Pēhea te mahi a te methylene blue? Te matū redox me ngā tikanga mahi

Ko tētahi ipu karāhe kua purua ki runga tēpu te whakamārama poto rawa, pono rawa hoki mō te mahi a te methylene blue. He wai, he glucose, he paku sodium hydroxide, me te nui o te tae kia tino kikorangi hōhonu te wai. Tatari mō ētahi meneti, ka memeha haere te kikorangi kia rite anō te ipu ki tētahi ipu wai noa. Rūrūhia, ka hoki wawe mai te tae. Kātahi ka memeha anō, ā, ka pēnei tonu i te mea e toe ana he glucose hei tuku irahiko, he oxygen hoki hei tango i aua irahiko.

Kāore he mea o te tae i rerekē, hāunga te maha o ngā irahiko e kawea ana e ia. Ina oxidised, he kikorangi. Ina reduced, kāore. Tata ki ngā kōrero katoa i roto i ngā tuhinga haumanu me ngā rangahau mō tēnei rāpoi ngota ka ahu mai i taua huringa kotahi ka taea te whakahoki, nā te mea ko te rāpoi ngota ka taea te tango irahiko i tētahi hoa me te tuku ki tētahi atu he kaikawe, ā, kāore he mahi a te kaikawe i a ia anake. Ko tāna mahi ka tino whakawhirinaki ki ngā mea kei ia pito.

E rua ngā āhua, me te take e whai tikanga ai te takirua

Ko te āhua oxidised he pūnaha mowhiti papatahi, he utu tōrunga tōna. Nā taua āhua papatahi, whai utu hoki, ka taea te tāpae ki ngā nucleic acids, te here ki ngā hanganga sialylated i runga i ngā membrane pūtau, me te ngongo kaha i te mārama kitea i waenga tata ki te 600 me te 700 nanometres, arā, ko te wāhanga o te tūāwhiorangi ka kitea e te karu tangata hei kikorangi.

He rerekē te āhua reduced. Kāore ōna utu, ka memeha ki te ngako kaua ki te wai, ā, kāore ōna tae. He tino iti tōna ionisation i te pH o roto i te tinana, kei te āhua o ētahi ōrau ruarua. Nō reira ka whakawhiti ngāwari te rāpoi ngota reduced i te membrane pūtau mā te diffusion, ā, kia tae ki roto, kei reira te taiao he kaha ake te oxidising, ka taea te re-oxidised, ā, ka mau tonu ki reira. He papatahi te pūnaha mowhiti oxidised; ka taea te kōpikopiko te mea reduced. Ko aua hua ā-hanganga, me te huringa tae anō hoki, he wāhanga motuhake nō te kōrero mō ēnei āhua e rua, ā, ka whakamāramatia whānuitia ake i te whakataurite o te methylene blue me te leucomethylene blue.

Te tango irahiko

Ka tango te tae oxidised i ngā irahiko mai i te whānuitanga o ngā kaituku. Ko te glucose i roto i te ipu whakaaturanga tētahi. I roto i te pūtau, ko ngā pyridine nucleotides reduced me ngā wāhanga o te mitochondrial electron transport chain ētahi atu. Ina reduced te methylene blue i roto i tētahi kiko e whai oxygen ana, ka pau i te huringa ka whakatūria e ia te reducing agent me te oxygen, ā, ka whakaputa reactive oxygen species, ko te hydrogen peroxide te mea matua. Ka puta anō te tae i taua huringa kāore i panonitia, kua rite ki te huri anō.

Ko taua kōrero whakamutunga te whakamārama i tētahi taupatupatu ka āhua hē noa ki te kore e mārama. E whakaahuatia ana te methylene blue i roto i ngā tuhinga hei pro-oxidant, hei antioxidant hoki, ā, e taea ana te tautoko i ngā whakaahuatanga e rua. Ka taea e ia te whakaiti i te whakaputanga superoxide mā te mahi hei artificial electron acceptor, ka whakapeka i te rere o ngā irahiko kia wehe atu i ngā wāhi whākōkī e tahuri ai te oxygen hei superoxide radicals. I roto i ngā ahurea pūtau ate kua whakaaturia ka whakakaha i ngā phase-2 antioxidant defence enzymes, tae atu ki te thioredoxin reductase 1 me te NADPH quinone oxidoreductase. Ko tēhea āhua o ēnei e kitea ana ka whakawhirinaki ki tēhea pito o te ara whakawhiti e hapa ana i ngā irahiko i taua wā. Kāore e oti pai te pātai pēnei i te "he antioxidant rānei te methylene blue" kia whakamāramatia ko tēhea pūnaha, ko tēhea concentration, me ngā mea kē atu kei reira.

Te tuku tonu i ngā irahiko

Kia mau ana te tae i tētahi irahiko tāpiri, e toru ngā āhuatanga tino rerekē ka taea te whai ake, ā, i te nuinga o te wā ka whakaurua katoatia ki raro i te pane kotahi. Kaua e pērā.

Ka taea e ia te tuku i te irahiko ki tētahi pokapū konganuku. Ko te tauira mārama rawa ko te haemoglobin kua oxidised mai i te ferrous state ki te ferric state. I taua āhua kāore e taea te kawe oxygen. I roto i ngā pūtau toto whero, ka reduce tētahi whākōkī i te tae, kātahi ka tukuna e te tae reduced ngā irahiko ki te oxidised haem iron mā te ara non-enzymatic, ka whakahoki mai i te haemoglobin mahi, ā, ka whakahoki hoki i te tae ki tōna āhua oxidised. Kāore te tae e pau i tēnei; ka huri tonu. Ko te horopaki haumanu e ahu mai ana i tēnei tauhohenga he kaupapa nō te hōhipera, ā, ko te whakamārama mō te methylene blue i te methemoglobinemia e kōrero ana mō te whakamahinga me te take e tino aroturukitia ai.

He kōrero tika mō ngā puna: kāore ngā arotake e rua e tūāpapa ana i tēnei tuhinga e whakaingoa i te reducing cofactor kotahi mō te taahiraa whākōkī; e kī ana tētahi ko NADH, ko tētahi ko NADPH. He tino rerekētanga tēnei, ā, kāore anō kia whakatauria i roto i ngā puna kei konei, nō reira ko te whakaahuatanga haumaru ko te tūranga o ia wāhanga, kaua ko te whakatau i tētahi ingoa cofactor kotahi.

Ka taea e ia te tuku pūngao, te tuku irahiko rānei, ki te oxygen, mēnā he mārama. Ka tū tēnei ara i raro anake i te illumination. Ka tae te tae kua excited ki tētahi triplet state, ā, mai i reira e rua ngā mechanism ka taea. I te tuatahi, ka pā tika te tae excited ki tētahi rāpoi ngota e tata ana, mā te tango hydrogen, mā te whakawhiti irahiko rānei, ka hanga radicals; ina tauhohe ki te wai mā tēnei ara, ka puta hydroxyl radicals. I te tuarua, ka tukuna te excitation energy ki te oxygen tonu, ka hua ko singlet oxygen, he species tino electrophilic ka memeha i roto i ngā microseconds, ā, e whakaaetia whānuitia ana koinei te ara matua e tūkinotia ai ngā pūtau microbial e te methylene blue kua whakamāramatia. Ko ngā tauhohenga ki ngā lipids me ngā peptides o te cell envelope, me ngā guanine bases i roto i te DNA, kei roto i ngā hua kua tuhia.

Ko te hua ā-mahi o tēnei ara, ka whakarerekē te illumination i ngā tatauranga mā ngā orders of magnitude. I roto i ngā raraunga i kohia e Wainwright rāua ko Crossley, ko te methylene blue ki Pseudomonas aeruginosa he minimum bactericidal concentration tata ki te 500 micromolar i te pōuri, ā, tata ki te 25 micromolar i raro i tētahi light dose o te 12 joules per square centimetre. Ki tētahi strain o Staphylococcus aureus, ko ngā uara i te pōuri me te illumination he 5 micromolar e rua. Arā, mēnā ka kiia rānei te rāpoi ngota he antimicrobial, ehara tērā i te āhuatanga o te rāpoi ngota anake; he āhuatanga nō te rāpoi ngota me te mārama.

Ka taea e ia te mahi tika i tētahi wāhi whākōkī, me te kore e whakamahi i te ara whakawhiti. Ka oxidise te methylene blue i te ferrous iron e herea ana ki te nitric oxide synthase, ka whakakore i te mahi a te whākōkī. Ka ārai i te soluble guanylate cyclase, ā, i waenga i te 1 me te 10 micromolar te concentration taiwhanga e whakamahia auautia ana mō taua kaupapa. Ka inhibit i te monoamine oxidase type A me tētahi IC50 kei waenga i te 27 me te 180 nanomolar, ā, koinei te mechanism kei muri i te interaction kua tino tuhia ki ngā serotonin reuptake inhibitors, me te take he kāwai motuhake ngā drug interactions o te methylene blue.

He tino rerekē ā-matū ēnei ara e toru. Ko te whakakotahi i aua ara ki roto i te kerēme kotahi e mea ana ka mahi te methylene blue mā te redox cycling te take matua e rangona ai te nuinga o ngā tuhinga mōna he tino māia, engari he rangirua tonu.

E whā ngā wehewehenga e whakatau ana mēnā he tikanga tō tētahi kōrero mō te mechanism

Ko tēhea āhua. Kāore e taea te whakawhiti noa i te tae reduced me te tae oxidised. Ka whakaatu te acetylcholinesterase inhibition i te raruraru: i roto i tētahi incubation in vitro roa, ka reduced haere te methylene blue ki tōna āhua kāore he tae, ā, ka heke te inhibition, nā te mea kāore te rāpoi ngota reduced e inhibit i taua whākōkī. Mēnā ka roa rawa te assay kia huri ai te āhua, ka rīpoatatia he pānga ngoikore ake, ka puta hoki he whakamārama hē.

Ko tēhea concentration. Ko te awhe taiwhanga mō te soluble guanylate cyclase inhibition he 1 ki te 10 micromolar. Kia whakakorea te glutamate-mediated transmission i roto i ngā rat hippocampal slices, i hiahiatia te 5 ki te 50 micromolar. Kua rīpoatatia ngā toxic effects i roto i te cell culture i runga ake i te 100 micromolar. Ehara ēnei i te whakamātau kotahi, ā, kāore tētahi mechanism kua whakaūngia i te 50 micromolar e noho aunoa hei mechanism mō tētahi tūroro he wāhanga noa iho o taua concentration tōna plasma concentration.

Ko tēhea route. Ko te absolute oral bioavailability tata ki te 72 per cent, ā, ko te terminal plasma half-life he 5 ki te 7 hours. Mā te oral administration ka nui ake ngā concentration i te intestine me te liver; mā te intravenous administration ka nui ake ngā concentration i te brain. Mā te route e whakatau ko tēhea kiko ka tūtaki ki ngā irahiko.

Ko tēhea model, ā, i kā rānei ngā rama. Ko te nuinga o ngā tuhinga mechanistic he cell culture me ngā rangahau rodent, ā, ko ngā hua in vitro mō tēnei rāpoi ngota ka whakawhirinaki ki te light exposure, membrane potential me te redox state o ngā pūtau, nā te mea kua ranea te rama microscope hei photosensitise i a ia. I waenga i te 65 me te 85 per cent o tētahi dose kua administered ka reduced ki te āhua kāore he tae i roto i ngā pūtau toto whero me te peripheral tissue. Kei waenganui ia o aua taurangi i tētahi mechanism mārama i roto i te rīhi whakamātau me tētahi kerēme mō te tangata.

He aha te take he pātai matū te pātai mō te purity

Ka demethylate te illumination i te methylene blue. Ko te hua tuatahi ko Azure B, kātahi ko Azure A, kātahi ko thionin, ā, ka nui ake te breakdown i te light intensity teitei i tērā o te mea iti. Nō reira, ko tētahi rāpoi ngota e whai hua ana nā tōna kaha ki te tango me te tuku irahiko, he rāpoi ngota hoki e tino rite ā-matū ana ōna likely degradation products, ā, ka noho tonu aua hua i roto i te otinga kotahi. Ehara te hanganga o ngā mea kei roto i te ipu i te taipitopito ā-āhua noa iho.

Koia te take ko te conformance ki te USP specification te whakamātautau whai tikanga mō te kaihoko. Ko tētahi hua kāore e ū ki taua paerewa he dye noa iho, ā, ka taea e te dye te kawe impurities, tae atu ki Azure B, heavy metals me residual solvents, kāore e hiahiatia e te tangata e horomia ana. Ko tētahi atu raruraru ko te kaihoko e whakamātau ana mō ngā heavy metals anake, kātahi ka whakaatu i te hua hei full compliance. Kua mahi ngātahi a Blupreme me tētahi pharmaceutical manufacturer o te methylene blue, ā, ka whakamātau i te full specification: identity, purity, organic impurities, residual solvents, elemental impurities, residue on ignition, microbial limits me bacterial endotoxins. Ka whakaputaina te tuhinga whakamātautau taiwhanga mō ia batch, ā, ko te kōwhiri supplier te nuinga he tirotiro mēnā kei reira taua tuhinga me ngā mea e kapi ana.

Kotahi te takirua ka taea te whakahoki. He maha ngā ara ka puta atu i reira. Mā te ara e whakatau te whānuitanga o te kerēme.