Methylene blue ndi matenda a Alzheimer: kutanthauzira mayesero

Mukafufuza methylene blue ndi matenda a Alzheimer, mumapeza nkhani ziwiri nthawi imodzi. Imodzi imati utoto wabuluu womwe wakhala ukugwiritsidwa ntchito kwa zaka zana unachepetsa kufulumira kwa kutayika kwa kukumbukira. Ina imati mayesero otsatira sanapambane. Nkhani zonsezi zimatchula zolemba zenizeni za kafukufuku. Kusokonezeka kumachokera pa kutenga zinthu zosiyanasiyana za mankhwala ngati kuti ndi mankhwala amodzi.

Si mankhwala amodzi. Mayesero oyambirira anayesa methylthioninium chloride ya mtundu wa oxidized, chinthu chabuluu chodziwika bwino. Mayesero onse otsatira a Alzheimer anayesa mtundu wa reduced womwe unapangidwa kuti ukhale wokhazikika, leuco-methylthioninium, womwe tsopano umatchedwa hydromethylthionine mesylate (HMTM). Milingo, kuyamwidwa m'thupi, ngakhalenso magulu oyerekezera amasiyana pakati pa mapulogalamu awiriwa. Mukasiyanitsa mankhwalawa, mbiri ya mayesero imakhala yomveka bwino, ndipo siipereka umboni wochirikiza kugwiritsa ntchito zowonjezera zakudya.

Mitundu iwiri ya mankhwala

Methylene blue ya m'botolo nthawi zambiri ndi methylthioninium chloride, yomwe imafupikitsidwa kuti MTC. Mbali yake yogwira ntchito ndi ayoni ya methylthioninium ya mtundu wa oxidized, MT+, molekyulu yokhala ndi chaji ya magetsi komanso mtundu wabuluu kwambiri. Chajiyi imabweretsa vuto m'matumbo. Kuti MT+ idutse bwino khoma la matumbo, iyenera kuyamba yasinthidwa mwa reduction kukhala mtundu wa leuco wopanda chaji komanso wopanda mtundu. Mmene gawo la reduction limachitikira zimasiyanasiyana, ndipo pa milingo yapamwamba kusungunuka ndi kuyamwidwa kwa MTC kumafika pa malire malinga ndi mlingo, zomwe ndi chimodzi mwa zifukwa zimene pulogalamu yoyambirira ya Alzheimer inakumana ndi mavuto pa kapangidwe ka mankhwalawo.

Mankhwala otsatira amapewa gawo limenelo. LMTM, yomwe ilinso ndi nambala ya TRx0237 ndipo tsopano imatchedwa HMTM, imapereka molekyulu ya mtundu wa reduced mwachindunji ngati mchere wa mesylate wokhazikika wa makhirisitali. Methylthioninium ya mtundu wa reduced yosakhala mu mchere imabwerera ku mtundu wabuluu mwa oxidation mkati mwa mphindi zochepa ikakhala mumlengalenga. Choncho, kapangidwe kake ka mchere ndi kamene kamapangitsa kuti ikhale mankhwala osungika m'malo mongokhala chinthu chochititsa chidwi mu labotale. Mwachidule: MTC ndi mankhwala oyambirira abuluu a mtundu wa oxidized omwe amasanduka ogwira ntchito m'thupi ndipo amayamwidwa mosiyanasiyana, pamene LMTM/HMTM ndi mtundu wa reduced wokhazikitsidwa kuti kuchuluka kwake komwe kumafika m'thupi kuzikhala kodziwikiratu. Zonena za mphamvu yogwira ntchito ya mtundu umodzi sizingagwiritsidwe ntchito pa winawo, ndipo za mitundu yonseyi sizingagwiritsidwe ntchito pa utoto wosungunuka wogulitsidwa popanda chilolezo cha dokotala. Ndi bwino kumvetsa kemisitire ya mitundu ya oxidized ndi reduced musanawerenge mutu uliwonse wa nkhani ya mayesero.

Njira yogwirira ntchito yomwe ikuyesedwa ilinso yopapatiza kuposa mmene nkhani zofalitsidwa zimasonyezera. Pulogalamuyi ikuyang'ana kusonkhanirana kwa tau, komwe mapuloteni a tau amaunjikana n'kupanga ulusi ndi mfundo zopotanapotana m'kati mwa maselo a mitsempha, osati zolembera za amyloid. Izi zikutanthauza kuti ndi njira ina yosiyana ndi ya ma antibody olimbana ndi amyloid. Ilinso pambali pa kafukufuku wina woyambirira wa njira zochotsera amyloid, usanayesedwe mwa anthu, komanso ndemanga zambiri za malingaliro okhudza mitochondria ndi kuteteza maselo a mitsempha, zomwe siziyenera kutengedwa ngati umboni wa mayesero azachipatala.

Mankhwala omwe anagwiritsidwa ntchito pa mayesero aliwonse

Ili ndi tebulo loyenera kusungidwa kuti mudzabwererenso. Mzere uliwonse umatchula mankhwala enieni, milingo, zotsatira zoyezedwa, ndi nambala yozindikiritsa mayesero, chifukwa zambiri mwa zidule za nkhani zimalakwitsa pa mfundo zimenezi.

Zolemba zonse: lipoti la Rember la gawo 2, mayesero oyambirira a LMTM a gawo 3, kuwunika gulu la otenga nawo mbali la gawo 3 lachiwiri, kuwunikanso ubale wa kuchuluka kwa mankhwala m'thupi ndi kusintha komwe kumaoneka, komanso cholemba cha kapangidwe ka mayesero a Lucidity.

Kuwerenga zotsatira zilizonse moganizira kapangidwe ka mayeserowo

Yambani ndi Rember. Inali ndi placebo yeniyeni, zomwe ndi zabwino, koma utoto wabuluu umapangitsa kuti kubisa amene akulandira mankhwala enieni kukhale kovuta. Kusintha kwa mtundu wa mkodzo ndi chimbudzi kungasonyeze amene akumwa mankhwala ogwira ntchito, ndipo ofufuzawo anavomereza kuti gulu la placebo linalibe chizindikiro chimenecho. Analekanitsa anthu oyesa chitetezo ndi anthu oyesa mphamvu yogwira ntchito, ndipo anatchula umboni wa zithunzi za m'thupi pochirikiza zotsatira, koma chiopsezo chakuti anthu angazindikire magulu awo chidakalipo. Mukawonjezera kuti chizindikiro cha phindu chinaoneka m'gulu laling'ono lokha komanso kuti mlingo wapamwamba kwambiri sunapambane, chigamulo choona mtima ndi chakuti zotsatirazo ndi zochititsa chidwi koma umboni wake ndi wosalimba. N'chifukwa chake pulogalamuyi inasinthira ku mankhwala atsopano m'malo mochita mayesero akuluakulu a MTC.

Mayesero awiri a LMTM a gawo 3 anathetsa vuto lobisa magulu mwa njira ina ndipo anabweretsa vuto latsopano. Kuti mkodzo ukhale wosintha mtundu m'gulu loyerekezera, mayesero onse awiri anapatsa gululo 8 mg/day ya LMTM yeniyeni. Ngati 8 mg/day imagwira ntchito yokha, ndiye kuti kuyerekezera mlingo wapamwamba ndi gulu loyerekezera kumakhala kuyerekezera mankhwala awiri, ndipo kusapezeka kwa kusiyana sikungasiyanitse pakati pa “onse amagwira ntchito” ndi “palibe amene amagwira ntchito.” Kuwunika komwe kunachitika pambuyo pake kwa anthu olandira mankhwala amodzi okha komanso kwa kuchuluka kwa mankhwala m'magazi kumasonyeza kuti mlingo wochepawo unali kugwiradi ntchito. Zolemba zowunika kafukufuku wa ukalamba zimakambirana vutoli la kumasulira kafukufuku kukhala chithandizo, koma kuwunika kumeneku sikusunganso kugawa m'magulu mwachisawawa. Kaya wodwala anali kumwa LMTM yokha kapena limodzi ndi mankhwala wamba a Alzheimer zinadalira mankhwala omwe anali atamulembera kale, osati kusankha mwachisawawa. Choncho, kusiyana pa kulembedwa kwa mankhwala ndi pa thanzi loyambirira kungafotokoze mbali ya kusiyana kwa zotsatira. Kafukufuku wa ubale pakati pa kuchuluka kwa mankhwala m'thupi ndi kusintha komwe kumaoneka umalimbitsa kufotokoza kwa mmene mankhwalawo angagwirire ntchito, koma supereka kuyerekezera komwe kukusowa ndi placebo yopanda ntchito.

Kenako Lucidity inabwereza njira yomweyi pa milingo yochepa. Gulu loyerekezera linkalandira milingo yaying'ono ya MTC kawiri pa sabata, yongofuna kupatsa mkodzo mtundu. Komabe, anthu ambiri m'gululo anasonkhanitsa kuchuluka kwa mankhwala komwe kungagwire ntchito m'thupi. Wothandizira kafukufukuyu ananena momveka bwino kuti kuyerekezera komwe kunakonzedwa ndi placebo yosagwira ntchito sikunatheke. Malipoti otsatira amatsindika kusiyana kwa zizindikiro za m'thupi ndi kwa kuyamba mochedwa, zomwe zimathandiza kumvetsa mmene matendawa amachitikira, koma sizofanana ndi kupambana placebo m'mayesero omwe kuyerekezera kwawo kunakonzedweratu. Pofika mu 2024 mpaka 2025, mankhwalawa anali akadali ofufuzidwa; pempho la chilolezo ku UK linali litaperekedwa, ndipo cholemba chotsimikizira zizindikiro za m'thupi chinali chikadali kuwunikidwa ndi akatswiri ena.

Zimene izi zikutanthauza kwa wowerenga amene akuganizira methylene blue

Pali mfundo zitatu zothandiza.

Choyamba, mankhwala a m'mayesero si ofanana ndi chowonjezera zakudya. HMTM ndi mchere wa mankhwala woyeretsedwa wa mtundu umodzi, womwe umaperekedwa pa 8 mpaka 16 mg/day mu pulogalamu yapano. Methylene blue ya m'botolo nthawi zambiri ndi chloride ya mtundu wa oxidized, yokhala ndi kuyera kosiyanasiyana, yoyezedwa ndi chodonthozera, komanso yosiyana pa kuyamwidwa ndi zinthu zosafunika zomwe imakhala nazo. Kuthekera kolekerera milingo yochepa ya HMTM m'mayesero sikutiuza chilichonse chokhudza kudzipatsa utoto wosungunuka kwa nthawi yaitali.

Chachiwiri, zizindikiro za mavuto a chitetezo zomwe zinaoneka pa nthawi ya milingo yapamwamba ziyenera kutengedwa mozama ngakhale kuti milingo yapano ndi yochepa. Mu pulogalamu yayikulu ya gawo 3, kutsegula m'mimba kunakhudza pafupifupi wodwala m'modzi mwa anayi olandira mlingo wapamwamba. Nseru, kusanza, ndi kufuna kukodza mwadzidzidzi zinawonjezekanso momveka bwino. Anthu okhala ndi kuperewera kwa G6PD sanaloledwe kulowa m'mayesero chifukwa mankhwala a methylthioninium angayambitse kuwonongeka kwa maselo ofiira a magazi m'gulu limenelo. Kuyanjana kwake ndi mankhwala ochiza kuvutika maganizo omwe amakhudza serotonin ndi chenicheni pa momwe mankhwala amagwirira ntchito, chifukwa methylene blue ndi yoletsa MAO-A yamphamvu yomwe kuletsa kwake kumatha kubwerera m'mbuyo. Izi zili choncho ngakhale kuti mayesero a Alzheimer analemba zizindikiro za kanthawi kochepa mwa ogwiritsa ntchito SSRI ochepa, osati matenda a serotonin syndrome otsimikiziridwa. Aliyense amene akuphatikiza mankhwalawa amafunikira kuyang'aniridwa ndi katswiri wa zachipatala, mfundo yomwe imafotokozedwa mwatsatanetsatane m'buku lotsogolera la chitetezo ndi kuyanjana kwa mankhwala.

Chachitatu, ziyembekezo zanu zigwirizane ndi msinkhu wa umboni womwe ulipo. Chizindikiro cha phindu m'gulu laling'ono, kuphatikiza mayerekezero awiri ogawa anthu mwachisawawa omwe sanasonyeze kupambana, komanso gulu loyerekezera lokhala ndi zinthu zosokoneza kumasulira zotsatira, ndi lingaliro loyenera kufufuzidwa, osati upangiri wa chithandizo. Mabanja omwe akuganizira njira zosiyanasiyana adzapeza zambiri zothandiza pofufuza mmene zisankho za chisamaliro cha Alzheimer zimapangidwira kwenikweni, m'malo motsatira ndondomeko iliyonse ya kugwiritsa ntchito utoto yomwe ikufalitsidwa pa intaneti.

Mfundo yaikulu ndi yosavuta kufotokoza m'chiganizo chimodzi. Methylene blue ya mtundu wa oxidized inapereka chizindikiro chimodzi chosalimba cha phindu mu gawo 2, chokhala ndi chenjezo pa kubisa magulu ndi kuyamwidwa; mankhwala ake otsatira a mtundu wa reduced sanapambane m'mayerekezero awiri a milingo ogawa anthu mwachisawawa; ndipo pulogalamu ya milingo yochepa sinaperekebe kupambana komveka bwino poyerekeza ndi placebo. Izi zingasinthe ndi zolemba zam'tsogolo kapena kuwunika kwa mabungwe olamulira mankhwala. Mpaka zitasintha, methylene blue ya matenda a Alzheimer ili m'gulu la sayansi yozama yomwe sinasandukebe chithandizo chamankhwala.