Imethylene blue neoksijini phantsi koxinzelelo oluphezulu: ukuvavanya amabango onyango oludibeneyo

Iphepha lekliniki linikezela ngemethylene blue ne-HBOT ukuze kuphuculwe amandla, ukusebenza kwengqondo, okanye ukubuyela kwimeko yesiqhelo. Ngamanye amaxesha kongezwa iphaneli yokukhanya okubomvu, ize le nkonzo ibizwe ngokuba yimethylene blue, ukukhanya okubomvu neoksijini phantsi koxinzelelo oluphezulu. Iphepha likhankanya imitochondria, ukuhanjiswa kweoksijini, namaphepha ophando ambalwa. Ixabiso libalwa ngeseshoni nganye. Umbuzo ofunekayo kumfundi ucace ngakumbi kunokubuza ukuba icandelo ngalinye livakala linengqiqo na. Kukuba ukhona na umntu ovavanye kanye le ndibaniselwano waza walinganisa inzuzo eyongezelelweyo xa ithelekiswa necandelo ngalinye lodwa.

Lo mbuzo ngumba wolu phononongo. Le nkonzo idibanisa ukuya kutsho kumanyathelo amane anokutshintshwa ngokuzimeleyo: uxinzelelo lwegumbi, idosi yeoksijini, ukwakhiwa kwechiza nexesha lokulinika, kunye nokuchanabeka ekukhanyeni. Ubungqina becandelo elinye abukho bubungqina bendibaniselwano yonke, kwaye esona siphumo sithe ngqo sale ndibaniselwano salatha ekwandisweni kokubulawa okubangelwa yinkqubo yephotodynamic, kunokuphuculwa ngokubanzi kokusebenza kwemitochondria.

Amanyathelo amane abizwa ngegama elinye

Uxinzelelo ngumba wokuqala. Unyango lweoksijini phantsi koxinzelelo oluphezulu olusetyenziswa ezikliniki, oludla ngokubizwa ngokuba yi-HBOT, luthetha ukuphefumla ioksijini exineneyo phantsi koxinzelelo olungaphezulu kolomoya ojikelezileyo, ngokuqhelekileyo malunga ne-1.9 ukuya kwi-3.0 atmospheres absolute, ngamaxesha okuphefumla ioksijini amalunga nemizuzu engama-90 ukuya kwi-120, kuquka ikhefu lokuphefumla umoya oqhelekileyo. Kwigumbi elithatha umntu omnye, uxinzelelo lonyuswa ngeoksijini; kwigumbi elithatha abantu abaninzi, lonyuswa ngomoya oqhelekileyo ngoxa isigulana siphefumla ioksijini ngesigqubuthelo sentloko okanye ngemaski. Uxinzelelo nesabelo seoksijini zitshintsha ngokwahlukeneyo, ngoko ukubiza inkonzo ngokuba yeyoxinzelelo oluphezulu oluthambileyo ngaphandle kwala manani mabini akucacisi nokuba liliphi.

Ukuhanjiswa kweoksijini ngumba wesibini. Kwi-2 atmospheres kusetyenziswa ioksijini ecocekileyo, ioksijini enyibilikileyo kwiplasma inyuka kakhulu ngaphezu kwenqanaba eliqhelekileyo, ukongeza kwioksijini ebotshelelwe kwihemoglobin. Eso sabelo sinyibilikileyo sixhasa ukusetyenziswa okwamkelweyo, njengokuvaleka kwemithambo ngenxa yegesi kunye nezicubu ezifakelweyo ezingafumani gazi laneleyo, ezikuluhlu lweemeko ekucetyiswa kuzo olu nyango yi-Undersea and Hyperbaric Medical Society. Sikwabangela neziphumo ezinobungozi: ukwenzakala kweendlebe neesinusi ngenxa yotshintsho loxinzelelo, ityhefu yeoksijini emiphungeni, ukungaboni kakuhle izinto ezikude okwethutyana, kunye nokuxhuzula xa uxinzelelo lweoksijini luphezulu ngakumbi.

Ukwakhiwa kwechiza ngumba wesithathu. Ebumnyameni, le dayi isebenza kumjikelo we-redox nanjengomthwali wee-electron ongomnye, yamkele ii-electron ukuze yenze ileucomethylene blue ize izidlulisele phambili ngoxa ibuyela kumjikelo, njengoko kuchaziwe kwinqaku elithi indlela imethylene blue esebenza ngayo ukudlulisa ii-electron. Imveliso, indlela yokuyinika, idosi nge-mg per kg, kunye nexesha lokuyinika xa lithelekiswa neseshoni yegumbi, zonke zingena apha. Ileyibhile yase-US yechiza elitofwayo ibandakanya imethemoglobinemia efunyenweyo ngedosi eyi-1 mg per kg ngokwe-nkcazelo yokumiselwa kweProvayBlue, engeyiyo idosi eqinisekisiweyo yeeseshoni zendibaniselwano ezikhethwa ngumntu.

Ukuchanabeka ekukhanyeni ngumba wesine, ofumaneka kwezinye zezi nkonzo kuphela. Ukukhanya okubomvu kwi-630 ukuya kwi-680 nm kudibana noluhlu apho idayi ifunxa ukukhanya kufuphi ne-664 nm, kwaye kunokuqhuba iinkqubo zekhemikhali zento evuselelwa kukukhanya; ukukhanya kwe-infrared ekufuphi kwi-810 nm akuyivuseleli ngokuthe ngqo kakuhle le dayi, njengoko kuphononongwe kwinqaku elithi imethylene blue nonyango lokukhanya okubomvu. Ubude bamaza, amandla okukhanya afika kwiyunithi yendawo, amandla ewonke afika kwiyunithi yendawo, kunye nexesha eliphakathi kokunikwa kwechiza nokukhanya zimisela indlela le nkqubo esebenza ngayo, ngokwesikhokelo sobude bamaza, amandla okukhanya afika kwindawo, kunye nejiyometri. Ukukhanya okubomvu ngaphandle kwala manani kufana nokuthetha ngonyango loxinzelelo oluphezulu ungakhange uchaze uxinzelelo.

Oko kwavavanywa ngokwenene kuphando lwendibaniselwano

Akukho lingo lilawulwayo ebantwini elifunyenwe kolu phononongo elibonisa inzuzo eyongezelelweyo kuwo wonke umzimba yemethylene blue kunye ne-HBOT yokwenene xa ithelekiswa nala macandelo mabini ngokwahlukeneyo. Ubungqina obukhoyo buwela kumaqela amathathu, kwaye ngalinye liphendula umbuzo owahlukileyo.

Olona vavanyo luthe ngqo lwendibaniselwano lwenziwa ngaphandle komzimba. UBisland noogxa bakhe bachanaba i-S. aureus ne-P. aeruginosa, zombini zidadayo nezikwifilimu yezinto eziphilayo, kwidayi kunye nokukhanya okubomvu okuhluziweyo kwi-600 ukuya kwi-800 nm, kukho okanye kungekho ioksijini ecocekileyo kwi-2 atmospheres, njengoko kuxelwe kolu phando lweoksijini nenkqubo yephotodynamic. Ukongeza ioksijini phantsi koxinzelelo kwandisa ukubulawa ngaphezu kweyunithi enye yelogarithm kwi-5 J per square cm nangaphezu kweeyunithi ezimbini zelogarithm kwi-10 J per square cm. Le yinzuzo yokwenene eyongezwa yioksijini kunyango lwephotodynamic kwisitya selabhoratri, hayi ubungqina bokuba ioksijini phantsi koxinzelelo kunye nedayi ziphucula ukusebenza kwengqondo okanye amandla ebantwini.

Olona vavanyo lwezilwanyana olusondeleyo olwahlula izinto lwazidibanisa lwasebenzisa ioksijini eninzi phantsi koxinzelelo oluqhelekileyo, hayi i-HBOT. URodriguez noogxa bakhe babela iimpuku ezinomthambo ovaliweyo kangangemizuzu engama-60 ukuba zifumane umoya oqhelekileyo okanye ioksijini, nganye kwezi idityaniswe nolwelo lokuthwala ichiza olungenachiza okanye idayi eyi-1 mg per kg, kolu phando lokubuyela kwimeko yesiqhelo emva kwestroke. Indibaniselwano yaphucula ukubuyela kokusebenza xa ithelekiswa necandelo ngalinye lodwa, nangona umthamo wezicubu ezifileyo ngenxa yokunqongophala kwegazi wawufana noweqela elifumene idayi yodwa. Kuba akukho nto yafakwa phantsi koxinzelelo olongezelelweyo, oku kuxhasa intsebenziswano yeoksijini nedayi ngaphandle kokutsho ukuba i-2 ukuya kwi-3 atmospheres yongeza nantoni na ngaphezu kweoksijini.

Iingxelo ebantwini zezamatyala ezigulana ezizodwa. Umntu oneminyaka engama-52 owayenemethemoglobinemia efunyenweyo enzima wafumana ioksijini kunye nedayi eyi-1 mg per kg efakwe emthanjeni, kwalandela i-HBOT malunga ne-2.2 atmospheres kangangemizuzu engama-90, njengoko kuchaziwe kule ngxelo yetyala likaxakeka. Unyango lokuhlangula olunikelwa ngokulandelelana alunakwahlula ukuhamba kwemeko ngokwemvelo kwiziphumo zedayi, zeoksijini nezoxinzelelo. Kwelinye ityala elinxulumene nedapsone, elinika umzekelo ochaseneyo, i-2.5 atmospheres kangangeeyure ezi-2 yenza umahluko omncinane ngaphambi kokuba idayi eyi-1.5 mg per kg isebenze ngokukhawuleza, njengoko kuxelwe kule ngxelo yonyango olulandelelanayo. Oku kuyaphikisana nengcinga yokuba i-HBOT inokuthatha indawo yedayi, kodwa akuvavanyi unyango olunikelwa ngaxeshanye. Amaphepha ophando ngeempuku asebenzisa i-810 nm, adla ngokukhankanywa, avavanya idayi kunye nokukhanya kungekho gumbi loxinzelelo konke konke; afumaneka phantsi kwe-PMID 35059872 ne-PMID 31372913, ngoko akanakuqinisekisa inkqubo yonyango lwegumbi.

Kutheni ioksijini eyongezelelekileyo nedayi ye-redox zingathethi ngokuzenzekelayo intsebenziswano enenzuzo

Umjikelo we-redox wedayi ngokwawo usebenzisa ioksijini: idayi efakwe emthanjeni kumanqanaba e-micromolar yandisa ukusetyenziswa kweoksijini ngumzimba wonke malunga nesiqingatha kwiimpuku, kwaye idayi ekwimo encitshisiweyo yayidlulisela ii-electron ngqo kwioksijini, kolu phando lwemetabolism. Impembelelo yayo kwiintlobo zeoksijini ezisebenza ngekhemikhali ixhomekeke kwizinto ekusebenza kuzo inkqubo: yayinyuka ngezinto ezisetyenziswa yi-complex I ize yehle nge-succinate kwimitochondria yentliziyo ekhutshwe kwizicubu (uphando ngezinto ezisetyenziswa yinkqubo). Ngaphandle kokukhanya, kukho iingqikelelo ezimbini ezinokwenzeka: ioksijini eyongezelelweyo ixhasa ukuphinda ioksidayizwe kwedayi apho ukuhanjiswa kuphazamisekile, okanye yandisa ukuhamba kweenkqubo zeoksideshini kumjikelo wedayi. Akukho mgaqo uthi idayi iba nesakhono esingakumbi sokuthintela ioksideshini njengoko uxinzelelo lunyuka.

Ukongeza ukukhanya okubomvu kutshintsha indlela yokusebenza. Idayi evuselelwe kukukhanya idlulisela amandla okanye ii-electron kwioksijini ize yenze iintlobo ezibangela ioksideshini, kuquka i-singlet oxygen; yiyo loo nto ioksijini eyongezelelweyo yandisa ukubulawa kweebhaktheriya kwisiphumo sovavanyo lwesitya. Kwaloo nkqubo yekhemikhali yenzakalisa into engafanelekanga xa ijoliswe kuyo: idayi ekhanyiselweyo kwimitochondria yesibindi sempuku ekhutshwe kwizicubu yabangela ukwakheka kwezinto ezibangela ioksideshini, ukuphela kweglutathione, ukuqhawuka konxibelelwano phakathi kweenkqubo zokuvelisa amandla, kunye nokuncipha kwemveliso ye-ATP, kolu phando lwetyhefu ebangelwa kukukhanya kwimitochondria. Intsebenziswano ebonisiweyo yityhefu kwiiseli ebangelwa yinkqubo yephotodynamic, efanele ukubulala iintsholongwane kunokunika amandla kwizicubu ezisempilweni.

Ukhuseleko luxhomekeke kwinkonzo ethile, hayi kwidayi ngokubanzi

Umba ngamnye ufuna uhlolo lwawo, kwaye indibaniselwano yongeza iindawo apho izinto zinokusebenzisana khona ezingagutyungelwayo liphepha eliqhelekileyo lokhuseleko lwedayi.

Uhlolo ngaphambi kokungena kwigumbi luqala ngeengozi zoxinzelelo neoksijini: umoya onganyangwanga oqokelelene phakathi komphunga nodonga lwesifuba, isifo semiphunga esithintela ukuhamba komoya okanye esineengxowa zomoya ezandileyo, ukungakwazi ukulinganisa uxinzelelo ezindlebeni, imbali yokuxhuzula, utyando lwamva nje lwesifuba okanye lwamehlo, kunye nezixhobo ezifakelwe emzimbeni. Uthintelo lomlilo kufuneka lwakhiwe kwinkqubo. Ileta ye-FDA ngokusetyenziswa ngokukhuselekileyo kwezixhobo zoxinzelelo oluphezulu ifuna ukuthotyelwa kwemiyalelo yomenzi, uqhagamshelo lokhuseleko lombane emhlabeni, uqeqesho lwabasebenzi, ukubekwa esweni rhoqo, ukugcinwa kwezixhobo zikwimeko efanelekileyo, ukungangeniswa kwezinto zombane ezingavumelekanga, kunye neempahla ezifanelekileyo phantsi kwe-NFPA 99 ne-ASME PVHO-1. Iphaneli yokukhanya mayingaze ingeniswe nje kwigumbi elineoksijini eninzi; ukufaneleka kwayo kufuneka kubhalwe kwimiyalelo yegumbi nakwinkqubo yokhuseleko emlilweni.

Uhlolo lwechiza lulandela ileyibhile yedayi. Ukunqongophala kwe-G6PD yimeko echazwe kwileyibhile apho ichiza lingamele lisetyenziswe; idayi sisithinteli se-monoamine oxidase esinesilumkiso esibiyelwe ngebhokisi ngomngcipheko we-serotonin syndrome xa isetyenziswa namachiza asebenza kwiserotonin kunye nezinye iiopioid. Ugqirha omisela ichiza kufuneka alawule naluphi na utshintsho lwamayeza, kwaye ukukhulelwa kunye nokusebenza kwezintso nesibindi kufuneka kuhlolwe. Idayi ikwaphazamisa umlinganiselo weoksijini ngesixhobo se-pulse oximetry, ngoko inqanaba lokuzaliswa kweoksijini kufuneka lilinganiswe ngenye indlela xa ukuchaneka kubalulekile. Lo mahluko ubalulekile kubafundi abaza namanqanaba asezantsi eoksijini kwisifo semiphunga okanye neemeko zokudinwa ezifana ne-ME/CFS.

Igumbi elivunyelwe yi-FDA alithethi ukuba le arhente ivavanye imethylene blue ne-HBOT okanye nayiphi na inkqubo ejolise kwimitochondria, ekusebenzeni kwengqondo, okanye kubomi obude. Amagumbi ngokuqhelekileyo zizixhobo ze-Class II ezivunyelwa ngendlela ye-510(k) kwiimeko ezibhalwe kwiileyibhile zazo. Ileta ye-FDA engentla lunxibelelwano lokhuseleko, hayi isiqinisekiso sokusebenza konyango.

Uluhlu lokuhlola ubungqina bendibaniselwano: isixhobo sokuqala esenzelwe eli nqaku

Sebenzisa olu luhlu ukuhlola iphepha lophando okanye iphepha lekliniki. Inkqubo ethembekileyo ichaza yonke into kolu luhlu ngokubhaliweyo. Ukuba kukho into engekhoyo, ibango alicaciswanga ngokwaneleyo, kunokuba libe nethemba lenzuzo.

Amacandelo: imodeli yegumbi nesimo sayo sokuvunyelwa; ukuba lithatha umntu omnye okanye abantu abaninzi; uxinzelelo oluchanekileyo nge-atmospheres absolute; isabelo seoksijini ephefumlwa sisigulana; ixesha leoksijini kunye namakhefu okuphefumla umoya oqhelekileyo; ixesha elipheleleyo egumbini; inani leeseshoni nokuba zibakho kangaphi. Imveliso yechiza nokwakhiwa kwayo; indlela yokulinika; idosi nge-mg per kg; eyona dosi iqokelelweyo iphezulu; ixesha eliphakathi kokunikwa kwedosi nokungena egumbini. Ukuba ukukhanya kuqukiwe: ubude bamaza; amandla okukhanya afika kwiyunithi yendawo; amandla ewonke afika kwiyunithi yendawo; ubude bexesha; ixesha lokukhanya xa lithelekiswa nokunikwa kwedayi; kunye nokuba umthombo wokukhanya ungaphakathi okanye ungaphandle kwegumbi, kukho amaxwebhu aqinisekisa ukufaneleka kwawo phantsi koxinzelelo oluphezulu.

Amaqela okuthelekisa: kuphando, amaqela kufuneka aquke indibaniselwano, icandelo ngalinye lodwa, kwaye ukuba kunokwenzeka iqela lonyango olulinganiswayo olungenalo inyathelo elisebenzayo okanye iqela lokhathalelo oluqhelekileyo, kubekho ukwabiwa ngokungakhethiyo kunye nesiphumo esiphambili esichazwe kwangaphambili. Uthotho lwemilinganiselo yangaphambi nasemva kwenkonzo edibeneyo alunakuthi inzuzo ibangelwe yindibaniselwano. Kwiphepha lekliniki, buza ukuba ngawaphi kula maqela asetyenziswa ngokwenene ngamaphepha ophando akhankanyiweyo. Ukukhankanya amalingo edayi yodwa kunye namalingo e-HBOT yodwa kukudibanisa izinto ngoluhlu lwemithombo, hayi ubungqina bentsebenziswano enenzuzo.

Iziphumo: chaza isiphumo esilinganisiweyo, indlela yokusilinganisa, kunye nexesha esilinganiswa ngalo. Izikali zokusebenza, imithamo yeendawo ezonakeleyo, amanani eentsholongwane, kunye namanqaku eempawu ngamabango ahlukeneyo afuna izixhobo ezahlukeneyo. Utshintsho kwimilinganiselo esetyenziswa njengommeli ngexesha leseshoni, njengexabiso eliphezulu kwisixhobo sokubeka esweni ngoxa umntu ephefumla ioksijini, aluqinisekisi inzuzo ehlala ihleli.

Amanyathelo okhuseleko: uhlolo olubhaliweyo lwesifo semiphunga, ukulinganiswa koxinzelelo ezindlebeni, imbali yokuxhuzula, isimo se-G6PD, amayeza asebenza kwiserotonin naweeopioid, ukukhulelwa, kunye nokusebenza kwezintso nesibindi; ukubekwa esweni rhoqo ngabasebenzi abaqeqeshelwe iinkqubo zoxinzelelo oluphezulu; iinkqubo zokujongana nokwenzakala okubangelwa lutshintsho loxinzelelo kunye netyhefu yeoksijini; isicwangciso sokunciphisa uxinzelelo kwiimeko zikaxakeka; amanyathelo othintelo lomlilo noluhlu lwezinto ezingavumelekanga; ukubhalwa kweziganeko ezingathandekiyo; kunye nesicwangciso esichaziweyo sokubeka esweni ioksijini, kuthathelwa ingqalelo ukuphazamiseka kwe-pulse oximetry okubangelwa yidayi.

Xa iphepha lingakwazi ukunika ezi nkcukacha, sebenzisa kwaloo ndlela yokuqinisekisa obuya kuyisebenzisa ukuhlola inkqubo yonyango efunyenwe kwi-intanethi. Cela upapasho oluvavanye kanye loo ndibaniselwano, funda ukuba ngawaphi amaqela asetyenzisiweyo, kwaye ungayamkeli indlela yokusebenza enengqiqo njengesiphumo esilinganisiweyo. Indibaniselwano evakala ihambelana isenokuba ayikavavanywa, kwaye kule meko intsebenziswano enye evavanyiweyo yandisa inkqubo yekhemikhali obungafuni kwaphela ukuba ijoliswe kwizicubu ezisempilweni.