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Analysis and Biochemistry of Less Current Steroids - Neuroactive Steroids and Their Sulfates
Včeláková, Helena ; Hill, Martin (advisor) ; Ventura, Karel (referee) ; Meloun, Milan (referee)
Disertation work brings new findings in the field ofbiochemistry and analysis of neuroactive steroids. The pubrications invorved to the dissertation work dear with biochemicar anarysis of neuroactive steroids and its apprication in biomedicine. Some endogenous steroids can act as efficient neuromodurators' These substances are known as neuroactive steroids' If they are synthesized directly in the central nervous system, they have been named the neurosteroids (Schreiber 1980; corpechot, Rober et ar. rggl). some of the neuroactive steroids act as neuroactivators, the others are neuroinhibitors (Kimonides, Khatibi et al. l99g; Kaasik, Kalda et al. 2001; Lockhart, Warner et al. 2002). The neuroactive steroids operate usually as modulators of membrane receptors (GABA_ receptors and NMDA_receptors) responsible for the permeability of ion channels in neuronal cells. Generally, while physiologic functions and pharmacokinetics of endogenous neuroactive steroids studied on animals was investigated (Wang, Wahlstrom et al. 1997; Norberg, Backstrom et al. 19gg), the number of studies concerning neuroactive steroids in human body fluids and tissues in connection with physiology is insufficient (Bicikova, Tallova et al. 2000; Strohle, Romeo et al. 2003). The main problem is probably laboriousness of corresponding...
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Steroid metabolome in human physiology and pathophysiology.
Hána, Václav ; Hill, Martin (advisor) ; Meloun, Milan (referee) ; Čáp, Jan (referee)
Many studies have shown steroid hormone changes in adrenal incidentalomas with subclinical hypercortisolism and various forms of Cushing's syndrome. The aim of our work was to measure, using novel steroid GC-MS/MS measurement procedure, complex picture of many steroids in these patients. With the knowledge of these changes we could better explain causal pathophysiologic changes. In the study on patients with adrenal incidentalomas we described complex steroid changes in patients with subclinical hypercortisolism. Previous studies showed decrease of DHEAS in subclinical hypercortisolism. We confirmed this finding and described a decrease in other androgens and their metabolites. We also evaluated their sensitivity and specificity when compared to routinely used parameters for diagnosis of subclinical hypercortisolism. Furthermore, we looked at the alterations in all measured steroids and their changes in the 1 mg dexamethasone suppression test. In another study, we analyzed steroid changes in various forms of Cushing's syndrome. We confirmed the decrease of adrenal androgens in the ACTH independent forms and mild increase in the ACTH dependent forms. We also described elevations of mineralocorticoid precursors in central and ectopic forms of ACTH secretion. In the distinction of ectopic and central...
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Analysis and Biochemistry of Less Current Steroids - Neuroactive Steroids and Their Sulfates
Včeláková, Helena ; Hill, Martin (advisor) ; Ventura, Karel (referee) ; Meloun, Milan (referee)
Disertation work brings new findings in the field ofbiochemistry and analysis of neuroactive steroids. The pubrications invorved to the dissertation work dear with biochemicar anarysis of neuroactive steroids and its apprication in biomedicine. Some endogenous steroids can act as efficient neuromodurators' These substances are known as neuroactive steroids' If they are synthesized directly in the central nervous system, they have been named the neurosteroids (Schreiber 1980; corpechot, Rober et ar. rggl). some of the neuroactive steroids act as neuroactivators, the others are neuroinhibitors (Kimonides, Khatibi et al. l99g; Kaasik, Kalda et al. 2001; Lockhart, Warner et al. 2002). The neuroactive steroids operate usually as modulators of membrane receptors (GABA_ receptors and NMDA_receptors) responsible for the permeability of ion channels in neuronal cells. Generally, while physiologic functions and pharmacokinetics of endogenous neuroactive steroids studied on animals was investigated (Wang, Wahlstrom et al. 1997; Norberg, Backstrom et al. 19gg), the number of studies concerning neuroactive steroids in human body fluids and tissues in connection with physiology is insufficient (Bicikova, Tallova et al. 2000; Strohle, Romeo et al. 2003). The main problem is probably laboriousness of corresponding...
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