Imikhiqizo

I-1.Izindlela zokuphrofayili ze-Metabolite zingamathuluzi abalulekile okulinganisa amachibi e-metabolite ezinhlelweni zebhayoloji.Nakuba izindlela eziningi zokuhlonza i-metabolite zibika ukuqina okuhlobene noma zincike kumazinga ambalwa angaphakathi amele wonke ama-metabolite, imfuneko yokugcina yencazelo yobuningi yechibi le-metabolite kumaseli ezinto eziphilayo kanye noketshezi ukunqunywa kokugxilisa okuphelele.Sibika lapha indlela ye-high-throughput ne- sensitive gas chromatography/tandem mass spectrometry (GC/MS/MS) ehloselwe indlela ye-metabolite ehlosiwe evumela ukulinganisa okuphelele kwawo wonke ama-metabolite atholiwe.Indlela isuselwe ekukhishweni kwe-methyl chloroformate kanye nokulinganisa ngamasampula e-spiking anamazinga e-metabolite akhishwe ngokuhlukile ngama-reagents akhishwe.I-ionization yomthelela yama-electron evamile ithathelwa indawo yi-ionization yamakhemikhali enhle njengoba le yokugcina ngokwezinga elikhulu igcina i-ion yamangqamuzana nezinye izingcezu zesisindo samangqamuzana aphezulu.Lokhu kukwenze kwaba lula ukukhetha ukuguqulwa okuhlukile kwe-MS/MS phakathi kwama-metabolite amaningi ahlanganisayo.Njengamanje, indlela yenoveli ye-GC/MS/MS ihlanganisa ama-metabolite avamile angama-67 iningi lawo elingamaqembu ama-amino nama-nonamino organic acid.Sikhombisa ukusebenza kwendlela kumasampula omchamo neserum.Indlela iwukuthuthuka okuphawulekayo kwendlela yamanje yokwenza iphrofayili ye-GC/MS ye-metabolite yama-amino acid nama-nonamino organic acids.

I-2.24S-Hydroxycholesterol (24OHC) kanye ne-27-hydroxycholesterol (27OHC) ama-oxysterol amabili afanayo ngokwesakhiwo anemvelaphi ehlukene--yangaphambili cishe yakheka ngokukhethekile ebuchosheni futhi lena yakamuva yakheka kancane ebuchosheni kunezinye izitho eziningi.I-HYPOTHESIS IYAHLOLWA: Ukulimala kwe-neuronal kanye/noma ukususwa kwe-myelination kubangela ukwanda kokugeleza kwe-24OHC kusuka ebuchosheni kuya ku-cerebrospinal fluid (CSF), kanti ukukhubazeka kwegazi nobuchopho kubangela ukuguquguquka okukhulayo kwe-27OHC kusukela ekujikelezeni ku-CSF.Isotope dilution-mass i-spectrometry yasetshenziselwa ukuhlola ama-oxysterol amabili ku-CSF kanye ne-plasma evela ezigulini ezingaphezu kuka-250 ezinezifo ezihlukene ze-neurological and geriatric.Amazinga e-CSF ama-oxysterol amabili athinteke kakhulu izifo ezihlukene kunamazinga e-plasma.Iziguli ezinezifo ezisebenzayo ze-demyelinating zase zinyukile amazinga we-24OHC ku-CSF enesilinganiso esiphezulu esingu-24OHC/27OHC.Iziguli ezine-meningitis ngokuvamile zazinamazinga aphezulu womabili ama-steroid anesilinganiso esiphansi esingu-24OHC/27OHC.Iziguli ezinesifo i-Alzheimer's zazinamazinga anyuswe kancane we-24OHC ku-CSF ngokukhuphuka okuncane ku-27OHC.Iziguli ezine-multiple sclerosis zazinomkhuba wokuba namazinga aphezulu e-24OHC phakathi nezikhathi ezisebenzayo ezinezinga eliphezulu le-24OHC / 27OHC.Izilinganiso zama-oxysterol amabili ku-CSF ne-plasma zingase zengeze kakhulu ezindleleni ezikhona ze-biochemical zokuhlola izifo ze-neurological.