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Novel approaches to diagnosis and treatment of selected endocrine disorders
Ježková, Jana ; Marek, Josef (advisor) ; Haluzík, Martin (referee) ; Vladyka, Vilibald (referee)
Je známou zkušeností, že hyperkortizolismus urychluje aterosklerotické děje. Ty je možné sledovat ultrazvukovým vyšetřováním karotid a nověji též vyšetřováním cévní mikrocirkulace laser-Dopplerovskou metodou. Pro urychlení aterosklerotických změn u nemocných s Cushingovým syndromem jsou nesporně důležité známé faktory: hypertenze, obezita a hyperlipidemie. К nim se počítá zvýšená inzulínová rezistence, ale nemocní s floridním hyperkortizolismem mají normální hladiny glykemie a imunoreaktivního inzulínu. К aterogenezi u floridního hyperkortizolismu může přispívat zvýšená tvorba volných kyslíkových radikálů vznikajících při oxidaci lipidů a zvýšené hladiny pozitivního proteinu akutní fáze-orosomukoidu. Imunosupresivní charakter se projevuje snížením hladin autoprotilátek a snížením hladiny intercelulární adhezivní molekuly-1 (ICAM-1). К urychlení aterogeních dějů dochází i u nemocných, kteří jsou již dlouhou dobu po úspěšné normalizaci hyperkortizolemie. I když čerstvě operovaní a normalizovaní nemocní ztrácí do jednoho roku svou Cushingovskou obezitu, dochází později u operovaných nemocných opět к nadváze. Ta je spojena s poruchami lipidového spektra a u čtvrtiny nemocných i s hypertenzí. Nemocné po operaci pro Cushingův syndrom je nutné pravidelně sledovat, i když jsou dlouhodobě normalizováni. Je třeba u...
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The influence of pharmacology and reduction diet on metabolism of adipose tissue in obese patients with diabetes type 2
Anderlová, Kateřina ; Haluzík, Martin (advisor) ; Vítek, Libor (referee) ; Stárka, Luboslav (referee)
Insulin resistance, obesity, type 2 diabetes mellitus and their complications are linked together under definition called Metabolic or Reaven Syndrome. The presence of Metabolic Syndrome increases the risk of atherosclerosis and consequently cardiovascular morbidity and mortality. Metabolic Syndrome belongs among civilization diseases and due to changes in our life styles becomes major health and social-economic issue. The insulin resistance is considered primary pathology that may induce other components of Metabolic Syndrome. Research conducted within last decade brought significant results and showed how important is the adipose tissue in the development of insulin resistance especially in the context of discovery of endocrine function of adipose tissue. The existence of nuclear receptors PPAR (peroxisome proliferator activated receptor) could explain the interaction between particular tissues and hormonal factors which may induce insulin resistance. When the PPAR receptors are bound by lipophilic ligands they directly affect transcriptional processes in cell nucleus and induce expression of genes involved in metabolism of lipids and carbohydrates, in the regulation of inflammation, in tumor growth regulation, in immune response, in cell differentiation and etc. In current medical practice...
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Coincidental finding of hyperglycemia in children and adolescents
Feigerlová, Eva ; Lebl, Jan (advisor) ; Houšťková, Hana (referee) ; Haluzík, Martin (referee) ; Stárka, Luboslav (referee)
Donedávna se v souvislosti s diabetem v pediatrické populaci uvažovalo téměř výhradně O diabetu mellitu I. typu (Tl DM) s jeho typickou klinickou symptomatologií zahrnující polyurii, polydipsii, váhový úbytek a případně projevy ketoacidÓzy. Nyní na diabetes mellitus dětského věku a adolescence pohlížíme jako na heterogenní onemocnění zahrnující skupinu poruch s rozdílnou patogenezí, průběhem a odpovědí na léčbu (ADA 2005). V některých případech je klinická symptomatologie velmi sporá a může se omezit jen na náhodné zjištění mírné hyperglykémie v rámci vyšetřování pro různé klinické stavy. Náhodnou hyperglykémií se rozumí zvýšená glykémie nad referenční mez u jinak zdravého, klinicky asymptomatického jedince, stanovená z náhodného žilního odběru nalačno za bazálních podmínek (např. v rámci preventivní prohlídky) či během zátěžové situace (např. v průběhu akutně probíhající onemocnění, v souvislosti s chirurgickým zákrokem či úrazem). Dle definice (ADA 2005, WHO 1999) se za fyziologické považují hodnoty plazmatické glykémie nalačno nižší než 5,6 mmol/I za předpokladu dodržení podmínek preanalytické přípravy. Normální hodnota glykémie měřená 2 hodiny po standartní zátěži v průběhu OGTI (orálního glukózového tolerančního testu) je nižší než 7,8 mmolll. I přes existenci jasných kritérií nepovažuj í některé...
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The influence of deep hypothermia on the endocrine function of adipose tissue
Drápalová, Jana ; Haluzík, Martin (advisor) ; Flachs, Pavel (referee)
Introduction and aims: Deep hypothermia is a medical method used in a variety of car- diological operations. Adipose tissue is one of the main endocrine organs and therefore its en- docrine function significantly influences the state of a patient. The aim of this study was to explore the influence of deep hypothermia on the expression of selected proteins in adipose tissue, which has yet to be described in scientific literature. Material and methods: Samples of subcutaneous and visceral fat were taken from 10 pa- tients, who underwent planned surgery for pulmonary hypertension. The samples were taken at the beginning and the end of hypothermia, and at the end of the operation, respctively. Real-time PCR method was used to determine relative gene expression of selected adipocy- tokines (BCL-2, GLUT1, GPX1, HIF1- , IL-6, IRS1, MCP1, MIF, MT3, TNF-) from total fat and isolated adipocytes. Results: Gene expression of GLUT1 (total subcutaneous fat), HIF1- (total subcutaneous and visceral fat) and IL-6 a MCP-1 (in all tissues) at the end of the operation was significantly higher compared to the gene expression at the beginning and end of hypothermia. Gene ex- pression of TNF- in total subcutaneous fat increased significantly at the end of the operation compared to the beginning of hypothermia. Gene...
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Labeling of pancreatic islets with superparamagnetic iron oxide nanoparticles for magnetic resonance imaging
Berková, Zuzana ; Saudek, František (advisor) ; Mandys, Václav (referee) ; Haluzík, Martin (referee)
Type I diabetes mellitus is primarily an autoimmune disease resulting from selective destruction of insulin producing pancreatic beta cells. Transplantation of purified pancreatic islets is an alternative method for standard insulin therapy of these patients. Though the islet transplantation represents a promising approach for a selected group of patients, there is still a number of problems to be solved and one of them, perhaps the most important, is the lack of a reliable method of transplanted islets monitoring. (...) The results of this experimental study lead to the improvement of the labeling protocol in experimental transplantation and to its translation into clinical research. While different methods such as PET and SPECT will be soon available for shorttime in vivo followup of transplanted pancreatic islet, magnetic resonance imaging represents so far the only available technique able to provide a direct, longterm and reliable visualization of the transplanted islets with sufficient spatial resolution. At present, is this method ready for clinical application.
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Options of continual glycemia monitoring in critically ill patients and treatment of hyperglycemia with the use of insulin algorithms
Bláha, Jan ; Haluzík, Martin (advisor) ; Matějovič, Martin (referee) ; Vaněk, Tomáš (referee)
Glycaemia control is nowadays one of the most discussed topics in intensive care. The landmark Leuven study, which has brought hyperglycaemia in intensive care to the centre of interest, demonstrated that tight glycaemia control (TGC) targeted to maintain euglycaemia between 4.4 to 6.1 mmol/l reduced mortality and frequency of organ complications associated with critical illness. Although this study was published eight years ago, there is still no general agreement about approach to tight glycaemia control in critically ill patients. Doubts have been raised about both the universality of intensive glycaemia control, and especially its safety in terms of potential damage to patients by episodes of hypoglycaemia. Our studies did not focus on questions of importance or risk of TGC, but we concentrated on key point of hole TGC concept - on glycaemia control in critically ill patients itself. The aims of our studies were the research of subcutaneous adipose tissue as an alternative-site for continuous glucose measurements in ICU patients, and comparison and development of insulin algorithms for hyperglycaemia treatment and normoglycaemia management. We demonstrated good correlation between arterial and interstitial subcutaneous glucose concentrations in critically ill patients undergoing deep hypothermia. We...
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Adipose tissue and its role in development of insulin resistance and systemic inflammatory reaction
Roubíček, Tomáš ; Haluzík, Martin (advisor) ; Stárka, Luboslav (referee) ; Housa, Daniel (referee)
Hyperglycemia and insulin resistance are tightly interconnected pathophysiological conditions that increase the risk for development of cardiovascular diseases. Our current knowledge indicates that one of important reasons leading to the development of insulin resistance could lies in a dysfunction of adipose tissue with subsequent ectopic lipids accumulation in muscles and liver. Adipose tissue represents the main body storage site of energy. Furthermore, adipose tissue is also an active endocrine organ producing numerous biologically active molecules, e.g. cytokines, proinflammatory or to a lesser degree anti-inflammatory factors or components of the renin-angiotensin-aldosterone system. Some of the components of the local renin-angiotensin-aldosterone system produced by the adipose tissue can directly induce local insulin resistance within the adipose tissue. Hyperglycemia and insulin resistance are also common in critically ill patients and exaggeration of insulin resistance in these patients is accompanied by increased morbidity and mortality. Our previous study has demonstrated that adipose tissue plays an important role in the development of hyperglycemia and insulin resistance in critically ill patients by production of numerous proinflammatory cytokines. First part of this dissertation thesis is...
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Insulin secretion in women with polycystic ovary syndrome
Grimmichová, Tereza ; Haluzík, Martin (advisor) ; Marešová, Dana (referee) ; Rešlová, Taťána (referee)
Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies occuring in 5-10% women in their fertile years. The incidence of impaired glucose tolerance and diabetes mellitus type 2 is significantly increased in PCOS. Hyperinsulinaemia and insulin resistance are present in a relevant number of PCOS women. In our projects we therefore concentrated on various aspects of insulin secretion in PCOS women. We used different approaches and calculations, which are complementary to each other and provide a more detailed insight into possible beta cell dysfunction. Aims of our studies were 1) examine how the beta cell function is influenced by the family history of DM 2, 2) examine the insulin pulsatile secretion, 3) examine the secretion of incretins and 4) examine the prevalence of glucose intolerance and its potential prediction in PCOS women. 1) Decreased insulin sensitivity was observed only in PCOS women with the positive family history of DM 2 in comparison to healthy controls. If these women have normal glucose tolerance, they compensate the decreased insulin sensititivity by the increased insulin secretion. 2) Lean PCOS women had similar insulin pulsatile secretion patterns with the exception of broader insulin peaks in comparison to healthy controls. Insulin sensitivity was not associated...
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Endocrine function of adipose tissue and its role in development of atherosclerosis.
Bošanská, Lenka ; Haluzík, Martin (advisor) ; Vokurka, Martin (referee) ; Kříž, Jan (referee)
Adipose tissue represents a multi-functional endocrine organ. Obesity may lead to the increased release of proinflammatory factors and adhesion molecules from adipose tissue, thus playing an important role in the development of atherosclerosis. Recent research studies were focused on the mechanisms of the endothelial dysfunction, low-grade inflammation and adipose tissue endocrine function dysregulation, and their mutual relationships. These processes are of a great interest due to their clinical relevance and increasing numbers of patients suffering from cardiovascular diseases or being at high risk of early atherosclerosis progression. Exact mechanisms and interrelationships of these factors are yet to be fully clarified. (...) Results of this project may represent another step on the way to the detailed explanation of the mechanisms and relationships between adipose tissue endocrine function or dysfunction and atherosclerosis development. Better understanding and ability to prevent or treat the negative metabolic effects of adipose tissue-derived molecules would be of great importance for numbers of patients at high risk of cardiovascular diseases.
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