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Hypoxia in aviation
Doležel, Jan ; Šplíchal, Miroslav (referee) ; Hammer, Jaromír (advisor)
This bachelor thesis focuses on hypoxia in general and commercial civil aviation. The goal of the thesis is to create a general overview of hypoxia in aviation and the dangers connected to it. The thesis includes chapters describing the physiological principles of the human body, the physical laws associated with hypoxia, and the on-board oxygen and pressurization of aircraft. At the end of the thesis the author made an analysis of two aviation accidents caused by hypoxia.
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Synthesis of NIR Reductive Probes to Monitor Hypoxia During Fungal Infection
Kárníková, Tereza ; Baszczyňski, Ondřej (advisor) ; Míšek, Jiří (referee)
Invasive fungal infections represent a significant problem, resulting in approximately 1.5 million deaths worldwide annually. Among the most common invasive fungal infections are aspergillosis and candidiasis. Both opportunistic infections have a high mortality rate (50% and 27%, respectively). The diagnosis of these infections is often complex, leading to delayed detection and an increased risk of complications. Recently, near-infrared (NIR) hypoxia probes have been investigated for the diagnosis and monitoring of fungal infections. These probes enable non-invasive measurement of tissue oxygen concentration and can contribute to early diagnosis of fungal infections. Hypoxia can also be a relevant target for the delivery of antifungal agents. For this reason, a series of hypoxia-selective probes has been developed. These probes contain N-methyl-2-nitroimidazole and a fluorophore that absorbs in the near-infrared spectrum. We anticipate that probes will function as follows: the reducible breakdown of N- methyl-2-nitroimidazole in a hypoxic environment will activate the probe, leading to the release of the fluorophore, which absorbs in the near-infrared spectrum. Confocal microscopy will be used to observe whether the fluorophore is selectively released in the hypoxic environment or at the site of...
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Hif1a role in cardiovascular function and heart disease
Matějková, Kateřina ; Pavlínková, Gabriela (advisor) ; Holzerová, Kristýna (referee)
Hypoxia inducible factor 1 alpha (HIF1A) is a transcriptional factor, which plays a central role in the maintenance of homeostasis under hypoxic conditions. It regulates a wide variety of genes encoding proteins that influence metabolism, extracellular matrix composition, oxidoreductase activity or angiogenesis in response to reduced oxygen levels. When HIF1A protein function is impaired, the organism is unable respond appropriately to hypoxia. Altered HIF1A regulation can result in severe tissue damage and eventually lead to death. The heart, as an organ with a huge oxygen consumption, is susceptible to various pathologies caused by hypoxic stress. The role of HIF1A in the heart is rather ambiguous and remains to be elucidated. It plays a role in cardioprotective mechanisms but also promotes the development of inflammation and apoptosis. This thesis aims to clarify the role of HIF1A in maintaining physiological functions of the heart during adaptation to hypoxic conditions using a mouse model with heterozygous Hif1a+/- deletion. Experiments involving molecular and cell biology methods performed on left ventricular tissue were preceded by bioinformatic analysis of data obtained by RNA sequencing of isolated cardiomyocytes. RNA sequencing data were analyzed using the R scripting language (packages...
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Perinatal hypoxia: mechanisms and etiology
Laštůvka, Zdeněk ; Riljak, Vladimír (advisor) ; Cendelín, Jan (referee) ; Vízek, Martin (referee)
Perinatal asphyxia is a condition resulting from hypoxic-ischemic injury in utero or during birth and causing perinatal morbidity and mortality. Up until now, numerous models of neonatal hypoxia-ischemia were created and presented simulating brain damage patterns and motor deficits. Rice-Vannucci model is a leading representative of animal rodent models of hypoxic injury. It uses unilateral ligation of the common carotid artery in combination with exposure to hypoxic environment. Seven-day-old mouse pups underwent unilateral ligation of the common carotid artery in combination with exposure to 8 % oxygen hypoxic air (Rice-Vannucci model modification). Experimental groups with isolated carotid artery ligation or only exposure to hypoxia were created, too. To assess the spontaneous behavior changes of mice we used an automated system for the continuous tracking of small rodent behavior (LABORAS ™). On postnatal day 60, the spontaneous behavior of mice was analyzed in various behavioral domains. The observed areas for histological analysis were the cerebral cortex, CA1 and CA3 regions of the hippocampus, hilus, and the dorsal and ventral blades of the dentate gyrus. Induced hypoxia and ischemia together generated substantial behavioral and morphological changes which led to significant differences in...
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The detection of hypoxic markers in head and neck tumours
Šťovíčková, Eliška ; Šmahelová, Jana (advisor) ; Rösel, Daniel (referee)
Head and neck cancers (HNSCC) are heterogeneous group of tumours. Risk factors are mainly smoking and alcohol consumption. Some of these tumours are associated with human papillomavirus (HPV) infection, which is a significant positive prognostic factor. These tumours differ from HPV-negative tumours in clinicopathological characteristics, tumour microenvironment and response to treatment. Hypoxia is commonly found in tumors including HNSCC and is a significant prognostic and predictive factor. Elucidating the degree of hypoxia in relation to HPV infection could partly explain the differences in prognosis of these patients and allow more appropriate choice of therapy. Aspartate-β-hydroxylase is also a significant negative prognostic factor in a number of tumours, but its role in HNSCC has not yet been investigated. I focused on the detection of hypoxic markers and aspartate-β-hydroxylase expression in samples from HNSCC patients at the mRNA level by quantitative PCR and at the protein level by multispectral immunohistochemistry. The expression levels of these markers were compared in tumors stratified according to viral etiology and other characteristics such as smoking, localization or tumor stage. HPV infection had the highest impact on the expression of these markers, but the results cannot point to a...
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Hypoxia in aviation
Doležel, Jan ; Šplíchal, Miroslav (referee) ; Hammer, Jaromír (advisor)
This bachelor thesis focuses on hypoxia in general and commercial civil aviation. The goal of the thesis is to create a general overview of hypoxia in aviation and the dangers connected to it. The thesis includes chapters describing the physiological principles of the human body, the physical laws associated with hypoxia, and the on-board oxygen and pressurization of aircraft. At the end of the thesis the author made an analysis of two aviation accidents caused by hypoxia.
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Differences in histone acetylation in normoxia and hypoxia
Čepek, Pavel ; Poljaková, Jitka (advisor) ; Eckschlager, Tomáš (referee)
Histones and their N and C terminal tails undergo different covalent modifications that regulate gene transcription. Among these histone modifications are methylation, ubiquitinilation, SUMOylation, ADP- ribosylation, phosphorylation, proline izomerization, deimination and acetylation. Histone acetylation is regulated by histonacetyltransferases (HATs) and histondeacetylases (HDACs). The balance between acetylation/deacetylation influences chromatin condensation and thus regulates gene transcription. Acetylation balance is disrupted in many human cancers and this fact can contribute to the development of malignant diseases. Histondeacetylase inhibitors (HDACi) can restore this acetylation imbalance. One of these HDACi is valproic acid (VPA) which has been used in treatment of epilepsy for decades. VPA shows antitumour effect in many studies. Decreased expression of n-myc oncoprotein, inhibition of tumour growth and angiogenesis are one of these anticancer effects observed in neuroblastoma cell lines after treatment with VPA. Despite the fact that exact mechanism of antitumour effect of VPA remains unclear, one of the most important mechanisms is hyperacetylation of histone H3 and H4. It is shown in this work that VPA increases acetylation of histones H3 and H4 in human neuroblastoma cell lines...
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Mitochondrial production of reactive oxygen species and its role in physiological regulations
Holzerová, Eliška ; Mráček, Tomáš (advisor) ; Kalous, Martin (referee)
The production of mitochondrial reactive oxygen species and the resulting oxidative stress is an important phenomenon driving long-lasting research and intense discussions. Knowledge of exact mechanisms of reactive oxygen species production and pathways leading to their formation could help us to directly affect their production, a task with potential terapeutic implications. The molecular nature of the production of reactive oxygen species by some enzymes has already been well documented, but others still remain controversial and current theories are obviously far from the truth. Much more interesting is the question of physiological importace of this production. The reactive oxygen species were considered harmful factors clearly distorting the integrity of the organism for a long time. However, recent research suggest that their existence can also be beneficial and effective. Evidently they can serve as a signaling molecules in several metabolic and regulatory pathways occurring in the organism. This bachelor thesis offers insight into the current state of knowledge. It focuses on the most detailed description of the reactive oxygen species production by mitochondrial respiratory chain enzymes. Furthermore, it deals with some signaling cascades, where involvement of mitochondrially generated...
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Target genes and regulation of hypoxia inducible factors HIF1a a HIF2a
Blahová, Tereza ; Žurmanová, Jitka (advisor) ; Alánová, Petra (referee)
Oxygen supply is necessary for today's form of life on Earth. Molecular oxygen is a terminal electron acceptor in mitochondrial respiratory chain and enables the efficient production of ATP by oxidative phosphorylation. The lack of availability of oxygen decreases energy production and can endanger the processes maintaining homeostasis. Therefore the compensatory mechanisms were developed by which cells respond to hypoxia. The master regulator of cellular responses is the hypoxia inducible transcription factor, HIF. In general HIF-1 isoform supports glucose availability and glycolysis; also attenuates energy-consuming processes and thus reduces energy loss. HIF-2 isoform stimulates antioxidant mechanisms to reduce the amount of reactive oxygen species which could cause cellular damage. At the same time, both of isoforms contribute to increasing the supply of oxygen by activating erythropoiesis and angiogenesis in the affected area. HIFs provide these changes either directly, by using their target genes, or by interactions with other transcription factors and signaling pathways.
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