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Mesenchymal stromal cells and biological scaffolds for neural tissue regeneration
Kočí, Zuzana ; Kubinová, Šárka (advisor) ; Filová, Eva (referee) ; Zach, Petr (referee)
Despite tremendous progress in medicine, injuries of the adult central neural system remain without satisfactory solution. Regenerative medicine employs tissue engineering, cellular therapies, medical devices, gene therapy, or growth factors with the aim to bridge the lesion, re-establish lost connections and enhance endogenous repair in order to restore neural function. The aim of my thesis was to evaluate therapeutic potential of two approaches, transplantation of human mesenchymal stromal cells (hMSCs) and biological scaffolds derived from extracellular matrix (ECM) for neural regeneration, particularly in models of spinal cord injury (SCI). First, hMSCs from various sources - bone marrow (BM), adipose tissue (AT) and Wharton's jelly (WJ) - were isolated and characterized in vitro. All cell types met the minimal criteria for MSC phenotype and displayed similar properties in terms of their surface marker expression, differentiation potential, migratory capacity, and secretion of cytokines and growth factors. On the other hand, the cell yield from WJ and AT was significantly higher, and MSCs isolated from these tissues proliferated better than from BM. Therapeutic effect of intrathecal application of hWJ-MSCs was then evaluated in SCI compression model in rats. The effect of low (0.5 million) and...
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The role of adipose tissue in the whole-body energy metabolism in mice with different genetic background
Funda, Jiří ; Janovská, Petra (advisor) ; Pecina, Petr (referee) ; Žurmanová, Jitka (referee)
Adipose tissue greatly contributes to the maintenance of the whole-body energy homeostasis. White adipose tissue (WAT) is the most important storage of metabolic energy in the body, while brown adipose tissue (BAT) enables the body to survive in cold environment by transforming metabolic energy to heat. Both WAT and BAT have a critical role in the control of systemic levels of fatty acids, which is necessary for the maintenance of the energy homeostasis and for the prevention of lipotoxic damage of non-adipose tissues. Abundant lipid accumulation can lead to the development of obesity, which is often accompanied by metabolic disorders such as type 2 diabetes and by the impairment of adipose tissue metabolic functions. Healthy adipose tissue prevents from the development of metabolic disorders associated with obesity by buffering the excess of nutrients. The key processes for efficient buffering of fatty acids are futile triacylglycerols/fatty acid cycling (TAG/FA cycling) and fatty acid oxidation. These processes occur in both WAT and BAT and their rates are largely affected by a set of transcriptional regulators, especially peroxisome proliferator-activated receptors (PPARs) and their coactivators. Bioactive molecules such as hormones, polyunsaturated fatty acids (PUFA) or pharmaceutics such as...
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Physiological relevance of futile cycling based on lipolysis and fatty acid re-esterification in white adipose tissue
Funda, Jiří ; Flachs, Pavel (advisor) ; Kolář, David (referee)
AJ The thesis deals with the task of futile metabolic cycling, mainly on the cycle including lipolysis and fatty acid re-esterification, which takes place in white adipose tissue. This cycle plays some essential roles in organism, including regulation of important metabolic pathways in lipid metabolism and also exhibit certain influence on the whole body energy metabolism. First part of the thesis is focused on general properties of futile metabolic cycles and shows some examples of their functions in organism. Next part presents detail view on single steps making the whole lipolysis/re-esterification cycle. Considerable part deals with the ways of regulation of futile cycle activity. This approach may increase an impact of futile cycling on processes under its influence. Physiological relevance of futile metabolic cycle based on lipolysis and fatty acid re-esterification in white adipose tissue was described in numerous studies. This thesis shows their results for a purpose to provide a summary of functions of this system in physiology of mammals. Key words futile metabolic cycle, lipolysis, re-esterification, fatty acids, adipose tissue
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Evaluation of Selected Biochemical Markers of Metabolic Syndrome and Adipose Tissue After Bariatric Surgery
Horká, Veronika ; Bužga, Marek (advisor) ; Holéczy, Pavol (referee)
The diploma thesis deals the problematics of weight reduction with the using of bariatric- metabolic surgery and focuses on the changing risk components of the metabolic syndrome during one year long observation of 45 probands who have undergone Partial Jejuno-Ileal Diversion, Laparoscopic Sleeve Gastrectomy or Laparoscopic Gastric Plication. The main aim of the diploma thesis is to evaluate the changing risk components of the metabolic syndrome during weight reduction after undergoing bariatric surgery. The thesis shows that in the studied sample of bariatric patients it is an effective method of weight reduction (in PJID the success rate was 48 % EWL, in LGCP 51 % EWL and the most successful was LSG with 76 % EWL) with metabolic effect such as for example observed positive changes in risk components of the metabolic syndrome - reduction of morning glucose levels, increase of HDL cholesterol and decrease of triacylglycerols in the blood, decrease of waist circumferences and decrease of blood pressure or elimination of metabolic syndrome. Up to 68.9 % of the monitored probands showed signs of metabolic syndrome when evaluating the initial measurement before bariatric surgery, the remaining 22.2 % of the probands showed the signs after the year's observation. As part of the risk assessment for the...
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Monocyte adhesion to endothelium and atherogenesis
Kauerová, Soňa
Despite the availability of effective therapy of hypercholesterolemia and hypertension, cardiovascular mortality continues to be very high in the Western world. Inflammatory changes occurring in the arterial wall as well as in the adipose tissue play a major role in the development of atherosclerosis. Macrophages are involved in the process of atherogenesis as early as atherosclerosis begins to develop, when, still as monocytes, they migrate and adhere to the arterial wall as a result of endothelial activation and stimulation by pro-inflammatory substances. Adipose tissue has long been recognized as an important endocrine organ, with part of adipose tissue made up by a large amount of macrophages capable of producing a large number of pro-inflammatory cytokines, which contribute to the development of low-grade chronic inflammation important in the development of atherosclerosis. In samples of subcutaneous, visceral and perivascular adipose tissue (SAT, VAT, and PVAT, respectively) obtained from healthy subjects (living kidney donors, LKD), we analyzed macrophages and their polarization, gene expression of pro-inflammatory cytokines and the effect of substances released by VAT on the level of monocyte adhesion to the endothelium. In some analyses, we included samples of SAT, VAT and PVAT obtained...
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Factors affecting glucose metabolism and inflammatory response in critically ill patients
Kotulák, Tomáš ; Haluzík, Martin (advisor) ; Maruna, Pavel (referee) ; Šenolt, Ladislav (referee)
Hyperglycemia in critically ill patients was considered for many years an adaptive response to stress conditions being present in both patients with and without previous history of diabetes. Hyperglycemia is caused mainly by peripheral insulin resistance induced by the factors acting counteracting insulin signalling at the postreceptor level. Furthermore, hyperglycemia itself can then increase serum levels of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-6 (Il-6) and interleukin-8 (Il- 8) and others. On the contrary, peripheral insulin resistance induced by pro- inflammatory cytokines may further potentiate hyperglycemia. White adipose tissue represents in addition to its energy storage function also a very active endocrine active organ. In addition to regulation of a number of metabolic processes it also significantly modulates the inflammatory response. In critically ill patients, adipose tissue changes its morphology, i.e. the adipocytes are shrinking and adipose tissue is abundantly infiltrated by macrophages. Paradoxically, overweight and obese critically ill patients have lower mortality than underweight, lean and morbidly obese subjects. In our studies, we selected population of the patients undergoing elective major cardiac surgery with extracorporeal...
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Acipimox during Short-Term Exercise Exerts A Negative Feedback of Growth Hormone on Ghrelin Secretion in Patients with Bulimia Nervosa and in Healthy Women: The Role of Lipolysis
Smitka, Kvido ; Nedvídková, Jara (advisor) ; Kršek, Michal (referee) ; Čáp, Jan (referee)
Title: Acipimox during Short-Term Exercise Exerts A Negative Feedback of Growth Hormone on Ghrelin Secretion in Patients with Bulimia Nervosa and in Healthy Women: The Role of Lipolysis Objective: Eating disorders, such as bulimia nervosa (BN) and anorexia nervosa (AN), are characterized by abnormal eating behavior. The main features of BN are binge-eating and inappropriate compensatory methods to prevent weight gain. The appetite-modulating peptide ghrelin is secreted by the stomach and shows a strong release of growth hormone (GH). A potential GH-ghrelin feedback loop between stomach and the pituitary has been recently reported. Acipimox (Aci), an analogue of nicotinic acid, inhibits lipolysis in adipose tissue (AT) and reduces plasma glycerol and free fatty acids (FFA) levels. Exercise and Aci are stimulators of GH secretion. We suppose that a negative feedback from increased GH levels during exercise may play a role in reducing plasma ghrelin levels. We surmised that altered baseline activity and exercise-induced activation of the sympathetic nervous system (SNS) results in excessive stimulation of lipolysis associated with negative energy balance and may lead to abnormal AT metabolism in patients with BN. Disruption of the gut-brain-AT axis might be involved in the pathogenesis of BN. The...
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Monocyte adhesion to endothelium and atherogenesis
Kauerová, Soňa
Despite the availability of effective therapy of hypercholesterolemia and hypertension, cardiovascular mortality continues to be very high in the Western world. Inflammatory changes occurring in the arterial wall as well as in the adipose tissue play a major role in the development of atherosclerosis. Macrophages are involved in the process of atherogenesis as early as atherosclerosis begins to develop, when, still as monocytes, they migrate and adhere to the arterial wall as a result of endothelial activation and stimulation by pro-inflammatory substances. Adipose tissue has long been recognized as an important endocrine organ, with part of adipose tissue made up by a large amount of macrophages capable of producing a large number of pro-inflammatory cytokines, which contribute to the development of low-grade chronic inflammation important in the development of atherosclerosis. In samples of subcutaneous, visceral and perivascular adipose tissue (SAT, VAT, and PVAT, respectively) obtained from healthy subjects (living kidney donors, LKD), we analyzed macrophages and their polarization, gene expression of pro-inflammatory cytokines and the effect of substances released by VAT on the level of monocyte adhesion to the endothelium. In some analyses, we included samples of SAT, VAT and PVAT obtained...
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Autophagy in adipose tissue
Somova, Veronika ; Krulová, Magdaléna (advisor) ; Zouhar, Petr (referee)
Autophagy is an essential mechanism of recycling, which represents a path leading to utilization and reorganization of intracellular components (nutrients, organelles, etc). Recent studies on adipose tissue have shown, that autophagy plays crucial role in differentiation of the adipocytes precursors and in phenotypic tissue transformations. The aim of this thesis is to summarize the characteristics of autophagy in terms of various adipose tissues as well as to present the regulation of autophagy as a potentially useful in therapy focused on obesity treatment. However, with the regulation of autophagy, there are risks that will also be considered in the present thesis. Keywords: autophagy, adipose tissue, therapy
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Identification of biomarkers involved in the pathophysiology of gestational diabetes mellitus.
Šimják, Patrik ; Pařízek, Antonín (advisor) ; Karásek, David (referee) ; Novotný, Zdeněk (referee)
Identification of biomarkers involved in the pathophysiology of gestational diabetes mellitus ABSTRACT Gestational diabetes mellitus is a disorder of glucose metabolism that occurs in pregnancy and resolves after delivery. Increasing production of pregnancy-related hormones leads to insulin resistance which is not adequately compensated by increased insulin secretion. Since obesity is an important risk factor for gestational diabetes and is also associated with adipose tissue dysfunction and increased peripheral insulin resistance, the question arises as to what extent is the adipose tissue involved in the development of gestational diabetes. The first part of the thesis focuses on the identification of changes in plasma concentration and mRNA expression of adipokines fetuin A, fetuin B and FGF21. In our study we did not show that the presence of gestational diabetes significantly influenced the plasma concentration of fetuin A, fetuin B and FGF21 during pregnancy. An important finding was that women who had pregnancy complicated with gestational diabetes had a significantly higher concentration of FGF21 several months after delivery in comparison to healthy pregnant women. We have been able to demonstrate the production of fetuin A in the placenta and fetuin B in perineal and subcutaneous tissue. However,...
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