Paul Ehrlich n'ubururu bwa metilene: uko irangi ryagize uruhare mu kuvumbura imiti

Umusanzu wa Paul Ehrlich mu buvuzi ntiwari umuti. Wari igitekerezo cy'uburyo umuti ukwiye gusuzumwa.

Mu 1878 yatanze inyandiko yo kubona impamyabumenyi y'ikirenga, igice cyayo cya mbere cyari gifite umutwe ugira uti "Gusobanukirwa gusiga irangi hashingiwe ku butabire." Yavugaga ko gusiga agace k'ingirangingo irangi no kurangi umwenda bikurikiza ihame rimwe. Muri byombi, ibara rifata kubera ubushobozi bw'irangi n'ibyo risigwa bwo kwifatanya mu buryo bw'ubutabire, atari ukubera ko ingirangingo zinyunyuza ibintu, zifite ibinure, cyangwa ziteye ku buryo zifata ibinyabutabire bitanga ibara. Ehrlich yakuze areba mubyara we Karl Weigert, inzobere mu gusuzuma indwara mu ngirangingo, ategura uduce twasizwe irangi. Icyamushishikazaga si amashusho yabonaga, ahubwo ni uko irangi ryatoranyaga aho rijya.

Icyo gitekerezo gisa n'icyoroheje. Nyamara si ko kiri. Niba irangi ryifatanya n'ingirangingo kubera impamvu z'ubutabire, uko iryo rangi rigaragara bigaragaza imiterere y'ubutabire y'izo ngirangingo. Ikirahure cya mikorosikopi kiriho agace kasizwe irangi ntikiba kikiri ishusho gusa; gihinduka igipimo.

Yahise yubakira kuri icyo gitekerezo. Mu 1880 yavanze ubururu bwa metilene na fuchsin ya aside, yita urwo ruvange irangi ridafite aside cyangwa alikali, neutralen Farbkörper. Rwatandukanyaga ubwoko butandukanye bw'uturemangingo twera tw'amaraso, mu gihe amarangi yakoreshwaga ukwawo icyo gihe atabishoboraga. Nyuma y'imyaka ibiri yerekanye uburyo bwo gusiga bagiteri z'igituntu irangi rya methyl violet, maze Koch atangira gukoresha ubwo buryo mu kazi ke.

Igitekerezo cyaje guha ubwo buryo bwose urufatiro rumwe ni ikindi kibazo, kandi igihe cyatangiriyeho gikunze kwitiranywa. Igitekerezo cya Ehrlich cy'amashami yo ku ruhande rwa molekile, cyavugaga ko ikinyabutabire kigira icyo gikora ku karemangingo kubera ko bihuje mu buryo bw'ubutabire, cyavutse mu myaka ya 1890, atari mu myaka y'ubushakashatsi bwe ku marangi. Icyo ubushakashatsi bwa mbere bwatanze ni ukwemera kwari kwarabubanjirije: ubushobozi bwo gutoranya bushingiye ku butabire, bityo bushobora gushakishwa aho gutegereza kubugwaho ku bw'amahirwe.

Ubushakashatsi bwahinduye irangi ikarita

Mu 1885 Ehrlich yasohoye igitabo cy'ubushakashatsi ku mwuka wa ogisijeni ikinyabuzima gikenera, gifite umutwe wungirije uvuga ko ari ubushakashatsi bwo gusesengura hifashishijwe amabara. Uburyo bwacyo bwari ugutera amarangi afite ibara rihinduka bitewe n'urwego rw'itakaza rya elegitoroni, hanyuma akagereranya uko ingingo zitandukanye zayongeraga elegitoroni cyangwa zayagumishaga uko ari. Irangi ryakoreshwaga nk'igikoresho, nk'uko hakoreshwa igipimabushyuhe: ryagaragazaga imiterere yo mu ngirangingo itashoboraga gusuzumwa mu buryo butaziguye. Ehrlich ubwe yavuze ko intego yari ukumenya, hifashishijwe amarangi yihariye, ubushobozi bw'ingingo nzima bwo kongera elegitoroni ku binyabutabire.

Ibyavuye ku bururu bwa metilene byatangajwe mu 1886, mu nyandiko ku mikorere y'irangi ku ngirangingo nzima z'imyakura, yari yarasomewe umuryango w'abaganga mu Ukuboza kwabanje. Ubururu bwa metilene bwinjijwe mu maraso atembera mu nyamaswa nzima, hanyuma uduce duto tw'ingirangingo turavanwamo dushyirwa mu mwuka. Ibyo byatumye irangi ritagira ibara ryari ryarahateraniye ritakaza elegitoroni, ryongera kuba ubururu kandi rigaragaza aho ryari ryarakusanyirijwe. Uturemangingo tw'imyakura n'udutsi tw'imyakura byafashe irangi, kandi byaritoranyije ku rugero rwatumye ubwo buryo buba uburyo busanzwe bwo kugaragaza ingirangingo z'imyakura. Icyo kinyabutabire nticyari kikiri irangi gusa risigwa agace k'ingirangingo zapfuye kari ku meza ya laboratwari. Cyari ikimenyetso cyikwirakwizaga mu mubiri muzima, kandi uko cyikwirakwizaga byashoboraga gusomwa.

Umutungo w'irangi wari inyuma y'ubwo bushakashatsi bwombi ukwiye kuvugwa mu buryo bwumvikana, kuko ibindi byose muri iyi nkuru biwushingiyeho. Ubururu bwa metilene bushobora guhinduka bukongera gusubira uko bwari. Iyo bwongewe elegitoroni, buhinduka leucomethylene blue itagira ibara, kandi iyo buhuye na ogisijeni busubira kuba iyoni y'ubururu ifite umuriro mwiza. Uruvange rw'irangi na glucose mu icupa rifunze ntirugira ibara; iyo icupa rifunguwe, ruhinduka ubururu. Bivugwa ko Ehrlich yerekanye ibyo mu buryo butaziguye akoresheje chloride y'icyuma ndetse n'umwuka ku duce twasizwe irangi, akareba ibara rigaruka. Irangi rihindura ibara bitewe n'uko ibirikikije bitanga cyangwa byakira elegitoroni ni igikoresho cyo gusuzuma ibyo birikikije.

Bityo, imitungo ibiri yari ibangikanye. Irangi ryashoboraga gutandukanya ingirangingo imwe n'indi. Kandi irangi ryashoboraga kugaragaza ibara cyangwa kuritakaza bitewe n'ihinduka ry'urwego rw'itakaza rya elegitoroni.

Iyo bisuzumwe uhereye ku byaje nyuma, uwo mutungo wa kabiri ni intangiriro yo kuvura hifashishijwe ibinyabutabire. Niba ikinyabutabire cyifatanya n'ubwoko bumwe bw'ingirangingo nticyifatanye n'ubundi, icyo kinyabutabire gishobora kugera ku bwoko bumwe bw'ibinyabuzima ntikigere ku bundi. Ehrlich yavuze uwo mwanzuro mu buryo butaziguye: niba ikinyabuzima gitera indwara gishobora gusigwa irangi kitoranyijwe, uko gufata irangi gushobora kugaragaza ko icyo kinyabuzima cyangizwa mu buryo bwihariye. Bityo, irangi ryashoboraga gukoreshwa nk'umuti ugamije kwibasira ikinyabuzima cyateye umubiri aho kwibasira umurwayi.

Igerageza rya mbere ku murwayi ntiryari irya malariya. Mu 1890, Ehrlich n'umuganga w'indwara zo mu mutwe Arthur Leppmann batangaje ko ubururu bwa metilene bwagabanyaga ububabare buturuka ku myakura no ku ndwara za rumatizime zo mu mikaya, mu ngingo no mu mitsi ihuza imikaya n'amagufwa. Abo bagabo bombi baganiriye niba uwo muti washoboraga kugira icyo ukora ku ndwara zo mu mutwe, bafata icyemezo cyo kutabigerageza. Umuganga w'Umutaliyani Pietro Bodoni wo muri Genoa we yarabikoze. Inyandiko ye yo mu 1899 ifite umutwe uvuga ku ngaruka zo gutuza mu buryo butandukanye bw'indwara zituma umuntu atakaza ubushobozi bwo kumenya ibiriho: yasobanuye gutuza kw'abarwayi cumi na bane bari bafite imyitwarire y'umutekano muke, anavuga ko abandi baganga bo muri Genoa bari basanzwe bakoresha iryo rangi ku bw'iyo ntego. Gutuza umurwayi si ukugira icyo ukora ku ndwara, kandi iryo tandukaniro rikomeza kugaruka muri aya mateka.

Ubushakashatsi kuri malariya bwaje mu 1891, bukorwa na Ehrlich hamwe n'inzobere mu gusuzuma indwara mu ngirangingo Paul Guttmann, mu bitaro bya Moabit i Berlin. Ubururu bwa metilene bwahawe abarwayi babiri, kandi raporo yasohotse muri Berliner klinische Wochenschrift yo ku wa 28 Nzeri 1891. Mu murwayi wa mbere, yafashe 0.5 g y'irangi icyarimwe ku mugoroba wo ku wa 29 Kamena; igitero cy'indwara cyari gitegerejwe nticyaje uko cyari cyitezwe, kandi ikibazo cyonyine cyanditswe nyuma yaho cyari ukunyara bigoye kandi bibabaza ku rugero ruto, inkari zifite ibara ry'ubururu. Ibitero by'umuriro byashize mu minsi ya mbere, kandi udukoko twari twavuye mu maraso bitarenze umunsi wa munani. Abanditsi ubwabo bashoje bavuga ko ibyo bari biteze byose byari byagezweho. Igerageza ku barwayi babiri ridafite itsinda ryo kugereranya ntiritanga gihamya. Ibisobanuro birambuye ku bururu bwa metilene na malariya, birimo n'amagerageza yo muri iki gihe, biri ku rupapuro rwabyo. Ikibazo gishishikaje hano cyo kirarushijeho kuba gito: ni ibihe bitekerezo bya Ehrlich byakomeje guhama nyuma yo guhura n'agakoko ka malariya?

Aho ibitekerezo byahagaze n'aho byananiranye

Nta byinshi mu bisobanuro by'uburyo bukora byakomeje guhama, nibura atari uko Ehrlich yari yabitanze. Igisobanuro cyoroshye, kivuga ko iyoni ifite umuriro mwiza, igizwe n'impeta eshatu ziri mu ishusho irambuye, inyura hagati y'ibice bibiri bibiri by'ifatizo bya ADN y'agakoko, ntigihama kuri Plasmodium. Akaremangingo gatukura k'amaraso kanduye kongera elegitoroni ku bururu bwa metilene ku buryo bworoshye cyane, ku buryo butagera ku gakoko bukiri iyoni irambuye ifite umuriro mwiza. Igitekerezo cyo kwinjira hagati y'ibice by'ifatizo bya ADN gihuye n'amarangi ya acridine ntigihuye n'iri.

Ibyo ibimenyetso bishyigikira biragoye kurushaho. Ubururu bwa metilene bubuza glutathione reductase y'agakoko gukora ku rugero rw'ubwinshi bushobora kuboneka mu murwayi. Bubuza haem guhinduka haemozoin, ikinyabutabire gitanga ibara kidakora agakoko gakora kugira ngo katangizwa n'uko ubwako gasenya hémoglobine. Ibyo bubikora ku rugero hafi rungana n'urwa chloroquine kandi ruruta kure urwa quinine. Kuzunguruka kwabwo hagati yo kwakira no gutanga elegitoroni na byo bitanga ubwoko bwa ogisijeni bwitabira cyane mu karemangingo gasanzwe bubukora. Ntabwo haramenyekana neza ari iki muri ibyo ari bwo buryo nyabwo bukora, cyangwa niba byose bigira uruhare.

Hari ikindi kibazo gikomeye, kandi kigomba kuyobora uko dusoma ibyavuzwe byose mu mateka kuri iki kinyabutabire. Ubururu bwa metilene bwacuruzwaga muri icyo gihe ntibwari ikinyabutabire kimwe gusa. Ingero zabwo zarimo azure B, ikinyabutabire gifitanye isano na bwo gikurwaho itsinda rimwe rya methyl, kandi ibisukika byabwo byamaze igihe byakusanyaga byinshi byayo. Azure B ni irangi ritanga amabara atandukanye bitewe n'icyo ryifatanyije na cyo, kandi rifite ibindi ryibasira: risiga ADN y'imigozi ibiri ubururu bwijimye na RNA icyatsi. Uruvange rw'amarangi abiri ajya ahantu hatandukanye, ku bipimo nta muntu wanditse, ntirushobora gushyigikira imvugo isobanutse neza ku cyo ubururu bwa metilene bururimo bwakoze.

Irangi ubwaryo ntiryigeze risimbura quinine. Uburyo bwakoreshejwe bwo bwagize umusaruro mwiza kurushaho. Wilhelm Roehl, umunyeshuri wa Ehrlich wakoreraga ikigo cyahuzaga ubucuruzi bw'amarangi n'imiti IG Farben, yakomeje guteza imbere ibikomoka ku marangi nk'imiti y'indwara zo mu turere dushyuha. Yatanze n'igikoresho cyari kibura: inyoni ya kanari yandujwe malariya y'inyoni, ikoreshwa buri gihe mu gusuzuma ibinyabutabire byashoboraga kuba imiti. Werner Schulemann yahise ahindura ishami ryo ku ruhande rwa molekile, maze umunyu wa phenothiazinium wavuyemo ukiza ubwandu bwari bwatewe mu igerageza. Wakomezaga guhindura abarwayi ubururu.

Icyaje kuramba si irangi cyangwa imiterere y'impeta, ahubwo ni ishami ryo ku ruhande rwa molekile. Kongeraho itsinda rya dialkylaminoalkylamino byahinduye imyitwarire ya molekile, kandi icyo gice cyarokotse impinduka zose zaje gukurikiraho mu kuyubaka. Iyo iryo tsinda rigumishijweho, impeta ya phenothiazinium igasimbuzwa iya acridine, havamo quinacrine. Iyo hashyizwemo quinoline, havamo chloroquine. Pamaquine, primaquine na amodiaquine, byose bikiri mu rutonde rw'imiti ya malariya, bifite iryo tsinda rimwe. Ikinyabutabire kitageze ku ntego nk'umuti cyatanze igice cyageze kuri iyo ntego.

Isano n'imiti ikoreshwa ku ndwara zituma umuntu atakaza ubushobozi bwo kumenya ibiriho inyura ku mpeta, aho kunyura ku muti. Gusobanura imiterere y'ubururu bwa metilene ni byo byatumye Heinrich August Bernthsen agera ku miterere shingiro ya phenothiazine mu 1883. Iyo miterere, yahindurwaga hongerwaho amatsinda mu buryo butandukanye, ni yo abahanga mu butabire bo muri Rhône-Poulenc bakoragaho mu myaka ya 1940 bashaka imiti ibuza histamine gukora. Kimwe muri ibyo binyabutabire cyakozwe hafi y'iherezo rya 1950, kigeragezwa n'umuganga ubaga Henri Laborit, wabonye ko cyatumaga abarwayi batuza kandi ntibite cyane ku bibakikije. Imikoreshereze yacyo ya mbere yatangajwe mu kuvura indwara zo mu mutwe, ku murwayi wari ufite mania, yabaye muri Mutarama 1952. Umuti wa mbere w'indwara zituma umuntu atakaza ubushobozi bwo kumenya ibiriho si inkomoko ya hafi y'umuti wa malariya wa Ehrlich; ahubwo ni umuvandimwe wa kure w'irangi yahereyeho.

Imigenzo itatu dukwiye gukura muri aya mateka

1. "Umuti wa mbere wakozwe n'ubutabire wakoreshejwe mu buvuzi" bisobanura icyiciro, kandi ibisabwa kugira ngo iyo mvugo ibe nyayo birenze ibyo isa n'ivuga. Iyo mvugo yaramenyerewe; isesengura rya Schirmer n'abo bakoranye rikunze kwifashishwa muri Neurobiology of Aging ryita ubururu bwa metilene umuti wa mbere rwose wakozwe wose n'ubutabire wakoreshejwe mu buvuzi. Chloral hydrate yatangiye gukoreshwa nk'umuti wo gutuza wakozwe n'ubutabire mu 1869, imyaka irenga makumyabiri mbere yaho. Inyandiko yo mu 1891 ubwayo itanga igice cy'igisubizo, kuko abanditsi bayo bavuga imiti igabanya umuriro yakozwe n'ubutabire yari yarananiwe kuri malariya, harimo quinoline, antipyrine na antifebrin. Umuti wa Ehrlich ubwe wari urimo arsenic, wo kuvura mburugu, waje nyuma yaho. Imvugo ishobora gushyigikirwa ni ivuga ku buryo bwakoreshejwe aho kuvuga ku wabanje: ubururu bwa metilene buri mu binyabutabire bya mbere byakozwe n'ubutabire byatoranyijwe kugira ngo byibasire ikinyabuzima runaka hashingiwe ku gitekerezo cy'ubutabire gisobanura ubushobozi bwo gutoranya.
2. Kugera ahantu hatoranyijwe si ugutanga inyungu zitoranyijwe. Icyo Ehrlich yabonye mu 1886 ni uko irangi rijya mu ngirangingo z'imyakura. Aho ikinyabutabire kijya n'icyo gikora kigeze yo ni ibipimo bibiri bitandukanye, kandi icya mbere kiroroshye cyane gupima. Icyo cyuho ni cyo cyakomeje kubamo ibyavuzwe byinshi ku bururu bwa metilene n'ubwonko kuva icyo gihe.
3. Ubuziranenge ni igice cy'ibimenyetso, si icyamamaza. Ni yo mpamvu nyirizina inyandiko z'amateka zidasobanutse neza. Utuntu duto dutandukanye mu miterere duhindura aho iki kinyabutabire kijya; ni yo mpamvu icyemezo cy'isesengura kigomba guhuzwa n'icyiciro runaka cy'ibicuruzwa byakorewe rimwe, aho gutangwa nk'imvugo rusange ivuga ko igicuruzwa cyageragejwe. Umucuruzi uvuga ko igicuruzwa cye cyujuje ibisabwa n'inyandiko yihariye yo mu gitabo cy'ibipimo by'imiti, kandi yarasuzumye gusa ibyuma biremereye, aba avuga ibirenze ibyo raporo ishyigikira. Blupreme ikura ubururu bwa metilene ku ruganda rukora imiti kandi igasuzuma ibipimo byose biteganywa n'iyo nyandiko: umwirondoro w'ikinyabutabire, ubuziranenge, umwanda w'ibinyabutabire ngenga, ibisigazwa by'ibinyabutabire bishongesha, umwanda w'ibinyabutabire by'ibanze, ibisigazwa nyuma yo gutwika, imipaka y'udukoko dutaboneshwa amaso n'uburozi bwa endotoxine buturuka kuri bagiteri. Raporo itangazwa hamwe n'igicuruzwa, kandi urupapuro rw'ubururu bwa metilene bwo ku rwego rwa USP rusobanura iyo mipaka n'impamvu igisubizo cya azure B ari cyo kigomba kubanza kurebwa.

Inkomoko z'amakuru zikurikiranye ku matariki

Uruhererekane rw'ibikorwa by'ingenzi rukurikiranye ku matariki, harimo ubutabire bw'amarangi bwabanjirije Ehrlich n'inzego z'ubuziranenge n'ibipimo byaje nyuma ye, rusobanurwa ukwabwo mu mateka y'ubururu bwa metilene. Umwirondoro w'ikinyabutabire ubwacyo usobanurwa mu nyandiko ivuga ku cyo ubururu bwa metilene ari cyo.

Amashusho ashingirwaho muri iyi nkuru, yongeye kugaragazwa mu isesengura ryo mu 2012 rya Krafts, Hempelmann na Skórska-Stania, ntabwo afite agaciro kamwe k'ibimenyetso, kandi urugero rumwe rugaragaza impamvu. Ishusho yo mu 1891 ni inyandiko y'ibanze y'igerageza; ifoto yo mu 1910 iri iruhande rwayo igaragaza igihe izina rye ryari rizwi, nta kindi. Impapuro zo mu ikayi ya Andersag yo mu 1934 ni ibimenyetso bitaziguye by'isimbuzwa rya quinoline, byanditswe n'umuhanga mu butabire ubwe.

Incamake ivugisha ukuri y'ubushakashatsi bwa Ehrlich ku marangi ni uko yasobanukiwe ubushobozi bwo gutoranya n'icyo yagombaga kwibasira, ariko akayoba ku buryo byakoraga. Ubururu bwa metilene koko bwikusanyiriza mu ngirangingo z'imyakura kandi koko bwangiza agakoko ka malariya. Ntabwo bukora icya kabiri kubera icya mbere, kandi impamvu y'ubutabire yatanze kuri byombi ntiyari yo. Icyo yerekanye ku buryo budashidikanywaho cyararambye kurusha igisobanuro nyacyo cy'imikorere: ikinyabutabire gishobora gutoranywa aho kukigwaho ku bw'amahirwe, kandi kigatoranywa hashingiwe ku bimenyetso byakusanyijwe mbere y'uko umuntu uwo ari we wese agiha umurwayi.