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Health status of selected cloven-hoofed breeds and results of its control
Řezníček, Josef ; Lamka, Jiří (advisor) ; Vokřál, Ivan (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Josef Řezníček Supervisor: Prof. RNDr. Jiří Lamka, CSc. Title of diploma thesis: Health status of selected cloven-hoofed breeds and results of its control This thesis deals with monitoring of parasitological situation of cloven-hoofed populations in two breeds of different breeding type. In game park breed of red and fallow deer, the helmintological examinations proved presence of infectious stages of roundworms and flukeworms. Correction of parazitostatusIt was made by administration of albendazole. The effectiveness of treatment was evaluated as corresponding with initial requirement. In free hunting ground the roe deer population was parasitologically monitored during vegetative period of hunting season of the 2011 year. The examinations proved presence of lungworms (dominantly small type) despite of ivermectin administrations used during previous winters. Results of this examinations can lead owner of the roe deer brees to assume treatment effectivity.
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The use of LC/MS for the Study of Biotransformation of Xenobiotics in Helminths
Vokřál, Ivan ; Szotáková, Barbora (advisor) ; Lísa, Miroslav (referee) ; Horák, Petr (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate Mgr. Ivan Vokřál Supervisor Doc. Ing. Barbora Szotáková, Ph.D. Title of Doctoral Thesis The use of LC/MS for the study of biotransformation of xenobiotics in helminths Annually, parasites cause many losses regarding not only human lives but also the livestock. One of the most effective weapons that can be used against them are anthelmintics. However, in many cases anthelmintics cease to work and resistance development occurs. One of the possible mechanisms of resistance is the biotransformation of the drug to ineffective or less active products by the parasite. The aim of this work was to bring new knowledge about the biotransformation of drugs in helminths. Emphasis was given to the relationship between biotransformation and the resistance of parasites against anthelmintic drugs. A possible technique to achieve this goal is to study directly the products of biotransformation, i.e. metabolites. As this issue is nowadays most frequently solved by liquid chromatography and mass spectrometry, we used this technique to meet our goals. Biotransformation was studied in representatives of tapeworms, flukes and roundworms. Where possible, economically important representatives as Barber's pole...
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Current options for pharmacotherapy of anxiety and sleep disorders
Böhmová, Kateřina ; Vokřál, Ivan (advisor) ; Skálová, Lenka (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Kateřina Böhmová Supervisor: prof. MUDr. Hrdina Radomír, CSc., PharmDr. Bc. Kotolová Hana, Ph.D., PharmDr. Vokřál Ivan, Ph.D. Title of diploma thesis: Current options for pharmacotherapy of anxiety and sleep disorder Anxiety and sleep disorders belong to common medical conditions. Anxiety attacks are recurring unpleasant emotional states. Sleep disorders are characterized by an insufficient or excessive amount of sleep or its poor quality, which persist for a significant time period. These common disorders represent an important medical and socioeconomic problem. Opinions about etiopathogenesis and classification are constantly evolving. Complex treatment includes mostly removing the cause, lifestyle changes, psychotherapy, and pharmacotherapy. Antidepressants from SSRI or SNRI group are considered to be the drugs of the first choice in frequent anxiety disorders. The treatment of insomnia depends mainly on the type of disorder. Hypnotics should be reserved especially for short-term and transient forms of insomnia, the treatment of which must be started as soon as possible together with the cognitive component and the elimination of the primary cause of this insomnia. In the chronic...
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The study of possible use of sertraline against gastrointestinal nematodes
Vodvárková, Nikola ; Skálová, Lenka (advisor) ; Vokřál, Ivan (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Nikola Vodvárková Supervisor: prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: The study of possible use of sertraline against gastrointestinal nematodes Haemonchus contortus is a widespread parasitic nematode infecting the gastrointestinal tract of many small ruminants that causes enormous damage to animal production every year. It is responsible for a disease in its host called Haemonchosis the main characteristic of which is anaemia caused by severe blood loss. This is responsible for the reduced productivity of the animal, and in some cases results in the death of the host. A relatively limited range of anthelmintic drugs is used for the treatment of Haemonchosis with new substances rarely being added to the list of treatments. Due to the massive use of the same anthelmintic drugs and the parasites adaptability, extensive resistance is pervasive with current treatments being no longer effective. For this reason it has become necessary to look for new effective drugs that have a different mechanism of action (MOA). One possibility is to test the anthelmintic efficacy of common drugs from other therapeutic groups. In this work, the potential anthelmintic effect, metabolism and toxicity...
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In vitro and ex vivo study of drug-drug interactions of antivirals on intestinal membrane transporters
Halodová, Veronika ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Veronika Halodová Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: In vitro and ex vivo study of drug-drug interactions of antivirals on intestinal membrane transporters Tenofovir (TFV) is the first-line agent in the treatment of hepatitis B virus (HBV) infection for patients aged over 12 years and one of the first-line choices for the combination antiretroviral therapy (cART) of infections caused by human immunodeficiency virus (HIV). Two commercially available prodrugs have been developed for oral administration of TFV, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF). These prodrugs increase TFV membrane permeability and oral bioavailability. One of the factors that can affect the bioavailability of orally administrated drugs is active transport mediated by efflux transporters, mainly by P-glycoprotein (ABCB1, P-gp) and Breast cancer resistance protein (ABCG2, BCRP). It has been already proved that TDF and TAF are substrates of both of these transporters. The goal of this diploma thesis was to use in vitro and ex vivo models of intestinal barrier to assess the impact of the efflux transporters on TDF and TAF transport in the intestine and on their...
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Optimization of the method for viability testing in Haemonchus contortus
Mašátová, Eva ; Skálová, Lenka (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Eva Mašátová Supervisor: prof. RNDr. Lenka Skálová, Ph.D. Consultant: Mgr. Linh Thuy Nguyen Title of diploma thesis: Optimization of the method for viability testing in Haemonchus contortus Barber's pole worm (Haemonchus contortus) is one of the most widespread pathogenic nematodes of the Trichostrongylidae family parasitizing in the abomasum of small ruminants, mainly in sheep. The most common symptoms of haemonchosis are anaemia, lack of thriving and weight loss. Young animals can also die. A significant complication in the treatment of haemonchosis is the rapidly developing resistance of the barber's pole worm to the administered drugs, which has become a global problem in recent years. This work focused on testing the efficacy of benzimidazole anthelmintics (thiabendazole and albendazole) in three strains of barber's pole worm, which differ in their drug sensitivity. We worked with strains: ISE (Inbred Susceptible Edinburgh) strain - sensitive, IRE (Inbred Resistant Edinburgh) strain - resistant and WR (White-River) strain - multi- resistant. The egg hatch test (EHT) was used to monitor the drug effectiveness and thus to monitor the level of resistance. Eggs from individual strains were...
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The results of long term monitoring of parazitostatus and its control in wild boar game preserve
Dúžková, Markéta ; Lamka, Jiří (advisor) ; Vokřál, Ivan (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Mgr. Markéta Dúžková Supervisor: prof. RNDr. Jiří Lamka, CSc. Title of rigorosum thesis: The results of long term monitoring of parasitostatus and its control in wild boar game preserve The rigorosum thesis is monitoring parasitostatus of wild boar game enclosure near village Tuř in years 2013 - 2019. The ivermectin-based drug was administered by injection to animals, which had been purchased from various localities in Czechia and Slovakia, during the establishing of the game enclosure. The parasitostatus control took place at the occasion of annual hunting activities, where coprological samples were collected since 2013. These samples were subjected to the parasitological screening by qualitative ovoscopy technique in the laboratory. The four parasitosis were observed, whose cause were Strongyloides spp., Trichuris suis, Metastrongylus spp. and Globocephalus spp. There were collected lung samples since 2015 as a metastrongylosis incidence checking. The last sampling was in 2019. The compiled results of all parasitological screenings point out to the upward tendency in prevalence of the parasitoses, primarily the metastrongylosis and the trichuriosis.
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Characterization of ligand binding to M1 muscarinic acetylcholine receptor using fluorescence anisotropy method
Danková, Hana ; Vokřál, Ivan (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Hana Danková Supervisors: Prof. Ago Rinken, PhD. MSc. Tõnis Laasfeld PharmDr. Ivan Vokřál, PhD. Title of diploma thesis: Characetrization of ligand binding to M1 muscarinic receptor using fluorescence anisotropy method Muscarinic acetylcholine receptors (mAChRs), members of the superfamily of G-protein coupled receptors (GPCRs), regulate vital physiological processes and are important targets in drug research. Five different subtypes (M1 - M5) have been identified. M1 mAChR is mainly distributed in the central nervous system and is linked to pathophysiology of neurodegenerative diseases. In recent years, fluorescent methods have been frequently used in studies of ligand binding to receptors. The fluorescence anisotropy (FA) is a homogenous assay to characterize ligand binding to receptors. In this work, we have evaluated the FA method with fluorescent ligand MK342 binding to M1 mAChRs expressed on budded baculovirus (BBV) particles. The fluorescence ligand was binding with the high affinity (4,4 nM) to M1 receptor in constructed BBV preparation. The apparent binding affinities (pKi) of eleven classical and three bitopic muscarinic ligands were screened and compared to previously published...
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Effect of anthelmintics on the transport of drugs in the intestine
Štefanová, Anna ; Vokřál, Ivan (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Bc. Anna Štefanová Supervisor: PharmDr. Ivan Vokřál, Ph.D. Title of diploma thesis: Effect of anthelmintics on the transport of drugs in the intestine Several classes of drugs are currently available for the treatment of helminthiasis in humans and animals, the so-called anthelmintics. Most of these drugs are administered by the oral route, where absorption into the systemic circulation occurs through the intestinal barrier. However, the course and extent of this absorption may be limited by biotransforming enzymes and transport proteins, in particular the family of so-called ATP-binding cassette transporters. These transporters are capable of returning many xenobiotics, including many drugs, back into the lumen of the gut and are the first line of defence against the entry of these substances into the body. An important representative of this group of transporters is P-glycoprotein, which is known for its broad substrate specificity. On this transporter, drugs can act as substrates but also as inhibitors and/or inducers, which may lead to the risk of drug-drug interactions. There is relatively little information about the effect of anthelmintics on P-glycoprotein inhibition. The most studied...
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