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I-centrifugation yonyango ethembekileyo iye yafuna ngokwembali ukusetyenziswa kwezixhobo zorhwebo ezibizayo, ezinkulu, kunye nezixhomekeke kumbane, ezihlala zingafumaneki kwiisethingi ezinobuncwane.Nangona ii-centrifuge ezininzi eziphathwayo, ezingabizi kakhulu, ezingezizo iimoto ziye zachazwa, ezi zisombululo zijolise ikakhulu kwizicelo zokuxilonga ezifuna umthamo omncinci we-sedimentation.Ukongezelela, ukuyila kwezi zixhobo zihlala zifuna ukusetyenziswa kwezinto ezikhethekileyo kunye nezixhobo ezingafumanekiyo ngokuqhelekileyo kwiindawo ezingagcinwanga.Apha sichaza uyilo, ukudibanisa, kunye nokuqinisekiswa kovavanyo lwe-CentREUSE, ixabiso eliphantsi kakhulu, elisebenza ngabantu, i-centrifuge ephathekayo esekwe kwinkunkuma kwizicelo zonyango.I-CentREUSE ibonisa i-avareji yamandla e-centrifugal ye-10.5 i-related centrifugal force (RCF) ± 1.3.Ukumiselwa kwe-1.0 ml ye-vitreous suspension ye-triamcinolone emva kwemizuzu ye-3 ye-centrifugation kwi-CentREUSE yayifaniswa naloo emva kweeyure ze-12 ze-gravity-mediated sedimentation (0.41 ml ± 0.04 vs 0.38 ml ± 0.03, p = 0.14).Ukuqina kwentlenga emva kwe-CentREUSE centrifugation imizuzu emi-5 kunye ne-10 xa kuthelekiswa naleyo iqatshelweyo emva kokufakwa kwe-centrifugation kwi-10 RCF (0.31 ml ± 0.02 vs. 0.32 ml ± 0.03, p = 0.20) kunye nama-50 RCF (0.20 ml) kwisixhobo sorhwebo esifana ne-5 imizuzu ± . 0.02 vs. 0.19 ml ± 0.01, p = 0.15).Iitemplates kunye nemiyalelo yokwakha ye-CentREUSE ibandakanyiwe kwesi sithuba somthombo ovulekileyo.
I-Centrifugation linyathelo elibalulekileyo kwiimvavanyo ezininzi zokuxilonga kunye nokungenelela kwonyango1,2,3,4.Nangona kunjalo, ukufezekisa i-centrifugation eyaneleyo kuye kwafuna ngokwembali ukusetyenziswa kwezixhobo zorhwebo ezibizayo, ezinkulu, kunye nezixhomekeke kumbane, ezihlala zingafumaneki kwi-resource-limited settings2,4.Kwi-2017, iqela likaPrakash lazisa i-centrifuge encinci ye-manual manual (ebizwa ngokuthi "i-puffer yephepha") eyenziwe kwizinto ezenziwe ngaphambili ngexabiso le-0.20 ($)2.Ukusukela ngoko, i-paper fugue iye yabekwa kwiindawo ezisikelwe umda kwizixhobo zokuxilonga ezinomthamo ophantsi (umz. ulwahlulo olusekwe kuxinaniso lwamalungu egazi kwiityhubhu ze-capillary ukubona izifunxi-gazi zemalariya), ngaloo ndlela kuboniswa isixhobo esiphathwayo esinexabiso eliphantsi kakhulu.i-centrifuge 2.Ukusukela ngoko, ezinye izixhobo ezixineneyo, ezingabizi kakhulu, ezingezizo iimoto ziye zachazwa4,5,6,7,8,9,10.Nangona kunjalo, uninzi lwezi zisombululo, njengomsi wephepha, zenzelwe iinjongo zokuxilonga ezifuna umthamo omncinci wentlenga kwaye ke ngoko azinakusetyenziswa ukumisa iisampulu ezinkulu.Ukongezelela, ukuhlanganiswa kwezi zisombululo zihlala zifuna ukusetyenziswa kwezinto ezikhethekileyo kunye nezixhobo ezihlala zingekho kwiindawo ezingagcinwanga4,5,6,7,8,9,10.
Apha sichaza uyilo, ukudibanisa, kunye nokuqinisekiswa kovavanyo lwe-centrifuge (ebizwa ngokuba yi-CentREUSE) eyakhiwe ngenkunkuma ye-fugue yesiqhelo kwizicelo zonyango ezifuna imithamo ephezulu ye-sedimentation.I-Case 1, i-3 Njengobungqina bengcamango, sivavanye isixhobo ngongenelelo lwangempela lwe-ophthalmic: imvula yokunqunyanyiswa kwe-triamcinolone kwi-acetone (TA) kwi-injection elandelayo ye-bolus drug kwi-vitreous body of the eye.Nangona i-centrifugation yoxinaniso lwe-TA lungenelelo oluvunyiweyo lweendleko eziphantsi kunyango lwexesha elide leemeko ezahlukeneyo zamehlo, isidingo se-centrifuges ekhoyo ngokurhweba ngexesha lokuqulunqwa kweziyobisi ngumqobo omkhulu wokusetyenziswa kolu nyango kwiindawo ezinobuncwane obulinganiselweyo1,2, 3.xa kuthelekiswa neziphumo ezifunyenwe ngee-centrifuge eziqhelekileyo zorhwebo.Izifanekiso kunye nemiyalelo yokwakha i-CentREUSE ibandakanyiwe kulo mthombo ovulekileyo wokuthumela kwindawo ethi "Ulwazi oluninzi".
I-CentREUSE inokwakhiwa phantse yonke ngokusuka kwizinto ezilahliweyo.Zombini iikopi zetemplate yesemi-circular (Figure Supplementary Figure S1) zaprintwa kwiphepha eliqhelekileyo le-US carbon letter (215.9 mm × 279.4 mm).Ezi templates zincanyathiselweyo njengesetyhula zimbini zichaza iimpawu ezintathu eziphambili zoyilo zesixhobo se-CentREUSE, kubandakanywa (1) umphetho ongaphandle wediski yokusonta eyi-247mm, (2) yenzelwe ukufaka isirinji eyi-1.0ml (ene-cap kunye neplunger eshunquliweyo).iigrooves kwi-shank) kunye (3) namanqaku amabini abonisa indawo yokugqobhoza imingxuma ukuze intambo idlule kwidiski.
Namathela (umzekelo, kunye ne-adhesive yenjongo yonke okanye iteyiphu) ithempleyithi kwibhodi yentlaka (ubungakanani obuncinci: 247 mm × 247 mm) (Figure Supplementary Figure S2a).Ibhodi ye-corrugated Standard "A" (i-4.8 mm ubukhulu) isetyenziswe kolu cwaningo, kodwa ibhodi edibeneyo yobunzima obufanayo ingasetyenziswa, njengebhodi edibeneyo kwiibhokisi zokuthumela ezilahliweyo.Ukusebenzisa isixhobo esibukhali (njenge-blade okanye isikere), sika ikhadibhodi ecaleni komda wediski yangaphandle echazwe kwithemplethi (i-Supplementary Figure S2b).Emva koko, usebenzisa isixhobo esincinci, esibukhali (njengencam yepeni yebhola), yenza i-perforations ezimbini ezigcweleyo kunye ne-radius ye-8.5 mm ngokweempawu ezilandelwa kwi-template (i-Supplementary Figure S2c).Iindawo zokubeka ezimbini ze-1.0 ml iisirinji zisikwa kwi-template kunye nomgangatho ongaphantsi wekhadibhodi usebenzisa isixhobo esibukhali njenge-razor blade;kufuneka kuthathelwe ingqalelo ukuba ungonakalisi i-corrugated layer okanye i-surface layer eseleyo (Umfanekiso owongezelelweyo S2d, e) .Emva koko, tsala intambo yomqhaphu (umzekelo, intambo yomqhaphu yokupheka eyi-3mm okanye nawuphi na umsonto ofana nokutyeba nokunwebeka) kwimingxunya emibini kwaye ubophe ikhonkco elijikelezileyo kwicala ngalinye lediski malunga ne-30cm ubude (Fig S2f).
Gcwalisa iisirinji ezimbini ze-1.0 ml malunga nemithamo elinganayo (umz. 1.0 ml ye-TA suspension) kunye nekepusi.Intonga ye-syringe plunger yanqunyulwa kwinqanaba le-barrel flange (Figure Supplementary Figure S2g, h).I-cylinder flange igutyungelwe ngoluhlu lwe-tape ukukhusela ukukhutshwa kwepiston enqanyuliweyo ngexesha lokusetyenziswa kwezixhobo.Isirinji nganye ye-1.0 ml yafakwa kwisirinji kakuhle kunye ne-cap ejongene nombindi wediski (uMzobo owongezelelweyo S2i).Isirinji nganye yadityaniswa ke ubuncinane kwidiski enetape yokuncamathelisa (Supplementary Figure S2j).Ekugqibeleni, gqibezela i-asembly ye-centrifuge ngokubeka iipeni ezimbini (ezifana neepensile okanye izixhobo ezifanayo ezomeleleyo ezimile okwentonga) ekupheleni kwentambo ngaphakathi kwe-loop (Umfanekiso 1).
Imiyalelo yokusebenzisa i-CentREUSE iyafana naleyo yeethoyi zokusonta eziqhelekileyo.Ujikelezo luqalwa ngokubamba isiphatho esandleni ngasinye.Ukucotha kancinci kwiintambo kubangela ukuba idiski igingqike phambili okanye ngasemva, ibangele ukuba idiski ijikeleze phambili okanye ngasemva ngokulandelanayo.Oku kwenziwa izihlandlo eziliqela ngokucothayo, ngendlela elawulwayo ukuze imitya ijike.Emva koko yeka intshukumo.Njengoko imitya iqalisa ukuqhawuka, umqheba utsalwa ngamandla de intambo zibe mbi, nto leyo ebangela ukuba idiski ijikeleze.Ngokukhawuleza ukuba umtya ukhululwe ngokupheleleyo kwaye uqala ukubuyisela umva, isibambo kufuneka sikhululeke kancinci.Njengoko intambo iqala ukukhulula kwakhona, sebenzisa uchungechunge olufanayo lweentshukumo ukugcina isixhobo sijikeleza (ividiyo S1).
Kwizicelo ezifuna i-sedimentation yokunqunyanyiswa nge-centrifugation, isixhobo sasijikeleziswa ngokuqhubekayo de i-granulation eyanelisayo iphunyezwe (Umfanekiso owongezelelweyo S3a,b).Amasuntswana antsonkothileyo aya kubumba ekupheleni kweplunger yombhobho wesirinji kwaye i-supernatant iya kugxila kwincam yesirinji.I-supernatant yatsalwa ngokususa iteyiphu egquma umphanda weflange kwaye yazisa iplunger yesibini ukutyhala ngokucothayo iplunger yalapha ukuya kwincam yesirinji, ime xa ifikelela kwintlenga ekhompawundi (Supplementary Figure S3c,d).
Ukumisela isantya sokujikeleza, isixhobo se-CentREUSE, esixhotyiswe ngeesirinji ezimbini ze-1.0 ml ezizaliswe ngamanzi, zirekhodwe ngekhamera yevidiyo yesantya esiphezulu (iifreyimu ze-240 ngesekhondi) kwi-1 min emva kokufikelela kwi-oscillation eqhubekayo.Abamakishi kufuphi nomda wediski ejikelezayo balandelwa ngesandla kusetyenziswa uhlalutyo lwesakhelo-nge-frame yeerekhodi ukumisela inani leenguqu ngomzuzu (rpm) (Amanani 2a-d).Phinda kwakhona n = 10 imizamo.Amandla aphakathi kwe-centrifugal (RCF) kwindawo esembindini yomphanda wesirinji ibalwa kusetyenziswa le fomula ilandelayo:
Ubalo lwesantya esijikelezayo nge-CentREUSE.(A–D) Ulandelelwano lwemifanekiso emele ebonisa ixesha (imizuzu: imizuzwana. milliseconds) ukugqiba ukujikeleza kwesixhobo.Iintolo zibonisa iimpawu zokulandelela.(E) Ubungakanani be-RPM kusetyenziswa i-CentREUSE.Imigca imele intsingiselo (ebomvu) ± ukutenxa okusemgangathweni (okumnyama).Amanqaku amele uvavanyo lomntu ngamnye lwemizuzu eyi-1 (n = 10).
Isirinji ye-1.0 ml equkethe ukumiswa kwe-TA kwi-injection (40 mg / ml, i-Amneal Pharmaceuticals, i-Bridgewater, i-NJ, i-USA) yayiyi-centrifuged kwi-3, i-5 kunye ne-10 imizuzu usebenzisa i-CentREUSE.I-Sedimentation esebenzisa obu buchule yathelekiswa naleyo iphunyeziweyo emva kwe-centrifugation kwi-10, i-20, kunye ne-50 RCF usebenzisa i-A-4-62 i-rotor ye-5 min kwi-benchtop centrifuge ye-Eppendorf 5810R (eHamburg, eJamani).Isixa semvula siye sathelekiswa nesixa semvula efunyenwe kusetyenziswa imvula exhomekeke kumxhuzulane ngamaxesha ahlukeneyo ukusuka kwi-0 ukuya kwimizuzu engama-720.Itotali ye-n = 9 ukuphindaphinda okuzimeleyo kwenziwa kwinkqubo nganye.
Lonke uhlalutyo lwamanani lwenziwa kusetyenziswa isoftware yePrism 9.0 (GraphPad, San Diego, USA).Amaxabiso aboniswa njengentsingiselo ± ukutenxa okusemgangathweni (SD) ngaphandle kokuba kuphawulwe ngenye indlela.Iindlela zeqela zithelekiswe kusetyenziswa i-t-test enemisila emibini ye-Welch.I-Alpha ichazwa njengo-0.05.Kwi-subsidence exhomekeke kumxhuzulane, imodeli yokubola kwesigaba esinye se-exponential yafakwa kusetyenziswa ubuncinci-squares regression, ukuphatha amaxabiso aphindaphindiweyo y kwixabiso elinikiweyo elingu x njengendawo enye.
apho ux lixesha kwimizuzu.y – umthamo wentlenga.y0 lixabiso likay xa ux enguziro.Ithafa lixabiso elingu y kangangemizuzu engenasiphelo.I-K yireyithi engaguqukiyo, echazwa njenge-reciprocal yemizuzu.
Isixhobo se-CentREUSE sibonise i-oscillations ethembekileyo, elawulwayo engabonakaliyo esebenzisa iisirinji ezimbini eziqhelekileyo ze-1.0 ml ezizaliswe yi-1.0 ml yamanzi nganye (ividiyo ye-S1).Kwi-n = izilingo ze-10 (i-1 iminithi nganye), i-CentREUSE inesantya esijikelezayo se-359.4 rpm ± 21.63 (uluhlu = 337-398), okubangelwa ukubalwa kwe-centrifugal force ye-10.5 RCF ± 1, 3 (uluhlu = 9.2-12.8. ).(Umfanekiso 2a-e).
Iindlela ezininzi zokumiswa kwe-pelleting ye-TA kwi-1.0 ml yesirinji ziye zavavanywa kwaye zithelekiswa ne-CentREUSE centrifugation.Emva kweeyure ze-12 zokuhlaliswa kokuxhomekeka kobunzima, umthamo we-sediment ufikelele kwi-0.38 ml ± 0.03 (i-Supplementary Fig. S4a,b).I-TA exhomekeke kwi-Gravity-dependent deposition ihambelana ne-single-phase-exponential decay model (elungiswe yi-R2 = 0.8582), okubangelwa i-plateau eqikelelwayo ye-0.3804 mL (i-95% yexesha lokuzithemba: 0.3578 ukuya kwi-0.4025) (I-Supplementary Figure S4c).I-CentREUSE ivelise i-avareji ye-sediment volume ye-0.41 ml ± 0.04 ngemizuzu emi-3, eyayifana nexabiso eliqhelekileyo le-0.38 ml ± 0.03 eliqatshelwe ukuchithwa kwentlenga exhomekeke kumxhuzulane kwiiyure ze-12 (p = 0.14) (Fig. 3a, d, h). .I-CentREUSE inike umthamo oxineneyo kakhulu we-0.31 ml ± 0.02 ngemizuzu emi-5 xa kuthelekiswa nomlinganiselo we-0.38 ml ± 0.03 oqatshelwe ukuchithwa kwentlenga esekelwe kumxhuzulane kwiiyure ze-12 (p = 0.0001) (Umfanekiso 3b, d, h).
Uthelekiso loxinaniso lweepellet ze-TA oluphunyezwe yi-CentREUSE centrifugation kunye nomxhuzulane olungisayo ngokuchasene ne-standard industrial centrifugation (A–C).Imifanekiso emeleyo yokumiswa kwe-TA ene-precipitated kwi-1.0 ml yesirinji emva kwe-3 min (A), i-5 min (B), kunye ne-10 min (C) yokusetyenziswa kwe-CentREUSE.(D) Imifanekiso emele ye-TA egciniweyo emva kwe-12 h yokuhlalisa ubunzima.(EG) Imifanekiso emeleyo ye-TA ene-precipitated emva kwe-centrifugation yorhwebo eqhelekileyo kwi-10 RCF (E), i-20 RCF (F), kunye ne-50 RCF (G) kwi-5 min.(H) Umthamo we-Sediment ulinganiswe kusetyenziswa i-CentREUSE (3, 5, kunye ne-10 min), intlenge ye-gravity-mediated sedimentation (12 h), kunye ne-standard industry centrifugation kwi-5 min (10, 20, kunye ne-50 RCF).Imigca imele intsingiselo (ebomvu) ± ukutenxa okusemgangathweni (okumnyama).Amachaphaza amele ukuphindaphinda okuzimeleyo (n = 9 kwimeko nganye).
I-CentREUSE ivelise umthamo ophakathi kwe-0.31 ml ± 0.02 emva kwemizuzu ye-5, efana ne-0.32 ml ± 0.03 ebonwa kwi-centrifuge yorhwebo eqhelekileyo kwi-10 RCF kwimizuzu emi-5 (p = 0.20), kwaye ingaphantsi kancinci kunomthamo ophakathi. efunyenwe nge-20 RCF yabonwa kwi-0.28 ml ± 0.03 imizuzu emi-5 (p = 0.03) (Umfanekiso 3b, e, f, h).I-CentREUSE ivelise umthamo ophakathi kwe-0.20 ml ± 0.02 ngemizuzu eyi-10, eyayifana nje ne-compact (p = 0.15) xa kuthelekiswa nomthamo we-0.19 ml ± 0.01 kwimizuzu emi-5 eqatshelwe nge-centrifuge yorhwebo kwi-50 RCF (Umfanekiso 3c, g, h)..
Apha sichaza uyilo, ukudibanisa, kunye novavanyo lokuqinisekiswa kwe-ultra-low-cost-low-cost, ephathekayo, esebenza ngabantu, i-centrifuge esekwe ephepheni eyenziwe kwinkunkuma eqhelekileyo yonyango.Uyilo lusekelwe kakhulu kwi-centrifuge esekelwe ephepheni (ebizwa ngokuba "yi-fugue yephepha") eyaziswa liqela likaPrakash ngo-2017 kwizicelo zokuxilonga.Ngenxa yokuba i-centrifugation iye yafuna ngokwembali ukusetyenziswa kwezixhobo zorhwebo ezibizayo, ezinkulu, kunye nezixhomekeke kumbane, i-centrifuge yePrakash ibonelela ngesisombululo esihle kwingxaki yokufikelela okungakhuselekanga kwi-centrifugation kwi-resource-limited settings2,4.Ukusukela ngoko, i-paperfuge ibonise into esebenzayo kwizicelo ezininzi zoxilongo ezinomthamo ophantsi, ezinje ngoxinaniso olusekwe kulwahlulo lwegazi lokufumanisa isifo seengcongconi.Nangona kunjalo, ngokolwazi lwethu olungcono, izixhobo ezifanayo ze-centrifuge ezisekelwe kwi-ultra-ixabiso eliphantsi azizange zisetyenziselwe iinjongo zonyango, iimeko ezifuna i-sedimentation yevolumu enkulu.
Ngaloo nto engqondweni, injongo ye-CentREUSE kukwandisa ukusetyenziswa kwe-centrifugation yephepha kungenelelo lonyango.Oku kwaphunyezwa ngokwenza uhlengahlengiso oluninzi kuyilo lwePrakash iveza.Ngokucacileyo, ukunyusa ubude beesirinji ezimbini eziqhelekileyo ze-1.0 ml, i-CentREUSE iqulethe i-disk enkulu (i-radius = 123.5 mm) kuneyona enkulu i-wringer yephepha ye-Prakash evavanyiweyo (i-radius = 85 mm).Ukongeza, ukuxhasa ubunzima obongezelelweyo be-1.0 ml yesirinji ezaliswe lulwelo, i-CentREUSE isebenzisa amakhadibhodi amazinki endaweni yekhadibhodi.Ngokudibeneyo, olu tshintsho luvumela i-centrifugation yemithamo emikhulu kunezo zivavanyiweyo kwisicoci sephepha sePrakash (okt iisirinji ezimbini ze-1.0 ml ezine-capillaries) ngelixa zixhomekeke kumacandelo afanayo: i-filament kunye nemathiriyeli esekwe kwiphepha.Ngokucacileyo, ezinye ii-centrifuge ezininzi ezingabizi kakhulu zichazwe ngeenjongo zokuxilonga4,5,6,7,8,9,10.Ezi ziquka ii-spinners, ii-salad beaters, ii-egg beaters, neetotshi zezandla zezixhobo ezijikelezayo5, 6, 7, 8, 9. Noko ke, uninzi lwezi zixhobo azenzelwanga ukuphatha imiqulu ukuya kutsho kwi-1.0 ml kwaye zibandakanya izinto ezidla ngokubiza imali eninzi. kwaye azifikeleleki kunezo zisetyenziswe kwiphepha le-centrifuges2,4,5,6,7,8,9,10..Enyanisweni, izinto zephepha ezilahliweyo zihlala zifumaneka kuyo yonke indawo;umzekelo, eUnited States, iphepha kunye ne-paperboard akhawunti ngaphezu kwe-20% yenkunkuma eqinileyo kamasipala, ebonelela ngobuninzi, obungabizi, okanye umthombo wamahhala wokwakha i-centrifuges yamaphepha.umz. i-CentREUSE11.Kwakhona, xa kuthelekiswa nezinye izisombululo zeendleko eziphantsi ezipapashwe, i-CentREUSE ayifuni i-hardware ekhethekileyo (efana ne-3D yoshicilelo lwe-hardware kunye nesofthiwe, i-laser cutting hardware kunye ne-software, njl..Aba bantu bakwimo engqongileyo 4, 8, 9, 10.
Njengobungqina bokuba luncedo olusebenzayo lwephepha lethu le-centrifuge kwiinjongo zonyango, sibonisa ukulungiswa ngokukhawuleza nokuthembekileyo kokumiswa kwe-triamcinolone kwi-acetone (TA) ye-vitreous bolus injection-ungenelelo olusekelwe kwindleko ephantsi yonyango lwexesha elide lwezifo ezahlukeneyo ze-ocular1. ,3.Ukubeka iziphumo emva kwemizuzu ye-3 kunye ne-CentREUSE yafaniswa neziphumo emva kweeyure ze-12 zokuhlaliswa kwe-gravity-mediated.Ukongezelela, iziphumo ze-CentREUSE emva kwe-centrifugation ye-5 kunye ne-10 imizuzu igqithise iziphumo eziza kufumaneka ngokuxhuzula kwaye zifana nezo zibonwa emva kwe-industrial centrifugation kwi-10 kunye ne-50 RCF yemizuzu emi-5, ngokulandelanayo.Ngokucacileyo, kumava ethu, i-CentREUSE ivelisa ujongano olubukhali kwaye olugudileyo lwentlenga kunezinye iindlela ezivavanyiweyo;oku kunqweneleka njengoko kuvumela uvavanyo oluchanekileyo lwedosi yeyeza elilawulwayo, kwaye kulula ukususa i-supernatant kunye nokulahlekelwa okuncinci komthamo we-particle.
Ukukhethwa kwesi sicelo njengobungqina bengcamango kwakuqhutywa yimfuneko eqhubekayo yokuphucula ukufikelela kwi-intravitreal steroids esebenza ixesha elide kwiindawo ezilinganiselweyo.I-Intravitreal steroids isetyenziswa ngokubanzi ukunyanga iimeko zamehlo ezahlukeneyo, kubandakanywa i-diabetic macular edema, i-macular degeneration ehlobene neminyaka, i-retinal vascular occlusion, uveitis, i-radiation retinopathy, kunye ne-cystic macular edema3,12.Kwi-steroids ekhoyo kulawulo lwe-intravitreal, i-TA ihlala iyeyona isetyenziswa kakhulu kwihlabathi liphela12.Nangona amalungiselelo angenayo i-TA preservatives (PF-TA) ekhoyo (umzekelo, iTriesence [40 mg/mL, Alcon, Fort Worth, USA]), amalungiselelo ane-benzyl alcohol preservatives (umz., Kenalog-40 [40 mg/mL, Bristol- Myers Squibb, New York, USA]) uhlala engoyena udumileyo3,12.Kufuneka kuqatshelwe ukuba iqela lokugqibela lamachiza livunyiwe yi-US Food and Drug Administration (FDA) yokusetyenziswa kwe-intramuscular and intraarticular kuphela, ngoko ke ulawulo lwe-intraocular lubhekwa njenge-3, 12 engabhaliswanga.Nangona idosi etofwayo ye-intravitreal TA ihluka ngokwesalathiso kunye nobuchule, idosi exhaphakileyo exelwayo yi-4.0 mg (okt umthamo wokutofa we-0.1 ml ukusuka kwisisombululo se-40 mg/ml), edla ngokunika ixesha lonyango malunga neenyanga ezi-3. , 12, 13, 14, 15.
Ukwandisa ixesha lesenzo se-intravitreal steroids kwizifo ezingapheliyo, ezinzima okanye eziphindaphindiweyo zamehlo, izixhobo ezininzi ze-steroid ezifakwe ixesha elide okanye injectable ziye zaziswa, kuquka i-dexamethasone 0.7 mg (Ozurdex, Allergan, Dublin, Ireland), Relax fluoride acetonide 0.59 mg (Retisert , Bausch kunye neLomb, Laval, Canada) kunye ne-fluocinolone acetonide 0.19 mg (Iluvien, Alimera Sciences, Alpharetta, Georgia, USA) 3,12.Nangona kunjalo, ezi zixhobo zineentsilelo ezininzi ezinokubakho.E-United States, isixhobo ngasinye sivunyiwe kuphela kwiimpawu ezimbalwa, ukunciphisa ukhuseleko lwe-inshurensi.Ukongezelela, ezinye izixhobo zifuna ukufakelwa kotyando kwaye zingabangela iingxaki ezizodwa ezifana nokufuduka kwesixhobo kwigumbi langaphambili3,12.Ukongeza, ezi zixhobo zithande ukufumaneka kancinci kwaye zibiza kakhulu kune-TA3,12;kumaxabiso angoku ase-US, i-Kenalog-40 ixabisa malunga ne-$ 20 nge-1.0 ml yokunqunyanyiswa, ngelixa i-Ozurdex, i-Retisert, kunye ne-Iluvien explants.Imali yokungena imalunga ne-1400 yeedola., $20,000 yaye $9,200 ngokulandelelanayo.Ngokudibeneyo, ezi zinto zinciphisa ukufikelela kwezi zixhobo kubantu abakwisethingi esinezibonelelo.
Iinzame zenziwe zokwandisa umphumo we-intravitreal TA1,3,16,17 ngenxa yeendleko zayo eziphantsi, imbuyekezo yesisa, kunye nokufumaneka okukhulu.Ngenxa yokunyibilika kwayo okuphantsi kwamanzi, i-TA ihlala iliso njengendawo yokugcina, ivumela ukusasazwa kweziyobisi ngokuthe ngcembe kwaye ngokuthe rhoqo, ngoko ke umphumo ulindeleke ukuba uhlale ixesha elide kunye neendawo zokugcina ezinkulu1,3.Ukuza kuthi ga ngoku, iindlela ezininzi ziye zaphuhliswa ukuze kugxininiswe ukunqunyanyiswa kwe-TA ngaphambi kokutofa kwi-vitreous.Nangona iindlela ezisekelwe kwi-passive (okt ukuxhomekeka kobunzima) ukuhlaliswa okanye i-microfiltration ichazwe, ezi ndlela zithatha ixesha kwaye zinika iziphumo eziguquguqukayo15,16,17.Ngokuchasene noko, uphononongo lwangaphambili lubonise ukuba i-TA inokugxininiswa ngokukhawuleza nangokuthembekileyo (kwaye ngaloo ndlela inyathelo elide) nge-centrifugation-assisted precipitation1,3.Ukuqukumbela, ukulungelelaniswa, ixabiso eliphantsi, ubude bexesha, kunye nokusebenza kakuhle kwe-TA egxininiswe kwi-centrifugally kwenza olu ngenelelo lube lukhetho olukhangayo kwizigulane kwiindawo ezinobuncwane obulinganiselweyo.Nangona kunjalo, ukungabikho kokufikelela kwi-centrifugation ethembekileyo kunokuba ngumqobo omkhulu wokuphumeza olu ngenelelo;Ngokujongana nalo mbandela, i-CentREUSE inokunceda ukwandisa ukufumaneka konyango lwe-steroid yexesha elide kwizigulane kwiindawo ezilinganiselweyo.
Kukho imida kuphononongo lwethu, kuquka ezo zinxulumene nokusebenza kwemveli kwisixhobo se-CentREUSE.Isixhobo siyi-oscillator engasiyo i-linear, i-non-conservative oscillator exhomekeke kwigalelo lomntu kwaye ngoko ayikwazi ukubonelela ngezinga elichanekileyo kunye neliqhubekayo lokujikeleza ngexesha lokusetyenziswa;Isantya sokujikeleza sixhomekeke kwizinto ezininzi ezahlukeneyo, ezifana neempembelelo zomsebenzisi kwinqanaba lobunini besixhobo, imathiriyeli ethile esetyenziswa ekudibaneni kwesixhobo, kunye nomgangatho woqhagamshelo olusontiweyo.Oku kuhluke kwizixhobo zorhwebo apho isantya sokujikeleza singasetyenziswa ngokuqhubekayo nangokuchanekileyo.Ukongeza, isantya esiphunyezwe yi-CentREUSE sinokuthathwa njengento eqhelekileyo xa kuthelekiswa nesantya esiphunyezwe zezinye izixhobo ze-centrifuge2.Ngethamsanqa, isantya (kunye ne-centrifugal force ehambelanayo) eyenziwe sisixhobo sethu yayanele ukuvavanya ingcamango echazwe kwisifundo sethu (okt, i-TA deposition).Isantya sokujikeleza sinokunyuswa ngokukhanyisa ubunzima bediski ephakathi 2;oku kungafezekiswa ngokusebenzisa izinto ezikhaphukhaphu (ezifana nekhadibhodi ebhityileyo) ukuba yomelele ngokwaneleyo ukuba ibambe iisirinji ezimbini ezizaliswe lulwelo.Kwimeko yethu, isigqibo sokusebenzisa i-standard "A" yekhadibhodi edibeneyo (i-4.8 mm ubukhulu) yenziwe ngamabomu, njengoko le nto ifumaneka rhoqo kwiibhokisi zokuthumela kwaye ngoko ifumaneka lula njengento enokuphinda isetyenziswe.Isantya sokujikeleza sinokunyuswa ngokunciphisa i-radius ye-disk central 2.Nangona kunjalo, iradiyasi yeqonga lethu lenziwe ngamabom ukuba libe likhulu xa lithelekiswa nelinye ukuze kungene i-1.0 ml yesirinji.Ukuba umsebenzisi unomdla kwi-centrifuging imikhumbi emifutshane, i-radius ingancitshiswa-utshintsho oluqikelelwayo olukhokelela kwizantya eziphezulu zokujikeleza (kunye nemikhosi ephezulu ye-centrifugal).
Ukongezelela, asizange sivavanye ngononophelo impembelelo yokukhathala komsebenzisi ekusebenzeni kwezixhobo.Okubangel’ umdla kukuba, amalungu aliqela eqela lethu akwazi ukusebenzisa esi sixhobo kangangemizuzu eli-15 ngaphandle kokudinwa okuphawulekayo.Isisombululo esinokubakho sokudinwa kwabaqhubi xa kufuneka ii-centrifuges ezinde kukujikeleza abasebenzisi ababini okanye ngaphezulu (ukuba kunokwenzeka).Ukongezelela, asizange sihlolisise ngokungqongqo ukuqina kwesixhobo, ngenxa yokuba iinqununu zesixhobo (ezifana nekhadibhodi kunye nentambo) zinokuthi zitshintshwe ngokulula kwixabiso elincinci okanye elingekho kwimeko yokugqoka okanye umonakalo.Okubangela umdla kukuba, ngexesha lovavanyo lwethu lokulinga, sasebenzisa isixhobo esinye kangangemizuzu engama-200 iyonke.Emva kweli xesha, ekuphela kophawu olubonakalayo kodwa oluncinci lokunxitywa kukugqobhoza ecaleni kwemisonto.
Olunye umda wesifundo sethu kukuba asizange silinganise ngokuthe ngqo ubunzima okanye ubuninzi be-TA egciniweyo, enokufezekiswa ngesixhobo se-CentREUSE kunye nezinye iindlela;endaweni yoko, uqinisekiso lwethu lovavanyo lwesi sixhobo lwalusekwe kumlinganiselo woxinaniso lwentlenga (kwi-ml).umlinganiselo ongathanga ngqo woxinaniso.Ukongeza, asikhange sivavanye i-CentREUSE Concentrated TA kwizigulana, nangona kunjalo, ekubeni isixhobo sethu sivelisa iipellets ze-TA ezifanayo nezo zaveliswa kusetyenziswa i-centrifuge yorhwebo, sicinge ukuba i-CentREUSE Concentrated TA iya kusebenza kwaye ikhuseleke njengoko ibisetyenziswa ngaphambili.kuncwadi.ingxelo yezixhobo eziqhelekileyo ze-centrifuge1,3.Izifundo ezongezelelweyo ezibalula elona xabiso le-TA elilawulwayo emva koqingqo lwe-CentREUSE lunokunceda ukuvavanya ngakumbi ukuba luncedo kwesixhobo sethu kwesi sicelo.
Ngokolwazi lwethu, i-CentREUSE, isixhobo esinokwakhiwa ngokulula kwinkunkuma efumanekayo, yi-centrifuge yokuqala eyenziwe ngumntu, ephathekayo, enexabiso eliphantsi kakhulu ukuba isetyenziswe kwimeko yonyango.Ukongeza ekukwazini ukubeka i-centrifuge imiqulu emikhulu, i-CentREUSE ayifuni ukusetyenziswa kwezinto ezikhethekileyo kunye nezixhobo zokwakha xa kuthelekiswa nezinye ii-centrifuges zexabiso eliphantsi ezipapashwe.Ukusebenza okubonakalisiweyo kwe-CentREUSE ngokukhawuleza nangokuthembekileyo kwe-TA yemvula kunokunceda ukuphucula ukufumaneka kwexesha elide le-intravitreal steroid kubantu abakwiisethingi ezinobuncwane, ezinokunceda ukuphatha iimeko ezahlukeneyo ze-ocular.Ukongeza, izibonelelo zee-centrifuge zethu eziphathwayo eziqhutywa ngabantu zinokuqikelelwa zinwenwele kwiindawo ezinobutyebi obufana namaziko ezempilo emfundo ephakamileyo kunye namaziko ezempilo kumazwe aphuhlileyo.Phantsi kwezi meko, ubukho bezixhobo ze-centrifuging bunokuqhubeka bukhawulelwe kwiilebhu zeklinikhi kunye nophando, kunye nomngcipheko wokungcolisa iisirinji ngolwelo lomzimba womntu, iimveliso zezilwanyana, kunye nezinye izinto eziyingozi.Ukongeza, ezi lebhu zihlala zibekwe kude nendawo yokhathalelo lwezigulana.Oku, kwakhona, kunokuba ngumqobo wokulungiselela ababoneleli bezempilo abafuna ukufikelela ngokukhawuleza kwi-centrifugation;ukuhambisa i-CentREUSE inokusebenza njengendlela ephathekayo yokulungiselela ukungenelela kwonyango kwixesha elifutshane ngaphandle kokuphazamisa kakhulu ukunakekelwa kwesigulane.
Ngoko ke, ukwenza kube lula ukuba wonke umntu alungiselele ukungenelela kwezonyango ezifuna i-centrifugation, itemplate kunye nemiyalelo yokudala i-CentREUSE ifakwe kule mpapasho yomthombo ovulekileyo phantsi kwecandelo loLwazi olongezelelweyo.Sikhuthaza abafundi ukuba bayilwe ngokutsha i-CentREUSE njengoko kufuneka.
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I-SM ixhaswa ngenxalenye yesipho kwi-Mukai Foundation, iMassachusetts Eye and Ear Hospital, eBoston, eMassachusetts, eU.SA.
ISebe le-Ophthalmology, i-Harvard Medical School, i-Massachusetts Eye and Ear, i-243 uCharles St, eBoston, eMassachusetts, 02114, eU.SA