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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.
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Experimental murine leishmaniasis and its application for drug discovery and study of host-pathogen interactions
Grekov, Igor ; Lipoldová, Marie (advisor) ; Krulová, Magdaléna (referee) ; Šírová, Milada (referee)
Leishmania spp. have a great clinical significance, being a causative agent of leishmaniasis. Leishmania is transmitted to its vertebrate hosts by phlebotomine sand flies. In vertebrates, the parasites infect professional phagocytes (neutrophils, monocytes and macrophages) and a variety of other cells. Clinical symptoms of leishmaniasis range from lesions, local or disseminated, to mucosal and visceral pathology. Twelve million people are infected with Leishmania and 350 million people are under risk of infection in 88 countries. Yet, no vaccine has been developed and the treatment needs significant improvement. In this regard, animal models of leishmaniasis play a key role in understanding the mechanisms of the disease and in finding ways to treat and prevent it. This thesis summarizes the results of my Ph.D. project devoted to refinement of procedures relevant to Leishmania studies and to the use of the optimized protocols for gene mapping and search for antileishmanial drugs. Large-scale cultivation of infective Leishmania parasites is important in a wide range of experimental setups. We adapted a biphasic SNB-9 medium for the large-scale cultivation of Leishmania and compared it with a common liquid medium. We also modified and optimised detection and quantification of Leishmania with PCR-ELISA by using...
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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.
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|
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Experimental murine leishmaniasis and its application for drug discovery and study of host-pathogen interactions
Grekov, Igor ; Lipoldová, Marie (advisor) ; Krulová, Magdaléna (referee) ; Šírová, Milada (referee)
Leishmania spp. have a great clinical significance, being a causative agent of leishmaniasis. Leishmania is transmitted to its vertebrate hosts by phlebotomine sand flies. In vertebrates, the parasites infect professional phagocytes (neutrophils, monocytes and macrophages) and a variety of other cells. Clinical symptoms of leishmaniasis range from lesions, local or disseminated, to mucosal and visceral pathology. Twelve million people are infected with Leishmania and 350 million people are under risk of infection in 88 countries. Yet, no vaccine has been developed and the treatment needs significant improvement. In this regard, animal models of leishmaniasis play a key role in understanding the mechanisms of the disease and in finding ways to treat and prevent it. This thesis summarizes the results of my Ph.D. project devoted to refinement of procedures relevant to Leishmania studies and to the use of the optimized protocols for gene mapping and search for antileishmanial drugs. Large-scale cultivation of infective Leishmania parasites is important in a wide range of experimental setups. We adapted a biphasic SNB-9 medium for the large-scale cultivation of Leishmania and compared it with a common liquid medium. We also modified and optimised detection and quantification of Leishmania with PCR-ELISA by using...
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