"NB7569"
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Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
Přeruš. str. : tab., grafy ; 30 cm
Projekt je zaměřen na hodnocení aktivity sympatického nervového systému a změn jednotlivých částí metabolizmu katecholaminů na lokální úrovni a za různých patologických situací. Budou vyšetřovány zdravé kontroly, pacienti s hyperkortizolismem, obezitou,Lokální metabolizmus katecholaminů v tukové tkáni in vivo bude posuzován metodou mikrodialýzy, která je ve světě u lidí běžně používána. Koncentrace katecholaminů a jejich metabolitů v mikrodialyzátu reflektují jejich koncentrace tkáňové. Výzkum změn funkce sympatického nervového systému v tukové tkáni obézních pacientů a rozdíly oproti pacientům s hyperkortizolismem přispějí k objasnění patogenezy trunkální obezity u hyperkortizolismu. Tento problém nebyl dosud plně objasněn. Dále budou studovány změnyfunkce sympatického nervového systému vtukové tkáni u hypertyreózy a hypotyreózy před a po léčbě. Tyto změny rovněž nebyly dosud plně charaketrizovány.; The aim of the project is to evaluate local activity of sympathetic nervous systém and specific changes in metabolism of catechols in the adipose tissue. The local sympathetic function will be evaluated using clinical microdialysis. Concentration of various substances in microdialysate reflects their concentrations in interstitial fluid. We will examine healthy controls and patients with obesity, chronic hypercortisolaemia, hyperthyroidism and hypothyroidism. The diferences in sympathetic function between patients with simple obesity and central obesity during chronic hypercortisolaemia give us an insight into mechanisms that are involved in development of typical central obesity. The characterization of specific changes in sympathetic function in adipose tisue of patients with hypothyroidism and hyperthyroidism has not been completely described so far and could explain some clinical symptoms.
- MeSH
- adrenokortikální hyperfunkce MeSH
- hypertyreóza MeSH
- hypotyreóza MeSH
- mikrodialýza MeSH
- obezita MeSH
- sympatický nervový systém MeSH
- tuková tkáň MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- endokrinologie
- neurologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
Cushing's syndrome is associated with typical central redistribution of adipose tissue. The aim of the study was to assess lipolysis and catecholamines and their metabolites in subcutaneous abdominal adipose tissue using an in-vivo microdialysis technique. Nine patients with Cushing's syndrome and nine age-, gender- and body mass index (BMI)-matched control subjects were included in the study. Local glycerol concentrations were significantly increased in subcutaneous adipose tissue of patients with Cushing's syndrome (p<0.001). Plasma noradrenaline, dihydroxyphenylglycol and dihydroxyphenylalanine were decreased in patients with Cushing's syndrome (p<0.02, p<0.05, and p<0.02, respectively). Adrenaline, noradrenaline, dihydroxyphenylglycol and dihydroxyphenylalanine concentrations in subcutaneous abdominal adipose were non-significantly higher in patients with Cushing's syndrome. In conclusion, we showed that lipolysis in subcutaneous adipose tissue of patients with Cushing's syndrome is significantly increased as compared to healthy subjects. This finding together with non-significantly increased local catecholamine concentrations in these patients suggests a possible link between increased lipolysis and catecholaminergic activity in subcutaneous adipose tissue.
- MeSH
- Cushingův syndrom etiologie metabolismus MeSH
- financování vládou MeSH
- glycerol metabolismus MeSH
- hydrokortison chemie metabolismus MeSH
- interpretace statistických dat MeSH
- katecholaminy metabolismus MeSH
- lidé MeSH
- lipolýza genetika MeSH
- noradrenalin metabolismus MeSH
- obezita etiologie metabolismus MeSH
- tuková tkáň enzymologie metabolismus patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
BACKGROUND: Adipose tissue produces both vascular growth factors and inhibitors. Since obesity is associated with expansion of the capillary bed in regional adipose depots the balance between these factors may favor angiogenesis. OBJECTIVE: To investigate the relationship between body mass index and serum concentrations of vascular growth factors in human subjects. METHODS: Vascular endothelial growth factor (VEGF), VEGF-C, VEGF-D, soluble VEGF receptor-2 (sVEGFr2), hepatocyte growth factor (HGF), angiopoietin-2, angiogenin and endostatin concentrations were measured in serum collected from 58 lean (24 males, 34 female, mean BMI, 22.2+/-0.3) and 42 overweight and obese (16 males and 26 females, mean BMI, 33.5+/-1.2) subjects after an overnight fast. RESULTS: Sexual dimorphism was apparent in the serum concentrations of VEGF-C, VEFG-D and angiopoietin-2 with significantly higher levels in female compared to male subject. VEGF, VEGF-C, VEGF-D, soluble VEGF receptor-2, angiopoietin-2, angiogenin and endostatin but not HGF were significantly elevated in overweight and obese subjects. Positive correlations between BMI and the serum concentrations of VEGF-C, VEGF-D, sVEGF-R2, angiopoietin-2, angiogenin and endostatin were observed even after adjustment for gender and age. CONCLUSIONS: Increased levels of vascular growth factors as well as the angiogenesis inhibitor endostatin are present in overweight and obese subjects and may contribute to previously documented increased risk of metastatic disease in obese subjects with cancer.
- MeSH
- adiponektin krev MeSH
- analýza rozptylu MeSH
- angiogenní proteiny * krev MeSH
- angiopoetin-2 krev MeSH
- dospělí MeSH
- endostatiny * krev MeSH
- hepatocytární růstový faktor krev MeSH
- inzulinová rezistence MeSH
- leptin krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- lineární modely MeSH
- nadváha MeSH
- obezita * krev MeSH
- pankreatická ribonukleasa krev MeSH
- pohlavní dimorfismus MeSH
- receptor 2 pro vaskulární endoteliální růstový faktor krev MeSH
- vaskulární endoteliální růstový faktor A krev MeSH
- vaskulární endoteliální růstový faktor C krev MeSH
- vaskulární endoteliální růstový faktor D krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
BACKGROUND: Vascular growth factors are important not only in angiogenesis but also for the maintenance of normal endothelial integrity and function. Elevated levels of vascular endothelial growth factor (VEGF), angiopoietin-2, hepatocyte growth factor (HGF), endostatin and angiogenin have been associated with endothelial dysfunction and atherosclerosis. Both acromegaly and growth hormone deficiency (GHD) are associated with endothelial dysfunction and changes in blood vessel morphology. AIM: To investigate the effect of GH status on the circulating levels of angiogenic factors. DESIGN: We measured the levels of six endothelial growth modulators, four angiogenic growth factors and two inhibitors of angiogenesis in 35 untreated acromegalics, 36 untreated GH-deficient subjects and 101 normal control subjects. Fifteen GH-deficient subjects were also studied before and 1 year after treatment with GH. RESULTS: Mean angiogenin concentrations were increased in acromegaly and decreased in GH-deficient subjects compared to control subjects. Endostatin levels showed a similar pattern although the elevated levels in acromegalic subjects did not achieve statistical significance. Angiogenin and endostatin levels both correlated significantly with IGF-I levels (R = 0.61, P < 0.001 and R = 0.22, P < 0.01, respectively). The relationship between angiogenin and IGF-I levels remained significant even after correction for gender, age, body mass index (BMI) and insulin resistance. There were no significant differences in the levels of HGF, VEGF, VEGF-C or angiopoietin-2 between the three groups. VEGF-D levels were elevated in both acromegalic and GH-deficient male subjects. A similar pattern was apparent in female subjects. After GH treatment, a significant reduction in VEGF-D levels and a significant rise in endostatin levels were observed in GH-deficient subjects. A nonsignificant increase in angiogenin levels was also observed. CONCLUSION: These data indicate that significant perturbations in the levels of vascular growth modulators are present in both acromegaly and GHD. While changes in endostatin and angiogenin levels appear to correlate with IGF-I levels, VEGF-D levels show similar perturbations in both acromegaly and GHD. Further studies are required to determine the relationship of the perturbations to endothelial dysfunction in these conditions.
- MeSH
- akromegalie krev patofyziologie MeSH
- angiopoetin-2 krev MeSH
- dospělí MeSH
- endostatiny krev MeSH
- hepatocytární růstový faktor krev MeSH
- inhibitory angiogeneze krev MeSH
- insulinu podobný růstový faktor I analýza MeSH
- látky indukující angiogenezi * krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidský růstový hormon fyziologie nedostatek MeSH
- menopauza fyziologie MeSH
- pankreatická ribonukleasa krev MeSH
- sexuální faktory MeSH
- vaskulární endoteliální růstový faktor A krev MeSH
- vaskulární endoteliální růstový faktor C krev MeSH
- vaskulární endoteliální růstový faktor D krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- dospělí MeSH
- finanční podpora výzkumu jako téma MeSH
- hypertyreóza patologie MeSH
- hypotyreóza patologie MeSH
- lidé MeSH
- nemoci endokrinního systému diagnóza patologie MeSH
- nemoci nadledvin patologie MeSH
- pohlavní hormony metabolismus MeSH
- růstový hormon metabolismus MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH