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Iron and regulation of its metabolism in inflammation and disorders of erythropoiesis.
Gurieva, Iuliia ; Vokurka, Martin (advisor) ; Kaňková, Kateřina (referee) ; Pláteník, Jan (referee)
Iron is a metal element with crucial roles in human organism. Both iron deficiency and iron overload are important pathologies. Hepcidin, a peptide synthetized in the liver, is a key iron regulatory hormone. Increased amount of iron and inflammation stimulate its expression while iron deficiency and activated erythropoiesis cause hepcidin downregulation. The regulation of hepcidin expression on the molecular level and its hierarchy and interactions are not completely known. The main regulatory pathway is BMP/ SMAD which reacts to the iron amount in the organism. Several molecules, including hemojuvelin and HFE, are involved in this pathway and their mutations are linked to inappropriately low hepcidin production, iron overload and hereditary hemochromatosis. Erythroid regulation with suppressive action on hepcidin expression is known only partially as well as its connection to the BMP/ SMAD pathway. Recently, two new negative regulators of hepcidin expression have been described. Membrane enzyme present in hepatocytes - matriptase-2 (MT-2, TMPRSS6) and soluble factor secreted by erythroblasts - erythroferrone (ERFE). The aim of our work was to investigate how MT-2 is involved in the erythroid regulatory pathway, and whether it can represent the molecule where various regulatory pathways interact....
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Benefit of assesment of cytokines in inflammatory postoperative complications
Chachkhiani, Ivane ; Gürlich, Robert (advisor) ; Vokurka, Martin (referee) ; Adamec, Miloš (referee)
Infection and the resulting sepsis continue to be important causes of morbidity in surgical patients. Cytokine network causes activation of neutrophils and vascular endothelium with increased upregulation of adhesion molecules, setting at a train of pathogenic inflammatory reactions in the host. Increased concentrations of inflammatory cytokines observed in the initial phase of postoperative complications have a great significance in forecasting a potentially fatal outcome of the disease and can be used for an early diagnosis of systemic complications.Prospective, clinical trial. Levels of cytokines, procalcitonin (PCT), leptin and acute phase proteins (APP) were measured before and after the operation (planned resection of colorectal cancer) and compared with levels in sepsis. Cytokine levels were measured by ELISA method. APP were estimated by nephelometric analysis.PCT was measured by immunoluminometric analysisDuring the first 24 h after the planned resection of colorectal cancer there was a significant increase in serum concentration of interleukin (IL)-6 which declined in next 48 to 72 h. Serum concentration of tumor necrosis factor (TNF)was the highest between 18 to 24 h after the operation. IL-1 had a stable serum concentration without significant elevation. Serum concentration of IL-8 rose after 36...
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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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Study success in view of modern daat analyzing method
Štuka, Čestmír ; Svačina, Štěpán (advisor) ; Vokurka, Martin (referee) ; Dušek, Ladislav (referee)
The aim of the project is to find, by statistical analysis of the date available at the time of entrance examination, parameters that predict the student's ability to finish his/her studies successfully. In first part of this study, we will discuss admission criteria based on admission test (AT) and on undergraduate grade-point average (uGPA) supplemented by three other criteria (high school graduation in year of admission, performance in profile classes and so on. Admission test shows to be a good predictor of academic performance. Admitting part of students on the basis of their GPA is shown to improve prediction of academic performance. General aptitude test (GAT) was temporarily added to admission process at the First Faculty of Medicine of Charles University in Prague (FFM). To prove predictive validity of GAT and to compare it with validity of current scientific knowledge test (ST). The added value of GAT was also examined. Prediction validity was estimated by Pearson correlation within cohorts (years 2002 - 2009) and by the correlation after each variable has been group-mean centred for all cohorts together. Incremental validity was assessed by testing submodels in linear and logistic regression models. The first year of studies is shown to be crucial for overall academic performance at FFM. Although...
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Iron and regulation of its metabolism in inflammation and disorders of erythropoiesis.
Gurieva, Iuliia ; Vokurka, Martin (advisor) ; Kaňková, Kateřina (referee) ; Pláteník, Jan (referee)
Iron is a metal element with crucial roles in human organism. Both iron deficiency and iron overload are important pathologies. Hepcidin, a peptide synthetized in the liver, is a key iron regulatory hormone. Increased amount of iron and inflammation stimulate its expression while iron deficiency and activated erythropoiesis cause hepcidin downregulation. The regulation of hepcidin expression on the molecular level and its hierarchy and interactions are not completely known. The main regulatory pathway is BMP/ SMAD which reacts to the iron amount in the organism. Several molecules, including hemojuvelin and HFE, are involved in this pathway and their mutations are linked to inappropriately low hepcidin production, iron overload and hereditary hemochromatosis. Erythroid regulation with suppressive action on hepcidin expression is known only partially as well as its connection to the BMP/ SMAD pathway. Recently, two new negative regulators of hepcidin expression have been described. Membrane enzyme present in hepatocytes - matriptase-2 (MT-2, TMPRSS6) and soluble factor secreted by erythroblasts - erythroferrone (ERFE). The aim of our work was to investigate how MT-2 is involved in the erythroid regulatory pathway, and whether it can represent the molecule where various regulatory pathways interact....
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Stress and functional disorders of stomach
Marková, Jana ; Maruna, Pavel (advisor) ; Vokurka, Martin (referee)
This bachelor thesis deals with issues of stress and relationship between stress and functional disorders of the stomach. Theoretical part describes stomach - its anatomy and physiology with emphasis on regulatory mechanisms. In the theoretical part, stress is handled complexly - from the physiological, pathophysiological and psychological point of view. The stress response is described in detail with its effects on the human organism. Separate chapters are dedicated to the effects of chronic stress on the human psyche and gastrointestinal tract. Functional disorders of the stomach are precisely explored - its classification, epidemiology, pathophysiology, diagnostics and therapy are described. Practical part has two parts. First part is an online anonymous questionnaire study distributed among the general public. This questionnaire deals especially with the stress - frequency of feelings of stress, symptoms of stress and how can stress affect the health of the research sample. This part also studies awareness of functional gastrointestinal disorders in general public. Second study examines problematics of functional disorders of the stomach amongst patients of IV. internal clinic of Všeobecná fakultní nemocnice. It is designed as a broad questionnaire study focused on circumstances of the...
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Study success in view of modern daat analyzing method
Štuka, Čestmír ; Svačina, Štěpán (advisor) ; Vokurka, Martin (referee) ; Dušek, Ladislav (referee)
The aim of the project is to find, by statistical analysis of the date available at the time of entrance examination, parameters that predict the student's ability to finish his/her studies successfully. In first part of this study, we will discuss admission criteria based on admission test (AT) and on undergraduate grade-point average (uGPA) supplemented by three other criteria (high school graduation in year of admission, performance in profile classes and so on. Admission test shows to be a good predictor of academic performance. Admitting part of students on the basis of their GPA is shown to improve prediction of academic performance. General aptitude test (GAT) was temporarily added to admission process at the First Faculty of Medicine of Charles University in Prague (FFM). To prove predictive validity of GAT and to compare it with validity of current scientific knowledge test (ST). The added value of GAT was also examined. Prediction validity was estimated by Pearson correlation within cohorts (years 2002 - 2009) and by the correlation after each variable has been group-mean centred for all cohorts together. Incremental validity was assessed by testing submodels in linear and logistic regression models. The first year of studies is shown to be crucial for overall academic performance at FFM. Although...
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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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Endocrine function of adipose tissue and its role in development of atherosclerosis.
Bošanská, Lenka ; Haluzík, Martin (advisor) ; Vokurka, Martin (referee) ; Kříž, Jan (referee)
Adipose tissue represents a multi-functional endocrine organ. Obesity may lead to the increased release of proinflammatory factors and adhesion molecules from adipose tissue, thus playing an important role in the development of atherosclerosis. Recent research studies were focused on the mechanisms of the endothelial dysfunction, low-grade inflammation and adipose tissue endocrine function dysregulation, and their mutual relationships. These processes are of a great interest due to their clinical relevance and increasing numbers of patients suffering from cardiovascular diseases or being at high risk of early atherosclerosis progression. Exact mechanisms and interrelationships of these factors are yet to be fully clarified. (...) Results of this project may represent another step on the way to the detailed explanation of the mechanisms and relationships between adipose tissue endocrine function or dysfunction and atherosclerosis development. Better understanding and ability to prevent or treat the negative metabolic effects of adipose tissue-derived molecules would be of great importance for numbers of patients at high risk of cardiovascular diseases.
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