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lmportance of epicardial fat in heart diseases: new mechanism of action and their therapeutic implication
Matloch, Zdeněk ; Haluzík, Martin (advisor) ; Maruna, Pavel (referee) ; Lipš, Michal (referee)
It was documented earlier that epicardial fat is a source of pro-inflammatory mediators under basal conditions (Mazurek, Zhang et al. 2003, Baker, Silva et al. 2006). It was also found that during cardiac surgery there is an increased expression of mRNA for pro- inflammatory cytokines in both epicardial and subcutaneous adipose tissue (Kremen, Dolinkova et al. 2006). During advanced heart failure, an inflammation of adipose tissue and resistance to adiponectin was also discovered (Khan, Kato et al. 2012). As part of the project, we tested the hypothesis that changes in levels of pro-inflammatory and anti-inflammatory cytokines, including their expression in adipose, muscle and heart tissue, as well as changes in insulin resistance and lipid profile parameters, are dependent on the type of underlying disease of patients, either the presence of CAD or valve degeneration. The aim of our project was to investigate metabolic changes in various fat tissues, insulin resistance, pro-inflammatory and anti-inflammatory cytokines plasmatic levels and their mRNA expressions in patients with coronary artery disease (CAD) undergoing either elective coronary artery bypass surgery (CABG) or isolated valve replacement. Our patients underwent several blood tests and measurements like anthropometric, biochemical, and...
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Molecular mechanisms linking adipose tissue dysfunction and atherosclerotic complications
Kratochvílová, Helena ; Haluzík, Martin (advisor) ; Bužga, Marek (referee) ; Cibičková, Ľubica (referee)
Obesity and its associated comorbidities increase the risk of mortality. The development of subclinical inflammation associated with obesity also plays a significant role in this. In our work, we focused on changes in the endocrine and mitochondrial function of adipose tissue and their relationship to cardiovascular complications. The first part of the thesis focuses on determining the expression of mitochondrial and endoplasmic reticulum genes in epicardial and subcutaneous adipose tissue, intercostal muscle or right myocardial atrium in patients with atherosclerotic coronary artery disease. Patients with coronary artery disease had reduced expression of several mitochondrial chain genes in epicardial adipose tissue compared to subcutaneous adipose tissue and other tissues, while no change in endoplasmic reticulum gene expression in the above-mentioned tissues has been demonstrated. Based on decreased mitochondrial gene expression in patients with coronary artery disease, we conclude that mitochondrial dysfunction of epicardial adipose tissue may contribute to the development of coronary atherosclerosis. The second part of the thesis is focused on neudesin, new potentional regulator of energy metabolism, in obese patients with type 2 diabetes mellitus (T2DM), who underwent various weight reduction...
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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 Effect of Bariatric Operations on the Compensation of Diabetes Mellitus
Horáková, Jitka ; Matoulek, Martin (advisor) ; Haluzík, Martin (referee)
This bachelor thesis deals with the problem of obesity and diabetes mellitus in today's society. The theoretical part brings a closer look at the problem of obesity, the complications resulting from it and the possible ways of therapy. Further it discusses the problem of diabetes mellitus and the influence of obesity on diabetes mellitus type 2 that causes serious health complications. The thesis describes the treatment options of the mentioned diseases, especially focusing on lifestyle changes (dietary regimen, physical activity) and bariatric surgery that significantly contributes to weight reduction and reduction of complications risks. The practical part of the thesis deals with the research in this area, comparing a group of diabetic and non-diabetic patients undergoing the bariatric surgery. Furthermore, it focuses on the impact of the bariatric surgery on the compensation of diabetes mellitus. Keywords: obesity, diabetes mellitus, dietary treatment, bariatric operations
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Reduction Modes to 3rd Medical Department in the Treatment of Obesity and Metabolic Syndrome and their Effect on the Outcome of Bariatric Operations
Jungová, Ivana ; Matoulek, Martin (advisor) ; Haluzík, Martin (referee)
(teze): Úvod: Redukční režimy na 3. interní klinice VFN Praha v léčbě obezity a metabolického syndromu a jejich vliv na úbytek hmotnosti po bariatrické operaci při aplikaci těsně před zákrokem. Metody: Porovnávání shromážděných dat týkajících se redukce hmotnosti v době před a 1 rok po bariatrickém zákroku pro dvě skupiny pacientů. Jedna skupina absolvovala těsně před operativním výkonem redukční pobyt. Druhá skupina byla přijata k operačnímu řešení z ambulantního režimu. Výsledky: Obě skupiny pacientů ve sledované době (1 rok po operaci) svou hmotnost významně redukovaly, vyšší úbytek v kilogramech po roce od zákroku byl zaznamenán u skupiny s redukčním pobytem (23,02 kg), u skupiny bez redukčního pobytu byl průměrný úbytek hmotnosti 21,17 kg. Po porovnání úbytku hmotnosti z průměrné hodnoty životního maxima skupin má významně vyšší redukci skupina s redukčním pobytem (51,9 kg), skupina bez redukčního pobytu redukovala ze svého životního maxima průměrně o 32 kg. Hodnota EWL (Excess Weight Loss) jeden rok po operaci byla vyšší u skupiny bez redukčního pobytu (39,36 %), u skupiny s redukčním pobytem dosáhla hodnoty 33,509 %. Stejně tak hodnotu EBMIL (Excess BMI Loss) měla skupina bez redukčního pobytu vyšší než skupina s redukčním pobytem. Procentuální roční úbytek hmotnosti byl u obou skupin...
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Signalling of protein kinase B and expression of cyclooxygenase in early phases of diabetic nephropathy
Ždychová, Jana ; Komers, Radko (advisor) ; Haluzík, Martin (referee) ; Matoušovic, Karel (referee) ; Škrha, Jan (referee)
Introduction: Renal hypertrophy, extracellular matrix accumulation, aItered apoptosis as well as changes in regional hemodynamics have been implicated in the pathophysiology of nephropathy in diabetes mellitus (DM). On the molecular level the detailed mechanisms for development of diabetic nephropathy (DN) have becn intensively studied. Insulin induces a variety of biologicaI effects in a number of cell types via phosphatidylinositol-3 kinase (PI3K)/Akt kinase signaling pathway. Considering multiple function of Akt that incIude potentiaIly hannful pro-growth effects mediated by mTOR and cyclooxygenas-2 (COX-2), as well as protective effects mediated by endotheliaI nitric oxide synthase (eNOS), it is possible that aIterations in activities of Akt may play role in the pathophysiology ofDN. Renal corticaI activity and expression of Akt, its down-strearn effectors mTOR, eNOS, and "C<JIX-:Z. as well as PTEN, an endogenous Akt inhibitor, were investigated in streptozotocin (STZ): diabetic rats as a model of Type 1 DM with different levels of glycenůc control, and in Zucker ~d.iabetic fatty rats, a model ofDM2, and in nondiabetic rats as controls. Methods: Akt activity was measured by kinase assay. Protein expressions were measured by .immunoblotting and immunohistochemistry in renal cortex of 4- and 12- week old...
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Neural mechanisms in the pathogenesis of spontaneous hypertension in the rat
Vavřínová, Anna ; Zicha, Josef (advisor) ; Haluzík, Martin (referee) ; Neckář, Jan (referee)
Both sympathoneural and sympathoadrenal systems are involved in the regulation of arterial blood pressure and in the pathogenesis of hypertension. Spontaneously hypertensive rats (SHR), the mostly used animal model of genetic hypertension, is characterized by multiple molecular, morphological and functional alterations at different levels of sympathoneural and sympathoadrenal systems. The study of young prehypertensive SHR allows to reveal the abnormalities preceding hypertension development, whereas adult SHR with established hypertension offers a better model for the treatment of human essential hypertension. The aim of my PhD Thesis was to describe abnormalities in sympathoneural and sympathoadrenal systems in SHR under different conditions. Firstly, ontogenetic differences which might contribute to hypertension development were determined. Secondly, the effect of chemical sympathectomy induced by guanethidine in adulthood on cardiovascular parameters and on the compensatory mechanisms counteracting the reduction of blood pressure were studied. Thirdly, stress-induced cardiovascular response and stress-induced changes of sympathoneural and sympathoadrenal systems were described in adult SHR. My Thesis brought several important results. The increased adrenal catecholamine content and the...
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New regulatory metabolic factors in patients with obesity and type 2 diabetes mellitus
Matějková, Mirka ; Haluzík, Martin (advisor) ; Flachs, Pavel (referee)
Fibroblast growth factors are proteins with diverse biological function in development, tissue repair, and metabolism. The human FGF gene family consists of 22 members. FGF 19 subfamily includes FGF 19, FGF 21, and FGF 23. They act as systemic factors in an endocrine manner. FGF 19 subfamily requires klotho protein as a cofactor for its action. FGF 19 produced by intestine acts mainly in the liver through FGFR4, where it inhibits bile acid and fatty acid synthesis. FGF 21 is produced by the liver and contributes to the regulation of carbohydrate and lipid metabolism through modulation of glucose uptake in adipocytes. Serum FGF 21 levels are increased in patients with obesity and type 2 diabetes mellitus. Serum FGF 19 levels are on the contrary decreased in patients with obesity and type 2 diabetes mellitus and more probably depend on the nutritional status of the organism than on the glucose metabolism and insulin sensitivity. Key words: type 2 diabetes mellitus, FGF 19, FGF 21, obesity, adipose tissue
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Genetics MODY diabetes
Dušátková, Petra ; Cinek, Ondřej (advisor) ; Haluzík, Martin (referee) ; Gašperíková, Daniela (referee)
The most common form of monogenic diabetes is MODY (Maturity-Onset Diabetes of the Young). It ranks among genetic defects of the β cell. It is clinically heterogenous group of disorders characterised with non insulin-dependent diabetes mellitus with autosomal dominant inheritance and age at diagnosis up to 40 years. We specified the diagnosis of MODY in more than 240 Czech families using molecular-genetic approach. The most common subtype of MODY is GCK-MODY which was proved in 376 subjects from 175 families. The risk of macrovascular complications in patiens with GCK-MODY was not detected. Additionally, we tested the ancestral origin of 4 recurrent mutations in the GCK gene causing GCK-MODY using genetic and statistical methods. We showed that three mutations (p.Glu40Lys, p.Leu315His, p.Gly318Arg) spread approximately 82-110 generations ago due to a founder effect. We also dealed with the impact of the rs560887 polymorphism on the phenotype of the patients with GCK-MODY. The genotype GG was associated with higher level of glycated haemoglobin. Analysis of patients suspect for HNF1A- or HNF4A-MODY revealed the probably first evidence of patient with HNF1A-MODY present with macrosomia and recurring ketotic hypoglycaemias in the childhood. The rare MODY genes were investigated in patients fulfilling the...
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