I-methylene blue ne-HBOT: ingabe umoya-mpilo ngaphansi kwengcindezi ephezulu wengeza inzuzo?

Ikhasi lomtholampilo linikeza i-methylene blue ne-HBOT ukuze kuthuthukiswe amandla, ukusebenza kwengqondo, noma ukululama. Ngezinye izikhathi kwengezwa iphaneli yokukhanya okubomvu, bese iphakheji ibizwa ngokuthi i-methylene blue nokukhanya okubomvu nomoya-mpilo ngaphansi kwengcindezi ephezulu. Ikhasi licaphuna ama-mitochondria, ukuhanjiswa komoya-mpilo, namaphepha ocwaningo ambalwa. Intengo ikhokhiswa ngeseshini ngayinye. Umbuzo odingwa umfundi uqondene kakhulu nokuthile kunokuthi ingxenye ngayinye izwakala inengqondo yini. Uthi ingabe ukhona owahlola le nhlanganisela uqobo walinganisa inzuzo eyengeziwe uma kuqhathaniswa nengxenye ngayinye isetshenziswa yodwa.

Lowo mbuzo uyisihloko salokhu kubuyekezwa. Iphakheji iqukethe izindlela zokungenelela ezifika kwezine ezingashintshwa ngokuzimela: ingcindezi yegumbi, umthamo womoya-mpilo, ukwakheka komuthi nesikhathi sokuwusebenzisa, nokuchayeka ekukhanyeni. Ubufakazi bengxenye eyodwa abuyona ubufakazi bephakheji, futhi umphumela oqondile onamandla kakhulu wenhlanganisela ukhomba ekwandisweni kokubulala nge-photodynamic kunasekuthuthukisweni okuvamile kokusebenza kwama-mitochondria.

Izindlela ezine zokungenelela zibizwa ngegama elilodwa

Ingcindezi iwumqondo wokuqala. Ukwelashwa komtholampilo ngomoya-mpilo ngaphansi kwengcindezi ephezulu, okuvame ukubizwa ngokuthi i-HBOT, kusho ukuphefumula umoya-mpilo ogxile kakhulu ngaphansi kwengcindezi engaphezu kweyendawo ezungezile, ngokuvamile cishe kuma-atmosphere angu-1.9 kuya ku-3.0 engcindezi ephelele, ngezikhathi zokuphefumula umoya-mpilo ezingaba yimizuzu engu-90 kuya ku-120, kuhlanganise namakhefu okuphefumula umoya ojwayelekile. Egumbini lomuntu oyedwa ingcindezi inyuswa ngomoya-mpilo; egumbini labantu abaningi inyuswa ngomoya ojwayelekile kuyilapho isiguli siphefumula umoya-mpilo ngehood noma ngemaski. Ingcindezi nengxenye yomoya-mpilo engxubeni ziyashintsha ngokwehlukana, ngakho igama elithi ingcindezi ephezulu ethambile ngaphandle kwazo zombili izinombolo alicacisi nokukodwa kwalokhu.

Ukuhanjiswa komoya-mpilo kuwumqondo wesibili. Kuma-atmosphere angu-2 kusetshenziswa umoya-mpilo omsulwa, umoya-mpilo oncibilikile ku-plasma ukhuphuka kakhulu ngaphezu kokujwayelekile, ngaphezu komoya-mpilo oboshelwe ku-hemoglobin. Leyo ngxenye encibilikile iyisisekelo sokusetshenziswa okwamukelwe njengokuvaleka kwemithambo ngegesi kanye nezicubu ezifakelwe ezisengozini, ezikuhlwini lwezimo ezifanele ukwelashwa lwe-Undersea and Hyperbaric Medical Society. Iphinde ibe yisisekelo semiphumela enobuthi: ukulimala kwezindlebe nama-sinus ngenxa yengcindezi, ubuthi bomoya-mpilo emaphashini, ukubona eduze kuphela okwesikhashana, nokuquleka lapho ingcindezi yomoya-mpilo iphezulu kakhulu.

Ukwakheka komuthi kuwumqondo wesithathu. Ebumnyameni udayi usebenza njengento ejikeleza phakathi kokuncishiswa nokufakwa kwe-oksijini, noma i-redox, nanjengesithwali esihlukile sama-electron, wamukela ama-electron ukuze wakhe i-leucomethylene blue bese uwadlulisela phambili njengoba uphinda umjikelezo, njengoba kuchazwe kokuthi i-methylene blue isebenza kanjani njengomdluliseli wama-electron. Umkhiqizo, indlela yokuwufaka emzimbeni, umthamo ngama-mg nge-kg, nesikhathi sokuwusebenzisa maqondana neseshini yegumbi konke kungena lapha. Ilebula yomjovo yase-US ihlanganisa i-methemoglobinemia etholakale kamuva ngomthamo ongu-1 mg nge-kg ngokwemininingwane yokunikeza i-ProvayBlue, okungesona isilinganiso esiqinisekiswe ngezivivinyo sezeshini zenhlanganisela ezikhethwa umuntu ngaphandle kwesimo esiphuthumayo.

Ukuchayeka ekukhanyeni kuwumqondo wesine, otholakala kuphela kwezinye izinsizakalo ezinikezwayo. Ukukhanya okubomvu ku-630 kuya ku-680 nm kudlulela ebhandeni lapho udayi umunca khona ukukhanya eduze kuka-664 nm futhi kungaqalisa ukusabela kwamakhemikhali kwento ezwela ukukhanya; ukukhanya kwe-infrared eseduze ku-810 nm akuwuvuseleli kahle udayi ngokuqondile, njengoba kubuyekezwe kokuthi i-methylene blue nokwelashwa ngokukhanya okubomvu. Ubude begagasi, amandla okukhanya afinyelela endaweni ngeyunithi ngayinye yendawo, amandla okukhanya aqoqekayo ngeyunithi ngayinye yendawo, nesikhawu phakathi kokusebenzisa umuthi nokukhanya kunquma uhlobo lwenqubo, ngokomhlahlandlela wobude begagasi, amandla okukhanya afinyelela endaweni, nokuma kwezinto. Ukukhanya okubomvu ngaphandle kwalezo zinombolo kufana, emkhakheni wokukhanya, nokusho ingcindezi ephezulu ngaphandle kokucacisa ingcindezi.

Lokho imibhalo yocwaningo ngenhlanganisela eyakuhlola ngempela

Alukho ucwaningo olulawulwayo kubantu olutholakele kulokhu kubuyekezwa olubonisa inzuzo eyengeziwe emzimbeni wonke ye-methylene blue kanye ne-HBOT yangempela uma kuqhathaniswa nazo zombili izingxenye ngokwehlukana. Okukhona kuwela emaqenjini amathathu, futhi ngalinye liphendula umbuzo ohlukile.

Ukuhlolwa okuqonde kakhulu enhlanganiselweni kwenziwa ngaphandle komzimba. UBisland nozakwabo bachaya i-S. aureus ne-P. aeruginosa, kokubili ezintantayo nezisembozweni samagciwane, kudayi nokukhanya okuhlungiwe okubomvu ku-600 kuya ku-800 nm, kunomoya-mpilo omsulwa kuma-atmosphere angu-2 noma ungekho, njengoba kubikwe kulolu cwaningo lomoya-mpilo ne-photodynamic. Ukwengezwa komoya-mpilo ocindezelwe kwandisa ukubulala ngeyunithi ye-log engaphezu kweyodwa ku-5 J nge-cm eyisikwele nangamayunithi e-log angaphezu kwamabili ku-10 J nge-cm eyisikwele. Lokho kuyinzuzo eyengeziwe yangempela yomoya-mpilo ekwelashweni nge-photodynamic esitsheni selabhorethri, hhayi ubufakazi bokuthi umoya-mpilo ocindezelwe kanye nodayi kuthuthukisa ukusebenza kwengqondo noma amandla kubantu.

Ukuhlolwa kwezilwane okusondelene kakhulu okwahlola izinhlanganisela zezici kwasebenzisa umoya-mpilo oweqile ngaphansi kwengcindezi evamile, hhayi i-HBOT. URodriguez nozakwabo babela amagundane ayenomthambo ovalekile imizuzu engu-60 ukuba athole umoya ojwayelekile noma umoya-mpilo, ngakunye kuhlanganiswe noketshezi oluthwala umuthi ngaphandle komuthi noma udayi ongu-1 mg nge-kg, kulolu cwaningo lokululama ngemva kwesifo sohlangothi. Inhlanganisela yathuthukisa ukululama kokusebenza ngaphezu kwanoma iyiphi ingxenye iyodwa, nakuba umthamo wezicubu ezifile wawufana nalowo wodayi kuphela. Njengoba kungekho okwafakwa ngaphansi kwengcindezi ephezulu, lokhu kusekela ukusebenzisana komoya-mpilo nodayi ngaphandle kokusho ukuthi ama-atmosphere angu-2 kuya ku-3 engeza okuthile yini ngaphezu komoya-mpilo.

Imibiko yabantu isezingeni lezigameko ngazinye. Umuntu oneminyaka engu-52 owayene-methemoglobinemia etholakale kamuva enzima wanikezwa umoya-mpilo kanye nodayi ongu-1 mg nge-kg ngomthambo, kwalandela i-HBOT kuma-atmosphere acishe abe ngu-2.2 imizuzu engu-90, njengoba kuchazwe kulo mbiko wesigameko esiphuthumayo. Ukwelashwa kokuhlenga okulandelanayo akukwazi ukuhlukanisa indlela isimo esingaqhubeka ngayo ngokwaso nemiphumela yodayi, yomoya-mpilo, neyengcindezi. Isigameko se-dapsone esiveza okuphambene sathola ukuthi ama-atmosphere angu-2.5 amahora angu-2 enza okuncane ngaphambi kokuba udayi ongu-1.5 mg nge-kg usebenze ngokushesha, njengoba kubikwe kulesi sigameko sokwelashwa okulandelanayo. Lokho kuphikisa ukusebenzisa i-HBOT esikhundleni sodayi, ngaphandle kokuhlola ukwelashwa ngakho kokubili ngesikhathi esisodwa. Amaphepha amagundane okukhulunywa ngawo njalo asebenzisa u-810 nm ahlola udayi nokukhanya ngaphandle kwegumbi nhlobo, afakwe ohlwini ngaphansi kwe-PMID 35059872 ne-PMID 31372913, ngakho awakwazi ukuqinisekisa inqubo esebenzisa igumbi.

Kungani umoya-mpilo owengeziwe kanye nodayi we-redox kungasho ngokuzenzakalelayo ukuthi kuyasebenzisana kuthuthukise umphumela

Ukujikeleza kwe-redox kukadayi ngokwakho kusebenzisa umoya-mpilo: udayi onokugxila kwezinga le-micromolar ofakwe ngomthambo wakhuphula ukusetshenziswa komoya-mpilo emzimbeni wonke cishe ngesigamu emagundaneni, udayi osesimweni esincishisiwe udlulisela ama-electron ngokuqondile emoyeni-mpilo, kulolu cwaningo lokuguqulwa kwamakhemikhali emzimbeni. Umphumela wawo ezinhlotsheni zomoya-mpilo ezisebenza kakhulu uncike ezintweni ezisetshenziswa ekusabeleni, ukhuphuka ngezinto ezisetshenziswa yi-complex I bese wehla nge-succinate kuma-mitochondria enhliziyo ahlukanisiwe (ucwaningo lwezinto ezisetshenziswa ekusabeleni). Ngaphandle kokukhanya kunezincazelo ezimbili ezisacutshungulwa: umoya-mpilo owengeziwe usekela ukufakwa kwe-oksijini kabusha kudayi lapho ukuhanjiswa kuphazamisekile, noma wandisa ukugeleza kokusabela okufaka i-oksijini okubangelwa ukujikeleza kukadayi. Awukho umthetho othi udayi uba namandla ngokwengeziwe okulwa nokufakwa kwe-oksijini njengoba ingcindezi ikhuphuka.

Ukwengeza ukukhanya okubomvu kushintsha indlela yokusebenza. Udayi ovuselelwe ukukhanya udlulisela amandla noma ama-electron emoyeni-mpilo futhi udale izinhlobo zamakhemikhali ezifaka i-oksijini, kuhlanganise nomoya-mpilo oyi-singlet, yingakho umoya-mpilo owengeziwe wandisa ukubulawa kwamagciwane emiphumeleni yesitsha selabhorethri. Ukusabela kwamakhemikhali okufanayo kulimaza into engahlosiwe: udayi okhanyiselwe kuma-mitochondria ahlukanisiwe esibindi segundane wabangela ukwakheka kwezinto ezifaka i-oksijini, ukuphela kwe-glutathione, ukunqamuka kokuxhumana kwezinqubo zokukhiqiza amandla, nokuncipha kokukhiqizwa kwe-ATP, kulolu cwaningo lobuthi bokukhanya kuma-mitochondria. Ukusebenzisana okwandisa umphumela okubonisiwe kuwubuthi be-photodynamic obubulala amaseli, obufanele ukubulala amagciwane kunokunika izicubu ezinempilo amandla.

Ukuphepha kuqondene nensizakalo, akukhona okudayi ngokujwayelekile

Umqondo ngamunye udinga ukuhlolwa kwawo, futhi inhlanganisela yengeza izindawo zokusebenzisana ezingeke zihlanganiswe ikhasi elivamile lokuphepha kukadayi.

Ukuhlolwa ngaphambi kokusebenzisa igumbi kuqala ngezingozi zengcindezi nomoya-mpilo: umoya phakathi kwephaphu nodonga lwesifuba ongakalashwa, isifo samaphaphu esivimbelayo noma esinamabhamuza amakhulu omoya, ukungakwazi ukulinganisa ingcindezi ezindlebeni, umlando wokuquleka, ukuhlinzwa kwakamuva kwesifuba noma kwamehlo, namadivayisi afakelwe emzimbeni. Ukulawulwa komlilo kuyingxenye eyisisekelo yokwakhiwa nokusebenza kwesistimu. Incwadi ye-FDA ngokusetshenziswa ngokuphepha kwamadivayisi engcindezi ephezulu idinga ukulandela imiyalelo yomkhiqizi, ukuxhuma ugesi emhlabeni, ukuqeqeshwa kwabasebenzi, ukugadwa okuqhubekayo, ukunakekelwa kwedivayisi, ukungavunyelwa kwezinto zikagesi ezinqatshelwe, nezingubo ezihambisana nezimfuneko ze-NFPA 99 ne-ASME PVHO-1. Iphaneli yokukhanya akumele imane ifakwe egumbini elinomoya-mpilo omningi; ukuhambisana kwayo kufanele kubhalwe emiyalelweni yegumbi nasohlelweni lokuphepha emlilweni.

Ukuhlolwa ngaphambi kokusebenzisa umuthi kulandela ilebula yodayi. Ukushoda kwe-G6PD kuyisimo ilebula esithi umuthi akufanele usetshenziswe kuso; udayi uyisivimbi se-monoamine oxidase esinesexwayiso esisebhokisini mayelana nesifo se-serotonin uma usetshenziswa nemithi ethinta i-serotonin namanye ama-opioid. Udokotela onikeza umuthi kufanele aqondise noma yiluphi ushintsho emithini, futhi ukukhulelwa kanye nokusebenza kwezinso nesibindi kudinga ukubuyekezwa. Udayi uphinde uphazamise ukukalwa komoya-mpilo egazini nge-pulse oximetry, ngakho ukugcwala komoya-mpilo kudinga indlela ehlukile lapho ukunemba kubalulekile. Lo mehluko ubalulekile kubafundi abafika nezilinganiso eziphansi zomoya-mpilo ngenxa yesifo samaphaphu noma nezimo zokukhathala ezifana ne-ME/CFS.

Igumbi elivunyelwe yi-FDA alisho ukuthi le nhlangano yahlola i-methylene blue ne-HBOT noma iyiphi inqubo yama-mitochondria, yokusebenza kwengqondo, noma yokuphila isikhathi eside. Amagumbi ngokuvamile angamadivayisi e-Class II avunyelwa ngendlela ye-510(k) ezimweni ezibhalwe emalebuleni awo. Incwadi ye-FDA engenhla iwumyalezo wokuphepha, hhayi ukugunyazwa kokusebenza kokwelashwa.

Uhlu lokuhlola ubufakazi benhlanganisela: ithuluzi lokuqala elenzelwe lesi sihloko

Sebenzisa lolu hlu ukuhlola iphepha locwaningo noma ikhasi lomtholampilo. Inqubo ethembekile isho umugqa ngamunye ngokubhaliwe. Uma kukhona umugqa ongekho, isimangalo asicacisiwe ngokwanele kunokuba sibonise ithemba.

Izingxenye: imodeli yegumbi nesimo sokuvunyelwa kwayo; igumbi lomuntu oyedwa noma labantu abaningi; ama-atmosphere engcindezi ephelele aqondile; ingxenye yomoya-mpilo ephefumulwa isiguli; isikhathi somoya-mpilo esinamakhefu okuphefumula umoya ojwayelekile; isikhathi esiphelele egumbini; inani lezeshini nokuthi zenzeka kangaki. Umkhiqizo womuthi nokwakheka kwawo; indlela yokuwufaka emzimbeni; umthamo ngama-mg nge-kg; umthamo omkhulu oqoqekayo; isikhawu phakathi kokunikezwa komuthi nokungena egumbini. Uma kufakwa ukukhanya: ubude begagasi; amandla okukhanya afinyelela ngeyunithi ngayinye yendawo; amandla okukhanya aqoqekayo ngeyunithi ngayinye yendawo; ubude besikhathi; isikhathi maqondana nokusebenzisa udayi; nokuthi umthombo ungaphakathi noma ngaphandle kwegumbi, kunemibhalo eqinisekisa ukuhambisana kwawo nengcindezi ephezulu.

Izinto zokuqhathanisa: ocwaningweni, amaqembu kufanele afake inhlanganisela, ingxenye ngayinye iyodwa, futhi okungcono kakhulu kube neqembu elithola ukungenelela mbumbulu noma ukunakekelwa okujwayelekile, ngokwabiwa okungahleliwe nangomphumela oyinhloko ocaciswe kusengaphambili. Uchungechunge lwezilinganiso zangaphambi nangemva kokusebenzisa iphakheji ephelele alukwazi ukukhomba ukuthi inzuzo ibangelwe yinhlanganisela. Ekhasi lomtholampilo, buza ukuthi yimaphi kulawo maqembu asetshenziswa ngempela amaphepha acashuniwe. Ukucaphuna izivivinyo zodayi kuphela kanye nezivivinyo ze-HBOT kuphela kuwukuhlanganisa ngokohlu lwemithombo, hhayi ubufakazi bokusebenzisana okwandisa umphumela.

Imiphumela: chaza iphuzu lomphumela, indlela yokulinganisa, nesikhathi sokulinganisa. Izikali zokusebenza, imithamo yezicubu ezilimele, izibalo zamagciwane, namaphuzu ezimpawu kuyizimangalo ezihlukene ezinamathuluzi ahlukene. Izinguquko zezilinganiso ezimelela umphumela ngesikhathi seseshini, njengokufundwa okuphezulu emshinini wokuqapha lapho umuntu ephefumula umoya-mpilo, azifakazeli inzuzo ehlala isikhathi eside.

Izilawuli zokuphepha: ukuhlolwa okubhaliwe kwesifo samaphaphu, ukulinganisa ingcindezi ezindlebeni, umlando wokuquleka, isimo se-G6PD, imithi ethinta i-serotonin nama-opioid, ukukhulelwa, nokusebenza kwezinso nesibindi; ukugadwa okuqhubekayo ngabasebenzi abaqeqeshelwe ingcindezi ephezulu; izinqubo zokulimala ngenxa yengcindezi nobuthi bomoya-mpilo; uhlelo lokwehlisa ingcindezi esimweni esiphuthumayo; izilawuli zomlilo nohlu lwezinto ezinqatshelwe; ukubhalwa kwezehlakalo ezingathandeki; nohlelo oluchaziwe lokuqapha umoya-mpilo ngenxa yokuthi udayi uphazamisa i-pulse oximetry.

Uma ikhasi lingakwazi ukunikeza le mininingwane, sebenzisa inqubo efanayo yokuqinisekisa obungayisebenzisa ukuhlola inqubo etholwe ku-inthanethi. Cela umbhalo oshicilelwe owahlola iphakheji uqobo, funda ukuthi wasebenzisa maphi amaqembu, futhi wenqabe ukuthatha indlela yokusebenza ebonakala inengqondo njengomphumela olinganisiwe. Inhlanganisela ezwakala ihambisana isengaba engakahlolwa, futhi kulokhu ukusebenzisana okukodwa okuhloliwe kwandisa ukusabela kwamakhemikhali obungeke ufune kuqondiswe ezicutshini ezinempilo.