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I-centrifugation yezokwelapha enokwethenjelwa ngokomlando ibidinga ukusetshenziswa kwempahla ebizayo, enkulu, futhi encike kugesi, ngokuvamile engatholakali kuzilungiselelo ezinomkhawulo wezinsiza.Nakuba kuye kwachazwa ama-centrifuge amaningana aphathekayo, angabizi, angeyona imoto, lezi zixazululo ngokuyinhloko zihloselwe izinhlelo zokuxilonga ezidinga amanani amancane uma kuqhathaniswa ne-sedimentation.Ukwengeza, ukuklanywa kwalezi zinsimbi kuvame ukudinga ukusetshenziswa kwezinto ezikhethekile namathuluzi angatholakali ezindaweni ezingagciniwe.Lapha sichaza ukuklanywa, ukuhlanganisa, kanye nokuqinisekiswa kokuhlolwa kwe-CentREUSE, i-centrifuge esekelwe kudoti ephathwayo ebiza kakhulu, esetshenziswa abantu, yezinhlelo zokwelapha.I-CentREUSE ibonisa amandla amaphakathi e-centrifugal angu-10.5 ahlobene ne-centrifugal force (RCF) ± 1.3.Ukumiswa kwe-1.0 ml ye-vitreous suspension ye-triamcinolone ngemva kwemizuzu engu-3 ye-centrifugation ku-CentREUSE kwaqhathaniswa nalokho ngemva kwamahora angu-12 okuchithwa kwe-gravity-mediated sedimentation (0.41 ml ± 0.04 vs 0.38 ml ± 0.03, p = 0.14).Ukuqina kwentlenga ngemva kokumiswa kwe-CentREUSE imizuzu emi-5 neyi-10 uma kuqhathaniswa nalokho okubonwa ngemva kokumiswa phakathi kwe-centrifugation ku-10 RCF (0.31 ml ± 0.02 vs. 0.32 ml ± 0.03, p = 0.20) kanye no-50 RCF (0.20 ml) imizuzu engu-5 efanayo kusetshenziswa okokusebenza kwezentengiso 0.02 vs. 0.19 ml ± 0.01, p = 0.15).Izifanekiso nemiyalelo yokwakha ye-CentREUSE ifakiwe kulokhu okuthunyelwe komthombo ovulekile.
I-Centrifugation iyisinyathelo esibalulekile ekuhlolweni okuningi kokuxilonga kanye nokungenelela kokwelapha1,2,3,4.Kodwa-ke, ukuzuza i-centrifugation eyanele ngokomlando kuye kwadinga ukusetshenziswa kwempahla ebizayo, enkulu, futhi encike kugesi, ngokuvamile engatholakali kuzilungiselelo ezinomkhawulo wezinsiza2,4.Ngo-2017, iqembu likaPrakash lethule i-centrifuge encane esekwe ephepheni yesandla (ebizwa ngokuthi “i-puffer yephepha”) eyenziwe ngezinto ezenziwe ngaphambili ngenani lika-$0.20 ($)2.Kusukela lapho, i-paper fugue iye yatshalwa ezindaweni ezinomkhawulo wezinsiza zezinhlelo zokusebenza zokuxilonga ezinevolumu ephansi (isb. ukuhlukaniswa okusekelwe ekumineni kwezingxenye zegazi kumashubhu e-capillary ukuze kutholwe izimuncagazi zikamalaleveva), ngaleyo ndlela kubonisa ithuluzi eliphathwayo eliphathwa umuntu elishibhe kakhulu.i-centrifuge 2.Kusukela ngaleso sikhathi, amanye amadivaysi amaningana ahlangene, angabizi, angenanjini achazwe4,5,6,7,8,9,10.Kodwa-ke, iningi lalezi zixazululo, njengentuthu yephepha, zenzelwe izinjongo zokuxilonga ezidinga umthamo omncane wokuthuthwa kwenhlabathi ngakho-ke azikwazi ukusetshenziselwa ukuhlanganisa amasampula amakhulu.Ukwengeza, ukuhlanganiswa kwalezi zixazululo kuvame ukudinga ukusetshenziswa kwezinto ezikhethekile namathuluzi avame ukungatholakali ezindaweni ezingagcinwanga kahle4,5,6,7,8,9,10.
Lapha sichaza ukuklanywa, ukuhlanganisa, kanye nokuqinisekiswa kokuhlolwa kwe-centrifuge (ebizwa ngokuthi i-CentREUSE) eyakhiwe kusuka kudoti we-fugue wephepha ovamile wezinhlelo zokusebenza zokwelapha ezidinga amavolumu aphezulu e-sedimentation.Ikesi 1, 3 Njengobufakazi bomqondo, sihlole idivayisi ngokungenelela kwangempela kwe-ophthalmic: imvula yokumiswa kwe-triamcinolone ku-acetone (TA) ngomjovo olandelayo womuthi we-bolus emzimbeni weso we-vitreous.Nakuba i-centrifugation ye-TA concentration iwukungenelela okuqashelwayo okunezindleko eziphansi zokwelashwa kwesikhathi eside kwezimo ezihlukahlukene zamehlo, isidingo sama-centrifuges atholakala ngokuthengiswa ngesikhathi sokwakhiwa kwezidakamizwa siyisithiyo esikhulu ekusetshenzisweni kwalokhu kwelashwa kuzilungiselelo ezinomkhawulo wezinsiza1,2, 3.uma kuqhathaniswa nemiphumela etholwe ngama-centrifuges avamile okuhweba.Izifanekiso nemiyalelo yokwakha i-CentREUSE ifakiwe kulokhu kuthunyelwa komthombo ovulekile kusigaba “solwazi olwengeziwe”.
I-CentREUSE ingakhiwa cishe yonke kusuka ku-scrap.Womabili amakhophi esifanekiso esiyi-semi-circular (Supplementary Figure S1) aphrintwe ephepheni elijwayelekile le-US carbon letter (215.9 mm × 279.4 mm).Izifanekiso ezimbili ezinamathiselwe eziyisiyingi eziyisiyingi zichaza izici ezintathu ezibalulekile zedizayini ye-CentREUSE, okuhlanganisa (1) unqenqema lwangaphandle lwediski yokuphotha engu-247mm, (2) yakhelwe ukuthwala isirinji engu-1.0ml (enekepisi neplunger enqanyuliwe).imifantu ku-shank) kanye (3) namamaki amabili abonisa lapho kufanele kubhojwe khona izimbobo ukuze intambo idlule kudiski.
Namathisela (isb. ngokunamathelisa okuyizinjongo zonke noma itheyiphu) isifanekiso ebhodini likathayela (usayizi omncane: 247 mm × 247 mm) (Umfanekiso Owengeziwe S2a).Ibhodi likathayela elijwayelekile elithi “A” (ugqinsi ongu-4.8 mm) lisetshenziswe kulolu cwaningo, kodwa ibhodi likathayela eliwugqinsi olufanayo lingasetshenziswa, njengebhodi likathayela elisuka emabhokisini okuthutha alahliwe.Usebenzisa ithuluzi elicijile (elifana neblade noma isikelo), sika ikhadibhodi onqenqemeni lwediski elingaphandle elichazwe kusifanekiso (Umfanekiso Owengeziwe S2b).Bese, usebenzisa ithuluzi elincane, elicijile (njengesihloko sepeni le-ballpoint), dala izimbobo ezimbili ezinogqinsi olugcwele ngobubanzi obungu-8.5 mm ngokwamamaki alandelelwe kusifanekiso (Umfanekiso Ongeziwe S2c).Izikhala ezimbili zamasirinji angu-1.0 ml zibe sezisikwa esifanekisweni kanye nongqimba olungaphezulu lwekhadibhodi kusetshenziswa ithuluzi elicijile njengensingo;ukunakekelwa kufanele kuthathwe ukuze kungalimazi ungqimba lukathayela olungaphansi noma ungqimba olungaphezulu olusele (Umfanekiso Owengeziwe S2d, e) .Bese, xhuma ucezu lwentambo (isb. 3mm intambo kakotini yokupheka noma yimuphi umucu ofana nokujiya nokunwebeka) emigodini emibili bese ubopha iluphu ohlangothini ngalunye lwediski cishe ngo-30cm ubude (I-Supplementary Fig. S2f).
Gcwalisa amasirinji amabili angu-1.0 ml ngamavolumu alinganayo (isb. 1.0 ml we-TA suspension) kanye nekepisi.Induku ye-syringe plunger yabe isinqanyulwa ezingeni le-barrel flange (Umfanekiso Owengeziwe S2g, h).I-cylinder flange ibe isimbozwa ngongqimba lwetheyiphu ukuvimbela ukukhishwa kwepiston encishisiwe ngesikhathi sokusebenzisa okokusebenza.Isipetu ngasinye esingu-1.0 ml sabe sesifakwa kusipetu kahle isivalo sibheke maphakathi nediski (Umfanekiso Owengeziwe S2i).Isirinji ngasinye sabe sesixhunywa okungenani kwidiski nge-adhesive tape (Supplementary Figure S2j).Ekugcineni, qedela ukuhlanganisa i-centrifuge ngokubeka amapeni amabili (njengamapensela noma amathuluzi aqinile amise okwenduku) ekugcineni kwentambo ngaphakathi kweluphu (Umfanekiso 1).
Imiyalo yokusebenzisa i-CentREUSE iyafana naleyo yamathoyizi okuphotha endabuko.Ukuzungezisa kuqalwa ngokubamba isibambo esandleni ngasinye.Ukuntenga kancane ezintanjeni kubangela ukuthi idiski inyakaze iye phambili noma emuva, okubangela ukuthi idiski ijikelezise phambili noma emuva ngokulandelana.Lokhu kwenziwa izikhathi eziningana kancane, ngendlela elawulwayo ukuze izintambo zigoqe.Bese umisa ukunyakaza.Njengoba izintambo ziqala ukuxega, isibambo sidonswa kanzima kuze kube yilapho izintambo ziguquguquka, okubangela ukuba i-disc ijikeleze.Ngokushesha lapho intambo ikhululiwe ngokuphelele futhi iqala ukuhlehla, isibambo kufanele sikhululeke kancane kancane.Njengoba intambo iqala ukuhlehla futhi, sebenzisa uchungechunge olufanayo lokunyakaza ukuze ugcine idivayisi ijikeleza (ividiyo S1).
Kuzinhlelo zokusebenza ezidinga ukumiswa kwe-sedimentation ngokumiswa kwe-centrifugation, idivayisi ibizungeziswa ngokuqhubekayo kuze kube yilapho kufinyelelwa imbudumbudu egculisayo (Umfanekiso Owengeziwe S3a,b).Izinhlayiya eziyinkimbinkimbi zizokwakheka ekugcineni kwe-plunger yombhobho wesirinji futhi i-supernatant izogxila ekugcineni kwesirinji.I-supernatant yabe isikhanywa ngokususa itheyiphu emboze umphetho womgqomo futhi yethule iplunger yesibili ukuze iphushe kancane kancane i-plunger yomdabu iye ngasephuzwini lomjovo, ime lapho ifika ku-compound sediment (Supplementary Figure S3c,d).
Ukuze unqume isivinini sokuzungeza, idivayisi ye-CentREUSE, efakwe amasirinji amabili angu-1.0 ml agcwele amanzi, yarekhodwa ngekhamera yevidiyo enesivinini esikhulu (amafreyimu angu-240 ngomzuzwana) imizuzu engu-1 ngemva kokufinyelela esimweni esiqinile se-oscillation.Omaka eduze konqenqema lwediski ephothayo balandelelwa ngesandla kusetshenziswa ukuhlaziya kohlaka ngefreyimu kokurekhodiwe ukuze kutholwe inani lama-revolution ngomzuzu (rpm) (Figure 2a-d).Phinda n = imizamo engu-10.I-related centrifugal force (RCF) endaweni emaphakathi yombhobho wesirinji bese ibalwa kusetshenziswa ifomula elandelayo:
Ukulinganisa isivinini esijikelezayo nge-CentREUSE.(A–D) Izithombe zokumela ezilandelanayo ezibonisa isikhathi (amaminithi: imizuzwana. ama-millisecond) ukuze kuqedelwe ukuzungezisa idivayisi.Imicibisholo ibonisa izimpawu zokulandelela.(E) Ukulinganisa kwe-RPM kusetshenziswa i-CentREUSE.Imigqa imele incazelo (ebomvu) ± ukuchezuka okujwayelekile (okumnyama).Amaphuzu amele ukuhlolwa ngakunye komzuzu ongu-1 (n = 10).
Isipetu esingu-1.0 ml esiqukethe ukumiswa kwe-TA komjovo (40 mg/ml, i-Amneal Pharmaceuticals, Bridgewater, NJ, USA) yafakwa i-centrifuged imizuzu engu-3, ​​5 kanye ne-10 kusetshenziswa i-CentREUSE.I-Sedimentation kusetshenziswa le nqubo iqhathaniswe naleyo efinyelelwe ngemva kokufakwa endaweni eyi-centrifugation ku-10, 20, kanye no-50 RCF kusetshenziswa i-rotor engu-A-4-62 imizuzu emi-5 ku-Eppendorf 5810R benchtop centrifuge (Hamburg, Germany).Inani lemvula liphinde laqhathaniswa nenani lemvula elitholwe kusetshenziswa imvula encike kumandla adonsela phansi ezindaweni ezihlukahlukene zesikhathi ukusuka kumaminithi angu-0 kuye kwangu-720.Ingqikithi ye-n = 9 ukuphindaphinda okuzimele kwenziwa ngenqubo ngayinye.
Konke ukuhlaziya kwezibalo kwenziwa kusetshenziswa isofthiwe ye-Prism 9.0 (GraphPad, San Diego, USA).Amanani ethulwa njengokuchezuka okujwayelekile ± okujwayelekile (SD) ngaphandle uma kuphawulwe ngenye indlela.Izindlela zeqembu ziqhathaniswe kusetshenziswa i-t-test enemisila emibili ye-Welch.I-Alpha ichazwa ngokuthi 0.05.Ngokuncika okuncike kumandla adonsela phansi, imodeli yesigaba esisodwa sokubola kwe-exponential yafakwa kusetshenziswa ukuhlehla kwesikwele esincane, kuphatha amanani aphindaphindiwe angu-y yenani elingu-x elinikeziwe njengephoyinti elilodwa.
lapho x isikhathi emaminithini.y – ivolumu yentlenga.U-y0 uyinani lika-y uma u-x enguziro.Ithafa linani lika-y imizuzu engapheli.U-K isilinganiso esingaguquki, esivezwa njengokuphindaphinda kwamaminithi.
Idivayisi ye-CentREUSE ibonise ama-oscillations athembekile, alawulwayo angenamugqa kusetshenziswa amasirinji amabili ajwayelekile angu-1.0 ml agcwele u-1.0 ml wamanzi lilinye (ividiyo S1).Ku-n = izilingo eziyi-10 (umzuzu ongu-1 ngalunye), i-CentREUSE yayinesivinini esijwayelekile sokujikeleza esingu-359.4 rpm ± 21.63 (ububanzi = 337-398), okuholela kumandla okubaliwe amaphakathi e-centrifugal angu-10.5 RCF ± 1, 3 (ububanzi = 9.2–12.8. ).(Umdwebo 2a-e).
Izindlela ezimbalwa zokudonsa ukumiswa kwe-TA kumasirinji angu-1.0 ml zahlolwa futhi zaqhathaniswa ne-CentREUSE centrifugation.Ngemva kwamahora angu-12 wokuxazulula okuncike ku-gravity, umthamo we-sediment ufinyelele ku-0.38 ml ± 0.03 (I-Supplementary Fig. S4a,b).Ukufakwa kwe-TA encike ku-Gravity kuhambisana nemodeli yesigaba esisodwa sokubola kwe-exponential (elungiswe ngu-R2 = 0.8582), okuholela ethafeni elilinganiselwe lika-0.3804 mL (95% isikhawu sokuzithemba: 0.3578 kuya ku-0.4025) (Umfanekiso Owengeziwe S4c).I-CentREUSE ikhiqize ivolumu ye-sediment eyisilinganiso engu-0.41 ml ± 0.04 emaminithini angu-3, ​​eyayifana nenani elilinganiselwe lika-0.38 ml ± 0.03 eliqashelwe ukuchithwa okuncike kumandla adonsela phansi amahora angu-12 (p = 0.14) (Fig. 3a, d, h) .I-CentREUSE inikeze ivolumu ehlangene kakhulu ka-0.31 ml ± 0.02 emaminithini angu-5 uma kuqhathaniswa nencazelo ye-0.38 ml ± 0.03 eqashelwa ukuchithwa okusekelwe amandla adonsela phansi emahoreni angu-12 (p = 0.0001) (Fig. 3b, d, h).
Ukuqhathaniswa kwe-TA pellet density okutholwe yi-CentREUSE centrifugation ngokuhlelwa kwamandla adonsela phansi kuqhathaniswa ne-standard industrial centrifugation (A–C).Izithombe ezimele ukumiswa kwe-TA okunciphile kumasirinji angu-1.0 ml ngemva kwamaminithi angu-3 (A), amaminithi angu-5 (B), kanye namaminithi angu-10 (C) okusetshenziswa kwe-CentREUSE.(D) Izithombe ezimelele ze-TA efakiwe ngemva kwamahora angu-12 wokuxazulula amandla adonsela phansi.(EG) Izithombe ezimele ze-TA encishisiwe ngemva kokugxilwa kwezentengiso okujwayelekile kokuthi 10 RCF (E), 20 RCF (F), kanye no-50 RCF (G) imizuzu emi-5.(H) Ivolumu ye-Sediment yalinganiswa kusetshenziswa i-CentREUSE (3, 5, ne-10 min), i-gravity-mediated sedimentation (12 h), kanye ne-industrial centrifugation emizuzwini emi-5 (10, 20, kanye no-50 RCF).Imigqa imele incazelo (ebomvu) ± ukuchezuka okujwayelekile (okumnyama).Amachashazi amele ukuphindaphinda okuzimele (n = 9 esimweni ngasinye).
I-CentREUSE ikhiqize ivolumu eyisilinganiso engu-0.31 ml ± 0.02 ngemva kwemizuzu engu-5, efana nencazelo engu-0.32 ml ± 0.03 ebonwa ku-centrifuge evamile yokuhweba ku-10 RCF imizuzu engu-5 (p = 0.20), futhi ingaphansi kancane kunevolumu yesilinganiso etholwe nge-20 RCF yabonwa ku-0.28 ml ± 0.03 imizuzu engu-5 (p = 0.03) (Fig. 3b, e, f, h).I-CentREUSE ikhiqize ivolumu eyisilinganiso engu-0.20 ml ± 0.02 emaminithini angu-10, eyayiminyene nje (p = 0.15) uma iqhathaniswa nevolumu eyisilinganiso engu-0.19 ml ± 0.01 ngemizuzu emi-5 ebonwa nge-centrifuge yokuhweba ku-50 RCF (Fig. 3c, g, h)..
Lapha sichaza ukuklanywa, ukuhlanganisa, kanye nokuhlolwa kokuqinisekisa kwe-centrifuge enezindleko eziphansi kakhulu, ephathekayo, esetshenziswa umuntu, eyenziwe ngemfucumfucu evamile yokwelapha.Umklamo usekelwe kakhulu ku-centrifuge esekelwe ephepheni (okubizwa ngokuthi "i-paper fugue") eyethulwe iqembu likaPrakash ngo-2017 ukuze kusetshenziswe ukuxilonga.Njengoba kucatshangelwa ukuthi i-centrifugation ngokomlando ibidinga ukusetshenziswa kwezinto zokuhweba ezibizayo, ezinkulu, nezincike kugesi, i-centrifuge ye-Prakash inikeza isisombululo esihle kakhulu senkinga yokufinyelela okungavikelekile ku-centrifugation ezilungiselelweni ezinomkhawulo wezinsiza2,4.Kusukela lapho, i-paperfuge ibonise usizo olusebenzayo ezinhlelweni ezimbalwa zokuxilonga ezinevolumu ephansi, njengokuhlukaniswa kwegazi okususelwa ekuminyana ukuze kutholwe umalaleveva.Kodwa-ke, ngokwazi kwethu, amadivaysi e-centrifuge ashibhile kakhulu afanayo awakaze asetshenziselwe izinjongo zokwelapha, izimo ezidinga ukuthungwa kwevolumu enkulu.
Unalokhu engqondweni, umgomo we-CentREUSE uwukwandisa ukusetshenziswa kwe-centrifugation yephepha ekungeneleleni kokwelapha.Lokhu kufezwe ngokwenza izinguquko ezimbalwa ekwakhiweni kombukiso wePrakash.Ngokuphawulekayo, ukuze kukhuliswe ubude bamasirinji amabili ajwayelekile angu-1.0 ml, i-CentREUSE iqukethe idiski enkulu (irediyasi = 123.5 mm) kunewringer enkulu yephepha ye-Prakash ehloliwe (irediyasi = 85 mm).Ngaphezu kwalokho, ukuze isekele isisindo esengeziwe sesipetu esingu-1.0 ml esigcwele uketshezi, i-CentREUSE isebenzisa amakhadibhodi kathayela esikhundleni sekhadibhodi.Ndawonye, ​​lezi zinguquko zivumela ukunwetshwa kwevolumu emikhulu kunaleyo ehlolwe kusihlanzi sephepha se-Prakash (okungukuthi amasirinji amabili angu-1.0 ml anama-capillary) kuyilapho esathembele ezingxenyeni ezifanayo: imicu kanye nezinto ezisekelwe ephepheni.Ngokuphawulekayo, amanye ama-centrifuge amaningana ashibhile asetshenziswa abantu achazwe ngezinjongo zokuxilonga4,5,6,7,8,9,10.Lokhu kuhlanganisa ama-spinner, ama-salad beater, ama-egg beater, namathoshi esandla emishini ezungezayo5, 6, 7, 8, 9. Nokho, iningi lale mishini ayakhelwe ukuphatha imiqulu efika ku-1.0 ml futhi iqukethe izinto ezivame ukubiza kakhulu. futhi ezingafinyeleleki kunalezo ezisetshenziswe ephepheni i-centrifuges2,4,5,6,7,8,9,10..Eqinisweni, izinto zephepha ezilahliwe zivame ukutholakala yonke indawo;isibonelo, e-United States, iphepha kanye ne-paperboard akhawunti ngaphezu kuka-20% wemfucuza kamasipala eqinile, ehlinzeka ngomthombo omningi, ongabizi, noma wamahhala wokwakha ama-centrifuges wephepha.isb CentREUSE11.Futhi, uma kuqhathaniswa nezinye izixazululo zezindleko eziphansi ezimbalwa ezishicilelwe, i-CentREUSE ayidingi i-hardware ekhethekile (njenge-hardware yokuphrinta ye-3D nesofthiwe, i-laser cutting hardware nesofthiwe, njll.) ukuze idalwe, okwenza ihadiwe ibe yinsiza ejulile..Laba bantu basendaweni 4, 8, 9, 10.
Njengobufakazi bokusebenza okuwusizo kwe-centrifuge yethu yephepha ngezinjongo zokwelapha, sibonisa ukulungiswa okusheshayo nokuthembekile kokumiswa kwe-triamcinolone ku-acetone (TA) yomjovo we-vitreous bolus-ukungenelela okusunguliwe okunezindleko eziphansi zokwelashwa kwesikhathi eside kwezifo ezihlukahlukene zamehlo1 ,3.Ukulungisa imiphumela ngemva kwemizuzu engu-3 nge-CentREUSE iqhathaniswe nemiphumela ngemva kwamahora angu-12 wokuxazulula okuqondiswa amandla adonsela phansi.Ukwengeza, imiphumela ye-CentreUSE ngemva kwe-centrifugation yemizuzu emi-5 neyi-10 yeqe imiphumela ezotholwa amandla adonsela phansi futhi yayifana naleyo ebonwa ngemva kwe-industrial centrifugation ku-10 kanye ne-50 RCF imizuzu emi-5, ngokulandelana.Ngokuphawulekayo, kokuhlangenwe nakho kwethu, i-CentREUSE ikhiqiza isixhumi esibonakalayo esibukhali futhi esishelelayo se-sediment-supernatant kunezinye izindlela ezihloliwe;lokhu kuyinto efiselekayo njengoba kuvumela ukuhlolwa okunembe kakhudlwana komthamo womuthi olawulwayo, futhi kulula ukususa i-supernatant ngokulahlekelwa okuncane komthamo wezinhlayiyana.
Ukukhethwa kwalolu hlelo lokusebenza njengobufakazi bomqondo kwakuqhutshwa isidingo esiqhubekayo sokuthuthukisa ukufinyelela kwe-intravitreal steroids esebenza isikhathi eside kuzilungiselelo ezinomkhawulo wezinsiza.I-Intravitreal steroids isetshenziselwa kakhulu ukwelapha izimo ezihlukahlukene zamehlo, okuhlanganisa i-macular edema yesifo sikashukela, ukuwohloka kwe-macular okuhlobene neminyaka, ukuvinjelwa kwe-retinal vascular occlusion, uveitis, i-radiation retinopathy, ne-cystic macular edema3,12.Kuma-steroid atholakalayo ekuphathweni kwe-intravitreal, i-TA isalokhu isetshenziswa kakhulu emhlabeni jikelele12.Nakuba amalungiselelo angenayo i-TA preservatives (PF-TA) etholakala (isb, i-Triesence [40 mg/mL, i-Alcon, i-Fort Worth, e-USA]), amalungiselelo ane-benzyl alcohol preservatives (isb, i-Kenalog-40 [40 mg/mL, Bristol- Myers Squibb, New York, USA]) isalokhu idume kakhulu3,12.Kumele kuqashelwe ukuthi iqembu lokugcina lezidakamizwa livunyelwe yi-US Food and Drug Administration (FDA) ukuze kusetshenziswe i-intramuscular and intraarticular kuphela, ngakho ukuphathwa kwe-intraocular kubhekwa njengokungabhalisiwe 3, 12.Nakuba umthamo womjovo we-intravitreal TA wehluka ngokuya ngenkomba nendlela yokusebenza, umthamo ovame ukubikwa ngu-4.0 mg (okungukuthi umthamo womjovo ongu-0.1 ml kusixazululo esingu-40 mg/ml), okuvamise ukunikeza isikhathi sokwelashwa cishe izinyanga ezi-3. , 12, 13, 14, 15.
Ukuze kunwetshwe isikhathi sokusebenza kwe-intravitreal steroids ezifweni zamehlo ezingamahlalakhona, ezinzima noma eziphindaphindekayo, kuye kwethulwa amadivaysi amaningi e-steroid asebenza isikhathi eside angafakwa noma ajovwe, okuhlanganisa i-dexamethasone 0.7 mg (Ozurdex, Allergan, Dublin, Ireland), Relax fluoride acetonide 0.59 mg (Retisert , Bausch and Lomb, Laval, Canada) kanye ne-fluocinolone acetonide 0.19 mg (Iluvien, Alimera Sciences, Alpharetta, Georgia, USA)3,12.Kodwa-ke, lawa madivayisi anezinkinga ezimbalwa ezingase zibe khona.E-United States, idivayisi ngayinye igunyazwe kuphela izinkomba ezimbalwa, ezikhawulela ukufakwa komshwalense.Ukwengeza, amanye amadivaysi adinga ukufakelwa kokuhlinzwa futhi angabangela izinkinga eziyingqayizivele njengokuthuthela kwedivayisi ekamelweni elingaphambili3,12.Ukwengeza, lawa madivaysi avame ukutholakala kalula futhi abiza kakhulu kune-TA3,12;ngamanani amanje ase-US, i-Kenalog-40 ibiza cishe u-$20 nge-1.0 ml yokumiswa okwesikhashana, kuyilapho i-Ozurdex, i-Retisert, ne-Iluvien ichaza.Imali yokungena ingaba ngu-$1400., $20,000 kanye ne-$9,200 ngokulandelana.Ndawonye, ​​lezi zici zikhawulela ukufinyelela kulawa madivayisi kubantu abakuzilungiselelo ezikhawulelwe yinsiza.
Imizamo yenziwe yokwelula umphumela we-intravitreal TA1,3,16,17 ngenxa yezindleko zayo eziphansi, imbuyiselo enkulu kakhulu, nokutholakala okukhulu.Uma kubhekwa ukuncibilika kwayo okuphansi kwamanzi, i-TA ihlala iso njengedepho, ivumela ukusakazeka kwezidakamizwa kancane kancane futhi njalo uma kuqhathaniswa, ngakho umphumela kulindeleke ukuthi uhlale isikhathi eside ngamadepho amakhulu1,3.Kuze kube manje, izindlela ezimbalwa zenzelwe ukugxilisa ukumiswa kwe-TA ngaphambi kokujova ku-vitreous.Nakuba izindlela ezisekelwe ku-passive (okungukuthi kuncike kumandla adonsela phansi) zichazwe, lezi zindlela zidla isikhathi futhi zinikeza imiphumela eguquguqukayo15,16,17.Ngokuphambene nalokho, izifundo zangaphambilini zibonise ukuthi i-TA ingagxilwa ngokushesha nangokuthembekile (futhi ngaleyo ndlela isenzo eside) ngemvula yokusiza i-centrifugation1,3.Sengiphetha, ukunethezeka, izindleko eziphansi, ubude besikhathi, kanye nempumelelo ye-TA egxiliswe yi-centrifugally kwenza lokhu kungenelela kube inketho ekhangayo ezigulini ezilungiselelweni ezinomkhawulo wezinsiza.Nokho, ukuntula ukufinyelela ku-centrifugation okuthembekile kungaba isithiyo esikhulu ekusebenziseni lokhu kungenelela;Ngokubhekana nalolu daba, i-CentREUSE ingasiza ekwandiseni ukutholakala kokwelashwa kwe-steroid yesikhathi eside ezigulini ezilungiselelweni ezinomkhawulo wezinsiza.
Kunemikhawulo ethile ocwaningweni lwethu, okufaka phakathi leyo ehlobene nokusebenza kwento kagesi ye-CentREUSE.Idivayisi iyi-oscillator engaqondile, engagcini nje ethembele ekufakweni komuntu ngakho-ke ayikwazi ukuhlinzeka ngezinga elinembile neliqhubekayo lokuzungeza ngesikhathi sokusetshenziswa;isivinini sokuzungezisa sincike kokuhlukile okuningana, okufana nomthelela womsebenzisi ezingeni lobunikazi bedivayisi, izinto ezithile ezisetshenziswa ekuhlanganiseni okokusebenza, kanye nekhwalithi yokuxhuma okuphothwayo.Lokhu kuhlukile kumishini yokuthengisa lapho isivinini sokujikeleza singasetshenziswa ngokuqhubekayo nangokunembile.Ngaphezu kwalokho, isivinini esitholwe yi-CentREUSE singathathwa njengesinesizotha uma siqhathaniswa nesivinini esitholwe amanye amadivaysi e-centrifuge2.Ngenhlanhla, isivinini (kanye namandla e-centrifugal ahlobene) akhiqizwe idivayisi yethu kwanele ukuhlola umqondo onemininingwane ocwaningweni lwethu (okungukuthi, ukubekwa kwe-TA).Ijubane lokujikeleza linganyuswa ngokukhanyisa ubukhulu bediski ephakathi 2;lokhu kungafezwa ngokusebenzisa impahla elula (efana nekhadibhodi elincanyana) uma iqine ngokwanele ukubamba amasirinji amabili agcwele uketshezi.Esimweni sethu, isinqumo sokusebenzisa amakhadibhodi afakiwe “A” ajwayelekile (ubukhulu obungu-4.8 mm) sasingamabomu, njengoba le nto ivame ukutholakala emabhokisini okuthumela ngakho-ke itholakala kalula njengezinto ezigaywa kabusha.Isivinini sokujikeleza singabuye senyuswe ngokunciphisa i-radius ye-disk ephakathi 2.Kodwa-ke, irediyasi yeplathifomu yethu yenziwe ngamabomu yaba nkulu ngokuqhathaniswa ukuze ifake isirinji engu-1.0 ml.Uma umsebenzisi enentshisekelo yokubeka imikhumbi emifushane phakathi nendawo, irediyasi ingancishiswa—ushintsho olungabikezela ukuthi luphumela kuzivinini eziphezulu zokuzungeza (kanye namandla amakhulu okungenzeka amaphakathi).
Ngaphezu kwalokho, asikahlolisisi ngokucophelela umthelela wokukhathala komsebenzisi ekusebenzeni kwemishini.Ngokuthakazelisayo, amalungu amaningana eqembu lethu akwazile ukusebenzisa idivayisi imizuzu engu-15 ngaphandle kokukhathala okuphawulekayo.Isixazululo esingaba khona sokukhathala komsebenzisi lapho kudingeka ama-centrifuge amade ukuzungezisa abasebenzisi ababili noma ngaphezulu (uma kungenzeka).Ngaphezu kwalokho, asizange sikuhlole ngokujulile ukuqina kwedivayisi, ngokwengxenye ngenxa yokuthi izingxenye zedivayisi (ezifana nekhadibhodi nentambo) zingashintshwa kalula ngezindleko eziphansi noma ezingekho esimweni lapho zigugile noma zilimale.Kuyathakazelisa ukuthi phakathi nokuhlolwa kwethu komshayeli wendiza, sasebenzisa umshini owodwa ingqikithi yemizuzu engama-200.Ngemuva kwalesi sikhathi, okuwukuphela kwesibonakaliso esibonakalayo kodwa esincane sokuguga ukubhoboza emicu.
Omunye umkhawulo wocwaningo lwethu ukuthi asizange silinganise ngokuqondile ubukhulu noma ukuminyana kwe-TA efakiwe, okufinyeleleka ngedivayisi ye-CentREUSE nezinye izindlela;esikhundleni salokho, ukuqinisekiswa kwethu kokuhlolwa kwale divayisi bekusekelwe esilinganisweni sokuminyana kwentlenga (ngama-ml).isilinganiso esingaqondile sokuminyana.Ngaphezu kwalokho, asizange sihlole i-CentREUSE Concentrated TA ezigulini, nokho, njengoba idivayisi yethu ikhiqize ama-pellets e-TA afana nalawo akhiqizwa kusetshenziswa i-centrifuge yezohwebo, sicabange ukuthi i-CentREUSE Concentrated TA izosebenza kahle futhi iphephe njengoba isetshenziswe ngaphambilini.ezincwadini.kubikwe kumadivayisi ajwayelekile e-centrifuge1,3.Ucwaningo olwengeziwe olulinganisa inani langempela le-TA elilawulwa ngemuva kokuqinisa i-CentREUSE lungasiza ngokuqhubekayo ukuhlola ukuba wusizo kwangempela kwedivayisi yethu kulolu hlelo lokusebenza.
Ngokwazi kwethu, i-CentREUSE, ithuluzi elingakhiwa kalula ngemfucumfucu etholakala kalula, iyi-centrifuge yephepha yokuqala enamandla abantu, ephathekayo, nengabizi kakhulu ukuthi isetshenziswe endaweni yokwelapha.Ngaphezu kokukwazi ukufaka i-centrifuge amavolumu amakhulu ngokuqhathaniswa, i-CentREUSE ayidingi ukusetshenziswa kwezinto ezikhethekile namathuluzi wokwakha uma kuqhathaniswa namanye ama-centrifuge abiza kancane ashicilelwe.Ukusebenza okubonisiwe kwe-CentREUSE emvula esheshayo nethembekile ye-TA kungasiza ekuthuthukiseni ukutholakala kwe-intravitreal steroid yesikhathi eside kubantu abasezilungiselelweni ezikhawulelwe yinsiza, engasiza ekwelapheni izimo ezihlukahlukene ze-ocular.Ukwengeza, izinzuzo zama-centrifuge ethu aphathwayo anamandla abantu zibikezelwa zidlulela ezindaweni ezinothile ngezinsiza ezifana nezikhungo zezempilo ezinkulu kanye nezikhungo zezempilo emazweni athuthukile.Ngaphansi kwalezi zimo, ukutholakala kwemishini ye-centrifuging kungase kuqhubeke kukhawulelwe kulabhorethri yomtholampilo neyocwaningo, ngengozi yokungcolisa amasirinji ngoketshezi lomzimba womuntu, imikhiqizo yezilwane, nezinye izinto eziyingozi.Ngaphezu kwalokho, la ma-laboratories avame ukuba kude nendawo yokunakekela iziguli.Lokhu, kungase kube isithiyo sokusebenza kubahlinzeki bezempilo abadinga ukufinyelela ngokushesha ku-centrifugation;ukuthunyelwa kwe-CentREUSE kungasebenza njengendlela esebenzayo yokulungiselela ukungenelela kokwelapha esikhathini esifushane ngaphandle kokuphazamisa kakhulu ukunakekelwa kwesiguli.
Ngakho-ke, ukwenza kube lula kuwo wonke umuntu ukulungiselela ukungenelela kokwelapha okudinga i-centrifugation, ithempulethi nemiyalo yokudala i-CentREUSE ifakiwe kulokhu kushicilelwa komthombo ovulekile ngaphansi kwesigaba Solwazi Olwengeziwe.Sikhuthaza abafundi ukuthi bahlele kabusha i-CentREUSE njengoba kudingeka.
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I-SM isekelwa ngokwengxenye isipho esiya ku-Mukai Foundation, i-Massachusetts Eye and Ear Hospital, e-Boston, Massachusetts, USA.
Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear, 243 Charles St, Boston, Massachusetts, 02114, USA