Paul Ehrlich me te kahurangi metilīni: te āwhina a tētahi waikano ki te whakawhanake i te tūhura rongoā

Ehara te takoha a Paul Ehrlich ki te ao hauora i te rongoā. He whakaaro kē mō te āhua o te tirotiro i tētahi rongoā.

I 1878 ka tukuna e ia tētahi tuhinga kairangi, ko te taitara o tōna wāhanga tuatahi ko "Te Ariā Matū o te Whakapoke ki te Waikano." Ko tāna tohe, he ōrite te pūtake o te whakapoke i tētahi tapahanga kiko ki te waikano me te tae i tētahi papanga. I ngā mahi e rua, ka piri te tae nā te hononga matū i waenga i te waikano me te rawa, ehara i te mea nā te kaha ngongo o te kiko, nā tōna hinuhinu, nā tōna hanga rānei e mau ai te matūriki tae. I tipu ake a Ehrlich e mātakitaki ana i tōna whanaunga, i te mātanga mātai mate a Karl Weigert, e whakarite ana i ngā tapahanga kua whakapokea ki te waikano. Ko te mea i kapohia ai tōna aro ehara i ngā whakaahua, engari ko te kōwhiri a te waikano i tōna wāhi haere.

Ki te whakarongo noa, he kerēme iti tēnei. Heoi, he kerēme nui. Ki te here tētahi waikano ki tētahi kiko nā ngā take matū, he pūrongo te tauira whakapoke mō te matū o taua kiko. Ka mutu te noho o te papa karāhe kua whakapokea hei whakaahua noa, ka noho kē hei inenga.

I whakawhanake tonu ia i taua whakaaro. I 1880 ka whakakotahitia e ia te kahurangi metilīni me te fuchsin waikawa, ā, ka tapaina te ranunga he waikano kūpapa, he neutralen Farbkörper. I taea e tēnei te wehewehe ngā momo pūtau toto mā, kāore i taea e ngā waikano takitahi i whakamahia i taua wā. E rua tau i muri mai, ka whakaaturia e ia tētahi tikanga whakamahi i te methyl violet hei whakapoke i ngā huakita kōpura, ā, ka whakamahia e Koch taua tikanga i āna ake mahi.

He kaupapa motuhake te ariā i muri mai i hoatu ai he tūāpapa kotahi ki ēnei mahi, ā, he rite tonu te whakakotahingia hētia o ōna rā ki ngā rā o ngā mahi o mua. Nō ngā tau 1890 te ariā mekameka taha a Ehrlich, arā, te whakaaro ka pā tētahi matū ki tētahi pūtau nā te hototahi matū o rāua. Ehara i te mea nō ngā tau o āna mahi waikano. Ko te whakapono i whakatūria e ngā mahi o mua ko tēnei: he take matū tō te whāiti o te mahi, nō reira ka taea te rapu, kaua e tatari kia tūpono noa.

Te whakamātautau i huri ai te waikano hei mahere

I 1885 ka whakaputaina e Ehrlich tētahi pukapuka rangahau mō ngā hiahia hāora o te rauropi. Ko tōna taitara tāpiri, he rangahau tātari tae. Ko tōna tikanga he wero i ngā waikano e whakawhirinaki ana tō rātou tae ki te āhua hāoratanga, kātahi ka whakataurite i te whakahekenga matū, i te pupuritanga rānei, o aua waikano e ngā whēkau rerekē. I whakamahia te waikano hei taputapu ine, pērā i te ine pāmahana: i whakaatu i ngā āhuatanga o roto i te kiko kāore e taea te tirotiro tōtika. Ki tā Ehrlich ake whakamārama, ko te whāinga he whakatau, mā te āwhina a ētahi waikano motuhake, i te kaha whakaheke matū o ngā whēkau ora.

I puta te kitenga mō te kahurangi metilīni i 1886, i roto i tētahi tuhinga mō te tauhohenga o te waikano ki te kiko io ora, i pānuitia ki tētahi rōpū hauora i te Tīhema o mua. I whakaurua te kahurangi metilīni ki te rerenga toto o tētahi kararehe ora, kātahi ka tangohia ētahi tapahanga angiangi o te kiko, ka whakatakotoria ki te hau. Nā reira i hāoratia anō ai te waikano taekore kua putu, ka hoki ki te kahurangi, ka whakaatu hoki i ōna wāhi putunga. I mau te tae ki ngā pūtau io me ngā kaka io, ā, he tino whāiti te mau o te tae, nā reira ka noho te tikanga hei tikanga paerewa mō te whakaatu i te kiko io. Kua kore taua pūhui e noho noa hei matū tae ka pania ki tētahi tapahanga kiko mate i runga i te tēpu mahi. He tohu kē i tohatoha i a ia anō i roto i tētahi tinana ora, ā, ka taea te pānui i taua tohatoha.

Me whakamārama mārama te āhuatanga i tūāpapa ai ēnei whakamātautau e rua, nā te mea e whakawhirinaki ana ngā mea katoa o tēnei kōrero ki taua āhuatanga. Ka taea te whakahoki te kahurangi metilīni i waenga i ōna āhua matū. He taekore tōna āhua kua whakahekea, arā, te leucomethylene blue, ā, ina pā ki te hāora ka hoki ki te katote tōrunga kahurangi. He taekore tētahi wairewa kūhuka o te waikano i roto i tētahi ipu kua hiritia; whakatuwheratia te ipu, ka kahurangi. E ai ki ngā pūrongo, i whakaaturia tōtikatia e Ehrlich tēnei āhuatanga mā te whakamahi i te iron chloride me te hau ki ngā tapahanga kua whakapokea, me te mātakitaki i te hokinga mai o te tae. Ko te waikano e huri ana tōna tae i runga i te āhua hāoratanga-whakahekenga o tōna taiao, he taputapu tūhura i taua taiao.

Nō reira, e rua ngā āhuatanga i noho tahi. Ka taea e tētahi waikano te wehewehe tētahi kiko i tētahi atu. Ā, ka taea te whakakā, te whakaweto hoki i te tae o tētahi waikano mā te panoni i te āhua hāoratanga.

Ki te titiro whakamuri, ko te āhuatanga tuarua te tīmatanga o te haumanu matū. Ki te here tētahi pūhui ki tētahi momo kiko, engari kāore ki tētahi atu, tērā pea ka tae taua pūhui ki tētahi momo rauropi, engari kāore ki tētahi atu. I whakapuakina tōtikatia e Ehrlich taua whakatau: ki te taea te whakapoke whāiti i tētahi tukumate, tērā pea he tohu taua whakapoke mō tētahi pānga kino motuhake ki taua tukumate. Nō reira, tērā pea ka taea te whakamahi i tētahi waikano hei rongoā e arotahi ana ki te rauropi whakaeke, kaua ki te tūroro.

Ehara te whakamātautau tuatahi ki tētahi tūroro i te whakamātautau mō te malaria. I 1890, i te taha o te mātanga mate hinengaro a Arthur Leppmann, ka pūrongotia e Ehrlich te whakahekenga o te mamae e te kahurangi metilīni i ngā mate mamae io me ngā mate rūmātiki o ngā uaua, ngā hononga me ngā iohere. I matapaki ngā tāne tokorua mēnā ka pā pea te rongoā ki ngā mate hinengaro, ā, ka whakatau kia kaua e whakamātauria. Heoi, ka koke tonu tētahi rata nō Itāria, a Pietro Bodoni nō Genoa. Ko te taitara o tana tuhinga o 1899 e pā ana ki te mahi whakatau mauri i ngā momo mate hinengaro wehe mooni: i whakaahuatia e ia te tau o te mauri o ngā tūroro tekau mā whā e ohooho ana, ā, i tuhia e ia kua whakamahia kētia te waikano e ētahi atu rata o Genoa mō taua take. Ehara te whakatau mauri i te pānga ki te mate ake, ā, ka ara tonu taua wehewehenga i roto i tēnei hītori.

I tīmata te mahi malaria i 1891, i te taha o te mātanga mātai mate a Paul Guttmann, i te hōhipera o Moabit i Berlin. I hoatu te kahurangi metilīni ki ngā tūroro tokorua, ā, ka puta te pūrongo i te Berliner klinische Wochenschrift o te 28 o Hepetema 1891. I te kēhi tuatahi, ka kai te tūroro i te 0.5 g o te waikano i te wā kotahi i te ahiahi o te 29 o Hune; kāore i puta katoa te whakaeke mate i tūmanakohia, ā, ko te amuamu anake i tuhia i muri mai he uaua, he mamae paku te mimi, me te kahurangi o te mimi. I ngaro ngā whakaeke kirikā i ngā rā tuatahi, ā, i ngaro ngā pirinoa i te toto i mua, i te rā tuawaru rānei. Ko te whakarāpopototanga a ngā kaituhi ake, kua tino tutuki katoa ō rātou tūmanako. Ehara ngā kēhi e rua kāore he rōpū whakataurite i te taunakitanga whakatau. Kei tōna ake whārangi te kōrero whānui ake mō te kahurangi metilīni me te malaria, tae atu ki ngā whakamātautau o ēnei rā. He whāiti ake te pātai e arohia ana i konei: e hia o ngā whakaaro a Ehrlich i mau tonu i te whakamātautanga ki te pirinoa.

Ngā wāhi i tika ai te whakaaro me ngā wāhi i hē ai

He iti noa ngā kōrero mō te pūnaha mahi i mau tonu, i te iti rawa, kāore i mau i te āhua i whakaarohia e Ehrlich. Kāore e tika mō Plasmodium te whakamārama māmā e mea ana ka kuhu tētahi katote tōrunga papatahi, e toru ōna mowhiti, ki waenga i ngā takirua pūtake o te DNA o te pirinoa. He māmā rawa te whakahekenga matū o te kahurangi metilīni e tētahi pūtau toto whero kua pangia, nō reira kāore rawa e tae ki te pirinoa hei katote tōrunga papatahi. Ko te kōrero mō te kuhu ki waenga i ngā takirua pūtake e hāngai ana ki ngā waikano acridine, kāore e hāngai ki tēnei.

He uaua ake te whakamārama e tautokona ana e ngā taunakitanga. Ka aukati te kahurangi metilīni i te glutathione reductase o te pirinoa i ngā kukūtanga ka taea te tae atu i roto i te tūroro. Ka aukati i te hurihanga o te haem hei haemozoin, arā, te matū tae ngoikore ki te tauhohe ka hangaia e te pirinoa kia kore ai e paihanatia e tāna ake nakunaku i te haemoglobin. He āhua ōrite tōna kaha ki te chloroquine, ā, he kaha ake i tō te quinine. Mā tana huringa hāoratanga-whakahekenga e whakaputa hoki ngā momo hāora tauhohe i roto i tētahi pūtau e whakaputa ana kē i aua momo. Kāore anō kia tau ko tēhea te pūnaha mahi tūturu, mēnā rānei ka whai wāhi katoa.

He raruraru anō, ā, me whai pānga ki te pānuitanga o ngā kerēme hītori katoa mō tēnei pūhui. Ehara te kahurangi metilīni arumoni o taua wā i te matū kotahi. I roto i ngā tauira ko te Azure B, te pūhui whanaunga kua tangohia tētahi rōpū methyl, ā, i putu haere te nui o taua matū i ngā wairewa tawhito. He waikano panoni tae te Azure B, ā, he rerekē ōna whāinga: ka whakapoke i te DNA whenu rua kia kahurangi hōhonu, me te RNA kia kākāriki. Kāore e taea e tētahi ranunga waikano e rua, he rerekē ō rāua wāhi haere, kāore hoki i tuhia ō rāua ōwehenga, te tautoko i tētahi whakatau mārama mō te mahi a te kahurangi metilīni o roto.

Kāore te waikano ake i whakakapi i te quinine. He pai ake te hua o te tikanga. Ko Wilhelm Roehl, te tauira a Ehrlich e mahi ana mō te rōpū kamupene waikano, rongoā hoki a IG Farben, i tohe tonu ki te whakamahi i ngā pārōnaki waikano hei rongoā mō ngā whenua pārūrū. Nāna hoki i whakarato te taputapu i ngaro: te manu canary kua pangia ki tētahi malaria manu, hei whakamātautau auau mō ngā pūhui e whakaarohia ana. Kātahi ka panonitia e Werner Schulemann te mekameka taha, ā, ka whakaorangia te whakapokenga whakamātautau e te tote phenothiazinium i puta mai. I kahurangi tonu ngā tūroro nā taua matū.

Ko te hua i mau roa, ehara i te waikano, ehara hoki i te pūnaha mowhiti, engari ko te mekameka taha. Nā te tāpiri i tētahi rōpū dialkylaminoalkylamino i panoni te whanonga o te rāpoi ngota, ā, i mau tonu taua wāhanga i ia hoahoatanga anō o muri mai. Puritia taua rōpū, whakakapia te mowhiti phenothiazinium ki tētahi acridine, ko te quinacrine te hua. Whakakapia ki tētahi quinoline, ko te chloroquine te hua. Ko te pamaquine, te primaquine me te amodiaquine, kei roto tonu katoa i te rārangi rongoā malaria, e mau ana i taua rōpū. Nā te pūhui kāore i angitu hei maimoatanga i whakarato te wāhanga i angitu.

Ko te hononga ki ngā rongoā ārai mate hinengaro wehe mooni e haere ana mā te mowhiti, kaua mā te rongoā. Nā te whakamārama i te hanga o te kahurangi metilīni i kitea ai e Heinrich August Bernthsen te karihi phenothiazine taketake i 1883. Ko taua anga, me ngā whakakapi rerekē, te mea i mahia e ngā kaimātai matū o Rhône-Poulenc i ngā tau 1940 i a rātou e rapu ana i ngā rongoā ārai histamine. I waihangatia tētahi o aua pūhui i te takiwā o te mutunga o 1950, ā, i whakamātauria e te rata pokanga a Henri Laborit, nāna i kite ka tau, ka kore hoki e aro nui ngā tūroro. I Hānuere 1952 ka puta te whakaputanga tuatahi mō tōna whakamahinga i te haumanu mate hinengaro, ki tētahi tūroro whai mania. He iti ake te tika o te kī he uri te rongoā ārai mate hinengaro wehe mooni tuatahi nō te rongoā malaria a Ehrlich; he whanaunga tawhiti kē nō te waikano i tīmata ai ia.

E toru ngā ritenga o tēnei wāhanga hītori hei pupuri

1. E whakaahua ana te kōrero "te rongoā waihanga tuatahi i whakamahia i te ao hauora" i tētahi kāwai, ā, he nui ake ngā here i tā te kīanga e tohu ana. Kua mau tonu taua kīanga; e kī ana tētahi arotake e tino whakahuatia ana nā Schirmer me ōna hoa i roto i Neurobiology of Aging, ko te kahurangi metilīni te rongoā waihanga katoa tuatahi rawa i whakamahia i te ao hauora. I whakaurua te chloral hydrate hei rongoā whakatau mauri waihanga i 1869, neke atu i te rua tekau tau i mua. Kei te tuhinga o 1891 anō tētahi wāhanga o te whakautu, nā te mea ka whakaingoatia e ōna kaituhi ngā rongoā whakaheke kirikā waihanga kua rahua kē mō te malaria, tae atu ki te quinoline, te antipyrine me te antifebrin. I muri noa atu ka puta tā Ehrlich ake pūhui arsenic mō te pakewakewa. Ko te putanga o te kerēme e taea ana te tautoko e pā ana ki te tikanga, kaua ki te mea tuatahi: ko te kahurangi metilīni tētahi o ngā pūhui waihanga tōmua rawa i kōwhiria kia pā ki tētahi rauropi motuhake i runga i tētahi ariā matū mō te whāiti o te mahi.
2. Ehara te tohatoha whāiti i te painga whāiti. Ko te kitenga a Ehrlich i 1886, ka haere te waikano ki te kiko io. He inenga motuhake te wāhi e haere ai tētahi pūhui me tana mahi ina tae atu, ā, he tino māmā ake te ine i te mea tuatahi. Mai i taua wā, ko taua āputa te wāhi i noho ai te nuinga o ngā kerēme mō te kahurangi metilīni me te roro.
3. Ko te parakore tētahi wāhanga o ngā taunakitanga, ehara i te hokohoko. Nā tēnei tonu i rangirua ai ngā tuhinga hītori. Ka panoni ngā rerekētanga iti o te hanga i te wāhi e haere ai tēnei pūhui. Nō reira me here tētahi tiwhikete tātari ki tētahi puranga motuhake, kaua e tuku hei kī noa kua whakamātauria tētahi hua. Ki te kerēme tētahi kaihoko e ū ana ki te tuhinga paerewa o te pukapuka rongoā, engari ko ngā konganuku taumaha anake āna e whakamātautau ana, he nui ake tana kerēme i tā te pūrongo e tautoko ana. Ka whiwhi a Blupreme i te kahurangi metilīni mai i tētahi kaihanga rongoā, ā, ka whakamātautau i te huinga whakaritenga katoa kua whakatakotoria e te tuhinga paerewa: te tuakiri, te parakore, ngā poke waro, ngā whakarewa toenga, ngā poke huānga, ngā toenga whai muri i te tahunga, ngā paepae moroiti me ngā endotoxin huakita. Ka whakaputaina te pūrongo ki te taha o te hua, ā, e whakamārama ana te whārangi kahurangi metilīni kōeke USP i aua paepae me te take ko te kitenga mō te Azure B te mea tuatahi hei rapu.

He ara puna kōrero me ōna rā

Kua whakatakotoria motuhaketia te raupapa whai rā o ngā tohu nui, tae atu ki te matū waikano i mua i a Ehrlich me ngā kōeke me ngā whakaritenga i muri i a ia, i roto i te hītori o te kahurangi metilīni. Ko te tuakiri ake o te pūhui e whakamāramatia ana i te whakamārama he aha te kahurangi metilīni.

Kāore e ōrite te uara taunakitanga o ngā whakaahua e tūāpapa ana i tēnei kōrero, kua tāruatia i roto i te arotake o 2012 nā Krafts, Hempelmann me Skórska-Stania, ā, ka whakaaturia te take e tētahi tauira. Ko te whakaahua o 1891 te tuhinga taketake o te whakamātautau; ko te whakaahua tangata o 1910 kei tōna taha he tohu noa i te ingoa rongonui i taua wā, kāore he mea atu. Ko ngā whārangi o te pukatuhi a Andersag o 1934 te tohu tōtika o te whakakapinga quinoline, nā te ringa ake o te kaimātai matū i tuhi.

Ko te whakarāpopototanga pono o ngā whakamātautau waikano a Ehrlich, i tika tana mōhio ki te whāiti o te mahi me te whāinga, engari i hē tana mōhio ki te pūnaha mahi. Ka kukū tonu te kahurangi metilīni ki te kiko io, ā, ka whakararu tonu i te pirinoa malaria. Kāore te mea tuarua e puta nā te mea tuatahi, ā, i hē te take matū i whakatakotoria e ia mō ngā mea e rua. Ko tana i whakaatu ai, kāore e taea te whakahē, he roa ake tōna uara i tō tētahi pūnaha mahi tika: ka taea te kōwhiri i tētahi pūhui, kaua e kitea tūponotia noa, ā, ka taea te kōwhiri i runga i ngā taunakitanga kua kohia i mua i te hoatutanga a tētahi ki te tūroro.