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The role of stable analogs of prolactin-releasing peptide in obesity and hypertension.
Neprašová, Barbora ; Maletínská, Lenka (advisor) ; Poledne, Rudolf (referee) ; Rossmeisl, Martin (referee)
Anorexigenic neuropeptides have the potential to decrease food intake and ameliorate obesity and its complications such as high blood glucose or high blood pressure. However, they are not able to cross the blood-brain barrier after peripheral application. Recently, we have designed and synthesized lipidized analogs of prolactin-releasing peptide (PrRP), which resulted in stabilization of the molecule and allowed us to apply the peptide to the periphery to achieve its central biological effect, as it was demonstrated by increased neuronal activity shown by c-Fos in particular hypothalamus nuclei. The aim of this study was to choose the effective dose in acute food intake experiments and then to characterize the subchronic effect of palmitoylated PrRP analogs in mouse and rat models of obesity and diabetes. Several animal models were used: diet-induced obese (DIO) mice (C57Bl/6J), DIO Sprague-Dawley rats, and two rat models with leptin receptor-deficiency: Zucker diabetic (ZDF) rats and spontaneously hypertensive (SHROB) rats. Consumption of a high-fat diet in DIO mice and rats increased their body weight and blood pressure. Two-week intraperitoneal treatment with palmitoylated PrRP31 lowered the food intake, body weight, and returned the blood pressure to normal levels. This treatment also improved...
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Physiological aspects of body composition measurements
Větrovská, Renata ; Matoulek, Martin (advisor) ; Poledne, Rudolf (referee) ; Brychta, Tomáš (referee)
Determination of body composition or amount and decomposition of body fat belongs to the basic clinical examination of an obese patient. But methods used to determine the amount of fat in obese population are often innacurate. And it's adipose tissue and its measurable parameters which can provide us range of information for the further process of the reductive treatment. The main goal of this work is to evaluate the physiological aspects of body composition measurement in several areas: (I) To determine whether the values of body fat measured by most commonly used methods are comparable to those measured by method DEXA. (II) To determine whether the values of the amount of body fat measured by different methods vary depending on the amount of BMI and adipose tissue in the body and assess whether the available bioimpendance methods can measure the functional state of body fat. (III) To assess the resting energy expenditure in relation to body composition and physical activity. (IV) To determine whether the body composition will affect the resulting reduction after excercise program for women with overweight and obesity. (V) To verify whether changes in the values of BOHB (Beta Hydroxybutyrate) after physical activity could be the predictor of weight losses and changes of body composition. Based on...
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Effect of selected nutrients on skeletal muscle mitochondrial metabolism
Tůmová, Jana ; Anděl, Michal (advisor) ; Poledne, Rudolf (referee) ; Drahota, Zdeněk (referee)
Skeletal muscle plays an important role in the maintenance of whole-body metabolic homeostasis. Metabolic alterations of skeletal muscle contribute to the pathogenesis of a wide range of human diseases, such as obesity, type 2 diabetes and hypertension. Relative excess and suboptimal composition of nutrients negatively affect skeletal muscle metabolism and a better understanding of mechanisms involved in these changes is of central importance. The aim of the work presented in this thesis was to explore cell viability and mitochondrial respiratory parameters following experimentally induced changes in the availability or composition of selected nutrients (fatty acids and glutamine). We attempted to elucidate the mechanisms responsible for the observed changes, such as mitochondrial DNA (mtDNA) damage, or nuclear receptors activation. The studies were performed in vitro on skeletal muscle cell culture models. In addition, we examined mitochondrial function and fat accumulation in skeletal muscle of vegans, i.e. subjects consuming a strict plant-based diet. Using C2C12 skeletal muscle cells we studied the effects of free fatty acids (FFA). We found that relatively low doses of saturated palmitic acid increased hydrogen peroxide production and induced mtDNA damage, mitochondrial respiratory dysfunction...
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The use of PAPP-A/proMBP complex in early diagnosis and prevention of coronary artery disease and in the improvement of therapeutic and preventive care of patients and their families in risk.
Hájek, Petr ; Macek, Milan (advisor) ; Kalousová, Marta (referee) ; Poledne, Rudolf (referee)
Majority of medical decisions are based on results of diagnostic tests that help to differentiate normal from abnormal. The choice of appropriate test and its intepretation are neccessary steps for correct diagnosis and treatment strategy determination. Rapid prove of acute coronary syndrome (ACS) plays a key role in choice of optimal treatment strategy, because timing of intervention directly influences prognosis of the patient. Pregnancy-associated plasma protein-A (PAPP- A) has been studied as a promising marker of ACS. For PAPP-A evaluation in patients with coronary atherosclerosis, we have chosen commercially available system Kryptor that had been verified in prenatal screening of pregnancies in risk. PAPP-A belongs among metalloproteinases. It is important marker of physiological development of placenta and fetus. The only proven physiological role of PAPP- A is the enabling of bioavailability of insulin-like growth factor (IGF). IGF as a growth factor, plays significant role in atherosclerosis development, but also it might contribute to healing processes connected with tissue injury. Nevertheless, PAPP-A role in plaque destabilization has not been proven yet, although it was found in other metaloproteinases. In our pilot study, we confirmed the use of Kryptor system also for patients with coronary...
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Pathogenesis of hypercholesterolemia in Prague hereditary hypercholesterolemic (PHHC) rat
Rybáková, Kateřina ; Vlachová, Miluše (advisor) ; Poledne, Rudolf (referee)
Hypercholesterolemia represents a major risk factor of cardiovascular disease. A number of experimental models is used for study of hypercholesterolemia pathogenesis and therapy. This thesis concentrates on characterization of one of these models. Prague hereditary hypercholesterolemic (PHHC) rat is such a suitable model for study of hypercholesterolemia. Although the majority of plasma cholesterol is transported by high density lipoprotein in PHHC rat fed standard diet, PHHC rat fed cholesterol diet develops hypercholesterolemia comparable to that of humans. The advantage of this model is that hypercholesterolemia develops without the need for addition of bile acids or other hepatotoxic substances to the diet. The hypercholesterolemia of PHHC rat is caused by slowed down catabolism of cholesterol-rich very low density lipoprotein (VLDL). These cholesterol-rich particles are synthesized in the liver. We found out that PHHC rat fed 1% cholesterol diet accumulates cholesteryl esters (CE) in the liver and also in the VLDL. Acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP) may participate in the increased incorporation CE into VLDL. We found out no difference in ACAT and MTP activities in the liver between PHHC rats and control animals. Neither ACAT activity...
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Pathophysiology and clinical implications of late coronary thrombosis after implantation of drug eluting stents in patients with manifest atherosclerosis
Jakabčin, Jozef ; Červinka, Pavel (advisor) ; Poledne, Rudolf (referee) ; Mates, Martin (referee)
Pathophysiology and clinical implications of late coronary thrombosis after implantation of drug eluting stents in patients with manifest atherosclerosis Abstract Drug-eluting stents (DES) have markedly reduced restenosis rates compared with bare metal stents (BMS) in controlled randomized trials. Concerns have been raised about a possibly increased incidence of stent thrombosis (ST) after discontinuation of dual antiplatelet treatment compared with BMS. While a restenosis is relatively benign process, this serious complication is an issue because mortality of such event is reaching almost 50%. Among well recognized predictors of late stent thrombosis (delayed endothelisation, renal failure, bifurcation lesions, diabetes, premature antiplatelet therapy discontinuation, slow thrombus disappearance), the stent under expansion and stent deployment technique are also considered to be a contributor for development of late stent thrombosis. There was a paucity of data regarding the IVUS guidance during DES implantation. The aim of this study was to assess the role of IVUS guidance during implantation of DES on longterm outcome in patients with high clinical and angiographic risk profile. Methods: Between January 2004 and December 2005, 2110 patients underwent percutaneous coronary intervention, including 276...
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Iron metabolism, oxidative stress and progression of atherosclerosis
Syrovátka, Petr ; Kraml, Pavel (advisor) ; Poledne, Rudolf (referee) ; Vokurka, Martin (referee)
Ferritin, oxidative stress and insulin resistance Aim: The aim of our cross-sectional study was to assess the relationships between body iron stores, oxidative stress and impaired insulin sensitivity in a cohort of healthy men in primary prevention of cardiovascular disease. Methods: We examined 151 volunteers, aged 35- 60 years. Anthropometric parameters, markers of metabolic syndrome, insulin resistance, inflammatory markers, parameters of oxidative stress and parameters of endothelial dysfunction were measured. Results: Ferritin correlated positively with waist circumference, body mass index, impaired insulin sensitivity, plasma triglycerides and inversely with high-density lipoprotein cholesterol. We observed positive correlations between ferritin, oxidized low-density lipoprotein and advanced oxidation protein products after adjustment for age, waist circumference, body mass index and measured inflammatory markers (high-sensitivity C-reactive protein, fibrinogen, interleukin-6 and tumor necrosis factor-α). In a stepwise multiple regression analysis, triglycerides, waist circumference and elevated transaminases were independent determinants of the serum ferritin level. Conclusions: Our results provide evidence for a relationship between plasma ferritin and oxidative modification of lipids as...
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Factors influencing the metabolism of homocysteine in selected diseases with complex etiopathogenesis
Veselá, Kamila ; Anděl, Michal (advisor) ; Nečas, Emanuel (referee) ; Rušavý, Zdeněk (referee) ; Poledne, Rudolf (referee)
At present, the great medicine to develop molecular genetic techniques, which significantly help to explain the causes of illnesses. In some diseases the genetic basis is well known. These are primarily contingent on monogenic diseases. Unfortunately, many diseases remain the genetic cause is still unknown. The largest group is the so-called complex diseases, where the origin and development of disease involving both genetic and nongenetic factors. These diseases include atherosclerosis, diabetes mellitus, orofacial clefts, preeclampsia, neural tube defects, and many others. Complex diseases are serious health and social problem in developed countries. Clasification of risk factors is the subject of much attention, because knowledge of these factors offer opportunities for effective prevention and treatment. The aim of my work was to obtain new knowledge of factors affecting homocysteine metabolism with regard to the formation of some complex diseases in the Czech population.
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