAECs) were treated with alternating normal (5 mM) and high (25mM) glucose for 7 days. The control group, was treated with a constant level of normal glucose. Gene expression of endoglin, eNOS, VCAM-1, HIF1α, KLF6, RELA and LXR was measured by quantitative real-time PCR. Flow cytometry was used to detect endoglin and VCAM-1 protein levels. Results: Treatment with high levels of glucose resulted in significantly increased expression of endoglin, eNOS, VCAM-1, HIF1α, RELA and LXR by means of PCR. The flow cytometry method showed a significant difference in protein levels in both endoglin and VCAM-1. Conclusions: The results of this diploma thesis showed that oscillating glucose increases the expression of endoglin and other biomarkers of endothelial...
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Copper reducin properties of a series of xanthe-3-ones
Kopková, Nikola ; Mladěnka, Přemysl (advisor) ; Němečková, Ivana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Candidate: Nikola Kopková, MSc Consultant: Assoc. Prof. Přemysl Mladěnka, PharmD., Ph.D. Title of diploma thesis: Copper reducing properties of a series of xanthen-3-ones Key words: copper, reduction, xanthene-3-one, homeostasis Copper is present as a trace element in all tissues and is essential in cellular respiration, in the biosynthesis of neurotransmitters, for the scavening of reactive oxygen species, and is also a cofactor for various enzymes. Disruption of homeostasis can lead to liver and CNS damage, and tumor formation. Typical examples of an imbalance in copper homeostasis represents Wilson and Menkes disease. Xanthene derivatives are biologically active compounds with a possible broad therapeutic spectrum. Some of these derivatives have antitumor, antipyretic, immunomodulatory, antioxidant and other positive biological activities. The aim of this work was to determine whether 2,6,7-trihydroxyxanthen-3-one derivatives have the ability to reduce cupric ions and possibly to detect the effect of various substituents on this ability. As a methodology, a spectrophotometric method based on bathocuproindisulfonic acid as an indicator was used. Ten compounds were tested at different pH values. All...
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Morphological alterations in kidneys in mice with high soluble endoglin levels
Vyskočilová, Martina ; Němečková, Ivana (advisor) ; Nachtigal, Petr (referee)
Masters thesis Morphological alterations in kidneys in mice with high soluble endoglin levels Author: Bc. Martina Vyskočilová Study program: Medical bioanalytics Charles University Faculty of Pharmacy in Hradec Králové Background: Endoglin (Eng) is a transmembrane glycoprotein also known as an accesory receptor type III for a TGF-β molecule which is expressed primarily on the surface of endothelial cells. Endoglin plays a role in vascular homeostasis, angiogenesis and cardiovascular development. Soluble endoglin (sEng) which is formed by a cleavage of an extracelullar part of a membrane-bound endoglin scavenges the TGF-β molecules in the serum and blocks their binding to the membrane-bound receptor. Soluble endoglin is considered as a trigger of an endothelial dysfunction which is associated with cardiovascular diseases and patogenesis of preeclampsia. The aim of this study is to describe possible effect of high levels of a soluble endoglin on kidney tissue of transgenic mice in comparison with kidneys of mice with low levels of a human soluble endoglin. Methods: Kidneys of twelve months old mice with high and normal levels of a human soluble endoglin on a standard laboratory diet were fixed in 4% formaldehyde, embedded in paraffin and sliced into 7 μm thin sections. One of these sections was...
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Osteoporosis - Current trends in diagnostics and therapy
Klčová, Silvia ; Kudláčková, Zděnka (advisor) ; Němečková, Ivana (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Author: Silvia Klčová Thesis supervisor: PhDr. Zděnka Kudláčková, Ph.D. Form: Bachelor thesis Study programme: Medical bioanalytics Thesis title: Osteoporosis - Current trends in diagnostics and therapy Background: This bachelor thesis is focused on elucidating the problem of osteoporosis. The aim of this work is to summarize current knowledge about this disease, especially about the methods of its diagnosis and therapy. Main findings: Osteoporosis is a progressive metabolic bone disease that is based on an imbalance in bone remodeling. This disease is characterized by a loss of bone tissue and the formation of porous bones, that are prone to fracture. Fractures are the most serious complication of osteoporosis. This thesis describes in detail the currently used diagnostic methods and therapeutic principles. Recognition of the presence of osteoporosis and subsequent initiation of therapeutic measures is essential for the management of this condition. There are several instrumental and laboratory methods used for diagnosis, which are based on different principles. Pharmacotherapy affecting bone remodeling, by inducing changes in the presence or functionality of executive bone cells, is...
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Effect of glucose treatment on endoglin and biomarkers of endothelial dysfunction in endothelial cells
Adamcová, Adriana ; Nachtigal, Petr (advisor) ; Němečková, Ivana (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Title of Diploma Thesis: Effect of glucose treatment on endoglin and biomarkers of endothelial dysfunction in endothelial cells Author: Adriana Adamcová Supervisor of Diploma Thesis: prof. PharmDr. Petr Nachtigal, Ph.D. Background: The aim of this thesis was to evaluate the expression of endoglin and biomarkers of endothelial dysfunction (eNOS, VCAM-1) in aortic endothelial cells exposed to oscillating glucose. Methods: Human aortic endothelial cells (HAECs) were treated with alternating normal (5 mM) and high (25mM) glucose for 7 days. The control group, was treated with a constant level of normal glucose. Gene expression of endoglin, eNOS, VCAM-1, HIF1α, KLF6, RELA and LXR was measured by quantitative real-time PCR. Flow cytometry was used to detect endoglin and VCAM-1 protein levels. Results: Treatment with high levels of glucose resulted in significantly increased expression of endoglin, eNOS, VCAM-1, HIF1α, RELA and LXR by means of PCR. The flow cytometry method showed a significant difference in protein levels in both endoglin and VCAM-1. Conclusions: The results of this diploma thesis showed that oscillating glucose increases the expression of endoglin and other biomarkers of endothelial...
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Soluble endoglin: effect on bile acids and cholesterol transport in livers
Grešková, Mária ; Nachtigal, Petr (advisor) ; Němečková, Ivana (referee)
Maria Greskova Soluble endoglin: effect on bile acids and cholesterol transport in livers Diplomathesis Charles University in Prague, Faculty of Pharmacy in Hradec Kralové Pharmacy Background: Increased plasma levels of soluble endoglin (sEng) have been shown in patients with acute heart failure, hypertension, diabetes mellitus type 2, and other metabolic and cardiovascular diseases such as e.g. hypercholesterolemia, atherosclerosis and cystic fibrosis, which influence as well liver functions. As there are no available data showing effect of sEng on the transport of cholesterol and bile acids, the aim ofthis diplomathesis wasto describe them. Methods: In this study were used six months-old female mice with high level of sEng on CBAxC57BL/6J background and control mice (n = 8, in each group) fed with chow diet for three months. /n vivo study was performed to analyze bile flow. mRNA expression of proteins responsible for cholesterol and bile acids transport and metabolism in the liver was performed by qRT-PCR. Results: sEng did not lead to changes neither in the bile flow nor in the concentration of cholesterol in plasma and liver. There were found no changes in the mRNAexpression of Sr-b1, Hmgcr, Abcg5, Abcg$, Acat2, Abcb4, Abcb11, Abcc2. sEng led to decrease in mRNAexpression of Cyp7al. Conclusion:...
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Study of the variations in the expression of different adhesion and cytoskeletal proteins of podocytes (E-Cadherin, Podocin, Vimentin) due to Bisphenol A
Chvojanová, Zuzana ; Kovařík, Miroslav (advisor) ; Němečková, Ivana (referee)
Charles University, Faculty of Pharmacy in Hradec Králové, Department of Biological and Medical Sciences The University of Alcalá, Faculty of Medicine, Department of biomedicine and biotechnology Student: Zuzana Chvojanová Supervisor: PharmDr. Miroslav Kovařík, Ph.D. Consultant: María Isabel Arenas Jimenéz Title of the diploma thesis: Study of the variations in the expression of different adhesion and cytoskeletal proteins of podocytes (E-Cadherin, Podocin, Vimentin) due to Bisphenol A Bisphenol A (BPA) is one of the most widespread compounds in the world, producing over 6 billion metric tons per year. It is widely used as part of polycarbonate plastics and epoxy resins, from which reusable plastic bottles, food boxes and some medical equipment are made. It is also used to coat the inner layer of the cans. Previous studies have shown that BPA contributes to many chronic diseases in the human body, such as kidney disease - diabetic nephropathy. Podocytes - terminally differentiated cells of the Bowman's capsule in glomerulus - are an integral part of the filtration barrier, where they play an important role in preventing the plasmatic proteins from penetrating to the urine. Therefore, in this study, we looked at the effect of BPA on these cells and their particular proteins, using both in vivo and...
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Soluble endoglin effects on endothelial dysfunction markers in mouse aorta
Kalmanová, Lenka ; Nachtigal, Petr (advisor) ; Němečková, Ivana (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Title of Diploma Thesis: Soluble endoglin effects on endothelial dysfunction markers in mouse aorta Author of Diploma Thesis: Lenka Kalmanová Supervisor of Diploma Thesis: prof. PharmDr. Petr Nachtigal, Ph.D. Background: The aim of the presented diploma thesis was to identify and subsequently evaluate the expression of endothelial dysfunction markers (ICAM-1, VCAM-1, P- selectin) in aortas of two groups of transgenic mice. The difference between control and experimental group was in the level of human soluble endoglin. Methods: 12 months old male mice of transgenic strain CBAxC57BL/6J with inserted genetic information for the expression of human soluble endoglin were utilized for the experiment. The mice were divided into two groups - the experimental group (high levels of sEng) and the control group (low levels of sEng) by ELISA analysis of levels of sEng in plasma. Both groups of mice were fed with standard laboratory rodent diet. Western blot analysis of adhesion molecules ICAM-1, VCAM-1 and P-selectin in mouse aorta and subsequently ELISA analysis of plasma levels of sVCAM-1 molecule were performed. Total cholesterol and triacylglycerol levels were demonstrated by biochemical analysis....
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