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Assessing and Reducing the Impact of so called Black Swans in Launching New Medicines
Ženatá, Lucie ; Štohanslová, Barbora (referee) ; Adamec, Vladimír (advisor)
The diploma thesis is focused on the analysis and evaluation of risks in the introducing of new drug in the case of unexpected mass infections from the point of view of black swans. This thesis acquaints itself with the current state of the problematics, explains the terminology and meaning of black swans and gives examples of biological black swans. On the basis of the analysis and the available informations is proposed a risk assessment approach together with proposals how to reduce or eliminate possible risks.
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Treatment and drug development against free-living pathogenic amoebae
Jankovcová, Klára-Marie ; Mach, Jan (advisor) ; Vinopalová, Martina (referee)
Free-living pathogenic amoebae are cosmopolitan unicellular eukaryotic organisms, which can cause several serious infections in humans and animals. They are causative agents of amoebic encephalitis, which are very rare and acute diseases of the central nervous system, that almost always lead to the death of the patient. Even though the importance of these pathogens has been increasing in recent years, the development of treatment procedures and drugs against them is very ineffective and unsatisfactory. Treatment and drug development is complicated mainly because of the complex biological structure of pathogens and limited knowledge of metabolic pathways and the biochemical reactions that are occurring in them, which are crucial for the development of effective drugs. In this bachelor thesis I focus on the pathogenic species Naegleria fowleri, Balamuthia mandrillaris and the pathogenic genus Acanthamoeba, which is the causative agent of encephalitis and acanthamoeba keratitis. In the first part of this bachelor thesis, I generally characterize the different representatives of free- living pathogenic amoebae and describe the clinical picture of individual diseases. In the second part I address the issue of treatment. Firstly, I describe current therapeutic options and issues of the treatment of...
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Ames test in the drug development
Klaučová, Martina ; Pávek, Petr (advisor) ; Konečná, Klára (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Martina Klaučová Supervisor: prof. PharmDr. Petr Pávek, Ph.D. Consultant: PharmDr. Ivona Pávková, Ph.D. Diploma thesis title: Ames test in the drug development Background: Thesis objective is the determination of potential genotoxicity of newly developed drugs within primary testing and the introduction of the Ames microfluctuation test which can be used in common laboratory conditions. Methods: I used commercially supplied kit based on the principles of Ames test which detects reverse mutation through colour changes of the samples using bacterial strains S. typhimurium. At first I had to study literary sources and then I could design the procedures of the Ames microfluctuation test, preparation of the chemicals and storage of the strains which are optimal for all laboratories. Results: The drug samples T6445 and T6447 with 30 µM concentration tested by metabolic activation S9 on bacterial strain ST TA 98 show genotoxicity. The sample UOCHB1 with 30 µM concentration tested without activation shows possible genotoxicity on both strains ST TA 98 and ST TA 100. Other samples do not show any toxicity. I used 3 different procedures during the designation of assay. The most suitable version of the...
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Ames test in the drug development
Klaučová, Martina ; Pávek, Petr (advisor) ; Konečná, Klára (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Martina Klaučová Supervisor: prof. PharmDr. Petr Pávek, Ph.D. Consultant: PharmDr. Ivona Pávková, Ph.D. Diploma thesis title: Ames test in the drug development Background: Thesis objective is the determination of potential genotoxicity of newly developed drugs within primary testing and the introduction of the Ames microfluctuation test which can be used in common laboratory conditions. Methods: I used commercially supplied kit based on the principles of Ames test which detects reverse mutation through colour changes of the samples using bacterial strains S. typhimurium. At first I had to study literary sources and then I could design the procedures of the Ames microfluctuation test, preparation of the chemicals and storage of the strains which are optimal for all laboratories. Results: The drug samples T6445 and T6447 with 30 µM concentration tested by metabolic activation S9 on bacterial strain ST TA 98 show genotoxicity. The sample UOCHB1 with 30 µM concentration tested without activation shows possible genotoxicity on both strains ST TA 98 and ST TA 100. Other samples do not show any toxicity. I used 3 different procedures during the designation of assay. The most suitable version of the...
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Ames test in the drug development
Klaučová, Martina ; Pávek, Petr (advisor) ; Konečná, Klára (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Martina Klaučová Supervisor: prof. PharmDr. Petr Pávek, Ph.D. Consultant: PharmDr. Ivona Pávková, Ph.D. Diploma thesis title: Ames test in the drug development Background: Thesis objective is the determination of potential genotoxicity of newly developed drugs within primary testing and the introduction of the Ames microfluctuation test which can be used in common laboratory conditions. Methods: I used commercially supplied kit based on the principles of Ames test which detects reverse mutation through colour changes of the samples using bacterial strains S. typhimurium. At first I had to study literary sources and then I could design the procedures of the Ames microfluctuation test, preparation of the chemicals and storage of the strains which are optimal for all laboratories. Results: The drug samples T6445 and T6447 with 30 µM concentration tested by metabolic activation S9 on bacterial strain ST TA 98 show genotoxicity. The sample UOCHB1 with 30 µM concentration tested without activation shows possible genotoxicity on both strains ST TA 98 and ST TA 100. Other samples do not show any toxicity. I used 3 different procedures during the designation of assay. The most suitable version of the...
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The metabolism of amino acids in parasitic and anaerobic protists
Jakubec, Dávid ; Šuťák, Róbert (advisor) ; Hrdý, Ivan (referee)
Parasitic protists are the cause of countless pathological conditions and economic issues in many parts of the world. While being phylogenetically unrelated, they share many similarities in their approach to satisfying the essential needs. Unlike the much studied energy metabolism, amino acids utilisation pathways are rather unexplored areas. This review shows that in many cases, the parasitic life style has not had the same impact on the amino acid metabolism as it did on the energy metabolism of the protists, which is often severely reduced. Novel pathways have been found in many of the organisms in question, for the biosynthesis of amino acids deemed both essential and non-essential in humans. The arginine dihydrolase pathway found in Trichomonas and Giardia represents a complely new way of utilising the said amino acid. The metabolism of sulfur-containing amino acid has been a matter of intensive research for their non-proteogenic roles. Polyamines are organic nitrogenous compounds involved in many vital processes in the cells, including DNA replication and protein translation. The synthesis of polyamines and their derivatives is elucidated, as it is directly connected to the amino acid metabolism. Finally, the exploitation of the unique pathways described integrates the previous research with the aim...
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Assessing and Reducing the Impact of so called Black Swans in Launching New Medicines
Ženatá, Lucie ; Štohanslová, Barbora (referee) ; Adamec, Vladimír (advisor)
The diploma thesis is focused on the analysis and evaluation of risks in the introducing of new drug in the case of unexpected mass infections from the point of view of black swans. This thesis acquaints itself with the current state of the problematics, explains the terminology and meaning of black swans and gives examples of biological black swans. On the basis of the analysis and the available informations is proposed a risk assessment approach together with proposals how to reduce or eliminate possible risks.
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Vývoj léků z pohledu risk managementu
Hulín, Michal ; Hnilica, Jiří (advisor) ; Mead, James (referee)
The purpose of this diploma thesis is to understand financing of drug development from an enterprise risk management perspective as well as to critically assess the efficiency of the ISO framework and risk management techniques used for determining whether to fund drug development or not. The diploma thesis is divided into theoretical and practical part. The first part starts with perception and assessment of uncertainty and risk in the past. It describes how risk-averse individuals attempted to deal with uncertainty and different risk. This is followed by the evolution of traditional risk management into the fast developing enterprise risk management. The text further analyses commonly used risk management standards COSO ERM and ISO 31000:2009. However, the main focus is on the critical assessment of analytical tools which are frequently used for evaluating and assessing risks, especially financial ones, during drug development. The theoretical part is finished by a drug development process, whose phases are briefly described. The practical part was written in co-operation with AstraZeneca, a top-notch pharmaceutical company. The overview of its business is preceded by an explanation of current issues in the pharmaceutical industry. Furthermore, the risk analysis is conducted with respect to the ISO framework. Subsequently, selected risk assessment techniques are applied on the simplified financial model of two different drugs, which was created based on AstraZeneca's real data. These risk assessment tools are used in different phases of drug development so it could be seen clearly how the results are changing during a project. The outcomes of this risk analysis are compared with original plans used by AstraZeneca which were used for deciding whether to fund drug development or not.
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