I-methylene Blue ye-MCAS nokunganyamezeli ihistamine: ubungqina

I-methylene blue ayilonyango olumiselweyo lwesifo sokuvuseleleka kweeseli zemasti (MCAS) okanye lokunganyamezeli ihistamine. Uncwadi olufunyenwe ukulungiselela eli nqaku aluzange lubonelele ngeemvavanyo ezilawulwayo kwizigulana ezibonisa inzuzo eqhubekayo kuyo nayiphi na kwezi meko. Iziphumo ezikhoyo ziquka iimvavanyo zaselabhoratri nengxelo yetyala elimalunga nexesha elijikeleze utyando, eziphendula imibuzo enomda omncinane.

Lo mahluko ubalulekile kuba “inciphisa ukudumba,” “izinzisa iiseli zemasti,” nokuthi “isusa ihistamine” zichaza iziphumo ezahlukeneyo. Ubungqina besinye abunakusetyenziswa nje ukuxhasa ezinye.

Amagama amathathu ekufuneka ahlale ahluliwe

I-MCAS ibhekisela kwiziganeko eziphindaphindayo ezichaphazela umzimba wonke zokukhutshwa kwezinto ezidlulisa imiqondiso ziiseli zemasti. Ihistamine yenye yezi zinto, kodwa iiseli zemasti zivelisa nezinye izinto ezidlulisa imiqondiso. I-American Academy of Allergy, Asthma & Immunology ichaza uvavanyo lwe-MCAS njengoludibanisa iziganeko ezineempawu ezithile, ukunyuka kwezinto ezifanelekileyo ezidlulisa imiqondiso ngexesha leempawu xa kuthelekiswa nenqanaba lesiqhelo, kunye nokusabela kunyango olujolise kwezo zinto. Ingqokelela yeempawu iyodwa ayiqinisekisi uxilongo.

Ialeji ekhawulezayo elamliweyo yi-IgE ibandakanya ukusabela kwenkqubo yokhuselo lomzimba kwinto ethile ebangela ialeji. Ukubophelela kwaloo nto kwi-IgE ekwiiseli zemasti kunokubangela ukukhutshwa kwezinto ezidlulisa imiqondiso. Le ndlela iqhelekileyo yealeji inokubandakanya iiseli zemasti ngaphandle kokuba wonke umntu onealeji abe ne-MCAS engaziwayo imbangela yayo. “Ialeji” ikwabandakanya neendlela ezingaphaya kwale ndlela yokusabela ngokukhawuleza.

Ukunganyamezeli ihistamine kudla ngokusetyenziswa ukubhekisela ekusabeleni okungathandekiyo ekurhanelwa ukuba kubangelwa yihistamine ekutyeni. Akuthethi into enye nealeji yokutya okanye i-MCAS. Isikhokelo sika-2021 semibutho emininzi esimalunga nehistamine eginyiweyo sichaza ubungqina obunomda nobuphikisanayo obunxulumanisa ukutyiwa kwayo neempawu ezinokuphinda zibonakale phantsi kweemeko ezifanayo, kwaye silumkisa ukuba imilinganiselo ye-diamine oxidase kwiserum ayinakuqinisekisa uxilongo. Eli gama lichaza ingcaciso ecetywayo yeempawu; ukusabela ekutyeni akubonisi ngokwako ukuba ukuqhekeka kwehistamine akwanelanga.

Oko kwakulinganiswa ngokwenene ziimvavanyo zeeseli zemasti

Iziphumo zovavanyo ezithe ngqo azixhasi ingcaciso elula yokuba i-methylene blue ithintela ngokuthembekileyo ukukhutshwa kwezinto ziiseli zemasti.

Kuphononongo lukaKimura noogxa bakhe lwango-1999 lokujikeleza kwegazi kwimithambo emincinane yeempuku, abaphandi bajonga iiseli zemasti ezisecaleni kwemithambo emincinane ye-mesentery besebenzisa imikroskopu kwizicubu eziphilayo. Ukugalela isisombululo se-methylene blue phezu kwezicubu kuloo ndawo kwi-50 micromolar kwabangela ukukhutshwa kweegranule. Iiseli ezimhlophe zegazi nazo zancamathela ngakumbi kumaleko wangaphakathi womthambo zaza zaqengqeleka kancinci. Unyango lwangaphambili nge-ketotifen lwaluthintela olo khutshelo lweegranule. Olu yayilulungiselelo lovavanyo lwesilwanyana olwaluhlola ukuhanjiswa kwemiqondiso enxulumene ne-nitric oxide, kungekhona unyango oluthathwa ngomlomo ngabantu abane-MCAS.

Uphononongo lwango-2001 lweebasophil zabantu neeseli zemasti ezikumngxuma wesisu weempuku lwalinganisa ukukhutshwa kwehistamine ngokuthe ngqo. I-methylene blue ayizange itshintshe ukukhutshwa kwesiqhelo okanye oko kuvuselelwe yinkqubo yokhuselo lomzimba kwiibasophil zabantu phantsi kweemeko ezavavanywayo. Iibasophil ziiseli zokhuselo lomzimba ezinxulumene neeseli zemasti, kodwa azinakuthathwa njengeziseli zemasti ezisezicubwini.

Olunye uvavanyo olwalusebenzisa umgca weeseli zeempuku i-RBL-2H3 alufumananga mpembelelo ye-methylene blue ekukhutshweni kwehistamine kwesiqhelo okanye okubangelwa yi-L-arginine. Umgca weeseli, iiseli ezikhutshwe zodwa, kunye neeseli zemasti kulungiselelo oluphilayo lwemithambo emincinane ziyahluka kwimiqondiso ezingqongileyo nakwizinto ezichanabekwa kuzo kuvavanyo. Isiphumo sokungabikho kwempembelelo okanye isiphumo sokukhutshwa kweegranule kwezi modeli asiqikeleli zonke iindlela abantu abanokusabela ngazo. Xa zidityanisiwe, ezi ziphumo zenza kube nzima ukuthethelela ibango elibanzi lokuba “sisizinzisi seeseli zemasti.”

Imilinganiselo yokudumba ngokubanzi ikude ngakumbi nombuzo wonyango. Utshintsho kwi-cytokine okanye kwiproteni edlulisa imiqondiso alunakuqinisekisa ukuncipha kokukhutshwa kweegranule ziiseli zemasti ngaphandle kokuba oko kuye kwalinganiswa. Nokuncipha okuqinisekisiweyo kokukhutshwa kwezinto ezidlulisa imiqondiso kusaya kufuna ubungqina kwizigulana ukuqinisekisa ukwehla kweziganeko okanye ukuphucuka kokusebenza kwemihla ngemihla. Umahluko phakathi kwemiqondiso yokudumba neziphumo zempilo uyasebenza nalapha.

Ityala lasesibhedlele liphendula umbuzo owahlukileyo

Ingxelo yetyala lango-2017 lokususwa kwehlwili kumthambo wemiphunga ichaza isigulana ekusenokwenzeka ukuba sasinengxaki yeeseli zemasti, esathi emva kotyando saphuhlisa umothuko obangelwa kukwandiswa kwemithambo yegazi. Isigulana safumana izithinteli ze-H1 ne-H2, iisteroid, ne-methylene blue, kwaza kwaphucuka ukuhamba kwegazi noxinzelelo lwalo.

Oko kukuqatshelwa kwezonyango, kodwa isiphumo sasikukubuyela kokujikeleza kwegazi kwimeko entsonkothileyo yotyando. Kwanikwa unyango oluninzi, kwakungekho qela lothelekiso, kwaye uxilongo lwalungaqinisekanga. Le ngxelo ayinakwahlula igalelo le-methylene blue, ibonise ukuba yayimisa ukukhutshwa kwezinto ezidlulisa imiqondiso, okanye iqinisekise ukuba ukusetyenziswa kwayo ngokuphindaphindiweyo kuphucula ukusabela okungapheliyo ekutyeni. Ukuphucula iziphumo zesiganeko kuxinzelelo lwegazi nokuthintela eso siganeko ziinjongo ezahlukeneyo zonyango.

Ukuthelekisa imeko nesiphumo esilinganiswayo

Sebenzisa olu thelekiso ukuchonga oko kuya kufuneka ngokwenene ukuze kuqinisekiswe inzuzo ecetywayo. Iimfuno zobungqina ezingezantsi ziyindibaniselwano yokuqala yomahluko woxilongo noweemvavanyo ochazwe ngasentla, azisisixhobo soxilongo esiqinisekiswe ngokuvavanywa.

Impembelelo ecetywayo	Imeko okanye inkqubo efanelekileyo	Ubungqina obuya kuyixhasa	Oko kuya kuhlala kungaqinisekiswanga
Ithintela ukuvuseleleka kweeseli zemasti	Ukukhutshwa kwezinto ezidlulisa imiqondiso ziiseli zemasti kwimodeli echaziweyo	Imilinganiselo elawulwayo yokukhutshwa kweegranule nezinto ezifanelekileyo ezidlulisa imiqondiso, kunye nolawulo oluqinisekisa ukuphila kweeseli	Inzuzo kubantu abane-MCAS eqinisekisiweyo
Ilawula i-MCAS	Iziganeko eziphindaphindayo ezichaphazela umzimba wonke ezichazwe ngokovavanyo lwezonyango	Iziphumo ezilawulwayo kwizigulana, njengokuphindaphinda kweziganeko, ubunzima bazo, ukusebenza, nemiphumo engathandekiyo, kunye novavanyo olufanelekileyo lwezinto ezidlulisa imiqondiso	Ukuba inzuzo ivela ekuqhekekeni ngokukhawuleza kwehistamine
Iphucula ukusabela kwihistamine enxulumene nokutya	Iimpawu ezinokuphinda zibonakale phantsi kweemeko ezifanayo ezinxulumene nehistamine eginyiweyo emva kokuhlolwa kwezinye iingcaciso	Uthelekiso lweempawu olufihlwe ulwazi lwamaqela nolubekwe esweni phantsi kweemeko ezifanayo ezimiselweyo	Ukunqongophala kwe-DAO okungunobangela okanye inzuzo kwialeji elamliweyo yi-IgE
Ikhawulezisa ukususwa kwehistamine	Imetabolism yehistamine	Imilinganiselo eqinisekiswe ngokuvavanywa yendlela umzimba ophatha ngayo ihistamine phantsi kokuchanabeka okulawulwayo, kunye nobungqina obujoliswe kwi-enzyme ethile	Ukuncipha kweempawu okanye kweziganeko zeeseli zemasti
Iphucula umothuko okanye ukudumba ngokubanzi	Ukusilela kokujikeleza kwegazi okanye indlela ethile yokudumba	Iziphumo zokuhamba kwegazi noxinzelelo lwalo okanye isiphumo sokudumba esilinganiswa ngokwenene, kunye neqela okanye indlela efanelekileyo yothelekiso	Ukuthintelwa kwealeji, kweziganeko ze-MCAS, okanye kokunganyamezeli ukutya

Ukuqhekeka kwehistamine asikokuthintelwa kwe-MAO

Ihistamine ineendlela ezimbini eziphambili zemetabolism ezibandakanya i-diamine oxidase (DAO) ne-histamine N-methyltransferase (HNMT). Ezi zi-enzyme ezahlukileyo kwi-monoamine oxidase A (MAO-A). Umfanekiso weqweqwe wahlula ukukhutshwa kwezinto ezidlulisa imiqondiso kwezi ndlela zokuqhekeka; iilebhile zawo zee-enzyme zichonga iindlela, kungekhona iimveliso ezenziwe ngehistamine.

URamsay noogxa bakhe babonisa ukuthintelwa kwe-MAO-A yi-methylene blue, isiphumo esibalulekileyo kwityhefu yeserotonin. Ukuthintela i-MAO-A akubobungqina bokuba umsebenzi we-DAO okanye we-HNMT uyanda, kwaye akubonisi ukususwa ngokukhawuleza kwehistamine. Amagama ee-enzyme afanayo awaqinisekisi impembelelo yonyango efanayo.

Kukwakho nomahluko wophando onokungaqatshelwa lula. Uphononongo lwango-2020 lovavanyo lwe-DAO olubandakanya izigulana ezingama-22 nabantu abangama-22 beqela lolawulo lwavelisa i-methylene blue njengemveliso enombala yentsabelwano yaselabhoratri eyayisetyenziselwa ukuqikelela umsebenzi we-enzyme. Abathathi-nxaxheba babenganyangwa nge-methylene blue. Ngoko ukufumana omabini la magama kwiphepha lophando akuthethi ukuba luphononongo lonyango.

Kutheni utshintsho lweempawu lungenakuqinisekisa indlela yokusebenza

Ingxoxo yeqonga eyabangela lo mbuzo iquka iingxelo zokuphucuka kokwetyisa nokuncipha kwesidingo esingxamisekileyo sokuchama emva kwe-methylene blue. Ezo ngxelo zichaza utshintsho oluvakalelwa ngabantu. Azilinganisi ubungakanani behistamine, aziqinisekisi i-MCAS, okanye zibonise ukuba izicubu zesinyi azisachaphazeleki yihistamine.

Iimpawu zinokuguquguquka xa kutshintsha ukutya, icaffeine, amanzi asemzimbeni, amayeza, nezinye izinto umntu achanabekwa kuzo. Into eqatshelweyo inokuchaneka ngaphandle kokuba ingcaciso ecetywayo yayo ichaneke. Isidingo esingxamisekileyo sokuchama naso sifuna uvavanyo lwaso: iimpawu zesinyi nosulelo oluqinisekisiweyo lomjelo womchamo zizinto ezahlukeneyo ezifunyaniswe kuvavanyo. Ukuthomalala kweempawu kukodwa akunakuchonga usulelo okanye ukusebenza kweeseli zemasti njengonobangela.

Ukusabela ngokugqithisileyo kusabalulekile

I-methylene blue ngokwayo inokubangela ukusabela ngokugqithisileyo. Ulwazi lokumiselwa kwe-PROVAYBLUE efakwa emthanjeni luchaza i-anaphylaxis kwaye luyakwalela ukusetyenziswa kwayo emva kokusabela ngokugqithisileyo okukhulu kwimveliso yodidi lwe-methylene blue. Lukwalumkisa ngesifo seserotonin xa idibene namayeza asebenzisanayo kwaye luyakwalela ukusetyenziswa xa kukho ukunqongophala kwe-G6PD. Le lebhile iqinisekisa iingozi ezibalulekileyo; ayilinganisi bonke ubungozi bemveliso ethathwa ngomlomo engekaphononongwa.

Ubungqina abukuthetheleli ukusebenzisa i-methylene blue endaweni yamayeza amiselweyo athintela ihistamine okanye olunye ukhathalelo olumiselweyo. Ubunzima bokuphefumla, ukudumba komqala, okanye ukuwa ngenxa yokugula kufuna uncedo lwezonyango olungxamisekileyo, kungekhona ukuzama idayi. Xa ulungiselela ingxoxo nogqirha, yiza nebango elichanekileyo, imveliso, amayeza owasebenzisayo ngoku, nembali yeempawu, usebenzisa le mibuzo onokuyibuza nge-methylene blue. Umbuzo osebenzayo ngowokuba loluphi uxilongo nesiphumo unyango olucetywayo olujolise kuzo, nokuba bukhona na ubungqina bokuxhasa olo setyenziso lukhethekileyo.