Imethylene blue yenkumbulo nogxininiso: oko kwalinganiswa zizilingo ebantwini

Iphepha lika-2023 ngemethylene blue nobuchopho bomntu ophilayo liqala ingxoxo yalo ngesivakalisi esiphindwa ngoku kuphononongo, kwiividiyo nakumaphepha eemveliso: le khompawundi “yaboniswa ikwaphucula ukusebenza kokuqonda, ukufunda nenkumbulo ebantwini nakwizilwanyana zamalinge, ngokuxhomekeke kwidosi.”

Icala leso sivakalisi elithetha ngezilwanyana kulula ukulixhasa. Icala elithetha ngabantu lixhomekeke kwinani elincinci lamalinge, yaye ukuwafunda kwenza ukuba ibinzana elithi “ukusebenza kokuqonda” lahlulwe libe ngamacandelo alo. Uphando olwenziwe kweli nqaku lufumene izifundo ezintlanu ebantwini ezinesiphumo esilinganisiweyo sokuqonda okanye semifanekiso yobuchopho, kunye nezilingo ezintathu zotyando ezinesiphumo sokuqonda. Ilinge elinye kubantu abadala abasempilweni lavelisa ukuphucuka kwenkumbulo, kodwa oko akuzange kuhlale kubonakala kuthelekiso phakathi kwamaqela.

Iintlobo ezine zeziphumo ebantwini zidla ngokuphathwa njengento enye

Xa uyifunda uye ezantsi le theyibhile, indlela yeziphumo iyabonakala. Izifundo ezinesiphumo sokuqonda esilinganiswa ngokwenene zezo zotyando, yaye zasebenzisa iyeza elifakwa emthanjeni kwizigulana eziphantsi kweanesthesia. Izifundo kumavolontiya asempilweni zalinganisa imiqondiso yobuchopho kunokucinga.

Okwafunyanwa lilinge lika-2016 kubantu abadala abasempilweni

Esona sifundo sibhekiswa kuso kakhulu ebantwini sanika abantu abadala abasempilweni abangama-26 idosi enye ye-280 mg ngomlomo, malunga ne-4 mg/kg, okanye ikhapsuli yeplacebo ezaliswe nge-FD&C blue no. 2 ukuze zombini zibonakale zifana. Abathathi-nxaxheba baskenwa ngaphambi kokunikwa idosi baza baphinda baskenwa emva kweyure, ngoxa besenza umsebenzi wokuphaphama nokuphendula ngokwasengqondweni nangokwasemzimbeni, olinganisa indlela umntu akhawuleza ngayo ukuqaphela uphawu olubonakalayo olulula, kunye nomsebenzi wokuthelekisa nesampulu emva kokulibaziseka, ovavanya inkumbulo yexesha elifutshane yezinto ezibonwayo.

Iimpendulo zobuchopho zatshintsha. Imethylene blue yandisa umqondiso kwi-insular cortex kumacala omabini ngexesha lomsebenzi wengqalelo (Z = 2.9 to 3.4, P = .01 to .008), nakwimimandla ye-prefrontal, parietal ne-occipital ngexesha lomsebenzi wenkumbulo (Z = 2.9 to 4.2, P = .03 to .0003).

Iziphumo zokuziphatha zezona zishwankathelwa kakhulu xa eli bali libaliswa kwakhona.

1. Ixesha lokuphendula alizange liphucuke. Iqela leplacebo lasuka kwiimilisekondi ezingama-230 laya kwezingama-220. Iqela lemethylene blue lasuka kwiimilisekondi ezingama-230 laya kwezingama-230. Uthelekiso phakathi kwamaqela lwavelisa F = 0.65, P = .43.
2. Iimpendulo ezichanekileyo zokukhumbula zonyuka malunga ne-7% ngaphakathi kweqela elanikwa iyeza, P = .01 kuthelekiso lwangaphambi nasemva ngaphakathi kwelo qela.
3. Loo 7% ayizange ihlale ibalulekile kuvavanyo phakathi kwamaqela. Uthelekiso lwemilinganiselo ephindaphindiweyo yotshintsho kwiimpendulo ezichanekileyo lwavelisa F = 2.96, P = .09.

Utshintsho ngaphakathi kweqela oluhamba nesiphumo sentsebenziswano esingabalulekanga ngokwezibalo luphawu lwesiphumo esinokuba sesokwenene okanye sibe yinguqu engahleliweyo. Isigqibo sephepha ngokwalo sinomda ofanelekileyo: iziphumo “zixhasa uluvo lokuba imethylene blue iphucula ukusebenza kwenkumbulo” yaye zibonelela ngesiseko sezilingo ezizayo. Isiseko asisosiphumo esiqinisekisiweyo. Uphononongo lwethu lobungqina obubanzi ebantwini lulandelela oko kuye kwakhiwa phezu kwaso ukususela ngoko.

Oko iimvavanyo zikulinganisayo ngokwenene

Akukho nasinye kwezi zixhobo silinganisa “inkumbulo” okanye “ugxininiso” ngendlela umfundi athetha ngayo. Ngasinye sifuna into ethile kumntu size sinike amanqaku kwimpendulo, yaye imida yesixhobo ibeka imida yebango ngalinye elenziwa kuso.

Ngoko isiphumo sinokomelela ngokwezibalo kodwa sibe nomda omncinci. Ixesha lokuphendula elingatshintshiyo libonisa ukuba ukuqaphela uphawu akukhawulezanga; alikukhupheli ngaphandle ukukhumbula ngcono isifundo. Amanqaku aphucukayo ovavanyo lokuthelekisa nesampulu emva kokulibaziseka athetha ukuba umfanekiso waqatshelwa ngokuchanekileyo rhoqo ngakumbi; awathethi ukuba umntu uya kukhumbula igama ngomso. Isikhokelo sendlela uncwadi lophando ngezilwanyana olulinganisa ngayo inkumbulo silandela lo mahluko nakwiindlela ezibhidayo nakwiimvavanyo zokuqaphela izinto ezisisiseko samabango amaninzi.

Isifundo esihamba naso asizange sirekhode manqaku konke konke

Kwa-inkqubo yophando efanayo yapapasha uhlalutyo lwesibini oluphuma kwixesha elifanayo lokubhalisa abathathi-nxaxheba, kwiyunivesithi efanayo, ngedosi efanayo nangeplacebo efanayo, ngeli xesha ijonga unxibelelwano ngexesha lokuphumla. Kwabhaliswa abathathi-nxaxheba abangamashumi amabini anesibhozo; uhlalutyo lwemifanekiso lwasebenzisa malunga ne-13 ukuya kwi-15 kwiqela ngalinye.

Imethylene blue yanxulunyaniswa nokuncipha kokuhamba kwegazi ebuchotsheni kuthungelwano lokubona nokuqonda indawo, kunye nokomelela konxibelelwano ngexesha lokuphumla kwizibini ezininzi zemimandla, kuquka ihippocampus yasekhohlo necerebellum yasekunene. Zombini ziingqwalaselo ezinomdla ngendlela uthungelwano olusebenza ngayo. Akukho nanye esisiphumo senkumbulo, yaye iphepha ngokwalo liyatsho: “Ukungabikho kwamanqaku okuziphatha kwesi sifundo nako kungumda.”

Iingxelo ezimbini ezivela kwiqela elinye, kwixesha elinye lokubhalisa nangendlela yedosi enye, zilinge elinye, hayi amabini. Ubungqina bemifanekiso yobuchopho bomntu ngenzuzo yokuqonda abukaphindwa ngokuzimeleyo.

Isifundo esizimeleyo safumana utshintsho oluya kwelinye icala

Umlinganiselo ozimeleyo wavela kwelinye iqela elasebenzisa nenye indlela yokufaka iyeza. USingh noogxa bakhe banika abafazi abasempilweni abasibhozo ukufakwa emthanjeni kweplacebo kunye ne-0.5 ne-1 mg/kg yemethylene blue ngeentsuku ezahlukeneyo, baza balinganisa ukuhamba kwegazi ebuchotsheni, ukukhutshwa kweoksijini egazini, nesantya sokusetyenziswa kweoksijini kwimetabolism yobuchopho.

Zontathu zehla. Ukuhamba kwegazi kubuchopho bonke kwehla malunga ne-8% kuzo zombini iidosi, yaye isantya sokusetyenziswa kweoksijini kwimetabolism sehla ngokubalulekileyo ngokwezibalo. Ababhali babexele kwangaphambili ukuba kuya kubakho ukwanda, baza bakuchaza ngokucacileyo oku kujika, benika iinkcazelo ezimbini: ezi dosi zikuluhlu apho iziphumo zemethylene blue zitshintsha ekukhuthazeni ziye ekuthinteleni, yaye ubuchopho obusempilweni busenokuba nendawo encinci yokuphucuka.

Oko kujika sesona sizathu sokuba ukutolika le khompawundi ngokuthi “okuninzi kungcono” kungasebenzi. Isikhokelo sehormesis sichaza ukumila kwegophe; uluhlu lweedosi oluchazwa njengoluphuculayo kolu ncwadi luphakathi kwe-0.5 ne-4 mg/kg, yaye amaphepha alusebenzisayo athi ngaphezu kwe-10 mg/kg icala lesiphumo liyajika.

Isiphumo sokuqonda esatshintshayo yidelirium emva kotyando

Idelirium yimeko yokubhideka ebukhali ekhula kwiiyure ukuya kwiintsuku, edla ngokuvela kubantu abadala emva kotyando olukhulu. Ayifani nokukhumbula apho izitshixo zikhoyo, kodwa ilinganiswa ngezixhobo eziqinisekisiweyo, yaye sisiphumo sokuqonda.

Izilingo ezintathu ezabelwa ngokungakhethiyo ziye zavavanya ukuba idosi efakwa emthanjeni ngexesha lotyando iyayinciphisa na.

Ulingo luka-2021 lwaxela nokuba ukuphazamiseka kokuqonda kwangethuba emva kotyando ngosuku lwesixhenxe kwehla ukusuka kwi-40.2% ukuya kwi-16.1% (OR 0.30, 95% CI 0.16 to 0.57, P < .001). Uhlalutyo oludibanisa izilingo ezintathu luka-2026, oluquka izigulana ezingama-779, lwadibanisa umlinganiselo wamathuba oyi-0.35 (95% CI 0.23 to 0.53), kungekho kwahluka ngokwezibalo phakathi kwezifundo.

Ezi ziphumo zikhulu ngokwemigangatho yezonyango ejikeleze ixesha lotyando, kodwa azizange zingabi naziphumo zingafunekiyo. Kulingo lokutshintshwa kwamalungu adibanisa amathambo, umkhuhlane emva kotyando wawuxhaphake ngakumbi kwiqela elanikwa iyeza, i-16.5% xa ithelekiswa ne-7.4% (P = .039). Izilingo zotyando lwepancreas nezokutshintshwa kwamalungu adibanisa amathambo ziye zatsala iileta ezipapashiweyo eziya kumhleli, into eyenzeka xa isiphumo siqala ukutshintsha indlela yokunyanga, neyikwabonisa ukuba iinkcukacha ziyaphononongwa.

Kukho nobungqina obulinganisa oku. Uhlalutyo lothungelwano oludibanisa izifundo luka-2026 kwi-The BMJ lwadibanisa izilingo ezili-158 nezigulana ezingama-41,084 ukuze lubeke amayeza ngolandelelwano lokuthintela idelirium. Lwachonga idexmedetomidine njengelona lithembekileyo, kunye neecorticosteroids, amayeza avuselela izamkeli zemelatonin, iparecoxib, iolanzapine neinsulin efakwa ngempumlo. Imethylene blue yayingekho phakathi kwamanyathelo abizwa kolo hlalutyo.

Kutheni impumelelo kwigumbi lotyando ingadluleli ekufundeni

Iiyantlukwano ezine zahlula ezi meko.

1. Abantu ekufundwa ngabo. Izilingo zabhalisa abantu abangaphezu kweminyaka engama-60 ababetyandwa kakhulu, iqela elinomngcipheko ophezulu wokubhideka kwasekuqaleni. Ukuthintela imeko yokubhideka kubuchopho obusesichengeni akufani nokuphucula ubuchopho obusebenza kakuhle.
2. Indlela yokufaka iyeza nemeko. Sonke isiphumo esihle savela ekufakweni emthanjeni ngexesha leanesthesia. Ikhapsuli ibangela ukuba umzimba ufumane iyeza ngendlela eyahlukileyo; uthelekiso lweendlela zokufaka iyeza luchaza ukuba lingakanani iyeza elithathwe ngomlomo elifikelela ebuchotsheni.
3. Isiphumo. Idelirium sisiganeko sezonyango esivavanywa ziingcali zonyango ngezixhobo ezicwangcisiweyo. Ukugcina ugxininiso lonke ixesha lasemva kwemini emsebenzini akunjalo, yaye ulingo olungakwazi ukufihla kakuhle ukuba ngubani ofumana luphi unyango luya kuba nobunzima bokukulilinganisa.
4. Indlela ecetywayo yokusebenza. Amaphepha otyando athi isiphumo sibangelwa kukuncipha kokudumba kuwo wonke umzimba nokugcinwa komqobo ophakathi kwegazi nobuchopho, kunye ne-IL-6 ephantsi. Leyo yingxoxo eyahlukileyo kwibali lokudluliselwa kwee-electron kwiimitochondria elisetyenziselwa ukuthengisa ugxininiso, yaye ubungqina ebantwini buxhasa eyokuqala kakhulu kuneyesibini.

Ilinge elinye ebantwini elafumana inkumbulo engcono

Kulingo luka-2014 kwi-American Journal of Psychiatry, abantu abadala abangama-42 ababenoloyiko olukhulu lweendawo ezivaliweyo banikwa i-260 mg yemethylene blue okanye iplacebo ngoko nangoko emva kweeseshoni ezintandathu zokujongana nento eyoyikwayo, nganye ithatha imizuzu emihlanu kwigumbi elivaliweyo. Inkumbulo yemeko yoqeqesho, eyavavanywa emva kosuku olunye nasemva kweentsuku ezingama-30, yayingcono kwiqela elanikwa iyeza.

Isiphumo soloyiko sasixhomekeke kwimeko. Abathathi-nxaxheba abagqiba iseshoni yokujongana nento eyoyikwayo benoloyiko oluncinci baqhuba ngcono kwinyanga kamva ukuba babefumene imethylene blue; abo iiseshoni zabo zaphela kakubi babethanda ukuqhuba kakubi ngakumbi. Ngoko eyona nto isondeleyo kwisiphumo senkumbulo esibonisiweyo kuncwadi lophando ebantwini yinkumbulo yesiganeko esinye sokufunda elebhu, eyaphucuka xa iyeza lanikwa emva kwesiganeko. Isikhokelo sonyango lokujongana nento eyoyikwayo siphonononga loo ndlela yeziphumo.

Apho yakhangelwa khona yaza ayafunyanwa

Olona vavanyo lude ebantwini lwemethylene blue nokuqonda lwaqhuba iinyanga ezintandathu. Kwisifundo sokutshintshana konyango esabelwa ngokungakhethiyo kwisiphazamiso sebipolar, izigulana ezingama-37 ezazisele zithatha ilamotrigine zafumana i-15 mg njengolawulo olwalubonakala lusebenza okanye i-195 mg njengedosi esebenzayo. Amanqaku okudakumba nokuxhalaba aphucuka kwidosi ephezulu. Ingxelo yephepha ngokuqonda ingumgca omnye: “Iziphumo zemethylene blue kwiimpawu zokuqonda zazingabalulekanga ngokwezibalo.”

Uyilo lwalusebenzisa ulawulo olusebenzayo kuba imethylene blue itshintsha umbala womchamo, yaye ababhali bagqiba kwelokuba iplacebo engasebenziyo yayingayi kukwazi ukugcina unyango lufihlakele. Loo ngxaki yokufihla unyango iyaphinda kulo lonke eli candelo, yaye isikhokelo sesizathu sokuba kube nzima ukufihla unyango kwizilingo zemethylene blue sichaza indlela oko okuchaphazela ngayo ukutolikwa kweziphumo ezixhomekeke kumava omntu.

Ezona zilingo zikhulu zenkumbulo ebantwini zasebenzisa enye ikhompawundi

Olona vavanyo lukhulu lweyeza losapho lwemethylene blue lwenkumbulo lwaluyinkqubo ye-Alzheimer, yaye aluzange lusebenzise imethylene blue. Lwasebenzisa ihydromethylthionine mesylate, uhlobo oluncitshiswe ngokwekhemikhali lwesiseko esifanayo sephenothiazine oluzinziswe njengetyuwa, olwaphuhliswa njengesithinteli sokudibana kweeproteni zetau. Olona lingo lwamva nje lwesigaba 3 lwabhalisa abathathi-nxaxheba abangama-598 abanokuphazamiseka kokuqonda okungephi okanye isifo sengqondo esixhalabisayo se-Alzheimer esingephi ukuya kwesiphakathi kumaziko angama-82, yaye aluzange lufikelele kwiziphumo zalo ezibini eziphambili kwiiveki ezingama-52. Isizathu esichaziweyo sifundisa lukhulu: iqela lolawulo laphucuka, nto leyo ababhali abayinxulumanisa nolawulo ngokwalo, i-4 mg yemethylthioninium chloride kabini ngeveki, eyakhethwa njengento engasebenziyo yokufaka umbala kumchamo ukuze kugcinwe ukufihlwa konyango. Umahluko obalulekileyo ngokwezibalo wavela kuphela kwiqela elincinci elinokuphazamiseka kokuqonda okungephi, kwiiveki ezingama-78 nezili-104, kuhlalutyo lokuqalisa okulibazisekileyo. Ingxelo yangaphambili yesigaba 3 yenkqubo efanayo yafumana iziphumo zayo ezibalulekileyo kuhlalutyo olwaluhlaziyiwe ngaphambi kokutyhilwa konyango, kuthelekiswa amaqela amancinci onyango ngeyeza elinye awayengabelwanga ngokungakhethiyo. Isikhokelo sezilingo ze-Alzheimer sihlalutya oko ezo zilingo zikungqinayo.

Indlela esiya kuba ngayo isifundo esifanele ukukholelwa

Ulingo olunokuxhasa ibango ngenkumbulo okanye ugxininiso luya kufuna abantu abadala abasempilweni abangenasikhalazo sokuqonda esele sikhona, iidosi eziphindaphindiweyo kangangeeveki, uthelekiso olufihla ukuba yeyiphi ikhapsuli enantoni, iziphumo ezimiselwe kwangaphambili, kunye neqela labaphandi elizimeleyo. Akukho nto ingafanelekanga kolo luhlu. Kuphela nje ayikenziwa.

Ukuba usacinga ukuyisebenzisa

Imiba emibini yokhuseleko iza ngaphambi kwayo nayiphi ingxoxo yenzuzo. Imethylene blue ithintela imonoamine oxidase A, nto leyo eyenza ukusetyenziswa kwayo kunye namayeza amiselweyo okudakumba namanye amayeza achaphazela iserotonin kube ngumcimbi obalulekileyo, yaye inkxalabo sisifo seserotonin kunokuba ibe lunxibelelwano olungephi. Ikwangavumelekanga xa kukho ukusilela kwe-G6PD ngenxa yeanemia ebangelwa kukutshatyalaliswa kweeseli ezibomvu zegazi. Isalathiso sokhuseleko kunye nesikhokelo sonxibelelwano lwamayeza zicwangcisa loo mibuzo ngokweendidi zamayeza.

Ukuba inkumbulo okanye ukukwazi ukugxila kutshintshile ngokwenene, inyathelo lokuqala ayisosongezelelo. Isifo sedlala lengqula, ukunqumama kokuphefumla ebuthongweni, i-B12 ephantsi, ukudakumba namayeza aliqela amiselweyo avelisa kanye uphawu oluthengelwa iyeza lokuphucula ukuqonda, yaye isikhokelo sobungqina bedlala lengqula sibonisa ukuba kangaphi kukho unobangela onokunyangwa ngaphantsi kwalo.

Into esetyenziswayo yinxalenye etshintshayo kwisifundo ngasinye esingentla

Yonke idosi echazwe apha yayisisixa esilinganisiweyo sekhompawundi echaziweyo, evela kumenzi wamayeza, ehamba nesatifikethi sohlalutyo. Ibhotile evela kumthengisi ongaqinisekiswanga ayiyiyo loo nto. Ukuthobela imonograph ye-USP ngumgangatho umthengi anokuwujonga, yaye into engawuthobeliyo kusenokwenzeka ukuba yeyenqanaba lokusetyenziswa kumalaphu, enokuthwala ukungcola kwezinto eziphilayo ezifana ne-Azure B, iintsalela zezinyibilikisi nezinyithi ezinzima kumanqanaba ancitshiswa ngumgangatho ochaziweyo wamayeza. Oko ukuchazwa njenge-USP kukungqinayo nokungakungqiniyo kuchaza elo nqanaba ngokwalo.

Uninzi lwabathengisi abachaza imveliso njengevavanywe liqela lesithathu luvavanya izinyithi ezinzima kuphela luze lubonise elo qela linye leemvavanyo njengokuthobela ngokupheleleyo. Blupreme ivavanya wonke umgangatho ochaziweyo we-USP: isazisi, ubunyulu, ukungcola kwezinto eziphilayo, iintsalela zezinyibilikisi, ukungcola kwee-elementi, intsalela emva kokutshiswa, imida yeentsholongwane, kunye nee-endotoxin zebhaktheriya. Ibhetshi nganye ithunyelwa nesatifikethi sohlalutyo, yaye ukusifunda ngokuchanekileyo kuthetha ukuthelekisa inombolo yebhetshi nelebhu nebhotile oyiphetheyo. Akukho nanye kwezo zinto eyenza inzuzo yokuqonda, yaye imveliso engenako ukubhala ubungqina besazisi sayo yindawo engafanelekanga yokuqala ukuvavanya ibango.

Isigqibo

Akukho lingo linike imethylene blue kubantu abadala abasempilweni laza labonisa inzuzo yenkumbulo okanye yengqalelo kuneplacebo. Ilinge lika-2016 latshintsha imiqondiso yobuchopho, lashiya ixesha lokuphendula lingatshintshanga, laza lavelisa ukuphucuka kokukhumbula okwakungabalulekanga ngokwezibalo xa amaqela ethelekiswa. Iphepha elihamba nalo alizange lirekhode manqaku eemvavanyo. Iqela elizimeleyo lafumanisa ukuba ukuhamba kwegazi nokusetyenziswa kweoksijini kwimetabolism kwakusihla, kunganyuki.

Isiphumo sokuqonda ebantwini esixhaswa bubungqina sivela kutyando, apho idosi efakwa emthanjeni kwizigulana ezikhulileyo yanciphisa izinga ledelirium emva kotyando malunga nesiqingatha kwizilingo ezintathu nakuhlalutyo oluzidibanisayo. Eso sisiphumo sokwenene ngezigulana ezigula ngokubukhali, yaye olona hlanganiso lukhulu oluzimeleyo lophando lokuthintela idelirium aluzange luchonge eli yeza ngokukhethekileyo. Libango elinomda omncinci kakhulu kunelo lithengiswayo, yaye indawo yalo isesibhedlele.

Imephu yeendlela zokusebenza kwiiseli ichaza oko le khompawundi ikwenzayo kwiimodeli zaselebhu, uphononongo lobungqina be-ADHD lulandela umbuzo wengqalelo kubantu abafunyaniswe beneso sifo, yaye ithala lophando lidwelisa izifundo ezixhasa ibango ngalinye kweli phepha.