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Circadian regulation of body temperature
Knobloch, František ; Bendová, Zdeňka (advisor) ; Horníková, Daniela (referee)
This thesis addresses the topic of circadian control of body temperature, a key aspect for understanding the temporal regulation of the body and its influence on physiological processes. Temperature is a strong signal that is under the strict control of the thermoregulatory system, which very effectively prevents major fluctuations even under non-standard conditions. Although the daily rhythm in body temperature oscillates within a very narrow range, it is an important information for all the cells of our body, which contributes to their coordinated functioning. This thesis synthesizes the available knowledge on how the circadian system creates this rhythm and how temperature and factors that influence body temperature may in turn enter into the temporal regulation of our body. The aim is to contribute to a better understanding of the dynamics between the circadian system and thermoregulation, and to highlight the many bidirectional connections that may overlap with countless other physiological processes.
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Brown adipose tissue and its positive effects
Máchová, Magdaléna ; Horníková, Daniela (advisor) ; Haasová, Eliška (referee)
Brown adipose tissue (BAT) is a specialized type of adipose tissue that plays an important role in non-shivering thermogenesis which is induced most often after cold acclimation. However, many studies have also highlighted the role of BAT in influencing the cardiovascular system and thus obesity, diabetes mellitus type 2, atherosclerosis, and insulin resistance. BAT has a protective effect against oxidative stress and recent studies suggest that it also has a potential therapeutic relevance for the treatment of cancer and osteoporosis, while it may also play a role in the body's immunomodulatory effects. Key words: brown adipose tissue, non-shivering thermogenesis, cold acclimation, β-adrenergic receptors, therapeutic potential
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Cardioprotective effects of sodium-glucose cotransporter SGLT2 inhibitors.
Thořová, Markéta ; Horníková, Daniela (advisor) ; Vávra, Jiří (referee)
Cardiovascular diseases are one of the most common causes of death in both non-diabetic and diabetic patients. Nowadays, a large number of drugs target cardiovascular problems. One of the very promising therapies is the use of sodium-glucose cotransporter type 2 (SGLT2) inhibitors. SGLT2 inhibitors have gained a wide interest in the treatment of type 2 diabetes (DM2) due to their ability to lower blood glucose levels independently of insulin action. However, in addition to their main effect on glycemic control, there is increasing evidence of their beneficial effects on the cardiovascular system beyond their hypoglycaemic effects. These drugs reduce hyperglycemia, hypertension, and improve diabetic retinopathy through multiple mechanisms, many of which have not been fully explained. The main focus has been on identifying the mechanisms through which these drugs affect the heart and blood vessels, whether by reducing blood pressure, affecting cardiac cells, or improving metabolic processes in blood vessels. Key words: SGLT2, inhibitors of SGLT2, cardioprotective effect, diabetes mellitus, heart
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The effect of chronic cold on Ca2+-ATPase (SERCA2) in rat heart
Šeovićová, Maja ; Horníková, Daniela (advisor) ; Nováková, Olga (referee)
Acute cold exposure is a significant stressor activating heat production by shivering after the prolonged exposure cellular oxidative stress increases. Chronic exposure to cold lasting at least 2 weeks leads to the development of cold acclimatization. The main thermogenic role is taken over by non-shivering thermogenesis taking place in brown adipose tissue, which significantly increases its weight due to cold. Cardiac hypertrophy, hypertension and impaired renal function are frequently observed pathologies of acclimatization at 4-5 řC. Our laboratory recently introduced a model of mild chronic cold acclimatization at 8 řC, during which no damage to the heart or kidneys occurs and has proven cardioprotective effect on reducing infarct size. Hence, the influence of this cold acclimatization model on the other cellular and molecular processes needs to be investigated. The cardioprotective effect of cold acclimatization includes changes in β-AR signaling, activation of anti-apoptotic pathways or augmentation of the antioxidant system. The aim of this thesis was to investigate the effect of cold acclimation and subsequent reacclimation on proteins regulating Ca2+ levels in the rat heart (SERCA2 and phospholamban) and on the stimulation of regulatory proteins β-arrestin 1/2 and protein kinase PDPK1. The...
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Mechanism of hypertrophic cardiomyopathy
Hadravová, Kateřina ; Horníková, Daniela (advisor) ; Benák, Daniel (referee)
Cardiomyopathies are a group of chronic cardiac diseases of unclear etiology. We can separate them by morphological and functional signs into restrictive, dilated and hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy is a relatively common disease in which the development of cardiac hypertrophy is not based on risk factors such as hypertension or atherosclerosis. Compared to acquired cardiac hypertrophy the hypertrophic cardiomyopathy is mainly caused by hereditary mutations. These mutations are mostly in genes for myosin heavy chain β and myosin binding protein C. Cardiac hypertrophy also presents with changes in the extracellular matrix caused by matrix metaloproteinases. They have a big impact on the morphology of cardiomyocytes and their loss, which in turn cause hypertrophy or left ventricle dilation. From medical point of view emphasis is put on prevention and early diagnosis using blood biomarkers. Among singnificant biomarkers are micro-RNAses, vascular endothelial growth factor B, NAD - dependent deacetylase sirtuin-3, growth/differentiation factor 15, glycoprotein 130 and calmodulin - dependent proteinkinase II. Causal treatment doesn't unfortunately exist, therefore symptomatic treatment is deployed using β blockers and calcium channel blockers. Newly used drugs include an...
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Cardiotoxic effects of anthracyclines in oncological treatment
Tekáčová, Kateřina ; Horníková, Daniela (advisor) ; Vávra, Jiří (referee)
Anthracyclines are antitumor antibiotics used during chemotherapy in cancer patients. Treatment with anthracyclines has good results but a side effect is significant cardiotoxicity. This bachelor thesis describes the mechanisms of action of anthracyclines which are essential in cancer therapy and may be risky for patients. The thesis also defines the term of cardiotoxicity and summarizes factors that may increase the risk of cardiotoxicity. The most commonly used agents in the anthracycline series are briefly described. Cardiotoxicity can be detected by cardiac markers, especially particular troponin and diagnostic methods. The last chapter describes the groups of substances that reduce the cardiotoxic effects of anthracyclines. Key words: heart, anthracyclines, cardiotoxicity, chemotherapy, onkology treatment
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The effect of pineal melatonin on insulin production
Hovorková, Adéla ; Bendová, Zdeňka (advisor) ; Horníková, Daniela (referee)
Both production and secretion of insulin depend on the circadian rhythms. These are set by the internal circadian clock reacting to the external stimuli such as the light or the darkness. The central clock synchronization of the rhythmic processes in the organism is formed by the structure so-called suprachiasmatic nucleus. Secretion of melatonin, aka "hormone of the night," is controlled by the central clock and serves to align them with the peripheral clocks. Peripheral clocks are located, for example, in pancreas, liver or other body organs. Langerhans' islets in pancreas consist of -, - and -cells. These play an important role in maintaining glucose homeostasis as they produce hormones insulin and glucagon, key blood glucose level regulators. This text describes how the corruption of circadian system by a light pulse at night impacts insulin secretion. A phase shift results in melatonin secretion anomaly (increase), which inhibits insulin levels and thus gives rise to elevated glucose levels. Hyperglycaemia and insulin resistance because of a long-term rhythm corruption may result in type 2 diabetes. Key words: circadian rhythm, SCN, melatonin, MT1 receptor, MT2 receptor, β-cell, insulin, glucagon, insulin resistance, type 2. diabetes
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The role of uncoupling proteins (UCP) in cardioprotection
Furmánková, Tereza ; Horníková, Daniela (advisor) ; Adamcová, Kateřina (referee)
Cardiovascular disease (CVD) is the world's leading cause of death. Almost 18 million people die of CVD each year, and the prevalence continues to rise for both men and women. It is now clear that the maintenance of mitochondrial membrane potential can play an important role in the pathophysiology of the heart and it is involved in cardioprotective mechanisms. Mitochondrial membrane potential can be affected in a various of ways, one of them is the stimulation of uncoupling proteins. An elaboration of previous findings in this work has shown that uncoupling proteins have the effect of reducing oxygen radicals, inhibiting apoptosis, affect the production of ATP and atherosclerotic plaques and protect the heart from lipid toxicity. There are several ways to regulate their gene expression, and influencing these pathways may be a way to achieve cardioprotection. Key words: uncoupling proteins, mitochondria, cardioprtoection, thyroid hormones, fatty acids, adipose tissue, reactive oxygen species, FGF21
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