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Risk factors for atherosclerosis and its potential pharmacological effects in patients with coronary artery disease and lower limb
Hromádka, Milan ; Filipovský, Jan (advisor) ; Piťha, Jan (referee) ; Šimon, Jaroslav (referee)
1 Statin therapy in patients with peripheral artery obstructive disease (PAOD) 1.1 Patients with lipid metabolism disorders Simvastatin therapy with the dose titration adjusted to the effect led to the prolongation of claudication interval and to the elevation of ankle-brachial pressure index, which was statistically significant at the interval of 18 months after starting the therapy. At the same time we observed normalization of lipid levels and the lowest levels of oxidative stress markers. Statin use was also associated with lowering homocysteine level. 1.2 Patients without lipid metabolism disorders - the influence on laboratory parameters and functional capacity In patients without lipid metabolism disorder, treated with simvastatin 20 mg daily, we noted an improvement, i.e. prolongation of claudication interval and elevation of ankle-brachial pressure index, while in the control group treated only with a diet we observed further deterioration of capacity. In the control group, the parameters of lipid metabolism were statistically significantly worse after six months and this trend remained even in further control visits with HDL cholesterol slightly lowering. In the simvastatin group, a statistically significant decrease of LDL occurred during several months as well as elevation of HDL...
Cardiovascular complications in patients with end-stage renal disease.
Valeriánová, Anna ; Malík, Jan (advisor) ; Zemánek, David (referee) ; Piťha, Jan (referee)
Patients with end-stage renal disease frequently suffer from cardiovascular complications. Many factors contribute to their development: hyperkinetic circulation caused by anaemia, fluid retention and by presence of dialysis arteriovenous access; metabolic changes leading to acceleration of atherosclerosis and increase of vascular stiffness and also fluctuation of blood pressure and organ perfusion during haemodialysis, that cause repeated tissue hypoxia. We performed our research on patients in chronic haemodialysis programme. The project studying long-term patency of dialysis access showed that dialysis graft patency is negatively influenced by presence of coronary artery disease and low serum concentrations of cholesterol. In our studies about tissue hypoxia we proved that haemodialysis patients suffer from hypoxia of cerebral tissue and muscle tissue of the dialysis access arm, and that the hypoxia worsens during dialysis. Factors associated with brain hypoxia are presence of heart failure, higher BNP levels and higher erythrocyte distribution width. One of the serious consequences of brain hypoxia is development of cognitive deficit. Among the negative impact of haemodialysis on the heart, we observed left atrial dysfunction, which is a consequence of long-term remodelling and cannot be...
Role of endothelial and vascular smooth muscle cells in the origin, progression and therapy of vascular diseases
Chlupáč, Jaroslav ; Bačáková, Lucie (advisor) ; Piťha, Jan (referee) ; Sedmera, David (referee)
Introduction: Vascular surgery for atherosclerosis is confronted by the lack of a suitable bypass material. Synthetic vascular prostheses include polyethylene terephthalate (PET) and expanded polytetrafluoroethylene (ePTFE). However, these materials become thrombosed in small-caliber applications (<6 mm) because of the lack of an endothelium. The objectives of this study were to make modifications to clinically-used PET vascular prostheses with tissue-engineered surfaces to improve their bio-compatibility towards vascular smooth muscle cells (VSMC) and endothelial cells (EC). Methods: Blood coagulation protein fibrin (Fb) and extracellular matrix proteins collagen (Co), laminin (LM) and fibronectin (FN) were used. Cell adhesive assemblies were prepared: Co, Co/LM, Co/FN, Co/Fb, Co/Fb/FN. Cell culture experiments were performed: (1) planar static, (2) planar dynamic with simulation of blood flow, (3) tubular dynamic, and (4) animal porcine implantation. Results: The growth of EC and VSMC on commercial prostheses (ePTFE, PET and PET/Co) was low. The growth of both cell types was lower on PET/Co than on PET. After modification with protein assemblies, the highest numbers of EC were reached on PET/Co and on PET/Co +Co/Fb. There was no difference in the densities of VSMC among various assemblies. The...
The Effects of Statins on TGF-ß1 Signaling in Vivo and in Vitro
Zemánková, Lenka ; Nachtigal, Petr (advisor) ; Piťha, Jan (referee) ; Mladěnka, Přemysl (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Department of Biological and Medical Sciences Candidate Mgr. Lenka Zemánková Supervisor Doc. PharmDr. Petr Nachtigal, Ph.D. Title of Doctoral Thesis The effects of statins on TGF-β1 signaling in vivo and in vitro. This doctoral dissertation summarizes the effects of statins and inflammation on TGF-β1 signaling both in vivo and in vitro, especially the role of endoglin in the endothelial cells. Transforming growth factor-β (TGF-β) is a multifunctional factor that regulates various cell specific functions in atherogenesis. Endoglin (TGF-βRIII, CD105) is known as accessory TGF β receptor, and it is able to modulate activity of TGF-β1 and TGF-β receptors. Previous studies demonstrated relation between endoglin and eNOS expression in blood vessels suggesting crucial role of endoglin in endothelial cell functions. Our in vivo experimental studies, were focused on the expressions of TGF-β family members, on endoglin expression in aorta and its blood serum levels. We wanted to evaluate, whether these proteins are affected by cholesterol levels or atorvastatin treatment in different types of diet in mice. Immunohistochemical analysis showed the expression of endoglin in intact endothelium and in endothelium covering...
Determinants of premature atherosclerosis in children with end-stage renal disease
Dvořáková, Hana Marie ; Piťha, Jan (advisor) ; Teplan, Vladimír (referee) ; Vaverková, Helena (referee)
Children with chronic renal failure are at extremely high risk of premature cardiovascular disease. In our work, we have shown that the measurement of carotis intima- media thickness (CIMT) with high resolution ultrasound is a suitable method for the diagnosis of early atherosclerotic changes especially in younger children. In contrast, flow mediated dilatation (FMD) according to our experience is not very suitable method for investigations in pediatrics because of its high variability. In our group of patients we did not find correlation of preclinical atherosclerosis measured by CIMT with any of the traditional cardiovascular risk factors (hypertension, dyslipidemia, overweight expressed as body mass index). In contrast, a significant negative correlation was found in the ESRD patients between the CIMT and serum bilirubin and albumin. On the one hand, these findings could indicate an impaired defending mechanisms against oxidative stress, which are considered one of the key factors in the development of atherosclerotic process, on the other hand they indicated an important role played by nutritional status in children with ESRD. In addition, we found strong evidence for significant correlations between CIMT and proteinuria as another discussed cardiovascular risk factor in boys, but not in girls. To our...
Preclinical atherosclerosis of peripheral arteries and its relation to venous thrombosis in patiens with thrombophilias
Auzký, Ondřej ; Piťha, Jan (advisor) ; Karetová, Debora (referee) ; Vaverková, Helena (referee)
The aim of our study was to evaluate association between venous disorders and preclinical atherosclerosis and its risk factors. The study was particularly focused on the association between cardiovascular risk factors and preclinical atherosclerosis with venous diseases represented by venous thromboembolism and/or symptoms of chronic venous disease evaluated by standard protocol. In our first study we evaluated the association between preclinical atherosclerosis and prevalence of venous thromboembolic events in patients with thrombophilias. Preclinical atherosclerosis might increase through its procoagulative action the risk of venous thromboembolism. Presence of preclinical atherosclerosis in common carotid and femoral arteries measured by ultrasound was assessed by Belcaro score (based mainly on presence of plaques) and by measurements of intima media thickness in the same location in 109 patients (43 men, mean age 41.5 ± 13 years) with established thrombophilias. Other parameters under study were age, presence of traditional cardiovascular risk factors, anthropometric and clinical data including blood pressure measurements and medication. The differences between 4 patients with (n = 47) and without (n = 62) thromboembolic events were assessed by paired t-test and chi square tests. In patients with a...
Wall shear stress and its role in progress of atherosclerosis
Chytilová, Eva ; Malík, Jan (advisor) ; Horký, Karel (referee) ; Piťha, Jan (referee)
Atherosclerosis is associated with systemic risk factors such as hypertension, hyperlipidemia, diabetes mellitus and smoking. Nonetheless, atherosclerosis is a focal disease, preferentially affecting predisposed areas. The main local hemodynamic factor is wall shear stress, the frictional force acting tangencially on the endothelial cell surface. The effect of wall shear stress depends on its magnitude and direction, as well as on the characteristic of vessel geometry and blood flow. Wall shear stress is an important determinant of endothelial function and phenotype. Previous research showed that arterial sites with chronically low WSS are more prone to the development of atherosclerotic plaques. Mostly, it is the case of outer wall of arterial bifurcations, where the stroma of vessel wall prevents arterio-constriction in response to low WSS. However, lower WSS was described also in straight arterial segments, such as carotid arteries, in the presence of atherosclerosis risk factors.
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Jehlička, Petr ; Piťha, Jan (advisor) ; Urbanová, Zuzana (referee) ; Malík, Jan (referee)
MUDr. JEHLIČKA SUMMARY This study has focused on a new method for the assessment of endothelial dysfunction (ED) using the Deceleration Index (DI). A total of 242 ultrasonographic examinations were performed in 92 children (FH 32, DM1 30, healthy controls 3O). The average DI values were 21.8%(±9.4)in healthy children, 19.9%(±9)in FH and 17.6%(±14)in the DM1 group. There were statistically insignificant differences between the study groups. This was most probably due to the high biological variability of the method employed. The coefficient of variation of DI was 1.02 (0.68 -1.53). Therefore, the clinical usefulness of DI is limited with regards to the individual assessment of ED and thus for the prediction of cardiovascular risk. The association of ADMA and oxLDL with ED and their superior sensitivity compared to DI and FMD has been confirmed in our study. Folic acid supplementation did not lead to a statistically signifiant improvement of DI and FMD. Similarly, plasma levels of ADMA and oxLDL remained unchanged despite a decrease of homocysteine and hsCRP in these children. This finding demonstrates a complicated relationship between ADMA, homocysteine and folic acid. The protective effect of folic acid on ED in high risk children was not confirmed in this study.

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1 Piťha, Jiří
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