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Masiraidhi anoratidza zvinyorwa zvitatu pane siraidhi.Shandisa mabhatani ekumashure neanotevera kufamba nemumasiraidhi, kana mabhatani ekudzora masiraidhi ari kumagumo kuti ufambe nemumasiraidhi ega ega.
Kuvimbika kwekurapa centrifugation kwagara kuchida kushandiswa kwemidziyo inodhura, yakakura, uye inotsamira pamagetsi, iyo isingawanzo kuwanikwa muzvigadziriso-zvishoma.Kunyangwe akati wandei anotakurika, asingadhure, asiri-motorized centrifuges akatsanangurwa, mhinduro idzi dzakanyanya kuitirwa kuongororwa kwekushandisa kunoda mashoma mavhoriyamu e sedimentation.Mukuwedzera, kugadzirwa kwezvigadziri izvi zvinowanzoda kushandiswa kwezvinhu zvakakosha uye zvishandiso zvisingawanzo kuwanikwa munzvimbo dzisina kuchengetedzwa.Pano tinotsanangura dhizaini, kusangana, uye kuyedza kusimbiswa kweCentREUSE, mutengo wakaderera, unoshandiswa nevanhu, unotakurika tsvina-yakavakirwa centrifuge yekurapa maapplication.CentREUSE inoratidza avhareji yepakati pesimba re10.5 hama centrifugal force (RCF) ± 1.3.Kugadziriswa kwe 1.0 ml vitreous suspension ye triamcinolone mushure memaminitsi matatu e centrifugation muCentREUSE yakafananidzwa neiyo mushure memaawa gumi nemaviri emagetsi-mediated sedimentation (0.41 ml ± 0.04 vs 0.38 ml ± 0.03, p = 0.14).Sediment thickening mushure meCentREUSE centrifugation kwemaminitsi mashanu uye gumi zvichienzaniswa neyakaonekwa mushure mekuisa centrifugation pa10 RCF (0.31 ml ± 0.02 vs. 0.32 ml ± 0.03, p = 0.20) uye 50 RCF (0.20 ml) kwemaminetsi akafanana ± ± 5 maminetsi 0.02 vs. 0.19 ml ± 0.01, p = 0.15).Iwo matemplate uye mirairo yekuvaka yeCentREUSE inosanganisirwa mune ino yakavhurwa sosi positi.
Centrifugation inhanho yakakosha muongororo dzakawanda dzekuongororwa uye kupindira kwekurapa1,2,3,4.Zvisinei, kuwana centrifugation yakakwana yakagara ichida kushandiswa kwezvinhu zvinodhura, zvakakura, uye zvemagetsi zvekutengesa, izvo zvisingawanzowaniki mune zvigadziriswa-zvishoma zvirongwa2,4.Muna 2017, boka raPrakash rakaunza diki pepa-based manual centrifuge (inonzi "bepa puffer") yakagadzirwa kubva kune zvakagadzirirwa zvinhu pamutengo we $ 0.20 ($)2.Kubva ipapo, mapepa fugue akaiswa munzvimbo-zvishoma-zvishoma zvigadziriso zveakaderera-vhoriyamu yekuongorora maapplication (semuenzaniso density-based kupatsanurwa kwezvikamu zveropa mucapillary chubhu kuona utachiona hwemalaria), zvichiratidza chiridzwa chakachipa chinotakurika chine simba remunhu.centrifuge 2 .Kubva ipapo, mamwe akati wandei compact, isingadhure, isiri-motorized centrifugation zvishandiso zvakatsanangurwa4,5,6,7,8,9,10.Nekudaro, mazhinji emhinduro idzi, sehutsi hwemapepa, anoitirwa kuongororwa zvinoda mavhoriyamu madiki uye nekudaro haagone kushandiswa kuisa centrifuge masampuli makuru.Mukuwedzera, kuungana kwezvigadziriso izvi zvinowanzoda kushandiswa kwezvinhu zvakakosha uye zvishandiso zvisingawanzowaniki munzvimbo dzisina kuchengetwa4,5,6,7,8,9,10.
Pano tinotsanangura dhizaini, kuungana, uye kuyedza kusimbiswa kwecentrifuge (inonzi CentREUSE) yakavakwa kubva kune yakajairwa mapepa fugue tsvina yekurapa maapplication ayo anowanzoda akakwira sedimentation mavhoriyamu.Case 1, 3 Sehumbowo hwepfungwa, takaedza mudziyo nekupindira kwemaziso chaiwo: kunaya kwekumiswa kwe triamcinolone muacetone (TA) yekutevera jekiseni remushonga we bolus mu vitreous body yeziso.Kunyange zvazvo centrifugation yeTA concentration ndeyekupindira kunozivikanwa kwemutengo wakaderera wekurapa kwenguva refu kwemamiriro akasiyana-siyana emaziso, kudiwa kwekutengesa centrifuges panguva yekugadzirwa kwezvinodhaka ndicho chipingamupinyi chikuru chekushandiswa kwechirwere ichi mune zvigadziriswa-zvishoma zvirongwa1,2, 3.zvichienzaniswa nemhedzisiro inowanikwa neyakajairwa kutengeserana centrifuges.Matemplate uye mirairo yekuvaka CentREUSE inosanganisirwa mune ino yakavhurika sosi kutumira muchikamu che "Mamwe Ruzivo".
CentREUSE inogona kuvakwa ingangoita zvachose kubva kune zvimedu.Makopi ese ari maviri esemi-denderedzwa template (Supplementary Figure S1) akadhindwa payakajairwa US carbon letter paper (215.9 mm × 279.4 mm).Iwo akabatanidzwa maviri semi-denderedzwa matemplate anotsanangura matatu akakosha magadzirirwo emudziyo weCentREUSE, kusanganisira (1) rimu rekunze re247mm spinning disk, (2) rakagadzirirwa kugarisa 1.0ml sirinji (ine cap uye akagurwa plunger).migero mushangi) uye (3) mavanga maviri anoratidza pokubaya maburi kuitira kuti tambo ipfuure nepadisiki.
Batira (semuenzaniso neadhesive-chinangwa-chese kana tepi) template kune corrugated board (minimum size: 247 mm × 247 mm) (Supplementary Figure S2a).Standard "A" corrugated board (4.8 mm gobvu) yakashandiswa muchidzidzo ichi, asi corrugated board yehukobvu hwakafanana inogona kushandiswa, senge corrugated board kubva kumabhokisi ekutakura akaraswa.Uchishandisa mudziyo unopinza (wakadai sechipiko kana chigero), cheka kadhibhodhi pamucheto wedhisiki rekunze rinotsanangurwa pane template (Supplementary Figure S2b).Zvadaro, uchishandisa mudziyo wakamanikana, wakapinza (wakaita sepamuromo wepeni), gadzira maviri akazara-kukora perforations ane radius ye8.5 mm zvichienderana nezviratidzo zvakatevedzwa patemplate (Supplementary Figure S2c).Nzvimbo mbiri dzemajekiseni e1.0 ml dzinobva dzachekwa kubva patemplate uye nepamusoro pepamusoro pekadhibhodhi pachishandiswa mudziyo wakanongedza sereza;kuchenjerera kunofanira kutorwa kuti kurege kukuvadza pasi pasi corrugated layer kana yakasara pamusoro pepamusoro (Supplementary Figure S2d, e) .Wadaro, pinza chidimbu chetambo (semuenzaniso 3mm yekubikisa tambo yedonje kana chero shinda yakafanana ukobvu uye elasticity) kuburikidza nemaburi maviri uye sunga chiuno kumativi ega ega edhisiki kureba 30cm (Supplementary Fig. S2f).
Zadza majekiseni maviri ane 1.0 ml ane anenge mavhoriyamu akaenzana (eg 1.0 ml yeTA suspension) uye cap.Sirinji plunger tsvimbo yakabva yadimburwa pamwero webarrel flange (Supplementary Figure S2g, h).Iyo cylinder flange inozofukidzwa netambo ye tepi kudzivirira kubuda kweiyo truncated piston panguva yekushandiswa kwemidziyo.Imwe neimwe sirinji ye1.0 ml yakazoiswa mujekiseni mutsime nekepisi yakatarisana nepakati pedhisiki (Supplementary Figure S2i).Sirinji yega yega yakazonamirwa kune kanenge disc ine adhesive tepi (Supplementary Figure S2j).Pakupedzisira, pedzisa kusangana kwe centrifuge nekuisa mapeni maviri (akadai semapenzura kana maturusi akasimba akafanana netsvimbo) pamagumo etambo mukati mechiuno (Mufananidzo 1).
Mirayiridzo yekushandisa iyo CentREUSE yakafanana neyechinyakare kuruka matoyi.Kutenderera kunotanga nekubata mubato muruoko rumwe norumwe.Kunonoka zvishoma mutambo kunoita kuti dhisiki ritenderere mberi kana kumashure, zvichiita kuti dhisiki ritenderere mberi kana kumashure.Izvi zvinoitwa kakawanda nenzira inononoka, inodzorwa kuitira kuti tambo dzimonere.Zvadaro mira kufamba.Tambo dzacho padzinotanga kusununguka, mubato unodhonzwa nesimba kusvikira tambo dzati nyangarara, zvichiita kuti dhisiki ritenderere.Kana tambo yacho ichinge yasununguka zvachose uye inotanga kudzoka shure, mubato wacho unofanirwa kusununguka zvishoma nezvishoma.Sezvo tambo inotanga kusunungura zvakare, shandisa zvakafanana zvakatevedzana zvekufambisa kuchengetedza mudziyo uchitenderera (vhidhiyo S1).
Pazvikumbiro zvinoda sedimentation yekumiswa ne centrifugation, mudziyo wakaramba uchitenderedzwa kusvika granulation inogutsa yawanikwa (Supplementary Figure S3a,b).Complex particles anozoumba pamagumo eplunger yesirinji barrel uye supernatant inonangana kumuromo wesirinji.Iyo supernatant yakabva yadirwa nekubvisa tepi yakavhara mbiya flange uye nekuunza yechipiri plunger kuti zvishoma nezvishoma isundire plunger yekuzvarwa yakananga kumuromo wejekiseni, ichimira kana yasvika kune kommboni sediment (Supplementary Figure S3c,d).
Kuti uone kumhanya kwekutenderera, mudziyo weCentREUSE, wakashongedzerwa nemasirinji maviri e1.0 ml akazadzwa nemvura, yakanyorwa nekamera yevhidhiyo yepamusoro (240 mafuremu pasekondi) kwemaminetsi 1 mushure mekusvika kune yakadzikama oscillation.Makareki ari padyo nemupendero wedhisiki yekutenderera akateedzerwa nemaoko uchishandisa furemu-ne-furemu kuongororwa kwezvakarekodhwa kuona huwandu hwekuchinja paminiti (rpm) (Figures 2a-d).Dzokorora n = 10 kuedza.Iyo hama ye centrifugal force (RCF) iri pakati pechirongo chesirinji inozoverengerwa uchishandisa formula inotevera:
Kutenderera kumhanya quantification neCentREUSE.(A–D) Mifananidzo inomiririra inotevedzana inoratidza nguva (maminitsi: masekonzi. milliseconds) kupedzisa kutenderera kwemudziyo.Miseve inotaridza zvicherechedzo.(E) RPM quantification uchishandisa CentREUSE.Mitsara inomiririra zvinoreva (tsvuku) ± kutsauka kwakajairwa (dema).Zvibodzwa zvinomiririra miedzo yemaminitsi e1 (n = 10).
Sirinji ine 1.0 ml ine TA kuturikwa jekiseni (40 mg/ml, Amneal Pharmaceuticals, Bridgewater, NJ, USA) yakaiswa centrifuged ye3, 5 uye 10 maminetsi uchishandisa CentREUSE.Sedimentation uchishandisa nzira iyi yakaenzaniswa neiyo yakaitwa mushure mekuisa centrifugation pa10, 20, uye 50 RCF uchishandisa A-4-62 rotor kwemaminetsi mashanu pane Eppendorf 5810R benchtop centrifuge (Hamburg, Germany).Huwandu hwekunaya kwemvura hwakafananidzwawo nehuwandu hwekunaya kwakawanikwa pachishandiswa giravhiti-inotsamira kunaya panguva dzakasiyana kubva pa0 kusvika 720 maminetsi.Zvose zve n = 9 kudzokorora kwakazvimiririra kwakaitwa kune imwe neimwe nzira.
Yese ongororo yenhamba yakaitwa pachishandiswa Prism 9.0 software (GraphPad, San Diego, USA).Hunhu hunounzwa sezvinoreva ± yakajairwa kutsauka (SD) kunze kwekunge zvataurwa neimwe nzira.Kureva kweboka kwakafananidzwa uchishandisa maviri-tailed Welch-corrected t-test.Alpha inotsanangurwa se 0.05.Kune giravhiti-inotsamira subsidence, imwe-phase exponential decay modhi yakaiswa uchishandisa kushoma-squares regression, kubata inodzokororwa y kukosha kweiyo yakapihwa x kukosha sechinhu chimwe chete.
apo x ndiyo nguva mumaminetsi.y - sediment volume.y0 kukosha kwey kana x ari zero.Bani ndiro kukosha y kwemaminetsi asingaperi.K ndiyo chiyero chinogara chiripo, inoratidzwa sekudzokorora kwemaminetsi.
Iyo CentREUSE mudziyo wakaratidza kuvimbika, kudzorwa kusiri-mutsara oscillations uchishandisa maviri akajairwa 1.0 ml majekiseni akazadzwa ne1.0 ml yemvura imwe neimwe (vhidhiyo S1).Mu n = 10 miedzo (1 miniti imwe neimwe), CentREUSE yaive neavhareji yekutenderera kumhanya kwe359.4 rpm ± 21.63 (range = 337-398), zvichikonzera kuverengerwa kwepakati centrifugal simba re10.5 RCF ± 1, 3 (renji = 9.2-12.8. )(Mufananidzo 2a-e).
Nzira dzinoverengeka dzekupetera TA kumiswa mumasirinji e1.0 ml akaongororwa uye akaenzaniswa neCentREUSE centrifugation.Mushure memaawa gumi nemaviri ekugadzirisa kunoenderana negiravhiti, iyo sediment volume yakasvika 0.38 ml ± 0.03 (Supplementary Fig. S4a, b).Gravity-dependent TA deposition inopindirana ne-single-phase exponential decay model (yakagadziriswa neR2 = 0.8582), zvichiita kuti inofungidzirwa nzvimbo ye 0.3804 mL (95% nguva yekuvimba: 0.3578 kusvika 0.4025) (Supplementary Figure S4c).CentREUSE yakagadzira avhareji sediment vhoriyamu ye0.41 ml ± 0.04 pamaminitsi matatu, iyo yakanga yakafanana nehuremu hwe 0.38 ml ± 0.03 yakacherechedzwa kune giravhiti-inotsamira sedimentation pamaawa gumi nemaviri (p = 0.14) (Fig. 3a, d, h) .CentREUSE yakapa yakawedzera compact volume ye 0.31 ml ± 0.02 pamaminetsi mashanu kana ichienzaniswa neinorehwa 0.38 ml ± 0.03 inocherechedzwa nekuda kwegiravhiti-based sedimentation pamaawa gumi nemaviri (p = 0.0001) (Fig. 3b, d, h).
Kuenzanisa kweTA pellet density yakaitwa neCentREUSE centrifugation negiravhiti kugadzirisa maringe neyakajairwa maindasitiri centrifugation (A-C).Mifananidzo inomiririra yeprecipitated TA suspensions mumasirinji e1.0 ml mushure me3 min (A), 5 min (B), uye 10 min (C) yeCentREUSE kushandiswa.(D) Mumiririri mifananidzo yeTA yakaiswa mushure me12 h yemagetsi ekugadzirisa.EG(H) Sediment vhoriyamu yakaverengerwa pachishandiswa CentREUSE (3, 5, uye 10 min), gravity-mediated sedimentation (12 h), uye yakajairwa maindasitiri centrifugation pa5 min (10, 20, uye 50 RCF).Mitsara inomiririra zvinoreva (tsvuku) ± kutsauka kwakajairwa (dema).Madotsi anomiririra kudzokorora kwakazvimiririra (n = 9 kune yega yega mamiriro).
CentREUSE yakagadzira huremu hwe 0.31 ml ± 0.02 mushure memaminitsi mashanu, iyo yakafanana neyo 0.32 ml ± 0.03 yakaonekwa mune yakajairwa commercial centrifuge pa10 RCF kwemaminetsi mashanu (p = 0.20), uye yakaderera zvishoma pane inorehwa vhoriyamu. yakawanikwa ne20 RCF yakaonekwa pa 0.28 ml ± 0.03 kwemaminitsi mashanu (p = 0.03) (Fig. 3b, e, f, h).CentREUSE yakagadzira huremu hwe 0.20 ml ± 0.02 pamaminitsi gumi, iyo yakanga yakangofanana (p = 0.15) kana ichienzaniswa nehuwandu hwe 0.19 ml ± 0.01 pamaminitsi mashanu akaonekwa nekutengesa centrifuge pa50 RCF (Fig. 3c, g, h)..
Pano tinotsanangura dhizaini, kuungana, uye kuyedza kuongororwa kweyekupedzisira-yakaderera-mutengo, inotakurika, inoshandiswa nevanhu, mapepa-based centrifuge yakagadzirwa kubva kune yakajairwa marara ekurapa.Iyo dhizaini yakavakirwa zvakanyanya papepa-based centrifuge (inonzi "bepa fugue") yakaunzwa neboka raPrakash muna 2017 yekuongorora mashandisirwo.Tichifunga kuti centrifugation yagara ichida kushandiswa kwemidziyo inodhura, yakakura, uye inotsamira pamagetsi, Prakash's centrifuge inopa mhinduro inoyevedza kudambudziko rekusachengeteka kwekuwana centrifugation mune zvigadziriso-zvishoma marongero2,4.Kubva ipapo, paperfuge yakaratidza kushandiswa kunoshanda mune akati wandei-akaderera-vhoriyamu yekuongorora mashandisirwo, senge density-based blood fractionation yekuona marariya.Nekudaro, kusvika pakuziva kwedu, akafanana-achipa-akachipa mapepa-based centrifuge zvishandiso hazvina kushandiswa pakurapa zvinangwa, izvo zvinowanzoda hombe vhoriyamu sedimentation.
Uine izvi mupfungwa, chinangwa cheCentREUSE ndechekuwedzera kushandiswa kwebepa centrifugation mukupindira kwekurapa.Izvi zvakawanikwa nekugadzirisa akati wandei kudhizaini yePrakash inoratidza.Zvinonyanya kukosha, kuwedzera urefu hwemasirinji maviri akajairwa 1.0 ml, CentREUSE ine dhisiki hombe (radius = 123.5 mm) kupfuura yakakura Prakash bepa wringer yakaedzwa (radius = 85 mm).Pamusoro pezvo, kutsigira huremu hwesirinji ye1.0 ml yakazadzwa nemvura, CentREUSE inoshandisa makadhibhokisi ane marara panzvimbo pekadhibhodhi.Pamwe chete, shanduko idzi dzinobvumira centrifugation yemavhoriyamu akakura kupfuura ayo akaedzwa muPrakash paper cleaner (kureva majekiseni maviri e1.0 ml ane capillaries) achiri kuvimba nezvikamu zvakafanana: filament uye mapepa-based material.Zvinokosha, mamwe akati wandei asingadhure-ane simba centrifuges akatsanangurwa nekuda kwekuongorora 4,5,6,7,8,9,10.Izvi zvinosanganisira maspiner, masalad beater, mazai anorova mazai, uye matochi emaoko emidziyo inotenderera5, 6, 7, 8, 9. Zvisinei, mizhinji yemidziyo iyi haina kugadzirwa kuti ibate mavhoriyamu anosvika 1.0 ml uye ine zvinhu zvinowanzodhura. uye isingasvikike pane iyo inoshandiswa mubepa centrifuges2,4,5,6,7,8,9,10..Kutaura zvazviri, mapepa akaraswa anowanzowanikwa kwose kwose;semuenzaniso, kuUnited States, mapepa uye mapepa epamusoro anodarika makumi maviri muzana emarara emarara, achipa yakawanda, isingadhuri, kana kunyange yemahara sosi yekuvaka bepa centrifuges.semuenzaniso CentREUSE11.Zvakare, zvichienzaniswa nemamwe akati wandei akaderera mutengo mhinduro dzakaburitswa, CentREUSE haidi yakasarudzika hardware (senge 3D kudhinda Hardware uye software, laser yekucheka Hardware uye software, nezvimwewo) kugadzira, ichiita kuti Hardware iwedzere kusimba..Vanhu ava vari munharaunda 4, 8, 9, 10.
Sehumbowo hwekubatsira kunoshanda kwebepa redu centrifuge nekuda kwekurapa, tinoratidza kukurumidza uye kwakavimbika kugadzirisa kwe triamcinolone kumiswa muacetone (TA) ye vitreous bolus jekiseni-yakagadziriswa yakaderera-inodhura kupindira kwekurapa kwenguva refu kwezvirwere zvakasiyana-siyana zvemaziso1 ,3.Kugadzirisa mibairo mushure memaminitsi matatu neCentREUSE yakafananidzwa nemhedzisiro mushure memaawa gumi nemaviri ekugadzirisa-kwepakati pekugadzirisa.Mukuwedzera, CentREUSE migumisiro mushure me centrifugation ye 5 uye 10 maminetsi yakapfuura migumisiro yaizowanikwa negiravhiti uye yakafanana neyo yakaonekwa mushure mekugadzirwa kwemaindasitiri pa10 uye 50 RCF kwemaminitsi mashanu, zvichiteerana.Zvikuru, muchiitiko chedu, CentREUSE inogadzira yakapinza uye yakatsetseka sediment-supernatant interface kupfuura dzimwe nzira dzakaedzwa;izvi zvinodikanwa sezvo zvichibvumira kuongororwa kwakanyatsojeka kwedhesi yemishonga inoshandiswa, uye zviri nyore kubvisa iyo supernatant nekurasikirwa kuduku kwehuwandu hwehuwandu.
Sarudzo yechishandiso ichi sehumbowo hwepfungwa yakafambiswa nekudikanwa kunoenderera mberi kwekuvandudza kuwana kune-refu-kuita intravitreal steroids mune zviwanikwa-zvishoma zvigadziriso.Intravitreal steroids inoshandiswa zvakanyanya kurapa zvakasiyana-siyana zvemaziso, kusanganisira chirwere cheshuga macular edema, zera-related macular degeneration, retinal vascular occlusion, uveitis, radiation retinopathy, uye cystic macular edema3,12.Pakati pemasteroid anowanikwa kune intravitreal administration, TA inoramba iri inonyanya kushandiswa pasi rose12.Kunyange zvazvo gadziriro dzisina TA preservatives (PF-TA) dziripo (semuenzaniso, Triesence [40 mg/mL, Alcon, Fort Worth, USA]), magadzirirwo ane benzyl alcohol preservatives (eg, Kenalog-40 [40 mg/mL, Bristol- Myers Squibb, New York, USA]) anoramba achinyanya kufarirwa3,12.Zvinofanira kuonekwa kuti boka rekupedzisira remishonga inobvumirwa neUnited States Food and Drug Administration (FDA) yekushandiswa kwemukati uye intraarticular chete, saka intraocular administration inofungidzirwa isina kunyoreswa 3, 12.Kunyange zvazvo jekiseni rejekiseni re intravitreal TA richisiyana zvichienderana nechiratidzo uye nzira, iyo inowanzotaurwa dose i 4.0 mg (kureva jekiseni vhoriyamu ye 0.1 ml kubva ku40 mg/ml solution), iyo inowanzopa nguva yekurapa kweinenge 3 mwedzi Migumisiro 1. , 12, 13, 14, 15.
Kurebesa kuita kwe intravitreal steroid muzvirwere zvisingaperi, zvakakomba kana zvinodzokororwa zvemaziso, akati wandei-akareba-achibatika kana injectable steroid michina yakaunzwa, kusanganisira dexamethasone 0.7 mg (Ozurdex, Allergan, Dublin, Ireland), Relax fluoride acetonide 0.59 mg (Retisert , Bausch uye Lomb, Laval, Canada) uye fluocinolone acetonide 0.19 mg (Iluvien, Alimera Sciences, Alpharetta, Georgia, USA) 3,12.Nekudaro, zvishandiso izvi zvine akati wandei anogona kukanganisa.MuUnited States, mudziyo wega wega unongotenderwa zviratidzo zvishoma, kudzikamisa kuvharwa kweinishuwarenzi.Pamusoro pezvo, mamwe maturusi anoda kuisirwa kuvhiyiwa uye anogona kukonzera kusarudzika matambudziko sekutama kwemudziyo mukamuri yepamberi3,12.Mukuwedzera, zvigadzirwa izvi zvinowanzove zvisingawaniki nyore uye zvakanyanya kudhura kupfuura TA3,12;pamitengo yazvino yeUS, Kenalog-40 inodhura madhora makumi maviri pa1.Mari yekupinda inenge $1400., $20,000 uye $9,200 zvichiteerana.Pamwe chete, zvinhu izvi zvinomisa kupinda kune aya maturusi kune vanhu vari mumamiriro-akamanikidzwa zvigadziriso.
Kuedza kwakaitwa kuti kuwedzere kushanda kwe intravitreal TA1,3,16,17 nekuda kwemutengo wayo wakaderera, kubhadhara kwakanyanya, uye kuwanikwa kukuru.Tichifunga nezvekudzikira kwayo kwemvura kunyungudika, TA inoramba iri muziso sedhipatimendi, ichibvumira zvishoma nezvishoma uye zvinogara zvichipararira zvinodhaka, saka mhedzisiro inotarisirwa kugara kwenguva yakareba nemadepo akakura1,3.Kuti izvi zviitike, nzira dzinoverengeka dzakagadzirwa kuti dzitarise iyo TA kumiswa isati yaiswa jekiseni mu vitreous.Kunyange zvazvo nzira dzakavakirwa pakuita (kureva giravhiti inotsamira) kugadzirisa kana microfiltration yakatsanangurwa, nzira idzi dzinotora nguva uye dzinopa mhinduro dzakasiyana15,16,17.Kusiyana neizvi, zvidzidzo zvekare zvakaratidza kuti TA inogona kukurumidza uye yakavimbika yakanangidzirwa (uye nokudaro kuita kwenguva refu) ne centrifugation-assisted precipitation1,3.Mukupedzisa, iko nyore, mutengo wakaderera, nguva, uye kushanda kwe centrifugally yakanangidzirwa TA kunoita kuti kupindira uku kuve sarudzo inokwezva kune varwere mune zviwanikwa-zvishoma zvigadziriso.Zvisinei, kushayikwa kwekuwana centrifugation yakavimbika inogona kuva chipingamupinyi chikuru chekushandisa kupindira uku;Nekugadzirisa nyaya iyi, CentREUSE inogona kubatsira kuwedzera kuwanikwa kwenguva refu steroid therapy kune varwere vari muzvirongwa-zvishoma.
Pane zvimwe zvipimo mukudzidza kwedu, kusanganisira izvo zvine chekuita nekushanda kwechishandiso cheCentREUSE.Chigadzirwa chacho hachina-mutsara, chisingaiti-chinochengetedza oscillator chinovimba nekuisa kwevanhu uye naizvozvo haigoni kupa yakarurama uye inogara ichitenderera chiyero panguva yekushandiswa;kumhanya kwekutenderera kunotsamira pane zvakati wandei, senge pesvedzero yemushandisi pachiyero chemuridzi wemudziyo, zvinhu zvakashandiswa pakuunganidzwa kwemidziyo, uye kunaka kwezvinobatanidzwa zviri kuruka.Izvi zvakasiyana nemidziyo yekutengeserana uko kukurumidza kutenderera kunogona kushandiswa nguva dzose uye nemazvo.Pamusoro pezvo, kumhanya kunowanikwa neCentREUSE kunogona kutariswa kunyoro kana zvichienzaniswa nekumhanya kunowanikwa nemamwe macentrifuge zvishandiso2.Sezvineiwo, kumhanya (uye yakabatana centrifugal simba) yakagadzirwa nemudziyo wedu yaive yakakwana kuyedza iyo pfungwa yakatsanangurwa muchidzidzo chedu (kureva, TA deposition).Iyo yekutenderera inomhanyisa inogona kuwedzerwa nekurerutsa huwandu hwepakati disk 2;izvi zvinogona kuwanikwa nekushandisa chinhu chakareruka (senge kadhibhodhi rakatetepa) kana rakasimba zvakakwana kubata majekiseni maviri akazadzwa nemvura.Kwatiri, sarudzo yekushandisa yakajairwa "A" slotted kadhibhodhi (4.8 mm gobvu) yaive nemaune, sezvo chinhu ichi chinowanzo kuwanikwa mumabhokisi ekutumira uye saka inowanikwa nyore nyore sechinhu chinodzokororwa.Iyo inotenderera inomhanya inogonawo kuwedzerwa nekuderedza radius yepakati disk 2.Nekudaro, radius yepuratifomu yedu yakaitwa nemaune yakakura kuti iwane 1.0 ml sirinji.Kana mushandisi achifarira centrifuging zvikepe zvipfupi, radius inogona kuderedzwa-shanduko inofanotaura inoguma nekukwira kwepamusoro kutenderera (uye pamwe nepamusoro centrifugal masimba).
Uye zvakare, isu hatina kunyatsoongorora kukanganisa kwevashandi kuneta pakushanda kwemidziyo.Zvinofadza kuti nhengo dzakawanda dzeboka redu dzakakwanisa kushandisa mudziyo wacho kwemaminitsi gumi nemashanu pasina kuneta kunooneka.Iyo inogona kugadzirisa kune mutyairi kuneta kana ma centrifuge marefu achidikanwa ndeye kutenderedza vashandisi vaviri kana kupfuura (kana zvichibvira).Pamusoro pezvo, isu hatina kunyatsoongorora kusimba kwechigadzirwa, muchidimbu nekuti zvikamu zvechigadzirwa (senge kadhibhodhi netambo) zvinogona kutsiviwa nyore nyore padiki kana pasina mutengo kana ikasakara kana kukuvara.Sezvineiwo, panguva yedu yekuyedzwa kwemutyairi, takashandisa mudziyo mumwe kweanopfuura maminetsi mazana maviri.Mushure menguva iyi, chiratidzo chega chega chinoonekwa asi chidiki chekupfeka ndechekuputika netambo.
Chimwe chinogumira pakudzidza kwedu ndechekuti isu hatina kunyatso kuyera huwandu kana density yeakaiswa TA, inogoneka neCentREUSE mudziyo nedzimwe nzira;pachinzvimbo, yedu yekuyedza ongororo yemudziyo uyu yaive yakavakirwa pachiyero che sediment density (mu ml).chiyero chisina kunanga che density.Pamusoro pezvo, hatina kuyedza CentREUSE Yakatarisana neTA kune varwere, zvisinei, sezvo mudziyo wedu wakagadzira TA pellets yakafanana neyakagadzirwa uchishandisa centrifuge yekutengesa, isu takafungidzira kuti CentREUSE Yakanangana TA yaizoshanda uye yakachengeteka seyakamboshandiswa.mumabhuku.yakashumwa kune yakajairwa centrifuge zvishandiso1,3.Zvidzidzo zvekuwedzera zvinoyera huwandu chaihwo hweTA inopihwa mushure meCentREUSE fortification inogona kubatsira kuwedzera kuongorora kukosha chaiko kwechishandiso chedu muchishandiso ichi.
Sekuziva kwedu, CentREUSE, mudziyo unogona kugadzirwa nyore nyore kubva kune tsvina inowanikwa nyore, ndiyo yekutanga-inogonesa vanhu, inotakurika, yepamusoro-yakaderera-inodhura bepa centrifuge kuti ishandiswe munzvimbo yekurapa.Pamusoro pekukwanisa kuisa centrifuge mavhoriyamu akakura, CentREUSE haidi kushandiswa kwezvinhu zvine hunyanzvi uye maturusi ekuvaka zvichienzaniswa nemamwe macentrifuge anodhura akaburitswa.Iyo yakaratidza kushanda kweCentREUSE mukukurumidza uye yakavimbika TA kunaya kunogona kubatsira kuvandudza kwenguva yakareba intravitreal steroid kuwanikwa muvanhu vari muzvishandiso-zvishoma zvigadziriso, izvo zvinogona kubatsira kubata akasiyana mamiriro emeso.Pamusoro pezvo, mabhenefiti emacentrifuge edu anotakurika anofambiswa nevanhu anofanotaura kusvika kunzvimbo dzine zviwanikwa zvakaita senzvimbo dzehutano dzepamusoro-soro uye quaternary hutano munyika dzakabudirira.Pasi pemamiriro ezvinhu aya, kuwanikwa kwemidziyo yecentrifuging inogona kuramba ichingogumira kumakiriniki uye mumarabhoritari ekutsvagisa, paine njodzi yekusvibisa majekiseni nemvura yemuviri wemunhu, zvigadzirwa zvemhuka, uye zvimwe zvinhu zvine njodzi.Pamusoro pezvo, marabhoritari aya anowanzo kuwanikwa kure nenzvimbo yekutarisira varwere.Izvi, zvakare, zvinogona kuva chipingamupinyi chekugadzirisa kune vatapi vehutano vanoda kukurumidza kuwana centrifugation;kuendesa CentREUSE inogona kushanda senzira inoshanda yekugadzirira kupindira kwekurapa munguva pfupi pasina kukanganisa zvakanyanya kutarisirwa kwevarwere.
Naizvozvo, kuita kuti zvive nyore kumunhu wese kugadzirira kupindira kwekurapa kunoda centrifugation, template nemirayiridzo yekugadzira CentREUSE inosanganisirwa mune ino yakavhurika sosi kudhindwa pasi peChikamu Ruzivo Rwekuwedzera.Tinokurudzira vaverengi kuti vagadzirise CentREUSE sezvinodiwa.
Data inotsigira zvakabuda muchidzidzo ichi inowanika kubva kumunyori weSM kana wakumbira zvine musoro.
Ober, MD uye Valizhan, S. Nguva yekuita kwe triamcinolone acetone mu vitreous pa centrifugation concentration.Retina 33, 867–872 (2013).
Bhamla, MS nevamwe.Manual Ultra-yakachipa centrifuge yepepa.National Biomedical Science.project.1, 0009. https://doi.org/10.1038/s41551-016-0009 (2017).
Malinovsky SM uye Wasserman JA Centrifugal concentration ye intravitreal suspension ye triamcinolone acetonide: isingadhuri, iri nyore uye inogoneka kune imwe nguva yakareba steroid administration.J. Vitrain.diss.5. 15–31 (2021).
Huck, ndichamirira.Isingadhure yakavhurika sosi centrifuge adapta yekuparadzanisa mahombe eropa ekiriniki.PLOS Imwe.17.e0266769.https://doi.org/10.1371/journal.pone.0266769 (2022).
Wong AP, Gupta M., Shevkoplyas SS uye Whitesides GM Iyo whisk yakafanana necentrifuge: kupatsanura plasma yevanhu kubva muropa rose mune zviwanikwa-zvishoma zvigadziriso.rabhoritari.chip.8, 2032–2037 (2008).
Brown, J. nevamwe.Manual, inotakurika, yakaderera-mutengo centrifuge yeanemia kuongororwa mune zviwanikwa-zvishoma marongero.Ehe.J. Trope.mushonga.mwando.85, 327–332 (2011).
Liu, K.-H.wait.Plasma yakaparadzaniswa uchishandisa spinner.anus.Chemical.91, 1247–1253 (2019).
Michael, I. et al.Spinner yekukurumidza kuongororwa kwehutachiona hwehutachiwana.National Biomedical Science.project.4, 591–600 (2020).
Lee, E., Larson, A., Kotari, A., uye Prakash, M. Handyfuge-LAMP: Isingadhure electrolyte-isina centrifugation yekuonekwa isothermal yeSARS-CoV-2 mumate.https://doi.org/10.1101/2020.06.30.20143255 (2020).
Lee, S., Jeong, M., Lee, S., Lee, SH, uye Choi, J. Mag-spinner: Chizvarwa chinotevera chezvakanakira, zvinokwanisika, zviri nyore uye zvinotakurika (FAST) magineti ekuparadzanisa masisitimu.Nano Advances 4, 792–800 (2022).
US Environmental Protection Agency.Advancing Sustainable Materials Management: A 2018 chokwadi pepa rinoongorora mafambiro mukugadzirwa kwezvinhu uye manejimendi muUnited States.(2020).https://www.epa.gov/sites/default/files/2021-01/documents/2018_ff_fact_sheet_dec_2020_fnl_508.pdf.
Sarao, V., Veritti, D., Boschia, F. uye Lanzetta, P. Steroids yekurapa intravitreal yezvirwere zveretinal.sainzi.Journal Mir 2014, 1–14 (2014).
Doro, masikati tii, etc. Intraocular concentrations uye pharmacokinetics ye triamcinolone acetonide mushure mejojo re intravitreal.Ophthalmology 110, 681-686 (2003).
Audren, F. nevamwe.Pharmacokinetic-pharmacodynamic modhi yemhedzisiro ye triamcinolone acetonide pane yepakati macular ukobvu mune varwere vane chirwere cheshuga macular edema.invest.ophthalmology.zvinooneka.sainzi.45, 3435–3441 (2004).
Ober, MD et al.Iyo chaiyo dose ye triamcinolone acetone yakayerwa neyakajairwa nzira ye intravitreal jekiseni.Ehe.J. Ophthalmol.142, 597–600 (2006).
Chin, HS, Kim, TH, Mwedzi, YS uye Oh, JH Yakanyanyisa triamcinolone acetonide nzira ye intravitreal jekiseni.Retina 25, 1107–1108 (2005).
Tsong, JW, Persaud, TO & Mansour, SE Quantitative kuongororwa kweyakaiswa triamcinolone yejekiseni.Retina 27, 1255–1259 (2007).
SM inotsigirwa muchidimbu nechipo kuMukai Foundation, Massachusetts Eye and Ear Hospital, Boston, Massachusetts, USA.
Dhipatimendi reOphthalmology, Harvard Medical School, Massachusetts Eye and Ear, 243 Charles St, Boston, Massachusetts, 02114, USA
Nguva yekutumira: Feb-25-2023