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Treatment of peptic ulcer
Sakač, Jiří ; Tilšer, Ivan (advisor) ; Hrdina, Radomír (referee)
Topic: Treatment of peptic ulcers Autor: Jiří Sakač Peptic ulcers represent one of the most widespread gastrointestinal disease all over the world. It occurs the most in the middle and high aged people. It is a multifactorial disease, which is developed by dysbalanc between agresive and protective factors. Its occurrence and incidence is associated with presence of the infection Helicobacter pylori in gastrointestinal tract. H. pylori is the main risk faktor for a diverse spectrum of gastrointestinal diseases, and it makes first damage of mucous membrane. Comprehensive individual treatment consist of non-pharmacological lifestyle modification and pharmacological treatment. In the treatment, there are used drugs, which inhibite secretions of the agresive hydrochloric acid (H2-receptor antagonist, proton pumps inhibitors), cytoprotective drugs (sucralfat, bismut`s salts, syntetic analogs of prostaglandins) and drugs for eradication of H. pylori - antibiotics and chemoterapeutics. Accurate diagnosis, timely and efective treatment reduce a risk of recurrence and the complications; which can endanger patient's life (bleeding, penetration, perforation); and they can accelerate final healing most of the ulcers.
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Review of the therapy of atopic dermatitis
Moravcová, Lucie ; Hrdina, Radomír (advisor) ; Jílek, Petr (referee)
REVIEW OF THE THERAPY OF ATOPIC DERMATITIS This dissertation shows the outline of present possibilities in the cure of atopic dermatitis with a view to new knowledge. The therapy's section is divided into the local therapy, system therapy and phototherapy. Every substance shows the principle of effect, averse effect, contra-indication, drug interaction and recommendation for which stadium of the illness should be indicated. Phototherapy deals with UVA, UVB and PUVA. The next part is about the most frequent complication of atopic dermatitis, the micro-organism colonized the skin. The last part shortly deals with the prevention of atopic dermatitis. The aim of the therapy of atopic dermatitis is to gain control over the symptomps of the illness and improve the life quality. The first choice's medicine are topic corticosteroids. Other posibility of choice are immunomodulators, pimecrolimus and tacrolimus. Very important is also using of emolients in all stadiums of the illness. The great hope for the therapy of AD represents inhibitors of phosphodiesterase, antagonists of leukotriene, interferon-γ, intravenous immunoglobulin and monoclonal antibodies.
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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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Influence of Polyphenolic Substances with Iron Chelating Activity in Model of Acute Myocardial Infarction and Oxidation Stress Induced by Catecholamines
Zatloukalová, Libuše ; Hrdina, Radomír (advisor) ; Tilšer, Ivan (referee) ; Patočka, Jiří (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate Mgr. Libuše Zatloukalová Supervisor Prof. MUDr. Radomír Hrdina, CSc. Title of Doctoral Thesis Influence of polyphenolic substances with iron chelating activity in model of acute myocardial infarction and oxidation stress induced by catecholamines Background and aim: Ischaemic heart disease (IHD) and particularly its most serious form - acute myocardial infarction (AMI) - represents significant health problem in the developed countries with relatively high mortality. Within multifactorial pathogenesis of AMI, reactive oxygen and nitrogen species (RONS) generated by free iron catalytic effect and increased activity of the sympathetic nervous system accompanied with a release of the catecholamines play a significant role. Large doses of the synthetic katecholamine isoprenaline has been used as a suitable experimental model of AMI. AIM is considered as typical form of ischaemic-reperfusion (I-R) injury. RONS, which are excessively released during the first minutes of reperfusion, play a significant role in the pathogenesis of myocardial I-R injury. Free iron significantly increases the process of RONS generation. Use of iron chelators could have protective influence in I-R injury and...
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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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Treatment of epilepsy
Chaloupková, Lucie ; Hrdina, Radomír (advisor) ; Tilšer, Ivan (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Lucie Chaloupková Supervisor: Prof. MUDr. Radomír Hrdina, CSc. Title of diploma thesis: Treatment of epilepsy Epilepsy is a serious chronic disease affecting all ages which can be characterized by recurrent epileptic attacks. It affects about 1,3-4 % of the population and endangers the patient's life at every incoming attack. Long-term treatment must be preceded by thorough diagnosis and classification of the disease, which can be very difficult. The aim of the treatment is to prevent recurrent epileptic attacks, or at least mitigate them while minimizing the side effects of the treatment and reducing the negative impact on the quality of life. When choosing a suitable drug for an adult, the doctor usually decides individually depending on the type of epileptic attack. In children, the choice of the treatment often depends on the diagnosed type of syndrome, which appears more in the lower age category than in adult patients. The doctor should follow expert standards of the treatment of epilepsy, and also their own most recent experience and knowledge gained during the course of lifelong learning. The therapy begins with monotherapy, and only when not successful, it is necessary to...
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Treatment of diabetes mellitus
Hrouzková, Šárka ; Tilšer, Ivan (advisor) ; Hrdina, Radomír (referee)
DM is metabolic disorder characterized with hyperglycaemia at absolute shortage of endogenous insulin (DM1T), or at its relative shortage (DM2T). DM1T is a symptom of B-cell destruction in islets of pancreas Langerhans that occurs mostly on autoimmune basis. Lack of insulin results in disorder of glucose use and in increased catabolism of fat and proteins. The result of this disorder is hyperglycaemia, glycosuria, polyuria, thirst, eventually ketoacidotic coma. DM2T which prevalence is continuously increasing represents significant medical, social and economic problem. DM2T develops due to insulin resistance and later due to insufficient insulin secretion after each meal. Insulin resistance mostly develops in connection with obesity. In the course of disorder the defect of insulin secretion gradually worsens and micro and macro vascular complications develops that are the most frequent cause of death of patient suffering from the disorder. Diabetes treatment is of complicated and complex nature that has to be based on simultaneous intensive therapy, prevention, collaboration with patient, education, individual adjustment of treatment and therapeutic goals. The Czech Republic belongs to a few countries where diabetology as an independent branch of medicine exists. The goal of treatment is to ensure...
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Prodysrrhythmogenic effects of drugs
Péter, Bohuš ; Hrdina, Radomír (advisor) ; Tilšer, Ivan (referee)
The most common cardiac arrhythmia is atrial fibrillation. In most patients it is not the only heart disease. The main goal of therapy is to maintain a normal heart rhythm. This can be achieved by restoring the sinus rhythm or by controlling the ventricle response. The anticoagulation therapy may be needed to reduce the risk of tromboembolism. Several arrhythmias, including atrial fibrillation can be treated by a catheter ablation. This method is highly successful in treatment of supraventricular arrhythmias. The long-therm treatment of ventricular arrhythmias may require implantation of a cardioverter-defibrilator. Serious bradycardias are treated by permanent cardiac stimulation. The efficacy of pharmacologic treatment can be proved only in a clinical trial. Methods of preclinical identification of proarrhythmogenic substances are quite limited. Electrophysiology, drug effects, effects of genetic polymorphism can be studied mostly on models and preparations. Use of antiarrhythmics from groups IA and IB of the Vaughan Williams classification is now limited. Besides the beta blockers used in various indications, the antiarrhythmics from group III are most often used. It is likely that a new drug, dronedarone will be approved for treatment of atrial fibrillation. Positive effect on mortality, and in...
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Drug-drug interactions and side effects of warfarin.
Prášková, Pavla ; Pávek, Petr (advisor) ; Hrdina, Radomír (referee)
Warfarin is the most frequently used drug of a group of oral anticoagulants. I t is a racemic mixture of S- and R-warfarin, the S- warfarin has a 5 times higher efficiency. Warfarin, like other 4hydroxycumarin derivates used as oral anticoagulants, acts as an antagonist of vitamin K inhibits vitamin K dependent synthesis of biologically active forms of calcium-dependent coagulation factors. The target enzyme for warfarin is vitamin K epoxide reduktase complex 1 VKORC1. 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. Effective warfarin therapy is complicated by inter-individual variability in metabolism. Recent studies have demonstrated that CYP3A isoforms libely contribute to clinical outcomes and patient responses. Despote a significant focus on CYP3A4, little is known about CYP3A5 and CYP3A7.
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