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Influence of Cholestatic Liver Injury on the Elimination and Transport of Drugs
Brčáková, Eva ; Štaud, František (advisor) ; Tilšer, Ivan (referee) ; Lotková, Halka (referee)
The liver is a unique organ with a number of vital functions. Pivotal one is its participation on bile formation and secretion, import, detoxification and excretion of endogenous substances and xenobiotics. Bile formation is essential for both absorption of lipids in intestine and excretion of various endogenous compounds and xenobiotics (e.g. bile acids, bilirubin, cholesterol, phospholipids and drugs). This function is markedly impaired during extrahepatic and intrahepatic cholestasis with partial or complete stoppage of bile flow. Consequently, hepatic and further systemic accumulation of toxic biliary constituents, such as bile acids and bilirubin, occurs. In an effort to compensate this situation, spontaneous anti-cholestatic mechanisms are activated, which provide alternative excretory routes for toxic accumulating compounds (e.g. renal elimination of bile acids and xenobiotics into urine). These mechanisms include changes in the expression, localization and function of respective transporters in liver and kidneys. Another mechanism with a significant impact on bile formation and transport of compounds between bile and blood is blood-biliary barrier formed by connection of hepatocytes by "tight-junctions" and "gap-junctions". While "gap-junctions" exchange substances among cells,...
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Study of the Function of Reproductive Barriers for Use in Vivo and in Vitro Models
Pospěchová, Kateřina ; Semecký, Vladimír (advisor) ; Jirásek, Jan Evangelista (referee) ; Stingl, Josef (referee)
Summary: The main limiting factor of distribution of the drugs in the body is the presence of physiological barriers. Placental and blood-testis-barrier are two barriers that were studied in this thesis. The placenta is an important endocrine organ bringing maternal and fetal blood into proximity, allowing exchange of nutrients and waste products. In addition, the placenta acts as the barrier between the mother and fetus, and plays an important role in fetal protection. The key rate-limiting layer in the placenta is the single layer of syncytiotrophoblast. The placental trophoblast contains multiple drug transporters and metabolizing enzymes that control maternofetal exchange of nutrients and hormones, or which form placental "metabolic" barrier. Moreover, several members of the nuclear receptor superfamily are expressed in placental trophoblasts. They regulate transcription of the genes involved in nutrient transport, mineral metabolism, proliferation and differentiation. Moreover it was suggested that they control expression of placental drug transporters and xenobiotic metabolizing enzymes. Germ cells in the testis are protected mainly by the presence of blood testis barrier, formed by the tight or adherens junctions between Sertoli cells. Moreover, intercellular junctions between Sertoli and germ cells...
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Modeling water and pesticide transport in tropical soils
Pavelková, Helena ; Vogel, T.
This study was elaborated within a research project supported by the Hawaii Department of Agriculture (HDOA). The purpose of the project is to evaluate the likelihood of leaching of pesticides to ground water in tropical soils and to compare the transport of pesticides with tracer (bromide ion). Several field and laboratory experiments were caried out on Hawaiian Islands. Data from these experiments were compared with one?dimensional model of water and solute transport. In this paper, current results of modeling water and solute transport (atrazine and bromide ion) are presented.
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Competition in air transport in the Czech Republic in 2006-2011
Bartoňová, Kristýna ; Ševčík, Miroslav (advisor) ; Zeman, Karel (referee)
The aim of this thesis is to provide a market analysis in the field of air transport in the Czech Republic in period of 2006-2011 and to assess the development of competitiveness of CSA in these years . During a few decades, air travel have managed to build solid position in the transport market and has become an integral part of the economy. It represents the fastest and most modern way of traveling long distances. In addition, its popularity and availability improves year to year. During the twenties, Czech Airlines were among the pioneers of aviation, but is currently facing problems due to increasing competition from low cost carriers in the Czech Republic. CSA also face problems within the company, which significantly affect the running of the company and was forced to accede to the steps of restructuring. The Bachelor's thesis also deals with development of low-cost airlines and their effect on. Using survey find what factors play the most signifiant role of potential clients' selection of airlines and how they perceive the development of affairs around the company CSA. By analyzing the survey and the findings, the paper aims at suggesting a possibility how the company may attract new clients.
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Transport mechanisms of drugs trough the blood-brain barrier and their influencing by L-carnitine.
Havelek, Radim ; Herink, Josef (advisor) ; Kudláčková, Zděnka (referee)
Many neurodegenerative diseases, cancer and infections of the brain become more prevalent as population become older. That is one of the reasons, why blood-brain barier and it's transport mechanisms are intensively investigated. The blood-brain barrier is a unique membranous barrier that tightly segregates the brain from the circulating blood. The blood- brain barrier is formed by the connection of closely adjacent tight junctions between the capillary endothelial cells, which are not fenestrated and which display minimal pinocytosis. The capilary endothelial cells form a polarized barrier, which regulates transport of molecules across the blood-brain barrier. L-carnitine is compound necessary in the peripheral tissues for a transfer of fatty acids for their oxidation within the cell, it accumulates in the brain despite low β-oxidation in this organ. In order to enter the brain, L-carnitine has to cross the blood- brain barrier via specific carnitine transporters. The aim of this work was to describe recent information about blood-brain barrier, L-carnitine, transport mechanisms across blood-brain barrier and to find whether administration of L-carnitine can affect effect of 7- methoxytacrine. As a marker of the effect of drugs tested was chosen determination of activity of AChE by Ellman method in...
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MRP transporters in the placenta
Dvořáková, Marie ; Čečková, Martina (advisor) ; Pávek, Petr (referee)
The MRP mebrane proteins, which belong to the ABC transporter family, comprise currently 9 members. The MRP transport proteins are expressed in various tissues of the organism, including placenta. The major physiological role of the multidrug transporters is the transport of many endogenous and exogenous compounds, including drugs, across the cell membrane. This thesis summarizes up to date information concerning expression and function MRP transporters in placenta a and in other tisssues in organism. Only five MRP transporters have been detected in placenta, namely MRP1, MRP2, MRP3, MRP5 a MRP8. Expression of all this proteins in placenta changes with progress of the pregnancy. MRP transporters help to protect fetus from potentially toxic substances, on the other hand some of them can facilitate the passage of substances across placenta. Some MRPs possess specific physiological functions in placenta. For example, MRP1 influences apoptosis, MRP5 participates in NO-dependent vasodilatation in fetal vessels.
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BCRP in the placenta - expression, lokalization, function
Šobáňová, Ivana ; Štaud, František (advisor) ; Nachtigal, Petr (referee)
Breast cancer resistance protein (BCRP, ABCG2, ABCP, MXR) is the 72 kDa multidrug resistance protein belonging to the family of ABC transporters. This efflux transporter is able to distinguish and actively extrude a wide variety of chemically and structurally unrelated compounds out of cells. BCRP is most expresse in the majority of human tissues, most abundantly it is expressed in the apical membrane of placental syncytiotrophoblasts. This localization predetermines BCRP to play an important role in protecting the fetus by limiting the penetration of various xenobiotics across the placental barrier. Because of the need to treat some diseases even during pregnancy the knowledge of transplacental pharmacokinetics becomes necessary for evaluation of potential toxicity and therapeutic value of the drugs in pregnancy. The aim of this work is to summarize the current knowledge concerning the expression, localization, polymorphism and function of BCRP transporter in placenta and also the role of BCRP in pharmacotherapy in pregnancy.
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