Methylene blue pakurovedza muviri nekupora: chii chakayerwa chaizvo

Muna March 2022 mumhanyi wemarathon wepamusoro akabudisa mashoko ekurumbidza piritsi rinonyungudutswa mumuromo remethylene blue, achibhadharwa nekambani, achiti “rinogona kubatsira kuvandudza kutarisisa, kutsungirira uye kurara” uye kuti airishandisa asati aita kurovedza muviri kwakaoma. Vhiki rimwe chetero, vanachiremba vakataurwa munhau dzenyika vakatsanangura tsika iyi yaipararira vachiti vanhu vane mukurumbira pasocial media vaiva kumedza mushonga wekuchenesa matangi ehove. Hapana pamaonero aya anopindura mubvunzo une mumhanyi chaizvo.

Pane munhu akambopa vanhu methylene blue akayera kuti vakamhanya kure zvakadii, nekukurumidza zvakadii, kana kuti vakapora zvakanaka zvakadii here? Kutsvaga kwakaitwa nokuda kwechinyorwa ichi hakuna kuwana kana chidzidzo chimwe chete chakadzorwa muvanhu chakayera kugona kurovedza muviri kana kupora. Zvidzidzo zvinotevedzana zvichitaurwa zvinobatanidza marudzi matatu emhuka, zvinhu zvakasiyana-siyana zvakagadzirirwa murabhoritari, uye chinhu chimwe chisiri methylene blue zvachose.

Kutsungirira, kupora, uye mashandiro acho zvirevo zvakasiyana

Chiratidzo chinogona kuchinja chichienda kudivi rinopesana nekugona kuita, kana kuchinja pasina kugona kuita kuchinja zvachose. Iyi haisi nyaya diki yehunyanzvi: ndiwo mamiriro chaiwo akawanikwa muchidzidzo chemethylene blue nekurovedza muviri chinonyanya kutaurwa.

Chidzidzo cheimbwa chakashandisa dhayi yakasiyana

Gwaro rinonyanya kutaurwa panyaya yemethylene blue nekurovedza muviri ndere chidzidzo chaImai nevamwe cha1986 cheimbwa dzisina kurariswa dzichimhanya patreadmill. Chakaedza kuona kana kuwedzera kweropa rinopombwa nemwoyo pakurovedza muviri kuchitsamira pamamiriro eredox munyama dzemuviri, chichishandisa chinotsanangurwa muchikamu chemaitirwo se“4 mg/kg yenew methylene blue 3,7-bis(ethylamino)-2,8-dimethylphenazothonium chloride, Eastman Kodak Company”. New methylene blue imwe dhayi yerudzi rwethiazine yakasiyana, ine mapoka maviri eethylamino panzvimbo pemapoka maviri edimethylamino ari mumethylene blue, uye inonyanya kuzivikanwa sedhayi yekuratidza mareticulocyte. Mugumisiro unowanikwa nayo hausi mugumisiro unowanikwa nemethylene blue.

Chidzidzo ichi chichiri kukosha, nokuti chinoratidza zvakajeka kuti chiratidzo nemashandiro emuviri zvinogona kuchinja zvakasiyana. Imbwa dzakamhanya muzvikamu zviviri zvemaminitsi 20, pa2.5 uyezve pa5.0 mph, panzvimbo yakakwira ne6 muzana. Kurovedza uku kwakapeta kaviri ropa rinopombwa nemwoyo uye kwakawedzera kushandiswa kweoxygen nemuviri wose katatu kusvika kana mumapoka ose. Muboka rakapiwa mvura ine munyu reshiyo yelactate nepyruvate muropa remutsinga dzinobva pamwoyo yakakwira kubva pa6.0 kusvika pa9.97. Muboka rakapiwa dhayi haina kukwira.

Zviyero zvose zvemashandiro zvakanga zvisina kuchinja. Kurova kwemwoyo, simba reropa mutsinga dzinobva pamwoyo, kugona kwekamuri repasi rekuruboshwe remwoyo kubatana, uye macatecholamine muplasma zvakakwira zvakafanana mumapoka ose, uye hukama pakati peropa rinopombwa nemwoyo nekushandiswa kweoxygen nemuviri wose hwakanga husina musiyano unokosha pazviverengero. Vanyori vanogumisa kuti shanduko dzereshiyo “hadzisi idzo dzinokonzera kukurudzirwa kwekutenderera kweropa kunoitika pakurovedza muviri kuri nyore kusvika kuri pakati nepakati.”

Reshiyo iyi ine uchapupu husina kusimba sezvainotaridzika. Yakadzikira nokuti pyruvate yakakwira, kubva pa0.14 kusvika pa0.38 mmol parita, uku lactate ichikwirawo, kubva pa1.05 kusvika pa2.85 mmol parita. Muimbwa dzakapiwa dhayi dzakazorora, kushandiswa kweoxygen kwakakwira zvishoma, pH yeropa remutsinga dzinobva pamwoyo yakakwira, uye carbon dioxide yakadzikira. Vanyori vanoti shanduko idzi “dzakafanana” nedze2,4-dinitrophenol, chinhu chinopatsanura kufema kwemitochondria nekugadzirwa kweATP. Kumhanya kwacho kwakanga kwakatemerwa nemaitirwo emuedzo, saka hapana imbwa yakamhanyiswa kusvika yaneta chose.

Chidzidzo chekushambira kwemakonzo, neuwandu hwacho

Mugumisiro wakasimba kupfuura mimwe wekugona kuita mumhuka unobva mumuedzo waPeng nevamwe wa2025 wakabudiswa muFrontiers in Behavioral Neuroscience. Makonzo akashambira usiku hunotevedzana kwemazuva gumi, aine zviremu zvakaenzana ne3 muzana yehuremu hwemuviri zvakasungirirwa pamiswe yawo, kwemaawa anenge maviri kana kupfuura pausiku, kusvikira asvika pachiyero chakatemerwa chekuneta chose. Mushure mechikamu chimwe nechimwe, rimwe boka rakapiwa methylene blue nemumhino uye rimwe rakapiwa mvura ine munyu nenzira imwe chete. Makonzo akapiwa methylene blue akashambira kwenguva yakareba asati asvika pazviyero zvekuneta chose, akafamba zvakanyanya munzvimbo yakavhurika zuva rakatevera, akaratidza maitiro mashoma akafanana nekuzvidya mwoyo, uye aiva nekurasikirwa nemaneuron, kukanganisika kwemyelin, uye kupatsanuka kwemitochondria kushoma muhippocampus nemustriatum.

Uwandu hwakapiwa hunowanzosiyiwa panotsanangurwazve chidzidzo ichi. Mvura ine mushonga we1 muzana ine 10 mg/mL; mamicrolitre gumi akaiswa mumhino imwe neimwe, saka uwandu hwose hwaiva anenge mamicrolitre 20, kana 0.2 mg pakonzo pachikamu chimwe nechimwe. Kuisa nemumhino kunosarudzwa kuti chinhu chisvike kuuropi nenzira dzetsinga yekunhuwidza netsinga yetrigeminal, uye vanyori vanoti chidzidzo chavo “hachina kuyera maitiro eoxidation, kuzvimba, kana uwandu hwemahormone muuropi nemuplasma.” Danho rinotevera ravanokurudzira nderekudzidza “migumisiro yose yekushandisa MB sechinowedzerwa usati warovedza muviri.”

Ndizvo zvingada mumhanyi kuti zviedzwe. Maitirwo aya akapa chinhu ichi mushure mebasa, kuti aderedze kukuvara. Kushambira kwenguva yakareba zuva rinotevera mumuedzo wemakonzo akange aneta chose mugumisiro wekupora, kwete mugumisiro unotaura nezvemunhu akadzidzira kurovedza anochitora asati atanga chikamu.

Kwakabva izwi rokuti “kutsungirira”

Chidzidzo chembeva chinowanzotsanangurwa sechakaratidza kuvandudzwa kwekutsungirira ibasa raGureev nevamwe ra2016 rakabudiswa muNeuroscience Research. Mbeva dzakanwa mvura yaiva nemethylene blue pa15 mg/kg pazuva kwemazuva 60. “Kutsungirira kwemuviri” kunotaurwa uku muedzo wetambo, kana wembariro dzakachinjika, unoyera pamwe chete simba rekubata, kushanda pamwe chete kwenhengo pakufamba, uye kugadzikana kwemuviri. Mbeva dzaiva pakati pezera dzisina kupiwa methylene blue dzakawana 1.17; dzakapiwa dzakawana 2.23, pedyo nechiyero chembeva dzakura asi dzisati dzachembera. Mbeva idzodzo dzakura hadzina kuvandudzika pachinhu chipi nechipi.

Kushandiswa kweoxygen pakuzorora kwakakwira neanenge 15 muzana. Kugadzirwa kwehydrogen peroxide mumitochondria yeuropi kwakakwira kubva pa94.9 kusvika pa176.7 pmol paminiti pamilligram yeprotein. DNA yemitochondria yakawedzera ka2.3. Izvozvo zvinoratidza kuwedzera kwekuparadzwa nekutsiviwa kwemitochondria mumhuka dziri kuchembera, pamwe nemasaini ane chokuita neoxidation anozvikurudzira. Hazviratidzi kuti mutambi ane utano angamhanya nekukurumidza.

Miedzo yemasero, nemiganhu yayo

Louters nevamwe vakashuma muna 2005 kuti methylene blue inokurudzira kufambiswa kweglucose kuburikidza neGLUT1 mumasero efibroblast eL929, zvichiwedzera kusvika pa800 muzana pa50 micromolar. Chidzidzo chakatevera muna 2008 chakaratidza kuti methyl-beta-cyclodextrin inosunga methylene blue zvakananga ichivhara mugumisiro wacho. Izvozvo zvakawanikwa mumutsara wemasero anokuriswa murabhoritari, uye hazvina kumboratidzwa mumasuru anofambisa mapfupa.

Mashandiro acho pachawo achiri kukakavadzanwa

Muchidzidzo chaTretter nevamwe cha2014 chemitochondria yakaparadzaniswa nehuropi hweguinea pig, methylene blue iri pa100 nanomolar kusvika pa1 micromolar yakawedzera kushandiswa kweoxygen pakuzorora, yakadzorera musiyano wemagetsi pamembrane nekugadzirwa kweATP apo Complex I kana Complex III yakanga yavharirwa, uye yakawedzera kugadzirwa kwehydrogen peroxide. Chinokosha ndechekuti “kufema kwakakurudzirwa neADP hakuna kukanganiswa neMB pachinhu chipi nechipi chezvinhu zvaishandiswa pakufema” zvakaedzwa. Kufema kwakanyanya kwakabatana nekugadzirwa kweATP, uko ndiko kunotsigira chirevo chekurovedza muviri, hakuna kuwedzera.

Muchidzidzo chakatevera chaGureev nevamwe cha2019, rabhoritari imwe chete yakabudisa mugumisiro wembeva yakawana kuti methylene blue “inotadza kudzoreredza musiyano wemagetsi pamembrane nekufema kwakavharirwa neantimycin” mumitochondria yeuropi hwembeva, uye yakagumisa kuti nzvimbo inogamuchira maelectron inzvimbo yeQo yeComplex III, kwete chimwe chinhu chiri mberi kwayo munhevedzano yacho. Tsananguro iri nyore yekuti dhayi inotakura maelectron ichiapfuudza pachikamu chakavharwa chenhevedzano yekufema haishandi pazvinhu zvose zvakagadzirirwa miedzo.

Hapana pane izvi chinobvisa mukana wekuti pave nemugumisiro muvanhu. Asi zvinoreva kuti nharo inongotsamira pamashandiro acho, ichitora mashandiro emakemikari emitochondria anobvira semugumisiro wakatoratidzwa, ine matambudziko mukati memashandiro acho pachawo.

Matambudziko maviri ekuronga muedzo wevanhu angada kugadziriswa

Zvakaoma kuvanza kuti ndiani apiwa methylene blue. Inoshandura weti kuva yebhuruu-girini uye vanhu vanozviona. Muedzo wa2017 webipolar disorder wakachinjanisa zvakapiwa vatori vechikamu wakazvitaura pachena: “Takasarudza marongerwo aya nokuti methylene blue inoshandura ruvara rweweti, saka hatina kukwanisa kushandisa placebo yechinyakare.” Muedzo iwoyo wakaenzanisa uwandu hushoma neuwandu hwakawanda pane kuenzanisa nepiritsi risina chinhu chinoshanda.

Dambudziko iri rakakura mukutsvakurudza kwekurovedza muviri kupfuura munenge mimwe minda yose, nokuti kunzwa kuoma kwekurovedza nekugona kumhanya mumuedzo wenguva zvinokanganiswa zvakanyanya nezvinotarisirwa. Muedzo usingakwanisi kuvanza kune vatori vechikamu kuti vapiwa chii unenge wayera kutenda kwavo sezvawayera mushonga.

Pane nzira yakanyorwa yekugadzirisa izvi. Muedzo wa2016 wekutora mifananidzo yemuviri muvanhu vakuru 26 vane utano, vakagoverwa mapoka zvisina kusarudzwa, wakapa 280 mg yemethylene blue yemhando yeUSP, anenge 4 mg/kg, kana placebo yedhayi yezvokudya yeFD&C blue no. 2 mumacapsule akafanana asingaratidzi zviri mukati. Wakakumbira vatori vechikamu kuti vaite weti vasati vapiwa, asi kuti vasazoiita zvakare, “kuti ruvara rupi norupi rweweti rusakanganisa kuvanzwa kwekuti ndiani apiwa chii.”

Dambudziko rechipiri uwandu nenzira yekuipinza mumuviri. Chimwe chikamu chemethylene blue inomedzwa chinobudiswa muweti, uye huwandu hunosvika muuropi mushure mekuimedza hunenge huri hafu yehunosvika mushure mekuipinza mutsinga, sezvinotaurwa neboka raGureev richitaura nezvebasa raPeter nevamwe pamusoro pekufamba kwemushonga mumuviri. Kuisa mumhino dzekonzo hakufanani nekumedza capsule, uye uwandu hwakashandiswa muvanhu mubasa rakabudiswa huri pakati pe0.5 ne4 mg/kg, huku muedzo wekutora mifananidzo wa2016 uchitaura kuti pamusoro pe10 mg/kg pane mugumisiro wakapesana.

Zvidzidzo zvevanhu zvinoyera zvimwe zvinhu

Miedzo miviri yakadzorwa muvanhu inotaurwa pakutsanangurwazve nyaya iyi, uye hapana yakayera kurovedza muviri. Mumuedzo wekutora mifananidzo wa2016, nguva yekupindura uri wakangwarira haina kuratidza kudyidzana kwakakosha pakati pemushonga nenguva, placebo iine 230 yozova 220 milliseconds uye methylene blue iine 230 yozoramba iri 230 milliseconds, P = .43. Muchidzidzo cha2023 chekuisa mutsinga muvakadzi vasere vane utano, kuyerera kweropa muuropi nekukurumidza kushandiswa kweoxygen muuropi zvose zvakadzikira pane kukwira. Gwaro reuchapupu pamusoro pesimba nekuneta rinotsanangura zvose zviri zviviri.

Kana ukasarudza kuiedza zvakadaro

Kuzviedza pachako hakuratidzi kuti chinhu chinoshanda, asi unogona kunyora zvakakwana kuti usazvinyengera. Nyora chigadzirwa neboka rachakabva, nzira yekuchipinza mumuviri, nguva yachakatorwa usati warovedza, chikamu chaicho chekurovedza chine daro kana mutoro, kuoma kwekurovedza kwawakanzwa pachiyero chine nhamba, kurara, caffeine nemishonga ipi neipi, uye kurwadza kwemasuru zuva rinotevera nekugona kuita mushure memaawa 48 muchikamu chemhando imwe chete. Zvadaro dzokorora zvikamu zvakafanana usina kuchishandisa.

Munhu mumwe anotevera chinhu chimwe chete haakwanisi kupatsanura mugumisiro wemushonga kubva pakusimba kwemuviri, chido chekuita, mamiriro ekunze, uye kuchinja-chinja kwakajairika kwekurovedza. Chikamu chezvaunonzwa ndicho chinonyanya kukwanisa kukutsausa.

Methylene blue inewo njodzi dzisinei nekugona kuita. Inovharira monoamine oxidase A, zvichiita kuti ive nenyaya dzinoda kufungwa nezvadzo kana ichishandiswa pamwe nemishonga yakanyorerwa yekurapa kuora mwoyo nemimwe mishonga inoshanda neserotonin. Haifaniri kushandiswa kana paine kushomeka kweG6PD nokuda kwenjodzi yekushaya ropa kunokonzerwa nekuparara kwemasero matsvuku eropa. Gwaro rekuchengeteka rinotsanangura zvose zviri zviviri, uye gwaro rekudyidzana kwemishonga rinoronga mibvunzo yemishonga nemapoka ayo. Kana uchikwikwidza pasi pemitemo inorambidza kushandiswa kwezvinhu zvinopa mukana usiri pamutemo, tarisa mitemo yacho pane kuvimba nezvinotaurwa nemutengesi.

Chinhu chinoshandiswa chinokwanisa kuchinja mumuedzo mumwe nomumwe uri pamusoro

Uwandu hwose hwatsanangurwa pano hwaiva huwandu hwakayerwa hwechinhu chakanyatsotsanangurwa. Bhodhoro rinobva kumutengesi asina kusimbiswa harisi izvozvo. Kuenderana negwaro rezvinodiwa reUSP ndicho chiyero chinogona kutariswa nemutengi, uye chinhu chisingaenderani naro chingangova chemhando inoshandiswa pamachira. Chinogona kuva nezvinosvibisa zvinobva mumakemikari eorganic zvakadai seAzure B, zvinonyungudutsa zvinenge zvasara, nesimbi dzinorema zviri pauwandu hunorambidzwa nezvinodiwa pamushonga. Zvinoratidzwa nezita reUSP nezvarisingaratidzi zvinotsanangura mhando yacho, uye nzira dzekuongorora zvinosvibisa dzinotsanangura zvinotsvakwa nerabhoritari.

Vatengesi vakawanda vanoti chigadzirwa chakaongororwa nesangano rakazvimirira vanongotarisa simbi dzinorema chete, vozopa seti iyoyo chete yemiedzo sokunge yazadzisa zvose zvinodiwa. Blupreme inoongorora zvose zvinodiwa neUSP: kuti chinhu chacho ndechipi, kuchena kwacho, zvinosvibisa zveorganic, zvinonyungudutsa zvinenge zvasara, zvinosvibisa zviri maelement, zvinosara mushure mekupiswa, miganhu yezvipenyu zvidiki, uye maendotoxin emabhakitiriya. Boka rimwe nerimwe rechigadzirwa rinotumirwa riine chitupa chekuongorora, uye kuchiverenga nemazvo zvinoreva kuenzanisa nhamba yeboka nerabhoritari nebhodhoro raunaro.

Mhedziso

Hapana chidzidzo chakadzorwa muvanhu chakayera methylene blue maererano nekutsungirira, kukurumidza, simba, kana kupora. Chidzidzo cheimbwa chinotaurwa pamusoro pemugumisiro palactate chakashandisa dhayi yakasiyana uye hachina kuwana musiyano mukugona kuita. Chidzidzo chekushambira kwemakonzo chakapa 0.2 mg nemumhino mushure mebasa. Chidzidzo chembeva chakapa hwaro hweizwi rokuti “kutsungirira” chakashandisa muedzo wekubata nekushanda pamwe chete kwenhengo mumhuka dziri kuchembera, uye mashandiro acho achiri kukakavadzanwa mumabhuku ekutsvakurudza kwemitochondria.

Saka chasara itsananguro yemashandiro inogona kuva yechokwadi, boka remigumisiro midiki yemhuka, dambudziko rimwe rekuronga muedzo rine mhinduro yakanyorwa, uye kusavapo kwemashoko akayerwa ekugona kuita muvanhu. Ongororo yeuchapupu hwekubatsira muvanhu inoisa zvirevo zvekurovedza muviri pamwe nezvimwe zvidzidzo zvevanhu, uye raibhurari yekutsvakurudza inoronga zvidzidzo zviri shure kwechirevo chimwe nechimwe.

Kana uri kurovedza uchigadzirira chimwe chinhu, chinhu chine uchapupu hwakasimba kupfuura zvimwe zvinotsigira basa racho ndiko kurovedza kwacho.