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Effect of anthelmintics on expression of selected plant enzymes
Navrátilová, Martina ; Matoušková, Petra (advisor) ; Novotná, Eva (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Martina Navrátilová Supervisor: Ing. Petra Matoušková, Ph.D. Title of diploma thesis: Effect of anthelmintics on expression of selected plants enzymes Fenbendazole (FEN) is a broad-spectrum benzimidazole anthelmintic that is widely used to prevent and treat helminthoses in farm animals. The use of anthelmintics is associated with the risk of their transfer to the environment, where they can potentially affect non-target organisms, including plants. They come into contact with anthelmintics and their metabolites mainly due to the fertilization of farmland with manure and/or come directly into contact with the excrements of treated animals on pastures. There have not been many studies focused on the cell physiology and cell metabolism of plants affected by anthelmintics, which lead to our participation in a study which dealt, in part, with the influence of FEN on the transcriptome and gene expression in model plant Arabidopsis thaliana. A. thaliana is a monocotyledonous plant, which is a very common model organism of higher plants. Its genome was also published in 2000, allowing extensive research into gene expression. The aim of this work was to monitor expression of selected A....
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The effect of alpha-humulene and carophyllene oxide in ovarian cancer cells
Žáková, Kateřina ; Matoušková, Petra (advisor) ; Svobodová, Hana (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Kateřina Žáková Supervisor: Ing. Petra Matoušková, Ph.D. Title of diploma thesis: The effect of alpha-humulene and caryophyllene oxide in ovarian cancer cells. Sesquiterpenes α-humulene and β-caryophyllene oxide are substances with antiproliferative activity against number of tumor cell lines. In this study, the antiproliferative efect of α-humulene and β-caryophyllene oxide was tested alone and in combination with doxorubicin, using neutral red uptake assay. Doxorubicin- sensitive cell line A2780 was more sensitive to the action of doxorubicin and sesquiterpenes than SKOV3 cell line, which is naturally doxorubicin-resistant. To determine the interactions between sesquiterpenes and doxorubicin, software program CalcuSyn which is based on Chou-Talay method was used. The combination indexes ofsesquiterpenes with doxorubicin were determined. Both sesquiterpenes had antagonistic effect on doxorubicin in A2780 cell line and synergistic effect on SKOV3 cell line. The mechanism of the antiproliferative effect of all three tested substances is explained by the production of ROS. For the determination of pro-oxidant effects of the tested substances the DCF assay was used. Our results showed good...
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Effect of monepantel on the expression of selected enzymes in Haemonchus contortus
Jelenková, Klára ; Matoušková, Petra (advisor) ; Raisová Stuchlíková, Lucie (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Klára Jelenková Supervisor: Ing. Petra Matoušková, Ph.D. Title of diploma thesis: Effect of monepantel on the expression of selected enzymes in Haemonchus Contortus Barber's pole worm (Haemonchus contortus) is parasitic nematode which is the cause of haemonchosis, worldwide distributed disease of small ruminants leading to decrease in productivity and in many cases even to animals death. For prevention and treatment of this disease are used drugs for a long time - anthelmintics. Due to their frequent use and lack of innovation in this group of drugs parasites have gradually built an extensive resistance to these drugs. New hope in therapy of haemonchoses is monepantel, drug belonging to aminoacetonitrile derivatives which have unique mechanism of action. This drug was launched more than 25 years after registration of the last drug from the group of anthelmintics. Despite the initial great success information about occurrence of resistance often appear in recent years. Current knowledge about the mechanisms of resistance development and the factors that influence them is as well as information about drug action at the molecular level still insufficient. To limit the development of...
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Identification of new potent inhibitors of selected mycobacterial enzyme
Komrsková, Jitka ; Novotná, Eva (advisor) ; Matoušková, Petra (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Jitka Komrsková Supervisor: Mgr. Eva Novotná, Ph.D. Title of Diploma Thesis: Identification of new potent inhibitors of selected mycobacterial enzyme Mycobacterium tuberculosis remains one of the deadly pathogens, which are threat for people around the world. The combination of antituberculotic drugs is effective but the treatment is prolonged and sometimes it is not successful because of multiresistant forms of tuberculosis and also co-infection with HIV, that are the problems in last a few years. Therefore, it is necessity to find a new drug against tuberculosis, which will be effective against resistant forms of mycobacterium and can be used for HIV therapy. Enzyme isocitratelyase performs a potentially drug target against Mycobacterium tuberculosis. This enzyme plays a key role of glyoxylate pathway, where catalyzes the conversion of isocitrate to succinate and glyoxylate. This enzyme is necessary for mycobacterial survive during acute phase of the infection. The aim of this work is to determine that the activity of isocitratelyase is inhibited by S-benzylisothiosemicarbazones and flavonoids and so they could be new potentially antituberculotic drugs. Activity of this enzyme was...
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Influence of TNF-α on hENaC subunits expression
Martan, David ; Svobodová, Hana (advisor) ; Matoušková, Petra (referee)
University of Vienna Faculty of Life Sciences Department of Pharmacology and Toxicology Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: David Martan Supervisors: Prof. Dr. Rosa Lemmens-Gruber, PharmDr. Hana Bártíková, Ph.D. Title of the diploma thesis: Influence of TNF-α on hENaC subunits expression The human amiloride-sensitive epithelial sodium channel (hENaC) is a type of ion channel which has the ability to control salt and water homeostasis. Therefore it is one of the main driving forces for the reabsorption of water through the alveolar epithelium. A dysfunction of this channel, respectively of this control mechanism, leads to a very severe disease - pulmonary edema and several other pathological conditions. Previous studies tested a drug called AP301, recently named solnatide. AP301 is a cyclic protein comprising the human tumour necrosis factor lectin-like domain sequence. This drug was recently developed as a potential treatment of pulmonary edema. The principle is that it activates hENaC by increasing the open probability. It was also shown that AP301 transiently increases the expression of hENaC subunits in mammalian cells. In this study we used the Western blot method to test the influence of tumour necrosis factor α...
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Role of disulphide bonds in hA2A subtype adenosine receptor
Zappe, Lukáš ; Matoušková, Petra (advisor) ; Bárta, Pavel (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Lukáš Zappe Supervisor: Ing. Petra Matoušková Ph.D., PD Dr. Anke C. Schiedel Title of diploma thesis: Role of disulphide bonds in hA2A subtype adenosine receptor The adenosine A2A receptor belongs to the G protein coupled receptor family (GPCR). GPCRs are the targets of almost 40% of the drugs on the market. GPCRs are characterized by seven transmembrane helices, which are linked by three extracellular and three intracellular loops (ECL and ICL). The structure of the receptor has been revealed by crystallography, hence we know that ECL1 and ECL2 are connected by several disulphide bonds. The ECL2 is believed to be involved in ligand binding and recognition. In order to understand the relevance of those disulphide bonds involved in this process, four adenosine A2A receptor mutants were generated by one-site direct mutagenesis, in which the cysteine residues were replaced with serine residues (C146S, C159S, C166S and C146S- C159S). These receptor mutants were expressed in the mammalian cell line, CHO K1(Chinese Hamster Ovary) and the receptor expression was tested with ELISA (Enzyme- linked immunosorbent assay). The determination of ligand binding has been carried out by radioligand...
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The pharmacokinetics of ivermectin in the feces of Ovis ammon
Lokvencová, Kateřina ; Raisová Stuchlíková, Lucie (advisor) ; Matoušková, Petra (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Kateřina Lokvencová Tutor: RNDr. Lucie Raisová Stuchlíková, Ph.D. Title of Thesis: The pharmacokinetics of ivermectin in the feces of Ovis ammon Keywords: Anthelmintics, ivermectin, sheep, pharmacokinetics, excretion Infection with internal parasites is one of the most common diseases in sheep worldwide and causes significant economic losses. The nematode (Haemonchus contortus) is among to the particularly problematic representatives. Anthelmintics are used to treat helmintoses and they are divided into the several classes. The class of macrocyclic lactones includes ivermectin (IVE), which is especially popular for wide range of efficacy and low toxicity. However, the study of IVE pharmacokinetics is difficult, because it depends on many factors. Considerable attention is directed to the elimination of IVE, because its residuals in dung can adversely affect the environment and thus promote the emergence of resistance. The aim of this study was study of the elimination of IVE in sheep, especially the study of excretion profile. IVE (dose 0.2 mg/kg of body weight) was subcutaneously administered to sheep, followed by sampling of faeces at specified intervals. Ultra-high performance...
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basic characterization of human enzymes DHRS7B and DHRS7C
Tučková, Tereza ; Zemanová, Lucie (advisor) ; Matoušková, Petra (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Tereza Tučková Supervisor: RNDr. Lucie Zemanová, Ph.D. Title: Basic characterization of human enzymes DHRS7B and DHRS7C Human enzymes of the short-chain dehydrogenase/reductase (SDR) superfamily play an important role in wide range of biochemical pathways. They are involved in metabolism of lipids, saccharides, amino acids, steroid hormones, retinoids, prostaglandins etc. Besides physiological processes, they take part in development of several serious diseases, e.g. hormone-dependent cancer, metabolic syndrome, diabetes mellitus. Moreover, SDR enzymes contribute to biotransformation of xenobiotics. Nevertheless, approximately 30 % of SDRs remain completely uncharacterized. Human dehydrogenase/reductase SDR family members 7B (DHRS7B) and 7C (DHRS7C) belong to poorly characterized members of the SDR superfamily. According to in silico predictions, both enzymes are membrane bound and involved in reductive reactions. The aim of this study was to determine their basic biochemical properties. The results show that both enzymes interact with the membrane of endoplasmic reticulum and face cytosol. The pilot screening of enzymatic activity was performed. Reducing activity was detected towards e.g....
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