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The size of individual lipoproteins in various pathological conditions
Dušejovská, Magdaléna ; Žák, Aleš (advisor) ; Kalousová, Marta (referee) ; Kraml, Pavel (referee)
Metabolic syndrome (MS) and end-stage renal disease (ESRD) represent two clinical- pathologic states with increased risk of atherosclerotic cardiovascular complications with considerable impact on the quality of life of the patients. The knowledge about the changes in distribution of individual lipoprotein subfractions could countribute to the estimation of risk of atherosclerosis development. The studies presented in this thesis aimed at analyses of subfractions of LDL and HDL in the abovementioned pathologic states; moreover, we tried to elucidate the associations of changes in lipoprotein subfractions with clinical as well as biochemical alterations. The Study I was a placebo controlled study observing the effect of polyunsaturated fatty acids of n-3 family (PUFA n-3) administration to patients with MS who were divided to statin-treated ones (36 patients), and those without statin therapy (24 probands). The Study II comprised of 57 patients with ESRD on high volume haemodiafiltration (HV-HDF). In this Study, the parameters after 5-year follow-up were compared with baseline characteristics. Also, we included comparisons with the control group of 50 age and sex matched patients without the signs of ESRD. In Study I, we observed lowering of triacylglycerol and cholesterol content in VLDL...
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Genetic factors responsible for development of metabolic syndrome
Mirchi, Lukáš Farhád ; Liška, František (advisor) ; Černá, Marie (referee) ; Mlejnek, Petr (referee)
Metabolic syndrome (MetS) is a worldwide highly prevalent disease defined as a clustering of at least three of the following conditions: central obesity, hypertension, diabetes, high level of low-density lipoproteins, low level of high-density lipoprotein or high level cholesterol. MetS is a multifactorial disease which is caused by both environmental factors and a heritable component. Unfortunately, because of its ever rising worldwide incidence MetS emerges as a worldwide epidemic and a heavy socioeconomic burden. In order to effectively fight the MetS pandemic, it is vital to dissect the genetic background and mechanisms that underlie MetS and its individual components, a goal that is profoundly benefitted by physiological and genetic studies in animal models of MetS. The aim of this thesis was to dissect the genetic background of metabolic syndrome by using comparative transcriptomic analysis in relevant organs obtained from genetically defined rodent models. Each of our genetically defined rat strains is phenotypically distinct in terms of manifesting individual components of MetS. We present three separate transcriptomic experiments in order to unravel the genetic background of MetS. First, we performed the global comparative transcriptomic analysis of left ventricular tissue from SHR and...
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Nonlinear methods of heart rate variability analysis in metabolic syndrome
Vaňková, Eliška ; Kozumplík, Jiří (referee) ; Kubičková, Alena (advisor)
This work deals with the problematic of heart rate variability of patients with metabolic syndrome. Includes the theory, which describes the heart rate variability and the methods for its analysing. Especially it specifies nonlinear methods, particularly Lyapunov exponent and its calculation in Matlab software. Algorithm of the calculation is applicated to already measured tachogram of the healthy people and patients with the metabolic syndrome. Further, this work deals with general valorization of the results using Lyapunov exponent and her eis also done the statistical evaluation.
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Automatic Analysis of Heart Rate Variability Signals
Kubičková, Alena ; Halámek, Josef (referee) ; Lhotská, Lenka (referee) ; Kozumplík, Jiří (advisor)
This dissertation thesis is dedicated to the heart rate variability and methods of its evaluation. It mainly focuses on nonlinear methods and especially on the Poincaré plot. First it deals with the principle and nature of the heart rate variability, then the ways of its representation, linear and also nonlinear methods of its analysis and physiological and pathophysiological influence on heart rate variability changes. In particular, there is emphasis on the metabolic syndrome. In the next section of the thesis there are compared and evaluated different ways of representation of the heart rate variability and further are tested selected methods of heart rate variability analysis on unique data from patients with the metabolic syndrome and healthy subjects provided by the Institute of Scientific Instruments, Academy of Sciences of Czech Republic. In particular, they are used the Poincaré plot and its parameters SD1 and SD2, commonly used time domain and frequency domain parameters, parameters evaluating signal entropy and the Lyapunov exponent. SD1 and SD2 combining the advantages of time and frequency domain methods of heart rate variability analysis distinguish successfully between patients with the metabolic syndrome and healthy subjects.
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Mechanisms of comorbidity of metabolic and neurodegenerative diseases
Tauchman, Martin ; Telenský, Petr (advisor) ; Brožka, Hana (referee)
In Czechia, number of people with neurodegenerative diseases is in the hundreds of thousands, and the lifetime health care costs and social impact of each patient's disease reach hundreds of thousands of euros, but these costs could be reduced by early and effective intervention. Its correct implementation could be helped by knowledge of causal links between neurodegenerative and metabolic diseases, whose prevalence is correlated in the population. One of the important factors is an increased pro-inflammatory immune response. In people with obesity and type 2 diabetes mellitus, systemic inflammation evolves into neuroinflammation, which subsequently leads to neurodegeneration. Another mechanism is hyperglycaemia, which is a consequence of insulin resistance. Hyperinsulinaemia and hyperglycaemia lead to impaired expression of glucose transporters and insulin-degrading enzyme, resulting in reduced clearance of amyloid beta. Genetic background is also recognized as a highly influential factor, affecting various mechanisms in both beneficial and harmful ways. Lifestyle is also an important factor. In general, smoking and alcohol consumption are harmful to health. Both increased consumption of alcoholic beverages and smoking tobacco products can lead to metabolic disorders as well as neurodegeneration. On the...
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Nutrigenetic analysis of metabolic syndrome: the role of spontaneously hypertensive rat chromosome 4
Petrů, Karolína ; Šeda, Ondřej (advisor) ; Malínská, Hana (referee)
Metabolic syndrome (MetS) is a complex condition with a number of interacting genes, epigenetic and environmental factors underlying its pathogenesis. The analysis of genetic component of MetS showed that number of defining parameters of the syndrome is linked to regions of rat chromosome 4. In order to verify these quantitative trait loci (QTL), a double congenic strain was derived with parts of chromosome 4 of spontaneously hypertensive rat (SHR, an inbred MetS model) origin introgressed onto genomic background of congenic Brown Norway strain (BN-Lx). The aim of the proposed thesis is comprise detail genetic mapping of differential segments of the above mentioned double congenic strain BN-Lx.SHR4 and comparison of its metabolic profile under different dietary conditions with varying carbohydrate and fat content. Utilizing DNA sequence and gene expression comparisons, candidate genes or polymorphisms for the MetS aspects and potential nutrigenetic interactions will be identified. Key words: nutrigenetics, experimental models, metabolic syndrome, congenic strain, genotyping, rat
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Peptides regulating food intake and their role in metabolic syndrome
Buderová, Markéta ; Maletínská, Lenka (advisor) ; Hojná, Silvie (referee)
Unhealthy lifestyle together with genetic factors can lead to serious health problems like metabolic syndrome (MetS). MetS is a cluster of risk factors such as abdominal obesity, dyslipidemia, insulin resistance and hypertension. Each component of MetS contributes to cardiovascular diseases, type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease. Treatment of MetS is primarily focused on lifestyle modification, especially weight loss. In severe cases, pharmacological treatment is also used. Pharmacological treatment includes peptide analogues that regulate food intake. Anorexigenic (food- reducing) peptides are involved in the regulation of food intake, together with orexigenic (food- increasing) peptides, which thus play an important role in maintaining energy homeostasis. Several analogues of anorexigenic peptides regulating food intake are already used for the treatment of obesity or T2DM. Other peptide analogues are in preclinical stages of testing or in the development of stable analogues. Elucidating the physiology and pathology of both anorexigenic and orexigenic peptides in the regulation of food intake may contribute to finding potential treatments for metabolic, cardiovascular, and other disorders.
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Effects of stable analogs of anorexigenic neuropeptides in models of metabolic syndrome
Mráziková, Lucia ; Maletínská, Lenka (advisor) ; Kříž, Jan (referee) ; Bardová, Kristina (referee)
Obesity is a worldwide health problem and an effective treatment is still scarce. Anorexigenic neuropeptides, such as prolactin-releasing peptide (PrRP), have a potential for the treatment of obesity and its complications, but in their natural form they have several limitations such as poor bioavailability, low stability and inability to cross the blood-brain barrier after peripheral administration. Recently we have designed lipidized analogs of PrRP. Lipidization makes this peptide more stable and able to act centrally after peripheral administration. The aim of this study was to investigate the chronic effect of PrRP palmitoylated at position 11 (palm11 -PrRP31) on obesity and obesity-related metabolic parameters and to clarify mechanisms of its action. We used three rodent models of obesity: Wistar Kyoto (WKY) rats with high-fat diet-induced obesity (DIO) having intact leptin and leptin receptor as well as rodents with disrupted leptin function: leptin deficient ob/ob mice and fa/fa rats with a disturbed leptin signaling. Consumption of a high-fat diet in DIO WKY rats increased their body weight, caused strong glucose intolerance and increased liver mRNA expression of enzymes of de novo lipogenesis. Palm11 -PrRP31 treatment significantly decreased cumulative food intake, body weight, plasma...
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Selected aspects of methotrexate treatment in patients with rheumatoid arthritis
Hloch, Karel ; Pávek, Petr (advisor) ; Souček, Miroslav (referee) ; Tomčík, Michal (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Training Workplace Department of Social and Clinical Pharmacy Doctoral Degree Program Clinical and Social Pharmacy Candidate MSc. Karel Hloch Supervisor prof. PharmD. Petr Pávek, Ph.D. Advisor assoc. prof. MUDr. Tomáš Soukup, Ph.D.; PharmD. Martin Doseděl, Ph.D. Title of Doctoral Thesis: Selected aspects of methotrexate treatment in patients with rheumatoid arthritis Introduction and objectives Rheumatoid arthritis (RA) is an autoimmune disease typically connected with chronic inflammation of the joints, causing their swelling and pain. The prevalence of RA is about 1% in the general population. A crucial role in higher morbidity and mortality in RA patients has been associated with increased inflammatory activity. Methotrexate (MTX), a drug with immunosuppressive activity, is the most frequent drug of choice used in RA therapy. It seems that main anti-inflammatory effect is mediated via release of purine nucleoside adenosine. The status of patients with inflammatory diseases is influenced by activation of A2a and A3 adenosine receptors. High caffeine (adenosine receptor antagonist) consumption may therefore lead to alteration of MTX treatment efficacy. 1) The aim of first study was to determine whether RA patients who had discontinued...
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