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Cytotoxicity of new taxol derivatives in selected tumor cell lines
Némethová, Ingrid ; Skálová, Lenka (advisor) ; Kvasničková, Eva (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Ingrid Némethová Supervisor: Doc. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: Cytotoxicity of new taxol derivatives in selected tumor cell lines. Paclitaxel (Taxol, PTX) is a natural product with antitumor activity, used in the treatment of various types of solid tumors, especially breast and ovarian cancer. It belongs to the so-called mitotic poisons, which cause cell cycle arrest and apoptosis of cells by interference with microtubule dynamics. The aim of this study was to compare the antiproliferative effect of PTX and its derivatives, prepared in the ÚEB AVČR by conjugation of peptide receptor agonists for gonadotropin-releasing hormone (GnRH) within a targeted cancer therapy. For the experiment was chosen cell line MCF-7, which is derived from breast adenocarcinoma and has receptors for GnRH. The results were evaluated by two different methods (NRU, MTT). Of the six tested substances showed derivative MP 265 the most significant antiproliferative effect. When using the other substances occurred more pronounced decrease in cell-life at higher concentrations compared to PTX.
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Determination of selected pesticides and their metabolites by LC/MS
Kořínková, Petra ; Tesařová, Eva (advisor) ; Trešl, Ivan (referee)
Pesticides are the substances designed for destroying, preventing and controlling of pests and protection of plants. Their wide usage in agriculture causes contamination of ground, surface and drinking water, because wastewater treatment plants are not able to remove them. Mostly used pesticides are triazine based pesticides. However their usage is worldwide reduced because of their negative influences on human health and contamination of environment especially with their metabolites, about their toxicity are no information. A method for determination of triazine pesticides atrazine, cyanazine, propazine, simazine, terbuthylazine and their metabolites hydroxytrazine, desethylatrazine, desisopropylatrazine, hydroxyterbuthylazine a desethylterbuthylazine was developed and validated in this diploma work. The determination was realized by LC-MS/MS with electrospray ionization. LOD ranged between 0.5-3.2 pg/ml and LOQ between 1.5-9.6 pg/ml. A test of stability of the maternal substances of these pesticides was performed, in which temperature was found to have the biggest influence on their degradation. A monitoring of the presence of triazine pesticides and their metabolites in water was carried out in Czech Republic. Low concentrations of the maternal substances in surface water and ground water were...
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Determining the compression behaviour of fillers and talc.
Hofmanová, Tereza ; Řehula, Milan (advisor) ; Špaček, Vladimír (referee)
Determining the compression behaviour of fillers and talc Abstract The aim of this study was to determine how do the type of filler, presence of lubricant, size of compression force and compression with dwell time or without dwell time influence values of energy compression of tablets. Materials used were microcrystalline cellulose (Avicel PH 200), lactose monohydrate (Tablettose® 70) and talc. Mixtures with the 0%, 0,5% and 1% concentration of talc were prepared in a blending cube. Tablets with a weight of 500 mg were compacted in the compaction machine T1 - FRO 50 with the compaction force of 5 kN, 10 kN and 15 kN. Force-displacement curves were obtained from the resulting values of measurements of individual compaction processes, and numerical values of a plastic energy (E2), an elastic energy (E3), and Elis (E2 + E3) were calculated from them. Obtained data were statistically evaluated according to the Stats-Otto method. It results from these calculated values that the plasticity increases and the elasticity decreases during the compression with dwell time. Parameters E2, E3 and Elis increase with an increasing applied pressure. As expected, energy E2 and Elis did not decrease and energy E3 did not increase with the raising concentration of lubricant. This is caused by the character of the used...
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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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Toxicology of smoking
Hniličková, Petra ; Vopršalová, Marie (advisor) ; Žáčková, Pavla (referee)
TOXICOLOGY OF SMOKING Master's Thesis Petra Hniličková Charles University in Prague Faculty of Pharmacy in Hradec Králové, Heyrovského 1203, Hradec Králové Department of Pharmacology and Toxicology This master's thesis is engaged in problems of smoking, because smoking repre- sents with its addictive character and health effects one of important medical problems. In one cigarette is in addition to nicotine (a vegetable alkaloid which is addictive) included a large number of harmful chemicals. The tobacco smoke contains toxic gases (carbon monoxide, nitrogen oxides, ammonia), nitrosamines, polycyclic aromatic hydro- carbons, aromatic amines, heavy metals (such as nickel, cadmium, arsenic and polonium-210) and solid particles (mainly tar). All of these chemicals are harmful to human body and their effect is hard to predict because harmful pollutants from tabacco smoke work in combination. About 4.8 million people annually die of diseases caused by smoking. In this thesis are described the most frequent causes of death, such as car-diovascular diseases, cancer (especially lung cancer), chronic obstructive lung disease (CHOPN) and others. Individual chapters are dedicated to problems of second-hand smoke and legislative measures to prevent damages caused by tobacco products.
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The study of membrane receptors by radioligands binding
Rejhová, Alexandra ; Hudeček, Jiří (advisor) ; Hejnová, Lucie (referee)
Drug addiction, opiates respectively, is a social problem which seriousness is currently on the rise. One of key elements causing addiction is tolerance to increasing doses of drug causing abstinence syndrome during withdrawal and craving. Opioid receptors are members of a large group of receptors coupled with heterotrimeric G-proteins (GPCR), whose properties can be investigated using agonist- stimulated binding [35 S] GTPγS. Many extracellular signals are transferred into a cell through GPCR. Opioid receptor agonists inhibit the activity of adenylyl cyclase and are coupled with G-protein group Gi/Go. This work is devoted to the study of changes in isolated plasma membranes of rat forebrain containing opioid receptors of healthy subjects with membranes acquired from morphine addicted subjects. The rats were long-term morphine treated in increasing doses, to develop the dependency. The comparison is done firstly by binding of [3 H]ouabain to Na,K-ATPase, which proves to be a negative standard of changes, secondly by binding [35 S]GTPγS to G-proteins, thereby providing the functional activity of G-protein in stimulating the binding by the agonist of δ-opioid receptors DADLE or agonist of µ-opioid receptors DAMGO. Furthermore, it has been studied the influence of prostaglandin E1 on binding [35...
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System approach to assessing the extent of environmental damages in terms of the risk engineering
Schüllerová, Barbora ; Adamec, Vladimír ; Tragan, Tomáš
Road accidents have resulted not only in loss of human life, health and material damage, but also in the environmental damages caused by leaks of operating fluids or transported hazardous substances. Determining the severity and extent of the occurred accident is based on the expertise of experts. Besides the common methods, the risk engineering methods can be applied while resolving this issue. The contribution introduces the possibilities of using selected methods of risk analysis, which are the core of risk engineering, as a support tool for determining the extent of the damage incurred on the environmental components, including recommended procedures, combinations and applications of these methods.
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The effects of coumarins on the cardiovascular system
Růžičková, Alena ; Mladěnka, Přemysl (advisor) ; Doseděl, Martin (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Alena Růžičková Supervisor: Dr. Přemysl Mladěnka, Ph.D. Title of Thesis: The effects of coumarins on the cardiovascular system Coumarins constitute a very large category of natural polyphenolic substances, which are composed of a benzene and a α-pyrone ring. Coumarin is the basic compound, called also 1,2-benzopyrone. Cardiovascular diseases are still the major cause of morbidity and mortality in the world. That is the reason why a research aimed at substances which could have positive effect on these diseases is very beneficial. It appears that coumarins seem to be promising medicaments for certain cardiovascular diseases. Besides the well-known anticoagulant effect of warfarin and its related substances have some coumarins antiplatelet, antioxidant, antihypertensive, antiedematogenic, hypolipidaemic and anitarrhythmic effects. Antiplatelet effect of coumarin is mediated by inhibition of cAMP-phosphodiesterase, lowering of intracellular Ca2+ or by inhibition of thromboxane synthesis. Antihypertensive effects are partly linked with antioxidant activity, but also inhibition of cGMP phosphodiesterase, calcium channel blocking and increased production of prostaglandins have probably...
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Advances in antithrombotic prophylaxis and therapy
Vykrutová, Iva ; Tilšer, Ivan (advisor) ; Melicharová, Ludmila (referee)
Thrombotic disease and it's consequences are worlwide one of the leading causes of death. There are prescribed anticoagulants for treatment and prevention. Currently these prescribed drugs - cumarins, unfractioned and fractioned heparins, which have many adverse effects are tried to be replaced. This review is focused on summary informations about two new anticoagulants drug - direct inhibitor f Xa (rivaroxaban) and direct thrombin inhibitor (dabigatran), which could substitude currently used drugs in future. These new substances were clinical tested, where proved safety and efficiency. In these days their indication allow for patients after knee and hip joint replacement. Advantages of rivaroxaban and dabigatran: per os aplication once a day predictable pharmacokinetics and therapeutic response low potencial of drug interaction no needs of monitoring of coagulation Disadvantages of rivaroxaban and dabigatran: limited experience yet significant financial cost unknow antidote In the future these drug could be used for other indications.
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Development trends of using illegal drugs in young people in The Czech Republic in the years 2000-2008
Gogorová, Lucia ; Kottnauerová, Stanislava (advisor)
This writing is about drug abuse among young people in The Czech Republic in last decade and it is based on all the data collected by many institutions which are interested in addiction to drugs. The first four chapters, a theoretic part, are dedicated to characteristics and history of all drugs and also to prevention of drug abuse and politics against using drugs. Characteristics of all groups of drugs and health complications that are caused by using drugs are in the first chapter. The second one is talking about the history of drugs. The part which presents international and national politics against drug abuse is including all the institutions and their work. Influence of parents and other family members is very important, as much as preventive programmes at schools - about this all is another chapter. Some information about contact centres and some advice what to do in very risky situations associated with using drugs are also in the same chapter. Graphs of trends on drug abuse were created for The Czech Republic and also for Slovakia, then these two countries were compared. The last part is about The European region, but only using the cannabis was the main point of view.
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