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Pharmacological Influence on Atherogenesis in Experimental Animal Models of Atherosclerosis
Rathouská, Jana ; Nachtigal, Petr (advisor) ; Vrablík, Michal (referee) ; Vohnout, Branislav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Mgr. Jana Rathouská Supervisor: Doc. PharmDr. Petr Nachtigal, Ph.D. Title of Doctoral Thesis: Pharmacological influence on atherogenesis in experimental animal models of atherosclerosis Atherosclerosis is a slow inflammatory process in arterial walls which is, as a part of cardiovascular diseases, the main source of morbidity and mortality in developed countries. However, searching for the possibilities of atherosclerosis treatment requires detailed knowledge of pathogenesis of the disease itself. The use of mouse models offers one of the possibilities of studying the pathogenesis of atherosclerosis, which enables a number of interventions that would not be acceptable in human medicine. By using the high content lipid diet, we are able to induce the changes of lipid spectrum in mice. Moreover, if a targeted genetic manipulation is used, one can reach considerably advanced plaques in a relatively short time period. It is also possible to interfere in the process of atherogenesis in mouse models by using some hypolipidemic drugs, for example from the statin group that were represented in our studies by atorvastatin. By observing the vessel's reactivity to atorvastatin dosage,...
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Evaluation of the pharmacological properties of new potential drugs for Alzheimer's disease
Čechová, Pavlína ; Šorf, Aleš (advisor) ; Urbánková Rathouská, Jana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Social and Clinical Pharmacy Student: Pavlína Čechová Supervisor: PharmDr. Aleš Šorf, Ph.D. Consultant: mjr. PharmDr. Vendula Hepnarová, Ph.D. Title of diploma thesis: Assessment of pharmacological properties of new potencial drugs for Alzheimer's disease treatment Alzheimer's disease is a neurodegenerative disease with a progressive and irreversible course. The cause of AD is still not exactly known. There are currently four drugs available that have been approved by the State Institute for Drug Control. Three of them act as cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and the fourth one as a N-methyl-D-aspartate (NMDA) receptor antagonist (memantine). Unfortunately, these drugs do not affect the course of the disease and provide only temporary symptomatic relief. An important area of current research is MTDLs (Multi-Target Directed Ligands), which act on multiple target structures related to the pathophysiology of the disease. These agents represent a promising therapeutic strategy. The aim of the study was to measure the ability to inhibit human acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) of 58 new potential MTDLs derived from biphenyl and benzhydryl using Ellman's method, as well as...
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Laboratory diagnosis of microRNA in different diagnostic groups
Hrachovcová, Eliška ; Urbánková Rathouská, Jana (advisor) ; Tripská, Katarína (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Student: Bc. Eliška Hrachovcová Supervisor: PharmDr. Jana Rathouská, Ph.D. Consultant: doc. RNDr. Pavlína Kušnierová, Ph.D. Title of diploma thesis: Laboratory diagnostics of microRNAs in different diagnostic groups Background: Identification of potential miRNA targets for differential diagnosis of patients with atherosclerosis and dementia. Comparison of miRNA expression and uptake in serum samples with cerebrospinal fluid samples. Selection of appropriate miRNAs for differential diagnosis in patients with atherosclerosis and dementia. Furthermore, the selection of miRNA targets with the most significant fold-change and also the lowest p-value for subsequent validation studiues. Methods: To identify potential miRNAs, the received samples were centrifuged, aliquoted and stored at - 80C. miRNAs were isolated using the iCatcher Circulating cfRNA 1000 kit and the CatchGene isolator. Reverse transcription and amplification with detection were then performed. Data were processed in Excel and then statistically processed in GenEx using Mann-Whitney test. Results: The results were evaluated for 2 groups of patients: group A (samples of patients with Parkinson's disease and dementia) and group B (with...
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Effect of glipizide on the expression and function of endoglin and related biomarkers of endothelial dysfunction in diabetes mellitus type II
Vochozková, Iva ; Tripská, Katarína (advisor) ; Urbánková Rathouská, Jana (referee)
8 ABSTRACT Charles University, Faculty of Pharmacy in Hradec Kralové Department of Biological and Medical Sciences Title of Diploma Thesis: Effect of glipizide on the expression and function of endoglin and related biomarkers of endothelial dysfunction in type II diabetes mellitus Author: Iva Vochozková Supervisor of Diploma Thesis: PharmDr. Katarína Tripská, Ph.D. Aim: The aim of this thesis was to determine how glipizide affects the expression and function of endoglin, its transcription factors and related biomarkers of endothelial dysfunction, soluble endoglin levels and monocyte adhesion to human diabetic coronary artery endothelial cells. Methods: In this thesis we worked with human diabetic coronary artery endothelial cells. These were premedicated with glipizide at various times and concentrations. We measured protein expression of endoglin and biomarkers of endothelial dysfunction using flow cytometry. We also measured monocyte adhesion to endothelial cells using flow cytometry. We detected soluble endoglin levels by ELISA and measured mRNA expression of endoglin, its transcription factors and markers of inflammation by PCR. Results: We demonstrated that premedication with 200µM concentration of glipizide led to a decrease in endoglin protein expression after 24 and 48 hours. The protein expression...
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Covid-19: vaccination, undergoing illness and post-Covid syndrome
Fořtová, Karolína ; Urbánková Rathouská, Jana (advisor) ; Jílek, Petr (referee)
Aim: The aim of this thesis is to firstly introduce the reader to the theoretical part of Covid-19 disease and in the experimental part to investigate the vaccination rate of the respondents, the prevalence of the disease, the symptoms of the disease, the prevalence of post-Covid syndrome, or the involvement of specific organ systems in post-Covid syndrome. Furthermore, the aim was to investigate the influence of individual factors (age, sex, active smoking, BMI, comorbidities, vaccination, virus variant) on the course of the disease and post- Covid syndrome. Methods: The questionnaire study included 752 respondents of both genders and of all ages. Data collection was conducted within the Czech Republic between June 2023 and January 2024. MS Excel was used for statistical evaluation and Power Bl was used for data visualization. Results: 84.18% of the respondents were vaccinated. 72.61% of the respondents underwent Covid-19 and most of them became ill in the vaccine-free state (52.20%). The most common symptoms were severe fatigue (62.09%), increased temperature/fever (62.27%), muscle and joint pain (56.96%) and headache (56.04%). Post-Covid syndrome was/is suffered by 62 respondents (11.36%) and the most affected organ systems were lungs (46.77%), nervous system (32.26%), senses (30.65%), muscles...
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Pharmacological modulation of endoglin expression in the liver in an animal model of nonalcoholic steatohepatitis
Moeini, Sepideh ; Nachtigal, Petr (advisor) ; Urbánková Rathouská, Jana (referee)
Játra hrají ústřední roli v lidské fyziologii a jejich zranitelnost vůči metabolickým poruchám, jako je nealkoholická steatohepatitida (NASH), podtrhuje potřebu účinných terapeutických zásahů. Tato práce zkoumá potenciál M1043, monoklonální protilátky cílené na endoglin (ENG), při zmírňování poškození jater spojeného s progresí NASH. ENG, je koreceptor pro transformující růstový faktor (TGF)-β, který se podílí na různých patologických procesech, včetně fibrózy a angiogeneze. U NASH jsou pozorovány zvýšené hladiny solubilního ENG (sENG) a transmembránového ENG, což naznačuje jeho zapojení do progrese onemocnění. Kromě toho hrají intracelulární adhezní molekula-1 (ICAM-1) a vaskulární adhezní molekula-1 (VCAM-1) klíčovou roli v zánětu a endotelové dysfunkci, což jsou klíčové rysy NASH. V této studii byli myší samci rozděleni do kontrolní skupiny, skupiny (vysokotukové diety) CDAA+rat IgG a skupiny CDAA+M1043, přičemž poslední dvě skupiny byly krmeny CDAA- HFD vyvolávající změny NASH. Myši byly po dobu čtyř týdnů léčeny přípravkem M1043 a vzorky jater byly analyzovány na expresi proteinů ENG, ICAM-1 a VCAM-1. Výsledky ukázaly, že CDAA-HFD vyvolala poškození jater, což se projevilo zvýšením jaterních enzymů a zvýšenou expresí ENG, ICAM-1 a VCAM-1. Důležité je, že podávání M1043 významně zabránila...
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Ovarian carcinomas - the influence of the Rho kinase family on cell migration
Barešová, Veronika ; Urbánková Rathouská, Jana (advisor) ; Fikrová, Petra (referee)
Author: Veronika Barešová Title: Ovarian carcinomas - the influence of Rho family kinases on cell migration Diploma thesis Charles University, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Ovarian carcinomas are the deadliest group of gynecological malignancies. This is due to a high rate of metastasis and acquired drug resistance. Metastasis is characterized by a phenotypic change of cells from epithelial to mesenchymal, resulting in the loss of cell-cell and cell-extracellular matrix contacts and subsequent cell movement. This process is called epithelial-mesenchymal transition and has been shown to also play a role in cell resistance to cisplatin. The movement of individual cells is mediated by the Rho GTPase family and can be divided into mesenchymal and amoeboid types. The amoeboid type is characterized by the Rho/ROCK signaling pathway, while mesenchymal movement is mediated by the Rac/Cdc42 pathways. In my thesis, we investigated the differences in expression of selected proteins in both signaling pathways in ovarian carcinoma cells. Initially, we focused on comparing the A2780 and A2780cis cell lines, which are resistant to cisplatin. We monitored markers of amoeboid movement, RhoA and phosphorylated myosin, and markers of mesenchymal movement, Wave-2,...
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Evaluation of muscle strength and endurance of lactating women
Melicharová, Nikola ; Kovařík, Miroslav (advisor) ; Rathouská, Jana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Student: Nikola Melicharová Supervisor of master thesis: PharmDr. Miroslav Kovařík, Ph.D. Title of master thesis: Evaluation of muscle strength and endurance of lactating women This work aims to evaluate the change in the parameters of muscle strength and endurance of the upper and lower limbs in women during breastfeeding. Compare these measured values between the right and left limbs. Another goal is to test the connection between dynamometric parameters and the intake of micronutrients in food supplements. 10 lactating women aged 29-39 took part in the measurement. The women were examined four times. The first examination L1 took place on average 29 ± 5 days postpartum, the second L2 93 ± 29, the third L3 179 ± 15, and the last measurement was L4 274 ± 3 days postpartum. A digital pinch/grip analyzer and digital myometer were used to measure muscle strength and endurance of the upper and lower limbs. We used the BCM - Body Composition Monitor device to measure fat-free mass. Weight was measured for women using a body analysis scale from Tanita. When evaluating the measured results, we discovered a statistically significant difference between the values of the maximum strength of the left hand...
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