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Determination of selected biomarkers of nephrotoxicity in urine and plasma.
Pražáková, Aneta ; Maixnerová, Jana (advisor) ; Bárta, Pavel (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Aneta Pražáková Supervisor: RNDr. Jana Maixnerová, Ph.D. Title of diploma thesis: Determination of selected biomarkers of nephrotoxicity in urine and Plasma The discovery and development of novel biomarkers, that can be used for diagnosis of kidney damage earlier and more accurately, are needed for the effective prediction of drug-induced nephrotoxicity. Mechanisms of drug-induced nephrotoxicity include changes in glomerular hemodynamics, tubular cell cytotoxicity, inflammation, crystalline nephropathy, etc. Detection at initial stage of damage using sensitive and specific biomarkers belongs between one of the most important strategies in the treatment of acute kidney injury and renal failure. Although some these biomarkers do not show specificity and sensitivity, several promising biomarker candidates have been established recently to evaluate nephrotoxicity, e.g. selected KIM-1, cystatin C and NGAL. The advantages of these biomarkers compared to traditionally used biomarkers are higher sensitivity, specificity, just mentioned early diagnosis and non-invasiveness (the possibility of determination levels of the biomarkers from blood or urine). The aim of this diploma thesis was to determine...
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Study of cytotoxicity of newly prepared bronchodilators in vitro
Havelková, Michaela ; Smutná, Lucie (advisor) ; Bárta, Pavel (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Michaela Havelková Supervisor: PharmDr. Lucie Hyršová, PhD. Title of diploma thesis: Study of cytotoxicity of newly prepared bronchodilators in vitro This diploma thesis is focused on the determination the influence of developmental bronchodilatory active substances on viability of model tumor cell lines of human liver cells HepG2 and human lung cells HCC827. These potential drugs are theoretically suitable for the treatment of asthma bronchiale and COPD. The tested compounds (VN014a, VN015a, VN045b, VN122c) were derived from structure of the quinazoline alkaloids vasicine and vasicinone, which are substances contained in the Justicia adhatoda plant. The plant originated in India is widely used in traditional Ayurvedic medicine besides others to treat respiratory problems. The combination of both alkaloids showed significant bronchodilation activity. Cytotoxic activity of compounds was tested using colorimetric method by measuring cell metabolic activity based on reduction of tetrazolium compound. The IC50 value was determined for each studied compound on both used cell lines to assess the influence on cell viability. Overall, the tested developmental bronchodilators proved cytotoxic effect...
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Study of transport of protein molecules across cell membranes
Hornová, Aneta ; Smutná, Lucie (advisor) ; Bárta, Pavel (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Aneta Hornová Supervisor: PharmDr. Lucie Hyršová, Ph.D. Title of diploma thesis: Study of transport of protein molecules across cell membranes Kidney transporters are found mainly in the proximal tubules, they participate in the secretion and reabsorption of endogenous and exogenous substances. Plenty of kidney transporters have been identified, however this diploma thesis is focused on megalin. Specifically, we dealed with determination of transport of peptides via this renal transporter in HK-2 and JEG-3 cell lines. Megalin is a glycoprotein whose main function is tubular reabsorption of albumin filtered in glomerules and other high molecular weight substances. Another endogenous substrates of megalin are e.g. transcoblamine - vitamin B12, insulin or light chains of immunoglobulins. It is also able to transport some drugs like aminoglycoside and polypeptide antibiotics. Within this work, we investigated the influence of reduced expression of megalin on the transport of albumin and anti-VEGFR2 aptamer. Reduction of expression was achieved by transfection of cells with siRNA against the LRP2 gene. Lower expression of LRP2 led to reduction of transport of albumin and anti-VEGFR2 aptamer into...
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In vitro saturation study of gallium-67 and zirconium-89 labelled monoclonal antibody ramucirumab on SKOV-3 cell line
Holodňáková, Nikola ; Bárta, Pavel (advisor) ; Smutná, Lucie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Student: Nikola Holodňáková Supervisor: Mgr. Pavel Bárta, Ph.D. Name of the work: In vitro saturation study of gallium-67 and zirconium-89 labelled monoclonal antibody ramucirumab on SKOV-3 cell line. Targeted biological treatment becomes more and more important with the development of a new therapy in oncology. It stimulates immune system to eliminate cancer cells. Significant progress has been made since the introduction of monoclonal antibodies. They represent one of the newest possibility used in diagnosis and treatment of tumours. The ability of the monoclonal antibody ramucirumab is to recognize and bind specifically to tumour cell antigens such as the VEGF type 2 receptor (VEGFR-2) and thus to supress angiogenic process. Anti-angiogenic ramucirumab inhibits this receptor via blocking of VEGF binding sites, which prevents the growth of tumours. It is possible to increase antitumor effect of monoclonal antibodies by their combination with other molecules like radionuclides, toxins and cytostatics when forming the so called conjugates. Prepared immunoconjugates serve as diagnostic and therapeutic tools also in Nuclear Medicine. The aim of the experimental work in was the preparation of...
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The level of digital competencies in the area Safety for students of secondary schools
Bárta, Pavel ; Jeřábek, Tomáš (advisor) ; Rambousek, Vladimír (referee)
This thesis researches and maps the development of the level of digital competencies in the area Safety during the four-year studies of students and corresponding years of multi-year grammar schools who complete their secondary school leaving examination. The introductory part of the thesis defines the corresponding competencies and definitions of terms that are directly related to the problematics, especially: literacy (digital, information), competencies (digital), etc. From these competencies are specified those that are directly related to Safety. This is followed by an analysis and mapping of national and international researches of the level and development of pupils' digital competencies. The research part of this thesis includes concept, realizationd and evaluation of data of research survey. The goal of research survey is determination of level of given competencies of pupils and the impact of education on their develompent. Based on the results of the research survey, factors are identified that have a direct impact on the development of these competencies in examined secondary school students. In order to extend the applicability of the results, data are collected at schools that teach courses with a diametrically different focus. The output data of research survey includes results of...
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The determination of fatty acid levels in the tissues of healthy, suddenly deceased persons and polymorbid patients
Novotná, Monika ; Kuchařová, Monika (advisor) ; Bárta, Pavel (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Candidate: Monika Novotná Supervisor of Diploma Thesis: Mgr. Monika Kuchařová, Ph.D. Title of Diploma Thesis: The determination of fatty acid levels in the tissues of healthy, suddenly deceased persons and polymorbid patients The aim of the thesis was to determine the levels of 14 fatty acids in tissues of suddenly deceased, otherwise healthy individuals and in the group of polymorbid, chronic patients. It was a comparison of fatty acid levels in seven tissues of the human body: subendocardial left ventricular tissue, liver parenchyma tissue, kidney cortex, adrenal tissue, skeletal muscle, abdominal subcutaneous adipose tissue, and brain tissue. Each group included 10 deceased patients. The theoretical part incudes fatty acids as the main component of lipids. It deals mainly with the group of polyunsaturated fatty acids and their relation to pathologies in the human body. Gas chromatography, thanks to which we analyzed the fatty acid spectrum, is also described. The experimental part consists of the basic characteristics of the research groups, the description of the workflow and the results. Statistically processed data are divided into categories by individual fatty acids and other monitored...
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Study of cytotoxicity of newly prepared bronchodilators in vitro
Havelková, Michaela ; Hyršová, Lucie (advisor) ; Bárta, Pavel (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Michaela Havelková Supervisor: PharmDr. Lucie Hyršová, PhD. Title of diploma thesis: Study of cytotoxicity of newly prepared bronchodilators in vitro This diploma thesis is focused on the determination the influence of developmental bronchodilatory active substances on viability of model tumor cell lines of human liver cells HepG2 and human lung cells HCC827. These potential drugs are theoretically suitable for the treatment of asthma bronchiale and COPD. The tested compounds (VN014a, VN015a, VN045b, VN122c) were derived from structure of the quinazoline alkaloids vasicine and vasicinone, which are substances contained in the Justicia adhatoda plant. The plant originated in India is widely used in traditional Ayurvedic medicine besides others to treat respiratory problems. The combination of both alkaloids showed significant bronchodilation activity. Cytotoxic activity of compounds was tested using colorimetric method by measuring cell metabolic activity based on reduction of tetrazolium compound. The IC50 value was determined for each studied compound on both used cell lines to assess the influence on cell viability. Overall, the tested developmental bronchodilators proved cytotoxic effect...
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Determination of selected biomarkers of nephrotoxicity in urine and plasma.
Pražáková, Aneta ; Maixnerová, Jana (advisor) ; Bárta, Pavel (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Aneta Pražáková Supervisor: RNDr. Jana Maixnerová, Ph.D. Title of diploma thesis: Determination of selected biomarkers of nephrotoxicity in urine and Plasma The discovery and development of novel biomarkers, that can be used for diagnosis of kidney damage earlier and more accurately, are needed for the effective prediction of drug-induced nephrotoxicity. Mechanisms of drug-induced nephrotoxicity include changes in glomerular hemodynamics, tubular cell cytotoxicity, inflammation, crystalline nephropathy, etc. Detection at initial stage of damage using sensitive and specific biomarkers belongs between one of the most important strategies in the treatment of acute kidney injury and renal failure. Although some these biomarkers do not show specificity and sensitivity, several promising biomarker candidates have been established recently to evaluate nephrotoxicity, e.g. selected KIM-1, cystatin C and NGAL. The advantages of these biomarkers compared to traditionally used biomarkers are higher sensitivity, specificity, just mentioned early diagnosis and non-invasiveness (the possibility of determination levels of the biomarkers from blood or urine). The aim of this diploma thesis was to determine...
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The preparation and the following in vitro saturation study of the radiopharmaceutical 99mTc-DTPA-ramucirumab on PC-3 cell line
Sabolová, Klaudia ; Bárta, Pavel (advisor) ; Janoušek, Jiří (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Student: Klaudia Sabolová Supervisor: Mgr. Pavel Bárta, Ph.D. Title of diploma thesis: The preparation and the following in vitro saturation study of the radiopharmaceutical 99m Tc-DTPA-ramucirumab on PC-3 cell line In cancer treatment, immunology is given prominence, which compared with chemotherapy and radiotherapy has a lower risk of side effects on healthy tissues. Immunotherapy includes application of monoclonal antibodies aimed at some tumour antigens using either non conjugated monoclonal antibodies or conjugated ones with an appropriate effector element, such as radionuclide. Angiogenesis plays the important role in pathogenesis of tumour diseases. Angiogenic process is regulated mostly by the interactions among vascular growth factors (VEGFs) and VEGF receptors (VEGFR). The main regulator of angiogenesis is VEGF-A. The blocking of the interaction among VEGF-A and its receptors VEGFR-1 and VEGFR-2 inhibits angiogenesis, and so does the growth of tumours. Ramucirumab is the monoclonal antibody with antiangiogenic effect, which blocks this interaction by its binding to the extracellular VEGFR-2 domain with high affinity. The presented study is focused on ramucirumab...
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