Pomen določanja koncentracij uremičnih toksinov pri otrocih s spektrom avtističnih motenj

Purkat, Sara (author), Osredkar, Joško (mentor)

Otroci s spektrom avtističnih motenj imajo pogosto težave s črevesjem, kot sta zaprtje in diareja. Te težave bi bile lahko vzrok povečane sinteze triptofana v črevesju, ki se nato v povečani meri absorbira v krvni obtok in pretvori v uremične toksine. Uremični toksini v povečanih koncentracijah delujejo kot ojačevalci oksidativnega stresa, kar v možganih potencialno vpliva na mikrocirkulacijo in delovanje možganskih celic, za kar se je v zadnjih letih izkazalo, da vpliva na razvoj in resnost kognitivnih motenj. Zaradi tega smo se v okviru magistrske naloge odločili za določanje koncentracij treh uremičnih toksinov v urinu: simetrični dimetilarginin, asimetrični dimetilarginin in indoksil sulfat. Koncentracije teh smo pomerili z encimsko imunskimi testi pri 143 otrocih z diagnosticiranim spektrom avtističnih motenj in pri 47 zdravih otrocih. Podatke smo nato ovrednotili in statistično primerjali parametre med skupinama. Koncentracije zgoraj naštetih parametrov smo prav tako primerjali med podskupinama spektra avtističnih motenj (avtizem in Aspergerjev sindrom) ter kontrolno skupino. Nato smo vrednosti parametrov primerjali tudi znotraj testne skupine, in sicer glede na stopnjo izraženosti motnje, glede na spol in glede na starost,ter opazovali, ali med njimi obstajajo statistično značilne razlike. Rezultati so pokazali, da imajo otroci s spektrom avtističnih motenj v primerjavi z zdravo kontrolno skupino značilno nižje koncentracije simetričnega in asimetričnega dismetilarginina v krvi, medtem ko teh razlik pri indoksil sulfatu nismo uspeli dokazati. Otroci z avtizmom in otroci z Aspergerjevim sindrom imajo značilno nižje koncentracije simetričnega in asimetričnega dimetilarginina v primerjavi z zdravimi otroki. S primerjavo avtističnih otrok in otrok z Aspergerjevim sindromom smo odkrili, da imajo prvi značilno višja razmerja simetričnega in asimetričnega dimetilargina s kreatininom. Primerjava koncentracij parametrov med spoloma ni pokazala nobenih statistično značilnih razlik, prav tako razlik nismo uspeli dokazati s primerjavo otrok glede na starost. Glede na stopnjo izraženosti (blaga, zmerna in težja oblika) smo sicer pričakovali, da se bodo koncentracije parametrov razlikovale, vendar nam razlik v koncentracijah uremičnih toksinov v urinu prav tako ni uspelo dokazati.

• Language: Slovenian
• Keywords: spekter avtističnih motenj, simetrični dimetilarginin, simetrični dimetilarginin, indoksil sulfat
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2021
• PID: 20.500.12556/RUL-127450
• Publication date in RUL: 08.06.2021

Secondary language

• Language: English
• Title: Importance of uremic toxins determination in children with autistic spectrum disorders

Abstract

Children with autism spectrum disorder often have intestinal problems, such as constipation and diarrhea. The following could be the cause of the increased synthesis in tryptophan in intestinal tract, which could lead to increased absorption in blood stream and its metabolism into uremic toxins. Uremic toxins in higher concentration amplify oxidative stress, which could potentially have effect on microcirculation of the brain and function of the brain cells, which has lately shown to have effect on cognitive disorders development. Because of that, we decided to measure concentrations of three uremic toxins in urine sample: symmetrical dimethylarginine, asymmetrical dimethylarginine and indoxyl sulfate. Concentration measurement was done on 143 urine samples of children with autism spectrum disorder and on 47 urine samples of healthy children by using enzyme-linked immunosorbent assay. Results were then statistically analyzed and then compared between groups of children with autism spectrum disorder and healthy children. We also compared results between subgroups of children with spectrum disorder, which are autism and Asperger syndrome and control group. Concentrations of the parameters were also compared based on the gender, age and severity level of disorder in children with autism spectrum disorder. The results showed, that children with autism spectrum disorder compared to healthy children have statistically significant lower concentration of symmetrical and asymmetrical dimethylarginine, while significant difference in concentration of indoxyl sulfate was not proven. Children with autism and Asperger syndrome were also proven to have significant lower concentration of symmetrical and asymmetrical dimethylarginine than healthy children. When comparing between subgroups, we could only prove significant higher ratios of symmetrical and asymmetrical dimethylarginine with creatinine in children with autism compared to those with Asperger syndrome. Gender comparison of the parameters in the children with the autism spectrum disorder failed to yield any significant difference, which goes the same for the comparison based on the age of the children with autism spectrum disorder. We also failed to demonstrate any significant differences between groups that based on the severity level of the autism spectrum disorder (mild, moderate and severe).

• Keywords: autism spectrum disorder, asymmetric dimethylarginine, symmetric dimethylarginine, indoxyl sulfate