Inqaku
Imethylene eluhlaza okwesibhakabhaka ye-COVID-19 ne-COVID ehlala ixesha elide: ubungqina
Umdla kwimethylene eluhlaza okwesibhakabhaka ye-COVID waqala ngombuzo ofanelekileyo. Le khompawundi inexabiso eliphantsi, kudala isetyenziswa kwezonyango, yaye umsebenzi waselebhoratri wabonisa ukusebenza kwayo ngokuchasene ne-SARS-CoV-2. Kodwa loo mbuzo mnye wakhawuleza wahlukana waba yimibuzo emithathu eyahlukileyo, yaye abafundi abayixubayo baya kubutolika ngendlela engachanekanga ubungqina.
Le mibuzo mithathu yile: ingaba iyalunyanga usulelo olukwisigaba esibukhali kwizigulana, ingaba iyayiphelisa intsholongwane amandla okusulela ngaphandle komzimba, yaye ingaba iyanceda kwiimpawu zasemva kwesigaba esibukhali ezaziwa njenge-COVID ehlala ixesha elide. Ngamnye unendlela eyahlukileyo yokuyila isifundo, umlinganiselo owahlukileyo wesiphumo, nempendulo eyahlukileyo. Eli nqaku liyigcina yahlukile, lize ligqibe ngerejista onokuyijonga ngaphambi kokwenza nasiphi na isigqibo nogqirha.
Usulelo olukwisigaba esibukhali: umqondiso ophindaphindayo wokuphucuka kweoksijini ngaphandle kobungqina bokuphilisa
Izizathu zokuqala zokuyisebenzisela injongo entsha zachazwa kuphononongo oluchazayo luka-2021 olwahlola ifamakholoji yemethylene eluhlaza okwesibhakabhaka lwaza lwadwelisa iimvavanyo ezintlanu ezibhalisiweyo zemethylene eluhlaza okwesibhakabhaka kulawulo lwe-COVID-19. Olo phononongo luluncedo njengesikhokelo sokuqala, hayi njengobungqina. Lwacebisa iindlela zokusebenza ezifana nokujikeleza kwe-redox nokuncipha komonakalo obangelwa yi-oxidation, lwaza lwadwelisa iimvavanyo ezazininzi kuzo zingekagqitywa ngelo xesha. Isimo sezi mvavanyo sitshintshile ukususela ngoko, ngoko ke ungeno ngalunye kufuneka lujongwe ngokutsha kunokuba kuthenjwe uluhlu luka-2021.
Indlela ezihamba ngayo iziphumo kwiimpapasho zamva iyafana ngokwaneleyo ukuba ingachazwa. Izifundo ezininzi kwizibhedlele zaseIran zavavanya imethylene eluhlaza okwesibhakabhaka njengenxalenye yendibaniselwano eyongezwa kukhathalelo oluqhelekileyo, zaza zaxela ukuphucuka kokufumana ioksijini kwixesha elifutshane nokufutshane kwamaxesha okuhlala esibhedlele. Kwingxelo enye yesigaba 2 enezigulana ezingama-80, ixesha lokuhlala lalimalunga neentsuku ezisi-7 ngendibaniselwano xa kuthelekiswa neentsuku ezimalunga ne-12 ngokhathalelo oluqhelekileyo kuphela. Ingxelo enkulu efana neyesigaba 3, enezigulana ezingama-223, yalatha kwicala elifanayo kodwa ayizange ifikelele ekubalulekeni ngokweenkcukacha-manani malunga nokusweleka. Ezi zizifundo ezingafihliyo ukuba ngubani ofumana oluphi unyango, zesicwangciso sonyango esinamacandelo amaninzi; oku kubalulekile ngenxa yezizathu esibuyela kuzo ngezantsi.
Isifundo esitsha esabelwa amaqela ngokungakhethiyo siwenza ucace ngakumbi lo mfanekiso. Kwizigulana ezili-122 ezazisesibhedlele zine-COVID-19 ne-ARDS, iqela elafumana imethylene eluhlaza okwesibhakabhaka ngomlomo kunye nonyango oluqhelekileyo labonisa ukunyuka okukhulu kokuzaliswa kwegazi yioksijini kunelo lafumana unyango oluqhelekileyo kuphela, kwakho nokunxulumana okubalulekileyo phakathi kweqela nexesha. Sekunjalo, ixesha lokuhlala esibhedlele nokusweleka emva kwenyanga enye nangemva kweenyanga ezintathu akuzange kwahluke kakhulu ngokweenkcukacha-manani kolo lingo lwe-ARDS olwabelwa amaqela ngokungakhethiyo. Uthotho oluncinci lokuzama ukusindisa izigulana ezingama-50 ezigula kakhulu, olwalungenalo iqela lothelekiso, lwazinikela imethylene eluhlaza okwesibhakabhaka ngomthambo lwaza lwaxela imilinganiselo ephezulu yeoksijini emva konyango. Kodwa, ngenxa yokusweleka kwabangama-20 nokungabikho kweqela lothelekiso, olo thotho lweemeko zokuzama ukusindisa izigulana alunakubonisa ukuba iyeza labangela olo tshintsho.
Olona vavanyo lunamandla lwempembelelo echasene nentsholongwane, olwaluthelekisa ne-placebo, lwalatha kwelinye icala. Ulingo NCT04635605 lwabela izigulana ezingalaliswanga esibhedlele ngokungakhethiyo ukuba zifumane idosi enye yemethylene eluhlaza okwesibhakabhaka ngomlomo okanye i-placebo, lwaza lwalinganisa ubungakanani bentsholongwane nokuphela kwayo. Isiphumo asizange sibonise ukusebenza ngokuchasene nentsholongwane, njengoko kushwankathelwe kwingxelo yolingo epapashiweyo. Ukulaliswa esibhedlele nako akuzange kunciphe kolunye ulingo olunxulumene nolu kodwa olwahlukileyo, olwavavanya iplasma yabantu abachachileyo eyayinyangwe ngemethylene eluhlaza okwesibhakabhaka ngaphambi kokutofelwa. Eso sifundo sezigulana ezingama-376 ezingalaliswanga esibhedlele safumana amazinga okulaliswa esibhedlele notshintsho kubungakanani bentsholongwane aphantse afana kumaqela eplasma nawe-placebo kulingo lweplasma lwe-COnV-ert. Ukunyanga iplasma ngemethylene eluhlaza okwesibhakabhaka yinkqubo yokulungisa imveliso yegazi, hayi unyango lwemethylene eluhlaza okwesibhakabhaka olusebenza kuwo wonke umzimba, ngoko akufanele kubalwe njengovavanyo lokuthatha eli yeza.
Ngamafutshane: imethylene eluhlaza okwesibhakabhaka ye-COVID ibonisa umqondiso ophindaphindayo kwimilinganiselo yokufumana ioksijini, kodwa akukho bungqina bukholisayo bokuphela kwentsholongwane ngokukhawuleza, ukuncipha kokulaliswa esibhedlele, okanye ukuncipha kokusweleka. Ukuzaliswa kwegazi yioksijini kufanelekile ukulandelelwa, kodwa akuyonto inye nokuphiliswa kosulelo.
Abafundi abangaqhelananga nendlela imethylene eluhlaza okwesibhakabhaka esebenza ngayo njenge-arhente ye-redox ngamanye amaxesha balindela ukuba ukuphucuka kweoksijini kuthethe ukubulawa kwentsholongwane. Akunjalo. Ukufumana ioksijini kubonisa umonakalo wemiphunga, ukusebenza kwehemoglobin, nokujikeleza kwegazi. Ubungakanani bentsholongwane bubonisa ukuphindaphindeka kwayo. Iyeza linokuchaphazela enye ngaphandle kokuchaphazela enye.
Ukupheliswa kokukwazi kwentsholongwane ukusulela elabhoratri: iziphumo ezomeleleyo, intsingiselo elinganiselweyo
Elabhoratri iziphumo zibonakala zinamandla kakhulu, yaye loo mahluko udida izishwankathelo ezininzi. Umsebenzi wokuqala wokukhulisa iiseli waxela ukuba iziphumo ezifikelela kwisiqingatha sempembelelo ephezulu ngokuchasene ne-SARS-CoV-2 kwiiseli ze-Vero E6 zifumaneka kumaqondo asezantsi e-micromolar. Oku kwanika isizathu solingo ebantwini esiphawulwe kwizifundo zokuqala zokukhulisa iiseli. Iimvavanyo zokudibana ngqo zaza zabonisa ukuba imethylene eluhlaza okwesibhakabhaka yonakalisa i-RNA yentsholongwane emva kweeyure zokudibana nayo, nokuba ingavuswanga kukukhanya, njengakumsebenzi kaCagno noogxa bakhe.
Ngokukhanya, impembelelo iba nkulu ngakumbi. Ukudibanisa imethylene eluhlaza okwesibhakabhaka nokukhanya kwelaser ebomvu kwaphelisa ngokupheleleyo amandla okusulela kwimixube enobuninzi obuphezulu bentsholongwane, kwaza kwakhusela iiseli ezibekwe kumaleko omnye kwisifundo sokupheliswa kokusulela ngokusebenza kokukhanya. Umsebenzi weemveliso zegazi ubonisa okufanayo: malunga ne-0.8 micromolar yemethylene eluhlaza okwesibhakabhaka kunye nokukhanya okubonakalayo kwanciphisa ukukwazi kwe-SARS-CoV-2 ukusulela kwiplasma malunga namanqanaba amahlanu aphindwe kalishumi, ngoxa imethylene eluhlaza okwesibhakabhaka ngaphandle kokukhanya yenza okuncinci kakhulu, ngokweemvavanyo zokunciphisa iintsholongwane eziyingozi kwiplasma. Ukubulawa kweentsholongwane okufanayo kwiisampulu zeklinikhi ngokukhanyiselwa ixesha elifutshane kwaxelwa kwisifundo samva sokubulala iintsholongwane kwiisampulu.
Indlela echanekileyo yokuqonda oku kukuyibona njengesibulali seentsholongwane ezingaphandle kweeseli, hayi njengeyeza elichasene neentsholongwane ezingaphakathi kweeseli. Isifundo sika-2024 sendlela yokusebenza sawenza wacaca lo mahluko: imethylene eluhlaza okwesibhakabhaka yawaphelisa ngokungenakubuyiselwa amandla okusulela amasuntswana e-coronavirus angaphandle kweeseli ebumnyameni, kodwa yayingenampembelelo ibonakalayo xa iiseli sele zosulelekile. Ukunikwa kwayo ngomlomo akuzange kukhusele iimpuku ezazisesichengeni kusulelo olubulalayo kolo thelekiso lwangaphandle nolwangaphakathi kweeseli.
Loo mahluko uchaza indlela ezihamba ngayo iziphumo zeklinikhi. Ikhompawundi inokuba sisibulali seentsholongwane esisemagqabini kwimiphezulu, kwiisampulu, okanye kwiplasma, ingakumbi xa kukho ukukhanya, ize sekunjalo isilele njengeyeza elichasene neentsholongwane elisebenza kuwo wonke umzimba, kuba izicubu ezosulelekileyo zeendlela zokuphefumla ziyimeko eyahlukileyo kwityhubhu yovavanyo. Ukupheliswa kokusulela elabhoratri kuxhasa ukusetyenziswa kwayo kukhuseleko lwezixhobo negazi. Akungqini ukuba imethylene eluhlaza okwesibhakabhaka ye-COVID lunyango lwezigulana oluqinisekisiweyo.
I-COVID ehlala ixesha elide: yingcamango kuphela, akukho lingo lugqityiweyo olwabelwa amaqela ngokungakhethiyo
Ubungqina bemethylene eluhlaza okwesibhakabhaka ye-COVID ehlala ixesha elide bukwinqanaba elisezantsi nangakumbi. Iphepha lika-2021 elisoloko licatshulwa, elinesihloko esiquka amazwi athi "ukudakumba emva kwe-COVID", yileta ebeka ingcamango, hayi ulingo. Licebisa iindlela ezinxulumene neemitochondria nokudumba kwenkqubo yemithambo-luvo ekunokwenzeka ngazo inzuzo, kodwa alixeli ziphumo zasemva kwesigaba esibukhali ezithelekiswe neqela lolawulo kwileta yengcamango ngeempawu zasemva kwe-COVID. Leyo yingcamango yokuqala, hayi isiphumo.
Ukuza kutsho ekupheleni kuka-2026, asifumani lingo libhalisiweyo nelugqityiweyo olwabelwa amaqela ngokungakhethiyo oluvavanya imethylene eluhlaza okwesibhakabhaka ngokukodwa kwiziphumo eziqhubekayo esele zimiselwe emva kwesigaba esibukhali. Iingxelo ezincinci ezalandela izigulana ezazikwisigaba esibukhali emva kwemethylene eluhlaza okwesibhakabhaka okanye unyango olusebenzisa ukusebenza kokukhanya, zaza zabuza ngeempawu eziqhubekayo, azinakugcwalisa eso sikhewu. Zincinci, azinamaqela olawulo, yaye zidla ngokudibanisa imethylene eluhlaza okwesibhakabhaka nonyango lokukhanya okanye amanye amayeza, ngoko azinakubonisa ukuthintelwa okanye ukunyangwa kwe-COVID ehlala ixesha elide.
Nabani na ovavanya ibango apha kufuneka abuze imibuzo emithathu. Ingaba abantu abafundwayo bachazwe njengabakwinqanaba lasemva kwesigaba esibukhali kunokuba bakwisigaba esibukhali. Ingaba bekukho iqela lolawulo. Ingaba ukudinwa, ukungakwazi ukumelana nomgudu, ubunzima bokucinga, okanye olunye uphawu oluchazwe kwangaphambili lwalulinganiswa ngesikali esiqinisekisiweyo. Ukuba impendulo kuwo nawuphi na kule mibuzo ngu-hayi, loo ngxelo yinkcazelo engasemva, hayi ubungqina bokusebenza.
Inqaku ngezicwangciso zonyango ezidityanisiweyo nenaltrexone yedosi ephantsi
Ezinye izicwangciso zonyango ezikwi-intanethi zidibanisa imethylene eluhlaza okwesibhakabhaka nenaltrexone yedosi ephantsi yokudinwa emva kosulelo lwentsholongwane. Oku kudala ingxaki yokuchonga unobangela. Xa iindlela ezimbini zongenelelo ziqala kunye zize iimpawu zitshintshe, olo tshintsho aluchongi ukuba loluphi ungenelelo olube negalelo, ukuba ingaba lukhona olunegalelo, okanye ukuba indibaniselwano ikhuselekile. Ukuchacha ngokwemvelo, ukuphumla, impendulo kwi-placebo, nokhathalelo olwenziwa ngaxeshanye nako kungachaza ukuphucuka.
Loo ngqiqo iyasebenza nakulingo lwe-COVID ekwisigaba esibukhali olusebenzisa indibaniselwano olukhankanywe ngasentla, apho imethylene eluhlaza okwesibhakabhaka yanikwa kunye nevithamin C, i-N-acetylcysteine, okanye ezinye ii-arhente ecaleni kokhathalelo oluqhelekileyo. Ukuhlala ixesha elifutshane kwiqela lendibaniselwano akuyichongi ngokwahlukeneyo impembelelo yemethylene eluhlaza okwesibhakabhaka. Abafundi abathatha imethylene eluhlaza okwesibhakabhaka kunye nezinye izongezelelo okanye amayeza kufuneka baphonononge nogqirha ulwazi lokusebenzisana kwamayeza neemeko ekungafanelekanga ukusetyenziswa kuzo, kunokuba bacinge ukuba ingxelo yomntu ngendibaniselwano iyasebenza nakubo. Inkcazelo yokhuseleko lwemethylene eluhlaza okwesibhakabhaka ibaluleke ngokukodwa kuba amayeza achaphazela iserotonin, ukunqongophala kwe-G6PD, ukungasebenzi kakuhle kwezintso, nokukhulelwa zitshintsha ngokupheleleyo indlela yokuvavanya umngcipheko.
Irejista yolingo nezifundo enemilinganiselo yeziphumo ethe ngqo kwimeko nganye
Sebenzisa le theyibhile njengomthombo wokuqala wokujonga kweli nqaku. Imeko ichaza ukuba ngowuphi umlinganiselo wesiphumo obalulekileyo. Amangenelo erejista abonisa isimo esaxelwa ukuya kutsho ekupheleni kuka-2026; qinisekisa isimo sangoku ngaphambi kokucaphula, kuba iingxelo zeerejista zihlaziywa emva kweempapasho.
| Isifundo | Imeko evavanyiweyo | Ungenelelo | Imilinganiselo yeziphumo ethe ngqo kwimeko | Isimo nesiphumo |
|---|---|---|---|---|
| NCT04370288 | I-COVID-19 ekwisigaba esibukhali, emandla | Imethylene eluhlaza okwesibhakabhaka 1 mg nge-kg kunye nevithamin C ne-N-acetylcysteine, kamva izicwangciso zemethylene eluhlaza okwesibhakabhaka ekwimo encitshisiweyo enikwa ngomlomo, kunye nokhathalelo oluqhelekileyo | Ukungadingi umatshini wokuphefumla ngosuku 7; iingxelo zamva: ukuzaliswa kwegazi yioksijini, izinga lokuphefumla, ubude bexesha lokuhlala, ukusweleka | Iingxelo ezifana nezesigaba 1 no-2 zichaza ukuphucuka kokufumana ioksijini nexesha elifutshane lokuhlala; unyango olungafihlwanga, isicwangciso sendibaniselwano, amaqela amancinci |
| NCT04547127 | I-COVID-19 ekwisigaba esibukhali | Isicwangciso esisekelwe kwimethylene eluhlaza okwesibhakabhaka kunye nokhathalelo oluqhelekileyo | Ukufumana ioksijini, imilinganiselo yokuchacha ngokweklinikhi | Idweliswe kuphononongo luka-2021; jonga irejista ukufumana isimo sangoku, akukho siphumo sigqityiweyo sikumgangatho ophezulu sokusebenza esiqinisekisiweyo |
| NCT04376788 | I-COVID-19 ekwisigaba esibukhali | Ungenelelo lwemethylene eluhlaza okwesibhakabhaka ngokongenelo lwerejista | Imilinganiselo yeziphumo zesimo seklinikhi ngokwerejista | Idweliswe kuphononongo luka-2021; jonga irejista ukufumana isimo sangoku ngaphambi kokucaphula |
| NCT04619290 | Inkqubo yezifo zemiphunga equka imeko ye-COVID | Ungenelelo lwemethylene eluhlaza okwesibhakabhaka ngokongenelo lwerejista | Imilinganiselo yeziphumo zokuphefumla ngokwerejista | Idweliswe kuphononongo luka-2021; jonga irejista ukufumana isimo sangoku ngaphambi kokucaphula |
| NCT04635605 | I-COVID-19 ekwisigaba esibukhali, izigulana ezingalaliswanga esibhedlele | Idosi enye yemethylene eluhlaza okwesibhakabhaka ngomlomo xa ithelekiswa ne-placebo | Utshintsho kubungakanani bentsholongwane, ukuphela kwentsholongwane | Lugqityiwe; alubonisi ukusebenza ngokuchasene nentsholongwane |
| NCT04621123 (COnV-ert) | I-COVID-19 ekwisigaba esibukhali, izigulana ezingalaliswanga esibhedlele | Iplasma yabantu abachachileyo encitshiswe iintsholongwane eziyingozi ngemethylene eluhlaza okwesibhakabhaka nokukhanya, xa ithelekiswa ne-placebo yamanzi anetyuwa | Ukulaliswa esibhedlele, ubungakanani bentsholongwane ngosuku 7 | Lugqityiwe kwizigulana ezingama-376; akukho mahluko ekulalisweni esibhedlele okanye kubungakanani bentsholongwane; luvavanya inkqubo yeplasma, hayi ukunikezelwa kwedosi esebenza kuwo wonke umzimba |
| IRCT20200409047007N2 | I-COVID-19 ekwisigaba esibukhali ene-ARDS, izigulana ezilaliswe esibhedlele | Imethylene eluhlaza okwesibhakabhaka ngomlomo kunye nonyango oluqhelekileyo (n ilingana nama-62) xa ithelekiswa nonyango oluqhelekileyo (n ilingana nama-60) | Indlela ukuzaliswa kwegazi yioksijini okutshintsha ngayo ekuhambeni kwexesha, ubude bexesha lokuhlala, ukusweleka emva kwenyanga 1 neenyanga 3 | Lugqityiwe kwizigulana ezili-122; ukuzaliswa kwegazi yioksijini kwaphucuka, ixesha lokuhlala nokusweleka akuzange kwahluke kakhulu ngokweenkcukacha-manani |
| Uthotho lokuzama ukusindisa izigulana ngeyeza lomthambo olungenalo iqela lolawulo | I-COVID-19 ekwisigaba esibukhali, ukunqongophala okumandla kweoksijini egazini | Imethylene eluhlaza okwesibhakabhaka ngomthambo 1 mg nge-kg ukuya kuthi ga kwiidosi ezintlanu | Umlinganiselo weoksijini, imfuneko yokuncediswa ukuphefumla, ukukhutshwa esibhedlele, ukufa | Izigulana ezingama-50; umlinganiselo weoksijini wenyuka, ezingama-30 zakhutshwa esibhedlele, ezingama-20 zasweleka; akukho qela lolawulo ngoko akukho bango lonobangela elinokwenziwa |
| Inkqubo yaselebhoratri yokupheliswa kokusulela | Ex vivo nakwi-in vitro, hayi kwizigulana | Imethylene eluhlaza okwesibhakabhaka inokukhanya okubomvu okanye okubonakalayo nangaphandle kwako; inkqubo yeplasma malunga ne-0.8 micromolar | Ukuncipha kokukwazi ukusulela ngokomlinganiselo we-log, TCID50, umonakalo we-RNA | Iziphumo ezomeleleyo zokupheliswa kokusulela ngaphandle kweeseli, ingakumbi ngokukhanya; zixhasa kuphela ukusetyenziswa ekubulaleni iintsholongwane |
| I-COVID ehlala ixesha elide neziphumo eziqhubekayo emva kwesigaba esibukhali | Iimpawu zasemva kwesigaba esibukhali esele zimiselwe | Akukho lingo lugqityiweyo lwemethylene eluhlaza okwesibhakabhaka olwabelwa amaqela ngokungakhethiyo oluchongiweyo | Izikali zeempawu ezichazwe kwangaphambili, imilinganiselo yokusebenza | Ubungqina abukho; kukho kuphela amaphepha eengcamango noqwalaselo lokulandelela olungenamaqela olawulo |
Indlela yokusebenzisa obu bungqina
Zigcine zahlukene ezi meko zintathu. Kusulelo olukwisigaba esibukhali, isishwankathelo esinyanisekileyo kukuba kusenokwenzeka ukuphucuka kokufumana ioksijini, kodwa impembelelo ekupheleni kwentsholongwane, ekulalisweni esibhedlele, okanye ekusindeni ayiqinisekiswanga. Ekuphatheni izinto zaselebhoratri, imethylene eluhlaza okwesibhakabhaka kunye nokukhanya yindlela eqinisekisiweyo yokupheliswa kokusulela kwiimeko evavanywe kuzo. Kwi-COVID ehlala ixesha elide, okwangoku akukho siseko solingo sonyango.
Nabani na ocinga ngokuyisebenzisa kufuneka axoxe nogqirha ngedosi, ixesha lokuyithatha, amayeza asebenzisana nayo, nokufaneleka kwakhe ukuyisebenzisa, aze ajonge ukuba ingaba iziphumo zolingo lwamva ziyayitshintsha na indlela yokulinganisa ubungqina. Iingxelo zolingo zihlaziywa emva kokuba uphononongo luye kupapasho, yaye eli candelo sele litshintshile kanye ukusuka kwizindululo ukuya kwiziphumo ezingaphelelanga. Lo mkhwa wokuphinda ujonge irejista ubaluleke ngaphezu kwaso nasiphi na isifundo esinye.