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Effect of selected drugs on mitochondrial metabolism in an in vitro model of human skeletal muscle
Krajčová, Adéla ; Anděl, Michal (advisor) ; Kieslichová, Eva (referee) ; Houštěk, Josef (referee)
Introduction: Increasing number of reports reflect that mitochondrial dysfunction can be induced by some of the commonly used drugs and can play a key role in the development of their adverse effects. One of these drugs is a phenol derivative propofol. Propofol is an intravenous, fast and short-acting hypnotic agent, routinely used either for induction and maintenance of anaesthesia during surgery, or for sedation in intensive care units. Propofol infusion syndrome (PRIS) is a rare, but serious adverse effect of the drug with a very high mortality. Typical features of the syndrome include metabolic acidosis, arrhythmias, ECG changes that are similar to those of Brugada syndrome, hypertriglyceridemia, fever, hepatomegaly, rhabdomyolysis, cardiac and/or renal failure. The risk of the syndrome increases with raising dose and duration of propofol administration (˃48 hours). The mechanism of the syndrome is still unknown: pilot studies performed on animal models are suggestive of its mitochondrial origin. In the first part of the study, we performed the analysis of 153 published case reports and all experimental studies related to PRIS. Another aim of the study was to test hypothesis of propofol- induced mitochondrial damage by in vitro exposure of human skeletal muscle-derived cells to a range of...
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Quantification of insulin secretion after administration of whey proteins in healthy subjects and in patients with type 2 diabetes
Wildová, Elena ; Anděl, Michal (advisor) ; Pelikánová, Terezie (referee) ; Škrha, Jan (referee)
INTRODUCTION: Milk and milk proteins have higher insulinogenic index than glycemic index. This feature is mainly attributed to whey proteins. The main goal of this thesis was to evaluate a C-peptide response after administration of whey proteins in healthy individuals (study 1) and in patients with type 2 diabetes mellitus (study 2) in comparison to other experimental stimulation tests. METHODS: Eight young, healthy (7 males, 1 female; aged 20-26 years), non-obese (BMI: 17 - 25.9 kg/mš) participants with normal glucose tolerance were enrolled for study 1. Each individual underwent six C-peptide secretion tests in total. Three secretion tests measured C-peptide response to orally administered substances: whey proteins only (OWT), whey proteins with glucose (OWGT) and glucose only (OGTT, reference); while the other three secretion tests measured C-peptide response to intravenously administered substances: arginine (AST), glucagon (GST) and glucose (IVGTT, reference). Sixteen overweight (BMI 26,4 - 29,8 kg/m2) patients with type 2 diabetes mellitus, good glycemic control and with preserved fasting serum C-peptide levels (0,94 ± 0, 07 nmol/l) were enrolled for study 2. Two oral stimulation tests - one with 75 g of glucose (OGTT) and the other with 75 g of whey proteins (OWIST) - were used for assessing...
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Lifestyle diseases, their causes and prevention.
Horáková, Aneta ; Raisová, Miloslava (advisor) ; Anděl, Michal (referee)
My bachelor thesis dealt with the issues of lifestyle diseases. The objective of this work was to use a questionnaire survey to find out whether and how the people are informed about these diseases. If they know causes related to them and how they try to prevent from them. I also was wondering whether the people on the basis of their age and their maximal attained educational are differently informed about these diseases. Aims of this work were completed fulfilled and the results showed that the respondents who were used in my questionnaire are sufficiently informed about these diseases and their prevention which they predominantly respect. As emerged from the work it would be appropriate to ensure that the society continues to be well - informed about these diseases. I personally would wish that people of all ages to regularly and consciously pay primarily attention to precautions of a healthy lifestyle which is the basis of prevention of lifestyle diseases.
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The incidence of specific islet cell autoantibodies in patients with HNF1A-MODY and HNF4A-MODY
Urbanová, Jana ; Anděl, Michal (advisor) ; Štechová, Kateřina (referee) ; Bém, Robert (referee)
Islet cell autoantibodies are associated with autoimmune insulitis and belong to the diagnostic criteria of Type 1 diabetes mellitus. However, growing evidence suggests that autoantibodies are present in other types of diabetes. Here, we focus on the autoantibody incidence in Czech patients with maturity-onset diabetes of the young (MODY) and analyze their functional relevance in terms of diabetes onset and control. Autoantibodies against glutamic acid decarboxylase 65 (GADA) and protein tyrosine phosphatase islet antigen 2 (IA-2A) were measured in a cohort of 28 Czech patients with MODY (all confirmed by genetic testing). Selected clinical data were correlated to the status and kinetics of autoantibodies. One quarter of patients with MODY examined (7/28; 25%) was positive for GADA or IA-2A. GADA were more prevalent (7/7) than IA-2A (1/7). The incidence of autoantibodies did not correlate with human leukocyte antigen status, nor with particular mutation in MODY genes. The patients who were positive for the autoantibodies developed diabetes later than those who were autoantibody- negative, but had worse glycaemic control. Expression of autoantibodies decreased with any improvement of diabetes compensation. Only one patient did not correspond to the above and displayed signs of combined signs of MODY...
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Nutritional Factors in Skeletal Muscle Insulin Resistance Development
Gojda, Jan ; Anděl, Michal (advisor) ; Saudek, František (referee) ; Prázný, Martin (referee)
Nutritional Factors in Skeletal Muscle Insulin Resistance Development Jan Gojda Abstract Background. Diet composition ranks among etiological factors of insulin resistance (IR) and diabetes. Vegans, people consuming exclusively plant-based diet, have significantly lower prevalence of IR and thus represent a suitable model population for study of nutritional factors on IR development. Branched chain amino acids (BCAA) ranks among these factors. Aims and hypothesis. Aim of the observational study was to prove that vegans have better glucoregulatory functions and thus to validate "vegan vs. omnivore" model. Aim of the consecutive interventional study was to prove in this model that dietary intervention with BCAA leads to a group sepcific changes in the insulin function mesures. Methods. 11 vegans and 10 omnivorous controls were recruited in the observational study. Hyperinsulinemic euglycemic clamp (HEC) and muscle (SM) biopsies (amount of intramyocellular lipids (IMCL), mtDNA and the activity of citrate synthase (CS)) were performed. 8 vegans and 8 omnivores were consequently subjected to the intervention with 15 or 20 g of BCAA respectively. The examination was performed at the baseline, after the intervention and after 6 months wash-out period: anthropometry, HEC, arginine test, SM biopsy (CS, activity of...
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Effect of selected nutrients on skeletal muscle mitochondrial metabolism
Tůmová, Jana ; Anděl, Michal (advisor) ; Poledne, Rudolf (referee) ; Drahota, Zdeněk (referee)
Skeletal muscle plays an important role in the maintenance of whole-body metabolic homeostasis. Metabolic alterations of skeletal muscle contribute to the pathogenesis of a wide range of human diseases, such as obesity, type 2 diabetes and hypertension. Relative excess and suboptimal composition of nutrients negatively affect skeletal muscle metabolism and a better understanding of mechanisms involved in these changes is of central importance. The aim of the work presented in this thesis was to explore cell viability and mitochondrial respiratory parameters following experimentally induced changes in the availability or composition of selected nutrients (fatty acids and glutamine). We attempted to elucidate the mechanisms responsible for the observed changes, such as mitochondrial DNA (mtDNA) damage, or nuclear receptors activation. The studies were performed in vitro on skeletal muscle cell culture models. In addition, we examined mitochondrial function and fat accumulation in skeletal muscle of vegans, i.e. subjects consuming a strict plant-based diet. Using C2C12 skeletal muscle cells we studied the effects of free fatty acids (FFA). We found that relatively low doses of saturated palmitic acid increased hydrogen peroxide production and induced mtDNA damage, mitochondrial respiratory dysfunction...
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Diabetes mellitus and impairment of intestinal barier function
Hoffmanová, Iva ; Anděl, Michal (advisor) ; Haluzík, Martin (referee) ; Keil, Radan (referee)
Introduction: Impairment of intestinal barrier function is involved in pathogenesis of immune mediated diseases (such as type 1 diabetes mellitus or celiac disease) and metabolic diseases (such as type 2 diabetes mellitus). Aims of study: The first aim was to analyze impairment of mucosal part of intestinal barrier in both type of diabetes and to describe differences when compared to celiac disease, which is a typical condition associated with impairment of intestinal barrier function. The second aim was to find a correlation between duration or compensation of diabetes and intestinal barrier desintegration in patients with both type of diabetes, and to find a correlation between body mass index and intestinal barrier desintegration in patients with type 2 diabetes. The third aim was to assess influence of gluten-free diet on improvement of small intestinal mucosal integrity in patient with celiac disease. Methods: The study was performed on 166 individuals including healthy controls and five group of patients with: type 1 diabetes mellitus with fading insulitis (T1D), type 1 diabetes mellitus with ongoing insulitus (T1D/INS), type 2 diabetes mellitus (T2D), untreated celiac disease (CLD), and celiac disease on gluten-free diet (CLD-GFD). We tested the marker of epithelial apoptosis - cytokeratin 18...
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