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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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Změny exprese signálních proteinů a genů v souvislosti s diabetickou nefropatií
Demová, Hana ; Černá, Marie (advisor) ; Viklický, Ondřej (referee) ; Kalousová, Marta (referee)
Hypothesis: I have investigated specific molecular and cell mechanisms that might be involved in the ethiopatogenesis of diabetic nephropathy. Their involvement might also be demonstrated in response to treatment of diabetic nephropathy. Aims: I have studied changes of signal transduction proteins (CAV-1, VEGF, RhoA) in renal cortical cells in the rat model of renal hypertension and in the rat model of type 1 diabetes. I also have performed analyses of polymorphisms in the genes involved in cell signaling with respect to their function in human study. Methods : The renal cortical expression of molecular targets CAV-1, VEGF, and RhoA have been assessed in addition to measurements of renal functional parameters in L-NAME-treated rats with or without a concomitant administration of atorvastatin (ATO) and have been compared to untreated control animals.
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Oxidative and carbonyl stress,microinflammation and cardiovascular risk in patiens with chronic kidney disease
Peiskerová, Martina ; Kalousová, Marta (advisor) ; Teplan, Vladimír (referee) ; Racek, Jaroslav (referee)
Short summary: Background: High cardiovascular risk in patients with chronic kidney disease is partly due to mineral dysbalance, microinflammation and oxidative stress. CKD patients accumulate traditional and non-traditional CV risk factors. FGF23, MMPs and PlGF belong among these non-traditional biomarkers of CV risk. FGF23 is a phosphaturic hormone and inhibitor of calcitriol synthesis. It is associated with vascular calcifications. Matrix-metalloproteinases (e.g. MMP-2, MMP-9) are proteolytic, proinflammatory enzymes, contributing to myocardial remodelation. Placental growth factor (PlGF) is a proangiogenic cytokine that is associated with LV hypertrophy in animal model. Plasmatic FGF23, MMPs and PlGF are elevated in CKD. Aim: We aimed to describe dynamic changes between several novel biomarkers of CV risk (FGF23, MMP-2, MMP-9 and PlGF) in CKD stages 1-5, to describe their mutual correlations and possible association with traditional CV risk markers. We studied possible association of laboratory and echocardiographic parameters in patients with CKD stages 2-4. Methods: In a cross-sectional study we evaluated 80 patiens with CKD 1-5 and 44 healthy controls. In a prospective study we evaluated echocardiographic and laboratory parameters in 62 patients with CKD 2-4 for an average study period of 36±10...
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Genetic backround and new biochemical markers in pathological pregnancy
Germanová, Anna ; Kalousová, Marta (advisor) ; Černá, Marie (referee) ; Bílek, Radovan (referee)
Receptor for advanced glycation end products (RAGE), its soluble form (sRAGE) and glyoxalase 1 (GLO 1) are important part of pathogenesis of many chronic diseases. The aim of this thesis was to elucidate role of sRAGE, four chosen RAGE polymorphisms and one GLO 1 polymorphism in physiologic pregnancy and in pregnancy with complications. Serum sRAGE levels were determined in healthy pregnant women (N=120) and in pregnancies complicated with threatening preterm labor (N=99), preeclampsia (N=35), intrauterine growth restriction (IUGR) (N=22) and intrahepatic cholestasis of pregnancy (ICP) (N=14). Four RAGE polymorphisms (RAGE -429T/C, -374A/T, RAGE Gly82Ser (557G/A), RAGE 2184A/G) and one glyoxalase 1 polymorphism GLO 1 Glu111Ala (419A/C) were studied in the same population of healthy pregnant women and women with pathological pregnancy. Serum sRAGE levels are low in comparison to non-pregnant controls, but they vary during the physiologic pregnancy. Serum sRAGE levels are low in the 1st trimester, increased in the 2nd trimester and again decreased in the 3rd trimester. Women with premature labor have significantly decreased serum sRAGE levels in comparison to women with threatening premature labor and in comparison to healthy pregnant women. sRAGE correlates negatively with leukocyte count in preterm...
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Pregnancy proteins - molecular biological and biochemical analysis
Muravská, Alexandra ; Kalousová, Marta (advisor) ; Černá, Marie (referee) ; Průša, Richard (referee)
The aim of this thesis was to establish methods for selected PAPP-A (Pregnancy- Associated Plasma Protein A) gene polymorphisms analysis and to study genetic background of PAPP-A and biochemical background of PAPP-A and PlGF (Placental Growth Factor) in relation to risk pregnancy. Secondly, the aim was to establish method for two-dimensional (2D) electrophoresis of amniotic fluid. Methods for analysis of ten PAPP-A gene polymorphisms were established. These polymorphisms, PAPP-A and PlGF levels were studied in together 165 women in third trimester pregnancies complicated with threatening preterm labor (n=98), preeclampsia (n=35), IUGR (Intrauterine Growth Restriction) (n=34) and ICP (Intrahepatic Cholestasis of Pregnancy) (n=15). 114 healthy pregnant women served as controls. The method for 2D electrophoresis of amniotic fluid was established. Preeclamptic patients had significantly higher frequency of TT genotype of Cys327Cys (C/T) PAPP-A gene polymorphism compared to controls. Patients with ICP had increased serum levels of PAPP-A compared to controls, in patients with threatening preterm labor PAPP-A levels were rather decreased. PlGF levels did not differ from control group in patients with ICP and threatening preterm labor. Positive correlation was found between PAPP-A and PlGF in group of...
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Novel biomarkers in patients with renal disease
Zakiyanov, Oskar ; Kalousová, Marta (advisor) ; Teplan, Vladimír (referee) ; Průša, Richard (referee)
Chronic kidney disease (CKD) and acute kidney injury (AKI) are major public health problems. It is important to be able to identify those at high risk of adverse outcome, CKD progression and associated cardiovascular disease. The aim of the thesis was to study novel promising biomarkers, their relationship to kidney function, chronic inflammation and/or cardiovascular risk - placental growth factor (PlGF), pregnancy associated plasma protein A (PAPP-A), matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), soluble receptor for advanced glycation end products (sRAGE), calcium binding protein S100A12 or extracellular newly identified RAGE binding protein (EN-RAGE), and high mobility group box protein-1 (HMGB-1) in patients with renal diseases including CKD, haemodialysis (HD), AKI patients, and healthy controls for comparison. First study revealed that PlGF is elevated in patients with decreased renal function. Second study demonstrated the association of MMP-2 and PAPP-A with proteinuria in patients with CKD. Moreover, serum MMP-2, MMP-9 and PAPP-A levels significantly differed in patients with various nephropathies. EN-RAGE levels are not elevated in patients with CKD, but are related to inflammatory status. PAPP-A, EN-RAGE and HMGB-1 levels are significantly elevated, but sRAGE and PlGF...
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Biomarkers of early renal injury
Fořtová, Magdaléna ; Průša, Richard (advisor) ; Kalousová, Marta (referee) ; Ryšavá, Romana (referee)
Aims: The thesis deals with the biomarkers of early renal injury, namely albuminuria and neutrophil gelatinase-associated lipocalin (NGAL). The aims in the case of albuminuria were the implementation of HPLC method, comparing HPLC with immunoturbidimetric (IT) method and monitoring the relationship to the diagnosis of diabetes mellitus. The aim of urinary NGAL (and eventually other markers) examination was to verify its reliability in the prediction of acute kidney injury (AKI). Methods: We investigated albuminuria in fresh urine samples in the groups of 636 diabetics and 456 nondiabetics using the HPLC method (Agilent 1200, Agilent Technologies, USA) and immunoturbidimetrically (Cobas Integra 400, Roche Diagnostics); we studied the correlations and relationships between albuminuria and glycated hemoglobin HbA1c. We investigated urinary NGAL by chemiluminescent microparticle immunoassay (Architect i4000, Abbott) in children's groups: 1) after renal transplantation (N = 15), 2) with acute or chronic kidney disease (N = 28); and in adult patient's groups: 1) after cardiac surgery (N = 10) and 2) post angiography (N = 41). Results: Albuminuria determined by HPLC was statistically significantly higher than albuminuria determined by IT. We excluded nonspecificity of the HPLC method. Results indicate...
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Pathobiochemistry of diabetes mellitus and its complications - oxidative stress, microinflammation and genetic predisposition.
Škrha, Jan ; Kalousová, Marta (advisor) ; Rybka, Jaroslav (referee) ; Bendlová, Běla (referee)
Diabetes is a chronic disease with high prevalence and significant morbidity. Chronic changes in the wall of small and large vessels lead to main diabetes complications. Apart from long- term hyperglycemia, several factors are involved in the development of diabetes vasculopathy. The aim of this work was to describe new early biomarkers of these vascular changes, to identify risky patients. Alongside, gene polymorphisms involved in protective pathways of glucose metabolism were studied. In three human studies with Type 1 (T1D) and Type 2 (T2D) diabetes patients special biochemical parameters of receptor for advanced glycation endproducts (RAGE) and its ligands, deglycation enzyme glyoxalase 1 (GLO1) and fructosamine 3-kinase (FN3K) gene polymorphisms were analyzed. Non-invasive measurement of glycation by skin autofluorescence (SAF) was assessed in all subjects. Soluble RAGE, HMGB1 and endothelial dysfunction markers were increased in patients with diabetes as compared with controls, however the differences between T1D and T2D were not significant. For the first time, an association between FN3K (rs1056534) and (rs3848403) polymorphism and sRAGE concentration in diabetes was shown. GLO1 (rs4746) polymorphism was associated with changes in endothelial dysfunction. Patients with diabetes had higher...
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