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The role of energy metabolism in cardioprotection induced by the adaptation to chronic hypoxia
Kolář, David ; Žurmanová, Jitka (advisor) ; Adamcová, Michaela (referee) ; Bardová, Kristina (referee)
Cardiac energy metabolism is the one of the most complex system in the body. To sustain life, but also to respond quickly to any sudden changes (e.g. running, emotional stress), the heart has developed a unique ability and has become a metabolic "omnivore". At physiological conditions, long chain fatty acids (LCFAs) present the major energetic source for the adult myocardium. However, the cardiac energy metabolism may be compromised during pathophysiological states. One of the most dangerous is, undoubtedly, ischaemia-reperfusion injury with its acute form, myocardial infarction. However, the adaptation to chronic hypoxia has been known for decades for its cardioprotective effect against I/R. Changes of cardiac energy metabolism induced by the adaptation have not been fully explored and the system conceals still too many secrets. This thesis has aimed to determine how adaptation to chronic hypoxia affects the cardiac metabolism of the rat LVs in the following set-ups: 1. The effect of chronic normobaric hypoxia (CNH; 3 weeks, 5500m) during a brief I/R protocol in vitro on the protein kinase B/hexokinase (Akt/HK) pathway, including the expression and phosphorylation of Akt, the expression and localization of HK, the expression of mitochondrial creatine kinase (mtCKS), and the level of Bcl-2 family...
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Mitochondrial dysfunctions in depression
Javorská, Jana ; Stuchlík, Aleš (advisor) ; Kolář, David (referee)
Depression (major depressive disorder; MDD) is a common and chronic psychiatric disorder. MDD causes a significant reduction in the quality of life, reduces the ability to work, and thus causes a burden on disabled patients, healthcare, and all of society. The pathophysiological features of depression are often ambiguous, and therefore current treatment for depression is insufficient. Chronic stress plays an important role in the pathogenesis of depression. It causes dysregulation of the hypothalamic-pituitary-adrenal axis (HPA axis) controlling cortisol release, imbalance of neurotransmitters and neuromodulators, and imbalance between pro- inflammatory and anti-inflammatory cytokines. Another neurobiological sign of depression is a disruption of energy metabolism in the brain, for which mitochondria are responsible. In addition to ATP, mitochondria also form reactive oxygen species (ROS). ROS are in excessive amounts during chronic stress and disrupt cellular energy. Therefore, substances related to mitochondrial energy and antioxidant effects are currently being investigated. Ketamine, dizocilpine and phencyclidine are particularly effective in mitochondrial metabolism. However, the clinical use of these substances is complicated by their hallucinogenic and neurotoxic effects. Antioxidants help...
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Cable supported bridge
Kolář, David ; Koláček, Jan (referee) ; Nečas, Radim (advisor)
The topic of this bachelor thesis is design of a footbridge across a river. The final version, which has been chosen from three designs differentiating in their static behaviour of the structure, is a cable-stayed footbridge. The chosen option is designed as a parabolic monolithic prestressed deck suspended by cables anchored to two cone shaped pylons. The structure is situated perpendicularly to the riverbed and its total length is 57,465 m. Softwares, such as SCIA Egineer 20.0 and MS Excel, were used for the calculations of internal forces and modelling calculation models and its verification by hand. The design of the prestressing force, assessment of utility limit state and serviceability limit state were done by hand according to valid standards and regulations. Partially simplified bearing capacity assessment of the pylons was solved by IDEA StatiCa 9 software and some of the results were verified by hand as well. The thesis disregards stages of construction and prestress losses are estimated.
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The role of energy metabolism in cardioprotection induced by the adaptation to chronic hypoxia
Kolář, David
Cardiac energy metabolism is the one of the most complex system in the body. To sustain life, but also to respond quickly to any sudden changes (e.g. running, emotional stress), the heart has developed a unique ability and has become a metabolic "omnivore". At physiological conditions, long chain fatty acids (LCFAs) present the major energetic source for the adult myocardium. However, the cardiac energy metabolism may be compromised during pathophysiological states. One of the most dangerous is, undoubtedly, ischaemia-reperfusion injury with its acute form, myocardial infarction. However, the adaptation to chronic hypoxia has been known for decades for its cardioprotective effect against I/R. Changes of cardiac energy metabolism induced by the adaptation have not been fully explored and the system conceals still too many secrets. This thesis has aimed to determine how adaptation to chronic hypoxia affects the cardiac metabolism of the rat LVs in the following set-ups: 1. The effect of chronic normobaric hypoxia (CNH; 3 weeks, 5500m) during a brief I/R protocol in vitro on the protein kinase B/hexokinase (Akt/HK) pathway, including the expression and phosphorylation of Akt, the expression and localization of HK, the expression of mitochondrial creatine kinase (mtCKS), and the level of Bcl-2 family...
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Intracellular domain of glutamate ion channels and its role in the emergence of pathophysiological states
Sadílková, Lucie ; Balík, Aleš (advisor) ; Kolář, David (referee)
Glutamate mediates most of the excitatory neurotransmissions in the central nervous system of mammals. Its effect depends on the presence of glutamate receptors on postsynaptic neurons. NMDA receptors are class of the ionotropic glutamate receptors and are necessary for normal brain function such as synaptic plasticity, learning, memory and correct development of neu- rons. NMDA receptors are also involved in the pathophysiology of many neurodevelopmental and neuropsychiatric diseases. The aim of this work is to evaluate the current knowledge of the role of the intracellular part of NMDA receptors for their function, particularly with respect to the regulation of their localization at excitatory synapses. In addition, it also provides an over- view of the genetic changes found in this part of the receptor, their effect on the functional properties of the receptor and then also a possible link to specific disease.
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The role of energy metabolism in cardioprotection induced by the adaptation to chronic hypoxia
Kolář, David
Cardiac energy metabolism is the one of the most complex system in the body. To sustain life, but also to respond quickly to any sudden changes (e.g. running, emotional stress), the heart has developed a unique ability and has become a metabolic "omnivore". At physiological conditions, long chain fatty acids (LCFAs) present the major energetic source for the adult myocardium. However, the cardiac energy metabolism may be compromised during pathophysiological states. One of the most dangerous is, undoubtedly, ischaemia-reperfusion injury with its acute form, myocardial infarction. However, the adaptation to chronic hypoxia has been known for decades for its cardioprotective effect against I/R. Changes of cardiac energy metabolism induced by the adaptation have not been fully explored and the system conceals still too many secrets. This thesis has aimed to determine how adaptation to chronic hypoxia affects the cardiac metabolism of the rat LVs in the following set-ups: 1. The effect of chronic normobaric hypoxia (CNH; 3 weeks, 5500m) during a brief I/R protocol in vitro on the protein kinase B/hexokinase (Akt/HK) pathway, including the expression and phosphorylation of Akt, the expression and localization of HK, the expression of mitochondrial creatine kinase (mtCKS), and the level of Bcl-2 family...
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The role of energy metabolism in cardioprotection induced by the adaptation to chronic hypoxia
Kolář, David ; Žurmanová, Jitka (advisor) ; Adamcová, Michaela (referee) ; Bardová, Kristina (referee)
Cardiac energy metabolism is the one of the most complex system in the body. To sustain life, but also to respond quickly to any sudden changes (e.g. running, emotional stress), the heart has developed a unique ability and has become a metabolic "omnivore". At physiological conditions, long chain fatty acids (LCFAs) present the major energetic source for the adult myocardium. However, the cardiac energy metabolism may be compromised during pathophysiological states. One of the most dangerous is, undoubtedly, ischaemia-reperfusion injury with its acute form, myocardial infarction. However, the adaptation to chronic hypoxia has been known for decades for its cardioprotective effect against I/R. Changes of cardiac energy metabolism induced by the adaptation have not been fully explored and the system conceals still too many secrets. This thesis has aimed to determine how adaptation to chronic hypoxia affects the cardiac metabolism of the rat LVs in the following set-ups: 1. The effect of chronic normobaric hypoxia (CNH; 3 weeks, 5500m) during a brief I/R protocol in vitro on the protein kinase B/hexokinase (Akt/HK) pathway, including the expression and phosphorylation of Akt, the expression and localization of HK, the expression of mitochondrial creatine kinase (mtCKS), and the level of Bcl-2 family...
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His bundle in phylogenesis, ontogenesis and pathology
Tremerová, Aneta ; Gregorovičová, Martina (advisor) ; Kolář, David (referee)
His bundle is a part of the cardiac conduction system of mammals, birds and crocodilians. His bundle is important for high cardiac output in endothermic vertebrates. His bundle is a connection between atria and ventricles in fibrous atrioventricular isolation and it serves as an electrical conduction pathway via bundle branches to ventricular apex, where ventricular contraction begins. Defect in cardiac conduction system leads to cardiac arrhytmia and can cause sudden cardiac death. Thesis describes development of His bundle in mammals and birds, its phylogenensis and atrioventricular conduction in other vertebrates. Thesis also describes disorders of atrioventricular canal development, fibrous anulus and His bundle such a preexcitation syndromes and congenital heart block. Thesis also depicts history of a discovery of the atrioventricular conduction tissue. Key words: cardiac conduction system, His bundle, atrioventricular canal, anulus fibrosus, ventricular preexcitation, perinatal AVRT, WPW syndrome, congenital heart block
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Adenosine signaling: the role in neuroprotection and neurodegeneration
Hrušovská, Kateřina ; Novotný, Jiří (advisor) ; Kolář, David (referee)
The aim of this bachelor thesis is to describe basic and the most important mechanisms of adenosine signaling, especially in the central nervous system, where the purine nucleoside adenosine plays important role like significant neuromodulator. Strong release of adenosine to extracellular space may occur under some pathological conditions. Adenosine works throught his four receptors, which have very diverse functions. Some effects are neuroprotective - these are predominantly mediated throught the inhibitory A1 receptor, which can reduce neurotoxicity, others may also induce neurodegeneration, mainly due to increased activation of A2A receptors. This signaling system can be diversely modulated, for example by inhibition of enzymes, which can provide adenosine formation or degradation, blocking its transporters, by agonists or adenosine antagonists, or by inhibition of second messengers and various protein kinases by which adenosine affects cellular processes. Interactions of adenosine receptors with other types of receptors in the brain are also important. Adenosine and adenosine receptors can participate in neurodegenerative processes. A detailed understanding of the specific effects of adenosine can bring great progress in the treatment of neurodegenerative diseases. At present, intensive...
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Peroxisomes and their role in energetic metabolism of the heart
Čejková, Denisa ; Kolář, David (advisor) ; Horníková, Daniela (referee)
Peroxisomes are small eucaryotic organelles, mainly known for their ability to create and break down hydrogen peroxide. However their enzymes play other significant roles, they participate in beta-oxidation of fatty acids with very long or branched chains, through alpha-oxidation they enable to process molecules that cannot go through beta- oxidation cycle, they also participate in early steps of synthesis of ether-lipid or bile acides. Above mentioned aspects make peroxisomes potentionally interesting for their possible influence on heart muscle metabolism, that is dependent on oxidative degradation of fatty acids, although not very much is known about this issue. The thesis focuses on biogenesis and function of peroxisomes, but also on their possible role in heart muscle metabolism.
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