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The enzymes of catecholamine metabolism in experimental hypertension.
Loučková, Anna ; Kuneš, Jaroslav (advisor) ; Klevstigová, Martina (referee)
Catecholamines dopamine, norepinephrine and epinephrine are significantly involved in regulation of blood pressure. The most important enzymes participating in their metabolism are tyrosin hydroxylase, DOPA dekarboxylase, dopamine β-hydroxylase and phenylethanolamine N-methyltransferase. This thesis summarizes current knowledge about these enzymes, focusing on their role in the development of essential hypertension. Experimental models are often used in the study of hypertension because of their practical and ethic reasons. Most findings were obtained in spontaneously hypertensive rats, due to their similarity to human essential hypertension. Metabolism of catecholamines in spontaneously hypertensive rat differs in many aspects from that of normotensive controls. The primary cause of this type of hypertension has not yet been distinguished from compensatory responses. However, prevention or slow-down the disease-development process can be achieved by various interventions. This information may help to identify new treatments for human hypertension.
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Cyclophosphamide effects on hematopoiesis
Renešová, Nicol ; Šefc, Luděk (advisor) ; Klevstigová, Martina (referee)
Cyclophosphamide is an alkylating agent developed in the 1960s for the use in treatment of cancerous diseases. Since its introduction, it has manifested various spectra of effects. Of uttermost importance are the impacts cyclophosphamide has on the hematopoietic system housed in the bone marrow of femoral and other bones. Hematopoiesis is a complex process which has been extensively studied for decades. The more it is known about the niches the hematopoietic stem cells occupy as well as of their life cycle, the more it is possible to design functional therapy for its malignancies and improve the survival rates. The effects of cyclophosphamide administration on hematopoietic system are divided into three major cathegories: myeloablation and myelosuppression, immunosuppression, and mobilisation of hematopoietic stem cells into the peripheral blood. The immunosuppression is achieved by systematic depletion of progenitors differentiating into lecocytes. Induced neutropenia and lymphopenia allow for management of autoimmune diseases and preservation of transplants. Mobilisation, a process opposite to stem cell homing, seems to be dependent on disruption of cellular adhesion (CRXCR4/SDF-1, VCAM-1/VLA-4) facilitated by proteases released into the environment after cyclophosphamide exposure.
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Myocardial cell signaling in spontaneously hypertensive rats with transgenic and congenic expression of CD36
Klevstigová, Martina ; Nováková, Olga (advisor) ; Kalous, Martin (referee) ; Zicha, Josef (referee)
Long-chain fatty acids (LCFA) are the primary energy source in the myocardium and an imbalance in the LCFA and glucose utilization could cause cardiovascular diseases. More than 50% of LCFA uptake by the heart is mediated by the fatty acid translocase CD36 and disruption of its function has been shown to impair cardiovascular functions. The spontaneously hypertensive rat (SHR) harbors a deletion variant of the Cd36 gene that results in reduced LCFA transport into myocytes. Therefore, the main aim of this thesis was to investigate the importance of a functional CD36 to sustain normal physiological functions of the heart. We used SHR and two genetic modified SHR strains, the congenic SHR-4 and the transgenic SHR-Cd36, with fully functional CD36. They differ in the CD36 expression and in the manner how they were derived from the SHR. CD36 has been proven to play a role in the pathogenesis of insulin resistance. Therefore we analyzed the effect of a functional CD36 on insulin resistance and protein kinase C (PKC) expression, which is known to be involved in the mechanism of insulin resistance, in the heart of SHR-4 and SHR. We showed that the SHR-4 had lower serum free fatty acids (FFA) and triacylglycerols (TAG) concentrations, indicating improved insulin sensitivity. Furthermore, SHR-4 had increased...
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Cyclophosphamide effects on hematopoiesis
Renešová, Nicol ; Šefc, Luděk (advisor) ; Klevstigová, Martina (referee)
Cyclophosphamide is an alkylating agent developed in the 1960s for the use in treatment of cancerous diseases. Since its introduction, it has manifested various spectra of effects. Of uttermost importance are the impacts cyclophosphamide has on the hematopoietic system housed in the bone marrow of femoral and other bones. Hematopoiesis is a complex process which has been extensively studied for decades. The more it is known about the niches the hematopoietic stem cells occupy as well as of their life cycle, the more it is possible to design functional therapy for its malignancies and improve the survival rates. The effects of cyclophosphamide administration on hematopoietic system are divided into three major cathegories: myeloablation and myelosuppression, immunosuppression, and mobilisation of hematopoietic stem cells into the peripheral blood. The immunosuppression is achieved by systematic depletion of progenitors differentiating into lecocytes. Induced neutropenia and lymphopenia allow for management of autoimmune diseases and preservation of transplants. Mobilisation, a process opposite to stem cell homing, seems to be dependent on disruption of cellular adhesion (CRXCR4/SDF-1, VCAM-1/VLA-4) facilitated by proteases released into the environment after cyclophosphamide exposure.
|
|
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The enzymes of catecholamine metabolism in experimental hypertension.
Loučková, Anna ; Kuneš, Jaroslav (advisor) ; Klevstigová, Martina (referee)
Catecholamines dopamine, norepinephrine and epinephrine are significantly involved in regulation of blood pressure. The most important enzymes participating in their metabolism are tyrosin hydroxylase, DOPA dekarboxylase, dopamine β-hydroxylase and phenylethanolamine N-methyltransferase. This thesis summarizes current knowledge about these enzymes, focusing on their role in the development of essential hypertension. Experimental models are often used in the study of hypertension because of their practical and ethic reasons. Most findings were obtained in spontaneously hypertensive rats, due to their similarity to human essential hypertension. Metabolism of catecholamines in spontaneously hypertensive rat differs in many aspects from that of normotensive controls. The primary cause of this type of hypertension has not yet been distinguished from compensatory responses. However, prevention or slow-down the disease-development process can be achieved by various interventions. This information may help to identify new treatments for human hypertension.
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