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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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Comparison of platelet aggregation in healthy population.
Minarovičová, Júlia ; Mladěnka, Přemysl (advisor) ; Hofman, Jakub (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Júlia Minarovičová Supervisor: prof. Přemysl Mladěnka, Pharm.D., Ph.D. Title of diploma thesis: Comparison of platelet aggregation in healthy population Platelets have an irreplaceable role in the process of aggregation. Nevertheless, their increased activity is associated with the development of many cardiovascular diseases. This process can be influenced by clinical used substances from the group of antiplatelet drugs, which differ in their effectiveness within the population. Within this study, platelet aggregation was tested using impedance aggregometry, whose principle is the change in electrical impedance between electrodes caused by the adhesion of activated platelets. Firstly, whole blood was incubated with clinically used antiplatelet drugs (ticagrelor, vorapaxar, and acetylsalicylic acid) and a flavonoid metabolite, 4-methylcatechol. Subsequently, a platelet aggregation inducer (ADP, thrombin receptor activating peptide 6 /TRAP/, collagen, arachidonic acid, ristocetin, U-46619, and platelet-activating factor /PAF/) was added, and the process was monitored for 6 minutes. The most potent inhibitor of the aggregation induced by arachidonic acid was acetylsalicylic acid in a concentration of 70 μM...
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Study of the mechanisms of action of phenolic compounds on vascular smooth muscle
Alves Dias, Patrícia Alexandra ; Mladěnka, Přemysl (advisor) ; Kyselovič, Ján (referee) ; Štengl, Milan (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Training Workplace Department of Pharmacology and Toxicology Doctoral Degree Program Pharmacology and Toxicology Candidate Patrícia Alexandra Alves Dias, M.Sc. Supervisor prof. Přemysl Mladěnka, Pharm.D., Ph.D. Advisor assoc. prof. Jana Pourová, Pharm.D., Ph.D. Title of Doctoral Thesis Study of the mechanisms of action of phenolic compounds on the vascular smooth muscle Cardiovascular diseases including hypertension, coronary artery disease, peripheral artery disease, and cerebrovascular disease remain the leading cause of death worldwide. In addition, discouraging estimations have suggested a future increase in the number of cardiovascular patients. Thus, novel treatment modalities are clearly needed to prevent or reverse these epidemic trends. Phenolic compounds contain one or more hydroxyl groups bound to a benzene ring. This class of chemicals includes: a) natural compounds (e.g., dietary polyphenols and small phenolic metabolites) referred to as nutraceuticals due to their claimed health-promoting effects and b) synthetic compounds (e.g., bisphenols) which, on the contrary, have been suggested to negatively affect human health. Even if there are claims that polyphenol-rich diet is associated with cardioprotective effects, important...
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Effects of isoflavonoids and their metabolites on vascular smooth muscles in vitro and in vivo
Migkos, Thomas ; Mladěnka, Přemysl (advisor) ; Studenik, Christian (referee) ; Trejtnar, František (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Pharmacology & Toxicology Candidate: Thomas Migkos, M.Sc. Supervisor: Prof. Přemysl Mladěnka, Pharm.D, Ph.D. Consultant: Assoc. Prof. Jana Pourová, Pharm.D, Ph.D. Title of dissertation thesis: Effects of isoflavonoids and their metabolites on vascular smooth muscles in vitro and in vivo The dietary intake of flavonoids seems to be inversely related to cardiovascular mortality, in particular on coronary artery disease. The consumption of isoflavonoids, one class of flavonoids, has been increasing in the general population, especially due to the use of food supplements and a variety of isoflavonoid-rich foods. Although their bioavailability is low, they undergo extensive gastrointestinal metabolism by human bacteria, leading to smaller metabolites with a much higher degree of bioavailability. However, detailed studies on the impact of individual pure isoflavonoids on vascular system were mostly missing and much less was known for the effect of their colonic metabolites in this field. In the present study sixteen isoflavonoids, four metabolites and the racemic mixture of one of them were initially screened ex vivo for their vasorelaxant properties on rat aortas. The most potent of them, biochanin A, glycitein, O-desmethylangolensin...
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The influence of metabolites and their parent phenolic compounds on blood platelets
Hrubša, Marcel ; Mladěnka, Přemysl (advisor) ; Moťovská, Zuzana (referee) ; Kollár, Peter (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department: Department of Pharmacology and Toxicology Candidate: Mgr. Marcel Hrubša Supervisor: Prof. PharmDr. Přemysl Mladěnka, Ph.D. Title of dissertation thesis: The influence of metabolites and their parent phenolic compounds on blood platelets Acute cardiovascular events (ACEs), such as stroke and acute coronary syndromes encompassing acute myocardial infarction, are one of the main causes of cardiovascular mortality in the world. Current pharmacotherapy focuses primarily on secondary prevention of their recurrence, where antiplatelet drugs play a key role. These drugs reduce platelet hyperreactivity, which is present in the majority of cardiovascular and metabolic diseases, and significantly decrease the risk of ACEs. However, the palette of currently available drugs faces many issues, such as resistance, high variability in both pharmacokinetics and pharmacodynamics, serious side effects and the route of administration. This thesis firstly briefly summarizes the current knowledge of platelet physiology along with available antiplatelet drugs and their mechanism of action. Second part of the theoretical introduction is dedicated to polyphenolic compounds, as polyphenol-rich diet is associated with many beneficial effects, particularly...
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Interaction of chalcones with transition metals II.
Šulcová, Martina ; Macáková, Kateřina (advisor) ; Mladěnka, Přemysl (referee)
Charles University in Prague Faculty of Phramacy in Hradec Králové Department of Pharmaceutical Botany Candidate: Martina Šulcová Supervisor: Assoc. Prof. Ing. Kateřina Macáková, Ph.D. Title of the diploma thesis: Interaction of chalcones with transition metals II. Copper is one of the essencial elements in human body which is involved in the functioning of many enzymes and metabolic pathways. Although it appears in trace amounts in the body, its functions are irreplaceable. However, the ion level must be kept in balance by the various mechanisms of the body. If there is an excess or deficiency of copper in the body, this condition can lead to the development of health issues. Chalcones are substances belonging to the group of flavonoids. Their polyphenolic structure does not have a closed ring C. Studies describe their anticancer, anti-inflammatory, antiviral, antidiabetic, antibacterial, antioxidant, immunosuppressive and other properties. Chosen substances in the group of dihydrochalcones (naringin dihydrochalcone, neohesperidin dihydrochalcone, phloretin, phlorizin) and chalcones (isoliquiritigenin, licochalcone A) were tested for their chelation and reduction activity of the copper ions in this diploma thesis. The activity was measured at different pH environments (7.5; 6.8; 5.5 and 4.5) and...
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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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Comparison of platelet aggregation in healthy population.
Minarovičová, Júlia ; Mladěnka, Přemysl (advisor) ; Hofman, Jakub (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Júlia Minarovičová Supervisor: prof. Přemysl Mladěnka, Pharm.D., Ph.D. Title of diploma thesis: Comparison of platelet aggregation in healthy population Platelets have an irreplaceable role in the process of aggregation. Nevertheless, their increased activity is associated with the development of many cardiovascular diseases. This process can be influenced by clinical used substances from the group of antiplatelet drugs, which differ in their effectiveness within the population. Within this study, platelet aggregation was tested using impedance aggregometry, whose principle is the change in electrical impedance between electrodes caused by the adhesion of activated platelets. Firstly, whole blood was incubated with clinically used antiplatelet drugs (ticagrelor, vorapaxar, and acetylsalicylic acid) and a flavonoid metabolite, 4-methylcatechol. Subsequently, a platelet aggregation inducer (ADP, thrombin receptor activating peptide 6 /TRAP/, collagen, arachidonic acid, ristocetin, U-46619, and platelet-activating factor /PAF/) was added, and the process was monitored for 6 minutes. The most potent inhibitor of the aggregation induced by arachidonic acid was acetylsalicylic acid in a concentration of 70 μM...
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Are currently used chelators of heavy metals also chelators of calcium and magnesium?
Skoupilová, Karolína ; Mladěnka, Přemysl (advisor) ; Šuťák, Róbert (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Karolína Skoupilová Supervisor: prof. Přemysl Mladěnka, Pharm.D., Ph.D. Title of diploma thesis: Are currently used chelators of heavy metals also chelators of calcium and magnesium? Calcium and magnesium are important elements for the human body. Calcium plays an important role in blood clotting and intracellular signalling, thus participating in muscle contraction and platelet aggregation, among other processes. Magnesium is a cofactor for many enzymes. A significant deficiency of both ions can manifest as disorders of heart rhythm and increased neuromuscular excitability. The aim of this study was to determine the chelating activity of currently used heavy metal chelators and to determine the stability of the indicator. First, the ideal pH for the experiment was determined. In the next step, the chelation rate of 21 known metal chelators was measured using an in vitro spectrophotometric method. Finally, the chelation of the most active calcium chelators was verified on platelet aggregation in a human blood sample. At the same time, the long-term stability of the indicator o- cresolphthalein complexone (CC) was determined. In the first step, pH 7.5 was chosen, which was the only one...
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The impact of benzoic acids, metabolites of flavonoids, on the iron-catalysed Fenton reaction
Klenovičová, Alexandra ; Mladěnka, Přemysl (advisor) ; Karlíčková, Jana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Alexandra Klenovičová Supervisor: Prof. Přemysl Mladěnka, PharmDr., Ph.D. Consultant: Zuzana Lomozová, Ph.D. Title of diploma thesis: The impact of benzoic acids, metabolites of flavonoids, on the iron-catalysed Fenton reaction Oxidative stress is a condition in which there is an increased production of free radicals that exceeds endogenous antioxidant activity and leads to damage of biomolecules. A number of human diseases are associated with oxidative stress. However the use of antioxidants has failed in clinical trials, but it is possible that the fact that antioxidants may preferentially exhibit prooxidant activity under elevated antioxidant concentrations in various pathophysiological conditions. Various in vitro and epidemiological studies have confirmed the presence of antioxidant and prooxidant properties in flavonoids. However, on the basis of their pharmacokinetics, it is evident that after their oral intake, significant metabolism in the colon takes place, where small phenolic substances are formed in interaction with the intestinal microflora. There is a possibility that the antioxidant and harmful prooxidant properties that have been attributed to flavonoids are in fact a...
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