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Název v anglickém jazyce: Evaluation of the efficacy of quarternary acetylcholinesterase reactivators in vivo.
Mackurová, Michaela ; Vopršalová, Marie (advisor) ; Pourová, Jana (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Performed at: University of defence in Brno, Faculty of Military Health Sciences in Hradec Králové, Department of Toxicology and Military Pharmacology Student: Michaela Mackurová Leader of diploma thesis: PharmDr. Marie Vopršalová, CSc. Supervisor: kpt. PharmDr. Vendula Hepnarová, Ph.D. Title of diploma thesis: Evaluation of the efficacy of quarternary acetylcholinesterase reactivators in vivo NPL belongs to compounds of organic phosphorus and they are very common cause of poisoning as organophosphorus nerve agent. They can be absorbed by various routes - inhalated, ingest or by transdermal penetration. The problem is ineffective therapy and there is still no broad-spectrum reactivator able to efficiently restore AChE activity after intoxication by various organophosphates that will penetrates into CNS. The main aim of this experiment was to determine and compare the reactivating efficacy of two newly developed oximes K869 and K870 with commonly used oximes K160 and HI-6 against intoxication of sarin. The activity of reactivation was determined by standard spectrophotometric Ellman's method with using male Wistar laboraty rats. The results were evaluated as percentage of reactivation...
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Establishment of screening methods to find new regulators of the activity of phosphoglycolate phosphatase
Troppová, Eva ; Vopršalová, Marie (advisor) ; Jirkovská, Anna (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Eva Troppová Supervisor: PharmDr. Marie Vopršalová, CSc. Specialized supervisor: Prof. Dr. Antje Gohla Title of diploma thesis: Establishment of screening methods to find new regulators of the activity of phosphoglycolate phosphatase This work deals with the siRNA-based genomic screening for the modification of phosphoglycolate phosphatase (PGP) activity. 235 proteins were affected by transient transfection of siRNAs in vitro. Each siRNA was used in duplicates and the control was carried out by two control siRNAs. After downregulation of protein by siRNA PGP activity was evaluated, whether any modifications of PGP activity have occurred. PGP was the main research target. The main goal of this study before the screening was to set up a method, to create a reliable protocol. The whole study was 96 plate well. It was necessary to find the right conditions to measure PGP activity in two cell types (HEK AD 293 and Hep G2). Subsequently, optimal conditions were set up to influence expression of the protein. The method was optimalized using PGP siRNAs and 2 types of transfection reagents were tested. During our study the following methods were used: PGP activity assay, Bicinchoninic acid...
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The effect of quercetin metabolite on the rat isolated arteries.
Rudišarová, Simona ; Vopršalová, Marie (advisor) ; Pourová, Jana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Simona Rudišarová Supervisor: PharmDr. Marie Vopršalová, CSc. Title of diploma thesis: The effect of quercetin metabolite on the rat isolated arteries This study is focused on the research of the effects of flavonol quercetin and its selected metabolites (3-(3-hydroxyphenyl)propionic acid and 3-hydroxybenzoic acid) on blood vessels in vitro. A standardized method of an isolated rat aorta was used. The aim of this study was to find out how substances act on the isolated aorta and if the effect of the effective metabolite is dependent on the presence of the endothelium in the vessel. After precontracting with noradrenaline, individual concentrations of the test substances were added to the aortic ring bath (final concentrations in the bath ranging from 10-7 to 10-3 M). From the measured values EC50 values (quercetin = 3,63 . 10-5 M, 3-(3-hydroxyphenyl)propionic acid = 3,21 . 10-6 M, 3-hydroxybenzoic acid = 4,38 . 10-5 M) were obtained and the corresponding DRC curves were constructed using S.P.E.L. Advanced Kymograph Software. The experiment was performed once again with quercetin and 3-(3-hydroxyphenyl)propionic acid on the endothelium-denuded vessel. According to the results is...
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The in vitro effects of selected substances on isolated rat aorta
Beránková, Anna ; Pourová, Jana (advisor) ; Vopršalová, Marie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Anna Beránková Supervisor: PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: The in vitro effects of selected substances on isolated rat aorta Flavonoids are a numerous group of secondary plant metabolites. Flavonoid compounds are substances widely extended in nature and many of them have a positive influence on human health, primarily for their vasodilatory, antioxidant and anti- inflammatory effects. Three substances were selected for this diploma theses: two substances of isoflavonoid group, genistin and genistein, and the end product of genistein metabolism, 4-ethylphenol. The aim of this work is examination of vasorelaxant effects of this substances in vitro. Vasorelaxing potential of tested substances was tested in vitro in isolated aortic rings of Wistar rat. The effect of increasing doses of individual substances in precontracted aortic rings with intact endothelium was measured. From the obtained values of vessel tension, the DRC curves and EC50 values were created. The results were evaluated. The results analysis shows, that genistein (EC50 2,903.10-5 M) had the most significant activity. Also genistin (EC50 4,045.10-4 M) and high doses of 4-ethylphenol (EC50 1,509.10-3 M) caused...
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Cardiovascular effects of isoflavonoids
Jančíková, Lenka ; Pourová, Jana (advisor) ; Vopršalová, Marie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Bc. Lenka Jančíková Supervisor: PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: Cardiovascular effects of isoflavonoids Background: The aim of this thesis is to summarize existing findings about natural vegetable substances known as phytoestrogens-isoflavones and to map the results of latest studies focused on cardiovascular effects of isoflavones. Main findings: Available data suggest that isoflavones and their metabolites have positive effect on human organism. These include antiaterosclerotic, antimenopausal and anticarcinogenic effects and a positive effect on osteoporosis. Positive effect on cardiovascular system includes antihypertensive, anti-inflammatory, anti-angiogenic, antiproliferative and antiaggregating effects. On the other hand, there are studies that point out possible risks related to mainly long-term use of isoflavones. Nevertheless, even though the findings of cardiovascular effects are not always consistent, most of them confirm positive effects of isoflavones on cardiovascular system. Conclusion: Isoflavones and their metabolites are a very interesting group of substances with natural origin and carry a potential for possible development of new drugs. Therefore, they...
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Recent trends in therapy of diabetes mellitus type II
Boučková, Karolína ; Herink, Josef (advisor) ; Vopršalová, Marie (referee)
The bachelor's thesis is adressed to diabetes mellitus type 2, the lifestyle disease. It characterizes all its kinds, the laboratory diagnostics and complications. The thesis also contains causes of its appereance, risk factors and clinical manifestations. Nowadays the disease is growing enormously, it strikes people of different ages and genders. That is why the selection of therapy is very important. Particular attention is paid to a standart therapy but also to the latest trends within pharmacological and non-pharmacological treatments. Thanks to suitable therapy and upholding the treatment plan patients can live their life to the full. Key words: diabetes mellitus type 2, clinical symptoms, therapy
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Experimental myocardial damage affected the administration of D-penicillamine.
Blažková, Edita ; Semecký, Vladimír (advisor) ; Vopršalová, Marie (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Bc. Edita Blažková Supervisor: doc. RNDr. Vladimír Semecký, CSc. Title of thesis: Experimental myocardial damage affected the administration of D-penicillamine D-penicillamine is a substance with a wide range of use for the treatment of various diseases, especially Wilson's disease. This standard chelator is known for its ability to bind copper nonspecifically. The first aim of the thesis was to describe in detaile histopathological changes of the myocardium exposed to the effect of catecholamine, namely isoprenaline and to compare these changes with the structure of control group myocardium. The main aim was to verify potentially cardioprotective effect of D-penicillamine on the model of catecholamine induced damage. The description of histological changes complements the extensive results of in vitro and in vivo analysis. The experiment was performed on adult male Wistar Han rats, which were divided into six groups. The first group was used as a control and only received saline, the second one and third one received D-PA alone at doses of 11 and 44 mg.kg-1 . The fourth group received only ISO in a single dose of 100 mg.kg-1 . The fifth and sixth groups were premedicated...
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Evaluation of a novel series of [1,2,4] triazolo [4,3-a] quinoxalines and related compounds: highly potent adenosine receptor antagonists
Krpelíková, Irena ; Vopršalová, Marie (advisor) ; Macháček, Miloš (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmacology and Toxicology, Czech Republic Performed at: University of Bonn, Pharmaceutical Institute, Department of Pharmaceutical Chemistry, Germany Candidate: Irena Krpelíková Supervisors: Prof. Dr. Christa Elisabeth Müller PharmDr. Marie Vopršalová, CSc. Title of diploma thesis: Evaluation of a novel series of [1,2,4]triazolo[4,3- ɑ]quinoxalines and related compounds: highly potent adenosine receptor antagonists Adenosine, a local modulator, acts in many diverse biological processes. Its effects are mediated through adenosine receptors (ARs). Four types of ARs have been described, A1, A2A, A2B and A3, which belong to the superfamily of G protein-coupled receptors. AR ligands are being developed as new drugs. This thesis deals with the study of a novel series of [1,2,4]triazolo[4,3- a]quinoxalines and related compounds as potential adenosine receptor antagonists. The presented results were obtained using radioligand binding assays. Series of quinoxalinones and tetrazoloquinoxalines exhibit significant selectivity for human (h) A3 ARs but their affinity is relatively low for tetrazoloquinoxalines and moderate for quinoxalinones. Triazoloquinoxalines comprise the largest group of this series. Generally, the R1...
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The in vitro effects of selected isoflavonoids on isolated rat aorta
Novýsedláková, Alena ; Pourová, Jana (advisor) ; Vopršalová, Marie (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Alena Novýsedláková Supervisor: PharmDr. Jana Pourová, PhD. Title of Thesis: In vitro effects od selected isoflavonoids on isolated rat aorta Abstract: The aim of this study was to determine whether the selected isoflavonoids are able to vasodilate aorta, what structural features might be responsible for a relaxing activity and estimate the mechanism of action. The experiment we carried out the classical in vitro method on the isolated rat aorta, and the results evaluated by the computer program GraphPad. Only glycitin did not show statistically significant relaxation of blood vessels, which can be attributed to ineffective glycosidic form. Other izoflavonoids- glycitein, daidzein and tectorigenin seem to be promising in terms of potential vasodilatation. Further studies would be needed to verify also the in vivo effects. Likely structural features include the hydroxy group at 7-position and a methoxy group at position 8 of the core od isoflavonoids. The mechanism of action is not yet known, but most likely appears endothelium-dependent mechanisms, alpha 1 receptor antagonism and agonism of muscarinic M3 receptor. It may be also involved in the effect of the antioxidant and...
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Elimination of alcohol in blood of patients treated with coumarin drugs
Kahounová, Jana ; Vopršalová, Marie (advisor) ; Trejtnar, František (referee)
CHARLES UNIVERSITY Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Jana Kahounová Supervizor: Doc. PharmDr. Marie Vopršálová, Ph.D. Ing. Jaroslav Procházka Title of diploma thesis: ELIMINATION OF ALKOHOL IN BLOOD OF PATIENTS TREATED WITH COUMARIN DRUGS Coumarin preparations are the most commonly used oral anticoagulants. The main representative is Warfarin. The most important function of warfarin is to reduce the formation of K-dependent coagulation factors in the liver. Alcohol is the oldest and most widely used addictive substance. Alcohol is the oldest and most commonly used substance. Society is tolerated and regular use of small doses of alcohol is considered "beneficial to health". The aim of my thesis was to find out how the concomitant use of coumarin drugs and alcohol interacts. There were tested 62 people (33 men and 29 women), of whom 27 people (14 men and 13 women) were treated with coumarin drugs, 35 people (19 men and 16 women) formed the control group of individuals without treatment with coumarin drugs. All people were given a standard dose of alcohol. The blood alcohol level (COBAS INTEGRA 400 plus) and INR (SYSMEX CA 1500) were measured in the time-0 (before administration), 1½ and 3 hours (after administration). The data obtained was...
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