Užívanie metylkobalamínu pri autizme
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1 Autistické centrum Andreas n.o.. máj 13 Informačné stretnutie pre rodičov o výsledkoch doterajších štúdií na Univerzite Komenského Užívanie metylkobalamínu pri autizme Katedra farmakológie a toxikológie, FaF UK Bratislava A. Čorejová, M. Rauová 1, D. Jánošíková, J. Repiský, V. Pospíšilová 3, M. Miková, K. Naďová, D. Chlebovská, J. Vojtikevičová, K. Naďová, D. Chlebovská, Hrabovská A., J. Kyselovič 1 Katedra analytickej chémie, Farmaceutická fakulta UK Bratislava Filozofická fakulta Trnavskej Univerzity v Trnave 3 Autistické centrum Andreas, Bratislava Autistické centrum FRANCESCO v Prešove
2 radiácia toxicita O zápal fajčenie voľné radikály z prostredia oxidačný stres chemikálie poškodenie DNA, lipidov, proteínov
3 FYZIOLOGICKY PATOLOGICKY Antioxidačné mechanizmy Voľné radikály Antioxidačné mechanizmy napr. glutation Voľné radikály PACKER, L., WEBER, S.U.: The role of vitamin E in the emerging field of nutraceuticals. In: KRAMER, K., HOPPE, P.P., PACKER, L.: Nutraceuticals in health and disease prevention. New York: Marcel Dekker, 1. s. 7-3.
4 metylb1 (inj., nosový spray) PATOLOGICKY autizmus antioxidačné mechanizmy GLUTATION Voľné radikály injekcie: intramuskulárne, intravenózne nasálne: sprej sirup perorálne: tablety, cmúľacie tablety, kapsuly, žuvacie tablety, perorálny sprej, lízanky, šumivé prášky Zlepšený antioxidačný stav Klinické benefity cieľ.... cieľ James SJ, Melnyk S, Fuchs G, Reid T, Jernigan S, Pavliv O, Hubanks A, Gaylor DW. Efficacy of methylcobalamin and folinic acidtreatment on glutathione redox status in children with autism. Am J Clin Nutr. 9 Jan;89(1):5-3.
5 Vitamín B1 kyanokobalamín aquakobalamín hydroxykobalamín deoxyadenosylkobalamín metylkobalamín hormóny, myelín, DNA, RNA, fosfolipidy, neurotransmitérov súčasťou antioxidačného systému v mozgu hyperhomocysteinémia obličkové zlýhanie ateroskleróza aktivuje tvorbu a udržuje fyziol. konc. homocysteínu znižuje glutamátovú toxicitu syntéza melatonínu nešp. bolesť bedrovej chrbtice Bellova obrna (obrna lícneho nervu) autizmus
6 HYPOTÉZA SLEDOVANIA Podávanie metylovaného vitamínu B1 v sirupovej forme zlepší behaviorálne vlastnosti u pacientov Schéma sledovania 1 x metylb1 Katedra farmakológie a toxikológie, FaF UK Bratislava metylb1 5µg/denne s autizmom zlepšením redoxného pomeru redukovaného k oxidovanému glutationu. x metylb1 pred užívaním metylb1 psychologické vyšetrenie biochemické hodnotenie z krvi metylb1 5µg/denne 3 x metylb1 metylb1 5µg/denne po 3 mesiacoch psychologické vyšetrenie biochemické hodnotenie z krvi bez metylb1 po 6mesiacoch psychologické vyšetrenie biochemické hodnotenie z krvi po 9 mesiacoch psychologické vyšetrenie po skončení užívania metylb1 psychologické vyšetrenie biochemické hodnotenie z krvi
7 1a. Pozitívne prejavy po užívaní metylb1
8 1b. Negatívne prejavy po užívaní metylb1
9 a. Glutationovýredoxnýstatus pred užívaním metylb1 8 Detský autizmus Aspergerov syndróm Zdravá kontrola kon ncentrácia µmol/l u zdravých jedincov (n= 11) GSH GSSG GSH/ GSSG GSH GSSG GSH/ GSSG.5. GSH GSSG GSH/ GSSG GSH GSSG GSH/ GSSG? Podávanie metylb1 pri Aspergerovom syndróme
10 b. Zmena redoxnéhostatusu po 3-mesačnom užívaní metylb1 Detský autizmus koncentr rácia µmol/l glutation vitamin B1 r r 6 8 koncentrácia µmol/l GSH GSSG GSH/GSSG 1. pred ODBER užívaním metylb1. po ODBER 3-mesačnom užívaní metylb1 zlepšil sa oxidačný status nepozorovali sme zvýšené konc. aminokyseliny homocysteín neboli pozorované zvýšené konc. aminokyseliny cystín nebol potvrdený deficit adenylosukcinázy
11 c. Zmena redoxnéhostatusu po 3-mesačnom užívaní metylb1 podľa veku kon ncentrácia µmol/l <7 rokov rokov >15 rokov GSH GSSG GSH/GSSG GSH GSSG GSH/GSSG GSH GSSG GSH/GSSG
12 Predbežné závery už po 3 mesačnej intervencii metylb1 došlo k zlepšeniu: glutationového redoxného statusu klinických prejavov kognitívnych vlastnosti, ale zdá sa, že hlavná úloha metyb1 bude spočívať v metylácii aj inej metabolickej cesty ako sme predpokladali
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