|
|
Factors influencing the metabolism of homocysteine in selected diseases with complex etiopathogenesis
Veselá, Kamila ; Anděl, Michal (advisor) ; Nečas, Emanuel (referee) ; Rušavý, Zdeněk (referee) ; Poledne, Rudolf (referee)
At present, the great medicine to develop molecular genetic techniques, which significantly help to explain the causes of illnesses. In some diseases the genetic basis is well known. These are primarily contingent on monogenic diseases. Unfortunately, many diseases remain the genetic cause is still unknown. The largest group is the so-called complex diseases, where the origin and development of disease involving both genetic and nongenetic factors. These diseases include atherosclerosis, diabetes mellitus, orofacial clefts, preeclampsia, neural tube defects, and many others. Complex diseases are serious health and social problem in developed countries. Clasification of risk factors is the subject of much attention, because knowledge of these factors offer opportunities for effective prevention and treatment. The aim of my work was to obtain new knowledge of factors affecting homocysteine metabolism with regard to the formation of some complex diseases in the Czech population.
|
|
|
Microvascular reactivityand endothelial function in patients with diabetes mellitus and other endocrinopathies
Horová, Eva ; Prázný, Martin (advisor) ; Rybka, Jaroslav (referee) ; Rušavý, Zdeněk (referee)
(EN) Endothelial dysfunction is an early marker of atherosclerotic and cardiovascular complications. It is also a target of research aimed at the factors and mechanisms leading to the vascular impairment. The aim of the thesis was to evaluate the microvascular reactivity and endothelial function in patients with specific metabolic and hormonal disorders. Four separate studies are included in the thesis. First, the influence of hypercortisolism and associated diseases on microvascular reactivity was evaluated in patients with Cushing's syndrome. Second, the changes in microvascular reactivity and endothelial function after standard breakfast were studied in patients with type 2 diabetes. Next two studies were done in type 1 diabetic patients. The impact of acute hyperglycemia on microvascular reactivity was evaluated during hyperinsulinemic isoglycemic and hyperglycemic clamp. Finally, the influence of glycemic variability and insulin treatment on microvascular reactivity and its possible relationship were studied in type 1 diabetic patients. The results indicate that microvascular reactivity and endothelial function are, among other factors, influenced by insulinemia and insulin resistance. Microvascular reactivity was predominantly impaired by the arterial hypertension and diabetes in patients...
|
|
|
Relationship of oxidative stress to parameters of diabetes control in development of vascular complications.
Pelcl, Tomáš ; Prázný, Martin (advisor) ; Rušavý, Zdeněk (referee) ; Šmahelová, Alena (referee)
The aim of this thesis is to contribute to the clarification of the pathogenesis of chronic complications of diabetes mellitus. The main goal of the research was glycaemic variability, its contribution to the activation of oxidative stress and its possible role in the process of advanced glycation, all beyond the scope of persistent hyperglycaemia itself. Another aim of the work is to contribute to the clarification of a possible relationship between glycaemic variability and vascular complications of diabetes. We were the first to describe the association between the concentrations of reactive aldehydes formed during lipid peroxidation and disorders of skin microvascular reactivity in patients with type 1 diabetes (DM1). Elevated markers of oxidative stress were found in this group, furthermore during the 3 years of follow-up higher plasma antioxidant activity was observed. These findings were not dependent of the method of glucose monitoring and glucose variability, which was lower in a subgroup of patients using real-time continuous glucose monitoring (rt-CGM), compared to a subgroup using conventional glucometers. However, it is clear, that hyperglycaemia alone induces increased oxidative stress in patients with diabetes. Simultaneously we observed the opposite process of oxidative stress...
|
|
|
Conservative Treatment of Acute Pancreatitis and Use of Enteral Nutrition
Česák, Vojtěch ; Rušavý, Zdeněk (advisor) ; Kvapil, Milan (referee) ; Sobotka, Luboš (referee)
Acute pancreatitis is a disease which can present in a mild or severe form. In the last few years, the incidence of acute pancreatitis has been steadily rising. The treatment of severe cases is complex and nutrition is one of the key treatment factors. Enteral and parenteral nutrition are documented parts of acute phase treatment included in many guidelines. However, there is a controversy about the timing of initiation of peroral nutrition after the acute phase of severe pancreatitis has resolved. This dissertation shows the results of monocentric prospective randomized trial which compares the safety and effectivity of peroral nutrition compared to enteral nutrition in patients with severe acute pancreatitis during hospitalization as well as in long term after hospital discharge. Patients with severe acute pancreatitis were randomized into two groups - enteral nutrition versus peroral nutrition. The randomized nutrition strategy was initiated within the first 14 days of hospitalization. We monitored the length of hospital stay, tolerance of nutrition, complications, body weight and nutrition parameters. The two groups did not differ significantly in the length of hospital stay. The number of complications was similar between the groups, there was no significant difference in the rate of acute...
|
|
|
Biomarkers in the diagnosis and treatment of diabetic complications
Šoupal, Jan ; Prázný, Martin (advisor) ; Rušavý, Zdeněk (referee) ; Rybka, Jaroslav (referee)
The main objective of this study was research on biomarkers used in both diagnosis and therapy of diabetic complications. The main focus of our work came to be on one of these biomarkers - glycemic variability (GV). High GV is linked with more frequent occurance of hypoglycemia. There are even indications it might contribute to development of diabetic complications. With modern technology - continuous glucose monitoring (CGM), we are now able to reliably describe, calculate and reduce GV. So far it is unclear whether increased GV can contribute to the development of microvascular complications (MVC) in type 1 diabetes (T1D). Studies published so far have assessed GV primarily from routine self-monitoring of blood glucose (SMBG) using glucometers. In the light of this uncertaity, the first part of this work compares GV calculated from CGM with the presence of MVC in T1D patients. GV calculated from CGM, but not from SMBG, proved to be significantly higher in T1D patients with MVC, even though there was no significant difference in glycated hemoglobin (HbA1c). This finding supports the hypothesis that higher GV is related to higher risk of MVC and that HbA1c does not describe diabetes control completely. Moreover, it was shown that GV calculated from SMBG is insufficient. There is still no fully...
|
|
|
Determinants of microvascular and macrovascular diabetic complications
Piťhová, Pavlína ; Kvapil, Milan (advisor) ; Rušavý, Zdeněk (referee) ; Jirkovská, Alexandra (referee)
Background: Diabetes mellitus both type 1 and 2 rank among the strongest predictors of cardiovascular diseases (CVD). We studied differences between type 1 and 2 diabetic women regarding association of risk factors and microvascular complications and association of cardiovascular risk factors with preclinical atherosclerosis expressed as intima-media thickness of common carotid and femoral arteries. Patients and methods: Women with type 1 (n=203) and type 2 diabetes (n=123) were examined. Microvascular complications were analyzed as follow: retinopathy, nephropathy, neuropathy and diabetic foot syndrome and their risk factors. Preclinical atherosclerosis markers expressed as ankle- brachial index (ABI) and toe-brachial index (TBI) and intima-media thickness of common carotic (IMT CCA) and femoral (IMT CFA) arteries meassured by high resolution ultrasound were analyzed with regard to the presence of cardiovascular risk factors. Most important results: No serious differences in risk factors for development of microvascular diabetic complications were found. Concerning preclinical atherosclerosis risk factors in type 1 diabetic women strong association between IMT CCA and body mass index, waist circumference, and total body fat was found in contrast to type 2 diabetic women. In type 2 diabetic women...
|
|
|
Obstetric interventions and pelvic floor disorders
Rušavý, Zdeněk ; Kališ, Vladimír (advisor) ; Roztočil, Aleš (referee) ; Mašata, Jaromír (referee)
Obstetric interventions and pelvic floor disorders - Abstract One of the principal objectives of obstetric interventions in the second stage of labor is prevention of pelvic floor trauma and associated pelvic floor disorders. The most commonly used and also most frequently discussed interventions are manual perineal protection and episiotomy. The majority of pelvic floor disorders are of subjective nature. Therefore, tools for objectification and severity quantification of these disorders are the key to reliable comparison and identification of the most effective interventions. The aim of the dissertation was to find the most effective modification of manual perineal protection, to compare two frequently used types of episiotomy regarding all pelvic floor disorders and finally to find a consensus on the most suitable instrument for anal incontinence severity assessment. Our studies concerning manual perineal protection experimentally described the direction and extent of perineal deformation during vaginal delivery. The subsequent studies on biomechanical model demonstrated that the most effective method of manual perineal protection in peak perineal strain reduction is when the fingers are placed on the perineum 6 cm laterally and 2 cm ventrally from the posterior commissure at both sides and are...
|
|
|
Comparison of metabolic parameters, hormonal level changes and cardiovascular risk in patients with gestational diabetes with healthy pregnant controls using ECG mapping method and other noninvasive cardiologic methodics
Žákovičová, Eva ; Charvát, František (advisor) ; Ošťádal, Petr (referee) ; Rušavý, Zdeněk (referee)
History of GDM not only increases the risk of developing type 2 diabetes mellitus, but also the risk of cardiovascular disease that is independent of type 2 DM. Hyperglycemia leads to significant electrophysiological, functional and structural changes in the cardiovascular system and they are interrelated. One of our main goals was to evaluate metabolic and hormonal changes and detect changes in the cardiovascular system and assess their mutual relations in condition of optimal metabolic control using a predetermined treatment algorithm. Echocardiography findings in our group of patients with GDM confirm the presence of incipient structural changes in left ventricular (significantly thicker IVS, PWD and RWT) compared to the control group. The original finding is that, under optimal compensation of diabetes any of monitored parameters of left ventricular diastolic function have not been changed. Furthermore, we found that complex metabolic care with optimal values of blood sugar together with weight gain monitoring in women with GDM leads to improvement of the 24-hour blood pressure profile without increased prevalence of non-dipper women and that nocturnal decline in BP depends on fasting plasma glucose. ECG body surface mapping did not show statistically significant changes in depolarization and...
|
|
|
Local and systemic pathological processes in diabetic foot diasease and their management
Dubský, Michal ; Jirkovská, Alexandra (advisor) ; Rušavý, Zdeněk (referee) ; Karetová, Debora (referee)
Local tissue factors, ischemia and infection (which are often the cause of re-ulceration) are the main pathogenetic factors for diabetic foot disease (DFD). Neuropathic bone metabolism disorder leads to Charcot osteoarthropathy (CHOA). The aim of this dissertation was to assess experimentally the effectiveness of new skin substitutes, evaluate local vasculogenesis in different types of cell therapy of DFD, the role of infection in recurrence of DFD and scintigraphic parameters of activity of CHOA. Our studies concerning local pathological processes in DFD experimentally proved that gelatine nanofibers accelerate wound healing and can be suitable scaffolds for cell transfer and skin regeneration and also that acellular porcine dermis is more effective in healing of chronic wounds then xenotransplants. Our studies concerning therapeutic vasculogenesis confirmed that efficacy of stem cells (SC) harvested from bone marrow is similar in efficacy to SC separated from peripheral blood after stimulation. We found no evidence for systemic vasculogenesis by means of a significant increase of pro-angiogenic cytokines, which confirms the paracrine effect of injected SC. We proved a significant correlation between angiogeneisis inhibitor (endostatin) and the number of injected SC, which could be an indicator of...
|
|
|
Microvascular reactivityand endothelial function in patients with diabetes mellitus and other endocrinopathies
Horová, Eva ; Prázný, Martin (advisor) ; Rybka, Jaroslav (referee) ; Rušavý, Zdeněk (referee)
(EN) Endothelial dysfunction is an early marker of atherosclerotic and cardiovascular complications. It is also a target of research aimed at the factors and mechanisms leading to the vascular impairment. The aim of the thesis was to evaluate the microvascular reactivity and endothelial function in patients with specific metabolic and hormonal disorders. Four separate studies are included in the thesis. First, the influence of hypercortisolism and associated diseases on microvascular reactivity was evaluated in patients with Cushing's syndrome. Second, the changes in microvascular reactivity and endothelial function after standard breakfast were studied in patients with type 2 diabetes. Next two studies were done in type 1 diabetic patients. The impact of acute hyperglycemia on microvascular reactivity was evaluated during hyperinsulinemic isoglycemic and hyperglycemic clamp. Finally, the influence of glycemic variability and insulin treatment on microvascular reactivity and its possible relationship were studied in type 1 diabetic patients. The results indicate that microvascular reactivity and endothelial function are, among other factors, influenced by insulinemia and insulin resistance. Microvascular reactivity was predominantly impaired by the arterial hypertension and diabetes in patients...
|
guest ::
