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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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Atherosclerosis, statins and fibrates treatment benefits
Vechtsalis, Sotiris ; Nachtigal, Petr (advisor) ; Rathouská, Jana (referee)
The goal of this Thesis is to analyze atherosclerosis and its relationship to Cardiovascular Disease, as well as the measures taken to oppose the development of an atherosclerotic lesion and its following complications. Aspects such as Diagnosis, Pathogenesis and alteration of endothelium, as well as complications and clinical manifestations associated to them will be stated. Pharmacological agents opposing the development of this disease will be analyzed, with agents opposing dyslipidemia - one of the major risk factors of developing atherosclerosis - being the center of this paper's focus. In the next chapters, new insight on preventing and treating atherosclerosis using statins and fibrates, analysis of individual statins benefits and toxicities as well as possibilities of their combination benefits and risks will be brought to light.
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Specialist public awareness of the tuberculosis vaccination
Ročková, Marcela ; Konečná, Klára (advisor) ; Rathouská, Jana (referee)
Discussions about vaccination against tuberculosis with BCG vaccine have been led for many years. The BCG vaccination belongs among the most controversial vaccinations at all, because the vaccine isn't very effective and its' application is also accompanied by a high incidence of complications. All these facts, with regard to the fact that the incidence of TBC in the Czech Republic is one of the lowest in Europe, have led to revaluation of the meaning about this vaccination and inicially it resulted in cancellation of revaccination for children of two and eleven years of age and afterwards in complete vaccination abolishment for children and newborns. The goal of this work was a finding, which attitudes towards vaccination against tuberculosis doctors advocate. I achieved this through the method using the questionnaire study on this topic. 489 respondents answered six simple questions focused on the issue of the BCG vaccination. Many results were surprising. 39 doctors didn't know, that the complete vaccination for children and newborns was abolished and 257 doctors disagreed with this decision. 296 doctors considered the declining incidence of tuberculosis as a reason, why the complete vaccination was cancelled. 476 doctors had a meaning, that it is necessary to continue with vaccination of...
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Western blot analysis of ICAM-1 and P-selectin protein expression in aorta of mice with high soluble endoglin levels.
Uhlířová, Barbora ; Rathouská, Jana (advisor) ; Konečná, Klára (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Author: Barbora Uhlířová Supervisor: PharmDr. Jana Rathouská, Ph.D. Title of Diploma Thesis: Western blot analysis of ICAM-1 and P-selectin protein expression in aorta of mice with high soluble endoglin levels Background: Detection and subsequent evaluation of the expression of adhesion molecules ICAM-1 and P-selectin in aorta of two groups of transgenic mice differing by levels of human serum endoglin that were fed a special high fat and cholesterol diet. Methods: We used six-month-old female transgenic mice capable of expressing of human endoglin, which was able to be determined after cleavage in the circulation (Soluble endoglin - sENG) by the use of an ELISA assay. Therefore, we were able to divide the mice into two groups - an experimental group (high levels of sENG) and a control group (very low sENG levels). For 3 months, both groups were given a special high fat and cholesterol diet. Biochemical analysis (total cholesterol levels), and Western blot analysis of molecules ICAM-1 and P-selectin in the homogenate of mouse aortas were carried out. Results: Biochemical analysis of total cholesterol in the blood revealed statistically no significant differences in the measured values...
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Changes of endothelial expression of endoglin during atherogenesis
Zajícová, Šárka ; Nachtigal, Petr (advisor) ; Rathouská, Jana (referee)
Šárka Zajícová Changes of endothelial expression of endoglin during atherogenesis Diploma thesis Charles University in Prague, Faculty of Pharmacy in Hradec Králové Specialist in Laboratory Methods Background: We observed the expression of endoglin in arteria brachiocephalica in the apoE−/− /LDLr−/− deficient mice after feeding them with the low carbohydrate, high protein diet. Methods: We used the female apoE−/− /LDLr−/− deficient mice, which we divided into two groups after 6 animals. One of these groups were fed by AIN-93G diet (control group) and the second one by low carbohydrate, high protein diet. Stereological and immunohistochemical analysis was performed in tissue sections of arteria brachiocephalica by means of ImmPRESSTM method with DAB detection. Results: Biochemical analysis showed a significant increase levels of total cholesterol after feeding with low carbohydrate, high protein diet. Immunohistochemical analysis, we demonstrated endoglin expression in endothleial cells, mostly covering atherosclerotic plaques in both groups apoE−/− /LDLr−/− deficient mice. Stereological analysis in mice fed with low carbohydrate, high protein diet showed weak endoglin expression when compared to group on chow diet. Conclusions: Mice fed with low carbohydrate, high protein diet showed increased...
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Thyroid gland and pregnancy
Christophorou, Neofyta ; Nachtigal, Petr (advisor) ; Rathouská, Jana (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of of Biological and Medical Sciences Candidate Neofyta Christophorou Consultant Assoc. Prof. PharmDr. Petr. Nachtigal, Ph.D. Title of Thesis Thyroid gland and pregnancy Thyroid physiology involves a range of biochemical processes in the human body, and is characterized by a respectively wide range of thyroid disorders. Thyroid hormones are produced by the thyroid gland, with through the sequestration of iodine as basic element. This process is regulated both intrathyroidally through enzymatic processes and extrathyroidally through the Hypothalamus-Pituitary-Thyroid-Axis (HPTA). The bioavailability of thyroid hormones and their biological activities in peripheral tissues are regulated by special enzymes called deiodinases. Pregnancy is a state of unique physiological adaptations for both the mother and the fetus that are governed by the maternal-fetal interaction through the placenta. Thyroid hormones are vital in maternal physiology throughout gestation as well as regulators of fetal development. The increased needs in thyroid hormone production during pregnancy pose a stress on thyroid and raise the needs for iodine intake. The inability of the thyroid gland to adapt to this state is marked by increased incidence of...
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Evaluation of DNA damage and repair in various pathological stages
Tenorová, Dana ; Němečková, Ivana (advisor) ; Rathouská, Jana (referee)
author: Dana Tenorová title: Evaluation of DNA damage and repair in various pathological stages Diploma thesis Charles University in Prague, Faculty of Pharmacy in Hradec Králové field of study: Specialist in Laboratory Methods Chronic obstructive pulmonary disease (COPD) is a serious disease characterized by airflow obstruction that is caused by chronic bronchitis or pulmonary emphysema. As a result of these changes occurs in the organism the oxidative stress with subsequent damage to various biomolecules, which can be measured using a wide range of methods. The primary aim of our study was the evaluation of DNA damage in patients with COPD and comparison to the damage found in the healthy control group. We used electrophoretic method comet assay and we analyzed various types of DNA damage - DNA single strand breaks (SSB), oxidized purines and oxidized pirimidines. We used two forms of this method, i.e. a classical alkaline comet assay and its enzymatic modification, where we worked with endonuclease III (Endo III) and formamidopyrimidin-DNA-glycosylase-III (FPG). Our results showed the significantly higher levels of DNA damage in patients with COPD compared with the control group, especially when using the modified comet assay. In conclusion, we have examined the possibility of comet assay...
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Chemokines of human epithelial cells.
Eisenhamerová, Hana ; Jílek, Petr (advisor) ; Rathouská, Jana (referee)
Organism is protected by many ways. Phagocytosis belongs aminy a nonspecific defensive function. Important part of phagocytosis is called chemotaxis. It is influenced by chemokines. We know 52 different chemokines and 20 their receptors. Chemokines are divided into four groups. They differ structurally and functionally. Chemokines play a role in activation of leukocytes in inflammation, in maturitationof cells and homeostasis. Chemokines are found in various diseases.
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Evaluation of usage nutritional supplements in the pregnancy.
Rathouská, Jana ; Vejsová, Marcela (referee) ; Hronek, Miloslav (advisor)
The assessment of dietary supplements income during pregnancy Nutritional needs are increased during pregnancy. Changes of hormonal levels induce alterations of physical and psychical status. Blood volume is increased and maternal metabolism is adjusted to ensure nutrition necessary for the right development of fetus. Requirements for energy, vitamins and minerals intake are increased. Requirements for micronutrients are rather specific, often the intake from food is not sufficient and supply by means of dietary supplements is necessary. Convenient structure of nutrition promotes physiological growth and development of fetus, reduces the risk of congenital malformations, prematurity labour, low birth weight and also protects mother's health. Objectives: To determine the intake of vitamin-mineral supplements by pregnant women, type of supplement (single-micronutrient or multivitamin-mineral supplementation), micronutrients most ingested, intake of supplements before- and during pregnancy and mother's supplementation in relation to the newborn anthropometrics measurements. Methods: Mothers completed a particular questionnaire about their supplementation. To record the whole course of pregnancy, the questionnaire was given to mothers every visit of prenatal care clinic, thus gestational ages < 20, 21-29, 30-36...
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