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Copper chelating potential of iron chelators from the group of aroylhydrazones
Kříž, Jakub ; Mladěnka, Přemysl (advisor) ; Bárta, Pavel (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Farmacology and toxicology Candidate Mgr. Jakub Kříž Consultant Doc. PharmDr. Přemysl Mladěnka, Ph.D. Title of Thesis Copper chelating potential of iron chelators from the group of aroylhydrazones Copper is one of the essential trace elements. It is present in two oxidation-reduction forms Cu+ and Cu2+ in the human body. The ability of an easy transformation between this two forms is the crucial feature for the activity of copper enzymes, like superoxide dismutase and cytochrome c oxidase. Copper kinetics is quite complicated. The key organ which affects copper kinetics is the liver, but the small intestine plays an important regulatory role too. There are disorders, which are associated with both copper deficiency and accumulation. The best known disorder caused by copper excess is Wilson's disease. It is caused by a mutation in the ATP7B gene. It codes a transporter, which is responsible for elimination of copper. Excessive accumulation of copper causes several symptoms, mainly hepatic and neurological problems. Wilson's disease is treated by chelators, which bind the excess of metal ions in the organism. The aim of my thesis was to verify the copper-chelation efficiency of three selected iron chelators. The...
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Comparison of Iron Chelating Activity of 8-hydroxyquinolines by Direct Spectrophotometry
Šulcová, Monika ; Mladěnka, Přemysl (advisor) ; Karlíčková, Jana (referee)
in English Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of pharmacology and toxicology Candidate: Monika Šulcová MSc. Consultant: Dr. Přemysl Mladěnka, Ph.D. Name of thesis: Comparison of iron chelating activity of 8-hydroxyquinolines by direct spectrophotometry Iron is a biogenic element needed for cell life. Excess iron can be very dangerous for the organism. Thus iron fate in the organism is meticulously regulated. The iron overload arises mainly as the result of frequent blood transfusion or some hematologic diseases. Toxicity of iron is based on the ability to catalyze the formation of reactive oxygen species. The risk can be reduced by the treatment with iron chelators. Iron chelators are compounds with different structures that are therapeutically used for iron intoxication, but are also examined in the treatment of neurodegenerative diseases, acute myocardial infarction and cancer. The ability to bind iron chelator depends not only on its structure, but also on pH. The aim of this work was to compare iron-chelating activity of 8- hydroxyquinolines (basic substance and its derivatives - 5,7-dichloro derivative cloroxin and 5-chlor-7-iod derivative clioquinol) by direct spectrophotometry and to find out the stoichiometry of their complexes with ferrous/ferric...
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The influence of polyphenolic compounds and their metabolites on platelet activation
Applová, Lenka ; Mladěnka, Přemysl (advisor) ; Bultas, Jan (referee) ; Šimůnek, Tomáš (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Applová Lenka, MSc. Supervisor: Assoc. Prof. Přemysl Mladěnka, PharmD., Ph.D. Title of Doctoral Thesis: The influence of polyphenolic compounds and their metabolites on platelet activation Blood aggregation is a very difficult and complex process, in which platelets play crucial role. On the other hand, their activation is excessive and therefore undesirable under pathophysiological conditions. Cardiovascular diseases are the most common cause of mortality in developed countries and unfortunately, despite significant advances in treatment, the Czech Republic remains in mortality from these diseases behind most Western European countries. Epidemiological studies suggest, that higher intake of (iso)flavonoids is associated with reduced cardiovascular mortality. It is also worth mentioning, that the Czech Republic is among European countries with the lowest content of flavonoids in diet. The aim of this doctoral thesis was to find out, if polyphenolic compounds, especially (iso)flavonoids and/or their metabolites, are able to influence platelet aggregation and thus indirectly to support epidemiological findings, i.e. whether there may be a link between these substances and possible positive...
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Screening of New Iron - and Copper - Chelating Substances - in vivo and in vitro Studies
Říha, Michal ; Mladěnka, Přemysl (advisor) ; Patočka, Jiří (referee) ; Tůmová, Lenka (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Michal Říha, MSc. First Supervisor: Assoc. Prof. Přemysl Mladěnka, Ph.D. Second Supervisor: Prof. Radomír Hrdina, M.D., Ph.D. Title of Doctoral Thesis: Screening of new iron- and copper-chelating substances - in vivo and in vitro studies Iron and copper are essential trace elements which play a role in a series of physiological processes in human organism. Homeostasis of these transition metals is meticulously regulated since free or loosely bound iron and copper can catalyse the production of free radicals. Hereditary hemochromatosis, transfusion hemosiderosis and Wilson's disease are associated with absolute iron and copper overload in the organism. Transition metal chelators have crucial significance for the treatment of these states. There are several other diseases with documented involvement of iron and/or copper in their pathophysiology. Examples are primarily neurodegenerative diseases, cardio- vascular diseases, tumours and diabetes mellitus. Various chelating compounds are examined in these possible indications. The aim of this doctoral thesis was to perform a screening of iron- and copper- chelating substances and to study their properties in detail using in vitro and...
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Development of a novel spectrophotometric method for zinc ions chelatation screening
Herbolt, Daniel ; Mladěnka, Přemysl (advisor) ; Kučera, Radim (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Daniel Herbolt, MSc. Supervisor: Assoc. Prof. Přemysl Mladěnka, Pharm.D., Ph.D. Title of rigorous thesis: Development of a novel spectrophotometric method for zinc ions chelatation screening Zinc is the only one trace metal, which is a cofactor for over 300 active enzymes. It is localized in all tissues and organs. Zinc deficiency can cause many diseases such as e.g. diabetes, disorders of hemostasis, and cancer. The toxicity of zinc is usually considered to be mild, but the imbalance of zinc, e.g. its presence in extracellular plaques by patients with Alzheimer's disease suggests a more complex relationship. The purpose of this work was to create a new spectrophotometric methodology for screening of chelation of zinc ions. The first step was to measure the spectra of the selected indicator dithizone and its complex with zinc and finding the ideal wavelengths for accurate determination of the linear concentration of zinc ions. Thereafter, the linearity was checked at two selected wavelengths. After that, the stability of dithizone and its complex with zinc was measured in relationship to time. The final phase was to validate the methodology on two known zinc chelators which were...
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Chelation of ferrous ions by derivatives of xanthene-3-one
Pohanová, Lucie ; Mladěnka, Přemysl (advisor) ; Hrdina, Radomír (referee)
v angličtině Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Lucie Pohanová Supervisor: Assoc. Prof.. Přemysl Mladěnka, Pharm.D., Ph.D. Title of Thesis: Chelation of ferrous ions by xanthen-3-one derivatives Iron is an essential element important for proper function of cells. Imbalance of iron levels can lead to serious diseases. Since there is no excretory mechanism, the homeostasis is regulated at the level of absorption in the intestine. The iron overload, which leads to tissue damage due to catalysis of the formation of free radicals, occur because of genetic disorders such as hemochromatosis or owing to frequent administration of transfusions. Rational therapy for iron overload is the administration of the chelators. The aim of this study was to evaluate the ability of derivatives of 2,6,7- trihydroxyxanthen-3-one (synthesized at the University of Sarajevo - Dr. Durić) to chelate iron in 4 (patho) physiologically relevant pH conditions. The ferrozine spectrophotometric method was used to determine the degree of chelation. Measurements showed dependency of the chelating effect on pH: lowering pH resulted in the decrease of the effect. At pH 7.5, most of the substances showed 100% ferrous ion chelation in the stoichiometric ratio of 1...
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Influence of selected substances with cardioprotective potential on iso-prenaline induced myocardial damage in a rat model.
Koulová, Jana ; Semecký, Vladimír (advisor) ; Mladěnka, Přemysl (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Jana Koulová Supervisor: Doc. RNDr. Vladimír Semecký, CSc. Title of thesis: Influence of selected substances with cardioprotective potential on iso- prenaline induced myocardial damage in a rat model. Cardiovascular diseases are one of the major cause of mortality. To clarify the pathogenesis of acute myocardial infarction (AMI) and to research cardioprotective substances, an iso- prenaline (ISO) model of rat myocardial damage is used. This study assessed the cardiopro- tective potential of intravenously administered rutin in a single dose 11.5 mg / kg in the rat myocardium, which was later given a single subcutaneous dose of ISO (100 mg / kg). The aim of the experiment was to study the functional, biochemical and histological changes occurring in the rat myocardium after 2 hours from application of ISO and rutin with ISO. Observed changes were compared among themselves and also compared to the control group, which was applied intravenously with solvent NaHCO3 in a single dose of 4.6 ml / kg. Functional parameters as heart rate and blood pressure after 2 hours from the application were consistent with the expected development presented in studies with ISO that have been made...
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Viral hepatitides and their pharmacotherapy
Klímková, Martina ; Mladěnka, Přemysl (advisor) ; Vokřál, Ivan (referee)
15. Abstract Viral hepatitis belongs to the most common infectious diseases in the world by this time. Typical areas of their appearance are countries of South America, South Asia and Africa. They are transmitted parenterally (hepatitis B, C, D) or via the faecal-oral route (hepatitis A, E). Infection starts the immune reaction with production of antibodies that often serve in confirmation of the definitive diagnose. The clinical manifestation of viral hepatitis involves gastrointestinal discomfort, jaundice and actually liver failure and death if the hepatitis is complicated or untreated. Hepatitis A and hepatitis E don not become chronic and patients do not have any health consequences after recovery. Chronic forms of hepatitis B, C, and D cause long-lasting complications. There is no need to use antiviral drugs in the therapy of hepatitis A and E, the symptomatological therapy is sufficient. The other types of hepatitis demand an antiviral therapy. The basic of this therapy are interferon and synthetic nucleoside analogues. Interferons start an appropriate immune reaction and destroy infected hepatocytes and synthetic antivirotics inhibit synthesis of viral nucleic acid. In the treatment of hepatitis B is used pegylated interferon α, ordinarily in combination with nucleoside analogues (lamivudin,...
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Pharmacotherapy of glaucoma
Konečná, Petra ; Hrdina, Radomír (advisor) ; Mladěnka, Přemysl (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Petra Konečná Supervisor: Doc. MUDr. Radomír Hrdina, CSc. Title of diploma thesis: Pharmacotherapy of glaucoma Glaucoma is one of the main causes of blindness in the world and its prevalence is progressively increasing. An early detection and an effective therapy are very important to prevent progression of this disease. Ways of treatment involve pharmacotherapy and laser or surgical interventions. The diploma thesis is concerned with pathophysiology, classification and detection of glaucoma. The main part focuses on a medical treatment, especially on individual groups of medications, which are used from the initial stage of the disease to maximally tolerated doses. Prostaglandin analogs, which are currently used as the first line of therapy and which are used with other medications in fixed or unfixed combinations, are described in detail. Glaucoma is unfortunately incurable but it is possible to prevent its exacerbation and an irreversible loss of sight. The thesis follows up and summarizes results from international studies dealing with an effect, an effectiveness and side effects of single groups of medications. The purpose was to organize new observations in one complex and...
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Treatment of diabetes mellitus with a focus on insulin therapy
Hrabáková, Jana ; Melicharová, Ludmila (advisor) ; Mladěnka, Přemysl (referee)
Charles Univerzity in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and toxikology Student: Jana Hrabáková Supervisor: PharmDr. Ludmila Melicharová Title of diploma thesis: Treatment of diabetes mellitus with a focus on insulin therapy The Diploma thesis "Treatment of diabetes mellitus with a focus on insulin therapy" deals with the basic description of the disease, identifies the physiological effects of insulin and points to the facts that occur in organism in its absence. The central part of the thesis are chapters focused on insulin therapy, which has brought significant breakthroughs in treatment of diabetes (especially of the type 1) during the last eighty years. Based on the gathered information, the thesis provides an overview of currently available insulin-based preparations and accessories that increase the comfort and quality of life of patients suffering from this disease. And last but not the least, the work also reviews the new research directions and potential options in insulin therapy that are still at early phases of development. This is the reason why insulin therapy is of great interest in current pharmaceutical research.
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