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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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Biological activity of flavonoids. IV.
Vlčková, Pavlína ; Spilková, Jiřina (advisor) ; Mladěnka, Přemysl (referee)
Pavlína Vlčková Biologické účinky flavonoidů Diplomová práce Univerzita Karlova v Praze, Farmaceutická fakulta v Hradci Králové Farmacie Flavonoids in the broad sense of the term are ubiquitous plant pigments. They are the most represented antioxidants in common diet. Flavonoids are found, for example in the onions, apples, chocolate, tea and wine. This work was aimed at gathering new findings on biological activity and mechanism of action of the most frequently occurring flavonoids: the flavonol quercetin, its glycoside rutin and flavanone glycosides hesperidin and diosmin and extracts containing these flavonoids. In addition to the antioxidant activity, flavonoids are very good inhibitors of apoptosis show a strong cytoprotective activity and are able to suppress various kinds of cancerous growth. They may also be used in diabetes mellitus therapy, therapy of cardiovascular and hepatic diseases, neural and GIT disorders and bacterial, viral, fungal and parasitic infections. The effects differ according to a particular type of flavonoids. Quercetin, according to the results of many studies, could have potential in the treatment of different types of cancer. Rutin is a great antioxidant and is featured in the treatment of commonly encountered diseases such as diabetes and gastric ulcers. Diosmin...
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Effect of Nicotinic Acid on infiltration of macrophages in the ischemic brain
Pokorná, Barbora ; Pávek, Petr (advisor) ; Mladěnka, Přemysl (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Kralove Department of Pharmacology and Toxicology Candidate: Barbora Pokorna Supervisor: Doc. PharmDr. Petr Pavek Ph.D. Specialized supervisor: Prof. Dr. med. Markus Schwaninger Title of diploma thesis: Effect of Nicotinic Acid on infiltration of macrophages in the ischemic brain Stroke is one of the leading causes of death worldwide and its effective protective treatment is still missing. Nicotinic acid has been a widely used substance to modify lipid profiles for many years and it successfully prevents clinical cardiovascular diseases. Recently explored receptor, GPR109A, causes its effect and it was found to be expressed in spleen, adipose, and immune cells including macrophages. The aim of this work is to investigate the effect of nicotinic acid on the infarct size during cerebral ischemia and to determine the role of macrophages in its effect. We compared two groups in our experiments, transgenic CD11bDTR mice and control wild type (WT) mice. Both groups were treated with diphtheria toxin (DT), then a middle cerebral artery occlusion was performed and afterwards mice were treated with either nicotinic acid or vehicle. We have found depletion of macrophages in CD11bDTR group induced by DT treatment and depletion of macrophages in WT...
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Rheumatic fever and its pharmacotherapy
Davidová, Kristýna ; Mladěnka, Přemysl (advisor) ; Vokřál, Ivan (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Kristýna Davidová Supervisor: Dr. Mladěnka Přemysl, Ph.D. Title of thesis: Rheumatic fever and its pharmacotherapy Rheumatic fever (RH) is a systemic inflammatory disease occurring as a result of untreated tonsillopharyngitis caused by β-haemolytic streptococcus of group A. It is an autoimmune response, which leads to the production of antibodies against bacterial antigens, which also recognize human targets which are similar to M protein in the wall of the β-hemolytic streptococci and thus damage human tissue as well. Disease affects many organs such as joints, central nervous system, subcutaneous tissue and skin, but leaves lasting effects only on the heart. Usually not all symptoms are present, carditis and chorea are more common in children, arthritis in adults. Chronic rheumatic heart disease as a consequence of rheumatic carditis is associated with high morbidity and mortality in developing countries, where its incidence is the highest. There is no specific treatment for RH. We use only symptomatic treatment or preventive tools. Regime measures, including bed rest are also important in the case of acute rheumatic fever (ARH). Symptomatically, we use salicylates for ARH...
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