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Current therapeutic options for the treatment of cystic fibrosis in children
Čapková, Lucie ; Pourová, Jana (advisor) ; Vopršalová, Marie (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Lucie Čapková Supervisor: PharmDr. Jana Pourová, Ph.D Title of diploma thesis: Current therapeutic options for the treatment of cystic fibrosis in children The aim of this thesis was to summarize current therapeutic options used for cystic fibrosis therapy in children. In the introduction, the pathogenesis of the disease, and methods of diagnosis are provided. The main part of the thesis is focused on the pharmacological possibilities of treatment including complications. In the concluding part, new options of causal therapy (currently in phase III clinical trials) are mentioned.
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In vitro assesment of skin permeation of caffeine using static Franz diffusion cells
Ostrovská, Lucie ; Vopršalová, Marie (advisor) ; Mladěnka, Přemysl (referee)
This thesis aims to the assessment of methods used in in vitro analysis of dermal permeation and absorption of caffeine. Guarantee of standard processes during an experiment is essential for the rightness of results evaluation and interpretation. First part is focused on alternatives and different transport ways of substances through the skin barrier. As transdermal drug delivery offers an increasing number of advantages, the number of studies performing transdermal experiments with drug delivery grows up. On the other hand we are also able to observe or predict the risk of intoxication of individuals after exposure to different kinds of chemicals. The standard methods assessment is of great importance to obtain reproducible results. In this thesis, caffeine was chosen as a model hydrophilic compound. Skin barrier was simulated by dermatomed pig skin of two different thicknesses from ear and abdomen. Eight experimets were carried out with different types of skin using Franz cells in two types of dosing - finite and infinite. Experimental part of the thesis aims on actual determination of caffeine permeation . Measurements were taken in receptor fluid, in particular layers of the skin and on its surface. Spectrophotometry and HPLC analysis were used for the assessment. The ability of caffeine...
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Hazardous substances leasing from plastic bottles
Najmanová, Iveta ; Vopršalová, Marie (advisor) ; Pourová, Jana (referee)
v anglickém jazyce Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Iveta Najmanová Supervisor: PharmDr. Marie Vopršálová, CSc. Title of diploma thesis: Hazardous substances that are released from plastic bottles This master thesis focuses on hazardous substances that are released from plastic bottles. Attention is paid especially to bisphenol A and antimony and their effects after oral administration. Given the fact that these substances are harmful to humans, most of the information about their effects was observed in epidemiological studies or studies conducted on laboratory animals and human tissues. The thesis documents the toxicological effects on the body, especially of bisphenol A. To a lesser extent and primarily because of the limited number of studies on this topic, it deals with the influence of antimony. This is a search thesis and the data are the sum of bibliographic records on the subject.
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Effects of selected drugs on activity of cholinesterases.
Štochlová, Karolína ; Vopršalová, Marie (advisor) ; Melicharová, Ludmila (referee)
We investigated the effect of selected compounds on acetylcholinesterase and butyrylcholinesterase. For our experimental research colorimetric Ellman method has been applied. The potency and the selectivity of tested compounds has been evaluated via their IC50 for AChE and BChE for. Inhibitory activity of tested compounds against AChE decreased in the order: quinacrine > 9-aminoacridine > proflavine > anatruxonium > BDMDAC > N-(4- trifluoromethylbenzyl) cinchoninium bromide > N-benzylquininium > URA 112 > URA 114 > chloroquine. Ajmaline, brucine, strychnine, tricyclic antidepressants (amitriptyline, nortriptyline, dosulepine), cyclizine and scopolamine exerted a low anticholinesterase activity (IC50 greater than 1 mM) and are therefore clinically insignificant. As the standard substances for comparison with the tested compounds, we used reversible cholinesterase inhibitors: etoproprazine and BW284c51 and as irreversible inhibitor ethylparaoxone. 9-aminoacridine showed the same efficacy as the irreversible standard compound, quinacrine even exceeded the efficiency by several orders of magnitude, however significant error was observed in that case. Other substances tested exerted a lower activity than the irreversible standard and furthermore, they did not reach the clinical efficacy of commonly used...
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Cytokine interactions of epithelial cells.
Handlovičová, Andrea ; Jílek, Petr (advisor) ; Vopršalová, Marie (referee)
The airway epithelial cells is strategically positioned at the interface with environtment, and thus plays a key role in host defence system. Epithelial cells do not provide only a mechanical barrier against the influence of potentially harmfull substances, but these cells are metabolic very active with an extensive secretory activity. Epithelial cells generate a large number of cytokines, especially chemokines (eg. IL-8, TSLP, RANTES), antimicrobial peptides in response to variety of stimuli eg. lipopolysacharide. Epithelial cells are involved in the balance of Th1/Th2/Th17 cells. Another relevance of epithelial cell is, that they amplify inflammatory processes and activity of effectory cells by inflammatory cytokines. Substantial new evidence indicates an importace of epithelial cells in their direction of recruitment immunity cells to the site of damage and they are involved in the reparation processes. Disorder of these cytokine regulations can be implicated in the development of diverse lung diseases such as eg. asthma or chronic obstructive pulmonary disease. Hence this field is intensively studying, so that could be find new targets of possible therapeutic interventions.
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The pharmacotherapy of the depression
Juřičková, Markéta ; Melicharová, Ludmila (advisor) ; Vopršalová, Marie (referee)
School: Charles University in Prague Faculty: Faculty of Pharmacy in Hradec Králové Study program: Pharmacy Department: Department of pharmacology and toxicology Academic year: 2010/2011 Author: Markéta Juřičková Supervisor: PharmDr. Ludmila Melicharová Title of diploma thesis: The pharmacotherapy of the depression This diploma thesis deals with the characterization of depression including its pathophysiology, causes, symptoms, progress as well as it classifies the types of depressive disorders. The diploma thesis deals with the treatment of depression, selection of antidepressants, using of antidepressants in children and adolescents, geriatric patients and pregnant women. It further describes individual groups of antidepressants, their mechanism of action, indications, contraindications and adverse effects. The thesis evaluates benefits of pharmacotherapy in depression treatment. It also classifies and describes the most common forms of psychotherapy. It further deals with other options in depression treatment like phototherapy, electroconvulsive therapy, physical activity, repetitive transcranial mechanical stimulation, vagus nerve stimulation and deep brain stimulation. It describes their mechanisms of action, adverse effects, indications and their benefits in depression treatment, especially...
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The Influencing of Anticholinesterase Activity of 7-methoxytacrine
Novotná, Petra ; Herink, Josef (advisor) ; Vopršalová, Marie (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of biological and medical sciences Candidate: Mgr. Petra Novotná Consultant: doc. MUDr. J. Herink, DrSc. Title of Thesis: The influencing of anticholinesterase activity of 7-methoxytacrine and galantamine by L-carnitine The aim of this work was to test the ability of L-carnitine (KAR) to increase the permeation of indirect parasympatomimetic 7-methoxytacrine (MEOTA) and galantamine (GAL) through the blood-brain barrier. The monitoring of acetylcholinesterase activity (AChE) in the parts of the brain chosen served as marker of changes presumed. All experiments were performed in laboratory rats, drugs tested were given systematically. The modificated Ellman's method for the determination of the AChE activity was used. The principle of this method is based on hydrolysis of acetylthiocholine iodide. The previous administration of KAR to MEOTA augmented the inhibition of AChE more in the frontal cortex, septum and basal ganglias and less in the hipocampus. Intraperitoneal administration of KAR was somewhat stronger in comparison with peroral one. Activity of AChE was more reduced after administration of MEOTA than after administration of GAL. Contemporary administration of KAR with MEOTA reduced AChE activity in the selected...
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Inhibition Potencial of Human Acetylcholinesterase Reactivators in vitro Testing
Šepsová, Vendula ; Vopršalová, Marie (advisor) ; Herink, Josef (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Kralove Department of Farmacology and Toxicology Candidate: Mgr. Vendula Šepsová Supervisor: PharmDr. Jana Ţďárová Karasová, PhD. Consultant: PharmDr. Marie Vopršalová, Csc. Title of thesis: Inhibition potencial of human acetylcholinesterase reactivators in vitro testing Tested reactivators are substances with oxime moiety attached to a ring with quaternary nitrogen, which enable binding to active site of acetylcholinesterase (AChE). This nucleophilic structure can reactivate inhibited AChE by organophosporus compounds. Reactivation is possible only if the bond between inhibitor and AChE is not established (Kassa, 2002). Reactivators have relative high affinity to active site of AChE. The value of affinity can be expressed by their values of inhibition potential. The aim of this study was observed influence of structural changes in oximes to AChE inhibition ability. This knowledge can be used in further designing new structures with peripheral and reversible activity against to AChE. The mechanism of peripheral inhibition against to AChE is already used in prophylaxis of nerve agent poisoning. The reversible inhibitor binds into AChE active site and thus, prevents subsequent binding of nerve agent. Reversible AChE inhibitors with peripheral...
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