Isihloko
I-methylene blue ye-COVID-19 ne-COVID ehlala isikhathi eside: ubufakazi
Intshisekelo nge-methylene blue ye-COVID yaqala ngombuzo onengqondo. Le nhlanganisela yamakhemikhali ishibhile, inomlando omude ekwelapheni, futhi umsebenzi waselabhorethri wabonisa ukuthi iyasebenza ngokumelene ne-SARS-CoV-2. Kodwa lowo mbuzo owodwa washeshe wahlukana waba imibuzo emithathu ehlukene, futhi abafundi abayixubayo bayobuqonda kabi ubufakazi.
Le mibuzo emithathu ithi: ingabe iyakwelapha ukutheleleka esigabeni sokuqala ezigulini, ingabe yenza igciwane lingasebenzi ngaphandle komzimba, futhi ingabe iyasiza ngezimpawu zangemva kwesigaba sokuqala ezaziwa ngokuthi i-COVID ehlala isikhathi eside. Ngamunye unendlela yokuhlela ucwaningo ehlukile, umphumela olinganiswayo ohlukile, nempendulo ehlukile. Lesi sihloko siyayihlukanisa bese siphetha ngerejista ongayihlola ngaphambi kokwenza noma yisiphi isinqumo nodokotela.
Ukutheleleka esigabeni sokuqala: inkomba ephindaphindayo yomoya-mpilo ngaphandle kobufakazi bokwelapheka
Isisekelo sokuqala sokusebenzisa lo muthi ngenjongo entsha sachazwa ekubuyekezweni okulandisayo kwango-2021, okwahlola indlela i-methylene blue esebenza ngayo njengomuthi futhi kwabala ukuhlolwa okubhalisiwe okuyisihlanu kwe-methylene blue ekulawuleni i-COVID-19. Lokho kubuyekeza kuyasiza njengemephu yokuqala, hhayi njengobufakazi. Kwaphakamisa izindlela zokusebenza ezifana nomjikelezo we-redox nokuncipha kokulimala okubangelwa i-oxidation, futhi kwabala ukuhlolwa okuningi okwakungakaqedwa ngaleso sikhathi. Isimo sokuhlolwa sesishintshile kusukela ngaleso sikhathi, ngakho ngakunye kudinga ukuhlolwa kabusha kunokuthembela ohlwini lwango-2021.
Iphethini ezincwadini ezashicilelwa kamuva iyavumelana ngokwanele ukuba ichazwe. Ucwaningo oluningana lwezibhedlela zase-Iran lwahlola i-methylene blue njengengxenye yenhlanganisela enezelwa ekunakekelweni okujwayelekile, futhi lwabika ukuthuthuka komoya-mpilo ngesikhathi esifushane nokuncipha kwezinsuku zokuhlala esibhedlela. Komunye umbiko wesigaba 2 weziguli ezingu-80, isikhathi sokuhlala sasicishe sibe izinsuku ezingu-7 ngenhlanganisela, uma kuqhathaniswa nezinsuku ezicishe zibe ngu-12 ngokunakekelwa okujwayelekile kuphela. Umbiko omkhulu wohlobo lwesigaba 3 weziguli ezingu-223 wabonisa indlela efanayo, kodwa umehluko wokufa wawungafinyeleli ekubalulekeni ngokwezibalo. Lolu ucwaningo olungafihli ukuthi ubani uthola luphi ukwelashwa, lohlelo olunezingxenye eziningi; lokhu kubalulekile ngenxa yezizathu esizobuyela kuzo ngezansi.
Ucwaningo olusha olwabela iziguli amaqembu ngokungahleliwe lucacisa isithombe. Ezigulini ezingu-122 ezazisesibhedlela zine-COVID-19 ne-ARDS, iqembu elathola i-methylene blue ngomlomo kanye nokwelashwa okujwayelekile labonisa ukwenyuka okukhulu kwezinga lokugcwala komoya-mpilo egazini kunalelo elathola ukwelashwa okujwayelekile kuphela, futhi ukuhlobana phakathi kweqembu nesikhathi kwakubalulekile ngokwezibalo. Nokho, isikhathi sokuhlala esibhedlela nokufa ngenyanga eyodwa nangezinyanga ezintathu kwakungahlukile kakhulu ngokwezibalo kulokho kuhlolwa kwe-ARDS okwabiwa ngokungahleliwe. Uchungechunge oluncane lokwelapha njengomzamo wokugcina, olungenalo iqembu lokuqhathanisa, lweziguli ezingu-50 ezazigula kakhulu ezanikezwa i-methylene blue emthanjeni, lwabika izilinganiso eziphakeme zomoya-mpilo ngemva kokwelashwa. Kodwa njengoba kwafa ezingu-20 futhi lungekho iqembu lokuqhathanisa, lolo chungechunge lwezigameko zokwelapha njengomzamo wokugcina alukwazi ukubonisa ukuthi umuthi yiwo owabangela ushintsho.
Ukuhlolwa okunamandla kakhulu komphumela wokulwa namagciwane, okunokuqhathanisa ne-placebo, kukhomba kolunye uhlangothi. Ukuhlolwa i-NCT04635605 kwabela iziguli ezingalalisiwe esibhedlela ngokungahleliwe ukuba zithole umthamo owodwa we-methylene blue ngomlomo noma i-placebo, kwase kukala inani legciwane nokususwa kwalo. Umphumela awuzange ubonise ukusebenza kahle ekulweni negciwane, njengoba kufingqiwe embikweni wokuhlolwa oshicilelwe. Ukulaliswa esibhedlela nakho akuzange kunciphe ekuhlolweni okuhlobene nalokho kodwa okuhlukile, okwahlola i-plasma yabantu ababelulama eyayicubungulwe nge-methylene blue ngaphambi kokumpontshelwa. Lolo cwaningo lweziguli ezingalalisiwe ezingu-376 lwathola amazinga ok ulaliswa esibhedlela nezinguquko zenani legciwane ezicishe zifane emaqenjini e-plasma nawe-placebo ekuhlolweni kwe-plasma i-COnV-ert. I-plasma ecubungulwe nge-methylene blue iyinqubo yomkhiqizo wegazi, hhayi ukwelapha nge-methylene blue esebenza emzimbeni wonke, ngakho akufanele ibalwe njengokuhlolwa kokuthatha lo muthi.
Ngamafuphi: i-methylene blue ye-COVID ibonisa inkomba ephindaphindayo ezilinganisweni zomoya-mpilo, kodwa ayibonisi ngokugculisayo ukususwa kwegciwane ngokushesha, ukuncipha kokulaliswa esibhedlela, noma ukuncipha kokufa. Izinga lokugcwala komoya-mpilo lifanele ukuqashwa, kodwa alifani nokwelapha ukutheleleka.
Abafundi abasanda kufunda ukuthi i-methylene blue isebenza kanjani njenge-ejenti ye-redox ngezinye izikhathi balindela ukuthi ukuthuthuka komoya-mpilo kusho ukubulawa kwegciwane. Akusho lokho. Ukutholakala komoya-mpilo kubonisa ukulimala kwamaphaphu, ukusebenza kwe-hemoglobin, nokujikeleza kwegazi. Inani legciwane libonisa ukuziphindaphinda kwalo. Umuthi ungathinta okunye ngaphandle kokuthinta okunye.
Ukwenza igciwane lingasebenzi elabhorethri: umphumela oqinile, incazelo elinganiselwe
Elabhorethri imiphumela ibonakala inamandla kakhulu, futhi lowo mehluko udida izifinyezo eziningi. Umsebenzi wokuqala wokukhulisa amaseli elabhorethri wabika ukuthi imiphumela efinyelela engxenyeni yomphumela omkhulu ngokumelene ne-SARS-CoV-2 kumaseli e-Vero E6 yayitholakala emazingeni aphansi e-micromolar. Lokhu kwanikeza isisekelo sokuhlolwa kubantu okuphawulwe ocwaningweni lokuqala lokukhulisa amaseli. Ukuhlolwa kokuchayeka ngokuqondile kwabe sekubonisa ukuthi i-methylene blue yayilimaza i-RNA yegciwane ngemva kwamahora okuthintana, ngisho ngaphandle kokuvulwa kokusebenza ngokukhanya, njengasemsebenzini ka-Cagno nozakwabo.
Ngokukhanya umphumela uba mkhulu kakhulu. Ukuhlanganisa i-methylene blue nokukhanya kwe-laser ebomvu kwenza izingxube eziwuketshezi ezinesilinganiso esiphezulu segciwane zingasebenzi ngokuphelele, futhi kwavikela izingqimba zamaseli ezinongqimba olulodwa ocwaningweni lokwenza igciwane lingasebenzi ngokusebenza kwamakhemikhali okubangelwa ukukhanya. Umsebenzi wemikhiqizo yegazi ubonisa okufanayo: cishe u-0.8 micromolar we-methylene blue kanye nokukhanya okubonakalayo kwanciphisa amandla e-SARS-CoV-2 okutheleleka ku-plasma cishe ngezigaba ezinhlanu zokuphindaphinda ngo-10, kuyilapho i-methylene blue ngaphandle kokukhanya yenza okuncane kakhulu, ngokusho kokuhlolwa kokunciphisa amagciwane abangela izifo ku-plasma. Ukubulala amagciwane okufanayo kumasampula athathwe ezigulini ngokuwakhanyisa isikhashana kwabikwa ocwaningweni lwakamuva lokubulala amagciwane kumasampula.
Indlela efanele yokukuqonda iwukubona lokhu njengento ebulala amagciwane ngaphandle kwamaseli, hhayi umuthi olwa namagciwane ngaphakathi kwamaseli. Ucwaningo lwango-2024 lwendlela yokusebenza lwawucacisa lo mehluko: i-methylene blue yenza izinhlayiya ze-coronavirus ezingaphandle kwamaseli zingasebenzi unomphela ebumnyameni, kodwa yayingacishe ibe namphumela lapho amaseli esevele ethelelekile. Futhi ukuyinikeza ngomlomo akuzange kuvikele amagundane asengozini ekuthelelekeni okubulalayo kulokho kuqhathaniswa kokusebenza ngaphandle nangaphakathi kwamaseli.
Lowo mehluko uchaza iphethini ebonakala ezigulini. Inhlanganisela yamakhemikhali ingaba yinhle kakhulu ekubulaleni amagciwane ezindaweni, kumasampula, noma ku-plasma, ikakhulukazi ngokukhanya, kodwa ihluleke njengomuthi olwa namagciwane emzimbeni wonke ngoba izicubu zemigudu yokuphefumula ezithelelekile ziyindawo ehlukile kushubhu lokuhlola. Ukwenza igciwane lingasebenzi elabhorethri kusekela ukusetshenziswa ekuphepheni kwemishini negazi. Akufakazeli ukuthi i-methylene blue ye-COVID iwukwelashwa kweziguli okuqinisekisiwe.
I-COVID ehlala isikhathi eside: umbono ongakahlolwa kuphela, akukho ukuhlolwa okwabiwa ngokungahleliwe okuqediwe
Ubufakazi be-methylene blue ye-COVID ehlala isikhathi eside busezingeni eliphansi nakakhulu. Iphepha lango-2021 elivame ukucashunwa, elinesisho esithi “post COVID blues” esihlokweni salo, liyincwadi ephakamisa umbono ongakahlolwa, hhayi ukuhlolwa. Liphakamisa izindlela ezihlobene nama-mitochondria nokuvuvukala kwezicubu zesimiso sezinzwa lapho inzuzo ingase ivele khona, kodwa alibiki imiphumela yangemva kwesigaba sokuqala eneqembu lokuqhathanisa encwadini ephakamisa umbono ngezimpawu zangemva kwe-COVID. Lowo ngumqondo wokuqala, hhayi umphumela.
Kuze kube sekupheleni kuka-2026 asitholi ukuhlolwa okubhalisiwe, okwabiwa ngokungahleliwe futhi okuqediwe, okuhlola i-methylene blue ngokuqondile ezinkingeni eziqhubekayo ezimisiwe zangemva kwesigaba sokuqala. Imibiko emincane eyalandela iziguli zesigaba sokuqala ngemva kwe-methylene blue noma ukwelashwa okusebenza ngokukhanya, yabuza ngezimpawu ezisaqhubeka, ayikwazi ukuvala lesi sikhala. Le mibiko mincane, ayinamaqembu okuqhathanisa, futhi ivame ukuhlanganisa i-methylene blue nokwelashwa ngokukhanya noma eminye imithi, ngakho ayikwazi ukubonisa ukuvimbela noma ukwelapha i-COVID ehlala isikhathi eside.
Noma ubani ohlola isimangalo lapha kufanele abuze imibuzo emithathu. Ingabe iqembu labantu lachazwa njengelisemva kwesigaba sokuqala kunokuba libe sesigabeni sokuqala? Ingabe lalikhona iqembu lokuqhathanisa? Ingabe ukukhathala, ukungakwazi ukubekezelela ukuzikhandla, ubunzima bokucabanga, noma olunye uphawu olwalunqunywe kusengaphambili lwalinganiswa ngesikali esiqinisekisiwe? Uma impendulo kunoma yimuphi wale mibuzo ingucha, umbiko uwulwazi lwesizinda, hhayi ubufakazi bokusebenza kahle.
Inothi ngezinhlelo zokwelapha ezihlanganisiwe ne-naltrexone yomthamo ophansi
Ezinye izinhlelo eziku-inthanethi zihlanganisa i-methylene blue ne-naltrexone yomthamo ophansi ukuze kubhekwane nokukhathala kwangemva kokutheleleka ngegciwane. Lokhu kudala inkinga yokunquma ukuthi ushintsho lubangelwe yini. Lapho izindlela ezimbili zokwelapha ziqala ndawonye bese izimpawu zishintsha, lolo shintsho alubonisi ukuthi iyiphi indlela ebambe iqhaza, ukuthi ikhona yini ebambe iqhaza, noma ukuthi inhlanganisela iphephile yini. Ukululama ngokwemvelo, ukuphumula, ukusabela ku-placebo, nokunakekelwa okwenzeka ngesikhathi esifanayo nakho kungachaza ukuthuthuka.
Lowo mqondo uyasebenza nasekuhlolweni okungenhla kwenhlanganisela ye-COVID esigabeni sokuqala, lapho i-methylene blue yanikezwa kanye novithamini C, i-N-acetylcysteine, noma ezinye izinto, kuhambisana nokunakekelwa okujwayelekile. Ukuhlala isikhathi esifushane eqenjini lenhlanganisela akuvezi umphumela we-methylene blue iyodwa. Abafundi abathatha i-methylene blue nezinye izithasiselo noma imithi kufanele babuyekeze nodokotela ulwazi ngokusebenzisana kwemithi nezimo lapho kungafanele isetshenziswe khona, kunokucabanga ukuthi indaba yomuntu osebenzise inhlanganisela iyasebenza nakubo. Imininingwane yokuphepha kwe-methylene blue ibaluleke ngokukhethekile ngoba imithi ethinta i-serotonin, ukushoda kwe-G6PD, ukungasebenzi kahle kwezinso, nokukhulelwa kushintsha ngokuphelele ukuhlolwa kobungozi.
Irejista yokuhlolwa nocwaningo enemiphumela elinganiswa ngokwesimo ngasinye
Sebenzisa leli thebula njengomthombo wokuqala wokubhekisela kulesi sihloko. Isimo sinquma ukuthi yimuphi umphumela olinganiswayo obalulekile. Okufakwe kwirejista kubonisa isimo njengoba sabikwa kuze kube sekupheleni kuka-2026; qinisekisa isimo samanje ngaphambi kokucaphuna, ngoba amarekhodi erejista asala emuva kokushicilelwa kwemibiko.
| Ucwaningo | Isimo esihloliwe | Indlela yokwelapha | Imiphumela elinganiswa ngokwesimo ngasinye | Isimo nomphumela |
|---|---|---|---|---|
| NCT04370288 | I-COVID-19 esigabeni sokuqala, enzima | I-methylene blue 1 mg per kg kanye novithamini C ne-N-acetylcysteine, kamuva izinhlelo ze-methylene blue esesimweni esincishisiwe enikezwa ngomlomo, kanye nokunakekelwa okujwayelekile | Ukungadingi umshini wokuphefumula ngosuku 7; imibiko yakamuva: izinga lokugcwala komoya-mpilo, isivinini sokuphefumula, isikhathi sokuhlala, ukufa | Imibiko yohlobo lwesigaba 1 no-2 ichaza ukuthuthuka komoya-mpilo nesikhathi sokuhlala esifushane; ukwelashwa okungafihliwe, uhlelo oluhlanganisiwe, amaqembu amancane |
| NCT04547127 | I-COVID-19 esigabeni sokuqala | Uhlelo olusekelwe ku-methylene blue kanye nokunakekelwa okujwayelekile | Ukutholakala komoya-mpilo, izilinganiso zokululama ngokwezempilo | Kufakwe ekubuyekezweni kwango-2021; hlola irejista ukuze uthole isimo samanje, awukho umphumela oqinisekisiwe wekhwalithi ephezulu wokuhlolwa kokusebenza kahle okuqediwe |
| NCT04376788 | I-COVID-19 esigabeni sokuqala | Ukwelapha nge-methylene blue ngokwalokho okufakwe kwirejista | Imiphumela elinganisa isimo sempilo ngokwerejista | Kufakwe ekubuyekezweni kwango-2021; hlola irejista ukuze uthole isimo samanje ngaphambi kokucaphuna |
| NCT04619290 | Uhlelo lwezifo zamaphaphu oluhlanganisa umongo we-COVID | Ukwelapha nge-methylene blue ngokwalokho okufakwe kwirejista | Imiphumela elinganisa ukuphefumula ngokwerejista | Kufakwe ekubuyekezweni kwango-2021; hlola irejista ukuze uthole isimo samanje ngaphambi kokucaphuna |
| NCT04635605 | I-COVID-19 esigabeni sokuqala, iziguli ezingalalisiwe | Umthamo owodwa we-methylene blue ngomlomo uma kuqhathaniswa ne-placebo | Ushintsho enanini legciwane, ukususwa kwegciwane | Kuqediwe; akuzange kubonise ukusebenza kahle ekulweni negciwane |
| NCT04621123 (COnV-ert) | I-COVID-19 esigabeni sokuqala, iziguli ezingalalisiwe | I-plasma yabantu ababelulama encishiswe amagciwane abangela izifo nge-methylene blue nokukhanya, uma kuqhathaniswa ne-placebo yamanzi anosawoti | Ukulaliswa esibhedlela, inani legciwane ngosuku 7 | Kuqediwe ezigulini ezingu-376; awukho umehluko ekulalisweni esibhedlela noma enanini legciwane; kuhlola inqubo ye-plasma, hhayi ukunikezwa komuthi osebenza emzimbeni wonke |
| IRCT20200409047007N2 | I-COVID-19 esigabeni sokuqala ene-ARDS, iziguli ezilalisiwe | I-methylene blue ngomlomo kanye nokwelashwa okujwayelekile (n ilingana no-62) uma kuqhathaniswa nokwelashwa okujwayelekile (n ilingana no-60) | Ukuhamba kwezinga lokugcwala komoya-mpilo ngokuhamba kwesikhathi, isikhathi sokuhlala, ukufa ezinyangeni 1 no-3 | Kuqediwe ezigulini ezingu-122; izinga lokugcwala komoya-mpilo lathuthuka, isikhathi sokuhlala nokufa akuzange kuhluke kakhulu ngokwezibalo |
| Uchungechunge lokwelapha nge-IV njengomzamo wokugcina olungenalo iqembu lokuqhathanisa | I-COVID-19 esigabeni sokuqala, ukushoda okukhulu komoya-mpilo egazini | I-methylene blue emthanjeni 1 mg per kg kuze kufike emithanjeni emihlanu | Isilinganiso somoya-mpilo, isidingo sokusizwa ukuphefumula, ukukhishwa esibhedlela, ukufa | Iziguli ezingu-50; isilinganiso somoya-mpilo senyuka, ezingu-30 zakhishwa, ezingu-20 zafa; alikho iqembu lokuqhathanisa ngakho akukho simangalo sembangela esingenziwa |
| Uhlelo lwaselabhorethri lokwenza igciwane lingasebenzi | I-ex vivo ne-in vitro, hhayi iziguli | I-methylene blue enokukhanya okubomvu noma okubonakalayo, nangaphandle kwakho; inqubo ye-plasma cishe ku-0.8 micromolar | Ukuncipha kwamandla okutheleleka ngesilinganiso se-log, TCID50, ukulimala kwe-RNA | Imiphumela emihle kakhulu yokwenza igciwane elingaphandle kwamaseli lingasebenzi, ikakhulukazi ngokukhanya; kusekela ukusetshenziswa ekubulaleni amagciwane kuphela |
| I-COVID ehlala isikhathi eside nezinkinga eziqhubekayo zangemva kwesigaba sokuqala | Izimpawu zangemva kwesigaba sokuqala esezimisiwe | Akutholakalanga ukuhlolwa kwe-methylene blue okwabiwa ngokungahleliwe okuqediwe | Izikali zezimpawu ezinqunywe kusengaphambili, izilinganiso zamandla okwenza imisebenzi | Ubufakazi abukho; kunamaphepha aphakamisa imibono kuphela nokubhekwa kokulandela iziguli okungenamaqembu okuqhathanisa |
Indlela yokusebenzisa lobu bufakazi
Hlukanisa lezi zimo ezintathu. Ngokutheleleka esigabeni sokuqala, isifinyezo esithembekile siwukuthi kungenzeka ukuthuthuka komoya-mpilo, kodwa umphumela ekususweni kwegciwane, ekulalisweni esibhedlela, noma ekusindeni awufakazelwe. Ngokuphathwa kwezinto elabhorethri, i-methylene blue enokukhanya iyindlela eqinisekisiwe yokwenza igciwane lingasebenzi ezimweni ehlolwe kuzo. Nge-COVID ehlala isikhathi eside, okwamanje asikho isisekelo sokuhlolwa sokuyisebenzisa ekwelapheni.
Noma ubani ocabanga ukuyisebenzisa kufanele axoxe nodokotela ngomthamo, isikhathi sokuyisebenzisa, imithi esebenzisana nayo, nokuthi uyafaneleka yini ukuyisebenzisa, futhi kufanele ahlole ukuthi imiphumela yokuhlolwa kwakamuva iyakushintsha yini ukuhlaziywa kwezinzuzo nobungozi. Amarekhodi okuhlolwa avuselelwa ngemva kokuba imibiko yokubuyekeza isiyoshicilelwa, futhi lo mkhakha usuvele washintsha kanye, usuka eziphakamisweni waya emiphumeleni engakapheleli. Lowo mkhuba wokuphinde uhlole irejista ubaluleke ngaphezu kwanoma yiluphi ucwaningo olulodwa.