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Monitoring of bone metabolism affected by selected drugs
Gradošová, Iveta ; Živná, Helena (advisor) ; Broulík, Petr (referee) ; Blahoš, Jaroslav (referee)
Monitoring of bone metabolism affected by selected drugs Osteoporosis is one of the most common metabolic bone diseases, which belong to civilization diseases, and is a major health and socioeconomic problem, particularly in the older age groups. Cardiovascular diseases are one of the great problems of our society and a leading cause of death worldwide. The major risk factors include hypercholesterolemia and arterial hypertension, which can be effectively reduced by several groups of drugs. At the present, not much attention has been paid to whether or how these drugs affect bone metabolism. With increasing age, people are more likely to develop hypertension and hypercholesterolemia with progressive loss of bone leading to osteoporosis. Many studies have suggested that antihypertensive and hypolipidemic drugs in some way influence bone metabolism. The subject of the present thesis was to investigate the effect of selected, frequently prescribed antihypertensive drugs (amlodipine, metoprolol), and hypolipidemic drugs (ezetimibe, atorvastatin) on bone metabolism in healthy male Wistar albino rats and in rats after orchidectomy (Wistar and spontaneously hypertensive rats). During my postgradual study, three experiments in rats with above mentioned drugs were performed. In the first experiment, drugs...
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Monitoring of bone metabolism affected by selected drugs
Gradošová, Iveta ; Živná, Helena (advisor) ; Broulík, Petr (referee) ; Blahoš, Jaroslav (referee)
Monitoring of bone metabolism affected by selected drugs Osteoporosis is one of the most common metabolic bone diseases, which belong to civilization diseases, and is a major health and socioeconomic problem, particularly in the older age groups. Cardiovascular diseases are one of the great problems of our society and a leading cause of death worldwide. The major risk factors include hypercholesterolemia and arterial hypertension, which can be effectively reduced by several groups of drugs. At the present, not much attention has been paid to whether or how these drugs affect bone metabolism. With increasing age, people are more likely to develop hypertension and hypercholesterolemia with progressive loss of bone leading to osteoporosis. Many studies have suggested that antihypertensive and hypolipidemic drugs in some way influence bone metabolism. The subject of the present thesis was to investigate the effect of selected, frequently prescribed antihypertensive drugs (amlodipine, metoprolol), and hypolipidemic drugs (ezetimibe, atorvastatin) on bone metabolism in healthy male Wistar albino rats and in rats after orchidectomy (Wistar and spontaneously hypertensive rats). During my postgradual study, three experiments in rats with above mentioned drugs were performed. In the first experiment, drugs...
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Monitoring of bone metabolism affected by selected drugs
Gradošová, Iveta ; Živná, Helena (advisor) ; Broulík, Petr (referee) ; Blahoš, Jaroslav (referee)
Monitoring of bone metabolism affected by selected drugs Osteoporosis is one of the most common metabolic bone diseases, which belong to civilization diseases, and is a major health and socioeconomic problem, particularly in the older age groups. Cardiovascular diseases are one of the great problems of our society and a leading cause of death worldwide. The major risk factors include hypercholesterolemia and arterial hypertension, which can be effectively reduced by several groups of drugs. At the present, not much attention has been paid to whether or how these drugs affect bone metabolism. With increasing age, people are more likely to develop hypertension and hypercholesterolemia with progressive loss of bone leading to osteoporosis. Many studies have suggested that antihypertensive and hypolipidemic drugs in some way influence bone metabolism. The subject of the present thesis was to investigate the effect of selected, frequently prescribed antihypertensive drugs (amlodipine, metoprolol), and hypolipidemic drugs (ezetimibe, atorvastatin) on bone metabolism in healthy male Wistar albino rats and in rats after orchidectomy (Wistar and spontaneously hypertensive rats). During my postgradual study, three experiments in rats with above mentioned drugs were performed. In the first experiment, drugs...
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Retinoid regulation of target gene transcription and antitumor activity of retinoid related molecules
Raška, Ivan ; Broulík, Petr (advisor) ; Kostrouch, Zdeněk (referee) ; Pokorný, Jaroslav (referee)
Nuclear Retinoic Acid (RA) Receptors (RARs) activate gene expression through dynamic interactions with coregulators in coordination with the ligand and phosphorylation processes. In the first part of this work, we showed that during RA-dependent activation of the RARq isotype, the pi 60 coactivator pCIP/ACTR/AIВ-1 /RAC-3/TRAM-1 /SRC-3 was phosphorylated by p38MAPK. SRC-3 phosphorylation was correlated to an initial facilitation of RARa-target genes activation, via the control of the dynamics of the interactions of the coactivator with RARa. Then phosphorylation inhibited transcription via promoting the degradation of SRC-3. In line with this, inhibition of p38MAPK markedly enhanced RARa-mediated transcription and RA-dependent induction of cell differentiation. SRC-3 phosphorylation and degradation occurred only within the context of RARa complexes, suggesting that the RAR isotype defined a phosphorylation code through dictating the accessibility of the coactivator to p38MAPK. We proposed a model in which RARa transcriptional activity was regulated by SRC-3 through coordinated events that are fine- tuned by RA and p38MAPK. The retinoid related molecules (RRMs), ST1926 and CD437, are promising anti-cancer agents. In the second part of this work, we compared the RAR trans-activating properties of the two RRMs...
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název v anglickém jazyce není uveden
Urban, Tomáš ; Tošovský, Jan (advisor) ; Broulík, Petr (referee) ; Stříteský, Martin (referee)
An increase in a mean age of the candidates for coronary artery bypass surgery is observed due to universal trend of the whole mankind to grow old. Standard methods using cardiopulmonary bypass and cardiac arrest have achieved undisputable reputation in cardiac surgery and in low-risk procedures they present excellent results. In comparison with younger groups of patients, the elderly showed higher risk of mortality, stroke and morbidity dependent on using cardiopulmonary bypass, general anesthesia and prolonged in-hospital stay. New trends in cardiac surgery seem to be the alternative to accomplish better outcome of this high-risk group of cardiac patients. Those are generally the procedures in surgery, anesthesia and postoperative care called "minimally invasive". An effort to minimize the surgical trauma, prolonged ventilation time and length of stay in postoperative ward as well as to offer prompt verticalisation, rehabilitation and shorter in-hospital stay are the key characters of the abovementioned procedure. The "Aortic No-touch Technique" is an up-to-date method with potential to fulfill the criteria of "minimal invasiveness". This is a procedure avoiding cardiac arrest, cardiopulmonary bypass and excessive aortic manipulation, using only pedicled or free arterial grafts, as composite grafts. Our...
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Bone metabolism, infection and ischemia in diabetic foot syndrome
Bém, Robert ; Jirkovská, Alexandra (advisor) ; Štěpán, Jan (referee) ; Broulík, Petr (referee)
The diabetic foot (DF) is one of the most frequent late complications of diabetes, which often leads to limb amputation and effects the quality of life in patients with diabetes. Ischaemia and infection play important role in pathogenesis of DF. One form of DF is Charcot neuroosteoarthropathy (CNO), defined as a noninfectious destruction of bones and joints in the foot due to diabetic neuropathy. The subject of the dissertation thesis was divided into 3 parts: bone metabolism and CNO, ischaemia and infection in DF and new methods in the treatment of DF. (...) In the third study, new quantitative scintigraphic parameters for assessment of CNO activity were defined and confirmed their satisfactory correlation with other parameters of CNO activity. In fourth and fifth study,good reproducibility was verified and efficiency of power spectral analysis of heart rate variability as a new method for diagnosis of autonomic neuropathy in patients with CNO. Sixth study refered to rare causes of atypical localization of CNO in the knee joint. Ischaemia and infection in DF were resolved in one study. In multivariate analysis of seventh study we approved, that risk factors for difficulty healing after minor amputation of the foot were low level of transcutaneous oxygen tension and high level of C-reactive protein before...
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