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Metabolism and efficacy of new potential anthelmintics
Zajíčková, Markéta ; Skálová, Lenka (advisor) ; Várady, Marián (referee) ; Vadlejch, Jaroslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Markéta Zajíčková Supervisor: Prof. RNDr. Lenka Skálová, Ph.D. Consultant: PharmDr. Ivan Vokřál, Ph.D. Title of Dissertation Thesis: Metabolism and efficacy of new potential anthelmintics Overpopulation of gastrointestinal nematodes represents global health and economical problem. Therefore, suitable solution in the form of effective anthelmintic treatment is needed. Several anthelmintics with distinct mechanism of action are available on the market, however, the widespread resistance limits their efficacy. As a consequence, finding a new possible alternative becomes important. In present dissertation thesis, the novel anthelmintic candidates were selected and their effect against model parasitic nematode Haemonchus contortus was examined. The studies encompassed three approaches within the field of drug discovery: new molecular entity identification and structure modification, drug repurposing, and medicinal plants screening. Newly synthesized compounds designated as BLK127, HBK4 and BLK127 derivatives, already known antipsychotic drug sertraline (SRT) and the extracts from eight European ferns species from genus Dryopteris, Athyrium and Blechnum were the subjects of our interests. Two...
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Metabolism and efficacy of new potential anthelmintics
Zajíčková, Markéta ; Skálová, Lenka (advisor) ; Várady, Marián (referee) ; Vadlejch, Jaroslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Markéta Zajíčková Supervisor: Prof. RNDr. Lenka Skálová, Ph.D. Consultant: PharmDr. Ivan Vokřál, Ph.D. Title of Dissertation Thesis: Metabolism and efficacy of new potential anthelmintics Overpopulation of gastrointestinal nematodes represents global health and economical problem. Therefore, suitable solution in the form of effective anthelmintic treatment is needed. Several anthelmintics with distinct mechanism of action are available on the market, however, the widespread resistance limits their efficacy. As a consequence, finding a new possible alternative becomes important. In present dissertation thesis, the novel anthelmintic candidates were selected and their effect against model parasitic nematode Haemonchus contortus was examined. The studies encompassed three approaches within the field of drug discovery: new molecular entity identification and structure modification, drug repurposing, and medicinal plants screening. Newly synthesized compounds designated as BLK127, HBK4 and BLK127 derivatives, already known antipsychotic drug sertraline (SRT) and the extracts from eight European ferns species from genus Dryopteris, Athyrium and Blechnum were the subjects of our interests. Two...
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Dominant protein antigens of Toxocara canis
Skulinová, Kateřina ; Kašný, Martin (advisor) ; Panská, Lucie (referee) ; Vadlejch, Jaroslav (referee)
Larval toxocarosis is a worldwide widespread zoonosis occurring in developed countries as well as developing countries. The disease is caused by roundworms of the genus Toxocara, primarily intestinal parasites of dogs, cats and other animals. Viable eggs released into the environment with the dog's faeces can infect not only definitive hosts, but also paratenic hosts, which include many vertebrates, some invertebrates, and also humans. In humans, larval migration can cause severe and irreversible tissue damage, which is characterized by various clinical forms of the disease. For the purposes of routine diagnosis of larval toxocarosis, the most frequently used method so far is ELISA and Western blot, which enable the reaction demonstration of specific antibodies with the larval excretory-secretory product (TES). TES is obtained for diagnostic purposes from larvae cultured in nutrient medium. The preparation of such an antigenic mixture is very laborious and may vary across the laboratories. Current research in the field of diagnosis of larval toxocarosis is therefore focused on the standardization of serodiagnostic procedures. A fundamental prerequisite is knowledge of the detailed composition of TES, especially antigenic (protein) molecules. However, the number of studies devoted to the...
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Adaptation mechanism of nematodes for harsh condition survival
Čermáková, Petra ; Vadlejch, Jaroslav (advisor) ; Kyriánová, Iveta Angela (referee)
Adaptation is a complex of mechanisms, thanks to which nematodes can endure unfavourable conditions. These can come from either external or internal environment. Which one would be dominating, depends on the exact lifestyle of a certain nematode e.g. nematodes living in free nature must deal with environmental changes, parasitic ones are influenced by viability of the host, but even in this case we cannot dismiss the role of environment. There is always a mutual bond between the parasite, host, and the environment. Nematodes usually resolve emergency situations in two ways. One way is to adapt to the new conditions so they can grow and reproduce. The other way is to choose an adaptation mechanism thanks to which nematodes will survive a threat temporarily. Adaptation mechanisms can vary between individual species or various stages of the same kind of nematodes. Universal adaptation behaviour among nematodes does not exist. Adaptation mechanisms of nematodes cause changes in their physiology, metabolism, morphology, development or growth, but also in their behaviour. The aim of this thesis is to gather information from academic literature and scientific articles and provide a closer description of nematodes and their most usual and important adaptation mechanisms. This is preceded by a general description of nematode biology for better understanding of the issue. Based on this information we can comprehend why nematodes are such a successful phylum. Nematodes can be also considered as pests having a negative impact on the economic and social sphere. Further knowledge of nematodes and their mechanisms of adaptation and exploration of their surprisingly resistant forms can lead to control their regulation.
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Influence of nematophagous fungi on populations of important phytoparasitic nematodes, family Heteroderidae, in the Czech Republic
Hussain, Manzoor ; Ryšánek, Pavel (advisor) ; Vadlejch, Jaroslav (referee)
We report on studies aimed to evaluate the effects of five nematophagous fungi on population dynamics of northern root knot nematode, Meloidogyne hapla and sugar beet cyst nematode, Heterodera schachtii in laboratory and greenhouse trials. During our biocontrol studies, mainly five fungal species Arthrobotrys oligospora, Dactylella oviparasitica, Clonostachys rosea, Stropharia rugosoannulata, and Lecanicillium muscarium were isolated from eggmasses of nematodes during root and soil samples collected in Czech Republic and tested against Meloidogyne hapla in carrots while Heterodera schachtii in sugar beet, both in-vitro and in-vivo fashions. All fungi exhibited varied type of infection on nematodes but L. muscarium proved to be the most potential bioagent in controlling nematode population enormously. Lecanicillium muscarium not only halted nematode reproduction factor (Pf/Pi) but also escalated plant growth. Plant root systems treated with L. muscarium were observed colonized by fungi while seen under microscope which depicted that fungi provided a protecting shield or body guard against plant parasitic nematodes. Moreover, L. muscarium was further compared with commercially available nematicides and a fertilizer to justify its highly potential for diminishing nematode population. L. muscarium along with nematicides and fertilizer had dramatic effects in reduction of both nematodes (M. hapla, H. schachtii) population in soil but improvement of plant growth was only noticed in case of L. muscarium. The chemical nematicide, Dazomet had some negative effects which appeared in the form of chlorotic spots on leaves which further suggested that there were some the phytotoxic effects.
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The occurrence of gastrointestinal nematodes to anthelmintic drugs in goat herds
Císlerová, Markéta ; Vadlejch, Jaroslav (advisor) ; Kyriánová, Iveta Angela (referee)
Parasitic nematodes are a cosmopolitan distribution group helminths causing the infections, which cause deterioration of health of infected animals. Frequent are indigestion e.g. diarrhea, dehydration, loss of appetite, but also to anemia. Gastrointestinal nematodes also have an impact on economic losses for farmers due to reduced production of milk and meat, the more difficult pregnancy rates, abortions, deaths during severe infections and high treatment costs. These consequences parasites worsen the overall welfare of animals, which should not be completely overlooked.
To eliminate gastrointestinal infections with broad use modern anthemintic of the following groups: benzimidazoles, imidazoles and macrocyclic lactones aminoacetonitrilové derivatives (AADs). AADs is a relatively new group of broad-spectrum anthlemintic. As an adjunct in the treatment available today increasingly researched, plants and their extracts anthelmintic effect.
After a few years since the introduction broad spectrum anthelmintic occurred first mention of resistance. Resistance is defined as the ability of the parasite to survive treatment with the recommended dose of anthelmintics that would normally be lethal to the parasite. Rapid development of resistance has caused particularly wrong drug administration procedures for the failure of the administration and also the fact that resistance is based genetic property. It is therefore very important along with the development of new effective drugs also strictly follow the prescribed procedures in the treatment.
Goats were previously treated with the same doses of anthelmintics like sheep and chronic administration of subtherapeutic doses of anthelmintic lead to faster development of resistance to anthelmintics. This was problematic, as it is known, goats have a faster metabolism and it contributed to the expansion resistance in goats.
The early detection resistance is needed to improve detection methods. Emphasis should be placed on simplicity, availability and cost efficiency that could be used directly to the farmer.
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Helminths of the European otter
Seemannová, Kateřina ; Vadlejch, Jaroslav (advisor) ; Lukáš, Lukáš (referee)
The target of this study was to explore a distribution and prevalence of parasitic helmints in population of wild European otters in the Czech Republic. For this purpose organization ALKA wildlife o.p.s. provided 15 cadavers of these animals. This gained experimental material was consequently subjected to a detailed parasitical examination. All examinations and analises were made in the parazitical laboratory of Department of Zoology and Fishers, Faculty of Agrobiology, food and natural resources in Czech University of Life Sciences in Prague. The discovered parazitic organisms were subsequently isolated and determined. This autopsy showed the occurrence of parasitic flukes of genus Metorchis. Prevalence was counted 13.33 % (two positive samples from all fifteen samples). In the first sample, there were found 17 flukes, in the second sample, there were found 11 flukes. The place of discovery of this samples was southern Bohemia. The occurence of other expected representers of tapeworms, roundworms and acanthocephala were not confirmed. Results can be disorted because of low number of examined biological material. But getting bigger amount of material is a problem because the European otters are protected by law.
The results show that in population of wild European otters occur parasitic flukes of genus Metorchis. Since this is the first mention of their occurrence in the Czech Republic, it would be appropriate to study this issue from now to get more results that would be more exact.
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Survey of parasitoses in beef cattle from two geographical areas of the Czech Republic
Kubelka, Lukáš ; Lukešová, Daniela (advisor) ; Vadlejch, Jaroslav (referee)
Research in this diploma thesis was focused on monitoring of the beef cattle parasites and periodically was done from April 2015 to November 2015 on three different farms in two different regions (Vysočina and Středočeský region) in the Czech Republic. 20 samples of fresh faeces were collected every month from each farm during morning. Processing and consequent evaluation of samples took place in parasitology laboratory at State Veterinary Institute in Jihlava. Samples were evaluated using a relatively new coprological technique FLOTAC, developed in Italy and recommended for parasitological qualitative and quantitative analysis of large farm animal eggs and oocysts. For each farm two pooled samples (10 g each) by subtracting 1 g of faeces from individual samples were used. Results were evaluated and statistically analysed by statistical software Statistica 13. There was occurrence of eggs of gastrointestinal nematodes (family Trichostrongylidae), tapeworms (Moniezia spp.) and oocysts of coccidia (Eimeria spp.) on all of the farms. Only on the farm 3 there was also occurrence of fluke eggs (Paramphistomum spp.). From the results it was evident, that farms that administered anthelmintic to livestock had significantly lower amounts of EPG/OPG in animal faeces. Despite of using pooled samples, method proved to be reliable and sensitive for monitoring of developing stages of livestock parasites. Even low amount of eggs or oocysts in animal faeces were detected by coprological technique FLOTAC.
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