|
Synthesis of Steroidal Modulators for Bile Acid Receptors
Kašpar, Miroslav ; Kudová, Eva (advisor) ; Drašar, Pavel (referee) ; Kvasnica, Miroslav (referee)
The Thesis comprises three major projects. The first project is concerned with the creation of a pregnane compound library that can be used to explore the structure-activity relationship with the TGR5 and FXR receptors. The project draws structural inspiration from Sato's work and involves the compound characterization, digitization, computational methods, and biochemical analysis of a historic group collection of steroids. The second project focuses on the synthesis of modified bile acids using Grignard, Wittig, cross-coupling, or cycloaddition reactions. The synthesized compounds were tested for their TGR5 and FXR activity, leading to the discovery of (E)-7-ethylidene-3α-hydroxy-5β- cholan-24-oic acid, which is known to be the only bile acid with TGR5/FXR dual action. In the last part of the Thesis, 16 oxidizing agents were tested on 5 substrates for their selectivity in oxidizing axial or equatorial hydroxyl groups.
|
|
Safety of magnetic resonance imaging for the examinated patient
Staněk, Jakub ; Kašpar, Miroslav (advisor) ; Daníčková, Kateřina (referee)
Magnetic resonance imaging is a modern radiological imaging method. It allows to diagnose pathological changes in the human body without any need to disrupt of its structure. The main advantage of NMR is that it does not use any harmful ionizing radiation. Because NMR is a relatively young technology, any harmful effects have not found yet on the human organism. But from the physical point of view the potential risks arise consequence of biological structures interaction and tissues with the static magnetic field, gradient magnetic field and high frequency electromagnetic field. Due to the development methods it leads to intensification of these fields inside the device. Master's thesis involved research of biophysical effects and potential risks of static magnetic field, gradient magnetic field and high frequency electromagnetic field used in magnetic resonance. Result interactions of these fields with investigated patients' bodies biological structures leads to heat induction inside their bodies. Temperature of the investigated parts of patient body is monitored. Ascertained data are evaluated by the Wilcoxon non-parametric test with simulation Monte Carlo.
|
|
Analýza variability tvorby xylému po obvodu kmene smrku ztepilého v rámci vegetačního období
Kašpar, Miroslav
Kašpar, M.: Analysis of the variability of xylene formation along the circumference of the spruce tree (Picea abies L.) during the vegetation period. Bachelor thesis. Mendel University in Brno. 2016 The bachelor thesis is focused on the analysis of the variability of xylum formation along the circumference of spruce stem in the vegetation period. Research on xylogenetic variability was carried out on the research area in Rájci-Němčice. The main task is to compare the variability of xylan production in the same old trees during the 2016 growing season. Sampling was performed at weekly intervals from 31 March to 10 November using trephor. From the collected microwells, continuous preparations were then made. The obtained data were compared with literary sources focused on similar issues.
|
|
Analýza procesů xylogeneze a floemogeneze u jedinců smrku ztepilého (Picea abies (L.) Karst.) ve dvou vegetačních obdobích
Kašpar, Miroslav
KAŠPAR M.: Analysis of xylogenis and floemogenesis of Norway Spruce (Picea abies (L.) Karst.) during two growing seasons. The thesis deals is focused on finding and evaluating the creation of wood and phloem of Norway spruce during the vegetation period 2015 and 2016 at the reasearch area Rájec-Němčice. Six representative trees were selected on the surface and samples were taken periodically. Permanent microscopic slides were prepared and examined for the samples obtained. The activity of cambium, the different phases of differentiation of wood and bast elements and the rate of growth using Gompertz function were evaluated. The data collected for each year were compared with each other and compared with the results of other authors. Growth variations were noted within two growing seasons. Statistically significant differences were seen in the number of kambia cells, whether in dormancy or during the active period. There were statistically significant differences at the time of termination of the individual cell phases. The different values of the years also resulted from the results of the Gompertz function. Generally speaking, in 2016 the growth dynamics was more intense and the number of cells generated was higher than in the previous year.
|
|
Synthesis of ligands for farnesoid X receptor
Kašpar, Miroslav ; Chodounská, Hana (advisor) ; Kasal, Alexander (referee)
Farnesoid X receptor is mostly expressed in liver cells and its activation may be used for the treatment of cirrhosis causing diseases, especially biliary cirrhosis and nonalcoholic steatosis. These two latter diseases are most common in developed countries and, as of date, no effective treatments are available. Therefore, the aim of this project is the design and synthesis of novel bile acid analogues with subsequent biological evaluation towards farnesoid X receptor. Thus, a series of new compounds were designed using computational modeling studies and chemical synthesis was done to develop structure-activity relationships. Chemical structure analysis and purity was confirmed by conventional analytical methods. Finally, synthetic compounds were profiled against farnesoid X receptor in collaboration with the Pharmaceutical faculty of Charles University in Hradec Králové. Keywords: farnesoid X receptor, FXR, bile acids
|
|
Preconcentration of hydride forming elements in quartz trap in connection with ICP-MS
Kašpar, Miroslav ; Matoušek, Tomáš (advisor) ; Rychlovský, Petr (referee)
Charles Uviversity in Prague Faculty of Science Department of Analytical Chemistry Student: Miroslav Kašpar Supervisor: RNDr. Tomáš Matoušek, Ph.D. Name of Thesis: Preconcentration of hydride forming elements in quartz trap with ICP-MS detection The aim of this thesis are pilot experiments employing quartz trap (QT) for preconcentration of hydride forming elements and their subsequent detection by inductively coupled plasma mass spectrometry (HG-QT-ICP-MS). Arsenic and antimony were chosen as model analytes. Preconcentration efficiency on quartz surface was studied in a trap, which was integrated into an interface between spray chamber and plasma torch. We have identified a critical loss of analyte during transportation, instability of the plasma due to sudden change of gas composition, poor repeatability and very quick release of Sb from the trap resulting in difficult quantification of Sb signal. Despite the efforts to resolve these experimental problems, so far we were unable to achieve improvements in analytical parameters compared to standard analytical methods. Keywords: Preconcentration, quartz trap, mass spectrometry with inductively coupled plasma, hydride generation, arsenic, antimony
|
|
Safety of magnetic resonance imaging for the examinated patient
Staněk, Jakub ; Kašpar, Miroslav (advisor) ; Daníčková, Kateřina (referee)
Magnetic resonance imaging is a modern radiological imaging method. It allows to diagnose pathological changes in the human body without any need to disrupt of its structure. The main advantage of NMR is that it does not use any harmful ionizing radiation. Because NMR is a relatively young technology, any harmful effects have not found yet on the human organism. But from the physical point of view the potential risks arise consequence of biological structures interaction and tissues with the static magnetic field, gradient magnetic field and high frequency electromagnetic field. Due to the development methods it leads to intensification of these fields inside the device. Master's thesis involved research of biophysical effects and potential risks of static magnetic field, gradient magnetic field and high frequency electromagnetic field used in magnetic resonance. Result interactions of these fields with investigated patients' bodies biological structures leads to heat induction inside their bodies. Temperature of the investigated parts of patient body is monitored. Ascertained data are evaluated by the Wilcoxon non-parametric test with simulation Monte Carlo.
|
| |
| |
| |