I-methylene blue yenkumbulo nokugxila: lokho izivivinyo kubantu ezakulinganisa

Iphepha lango-2023 elimayelana ne-methylene blue nobuchopho bomuntu ophilayo liqala ukwethula umbono walo ngomusho osuphindwa ezibuyekezweni, kumavidiyo, nasemakhasini emikhiqizo: le nhlanganisela yamakhemikhali "yaboniswa futhi ukuthi ithuthukisa amakhono okucabanga, ukufunda nenkumbulo kubantu nasezilwaneni ezisetshenziswa ezivivinyweni, kuye ngenani lomthamo."

Ingxenye yalowo musho ekhuluma ngezilwane kulula ukuyisekela. Ingxenye ekhuluma ngabantu incike ezivivinyweni ezimbalwa, futhi ukuzifunda kwembula izingxenye ezahlukene zenkulumo ethi "amakhono okucabanga". Ukusesha okwenzelwe lesi sihloko kwathola izifundo ezinhlanu kubantu ezazinesilinganiso sokugcina samakhono okucabanga noma sezithombe zobuchopho, kanye nezivivinyo ezintathu zokuhlinza ezazinomphumela ophathelene namakhono okucabanga. Isivivinyo esisodwa kubantu abadala abaphilile sabonisa ukuthuthuka kwenkumbulo, kodwa lokho akuzange kusekelwe lapho kuqhathaniswa amaqembu.

Izinhlobo ezine zemiphumela kubantu zivame ukuphathwa njengohlobo olulodwa

Uma ufunda leli thebula uye phansi, uyayibona iphethini. Izifundo ezinesilinganiso sokugcina sangempela samakhono okucabanga yilezo zokuhlinza, futhi zasebenzisa umuthi ofakwa emthanjeni ezigulini ezazingaphansi komuthi wokulalisa. Izifundo kumavolontiya aphilile zalinganisa amasignali obuchopho kunokucabanga.

Lokho okwatholwa yisivivinyo sango-2016 kubantu abadala abaphilile

Isifundo kubantu esicashunwa kakhulu sanikeza abantu abadala abaphilile abangu-26 umthamo owodwa ongu-280 mg ophuzwa ngomlomo, cishe 4 mg/kg, noma ikhepsuli ye-placebo egcwele i-FD&C blue no. 2 ukuze zombili zibukeke zifana. Ababambiqhaza bathathwa izithombe zobuchopho ngaphambi kokunikezwa umthamo, baphinde bathathwa ngemva kwehora, ngesikhathi benza umsebenzi wokuhlola ukuqapha nokusabela, olinganisa ukuthi umuntu ulubona ngokushesha kangakanani uphawu olulula olubonakalayo, kanye nomsebenzi wokufanisa isithombe nesampula ngemva kokulibaziseka, okuwukuhlolwa kwenkumbulo yokubona yesikhashana.

Ukusabela kobuchopho kwashintsha. I-methylene blue yandisa isignali ku-insular cortex ezinhlangothini zombili zobuchopho ngesikhathi somsebenzi wokunaka (Z = 2.9 kuya ku-3.4, P = .01 kuya ku-.008) nasezindaweni ze-prefrontal, parietal, ne-occipital ngesikhathi somsebenzi wenkumbulo (Z = 2.9 kuya ku-4.2, P = .03 kuya ku-.0003).

Imiphumela yokuziphatha yiyona ngxenye efushaniswa kakhulu lapho lokhu kulandiswa kabusha.

1. Isikhathi sokusabela asizange sithuthuke. Iqembu le-placebo lasuka ku-230 laya ku-220 milliseconds. Iqembu le-methylene blue lasuka ku-230 laya ku-230 milliseconds. Ukuqhathanisa phakathi kwamaqembu kwanikeza F = 0.65, P = .43.
2. Izimpendulo ezifanele zokukhumbula zenyuka cishe ngo-7% ngaphakathi kweqembu elanikezwa umuthi, P = .01 ekuqhathaniseni ngaphambi nangemva ngaphakathi kwalelo qembu.
3. Lokho kukhuphuka ngo-7% akuzange kusekelwe ukuhlolwa phakathi kwamaqembu. Ukuqhathanisa izilinganiso eziphindaphindiwe zoshintsho ezimpendulweni ezifanele kwanikeza F = 2.96, P = .09.

Ushintsho ngaphakathi kweqembu oluhambisana nomphumela wokusebenzisana ongabalulekile ngokwezibalo luwuphawu lomphumela ongase ube ngowangempela noma ongase ube ukuhlukahluka okungahleliwe. Isiphetho sephepha ngokwalo sinomkhawulo ofanele: okutholakele "kusekela umbono wokuthi i-methylene blue ithuthukisa ukusebenza kwenkumbulo" futhi kunikeza isisekelo sezivivinyo zesikhathi esizayo. Isisekelo asikona okutholakele. Ukubuyekezwa kwethu kobufakazi obubanzi kubantu kulandelela ukuthi kungakanani osekwakhiwe phezu kwaso kusukela ngaleso sikhathi.

Lokho ukuhlolwa okukulinganisayo ngempela

Alikho kulawa mathuluzi elilinganisa "inkumbulo" noma "ukugxila" ngendlela umfundi aqonde ngayo. Ngamunye ubeka isidingo esithile kumuntu bese unikeza amaphuzu empendulweni yakhe, futhi imikhawulo yethuluzi ibeka imikhawulo yazo zonke izimangalo ezenziwa ngalo.

Ngakho umphumela ungaba namandla ngokwezibalo kodwa ube nomkhawulo omncane. Isikhathi sokusabela esingashintshi siphikisa ukuthi uphawu lubonwa ngokushesha kakhudlwana; asiphikisi ukuthi isifundo esilalelwe singakhunjulwa kangcono. Ukuthuthuka kwamaphuzu okuhlolwa kokufanisa nesampula ngemva kokulibaziseka kusho ukuthi isithombe saqashelwa kaningi; akusho ukuthi lowo muntu uzokhumbula igama lomuntu kusasa. Umhlahlandlela wendlela imibhalo yocwaningo ngezilwane elinganisa ngayo inkumbulo ulandela lo mehluko ekuhlolweni ngezindlela eziyindida nasekuqashelweni kwezinto okuyisisekelo sezimangalo eziningi.

Isifundo esihambisana naso asizange siqophe noma yimaphi amaphuzu

Uhlelo olufanayo locwaningo lwashicilela ukuhlaziya kwesibili kusukela esikhathini esifanayo sokubhalisa, enyuvesi efanayo, ngomthamo ofanayo nange-placebo efanayo, kulokhu lubheka ukuxhumana kobuchopho ngesikhathi sokuphumula. Kwabhaliswa ababambiqhaza abangamashumi amabili nesishiyagalombili; ukuhlaziywa kwezithombe kwasebenzisa cishe abangu-13 kuya ku-15 eqenjini ngalinye.

I-methylene blue yayihlotshaniswa nokuncipha kokugeleza kwegazi ebuchosheni ngaphakathi kwenethiwekhi ephathelene nokubona nendawo, kanye nokuxhumana okunamandla ngesikhathi sokuphumula phakathi kwamapheya amaningana ezindawo, okuhlanganisa i-hippocampus yangakwesobunxele ne-cerebellum yangakwesokudla. Kokubili kungokubonwa okuthakazelisayo ngokusebenza kwenethiwekhi. Akukho kukho okuwumphumela wenkumbulo, futhi iphepha liyakusho lokho ngokwalo: "Ukungabi khona kwamaphuzu okuziphatha kulesi sifundo nakho kuwumkhawulo."

Imibiko emibili evela eqenjini elilodwa, esikhathini esisodwa sokubhalisa, ngomthamo owodwa, iyisivivinyo esisodwa, hhayi ezimbili. Ubufakazi bezithombe zobuchopho bomuntu benzuzo emakhonweni okucabanga abukaphindwa ngokuzimela.

Isifundo esizimele sathola ushintsho olubheke kolunye uhlangothi

Ukulinganisa okuzimele kwavela kwelinye iqembu futhi kwasebenzisa enye indlela yokunikeza umuthi. USingh nozakwabo banikeza abesifazane abaphilile abayisishiyagalombili ukuconselwa emthanjeni kwe-placebo kanye ne-methylene blue engu-0.5 no-1 mg/kg ngezinsuku ezihlukene, base belinganisa ukugeleza kwegazi ebuchosheni, ukukhishwa komoyampilo egazini, nezinga lokusetshenziswa komoyampilo ebuchosheni.

Zontathu zehla. Ukugeleza kwegazi ebuchosheni bonke kwehla cishe ngo-8% kuyo yomibili imithamo, futhi izinga lokusetshenziswa komoyampilo lehla ngokuphawulekayo ngokwezibalo. Ababhali babebikezele ukwenyuka futhi babika ngokucacile ukuguquka kolunye uhlangothi, benikeza izincazelo ezimbili: le mithamo isezingeni lapho imiphumela ye-methylene blue iguquka khona isuke ekukhuthazeni iye ekuvimbeleni, futhi ubuchopho obuphilile bungase bube nendawo encane yokuthuthukiswa.

Lokho kuguquka yisizathu sokuthi ukuhumusha le nhlanganisela ngokuthi "okuningi kungcono" kungasebenzi. Umhlahlandlela we-hormesis uchaza ukuma kwejika; uhla lwemithamo oluchazwa njengoluthuthukisayo kule mibhalo yocwaningo lungu-0.5 kuya ku-4 mg/kg, futhi amaphepha alusebenzisayo athi ngaphezu kuka-10 mg/kg ushintsho luya kolunye uhlangothi.

Isilinganiso sokugcina samakhono okucabanga esashintsha ukudideka ngemva kokuhlinzwa

I-delirium yisimo sokudideka esiqala ngokushesha emahoreni kuya ezinsukwini, ngokuvamile kubantu asebekhulile ngemva kokuhlinzwa okukhulu. Akufani nokukhumbula ukuthi okhiye bakuphi, kodwa kulinganiswa ngamathuluzi aqinisekisiwe, futhi kuwumphumela ophathelene namakhono okucabanga.

Izivivinyo ezintathu ezabela ababambiqhaza amaqembu ngokungahleliwe zihlole ukuthi umthamo ofakwa emthanjeni ngesikhathi sokuhlinzwa uyakunciphisa yini.

Isivivinyo sango-2021 saphinde sabika ukuthi ukuphazamiseka kwamakhono okucabanga ekuqaleni ngemva kokuhlinzwa ngosuku lwesikhombisa kwehla kusuka ku-40.2% kuya ku-16.1% (OR 0.30, 95% CI 0.16 kuya ku-0.57, P < .001). Ukuhlaziywa okuhlanganisiwe kwezivivinyo ezintathu kwango-2026, okubandakanya iziguli ezingu-779, kwahlanganisa isilinganiso samathuba esingu-0.35 (95% CI 0.23 kuya ku-0.53), kungekho ukungafani okuphawulekayo ngokwezibalo phakathi kwezifundo.

Imiphumela mikhulu ngokwezindinganiso zezokwelapha esikhathini esizungeze ukuhlinzwa, futhi yayingenazo izingozi zayo. Esivivinyweni sokushintshwa kwelunga, umkhuhlane ngemva kokuhlinzwa wawuvame kakhulu eqenjini elanikezwa umuthi, 16.5% uma kuqhathaniswa no-7.4% (P = .039). Izivivinyo zokuhlinzwa kwamanyikwe nokushintshwa kwelunga sezidonse izincwadi ezishicilelwe eziya kumhleli, okuyinto eyenzekayo lapho umphumela uqala ukushintsha indlela yokwelapha, futhi kuwuphawu lokuthi imininingwane iyahlolisiswa.

Kukhona nobufakazi obulinganisela lokhu. Ukuhlaziywa okuhlanganisiwe kwenethiwekhi kwango-2026 ku-The BMJ kwahlanganisa izivivinyo ezingu-158 neziguli ezingu-41,084 ukuze kukleliswa imithi yokuvimbela ukudideka. Kwagqamisa i-dexmedetomidine njengethembeke kakhulu, kanye nama-corticosteroid, imithi evuselela ama-receptor e-melatonin, i-parecoxib, i-olanzapine, ne-insulin efakwa emakhaleni. I-methylene blue yayingekho phakathi kwezindlela zokwelapha ezashiwo yilokho kuhlaziywa.

Kungani impumelelo egumbini lokuhlinza ingadluliseli ekufundeni

Kunomehluko omine ohlukanisa lezi zimo.

1. Abantu ababambiqhaza. Izivivinyo zabhalisa abantu abaneminyaka engaphezu kuka-60 ababehlinzwa kakhulu, okuyiqembu elinengozi ephakeme yokudideka kusukela ekuqaleni. Ukuvimbela isimo sokudideka ebuchosheni obusengozini akufani nokuthuthukisa obusebenza kahle.
2. Indlela yokunikeza umuthi nendawo. Yonke imiphumela emihle yavela ekuconselweni emthanjeni ngesikhathi isiguli singaphansi komuthi wokulalisa. Ikhepsuli inikeza ukuchayeka okuhlukile; ukuqhathaniswa kwezindlela zokunikeza umuthi kuchaza ukuthi kungakanani okuphuzwe ngomlomo okufinyelela ebuchosheni.
3. Umphumela. Ukudideka kuyisigameko sezokwelapha esihlolwa odokotela ngamathuluzi ahlelekile. Ukugxila okuqhubekayo ngesikhathi sokusebenza ntambama akunjalo, futhi isivivinyo esingakwazi ukufihla kahle kubabambiqhaza ukuthi bathola ini sizoba nobunzima bokukulinganisa.
4. Indlela okuhlongozwa ukuthi kusebenza ngayo. Amaphepha okuhlinza athi umphumela ubangelwa ukuncipha kokuvuvukala emzimbeni wonke nokugcinwa kwesithiyo esiphakathi kwegazi nobuchopho, kanye ne-IL-6 ephansi. Lokho kuhlukile endabeni yokudluliswa kwama-electron kuma-mitochondria esetshenziselwa ukuthengisa ukugxila, futhi ubufakazi kubantu busekela incazelo yokuqala kangcono kakhulu kuneyesibili.

Isivivinyo esisodwa kubantu esathola inkumbulo engcono

Esivivinyweni sango-2014 ku-American Journal of Psychiatry, abantu abadala abangu-42 ababenokwesaba okukhulu izindawo ezivalekile banikezwa 260 mg we-methylene blue noma i-placebo ngokushesha ngemva kwezikhathi eziyisithupha zokuchayeka, ngasinye esiyimizuzu emihlanu, egumbini elivalekile. Inkumbulo yesimo sokuqeqeshwa, eyahlolwa ngemva kosuku olulodwa nangemva kwezinsuku ezingu-30, yayingcono eqenjini elanikezwa umuthi.

Umphumela wokwesaba wawuncike ezimweni. Ababambiqhaza ababeqeda isikhathi sokuchayeka benokwesaba okuncane benza kangcono ngemva kwenyanga uma babethole i-methylene blue; ababambiqhaza izikhathi zabo ezaphela kabi babevame ukwenza kabi kakhulu. Ngakho into esondelene kakhulu nomphumela wenkumbulo obonisiwe emibhalweni yocwaningo kubantu yinkumbulo yesigameko esisodwa sokufunda elabhorethri, eyathuthukiswa lapho umuthi unikezwa ngemva kwesigameko. Umhlahlandlela wokwelapha ngokuchayeka uhlola leyo phethini.

Lapho yafunwa khona kodwa yangatholakala

Ukuhlolwa okude kakhulu kwe-methylene blue namakhono okucabanga kubantu kwathatha izinyanga eziyisithupha. Esifundweni se-bipolar disorder esabela abantu ngokungahleliwe bese beshintshana phakathi kwezindlela zokwelashwa, iziguli ezingu-37 ezazivele zithatha i-lamotrigine zathola 15 mg njengomthamo wokuqhathanisa obukeka usebenza noma 195 mg njengomthamo osebenzayo. Amaphuzu okucindezeleka nokukhathazeka athuthuka ngomthamo ophakeme. Umbiko wephepha ngamakhono okucabanga uwumugqa owodwa: "Imiphumela ye-methylene blue ezimpawini zamakhono okucabanga yayingabalulekile ngokwezibalo."

Uhlelo lwalusebenzisa umuthi osebenzayo njengokuqhathanisa ngoba i-methylene blue ishintsha umbala womchamo futhi ababhali babona ukuthi i-placebo engasebenzi yayingeke ikwazi ukugcina ukufihlwa kokwelashwa. Le nkinga yokufihla iyaphindaphinda kulo mkhakha, futhi umhlahlandlela wokuthi kungani kunzima ukufihla ukwelashwa ezivivinyweni ze-methylene blue uchaza lokho okwenzayo ekuhumusheni imiphumela encike ekuzibikeleni kwabantu.

Izivivinyo ezinkulu kakhulu zenkumbulo kubantu zasebenzisa inhlanganisela ehlukile

Ukuhlolwa okukhulu kakhulu komuthi womndeni we-methylene blue mayelana nenkumbulo kwakuwuhlelo lwe-Alzheimer's, futhi aluzange lusebenzise i-methylene blue. Lwasebenzisa i-hydromethylthionine mesylate, uhlobo oluncishisiwe lwengqikithi efanayo ye-phenothiazine oluzinziswe njengosawoti, olwathuthukiswa njengomuthi ovimbela ukunqwabelana kwe-tau. Isivivinyo sakamuva sesigaba 3 sabhalisa ababambiqhaza abangu-598 abanokuphazamiseka okuncane kwamakhono okucabanga noma ukuwohloka kwengqondo kwe-Alzheimer's okuncane kuya kokuphakathi ezikhungweni ezingu-82, futhi imigomo yaso emibili eyinhloko emasontweni angu-52 ayizange ifinyelelwe. Isizathu esishiwo siyafundisa: iqembu lokuqhathanisa lathuthuka, okuyinto ababhali abayibeka emuthini wokuqhathanisa uqobo, 4 mg we-methylthioninium chloride kabili ngesonto, owakhethwa njengombalisi womchamo ongasebenzi ukuze kugcinwe ukufihlwa kokwelashwa. Umehluko obalulekile ngokwezibalo wavela kuphela eqenjini elincane elalinokuphazamiseka okuncane kwamakhono okucabanga, emasontweni angu-78 nangu-104, ekuhlaziyweni kokuqalisa ukwelashwa okulibazisiwe. Umbiko wangaphambili wesigaba 3 wohlelo olufanayo wathola imiphumela yawo ebalulekile ekuhlaziyweni okwalungiswa ngaphambi kokwembulwa kokwelashwa, kuqhathaniswa amaqembu amancane ayethola umuthi owodwa futhi engabelwanga ngokungahleliwe. Umhlahlandlela wezivivinyo ze-Alzheimer's uchaza ukuthi lezo zivivinyo zifakazelani.

Ukuthi isifundo esifanele ukukholwa besingaba njani

Isivivinyo esingase sisekele isimangalo senkumbulo noma sokugxila besingadinga abantu abadala abaphilile abangenankinga ekhona yamakhono okucabanga, imithamo ephindaphindiwe emasontweni amaningana, indlela yokuqhathanisa efihla ukuthi iyiphi ikhepsuli equkethe ini, imiphumela ezolinganiswa enqunywe kusengaphambili, kanye neqembu labacwaningi elizimele. Akukho kulolo hlu okungenangqondo. Kumane nje kungakenziwa.

Uma usacabanga ukuyisebenzisa noma kunjalo

Amaphuzu amabili okuphepha andulela noma iyiphi ingxoxo yenzuzo. I-methylene blue ivimbela i-monoamine oxidase A, okuyibeka odabeni lokusebenzisana nemithi yokucindezeleka enqunywa udokotela kanye neminye imithi ethinta i-serotonin, futhi okukhathazayo yi-serotonin syndrome kunokusebenzisana okuncane. Akufanele futhi isetshenziswe uma kukhona ukushoda kwe-G6PD ngenxa yokuntuleka kwegazi okubangelwa ukubhidlika kwamangqamuzana abomvu egazi. Inkomba yokuphepha kanye nomhlahlandlela wokusebenzisana kwemithi kuhlelela leyo mibuzo ngokwezigaba zemithi.

Uma inkumbulo noma ukugxila kushintshe ngempela, isinyathelo sokuqala akusona isengezo. Isifo se-thyroid, ukumisa ukuphefumula ngesikhathi sokulala, i-B12 ephansi, ukucindezeleka, nemithi eminingana enqunywa udokotela kubangela sona kanye isimpawu umuntu athenga umuthi wokuthuthukisa ukucabanga ukuze asilungise, futhi umhlahlandlela wobufakazi be-thyroid ubonisa ukuthi kaningi kangakanani kunembangela engelapheka ngaphansi kwaso.

Into esetshenziswayo iwukuguquguquka kuso sonke isifundo esingenhla

Wonke umthamo ochazwe lapha wawuyinani elilinganisiwe lenhlanganisela ecacisiwe, evela kumkhiqizi wemithi, ehambisana nesitifiketi sokuhlaziywa. Ibhodlela elivela kumthengisi ongaqinisekisiwe alinjalo. Ukuhambisana nombhalo wezindinganiso we-USP kuyindinganiso umthengi angayihlola, futhi into engahambisani nawo kungenzeka ibe eyezinga lokusetshenziswa ezindwangwini, engase ibe nokungcola kwezinhlanganisela ze-organic okufana ne-Azure B, izincibilikisi ezisele, nezinsimbi ezisindayo emazingeni izimfuneko zemithi eziwabekela umkhawulo. Lokho ukuqokwa kwe-USP okukufakazelayo nokungakufakazeli kuchaza izinga ngokwalo.

Abathengisi abaningi abachaza umkhiqizo njengohlolwe uhlangothi lwesithathu bahlola izinsimbi ezisindayo kuphela bese bethula lelo qoqo elilodwa lokuhlolwa njengokuhambisana okuphelele nezindinganiso. Blupreme ihlola zonke izimfuneko ze-USP: ubunjalo, ubumsulwa, ukungcola kwezinhlanganisela ze-organic, izincibilikisi ezisele, ukungcola kwezakhi zamakhemikhali, insalela ngemva kokushiswa, imikhawulo yamagciwane, nama-endotoxin amagciwane. Iqoqo ngalinye lithunyelwa nesitifiketi sokuhlaziywa, futhi ukusifunda ngendlela efanele kusho ukufanisa inombolo yeqoqo nelabhorethri nebhodlela oliphethe. Akukho kulokho okudala inzuzo emakhonweni okucabanga, futhi umkhiqizo ongakwazi ukufakazela ubunjalo bawo ngemibhalo uyindawo engafanele ukuqala ukuhlola isimangalo.

Isiphetho

Asikho isivivinyo esinikeze i-methylene blue kubantu abadala abaphilile sabonisa inzuzo yenkumbulo noma yokunaka ngaphezu kwe-placebo. Isivivinyo sango-2016 sashintsha amasignali obuchopho, sashiya isikhathi sokusabela singashintshile, futhi sabonisa ukuthuthuka kokukhumbula okwakungabalulekile ngokwezibalo lapho kuqhathaniswa amaqembu. Iphepha elihambisana naso alizange liqophe amaphuzu okuhlolwa. Iqembu elizimele lathola ukugeleza kwegazi nokusetshenziswa komoyampilo kwehla, kungakhuphuki.

Umphumela wamakhono okucabanga kubantu onobufakazi obuqinile uvela ekuhlinzweni, lapho umthamo ofakwa emthanjeni ezigulini esezikhulile wehlisa cishe ngesigamu izinga lokudideka ngemva kokuhlinzwa ezivivinyweni ezintathu nasekuhlaziyweni okuhlanganisiwe. Lokho kuwukutholakele kwangempela okuphathelene neziguli ezigula kakhulu ngaleso sikhathi, futhi ukuhlanganiswa okukhulu kakhulu okuzimele kobufakazi bokuvimbela ukudideka akuzange kugqamise lo muthi. Kuyisimangalo esinomkhawulo omncane kakhulu kunaleso esisetshenziswa ekuthengiseni, futhi kufanele sibe esibhedlela.

Imephu yezindlela zokusebenza kumangqamuzana ichaza lokho le nhlanganisela ekwenzayo ezibonelweni zaselabhorethri, ukubuyekezwa kobufakazi be-ADHD kulandela umbuzo wokunaka kubantu abanokuxilongwa, futhi umtapo wocwaningo ukhomba izifundo ezisekela zonke izimangalo ezikuleli khasi.