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Proteomic analysis of selected oncohematological diseases
Pimková, Kristýna ; Dyr, Jan (advisor) ; Kodíček, Milan (referee) ; Petrák, Jiří (referee)
Oxidative stress is an important factor in carcinogenesis of oncohematological diseases. However its role in the pathogenesis of myelodysplastic syndromes (MDS) remains unclear. In this study, we have determined the oxidative status and evaluated proteomic changes in plasma of MDS patients as a consequence of oxidative dysbalance (oxidative modifications, protein-protein interaction and complex forming). We measured the levels of total cysteine, homocysteine, cysteinyglycine, glutathione, nitrites and nitrates in the plasma from 61 MDS patients and 23 healthy donors using high performance liquid chromatography. Glutathione and nitrites levels reduced significantly while other aminothiols levels increased significantly in plasma of MDS patients. This association with oxidative stress did not correlate with iron overload. We also found enhanced levels of asymmetric dimethylarginine in serums of middle aged patients with MDS that correlate to posttranslational modifications of proteins arginyl residues. Furthermore, carbonylated proteins level was significantly elevated in MDS patients compared to healthy donors. Using mass spectrometry, 5 S-nitrosylated blood platelets proteins were identified in plasma and blood platelets of MDS patients and set of 16 plasma proteins with high probability of...
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Platelet reactivity during antiplatelet therapy
Paulů, Petra ; Osmančík, Pavel (advisor) ; Dyr, Jan (referee) ; Ošťádal, Petr (referee)
INTRODUCTION: Dual antiplatelet therapy is the basis of the treatement of patients with coronary artery disease following PCI. It demonstrably reduces the risk of ischemic complications of these patients and thus the morbidity and mortality. Despite all the effort we can see the recurrence of ischemic complications and worsening the prognosis in considerable percentage of patients. Resistance to treatement and resistance to clopidogrel can be marked as reason of therapy failure. AIM: The aim of our study was to a) define the incidence of clopidogrel resistance in real practise b) specify the factors which are associated with clopidogrel resistance c) determine whether the platelet reactivity measured by VerifyNow can be influenced by clopidogrel dose titration d) define the factors which are associated with worse prognosis of patients treated with dual antiplatelet therapy METHODS: We enrolled consecutive patients after PCI who were indicated to dual antiplatelet therapy. The blood samples were drawn within 24 hours after PCI and standart biochemical, hematological and coagulation parametres were determined. Also the serology and genetic analysis and VerifyNow test to determine the platelet reactivity were done. The PRU cut off value 240 was specified as the borderline of ineffective answer to clopidogrel...
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Nanotechnology in the intensive care: Intravascular biocompatibility of carbon nanomaterials-effect of carbon nanotubes on blood platelets
Šemberová, Jana ; Straňák, Zbyněk (advisor) ; Dyr, Jan (referee) ; Hubálek Kalbáčová, Marie (referee)
Nanotechnology in the intensive care: Intravascular biocompatibility of carbon nanomaterials - effect of carbon nanotubes on blood platelets. EFFECT OF CARBON NANOTUBES ON BLOOD PLATELETS Carbon nanotubes (CNTs) are among the principal materials currently used in biomedical nanotechnologies. CNTs possess superior mechanical and chemical characteristics including enormous tensile strength, elasticity and conductivity. As a result they are very popular and attractive for use in various biomedical applications. Many of these applications may lead ultimately to contact of carbon nanomaterials and blood. Furthermore, CNTs may also be present intravascularly as a result of environmental or occupational exposure. Therefore, the investigation of the intravascular biocompatibility of CNTs is a critical safety issue. We studied the effects of structurally different purified CNT materials from different manufacturers on human platelets and compared their effects to amorphous carbon black nanoparticles (ACB), fullerene C60, fullerenol C60(OH)24 and NIST standard polystyrene nanobeads (PNBs). Using light transmission aggregometry of human platelet rich plasma, we found that various CNTs induce PLT aggregation and this occurs in a concentration dependent manner. In contrast to CNTs, ball-like shaped fullerene...
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Contribution to the pathophysiology of thrombophilic state after fractures surgery in patients over 75 years old
Kudrnová, Zuzana ; Kvasnička, Jan (advisor) ; Dyr, Jan (referee) ; Malý, Jaroslav (referee)
Introduction: Hip fracture surgery is the particular problem of very old patinets (>75 years), with high risk of VTE (up to 80%). It is essential to provide VTE prophylaxis. Patients advanced age and their polymorbidity contribute to the thrombophilic status. Objectives and methods: The aim of the study was to determine the changes of coagulation within the 28 post-operative days in 41 patients over 75 years who underwent hip fracture surgery. Another object was to determine acute phase response and an endothelial activation. The third task was to determine how affected is a key component of hemostasis, FXa activity by its specific inhibitor fondaparinux and enoxaparin, which inhibits FXa and thrombin in a 4:1 ratio and if there is bleeding complication in such a risk group patiens after antithrombotics long-term administration. Patients were randomly divided into two anticoagulant groups: fondaparinux (n = 23) and enoxaparin (n = 18). Results: Thrombophilia is demonstrated by a reactive increase of the most of these parameters preoperatively and reveals the effect of the initial trauma. A surgery further aggravates this reaction. This inflammatory and secondary prothrombogenic condition persisted until postoperative day 28. Both antithrombotics effectively inhibit thrombin generation without...
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The Use of Thromboelastography in Evaluation of Coagulation in Fenmales with Physiologial or Pathological Pregnancy
Polák, Ferdinand ; Závada, Josef (advisor) ; Dyr, Jan (referee) ; Feyereisl, Jaroslav (referee)
The Use of Thromboelastography in Evaluation of Coagulation in Females with Physiological or Pathological Pregnancy MUDr. Ferdinand Polák Abstract Introduction: The target of this study was to compare thromboelastography coagulation parameters in the following three groups: a) healthy pregnant women, b) healthy non-pregnant women and c) pregnant women with pathological pregnancy and also to compare it to reference limits for the common population. If appropriate, we would propose recommendations for new reference ranges for pregnant women in their third trimester. Materials and methods: Prospective observational study, comparing, by using thromboelastography, the blood samples of 60 healthy women in their third trimester of pregnancy (group GRAV) to the samples of the control group of 43 healthy non-pregnant fertile women (group NON-GRAV) and to the samples of 50 women with pathological pregnancy (preeclampsia, fetal death) in their third trimester (group PATOL). Selective percentiles were used to determine new reference limits. Results and conclusions: We found statistically significant differences between groups GRAV and NON-GRAV. Therefore, we established, based on our results, new thromboelastography reference limits for pregnant women. Coagulation changes during pathological pregnancy are less...
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Effects of valproic acid and its combinations with cytostatic agents on tumor cells in vitro
Hinďoš Hřebačková, Jana ; Dyr, Jan (advisor) ; Vávrová, Jiřina (referee) ; Entlicher, Gustav (referee)
Cancer is one of the most challenging problems the modern medicine is facing today. An increasing incidence and a great variability of tumor cells are the main reasons those drive the research to develop better diagnostics and therapeutic protocols. Histone deacetylase inhibitors, a group of epigenetic chemotherapeutics, are able to improve the performance of currently used anticancer agents. Vaplroic acid that is commonly used as antiepileptic drug exhibits a remarkable anticancer activity by itself as well as it is capable of therapy potentiation based on other therapeutic agents. Its effect to inhibit growth of tumor cells and induce apoptotic cell death seems to be even greater under hypoxic conditions (<1% O2). This study is focused on effect of valproic acid on neuroblastoma cell lines in vitro under normoxic and hypoxic conditions. We observed significantly greater efficacy of valproic acid in hypoxia compared to normoxia. The mechanism of induction of apoptotic cell death is based on disruption of the balance between pro- and antiapoptoic proteins. Intrinsic apoptotic pathway is probably initiated by the action of 19 kDa variant of proapoptotic protein Bax on mitochondrial membrane. Moreover, we examined the efficiency of a combined treatment of neuroblastoma cells with valproic acid and...
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Effects of valproic acid and its combinations with cytostatic agents on tumor cells in vitro
Hinďoš Hřebačková, Jana ; Dyr, Jan (advisor) ; Vávrová, Jiřina (referee) ; Entlicher, Gustav (referee)
Cancer is one of the most challenging problems the modern medicine is facing today. An increasing incidence and a great variability of tumor cells are the main reasons those drive the research to develop better diagnostics and therapeutic protocols. Histone deacetylase inhibitors, a group of epigenetic chemotherapeutics, are able to improve the performance of currently used anticancer agents. Vaplroic acid that is commonly used as antiepileptic drug exhibits a remarkable anticancer activity by itself as well as it is capable of therapy potentiation based on other therapeutic agents. Its effect to inhibit growth of tumor cells and induce apoptotic cell death seems to be even greater under hypoxic conditions (<1% O2). This study is focused on effect of valproic acid on neuroblastoma cell lines in vitro under normoxic and hypoxic conditions. We observed significantly greater efficacy of valproic acid in hypoxia compared to normoxia. The mechanism of induction of apoptotic cell death is based on disruption of the balance between pro- and antiapoptoic proteins. Intrinsic apoptotic pathway is probably initiated by the action of 19 kDa variant of proapoptotic protein Bax on mitochondrial membrane. Moreover, we examined the efficiency of a combined treatment of neuroblastoma cells with valproic acid and...
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Platelet reactivity during antiplatelet therapy
Paulů, Petra ; Osmančík, Pavel (advisor) ; Dyr, Jan (referee) ; Ošťádal, Petr (referee)
INTRODUCTION: Dual antiplatelet therapy is the basis of the treatement of patients with coronary artery disease following PCI. It demonstrably reduces the risk of ischemic complications of these patients and thus the morbidity and mortality. Despite all the effort we can see the recurrence of ischemic complications and worsening the prognosis in considerable percentage of patients. Resistance to treatement and resistance to clopidogrel can be marked as reason of therapy failure. AIM: The aim of our study was to a) define the incidence of clopidogrel resistance in real practise b) specify the factors which are associated with clopidogrel resistance c) determine whether the platelet reactivity measured by VerifyNow can be influenced by clopidogrel dose titration d) define the factors which are associated with worse prognosis of patients treated with dual antiplatelet therapy METHODS: We enrolled consecutive patients after PCI who were indicated to dual antiplatelet therapy. The blood samples were drawn within 24 hours after PCI and standart biochemical, hematological and coagulation parametres were determined. Also the serology and genetic analysis and VerifyNow test to determine the platelet reactivity were done. The PRU cut off value 240 was specified as the borderline of ineffective answer to clopidogrel...
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Proteomic analysis of selected oncohematological diseases
Pimková, Kristýna ; Dyr, Jan (advisor) ; Kodíček, Milan (referee) ; Petrák, Jiří (referee)
Oxidative stress is an important factor in carcinogenesis of oncohematological diseases. However its role in the pathogenesis of myelodysplastic syndromes (MDS) remains unclear. In this study, we have determined the oxidative status and evaluated proteomic changes in plasma of MDS patients as a consequence of oxidative dysbalance (oxidative modifications, protein-protein interaction and complex forming). We measured the levels of total cysteine, homocysteine, cysteinyglycine, glutathione, nitrites and nitrates in the plasma from 61 MDS patients and 23 healthy donors using high performance liquid chromatography. Glutathione and nitrites levels reduced significantly while other aminothiols levels increased significantly in plasma of MDS patients. This association with oxidative stress did not correlate with iron overload. We also found enhanced levels of asymmetric dimethylarginine in serums of middle aged patients with MDS that correlate to posttranslational modifications of proteins arginyl residues. Furthermore, carbonylated proteins level was significantly elevated in MDS patients compared to healthy donors. Using mass spectrometry, 5 S-nitrosylated blood platelets proteins were identified in plasma and blood platelets of MDS patients and set of 16 plasma proteins with high probability of...
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The Use of Thromboelastography in Evaluation of Coagulation in Fenmales with Physiologial or Pathological Pregnancy
Polák, Ferdinand ; Závada, Josef (advisor) ; Dyr, Jan (referee) ; Feyereisl, Jaroslav (referee)
The Use of Thromboelastography in Evaluation of Coagulation in Females with Physiological or Pathological Pregnancy MUDr. Ferdinand Polák Abstract Introduction: The target of this study was to compare thromboelastography coagulation parameters in the following three groups: a) healthy pregnant women, b) healthy non-pregnant women and c) pregnant women with pathological pregnancy and also to compare it to reference limits for the common population. If appropriate, we would propose recommendations for new reference ranges for pregnant women in their third trimester. Materials and methods: Prospective observational study, comparing, by using thromboelastography, the blood samples of 60 healthy women in their third trimester of pregnancy (group GRAV) to the samples of the control group of 43 healthy non-pregnant fertile women (group NON-GRAV) and to the samples of 50 women with pathological pregnancy (preeclampsia, fetal death) in their third trimester (group PATOL). Selective percentiles were used to determine new reference limits. Results and conclusions: We found statistically significant differences between groups GRAV and NON-GRAV. Therefore, we established, based on our results, new thromboelastography reference limits for pregnant women. Coagulation changes during pathological pregnancy are less...
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