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Ultrasonographic evaluation of cardiovascular abnormalities in patients with Fabry disease
Paleček, Tomáš ; Bultas, Jan (advisor) ; Pudil, Radek (referee) ; Kittnar, Otomar (referee)
Fabry disease is an X-linked glycosphingolipid storage disorder caused by deficient activity of the lysosomal enzyme α-galactosidase A. This leads to progressive intracellular accumulation of neutral glycosphingolipids, mainly globotriaosylceramide. Besides various extracardiac disease-related abnormalities, cardiovascular involvement represents a typical manifestation of Fabry disease. The primary underlying mechanism relies on pathological substrate accumulation in cardiomyocytes, conduction system cells, valvular fibroblasts, endothelial cells and vascular smooth muscle cells. The development of cardiac and vascular hypertrophy represents a characteristic cardiovascular feature of Fabry disease. The aim of our studies was to describe in detail cardiovascular abnormalities in patients with Fabry disease using ultrasonography, which currently represents basic noninvasive imaging modality in cardiology. We focused on structural and functional abnormalities of ventricles, valvular apparatus and their relationship to vascular involvement expressed on common carotid arteries. We also compared the diagnostic accuracy of the two novel echocardiographic methods used for the left ventricular diastolic function assessment. The possible existence of circulating proliferative factor, which might be associated with...
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The role of ATM in breast cancer
Soukupová, Jana ; Pohlreich, Petr (advisor) ; Souček, Pavel (referee) ; Foretová, Lenka (referee)
Incidence of breast cancer is continuously increasing in the Czech Republic. Tumor development is a result of gene alterations'accumulation, particulary associated with genes involved in regulation of cell growth and division. Hereditary carcinomas account for approximately 5-10% of all breast tumors and in 60-80% cases are caused by a germline mutation in the major predisposition genes BRCA1 and BRCA2. Nevertheless, other genes, mostly of lower penetrance, may play a role in breast pathogenesis such as the ATM tumor-suppressor gene. ATM is the apex of the repair pathway of DSB. This protein kinase activates through phosphorylation of its substrates cell cycle checkpoints, which leads either to the delay of the cell cycle progression until DSB are repaired or to the promotion of apoptosis. To sum up, the ATM gene seems to have a role in breast cancer development in a minority of the high-risk families in our population which is significantly lower compared to BRCA1/2 and it also seems to be involved in pathogenesis of sporadic breast cancer. Despite the ATM gene's length, we do not perform the preventive screening of this gene in breast cancer high-risk families. Nevertheless, we offer the molecular diagnostics of ATM to ataxia telangiectasia patients.
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MDOCTM effect on expression of cell adhesion molecules / / in the vessel wall of ApoE / LDLR-deficient mice
Drnek, Ludvik ; Nachtigal, Petr (advisor) ; Štaud, František (referee)
Atherosclerosis belongs to the cardiovascular diseases, which have been the most frequent cause of the morbidity and mortality in all the economically advanced countries of Europe and the USA in the last few years. The purpose of this thesis was to find some potential hypolipidemic and antiinflammatory effects of MDOC. The new potential substance belongs to the group of dietary fibre. ApoE/LDLr-deficient mice (n=8) was used in the study. The mice were fed with aterogenic diet containing 1.25% cholesterol for 8 weeks. In MDOC group, the mice were fed on the same aterogenic diet, with 5% MDOC added to this diet. Blood sample for the biochemical investigation were taken from animals. Then, partitions of the tissue formed by the aorta together with the upper part of the heart were taken, too. Then, a biochemical analysis of the blood was made and also in aortic sinus and arch an imunohistochemical and stereological analysis of the endothelial expression of VCAM-1 and ICAM-1 were performed. The results of the biochemical analysis showed that MDOC treatment resulted in a significant decrease of total cholesterol, VLDL and significant increase of HDL cholesterol. Stereological analysis of immunohistochemical staining showed significant decrease of VCAM-1 staining in the atherosclerotic lesion after the...
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The effect of tick salivary proteins on innate immunity cells
PÁLENÍKOVÁ, Jana
Saliva of Ixodid ticks contains a whole array of pharmacologically active molecules with vasodilatory, antihemostatic, and immunomodulatory activities. This thesis focuses on two types of salivary proteins, serpins and cystatins, and their role in immunomodulation. These protease inhibitors are known to affect many biological functions. To better understand their role in tick saliva we examined their effect on dendritic cells and their ability to modulate the immune response after pathogen infection. As model pathogens, Borrelia spirochetes and tick-borne encephalitis virus were used.
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Synthesis and cytostatic activity of 3,5-disubstituted pentenolides analogous to gelastatin
Pavlík, Jan ; Pour, Milan (advisor) ; Starý, Ivo (referee) ; Dvořák, Dalimil (referee)
Within the framework of this thesis, a large series of 5-(acyloxymethyl)-3-aryl-5,6- dihydro-2H-pyran-2-ones was prepared and their cytostatic activity investigated. The key steps in the preparation of the compounds were alkylation of esters of substituted phenylacetic acids with 2-iodomethyl-5,5-dimethyl-1,3-dioxane, followed by cyclization to furnish a saturated lactone into which a double bond was introduced in the next step. Some of the target compounds displayed interesting cytostatic activity (IC50 < 10 µmol/L) against a panel of standard cell lines including both leukemic cells and those derived from solid tumours. The activity against colorectal carcinoma HT29 cell line, which is otherwise resistant against the standard combination of cytostatic agents used in the treatment of these tumours is especially remarkable. In the next part, the development of the synthesis of the 5-alkylidene analogues of these compounds, which are also analogous to bioactive natural products, such as the gelastatins and CR377, is described. Successful strategy is based on the use of 2-iodo allylic alcohols as the starting materials, which are converted into the target 3-substituted-5-alkylidene pentenolides via an array of Pd-catalyzed reactions, including Sonogashira coupling with methyl propiolate,...
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Study of dielectrical properties of organic material thin films
Pospíšil, Jan ; Boušek, Jaroslav (referee) ; Mikula, Milan (referee) ; Zmeškal, Oldřich (advisor)
The dissertation is focused on the study of electric and especially dielectric properties of thin film organic materials with their huge potential for optoelectronics and other industrial sectors. The theoretical part deals with the use of organic materials in organic photovoltaic cells, the methods of deposition techniques and characterization. The theoretical knowledge of the dielectric spectroscopy, including methods for determining the physical properties and evaluation of experimental data are also described. The experimental part is devoted to the study of small molecule organic solar cells with bulk heterojunction composed of electron donor molecule of DPP(TBFu)2 and electron acceptor fullerene derivatives, such as PC60BM, PC70BM and TC60BM. The experimental part is divided into two main parts. The first part deals with the study of processes occurring at the interface between the active layer and the contact; the second part is focused on transport processes inside the structure of photovoltaic cells and also contains a study of perovskite solar cells.
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