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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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Troxerutin and its therapeutic use
Zuranová, Jana ; Mladěnka, Přemysl (advisor) ; Pávek, Petr (referee)
This diploma thesis is aimed at description characteristics and use of troxerutin in the clinical and the experimental practice. The first part of this thesis describes flavonoids as original substance. It includes theirs classification, chemical structure, common and potentionally beneficial pharmacodynamics properties. The main part of this thesis characterizes troxerutin. Troxerutin is a semisynthetic derivate of rutin. Its pharmacodynamics activities has been used therapeutically in the treatment of chronic venous insufficiency for more 30 years. Its positive is based on its antithrombotic, fibrinolytic, odemaprotective, blood viscosity and leukocyte endothelium-wall adherence decresing properties. Troxerutin directly affects erythrocytic aggregation particullary marked at high doses and it facilitation higher afflux of blood to the microcirculation. Its antioxidative effect is important too. The main indications of troxerutin at the present are chronic venous insufficiency and hemorrhoids. Simultaneously is experimentaly examined in a range of disorder, for example in the therapy of common cold, diabetic retinopathy and lymphoedema. In the Czech republic, troxerutin is available perorally in the form (Cilkanol® , Ginkor fort® and Venoruton® ) and locally as gel in Venoruton® gel.
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The effect of polyphenolic substances on vascular smooth muscle
Najmanová, Iveta ; Mladěnka, Přemysl (advisor) ; Tůmová, Lenka (referee) ; Klimas, Ján (referee)
[Sem zadejte text.] Abstract Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Iveta Najmanová, MCs First Supervisor: Assoc. Prof. Přemysl Mladěnka, Pharm.D., Ph.D. Second Supervisor: Marie Vopršalová, Pharm.D., Ph.D. Title of Doctoral Thesis: The effect of polyphenolic substances on vascular smooth muscle Polyphenolic substances are one of the most abundant secondary plant metabolites. Many substances from simple phenols with one benzene core to the polymeric compounds belong to these groups. Two groups, coumarins and flavonoids, were selected for this dissertation. The aim of this thesis was to analyse their effect on vascular smooth muscle in in vitro and in vivo conditions. In the case of coumarins, the aim was reached by writing of a review article. The effect of flavonoids, including their metabolites was experimentaly tested and some of the results have already been published. The first step in my research was to perform a screening of metabolites of quercetin, the most occuring flavonol in the human diet, and compare their vasorelaxant potential. Experiments were performed on isolated rat thoracic aorta. During the testing, the most effective metabolite was definitely 3-(3-hydroxyphenyl)propionic acid (3-HPPA), which was at least one order...
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Effect of lactoferrin on macroscopical and histological features in different tissues in rats. II. Liver and kidneys.
Škrle, Jan ; Semecký, Vladimír (advisor) ; Mladěnka, Přemysl (referee)
Lactoferin is an 80-kDa iron-binding glykoprotein. It shares a high degree of homology at amino acid sequence level and also the three dimensional conformation level with transferin. Both proteins are classified in the family of iron-binding glykoproteins, named transferin family. Afinity of Lf to iron is about 260times higher than that of transferin. (1) Lf is present physiologically in exocrine secretions, eg. tears, saliva, milk, sinovial fluid, seminal fluid and in the secondary granules of neutophils. (6) The precise function of Lf in organism is considered to be very complex and is still a hot subject of scientific disputation. Lf was documented to act as antimicrobial, antiinflamatory and antitumoral agent. (15,17) Another of its properties is ability to inhibit hydroxyl radical formation via Fenton reaction. (20) Because of good technological properties and it's physiological occurence Lf can be used as a therapeutical agent.(6) In our experiment we studied the influence of Lf on macroscopical and histological features in liver and kidney of the sewer-rat. We used two-dose model of i.v. Lf ( 50mg/kg in one dose and 3x 20 mg/kg in three days). The tissues of both models were used for histopatological analysis. We observed significant patological changes in kidney and liver after i.v....
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