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Effects of chronic growth hormone and melatonin administration on EEG delta power in old rats
Hlubuček, Petr ; Pávek, Petr (advisor) ; Mladěnka, Přemysl (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Petr Hlubuček Supervisor: Doc. PharmDr. Petr Pávek, Ph.D. Title of diploma thesis: Effects of chronic growth hormone and melatonin administration on EEG delta power in old rats. Slow wave sleep (SWS), characterized by an increase in delta power (typically 0.1-4 Hz) of EEG spectral analysis is considered to be a core component of deep sleep and is associated with sleep's anabolic restorative properties necessary for good mental and physical health. The reduction of delta power represents one of the hallmarks of sleep alterations with age. In order to study effects of chronic growth hormone (GH) and melatonin administration on sleep EEG power spectra, young (3-4 months) and old (22-23 months) male Wistar rats were implanted with EEG and EMG electrodes. During one month a group of old animals was treated with GH administered intraperitonealy (i.p.), second group of old animals was treated with melatonin diluted in drinking water. Additional two groups of young and old rats with no treatment served as controls. After the treatment, EEG and EMG were recorded and analyzed. Then Fast Fourier transform was used to compute spectral power of REM and NREM sleep. Our results show rapid...
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Determination of the Stoichiometric Ratio of Iron Chelators by Job's Method
Staňová, Zuzana ; Mladěnka, Přemysl (advisor) ; Hašková, Pavlína (referee)
in English Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Candidate: Zuzana Staňová, MSc. Consultanat: Přemysl Mladěnka, Ph.D. Title of Thesis: : Determination of the stoichiometric ratio of iron chelators by Job's method Iron is an important biogenic element affecting many biochemical reactions in the body. Its deficiency and excess cause pathophysiological changes in the organism. Excess of iron is very often the result of frequent blood transfusions in the treatment of hematologic diseases. It may also occur in iron metabolism disorders (chronic intoxication). Acute intoxication after ingestion of excessive amounts of iron is life threatening especially in children. Chelators are used to remove excess iron from the body. It is a heterogeneous group of substances capable of binding iron. Standard drug of this group is parenterally administered deferoxamine. Oral chelators (deferiprone, deferasirox) are also currently used. Other indications of these substances are now the subject of research, which investigates their potential benefits in cancer therapy and acute myocardial infarction. The pH changes play an important role in the pathogenesis of both mentioned conditions. In this work, the stoichiometric ratios of complexes of selected...
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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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Pharmacological characterization of human monoglyceride lipase cystein mutants
Kařízková, Julie ; Pourová, Jana (advisor) ; Mladěnka, Přemysl (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Julie Kařízková Supervisors: Docent Jarmo T. Laitinen, Ph.D., Juha R. Savinainen, Ph.D., PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: Pharmacological characterization of human monoglyceride lipase cystein mutants The therapeutic and psychotropic potential of Cannabis Sativa has been known for ages but the biochemical basis of physiological processes behind the scene was only recently revealed. The most psychotropic constituent of the plant, tetrahydrocannabinol (Δ 9 -THC), hits the function of the endocannabinoid system which includes the endocannabinoids, metabolic enzymes for the biosynthesis and degradation, and cannabinoid receptors which all were discovered and described quite recently. Through the past 20 years, more and more chemical compounds are being classified or at least studied as the endogenous ligands of the cannabinoid receptors, although the two most famous, explored and plentiful compounds are anandamide (AEA) and the primary endocannabinoid 2-arachidonoylglycerol (2-AG). The most frequent manner of 2-AG-degradation is enzymatic hydrolysis by monoglyceride lipase (MGL) and α/β-hydrolase domain-containing proteins ABHD6 and ABHD12. MGL has several critical...
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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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Iron-chelating Properties of Selected Novel Chelators from 4-acyl-5-pyrazolone Group
Matula, Aleš ; Mladěnka, Přemysl (advisor) ; Karlíčková, Jana (referee)
4 ABSTRACT Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Aleš Matula, MSc. Consultant: Dr. Přemysl Mladěnka, Ph.D. Title of Thesis: Iron-chelating properties of selected novel chelators from 4-acyl-5- pyrazolone group Both iron deficiency and iron overload play important roles in the pathophysiology of certain diseases. A suitable therapy in the case of iron overload represents the administration of iron chelators, especially in the treatment of hematological diseases, where the chronic iron overload occurs (a long-term usage of blood transfusions). The application of iron chelators for other diseases (acute myocardial infarction, cancer, etc.) appears as a promising tool as well. The current chelators suffer from a low level of compliance, efficiency, their poor activity in acidic environment or they reduce ferric ions to ferrous ions and that leads to oxidative stress. The subject of this thesis is to verify the iron-chelating properties of selected novel chelators from 4-acyl-5-pyrazolone group by use of UV-VIS spectrophotometric methods. Four compounds have been chosen: benzyl-, phenyl- and thienylderivatives of the basic structure and the derivative marked as H2Q4, which is a double molecule of the basic structure of...
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Usage of antibodies and immunoconjugates in the pharmacotherapy of cancer
Vaidlová, Alena ; Čečková, Martina (advisor) ; Mladěnka, Přemysl (referee)
4 ABSTRACT Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of pharmacology and toxicology Candidate: Alena Vaidlová Supervisor: Pharm.Dr. Martina Čečková, Ph.D. Title of diploma thesis: Usage of antibodies and immunoconjugates in the pharmacotherapy of cancer. This diploma thesis display posibility of tumor treatment by antibodies, their conjugates and antibody fragments. Antibody therapy uses natural antibody binding of tumor cell or other abnormal cell. Antibodies bind only cells with cellular biomarkers which are present on target cells. Binding initiate disposal process of damaged cell. Genetic engineering helps to create different antibodies and their conjugates with different qualities, especially various affinity to specific structures they recognise. Unconjugated antibodies are chimerical, humanized, pure human or pure murine. Conjugated antibodies are represented by imunoconjugates, conjugates with cytostatics, with enzymes, with phytogenic or animal toxines. Developement of antibodies has totally new phenomenon - creating of antibody fragments. These elements are products of genetic engineering and their utilization has a great future. This work summarizes the latest knowledge about using monoclonal antibodies and immuoconjugates in theanticancer therapy.
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Spectrophotometric assessment of iron chelation at different pH
Šulcová, Monika ; Mladěnka, Přemysl (advisor) ; Macáková, Kateřina (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Monika Šulcová Supervisor: PharmDr. Přemysl Mladěnka PhD. Title of Thesis: Spectrophotometric assessment of iron chelation at different pH Iron is an essential element for living cells. Dangerous for the organism can be its lack and abundance as well. Therefore, its level must be meticulously regulated. The most common cause of iron overload is the excess supply. The iron overload is mainly brought about frequent use of transfusion or hematologic diseases. Iron toxicity is based on the ability to catalyze the formation of free radicals that modify cellular macromolecules and cause tissue damage. The use of iron chelators is therefore a rational therapy of iron overload conditions. Iron chelators are molecules with different structures sparing the ability of iron binding, which results in iron elimination from the organism and prevent iron accumulation in tissues. It is mainly used for intoxication, but some of them are also used in other indications. Attention is paid to the chemotherapy and the treatment of neurodegenerative diseases. There are many methods for determination of iron levels. Ferrozine method can be successfully used for the assessment of ferrous ions chelation....
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Dissecting the role of GPR55 agonist lysophosphatidylinositol in mechanically evoked pain
Škoricová, Dagmar ; Pávek, Petr (advisor) ; Mladěnka, Přemysl (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Dagmar Škoricová Supervisors: Prof. Dr. Rohini Kuner Doc. PharmDr. Petr Pávek, Ph.D. Title of diploma thesis: Dissecting the role of GPR55 agonist lysophosphatidylinositol in mechanically evoked pain Recent studies have suggested that the orphan receptor GPR55 (G-protein coupled receptor 55) is possibly a novel cannabinoid receptor activated by multiple different cannabinoid ligands and also by the lysophospholipid L-α-lysophosphatidylinositol (LPI). GPR55 is reported to be expressed on sensory neurons and mice lacking GPR55 were shown to have reduced mechanical hypersensitivity in inflammatory and neuropathic pain models, suggesting a pronociceptive role of GPR55. LPI was found to be secreted in large quantities from varieties of cancer tissue. These facts led us to speculate that LPI released from cancer cells could sensitize nociceptors and thereby lead to cancer-induced pain. The aim of the study was to investigate the role of LPI in cancer induced, mechanically evoked pain and its possible underlying mechanism. We found that the dorsal root ganglion neurons are directly activated by LPI in vitro. We also found that LPI injected in the periphery leads to a mechanical...
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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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