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Mild therapeutical hypothermia and oxidative stress after cardiac arrest
Krüger, Andreas ; Ošťádal, Petr (advisor) ; Vízek, Martin (referee) ; Rokyta, Richard (referee)
Successfull cardiopulmonary resuscitation is an essential life-saving tool; nevertheless, general ischemia during cardiac arrest may trigger different pathways that could turn even into a fatal damage; this condition is called post-cardiac arrest syndrome. It has been repeatedly shown that oxidative stress (OS) plays one of the key roles in the development of ischemia-reperfusion injury. However, current evidence on the possible participation of OS in the pathogenesis of post-cardiac arrest syndrome is insufficient. We tested following hypotheses: (i) ischaemia-reperfusion injury after cardiac arrest is accompanied by OS and (ii) mild therapeutical hypothermia decreases OS cardiac arrest. In the experimental part of our work we studied the effects of hypothermia and normothermia on hemodynamic parameters, markers of organ damage and on the OS burden in porcine model of cardiac arrest. Furthermore, we compared the effects of hypothermia with ischaemic postconditioning and nitric oxide administration in the porcine model of extracorporeal cardiopulmonary resuscitation. We found protective effects of hypothermia on all major endpoints including OS in comparison with normothermia; moreover, hypothermia improved also selected variables compared to ischemic postconditioning and nitric oxide. In the...
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Possibilities of genetic testing in patients with pheochromocytoma and paraganglioma.
Turková, Hana ; Zelinka, Tomáš (advisor) ; Malík, Jan (referee) ; Fryšák, Zdeněk (referee)
1. Abstract Pheochromocytoma/ paraganglioma (FEO/PGL) may be developed on the basis of an inherited genetic mutation of different genes. They are associated with a high risk of developing of secondary hypertension, organ damage and metastatic disease that can be fatal. The aim was to focus on the possibility of genetic testing in patients with FEO/PGL, especially in patients with malignant tumors. The issue FEO/PGL, however, concerns not only the examination and assessment of risks arising therefrom, as well as other therapies and monitoring, including appropriate recommendations for clinical practice. We demonstrated a 20% incidence of cardiovascular (CV) complications before determining the final diagnosis of FEO/PGL, mainly arrhythmic, followed by complications of myocardial ischemia and accentuate atherosclerosis. Elevated levels of vitamin C and decreased levels of malondialdehyde (MDA) following the successful removal of the tumor demonstrated reduction of oxidative stress postoperatively. We found that early postoperative testing of levels of plasma metanephrines to confirm the success of surgical removal of FEO/PGL is already possible, since there was no significant correlation between plasma levels of metanephrines and postoperative examination interval. Distribution of frequency of metastatic...
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Changes of membrane-bound and soluble proteins of frontal rat brain cortex induced by morphine
Ujčíková, Hana
The aim of this Ph.D. thesis was to analyze the morphine-induced changes of frontal brain cortex protein composition in rats exposed to increasing doses of morphine (10-50 mg/kg) for prolonged period of time (10 days). The first part of this work was oriented to the analysis of the phenomenon of hypersensitization/superactivation of adenylyl cyclase (AC), which is regarded as one of the crucial molecular mechanisms causing drastic pathological consequences of drug addiction. The increase of AC activity represents a "compensatory" response and is functionally related to the desensitization of G protein response to prolonged morphine exposure of target cells. The clear desensitization of µ-OR- and δ-OR-stimulated G protein response by morphine was demonstrated in our laboratory by analysis of the dose-response curves of DAMGO and DADLE-stimulated, high-affinity [35 S] GTPγS binding in plasma membranes isolated from frontal brain cortex of rats exposed to morphine according to the same protocol as that used in my Ph.D. thesis (10-50 mg/kg, 10 days). The κ-OR-stimulated [35 S] GTPγS binding was unchanged. It has been determined the amount of all AC isoforms (AC I-IX) in plasma membranes (PM) isolated from control and morphine-treated rats which were sacrificed 24 hours since the last dose of morphine....
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Mechanisms of potential toxic effects of bisphenol A on the endocrine system
Zachardová, Lenka ; Novotný, Jiří (advisor) ; Rupert, Marian (referee)
Bisphenol A (BPA) has already been used in the chemical industry for several decades. Since that time, a huge amount of in vitro and in vivo studies have been accumulated summarizing the molecular mechanisms of BPA causing disruption in endocrine homeostasis in all kinds of biological models. It enters the body from external environment; however, the main source of penetration is through consumption of food and liquids that are in contact with materials containing the mentioned xenoestrogen. The hydroxyl group within BPA phenol ring enables binding to transmembrane G- protein-coupled estrogen receptors and a number of nuclear receptors affecting hormonal system and resulting in alterations in signalling pathways. BPA induces oxidative stress and interferes with regulation factors functions at gene, cell and tissue level. Disruptive effects are associated with developmental, reproductive, cardiovascular, immune and neurobiological disorders. This thesis is aiming to sum up existing findings about the molecular mechanisms of BPA toxicity in the endocrine system mainly using Mus musculus model. Keywords: BPA, endocrine system, nuclear receptors, GPER, oxidative stress.
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The impact of mutant huntingtin on oxidative stress in primary fibroblasts isolated from a new Huntington's disease knock in porcine model
Sekáč, Dávid ; Ellederová, Zdeňka (advisor) ; Hanzlíková, Hana (referee)
Huntington's chorea is a dominantly inherited disease caused by trinucleotide (Cytosine-Adenine -Guanine) expansion in a gene coding huntingtin protein. Carriers of these mutation show symptoms associated with motor impairment, a cognitive and psychiatric disturbance, which is called Huntington's disease (HD). The major sign of HD is striatal atrophy in the middle age of life. Since it is known that huntingtin protein participates in a lot of cellular processes, such as transcriptional regulation and metabolism, these processes change by its mutation. One of the features observed in HD pathogenesis is the presence of oxidative stress. The aim of the work was to monitor the molecular changes preceding the HD manifestation in the knock-in minipig model. As a material for monitoring molecular changes leading to this condition, primary fibroblasts were used. Whereas, the oxidative stress arises from an imbalance between oxidants and antioxidants, level of reactive species and lipid peroxidation together with expression of antioxidant response associated genes was measured. At the same time, expression of metabolic and DNA repair related genes was monitored. Although the differences in oxidative stress level or the expression of antioxidative response genes were not detected, the changes in the...
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Oxidative stress level as a marker of stress memory in selected genotypes of potato Solanum tuberosum ssp. tuberosum and ssp. andigena
Lotová, Gabriela ; Mašková, Petra (advisor) ; Lhotáková, Zuzana (referee)
Plants are exposed to the stress of the environment throughout their entire live. They therefore had to develop sophisticated mechanisms to avoid or tolerate stress. In some plants, repeated exposure to stress increases tolerance, which is known as stress memory. The aim of this study is to assess stress memory in terms of oxidative stress level. Content of malondialdehyde (MDA), reactive oxygen species (ROS) and the electrolyte leakage were chosen as markers of oxidative stress. Fresh weight, plant height and water content were also evaluated. The level of oxidative stress was assessed in several genotypes of Solanum tuberosum subspecies, Andigena and Tuberosum. In vitro culture did not work well for the evaluation of stress memory, ex vitro partially did. The content of MDA in 66B was significantly lower than in cv. Lada (Tuberosum) in root (in vitro) and shoot (ex vitro) in control groups as well as during water shortage. Treatment of acclimation-inducing cold before the stress-inducing cold had a variable effect on growth and electrolyte leakage according to the culture conditions. In vitro, the effect on electrolyte leakage in roots of cv. Lada was positive, in leaves of 66B (Andigena) it was negative. In ex vitro, a positive effect was found on electrolyte leakage in 66B leaves, but at the...
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Changes in anatomy of coniferous needles in response to anthropogenic pollution
Štěpánová, Kristýna ; Albrechtová, Jana (advisor) ; Votrubová, Olga (referee)
The anatomical structure of conifer needles is affected by external enviromental conditions. From abiotic factors, apart of irradiation, main determining factors are drought and extreme temperatures belonging to factors of climate change. Anthropogenic pollution has a significant position among the external abiotic factors that cause changes in the structure of needles. At present, the main polluting compounds are tropospheric ozone, SO2, NOx and PM. Due to the effect of atmospheric pollutants, the proportion of individual tissues in the needle changes, so does the proportion of intercellular spaces and the internal structure of cellular organelles, especially chloroplasts. Mesophyll cells show signs of degradation, especially around the substomatal cavity. There appears a visible damage on the needle surface - chloroses and necroses. The process of senescence speeds up during the activity of stress enviromental factors, such as anthropogenic pollution. The main objective of the present Thesis is to gather knowledge about changes of conifer needle structure, caused by anthropogenic pollution, especially ozone, SO2 and NOx, in combination with climate change factors - drought and extreme temperatures. The review is focused on modifications on various anatomic hierarchical levels, from visible...
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Biochemical characterization of tomato plants infected with fungal pathogens
Oušková, Marie ; Hýsková, Veronika (advisor) ; Kubíčková, Božena (referee)
Fungal pathogens including Verticillium longisporum which causes verticillium wilt are among the serious diseases of crops that easily spread worldwide. One of the ways to prevent fungal infection is to use fungal biocontrol agents applied as a seed coating. This control agent, the non-pathogenic oomycete Pythium oligandrum, enters the soil together with the seed and acts symbiotically in the plant's root system. On the one hand, it stimulates the plant's defence mechanism by secreting elicitors, and on the other hand, by providing tryptamine, it stimulates growth and increases the plant's fitness with auxin. In this work we studied the effect of seed treatment of Solanum lycopersicum L. cv. Micro-Tom with three different isolates of the genus Pythium (including the commercially used isolate M1 and two yet unused isolates X42 and X48) on the activities of antioxidant and NADP(H)-dependent enzymes in the leaves of plants infected with fungal pathogen V. longisporum. Two weeks after pathogen inoculation, no significant difference was found in the studied enzymes except for increased glucose-6phosphate dehydrogenase and NADP-malate dehydrogenase (oxaloacetate decarboxylation) activity in plants treated with X42 isolate and increased shikimate dehydrogenase activity and antioxidant capacity in plants...
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The role of oxidative stress in etiology of Alzheimer's disease
Šuláková, Anna ; Novotný, Jiří (advisor) ; Randáková, Alena (referee)
Oxidative stress is the result of an imbalance between the formation of reactive oxygen species and the ability of the body to detoxify these free radicals. As a result of this disbalance, harmful substances, especially peroxides and free radicals, accumulate in the body, resulting in damage of proteins, lipids and DNA leading to total cell destruction and necrosis. For this reason, oxidative stress contributes to the development of many serious diseases including atherosclerosis, many types of cancer, heart failure or neurodegenerative diseases such as Parkinson's disease, multiple sclerosis and Alzheimer's disease. Alzheimer's disease is a chronic neurodegenerative disease whose risk increases with age. It is an incurable disease affecting an ever increasing number of patient. Early AD symptoms include disorientation, loss of short-term memory, mood swings and problems with expression of thoughts. The causes of AD have not yet been fully clarified but there are speculations about importance of the role of tau-proteins and -amyloid plaques that form in AD progression. Oxidative stress can also play an important role, and may participate in the development of this disease. This work focuses mainly on the role of oxidative stress in pathophysiology and progression of AD. Key words:...
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Role of carbohydrate metabolism in defence against oxidative stress induced by arsenic
Kofroňová, Monika ; Lipavská, Helena (advisor) ; Száková, Jiřina (referee) ; Kovalíková, Zuzana (referee)
Heavy metal contamination significantly reduces crop yields, causing serious problems in agriculture and having a major impact on human health if these contaminants enter the food chain. Understanding the mechanisms of plant responses could help to increase their resistance to heavy metals as well as their potential use in phytoremediation. Carbohydrates play an important role in plant growth and development as well as in defense reactions. This work summarizes the results of four publications focused on the effects of arsenic and thorium on antioxidant mechanisms in tobacco plants and horseradish root crops. Attention is paid, among other things, to the dynamics of sugar contents, which are potentially important molecules involved in the fight against oxidative stress. The first publication summarizes arsenic effects on plant physiological parameters, focusing on arsenic tolerance-enhancing mechanisms as well as summarizing the ability of plants to cope with arsenic-induced oxidative and nitrosative stress. Emphasis was placed on, among other things, a topic that was unjustly neglected in previous publications - i.e. carbohydrate metabolism. Further work was already experimental and dealt with the study of arsenic as a trigger of oxidative stress in the root culture of horseradish and...
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