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Importance of glycolysis and oxidative phosphorylation in the metabolism of mesenchymal stem cells
Fráňová, Markéta ; Krulová, Magdaléna (advisor) ; Rohlenová, Kateřina (referee)
Mesenchymal stem cells (MSCs) are classified as multipotent stem cells. They possess the ability to differentiate into many cell types, promote angiogenesis, increase cell survival in damaged tissue and modulate the immune response. These functions of MSCs are used in the treatment of various injuries and some diseases. This work characterizes MSCs, with a focus on their energy metabolism, specifically on the switch in their metabolic phenotype between glycolysis and oxidative phosphorylation in different states of MSCs, during cell culture and after transplantation. Finally, two modulations of MSC metabolism are presented, including cultivation in a hypoxic environment and quiescence induced by serum deprivation, which increase cell survival under the ischemic conditions that MSCs enter after transplantation. Key words: mesenchymal stem cells, metabolism, glycolysis, oxidative phosphorylation
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Factors influencing intraspecific scaling of metabolic rate
Trubelová, Zuzana ; Starostová, Zuzana (advisor) ; Storch, David (referee)
The relationship between metabolic rate and animal body size of the animal has been studied for more than hundred years. Recently, attention of scientists moved from the interspecific to the intraspecific level. The work focuses on the intraspecific scaling of metabolism. When plotting the metabolic rate against body mass during ontogeny the resulting line often exhibits one or more breaks. Why these breaks (and thus reduction the metabolic rate) occur hasn't been fully explained. It is assumed that can be due to certain factors that affect an individual during development. Some of these factors came from the most famous of several hypotheses attempting to explain the scaling of metabolic rate. These hypotheses include the Metabolic Theory of Ecology (MTE), the Metabolic Level Boundaries (MLB), the Cell model and the Dynamic Energy Budget (DEB) hypothesis. There are several factors that could affect individuals during ontogeny. These include internal factors, which result from the internal processes within the body. These factors are often interrelated with each other in different ways; therefore, it is unlikely to choose only one particular factor which affects metabolic rate. The most frequently studied factors are changes of cell size and changes in the proportion of metabolically active...
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Comparison of methods of basal metabolism determination
Kosková, Martina ; Coufalová, Klára (advisor) ; Hráský, Pavel (referee)
Title: Comparison of individual methods of basal metabolism determination Objectives: The aim of the work is to compare the individual methods of basal metabolism. These values were measured by indirect calorimetry, plethysmography, bioelectric impedance and predictive equations. Methods: The research was attended by 31 people, including eight men and twenty-three women. All participants of my research were aged 21-30 years. None of the participants was a professional athlete, they were all healthy and none of the women were pregnant or had menstruation. The indirect calorimetry, bioelectronics impedance device Tanita MC - 980 and BOD POD were used to collect the data. Basal metabolic rates were calculated from the prediction equations by Harris & Benedict, Fleisch's equation and Schofield's equation using measured anthropometric values. Results: The results of the methods that have been used for this group of people vary, but the difference is not significant. If we choose as a reference method indirect calorimetry, we can't replace it by any other method. The results for other methods are not significantly different, so we can replace one method with another, except indirect calorimetry. From calculations, we also found out that fat free mass greatly influences the results of basal metabolic rate...
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Metabolic alterations in cancer cells and their implications in the therapy of acute leukemias
Harárová, Alžbeta ; Starková, Júlia (advisor) ; Mrvová, Silvia (referee)
Cancer metabolism differs from that of the healthy cells in several aspects. Aerobic glycolysis (e.g. converting pyruvate to lactate under normoxic conditions) was the first described metabolic alteration of cancer cells. Metabolic alterations have since been described in the tricarboxylic acid cycle, oxidative phosphorylation, in the metabolism of amino acids (especially glutamine, asparagine and serine) and also in the metabolism of fatty acids and cholesterol. The common feature of these changes is the tendency to prefer anabolic pathways, thus enabling fast proliferation of cancer cells. The study of cancer metabolism is particularly important in the case of cancer cells that show resistance to treatment, as their aberrant metabolism is not only a potential diagnostic marker but also a potential therapeutic target. The majority of metabolic alterations have been described for the first time in solid tumors, whereas only recently has the metabolism of acute leukamias gained more attention. Asparaginase is an example of a chemotherapeutic agent that targets a metabolic alteration of leukemic cells. Distinct metabolic profile is also associated with the glucocorticoid resistance. Detailled study of the metabolic alterations of leukemic cells has elucitated the mechanisms of the asparaginase and...
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Metabolism of uric acid during mammalian evolution
Mančíková, Andrea ; Krylov, Vladimír (advisor) ; Stibůrková, Blanka (referee)
Uric acid is the end product of purine metabolism of humans and some higher primates. In other mammals enzyme urate oxidase is capable to further convert uric acid to allantoin. During evolution of primates several mutations in urate oxidase gene had occured, led the enzyme to decrease its activity or to complete loss of function. What was the initial impetus for the utilization of uric acid and what biochemical traits of uric acid led to a tendency to retain a major of this metabolite production in the bloodstream? Uric acid has antioxidant capabilities and it is scavanger of free radicals. Increased levels of uric acid in blood has an effect on acute and chronic elevations of blood pressure. It is possible that hyperuricemia helped to maintain blood pressure under low-salt dietary conditions of primates during the Miocene. This mechanism probably have allowed to stabilize bipedalism our ancestors. Uric acid has an important role as a neuroprotector. As inhibitor the permeability blood-brain barrier, uric acid limits the infiltration of undesirable substances to the neurons and prevents central nervous system against the formation of inflammatory diseases. Such as neurodegenerative diseases may be caused by reduced serum uric acid levels. Uric acid protects against peroxinitrite damage tissues in the...
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Lipid composition of biological membranes and life-histories in songbirds
Šimonová, Kateřina ; Tomášek, Oldřich (advisor) ; Sam, Kateřina (referee)
Differences in the composition of cell membranes are considered to be the physiological mechanism responsible for different metabolic rates, life span and consequently, different life-histories. The membrane pacemaker theory suggests that higher membrane unsaturation may be an important factor responsible for higher metabolic rate and shorter life span of organisms. The alternative hypothesis, on the other hand, assumes that membranes can function as structural antioxidants, and thus that higher membrane unsaturation may be associated with longer life span. The aim of this work was to test how changes in the fatty acid composition of membranes depends on body size, latitude and altitude, within which different life-histories and metabolic rate were observed. Temperate and tropical lowland songbird species were chosen for the models testing the effect of latitude, and only tropical species of songbirds were chosen for the models testing the effect of altitude. Part of the work was molecular sex determination. Using gas chromatography and mass spectrometry, the amount of individual fatty acids contained in red blood cell phospholipids was obtained from blood samples. The results showed that the composition of the membranes in most cases correlates with body size, which also correlates with almost all...
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Effect of cholinesterase inhibitors on monoaminergic system and energic metabolism
Kalinová, Tereza ; Mladěnka, Přemysl (advisor) ; Štěpánková, Šárka (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Tereza Kalinová Supervisor: Assoc. Prof. Přemysl Mladěnka, Pharm.D., Ph.D. Mentor: Assoc. Prof. Jana Hroudová, Pharm.D., Ph.D. Title of diploma thesis: Effect of cholinesterase inhibitors on monoaminergic system and energy metabolism Cholinesterase (ChE) inhibitors play an essential role in the treatment of Alzheimer's disease (AD). They effect positively cognitive, functional and behavior symptoms of AD. Up to date, donepezil, rivastigmine and galantamine represent the only ChE inhibitors approved for AD treatment. The first ChE inhibitor was tacrine, which was withdrawn from market due to its toxicity and adverse effects. Recently, novel tacrine and 7-methoxytacrine (7-MEOTA) derivatives were synthetized and extensively investigated to find less toxic compounds affecting pathological mechanisms associated with development of AD. There is less known about effects of these drugs on mitochondrial functions and cellular energy metabolism. The aim of this project is to examine in vitro effects of ChE inhibitors on energy metabolism and cellular respiration, specifically on mitochondrial electron transport chain complexes and an enzyme of the citric acid cycle - citrate synthase. Inhibitory effects...
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Interaction of food additives with xenobiotic metabolising enzymes
Jandová, Eliška ; Hodek, Petr (advisor) ; Koblihová, Jitka (referee)
Recently the use of various food supplements as a part of a healthy lifestyle has been very popular. Although most of them are natural products, their excessive consumption may not always be beneficial for health. Dietary supplements are usually of a flavonoid character. Flavonoid compounds are found in plants and they have beneficial effects on human health. For their antioxidant, anti-allergy and chemopreventive effects they are extensively studied. However, in recent years the negative impacts of flavonoids have been described, often caused by their excessive consumption. It has been shown that they interact with cytochrome P450, which play an important role in the biotransformation of xenobiotics. The change in the metabolism of xenobiotics (whether drugs or carcinogens) can cause serious health problems, including a tumor growth. Beside cytochrome P450, there is another possible points of intervention, cytochrome b5 (or NADH:cytochrome b5 reductase), which effects the catalytic cycle of cytochrome P450. Another point of potential danger is the elimination of xenobiotics out of the organism. There is a complex system of transporters, in which P-glycoprotein plays a very significant role. P-glycoprotein is involved in transmembrane efflux of xenobiotics, preventing the aggregation of these...
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MR spectroscopy in patients with diabetes mellitus
Šedivý, Petr ; Štěpánková, Helena (advisor) ; Roztočil, Karel (referee)
This thesis deals with in vivo MR spectroscopy. Measurements in this thesis were performed on whole-body MR tomograph at the Institute for Clinical and Experimental Medicine in Prague. The objective of the thesis was to study differences in the biochemical processes and energy metabolism in the muscle tissue under physical workload between the groups of healthy subjects and patients with type 1 diabetes mellitus (DM1). We used phosphorous spectroscopy in combination with ergometer. The thesis is divided into five chapters. The first chapter describes theoretical introduction to in vivo 1 H and 31 P MR spectroscopy and muscle metabolism, the second chapter deals with the description of the experimental equipment and measurement, results of the thesis are reported in the third chapter and the fourth chapter is a discussion of results. Main result of this work is summarized in conclusion; we found differences between the metabolism of patients with DM1 and healthy volunteers.
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New findings of physiological and ecological aspects of hibernating bats
Ungrová, Zdislava ; Jahelková, Helena (advisor) ; Lučan, Radek (referee)
Bats can be found in almost all climatic zones. They have to deal with unfavorable conditions of environment to survive and reproduce sucessfully. Especially in temperate zones they have to deal with cold temperatures and lack of food during a winter season. To save energy bats enter a short, diurnal torpor or a hibernation. Usually, hibernation lasts all winter and is disturbed by short bouts of arousals. During both hibernation and torpor a physiological changes occur in bodies of bats. Body temperature decreases from endothermic levels, metabolic rates are reduced as well as respiratory rate and pulse. These changes are mainly influenced by weight and body size, diet, ambient temperature, sex and reproductive status. With the developement of new technologies, these changes can be measured more accurately than they have been in past, whether in a field or in a laboratory. But not all physiological processes are well explained. We have little knowledge especially about mechanism of arousal from hibernation. During awakening bats are infected by fungus Geomyces destructans that affects their immune system. In Norh America fungus causes a disease called White- Nose syndrome (WNS), that is responsible for death of millions of bats, especially endangered is Myotis lucifugus. In Europe, this disease is reffered...
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