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Enterohepatic circulation of bilirubin
Zelenka, Jaroslav ; Vítek, Libor (advisor) ; Entlicher, Gustav (referee) ; Červinková, Zuzana (referee)
Bilirubin is a main physiological product of heme degradation possessing important antioxidant and antiinflammatory properties. On the other hand, it could be neurotoxic during severe unconjugated hyperbilirubinemia combined with insufficiency of blood-brain barrier (neonatal jaundice). It is secreted from the body via bile and is further metabolized in the intestine. Part of the substance is reduced to urobilinoids, part is adsorbed to the intestinal content and some part could be reabsorbed back to the systemic circulation. This enterohepatically and enterosystemically circulating fraction varies in size depending on the rate of bilirubin secretion, solubility in the intestine and intensity of its intestinal metabolism. Under specific circumstances, EHC and ESC may significantly increase serum and bile bilirubin levels and influence physiological as well as pathological processes occuring in the body. Among the most important is the protective elevation of UCB levels in Gilbert syndrome subjects and dangerous increase in severity of neonatal jaundice. In the presented thesis, the mechanisms affecting EHC and ESC of bilirubin and tools for further research in BP metabolism were investigated. The solubility of intestinal UCB is strongly decreased by addition of divalent cations. However, such approach to...
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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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The role of a horse in the course of human history
Burešová, Lenka ; Opletalová, Lenka (referee) ; Czumalo, Vladimír (advisor)
The horse is a large odd-toed ungulate mammal, one of modern species of the genus Equus. Horses have long been among the most economically important domesticated animals and although their importance has declined with mechanization, they are still spread worldwide. The horse is a prominent being in religion, mythology and art; it has played an important role in transportation, agriculture and war and it has served as a source of food, fuel, and clothing, too. Most horse breeds are able to perform various kinds of work such as carrying humans on their backs or can be harnessed to pull objects such as carts or plows. Moreover, there are some horse breeds specially trained for certain tasks - lighter species of horses for racing or riding, heavier species for farming and other tasks requiring pulling power. Some horses, such as ponnies, can be kept as pets. In some societies, horses are still a source of food, both meat and milk; in others it is taboo to consume them. In industrialized countries horses are predominantly kept for leisure and sport, whereas in other parts of the world they are still used as working animals. Both horses and humans have coexisted together for thousand years wherefrom an extensive specialized vocabulary has arisen to describe each horse behavioral and anatomical characteristic with...
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STRAIN ENGINEERING OF THE ELECTRONIC STRUCTURE OF 2D MATERIALS
del Corro, Elena ; Peňa-Alvarez, M. ; Morales-García, A. ; Bouša, Milan ; Řáhová, Jaroslava ; Kavan, Ladislav ; Kalbáč, Martin ; Frank, Otakar
The research on graphene has attracted much attention since its first successful preparation in 2004. It possesses many unique properties, such as an extreme stiffness and strength, high electron mobility, ballistic transport even at room temperature, superior thermal conductivity and many others. The affection for graphene was followed swiftly by a keen interest in other two dimensional materials like transition metal dichalcogenides. As has been predicted and in part proven experimentally, the electronic properties of these materials can be modified by various means. The most common ones include covalent or non-covalent chemistry, electrochemical, gate or atomic doping, or quantum confinement. None of these methods has proven universal enough in terms of the devices' characteristics or scalability. However, another approach is known mechanical strain/stress, but experiments in that direction are scarce, in spite of their high promises.\nThe primary challenge consists in the understanding of the mechanical properties of 2D materials and in the ability to quantify the lattice deformation. Several techniques can be then used to apply strain to the specimens and thus to induce changes in their electronic structure. We will review their basic concepts and some of the examples so far documented experimentally and/or theoretically.
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Impact of pesticides on the gut microbiota of human
Kočová, Kateřina ; Rada, Vojtěch (advisor) ; Jakub, Jakub (referee)
Pesticides are substances or mixtures of substances used in agriculture against pests (animals, plants and parasitic fungi), who damage the crops, stocks of agricultural products, food and reduce livestock utility or threaten human health.
The thesis consists of two parts. The first (theoretical) part describes composition and function of gut microbiota; pesticides and their classification, environmental transport and effects of these substances on human health, and glyphosate as the active substance of herbicide Roundup, its mechanism of action, environmental fate and proven effects of glyphosate on human.
The aim of second (practical) part of this thesis was to test impact of pesticide Roundup on the gut microorganisms of human. The impact of pesticide was tested in in vitro pure cultures. Roundup was added in concentrations of glyphosate 17 g/L, 1,7 g/L and
0,17 g/L to the complex media and after cultivation the growth of microorganisms was evaluated. The next samples of stool were collected from human volunteers; these were cultivated similarly in the complex media with different concentrations of glyphosate. The total numbers of microorganisms, bifidobacteria, lactobacilli, enterococci and coliformn bacteria were defined after cultivation.
When the pesticide was tested in pure cultures, concentration of 17 g/L glyphosate significantly inhibited total bacterial growth (P < 0.05), at lower concentrations no difference was observed. The cultivated microorganisms from samples of stool demonstrated only that bifidobacteria are sensitive to glyphosate at the highest used concentration of this pesticide compared with the control sample.
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Oscillatory Power Generator Base on Mechanical Resonant Element
Mihalík, Vlastimil ; Houška, Pavel (referee) ; Hadaš, Zdeněk (advisor)
This work deals with the power supply of wireless sensors. When using a wireless sensor is desirable application of alternative energy sources, because the primary cells or batteries may reduce the extent or length of service of the sensor itself. Ambient energy can be used as a suitable alternative source. This energy must be in an appropriate form, which allows its conversion to electric energy. These appropriate, already used types include: solar en., temperature gradient en., en. of flowing liquids, vibration, etc. The advantage of vibrations is its presence in almost all mechanical systems. One of the possibilities for using the vibration of machine systems for power supply wireless sensors is using the vibration power generator with oscillating component. The generator must be designed so that its resonance frequency coincides with the frequency of vibration in the machine system. This method can be used only if the machinery system vibrations at least partially constant. Another option is to use the vibrations caused by, for example, transit transport, or different step acting factor. In this case, it is desirable that the generator is designed with variable resonant frequency, which can partly be achieved, for example, integrating several oscillating component in the body of generator. After the general analysis of the problem, graduation theses will be concerned with the possibility of use of energy from the short damped oscillation and step impulse. Focusing on a proposal of multi-element structures.
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Heat and mechanical resistance of zinc coating
Horák, Karel ; Dzimko, Marián (referee) ; Černý, Michal (advisor)
The work is aimed at studying the thermal degradation of the protective zinc coating. Its large part deals with the structure of the various stages of transition and their arrangement, the main emphasis is on analysis of brittle intermetallic phases, which arise due to increased temperature. Conclusion of the work is trying to clear itself causes degradation of this protective layer.
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Study of Platinum Cytotoxic Drug Interactions with ABCG2 Membrane Transporter
Bouška, Petr ; Čečková, Martina (advisor) ; Vacková, Zuzana (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Mgr. Petr Bouška Consultant: PharmDr. Martina Čečková, Ph.D. Title of Thesis: Study of platinum cytotoxic drug interactions with ABCG2 membrane transporter Platinum cytotoxic drugs pertain among most frequently used cytotoxic drugs. However, their usage is complicated with development of resistance which can be caused by few mechanisms. The aim of this study is to evaluate possible interactions of cisplatin, carboplatin and oxaliplatin with ABCG2 membrane efflux transporter which causes resistance to many cytotoxic drugs. Hoechst 33342 assay was performed on cell lines MDCKII (parent cell line) and MDCKII-ABCG2 (cell line genetically modified for expression of human ABCG2 gene). Intracellular concentration of Hoechst 33342 was not increased in presence of any tested cytotoxic drug; significant change of Hoechst 33342 intracellular fluorescence was observed only in presence of ABCG2 control substrate mitoxantron and ABCG2 inhibitor fumitremorgin C. Final results did not demostrate interactions of ABCG2 with any studied platinum cytotoxic. It shows insignificant interaction between ABCG2 and platinum cytotoxic drugs and so improbable effect of this transporter on toxicity reduction...
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Arctic tundra dendrochronology
Lehejček, Jiří ; Svoboda, Miroslav (advisor) ; Monika, Monika (referee)
Historically unprecedented environmental change in the Arctic ecosystems is often given into the context of its past and possible future development. In the region where instrumental meteorological observations are scarce archives need to be investigated in order to address this issues. The comprehensive synthesis one of the archives: long-live circumpolar evergreen Juniperus communis L. shrub is presented here. 20 individuals from southwest Greenland were investigated at the cell anatomy level to understand the ecology of the species and unhide its potential for environmental and climate reconstructions. The findings are as follows:
i) Stop of exponential cross-sectional conduit-lumen widening with increasing age is in contrast with conduit-lumen nature of trees. This indicates that shrubs do not need to saturate their water and nutrient demands via traits of classical hydraulic conductivity law but rather developed different mechanisms. Extreme weather conditions result in prostrate growth form. However, different weather factors probably influence shrub growth differently: While snow and wind act mechanically (a), temperature influences the form of growth physiologically (b). a) So long as the young shrub stem has high resilience to bend back to an upright position after snow melt and so long as it can withstand the wind during the vegetation season it most likely grows upright and the conduit-lumens widen. b) Temperature, resp. freeze-thaw events are responsible for the shrubs preference of safety (finite size of conduit-lumens) over hydraulic efficiency, thus not allowing for more primary growth. All of these (and other) factors are apparently working together and the transition of vertical to more horizontal growth is gradual. As a consequence, the conduit-lumen sizes may not have to be further increased (due to ecophysiological restrictions possibly also must not) because water is no longer transported against gravity.
ii) Observed age/growth trend has to be taken into consideration for further employment of the wood anatomical parameter in paleoenvironmental studies. That is, shrub cell parameters can only be used for this purposes if correctly detrended. This allows for more accurate as well as longer reconstructions because youth trend was often neglected in reconstructions based on shrub annual-rings.
iii) The south-western Greenland Ice-Sheet (GrIS) melt rates reconstruction is presented for the whole 20th century. This part of GrIS is considered as the most active. According to the presented reconstruction current GrIS melt rates are not uncommon for the last century being comparable to first decades of 20th century. This finding is particularly important contribution to the debate on Atlantic meridional overturning circulation (AMOC). Too high fresh water inputs into the Northern Atlantic from GrIS melting may slow down or even stop the AMOC which would result in more continental climate in Europe. Presented results indicate that this threshold lies higher than observed current melt rates of GrIS.
Fascinating Juniperus comunnis species has shown to be able to address many ecological as well as environmental open questions and due to its longevity and abundant distribution has a great potential to become an important player in the Arctic research.
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