National Repository of Grey Literature 145 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
An identification of selective antagonists of constitutive androstane receptor
Ondraszková, Karolína ; Smutný, Tomáš (advisor) ; Pourová, Jana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Karolína Ondraszková Supervisor: PharmDr. Tomáš Smutný, Ph.D. Title of diploma thesis: An identification of selective antagonists of constitutive androstane receptor The constitutive androstane receptor (CAR) is an important ligand-regulated xenosensor that regulates the transcription of important drug biotransforming enzymes (e.g. CYP2B6). The pregnane X receptor (PXR) belongs to the same family of nuclear receptors as the CAR. The structure and function of both receptors share many common features. However, PXR has a larger and more flexible ligand-binding domain. At present, a selective, highly potent and non- toxic inhibitor of CAR is not practically available. This work aims to determine the affinity of previously identified compounds in our group with antagonistic activity towards CAR. This is a replication study. For this purpose, we tested the compounds using gene reporter and two-hybrid assay. Of all the tested substances, we obtained desired results with substance 1A. Using the gene reporter assay method, we found that substance 1A can reduce basal CAR expression but also suppresses CAR activity induced by the model agonist CITCO. The high affinity of the substance for the...
Cathinones - recreational stimulants and their effects
Grosová, Aneta ; Pourová, Jana (advisor) ; Vopršalová, Marie (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Aneta Grosová Supervisor: doc. PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: Cathinones - recreational stimulants and their effects In this thesis, I address the issue of synthetic cathinones (SCs), which were first synthesized in the 1920s and initially explored for potential medical applications. By the early 21st century, these substances had become popular as recreational drugs due to their easy accessibility, low cost, and initially legal status. In the thesis, I particularly discuss the toxicokinetics and toxicodynamics of selected derivatives, classifying them into groups based on various properties. The work also deals with their chemical structure and its numerous variations, which not only allow for circumvention of the law but also lead to the creation of derivatives with various properties. Included are findings on the adverse effects of these drugs, and I also describe the effects that make them sought after by users. Additionally, I provide a brief history and the current situation on the market in Europe and the Czech Republic. The information was gathered from numerous studies found on online databases, particularly PubMed, PubChem, Web of Science, and...
Study of the cytostatic effects of sulfur mustard
Krejčová, Martina ; Pourová, Jana (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Martina Krejčová Supervisor: doc. PharmDr. Jana Pourová, Ph.D. Consultant: Mgr. Petr Jošt. Ph.D. Title of diploma thesis: Study of the cytostatic effects of sulfur mustard Sulfur mustard (HD) belongs to blistering agents used in chemical warfare. It is a bifunctional alkylating agent that covalently modifies DNA. The cytostatic effect of HD is characterized by halting cell division without cell death. The duration for which a cell can remain in this state depends on the extent of DNA damage, which can subsequently be converted into a cytotoxic effect leading to cell death. The aim of the study was to determine the concentration range of HD gas that exhibits cytostatic effects and to investigate the sensitivity of HaCaT skin keratinocyte cells synchronized in the G1, S, and G2/M phases of the cell cycle to alkylating damage induction following release from cell cycle blockage. The cytostatic effect was observed only at very low concentrations, in the range of units of µmol.l-1 . In our experiments, a concentration of 2 µmol.l-1 of HD prevented cell proliferation for 2 days. Lower, submicromolar concentrations, had a stimulatory effect on cell proliferation, while higher concentrations of HD...
Study of the vasodilatory effect of tamarixetin in an ex vivo porcine coronary vessel model
Gaidosová, Barbora ; Pourová, Jana (advisor) ; Smutný, Tomáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Barbora Gaidosová Supervisor: doc. PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: Study of the vasodilatory effect of tamarixetin in an ex vivo porcine coronary vessel model. Flavonoids, as one of the most common herbal substances, are known for their beneficial effects on the human organism and in particular on the cardiovascular system. The aim of this thesis was to screen ten substances contained in hawthorn for vasodilatory effects, select the most active one, and subsequently verify mechanism(s) of its vasodilatory action. The experiments were conducted on an ex vivo vascular model using the pig coronary artery. In screening, the tested substance was always cumulatively added to the precontracted arterial rings at increasing concentrations while monitoring the vasodilatation. Vasoactive inhibitors or agonists of several vasodilatory pathways were used for verification of possible mechanism(s) of action. The results showed that the most active vasodilatory substance was tamarixetine with an EC50 of 47.8 µmol.l-1 . The detail mode of action has not been discovered however tamarixetine has been shown to influence the voltage dependent calcium channels of L-type on the vascular smooth...
Vasodilatory effects of 3-hydroxy phenylacetic acid: ex vivo mechanism of action
Štefancová, Monika ; Pourová, Jana (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Monika Štefancová Supervisor: doc. PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: Vasodilatory effects of 3-hydroxy phenylacetic acid: ex vivo mechanism of action It is known from clinical studies that the intake of polyphenols from food acts as a prevention of cardiovascular diseases. However, the parent compounds themselves often have low bioavailability. The emphasis is therefore on their bioactive metabolites. 3-hydroxy phenylacetic acid (3-HPAA) is among such metabolites. The aim of this study was to verify the mechanism of the vasodilatory effect of 3-HPAA using standardized ex vivo method on an isolated pig coronary artery. The administration of 3-HPAA resulted in relaxation of maximally contracted segments of porcine artery by mechanism partially dependent on the integrity of endothelium. By inhibiting endothelial nitric oxide synthase, the relaxation was significantly impaired. The blockage of SKCa and IKCa channels, muscarinic receptors, cyclooxygenase or L-type calcium channels did not affect relaxation. Thus, 3-HPPA causes dose-dependent vasodilatation of coronary arteries ex vivo at least partially mediated by endothelium with the participation of nitric oxide. Key words:...
The role of drug transporters in activation of pregnane X receptor
Kejvalová, Kateřina ; Smutná, Lucie (advisor) ; Pourová, Jana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Kateřina Kejvalová Supervisor: PharmDr. Lucie Smutná, Ph.D. Title of diploma thesis: The role of drug transporters in activation of pregnane X receptor The nuclear pregnane X receptor (PXR) is involved in maintaining the homeostasis of endogenous substances as well as in regulation of excretion of exogenous substances. PXR activation regulates the expression of transport and biotransformation enzymes I. and II. phase. Due to the high flexibility of PXR ligand binding domain, it can be activated by a wide range of xenobiotics. Including e.g., rifampicin, well-known PXR agonist causes clinically significant drug-drug interactions. However, rifampicin is not stable under physiological conditions and degradation occurs (into rifampicin quinone, 25-desacetylrifampicin, 3-formylrifamycin SV and rifampicin N-oxide). The aim of our experiments was to compare the interspecies activation of PXR (human, monkey, mouse and rat) by rifampicin and its derivatives. Hence, gene reporter experiments were performed using the HepG2 cell line. Statistically significant results in PXR activation were observed for human hPXR and monkey oPXR for all rifampicin derivatives except 25- desacetylrifampicin. Similarity...
Vasodilatory effects of 4-methyl catechol: ex vivo mechanism of action
Kuzdřalová, Kateřina ; Pourová, Jana (advisor) ; Smutná, Lucie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Kateřina Kuzdřalová Supervisor: doc. PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: The mechanism of vasodilation effect of 4-methylcatechol ex vivo Keywords: rat, aorta, flavonoids, 4-methylcatechol, vascular smooth muscle, vasodilation Flavonoids belong to the group of polyphenolic bioactive substances found abundantly in plants, fruits and vegetables. Thanks to their pharmacological and biochemical effects, they play a crucial role for human health, especially in the prevention of numerous diseases - metabolic syndrome, osteoporosis, atherosclerosis and also diseases of a cardiovascular system. The aim of the diploma thesis was to determine the mechanism of the vasorelaxant effect of one of the most important metabolites of flavonoids - 4-methylcatechol. For the research we used a standardized ex vivo method on isolated Wistar rat aortic rings. We were able to confirm the vasodilatory effects of 4-methylcatechol. We also confirmed the fact that the flavonoid metabolite directly affects a vascular smooth muscle. Furthermore, we found that the tested compound potentiates the vasodilatory activity of sodium nitroprusside and forskolin, and that vasodilation depends on the activity of...
Current therapeutic options for the traetment of anorexia and bulimia
Kašová, Kristína ; Pourová, Jana (advisor) ; Vopršalová, Marie (referee)
1. Abstract Author: Title: Form: Name of University: Degree: Department of: Consultant: Kristína Kašová Current therapeutic options for the treatment of anorexia and bulimia Diploma Thesis Charles University in Prague, Faculty of Pharmacy in Hradec Králové Pharmacy Pharmacology and Toxicology PharmDr. Jana Pourová, Ph.D. The work deals with therapy of mental anorexia and bulimia and targets to collect the information about opportunities for pharmacotherapy of these diseases which can be provided as a supportive treatment together with psychotherapeutic-psychological methods. In recent years the incidence of eating disorders has rapidly increased and there are several reasons for this growth. We focus not only on the current therapeutic options for the treatment of these diseases but we also try to point out the danger which goes hand in hand with eating disorders, health complications and raising mortality of patients with the diagnosis of mental bulimia and mental anorexia. Key words: mental anorexia, mental bulimia, psychotherapeutical methods, pharmacotherapy
Vasodilatory effects of 3-hydroxy phenylacetic acid: ex vivo mechanism of action
Štefancová, Monika ; Pourová, Jana (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Monika Štefancová Supervisor: doc. PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: Vasodilatory effects of 3-hydroxy phenylacetic acid: ex vivo mechanism of action It is known from clinical studies that the intake of polyphenols from food acts as a prevention of cardiovascular diseases. However, the parent compounds themselves often have low bioavailability. The emphasis is therefore on their bioactive metabolites. 3-hydroxy phenylacetic acid (3-HPAA) is among such metabolites. The aim of this study was to verify the mechanism of the vasodilatory effect of 3-HPAA using standardized ex vivo method on an isolated pig coronary artery. The administration of 3-HPAA resulted in relaxation of maximally contracted segments of porcine artery by mechanism partially dependent on the integrity of endothelium. By inhibiting endothelial nitric oxide synthase, the relaxation was significantly impaired. The blockage of SKCa and IKCa channels, muscarinic receptors, cyclooxygenase or L-type calcium channels did not affect relaxation. Thus, 3-HPPA causes dose-dependent vasodilatation of coronary arteries ex vivo at least partially mediated by endothelium with the participation of nitric oxide. Key words:...
Vasodilatory effects of 4-methyl catechol: ex vivo mechanism of action
Kuzdřalová, Kateřina ; Pourová, Jana (advisor) ; Smutná, Lucie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Kateřina Kuzdřalová Supervisor: doc. PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: The mechanism of vasodilation effect of 4-methylcatechol ex vivo Keywords: rat, aorta, flavonoids, 4-methylcatechol, vascular smooth muscle, vasodilation Flavonoids belong to the group of polyphenolic bioactive substances found abundantly in plants, fruits and vegetables. Thanks to their pharmacological and biochemical effects, they play a crucial role for human health, especially in the prevention of numerous diseases - metabolic syndrome, osteoporosis, atherosclerosis and also diseases of a cardiovascular system. The aim of the diploma thesis was to determine the mechanism of the vasorelaxant effect of one of the most important metabolites of flavonoids - 4-methylcatechol. For the research we used a standardized ex vivo method on isolated Wistar rat aortic rings. We were able to confirm the vasodilatory effects of 4-methylcatechol. We also confirmed the fact that the flavonoid metabolite directly affects a vascular smooth muscle. Furthermore, we found that the tested compound potentiates the vasodilatory activity of sodium nitroprusside and forskolin, and that vasodilation depends on the activity of...

National Repository of Grey Literature : 145 records found   1 - 10nextend  jump to record:
Interested in being notified about new results for this query?
Subscribe to the RSS feed.