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Masilayidi owonetsa zolemba zitatu pa slide iliyonse.Gwiritsani ntchito mabatani akumbuyo ndi ena kuti mudutse zithunzi, kapena mabatani owongolera masilayidi kumapeto kuti mudutse silayidi iliyonse.
Thandizo lodalirika lachipatala lakhala likufuna kugwiritsa ntchito zipangizo zamalonda zodula, zazikulu, komanso zodalira magetsi, zomwe nthawi zambiri sizipezeka muzinthu zochepa.Ngakhale ma centrifuge angapo onyamula, otsika mtengo, osagwiritsa ntchito mota afotokozeredwa, mayankhowa amapangidwa makamaka kuti agwiritse ntchito matenda omwe amafunikira kuchuluka kwa sedimentation yaying'ono.Kuphatikiza apo, mapangidwe a zidazi nthawi zambiri amafuna kugwiritsa ntchito zida zapadera ndi zida zomwe sizipezeka m'malo osatetezedwa.Apa tikufotokoza momwe CentREUSE imapangidwira, kusonkhanitsa, ndi kuyesa kutsimikizira, mtengo wotsika kwambiri, woyendetsedwa ndi anthu, wotengera zinyalala wonyamula zinyalala pakugwiritsa ntchito achire.CentREUSE ikuwonetsa mphamvu yapakati pa 10.5 yolumikizana ndi centrifugal force (RCF) ± 1.3.Kukhazikika kwa 1.0 ml vitreous kuyimitsidwa kwa triamcinolone pambuyo pa mphindi 3 za centrifugation ku CentREUSE kunali kofanana ndi pambuyo pa maola 12 a sedimentation yamphamvu yokoka (0.41 ml ± 0.04 vs 0.38 ml ± 0.03, p = 0.14).Sediment thickening pambuyo CentREUSE centrifugation kwa mphindi 5 ndi 10 poyerekeza ndi anaona pambuyo centrifugation pa 10 RCF (0.31 ml ± 0.02 vs. 0.32 ml ± 0.03, p = 0.20) ndi 50 RCF (0.20 ml) kwa mphindi 5 zofanana ntchito ± malonda zida 0.02 vs. 0.19 ml ± 0.01, p = 0.15).Ma templates ndi malangizo omanga a CentREUSE akuphatikizidwa mu positi yotsegukayi.
Centrifugation ndi gawo lofunikira pakuyezetsa matenda ambiri komanso njira zochizira1,2,3,4.Komabe, kukwaniritsa centrifugation yokwanira m'mbiri yakale kumafuna kugwiritsa ntchito zipangizo zamalonda zamtengo wapatali, zazikulu, komanso zamagetsi, zomwe nthawi zambiri sizipezeka muzinthu zopanda malire2,4.Mu 2017, gulu la Prakash linayambitsa kabuku kakang'ono ka mapepala (otchedwa "puffer mapepala") opangidwa kuchokera ku zipangizo zopangira kale pamtengo wa $ 0.20 ($)2.Kuyambira pamenepo, paper fugue yakhala ikugwiritsidwa ntchito m'malo ocheperako pakuwunika kocheperako (monga kulekanitsa kachulukidwe kwa zigawo zamagazi m'machubu a capillary kuti azindikire tizilombo ta malungo), motero kuwonetsa chida chotsika mtengo kwambiri choyendetsedwa ndi anthu.centrifuge 2.Kuyambira pamenepo, zida zina zingapo zophatikizika, zotsika mtengo, zopanda injini za centrifugation zafotokozedwa4,5,6,7,8,9,10.Komabe, zambiri mwa njirazi, monga utsi wa pepala, zimapangidwira kuti zifufuze zomwe zimafuna kuchuluka kwa sedimentation yaying'ono motero sizingagwiritsidwe ntchito kuyika zitsanzo zazikulu.Kuonjezera apo, kusonkhanitsa mayankhowa nthawi zambiri kumafuna kugwiritsa ntchito zipangizo zapadera ndi zida zomwe nthawi zambiri sizipezeka m'madera osatetezedwa4,5,6,7,8,9,10.
Apa tikufotokoza mapangidwe, kusonkhanitsa, ndi kuyesa kutsimikizira kwa centrifuge (yotchedwa CentREUSE) yopangidwa kuchokera ku zinyalala wamba zamapepala kuti zigwiritsidwe ntchito pochiza zomwe nthawi zambiri zimafunikira kuchuluka kwa sedimentation.Mlandu 1, 3 Monga umboni wa lingaliro, tinayesa chipangizocho ndi njira yeniyeni ya ophthalmic: mpweya wa kuyimitsidwa kwa triamcinolone mu acetone (TA) chifukwa cha jekeseni wotsatira wa mankhwala a bolus mu thupi la vitreous la diso.Ngakhale kuti centrifugation ya TA ndende ndi njira yodziwika yotsika mtengo yopangira chithandizo chanthawi yayitali chamitundu yosiyanasiyana yamaso, kufunikira kwa ma centrifuges omwe amapezeka pamalonda panthawi yopanga mankhwala ndikolepheretsa kwambiri kugwiritsa ntchito mankhwalawa pazikhazikiko zopanda malire1,2, 3.poyerekeza ndi zotsatira zopezedwa ndi ochiritsira malonda centrifuges.Ma templates ndi malangizo omanga CentREUSE akuphatikizidwa muzolemba zotsegukazi mu gawo la "Zambiri Zambiri".
CentREUSE ikhoza kumangidwa pafupifupi kuchokera ku zinyalala.Ma template onse awiri a semi-circular template (Supplementary Figure S1) adasindikizidwa papepala lokhazikika la US carbon letter (215.9 mm × 279.4 mm).Ma tempuleti awiri ozungulira omwe aphatikizidwa amatanthauzira zofunikira zitatu za chipangizo cha CentREUSE, kuphatikiza (1) mbali yakunja ya 247mm spinning disk, (2) idapangidwa kuti izikhala ndi syringe ya 1.0ml (yokhala ndi kapu ndi plunger yodulidwa).mikwingwirima mu shank) ndi (3) zizindikiro ziŵiri zosonyeza malo obowola kuti chingwe chidutse pa litayamba.
Tsatirani (mwachitsanzo ndi zomatira kapena tepi) template ku bolodi yamalata (kukula kochepa: 247 mm × 247 mm) (Supplementary Figure S2a).Bolodi "A" yokhazikika (4.8 mm thick) inagwiritsidwa ntchito mu phunziroli, koma matabwa a malata a makulidwe ofanana angagwiritsidwe ntchito, monga bolodi lamalata kuchokera m'mabokosi otumizira otayidwa.Pogwiritsa ntchito chida chakuthwa (monga tsamba kapena lumo), dulani katoni m'mphepete mwa chimbale chakunja chomwe chafotokozedwa pa template (Supplementary Figure S2b).Kenako, pogwiritsa ntchito chida chopapatiza, chakuthwa (monga nsonga ya cholembera), pangani ma perforations awiri okhala ndi makulidwe amtundu wa 8.5 mm malinga ndi zizindikiro zomwe zatsatiridwa pa template (Supplementary Figure S2c).Mipata iwiri ya ma syrinji a 1.0 ml ndiye amadulidwa kuchokera pa template ndi pansi pa makatoni pogwiritsa ntchito chida chosongoka monga lumo;chisamaliro chiyenera kutengedwa kuti chisawononge chigawo chamalata kapena chotsalira pamwamba (Supplementary Figure S2d, e) .Kenako, sungani chingwe (monga chingwe cha thonje cha 3mm kapena ulusi wina uliwonse wokhuthala ndi wonyezimira) kupyola mabowo awiriwo ndi kumanga luko kuzungulira mbali zonse za diski utali wa 30cm (Supplementary Fig. S2f).
Lembani ma syrinji awiri a 1.0 ml ndi ma voliyumu pafupifupi ofanana (monga 1.0 ml ya kuyimitsidwa kwa TA) ndi kapu.Ndodo ya syringe plunger idadulidwa pamlingo wa mbiya flange (Supplementary Figure S2g, h).Silinda flange imakutidwa ndi wosanjikiza wa tepi kuteteza kutulutsa kwa pisitoni yoduliridwa panthawi yogwiritsira ntchito zida.Sirinji iliyonse ya 1.0 ml inayikidwa mu syringe bwino ndi kapu yoyang'ana pakati pa diski (Supplementary Figure S2i).Sirinji iliyonse idalumikizidwa ndi disc ndi tepi yomatira (Supplementary Figure S2j).Pomaliza, malizitsani kulumikiza centrifuge poyika zolembera ziwiri (monga mapensulo kapena zida zolimba zooneka ngati ndodo) kumapeto kwa chingwe mkati mwa lupu (Chithunzi 1).
Malangizo ogwiritsira ntchito CentREUSE ndi ofanana ndi zoseweretsa zachikhalidwe zopota.Kuzungulira kumayamba ndi kugwira chogwirira m'dzanja lililonse.Kutsika pang'ono mu zingwe kumapangitsa kuti diski igwedezeke kutsogolo kapena kumbuyo, zomwe zimapangitsa kuti diskiyo ikhale yozungulira kutsogolo kapena kumbuyo.Izi zimachitika kangapo pang'onopang'ono, molamulirika kotero kuti zingwezo zimapindika.Kenako siyani kuyenda.Zingwezo zikayamba kumasuka, chogwiriracho chimakokedwa mwamphamvu mpaka zingwezo zitaphwa, zomwe zimapangitsa kuti disikiyo izungulire.Chingwecho chikangomasulidwa ndikuyamba kubwerera, chogwiriracho chiyenera kumasuka pang'onopang'ono.Pamene chingwe chikuyambanso kumasuka, gwiritsani ntchito njira zomwezo kuti chipangizocho chizizungulira (kanema S1).
Pazofunsira zomwe zimafuna kuyimitsidwa kwa kuyimitsidwa ndi centrifugation, chipangizocho chinasinthidwa mosalekeza mpaka granulation yokhutiritsa idakwaniritsidwa (Supplementary Figure S3a,b).Tinthu tating'onoting'ono timapanga kumapeto kwa plunger ya mbiya ya syringe ndipo mphamvu yayikulu idzayang'ana kunsonga kwa syringe.Wopambanayo adatsanuliridwa ndikuchotsa tepi yomwe idaphimba mbiya ndikuyambitsa plunger yachiwiri kuti ikankhire pang'onopang'ono plunger yachibadwidwe kunsonga ya syringe, kuyima ikafika pamatope (Supplementary Figure S3c,d).
Kuti mudziwe liwiro lozungulira, chipangizo cha CentREUSE, chokhala ndi ma syringe awiri a 1.0 ml odzazidwa ndi madzi, chinalembedwa ndi makamera othamanga kwambiri (mafelemu a 240 pamphindi) kwa mphindi 1 atatha kufika pamtunda wokhazikika.Zolemba pafupi ndi m'mphepete mwa diski yozungulira zidatsatiridwa pamanja pogwiritsa ntchito kusanthula kwa chimango ndi chimango cha zojambulirazo kuti adziwe kuchuluka kwa kusintha pamphindi (rpm) (Zithunzi 2a-d).Bwerezani n = kuyesa 10.Mphamvu ya centrifugal (RCF) yomwe ili pakatikati pa mbiya ya syringe imawerengedwa pogwiritsa ntchito njira iyi:
Kuthamanga kwa liwiro lozungulira ndi CentREUSE.(A–D) Zithunzi zoyimilira motsatizana zosonyeza nthawi (mphindi: masekondi. mamilliseconds) kuti amalize kuzungulira kwachipangizo.Mivi imawonetsa zolembera.(E) RPM quantification pogwiritsa ntchito CentREUSE.Mizereyo imayimira tanthauzo (lofiira) ± kupatuka kokhazikika (kwakuda).Zotsatirazo zikuyimira kuyesa kwa mphindi imodzi (n = 10).
Sirinji ya 1.0 ml yokhala ndi kuyimitsidwa kwa TA kwa jekeseni (40 mg / ml, Amneal Pharmaceuticals, Bridgewater, NJ, USA) inali centrifuged kwa 3, 5 ndi 10 maminiti pogwiritsa ntchito CentREUSE.Sedimentation pogwiritsa ntchito njirayi inafaniziridwa ndi zomwe zinatheka pambuyo pa centrifugation pa 10, 20, ndi 50 RCF pogwiritsa ntchito A-4-62 rotor kwa 5 min pa Eppendorf 5810R benchtop centrifuge (Hamburg, Germany).Kuchuluka kwa mvula kunafanizidwanso ndi kuchuluka kwa mvula yomwe imapezeka pogwiritsa ntchito mvula yotengera mphamvu yokoka pa nthawi zosiyanasiyana kuyambira mphindi 0 mpaka 720.Chiwerengero cha n = 9 kubwereza kodziimira payekha kunkachitidwa pa ndondomeko iliyonse.
Kusanthula konse kwa ziwerengero kunachitika pogwiritsa ntchito pulogalamu ya Prism 9.0 (GraphPad, San Diego, USA).Makhalidwe amaperekedwa ngati akutanthauza ± kupatuka kokhazikika (SD) pokhapokha atadziwika mwanjira ina.Njira zamagulu zidafaniziridwa pogwiritsa ntchito mayeso owongolera a Welch okhala ndi michira iwiri.Alpha imatanthauzidwa kuti 0.05.Pakutsika kodalira mphamvu yokoka, mtundu wowola wagawo limodzi udayikidwa pogwiritsa ntchito masikweya-mabwalo ocheperako, kuchitira mobwerezabwereza ma y pamtengo woperekedwa x ngati mfundo imodzi.
kumene x ndi nthawi mu maminiti.y - kuchuluka kwa matope.y0 ndi mtengo wa y pamene x ndi ziro.Chigwacho ndi mtengo wa y kwa mphindi zopanda malire.K ndi mlingo wokhazikika, wofotokozedwa ngati kubwereza kwa mphindi.
Chipangizo cha CentREUSE chinawonetsa ma oscillation odalirika, olamulidwa osatsata mzere pogwiritsa ntchito ma syringe awiri a 1.0 ml odzazidwa ndi 1.0 ml yamadzi iliyonse (kanema S1).Mu n = mayesero a 10 (1 miniti iliyonse), CentREUSE inali ndi liwiro lozungulira la 359.4 rpm ± 21.63 (range = 337-398), zomwe zinachititsa kuti mphamvu ya centrifugal yowerengeka ya 10.5 RCF ± 1, 3 (siyana = 9.2-12.8. ).(Chithunzi 2a-e).
Njira zingapo zopangira kuyimitsidwa kwa TA mu ma syringe a 1.0 ml zidawunikidwa ndikuyerekeza ndi CentREUSE centrifugation.Pambuyo pa maola 12 akukhazikika modalira mphamvu yokoka, voliyumu ya sediment inafika 0.38 ml ± 0.03 (Supplementary Fig. S4a,b).Kuyika kwa TA komwe kumadalira mphamvu yokoka kumagwirizana ndi gawo limodzi lachiwonetsero chovunda (chokonzedwa ndi R2 = 0.8582), zomwe zimapangitsa kuti pakhale mtunda wa 0.3804 mL (95% nthawi yodalirika: 0.3578 mpaka 0.4025) (Supplementary Figure S4c).CentREUSE inapanga voliyumu ya 0.41 ml ± 0.04 pa mphindi 3, zomwe zinali zofanana ndi mtengo wapakati wa 0.38 ml ± 0.03 wowonedwa chifukwa cha matope otengera mphamvu yokoka pa maola 12 (p = 0.14) (mkuyu 3a, d, h) .CentREUSE inapereka voliyumu yocheperako kwambiri ya 0.31 ml ± 0.02 pa mphindi 5 poyerekeza ndi tanthauzo la 0.38 ml ± 0.03 lomwe limawonedwa chifukwa cha mphamvu yokoka yozikidwa pa maola 12 (p = 0.0001) (Mkuyu 3b, d, h).
Kuyerekeza kwa TA pellet density yopezedwa ndi CentREUSE centrifugation ndi mphamvu yokoka yokhazikika motsutsana ndi standard Industrial centrifugation (A-C).Zithunzi zoyimira za kuyimitsidwa kwa TA kunayimitsidwa mu ma syringe a 1.0 ml pambuyo pa 3 min (A), 5 min (B), ndi 10 min (C) ya CentREUSE ntchito.(D) Zithunzi zoyimira za TA yosungidwa pambuyo pa 12 h yakukhazikika kwa mphamvu yokoka.(EG) Zithunzi zoyimira za precipitated TA pambuyo pa centrifugation yokhazikika yamalonda pa 10 RCF (E), 20 RCF (F), ndi 50 RCF (G) kwa 5 min.(H) Voliyumu ya Sediment idawerengedwa pogwiritsa ntchito CentREUSE (3, 5, ndi 10 min), mphamvu yokoka (12 h), ndi centrifugation wamba yamakampani pa 5 min (10, 20, ndi 50 RCF).Mizereyo imayimira tanthauzo (lofiira) ± kupatuka kokhazikika (kwakuda).Madontho akuyimira kubwereza kodziyimira pawokha (n = 9 pa chikhalidwe chilichonse).
CentREUSE inapanga voliyumu ya 0.31 ml ± 0.02 pambuyo pa mphindi 5, zomwe zimafanana ndi tanthauzo la 0.32 ml ± 0.03 lomwe limawonedwa mu centrifuge wamba wamalonda pa 10 RCF kwa mphindi 5 (p = 0.20), komanso kutsika pang'ono kuposa kuchuluka kwapakati. anapezedwa ndi 20 RCF ankaona pa 0,28 ml ± 0.03 kwa mphindi 5 (p = 0.03) (mkuyu 3b, e, f, h).CentREUSE idatulutsa kuchuluka kwa 0.20 ml ± 0.02 pa mphindi 10, zomwe zinali zocheperako (p = 0.15) poyerekeza ndi kuchuluka kwa 0.19 ml ± 0.01 pa mphindi 5 zowonedwa ndi centrifuge yamalonda pa 50 RCF (Mkuyu 3c, g, ndi)..
Apa tikufotokoza mapangidwe, kusonkhanitsa, ndi kutsimikizira koyesera kwa centrifuge yotsika mtengo kwambiri, yonyamulika, yoyendetsedwa ndi anthu, yopangidwa ndi zinyalala zochiritsira.Mapangidwe ake makamaka amachokera ku pepala-based centrifuge (yotchedwa "paper fugue") yomwe inayambitsidwa ndi gulu la Prakash mu 2017 pofuna kufufuza ntchito.Popeza kuti centrifugation m'mbiri ankafuna kugwiritsa ntchito zipangizo zamalonda okwera mtengo, bulky, ndi magetsi, Prakash a centrifuge amapereka njira kaso pa vuto la kusatetezeka kupeza centrifugation mu gwero-zochepa zoikamo2,4.Kuyambira nthawi imeneyo, paperfuge yawonetsa zothandiza m'njira zingapo zodziwira matenda otsika kwambiri, monga kugawa magazi motengera kachulukidwe kuti athe kuzindikira malungo.Komabe, monga momwe tikudziwira, zida zofananira zotsika mtengo zokhala ndi mapepala za centrifuge sizinagwiritsidwe ntchito pazifukwa zochizira, zomwe nthawi zambiri zimafunikira kusungunuka kwa voliyumu yayikulu.
Poganizira izi, cholinga cha CentREUSE ndikukulitsa kugwiritsidwa ntchito kwa pepala centrifugation munjira zochiritsira.Izi zidatheka popanga zosintha zingapo pamapangidwe a chiwonetsero cha Prakash.Makamaka, kuti muwonjezere kutalika kwa ma syringe awiri a 1.0 ml, CentREUSE ili ndi disk yayikulu (radius = 123.5 mm) kuposa wringer yayikulu kwambiri ya Prakash yoyesedwa (radius = 85 mm).Kuphatikiza apo, pothandizira kulemera kowonjezera kwa syringe ya 1.0 ml yodzazidwa ndi madzi, CentREUSE amagwiritsa ntchito makatoni a malata m'malo mwa makatoni.Pamodzi, zosinthazi zimalola kukhazikika kwa ma voliyumu okulirapo kuposa omwe adayesedwa mu chotsukira pepala la Prakash (ie ma syrinji awiri a 1.0 ml okhala ndi ma capillaries) pomwe akudalira zigawo zofananira: filament ndi zinthu zochokera pamapepala.Makamaka, ma centrifuge angapo otsika mtengo opangidwa ndi anthu adalongosoledwa kuti azizindikira4,5,6,7,8,9,10.Izi zikuphatikizapo masipina, zomenyetsa saladi, zomenyetsa mazira, ndi miyuni yamanja ya zipangizo zozungulira5, 6, 7, 8, 9. Komabe, zambiri mwa zipangizozi sizinapangidwe kuti zigwire ma voliyumu mpaka 1.0 ml ndipo zimakhala ndi zipangizo zomwe nthawi zambiri zimakhala zodula kwambiri. ndi zosafikirika kuposa zomwe zimagwiritsidwa ntchito pamapepala a centrifuges2,4,5,6,7,8,9,10..Ndipotu, mapepala otayidwa nthawi zambiri amapezeka paliponse;mwachitsanzo, ku United States, mapepala ndi mapepala amaposa 20% ya zinyalala zolimba za tauni, zomwe zimapereka ndalama zambiri, zotsika mtengo, kapenanso zaulere zomangira ma centrifuges a mapepala.mwachitsanzo CentREUSE11.Komanso, poyerekeza ndi mayankho ena otsika mtengo omwe adasindikizidwa, CentREUSE safuna zida zapadera (monga zida zosindikizira za 3D ndi mapulogalamu, zida zodulira laser ndi mapulogalamu, etc.) kuti apange, kupangitsa kuti hardware ikhale yovuta kwambiri..Anthu awa ali mu chilengedwe 4, 8, 9, 10.
Monga umboni wothandiza wa pepala lathu la centrifuge pazifukwa zochiritsira, tikuwonetsa kukhazikika kwachangu komanso kodalirika kwa kuyimitsidwa kwa triamcinolone mu acetone (TA) kwa jakisoni wa vitreous bolus - njira yotsika mtengo yochizira matenda osiyanasiyana akhungu kwa nthawi yayitali. ,3.Kukhazikitsa zotsatira pambuyo pa mphindi za 3 ndi CentREUSE zinali zofanana ndi zotsatira pambuyo pa maola 12 akukhazikika mothandizidwa ndi mphamvu yokoka.Kuonjezera apo, zotsatira za CentREUSE pambuyo pa centrifugation kwa 5 ndi 10 maminiti adadutsa zotsatira zomwe zingapezeke ndi mphamvu yokoka ndipo zinali zofanana ndi zomwe zimawonedwa pambuyo pa centrifugation ya mafakitale pa 10 ndi 50 RCF kwa mphindi 5, motero.Makamaka, muzochitika zathu, CentREUSE imapanga mawonekedwe owoneka bwino komanso osalala kuposa njira zina zoyesedwa;izi ndi zofunika monga zimathandiza kuti kuwunika molondola mlingo wa mankhwala kutumikiridwa, ndipo n'zosavuta kuchotsa supernatant ndi kutayika kochepa kwa tinthu voliyumu.
Kusankhidwa kwa pulogalamuyi ngati umboni wa lingaliro kunayendetsedwa ndi kufunikira kosalekeza kopititsa patsogolo mwayi wopeza ma intravitreal steroids omwe amagwira ntchito nthawi yayitali m'makonzedwe ocheperako.Intravitreal steroids amagwiritsidwa ntchito kwambiri pochiza matenda osiyanasiyana a maso, kuphatikizapo matenda a shuga a macular edema, kuwonongeka kwa macular okhudzana ndi zaka, retinal vascular occlusion, uveitis, radiation retinopathy, ndi cystic macular edema3,12.Mwa ma steroid omwe amapezeka pa intravitreal administration, TA imakhalabe yomwe imagwiritsidwa ntchito kwambiri padziko lonse12.Ngakhale zokonzekera zopanda TA preservatives (PF-TA) zilipo (mwachitsanzo, Triesence [40 mg/mL, Alcon, Fort Worth, USA]), kukonzekera ndi benzyl mowa preservatives (mwachitsanzo, Kenalog-40 [40 mg/mL, Bristol- Myers Squibb, New York, USA]) akadali wotchuka kwambiri3,12.Tiyenera kuzindikira kuti gulu lomaliza la mankhwala limavomerezedwa ndi US Food and Drug Administration (FDA) kuti agwiritse ntchito intramuscular and intraarticular kokha, kotero kuti intraocular administration imatengedwa kuti ndi yosalembetsa 3, 12.Ngakhale jekeseni ya intravitreal TA imasiyanasiyana malinga ndi momwe akusonyezera komanso njira, mlingo wodziwika kwambiri ndi 4.0 mg (mwachitsanzo, voliyumu ya 0.1 ml kuchokera ku 40 mg/ml solution), yomwe nthawi zambiri imapereka chithandizo cha miyezi pafupifupi 3. , 12, 13, 14, 15.
Kutalikitsa zochita za intravitreal steroids mu matenda aakulu, aakulu kapena obwerezabwereza, zida zingapo za steroid zomwe zimagwiritsidwa ntchito kwautali kapena jekeseni zakhala zikudziwika, kuphatikizapo dexamethasone 0.7 mg (Ozurdex, Allergan, Dublin, Ireland), Relax fluoride acetonide 0.59 mg (Retisert (Retisert) , Bausch ndi Lomb, Laval, Canada) ndi fluocinolone acetonide 0.19 mg (Iluvien, Alimera Sciences, Alpharetta, Georgia, USA)3,12.Komabe, zidazi zili ndi zovuta zingapo.Ku United States, chipangizo chilichonse chimangovomerezeka pazowonetsa zochepa, ndikuchepetsa kuperekedwa kwa inshuwaransi.Kuphatikiza apo, zida zina zimafunikira kuyikidwa kwa opaleshoni ndipo zingayambitse zovuta zapadera monga kusamuka kwa chipangizo kupita kuchipinda cham'mbuyo3,12.Kuonjezera apo, zipangizozi zimakhala zosavuta kupezeka komanso zodula kwambiri kuposa TA3,12;pamitengo yapano yaku US, Kenalog-40 imawononga pafupifupi $20 pa 1.0 ml ya kuyimitsidwa, pomwe Ozurdex, Retisert, ndi Iluvien amawonjezera.Mtengo wolowera ndi pafupifupi $1400., $20,000 ndi $9,200 motsatana.Zonse pamodzi, zinthuzi zimachepetsa mwayi wopezeka pazidazi kwa anthu omwe ali ndi zopinga zambiri.
Kuyesera kwapangidwa kuti atalikitse zotsatira za intravitreal TA1,3,16,17 chifukwa cha mtengo wake wotsika, kubwezera mowolowa manja, komanso kupezeka kwakukulu.Chifukwa cha kusungunuka kwake kwamadzi otsika, TA imakhalabe m'maso ngati malo osungiramo zinthu, kulola kufalikira kwapang'onopang'ono komanso kosalekeza kwa mankhwala, motero zotsatira zake zikuyembekezeka kukhala nthawi yayitali ndi ma depot akuluakulu1,3.Kuti izi zitheke, njira zingapo zapangidwa kuti zikhazikitse kuyimitsidwa kwa TA kusanachitike jekeseni mu vitreous.Ngakhale kuti njira zozikidwa pa kukhazikika (mwachitsanzo, kudalira mphamvu yokoka) kukhazikika kapena kuchulukitsidwa kwa microfiltration zafotokozedwa, njirazi zimatenga nthawi ndipo zimapereka zotsatira zosiyana15,16,17.M'malo mwake, kafukufuku wam'mbuyomu awonetsa kuti TA imatha kukhazikika mwachangu komanso modalirika (ndipo motero kuchitapo kanthu nthawi yayitali) ndi mpweya wothandizidwa ndi centrifugation1,3.Pomaliza, kuphweka, kutsika mtengo, nthawi, komanso mphamvu ya centrifugally concentrated TA imapangitsa kuti izi zikhale njira yabwino kwa odwala omwe ali ndi zochepa zochepa.Komabe, kusowa kwa mwayi wodalirika wa centrifugation kungakhale chotchinga chachikulu pakuchita izi;Pothana ndi vutoli, CentREUSE ikhoza kuthandizira kukulitsa kupezeka kwa chithandizo chanthawi yayitali cha steroid kwa odwala omwe ali ndi zida zochepa.
Pali zolepheretsa mu kafukufuku wathu, kuphatikiza zomwe zimagwirizana ndi magwiridwe antchito a chipangizo cha CentREUSE.Chipangizocho ndi oscillator osagwirizana, osakhazikika omwe amadalira zomwe anthu amalowetsamo ndipo motero sangathe kupereka molondola komanso kosalekeza kusinthasintha panthawi yogwiritsira ntchito;kuthamanga kwa kasinthasintha kumadalira zinthu zingapo, monga kutengera kwa ogwiritsa ntchito pamlingo wa umwini wa chipangizocho, zida zapadera zomwe zimagwiritsidwa ntchito pophatikiza zida, komanso mtundu wa malumikizidwe omwe amakulungidwa.Izi ndizosiyana ndi zida zamalonda zomwe liwiro lozungulira lingagwiritsidwe ntchito mosasinthasintha komanso molondola.Kuphatikiza apo, liwiro lomwe CentREUSE limapeza limatha kuonedwa kuti ndi locheperako poyerekeza ndi liwiro lomwe zidapangidwa ndi zida zina za centrifuge2.Mwamwayi, liwiro (ndi mphamvu yogwirizana ndi centrifugal) yopangidwa ndi chipangizo chathu inali yokwanira kuyesa lingaliro lofotokozedwa mu phunziro lathu (ie, TA deposition).Kuthamanga kozungulira kumatha kuonjezedwa ndikuwunikira kuchuluka kwa diski yapakati 2;Izi zitha kuchitika pogwiritsa ntchito chopepuka (monga katoni yocheperako) ngati chili champhamvu chogwira majekeseni awiri odzaza ndi madzi.Kwa ife, chigamulo chogwiritsa ntchito "A" makatoni otsekedwa (4.8 mm wandiweyani) chinali dala, chifukwa nkhaniyi imapezeka nthawi zambiri m'mabokosi otumizira ndipo imapezeka mosavuta ngati zinthu zobwezeretsedwa.Kuthamanga kozungulira kungathenso kuwonjezereka mwa kuchepetsa radius yapakati disk 2.Komabe, radius ya nsanja yathu idapangidwa dala kuti ikhale yayikulu kuti ipeze syringe ya 1.0 ml.Ngati wogwiritsa ntchito ali ndi chidwi ndi zombo zazifupi zofikira pakati, utali wozungulirawu ukhoza kuchepetsedwa—kusintha komwe kumapangitsa kuti azithamanga kwambiri (ndiponso mphamvu zokulirapo za centrifugal).
Kuphatikiza apo, sitinawunike bwino momwe kutopa kwa opareshoni kumagwirira ntchito pazida.Chochititsa chidwi n’chakuti anthu angapo a m’gulu lathu anatha kugwiritsa ntchito chipangizochi kwa mphindi 15 popanda kutopa.Njira yothetsera kutopa kwa ogwiritsa ntchito ngati ma centrifuges ataliatali akufunika ndikuzungulira ogwiritsa ntchito awiri kapena kupitilira apo (ngati kuli kotheka).Kuonjezera apo, sitinayang'ane mozama za kulimba kwa chipangizocho, mwa zina chifukwa zigawo za chipangizo (monga makatoni ndi chingwe) zikhoza kusinthidwa mosavuta pamtengo waung'ono kapena wopanda pake pakawonongeka kapena kuwonongeka.Chosangalatsa ndichakuti pakuyesa kwathu, tidagwiritsa ntchito chipangizo chimodzi kwa mphindi zopitilira 200.Pambuyo pa nthawiyi, chizindikiro chokhacho chodziwika koma chaching'ono cha kutha ndikung'ambika pamodzi ndi ulusi.
Cholepheretsa china cha phunziro lathu ndikuti sitinayese mwachindunji kuchuluka kapena kuchuluka kwa TA yoyikidwa, yotheka ndi chipangizo cha CentREUSE ndi njira zina;m'malo mwake, kutsimikizira kwathu koyesera kwa chipangizochi kunali kozikidwa pa kuyeza kachulukidwe ka dothi (mu ml).mulingo wosalunjika wa kachulukidwe.Kuonjezera apo, sitinayese CentREUSE Concentrated TA kwa odwala, komabe, popeza chipangizo chathu chinapanga ma pellets a TA ofanana ndi omwe amapangidwa pogwiritsa ntchito centrifuge yamalonda, tinkaganiza kuti CentREUSE Concentrated TA idzakhala yothandiza komanso yotetezeka monga momwe tagwiritsira ntchito kale.m'mabuku.lipoti pa zipangizo ochiritsira centrifuge1,3.Kafukufuku wowonjezera wowerengera kuchuluka kwenikweni kwa TA yomwe imayendetsedwa pambuyo pa CentREUSE fortification ingathandize kuwunikanso momwe chipangizo chathu chimathandizira pakugwiritsa ntchito.
Kudziwa kwathu, CentREUSE, chipangizo chomwe chingapangidwe mosavuta kuchokera ku zinyalala zomwe zimapezeka mosavuta, ndizoyamba zogwiritsidwa ntchito ndi anthu, zonyamulika, zotsika mtengo kwambiri za pepala centrifuge zomwe zimagwiritsidwa ntchito pochiza.Kuphatikiza pakutha kuyika ma voliyumu okulirapo, CentREUSE safuna kugwiritsa ntchito zida zapadera ndi zida zomangira poyerekeza ndi ma centrifuge otsika mtengo omwe amasindikizidwa.Kuwonetsetsa kwamphamvu kwa CentREUSE pakugwa mwachangu komanso kodalirika kwa TA kungathandize kupititsa patsogolo kupezeka kwa intravitreal steroid kwa nthawi yayitali mwa anthu omwe ali ndi zida zochepa, zomwe zingathandize kuchiza matenda osiyanasiyana.Kuphatikiza apo, mapindu a ma centrifuges athu oyendetsedwa ndi anthu amafikira kumadera olemera kwambiri monga zipatala zazikulu zamaphunziro apamwamba apamwamba komanso quaternary m'maiko otukuka.Pansi pazimenezi, kupezeka kwa zida zopangira ma centrifuging kumatha kupitilira kuma labotale azachipatala ndi kafukufuku, ndi chiopsezo choyipitsa ma syringe ndi madzi am'thupi la munthu, zinthu zanyama, ndi zinthu zina zowopsa.Kuphatikiza apo, ma laboratorieswa nthawi zambiri amakhala kutali ndi malo osamalira odwala.Izi, zitha kukhala zovuta kwa othandizira azaumoyo omwe amafunikira kupeza mwachangu kwa centrifugation;kutumiza CentREUSE kungakhale njira yothandiza yokonzekera chithandizo chamankhwala pakanthawi kochepa popanda kusokoneza kwambiri chisamaliro cha odwala.
Choncho, kuti zikhale zosavuta kuti aliyense akonzekere chithandizo chamankhwala chomwe chimafuna centrifugation, template ndi malangizo opangira CentREUSE akuphatikizidwa m'buku lotseguka ili pansi pa gawo la Zowonjezera Zowonjezera.Timalimbikitsa owerenga kuti akonzenso CentREUSE ngati pakufunika.
Deta yochirikiza zotsatira za kafukufukuyu ikupezeka kuchokera kwa wolemba ma SM akafunsidwa.
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SM imathandizidwa mwa zina ndi mphatso ku Mukai Foundation, Massachusetts Eye and Ear Hospital, Boston, Massachusetts, USA.
Dipatimenti ya Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear, 243 Charles St, Boston, Massachusetts, 02114, USA