|
|
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...
|
|
|
Factors influencing the metabolism of homocysteine in selected diseases with complex etiopathogenesis
Veselá, Kamila ; Anděl, Michal (advisor) ; Nečas, Emanuel (referee) ; Rušavý, Zdeněk (referee) ; Poledne, Rudolf (referee)
At present, the great medicine to develop molecular genetic techniques, which significantly help to explain the causes of illnesses. In some diseases the genetic basis is well known. These are primarily contingent on monogenic diseases. Unfortunately, many diseases remain the genetic cause is still unknown. The largest group is the so-called complex diseases, where the origin and development of disease involving both genetic and nongenetic factors. These diseases include atherosclerosis, diabetes mellitus, orofacial clefts, preeclampsia, neural tube defects, and many others. Complex diseases are serious health and social problem in developed countries. Clasification of risk factors is the subject of much attention, because knowledge of these factors offer opportunities for effective prevention and treatment. The aim of my work was to obtain new knowledge of factors affecting homocysteine metabolism with regard to the formation of some complex diseases in the Czech population.
|
|
|
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...
|
|
|
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...
|
|
|
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...
|
|
| |
|
|
Quality of life with scleroderma
Bendlová, Iva ; Tomášková, Anežka (advisor) ; Anděl, Michal (referee)
This bachelor thesis deals with the evaluation of the quality of life with scleroderma, a chronic autoimmune disease. The work is focused on determining the health-related quality of life of patients with localized and systemic scleroderma. The values obtained are then compared with the quality of life of the healthy population and with the health-related quality of life of the patients with selected diseases (psoriasis, systemic lupus erythematosus, rheumatoid arthritis and breast cancer). The research was conducted in the form of a randomized SF-36 questionnaire, a globally used tool for assessing the quality of life in chronically ill patients, which evaluates 8 areas of life. The results of the SF-36 questionnaire were further evaluated by T-test to determine statistically significant values. This questionnaire was further extended by supplementary questions. The results show that patients with scleroderma do not achieve the same quality of life as a healthy population in all evaluated areas. Patients with scleroderma rate their quality of life worse than all selected diseases (except for patients with localized scleroderma compared to those with systemic lupus erythematosus). Keywords - scleroderma - localized scleroderma (morphea) - systemic scleroderma - quality of life (QoL) - health related...
|
|
|
So called special food for diabetic patients in Czech food stores
Pastorková, Eva ; Anděl, Michal (advisor) ; Šmejkalová, Vladimíra (referee)
The so-called special foods for diabetics in Czech food stores are in the focus of this theses. The theoretical part is a literature review devoted to the description of diseases diabetes mellitus with a view on the history, division of the disease, its treatment, related nutrition therapy, characteristics of the so-called special food for diabetics, and related regulations. The objective of the practical part is the survey of the supply of the so-called special food for diabetics in the Czech food stores. Selected examples demonstrated the nutritional value of the food in a focus and their suitability and importance for diabetes diet. Based on the survey, the supply of special food for diabetics was observed in 11 stores out of 13. The special food products were found in the special shelves without any further labeling or spread out among common food products. The food samples included a high amount of sweets often been characterized by a high amount of saturated fats, mono-/di-saccharides and low amount of fiber which are not in accordance with the nutritional recommendation for diabetes diet. Several food products possessed an advantage in terms of the low levels of saturated fats or mono- /di-saccharides. Nevertheless, only the nutritional value information is helpful to recognize these...
|
|
|
From diabetes, chronic pancreatitis to pancreatic cancer: miRNA - a new marker of pancreatic cancer?
Škrha, Pavel ; Anděl, Michal (advisor) ; Bendlová, Běla (referee) ; Krechler, Tomáš (referee)
From diabetes, chronic pancreatitis to pancreatic cancer: miRNA - a new marker of pancreatic cancer? Pavel Škrha Abstract Introduction: Pancreatic cancer ranks among the cancers with the worst prognosis. High lethality of the disease is caused by late diagnose and a lack of powerful and early markers. The goal of this study was to observe the presence of early unspecific signs of the disease (new-onset diabetes mellitus and weight loss) and to test selected miRNAs as markers of pancreatic cancer, with subanalysis according to specific criteria (diabetes mellitus/prediabetes, its type, weight loss, cancer stage and size of the primary tumor, presence of chronic pancreatitis in cancer patients). Patients and methods: We have included 77 patients with ductal pancreatic adenocarcinoma, 26 with chronic pancreatitis, 39 patients with type 2 diabetes mellitus without any tumor disease and 25 control subjects. In the cancer group, there were 60 patients who also had diabetes/prediabetes and 18 with chronic pancreatitis in their personal history. Significant weight loss (> 5 % of body weight in 3 months or > 10 % of body weight in 6 months) was observed in 52 patients with the cancer. Relative expressions of miRNAs (miR-21, miR-30, miR-192, miR-196, miR-200, miR-423) were measured in the serum by real-time PCR...
|
|
| |
guest ::
RSS feed.