National Repository of Grey Literature 39 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
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...
Effect of lipophilic cation on the toxicity of phosphonium salts in parasitic protists
Čadková, Aneta ; Mach, Jan (advisor) ; Trnka, Jan (referee)
The mitochondrion is an essential organelle responsible for energy metabolism and maintaining cellular homeostasis. Disruption of their function can have serious consequences for the entire cell and organism. Given their key role in the organism, they become an attractive target for drugs. In this thesis, we examine the impact and significance of phosphonium salts as potential mitochondrial-targeted therapeutics. The investigated compounds have modified anchors based on the commonly used triphenylphosphonium cation (TPP+ ). These substances have the ability to permeate the phospholipid bilayer and accumulate on the inner mitochondrial membrane. Our research focuses on selected model organisms of the class Kinetoplastida and opportunistic pathogenic fungi. These pathogenic organisms are responsible for severe infectious diseases in humans. Our aim is to compare the effectiveness of phosphonium salts with different anchor modifications against these organisms and attempt to elucidate their mechanism of action. We have found that the modified salts are capable of inhibiting the growth of parasitic protists at nM concentrations, affecting mitochondrial respiration, membrane potential, and mitochondrial integrity. However, there is no increase in the level of oxygen radicals. We are assuming that the...
Treatment options for untreatable amoeba Naegleria fowleri
Veselý, Martin ; Mach, Jan (advisor) ; Arbon, Dominik (referee)
Naegleria fowleri is a free-living protist which can penetrate the body of a previously healthy person and cause meningoencephalitis. The rapid course, disproportionately strong immune response and the lack of effective drugs are the reasons why this disease almost always ends fatally. Due to the relative rarity of this disease, it is not lucrative for pharmaceutical companies to develop a completely new drug. The only way to search for effective drugs is to test those that have already been approved for another purpose. However, clinical tests are not possible due to the low morbidity and rapid course of the disease, and research in this area is thus limited to animal models of the disease and evaluation of the effect of drugs against the pathogen in vitro. Currently used medication includes drugs that are highly toxic or poorly penetrate the site of inflammation. In the future, more effective chemotherapy against N. fowleri and more gentle towards patient could be used. This work summarizes knowledge about pathogenic amoeba, currently used drugs and presents new experimentally tested therapeutics.
Selective screening of antiparasitic substances
Wernerová, Klára ; Mach, Jan (advisor) ; Kovářová, Julie (referee)
The mitochondrion is the key organelle of the cell. It is involved in energy metabolism, the Krebs cycle, the respiratory chain, and the formation of Fe-S clusters, which form the structure of many proteins. Therefore, disruption of the mitochondria is usually fatal to the cell, especially if it contains only one mitochondrion, as is the case in Trypanosoma brucei brucei. The T. b. brucei parasite has become the primary model organism for our study because its basic biochemical processes are already well described, including mitochondrial metabolism, and it is also easy to cultivate in the laboratory. Other model organisms we used in this study were Leishmania mexicana, Cryptococcus neoformans and Candida albicans. All these organisms are causative agents of serious diseases, and although there are drugs against them, new drugs need to be developed due to the frequent emergence of resistances. Mitochondria-targeting drugs are promising for the pharmaceutical industry. In this work, we investigate the efficacy of compounds whose structure is composed of a mitochondrial phosphonium anchor linked to a carbon chain. These substances are capable of incorporation into the mitochondrial membranes. The work not only focuses on comparing the potency of the tested substances in selected model organisms, but...
Iron metabolism of parasitic amoeba Acanthamoeba castellanii
Krejbichová, Lucie ; Mach, Jan (advisor) ; Horáková, Eva (referee)
Acanthamoeba castellanii, an opportunistic parasitic amoeba, rarely causes infection in humans. Yet, the treatment and diagnosis is often complicated. It causes two diseases: granulomatous encephalitis and acanthamoeba keratitis (inflammation of the cornea of the eye). There is a modern way to deal with parasitic protists and other infectious diseases - interference with iron metabolism. Iron is a crucial element for living organisms; it is involved in many metabolic processes. However, it is also toxic for the organisms and therefore, its uptake, storage and homeostasis in the cell is a strictly controlled process. Ferric reductase takes part in iron homeostasis inside the acanthamoeba cell. Fluorescent microscopy has shown that ferric reductase is located in the vacuole membranes and its activity increases when iron availability decreases. This protein probably mediates the reduction of iron ions that are used in other cellular processes, especially for the transport of iron across membranes. Interestingly, the reduced availability of iron doesn't affect the mitochondrial Fe-S cluster pathway as we proved by fluorescent microscopy with an antibody against one of the proteins of this pathway (IscU). Iron deficiency doesn't affect respiration but alternative oxidase activity is reduced. Moreover, deprived...
Advances in treatment of human trypanosomiasis
Novotná, Kristýna Klára ; Mach, Jan (advisor) ; Grekov, Igor (referee)
Sleeping sickness is a human disease found in sub-saharan Africa, and is caused by a parasitic protozoan Trypanosoma brucei. Trypanosoma brucei species infects various mammals, however, only Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense subspecies are resistant to trypanolytic factors found in human blood serum. This work briefly summarizes known operating mechanisms of trypanolytic factors and resistance mechanisms of trypanosomes to these factors. The work covers mainly description and summarization of current diagnostic methods of sleeping sickness and used trypanocidal drugs. Majority of introduced methods shows high levels of sensitivity and specificity, however, for poor, disease affected areas they are often way too expensive. Prescribed drugs are expensive as well, and what's more, they are often ineffective against both subspecies and have severe side effects. Last part of the work is dedicated to potential development of new medicaments.
Naegleria: from free-living protist to brain eating deadly pathogen
Matějková, Magdalena ; Mach, Jan (advisor) ; Marková, Lenka (referee)
N. fowleri is mostly a free-living amoeboflagellate which, in favorable conditions, can occasionally adopt a parasitic lifestyle. In such cases, the amoeba becomes causative agent of primary amoebic meningoencephalitis, a severe and largely fatal disease occurring in several mammals including humans. The treatment of this disease is complicated by many unwanted side-effects of available drugs and a lack of prompt diagnostic methods. Within the Naegleria genus, N. fowleri is the only human pathogen. According to up-to-date knowledge, the pathogenicity of this species is due to its metabolic properties as well as to a particular set of proteins expressed by this protist. Besides a wide scale of enzymes, some of these proteins participate in the formation of cellular structures which are crucial for the pathogenesis. All these particularities should be targeted in a search for a better treatment. The thesis is focusing on a comparison of N. fowleri with related species N. gruberi and N. lovaniensis, stressing out the differences of N. fowleri from these non-pathogenic species. Key words: Naegleria fowleri, primary amoebic meningoencephalitis, immune response, pathogenesis, facultative parasitism
Current options of treatment for parasitic kinetoplastids
Čadková, Aneta ; Mach, Jan (advisor) ; Richterová, Lenka (referee)
Chagas disease, sleeping sickness and leishmaniasis are diseases occurring mainly in developing areas of Africa, America and Asia. They are caused by parasitic kinetoplastids from the genus Trypanosoma and Leishmania. These protozoans undergo morphologic transformations during their development leading to changes of their properties. They are characterized by complex mechanisms that allow them to evade the host's immunity. At the same time, because of these mechanisms and selection pressures, they are able to subsequently develop resistance to used drugs. The diseases caused by protozoa are classified as "neglected tropical diseases". The research and development of drugs against them is heavily underfunded. Currently used drugs are expensive, have a number of side effects, and due to lack of usage regulation develop resistance. The work first generally presents human parasites of the class Kinetoplastida. It further describes the treatment of diseases caused by the characterized species and focuses on a summary of currently used drugs, their mechanism, resistance and potential new drugs in clinical phases. Key words: kinetoplastids, Trypanosoma, Leishmania, treatment, disease, mechanism of action, resistance, nitroreductase
Legal regulation of weapons and ammunition in the Czech Republic and implementation of EU regulations
Mach, Jan ; Staša, Josef (advisor) ; Prášková, Helena (referee)
in English The introduction of this thesis explains the basic concepts of the legislative regulation of weapons and ammunition in the Czech Republic and their use in specific cases. This part also briefly presents the legal history of selected institutes of weapons legislation in the Czech Republic with EU law, in particular conditions and possession of weapons, business in the field of weapons and categorization of weapons. The next part analyzes Act No. 288/1995 Coll. again focusing on selected institutes important in the context of the implementation of EU law. The following are comparisons of Council Directive 91/477 / EEC in its original version with Act No. 119/2002 Coll. in the original wording and Council Directive 91/477 / EEC as amended by Directive 2008/51 / EC of the European Parliament and of the Council with Act No. 119/2002 Coll. as amended by Act No. 222/2017 Coll., with an overlap into certain legal regulations. The thesis also describes and analyzes the reasons for the adoption of Directive (EU) 2017/853 of the European Parliament and of the Council, the process of its adoption and the Czech Republic's lawsuit for its invalidity and describes the subsequent proceedings in front of the EU Court of Justice. Due to the lawsuit rejection, Czech Republic was forced to adopt an...

National Repository of Grey Literature : 39 records found   1 - 10nextend  jump to record:
See also: similar author names
15 MACH, Jiří
8 Mach, Jakub
20 Mach, Jan
1 Mach, Jaroslav
1 Mach, Jindřich
15 Mach, Jiří
2 Mach, Jonáš
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