Methylene Blue ndi Matenda a Bipolar: Kusanthula Kafukufuku wa Zachipatala

Mwachidule

Methylene blue yakhala ikufufuzidwa pa matenda a bipolar kwa nthawi yaitali kuposa mmene anthu ambiri amaganizira, kuyambira m’zaka za m'ma 1970 pamene ofufuza ankafuna njira zina m'malo mwa lithium ndiponso zothandizira kuwonjezera pa iyo. Umboni wonse ulipo ndi wochepa: kafukufuku mmodzi wa mndandanda wa odwala wopanda kubisa chithandizo, mayesero awiri akale okhala ndi gulu loyerekeza, ndi kafukufuku mmodzi wamakono wogawa anthu mwachisawawa kuti alandire chithandizo chilichonse motsatana. Chotsatira chofanana mwa onsewa ndi kuchepa kwa zizindikiro za kukhumudwa ndi zotsalira pamene methylene blue inawonjezeredwa pa chithandizo chomwe chinalipo kale. Palibe kafukufuku amene anasonyeza kuchepetsa mania, ndipo palibe amene anasonyeza bwino chizindikiro chosinthira ku mania, ngakhale kuti chiwerengero cha anthu chinali chochepa kwambiri kuti chithe kuthetsa funso la kusintha kumeneko. Aliyense wowunika mankhwalawa ayenera kuwerenga kafukufukuyu ngati wa chithandizo chowonjezera, osati ngati umboni wa kugwiritsa ntchito mankhwalawa okha, ndipo ayenera kuganizira machenjezo a kuyanjana kwa mankhwala asanafike pa mfundo iliyonse yokhudza kagwiritsidwe ntchito.

Chifukwa chake matenda a bipolar anakopa chidwi koyambirira

Maganizo oyambira sanali akuti methylene blue inkaoneka ngati mankhwala achizolowezi okhazikitsa maganizo. Kapangidwe kake kamafanana ndi ka phenothiazines, ndipo ofufuza oyambirira anaganiza kuti ingasinthe vanadate ya m'madzi a magazi kukhala mtundu wosagwira ntchito kwambiri, motero kusintha ntchito ya sodium-potassium ATPase imene imaganiziridwa kukhala yokhudzana ndi kusinthasintha kwa maganizo. Pofuna kuona ngati lingaliroli lingagwire ntchito, Naylor ndi anzake anapatsa chithandizo odwala awiri omwe maganizo awo ankasinthasintha mosalekeza ndipo anaona kuti nthawi imene maganizo awo anali okhazikika inatalika, zomwe zinalimbikitsa zonse zomwe zinatsatira. Nkhani ya Howland yokhudza mbiri ya methylene blue m’chipatala cha matenda a maganizo imafotokoza mmene ntchitoyi inayambira, kutsatira mankhwalawa kuchokera ku chinthu choyambira kupanga phenothiazine kufika ku mankhwala oyeserera okhudza maganizo.

Kafukufuku wotsatira wokhudza mmene mankhwalawa amagwirira ntchito unasintha maziko a lingaliroli kuti ayang’ane ntchito ya mitochondria ndi kukhazikika kwa njira za redox. Kusagwira bwino ntchito kwa mitochondria kwagwirizanitsidwa ndi matenda a bipolar kudzera mu kafukufuku wa mabanja, zomwe zapezeka pa kugwira ntchito kwa majini m'matupi a anthu atamwalira, ndi zitsanzo za nyama monga mbewa yokhala ndi jini ya POLG1 yosinthika, yomwe mikhalidwe yake yofanana ndi bipolar imayankha pang’ono ku lithium. Kuwunika kwa Alda kwa mu 2019 kwa methylene blue pa matenda a ubongo ndi maganizo kumati kuthekera kwa mankhwalawa kunyamula ma electron kudutsa malo otsekeka mu unyolo wonyamula ma electron, kuchepetsa kutuluka kwa mitundu ya oxygen yogwira ntchito kwambiri, kumapangitsa kukhala kothandiza pofufuza njira zosinthira ntchito ya mitochondria. Kuwunika kwina kwa methylene blue ngati mankhwala omwe angathe kugwiritsidwa ntchito pochepetsa kukhumudwa kumawonjezera kulepheretsa MAO-A, kutsekereza nitric oxide synthase ndi guanylate cyclase, ndiponso kuchepetsa kutupa pa kufotokoza mmene ingagwirire ntchito. Komabe, njira zimenezi ndi malingaliro oti ayesedwe. Funso la zachipatala ndi zimene mayesero anayeza, ndiponso mmene anachitikira.

Mayesero, limodzi ndi limodzi

Mndandanda wa odwala wa Narsapur ndi Naylor: odwala osayankha ku chithandizo, chithandizo chosabisidwa

Lipoti loyamba linali la mndandanda wa odwala 24 omwe anali ndi matenda osatha kapena oopsa, popanda gulu loyerekeza, omwe anapatsidwa methylene blue yowonjezera pa chithandizo pa 200 kapena 300 mg tsiku lililonse kwa nthawi kuyambira masiku angapo mpaka kupitirira chaka. Anthu khumi ndi asanu ndi anayi anali ndi matenda a bipolar (mania ndi kukhumudwa), ndipo 14 mwa anthu 19 amenewo anaonedwa kuti anachira bwino ndithu, kutanthauza kuti 74 peresenti anayankha ku chithandizo. Odwala atatu omwe matenda awo a bipolar ankaonedwa ngati osatsimikizika sanayankhe ku chithandizo.

Onani zimenezi ngati zoyambitsa malingaliro oti afufuzidwe, osati deta yotsimikizira mphamvu ya chithandizo. Panalibe kugawa anthu mwachisawawa, kubisa chithandizo, sikelo yovomerezeka yoyezera, ndipo mankhwala ena omwe ankagwiritsidwa ntchito sanafotokozedwe mokwanira. Chiwerengero cha 74 peresenti chochokera ku mndandanda wa odwala osayankha ku chithandizo, wopanda kubisa chithandizo, chimasonyeza kuweruza kwa woyang’anira ndi kusankha odwala mofanana ndi mmene chimasonyezera mphamvu ya mankhwala.

Naylor ndi anzake 1986: kupewa kubwereranso kwa matenda kwa zaka ziwiri posinthana chithandizo limodzi ndi lithium

Uwu unali kafukufuku wokhala ndi cholinga chachikulu kwambiri mwa oyambirira: mayesero a zaka ziwiri mwa odwala 31 okhala ndi matenda a bipolar, ogawa anthu mwachisawawa, osinthana chithandizo, komanso obisa chithandizo kwa odwala ndi ofufuza. Munthu aliyense ankayenera kulandira 300 mg tsiku lililonse kwa chaka chimodzi ndi 15 mg tsiku lililonse kwa chaka china, motsatira dongosolo losankhidwa mwachisawawa. Mlingo wa 15 mg unagwiritsidwa ntchito poyerekeza, makamaka chifukwa kusintha kwa mtundu wa mkodzo kunapangitsa kuti zikhale zosatheka kubisa mankhwala oyerekeza opanda mphamvu iliyonse. Chofunika kwambiri n’chakuti munthu aliyense anapitiriza kumwa lithium nthawi yonseyi, choncho kuyambira pachiyambi ichi chinali chithandizo chowonjezera choletsa kubwereranso kwa matenda.

Anthu khumi ndi asanu ndi awiri mwa 31 anamaliza zaka zonse ziwiri. Mwa omwe anamaliza, zizindikiro za kukhumudwa zinali zochepa kwambiri m’chaka cha 300 mg kuposa m’chaka cha 15 mg, pamene kuopsa kwa zizindikiro za mania sikunasiyane pakati pa milingo imeneyi. Chiwerengero cha kugonekedwa m’chipatala chinanenedwa kukhala chochepa panthawi ya mayesero kuposa kale, ngakhale kuti kuwunika kwa Alda kwa pambuyo pake kunanena kuti izi zinachitikanso pa nthawi za 15 mg, zomwe zimapangitsa kutanthauzira kukhala kovuta. Ofufuzawo anatchula okha zofooka zake: anthu ochepa, 45 peresenti osamaliza, masikelo osavuta oyezera, kukayikira ngati chithandizo chinabisidwa bwino, ndi kusatsimikiza ngati 15 mg inalibe mphamvu ya mankhwala. Nkhawa yomalizayi inadzapezeka kuti inali yomveka, monga momwe zafotokozedwera pansipa.

Kafukufuku wa Naylor wa mlingo wochepa pa kukhumudwa: chifukwa chake mankhwala oyerekeza a "placebo" angakhale anali ndi mphamvu

Kuyerekeza kotsatira kwa milungu itatu, kobisa chithandizo kwa odwala ndi ofufuza, kunayesa 15 mg tsiku lililonse motsutsana ndi placebo yopanda mphamvu mwa odwala 35 okhala ndi kukhumudwa koopsa, ndipo kunapeza kuti methylene blue inali yabwino kwambiri kuposa placebo. Gululi linali ndi anthu ambiri okhala ndi kukhumudwa kopanda mania, osati mayesero a bipolar, choncho kafukufukuyu ali m’gulu la umboni wa kukhumudwa mwachisawawa osati m’gulu la bipolar. Kufunika kwake kwa owerenga okhudza bipolar kuli pa njira ya kafukufuku: mlingo wa 15 mg womwe unagwiritsidwa ntchito poyerekeza m’mayesero onse awiri osinthana chithandizo unali utaposa kale placebo yopanda mphamvu. Choncho kusiyana kulikonse kwa chithandizo koyezedwa poyerekeza ndi 15 mg mwina kumachepetsa kusiyana konse kumene kukanapezeka poyerekeza ndi kusapereka mankhwala, komanso kumatanthauza kuti palibe mwa mayesero akalewo omwe anali ndi gulu lenileni la placebo.

Alda ndi anzake 2017: mayesero amakono a chithandizo chowonjezera chosinthana

Kafukufuku wochitidwa mosamalitsa kwambiri mpaka pano anagawa mwachisawawa akuluakulu 37 okhala ndi matenda a bipolar I kapena II ndi zizindikiro zotsalira kuti alandire methylene blue 195 mg tsiku lililonse poyerekeza ndi 15 mg tsiku lililonse, mlingo uliwonse kwa milungu 13 posinthana. Ichi chinali chithandizo chowonjezera momveka bwino: munthu aliyense anali atakhala wokhazikika pa lamotrigine kwa miyezi yosachepera itatu ndipo anapitiriza kuigwiritsa ntchito, pomwe lithium, divalproex, mankhwala oletsa psychosis, ndi mankhwala ochepetsa kukhumudwa analoledwa ngati milingo yake inali yosasintha. Mayeserowa ali pa PubMed 27284082. Zizindikiro zoyambira zinali zofatsa mpaka zapakatikati, ndipo avareji ya miyeso ya kukhumudwa ya Hamilton inali pafupifupi 7.6, pomwe ya Montgomery-Asberg inali pafupi ndi 12.7.

Zotsatira zinakomera 195 mg pa miyeso ya kukhumudwa ndi nkhawa. Mwa omwe anamaliza, kukula kwa zotsatira kunali pafupifupi 0.71 pa sikelo ya kukhumudwa ya Hamilton, 0.80 pa sikelo ya Montgomery-Asberg, ndi 0.79 pa sikelo ya nkhawa ya Hamilton, ndipo iliyonse inali yofunikira powerengera ziwerengero. Kusanthula kwa odwala onse 37 komwe kunagwiritsa ntchito muyeso womaliza wopezeka m'malo mwa miyeso yotsatira yomwe inasowa kunapereka zotsatira zofunikira zofanana. Miyeso ya mania inakhalabe yotsika komanso yosasintha, popanda kusiyana kobwera chifukwa cha chithandizo, ndipo mayeso osiyanasiyana a luso la kulingalira sanasonyeze phindu lofunikira pa kukumbukira mawu, luso lokonzekera ndi kuwongolera zochita, kapena miyeso ya kutchera khutu. Anthu khumi anasiya kutenga nawo mbali pazifukwa monga kuwonjezereka kwa zizindikiro za bipolar, nkhawa, kusungika kwa madzi m’thupi, ndi kubweza chilolezo chawo. Zotsatira zosafunika zinali makamaka kumva kutentha pokodza kwa kanthawi, kusokonezeka kwa m'mimba ndi matumbo, ndi kupweteka kwa mutu.

Tebulo la mayesero a zachipatala: zimene zinayesedwadi

Kuwerenga zotsatira zofanana moona mtima

Pali zinthu zitatu zomwe zikukhalabe zoona ngakhale titaganizira zofooka zake. Choyamba, mbali imene zotsatira zikulozera ndi yofanana: zizindikiro za kukhumudwa ndi zotsalira zinachepa pa mlingo wapamwamba m’mayeso onse awiri a bipolar okhala ndi gulu loyerekeza, ndipo kukula kwa zotsatira kunali kwapakatikati m’mayesero amakono. Chachiwiri, palibe m’kafukufukuyu chothandizira kunena kuti mankhwalawa amachepetsa mania. Mayesero omwe anayang’ana mania okha sanapeze phindu, ndipo kafukufuku wosinthana chithandizo sanapeze kusiyana kwa mania. Izi ndi kusapezeka kwa mphamvu yochepetsa mania, osati umboni wokhazikitsa maganizo kumbali zonse ziwiri za matendawa. Chachitatu, palibe chizindikiro cha mania choyamba chifukwa cha chithandizo chomwe chinaoneka, koma mawu amenewo ali ndi mphamvu yochepa. Miyeso ya mania yoyambira inali pafupi ndi ziro ndipo anthu omwe analandira mankhwalawa anali owerengeka m'makumi, choncho kafukufukuyu sakanatha kuzindikira chiopsezo chosinthira ku mania chofunika pa zachipatala. Mawu oyenera ndi akuti palibe chizindikiro cha kusintha chomwe chinaonedwa, osati kuti chiopsezo cha kusintha chinatsimikizidwa kuti kulibe.

Mavuto awiri a njira za kafukufuku ayenera kutsindika chifukwa amakhudza umboni wonsewu. Kubisa chithandizo kunali kosokonezeka chifukwa cha kapangidwe ka kafukufuku uliwonse wosinthana chithandizo, popeza methylene blue imasintha mtundu wa mkodzo ndipo mlingo wochepa woyerekeza unasankhidwa makamaka kuti utsanzire zimenezo, uku akuganiziridwa kuti ulibe mphamvu. Ndipo lingaliro limenelo silinali lolondola: mlingo wochepa unaposa placebo yopanda mphamvu pa kukhumudwa, kutanthauza kuti kuyerekeza kofunika kunali kwa milingo pakati pa njira ziwiri za chithandizo zomwe zonse zingakhale ndi mphamvu, osati kuyesa mankhwala motsutsana ndi placebo. Kukula kwa zotsatira koyezedwa m’njira imeneyi n’kovuta kutanthauzira ndipo sikungaphatikizidwe ndi mayesero achizolowezi a mankhwala ochepetsa kukhumudwa okhala ndi placebo yoyerekeza.

Kusunga malire a nkhaniyi n’kofunika. Awa ndi mayesero a bipolar okhala ndi miyeso yokhudza bipolar, ndipo sayenera kusakanizidwa ndi umboni wochokera ku magulu ena a anthu. Owerenga omwe akufuna kafukufuku wokhudzana nawo ayenera kuwerenga zotsatira za nkhawa, kafukufuku wa luso la kulingalira, ndi mbiri ya chitetezo ndi kuyanjana kwa mankhwala payokha, popeza chilichonse chimakhudza kapangidwe kosiyana ka kafukufuku ndi zinthu zosiyana zogwirizana ndi chiopsezo.

Chitetezo pamene mankhwala ambiri akugwiritsidwa ntchito pa bipolar

Machenjezo awiri amakhudza mwachindunji odwala a bipolar, omwe nthawi zambiri amapatsidwa mankhwala okhudza serotonin. Methylene blue ndi chinthu chimene thupi limapanga poikonza, Azure B, ndi zoletsa zamphamvu za MAO-A zomwe ntchito yake ingabwererenso, ndipo kuzigwiritsa ntchito limodzi ndi SSRIs, SNRIs, ndi mankhwala ena okhudza serotonin kungayambitse matenda a serotonin syndrome. Pafupifupi zochitika zonse za poizoni zomwe zalembedwa zinakhudza methylene blue yoperekedwa mumtsempha wa magazi, ndipo mayesero amakono a bipolar analola mankhwala ochepetsa kukhumudwa mwa anthu 20 mwa 37 popanda chochitika chokhudza serotonin. Komabe, zimenezi zochokera kwa anthu ochepa sizichotsa chenjezo la kuyanjana kwa mankhwala, ndipo zolemba zamakono za mankhwala operekedwa mumtsempha zili ndi chenjezo lokhala m’bokosi pa nkhaniyi. Payokha, kusowa kwa enzyme ya glucose-6-phosphate dehydrogenase ndi chifukwa chosagwiritsa ntchito mankhwalawa, chifukwa methylene blue ingayambitse kuwonongeka kwa maselo ofiira a magazi, ndipo mayesero amakono sanaphatikize odwala oterowo. Aliyense wophatikiza mankhwalawa amafunika kuyang’aniridwa ndi katswiri wa zachipatala; awa ndi mankhwala okhala ndi njira zenizeni zomwe zingayambitse mavuto, osati kuyanjana kosavulaza kwa mankhwala owonjezera zakudya.

Zimene tinganene pa funsoli pakadali pano

Kafukufuku wa methylene blue pa matenda a bipolar ndi wochepa, wakale, ndipo umangopereka zizindikiro za zomwe zingatheke, kuphatikizapo kafukufuku mmodzi wamakono woyambirira wochitidwa bwino. Chidule choona mtima ndi ichi: methylene blue yowonjezera pa chithandizo pa pafupifupi 195 mpaka 300 mg tsiku lililonse inachepetsa mobwerezabwereza zizindikiro za kukhumudwa ndi zotsalira mwa magulu ang’onoang’ono, inasonyeza chizindikiro cha kuchepetsa nkhawa kamodzi, sinasonyeze phindu pa luso la kulingalira, sinasonyeze kuchepetsa mania, ndipo sinasonyeze chizindikiro chosinthira ku mania chomwe magulu ang’onoang’ono amenewa akanatha kuzindikira. Mayesero akulu okhala ndi placebo yeniyeni yoyerekeza, magulu a anthu okhala ndi kukhumudwa koopsa kwa bipolar, kuyang’anira kusinthira ku mania kokonzedweratu, ndi njira zokwanira zobisira chithandizo sanachitidwe. Mpaka atachitika, methylene blue ikukhalabe chithandizo chowonjezera chomwe chikufufuzidwa pa nkhaniyi, chokopa chidwi chokwanira kuti chifufuzidwe mopitirira, koma chokhala ndi umboni wochepa kwambiri woti mfundo zotsimikizika zitengedwe.