Te puru metilīni mō te korikori me te whakaora: he aha ngā mea kua inea

I te Maehe 2022, i whakaputa tētahi kaioma maratona taumata tiketike i tētahi whakatairanga tautoko ā-pūtea mō tētahi rare ngote puru metilīni, e kī ana "ka āwhina pea ki te whakapai ake i te arotahi, te manawaroa me te moe", ā, ka whakamahia e ia i mua i ngā whakaharatau taumaha. I taua wiki tonu, i kī ngā tākuta i whakahuatia e ngā pāpāho ā-motu, ko te ia whānui ake he kaiārahi pāpāho pāpori e horomi ana i te wai horoi ipu ika. Kāore tētahi o aua tūnga e whakautu i te pātai tūturu a te kaioma.

Kua hoatu rānei e tētahi te puru metilīni ki te tangata, ka ine ai i te tawhiti, i te tere, i te pai rānei o tō rātou whakaora? Kāore ngā rapunga mō tēnei tuhinga i kite i tētahi rangahau whakahaere ki te tangata e whai putanga ana mō te mahi korikori, mō te whakaora rānei. Kei te ara tohutoro e toru ngā momo kararehe, ētahi tauira whakamātautau taiwhanga, me tētahi pūhui ehara rawa i te puru metilīni.

He kerēme rerekē te manawaroa, te whakaora, me te tukanga mahi

Ka neke pea tētahi tohu ki te ahunga kē atu i te mahi ā-tinana, ka neke rānei ahakoa kāore te mahi ā-tinana i panoni. Ehara tērā i te take hangarau iti noa: koirā tonu te tauira i te rangahau korikori mō te puru metilīni e tino whakahuatia ana.

He waikano kē tā te rangahau kurī i whakamahi

Ko te pepa e tino whakahuatia ana mō te puru metilīni me te korikori, ko te rangahau a Imai me ōna hoa i te tau 1986, i whakamahia ai he mīhini oma mō ngā kurī e mataara ana. I whakamātauria mēnā e whakawhirinaki ana te pikinga o te putanga toto o te manawa i te wā korikori ki te āhua hāora-whakaheke o ngā kiko, mā te whakamahi i tā te wāhanga tikanga i kī ai ko "4 mg/kg o te puru metilīni hou 3,7-bis(ethylamino)-2,8-dimethylphenazothonium chloride, Eastman Kodak Company". He waikano thiazine motuhake te puru metilīni hou, e rua ōna rōpū ethylamino ki ngā wāhi e rua ngā rōpū dimethylamino o te puru metilīni. Ko tōna whakamahinga e tino mōhiotia ana, he waikano mō ngā reticulocyte. Ko tētahi hua i puta mā taua waikano, ehara i te hua i puta mā te puru metilīni.

He mea nui tonu te rangahau, nā te mea koirā te whakaaturanga mārama rawa e taea ana e tētahi tohu me ngā mahi ahupūngao te panoni takitahi. I oma ngā kurī i ngā wāhanga e rua, e 20 meneti ia wāhanga, i te 2.5, kātahi i te 5.0 mph, i runga i te pikitanga 6 ōrau. Nā te korikori i rearua te putanga toto o te manawa, ā, i whakatoru ki te whakawhā te kohi hāora o te tinana katoa i ngā rōpū e rua. I te rōpū wai tote, i piki te ōwehenga lactate-ki-pyruvate o te toto i ngā ia-toto i te 6.0 ki te 9.97. I te rōpū i whiwhi i te maimoatanga, kāore i piki.

Kāore tētahi inenga o te mahi i panoni. I ōrite te pikinga o te auau patuki manawa, te pēhanga toto i ngā ia-toto, te kaha kōpeke o te rūma mauī o raro o te manawa, me ngā catecholamine o te wē toto i ngā rōpū e rua. Waihoki, kāore he rerekētanga ā-tatauranga i te hononga i waenga i te putanga toto o te manawa me te kohi hāora o te tinana katoa. Ko te whakatau a ngā kaituhi, ko ngā panoni o te ōwehenga "kāore he hononga take ki te whakaoho o te rere toto e puta ana i te korikori māmā ki te korikori āhua kaha."

He ngoikore ake taua ōwehenga i tōna āhua. I heke nā te pikinga o te pyruvate, i te 0.14 ki te 0.38 mmol mō ia rita, i te wā i piki hoki te lactate, i te 1.05 ki te 2.85 mmol mō ia rita. I ngā kurī i hoatu ai te waikano i te wā whakatā, i piki paku te kohi hāora, i piki te pH o te toto i ngā ia-toto, ā, i heke te hauhā. I kī ngā kaituhi he "rite" aua panoni ki ērā o te 2,4-dinitrophenol, he matū wetewete hononga mitokōria. Nā te kawa whakamātautau i whakarite te tere, nō reira kāore tētahi kurī i oma kia pau rawa tōna kaha.

Te rangahau kauhoe kiore nui, me tōna horopeta

Ko te hua mahi ā-tinana kararehe tino kaha, ko te whakamātau a Peng me ōna hoa i te tau 2025 i Frontiers in Behavioral Neuroscience. I kauhoe ngā kiore nui mō ngā pō karapīpiti tekau, me ngā taumaha e rite ana ki te 3 ōrau o te taumaha tinana kua herea ki ō rātou hiku, mō te rua hāora neke atu ia pō, kia tae ki tētahi paearu pau-kaha i whakatauria mā ngā piro. I muri i ia wāhanga, i whiwhi tētahi rōpū i te puru metilīni mā roto i te ihu, ā, i whiwhi tētahi atu rōpū i te wai tote mā taua ara anō. I roa ake te kauhoe o ngā kiore i whiwhi i te maimoatanga i mua i te tutuki o ngā paearu pau-kaha. I nui ake hoki tō rātou neke i te papa tuwhera i te rā i muri mai, i iti ake te whanonga rite ki te āwangawanga, ā, i iti ake te ngaronga pūtau io, te pakarutanga myelin, me te wāwāhitanga mitokōria i te hippocampus me te striatum.

Ka waiho nuitia te horopeta ki waho i ngā kōrero tuarua mō tēnei rangahau. Ko tētahi wairewa 1 ōrau he 10 mg/mL; tekau ngā microlitre i kuhuna ki ia pongāihu, nō reira e 20 microlitre pea te tapeke, arā, 0.2 mg mō ia kiore i ia wāhanga. Ka kōwhiria te tuku mā roto i te ihu kia tae ki te roro mā ngā ara io hongi me ngā ara io trigeminal. E kī ana ngā kaituhi, "kāore tā mātou rangahau i ine i ngā tauhohenga hāora, i te mumura, i ngā taumata taiaki rānei i te roro me te wē toto." Ko tā rātou tūtohutanga mō te mahi whai muri, kia rangahaua "ngā pānga whānui o te whakamahi MB hei tāpiringa i mua i te korikori."

Koinei te mea ka hiahia tētahi kaioma kia whakamātauria. I tēnei kawa, i hoatu te pūhui i muri i te mahi, hei whakaiti i te wharanga. Ko te kauhoe roa ake i te rā i muri mai, i tētahi tauira kiore kua pau te kaha, he kitenga mō te whakaora, ehara i te kitenga mō tētahi tangata kua whakaharatautia e tango ana i te horopeta i mua i tētahi wāhanga whakaharatau.

Nō hea te kupu "manawaroa"

Ko te rangahau kiore iti e kīia nuitia ana e whakaatu ana i te manawaroa pai ake, ko te mahi a Gureev me ōna hoa i te tau 2016 i Neuroscience Research. I inu ngā kiore i te wai whai puru metilīni i te 15 mg/kg ia rā mō ngā rā 60. Ko te "manawaroa ā-tinana" te whakamātautau taura, pae whakapae rānei, e whakatau tahi ana i te kaha kapo, te ruruku nekeneke, me te taurite. I whiwhi ngā kiore takawaenga-pakeke kāore i maimoatia i te piro 1.17; i whiwhi ngā kiore i maimoatia i te piro 2.23, e tata ana ki te taumata o ngā kiore pakeke. Kāore he mea i pai ake ki ngā kiore pakeke.

I piki te kohi hāora i te wā whakatā mā te 15 ōrau pea. I piki te hanga hauwai waikurate i ngā mitokōria o te roro, i te 94.9 ki te 176.7 pmol ia meneti mō ia milligram pūmua. I piki te DNA mitokōria mā te 2.3 whakareanga. He pikinga tērā o te whakahoutanga mitokōria i ngā kararehe e kaumātuatia ana, me ngā tohu hāora e akiaki ana i taua tukanga. Ehara i te whakaaturanga ka tere ake tētahi kaitākaro hauora.

Ngā whakamātau pūtau, me ō rātou rohe

I pūrongo a Louters me ōna hoa i te tau 2005 ka whakahohe te puru metilīni i te kawe kūhuka mā GLUT1 i ngā pūtau fibroblast L929, tae atu ki te 800 ōrau i te 50 micromolar. I whakaatu tētahi rangahau whai muri i te tau 2008 ka here tika te methyl-beta-cyclodextrin ki te puru metilīni, ā, ka aukati i te pānga. He kitenga tērā mō tētahi rārangi pūtau, kāore anō kia whakaaturia i ngā uaua kōiwi.

E tautohetia ana te tukanga mahi ake

I te rangahau a Tretter me ōna hoa i te tau 2014 mō ngā mitokōria kua wehea mai i ngā roro poaka kini, nā te puru metilīni i te 100 nanomolar ki te 1 micromolar i whakapiki te kohi hāora i te wā whakatā, i whakahoki te pūmanawa hiko o te kiriuhi me te hanga ATP i te wā i aukatia ai te Matatini I, te Matatini III rānei, ā, i whakapiki te hanga hauwai waikurate. Ko te mea hira, "kāore te hānga pungao i whakaohohia e te ADP i pāngia e MB, ahakoa tēhea o ngā matū pūtake" i whakamātauria. Kāore i piki te hānga pungao hono mōrahi, koirā te mea e whakawhirinaki ana ngā kerēme mō te korikori.

I te rangahau whai muri a Gureev me ōna hoa i te tau 2019, i kitea e taua taiwhanga anō nāna te hua kiore iti, "kāore e taea e te puru metilīni te whakahoki i te pūmanawa hiko o te kiriuhi me te hānga pungao kua aukatia e te antimycin" i ngā mitokōria roro o te kiore iti. I whakatau hoki rātou ko te kaiwhiwhi irahiko ko te wāhi Qo o te Matatini III, kaua ko tētahi mea kei tua atu i te mekameka. Kāore te pikitia māmā o te waikano e kawe ana i ngā irahiko kia hipa i tētahi mekameka hānga pungao kua aukatia e tika ana mō ia tauira whakamātautau.

Kāore tētahi o ēnei e whakakore ana i te tūponotanga o tētahi pānga ki te tangata. Engari, e tohu ana he raruraru kei roto tonu i te tukanga mahi mō te tohe e ahu mai ana i taua tukanga anake, e whakaarohia ai ngā tauhohenga matū mitokōria e āhua tika ana hei hua kua whakaūngia.

E rua ngā raruraru hoahoa me whakatika e tētahi whakamātautau tangata

He uaua te huna i te maimoatanga puru metilīni. Ka huri te mimi kia kahurangi-kākāriki, ā, ka kite te tangata. I kī tika te whakamātautau whakawhiti o te tau 2017 mō te mate rangirua: "I kōwhiria e mātou tēnei hoahoa nā te mea ka panoni te puru metilīni i te tae o te mimi, nō reira kāore i taea te whakamahi i tētahi rongoā horihori tikanga noa." I whakataurite taua whakamātautau i tētahi horopeta iti ki tētahi horopeta nui, kaua ki tētahi pire kore pānga.

He kino ake tēnei raruraru i te rangahau korikori i te nuinga o ngā horopaki kē, nā te mea ka tino pāngia te whakapau kaha e rangona ana me te mahi i tētahi whakamātautau ā-wā e te tūmanako. Ki te kore e taea e tētahi whakamātautau te huna i te maimoatanga mai i ōna kaiuru, kua ine taua whakamātautau i tētahi whakapono, pērā anō i tana ine i tētahi rongoā.

Kei te tuhia tētahi otinga. I te whakamātautau atahanga matapōkere o te tau 2016 ki ngā pakeke hauora 26, i hoatu te 280 mg puru metilīni kōeke USP, tata ki te 4 mg/kg, he rongoā horihori rānei nō te waikano kai FD&C puru nama 2, i roto i ngā kāpene puatakore ōrite. I tonoa ngā kaiuru kia mimi i mua i te hoatutanga o te horopeta, engari kia kaua e mimi anō, "kia kore ai e whakararu i te hunanga o te maimoatanga nā tētahi panonitanga o te tae mimi."

Ko te raruraru tuarua ko te horopeta me te ara tuku. Ka puta tētahi wāhanga o te puru metilīni ā-waha i te mimi, ā, ko te nui ka tae ki te roro i muri i te horopeta ā-waha, he haurua pea o tērā i muri i te horopeta ā-ia-toto, e ai ki ngā kōrero a te rōpū Gureev i a rātou e tohutoro ana i te rangahau nekehanga rongoā a Peter me ōna hoa. Kāore e taea te whakawhiti tika i te tuku mā te ihu ki te kiore nui ki tētahi kāpene. Ko te awhe horopeta tangata i ngā mahi kua whakaputaina he 0.5 ki te 4 mg/kg, ā, i tuhi te whakamātautau atahanga o te tau 2016 i te pānga kōaro i runga ake i te 10 mg/kg.

He mea kē tā ngā rangahau tangata e ine ana

E rua ngā whakamātau whakahaere ki te tangata ka puta i ngā kōrero tuarua mō tēnei kaupapa, ā, kāore tētahi i ine i te korikori. I te whakamātautau atahanga o te tau 2016, kāore te wā urupare mataara i whakaatu i tētahi pāhekoheko hira ā-tatauranga i waenga i te rongoā me te wā. Ko te rongoā horihori i te 230, kātahi i te 220 mirihakona, ā, ko te puru metilīni i te 230, kātahi i te 230 mirihakona, P = .43. I tētahi rangahau ā-ia-toto o te tau 2023 ki ngā wāhine hauora tokowaru, i heke kē te rere toto o te roro me te auau pākia hāora o te roro, kaua i piki. Kei te aratohu taunakitanga mō te pūngao me te ngenge ngā kōrero mō ēnei rangahau e rua.

Ki te whakatau koe ki te whakamātau tonu

Kāore tētahi whakamātau ki a koe anō e whakaū i te whai hua, engari ka taea te tuhi tika kia kore ai koe e whakapohehe i a koe anō. Tuhia te hua me te puranga, te ara tuku, te wā i mua i te whakaharatau, te wāhanga whakaharatau tika me tōna tawhiti, kawenga rānei, te whakapau kaha e rangona ana i runga i tētahi tauine tau, te moe, te kawheine me ngā rongoā katoa, me te mamae i te rā i muri mai me te mahi i muri i te 48 hāora i taua momo wāhanga whakaharatau anō. Kātahi ka whakahoki i aua wāhanga whakaharatau me te kore e whakamahi i te pūhui.

Kāore e taea e te tangata kotahi e whai ana i te taurangi kotahi te wehe i tētahi pānga rongoā i te whakapakari tinana, i te hihiri, i te huarere, me ngā rerekētanga noa o te whakaharatau. Ko te wāhanga ā-whaiaro te mea ka tino whakapohehe pea.

He tūraru anō tō te puru metilīni kāore e pā ana ki te mahi ā-tinana. Ka aukati i te monoamine oxidase A, nō reira he take hei whakaaro i te taha o ngā rongoā whakamauru pōuritanga kua tohua me ētahi atu rongoā e pā ana ki te serotonin. Kāore hoki e tika kia whakamahia e te hunga hapa G6PD nā te tūraru o te anemia nā te pakaru o ngā pūtau toto whero. Kei te aratohu haumaru ngā kōrero mō ēnei mea e rua, ā, ka whakarōpū te aratohu pāhekoheko rongoā i ngā pātai rongoā mā ia akomanga. Ki te whakataetae koe i raro i ngā ture ārai whakamahi matū whakapiki mahi, tirohia ngā ture kaua ko te kerēme a tētahi kaihokohoko.

He taurangi te matū i ia rangahau o runga

Ko ia horopeta kua whakaahuatia i konei he rahinga kua inea o tētahi pūhui kua tautuhia. Ehara tētahi pounamu nō te kaihoko kāore anō kia manatoko i tērā. Ko te ū ki te monograph USP te paerewa ka taea e te kaihoko te tirotiro. Ko te matū kāore e ū ana, he kōeke papanga pea, ā, tērā pea kei roto he poke waro pērā i te Azure B, he whakarewa toenga, me ngā konganuku taumaha kei ngā taumata ka herea e tētahi whakaritenga rongoā. Kei ngā mea ka whakaūngia, kāore hoki e whakaūngia, e te tohu USP ngā kōrero mō te kōeke, ā, kei ngā tikanga whakamātautau poke ngā kōrero mō ngā mea e rapua ana e tētahi taiwhanga.

Ko te nuinga o ngā kaihoko e kī ana kua whakamātauria tētahi hua e tētahi rōpū tuatoru, ka tirotiro i ngā konganuku taumaha anake, kātahi ka whakaatu i taua huinga whakamātautau kotahi me te mea nei kua tutuki te whakaritenga katoa. Ka whakamātautau a Blupreme i te whakaritenga USP katoa: te tuakiri, te parakore, ngā poke waro, ngā whakarewa toenga, ngā poke huānga, te toenga i muri i te tahu, ngā tepe moroiti, me ngā endotoxin huakita. Ka tukuna ia puranga me tētahi tiwhikete tātaritanga, ā, ko te pānui tika i taua tiwhikete ko te whakaōrite i te tau puranga me te taiwhanga ki te pounamu kei tō ringa.

Te whakatau matua

Kāore tētahi rangahau whakahaere ki te tangata i ine i te pānga o te puru metilīni ki te manawaroa, te tere, te kaha, te whakaora rānei. I whakamahia e te rangahau kurī e whakahuatia ana mō tētahi pānga lactate he waikano kē, ā, kāore i kitea he rerekētanga o te mahi ā-tinana. I hoatu e te rangahau kauhoe kiore nui te 0.2 mg mā roto i te ihu i muri i te mahi. Ko te rangahau kiore iti kei muri i te kupu "manawaroa" i whakamahi i tētahi whakamātautau kapo me te ruruku ki ngā kararehe e kaumātuatia ana, ā, e tautohetia ana te tukanga mahi i ngā tuhinga rangahau mitokōria.

Ko ngā mea e toe ana, he tukanga mahi e āhua tika ana, he huinga hua nō ngā kararehe iti, tētahi raruraru hoahoa rangahau kua tuhia tōna otinga, me te kore raraunga mō te mahi ā-tinana tangata. Ka whakatakoto te arotake o ngā taunakitanga painga ki te tangata i ngā kerēme korikori ki te taha o ērā atu tuhinga rangahau tangata, ā, ka whakarārangi te whare pukapuka rangahau i ngā rangahau kei muri i ia kerēme.

Ki te whakaharatau koe mō tētahi kaupapa, ko te taurangi whai taunakitanga kaha rawa ko te whakaharatau tonu.