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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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Effects of some flavonoids in isolated rat aortic rings
Pešková, Hana ; Vopršalová, Marie (advisor) ; Pourová, Jana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Hana Pešková Supervisor: PharmDr. Marie Vopršalová, CSc. Title of diploma thesis: Effects of some flavonoids in isolated rat aortic rings Flavonoids with their wide range of effects are known for having positive influence on human health. It mainly concerns significant antioxidant and anti- inflammatory characteristics and cardiovascular diseases incidence reducing effects. The aim of this study was examination of vasorelaxant effects of selected flavonoids from isoflavonoid group: formononetin, isoformononetin, prunetin and ononin, occuring especially in Fabaceae family. The vasorelaxation potential of tested substances was examinated in in vitro conditions on isolated aortic rings of rat. The effect of increasing doses of individual flavonoids on preparation, with intact endothelium after previous precontraction with norepinefrine, was monitored (10-5 M). From measured values, there were DRC curves, EC50 values created and an evaluation was made. According to analysis of the results, the most significat activity has fromononetin (EC50 2,081 . 10-5 M) and isoformononetin (EC50 2,081, 10-5 M). Ononin showed almost no vasodilatory effect.
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The effect of quercetin and its selected metabolites on isolated aortal rings of rat
Šumpelová, Kateřina ; Vopršalová, Marie (advisor) ; Herink, Josef (referee)
v anglickém jazyce Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Candidate: Mgr. Kateřina Šumpelová Supervisor: PharmDr. Marie Vopršalová, CSc. Title of rigorous thesis: The effect of quercetin and its selected metabolites on isolated aortal rings of rat Quercetin and it's metabolites are classified into the group of flavonoids. Flavonoid compounds are substances widely extended in nature. They below to the secondary metabolites of plants and have positive effect on live organism. Individual effects of flavonoids on the organism were described in this thesis, especially the effects on cardiovascular system. Flavonoids can have vasodilatory activity, antioxidant or anti-inflammatory effect. The experimental parts of the thesis dealing with the effect of quercetin and it's metabolites tamarixetin and isorhamnetin on isolated aortal rings of rat in vitro. Significant vasodilatory activity of these flavonoids was observed. The mechanism of the vasodilatory effect of qeurcetin was verified. Our experiments confirm the theory that the effect is independent on the function of endotel.
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Testing of transdermal permeation of selected xenobiotics
Stará, Veronika ; Herink, Josef (advisor) ; Vopršalová, Marie (referee)
This thesis first briefly mentions the characteristics of the skin and contains a review of current knowledge on the in vitro permeation testing of drugs through the skin. It describes the basic data about nerve agents and the possibilities of prophylaxis poisoning warfare agents focusing on preventive transdermal administration. The experimental work is focused on in vitro testing abilities oxime HI-6 and posibly other reactivators enzyme acetylcholinesterase penetrate through pig skin. Experiments were conducted in static diffusion cells Franz type. The amount of test substance leaked through the skin is determined in the sample of receptor fluid by HPLC. Keywords permeation in vitro; transdermal; pig skin; Franz cell; substance HI-6; antidota; nerve agents; acetylcholinesterase
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Comparison of efficacy of acetylcholinesterase inhibitors tacrine, rivastigmine and donepezil for the treatment of cognitive disorders induced by 3-quinuclidinyl benzylate in rat
Pavlíčková, Stela ; Vopršalová, Marie (advisor) ; Herink, Josef (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Mgr. Stela Pavlíčková Supervisor: PharmDr.Marie Vopršálová, CSc. Supervisor specialist: RNDr. Jan Misík, Ph.D. Title of rigorosa thesis: Comparison of efficacy of acetylcholinesterase inhibitors tacrine, rivastigmine and donepezil for the treatment of cognitive disorders induced by 3-quinuclidinyl benzylate in rat Alzheimer's disease is a severe neurodegenerative disorder connected with neuronal death, brain tissue loss and functional disruption of the cholinergic system. Pathophysiological changes are manifested especially as deterioration of memory and other cognitive functions. Current treatment consists mainly of pro-cognitive drugs - acetylcholinesterase inhibitors (previously - tacrine, today - donepezil, rivastigmine and galantamine) and NMDA (N-methyl-D- aspartate) antagonist memantine which can delay the disease progression. The aim of this study was to evaluate the therapeutic effect of three selected acetylcholinesterase inhibitors - tacrine, rivastigmine and donapezil on pharmacologically induced cognitive disorder in rats. As an amnesic drug, 3-quinuclidinyl benzilate was used and the effect of selected inhibitors was investigated using two different behavioral methods -...
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The effect of acetylcholinesterase reactivators on urinary bladder contraction
Rambousková, Lucia ; Vopršalová, Marie (advisor) ; Herink, Josef (referee)
Candidate: Mgr. Lucia Rambousková Title of thesis: The effect of acetylcholinesterase reactivators on urinary bladder contraction Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Supervisor: PharmDr. Marie Vopršálová, CSc. Consultant specialist: PharmDr. Vendula Šepsová, Ph.D Acetylcholinesterase (AChE) reactivators major mechanism is attributed to their ability to reactivate phosporylated enzyme, AChE. It has been thought that oxime might have additional direct pharmacological effect, other than AChE reactivation. The oximes may exert effects by interaction with cholinergic receptors. The most of them have antiniconitic or antimuscarinic properties, thus they protect against higher concentration of acetylcholine. The aim of this study was to evaluate the effect of reactivators K 203 and K 027. A contraction study on the rat urinary bladder has been chosen to investigate effect on muscarinic and purinergic receptors. Isolated strips of urinary bladder in the organ bath were used. There were three types of stimulation - electric stimulation (EFS), muscarinic receptor agonist methacholine (MCh) and purinergic receptor agonist adenosine triphosphate (ATP). In conclusion oxime K 027 has tendency to reduce the contraction (during EFS and MCh...
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Comparison of the effects of substances (VN 004 and VN 009) from derivative of vasicin on model of isolated trachea.
Vrátná, Sandra ; Vopršalová, Marie (advisor) ; Pourová, Jana (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Kralove Department of Pharmacology and Toxicology Candidate: Mgr. Sandra Vrátná Supervisor: PharmDr. Marie Vopršalová, Csc. Name thesis: Comparison of the effects of substances (VN 004 and VN 009) from derivative of vasicin on model of isolated trachea The aim of the thesis was to determine the in vitro activity of relaxing two structural modifications quinazoline alkaloids VN 004 (4- dimetylaminoetylsulfanylchinazolin) and VN 009 (N- [2- (piperidin-1-yl) ethyl] quinazolin-4-amine) on smooth muscle isolated rat trachea. They tested synthetic materials were derived from alkaloids vasicin and vasicinone contained in bushes Adhatoda vasica. On isolated rat trachea we were observed cumulative relaxation effect of single doses of the aforementioned compounds. From the measured values it was clearly evident that these synthetic quinazoline derivatives demonstrated on isolated rat trachea relaxing effect. Derivates with ethylaminfragment VN 009 was less effective derivative, but even so, demonstrated a greater activity than the standard theophylline. Conversely, stronger relaxation effect reported from the second derivatives with ethylsulfanyl fragment VN 004, the value of ED50 was 32.5 times lower than the ED50 of theophylline.
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Testing the efficacy of potential therapeutics for Alzheimer,s disease
Dolejšová, Adéla ; Herink, Josef (advisor) ; Vopršalová, Marie (referee)
Adéla Dolejšová Testing the efficacy of potential therapeutics for Alzheimer,s disease Charles University in Prague, Faculty of Pharmacy in Hradec Kralove Pharmacy The aim of this thesis was to find out whether already implemented Ellman's method, which is used to analyse irreversible inhibitors AChE, is going to be a suitable technique for measuring reversible inhibitors. Furthermore, the efficiency of newly synthesized AChE inhibitors was established. These inhibitors will be used for treating AD or as prophylaxis against neural paralytic substances. Moreover, it was compared affect the efficacy of AChE inhibitors after intramuscular and intraperitoneal administration. The measurements were done in vivo on potkan species Wistar. In the first experiment standard AChE (tacrin, 7-MEOTA, donepezil, rivastigmin) inhibitors were applied to verify the method. In the second experiment the newly synthesizes AChE (K 298, K 344, K 474) inhibitors were medicine. The results confirmed the effectiveness of the tested method on commonly used inhibitors such as donepezil and rivastigmin. Out of the newly synthesized K 298, K 344 and K 474 inhibitors none was proven to have any significant inhibiting activity. Key words: acetylcholinesterase, acetylcholinesterase inhibitors, Alzheimer disease, cholinergic system,...
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Monitoring of basic pharmacokinetic parameters of acetylcholinesterase inhibitors used in the treatment of Alzheimer's disease
Krejčiová, Markéta ; Doležal, Martin (advisor) ; Vopršalová, Marie (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Control of Pharmaceuticals Student: Markéta Krejčiová Supervisor: Prof. PharmDr. Martin Doležal, Ph.D. Supervisor specialist: Mjr. PharmDr. Jana Žďárová Karasová, Ph.D. Title of diploma thesis: Monitoring of basic pharmacokinetic parameters of acetylcholinesterase inhibitors used in the treatment of Alzheimer's disease Alzheimer's disease is a progressive irreversible neurodegenerative disorder that is globally associated with the most frequent cause of dementia. The pathophysiology of this illness is not fully understood yet. The commonly used treatment is still symptomatic, based on IAChE and memantine. Great attention is paid particularly to IAChEs and their derivatives, which arise from the basic structure of tacrine and 7-MEOTA. These two molecules were used as a reference for comparison with newly synthetized IAChE derivatives KB-36 and KB-38. Changes in plasma and brain tissue concentration levels were studied. The in vivo study was performed on rats (male, tribe Wistar). Equimolar doses were administered intramuscularly. Samples of plasma and brain tissue were evaluated by using HPLC techniques. The main aim was to determine the real concentration levels of all IAChE in both...
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