20.500.12556/RUL-169152 Klinični pomen določanja frakcij porfirinov v urinu otrok z motnjami avtističnega spektra The clinical value of porphyrin fractions determination in the urine of children with autism spectrum disorders Motnje avtističnega spektra so pervazivne razvojne motnje s kompleksno in heterogeno etiologijo. Zaenkrat se diagnoza postavi klinično na podlagi meril opredeljenih v Diagnostičnem in statističnem priročniku duševnih motenj. V zadnjem času pa močno narašča zanimanje za analizo nenormalnih profilov metabolitov v telesnih tekočinah otrok z motnjami avtističnega spektra. V sklopu magistrske naloge smo se osredotočili na povišane ravni porfirinov v urinu in njihov vpliv na resnost razvojnega zaostanka. Cilj magistrske naloge je bil dokaz povišanih ravni porfirinov in identifikacija frakcij, ki so za to povišanje odgovorne. Z zgodnejšo diagnozo bolezni bi namreč ciljno usmerjena intervencija lahko izboljšala prognozo bolezni. V naključnih vzorcih urina smo izmerili koncentracije celokupnih porfirinov ter posameznih frakcij. Za normalizacijo rezultatov smo določili še kreatinin v urinu. Že izračun povprečnih koncentracij porfirinov je pokazal povišane ravni pri otrocih z motnjami avtističnega spektra v primerjavi s kontrolami. Te razlike se v večji meri izrazijo šele pri starejših otrocih, kar je lahko posledica prisotnosti agensa v okolju. Enake rezultate smo dobili z analizo celotne populacije ter posameznih starostnih skupin z Mann-Whitneyevim U-testom. V urinu otrok, starejših od 10,1 let, so bile povišane vrednosti uroporfirinov, heptaporfirinov, koproporfirinov in celokupnih porfirinov. Drugi del magistrske naloge se je osredotočal na ugotavljanje korelacije med koncentracijo porfirinov in resnostjo razvojnega zaostanka na podlagi Ocenjevalne lestvice otroškega avtizma. Rezultati testa enakosti median niso pokazali statistično značilnih razlik med testno in kontrolno skupino. Prav tako nismo uspeli dokazati odstopanj v koncentracijah porfirinov glede na stopnjo izraženosti avtizma. Pri interpretaciji rezultatov je potrebno upoštevati vse dejavnike, ki potencialno vplivajo na koncentracijo porfirinov. Mednje prištevamo starost, spol ter številne druge dejavnike, ki delujejo na različne fiziološke sisteme. Glede na rezultate raziskave priporočamo rutinsko testiranje urinskih porfirinov pri posameznikih z visokim tveganjem za razvoj motenj avtističnega spektra. V prihodnosti bi bilo smiselno obravnavati rezultate v korelaciji s koncentracijami težkih kovin. Za dokaz pozitivne korelacije med porastom koncentracije porfirinov v urinu in resnostjo razvojnega zaostanka pa bi potrebovali metodološke pristope, ki upoštevajo kumulativno tveganje več dejavnikov. Autism spectrum disorders are pervasive developmental disorders with a complex and heterogeneous etiology. Currently a diagnosis is made clinically, based on criteria defined in the Diagnostic and Statistical Manual of Mental Disorders. Recently, however, there has been a growing interest in the analysis of abnormal metabolite profiles in body fluids of children with autism spectrum disorders. As part of the master's thesis, we focused on elevated levels of porphyrins in urine and their influence on the severity of developmental delay. The aim of the master's thesis was to demonstrate elevated levels of porphyrins in the urine and to identify the fractions responsible for this elevation. With an earlier diagnosis of the disease, a targeted intervention could improve the prognosis of the disease. The concentrations of total porphyrins and individual fractions were measured in random urine samples. To normalize the results, creatinine in the urine was also determined. The calculation of average concentrations of porphyrins showed elevated levels in children with autism spectrum disorders compared to controls. These differences are expressed to a greater extent in older children, which may be the result of the presence of an enviromental agent. The same results were obtained by analyzing the entire population and individual age groups with the Mann-Whitney U-test. In the urine of children older than 10,1 years, the levels of uroporphyrins, heptaporphyrins, coproporphyrins and total porphyrins were elevated. The second part of the master's thesis focuses on determining the correlation between the concentration of porphyrins and the severity of developmental delay, based on the Children's Autism Rating Scale. The results of the median equality test didn't show any statistically significant difference between the test and control group. We were also unable to demonstrate a difference in porphyrin concentrations depending on the level of autism. When interpreting the results, it is necessary to take into account all factors that potentially affect the concentration of porphyrins. These include age, gender and many other factors that affect various physiological systems. Based on the research results, we recommend routine testing of urinary porphyrins in individuals with a high risk for developing autism spectrum disorders. In the future, it would be reasonable to consider the results in correlation with heavy metal concentrations. In order to demonstrate a positive correlation between the concentration of porphyrins and the severity of the developmental delay, methodological approaches that take into account the cumulative risk of several factors would be needed. ASD porfirini CARS korelacija dejavniki ASD porphyrins CARS correlation factors true false false Slovenski jezik Angleški jezik Magistrsko delo/naloga 2025-05-15 08:45:04 2025-05-15 08:45:13 2025-05-16 03:56:43 0000-00-00 00:00:00 2025 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 1970-01-01 114743 24092.pdf 24092.pdf 1 A372759A08DCDF92D6567134F6931F96 12173789460584f1a1357072a3e9affab9000df156fae89b4ba9ae6f427113c1 eedf9750-3156-11f0-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=210343 Fakulteta za farmacijo 0 0 0