Methylene blue pa masewera olimbitsa thupi ndi kuchira: zimene zayesedwadi

Mu March 2022, wothamanga marathon wa mulingo wapamwamba analemba uthenga wolipiridwa wotsatsa piritsi loyamwa la methylene blue, ponena kuti “lingathandize kuwonjezera kusamala, kupirira ndi kugona” komanso kuti ankaligwiritsa ntchito asanachite masewera ovuta olimbitsa thupi. Sabata yomweyo, madokotala amene mawu awo analembedwa m’nyuzipepala za dziko anafotokoza khalidwe lofalalo ngati anthu otchuka pa malo ochezera a pa intaneti akumwa chotsukira thanki ya nsomba. Palibe mwa maganizo awiriwa amene amayankha funso lenileni la wothamanga.

Kodi pali amene wapatsa anthu methylene blue n’kuyeza mtunda umene anathamanga, liwiro lawo, kapena mmene anachirira? Kufufuza kochitira nkhaniyi sikunapeze ngakhale kafukufuku mmodzi woyerekeza magulu a anthu amene anayeza zotsatira za luso lochita masewera olimbitsa thupi kapena kuchira. Kafukufuku amene amatchulidwa motsatizana anagwiritsa ntchito mitundu itatu ya nyama, zinthu zosiyanasiyana zokonzedwa mu labotale, ndi mankhwala amodzi amene si methylene blue n’komwe.

Kupirira, kuchira, ndi mmene chinthu chimagwirira ntchito ndi zonena zosiyana

Chizindikiro chingasinthe mosiyana ndi luso lochita masewera, kapena chingasinthe popanda luso kusintha n’komwe. Imeneyi si mfundo yaing’ono ya ukatswiri: ndi zimene zinachitika mu kafukufuku wa methylene blue pa masewera olimbitsa thupi amene amatchulidwa kwambiri.

Kafukufuku wa agalu anagwiritsa ntchito utoto wina

Pepala limene limatchulidwa kwambiri pa nkhani ya methylene blue ndi masewera olimbitsa thupi ndi kafukufuku wa Imai ndi anzake wa 1986 wa agalu ogalamuka othamanga pa makina. Anafufuza ngati kuwonjezeka kwa magazi amene mtima umapopa pochita masewera kumadalira mkhalidwe wa redox m’minofu, pogwiritsa ntchito zimene gawo lofotokoza njira linatcha “4 mg/kg ya new methylene blue 3,7-bis(ethylamino)-2,8-dimethylphenazothonium chloride, Eastman Kodak Company”. New methylene blue ndi utoto wina wa thiazine, wokhala ndi magulu awiri a ethylamino pomwe methylene blue ili ndi magulu awiri a dimethylamino, ndipo umadziwika kwambiri ngati utoto wodetsera maselo a reticulocyte kuti awonekere pofufuza. Zotsatira zopezedwa pogwiritsa ntchito utotowu si zotsatira zopezedwa pogwiritsa ntchito methylene blue.

Kafukufukuyu akadali wofunika, chifukwa amasonyeza momveka kwambiri kuti chizindikiro ndi kagwiridwe ka thupi zingasinthe mosiyana. Agalu anathamanga magawo awiri a mphindi 20 pa 2.5 kenako 5.0 mph, pa malo okwera ndi 6 peresenti. Masewerawo anachulukitsa kaŵiri magazi amene mtima umapopa ndi kuwonjezera kugwiritsa ntchito oxygen kwa thupi lonse katatu mpaka kanayi m’magulu onse awiri. M’gulu lopatsidwa madzi amchere, chiŵerengero cha lactate ndi pyruvate m’magazi a m’mitsempha yochoka ku mtima chinakwera kuchokera pa 6.0 kufika pa 9.97. M’gulu lopatsidwa utotocho sichinakwere.

Miyezo yonse ya kagwiridwe ka thupi sinasinthe. Kugunda kwa mtima, kuthamanga kwa magazi m’mitsempha yochoka ku mtima, mphamvu yokokana ya chipinda cha kumanzere cha pansi cha mtima, ndi catecholamines m’madzi a magazi zinakwera mofanana m’magulu onse awiri, ndipo ubale wa magazi amene mtima umapopa ndi kugwiritsa ntchito oxygen kwa thupi lonse sunali wosiyana malinga ndi ziŵerengero. Olembawo anamaliza kuti kusintha kwa chiŵerengerochi “sikukuyambitsa kulimbikitsidwa kwa kayendedwe ka magazi komwe kumachitika pa masewera opepuka mpaka apakatikati.”

Chiŵerengerochi sichipereka umboni wamphamvu monga chimaonekera. Chinatsika chifukwa pyruvate inakwera, kuchokera pa 0.14 kufika pa 0.38 mmol pa lita, pamene lactate nayonso inakwera, kuchokera pa 1.05 kufika pa 2.85 mmol pa lita. Kwa agalu amene anapatsidwa utotowo ali opuma, kugwiritsa ntchito oxygen kunakwera pang’ono, pH ya magazi a m’mitsempha yochoka ku mtima inakwera, ndipo carbon dioxide inatsika. Olembawo anati kusintha kumeneku kunali “kofanana” ndi kwa 2,4-dinitrophenol, chinthu chimene chimasiyanitsa kupuma kwa mitochondria ndi kupanga ATP. Liwiro linakhazikitsidwa ndi ndondomeko ya kafukufukuyo, choncho palibe galu amene anathamangitsidwa mpaka kutopa kotheratu.

Kafukufuku wa makoswe osambira, ndi mlingo wake

Zotsatira zamphamvu kwambiri za luso lochita masewera m’nyama zili mu mayeso a Peng ndi anzake a 2025 mu Frontiers in Behavioral Neuroscience. Makoswe anasambira mausiku khumi otsatizana, ali ndi zolemera zofanana ndi 3 peresenti ya kulemera kwa thupi zomangidwa ku michira yawo, kwa maola osachepera awiri usiku uliwonse, mpaka kufika pa mulingo wa kutopa kotheratu umene unkayesedwa ndi mfundo. Pambuyo pa ulendo uliwonse, gulu limodzi linapatsidwa methylene blue kudzera m’mphuno ndipo lina linapatsidwa madzi amchere mofananamo. Makoswe opatsidwa methylene blue anasambira nthawi yaitali asanakwaniritse zizindikiro za kutopa kotheratu, anayendayenda kwambiri pamalo otseguka tsiku lotsatira, anasonyeza khalidwe lochepa lofanana ndi nkhawa, ndipo anali ndi kuchepa kwa kutayika kwa maselo a mitsempha, kuwonongeka kwa myelin, ndi kugawikagawika kwa mitochondria mu hippocampus ndi striatum.

Mlingowo nthawi zambiri umasiyidwa pofotokozanso kafukufukuyu. Madzi okhala ndi 1 peresenti ya mankhwalawa ali ndi 10 mg/mL; ma microlitre khumi anaikidwa m’dzenje lililonse la mphuno, choncho zonse pamodzi zinali pafupifupi ma microlitre 20, kapena 0.2 mg pa khoswe pa ulendo uliwonse. Kupereka kudzera m’mphuno kumasankhidwa kuti mankhwalawo afike ku ubongo kudzera m’njira za mitsempha ya kununkhiza ndi ya trigeminal, ndipo olembawo ananena kuti kafukufuku wawo “sanayeze zochitika za oxidation, kutupa, kapena milingo ya mahomoni mu ubongo ndi m’madzi a magazi.” Njira yotsatira imene analimbikitsa ndi kufufuza “zotsatira zonse za kugwiritsa ntchito MB monga chowonjezera asanayambe masewera olimbitsa thupi.”

Zimenezo ndi zimene wothamanga angafune kuti ziyesedwe. Ndondomeko imeneyi inapereka mankhwalawo pambuyo pa ntchito ya thupi, kuti ichepetse kuvulala. Kusambira nthawi yaitali tsiku lotsatira m’makoswe otopetsedwa ndi zotsatira zokhudza kuchira, osati zotsatira zokhudza munthu wophunzitsidwa amene wamwa mlingo asanayambe masewera.

Kumene mawu akuti “kupirira” anachokera

Kafukufuku wa mbewa amene nthawi zambiri amafotokozedwa kuti anasonyeza kuwonjezeka kwa kupirira ndi ntchito ya Gureev ndi anzake ya 2016 mu Neuroscience Research. Mbewa zinamwa madzi okhala ndi methylene blue pa mlingo wa 15 mg/kg patsiku kwa masiku 60. “Kupirira kwa thupi” kunali mayeso a chingwe, kapena zitsulo zopingasa, amene amaphatikiza mphamvu yogwira, kugwirizana kwa mayendedwe a thupi, ndi kusagwa poyeza mfundo. Mbewa za zaka zapakatikati zosapatsidwa mankhwalawo zinapeza 1.17; zopatsidwa mankhwalawo zinapeza 2.23, pafupi ndi mulingo wa mbewa zazikulu. Mbewa zazikulu sizinasonyeze kusintha kwabwino pa chilichonse.

Kugwiritsa ntchito oxygen popuma kunakwera pafupifupi 15 peresenti. Kupanga hydrogen peroxide mu mitochondria ya ubongo kunakwera kuchokera pa 94.9 kufika pa 176.7 pmol pa mphindi pa milligram ya mapuloteni. DNA ya mitochondria inachuluka ka 2.3. Zimenezi ndi kuwonjezeka kwa kusinthidwa kwa mitochondria m’nyama zokalamba, pamodzi ndi kutumiza zizindikiro kudzera mu oxidation komwe kumayendetsa kusinthako. Sizikusonyeza kuti katswiri wamasewera wathanzi angayende kapena kuthamanga msanga.

Mayeso a maselo, ndi malire ake

Louters ndi anzake ananena mu 2005 kuti methylene blue imalimbikitsa kulowetsedwa kwa glucose kudzera mu GLUT1 m’maselo a fibroblast a L929, mpaka 800 peresenti pa 50 micromolar. Kafukufuku wotsatira wa 2008 anasonyeza kuti methyl-beta-cyclodextrin imamangirira methylene blue mwachindunji n’kulepheretsa zotsatirazo. Zimenezi ndi zotsatira za mtundu wa maselo olimidwa mu labotale, zomwe sizinasonyezedwepo m’minofu yosuntha mafupa.

Ngakhale mmene imagwirira ntchito pakadalibe mgwirizano

Mu kafukufuku wa Tretter ndi anzake wa 2014 wa mitochondria yochotsedwa mu ubongo wa nkhumba za ku Guinea, methylene blue pa 100 nanomolar mpaka 1 micromolar inawonjezera kugwiritsa ntchito oxygen popuma, inabwezeretsa kusiyana kwa mphamvu yamagetsi pa nembanemba ndi kupanga ATP pamene Complex I kapena Complex III inalepheretsedwa, ndipo inawonjezera kupanga hydrogen peroxide. Chofunika kwambiri n’chakuti “kupuma kolimbikitsidwa ndi ADP sikunakhudzidwe ndi MB pa chilichonse mwa zinthu zoyambira” zimene zinayesedwa. Kupuma kwakukulu kwambiri kogwirizana ndi kupanga ATP, komwe zonena za masewera olimbitsa thupi zimadalira, sikunawonjezeke.

Mu kafukufuku wotsatira wa Gureev ndi anzake wa 2019, labotale yomweyo imene inapeza zotsatira za mbewa inapeza kuti methylene blue “imalephera kubwezeretsa kusiyana kwa mphamvu yamagetsi pa nembanemba ndi kupuma kolepheretsedwa ndi antimycin” mu mitochondria ya ubongo wa mbewa. Inamaliza kuti malo olandira ma electron ndi Qo a Complex III, osati malo ena aliwonse otsatira panjira imeneyi. Lingaliro losavuta lakuti utotowo umanyamula ma electron kudutsa mbali yotsekedwa ya unyolo wa kupuma siligwira ntchito m’zinthu zonse zokonzedwa kuti ziyesedwe.

Palibe mwa zimenezi chimene chimakana kuti pangakhale zotsatira mwa anthu. Koma zimatanthauza kuti mfundo yodalira mmene imagwirira ntchito yokha, imene imaona zochitika za mankhwala mu mitochondria zomwe zingatheke ngati kuti ndi zotsatira zotsimikizika, ili ndi mavuto ngakhale pa kufotokoza mmene imagwirira ntchitoyo.

Mavuto awiri a kapangidwe amene kafukufuku wa anthu ayenera kuthetsa

N’zovuta kubisa kwa otenga nawo mbali kuti apatsidwa methylene blue. Imasintha mkodzo kukhala wabuluu wobiriwira ndipo anthu amazindikira. Kafukufuku wa 2017 wa anthu omwe ali ndi bipolar disorder, amene anasinthana milingo ya mankhwala, ananena zimenezi mwachindunji: “Tinasankha kapangidwe kameneka chifukwa methylene blue imasintha mtundu wa mkodzo, choncho sitinathe kugwiritsa ntchito placebo yachizolowezi.” Kafukufukuyu anayerekeza mlingo wochepa ndi mlingo waukulu m'malo moyerekeza ndi piritsi lopanda mankhwala ogwira ntchito.

Vutoli ndi lalikulu kwambiri pa kafukufuku wa masewera olimbitsa thupi kuposa pafupifupi m’mbali zina zonse, chifukwa khama limene munthu akumva kuti akugwiritsa ntchito ndi zotsatira za mayeso othamanga pa nthawi zimakhudzidwa kwambiri ndi zimene akuyembekezera. Kafukufuku amene sangathe kubisa zimene otenga nawo mbali apatsidwa amakhala atayeza chikhulupiriro mofanana ndi mankhwala.

Pali njira yothetsera vutoli yolembedwa. Kafukufuku wa 2016 wogawa mwamwayi anthu akuluakulu athanzi 26 m’magulu ndi kuwajambula ubongo unapereka 280 mg ya methylene blue ya mulingo wa USP, pafupifupi 4 mg/kg, kapena placebo ya utoto wa chakudya wa FD&C blue no. 2 m’makapisozi ofanana osaonetsa mkati. Unapempha otenga nawo mbali kuti akodze asanapatsidwe mlingowo koma osakodzanso, “kuti tipewe kusokoneza kubisidwa kwa mankhwala chifukwa cha kusintha kulikonse kwa mtundu wa mkodzo.”

Vuto lachiwiri ndi mlingo ndi njira yoperekera. Mbali ya methylene blue yomwedwa pakamwa imatulutsidwa m’mkodzo, ndipo kuchuluka komwe kumafika ku ubongo ikamwedwa pakamwa ndi pafupifupi theka la komwe kumafika ikaperekedwa mumtsempha, monga gulu la Gureev limanenera potchula ntchito ya Peter ndi anzake yofufuza mmene mankhwala amayendera m’thupi. Kupereka m’mphuno mwa khoswe sikungafanane mwachindunji ndi kapisozi, ndipo milingo ya anthu mu kafukufuku wofalitsidwa ili pa 0.5 mpaka 4 mg/kg, pamene kafukufuku wojambula ubongo wa 2016 ananena kuti zotsatira zimakhala zosiyana pamwamba pa 10 mg/kg.

Kafukufuku wa anthu amayeza zinthu zina

Mayeso awiri oyerekeza magulu a anthu amatchulidwa pofotokozanso nkhaniyi, ndipo palibe amene anayeza masewera olimbitsa thupi. Mu kafukufuku wojambula ubongo wa 2016, nthawi yoyankhira pa mayeso a kukhala tcheru sinasonyeze kugwirizana kwakukulu pakati pa mankhwala ndi nthawi, ndipo gulu la placebo linali pa 230 kenako 220 milliseconds, pamene la methylene blue linali pa 230 kenako 230 milliseconds, P = .43. Mu kafukufuku wa 2023 wopereka mankhwala mumtsempha mwa akazi athanzi asanu ndi atatu, kuyenda kwa magazi mu ubongo ndi mulingo wa kugwiritsa ntchito oxygen mu ubongo zonse zinatsika m'malo mokwera. Buku lofotokoza umboni pa mphamvu ndi kutopa limafotokoza kafukufuku onse awiriwa.

Ngati mwasankha kuyesabe

Kudziyesa nokha sikudzatsimikizira kuti mankhwalawo amagwira ntchito, koma mungalembe zimene mwachita ndi zimene zachitika mokwanira kuti musadzinyenge. Lembani chinthucho ndi nambala ya gulu limene chinapangidwira, njira yoperekera, nthawi yomwe mwachigwiritsa ntchito musanayambe maphunziro, masewera enieni pamodzi ndi mtunda kapena kulemera komwe mwagwiritsa ntchito, khama limene mukumva pa sikelo ya manambala, kugona, caffeine ndi mankhwala aliwonse, komanso kupweteka kwa minofu tsiku lotsatira ndi luso lanu pakatha maola 48 pochita masewera amtundu womwewo. Kenako bwerezani masewera omwewo osachigwiritsa ntchito.

Munthu mmodzi amene akutsata chinthu chimodzi sichingamuthandize kusiyanitsa zotsatira za mankhwala ndi kulimba kwa thupi, chikhumbo chochita masewera, nyengo, ndi kusinthasintha kwachibadwa kwa maphunziro. Mbali ya mmene munthu amamvera ndiyo ingasocheretse kwambiri.

Methylene blue ilinso ndi zoopsa zosakhudzana ndi luso lochita masewera. Imalepheretsa monoamine oxidase A, zomwe zimabweretsa nkhani ya kuigwiritsa ntchito pamodzi ndi mankhwala olembedwa ndi dokotala ochepetsa kuvutika maganizo komanso mankhwala ena okhudza serotonin. Siyenera kugwiritsidwa ntchito kwa anthu omwe ali ndi kuperewera kwa G6PD chifukwa cha chiopsezo cha kuchepa kwa magazi chifukwa cha kuwonongeka kwa maselo ofiira. Buku lofotokoza chitetezo limafotokoza zonsezi, ndipo buku lofotokoza kugwirizana kwa mankhwala limagawa mafunso a mankhwala malinga ndi magulu awo. Ngati mumachita mipikisano yotsatira malamulo oletsa mankhwala owonjezera luso mosaloledwa, onani malamulo m'malo modalira zimene wogulitsa akunena.

Chinthu chogwiritsidwa ntchito ndi chimodzi mwa zinthu zosintha mu kafukufuku aliyense pamwambapa

Mlingo uliwonse wofotokozedwa pano unali kuchuluka koyezedwa kwa mankhwala odziwika bwino. Botolo lochokera kwa wogulitsa wosatsimikiziridwa silifanana ndi zimenezo. Kutsatira zofunikira zonse za methylene blue zolembedwa mu USP ndi muyezo umene wogula angathe kuona. Chinthu chosatsatira zofunikirazi chingakhale cha mulingo wogwiritsira ntchito pa nsalu, ndipo chingakhale ndi zonyansa za organic monga Azure B, zotsalira za zosungunulira, ndi zitsulo zolemera pa milingo imene zofunikira za mankhwala zimaika malire. Zimene dzina la USP limatsimikizira ndi zimene silitsimikizira zimafotokoza mulingowo, ndipo njira zoyezera zonyansa zimafotokoza zimene labotale imafufuza.

Ogulitsa ambiri amene amafotokoza chinthu kuti chayesedwa ndi gulu lodziyimira palokha amangofufuza zitsulo zolemera zokha, kenako amapereka mayeso amodziwo ngati kuti akwaniritsa zofunikira zonse. Blupreme imayesa zofunikira zonse za USP: kutsimikizira kuti ndi chinthu choyenera, kuyera kwake, zonyansa za organic, zotsalira za zosungunulira, zonyansa za ma element, zotsalira pambuyo powotcha, malire a tizilombo, ndi endotoxins za mabakiteriya. Gulu lililonse lopangidwa limatumizidwa ndi satifiketi ya zotsatira za kuyesa, ndipo kuiwerenga molondola kumatanthauza kufananitsa nambala ya gululo ndi labotale ndi botolo limene muli nalo.

Mfundo yaikulu

Palibe kafukufuku woyerekeza magulu a anthu amene wayeza methylene blue pa kupirira, liwiro, mphamvu, kapena kuchira. Kafukufuku wa agalu amene amatchulidwa pa zotsatira za lactate anagwiritsa ntchito utoto wina ndipo sanapeze kusiyana kwa luso lochita masewera. Kafukufuku wa makoswe osambira anapereka 0.2 mg kudzera m’mphuno pambuyo pa ntchito ya thupi. Kafukufuku wa mbewa amene anabweretsa mawu akuti “kupirira” anagwiritsa ntchito mayeso a kugwira ndi kugwirizana kwa mayendedwe m’nyama zokalamba, ndipo kafukufuku wofalitsidwa wokhudza mitochondria sakugwirizana pa mmene mankhwalawa amagwirira ntchito.

Chotsala ndi njira yogwirira ntchito yomwe ingaoneke yotheka, zotsatira zingapo za mayeso ang’onoang’ono a nyama, vuto limodzi la kapangidwe ka kafukufuku lokhala ndi njira yothetsera yolembedwa, komanso kusowa kwa deta ya luso lochita masewera mwa anthu. Ndemanga ya umboni wa phindu mwa anthu imaika zonena za masewera olimbitsa thupi pambali pa kafukufuku wina wa anthu, ndipo laibulale ya kafukufuku imandandalika kafukufuku amene ali kumbuyo kwa zonena zilizonse.

Ngati mukuphunzira kuti muchite chinachake, chinthu chimene chili ndi umboni wamphamvu kwambiri ndi maphunzirowo enieni.