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Evaluation of gene expression of selected ABC and SLC transporters in the HTR-8/SVneo cell line during stimulation with pro-inflammatory cytokines
Pokorná, Petra ; Čečková, Martina (advisor) ; Mladěnka, Přemysl (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Petra Pokorná Supervisor: Assoc. Prof. PharmDr. Martina Čečková, Ph.D. Consultant: Mgr. Simona Dudičová Title of diploma thesis: Evaluation of gene expression of selected ABC and OATP transporters in the HTR-8/SVneo cell line during stimulation with pro-inflammatory cytokines Placenta is the first and the largest fetal organ that gradually develops during pregnancy and plays an essential role in the development of the fetus. It fulfills the entire spectrum of functions, ensures the transport of nutrients to the fetus and the removal of waste substances back into the maternal circulation, protects the fetus from toxins, and at the same time fulfills a certain mechanical and especially immunological barrier between mother and fetus. One of the main functions of the placenta is the transport function which is made possible by membrane transporters present mainly in the syncytiotrophoblast layer of the placenta. Transporters in the human placenta can be divided into two families, SLC and ABC which are further divided into several subfamilies. The expression of transporters changes physiologically during pregnancy, but pathological conditions such as inflammation can also influence the expression....
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Evaluation of gene expression of selected ABC and SLC transporters in the HTR-8/SVneo cell line during stimulation with pro-inflammatory cytokines
Pokorná, Petra ; Čečková, Martina (advisor) ; Mladěnka, Přemysl (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Petra Pokorná Supervisor: Assoc. Prof. PharmDr. Martina Čečková, Ph.D. Consultant: Mgr. Simona Dudičová Title of diploma thesis: Evaluation of gene expression of selected ABC and OATP transporters in the HTR-8/SVneo cell line during stimulation with pro-inflammatory cytokines Placenta is the first and the largest fetal organ that gradually develops during pregnancy and plays an essential role in the development of the fetus. It fulfills the entire spectrum of functions, ensures the transport of nutrients to the fetus and the removal of waste substances back into the maternal circulation, protects the fetus from toxins, and at the same time fulfills a certain mechanical and especially immunological barrier between mother and fetus. One of the main functions of the placenta is the transport function which is made possible by membrane transporters present mainly in the syncytiotrophoblast layer of the placenta. Transporters in the human placenta can be divided into two families, SLC and ABC which are further divided into several subfamilies. The expression of transporters changes physiologically during pregnancy, but pathological conditions such as inflammation can also influence the expression....
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The role of astrocytes in the formation of brain edema
Heřmanová, Zuzana ; Anděrová, Miroslava (advisor) ; Pačesová, Dominika (referee)
Brain edema is a cause of mortality accompanying number of pathologies such as ischemia, traumatic brain injury, tumors or liver and kidney failure. It is described as a process of osmotic and water flux alterations, which lead to cell volume changes and to an increase in intracranial pressure. Brain edema is usually classified into two types: vasogenic and cytotoxic. Development of vasogenic edema is connected to the blood brain barrier disruption. Water accumulates in the extracellular space and exerts pressure on the cellular compartments of the tissue. The cytotoxic type of edema is characterized by water accumulation within the cells. The process of cellular volume enlargement is termed cellular swelling. Cytotoxic swelling is usually connected to glial cells, namely astrocytes, as these cells represent a part of the blood brain barrier and thus they influence homeostasis inside the brain. Water flows across cytoplasmic membrane through a system of specialized channels - aquaporins. For the brain edema formation, aquaporin 4 is the most important. It is localized on astrocytic membranes and using aquaporin-null mice, it has been shown, that it participates in water clearance in physiological and pathological conditions. Since the water fluxes are passive, the driving force for edema formation...
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In vitro and ex vivo study of drug-drug interactions of antiretrovirals on intestinal ATP-binding drug transporters
Jahodová, Michaela ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Bc. Michaela Jahodová Supervisor: PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: In vitro and ex vivo study of drug-drug interactions of antiretrovirals on intestinal ATP-binding drug transporters The absorption of orally administered drugs takes place especially in the intestine, where it can affect by the activity of drug's ABC transporters located on the apical membrane of the intestinal epithelium. Study of drug interactions in intestinal ABC transporters is essential to ensure effective and safe pharmacotherapy. Testing of bi- directional transport on Caco-2 cells is generally the preferred method for in vitro evaluation of substrates and inhibitors of ABC transporters. Drawbacks of the Caco-2 model increase the need and necessity to introduce new models. A great potential is the involvement of ex vivo methodologies in the human or rat intestine. The aim of the work was to introduce an in vitro methodology using the Caco-2 cell monolayer and the ex vivo methodology of precision-cut rat intestinal slices. By the bi-directional transport method, we analyzed drug interactions of the model substrate P-gp and BCRP Rhodamine 123 (RHD123) and clinically-used tenofovir...
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In vitro and ex vivo study of drug-drug interactions of antiretrovirals on intestinal ATP-binding drug transporters
Jahodová, Michaela ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Bc. Michaela Jahodová Supervisor: PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: In vitro and ex vivo study of drug-drug interactions of antiretrovirals on intestinal ATP-binding drug transporters The absorption of orally administered drugs takes place especially in the intestine, where it can affect by the activity of drug's ABC transporters located on the apical membrane of the intestinal epithelium. Study of drug interactions in intestinal ABC transporters is essential to ensure effective and safe pharmacotherapy. Testing of bi- directional transport on Caco-2 cells is generally the preferred method for in vitro evaluation of substrates and inhibitors of ABC transporters. Drawbacks of the Caco-2 model increase the need and necessity to introduce new models. A great potential is the involvement of ex vivo methodologies in the human or rat intestine. The aim of the work was to introduce an in vitro methodology using the Caco-2 cell monolayer and the ex vivo methodology of precision-cut rat intestinal slices. By the bi-directional transport method, we analyzed drug interactions of the model substrate P-gp and BCRP Rhodamine 123 (RHD123) and clinically-used tenofovir...
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The role of astrocytes in the formation of brain edema
Heřmanová, Zuzana ; Anděrová, Miroslava (advisor) ; Pačesová, Dominika (referee)
Brain edema is a cause of mortality accompanying number of pathologies such as ischemia, traumatic brain injury, tumors or liver and kidney failure. It is described as a process of osmotic and water flux alterations, which lead to cell volume changes and to an increase in intracranial pressure. Brain edema is usually classified into two types: vasogenic and cytotoxic. Development of vasogenic edema is connected to the blood brain barrier disruption. Water accumulates in the extracellular space and exerts pressure on the cellular compartments of the tissue. The cytotoxic type of edema is characterized by water accumulation within the cells. The process of cellular volume enlargement is termed cellular swelling. Cytotoxic swelling is usually connected to glial cells, namely astrocytes, as these cells represent a part of the blood brain barrier and thus they influence homeostasis inside the brain. Water flows across cytoplasmic membrane through a system of specialized channels - aquaporins. For the brain edema formation, aquaporin 4 is the most important. It is localized on astrocytic membranes and using aquaporin-null mice, it has been shown, that it participates in water clearance in physiological and pathological conditions. Since the water fluxes are passive, the driving force for edema formation...
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