Kristýna Paclíková Influence of resveratrol on bile flow Diploma thesis Charles University in Prague, Faculty of Pharmacy in Hradec Králové Pharmacy Background: Protective effect of resveratrol is shown in many experimental models of cholestasis, but its effect on bile production in healthy individuals has not been studied yet. As the use of resveratrol is frequent in population, the aim of this thesis was to investigate the effect of resveratrol on the bile flow in healthy animals and the clarification of the mechanism of this effect. Methods: Wistar rats (n = 6, in each group, weighing 280 to 320 g) were divided into two groups: control group (Control) and the group of rats administered with resveratrol (10mg/kg/day, p.o.) for 28 days (RES). In vivo clearance study was performed to analyze bile production. Analysis of mRNA and protein expression of the transport proteins was performed by qRT-PCR and Western blot. Results: Resveratrol led to a significant increase in the cumulative bile flow. Analysis of mRNA and protein expression of the transport proteins revealed that bile flow is changed due to posttranscriptional induction of canalicular transporters Bsep and Mrp2. Simultaneously, resveratrol led to induction of Mrp4 efflux protein, expressed at the basolateral membrane of hepatocytes....

The study of signaling pathways that modulate multidrug resistance The theme of cancer cell resistance to anti-cancer drugs including the common mechanisms of resistance development and the theory of cancer stem cells was introduced in the Introduction to the doctoral thesis. The theoretical part was focused more deeply on the two topics - the role of ATP-binding cassette (ABC) transport proteins and chromosomal abnormalities in the development of cancer chemoresistance. The possible therapeutic potential for the treatment of cancer was stressed for both topics. The Results were composed of the commentaries on the five published works, which the author of the thesis conducted as the main author. The first work brought the evidence supporting the hypothesis of the existence of ABC gene expression profiles (signatures), which are common to multiple types of tumors and are associated with significant clinical consequences. These general ABC gene expression profiles could possibly form a new hallmark of cancer. The second work studied more closely a group of acute myeloid leukemia patients, who did not achieve complete cytogenetic remission after two attempts to maintain remission of the malignant disease. The new entity, consisting of patients with the translocation t(2;11)(p21;q23) without the...

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Barbora Umanová Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Title of diploma thesis: Expression and function of placental drug transporters in health and disease There are many physiological changes during pregnancy. Placenta is a crucial organ which mediates exchange of nutrients, metabolites and respiratory gases, provides endocrine functions and fetal protection. A pregnant woman and her fetus may be exposed to various potentially harmful substances during pregnancy, including drugs that may endanger fetal health. Protection of the fetus from xenobiotics is enabled by drug transporters. Drug transporters are membrane proteins expressed in most tissues of the human body. In the placenta, they are localized in the placental syncytiotrophoblast and occur also in the endothelial cells of the fetal vessels. They belong into two large superfamilies of transporter proteins: ATB-binding cassette (ABC) and solute carrier (SLC). While ABC transporters mediate exclusively efflux of their substrates, SLC are predominantly influx transporters. Therefore, these transport proteins play a key role in the disposition of drugs, some of which facilitate drugs entry into a fetus, and others actively...

The study of signaling pathways that modulate multidrug resistance The theme of cancer cell resistance to anti-cancer drugs including the common mechanisms of resistance development and the theory of cancer stem cells was introduced in the Introduction to the doctoral thesis. The theoretical part was focused more deeply on the two topics - the role of ATP-binding cassette (ABC) transport proteins and chromosomal abnormalities in the development of cancer chemoresistance. The possible therapeutic potential for the treatment of cancer was stressed for both topics. The Results were composed of the commentaries on the five published works, which the author of the thesis conducted as the main author. The first work brought the evidence supporting the hypothesis of the existence of ABC gene expression profiles (signatures), which are common to multiple types of tumors and are associated with significant clinical consequences. These general ABC gene expression profiles could possibly form a new hallmark of cancer. The second work studied more closely a group of acute myeloid leukemia patients, who did not achieve complete cytogenetic remission after two attempts to maintain remission of the malignant disease. The new entity, consisting of patients with the translocation t(2;11)(p21;q23) without the...

English abstract Hydrothermal systems related to highly evolved granitic magmas host diverse mineralization styles and provide an important source of economic metals. This master thesis concentrates on description and interpretation of geological structure, petrographic and textural variability, alteration zoning and calculation of time-integrated fluid fluxes recorded in highly evolved granites and tin-mineralized greisens of the Horní Blatná massif in the Western Krušné hory pluton. The massif is a composite intrusion, which consists of a large number of intrusive units emplaced during two stages. The first stage is represented by sparsely porphyritic fine-grained low-lithian annite granites that can be correlated with marginal granites (G2) of the Fichtelgebirge (Smrčiny) batholith or with intermediate granites (Walfischkopf type) of the Western Krušné hory (Erzgebirge) pluton. Intrusive batches of the second stage progressively evolve from medium- to coarse-grained serial high-lithian annite and zinnwaldite granites with topaz and rare tourmaline towards aphyric fine-grained zinnwaldite (or trilithionite) granites. This suite corresponds to the EIB2 and EIB3 facies of the younger intrusive complex in the Western Krušné hory (Erzgebirge) pluton and it can be compared to the G3 Waldstein and G4 units in...

The aim of the study is the purification and characterization of hemelipoglycoprotein, a carrier protein from the ornate sheep tick Dermacentor marginatus. The protein was characterized by biochemical methods with emphasis on its glycosylation and native molecular weight, and examining its carbohydrate-binding specificity.

This diploma thesis is focused on fabrication of graphene field-effect transistors, characterisation of their transport properties and investigation of low-energy electron beam influence on the devices' properties under UHV conditions. The theoretical part of this work describes graphene fabrication methods, options of graphene transfer onto the substrates for graphene field-effect transistor manufacture. Furthermore, model of graphene doping via electrostatic interaction or photon, resp. electron beam exposition is explained. The experimental part of this work consist of manufacture of the graphene field-effect transistor in order to examine the change of its transport properties induced by doping of the graphene via low-energy electron beam exposition.

Detailed history of golf, golf carts and vehicles was described in analytic part of DT. Components and technical aspects of golf carts were listed in the technical part of the analysis. It also gives an overview of modern technologies available in these types of vehicles. Design part of DT maps current products on the market and their components influencing appearance of the vehicle. The final solution was chosen from three variants and brought the greatest added value. The original idea includes the way how to make handling of the vehicle easier, simplifies maintenance and reduces unnecessary preparation time of golf equipment for the game. New features have been presented in a single comprehensive and unique design.

Evolved silicic rocks display a variety of igneous textures, which can provide important information on crystallization kinetics and rheology in natural magma chambers. Individual kinetic effects such as diffusion rate, nucleation rate, growth rate and post-solidification modifications are likely to be reflected in the modal and textural appearance of the resulting rock. This work focuses on characterization and interpretation of solidification textures in a 600 m wide and 5 km long body of highly evolved, boron-rich aplites and pegmatites at the southern endocontact of the Říčany granite pluton (Central Bohemian Plutonic Complex). This rock suite is associated with biotite Říčany granite, hosting microgranite and aplite dyke swarm, and it is built up by massive tourmaline aplites, layered aplites with tourmaline-rich or locally garnet-rich bands, pegmatite pockets, pegmatite layers with unidirectional solidification textures (comb layers), megacryst zones (analogous to stockscheider), and late pegmatite dykes discordant to layering. Textural as well as modal variations are usually sharp and observable megascopically as well as on the microscale. All aplites and pegmatites usually contain similar proportions of quartz, albite-rich plagioclase, K-feldspar, various proportions of tourmaline (up to...

This thesis first briefly mentions the characteristics of the skin and contains a review of current knowledge on the in vitro permeation testing of drugs through the skin. It describes the basic data about nerve agents and the possibilities of prophylaxis poisoning warfare agents focusing on preventive transdermal administration. The experimental work is focused on in vitro testing abilities oxime HI-6 and posibly other reactivators enzyme acetylcholinesterase penetrate through pig skin. Experiments were conducted in static diffusion cells Franz type. The amount of test substance leaked through the skin is determined in the sample of receptor fluid by HPLC. Keywords permeation in vitro; transdermal; pig skin; Franz cell; substance HI-6; antidota; nerve agents; acetylcholinesterase