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The pharmacological therapy of arterial hypertension in special ambulances and general practitioners
Mlčochová, Michaela ; Mladěnka, Přemysl (referee) ; Tilšer, Ivan (advisor)
~ 3 ~ ABSTRACT Topic: Pharmacological treatment of arterial hypertension in specialist ambulance and at general practitioners Made by: Mgr. Michaela Mlčochová OBJECTIVE: The aim of the study is to evaluate and to compare pharmacological treatment of hypertension, effect of pharmacological interventions and risk profile of hypertensive patients in the cardiology ambulance of 1st Department of Medicine, University Hospital in Hradec Králové and in surgeries of general practitioners. METHOD: Only diagnosed, drug-treated hypertensive patients were incuded, fifty patients in each group. We compared medication, achieved blood pressure and risk profile. RESULTS: 78% of patients in the cardiology ambulance and 54% of patients at general practitioners achieved recommended blood pressure levels (BP < 140/90 mmHg). Combined therapy was used in the same rate in the both groups (78%). The most often prescribed medication were beta-blockers in cardiology ambulance and ACE inhibitors and diuretics at general practitioners. Complications of hypertension were more often in the cardiology ambulance (90% vs. 46%), respectively the risk factors were more often in the patients treated by general practitioners (86% vs. 62%). CONCLUSION: The therapy of arterial hypertension was more successful in the cardiology ambulance. But...
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Influence of rutin on experimental myocard injury.
Filipová, Veronika ; Mladěnka, Přemysl (referee) ; Semecký, Vladimír (advisor)
Abstact Rutin is a flavonol glycoside appearing in many kinds of plants, vegetable and fruits. There are numerous biological activities attached to it, such as antioxidant properties, hypertension treatment, anti-inflammatory effect, antihaemorrhagic activity, strengthening of capillaries, ability to regulate a capillary permeability and stabilization of blood platelets as well. Other qualities characteristic for rutin are antibacterial, antiviral and antiallergenic properties, antiprotozoal activities and anticarcinogenic effects. In recent years, the biological activity of rutin is the matter of many studies. The main objective of this thesis is to review an influence of rutin on experimental myocardium damage with usage of isoprenalin model of myocardium damage, which is causing morphological and biochemical changes of certain parameters. These changes can be compared to the myocardial infarction. Rutin was chosen to be a potentially cardio preventive substance and it was applied intravenously 5 minutes before an isoprenalin application. On experimented animals a plasma concentration of cardiac troponin T and histology images of the heart were judged. The concentration of cardiac troponin T was charted into a diagram and histological preparations (samples) were valuated by the medium of the light...
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Identifikace peptidického konjugátu s toxickým metabolitem paracetamolu N-acetyl-p-benzochinon iminem
Landíková, Kateřina ; Mladěnka, Přemysl (advisor) ; Vopršalová, Marie (referee)
Acetaminophen (paracetamol) is one of the most used analgesic drug. It is considered as a safe drug, although its administration in large doses can lead to due to known metabolism to impairment of hepatocytes with subsequent necrosis. Acetaminophen is metabolized primarily in the liver where it is converted to inactive compound by conjugation with sulphate or glucoronide. However a small proportion is metabolized by hepatic cytochrome P450 enzymes to a minor but toxic intermediate metabolite N-acetyl-p- benzoquinone imine (NAPQI). This metabolite binds with the macromolecules of the hepatic cells causing dysfunction of the enzymatic systems, structural and metabolic disarray and eventually necrotic cell death. This thesis is a part of larger work intended for preparation polyclonal antibodies which can be used for further research in vivo / in vitro. The objectives of this study are a) the confirmation that NAPQI is the toxic intermediate that can react with free thiol groups and b) the in vitro production of the formed NAPQI-peptide conjugate. Using dexamethasone-induced rat liver microsomal fraction led to the expected production of NAPQI, that was linked on a synthetic peptide containing free thiol group. This adduct was collected and purified by HPLC with gradient elution. The outcome of this...
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Study of selected drug-drug interactions of warfarin at the molecular level
Rulcová, Alice ; Pávek, Petr (advisor) ; Mladěnka, Přemysl (referee)
Xenobiotics are metabolized by hepatic biotransformation enzymes of cytochrome P450. Drug-drug interactions, where one substance increases the activity of biotransformation enzymes involved in the metabolism of other drug and accelerate its elimination, often occure in xenobiotics metabolism. The pregnane X receptor is a ligand-activated nuclear receptor, which plays central role in induction of numerous genes involved in the phase I. and II. of biotransformation including the most important hepatic enzyme CYP3A4. The aim of the diploma thesis was to examine interaction of warfarin and its enantiomers with PXR in terms of transactivation of CYP3A4 gene in hepatoma cell line HepG2 or in primary human hepatocytes. The cytotoxicity of warfarin was tested on cell line HepG2 using the MTT assay. Cytotoxic activity of warfarin didn't become evident in tested concentrations. Using the methods gene reporter assay and two-hybrid assay, we found that R-warfarin induces CYP3A4 gene expression through nuclear receptor PXR. Using the method RT-PCR, we observed induction effect of warfarin and its enantiomers on the CYP3A4 gene expression in isolated hepatocytes of two donors. I can conclude that activation of PXR by warfarin may cause pharmacokinetic drug-drug interactions of pharmaceuticals metabolized by CYP3A4.
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The influence of pH on iron chelation
Hrabalíková, Jitka ; Mladěnka, Přemysl (advisor) ; Hrdina, Radomír (referee)
v angličtině Iron is one of essential elements which are necessary for life of cells. Many important processes are connected with it and its insufficiency can lead to cell death. Iron excess can be dangerous, too; such situation can be triggered not only by acute intoxication, but it appears also chronically due to genetic abnormalities (hereditary hemochromatosis) or by frequent blood transfusions during treatment of thalassaemia, sideroblastic anemia or myelodysplastic syndrome. Iron chelators are used to cure these pathological states, but there have been currently analysed for the treatment of tumors or acute myocardial infarction as well. In pathogenesis of both of these disorders, iron and change of pH play significant roles. In this study, influence of pH on iron chelation abilities of various substances (deferoxamine, synthetic chelator SIH, flavonoids and synthetic coumarin 7,8-dihydroxy-4- methylcoumarin) was measured with the use of ferrozine as an indicator. The stability of complex chelator - iron in various pH was also tested. It was found that chelation activity of all tested substances and the stability of iron- chelator complex is increased with increasing pH. Strong chelators SIH and deferoxamine kept their effectiveness within pH from 7.5 to 5.5, whereas chelating activity of...
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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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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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The influence of intravenously administeres lactoferrin in early phase of coronnary thrombosis - histopathological analysis
Škrle, Jan ; Semecký, Vladimír (advisor) ; Mladěnka, Přemysl (referee)
Lactoferin (La) 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. Afinity of Lf to iron is about 260times higher than that of transferin. Lf is present physiologically in exocrine secretions, eg.: tears, saliva, milk, sinovial fluid, seminal fluid and in the secondary granules of neutophils. 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. These effects are probably based on its iron chelating properties. Similarly La inhibits hydroxyl radical formation via Fenton reaction due to chelation of free iron. The catecholamine model of myocardial injury, represented by administration of synthetic catecholamine isoprenaline (ISO), posseses many pathophysiological similarities with acute myocardial infarction (AMI). The only possibility for myocardial tissue recovery in AMI represents the reperfusion of ischaemic myocardium. But this process is associated with tissue derangement due to burst of hydroxyl radical catalyzed by free iron (Fenton reaction). Therefore La has been proposed to have potentially positive effects in a catecholamine...
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Effect of intravenously applicated lactoferine on early faze; of myocardial ischemia II. Biochemical examinations
Písaříková, Veronika ; Semecký, Vladimír (advisor) ; Mladěnka, Přemysl (referee)
Lactoferrin (Lf) is an 80-kDa iron-binding glykoprotein. Lf is present physiologically in exocrine secretions, eg. tears, saliva, milk, sinovial fluid, seminal fluid and in the secondary granules of neutophils. The precise function of Lf in organism is considered to be very complex and it is still a hot subject of scientific disputation. Lf was documented to act as antimicrobial, antiinflamatory and antitumoral agent. Another of its properties is ability to inhibit hydroxyl radical formation via Fenton reaction. Afinity of Lf to iron is about 260times higher than that of transferrin. Isoproterenol (ISO) has been used as a model compound to induce infarct-like lesions in the rat and various other animal species. Administration of necrotic dose of ISO caused ischaemia followed by damage of the myocardium. Ischaemia alters iron homeostasis and redox-active free iron, which catalyses ROS-generation. The only possibility for myocardial tissue recovery in acute moycardial infarction represents the reperfusion of ischemic myocardium. But the whole process is associated with damage of myocardium due to burst of hydroxyl radical catalyzed by free iron (Fenton reaction). In our experiment we studied the effects of Lf in a catecholamine model of myocardial injury. We had four experimental groups divided according to...
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New iron chelators and antioxidants in acute myocardial model / / infarction and oxidative stress-induced catecholamine / / - effect on the basic biochemical parameters
Mladěnka, Přemysl ; Hrdina, Radomír (advisor) ; Geršl, Vladimír (referee) ; Patočka, Jiří (referee)
I. SUMMARY Background: Iron is an essential element necessary for many physiological processes involving oxygen transport, DNA-synthesis and ATP-formation. The fate of iron in the organism is tightly regulated especially at the absorption and distribution level probably mainly due to lack of specific active iron excretion mechanism. Any derangement of iron homeostatis may lead to appearance of free (unbound or loosely bound) iron, which can catalyse reactive oxygen species (ROS) production by Haber-Weiss chemistry. Cardiovascular diseases, particularly coronary heart disease (CHD), remain notwithstanding recent scientific advances important therapeutic problem. The most serious form of CHD represents acute myocardial infarction (AMI). The pathophysiology of AMI involves in most cases initial ischaemic period caused by coronary blood flow derangement due to a thrombus formation. Ischaemia alters substantially tissue homeostasis with subsequent cytosolic free iron appearance. Reconstitution of coronary blood flow (reperfusion) represents the only way for myocardial tissue recovery although on the other hand, it is linked with a release of free redox-active iron in the circulation and formation of ROS both intracellularly as well extracellularly. Iron chelators are a large group of drugs with very...
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