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Study of the effect of myocardial fibrosis on elemental distribution in rat soft tissues using Laser Ablation ICP-MS
Machalová, Martina ; Zlámalová Gargošová, Helena (referee) ; Vašinová Galiová, Michaela (advisor)
The most common cause of death in the Czech Republic continue to be cardiovascular diseases. The field of heart failure therapy still keeps moving forward. Yet myocardial fibrosis is one of the consequences and causes of heart failure for which there exists no effective medical care. The solution would be predicting the advancement of fibrosis and a preventive therapy. Many medical methods are being developed now in this regard, and the element distribution in affected tissue could help them. That is the reason why this work centers on the research of the element distribution in rat hearts with an induced myocardial fibrosis. An influence of sample couloration on the analysis was observed during its course. Special attention was paid to the distribution of iron in the fibrotic tissue as well as to the comparisson of the images of myocardial fibrosis. It seems that the iron distribution specificly could be helpful in recognising a damaged myocardium.
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Changes in elemental distribution of rat liver tissue associated with myocardial fibrosis using LA-ICP-MS
Štrenclová, Eliška ; Zlámalová Gargošová, Helena (referee) ; Vašinová Galiová, Michaela (advisor)
Myocardial fibrosis is a pathological condition characterized by excessive accumulation of extracellular matrix in cardiac tissue, resulting in impaired cardiac function and potentially serious cardiovascular complications. However, recent studies suggest that myocardial fibrosis may affect not only cardiac tissue but also other organs such as the liver. The aim of this bachelor thesis was to investigate changes in the elemental distribution of liver tissue from healthy individuals by comparing the elemental distribution of liver tissue from individuals with myocardial fibrosis using the LA-ICP-MS method. When comparing the distribution maps of the control and experimental groups, changes were observed mainly in the distribution of iron isotopes; therefore, particular attention was later paid to it. The results of this research may contribute significantly to a better understanding of the relationship between myocardial fibrosis and liver tissue, and the knowledge gained may help to develop new diagnostic approaches.
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Applied pharmacokinetics in preclinical research
Královičová, Jana ; Šíma, Martin (advisor) ; Večeřa, Rostislav (referee) ; Kmoníčková, Eva (referee) ; Paluch, Zoltán (referee)
Title: Applied pharmacokinetics in preclinical research Author: Mgr. Jana Královičová Abstract: This thesis addresses the topic of development and practical utilization of rat models in preclinical pharmacokinetic studies. An analysis dealing with the impact of intra- and inter- individual variability on the results of animal comparative studies showed that cross-over design brings more accurate conclusions in these experiments than the often-used parallel setting. Results obtained on the basis of a parallel design significantly differed in our investigation (AUClast ranged from 9.62 to 44.62 mg/ml.min.g). Furthermore, in 4 cases out of 15 pair comparisons of individual parallel groups, the confidence interval did not include the 100% value. That means that in more than a quarter of studies it would be misjudged that the compared drug formulations have different pharmacokinetic properties, though they are in fact the same product. The practical use of cross-over design is demonstrated in pharmacokinetic studies comparing the absorption of various formulations with abiraterone and cinacalcet. In a fasted state, a new, innovated formulation with abiraterone was better absorbed than the reference (AUClast of a reference 30.3 mg/ml.min.g, innovated formulation 81.0 mg/ml.min.g). Thiscorresponds to anticipations...
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Study of the effect of myocardial fibrosis on elemental distribution in rat soft tissues using Laser Ablation ICP-MS
Machalová, Martina ; Zlámalová Gargošová, Helena (referee) ; Vašinová Galiová, Michaela (advisor)
The most common cause of death in the Czech Republic continue to be cardiovascular diseases. The field of heart failure therapy still keeps moving forward. Yet myocardial fibrosis is one of the consequences and causes of heart failure for which there exists no effective medical care. The solution would be predicting the advancement of fibrosis and a preventive therapy. Many medical methods are being developed now in this regard, and the element distribution in affected tissue could help them. That is the reason why this work centers on the research of the element distribution in rat hearts with an induced myocardial fibrosis. An influence of sample couloration on the analysis was observed during its course. Special attention was paid to the distribution of iron in the fibrotic tissue as well as to the comparisson of the images of myocardial fibrosis. It seems that the iron distribution specificly could be helpful in recognising a damaged myocardium.
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Effect of Wharton's jelly-derived mesenchymal stem cells secretome in the treatment of rat spinal cord injury
Jančová, Pavlína ; Chudíčková, Milada (advisor) ; Grobárová, Valéria (referee)
As previously shown, transplantation of Wharton's jelly-derived mesenchymal stem cells in the experimental model of spinal cord injury leads to the motor and sensory functions improvement, supports neuroregeneration, angiogenesis and provides immunomodulation. On the other hand, these cells have limited migration and survival capacity, and their therapeutic effect is mediated mostly by their secretome. Therefore, application of mesenchymal stem cells derived conditioned medium is studied as an alternative option for cell therapy. In this thesis, therapeutic effect of repeated intrathecal delivery of human Wharton's jelly-derived mesenchymal stem cells and their conditioned media in the treatment of spinal cord injury was compared. After induction of a balloon ischemic compression lesion, stem cells or conditioned media were administered weekly in three doses. Behavioral analyses were carried out up to nine weeks after spinal cord injury and revealed significant improvement of both treated groups compared to the untreated saline control. Application of stem cells and conditioned media also resulted in a higher amount of spared tissue and enhanced expression of genes related to neuroregeneration, although the size of glial scar was not reduced. Compared to application of stem cells, application of...
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Study of effects of prolonged administration of emtricitabine on expression of ABC efflux transporters in maternal and fetal organs
Havlová, Ivana ; Červený, Lukáš (advisor) ; Hofman, Jakub (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Ivana Havlová Supervisor: PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: Study of effects of prolonged administration of emtricitabine on expression of ABC efflux transporters in maternal and fetal organs The aim of this thesis was to evaluate the effect of chronic administration of antiretroviral substance emtricitabine (FTC) on expression of drug efflux ABC-binding cassette (ABC) transporters in the placenta, maternal and fetal organs (brain, liver, kidney, small intestine) of pregnant rats. We focused on two most important representatives of drug efflux ABC transporters, P-glycoprotein (MDR1) and Breast Cancer Resistance Protein (BCRP). Knowledge of FTC effects on gene expression of these transporters is crucial especially when using FTC in combination therapy, known as Highly Active Antiretroviral Therapy (HAART). Changes in MDR1/BCRP expression may lead to significantly altered pharmacokinetics of concomitantly administered drugs. First, bioavailability was analyzed. AUC of FTC (3,5 mg/kg) following i.m. administration was comparable to that one after i.v. administration allowing us to use i.m. application as a route of FTC administration to rats. Subsequently,...
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