Ngā whakamātautau i hono ai te kikorangi metilīni ki te whakahā pūtau

Ki te whakamahanatia te toto tangata kua tangohia tōna fibrin ki te 37 °C mō ngā hāora e toru, ka pau i a ia te rua ōrau pea o te hāora kei roto. Ki te tāpirihia he rahinga iti o te kikorangi metilīni i mua i te whakamahana, ka pau i taua toto anō te ono tekau mā rima ōrau pea. Kāore ngā pūtau i rerekē. Ko te wairewa anake i rerekē.

I ahu mai taua tau i tētahi pepa o 1928 nā George Harrop rāua ko E. S. Guzman Barron i Johns Hopkins. Koia te takenga mai o te kōrero e tāruaruatia whānuitia ana, e whakapai ana te kikorangi metilīni i te whakahā pūtau. Ehara taua kōrero i te kōrero hē, engari he whāiti ake tōna tikanga i tāna e rangona ai.

He aha rā tā te tau i te ripanga e ine ai

Ko te mea i inea i te mutunga ko te tangohanga hāora, mā te tātari haurehu. I tātari a Harrop rāua ko Barron i te toto kātahi anō ka tangohia mā te miro huruhuru i te 10 °C hei tango i ngā pūtau toto mā, ka whakakī i te tauira ki te hāora, ka wehea, ka tāpirihia he waikano ki tētahi wāhanga, ā, ka tātari i ngā wāhanga e rua i muri i te whakamahana. He uaua te tatauranga pūtau toto mā ki te neke ake i te kotahi mano pea mō ia mitamano pūtoru. I pūrongotia te paunga hāora hei wāhanga o te hāora tuatahi o te tauira kua ngaro.

I ine hoki rāua i te hauhā, ā, i reira ka hua ake he raruraru i te tikanga ine. I tuku te toto kua tangohia tōna fibrin i te hauhā tae atu ki te rua millimoles mō ia 100 mL i te hāora tuatahi o te whakamahana, nā ngā take kāore i pā ki te tauhohenga e rangahaua ana. Nā reira kāore i taea te whakamahi ngā ōwehenga whakahā o te toto katoa. Ko ngā pūtau kua horoia, kei roto i te wairewa a Locke, anake i whakaputa i ngā tau ka taea te whakamārama. I noho aua tau ki waenga i te 0.73 me te 0.80, ahakoa he waikano, kāore rānei.

Ehara taua kōrero iti i te mea horihori. I ēnei pepa, ko te tikanga o te kupu «whakahā» ko te whakawhiti haurehu i roto i tētahi ipu kati. Ka tirohia motuhaketia te āputa i waenga i te paunga hāora me te putanga pūngao whaihua i roto i ngā mea ka whakaaturia, kāore hoki e whakaaturia, e te paunga hāora mō te ATP.

I tino nui te tāpiritanga a te waikano ki ngā pūtau he iti rawa te whakahā

Tata kore rawa he paunga hāora ka taea te ine i ngā pūtau toto whero pakeke o ngā whāngote. He paunga hāora tō ngā pūtau toto whero whai karihi o ngā manu. I whakamātautau a Harrop rāua ko Barron i ngā momo e rua, ā, ko te rerekētanga te tūāpapa o tā rāua whakapae.

I ngā tauira whāngote, nā te waikano i whakapiki te paunga kia rua tekau ki te rima tekau whakareatanga. I te toto kuihi, kua whakahā kē ōna pūtau, kāore te auau i neke atu i te rua whakareatanga. Ka nui ake te whakahā i te tīmatanga, ka iti iho te mea ka taea e te waikano te tāpiri.

Ka kitea taua rerekētanga haere i roto tonu i te momo kotahi. Ko tētahi tauira toto tangata nō tētahi tūroro whai polycythemia vera, he pūtau kāore anō kia pakeke kei roto, i whakapau i te 11.3 ōrau o tōna hāora me te kore waikano. Ko te whakataurite, ko te 2.8 ōrau mō ngā pūtau kua horoia nō tētahi kaituku hauora. Nā te waikano i hiki noa ki te 63.4 ōrau: he whakaterenga e ono whakareatanga, i te wā i tata ki te toru tekau whakareatanga te whakaterenga o ngā pūtau noa. Nā te waikano i whakatata te whanonga o ngā pūtau pakeke ki tō ngā pūtau kāore anō kia pakeke; koirā tā ngā kaituhi i kī ai e mahia ana e ia.

Me i aukati te cyanide i taua pānga

I mōhiotia ka aukati te cyanide i te whakahāoratanga pūtau. Ahakoa tērā, i tāpiri a Harrop rāua ko Barron i taua matū me te waikano.

He tauira māngai ngā hua o te toto kau. I heke te nui o te hāora mai i te 22.61 ki te 22.03 rōrahi ia rau i roto i ngā hāora e toru, me te kore tāpiritanga. Ki te kikorangi metilīni, i heke ki te 12.84. Ki te kikorangi metilīni me te potassium cyanide kotahi haurima-mano molar, i heke ki te 12.74. Ko te tikanga, kāore te pānga o te waikano i whakarerekētia.

Whakaahua: he tuhinga whakahā moroiti haere tonu mō ngā pūtau toto whero tangata. E tohu ana te pere i te tāpiritanga o te kikorangi metilīni. I mua i tērā, he tata papatahi te rārangi; i muri iho, ka piki tonu. He tāruatanga nō Harrop rāua ko Barron, Journal of Experimental Medicine 48:207–223 (1928), PMID 19869478.

Ko tā rāua whakatau, i mahi te waikano hei kaikawe hāora, «e whakarato ana i tētahi matū kua ngaro i ngā pūtau toto whero kore karihi o ngā whāngote pakeke». E rua tau i muri mai, nā Michaelis rāua ko Salomon i te Rockefeller Institute i whakatakoto te taupatupatu ki tōna āhua pūmau. He «āhuatanga tūpono noa o te waikano» rānei te pānga o te waikano, he «tauira mō tētahi matū kāore anō kia mōhiotia i roto i ngā rauropi» rānei te waikano. Kāore anō kia whakatauria ko tēhea. Ko te mea kua rerekē, ka taea ināianei te whakaahua tino tōtika ake i ngā pūtau.

He pēnei anō te mahi a tētahi tangohanga ate

I whakaatu a Michaelis rāua ko Salomon ka whakaputa ngā tangohanga ki te wai makariri o ngā whēkau i taua whakaongaonga anō. Ko te ate kiore te mea kaha rawa, whai muri ko te tākihi, ko te kōateate, ko te raho. He iti, he kore rānei te pānga o te roro, te uaua, me te serum toto.

Kātahi rāua ka whakamātautau i te tangohanga ki te waro haukura. Kāore te whakahā i whakaaweawea e te tangohanga, e te waikano rānei i rerekē i roto i tētahi ranunga 98 ōrau waro haukura, 2 ōrau hāora. Nā taua ranunga haurehu anō i aukati te whakahā o te rewena me ngā pūtau toto whero whai karihi o ngā heihei, mā te 60 ki te 80 ōrau pea, e hāngai ana ki te whakamārama a Warburg mō tētahi whākōkī whakahā e pāngia ana e te waro haukura. Nō reira ehara taua matū kiko kāore i tautuhia i te whākōkī a Warburg.

He maha ngā matū i whakaarohia i whakakāhoretia i te roanga o te rangahau. Ko te glutathione kua whakahekea me te cysteine i whakaputa noa i te paunga hāora e hiahiatia ana mō tō rāua ake whakahāoratanga. I whakakāhoretia te whākōkī āwhina a Harden rāua ko Young, nā te mea ko te uaua te mea whai nui rawa i taua matū, engari ko tōna pānga tētahi o ngā mea iti rawa. I pā taua taupatupatu anō ki te cytochrome a Keilin, i tapaina i ngā tau ruarua o mua. Ko tā rāua ake whakaaro, nō te karihi pūtau te matū hohe, i kī rāua he whakaaro noa iho.

He here tō te pānga

Me noho tōtika tonu ngā pūtau. Nā te pakarutanga o ngā pūtau toto whero mā te wai māturu, mā te whakatio tāruarua rānei, i whakakore te urupare ki te waikano me te tangohanga. Nā te pakarutanga o tētahi wāhanga o ngā pūtau i whakaiti te urupare kia rite ki te nui o te pakarutanga.

I hiahiatia hoki te huka. I tautoko te glucose, te fructose, me te sucrose i te whakahā i whakaaweawea e te waikano; kāore te mannitol i pērā. Ki te kore he huka, kāore rawa he whakahā, ā, ko te āhua nei nā te waikano i tūkino ngā pūtau i taua tukanga. Nō reira, kāore te glucose i tāpirihia kotahi, e rua rānei ngā hāora i muri mai i whakaora i te whakahā. I whakapae ngā kaituhi e whakahāora ana te waikano i tētahi wāhanga hanga e hiahiatia ana e te pūtau.

Nā te whakamārama ki te rama i tino whakapiki te pānga o te waikano, ahakoa i mārama tonu te pānga i te pōuri. He rerekē te whanonga o ētahi atu waikano ka taea te whakaheke: i ōrite, i nui ake rānei te pānga o te kikorangi toluylene i tō te kikorangi metilīni, engari tata kore rawa he mahi a te indigo disulfonate. Kāore i puta he hononga mārama i waenga i te pūmanawa whakahāora-whakaheke o tētahi waikano me te nui o tōna pānga. Ki tā ngā kaituhi, nā te āheinga ki te whakawhiti i te kiriuhi me te paitini tēnei.

I whai te pānga i te whakatōī, kaua i te whakahā

I te rangahau a Barron o 1930, i neke atu ia i ngā pūtau e mānu ana i te wai ki ngā poro kiko nō ngā whēkau noa o ngā kiore me ngā puku kua whakatōngia.

I ngā kiko kāore he wehenga kūhuka i te aroaro o te hāora, kāore te kikorangi metilīni i mahi, i whakaiti paku rānei i te paunga hāora: i te tākihi mā te 14 ōrau pea, i te repe taiaki mā te 14 ōrau pea, i te ate mā te 5 ōrau pea. I ngā kiko e whakatōī ana i te aroaro o te hāora, i whakapiki ia i te paunga: i te kōateate mā te 8 ōrau pea, i te roro mā te 13 ōrau pea. Ko ngā pikinga i ngā puku i tīmata i te 27 ōrau pea i tētahi carcinoma ū tangata, tae atu ki te neke atu i te 80 ōrau i tētahi sarcoma heihei Rous. I āhua rite te pikinga ki te nui o te wehenga kūhuka i te aroaro o te hāora o ia kiko.

Whakaahua: he momo kiko kotahi ia ira. Ko te tuaka whakapae ko te wehenga kūhuka i te aroaro o te hāora; ko te tuaka poutū ko te huringa o te paunga hāora i muri i te kikorangi metilīni. He raraunga nō Barron, Journal of Experimental Medicine 52:447–456 (1930), Ripanga 6, PMID 19869777.

Kātahi te whakamātautau cyanide ka whakaputa i te āhua kōaro. I te aukatinga o te whakahā ki te cyanide i aua kiko kāore i urupare i mua, ā, i te putanga ake o te whakatōī, ka whakapiki anō te waikano i te paunga hāora: i te tākihi mā te 59 ōrau pea, i te ate mā te 19 ōrau pea, i te kōateate mā te 286 ōrau pea, i te raho mā te 200 ōrau pea.

I whakatakoto a Barron i te whakaaro ka taea te waikano te whakamahi hei whakamātautau i te kaha whakatōī o tētahi pūtau, kiko rānei. I whakakapi ia ki tētahi whakaaro tūpono: tērā pea, mā ngā whakatupuranga o te whakatipu puku ki tētahi papatipu whai waikano, ka pūmau te pākia o te puku kia rite ki tō te kiko noa. He pātai rangahau tērā i tuhia i te tau 1930. Ehara i te kerēme maimoatanga.

Ngā mea kāore rawa i taea e ngā whakamātautau te ine

I te tau 1928 me te tau 1930, ko te tikanga o te «whakahā» ko te paunga hāora. I pūrongotia tuatahitia te adenosine triphosphate i te tau 1929, ā, i te tau 1949 ka whakaaturia ka hanga ngā mitokōria kua wehea i ngā pūhui hākawa phosphate i a rātou e whakawhiti irahiko ana. Kāore tētahi o ngā pepa tōmua mō te kikorangi metilīni i taea te ine i te hanga pūngao, ā, kāore tētahi i kerēme pēnā.

Ko ngā pūtau te raruraru tuarua. Kāore he mitokōria i roto i ngā pūtau toto whero pakeke o ngā whāngote. I te wāhanga reticulocyte, ka whakakore rātou i ngā mitokōria me ngā ribosome mā te autophagy whiriwhiri, arā, te whakangaro whiriwhiri i ō rātou ake wāhanga. Koia te take e whakawhirinaki ai te pūtau toto whero pakeke ki te wehenga kūhuka mō tōna mahi, me tōna ara pentose phosphate mō te NADPH te nuinga, kaua mō te ATP. I ngā whakamātautau o 1928, kāore he mekameka kawe irahiko hei whakatika. Ahakoa he aha te mea nāna i whakapau te hāora, he mahi kē tāna.

Kua āhua pai ināianei te whakaahua i taua mahi kē. Ka tango te kikorangi metilīni i ngā irahiko mai i ngā taurite whakaheke o te pūtau, ka huri hei leucomethylene blue. Ka whakahāoratia anō taua matū e te hāora rāpoi, ka oti te huringa. I ngā pūtau toto whero tangata, mā te flavin reductase e whakawhirinaki ana ki te NADPH me ngā disulfide reductase e pā ana e mahi te wāhanga whakaheke. I kitea i tētahi rangahau o 1976 i whakamahi i te glucose kua tohua, ka whakaongaonga te waikano i te ara peka hexose monophosphate, ka whakawhirinaki te pānga i te kukū iti ki te oxyhemoglobin, ā, ka hangaia te hauwai peroxide i te kukū teitei ake, 0.1 mM. Ka tūtaki te waikano kua whakahekea ki te hāora, ka whakaputa i te peroxide, kaua i ngā hononga phosphate.

I ngā mitokōria, he nui ake te taupatupatu i tā ngā whakarāpopototanga rongonui e whakaae ai. Ki tā tētahi huinga rangahau, ka tango te waikano i ngā irahiko mai i te takiwā o te matatini I, ka tuku atu ki te cytochrome c. I kitea e tētahi atu, i ngā mitokōria roro kiore, kāore e taea e ia te whakaora i te whakahā i muri i te aukatinga antimycin. Nā taua rangahau i whakanoho kē te kaiwhiwhi irahiko ki te wāhi here ubiquinol o te matatini III. I kitea e tētahi tuatoru, ka whakapiki ngā kukū iti i te paunga hāora i te wā whakatā, engari kāore e whakarerekē i te whakahā kua whakaongaongatia e te ADP. Ko te kōrero tino hāngai mō tēnei, kāore rawa te paunga hāora i whakaaweawea e te kikorangi metilīni e whakawhirinaki ki te phosphorylation whakahāora: i mau tonu i te wā i aukatia ai te mekameka whakahā, i ngā whakaritenga hoki kāore he mekameka pērā.

Kei reira hoki ngā inenga hāngai o te āputa i waenga i aua rahinga e rua. I ngā mitokōria ate kiore kua wehea, nā te whakapiki i ngā kukū waikano i whakaheke ngā ōwehenga whakahaere whakahā, i pupuhi hoki ngā mitokōria. I kī ngā kaituhi ko tēnei te wetewete i te hononga o te phosphorylation whakahāora. I te ate kiore e rere ana te wai mā roto, nā te kikorangi metilīni i whakapiki te paunga hāora i te wā e heke ana te ōwehenga ATP-ki-te-ADP.

He ōrite te kōrero o ngā pūrongo haumanu. Ka maimoatia te methemoglobinemia ki te kotahi ki te rua mirikarama pea o te kikorangi metilīni mō ia kirokarama, mā roto i te ia toto, mā tētahi ara whakaheke e whakawhirinaki ana ki te NADPH. Mā ngā horopeta nui ake ka puta te mate e maimoatia ana. E ai hoki ki taua arotakenga, he kaha rawa te pānga patu paihana i ngā pūtau toto whero e noho tōtika ana, ā, ka iti iho mēnā kua pakaru ngā pūtau toto whero. Koinei te kitenga mō te pakarutanga pūtau toto whero o 1930 e puta anō ana, whitu tekau mā toru tau i muri mai, i te horopaki hōhipera. Ki te noho ngā pānga whaihua me ngā pānga kino o tētahi pūhui ki ngā taha e rua o tētahi paepae horopeta, ehara taua pūhui i te mea me whakatau tōna horopeta mai i tētahi inenga paunga hāora.

He aha i tika ai kia kōrerotia te puranga

I kite a Harrop rāua ko Barron i tētahi mea e tika ana kia pānuitia anō. Ka whakaputa te kikorangi metilīni ake i tētahi rārangi i te pūrere mātakitaki tūāwhiorangi, i waenga i ngā rārangi motuhake e rua o te methemoglobin, «e ngāwari ai te rangirua i te tirohanga noa». Ka taea e te waikano te tāwhai i te matū e rapua ana.

He āhua matū anō tō taua raruraru. Ko tētahi phenothiazine e pā ana, kei roto hei wāhanga iti, he whanonga whakahāora-whakaheke, he āheinga whakawhiti kiriuhi, he paitini hoki ōna ake. Mā tētahi take kua tuhia ka mārama te hiranga: i tētahi rangahau mō te tāpiri iodine ki te kikorangi metilīni, ko ngā tauira whai Azure B e 7 ki te 8 ōrau pea, i whakaputa i te Azure B kua tāpirihia ki te iodine te nuinga. Nā reira ko te poke, kaua ko te kikorangi metilīni, te mea matua o te tauhohenga.

Ko te tangata e whakamahi ana i te kikorangi metilīni hei matū tauhohe, i te taiwhanga, i te tēpu whakapoke tauira, i te ipu ika rānei, e mahi ana ki tētahi whakauru kāore i āta tautuhia, ki te kore te puranga i āta tirohia. Ko ngā matū e pā ana, te tuakiri, ngā poke huānga, ngā toenga whakarewa, me te toenga i muri i te tahu, he wāhanga o te whakamātautau, ehara i te tuhinga whakahaere noa e karapoti ana i taua whakamātautau. Ka whiwhi a Blupreme i tana kikorangi metilīni mai i tētahi kaihanga rongoā, ā, ka whakaputa i tētahi tiwhikete tātari katoa. Ka whakamātauria te whakaritenga USP katoa, kaua ko ngā konganuku taumaha anake. E whakamārama ana te aratohu pānui tiwhikete tātari me ngā mea ka whakapūmautia, kāore hoki e whakapūmautia, e te tohu kōeke USP i te huarahi hei whakataurite i te tuhinga ki te kerēme.

I tika te tau

He āta whakahaere ngā whakamātautau o 1928 me 1930, ā, kua mau tonu tā rātou kitenga matua: ka taea e tētahi waikano ka taea te whakaheke te whakapau hāora i tētahi pūtau he iti rawa te whakahā, kia maha ngā whakareatanga o tōna auau whakatā, me te kore e haere mā te wāhanga ka aukatia e te cyanide.

Ka puta te hapa i muri mai, ina pānuitia te «whakahā» ki tōna tikanga o nāianei. Ka whakaatu tētahi inenga whakawhiti haurehu kua tae ngā irahiko ki te hāora. Kāore e whakaatu ana i whakamahia tētahi o aua irahiko hei hanga ATP. I tētahi pūtau kāore he mitokōria, ko te āputa i waenga i aua kōrero e rua te whānui rawa ka taea. Ka whakatakoto te mahere whānui ake o ngā mahi a te kikorangi metilīni i roto i ngā pūtau i taua wehewehenga anō ki tētahi horopaki whānui ake, ā, ka whakamārama te hītori o te pūhui mai i te waikano ki te rongoā i te huarahi i tae tuatahi mai ai tētahi matū tae papanga ki ēnei whakamātautau.