Chinyorwa
Methylene Blue neChirwere cheBipolar: Kuongorora Tsvakurudzo yeKurapa
Muchidimbu
Methylene blue yava nenguva yakareba ichidzidzwa muchirwere chebipolar kupfuura zvinofungwa nevanhu vazhinji, kutanga kuma1970 apo vaongorori vaitsvaga zvinotsiva lithium nezvinowedzerwa pairi. Humbowo hwose huripo hushoma: chidzidzo chimwe chete chenhevedzano yevarwere chisina kuvanza kurapwa, miedzo miviri yekare yaiva nemapoka ekuenzanisa, uye chidzidzo chimwe chete chemazuva ano chekuchinjanisa kurapwa chichishandisa kugoverwa kwemapoka zvisina kurongwa. Chiratidzo chinoramba chichionekwa muzvidzidzo izvi ndechekuvandudzika kwezviratidzo zvekuora mwoyo nezvakanga zvasara apo methylene blue yakawedzerwa pakurapa kwaivapo. Hapana chidzidzo chakaratidza kuderedzwa kwemania, uye hapana chakabudisa chiratidzo chakajeka chekuchinjira kumania, kunyange zvazvo mapoka evatori vechikamu aiva madiki zvikuru kuti apedze mubvunzo wekuchinja uku. Ani naani ari kuongorora chinhu ichi anofanira kuverenga izvi sezvidzidzo zvekurapa kunowedzerwa pane kumwe, kwete sehumbowo hwekushandisa mushonga uyu uri woga, uye anofanira kufunga nezveyambiro dzekudyidzana kwemishonga asati aita mhedziso dzokushandisa.
Nei chirwere chebipolar chakatanga kufarirwa nokukurumidza
Chikonzero hachina kumbova chekuti methylene blue yaitaridzika semushonga wakajairika wekudzikamisa manzwiro. Pakuumbwa kwayo inofanana nemaphenothiazine, uye vaongorori vekutanga vakafungidzira kuti yaigona kushandura vanadate iri muplasma kuita chimiro chisinganyanyi kushanda, ichichinja mashandiro esodium-potassium ATPase anofungidzirwa kuva nechekuita nekuchinjachinja kwemanzwiro. Pakuedza kuona kana pfungwa iyi yaigona kushanda, Naylor nevamwe vakarapa varwere vaviri vaingoramba vachichinjachinja mamiriro emanzwiro, vakaona nguva refu dzemanzwiro akadzikama, izvo zvakakurudzira zvose zvakazotevera. Nhoroondo yaHowland yemethylene blue mukurapa kwepfungwa inoisa basa iri mumamiriro aro, ichitevera chinhu ichi kubva pakuva chinotangira phenothiazine kusvika pakuva chinhu chinoedzwa pakushandura mashandiro epfungwa.
Basa rakazotevera rokuongorora mashandiro aro rakashandura chikonzero chacho richitarisa mashandiro emitochondria nekuenzana kweoxidation nereduction. Kusashanda zvakanaka kwemitochondria kwakabatanidzwa nechirwere chebipolar kuburikidza nezvidzidzo zvemhuri, zvakawanikwa pakushanda kwemajini mushure mekufa, uye mhando dzemhuka dzinoshandiswa mutsvakurudzo, dzakadai segonzo rine shanduko yejini rePOLG1, iro rine maitiro akafanana nebipolar anopindura zvishoma kulithium. Ongororo yaAlda ya2019 yemethylene blue muzvirwere zvetsinga nepfungwa inotsanangura kuti kugona kwechinhu ichi kutakura maerekitironi achipfuura nzvimbo dzakavharika munhevedzano yekufambiswa kwemaerekitironi, zvichideredza kubuda kwemhando dzeoxygen dzinokurumidza kuita makemikari, kunochipa kukosha sechinhu chinobatsira kuongorora shanduko dzemashandiro emitochondria. Imwe ongororo yemethylene blue sechinhu chingashandiswa kurapa kuora mwoyo inowedzera kudziviswa kweMAO-A, kuvharwa kwenitric oxide synthase neguanylate cyclase, uye kuderedzwa kwekuzvimba kumufananidzo wemashandiro acho. Asi mashandiro aya ipfungwa dzichiri kufungidzirwa. Mubvunzo wekurapa ndewekuti miedzo yakayera chii, uye mumamiriro api.
Miedzo, mumwe nomumwe
Nhevedzano yevarwere yaNarsapur naNaylor: varwere vasingapinduri pakurapa, kurapwa kusina kuvanzwa
Mushumo wokutanga waiva wenhevedzano isina boka rekuenzanisa yevarwere 24 vaiva nechirwere chenguva refu kana chakanyanya, vakapiwa methylene blue yekuwedzera pakurapa pa200 kana 300 mg pazuva kwenguva dzaitangira pamazuva kusvika kupfuura gore. Gumi nevapfumbamwe vaiva nechirwere chebipolar (mania nekuora mwoyo), uye 14 pavanhu ivavo 19 vakanzi vakanga vavandudzika zvechokwadi, chikamu che74 muzana chevakapindura pakurapa. Varwere vatatu vane kuonekwa kwechirwere chebipolar kwaionekwa sekusina chokwadi havana kupindura pakurapa.
Izvi ngazvionekwe senzira yokubudisa pfungwa dzokuzoyedza, kwete semashoko anoratidza kushanda kwemushonga. Pakanga pasina kugoverwa kwemapoka zvisina kurongwa, pasina kuvanzwa kweruzivo rwekurapwa, pasina chikero chakamisikidzwa, uye mishonga yaishandiswa kare haina kutaurwa zvakakwana. Nhamba ye74 muzana inobva munhevedzano isina kuvanza kurapwa yevarwere vasingapinduri pakurapa inoratidza kutonga nokusarudza kwevaongorori zvakangofanana nezvainoratidza mashandiro emushonga.
Naylor nevamwe, 1986: kudzivirira kudzokazve kwechirwere kwemakore maviri nekuchinjanisa kurapwa pamwe nelithium
Iyi ndiyo yaiva yakanyanya kuda kuita zvakawanda pamiedzo yekutanga: muyedzo wemakore maviri wekuchinjanisa kurapwa, wakagovera varwere 31 vane chirwere chebipolar mumapoka zvisina kurongwa, varwere nevaongorori vasingazivi kuti kurapwa kupi kwaipiwa. Mumwe nomumwe aifanira kupiwa 300 mg pazuva kwegore rimwe uye 15 mg pazuva kwerimwe gore, muhurongwa hwakasarudzwa zvisina kurongwa. Mwero we15 mg ndiwo waishandiswa pakuenzanisa, wakasarudzwa zvikuru nokuti kuchinja kweruvara rweweti kwaiita kuti zvisabvire kuvanza placebo isingashandi zvachose. Chinokosha ndechekuti mumwe nomumwe akaramba achishandisa lithium nguva yose, saka kubva pakutanga uku kwaiva kurapa kwekuwedzera kudzivirira kudzokazve kwechirwere.
Gumi nevanomwe pavatori vechikamu 31 vakapedza makore ose ari maviri. Pakati pevakapedza, zviratidzo zvekuora mwoyo zvaiva zvishoma zvakanyanya mugore re300 mg pane mugore re15 mg, asi kukura kwezviratidzo zvemania hakuna kusiyana pakati pemwero miviri iyi. Huwandu hwekupinzwa muchipatara hwakanzi hwaiva hushoma panguva yemuyedzo kupfuura usati watanga, kunyange zvazvo ongororo yaAlda yakazotevera ichiti izvi zvakaitikawo panguva dze15 mg, izvo zvinoomesa kududzirwa kwezvakawanikwa. Vaongorori pachavo vakataura kusasimba kwacho: boka diki, 45 muzana vakarega kutora chikamu, zvikero zviri nyore, kusava nechokwadi kwekuvanzwa kweruzivo rwekurapwa, uye kusava nechokwadi chokuti 15 mg yaisashanda mumuviri. Kunetseka kwokupedzisira uku kwakazoratidza kuva kwechokwadi, sezvinotsanangurwa pasi apa.
Chidzidzo chaNaylor chekuora mwoyo pamwero mudiki: nei “placebo” ingave yaishanda
Kuenzanisa kwakazotevera kwemavhiki matatu, uko varwere nevaongorori vaisaziva kurapwa kwaipiwa, kwakaedza 15 mg pazuva ichienzaniswa neplacebo isingashandi muvarwere 35 vaiva nekuora mwoyo kwakanyanya, ndokuona methylene blue ichipfuura placebo zvakakosha maererano nenhamba. Iri raiva boka raizonyanya kuva nekuora mwoyo kusina mania, kwete muyedzo webipolar, saka riri muhumbowo hwekuora mwoyo huzhinji kwete muboka rebipolar. Kukosha kwaro kuvaverengi vanofarira bipolar kuri pamaitiro ekutsvakurudza: mwero we15 mg wakashandiswa pakuenzanisa mumiedzo yose miviri yekuchinjanisa kurapwa wainge watokunda placebo isingashandi. Saka musiyano wokurapa wakayerwa uchienzaniswa ne15 mg ungangoratidza musiyano uri mudiki pane musiyano wakazara waizoonekwa kana pasina kurapwa, uye zvinorevawo kuti hapana pamiedzo miviri yekare waiva neboka replacebo rechokwadi.
Alda nevamwe, 2017: muyedzo wemazuva ano wekuchinjanisa kurapwa kwekuwedzera
Chidzidzo chakanyanya kurongeka kusvika parizvino chakagovera vanhu vakuru 37 vane chirwere chebipolar I kana II nezviratidzo zvakasara, zvisina kurongwa, kuti vapiwe methylene blue 195 mg pazuva ichienzaniswa ne15 mg pazuva, mwero mumwe nomumwe kwemavhiki 13 vachichinjanisa. Uku kwakanga kuri kurapa kwekuwedzera zvakajeka: mumwe nomumwe akanga agadzikana achishandisa lamotrigine kwemwedzi ingangoita mitatu uye akaramba achiishandisa, uye lithium, divalproex, mishonga inorapa psychosis, nemishonga yekuora mwoyo zvaibvumirwa pamwero usingachinji. Muyedzo uyu wakanyorwa paPubMed 27284082. Zviratidzo pakutanga zvaiva zvishoma kusvika pakati nepakati, zvibodzwa zvekuora mwoyo pachikero chaHamilton zvichiita avhareji inenge 7.6, uye zveMontgomery-Asberg zviri pedyo ne12.7.
Zvakawanikwa zvakaratidza zviri nani pa195 mg pazviyero zvekuora mwoyo nekuzvidya mwoyo. Pakati pevakapedza, hukuru hwemhedzisiro hwaiva hunenge 0.71 pachikero chekuora mwoyo chaHamilton, 0.80 pachikero cheMontgomery-Asberg, uye 0.79 pachikero chekuzvidya mwoyo chaHamilton, chimwe nechimwe chichikosha maererano nenhamba. Ongororo yaishandisa kuyerwa kwekupedzisira kuripo pachinzvimbo chezviyero zvakazoshayikwa muvarwere vose 37 yakabudisawo zvakawanikwa zvakafanana uye zvakakosha maererano nenhamba. Zvibodzwa zvemania zvakaramba zviri pasi uye zvakagadzikana, pasina mhedzisiro yekurapa, uye boka remiedzo yekugona kufunga harina kuratidza kubatsira kwakakosha pakurangarira mashoko, kugona kuronga nekudzora zviito, kana zviyero zvekutarisa pfungwa. Vatori vechikamu gumi vakarega nokuda kwezvikonzero zvaisanganisira kuwedzera kwezviratidzo zvebipolar, kuzvidya mwoyo, kuungana kwemvura mumuviri, uye kubvisa mvumo yokutora chikamu. Migumisiro yakaipa yainyanya kuva kupisa pakuita weti kwaipfuura, kusagadzikana kwemudumbu nemuura, uye kutemwa nemusoro.
Tafura yemiedzo yekurapa: zvakanyatsoyedzwa
| Chidzidzo | Marongerwo uye n | Mwero wemethylene blue | Kurapwa kwaishandiswa pamwe nayo | Zviyero zvemhedzisiro | Mhedzisiro huru | Zvipingamupinyi |
|---|---|---|---|---|---|---|
| Narsapur naNaylor, nhevedzano isina kuvanza kurapwa | Nhevedzano yevarwere isina boka rekuenzanisa, 24 vose (19 vane bipolar) | 200 kusvika 300 mg pazuva, mazuva 3 kusvika mwedzi 19 | Varwere vasingapinduri pakurapa; mishonga yaishandiswa kare haina kutaurwa zvakakwana | Kutonga kwenyanzvi yekurapa pamusoro pekuvandudzika | 14 pavarwere 19 vebipolar vakanzi vakavandudzika | Hapana boka rekuenzanisa, hapana kuvanzwa kweruzivo rwekurapwa, kuyerwa kunotsamira pakutonga kwemunhu, kushandiswa kwakasiyana-siyana |
| Naylor nevamwe, 1986 | Kuchinjanisa kurapwa kwemakore 2, varwere nevaongorori vasingazivi kurapwa kwaipiwa, 31 vakatanga, 17 vakapedza | 300 mg ichienzaniswa ne15 mg, gore rimwe pamwero mumwe nomumwe | Lithium yakaramba ichishandiswa nevatori vechikamu vose | Zviyero zvezviratidzo zvekuora mwoyo nemania, kupinzwa muchipatara | Kuora mwoyo kushoma pa300 mg; hapana musiyano wemania | 45 muzana vakarega, zvikero zviri nyore, kuvanzwa kweruzivo rwekurapwa kwakakanganiswa, 15 mg ingangove yaishanda |
| Chidzidzo chaNaylor chemwero mudiki | Muyedzo weRCT wemavhiki 3, varwere nevaongorori vasingazivi kurapwa kwaipiwa, uchienzanisa neplacebo isingashandi, n=35, kuora mwoyo kwakanyanya | 15 mg pazuva | Mishonga yaishandiswa kare haina kutaurwa zvakakwana | Kukura kwekuora mwoyo | 15 mg yakapfuura placebo | Harisi boka rebipolar; hapana nhamba yehukuru hwemhedzisiro mupfupiso yakanyorwa |
| Alda nevamwe, 2017 | Kuchinjanisa kurapwa kwemavhiki 13, varwere nevaongorori vasingazivi kurapwa kwaipiwa, 37 vakagoverwa zvisina kurongwa, 27 vakapedza | 195 mg ichienzaniswa ne15 mg | Lamotrigine mune vose; lithium, divalproex, mishonga inorapa psychosis, nemishonga yekuora mwoyo zvaibvumirwa kana mwero wacho usina kuchinja | MADRS, HAM-D, HAM-A, YMRS, CGI-BP, kugona kufunga | Kuvandudzika kwekuora mwoyo nekuzvidya mwoyo kwakakosha maererano nenhamba pa195 mg; hapana mhedzisiro pam mania kana pakugona kufunga | Boka diki, zviratidzo zvakasara (kwete zvemamiriro akanyanya panguva iyoyo), mishonga yakawanda pamwe chete, mhedzisiro inosara kubva pachikamu chakapfuura, 15 mg ingangove yaishanda |
| Muyedzo waNaylor wemania | Chidzidzo chemania, varwere nevaongorori vasingazivi kurapwa kwaipiwa, n=18 | Mashoko acho haagoni kusimbiswa kubva mumushumo wakanyorwa | Hazvigoni kuwanikwa kubva mumushumo unowanikwa | Zviratidzo zvemania | Hapana kubatsira pakuderedza mania kwakaratidzwa | Mushumo wemapeji maviri, hapana pfupiso yakanyorwa, mwero nechikero hazvigoni kusimbiswa |
Kuverenga zvinoratidzwa nehumbowo nokutendeseka
Zvinhu zvitatu zvinoramba zvakamira kunyange zvichitariswa pamwe nezvipingamupinyi. Chokutanga, mhedzisiro inoenda kudivi rimwe chete: zviratidzo zvekuora mwoyo nezvakasara zvakavandudzika pamwero wakakwirira muzvidzidzo zvose zviri zviviri zvebipolar zvaiva nemapoka ekuenzanisa, uye hukuru hwemhedzisiro hwaiva pakati nepakati mumuyedzo wemazuva ano. Chechipiri, hapana mune zvakanyorwa izvi chinotsigira chirevo chokuderedza mania. Muyedzo wakanangana nemania hauna kuratidza kubatsira, uye zvidzidzo zvekuchinjanisa kurapwa hazvina kuwana musiyano wemania. Izvi zvinoreva kushaikwa kwehumbowo hwekushanda pakuderedza mania, kwete humbowo hwekudzikamisa manzwiro kumativi ose ari maviri. Chechitatu, hapana chiratidzo chemania yakatanga panguva yekurapwa chakaonekwa, asi chirevo ichocho hachina kurema kukuru. Zvibodzwa zvemania pakutanga zvaiva pedyo nezero uye mapoka akapiwa mushonga aingova nemakumi evanhu, saka zvidzidzo izvi zvaisagona kuona njodzi yekuchinjira kumania yaiva yakakura zvakakwana kuti ive yakakosha pakurapa. Matauriro akarurama ndeekuti hapana chiratidzo chekuchinja chakaonekwa, kwete kuti njodzi yekuchinja yakanga yarambwa.
Matambudziko maviri emaitiro ekutsvakurudza anofanira kusimbiswa nokuti anobata humbowo hwose huripo. Kuvanzwa kweruzivo rwekurapwa kwakakanganiswa namarongerwo acho muchidzidzo chimwe nechimwe chekuchinjanisa kurapwa, nokuti methylene blue inoshandura ruvara rweweti uye mwero mudiki wekuenzanisa wakasarudzwa chaizvo kuti utevedzere mhedzisiro iyoyo, uchifungidzirwa kuti hauiti basa. Uye fungidziro iyoyo haina kumira: mwero mudiki wakakunda placebo isingashandi pakuora mwoyo, zvichireva kuti kuenzanisa kukuru kwaiva kwekuyera mwero miviri inogona kushanda, kwete kuedza mushonga uchienzaniswa neplacebo. Hukuru hwemhedzisiro hunoyerwa nenzira iyi hwakaoma kududzira uye hahugoni kubatanidzwa nemiedzo yakajairika yemishonga yekuora mwoyo ine mapoka eplacebo.
Kusabuda pamiganhu yenyaya kunokosha pano. Iyi imiedzo yebipolar ine zviyero zvemhedzisiro yebipolar, uye haifaniri kusanganiswa nehumbowo hunobva kune mamwe mapoka evanhu. Vaverengi vanofarira tsvakurudzo dzine ukama nazvo vanofanira kutarisa zvakawanikwa pamusoro pekuzvidya mwoyo, tsvakurudzo yekugona kufunga, uye mashoko ekuchengeteka nekudyidzana kwemishonga zvakasiyana, nokuti chimwe nechimwe chine marongerwo ezvidzidzo uye zvinhu zvekufunga nezvenjodzi zvakasiyana.
Mamiriro ekuchengeteka pakushandisa mishonga yakawanda mubipolar
Yambiro mbiri dzine chokuita zvakananga nevarwere vebipolar, avo vanowanzopiwa mishonga inobata serotonin. Methylene blue nechigadzirwa chinobva pakuputswa kwayo mumuviri, Azure B, zvinodzivisa MAO-A zvine simba asi kudzivisa kwacho kuchikwanisa kudzokera shure, uye kuzvishandisa pamwe neSSRIs, SNRIs, nemimwe mishonga inobata serotonin kunogona kukonzera serotonin syndrome. Dzinenge nyaya dzose dzakabudiswa dzehuturu dzaisanganisira methylene blue yaipiwa mutsinga, uye muyedzo wemazuva ano webipolar wakabvumira mishonga yekuora mwoyo muvatori vechikamu 20 pa37 pasina chiitiko chine chokuita neserotonin. Asi chiitiko chidiki ichocho hachibvisi yambiro yekudyidzana kwemishonga, uye mashoko ari pachigadzirwa chinopiwa mutsinga parizvino ane yambiro iri mubhokisi panyaya iyi. Pamusoro pezvo, kushomeka kweglucose-6-phosphate dehydrogenase kunoita kuti methylene blue isafanira kushandiswa nokuti inogona kukonzera kuparara kwemasero matsvuku eropa, uye muyedzo wemazuva ano hauna kutora varwere vakadaro. Ani naani anosanganisa mishonga iyi anoda kutarisirwa nenyanzvi yekurapa; uku kushanda kwemishonga kune nzira chaidzo dzokukonzera kukuvadza, kwete kungodyidzana kusina ngozi kwechinowedzerwa pakudya.
Izvi zvinosiya mubvunzo papi
Zvakanyorwa pamusoro pemethylene blue muchirwere chebipolar zvishoma, zvekare, uye zvinopa pfungwa yokuti panogona kuva nekubatsira, pamwe nemuyedzo mumwe wemazuva ano wokutanga wakaitwa zvine mutsindo. Pfupiso yakatendeseka ndeiyi: methylene blue yakawedzerwa pakurapa pamwero unosvika 195 kusvika 300 mg pazuva yakaramba ichideredza zviratidzo zvekuora mwoyo nezvakasara mumapoka madiki, yakaratidza chiratidzo chekuderedza kuzvidya mwoyo kamwe chete, haina kuratidza kubatsira pakugona kufunga, haina kuratidza kuderedza mania, uye haina kuratidza chiratidzo chekuchinjira kumania chaigona kuonekwa nemapoka madiki aya. Miedzo mikuru ine placebo yechokwadi, mapoka ane kuora mwoyo kwebipolar kwakanyanya panguva iyoyo, kuongororwa kwekuchinjira kumania kwakatsanangurwa muyedzo usati watanga, uye nzira dzakakwana dzekuvanza ruzivo rwekurapwa haisati yaitwa. Kusvikira yaitwa, methylene blue inoramba iri chinhu chekuwedzera pakurapa chichiri kuferefetwa mumamiriro aya, chinonakidza zvakakwana kuti chidzidzwe zvakare asi chine humbowo hushoma zvikuru kuti hutsigire mhedziso.