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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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Cyclodextrin derivatives containing covalently bound volatile substances and studies of their release
Palágyi, Attila ; Jindřich, Jindřich (advisor) ; Smrček, Stanislav (referee)
The main aim of the work was to prepare a series of β-cyclodextrin derivatives containing covalently bound volatile compounds via an imine bond. The used volatile compounds were cinnamaldehyde, cyclamen aldehyde, lilal, benzaldehyde, anisaldehyde, vanillin, hexanal, heptanal, citral and 5-methylfurfural. Subsequently, the rate of the release of the active compound, as a function of the environment, was studied by 1 H NMR spectroscopy and static headspace-gas chromatography. Key words: cyclodextrin, aldehyde, imine, kinetics, controlled release
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Influence of different way of strength training on body composition, postural stability and muscle and explosive strength in Men's Physique and Street Workout Athletes
Regál, Ondřej ; Gryc, Tomáš (advisor) ; Šťastný, Petr (referee)
Title: Influence of different way of strength training on body composition, postural stability and muscle and explosive strength in Men's Physique and Street Workout Athletes Objectives: The aim of the thesis was to find out the level and the difference between the parameters of body constitution, postural stability and muscular and explosive force of upper and lower limbs with groups of Men's Physique and Street Workout athletes. Methods: The research sample was represented by two groups (Men's Physique competitors and Street Workout athletes). We assessed chosen parameters of body constitution by Tanita MC-980MA, postural stability by RS Footscan, explosive force (Kistler) and muscular force (Cybex Humac Norm and Takei A5401). Assessed parameters of body constitution were percentage of body fat and fatless matter. In the tests of postural stability, we assessed total travel way of the center of pressure (TTW) in chosen stands (open/closed eyes and one- leg left/right). When testing explosive force, overall produced maximal force and height of the leap were assessed. Muscular force of upper limbs was evaluated by produced force in kg and muscular force of lower limbs was assessed with the help of muscular force moment in concentric muscle activity with angular velocity 60ř·s-1. Result: We found...
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Geminal bis(phosphinates)
David, Tomáš ; Lukeš, Ivan (advisor) ; Grüner, Bohumír (referee) ; Růžička, Aleš (referee)
Slow complexation is one of the major limitations of current macrocyclic chela- tors utilized in nuclear medicine for complexation of metal radionuclides. This property can be improved by ligand design. Among metal radioisotopes, the copper ones (e.g. 60Cu, 61Cu, 62Cu, 64Cu and 67Cu) have become commonly available in recent years and cyclam-derived ligands are the most suitable ligands for Cu2+ complexation. To alter the complexation rate, bis(phosphinic acid) group is promising unit as it is able to complex metal ions in acidic solu- tions. However, geminal bis(phosphinates) represent poorly studied group of compounds and, thus, it is challenging to uncover their properties. Several simple amino-bis(phosphinates) were synthesized and its acid-base and coordi- nation properties were studied. Unlike structurally similar geminal bis(phosphonates), the title compounds showed negligible adsorption onto hydroxyapatite (commonly used model of bone tissue). The obtained knowledge dealing with geminal bis(phosphinates) was utilized in synthe- sis of two novel cyclam derivatives. The ligands (bearing either one geminal bis(phosphinate) or one geminal phosphino-phosphonate pendant arm) were synthesized by highly efficient procedure. The corresponding Cu2+ complexes are formed with very high rates and show...
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Selected ion flow tube mass spectrometry, SIFT-MS
Sovová, Kristýna
4 Abstract This thesis describes research that has been carried out during the years 2009-2013 as a part of my PhD project related to the method of selected ion flow tube mass spectrometry (SIFT- MS) and its application in interdisciplinary areas of research. SIFT-MS is a method that allows accurate quantification of trace gases and vapours presented in humid air with the focus on human breath; without any sample preparation and in real time. The thesis is divided into several parts. The first part reviews the history of mass spectrometry as a background for the quantitative analytical methods as PTR-MS and SIFT-MS. The second part discusses the detailed history of development of SIFT-MS, starting from principles of selected ion flow tube (SIFT) technique that has been used for study of ion- molecule reactions in the gas phase and forms the basis of SIFT-MS. The next part discusses volatile organic compounds of different biological origin: bacterial, plant and human breath metabolites that can be analyzed in real time using SIFT-MS. The main part "Results and Discussion" is divided into several subsections that serve as commentaries to the enclosed research papers published in peer reviewed journals. The first is a detailed step by step overview of the kinetics of ion molecule reactions which is the basis...
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Selected ion flow tube mass spectrometry, SIFT-MS
Sovová, Kristýna ; Španěl, Patrik (advisor) ; Glosík, Juraj (referee) ; Matejčík, Štefan (referee)
This thesis describes research that has been carried out during the years 2009-2013 as a part of my PhD project related to the method of selected ion flow tube mass spectrometry (SIFT-MS) and its application in interdisciplinary areas of research. SIFT-MS is a method that allows accurate quantification of trace gases and vapours presented in humid air with the focus on human breath; without any sample preparation and in real time. The thesis is divided into several parts. The first part reviews the history of mass spectrometry as a background for the quantitative analytical methods as PTR-MS and SIFT-MS. The second part discusses the detailed history of development of SIFT-MS, starting from principles of selected ion flow tube (SIFT) technique that has been used for study of ion-molecule reactions in the gas phase and forms the basis of SIFT-MS. The next part discusses volatile organic compounds of different biological origin: bacterial, plant and human breath metabolites that can be analyzed in real time using SIFT-MS. The main part "Results and Discussion" is divided into several subsections that serve as commentaries to the enclosed research papers published in peer reviewed journals. The first is a detailed step by step overview of the kinetics of ion molecule reactions which is the basis of...
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Modulation of HIV-1 Protease Activity
Pokorná, Jana ; Konvalinka, Jan (advisor) ; Šedo, Aleksi (referee) ; Ruml, Tomáš (referee)
HIV-1 protease plays a crucial role in the late state of the life cycle of HIV virus when it cleaves the viral polyprotein precursors into the structural and functional proteins. If it is effectively inhibited, HIV particles remain immature and noninfectious. The application of highly active antiretroviral therapy (HAART) including protease inhibitors can reduce plasma HIV-1 levels below the detection limit in adherent patients and thus dramatically change their life expectancy. The clinical utility of the first inhibitors was limited by severe side effects, low bioavailability, high pill burdens, and rapid development of viral resistance under the selection pressure of HIV antiretrovirals. To overcome these difficulties, second-generation inhibitors were developed. Despite an indisputable improvement they brought to antiretroviral therapy, the development of new highly active HIV-1 protease inhibitors with optimal pharmacokinetic properties, higher metabolic stability, little off-target activity, and particularly, more favorable resistance profiles is still of high importance. This thesis provides an overview of anti-HIV- drugs including development of substituted metallacarboranes, a new class of potent, unusual, nonpeptidic HIV protease inhibitors with therapeutic potential. Next, the impact of...
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Study of the cleavage kinetics of Gag polyprotein from HIV-1 virus by the viral proteinase
Krištofičová, Ivica ; Ingr, Marek (advisor) ; Martínek, Václav (referee)
Gag polyprotein is the precursor of HIV-1 structural proteins, required for correct assembly, budding and maturation of viral particle within HIV-1 life cycle. The process of maturation into an infectious virion is dependent on Gag and GagPol cleavage at nine predefined sites by HIV-1 proteinase. Its disruption is one of the main targets of HIV treatment. HIV-1, however, develops resistance to the proteinase inhibitors by creating mutations in both the proteinase and the substrate. The Gag processing by HIV-1 proteinase is a highly sequential process, that happens in specific order and rate. Previous biochemical studies determined the kinetic data of these processes using oligopeptides representing naturally occuring cleavage sites. This thesis describes the cleavage of the Gag polyprotein itself, which is the natural substrate of HIV-1 proteinase. For this purpose, the full-length Gag polyprotein was recombinantly prepared in bacterial expression system. The cleavage was carried out and its products were analyzed via SDS-PAGE and Western blotting. The substrate specificity of the wild-type and mutant HIV-1 proteinase with respect to the full-length wild-type Gag polyprotein was compared. Substantial differences were observed between the rates of individual steps of cleavage by the wild-type and mutant...
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Physics Simulation on GPU
Janošík, Ondřej ; Zemčík, Pavel (referee) ; Polok, Lukáš (advisor)
This thesis addresses the issue of rigid body simulation and possibilities of paralellization using GPU. It describes the basics necessary for implementation of basic physics engine for blocks and technologies which can be used for acceleration. In my thesis, I describe approach which allowed me to gradually accellerate physics simulation using OpenCL. Each significant change is described in its own section and includes measurement results with short summary.
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