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Vascular reactivity of carotid and renal arteries to natriuretic peptides: alterations due to diabetes
Čáňová, Kristýna ; Szotáková, Barbora (advisor) ; Boušová, Iva (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Universitat de Valencia, Facultat de Farmacia Departament de Fisiologia Candidate: Kristýna Čáňová Supervisor: Doc. Ing. Barbora Szotáková, Ph.D. Supervisor specialist: Dr. José M. Centeno Guil Title of diploma thesis: Vasclular reactivity of carotid and renal arteries to natriuretic peptides: alterations due to diabetes Diabetes is associated with increased prevalence of hypertension, cardiovascular and renal disease. Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) play an important task in cardiovascular pathophysiology and are considered to have cardioprotective and renoprotective effect in patients with diabetes. The aim of this work was to study the response of rabbit carotid and renal arteries to atrial and brain natriuretic peptides and whether this response is altered in diabetes. Six weeks after diabetes induction by alloxan, the renal and carotid arteries were isolated from the body and each segment was tested for isometric tension in an organ bath. All segments were preconcentrated with phenylephrine and then with the cumulative addition of doses of ANP and BNP (10-12 -10-7 M) to the organ bath, the concentration-response curves to ANP and BNP were measured. In all...
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Analysis of Growth-inhibitory Mechanism of Flubendazole in Malignant Melanoma Cells
Čáňová, Kristýna ; Rudolf, Emil (advisor) ; Slaninová, Iva (referee) ; Mandys, Václav (referee)
Analysis of growth-inhibitory mechanisms of flubendazole in malignant melanoma cells Malignant skin melanoma is at its advanced stage highly aggressive and chemoresistant to almost all currently available therapies. Moderns efforts are thus aimed to identify new targets in melanoma cells or to take advantage of novel indications of already approved drugs - a process called drug repurposing. This work was focused on evaluation of cell growth inhibitory properties of one such drug - flubendazole (FLU) - a widely used anthelmintic compound belonging to benzimidazole family. This drug specifically interacts with β-tubulin, which results in disruption of microtubule structure and function in the exposed cells. Several members of the benzimidazole family (including FLU) have already shown the growth inhibitory potential in tumor cells derived from breast, colon, blood and nervous system malignancies. Still, the specific activity of FLU in malignant melanoma has not been tested to the date. Cytotoxicity of FLU was tested in three malignant melanoma cell lines representing diverse melanoma molecular types (A-375, BOWES and RPMI-7951) during up to 72 hours using WST-1 and x-CELLigence assays. Based on achieved IC50 from individual cell lines, the 1 µM FLU concentration was selected for further testing. While...
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Vascular reactivity of carotid and renal arteries to natriuretic peptides: alterations due to diabetes
Čáňová, Kristýna ; Szotáková, Barbora (advisor) ; Boušová, Iva (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Universitat de Valencia, Facultat de Farmacia Departament de Fisiologia Candidate: Kristýna Čáňová Supervisor: Doc. Ing. Barbora Szotáková, Ph.D. Supervisor specialist: Dr. José M. Centeno Guil Title of diploma thesis: Vasclular reactivity of carotid and renal arteries to natriuretic peptides: alterations due to diabetes Diabetes is associated with increased prevalence of hypertension, cardiovascular and renal disease. Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) play an important task in cardiovascular pathophysiology and are considered to have cardioprotective and renoprotective effect in patients with diabetes. The aim of this work was to study the response of rabbit carotid and renal arteries to atrial and brain natriuretic peptides and whether this response is altered in diabetes. Six weeks after diabetes induction by alloxan, the renal and carotid arteries were isolated from the body and each segment was tested for isometric tension in an organ bath. All segments were preconcentrated with phenylephrine and then with the cumulative addition of doses of ANP and BNP (10-12 -10-7 M) to the organ bath, the concentration-response curves to ANP and BNP were measured. In all...
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Effect of flubendazole on proliferation of colorectal carcinoma cell lines in vitro
Čáňová, Kristýna ; Szotáková, Barbora (advisor) ; Jirkovská, Anna (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Kristýna Čáňová Supervisor: Doc. Ing. Barbora Szotáková, Ph.D. Supervisor specialist: RNDr. Věra Králová, Ph.D. Title of rigorous thesis: Effect of flubendazole on proliferation of colorectal carcinoma cell lines in vitro Flubendazole is widely used anthelmintic drug belonging to benzimidazole group. The molecular mechanism of action of flubendazole is based on specific binding to tubulin, which results in disruption of microtubule structure and function and in the interference with the microtubule-mediated transport of secretory vesicles in absorptive tissues of helminths. The microtubule-disrupting properties of benzimidazole derivatives raised recently interest in these compounds as possible anti-cancer agents. Because of available studies and pharmacological statements, it is supposed considerable concentrations of flubendazole in intestinal cells after p.o. administration could be reached, we performed this study to investigate the antiproliferative potential of flubendazole in a panel of intestinal cancer cell lines. The colorectal carcinoma cell lines SW480, SW620 and one cell line NCM460 isolated from normal colon mucosa were treated with different concentrations of flubendazole...
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