Methylene blue pakuora mwoyo nekuzvidya mwoyo: miedzo, miganhu, nenjodzi yekudyidzana kwemishonga

Methylene blue yave ichipiwa kuvarwere vepfungwa kubva kuma1890s, ichiedzwa mumiedzo yakadzorwa kubva kuma1980s, uye ichiongororwa mumhando dzemiedzo yemhuka dzinoratidza magirafu akajeka zvikuru ehukama pakati pemwero wemushonga nemhedzisiro yawo. Muverengi anotsvaga “methylene blue depression” anowana mhando idzi nhatu dzeuchapupu dzakasanganiswa, pasina zvinyorwa zvinojekesa kusiyana kwadzo.

Kusiyanisa uku kwakakosha. Uchapupu hwose hwakadzorwa muvanhu pamusoro pemamiriro emanzwiro hunobva mumiedzo miviri nemuyedzo mumwe wemurabhoritari wekutarisana nezvinotyisa, uye miedzo miviri yakanyoreswa yakapera anopfuura makore gumi apfuura. Chinyorwa ichi chinotsanangura zvakawanikwa nemumwe nemumwe. Hachikurudziri methylene blue semushonga wechirwere chemamiriro emanzwiro.

Nei dhayi yakazopedzisira iri muzvinyorwa zvemamiriro emanzwiro

Methylene blue ndiyo yaiva kemikari yokutanga yakagadzirwa zvachose nenzira dzekugadzira yakashandiswa semushonga. Monoamine oxidase A, inopfupikiswa kuti MAO-A, inoputsa serotonin, uye mishonga inoivharira yakatosimbiswa semishonga yekuora mwoyo. Ramsay, Dunford, naGillman vakayera zvainoita paMAO-A yemunhu yakacheneswa uye vakashuma mwero unoratidza simba rekuvharira waive pedyo ne27 nanomolar, nekuvharira kwaigona kudzoreka. MAO-B yaida kuwanda kwemushonga kwaipfuura ka makumi mashanu. Morekuru rimwe chete iri rinovharirawo nitric oxide synthase neguanylate cyclase, ndokusaka ongororo ya2017 yakaitwa naDelport nevamwe ichitsanangura kushanda kwaro pakurwisa kuora mwoyo sekunonangana nenzvimbo dzakawanda, kwete sechinobva pachigamuchiri chimwe chete.

Izvi zvinotsanangura nei zvinyorwa zvetsvakurudzo yemhuka zvichipa tariro asi zvichishamisa. Mumakonzo, methylene blue inoita kuti pave nemaitiro akafanana neanoonekwa kana mushonga wekuora mwoyo uchishanda, pamuyedzo wekushambira kunomanikidzwa, asi mukati memiganhu yemwero wemushonga chete: Eroglu naCaglayan vakawana mhedzisiro pakati pe15 ne30 mg/kg, asi hapana pa60 mg/kg, uye maitiro ekuderedza kuzvidya mwoyo aiteverawo girafu reU yakapidiguka. Kupinza jekiseni diki mudorsal periaqueductal gray kwakashanda pa30 nanomoles, asi kwete kunze kwemwero iwoyo. Izvi zvinonzi hormesis, uye girafu rakaita saizvozvo harigoni kushandiswa kufungidzira kuti kuwedzera mwero kuchawedzera mhedzisiro.

Miedzo yema1980s nemwero weplacebo ungangodaro usina kuva placebo

Naylor nevamwe vakaita muyedzo wemakore maviri wekuchinjanisa marapirwo usingazivikanwi nevatori vechikamu kana vatsvakurudzi muvarwere 31 vaiva nechirwere chebipolar, vachienzanisa 300 mg pazuva ne15 mg pazuva uku lithium ichiramba ichitorwa. Gumi nevanomwe vakapedza, uye kuora mwoyo kwakanga kwakaderera zvakakosha maererano nenhamba dzetsvakurudzo pamwero wakakwirira.

Magadzirirwo emuyedzo ane dambudziko rakakodzera kunzwisiswa, nokuti rinodzokororwa. Mamirigiramu gumi nemashanu pazuva akasarudzwa sechikamu che“placebo” vachifungidzira kuti aisazoshanda. Vanyori vakazonyora “kusava nechokwadi chekuvanzwa kwemishonga yaipiwa, uye kusava nechokwadi kana 15 mg yemethylene blue pazuva yaigona kunzi placebo kana kuti kwete.” Methylene blue inoita kuti weti ive yebhuruu yakasanganiswa negirini, saka murwere wese mumuyedzo wekuchinjanisa marapirwo aitora dhayi yaioneka kuti iri kuita chimwe chinhu munguva dzose mbiri. Kana mwero wakaderera waishanda, muyedzo wacho wakanga uchienzanisa mwero miviri yaishanda.

Muyedzo mupfupi wakaenzanisa 15 mg pazuva neplacebo chaiyo mukuora mwoyo kwakanyanya kwemavhiki matatu, muvarwere 35, uye wakawana kuvandudzika kwakakura zvakakosha maererano nenhamba dzetsvakurudzo kune vakatora methylene blue. Mavhiki matatu nevarwere makumi matatu nevashanu zvinopa chiratidzo chaicho, asi chidiki.

Muyedzo wekuchinjanisa marapirwo mubipolar: uchapupu hwakasimba kupfuura humwe muvanhu

Muyedzo unopa ruzivo rwakanyanya itsvakurudzo ya2017 yaAlda nevamwe, yakanyoreswa seNCT00214877. Yaiva nevatori vechikamu makumi matatu nevanomwe vaiva nechirwere chebipolar I kana II, vose vachitora lamotrigine semushonga wavo mukuru wekudzikamisa mamiriro emanzwiro, uye vazhinji vaine zviratidzo zvakasara zvisina kunyanya kukomba kana zvepakati. Magadzirirwo acho aiva ekuchinjanisa marapirwo pasina vatori vechikamu kana vatsvakurudzi kuziva kuti ndiani apiwa chipi: 15 mg pazuva kwemwedzi mitatu ichienzaniswa ne195 mg pazuva kwemwedzi mitatu, hurongwa hwekuti chii chitange huchisarudzwa zvisina kurongwa. Vanyori vakatsanangura chikonzero chekusarudza mwero wakaderera wekuenzanisa zvakajeka: “Takasarudza magadzirirwo aya nokuti methylene blue inoshandura ruvara rweweti, saka hatina kukwanisa kushandisa placebo yakajairika.”

Pakuongorora varwere 27 vakapedza:

• Kuora mwoyo kwakavandudzika zvakanyanya pamwero wakakwirira, neukuru hwemhedzisiro hwe0.71 pachiyero cheHamilton Depression Rating Scale (95% CI 0.15 kusvika 1.25, P = 0.034) uye 0.80 pachiyero cheMontgomery-Asberg Depression Rating Scale (95% CI 0.27 kusvika 1.30, P = 0.020).
• Kuzvidya mwoyo kwakavandudzika zvakanyanya pamwero wakakwirira, neukuru hwemhedzisiro hwe0.79 pachiyero cheHamilton Anxiety Rating Scale (95% CI 0.22 kusvika 1.33, P = 0.028). Zvinhu zvaiyera kuzvidya mwoyo mupfungwa ndizvo zvaitungamirira mhedzisiro yacho; kuzvidya mwoyo kunoratidzwa mumuviri kwakazosvika pakukosha maererano nenhamba dzetsvakurudzo pakuongorora kwaisanganisira vose vakanga varongerwa kurapwa chete.
• Zviratidzo zvemania zvakaramba zvakaderera uye zvakadzikama, pasina kuchinjira kuhypomania kana mania.
• Kugona kwepfungwa hakuna kuchinja pane chero rimwe remabasa matanhatu, aisanganisira kudzidza mashoko, kugona kuronga nekudzora zviito, uye kuyeuka zvakamboitika.

Gumi pavanhu 37 vakabuda mumuyedzo, mumwe nokuda kweweti yebhuruu, mumwe nokuti kuzvidya mwoyo kwakawedzera, uye mumwe mushure mekunge mamiriro ake echirwere anyanya kuipa. Mhedzisiro isingadiwi yaiva yenguva pfupi uye isina kunyanya kukomba, zvikuru kupisa munzira yeweti, manyoka, kusvotwa, nemusoro. Pakati pevatori vechikamu 20 ne27 vaitora mushonga wekuora mwoyo kana mushonga wepsychosis nguva yose, uye muyedzo hauna kushuma muchetura weserotonin.

Boka iri rakanga risina kuora mwoyo kwakanyanya. Pakutanga, zvibodzwa zvaiva 12.7 pachiyero cheMontgomery-Asberg, chinosvika ku60, uye 7.6 pachiyero cheHamilton chine zvinhu 17: zviratidzo zvakasara muvarwere vane mamiriro akanga adzikamiswa, kwete chirwere chikuru chekuora mwoyo. Ongororo yakarongeka yakazvimirira ya2021 yekurapa kuzvidya mwoyo mubipolar yakanga yadzikama inoverenga muyedzo uyu semumwe wemiedzo miviri chete yemishonga yakawana mhedzisiro yakanaka pakuzvidya mwoyo, pamiedzo gumi yakagovera marapirwo zvisina kurongwa yakaongororwa. Inocherechedzawo kuti kubuda kwevanhu vakawanda mumuyedzo nemhedzisiro isingadiwi yaioneka zvinogona kunge zvakakanganisa kuvanzwa kwemishonga yaipiwa.

Muyedzo mumwe chete wakadzorwa wekuzvidya mwoyo muvanhu

Muyedzo wokutanga wakadzorwa muvanhu wemethylene blue nekuzvidya mwoyo wakanga usiri muyedzo wekurapa, asi muyedzo wekusimbiswa kwendangariro. Telch nevamwe vakatora vanhu vakuru vaitya zvikuru nzvimbo dzakavharika, mumwe nemumwe achipedza zvikamu zvitanhatu zvekutarisana nekutya, chimwe nechimwe chemaminitsi mashanu, mukamuri yakavharika. Pakarepo mushure maizvozvo, uye mushure maizvozvo chete, vakapiwa 260 mg yemethylene blue kana placebo, pasina ivo kana vatsvakurudzi kuziva kuti ndiani apiwa chipi. Kuvaedza zvakare mwedzi mumwe gare gare mune imwe kamuri kwaiyera kana kutya kwakanga kwadzoka.

Mhedzisiro yakakamura boka. Vatori vechikamu vakapedza chikamu chekutarisana nekutya vaine kutya kushoma vakachengetedza kuvandudzika ikoko zviri nani zvikuru kana vakatora methylene blue, asi vaya vakapedza vachiri kutya vakaita zvakaipa kupfuura vakatora placebo. Mushonga wacho unoratidzika kusimbisa chero kudzidza kunenge kwaitika, saka chikamu chakasimbisa kutya chakazounza kutya kwakawanda. Kuyeuka mamiriro akanga akapoteredza chiitiko kwakavandudzika zvisinei, zvichisimbisa kuti mushonga wakasvika kuuropi. Mwero mumwe chete nenzira imwe chete yemuyedzo zvakaburitsa mhedzisiro inopesana zvichienderana nechinhu chimwe chete, inova nyaya yenei kunaka kwechikamu chekutarisana nekutya kuchisarudza mhedzisiro iyi.

Muyedzo wePTSD nemutongo wakazvimirira

Tsvakurudzo yakazotevera yakakura yaiva muyedzo waZoellner nevamwe wakagovera marapirwo zvisina kurongwa muPTSD yenguva refu, yakanyoreswa seNCT01188694. Varwere makumi mana nevaviri vakapiwa zvikamu zvishanu zvekutarisana nechiitiko chinotyisa mukufungidzira, chimwe pazuva, zvichiteverwa ne260 mg yemethylene blue; kana hurongwa humwe chete huchiteverwa neplacebo; kana kuiswa parunyorwa rwekumirira, vachizowana kurapwa kwakajairika kwekutarisana nekutya kwenguva yakareba.

Pamhedzisiro huru, iyo PTSD Symptom Scale yakayerwa nemuongorori akazvimirira, methylene blue haina kuratidza kusiyana neplacebo. Mhedzisiro yakabudiswa murejista inoratidza zvibodzwa zvemushure mekurapwa zve17.10 kune vakatora methylene blue zvichienzaniswa ne14.67 kune vakatora placebo, zvose zvavandudzika kubva panenge pa32 pakutanga. Musiyano wacho waifarira placebo.

Zvimwe zvakawanikwa zviviri zvechipiri zvakaratidza zvinopesana. Varwere vakawanda vakatora methylene blue vakaonekwa sevakabatsirwa nekurapwa, nenhamba inodiwa kurapwa kuti pave nemumwe munhu anobatsirwa iri 7.5, uye kunaka kweupenyu kwakavandudzika neukuru hwemhedzisiro hwe0.58. Kubatsirwa kwaienderana nekugona kwendangariro dzinoshandiswa panguva iyoyo, kwete nekuchinja kwezvitendero zvine chokuita nechiitiko chinoshungurudza.

Ongororo yakarongeka ya2023 yekushandurwa kwendangariro nemishonga mukurapwa kwepfungwa kunonangana nezviitiko zvinoshungurudza yakazoisa methylene blue pamwe nezvinhu zvisina kuratidza mhedzisiro yakakosha maererano nenhamba dzetsvakurudzo pakuderedza zviratidzo zvePTSD. Ndiyo dudziro yazvino yakazvimirira: haina kuratidzwa kuti haishandi, haina kusimbiswa kuti inoshanda, uye uchapupu hahuna kusimba zvakakwana kuti ishandiswe kunze kwehurongwa hwetsvakurudzo.

Chii chinosiyanisa mapoka evanhu

Verenga chikamu chekupedzisira uchichienzanisa nechechipiri, kwete nepfupiso yetsvakurudzo.

Hapana muyedzo pane iyi wakaedza methylene blue semushonga unoshandiswa woga pachirwere chikuru chekuora mwoyo, uye ClinicalTrials.gov haina kunyora tsvakurudzo itsva inoedza kupindira pachirwere chekuora mwoyo kana chekuzvidya mwoyo kupfuura miedzo miviri iri pamusoro, yakanyoreswa muna2003 na2009. Munhu anotsanangura methylene blue semushonga wekuora mwoyo wakasimbiswa ari kutsanangura fungidziro ine nzira yekushanda inonzwisisika uye muyedzo mumwe mudiki wakawana mhedzisiro yakanaka. Hapana muyedzo wakashuma kuchinjira kumamiriro emania.

Njodzi yekudyidzana kwemishonga ndiyo chikonzero chekuchenjerera

Methylene blue inovharira MAO-A. Izvozvo ndizvo zvinoita kuti ifarirwe pakutsvakurudza mamiriro emanzwiro, uye ndizvowo zvinoita kuti ive nenjodzi kana iri pamwe nemimwe mishonga inowedzera kushanda kweserotonin, kusanganisira mishonga mizhinji yekuora mwoyo. Mushonga unovharira MAO kana ukawedzerwa pamushonga unovharira kudzorerwa kweserotonin mumasero unowedzera kushanda kweserotonin nenzira mbiri dzakasiyana, uye kusanganiswa uku kunogona kukonzera muchetura weserotonin, dzimwe nguva unouraya.

Mushonga unopinzwa mutsinga une yambiro iri mubhokisi pamusoro peizvi. FDA yakayambira nezvekudyidzana uku muna2011, ikazoderedza nzvimbo yayaikoshesa ichinangana nekupinzwa mutsinga uye mimwe mishonga yekuora mwoyo. Methylene blue inosanganiswawo mune mimwe mishonga yekunyaradza kurwadza kwenzira yeweti, uye ndiko kwakabva kanenge chiitiko chimwe chete chemuchetura mushure mekuitora nemuromo, mumurwere aitora mishonga yakawanda inowedzera kushanda kweserotonin. Gwaro rekudyidzana kwemishonga rinotsanangura njodzi yacho zvichienderana neboka remushonga nenzira yaunopiwa nayo.

Hapana pamiedzo miviri yemamiriro emanzwiro inopikisa kunetseka uku, asi hapana inopedzawo nyaya yacho. Yose yakaitwa muvarwere vazhinji vaitora mimwe mishonga yepfungwa, uye hapana yakashuma muchetura weserotonin. Izvi zvinopa chivimbo mukati memiedzo midiki yaitariswa uye yaibvisa vamwe vanhu pakutora chikamu, kwete vimbiso yekuchengeteka pakuzvisanganisira mishonga. Muchetura weserotonin unoratidzwa nekushushikana kana kuvhiringidzika, fivha kana kudikitira zvakanyanya, kurova kwemwoyo nekukurumidza, kudedera, kuoma kwetsandanyama, uye kugwinha kusingadzorwi, uye hausi mamiriro ekuzviongororera kumba.

Hunhu hwechigadzirwa hunei nazvo

Mabhodhoro maviri ane chinyorwa chimwe chete anogona kusiyana pane zvimwe zviri mukati. Kutevedzera zvinodiwa negwaro reUSP ndizvo zvinogona kuongororwa nemutengi, uye chigadzirwa chisingazvitevedzeri chingangova chemhando inoshandiswa kupenda machira. Chinogona kuva netsvina yemakemikari akadai seAzure B neAzure C, zvisaririra zvezvinonyungudutsa, uye simbi dzinorema pamwero unoganhurirwa nezvinodiwa zvemhando yemishonga.

Vatengesi vazhinji vanoshandisa mashoko okuti “yakaedzwa nebato rakazvimirira” vanongoedza simbi dzinorema chete, vozopa boka iroro rimwe remiedzo sokunge rinokwanisa kuzadzisa zvose zvinodiwa. Blupreme inoedza zvose zvinodiwa neUSP: kuzivikanwa kwechinhu, kuchena kwacho, tsvina yemakemikari ane kabhoni, zvisaririra zvezvinonyungudutsa, tsvina yezvinhu zvemakemikari, zvisaririra mushure mekupiswa, miganhu youtachiona hudiki, uye maendotoxin ebhakitiriya, uye inobudisa chitupa chekuongorora pabatch imwe neimwe. Kuchiverenga nemazvo kunoreva kuongorora nhamba yebatch, rabhoritari, nzira dzakashandiswa, nemiganhu, panzvimbo pekungotsvaga chiratidzo chekuti chakapasa.

Mhedziso yakatendeseka

Muyedzo webipolar ndiwo uchapupu hwakasimba kupfuura humwe muvanhu, uye unoratidza mhedzisiro yepakati pemushonga unowedzerwa pane uripo pazviratidzo zvakasara muboka revanhu vane mamiriro akadzikama uye zviratidzo zvisina kunyanya kukomba. Muyedzo wekuora mwoyo kwakanyanya wakatora mavhiki matatu uye waiva nevarwere makumi matatu nevashanu. Muyedzo wekutya nzvimbo dzakavharika unoratidza mhedzisiro chaiyo pakusimbiswa kwendangariro inogona kushanda mune rimwe remativi maviri. Muyedzo wePTSD hauna kudzokorora kubatsirwa pamhedzisiro yawo huru. Hapana chakaedzwa kubva ipapo.

Izvi ndizvo zvinoita nzira yekushanda inovimbisa isati yava kurapwa, uye ndizvowo zvinoitika kana kemikari ichitengeswa ichivimba nesimba renzira yayo yekushanda panzvimbo pemhedzisiro yayo. Kana uchitora mushonga wekuora mwoyo wawakanyorerwa, mushonga unovharira MAO, opioid, kana chero mumwe mushonga unowedzera kushanda kweserotonin, runyorwa irworwo runofanira kuuya pakutanga kwehurukuro, pamberi pemubvunzo upi zvawo pamusoro pemwero wemushonga. Muunganidzwa wose wetsvakurudzo unonyora miedzo netsvakurudzo dzekuedza dziri shure kwezvirevo izvi. Tanga nepfupiso yemhedzisiro isingadiwi nemamiriro anoita kuti mushonga usashandiswa uye ongororo yezvinotsigirwa netsvakurudzo muvanhu, woverenga uchapupu hune chokuita nechirwere chebipolar chete kana chiri icho chirwere chakaonekwa kuti unacho. Usarega mushonga wawakanyorerwa kuti utsive nemushonga uchiri kuedzwa.