Methylene blue pa kukhumudwa ndi nkhawa: mayesero, malire, ndi chiopsezo cha kugwirizana kwa mankhwala

Methylene blue yakhala ikuperekedwa kwa odwala matenda a maganizo kuyambira m'ma 1890, yayesedwa m'mayesero oyendetsedwa ndi gulu loyerekezera kuyambira m'ma 1980, ndipo yaphunziridwa mu nyama zomwe zimasonyeza bwino kwambiri kugwirizana pakati pa mlingo ndi zotsatira zake. Munthu amene akufufuza za "methylene blue pa kukhumudwa" amapeza mitundu yonse itatu ya umboni itasakanizidwa, popanda zizindikiro zoisiyanitsa.

Kusiyanitsaku n'kofunika. Umboni wonse wa mayesero oyendetsedwa ndi gulu loyerekezera mwa anthu pa mmene munthu amamvera umachokera m'mayesero awiri ndi kafukufuku umodzi wa kukumana ndi zinthu zochititsa mantha mu labotale, ndipo mayesero onse awiri olembetsedwa anatha zaka zoposa khumi zapitazo. Nkhaniyi ikufotokoza zimene aliyense anapeza. Siikulimbikitsa methylene blue ngati chithandizo cha matenda a mmene munthu amamvera.

Chifukwa chake utoto unayamba kupezeka m'mabuku a kafukufuku wa mmene munthu amamvera

Methylene blue inali mankhwala oyamba kupangidwa kwathunthu mwaukadaulo omwe anagwiritsidwa ntchito ngati mankhwala ochizira. Monoamine oxidase A, yofupikitsidwa kuti MAO-A, imaphwanya serotonin, ndipo mankhwala amene amalepheretsa ntchito yake ndi mankhwala odziwika ochizira kukhumudwa. Ramsay, Dunford, ndi Gillman anayeza mmene imakhudzira MAO-A ya anthu yoyeretsedwa ndipo ananena kuti chiwerengero chokhazikika cha kuletsa kwake chinali pafupifupi 27 nanomolar, ndipo kuletsako kunkatha kubwerera m'mbuyo. MAO-B inkafuna kuchuluka koposa ka makumi asanu. Molekyulu yomweyi imalepheretsanso nitric oxide synthase ndi guanylate cyclase, n'chifukwa chake kuwunika kwa 2017 kwa Delport ndi anzake kumaona kuti ntchito yake yochepetsa kukhumudwa imakhudza zinthu zingapo m'malo mochokera pa cholandirira chimodzi chokha.

Izi zikufotokoza chifukwa chake kafukufuku wa nyama akusonyeza chiyembekezo komanso zinthu zachilendo. Mu makoswe, methylene blue imabweretsa khalidwe lofanana ndi limene limachokera ku mankhwala ochepetsa kukhumudwa pa mayeso okakamiza kusambira, koma m'malire ena a mlingo okha: Eroglu ndi Caglayan anapeza zotsatira pakati pa 15 ndi 30 mg/kg koma osati pa 60 mg/kg, ndipo khalidwe lochepetsa nkhawa linasonyezanso mpiringidzo wa U wotembenuzidwa womwewo. Kubaya pang'ono mu dorsal periaqueductal gray kunagwira ntchito pa 30 nanomoles koma osati kunja kwa malirewo. Izi zimatchedwa hormesis, ndipo mpiringidzo wa mawonekedwe amenewa sungagwiritsidwe ntchito kuneneratu zotsatira za milingo yapamwamba.

Mayesero a m'ma 1980 ndi mlingo wotchedwa placebo womwe mwina sunali placebo

Naylor ndi anzake anachita mayesero a zaka ziwiri osinthanitsa magulu a chithandizo, osadziwitsa odwala kapena ofufuza gulu lomwe munthu analimo mwa odwala 31 a matenda a bipolar, poyerekezera 300 mg patsiku ndi 15 mg patsiku pamene lithium inapitiriza kuperekedwa. Anthu khumi ndi asanu ndi awiri anamaliza, ndipo kukhumudwa kunali kochepa kwambiri pa mlingo wapamwamba, kusiyana komwe kunali kofunika pa ziwerengero.

Kapangidwe ka mayeserowa kali ndi vuto lofunika kulimvetsa, chifukwa limabwerezabwereza. Mamiligalamu khumi ndi asanu patsiku anasankhidwa kukhala gulu la "placebo" poganiza kuti mlingowo sungakhale ndi ntchito. Kenako olemba kafukufukuyo analemba za "kukayikira kwathu kuti magulu a chithandizo anabisikadi, ndi kusatsimikiza ngati 15 mg ya methylene blue patsiku ingatchedwe placebo." Methylene blue imasandutsa mkodzo kukhala wabuluu wobiriwira, choncho wodwala aliyense m'mayesero osinthanitsawo anali kumwa utoto womwe ntchito yake inkaoneka m'magawo onse awiri. Ngati mlingo wochepawo unali ndi ntchito, mayeserowo anayerekezera milingo iwiri yogwira ntchito.

Mayesero afupifupi anayerekezera 15 mg patsiku ndi placebo yeniyeni pa matenda oopsa a kukhumudwa kwa milungu itatu, mwa odwala 35, ndipo anapeza kuti kusintha kukhala bwino kunali kwakukulu kwambiri pa methylene blue, kusiyana komwe kunali kofunika pa ziwerengero. Milungu itatu ndi odwala makumi atatu ndi asanu zimapereka chizindikiro chenicheni, koma chaching'ono.

Mayesero osinthanitsa pa bipolar: umboni wamphamvu kwambiri mwa anthu

Mayesero opereka chidziwitso chochuluka kwambiri ndi kafukufuku wa 2017 wa Alda ndi anzake, wolembetsedwa ngati NCT00214877. Panali anthu makumi atatu ndi asanu ndi awiri a matenda a bipolar I kapena II, onse akumwa lamotrigine ngati mankhwala awo aakulu okhazikitsira mmene amamvera, ndipo ambiri anali ndi zizindikiro zotsalira zofatsa kapena zapakatikati. Mayeserowo anali osinthanitsa chithandizo, osadziwitsa odwala kapena ofufuza gulu lomwe munthu analimo: 15 mg patsiku kwa miyezi itatu poyerekezera ndi 195 mg patsiku kwa miyezi itatu, ndi dongosolo losankhidwa mwachisawawa. Olemba kafukufukuyo anafotokoza momveka bwino chifukwa chosankha mlingo wochepa ngati choyerekezera: "Tinasankha kapangidwe kameneka chifukwa methylene blue imasintha mtundu wa mkodzo, motero sitinathe kugwiritsa ntchito placebo yachizolowezi."

Pakuwunika odwala 27 omwe anamaliza:

• Kukhumudwa kunachepa kwambiri pa mlingo wapamwamba, ndi kukula kwa kusintha kwa 0.71 pa sikelo ya Hamilton Depression Rating Scale (95% CI 0.15 mpaka 1.25, P = 0.034) ndi 0.80 pa sikelo ya Montgomery-Asberg Depression Rating Scale (95% CI 0.27 mpaka 1.30, P = 0.020).
• Nkhawa zinachepa kwambiri pa mlingo wapamwamba, ndi kukula kwa kusintha kwa 0.79 pa sikelo ya Hamilton Anxiety Rating Scale (95% CI 0.22 mpaka 1.33, P = 0.028). Zinthu zoyezera nkhawa za m'maganizo ndi zomwe zinasonyeza kusinthaku; nkhawa zooneka m'thupi zinasonyeza kusiyana kofunika pa ziwerengero pokhapokha pa kuwunika komwe kunaphatikiza onse omwe anapatsidwa gulu la chithandizo.
• Zizindikiro za mania zinakhalabe zochepa komanso zokhazikika, popanda kusintha kupita ku hypomania kapena mania.
• Luso loganiza silinasinthe pa ntchito iliyonse mwa zisanu ndi chimodzi, kuphatikizapo kuphunzira mawu, luso lokonza ndi kuwongolera zochita, ndi kukumbukira zinthu zakale.

Anthu khumi mwa 37 anasiya mayeserowo, mmodzi chifukwa cha mkodzo wabuluu, mmodzi chifukwa nkhawa zinawonjezeka, ndipo mmodzi atatha kuipiraipira kwa matenda. Zotsatira zosafunika zinali zosakhalitsa komanso zofatsa, makamaka kutentha m'njira ya mkodzo, kutsegula m'mimba, nseru, ndi mutu. Anthu pakati pa 20 ndi 27 anali kumwa mankhwala a kukhumudwa kapena oletsa psychosis nthawi yonseyi, ndipo mayeserowo sananene za kuvulazidwa ndi serotonin yochuluka.

Gululi silinali la anthu okhumudwa kwambiri. Poyambira, chiwerengero chinali 12.7 pa sikelo ya Montgomery-Asberg, yomwe imafika pa 60, ndi 7.6 pa sikelo ya Hamilton ya zinthu 17: izi zinali zizindikiro zotsalira mwa odwala omwe matenda awo anali okhazikika, osati matenda aakulu a kukhumudwa. Kuwunika mwadongosolo kodziyimira pawokha kwa 2021 pa chithandizo cha nkhawa mwa anthu a bipolar omwe zizindikiro zawo zinachepa kumawerengera mayeserowa ngati amodzi mwa kafukufuku wa mankhwala awiri okha omwe anasonyeza zotsatira zabwino pa nkhawa, mwa mayesero khumi osankha magulu mwachisawawa omwe anawunikidwa, ndipo kumati kusiya mayesero kwa anthu ambiri ndi zotsatira zosafunika zooneka mosavuta mwina zinasokoneza kubisidwa kwa magulu a chithandizo.

Kafukufuku umodzi woyendetsedwa ndi gulu loyerekezera pa nkhawa mwa anthu

Kafukufuku woyamba woyendetsedwa ndi gulu loyerekezera mwa anthu pa methylene blue ndi nkhawa sunali mayesero a chithandizo koma kafukufuku wolimbitsa kukumbukira. Telch ndi anzake analemba anthu akuluakulu omwe anali ndi mantha aakulu a malo otsekedwa, ndipo aliyense anamaliza magawo asanu ndi limodzi a mphindi zisanu okumana ndi manthawo m'chipinda chotsekedwa. Atangomaliza, ndipo pambuyo pake pokha, anapatsidwa 260 mg ya methylene blue kapena placebo, popanda odwala kapena ofufuza kudziwa gulu lomwe munthu analimo. Kuyesanso patatha mwezi m'chipinda china kunayeza ngati mantha anabwerera.

Zotsatirazo zinasiyanitsa gululi. Anthu omwe anamaliza gawo lokumana ndi mantha ali ndi mantha ochepa anasungabe kusintha kwabwinoko kwambiri pa methylene blue, pamene omwe anamaliza akadali ndi mantha anachita moipa kuposa pa placebo. Mankhwalawo akuoneka kuti amalimbitsa chilichonse chomwe chinaphunziridwa, motero gawo lomwe linalimbitsa mantha linabweretsa mantha ochuluka. Kukumbukira zochitika ndi malo ake kunasintha kukhala bwino mulimonsemo, kutsimikizira kuti mankhwalawo anafika mu ubongo. Mlingo womwewo mu ndondomeko yomweyo unabweretsa zotsatira zotsutsana malinga ndi chinthu chimodzi, chomwe chikufotokozedwa mu chifukwa chake mmene gawo lokumana ndi mantha layendera kumatsimikizira zotsatira zake.

Mayesero a PTSD ndi chigamulo chodziyimira pawokha

Kafukufuku wokulirapo wotsatira anali mayesero a Zoellner ndi anzake osankha magulu mwachisawawa pa PTSD yokhalitsa, olembetsedwa ngati NCT01188694. Odwala makumi anayi ndi awiri anapatsidwa magawo asanu a tsiku ndi tsiku okumana ndi zochititsa mantha m'maganizo, otsatiridwa ndi 260 mg ya methylene blue, ndondomeko yomweyo yotsatiridwa ndi placebo, kapena anaikidwa pa mndandanda wodikira womwe pambuyo pake unalandira chithandizo chachizolowezi chokumana ndi zochititsa mantha kwa nthawi yaitali.

Pa zotsatira zazikulu, sikelo ya PTSD Symptom Scale yoyezedwa ndi wowunika wodziyimira pawokha, methylene blue sinasiyanire ndi placebo. Zotsatira zomwe zinaikidwa m'kaundula zikusonyeza ziwerengero za pambuyo pa chithandizo za 17.10 pa methylene blue poyerekezera ndi 14.67 pa placebo, ndipo zonse zinatsika kuchokera pa pafupifupi 32 poyambira. Kusiyanako kunakomera placebo.

Zotsatira ziwiri zina zinasonyeza mosiyana. Odwala ambiri pa methylene blue anawerengedwa kuti anasintha bwino ndi chithandizo, ndipo chiwerengero cha anthu ofunika kupatsidwa chithandizo kuti mmodzi apindule chinali 7.5; moyo wawo unasinthanso kukhala wabwino ndi kukula kwa kusintha kwa 0.58. Phindulo linadalira luso losunga ndi kugwiritsa ntchito chidziwitso m'maganizo kwakanthawi, osati kusintha kwa zikhulupiriro zokhudzana ndi zochitika zowawa.

Kenako kuwunika mwadongosolo kwa 2023 pa kusintha kukumbukira ndi mankhwala mu chithandizo cha maganizo chokhazikika pa zochitika zowawa kunaika methylene blue m'gulu la mankhwala omwe sanasonyeze kuchepa kwa zizindikiro za PTSD kofunika pa ziwerengero. Uku ndi kumvetsa kodziyimira pawokha komwe kulipo panopa: sikunatsimikizidwe kuti sikugwira ntchito, sikunatsimikizidwe kuti kumagwira ntchito, ndipo umboni wake siwamphamvu mokwanira kuti kugwiritsidwa ntchito kunja kwa ndondomeko ya kafukufuku.

Zimene zimasiyanitsa magulu a anthu

Werengani gawo lomaliza poyerekeza ndi lachiwiri, osati ndi chidule cha kafukufuku.

Palibe mayesero amenewa omwe anayesa methylene blue ngati chithandizo chokha cha matenda aakulu a kukhumudwa, ndipo ClinicalTrials.gov sililemba kafukufuku watsopano wa chithandizo pa matenda a kukhumudwa kapena nkhawa kuposa mayesero awiri omwe ali pamwambawa, omwe analembetsedwa mu 2003 ndi 2009. Aliyense amene akunena kuti methylene blue ndi mankhwala otsimikizidwa ochizira kukhumudwa akufotokoza lingaliro lomwe lili ndi njira yogwirira ntchito yomveka komanso mayesero amodzi ang'onoang'ono okhala ndi zotsatira zabwino ochirikiza lingalirolo. Palibe mayesero omwe ananena za kusintha kupita ku mania.

Chiopsezo cha kugwirizana kwa mankhwala ndi chifukwa chosamalira

Methylene blue imalepheretsa MAO-A. Zimenezi ndi zomwe zimapangitsa kuti ikhale yosangalatsa pa nkhani ya mmene munthu amamvera, ndipo ndi zomwenso zimapangitsa kuti ikhale yoopsa ikagwiritsidwa ntchito pamodzi ndi mankhwala ena okhudza serotonin, kuphatikizapo mankhwala ambiri a kukhumudwa. Mankhwala oletsa MAO akawonjezedwa pa mankhwala oletsa kubwezeretsedwa kwa serotonin m'maselo, amawonjezera ntchito ya serotonin kudzera m'njira ziwiri zosiyana, ndipo kuphatikizaku kungayambitse kuvulazidwa ndi serotonin yochuluka, komwe nthawi zina kumapha.

Mankhwala operekedwa m'mitsempha ali ndi chenjezo loikidwa m'bokosi pankhaniyi. FDA inachenjeza za kugwirizana kumeneku mu 2011 ndipo pambuyo pake inakhazikitsa chenjezolo makamaka pa kupereka m'mitsempha ndi mankhwala enaake a kukhumudwa. Methylene blue ilinso m'mankhwala ena ochepetsa ululu wa njira ya mkodzo, ndipo umu ndi mmene vuto limodzi kapena kuposerapo linachitikira munthu yemwe ankamwa mankhwalawa pakamwa pamene ankamwanso mankhwala angapo okhudza serotonin. Chitsogozo cha kugwirizana kwa mankhwala chimafotokoza chiopsezochi malinga ndi gulu la mankhwala ndi njira yoperekera.

Palibe mayesero a mmene munthu amamvera omwe amatsutsa nkhawayi, koma palibenso omwe amathetsa funsoli. Onse awiri anachitika mwa odwala omwe ambiri ankamwa mankhwala ena a matenda a maganizo, ndipo palibe omwe ananena za kuvulazidwa ndi serotonin yochuluka. Izi ndi zolimbikitsa m'mayesero ang'onoang'ono oyang'aniridwa, okhala ndi malamulo osaphatikiza anthu ena, koma sizitsimikizira chitetezo kwa munthu wosakaniza mankhwala yekha. Kuvulazidwa ndi serotonin yochuluka kumasonyeza kusakhazikika kapena kusokonezeka maganizo, kutentha thupi kapena kutuluka thukuta kwambiri, kugunda kwa mtima mwachangu, kunjenjemera, kuuma kwa minofu, ndi kugwedezeka kwa thupi kosalamulirika, ndipo si vuto loyenera kudziyesera kunyumba.

Mmene mulingo wa khalidwe la mankhwalawo umakhudzira nkhaniyi

Mabotolo awiri okhala ndi chizindikiro chofanana angakhale ndi zinthu zina zosiyana mkati. Wogula angayang'ane ngati mankhwalawo akutsatira zofunikira za monograph ya USP, ndipo mankhwala osatsatira zofunikirazo mwina ndi a mulingo wogwiritsidwa ntchito pa nsalu, omwe angakhale ndi zonyansa za organic monga Azure B ndi Azure C, zosungunulira zotsalira, ndi zitsulo zolemera pa milingo yomwe imachepetsedwa ndi zofunikira za mankhwala ochizira.

Ogulitsa ambiri omwe amagwiritsa ntchito mawu akuti "ayesedwa ndi gulu lodziyimira pawokha" amangoyesa zitsulo zolemera basi, kenako amaonetsa mayeso amodziwo ngati kuti akwaniritsa zofunikira zonse. Blupreme imayesa zofunikira zonse za USP: kutsimikizira mtundu wa mankhwala, kuyera kwake, zonyansa za organic, zosungunulira zotsalira, zonyansa za ma elementi, zotsalira pambuyo powotcha, malire a tizilombo, ndi endotoxins za mabakiteriya, ndipo imasindikiza satifiketi ya kusanthula ya gulu lililonse lopangidwa. Kuwerenga satifiketiyi molondola kumatanthauza kuyang'ana nambala ya gulu lopangidwa, labotale, njira zoyesera, ndi malire ake m'malo mongofunafuna chizindikiro chakuti yapambana.

Mfundo yomaliza yoona

Mayesero a bipolar ndiwo umboni wamphamvu kwambiri mwa anthu, ndipo amasonyeza kusintha kwapakatikati kuchokera ku chithandizo chowonjezera pa zizindikiro zotsalira mwa anthu omwe matenda awo anali okhazikika komanso zizindikiro zawo zinali zofatsa. Mayesero a kukhumudwa koopsa anali a milungu itatu ndi odwala makumi atatu ndi asanu. Kafukufuku wa mantha a malo otsekedwa amasonyeza kusintha kwenikweni pa kulimbitsa kukumbukira komwe kungapite mbali iliyonse. Mayesero a PTSD sanabwereze zotsatira zabwino pa muyeso wawo waukulu. Palibe china chomwe chayesedwa kuyambira pamenepo.

Umu ndi mmene njira yogwirira ntchito yopatsa chiyembekezo imaonekera isanakhale chithandizo, komanso ndi mmene zinthu zimaonekera pamene mankhwala akugulitsidwa chifukwa cha njira yake yogwirira ntchito m'malo mwa zotsatira zake. Ngati mumamwa mankhwala a kukhumudwa olembedwa ndi dokotala, mankhwala oletsa MAO, opioid, kapena mankhwala ena aliwonse okhudza serotonin, mndandandawu uyenera kukhala koyambirira kwa zokambirana, musanafunse za mlingo. Laibulale yonse ya kafukufuku imalemba mayesero ndi kafukufuku omwe akuchirikiza zonenazi. Yambani ndi chidule cha zotsatira zosafunika ndi zinthu zoletsa kugwiritsa ntchito mankhwalawa komanso kuwunika kwa zimene kafukufuku wa anthu amachirikiza, ndipo werengani umboni wokhudza matenda a bipolar makamaka ngati ndi matenda omwe munapezeka nawo. Musasiye mankhwala olembedwa ndi dokotala kuti muyambe kugwiritsa ntchito mankhwala oyeserera.