Iimveliso

I-1.Iindlela zeprofayili ye-Metabolite zizixhobo ezibalulekileyo zokulinganisa amachibi e-metabolite kwiinkqubo zezinto eziphilayo.Ngelixa uninzi lweendlela zeprofayili ze-metabolite zixela ubunzulu obunxulumeneyo okanye zixhomekeke kwimigangatho embalwa yangaphakathi emele zonke i-metabolites, eyona mfuno iphambili yenkcazo yobungakanani bechibi le-metabolite kwiiseli zebhayoloji kunye nolwelo kukumiselwa koxinzelelo olupheleleyo.Sinika ingxelo apha i-high-throughput and sensitive gas chromatography/tandem mass spectrometry (GC/MS/MS) ejolise kwindlela yeprofayili yemetabolite eyenza ubungakanani obupheleleyo bazo zonke iimetabolites ezichongiweyo.Indlela isekwe kwi-methyl chloroformate derivatization kunye nobungakanani ngeesampulu ze-spiking ezinemigangatho ye-metabolite ekhutshwe ngokwahlukileyo kunye ne-deuterated derivatization reagents.I-ionization ye-electron yesiko yempembelelo ye-elektroni ithathelwa indawo yi-ionization yeekhemikhali ezilungileyo kuba le yokugqibela ukuya kumlinganiselo omkhulu kakhulu igcina i-ion yemolekyuli kunye namanye amaqhekeza aphezulu obunzima bemolekyuli.Oku kwenza ukuba kube lula ukukhetha utshintsho olulodwa lwe-MS/MS phakathi kweemetabolites ezininzi ezidibanisayo.Okwangoku, inoveli ye-GC/MS/MS yendlela ibandakanya i-67 i-metabolites esisiseko eqhelekileyo apho uninzi lwazo zingamaqela e-amino kunye ne-nonamino organic acids.Sibonisa ukusetyenziswa kwendlela kumchamo kunye neesampuli ze-serum.Indlela iluphuculo olubonakalayo lwendlela yokusebenza yangoku yobuninzi be-GC/MS imetabolite yeprofayili yee-amino acids kunye ne-nonamino organic acids.

I-2.24S-Hydroxycholesterol (24OHC) kunye ne-27-hydroxycholesterol (27OHC) zi-oxysterols ezimbini ezifanayo ngokwemvelaphi yemvelaphi eyahlukileyo-yangaphambili iphantse yabunjwa ngokukodwa ebuchosheni kwaye le yokugqibela yenziwa kwinqanaba elingaphantsi kwengqondo kunamanye amalungu amaninzi.I-HYPOTHESIS IYA KUVAVANYWA: Umonakalo we-Neuronal kunye / okanye ukuchithwa kwe-demyelination kubangela ukunyuka kwe-24OHC ukusuka kwingqondo ukuya kwi-cerebrospinal fluid (CSF), kanti i-defect blood-brain barrier ibangela ukunyuka kwe-27OHC ukusuka kwi-circulation kwi-CSF.Isotope dilution-mass i-spectrometry yayisetyenziselwa ukuvavanya i-oxysterols ezimbini kwi-CSF kunye ne-plasma evela kwizigulane ezingaphezu kwe-250 ezinezifo ezahlukeneyo ze-neurological and geriatric.I-CSF-amanqanaba e-oxysterols amabini achaphazelekayo kakhulu kwizifo ezahlukeneyo kunamanqanaba e-plasma.Izigulane ezinezifo ezisebenzayo zokunciphisa i-demyelinating ziye zanda amanqanaba e-24OHC kwi-CSF kunye nomlinganiselo ophezulu we-24OHC / 27OHC.Izigulane ezine-meningitis ngokubanzi zinezinga eliphezulu zombini i-steroids kunye ne-24OHC / 27OHC ratio ephantsi.Izigulane ezine-Alzheimer's disease ziye zanda amanqanaba e-24OHC kwi-CSF kunye nokunyuka okuncinci kwi-27OHC.Izigulane ezine-multiple sclerosis zazinotyekelo lokuba namazinga aphezulu e-24OHC ngexesha lexesha elisebenzayo kunye ne-24OHC / 27OHC ratio.