|
|
Toll like receptors and myeloid cells in development and disease
Balounová, Jana ; Filipp, Dominik (advisor) ; Špíšek, Radek (referee) ; Vannucci, Luca Ernesto (referee)
Toll like receptors (TLRs) are germline-encoded pattern recognition receptors (PRRs) that play a central role in host cell recognition and responses to pathogens. Primarily they are responsible for induction and regulation of the innate and adaptive immune responses whereby the effector function is executed chiefly by differentiated myeloid cells. Somewhat unexpectedly, TLRs have been also shown to be involved in direct pathogen sensing by bone marrow-derived hematopoietic stem cells (HSCs) and hematopoietic progenitors when, under inflammatory conditions, the rapid generation of innate immune effector cells that effectively combat the infection is of utmost priority. While it has been recognized that the release of inflammatory cytokines from inflamed tissues along with the changes in proportions of differentiating cells in the bone marrow (BM) as well as the BM niche can nudge the differentiation of adult BM-derived cells towards myeloid cells and granulocytes, a direct role of TLRs expressed by HSCs in this process has been demonstrated only recently. However, whether a similar mechanism operates also during embryonic hematopoiesis is unknown. Here we show that TLRs and their adaptor proteins are functionally expressed during early stages of embryogenesis by short-lived maternally-transferred...
|
|
|
Functional role of HIF-1-regulated pathway in diabetic nephropathy
Nepomucká, Kateřina ; Konvalinka, Jan (advisor) ; Jonáková, Věra (referee)
Diabetic nephropathy (DN) remains the most common cause of end stage renal failure. Nearly 10% of patients with diabetes develop nephropathy. Hyperglycaemia in the kidneys leads to the activation of alternative metabolic pathways of glucose (glycation, activation of protein kinase C, and polyol pathway). These biochemical alterations lead to hypoxia and oxidative stress due to the increased formation of reactive oxygen species (ROS). Cellular response to hypoxia is controlled by hypoxia-induced factor 1 (HIF1), which is involved in the regulation of more than 800 genes. Target molecules of the HIF1 pathway participate in a wide range of physiological and pathological processes, e.g. angiogenesis, energy metabolism, apoptosis, migration, and proliferation. DN is associated with the pathological tissue remodelling process, epithelial-mesenchymal transition (EMT), and inflammation. HIF1 regulates key molecules of these pathological processes. EMT is regulated by TGFß1, CTGF, and SOX9. The progression of inflammation is regulated by VEGFA and AngII. The exact role of HIF1 signalling in the development of DN is not yet fully understood. This thesis evaluates the functional role of the HIF1 signalling pathway in the development of DN using a global heterozygous mutant with the deletion of the Hif1α gene....
|
|
|
Effects of selected biologically active natural compounds on mammalian energy metabolism
Seďová, Karolína ; Flachs, Pavel (advisor) ; Doleželová, Šárka (referee)
Obesity is associated with many diseases, particularly type 2 diabetes, hypertension, dyslipidemia , hyperglycemia and cardiovascular diseases. If a patient experiences at least a trio of these diseases are diagnosed metabolic syndrome. The prevalence of obesity and related diseases has increased at an alarming rate in recent years and has become a worldwide health problem. Cardiovascular disease is the leading cause of death worldwide. Some minor components which are commonly found in our diet (eg some plant metabolites), directly or indirectly affect energy metabolism of our body and thus can reduce or even prevent developing health complications associated with the metabolic syndrome. This thesis, aims to clearly summarize the findings and results of scientific studies on selected plant metabolites occurring in extracts of specific plants that have preventive or therapeutic effects on obesity and other components of the metabolic syndrome. This work describes the use of these substances in the pharmaceutical industry and the food industry, the primary natural resources , and mechanisms of action , including effective doses. Powered by TCPDF (www.tcpdf.org)
|
|
|
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.
|
|
|
Mechanisms of insulin resistance and β - cell failure in type 2 diabetes. Effective diet against o minous octet
Kahleová, Hana ; Pelikánová, Terezie (advisor) ; Haluzík, Martin (referee) ; Vondra, Karel (referee)
Background and Aims: Dietary intervention is one of the key components in type 2 diabetes (T2D) management. Vegetarian diet is a promising alternative in the nutritional treatment of T2D. The aims of our study were: 1. To compare the effects of vegetarian and conventional diabetic diet with the same caloric restriction on insulin resistance, volume of visceral fat and plasma concentrations of oxidative stress markers after a 12-weeks-diet-intervention and subsequent 12-weeks of diet plus aerobic exercise training in subjects with T2D. 2. To explore the effect of 12 weeks of diet intervention and subsequent 12 weeks of diet combined with aerobic exercise training on -cell function and to evaluate the role of gastrointestinal peptides in subjects with T2D. 3. To study quality of life, Beck depression score and changes in eating behaviour in response to a vegetarian and a conventional diabetic diet. 4. To explore the role of changes in fatty acid composition of serum phospholipids in diet-induced changes in insulin sensitivity in subjects with T2D. 5. To follow-up our patients 1 year from the end of the intervention.
|
|
| |
|
|
The Dog as a Supporting Part in Caring for Different Target Groups of Clients
Pecharová, Marie ; Vodáčková, Daniela (advisor) ; Havránková, Olga (referee)
The theoretical part describes the history and theory in the zoo-rehabilitation and canis- rehabilitation, its use as a therapy to improve physical and mental health on specific examples in each of the health and social area. In the area of assistance dogs and introduces the history of the field, with the methodology of selecting an appropriate dog and its training for the disabled. For signal dogs describes the history, function as a guard dog health deterioration of the patient when a dog detects, for example. upcoming epileptic seizure, diabetic coma, etc. Deaf dog for his master's notes on the sounds, for which it is trained. In the use of the dog - the mediator shows the use of a different method of communication when the dog is a mediator between the client and the therapist. It is used in situations where they are unable to make contact with the client. In the research section analysed the answers of helping dogs to questions posed in the questionnaire, and evaluated their experience with them. The questionnaire was, together with an accompanying letter handed over to organizations carrying out training to assist dogs. These organizations also have sent my cover letter with the questionnaire to its clients, and the clients themselves have filled in questionnaires and returned...
|
|
|
Differentiation of adult stem cells into insulin-producing beta cells
Koblas, Tomáš
Ph.D. Thesis abstract: Diabetes mellitus is a chronic disease characterized by a metabolic disorder in which there is a low level or complete lack of the insulin. Diabetes mellitus type 1 (DM1) is caused by an autoimmune reaction leading to the destruction of the insulin producing beta cells in the pancreas. In consequence, low or non-existent insulin production leads to a complete dependence on exogenous insulin supplementation. DM1 causes serious long-term complications. Although strict control of blood sugar could prevent the onset and development of diabetic complications only 5% of diabetic patients are able to achieve such control. Hence it is evident that the current methods of treatment are neither sufficient to treat this disease, nor prevent late complications in most patients. The most promising therapeutic approach in the treatment of diabetes is the restoring of insulin production. One such method is the transplantation of insulin-producing tissue. However, a lack of available insulin- producing tissue limits such therapeutic approach. Therefore an alternative source of insulin producing cells have to be found to obtain a sufficient amount of safe and efficient insulin producing tissue. Pancreatic stem/progenitor cells could represent such an available alternative source. Despite the evidence...
|
|
|
Role of peripheral blood monocytes and innate immunity in diabetes
Zinková, Alžběta ; Daňková, Pavlína (advisor) ; Novota, Peter (referee)
Introduction: Diabetes mellitus is a polygenic disease and its development is influenced to some extent by environmental factors as well. Innate immunity triggers nonspecifically first defense reactions after penetration of the pathogen into the body, while overstimulation components of innate immunity may give rise to autoimmune diseases, including diabetes type 1. The components of innate immunity are, among others, Toll-like receptors (TLRs) belonging to a group of the structures recognizing preserved molecular structures characteristic of pathogens. Toll-like receptors are abundantly expressed by monocytes which produce prolactin (PRL) having an immunostimulatory function. To clarify the role of innate immunity in the pathogenesis of diabetes, we focused on the expression of mRNA and protein expression of TLR2 and TLR4. The expression of PRL was studied only at the level of mRNA. Monocytes were separated by flow cytometry into classical (CD14++) and nonclassical (CD14+). We monitored their percentages and the degree of expression of CD14 antigen on their surface.The operational objective of this dissertation was to optimize the stimulation of monocytes for the planned study of the function of non-pituitary prolactin in vitro and determine the appropriateness of the use of healthy donors' buffy...
|
|
|
Molecular mechanisms in diabetic embryopathy
Čerychová, Radka ; Pavlínková, Gabriela (advisor) ; Kolář, František (referee)
Diabetic embryopathy is one of many serious complications associated with diabetes. It is known that maternal diabetes increases the frequency of congenital defects up to ten times. The most common defects are cardiovascular and neural tube defects. Molecular mechanisms of diabetic embryopathy are still not known. This work contributes to elucidation of molecular processes leading to development of cardiovascular defects in diabetic embryopathy. This study is based on observation that maternal diabetes affects transcriptional regulation of hypoxia-inducible factor 1 (HIF-1) in developing embryo. To study the influence of maternal diabetes on HIF-1 signaling pathway, we used mouse model heterozygous for "knock-out" of Hif1α gene. Our analyses showed the negative combinational effects of maternal diabetes and Hif1α+/- genotype on embryonic development and increased risk of diabetic embryopathy. Histological analysis demonstrated the increased incidence of cardiovascular defects, particularly defects of interventricular septum and hypoplastic compact left ventricular wall in embryonic day (E) 14.5 Hif1α+/- embryos compared to wt littermates from the diabetic pregnancy. Using qPCR, we analyzed gene expression changes in the embryonic hearts at E9.5 and E10.5. We selected genes important for the...
|
guest ::
