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Aspects of Gene Regulation of CYP3A4 in Hepatic Tissue.
Krausová, Lucie ; Štaud, František (advisor) ; Mičuda, Stanislav (referee) ; Skálová, Lenka (referee)
1 Summary CYP3A4 is an important enzyme involved in elimination of majority of metabolized xenobiotics. It plays a major role in the detoxification system of the human body, therefore it is responsible for many drug-drug interactions (DDIs). DDI present a complication of current pharmacotherapy, in the extreme they can lead in failure of therapy or in life-threatening toxic effects. DDIs are caused by changes in enzymatic activity of CYP3A4, which is highly variable among individuals. An important mechanism of modulating CAP3A4 activity is the regulation of inducible transcription by nuclear receptors, especially PXR, CAR and GR. The structure of CYP3A4 promoter and mechanisms of transcriptional regulation has been studding intensively for many years, but the research of relationship of nuclear receptors and transcriptional cofactors in CYP3A4 transactivation is still incomplete. Present work contributes to elucidation of some questions concerning the effects of azole antimycotics on CYP3A4 transcription via PXR, potency of valproic acid to activate PXR and CAR or determinants of CYP3A4 expression via GR in placental cells. The experiments were performed with up-to-date molecular biology methods and using in vitromodels of the primary human hepatocytes and hepatoma cell lines. To the aims of the doctoral...
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AWS Viscometry – Principles and Applications
Wein, Ondřej
Quantitative identification of Apparent wall slip (AWS) effect, accompanying the flow of colloidal dispersions in confined geometries, requires a specific modification of common viscometric methods. Essential distinction between common and AWS viscometry is outlined – including theoretical background, calibration, data acquisition, and downstream data treatment – and demonstrated for a class of rotational viscometers.
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Utilization of the database applications in clinical research
Telička, Zdeněk ; Jiskra, Jan (advisor) ; Doležal, Tomáš (referee)
The Diploma Thesis "Utilization of database applications in clinical research" deals with development of client-server database application for 3rd Medical Department, 1st Faculty of Medicine, Charles University in Prague. Application's aim is to store structured data of patients' examinations, treatments and biochemical results. Purpose of the application is to facilitate data processing for clinical research, which is very difficult, because information stored in hospital information system doesn't contain detailed records from medical examinations. Also, searching for several entries is slow. As well, application allows import patient identification data from hospital information system. This function provides physicians wide range of possibilities in data processing 4 and comparison in relation to treatments. Effective feature of this application is faster writing medical reports stored in information system because they are automatically generated from application's database.
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T cells labelling by bimodal contrast agent for in vivo studies of stroke
Krijt, Matyáš ; Poljaková, Jitka (advisor) ; Kříž, Jan (referee)
Stroke is a serious brain injury, which causes sudden death or terminates in permanent neurological disability. Nowadays, tissue plasminogen activator (tPA) is used as the only effective treatment of stroke. One of the potential targets for novel therapy are T cells. Even though the explicit role of T cells in the pathogenesis of brain injury, amounts and timing of all T cell subtypes infiltrating into brain during the stroke still needs further investigation. The research in this field is complicated by the lack of efficient methods for in vivo cell tracking. Therefore the aim of this thesis was to develop a method of T cells labelling by MRI contrast agent in order to investigate T cells distribution in ischemic mice model using in vivo MR imaging. T cells were isolated from C57/BL6 mice in two step isolation protocol using gradient centrifugation and magnetic separation with the efficiency of 97 %. The isolated cells were labelled with 100 μg Fe/mL of Molday ION Rhodamine B contrast agent. The labelling efficiency after 17 hours of cells incubation was higher than 99 %. The labelled cells were cultured with CD3 and CD28 antibodies resulting into the 74 % viability of labelled T cells compared to 83 % viability of non labelled T cells. The labelled T cells were visualized by fluorescent...
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Passivation of Aluminum and Aluminum Alloys in passivation baths without Cr6+ Compounds
Macháč, Pavel ; Tulka,, Jaromír (referee) ; Molliková, Eva (advisor)
This diploma thesis deals with evaluation of efficiency of protection conversion coatings created by passivation metals and alloys in passivation baths without chromium compounds. The theoretical part is initially concerned with question of electrochemical corrosion of metals, consequently there are mentioned different methods of corrosion protection. The main section of theoretical part of this thesis deals with chromate conversion coatings, description of their protective efficiency (including their unique self-healing effect) and then with account of new chromate-free conversion coatings occurring as chromate alternatives, whose usage is constrained because of their content of hexavalent chromium, which is highly toxic, oxidizing and also carcinogenic and thereby very dangerous for human body and the environment. Experimental part of this thesis is concerned with evaluation of efficiency of particular conversion coating which is quite commonly use in some applications as chromate alternative. It is chromate-free conversion coating which is created by passivation of metals or alloys in passivation bath Pragokor BP, which contains zirconium fluorocomplexes and is without any chromium or other toxic or ecologically unhealthy compounds. The influence of sealing of the coating in preparation Pragokor Seal Al and also other surface treatments such as application of conservation wax WAXENG or cold application of zinc coating were tested too. Efficiency of mentioned surface treatments was then evaluated on aluminum and steel by laboratory accelerated and atmospheric corrosion testing.
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Polarized Radiative Transfer in Solar Atmosphere
Štěpán, Jiří ; Heinzel, Petr (advisor) ; Degĺ Innocenti, Egidio Landi (referee) ; Bueno, Javier Trujillo (referee)
The adequate theoretical models of the NLTE radiative transfer are needed for interpretation of the complicated spectra emerging from the magnetized solar atmosphere. In the first part of the thesis, the quantum theory of polarization is reviewed along with the problem of NLTE radiative transfer of the 2nd kind. A general notation for a numerical treatment of the atomic density matrix is introduced. A lambda-operator splitting technique is presented and used for development of a novel preconditioning method analogous to the Jacobi iteration algorithm. Number of processes is taken into account: atomic polarization, level-crossings, Paschen-Back effect, Hanle and Zeeman effects, optical pumping, collisional (de)polarization. A nonlinear multigrid technique is developed in the framework of polarized radiative transfer theory and the eficiency of the method is discussed. The potential of this new solver is demonstrated on an example of transfer of the optically thick line of a multiterm atom in the Paschen-Back effect regime. In the second part of the thesis, the particular problem of impact polarization of the hydrogen H-alpha line in solar flares is considered. The semi-empirical models of the flaring chromosphere are used to find the differential effects of the proton beam on the line intensity and linear...
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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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Monitoring the effect of atorvastatin on the expression of endoglin / / and endothelial NO synthase (eNOS) in mouse model of atherosclerosis
Uhlárová, Iva ; Nachtigal, Petr (advisor) ; Štaud, František (referee)
Atherosclerosis, or sclerosis of arteries, is a degenerative disease of arteries. Sometimes it is called "the disease of 20th century". ApoE/LDL - receptor double knockout mice represent a new animal model for study of atherogenesis, which is characterized by severe hyperlipidaemia and atherosclerosis. Statins (or competitive inhibitors 3-hydroxyl-3-methyl-glutaryl-coenzym A-reductase) currently belong to the most efficient and the most useful hypolipidemic drugs for all over the world. They decrease mainly levels of total cholesterol and LDL cholesterol. The aim of this thesis was to describe the expression of endoglin in atherosclerotic plaques in apoE/LDL-receptor deficient mice. Moreover we wanted to determine endoglin colocalization with eNOS and the effect of atorvastatin treatment on the expression of both molecules. ApoE/LDLR-deficient mice on were subdivided into 2 groups. The control group of animals was fed with the western type diet. The same atherogenic diet was used in ATV group, where atorvastatin was added to the atherogenic diet at the dosage of 100 mg/kg per day. The results of this thesis confirmed the expression of endoglin in atherosclerotic lesions in ApoE/LDLR-deficient mice. The expression of endoglin was located on the aortic vascular endothelium and in other smaller...
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