Methylene blue don motsa jiki da farfaɗowa: abin da aka auna a zahiri

A watan Maris 2022, wata fitacciyar mai tseren gudun marathon ta wallafa tallan goyon baya da aka biya ta yi wa ƙwayar methylene blue da ake tsotsa, tana cewa tana "iya taimakawa wajen inganta mayar da hankali, juriya da barci", kuma tana amfani da ita kafin atisaye mai tsanani. A wannan makon, likitocin da jaridun ƙasa suka ambato sun bayyana wannan al'ada mai yaɗuwa a matsayin masu tasiri a kafafen sada zumunta suna shanye sinadarin tsaftace tankin kifi. Babu ɗaya daga cikin waɗannan ra'ayoyi da ya amsa tambayar da mai gudu yake da ita a zahiri.

Shin wani ya taɓa ba mutane methylene blue sannan ya auna nisan da suka iya yi, saurinsu, ko yadda suka farfaɗo? Binciken da aka yi don wannan maƙala bai gano ko da gwajin mutane guda ɗaya da ke da rukunin kwatantawa kuma ya auna sakamakon ƙwarewar motsa jiki ko farfaɗowa ba. Jerin binciken da ake ambata ya ƙunshi nau'in dabbobi uku, shirye-shiryen gwaji da dama a ɗakin bincike, da wani sinadari guda ɗaya wanda ba methylene blue ba ne kwata-kwata.

Juriya, farfaɗowa, da hanyar aiki ikirari ne daban-daban

Manuniya na iya sauyawa akasin ƙwarewar motsa jiki, ko kuma ta sauya ba tare da ƙwarewar motsa jiki ta sauya ko kaɗan ba. Wannan ba ƙaramin bambancin fasaha ba ne: shi ne ainihin tsarin da aka gani a binciken methylene blue kan motsa jiki da aka fi ambata.

Binciken karnuka ya yi amfani da wani rini na daban

Maƙalar da aka fi ambata game da methylene blue da motsa jiki ita ce binciken Imai da abokan aikinsa na 1986 kan karnuka masu farkawa da suka yi gudu a na'urar gudu. Ya gwada ko ƙaruwar yawan jinin da zuciya ke fitarwa yayin motsa jiki ta dogara da yanayin karɓa da bayar da electron a kyallen jiki, ta amfani da abin da sashen hanyoyin gwajin ya bayyana a matsayin "4 mg/kg na new methylene blue 3,7-bis(ethylamino)-2,8-dimethylphenazothonium chloride, Eastman Kodak Company". New methylene blue wani rinin thiazine ne na daban, yana da rukunin ethylamino biyu a inda methylene blue yake da rukunin dimethylamino biyu, kuma an fi saninsa a matsayin rinin reticulocyte. Sakamakon da aka samu da shi ba sakamakon da aka samu da methylene blue ba ne.

Har yanzu binciken yana da muhimmanci, domin shi ne mafi bayyanannen nuna cewa manuniya da aikin jiki na iya sauyawa dabam da juna. Karnuka sun yi gudu a matakai biyu na mintuna 20 kowanne, da saurin 2.5 sannan 5.0 mph, a gangara mai hawa kashi 6 cikin ɗari. Motsa jiki ya ninka yawan jinin da zuciya ke fitarwa sau biyu, ya kuma ƙara amfani da iskar oxygen na dukkan jiki ninki uku zuwa huɗu a rukunonin biyu. A rukunin da aka ba ruwan gishiri, rabon lactate zuwa pyruvate a jinin jijiyoyin da ke fita daga zuciya ya tashi daga 6.0 zuwa 9.97. A rukunin da aka ba rinin, bai tashi ba.

Babu wata ma'aunin aiki da ta sauya. Saurin bugun zuciya, matsin jini a jijiyoyin da ke fita daga zuciya, ƙarfin matsewar ɗakin zuciya na ƙasa na hagu, da catecholamines a ruwan jini sun ƙaru iri ɗaya a rukunonin biyu, kuma ba a iya bambanta alaƙar yawan jinin da zuciya ke fitarwa da amfani da iskar oxygen na dukkan jiki ta fuskar ƙididdiga ba. Marubutan sun kammala cewa sauye-sauyen rabon "ba su da alaƙar sanadi da ƙarfafa zagayawar jini da ke faruwa yayin motsa jiki mai sauƙi zuwa matsakaici."

Rabon bai da ƙarfin shaida kamar yadda yake bayyana. Ya ragu ne saboda pyruvate ya ƙaru, daga 0.14 zuwa 0.38 mmol a kowace lita, yayin da lactate ma ya ƙaru, daga 1.05 zuwa 2.85 mmol a kowace lita. A karnukan da aka ba rinin suna hutawa, amfani da iskar oxygen ya ɗan ƙaru, pH na jinin jijiyoyin da ke fita daga zuciya ya tashi, sannan carbon dioxide ya ragu. Marubutan sun ce waɗannan sauye-sauyen sun "yi kama" da na 2,4-dinitrophenol, wani sinadari da ke raba numfashin mitochondria da samar da ATP. Tsarin gwajin ya kayyade saurin gudu, don haka ba a sa wani kare ya yi gudu har ya gaji ƙwarai ba.

Binciken iyon beraye, da adadin da aka ba su

Sakamakon ƙwarewar motsa jiki mafi ƙarfi a dabbobi shi ne gwajin Peng da abokan aikinsa na 2025 a Frontiers in Behavioral Neuroscience. Beraye sun yi iyo na dare goma a jere, da nauyin da ya kai kashi 3 cikin ɗari na nauyin jikinsu a ɗaure a wutsiyoyinsu, aƙalla sa'o'i biyu kowane dare, har sai sun kai ma'aunin gajiya ƙwarai da aka tsara. Bayan kowane atisaye, an ba wani rukuni methylene blue ta hanci, wani kuma ya karɓi ruwan gishiri ta wannan hanyar. Berayen da aka ba methylene blue sun yi iyo na tsawon lokaci kafin su cika sharuɗɗan gajiya ƙwarai, sun fi motsi a fili buɗe washegari, sun nuna ƙarancin halaye masu kama da damuwa, kuma sun samu ƙarancin asarar ƙwayoyin jijiyoyi, tangarɗar myelin, da tarwatsewar mitochondria a hippocampus da striatum.

Ana yawan barin adadin da aka ba su a sake ba da labarin binciken. Maganin ruwa mai kashi 1 cikin ɗari shi ne 10 mg/mL; an saka microlita goma a kowace kafar hanci, don haka jimillar ta kai kusan microlita 20, ko 0.2 mg ga kowane bera bayan kowane atisaye. An zaɓi bayarwa ta hanci domin ya isa ƙwaƙwalwa ta hanyoyin jijiyar wari da jijiyar trigeminal, kuma marubutan sun bayyana cewa bincikensu "bai auna halayen oxidation, kumburi, ko matakan hormones a ƙwaƙwalwa da ruwan jini ba." Mataki na gaba da suka ba da shawara shi ne nazarin "cikakkun tasirin ƙarin MB kafin motsa jiki."

Wannan shi ne abin da mai gudu zai so a gwada. Wannan tsarin gwajin ya ba da sinadarin bayan aikin, domin rage rauni. Yin iyo na tsawon lokaci washegari a tsarin gwajin berayen da suka gaji ƙwarai sakamako ne game da farfaɗowa, ba sakamako game da ɗan Adam mai atisaye da ya ɗauki sinadarin kafin atisaye ba.

Daga ina kalmar "juriya" ta fito

Binciken ƙananan beraye da ake yawan bayyana a matsayin wanda ya nuna ingantacciyar juriya shi ne aikin Gureev da abokan aikinsa na 2016 a Neuroscience Research. Ƙananan beraye sun sha ruwa mai methylene blue a adadin 15 mg/kg a kowace rana na kwanaki 60. "Juriyar jiki" ita ce gwajin igiya, ko sanduna kwance, wanda yake haɗa auna ƙarfin riƙo, daidaituwar motsi, da iya riƙe daidaiton jiki. Ƙananan beraye masu matsakaicin shekaru da ba a ba sinadarin ba sun samu maki 1.17; waɗanda aka ba shi sun samu maki 2.23, kusa da matakin manyan ƙananan beraye. Manyan ƙananan beraye ba su samu ingantawa a komai ba.

Amfani da iskar oxygen yayin hutawa ya ƙaru da kusan kashi 15 cikin ɗari. Samar da hydrogen peroxide a mitochondria na ƙwaƙwalwa ya tashi daga 94.9 zuwa 176.7 pmol a kowace minti ga kowace milligram na furotin. DNA na mitochondria ya ƙaru ninki 2.3. Wannan yana nuna ƙaruwar sabuntawar mitochondria a dabbobi masu tsufa, tare da siginar oxidation da ke tura wannan sabuntawar. Ba nuna cewa ɗan wasa mai lafiya zai fi sauri ba ne.

Gwaje-gwajen ƙwayoyin halitta, da inda iyakarsu take

Louters da abokan aikinsa sun ba da rahoto a 2005 cewa methylene blue yana kunna jigilar glucose ta GLUT1 a ƙwayoyin fibroblast na L929, har zuwa kashi 800 cikin ɗari a 50 micromolar. Wani binciken biyo baya na 2008 ya nuna cewa methyl-beta-cyclodextrin yana ɗaure methylene blue kai tsaye kuma ya toshe tasirin. Wannan sakamako ne game da wani layin ƙwayoyin halitta na gwaji, wanda ba a taɓa nuna shi a tsokokin da ke motsa ƙasusuwa ba.

Ana saɓani kan hanyar aikin kanta

A binciken Tretter da abokan aikinsa na 2014 kan mitochondria da aka ware daga ƙwaƙwalwar aladun Guinea, methylene blue a 100 nanomolar zuwa 1 micromolar ya ƙara amfani da iskar oxygen yayin hutawa, ya dawo da bambancin ƙarfin lantarki tsakanin ɓangarorin membrane da samar da ATP lokacin da aka hana Complex I ko Complex III aiki, kuma ya ƙara samar da hydrogen peroxide. Muhimmin abu shi ne, "MB bai shafi numfashin da ADP ya ƙarfafa ba da kowanne daga cikin sinadaran da ake amfani da su" da aka gwada. Mafi girman numfashin da ke haɗe da samar da ATP, wanda ikirarin motsa jiki ya dogara da shi, bai ƙaru ba.

A binciken biyo baya na Gureev da abokan aikinsa na 2019, ɗakin binciken da ya samar da sakamakon ƙananan berayen ya gano cewa methylene blue "ya kasa dawo da bambancin ƙarfin lantarki na membrane da numfashin da antimycin ya hana" a mitochondria na ƙwaƙwalwar ƙananan beraye. Sun kammala cewa wurin karɓar electron shi ne wurin Qo na Complex III maimakon wani wuri da yake gaba a jerin. Sauƙaƙƙen hoton cewa rinin yana jigilar electrons ya wuce shingen da ya toshe sarkar numfashi ba ya tabbata a kowane samfurin gwaji.

Babu ɗaya daga cikin waɗannan da ya kore yiwuwar tasiri a mutane. Amma yana nufin cewa hujjar da ta dogara da hanyar aiki kaɗai, inda ake ɗaukar tsarin sinadarai na mitochondria mai yiwuwa a matsayin sakamakon da aka samu, tana da matsaloli a cikin hanyar aikin kanta.

Matsalolin tsara gwaji guda biyu da gwajin mutane zai buƙaci warwarewa

Yana da wuya a ɓoye wa mahalarta gwaji ko sun karɓi methylene blue. Yana sa fitsari ya zama shuɗi-kore kuma mutane suna lura. Gwajin 2017 kan cutar sauyin yanayin rai na bipolar, inda mahalarta suka karɓi hanyoyin gwajin bi da bi, ya faɗi haka kai tsaye: "Mun zaɓi wannan tsarin ne saboda methylene blue yana sauya launin fitsari, don haka ba za mu iya amfani da placebo na al'ada ba." Wannan gwajin ya kwatanta ƙaramin adadi da babban adadi maimakon kwatanta shi da ƙwayar da ba ta da sinadari mai aiki.

Matsalar ta fi tsanani a binciken motsa jiki fiye da kusan kowane fanni, domin tsammani yana shafar wahalar ƙoƙari da mutum yake ji da sakamakon gwajin gudu sosai. Gwajin da ba zai iya ɓoye wa mahalartansa abin da suka karɓa ba ya auna imani kamar yadda ya auna magani.

Akwai mafita da aka rubuta a bincike. Gwajin ɗaukar hoton cikin jiki na 2016 a manya masu lafiya 26, da aka raba su zuwa rukuni bisa bazuwar zaɓi, ya ba da 280 mg na methylene blue mai matsayin USP, kusan 4 mg/kg, ko placebo na rinin abinci FD&C blue no. 2 a cikin kapsul masu kama iri ɗaya waɗanda ba a iya ganin cikinsu. An kuma roƙi mahalarta su yi fitsari kafin karɓar adadin amma kada su sake yi, "domin kauce wa warware ɓoyewar abin da aka ba su saboda duk wani sauyin launin fitsari."

Matsala ta biyu ita ce adadi da hanyar bayarwa. Ana fitar da wani ɓangare na methylene blue da aka sha ta baki a fitsari, kuma adadin da yake isa ƙwaƙwalwa bayan shan sa ta baki yana kusan rabin wanda yake isa bayan bayarwa ta jijiya, kamar yadda rukunin Gureev ya lura yayin ambaton aikin Peter da abokan aikinsa kan yadda magani yake tafiya cikin jiki. Bayarwa ta hanci ga bera ba za a ɗauka iri ɗaya da kapsul ba, kuma adadin da aka yi amfani da shi a mutane a binciken da aka wallafa yana tsakanin 0.5 zuwa 4 mg/kg, yayin da gwajin ɗaukar hoto na 2016 ya lura da tasiri akasin haka sama da 10 mg/kg.

Binciken mutane yana auna wani abu dabam

Gwaje-gwajen mutane guda biyu da ke da rukunin kwatantawa suna bayyana a sake ba da labarin wannan batu, kuma babu ɗayansu da ya auna motsa jiki. A gwajin ɗaukar hoto na 2016, lokacin mayar da martani yayin sa ido bai nuna wata mu'amala mai muhimmanci ta ƙididdiga tsakanin magani da lokaci ba: placebo ya kasance 230 sannan 220 milliseconds, methylene blue kuma 230 sannan 230 milliseconds, P = .43. A wani binciken bayarwa ta jijiya na 2023 a mata masu lafiya takwas, kwararar jini a ƙwaƙwalwa da ƙimar amfani da iskar oxygen a ƙwaƙwalwa duka sun ragu maimakon ƙaruwa. Jagorar shaidar kuzari da gajiya ta tattauna duka biyun.

Idan ka yanke shawarar gwada shi duk da haka

Gwajin kai ba zai tabbatar da inganci ba, amma ana iya rubuta bayanansa da kyau yadda zai taimaka wajen kauce wa yaudarar kanka. Rubuta samfurin da rukunin samarwarsa, hanyar amfani, lokacin amfani kafin atisaye, ainihin atisayen tare da nisa ko nauyi, wahalar ƙoƙari da ka ji a kan ma'auni mai lambobi, barci, caffeine da duk wani magani, da raɗaɗin tsoka washegari da ƙwarewa bayan sa'o'i 48 a irin wannan atisayen. Sannan ka maimaita atisayen iri ɗaya ba tare da shi ba.

Mutum ɗaya da yake bin diddigin abu ɗaya ba zai iya raba tasirin magani da ƙarfin jiki, ƙwarin gwiwa, yanayi, da sauye-sauyen atisaye na yau da kullum ba. Ɓangaren abin da mutum ya ji shi ne mafi iya ruɗarwa.

Methylene blue kuma yana da haɗurra da ba su da alaƙa da ƙwarewar motsa jiki. Yana hana monoamine oxidase A aiki, wanda ya sa batun haɗa shi da magungunan damuwa da likita ya rubuta da sauran magungunan da ke shafar serotonin ya zama abin lura. Kuma bai dace a yi amfani da shi ga masu ƙarancin G6PD ba saboda haɗarin anemia sakamakon rushewar jajayen ƙwayoyin jini. Jagorar tsaro ta tattauna duka biyun, kuma jagorar hulɗar magunguna ta tsara tambayoyin magani bisa rukuni. Idan kana gasa a ƙarƙashin dokokin hana amfani da sinadaran ƙara ƙwarewa, duba dokokin maimakon ikirarin mai sayarwa.

Sinadarin kansa wani abu ne da zai iya sauya sakamako a kowane binciken da ke sama

Kowane adadi da aka bayyana a nan an auna shi ne daga takamaiman sinadari. Kwalba daga mai sayarwa da ba a tabbatar da shi ba ba haka take ba. Bin ƙa'idar takardar USP kan sinadarin shi ne ma'aunin da mai saye zai iya dubawa, kuma sinadarin da bai bi wannan ƙa'ida ba yana yiwuwa ya kasance na rina yadi. Irin wannan na iya ƙunsar ƙazantar sinadaran organic kamar Azure B, ragowar sinadaran narkarwa, da ƙarafa masu nauyi a matakan da ƙa'idar sinadarin magani take iyakancewa. Abin da matsayin USP yake tabbatarwa da abin da ba ya tabbatarwa ya tattauna matsayin inganci, kuma hanyoyin gwajin ƙazanta sun tattauna abin da ɗakin bincike yake nema.

Yawancin masu sayarwa da suke bayyana samfur a matsayin wanda wani ɓangare mai zaman kansa ya gwada suna duba ƙarafa masu nauyi kaɗai, sannan su gabatar da wannan jerin gwaje-gwajen guda ɗaya kamar ya cika duk ƙa'idar. Blupreme yana gwada cikakken tsarin ƙa'idodin USP: tabbatar da ainihin sinadarin, tsarki, ƙazantar sinadaran organic, ragowar sinadaran narkarwa, ƙazantar sinadaran asali, ragowar bayan ƙonewa, iyakokin ƙananan halittu, da endotoxins na ƙwayoyin bacteria. Ana aika kowane rukunin samarwa tare da takardar shaidar nazari, kuma karanta ta daidai yana nufin tabbatar da cewa lambar rukunin samarwa da ɗakin binciken sun dace da kwalbar da kake riƙe da ita.

A taƙaice

Babu binciken mutane da ke da rukunin kwatantawa da ya auna tasirin methylene blue kan juriya, sauri, ƙarfi, ko farfaɗowa. Binciken karnuka da ake ambata game da tasirin lactate ya yi amfani da wani rini na daban kuma bai gano bambanci a ƙwarewar motsa jiki ba. Binciken iyon beraye ya ba su 0.2 mg ta hanci bayan aikin. Binciken ƙananan beraye da ya haifar da kalmar "juriya" ya yi amfani da gwajin riƙo da daidaituwar motsi a dabbobi masu tsufa, kuma ana saɓani kan hanyar aikin a rubuce-rubucen binciken mitochondria.

Abin da ya rage shi ne hanyar aiki mai yiwuwa, wasu sakamako daga ƙananan gwaje-gwajen dabbobi, matsalar tsara gwaji guda ɗaya mai mafita da aka rubuta, da rashin bayanan ƙwarewar motsa jiki na mutane. Bitar shaidar fa'ida a mutane ta sanya ikirarin motsa jiki tare da sauran rubuce-rubucen binciken mutane, kuma ɗakin karatun bincike ya jera binciken da ke bayan kowane ikirari.

Idan kana atisaye domin wani buri, abin da yake da shaida mafi ƙarfi a bayansa shi ne atisayen kansa.