I-methylene blue ye-MCAS nokungabekezeleli i-histamine: lokho okuboniswa ubufakazi

I-methylene blue ayiyona indlela yokwelapha eqinisekisiwe ye-mast cell activation syndrome (MCAS), okuyisimo sokwenziwa kwamaseli e-mast asebenze, noma yokungabekezeleli i-histamine. Imibhalo yocwaningo etholwe ukuze kubhalwe lesi sihloko ayizange iveze ukuhlolwa okulawulwayo ezigulini okubonisa inzuzo eqhubekayo kunoma yisiphi salezi zimo. Okutholakele okukhona kuhlanganisa ukuhlolwa kwaselabhorethri nombiko wesigameko esihlobene nesikhathi sokuhlinzwa, okuphendula imibuzo elinganiselwe kakhulu.

Lo mehluko ubalulekile ngoba “kunciphisa ukuvuvukala,” “kuzinzisa amaseli e-mast,” kanye nokuthi “kususa i-histamine” kuchaza imiphumela ehlukene. Ubufakazi bomunye wale miphumela abunakumane busetshenziswe kweminye.

Amagama amathathu okufanele agcinwe ehlukene

I-MCAS iphathelene neziqephu eziphindaphindayo ezithinta umzimba wonke zokukhishwa kwezinto ezidlulisa amasignali ngamaseli e-mast. I-histamine ingenye yalezi zinto, kodwa amaseli e-mast akhiqiza nezinye izinto ezidlulisa amasignali. I-American Academy of Allergy, Asthma & Immunology ichaza ukuhlolwa kwe-MCAS ngokuhlanganisa iziqephu ezinezici ezithile, ukwanda kwezinto ezifanele ezidlulisa amasignali ngesikhathi sezimpawu uma kuqhathaniswa nezinga elivamile, kanye nokusabela ekwelashweni okuqondiswe kulezo zinto. Ukuba nezimpawu eziningana kuphela akuqinisekisi ukuthi umuntu unalesi simo.

Ukungezwani nezinto okwenzeka ngokushesha okulamulelwa yi-IgE kuhilela ukusabela kwamasosha omzimba entweni ethile ebangela ukungezwani. Ukubopha kwaleyo nto ku-IgE esemangqamuzaneni e-mast kungabangela ukukhishwa kwezinto ezidlulisa amasignali. Le ndlela eyaziwayo yokungezwani nezinto ingahilela amaseli e-mast ngaphandle kokuthi wonke umuntu ongezwani nezinto abe ne-MCAS engenambangela eyaziwayo. “Ukungezwani nezinto” kuhlanganisa nezindlela ezingaphezu kwale ndlela yokusabela ngokushesha.

Ukungabekezeleli i-histamine kuvame ukusetshenziswa ukuchaza ukusabela okubi okusolwayo ku-histamine esekudleni. Akufani nokungezwani nokudla noma i-MCAS. Umhlahlandlela ka-2021 wezinhlangano eziningi mayelana ne-histamine edliwayo uchaza ubufakazi obulinganiselwe nobuphikisanayo obuxhumanisa ukuyidla nezimpawu ezingaphinda zivele ngaphansi kwezimo ezifanayo, futhi uxwayisa ngokuthi izilinganiso ze-diamine oxidase ku-serum azikwazi ukuqinisekisa lesi simo. Leli gama liveza incazelo ehlongozwayo yezimpawu; ukusabela ekudleni kukodwa akufakazeli ukuthi ukuhlukaniswa kwe-histamine akwanele.

Lokho ukuhlolwa kwamaseli e-mast okwalinganisa ngempela

Okutholakele ekuhlolweni okuqondile akusekeli incazelo elula ethi i-methylene blue ivimbela ngokuthembekile ukukhishwa kwezinto ngamaseli e-mast.

Ocwaningweni lukaKimura nozakwabo lwango-1999 lokugeleza kwegazi emithanjeni emincane yamagundane, abacwaningi babheka amaseli e-mast aseduze kwemithambo emincane ebuyisela igazi esicutshini esisekela amathumbu, besebenzisa isibonakhulu sokubheka izicubu ezisaphila. Ukufaka i-methylene blue kuleyo ndawo ngokuyigelezisa phezu kwezicubu ku-50 micromolar kwabangela ukukhishwa kwezinhlamvana ezingaphakathi kwamaseli. Amaseli amhlophe egazi nawo anamathela kakhulu olwelwesini lomthambo futhi aginqika kancane kakhulu. Ukwelapha nge-ketotifen kusengaphambili kwavimbela lokho kukhishwa kwezinhlamvana. Lokhu kwakuwukuhlolwa kwesilwane okwakuhlola ukudluliswa kwamasignali okuhlobene ne-nitric oxide, hhayi ukwelashwa ngomlomo kwabantu abane-MCAS.

Ucwaningo lwango-2001 lwamaseli e-basophil abantu namaseli e-mast asemgodini wesisu wamagundane lwalinganisa ngokuqondile ukukhishwa kwe-histamine. Ezimweni ezahlolwa, i-methylene blue ayizange ishintshe ukukhishwa okuvamile noma ukukhishwa okwakhuthazwa amasosha omzimba kumaseli e-basophil abantu. Ama-basophil angamaseli amasosha omzimba ahlobene namaseli e-mast, kodwa awafani namaseli e-mast asezicutshini.

Okunye ukuhlolwa okwakusebenzisa ulayini wamaseli wamagundane we-RBL-2H3 akutholanga mphumela we-methylene blue ekukhishweni kwe-histamine okuvamile noma okubangelwa i-L-arginine. Ulayini wamaseli, amaseli ahlukanisiwe, namaseli e-mast ngaphakathi kwezicubu eziphilayo ezinemithambo yegazi emincane kuyehluka ngamasignali akuzungezile nangezinto akuchayeka kuzo ngesikhathi sokuhlolwa. Ukungatholakali komphumela noma ukukhishwa kwezinhlamvana kulezi zindlela zokuhlola akubikezeli zonke izindlela abantu abangasabela ngazo. Uma kuhlanganiswa, lokhu okutholakele kwenza kube nzima ukusekela isimangalo esibanzi sokuthi iyinto “ezinzisa amaseli e-mast.”

Izilinganiso ezivamile zokuvuvukala ziqhele nakakhulu embuzweni womtholampilo. Ukushintsha kwe-cytokine noma kwephrotheni edlulisa amasignali bekungeke kuqinisekise ukuncipha kokukhishwa kwezinhlamvana ngamaseli e-mast ngaphandle kokuthi lokho kulinganiswe. Ngisho nokuncipha okuqinisekisiwe kokukhishwa kwezinto ezidlulisa amasignali kusazodinga ubufakazi ezigulini ukuze kuqinisekiswe ukuthi kuneziqephu ezimbalwa noma ikhono elingcono lokwenza imisebenzi yansuku zonke. Umehluko phakathi kwamasignali okuvuvukala nemiphumela yezempilo uyasebenza lapha.

Isigameko sasesibhedlela siphendula umbuzo ohlukile

Umbiko wesigameko sango-2017 sokuhlinzwa ukuze kukhishwe ihlule emithanjeni yamaphaphu uchaza isiguli okungenzeka sasinesifo samaseli e-mast, esaba nokushaqeka kokujikeleza kwegazi ngenxa yokuvuleka kwemithambo ngemva kokuhlinzwa. Isiguli sathola izivimbeli ze-H1 ne-H2, ama-steroid, kanye ne-methylene blue, kwase kuba ngcono ukugeleza nokucindezela kwegazi.

Lokho kuwukubonwa kwasemtholampilo, kodwa umphumela wawuwukubuyiselwa kokujikeleza kwegazi esimweni esiyinkimbinkimbi sokuhlinzwa. Kwanikezwa izindlela zokwelapha eziningana, kwakungekho qembu lokuqhathanisa, futhi kwakungaqinisekile ukuthi isiguli sasinasiphi isifo. Umbiko awukwazi ukuhlukanisa umnikelo we-methylene blue, ukubonisa ukuthi yamisa ukukhishwa kwezinto ezidlulisa amasignali, noma ukuqinisekisa ukuthi ukusetshenziswa kwayo ngokuphindaphindiwe kuthuthukisa ukusabela okungapheli ekudleni. Ukuthuthukisa imiphumela yesiqephu ekucindezelekeni kwegazi nokuvimbela leso siqephu kuyizinhloso ezimbili ezihlukene zokwelapha.

Ukuqhathaniswa kwesimo nomphumela olinganiswayo

Sebenzisa lokhu kuqhathanisa ukuze ubone ukuthi inzuzo ehlongozwayo ibingadinga ini ngempela. Izidingo zobufakazi ezingezansi ziyinhlanganisela eyenziwe lapha yomehluko ekuxilongeni nasekuhlolweni ochazwe ngenhla, hhayi ithuluzi lokuxilonga eliqinisekisiwe.

Ukuhlukaniswa kwe-histamine akukhona ukuvinjelwa kwe-MAO

I-histamine inezindlela ezimbili eziyinhloko zokuguqulwa emzimbeni ezihilela i-diamine oxidase (DAO) ne-histamine N-methyltransferase (HNMT). Lawa ama-enzyme ahlukile ku-monoamine oxidase A (MAO-A). Isithombe sesembozo sihlukanisa ukukhishwa kwezinto ezidlulisa amasignali nalezi zindlela zokuhlukanisa; amalebula aso ama-enzyme akhomba izindlela, hhayi imikhiqizo eyenziwa nge-histamine.

URamsay nozakwabo babonisa ukuthi i-methylene blue ivimbela i-MAO-A, okuwumphumela ohlobene nobuthi be-serotonin. Ukuvinjelwa kwe-MAO-A akubona ubufakazi bokuthi umsebenzi we-DAO noma we-HNMT uyanda, futhi akubonisi ukususwa kwe-histamine ngokushesha. Ukufana kwamagama ama-enzyme akuqinisekisi ukuthi anomphumela ofanayo wokwelapha.

Kukhona futhi umehluko ocwaningweni okulula ukungawuqapheli. Ucwaningo lwango-2020 lokulinganisa i-DAO olwaluhilela iziguli ezingu-22 nabantu bokuqhathanisa abangu-22 lwakhiqiza i-methylene blue njengomkhiqizo onombala wenqubo yamakhemikhali yaselabhorethri eyayisetshenziselwa ukulinganisa umsebenzi we-enzyme. Ababambiqhaza babengalashwa nge-methylene blue. Ngakho ukuthola womabili la magama ephepheni locwaningo akusho ngempela ukuthi kuwucwaningo lokwelapha.

Kungani ukushintsha kwezimpawu kungeke kuqinisekise indlela yokusebenza

Ingxoxo yenkundla eyabangela lo mbuzo ihlanganisa imibiko yokugaya ukudla kangcono nokuncipha kwesidingo esiphuthumayo sokuchama ngemva kwe-methylene blue. Leyo mibiko ichaza izinguquko abantu abazizwayo. Ayilinganisi izinga le-histamine, ayiqinisekisi i-MCAS, futhi ayibonisi ukuthi izicubu zesinye sezingamelana ne-histamine.

Izimpawu zingaguquguquka ngesikhathi kushintsha ukudla, i-caffeine, amanzi athathwayo, imithi, nezinye izinto umuntu achayeka kuzo. Okubonwayo kungaba yiqiniso ngaphandle kokuthi incazelo yakho ehlongozwayo ibe yiqiniso. Isidingo esiphuthumayo sokuchama naso sidinga ukuhlolwa kwaso: izimpawu zesinye nokutheleleka okuqinisekisiwe komgudu womchamo kuyizinto ezimbili ezihlukene ezitholakalayo. Ukudamba kwezimpawu kuphela akukwazi ukukhomba ukuthi imbangela ukutheleleka noma ukusebenza kwamaseli e-mast.

Ukuzwela ngokweqile kusabalulekile

I-methylene blue ngokwayo ingabangela ukuzwela ngokweqile. Ulwazi lokunikeza i-PROVAYBLUE efakwa emthanjeni luchaza ukusabela okukhulu kokungezwani okubizwa nge-anaphylaxis futhi luthi akufanele isetshenziswe ngemva kokuzwela ngokweqile okukhulu emkhiqizweni wesigaba se-methylene blue. Luphinde luxwayise nge-serotonin syndrome lapho ihlanganiswa nemithi esebenzisanayo, futhi luthi akufanele isetshenziswe lapho kunokuntuleka kwe-G6PD. Lolu lwazi lomkhiqizo luqinisekisa izingozi ezibalulekile; alulinganisi zonke izingozi zomkhiqizo ophuzwa ngomlomo ongakahlolisiswa.

Ubufakazi abusisekeli isinqumo sokufaka i-methylene blue esikhundleni sama-antihistamine anqunyiwe noma okunye ukunakekelwa okuqinisekisiwe. Ubunzima bokuphefumula, ukuvuvukala komphimbo, noma ukuwa kudinga usizo lwezokwelapha oluphuthumayo, hhayi ukuzama into yokufaka umbala. Engxoxweni ehleliwe nomsebenzi wezempilo, letha isimangalo esiqondile, umkhiqizo, imithi oyisebenzisayo manje, nomlando wezimpawu, usebenzisa le mibuzo ongayibuza nge-methylene blue. Umbuzo obalulekile ukuthi ukwelashwa okuhlongozwayo kuhloselwe ukubhekana nasiphi isifo esixilongiwe namuphi umphumela, nokuthi bukhona yini ubufakazi balokho kusetshenziswa okuqondile.