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Production and characterisation of human C1 inhibitor and Plasmodium falciparum PfMSP3.1 recombinant proteins for structural studies
Čápová, Kateřina ; Konvalinka, Jan (advisor) ; Heidingsfeld, Olga (referee)
PfMSP3.1 is one of the surface proteins of the intracellular parasite Plasmodium falciparum, which causes malaria. As one of the evasion strategies of the immunity system of the human host this protein interacts with one regulator of the complement system - C1 inhibitor. Determining the exact binding site and its structural assessment would help to better understand the interaction between the parasite and the host, which is necessary for the disease progression and thus for the development of a potential therapy. In the theoretical part of the thesis, the life cycle of Plasmodium falciparum, the role of the parasite stage called merozoite, the role of its surface proteins, including merozoite surface protein 3, in the attack of red blood cells by the parasite, are described in more detail. It also briefly describes the complement system, its activation pathways and the regulation of these pathways. The experimental part includes the cloning of plasmids to produce C1 inhibitor and various forms of merozoite surface protein PfMSP3.1, transfection of S2 insect cells with these plasmids, subsequent protein expression in S2 cells and their purification. In the second half of the experimental part, we tried to create complexes of C1 inhibitor with individual PfMSP3.1 forms and an attempt to crystallize...
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Influence of avian Plasmodium on their hosts
Dulavová, Kristýna ; Svobodová, Milena (advisor) ; Vinkler, Michal (referee)
Avian malaria parasites of the genus Plasmodium are unicellular (and intracellular) protozoans of the group Haemospororida, using a blood-sucking insect (mosquito) as a vector and a bird as a vertebrate host. The effects of this disease, together with avian pox, have greatly influenced endemic populations of Hawaiian birds after introduction of a suitable vector to the islands by a human hand, leading to a drastic extinction of bird species; most of the remaining Hawaiian endemic species are now endangered. Apart from that, avian malaria is distributed nearly all over the world, infecting a variety of different hosts. This thesis is focused on the influence of avian malaria parasites mainly on their avian hosts. The most severe patologies caused by Plasmodium are associated with blood stages causing serious anemia in birds. More pathologies are connected with exoerythrocytic stages in the endothelial cells in various organs and are accompanied with external signs such as lethargy, respiratory distress, weakness, inappetence, sometimes weight loss and so on; different plasmodium species-bird host combinations have different outcomes. An interesting issue is the emerging tolerance against avian malaria in Hawaii Amakihi (Hemignathus virens), a species occupying low elevation areas of Hawaiian...
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Prevalence and risk factors of malaria among children under 5 years and the prevention and treatment regimens in the Kitase community of Ghana
Amponsah, Ebo Owusu
The purpose of this study was to investigate the incidence of malaria in children under the age of five living in the Kitase Community in Ghana, as well as possible causes, preventative measures, and therapeutic approaches. The principal goals of the research were accomplished through the use of a hospital-based cross-section design, which required the gathering of primary data from women living in the Kitase township, which is located within the Akuapim South Municipal Assembly in Ghana. For the analysis, we utilised version 16 of the STATA statistical software. The chi-squared test and logistic regression were performed to determine the relationship between malaria incidence and household and environmental characteristics. Findings showed that malaria prevalence among under 5 children was 19.62% with a total of 46.15% with at least occurrence of malaria illness in the past three months. Also, ownership of Long-Lasting Insecticidal Nets (LLINs) was 77.31%, and its use among 58.46% of mothers. However, Environmental characteristics such as bushes, waste dumpsites, stagnant water, and breeding areas around the house increase the odds of malaria infection by AOR of 1.885, 2.455, 2.197, and 2.060, respectively. Therefore, the study recommends that health authorities in the study area ensure the proper usage of LLINs (mosquito nets) through regular and effective education on preventive measures and ensure that good sanitation is observed in settlements.
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Periodic Water Bodies and Their Biota.
Bušová, Tereza ; Říhová, Dagmar (advisor) ; Škodová, Jana (referee)
This thesis is focused on a description of small periodic water bodies and their biota. These telms are formed as a result of heavy spring rains, floods, melting snow or the ground water level rising. They are formed on green parts, non-green parts or fallen parts of a plant (in that case they are called phytotelmes), in water-filled tree-holes (dendrotelmes), in fissures of rocks (lithotelms) or in various cavities, artificially created by human - in empty jars, water- filled tires, flower-holding vases in cemeteries etc. The thesis deals mainly with dendrotelmes and phytotelmes which are the most frequent, especially in tropics. It provides the information about their formation and animals that lives in these small habitats. Also, a taxonomical review of the main reported fauna was added for better orientation of the reader. The most common taxa which occur in temporary pools are families of mosquitoes (Culicidae), chironomids (Chironomidae) and ceratopogonids (Ceratopogonidae). There are also present other Dipteran larvae or larvae of scirtid beetles from the family Helodidae. Some of the animals living in the pools used different evolution strategies to be well adapted to deal with periodicity and drying out of the water bodies. Their overview is also included in this thesis. Furthermore,...
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Development of insecticides inhibiting acetylcholineseterase
Mányová, Brigita ; Vopršalová, Marie (advisor) ; Maixnerová, Jana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Brigita Mányová Supervisor: PharmDr. Marie Vopršalová, CSc. Supervisor-specialist: PharmDr. Vendula Hepnarová, Ph.D. Title of diploma thesis: Development of insecticides inhibiting acetylcholineseterase Pest insects cause problems and damage all over the world. They are vectors of serious diseases such as malaria, dengue fever, yellow fever, Zika virus disease and chikungunya disease. They cause huge damage to agricultural crops and are annoying to everyday life in living spaces. The aim of this diploma thesis was in vitro testing of selected compounds from the group of bis-isoquinoline and bispyridinium acetylcholinesterase inhibitors as potential insecticides. Another goal was also to create relationships between structure and effect. The ability of these compounds to inhibit both human (hAChE) and fly acetylcholinesterase (MdAChE) was evaluated. The modified Ellman spectrophotometric method was used. The half inhibitory concentration (IC50) values were obtained for both enzymes and the selectivity indexes (SI) were then calculated. Compounds having IC50s in micromolar or nanomolar range and exhibiting selectivity for MdAChE were most desirable. During the testing of these inhibitors, three...
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Evaluation of newly prepared insecticides in vitro
Tomáš, Ondrej ; Vopršalová, Marie (advisor) ; Herink, Josef (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Ondrej Tomáš Supervisor: PharmDr. Marie Vopršalová, CSc. Consultant supervisor: mjr. PharmDr. Vendula Hepnarová, Ph.D. Title of diploma thesis: Evaluation of newly prepared insecticides in vitro Malaria is a widespread infection and one of the most dangerous diseases transmitted by insects. It threatens lives of millions of people all around the world, thus its regulation is necessary. Most common malaria vectors are mosquitoes of genus Anopheles. Novel structures of insecticides with selective inhibition of mosquito acetylcholinesterase are subjects of research, with an intention to deal with this problem. The aim of this work was to test six newly prepared succinimide derivatives with insecticidal potential. The ability of these compounds to inhibit Anopheles gambiae mosquito (AgAChE) and human acetylcholinesterase (hAChE) was evaluated. Leading structures of these compounds were also tested to find relations between chemical structure and biological activity. The modified Ellman's method was used to obtain the half maximal inhibitory concentration (IC50) values for both enzymes. Tested substances were able to inhibit only hAChE and none of them displayed activity against AgAChE. Compound...
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Evaluation of newly prepared insecticides in vitro
Tomáš, Ondrej ; Vopršalová, Marie (advisor) ; Herink, Josef (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Ondrej Tomáš Supervisor: PharmDr. Marie Vopršalová, CSc. Consultant supervisor: mjr. PharmDr. Vendula Hepnarová, Ph.D. Title of diploma thesis: Evaluation of newly prepared insecticides in vitro Malaria is a widespread infection and one of the most dangerous diseases transmitted by insects. It threatens lives of millions of people all around the world, thus its regulation is necessary. Most common malaria vectors are mosquitoes of genus Anopheles. Novel structures of insecticides with selective inhibition of mosquito acetylcholinesterase are subjects of research, with an intention to deal with this problem. The aim of this work was to test six newly prepared succinimide derivatives with insecticidal potential. The ability of these compounds to inhibit Anopheles gambiae mosquito (AgAChE) and human acetylcholinesterase (hAChE) was evaluated. Leading structures of these compounds were also tested to find relations between chemical structure and biological activity. The modified Ellman's method was used to obtain the half maximal inhibitory concentration (IC50) values for both enzymes. Tested substances were able to inhibit only hAChE and none of them displayed activity against AgAChE. Compound...
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Current chemotherapy of protozoal parasitoses.
Valach, Marek ; Hrdý, Ivan (advisor) ; Arbon, Dominik (referee)
This work is devoted to the process of chemotherapy of diseases caused by parasitic protozoa. Even though being often shadowed by bacterial or viral infections, protozoan caused diseases affect hundreds of millions of people every year, especially in tropical and subtropical regions of the developing world. This great burden placed on inhabitants of these countries highlights the need for functional chemotherapeutics against these diseases, because vaccination is not yet an option. The goal of successful chemotherapy is either elimination or suppression of the parasite in the patient by exploiting its weaknesses in its life cycle or differences in physiology between the parasite and the host. The aim of this work is to provide an overview of chemotherapeutics currently approved for the treatment four most prevalent parasite diseases. The diseases are clearly described in the terms of symptoms, their socioeconomical impact and lifecycle of the parasite. An emphasis is placed on the description of mode of action of each chemotherapeutical agent and on mechanism allowing the parasite to resist the drug.
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Evaluation of newly prepared insecticides in vitro
Tomáš, Ondrej ; Vopršalová, Marie (advisor) ; Herink, Josef (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Ondrej Tomáš Supervisor: PharmDr. Marie Vopršalová, CSc. Consultant supervisor: mjr. PharmDr. Vendula Hepnarová, Ph.D. Title of diploma thesis: Evaluation of newly prepared insecticides in vitro Malaria is a widespread infection and one of the most dangerous diseases transmitted by insects. It threatens lives of millions of people all around the world, thus its regulation is necessary. Most common malaria vectors are mosquitoes of genus Anopheles. Novel structures of insecticides with selective inhibition of mosquito acetylcholinesterase are subjects of research, with an intention to deal with this problem. The aim of this work was to test six newly prepared succinimide derivatives with insecticidal potential. The ability of these compounds to inhibit Anopheles gambiae mosquito (AgAChE) and human acetylcholinesterase (hAChE) was evaluated. Leading structures of these compounds were also tested to find relations between chemical structure and biological activity. The modified Ellman's method was used to obtain the half maximal inhibitory concentration (IC50) values for both enzymes. Tested substances were able to inhibit only hAChE and none of them displayed activity against AgAChE. Compound...
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Iron homeostasis in malaria
Wernerová, Klára ; Šuťák, Róbert (advisor) ; Voleman, Luboš (referee)
Although malaria is a well-studied infectious disease, we are still unable to fight it effectively, as evidenced by a large number of infected people. Many drugs are available against malaria. However, because of incessantly emerging resistances, new, more effective antimalarials need to be developed. One possibility is to target the parasite's iron metabolism, the essential element of all organisms. Iron participates in DNA synthesis, respiration, energy production. It acts as a cofactor of ribonucleotide reductase, and metalloproteins with FeS clusters or heme. During the infection, the parasite must compete with the host for nutrients, including iron. The mechanism of iron uptake or excretion in malaria parasite is not completely clear. Only two iron transporters are known, but it is already evident, that there must be more of them. The Plasmodium parasite digests a large amount of hemoglobin, which is degraded into free heme and denatured globin. Free heme is toxic to the cell though. Plasmodium defends itself from the toxicity of free heme by forming chemically inert hemozoin. This unique mechanism of protection against the free heme toxicity is very useful for Plasmodium and other blood parasites, but it also becomes an advantageous target for drugs because the mechanism is present only in...
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