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Antiproliferative effects of heme catabolic pathway's products
Koníčková, Renata ; Vítek, Libor (advisor) ; Haluzík, Martin (referee) ; Farghali, Hassan (referee)
Presented work is focused on heme metabolism with the main interest in bile pigments. Recent data indicate that bilirubin is not only a waste product of the heme catabolic pathway, but also emphasize its important biological impacts, including possible antiproliferative effects. Until today metabolism of bilirubin has not been completely elucidated, which has prevented detailed evaluation of its potential anticancer action. The aim of this study was to clarify some aspects of heme catabolism with respect for antiproliferative properties of its products. Based on the fact that bilirubin potently affects carcinogenesis of the intestine, we initially investigated not properly known bilirubin metabolism by intestinal bacteria. We studied bilirubin neurotoxic effects in hyperbilirubinemic Gunn rats - its distribution in the brain tissue and its degradation during pathological conditions, such as severe newborn jaundice or Crigler-Najjar syndrome. Possible approaches to improve the treatment of severe unconjugated hyperbilirubinemias, combination of the phototherapy and human albumin administration were also investigated. The main reason of these studies was the fact that mechanisms of neurotoxic effects of bilirubin are predominantly identical with those, by which bilirubin inhibits cancer cells growth....
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The role of adipose tissue in the pathophysiology of obesity and anorexia nervosa
Kratochvílová, Helena ; Haluzík, Martin (advisor) ; Pavlišová, Jana (referee)
The view of adipose tissue and its significance in human pathophysiology has changed substantially in the recent couple of years. It has been shown that adipose tissue is not only a passive storage site for excess energy, but that it actively participates in the maintenance of whole-body homeostasis as an endocrine organ producing various hormones and other biologically active molecules, which by acting in an endocrine, paracrine as well as autocrine fashion affect different organs and systems. An intact regulation of adipose tissue processes plays an important role in sustaining the integrity of the organism, whereas its defects lead to the development of a number of diseases. This thesis focuses primarily on the significance of adipose tissue in the pathogenesis of obesity and anorexia nervosa. In the last years, the incidence of obesity rapidly increases ranking, along with its complications, among the world's leading health problems. Obesity is associated with endocrine dysfunction of adipose tissue characterized by disrupted production of adipose tissue hormones and cytokines resulting in the development of numerous disorders including type 2 diabetes mellitus and cardiovascular diseases. A completely opposite disorder, where, however, adipose tissue, or more precisely the absence of it, plays...
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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.
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The influence of central serotoninergic and dopaminergic activity on nutritional and metabolic parameters
Brunerová, Ludmila ; Anděl, Michal (advisor) ; Haluzík, Martin (referee) ; Yamamotová, Anna (referee)
THE INFLUENCE OF CENTRAL SEROTONINERGIC AND DOPAMINERGIC ACTIVITY ON NUTRITIONAL AND METABOLIC PARAMETERS MUDr. Ludmila Brunerová SUMMARY Introduction: Neuromediators dopamine and serotonin play a significant role in homeostatic and hedonic regulation of food intake, may exert direct metabolic effects and particularly serotonin influences affectivity. Their central activity could be quantified by functional tests. Common regulatory mediators of metabolism and affectivity represent an interesting research goal. Aims of study: The first aim was to describe the relationship between central serotoninergic activity measured by citalopram challenge test, affectivity, preference of macronutrients in food and metabolic profile in healthy men. The second aim was to confirm the use of sublingual apomorphine test as a functional test for assessment of central dopaminergic activity. The third aim was to reveal the relationship between central dopaminergic activity measured by sublingual apomorphine test, preference of macronutrients and metabolic profile. Methods: The study was performed on 42 healthy men (average age 43.5 ± 7.4 years and average BMI 27.4 ± 5.7 kg/mš) within 4 days with a week interval in between them. Anthropometric and...
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Bipolar Disorder and Diabetes Mellitus
Růžičková, Martina ; Höschl, Cyril (advisor) ; Haluzík, Martin (referee) ; Papežová, Hana (referee)
Despite lots of research, the genetic and pathophysiological basis of bipolar disorder (BD) remains unclear. One of the possible reasons is that BD spectrum comprises a heterogeneous group of different subtypes of the illness sharing certain pathophysiological or genetic mechanisms. Patients with co-morbid diabetes mellitus (DM) may represent such a subgroup of BD with a distinct pathophysiology and possibly different clinical characteristics of BD. This thesis is aimed at investigating the possible link between BD and DM. Bipolar patients have about 3 times higher risk of DM (type 2 in particular). The first part of my thesis outlines the possible links between DM and BD, including medication, alterations in the hypothalamo-pituitary axis and signal transduction, and genetics. In the second part, I examined the possible differences in clinical characteristics between patients with (N=26) and without (N=196) co-morbid DM. Next, I examined the variables showing differences between groups, using logistic regression. Patients were recruited via The Maritime Bipolar Registry. The prevalence of DM was 11.7%. Diabetic patients were significantly older than non-diabetic patients (P < 0.001), had higher rates of rapid cycling (P = 0.02), more chronic course of BD (P = 0.006), more disability (P < 0.001), lower...
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Novel metabolic regulators and proinflammatory factors in the etiopathogenesis of type 2 diabetes mellitus and obesity: the influence of pharmacological and dietary interventions
Mráz, Miloš ; Haluzík, Martin (advisor) ; Šenolt, Ladislav (referee) ; Hainer, Vojtěch (referee)
NOVEL METABOLIC REGULATORS AND PROINFLAMMATORY FACTORS IN THE ETIOPATHOGENESIS OF TYPE 2 DIABETES MELLITUS AND OBESITY: THE INFLUENCE OF PHARMACOLOGICAL AND DIETARY INTERVENTIONS MUDr. Miloš Mráz Doctoral Thesis ABSTRACT (EN) Identifying novel factors involved in the etiopathogenesis of obesity, diabetes mellitus and their complications has become one of the primary scopes of metabolic research in the last years. The aim of the present study was to evaluate the role of recently discovered metabolic and inflammatory regulators including fibroblast growth factors 19 and 21 and chemotactic cytokines in the development of obesity and type 2 diabetes mellitus (DM2). A total number of 182 patients were included into the study. They were divided into 3 groups - patients with obesity but without type 2 diabetes mellitus, individuals with obesity and type 2 diabetes mellitus and healthy control normal-weight subjects. Selected interventions included 2 to 3 weeks of very-low-calorie diet (VLCD - energy content 2500 kJ/day), 3 months of administration of PPARα receptor agonist fenofibrate and acute hyperinsulinemia during hyperinsulinemic isoglycemic clamp. Our results indicate that the increase of circulating FGF-21 levels after VLCD and fenofibrate treatment could contribute to positive metabolic effects of these...
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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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Preparation and characterization of GlnB22-insulin, a naturally occurring mutant in diabetic patients
Křížková, Květoslava ; Žáková, Lenka (advisor) ; Haluzík, Martin (referee)
Diabetes mellitus is a widespread disease which can be diagnosed in all age groups from newborns to seniors. Diabetes has multiple causes. The final disorder of blood glucose regulation is caused by a complex of factors and agents, in many cases by genetic defects connected with an unhealthy lifestyle. Moreover, a recently discovered form of diabetes, referred to as the monogenic diabetes, results from a gene mutation whereby only a single gene defect causes the onset of disease. The gene encoding the insulin primary structure belongs to several fundamental genes. Each change in a peptide chain is unique and leads to variation in this disease. Diagnosing patients with this mutation results in more detailed specification of their treatment and often also in the improvement of their living conditions. Mutations of the insulin gene have various symptoms. Some of the changes lead to the neonatal diabetes and patients are fully addicted to insulin since their birth. Other variations will never break out at their carriers. Seriousness of the disease course depends on characteristics of an original amino acid, its function in the insulin biosynthesis, its interaction with the insulin receptor, and on characteristics of a newly inserted amino acid and its influence on natural processes. The pathogenic...
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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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