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Genetic causes of medullary thyroid carcinoma and Hirschsprung's disease
Václavíková, Eliška ; Bendlová, Běla (advisor) ; Dvořáková, Lenka (referee) ; Stárka, Luboslav (referee)
Genetic causes of medullary thyroid carcinoma and Hirschsprung's disease Abstract Medullary thyroid carcinoma (MTC) and Hirschsprung's disease (HSCR) are classified as simple neurocristopathies, i.e. diseases linked to neural crest-derived cells. MTC is derived from parafollicular cells of the thyroid and HSCR is characterized by absence of enteric ganglia in the gastrointestinal tract. The RET proto-oncogene is only expressed in neural crest-derived cells, including parafollicular cells and enteric neurons. The RET encodes a transmembrane tyrosinekinase receptor that plays an important role during proliferation, differentiation and cell survival, and activates many signaling pathways. If the strictly regulated activation fails, e.g. due to mutations in the specific gene locations, the RET becomes a highly effective oncogene. Activating germline mutations in the RET proto- oncogene lead to hereditary forms of MTC, whereas sporadic forms of MTC are caused by somatic mutations in the tumor tissue. On the contrary, inactivating mutations induce migration failure of ganglion cell precursors during the development of enteric nervous system and result in the development of HSCR. In rare cases, the coexistence of both diseases is caused by mutations with a dual gain-of-function and loss-of-function character....
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Metabolic syndrome and steroid spectrum
Pospíšilová, Hana ; Stárka, Luboslav (advisor) ; Hána, Václav (referee) ; Fingerová, Helena (referee)
Sex steroids influence the storing of fat, and differences in the distribution of fat are a typical secondary sexual characteristic. Androgens act on fatty tissues in males either directly through stimulation of the androgen receptor or indirectly through aromatization of the estrogen receptor. Androgens can be classified as aromatizable or non-aromatizable. Testosterone (T) is the main aromatizable androgen, while its metabolite dihydrotestosterone (DHT) is a non-aromatizable androgen that acts only through the androgen receptor. It is precisely this difference in having activity only through the androgen receptor that has given rise to the hypothesis concerning the differing effects of DHT and T on body composition, with DHT possibly being responsible for male-type fat distribution. As part of my post-graduate studies we analyzed the dependence serum levels of T and DHT on age, as well as changes in their ratio with age. Further, we sought relationships between aromatizable and non-aromatizable androgens and metabolic and anthropometric parameters. We also focused on following any changes in steroidogenesis in obese males. We showed that before puberty the dominant androgen is rather DHT than T, that the fDHT/fT ratio during the life of adult males is constant, and that there is no evidence of a reversal...
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název v anglickém jazyce není uveden
Michalská, Dana ; Štěpán, Jan (advisor) ; Stárka, Luboslav (referee) ; Pavelka, Karel (referee)
Microdamage of bone tissue is one of important aspects of quality of bone. Marked suppression of bone turnover by bisphosphonates is associated with increased accumulation of bone microdamage in animal models. The purpose of our study was to test the hypothesis that long-term treatment with alendronate (ALN) results in accumulation of microdamage in bone in women after menopause and in that case to impairment of bone quality. In this cross-sectional study, 66 women with postmenopausal osteoporosis (mean age of 68.0 years, mean BMD T-score of - 1.7 at total hip and -2.8 at lumbar spine; 62% with prevalent fractures) were evaluated. Thirtyeight had been treated previously with ALN (10 mg/day for a mean duration of 63.6 months) while 28 were treatment naive (TN). Before initiation of ALN treatment, mean serum PINP, plasma CTX, and OC were significantly increased as compared with reference values in premenopausal women (P< 0.05). After 6 months of ALN treatment, the mean of biochemical bone markers indicated significant suppression of bone remodeling (-70.5%, -84.1%, and - 67.3% for PINP, CTX and OC, respectively; P< 0.05). After 43 months of ALN treatment, markers of degradation and synthesis of type 1 collagen were below the lower limit of normal reference range in 50% of women treated with ALN. Without...
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The incidence of thyroid in selected regions of the Czech Republic in terms of saturation with iodine
Dvořáková, Marcela ; Zamrazil, Václav (advisor) ; Topolčan, Ondřej (referee) ; Stárka, Luboslav (referee) ; Čáp, Jan (referee)
24 9. SUMMARY 1. Natural sources such as water or soil contain iodine in low amounts in the Czech Republic. 2. Clinical manifestations of iodopenia were severe and occured in certain geographical areas in the past. 3. Iodization of table salt started in the fifties of the last century as a result of extensive epidemiological research and since then it has significantly improved iodine saturation in general. 4. Further steps in iodine prophylaxis in the mid-nineties of the 20th century have improved iodine saturation according to ICCIDD/WHO criteria. 5. Resolution of iodine deficiency does not represent, however, a closed chapter. 6. Individuals at risk, such as pregnant or breastfeeding women and patients on a salt- restricted diet, are worthy of public health concern. 7. There needs to be increased awareness of chronic excess of iodine with respect to an increasing prevalence of autoimmune thyroid disorders. 8. There is a need to continue education of the general population focused on adequate iodine intake from various foods (see products, milk) and to maintain a daily iodine intake in the "optimal ranges". Based on the international criteria, the Czech Republic is iodine sufficient country. This happened due to a multidisciplinary collaboration coordinated by the Regional Iodine Deficiency Council...
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The influence of pharmacology and reduction diet on metabolism of adipose tissue in obese patients with diabetes type 2
Anderlová, Kateřina ; Haluzík, Martin (advisor) ; Vítek, Libor (referee) ; Stárka, Luboslav (referee)
Insulin resistance, obesity, type 2 diabetes mellitus and their complications are linked together under definition called Metabolic or Reaven Syndrome. The presence of Metabolic Syndrome increases the risk of atherosclerosis and consequently cardiovascular morbidity and mortality. Metabolic Syndrome belongs among civilization diseases and due to changes in our life styles becomes major health and social-economic issue. The insulin resistance is considered primary pathology that may induce other components of Metabolic Syndrome. Research conducted within last decade brought significant results and showed how important is the adipose tissue in the development of insulin resistance especially in the context of discovery of endocrine function of adipose tissue. The existence of nuclear receptors PPAR (peroxisome proliferator activated receptor) could explain the interaction between particular tissues and hormonal factors which may induce insulin resistance. When the PPAR receptors are bound by lipophilic ligands they directly affect transcriptional processes in cell nucleus and induce expression of genes involved in metabolism of lipids and carbohydrates, in the regulation of inflammation, in tumor growth regulation, in immune response, in cell differentiation and etc. In current medical practice...
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název v anglickém jazyce není uveden
Milotová, Martina ; Langmeier, Miloš (advisor) ; Kozler, Petr (referee) ; Stárka, Luboslav (referee)
The long-term consumption of ethanol by pregnant or nursing rat mothers results in extensive damage of the hippocampal area in their offspring. The histochemical methods combining bis-benzimide 33342 (Hoechst) and Fluoro-Jade B staining were used to detect ethanol effects on the structure of the rat hippocampus and gyrus dentatus during development and adult age (18, 35, 90 and 360 days old offspring). In all experimental groups, in all analyzed areas, degenerative changes were observed, loss of pyramidal and granular cells and neural cells with segmented nuclei. In animals, whose mothers drunk 20% ethanol, structural changes were more intensive when compared with the group consuming 10% ethanol. The highest density of the degenerating (FJ/B positive) cells was found in 18-days-old animals whose mothers were exposed to 20% ethanol. In the age of 90 and 360 days no degenerating cells were identified in the monitored areas. With respect to the properties of the ethanol and mechanism of its effect we suppose that exposure to ethanol during the perinatal period induced the neural cell loss by apoptotic mechanism. From the results of the work can be concluded: 1. The perinatal exposure to ethanol results in degeneration of neural cells in the hippocampus and gyrus dentatus (working hypothesis I was confirmed)....
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Immune abnormalities and infectious complications in patients with diabetic foot and therapy of diabetic foot by off-loading
Fejfarová, Vladimíra ; Jirkovská, Alexandra (advisor) ; Lacinová, Silvie (referee) ; Stárka, Luboslav (referee)
The diabetic foot (DF) develops based on a complex of patophysiological processes which are presented in patients with diabetic complications. DF significantly increases a patient morbidity and mortality and markedly impairs the quality of life of these patients. The theme of the dissertation "immunological abnormalities and infection complications in patients with the DF and therapy of the DF by off-loading" was divided into 3 parts: - abnormalities of immune functions in connection with diabetes and its complications, especially with the DF - infectious complications of the DF - therapy of the DF by off-loading. Problems concerning the impairment of immune functions in connection with diabetes and the DF were resolved in 5 studies, infectious complications of the DF in 3 studies and the therapy of the DF by off-loading similarly in 3 studies. Abnormalities of immune functions in connection with diabetes and its complications, especially with the DF The first study deals with the effect of acute hyperglycemia and/or hyperinsulinemia on function of PMN cells in healthy subjects. The aim of this study was to assess the effect of short lasting acute metabolic changes on phagocytosis and the respiratory burst of PMN cells in healthy subjects in vivo. Acute hyperglycemia and/or hyperinsulinemia were...
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Ghrelin in malnutrition of various etiologies Gherlin as a factor in the pathogenesis of systemic inflammatory response
Rosická, Martina ; Marek, Josef (advisor) ; Stárka, Luboslav (referee) ; Vrbíková, Jana (referee)
Ghrelin, the endogenous ligand for the growth hormone secretagogue receptor, was discovered in 1999 by Kojima et al. (Kojima et al. 1999). Ghrelin is composed of 28 amino acids, with a unique octanoyl modification of hydroxygroup on serine at the 3rd position. This peptide modification is entirely unique to the organism and is essential for the function of this peptide (Bednarek et al. 2000). Ghrelin is predominantly produced by cells in the oxyntic mucosa of the stomach (Date et al. 2000). According to the widespread distribution of the peptide and its receptor ghrelin has multiple biological effects. Ghrelin is a strong stimulator of the growth hormone secretion in the somatotroph cells of hypophysis (Takaya et al. 2000, Peino et al. 2000), plays an important role in signaling hypothalamic centers regulating feeding and caloric state (ghrelin leads to an increase of the food intake and a decrease of the energy expenditure) (Nakazoto et al. 2001). Its orexigenic effects are independent of growth hormone stimulation and appear to be mediated at least in part through activation of NPY/agouti gene-related protein neurons in the hypothalamic arcuate nucleus. The aim of our study is to demonstrate the change of active and total ghrelin in malnourished patient and during systemic inflammatory response and their...
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