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STUDY OF POTENTIAL PHARMACOLOGICAL PROTECTION OF CARDIAC CELLS AGAINST OXIDATIVE STRESS AND ANTRACYCLINE ANTICANCER DRUGS
Jansová, Hana ; Šimůnek, Tomáš (advisor) ; Hrdina, Radomír (referee) ; Jun, Daniel (referee)
CHARLES UNIVERSITY IN PRAGUE FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ DEPARTMENT OF BIOCHEMICAL SCIENCES Candidate: Mgr. Hana Jansová Supervisor: Doc. PharmDr. Tomáš Šimůnek, Ph.D. Title of Doctoral Thesis: STUDY OF POTENTIAL PHARMACOLOGICAL PROTECTION OF CARDIAC CELLS AGAINST OXIDATIVE STRESS AND ANTRACYCLINE ANTICANCER DRUGS Development of cardiovascular disorders is associated with various risk factors and oxidative stress plays an important role in many of them. Iron-catalysed production of highly toxic and reactive hydroxyl radicals may contribute to oxidative stress. Chelation of free iron seems to be a promising strategy to prevent the propagation of oxidative stress. However, the use of classic iron chelators in pathological conditions without iron overload is associated with the risk of toxicity due to the iron depletion. Hence, this study deals with cardioprotective properties of iron chelators as well as prochelators derived from them. We focused on prochelators with almost no affinity for iron ions until they are activated under disease-specific oxidative stress conditions. For a long time, it has been assumed that oxidative stress is also the main denominator in an anthracycline-induced cardiotoxicity. However, the previous studies suggested alternative mechanism(s). Therefore in the...
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Effectiveness of venlafaxine in the treatment of depression
Dagisová, Ruta ; Hrdina, Radomír (advisor) ; Herink, Josef (referee)
5 ABSTRACT The objective of this analysis was to determine the efficacy and acceptability of venlafaxine in comparison with that of placebo and other antidepressants in the treatment of major depression by pooling short-term clinical trials with in-patients and out-patients. Randomised controlled trials were identified by searching of databases Pub-Med Medline and Embase. In metaanalysis were combined 15 trials, three of them were controlled by placebo and 12 by reference drugs. Clinical trials had to use either HAM-D, MADRS or the CGI-I scales as their primary outcome measure and reported response rates, defined as 50% or greater decrease in depression severity (according to the HAM-D and MADRS) or score 1 (very improved) or 2 (improved) (according to the CGI-I scale) from baseline to endpoint. Acceptability to patients was assessed by comparison of total drop-outs in two arms of the trials. For each efficacy variable (e.g. rating scales HAM-D, MADRS and CGI) and for subgroups of placebo and reference drugs were conducted partial analysis. The statistical analysis of data-sets was performed with statistical program MIX, version 1.54. To estimate size-effect was calculated parameter relative risk (RR) and to determine its reliability was 95% confidence interval was estimated. To compare response rates among...
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Je centrální signalizace ghrelinem nezbytná pro odměnu ("reward") navozenou látkami vyvolávajícími závislost?
Urbanová, Daniela ; Hrdina, Radomír (advisor) ; Egecioglu, Emil (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Daniela Urbanová Supervisors: Dr. Elisabet Jerlhag Holm, Ph.D., associate professor Prof. MUDr. Radomír Hrdina, CSc. Title of diploma thesis: Is central ghrelin signalling required for reward induced by addictive drugs? Ghrelin increases food intake and appetite, given centrally as well as peripherally. Plasma levels of ghrelin are increased before meals and decreased after meals. It stimulates appetite by acting on the hypothalamic arcuate nucleus. Ghrelin is mainly produced in stomach. This peptide hormone activates the reward system, suggesting that ghrelin may increase the incentive value of motivated behaviours such as food seeking. The central ghrelin signaling system increases natural reward by consumption of food, as well as by using addictive drugs, such as alcohol and also by sucrose. The mechanism of ghrelin how to activate the reward system involves cholinergic and glutamatergic mechanism. Several other neurotransmitter systems, including GABA, NPY and endocannabinoids, regulate the activity of the reward system and therefore the possible ability of ghrelin to activate the reward systems. This was investigated in the present study. The aim of the present study was to...
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The pharmacotherapy of the venous thromboembolism
Hanzlíková, Pavla ; Melicharová, Ludmila (advisor) ; Hrdina, Radomír (referee)
Topic: Treatment of venous thromboembolism Author: Pavla Hanzlíková Venous thromboembolism is the designation for the states in which a new rising thrombus in the peripheral venous bloodstream can reach the pulmonary artery. These include deep vein thrombosis or phlebothrombosis legs and pulmonary embolism. Clinically, this is absolutely a different disease, but which are closely related and often occur together and have the same treatment. Anticoagulants, fibrinolytic, antiplatelet therapy with adenosine diphosphate receptor blockers, inhibitors of platelet glycoprotein receptor IIb / IIIa and venous medication are used in the treatment of thromboembolic disease. An important part of therapy are non- pharmacological approaches. Another promising treatment procedures are in a clinical testing.
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Determination of the stoichiometry of the copper complexes with dehydrosilybine A
Klimková, Kateřina ; Mladěnka, Přemysl (advisor) ; Hrdina, Radomír (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Kateřina Klimková Supervisor: Assoc. Prof. Přemysl Mladěnka, Pharm. D., Ph.D. Consultant: Assoc. Prof. Kateřina Valentová, Ph.D. Title of Thesis: Determination of the stoichiometry of the copper complexes with dehydrosilybin A Silymarin, the standardized extract of the milk thistle (Silybum marianum), is a widely used approved over-the-counter drug that is recommended for a number of liver diseases. Silymarin contains as one of its components 2,3-dehydrosilybinA, which has an appropriate metal binding site in its structure. In general, flavonolignans, due to their structure, can interact with transition metals in the gastrointestinal tract by forming complexes. This property can be useful for the protection against excessive amounts of metals in the body. The aim of this in vitro study was to analyse the interaction of 2,3-dehydrosilybin A with copper, which plays a crucial role in the organism as a cofactor of many enzymes. Although being an essential element, it can, however, be toxic at elevated levels. Stoichiometry, as one of the most important characteristics of the complex, was determined by UV-Vis spectrophotometry in four (patho)physiological pH conditions (4.5; 5.5; 6.8; 7.5)...
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Pharmacotherapy of migraine
Koblásová, Anna ; Hrdina, Radomír (advisor) ; Herink, Josef (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Anna Koblásová Supervisor: Doc. MUDr. Hrdina Radomír, CSc. Title of diploma thesis: Pharmacotherapy of migraine Migraine is a highly prevalent disorder characterized by periodic, unilateral, pulsatile headaches that begin in childhood, adolescence or an early adult life. This common primary headache disorder presents a serious medical and socio-economic problem. Opinions concerning an etiopathogenesis of migraine develop gradually. A comprehensive management of headache includes the treatment of the acute attack to relieve the pain and prophylactic therapy to reduce the frequency, severity and duration of attacks. Triptans are considered as the firstline treatment for acute care of migraine attacks, in spite of this some patiens do not respond adequately. Triptans are in some cases ineffective, in other ones contraindicated. The greatest need is for the new specific drugs. Specific mechanisms that participate in pathophysiology of migraine have been discovered and drugs interacting with these mechanisms are registered in the market. Although attacks commonly diminish in severity and frequency with age, it may actually worsen in some postmenopausal women, and estrogen therapy may...
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Current possibilities of the treatment of psoriasis
Zápotočný, Martin ; Hrdina, Radomír (advisor) ; Kudláčková, Zděnka (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Martin Zápotočný Supervisor: Doc. MUDr. Radomír Hrdina, CSc. Title of diploma thesis: Current possibilities of treatment of psoriasis Psoriasis is an uninfectious disease with a genetic predisposition. There are several types of psoriasis. Therapy is heterogenous with a different efficiency. A topical, physical and systemic treatments are used. Topical treatment is a basic treatment for psoriasis. There are keratolytics, emollients, topical corticosteroids, whose prolonged use may cause adverse effects. A vitamin D3 analogue, retinoids and cignoline are also parts of topical treatment. Physical treatment, mainly phototherapy, has thanks to its unique photobiological effect unsubstituable role in a psoriasis treatment. Recently phototherapy and photochemotherapy have been classified on the same level as systemic treatment. For cases that do not respond on standard local treatment and phototherapy, systemic treatment is reserved. We can differ drugs of the 1st line: acitretin, cyclosporine A, methotrexate and drugs of the 2nd line, that are biologics. Biopharmaceuticals present safer and more accurate interference into the pathophysiological processes of psoriasis. The aim of this...
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