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Pharmacological evaluation of potencial drugs for Alzheimer's disease treatment
Matoušková, Lenka ; Vopršalová, Marie (advisor) ; Říha, Michal (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Lenka Matoušková Supervisor: PharmDr. Marie Vopršalová, CSc. Consultant: PharmDr. Vendula Šepsová, Ph.D. Title of diploma thesis: Pharmacological evaluation of potencial drugs for Alzheimer's disease treatment Alzheimer's disease (AD) is a neurodegenerative disease characterized by aggregates of beta-amyloid, neurofibrillary tangles of tau protein and by the loss of cholinergic neurons in the basal forebrain and hippocampus. Cause of AD is still unknown and only symptomatic treatment is available thanks to inhibitors of acetylcholinesterase (AChE) and memantine, inhibitor of glutamate receptors. M1 muscarinic positive allosteric modulators (PAM) represent another variant of treatment that can improve cholinergic transmission. Thanks to their selectivity, they are able to decrease side effects. The aim of the study was to measure novel compounds' abilities to inhibit AChE and BChE and simultaneously act as PAM of M1 receptors. Enzymes inhibition was measured according to Ellman's method and IC50 values were determined. For fluorescent measurement of compounds interaction with muscarinic receptor the CHO cell line stably expressing the M1 receptor subtype was used. Statistical analysis...
Testing antioxidant properties of selected acetylcholinesterase inhibitors
Kucková, Jana ; Vopršalová, Marie (advisor) ; Herink, Josef (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Jana Kucková Supervisor: PharmDr. Marie Vopršalová, CSc. Title of diploma thesis: Testing antioxidant properties of selected acetylcholinesterase inhibitors Very widespread Alzheimer's disease is typical by a complex pathology. Its causality is not clearly understood. There is increasing discussion due to the negative impact of free radicals on this disease formation. There are testing new substances that have also antioxidant properties, in addition to their classical effects. The aim of this diploma thesis is spectrophotometric testing of antioxidant properties of selected acetylcholinesterase inhibitors. It is based on DPPH test where the presence of antioxidants with antiradical activity causes the reduction of the color stable 2,2-diphenyl-1- picrylhydrazyl (DPPH) radical to a colorless molecule. The principle of the method is the measurement of decrease in absorbance (decolorization) of selected substances that are directly proportional to the antioxidant (antiradical) efficacy of the analyzed inhibitors. It focuses on twelve samples, Phenothiazine, which is the leader structure of new inhibitors synthesis, and two standards. Antioxidant activity is expressed as the effective...
Development of insecticides inhibiting acetylcholineseterase
Mányová, Brigita ; Vopršalová, Marie (advisor) ; Maixnerová, Jana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Brigita Mányová Supervisor: PharmDr. Marie Vopršalová, CSc. Supervisor-specialist: PharmDr. Vendula Hepnarová, Ph.D. Title of diploma thesis: Development of insecticides inhibiting acetylcholineseterase Pest insects cause problems and damage all over the world. They are vectors of serious diseases such as malaria, dengue fever, yellow fever, Zika virus disease and chikungunya disease. They cause huge damage to agricultural crops and are annoying to everyday life in living spaces. The aim of this diploma thesis was in vitro testing of selected compounds from the group of bis-isoquinoline and bispyridinium acetylcholinesterase inhibitors as potential insecticides. Another goal was also to create relationships between structure and effect. The ability of these compounds to inhibit both human (hAChE) and fly acetylcholinesterase (MdAChE) was evaluated. The modified Ellman spectrophotometric method was used. The half inhibitory concentration (IC50) values were obtained for both enzymes and the selectivity indexes (SI) were then calculated. Compounds having IC50s in micromolar or nanomolar range and exhibiting selectivity for MdAChE were most desirable. During the testing of these inhibitors, three...
Misuse of doping substances
Valová, Katarína ; Vopršalová, Marie (advisor) ; Jirkovský, Eduard (referee)
Charles University in Prague Faculty of pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Katarína Valová Supervisor: PharmDr. Marie Vopršálová, CSc. Title of diploma thesis: Misuse of doping substances My diploma thesis describe the term doping, possible causes of doping and its prevalence. It contains the outline of doping substances and methods, the characteristics of individual groups, the mechanism of action as well as the adverse effects of the substances on the health of sportsmen. I also focused on anti-doping organs and testing methods or describing new possibilities in in the fight against doping. I briefly described the process of the doping control and as well as the sanctions.
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...
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...
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...
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...
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...
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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