Paul Ehrlich ndi methylene blue: mmene utoto unathandizira kupanga njira zopezera mankhwala

Chimene Paul Ehrlich anathandizira pa zachipatala sichinali mankhwala. Chinali maganizo okhudza mmene mankhwala angafufuzidwire.

Mu 1878 anapereka chikalata cha kafukufuku wa digiri ya udokotala chimene gawo lake loyamba linali ndi mutu wakuti "Kumvetsa Kupaka Utoto Monga Nkhani ya Kemistri." Mfundo yake inali yakuti kupaka utoto kagawo ka minofu ndi kudaya nsalu kumatsatira mfundo zofanana. Pazochitika zonsezi, mtundu umamatira chifukwa cha kugwirizana kwa mankhwala pakati pa utoto ndi chinthu chimene chikudayidwa, osati chifukwa chakuti minofuyo imayamwa zinthu, ili ndi mafuta, kapena ili ndi maonekedwe otchera tinthu ta mtundu. Ehrlich anakula akuona msuweni wake, katswiri wa matenda Karl Weigert, akukonza tigawo ta minofu topakidwa utoto. Chimene chinamukopa sichinali zithunzizo, koma mfundo yakuti utotowo unkasankha kumene ukupita.

Mawu amenewa akuoneka ngati akunena zochepa. Koma si choncho. Ngati utoto umamangirira ku minofu chifukwa cha kugwirizana kwa mankhwala, ndiye kuti mmene utotowo wafalikira kumasonyeza kemistri ya minofuyo. Kagawo kopakidwa utoto pa galasi loonera ndi maikulosikopu sikukhalanso chithunzi chabe, koma kumakhala muyeso.

Nthawi yomweyo anayamba kugwiritsa ntchito mfundo imeneyi. Mu 1880 anasakaniza methylene blue ndi acid fuchsin n'kutcha chisakanizocho utoto wosalowerera mbali iliyonse, neutralen Farbkörper. Unathandiza kusiyanitsa mitundu ya maselo oyera a magazi pamene utoto uliwonse umene unkagwiritsidwa ntchito paokha panthawiyo sunathe kutero. Patatha zaka ziwiri, anafotokoza njira yogwiritsa ntchito methyl violet popaka utoto mabakiteriya a chifuwa chachikulu, ndipo Koch anayamba kugwiritsa ntchito njirayo pa ntchito yake.

Chiphunzitso chimene pambuyo pake chinapatsa njira zimenezi maziko amodzi ndi nkhani ina, ndipo nthawi imene chinayamba nthawi zambiri imaphatikizidwa molakwika ndi ya ntchito zoyambirirazo. Chiphunzitso cha Ehrlich cha maunyolo a pambali, chakuti chinthu chimagwira ntchito pa selo chifukwa chakuti ziwirizo zimagwirizana pa kemistri, chinayamba m'zaka za m'ma 1890, osati m'zaka zimene ankafufuza utoto. Chimene ntchito zoyambirirazo zinapereka chinali chikhulupiriro choyambirira: kusankha kumene chinthu chimapita kumadalira kemistri, choncho kusankha kumeneko kungafufuzidwe m'malo mongokupezera mwangozi.

Kuyesa kumene kunasandutsa utoto kukhala mapu

Mu 1885 Ehrlich anafalitsa buku la kafukufuku lofotokoza kufunikira kwa okosijeni m'thupi la chamoyo, lokhala ndi mutu waung'ono wakuti kafukufuku wosanthula mitundu. Njira yake inali kubaya utoto umene mtundu wake umadalira mlingo wa okosideshoni, kenako kuyerekezera mmene ziwalo zosiyanasiyana zinkachepetsera okosideshoni yake kapena kuusunga mmene unalili. Utotowo unkagwiritsidwa ntchito ngati chida, mofanana ndi mmene amagwiritsira ntchito choyezera kutentha: unkasonyeza mikhalidwe ya mkati mwa minofu imene sikanatha kuonedwa mwachindunji. Ehrlich mwiniwake anati cholinga chake chinali kudziwa mphamvu ya ziwalo zamoyo yochepetsera okosideshoni, mothandizidwa ndi utoto winawake.

Zotsatira za methylene blue zinaonekera mu 1886, m'chikalata chokhudza mmene utotowo umachitira ukakumana ndi minofu yamoyo ya mitsempha, chimene chinawerengedwa ku bungwe la zachipatala mu December wa chaka chapitacho. Methylene blue analowetsedwa m'magazi oyenda a nyama yamoyo, kenako tigawo tating'ono tating'ono ta minofu tinachotsedwa n'kuikidwa pa mpweya. Izi zinachititsa kuti utoto wopanda mtundu umene unasonkhana m'minofuyo ubwerere ku mtundu wabuluu mwa okosideshoni, n'kusonyeza kumene unasonkhana. Maselo a mitsempha ndi ulusi wa mitsempha zinatenga mtunduwo, ndipo zinasankha kuutenga mokwanira kuti njirayo ikhale njira yovomerezeka yosonyezera minofu ya mitsempha. Chinthucho sichinalinso utoto wopaka kagawo ka minofu yakufa pa tebulo la ntchito. Chinali chizindikiro chimene chinkafalikira chokha m'thupi lamoyo, ndipo kufalikira kwake kunkatha kuwerengedwa.

Khalidwe limene linali maziko a kuyesa konseku liyenera kufotokozedwa momveka bwino, chifukwa nkhani yonseyi imadalira ilo. Methylene blue amatha kusintha n'kubwereranso mmene analili. Mtundu wake wochepetsedwa okosideshoni, leucomethylene blue, ulibe mtundu, ndipo ukakumana ndi okosijeni umabwerera kukhala ayoni yabuluu yokhala ndi chaji yabwino. Utotowo ukasungunulidwa m'madzi a glucose m'chidebe chotsekedwa, umakhala wopanda mtundu; chidebecho chikatsegulidwa, umasanduka wabuluu. Ehrlich akuti anasonyeza zimenezi mwachindunji mwa kuika iron chloride komanso mpweya pa tigawo ta minofu topakidwa utoto, n'kuona mtunduwo ukubwerera. Utoto umene umasintha mtundu malinga ndi mkhalidwe wa redox wa malo ouzungulira ndi chida chofufuzira malowo.

Choncho makhalidwe awiri anali limodzi. Utoto unkatha kusiyanitsa minofu ina ndi inzake. Ndipo utoto unkatha kuonetsedwa kapena kubisidwa mwa kusintha mlingo wa okosideshoni.

Tikayang'ana m'mbuyo, khalidwe lachiwirili ndilo chiyambi cha chithandizo cha mankhwala olimbana ndi tizilombo toyambitsa matenda. Ngati chinthu chimamangirira ku mtundu wina wa minofu koma osati wina, ndiye kuti chinthu chomwecho chingafike ku mtundu wina wa chamoyo koma osati wina. Ehrlich ananena maganizo otsatira amenewa mwachindunji: ngati tizilombo toyambitsa matenda tikanatha kupakidwa utoto mosankhidwa, kupaka utotoko kukanatha kusonyeza kuvulazidwa kwapadera kwa tizilomboto. Choncho utoto ukanatha kugwiritsidwa ntchito ngati mankhwala, olunjika pa wolowerera m'thupi m'malo molunjika pa wodwalayo.

Kuyesedwa koyamba mwa wodwala sikunali kwa malungo. Mu 1890, limodzi ndi katswiri wa matenda a maganizo Arthur Leppmann, Ehrlich ananena kuti methylene blue anachepetsa ululu wokhudzana ndi mitsempha komanso matenda a rheumatism m'minyewa, m'malo olumikizana mafupa ndi m'mitsempha yolumikiza minyewa ku mafupa. Amuna awiriwa anakambirana ngati mankhwalawo akanatha kugwira ntchito pa matenda a maganizo ndipo anasankha kusawayesa. Dokotala wa ku Italy, Pietro Bodoni wa ku Genoa, anapitiriza kuwayesa ngakhale zinali choncho. Mutu wa chikalata chake cha 1899 umatchula mphamvu yokhazika mtima pansi pa mitundu yosiyanasiyana ya matenda a psychosis: anafotokoza kukhazikika kwa odwala khumi ndi anayi amene anali osakhazikika, ndipo ananena kuti madokotala ena a ku Genoa anali atayamba kale kugwiritsa ntchito utotowo pa cholinga chomwecho. Kukhazika wodwala pansi sikutanthauza kuchitapo kanthu pa matendawo, ndipo kusiyana kumeneku kumabwerezabwereza m'nkhaniyi.

Ntchito yokhudza malungo inayamba mu 1891, limodzi ndi katswiri wa matenda Paul Guttmann, ku chipatala cha Moabit ku Berlin. Methylene blue anaperekedwa kwa odwala awiri, ndipo lipoti linafalitsidwa mu Berliner klinische Wochenschrift ya 28 September 1891. Pa wodwala woyamba, anatenga 0.5 g ya utotowo nthawi imodzi madzulo a 29 June; kuukira kwa malungo kumene kunkayembekezeredwa sikunachitike mokwanira, ndipo dandaulo lokhalo limene linalembedwa pambuyo pake linali kuvutika pang'ono pokodza ndi mkodzo wabuluu. Kuukira kwa kutentha thupi kunatha m'masiku oyambirira, ndipo tizilomboto tinali titachoka m'magazi pofika tsiku lachisanu ndi chitatu. Chidule cha olemba lipotilo chinali chakuti zimene ankayembekezera zinakwaniritsidwa kwathunthu. Milandu iwiri yopanda gulu loyerekezera si umboni wotsimikizira. Nkhani yatsatanetsatane ya methylene blue ndi malungo, kuphatikizapo kuyesa kwamakono, ili pa tsamba lake. Funso lofunika pano ndi locheperapo: ndi mbali yanji ya maganizo a Ehrlich imene inakhalabe yolondola itakumana ndi tizilomboto?

Pamene maganizo ake anagwira ntchito ndi pamene analephera

Zambiri za mmene ankaganizira kuti mankhwalawo amagwirira ntchito sizinakhalebe zolondola, makamaka osati monga Ehrlich anafotokozera. Kufotokoza kosavuta kwakuti ayoni yathyathyathya yokhala ndi chaji yabwino ndi mphete zitatu imalowa pakati pa mapeyala a maziko a DNA ya tizilombo sikugwirizana ndi Plasmodium. Methylene blue amachepetsedwa okosideshoni mosavuta kwambiri ndi selo lofiira la magazi lokhala ndi tizilombo moti safika konse ku tizilomboto ali ayoni yathyathyathya yokhala ndi chaji yabwino. Kufotokoza kwa kulowa pakati pa maziko a DNA kumene kumagwirizana ndi utoto wa acridine sikugwirizana ndi utoto uwu.

Zimene umboni umachirikiza n'zovuta kwambiri. Methylene blue amalepheretsa glutathione reductase ya tizilomboto pamlingo umene ungafikidwe m'thupi la wodwala. Amaletsa kusandulika kwa haem kukhala haemozoin, utoto wosagwira ntchito pa kemistri umene tizilomboto timapanga kuti tisawonongedwe ndi poizoni wochokera ku kugaya kwathu haemoglobin. Amatero pafupifupi mofanana ndi chloroquine, komanso kwambiri kuposa quinine. Kusinthasintha kwake kwa redox kumapanganso mitundu ya okosijeni yogwira ntchito kwambiri mu selo limene likupanga kale mitundu imeneyi. Sitikudziwa bwinobe kuti ndi iti mwa njira zimenezi imene ili yeniyeni, kapena ngati zonse zimathandizira.

Palinso vuto lina, ndipo liyenera kutsogolera mmene mawu aliwonse a m'mbiri okhudza chinthuchi amawerengedwera. Methylene blue wogulitsidwa panthawiyo sanali chinthu chimodzi chokha. Zitsanzo zake zinali ndi azure B, chinthu chofanana naye koma chochotsedwa gulu limodzi la methyl, ndipo madzi osungunulira akakhala akale ankasonkhanitsa azure B wambiri. Azure B ndi utoto umene umasiyana mtundu malinga ndi chimene ukumangirira, ndipo umalunjika ku zinthu zina: umapaka DNA ya maunyolo awiri mtundu wabuluu wakuda ndi RNA mtundu wobiriwira. Chisakanizo cha utoto uwiri wopita kumalo osiyanasiyana, m'magawo amene palibe amene analemba, sichingapereke umboni womveka bwino wa zimene methylene blue amene anali mmenemo anachita.

Utoto wokhawo sunalowe m'malo mwa quinine. Njirayo ndiyo inachita bwino kwambiri. Wophunzira wa Ehrlich, Wilhelm Roehl, amene ankagwira ntchito ku kampani yophatikiza utoto ndi mankhwala ya IG Farben, anapitiriza kulimbikitsa zinthu zochokera ku utoto ngati mankhwala a matenda a m'madera otentha. Anaperekanso chida chimene chinkasowa: mbalame ya canary yopatsidwa malungo a mbalame, yoti izigwiritsidwa ntchito nthawi zonse poyesa zinthu zomwe zikanakhala mankhwala. Kenako Werner Schulemann anasintha unyolo wa pambali, ndipo mchere wa phenothiazinium umene unapangidwa unachiza matenda amene anayambitsidwa poyeserawo. Unkasandutsabe odwala kukhala abuluu.

Chimene chinakhalitsa sichinali utotowo kapena dongosolo la mphete zake, koma unyolo wa pambali. Kuwonjezera gulu la dialkylaminoalkylamino kunasintha khalidwe la molekyuluyo, ndipo kagawo kameneka kanasungidwa pakusintha kulikonse komwe kunachitika pambuyo pake. Gulu limenelo likasungidwa koma mphete ya phenothiazinium n'kusinthidwa ndi acridine, zotsatira zake ndi quinacrine. Ikasinthidwa ndi quinoline, zotsatira zake ndi chloroquine. Pamaquine, primaquine ndi amodiaquine, onse amene akadalipo pa mndandanda wa mankhwala a malungo, ali ndi gulu lomwelo. Chinthu chimene chinalephera monga chithandizo chinapereka kagawo kamene kanapambana.

Kugwirizana kwake ndi mankhwala a psychosis kumachokera ku mpheteyo m'malo mochokera ku mankhwalawo. Kufotokoza kapangidwe ka methylene blue ndiko kunatsogolera Heinrich August Bernthsen ku maziko a phenothiazine mu 1883. Maziko amenewo, osinthidwa m'njira zosiyanasiyana, ndi amene akatswiri a kemistri ku Rhône-Poulenc ankagwira ntchito nawo m'zaka za m'ma 1940 pofunafuna mankhwala oletsa histamine. Chimodzi mwa zinthu zimenezo chinapangidwa chakumapeto kwa 1950 ndipo chinayesedwa ndi dokotala wa opaleshoni Henri Laborit, amene anaona kuti chimasiya odwala ali okhazikika komanso osasamala zimene zikuchitika. Kugwiritsidwa ntchito kwake koyamba pa matenda a maganizo kumene kunafalitsidwa, mwa wodwala wa mania, kunachitika mu January 1952. Mankhwala oyamba a psychosis si ochokera mwachindunji ku mankhwala a malungo a Ehrlich, koma ndi achibale akutali a utoto umene anayambira nawo.

Zizolowezi zitatu zoyenera kusunga kuchokera m'nkhaniyi

1. Mawu akuti "mankhwala oyamba opangidwa ndi kemistri kugwiritsidwa ntchito pachipatala" amafotokoza gulu linalake, ndipo zofunika kuwamveketsa ndi zambiri kuposa mmene mawuwo akuonekera. Mawu amenewa akhala ofala; ndemanga ya Schirmer ndi anzake imene imatchulidwa kawirikawiri mu Neurobiology of Aging imatcha methylene blue mankhwala oyambirira kwambiri opangidwa kwathunthu ndi kemistri kugwiritsidwa ntchito pachipatala. Chloral hydrate anayamba kugwiritsidwa ntchito ngati mankhwala okhazika mtima pansi opangidwa ndi kemistri mu 1869, zaka zoposa makumi awiri m'mbuyomo. Chikalata cha 1891 chimapereka mbali ina ya yankho, chifukwa olemba ake amatchula mankhwala ochepetsa kutentha thupi opangidwa ndi kemistri amene anali atalephera kale polimbana ndi malungo, kuphatikizapo quinoline, antipyrine ndi antifebrin. Mankhwala a Ehrlich omwe anali ndi arsenic ochizira chindoko anabwera pambuyo pake. Mawu amene angachirikizidwe ndi umboni akukhudza njira osati kukhala woyamba: methylene blue ali m'gulu la zinthu zoyambirira zopangidwa ndi kemistri zimene zinasankhidwa kuti zilimbane ndi chamoyo chinachake potengera chiphunzitso cha kemistri cha kusankha kumene chinthu chimagwira ntchito.
2. Kufalikira mosankha sikutanthauza kupindulitsa mosankha. Zotsatira za Ehrlich za 1886 zinali zakuti utotowo umapita ku minofu ya mitsempha. Kumene chinthu chimapita ndi zimene chimachita chikafika kumeneko ndi miyeso iwiri yosiyana, ndipo woyambawo ndi wosavuta kwambiri kuyeza. Kusiyana kumeneko ndi kumene mawu ambiri onena za methylene blue ndi ubongo akhala akuchokera kuyambira nthawi imeneyo.
3. Kuyera kwa chinthu ndi mbali ya umboni, osati ya kutsatsa malonda. Zolemba za mbiriyi sizili zomveka bwino chifukwa cha zimenezi. Kusiyana pang'ono kwa kapangidwe kumasintha kumene chinthuchi chimapita. N'chifukwa chake chikalata cha zotsatira za kusanthula chiyenera kugwirizanitsidwa ndi gulu linalake la zinthu zopangidwa nthawi imodzi, m'malo mongoperekedwa ngati umboni wakuti chinthucho chimayesedwa. Wogulitsa amene akunena kuti chinthu chikugwirizana ndi mfundo za m'buku lovomerezeka la miyezo ya mankhwala koma akungoyesa zitsulo zolemera zokha akunena zambiri kuposa zimene lipotilo limachirikiza. Blupreme amatenga methylene blue kuchokera kwa wopanga mankhwala ndipo amayesa zofunikira zonse zimene buku la miyezolo limatchula: kutsimikizira kuti ndi chinthu chenicheni, kuyera kwake, zonyansa za organic, zotsalira za zosungunulira, zonyansa za maelementi, zotsalira pambuyo powotcha, malire a tizilombo tating'onoting'ono ndi maendotoxin a mabakiteriya. Lipotilo limafalitsidwa pamodzi ndi chinthucho, ndipo tsamba la methylene blue wa mulingo wa USP limafotokoza malire amenewo komanso chifukwa chake zotsatira za azure B ndi zimene ziyenera kuyang'anidwa poyamba.

Mndandanda wa magwero ndi masiku ake

Mndandanda wa zochitika zofunika ndi masiku ake, kuphatikizapo kemistri ya utoto imene inalipo Ehrlich asanayambe ndi milingo komanso zofunikira zimene zinabwera pambuyo pake, wafotokozedwa padera mu mbiri ya methylene blue. Kufotokozera chinthu chenichenicho kuli pa tsamba la kodi methylene blue ndi chiyani.

Zithunzi zimene nkhaniyi yatengera, zosindikizidwanso mu ndemanga ya 2012 ya Krafts, Hempelmann ndi Skórska-Stania, sizili ndi phindu lofanana monga umboni, ndipo chitsanzo chimodzi chimasonyeza chifukwa chake. Chithunzi cha 1891 ndi cholemba choyambirira cha kuyesako; chithunzi cha munthu cha 1910 chimene chili pambali pake chimangosonyeza nthawi ya kutchuka kwake, osati china chilichonse. Masamba a m'buku la zolemba la Andersag la 1934 ndi umboni wachindunji wa kusintha pogwiritsa ntchito quinoline, wolembedwa ndi dzanja la katswiri wa kemistriyo.

Chidule choona mtima cha kuyesa kwa Ehrlich ndi utoto ndi chakuti anapeza bwino kusankha kwa utotowo ndi chimene unkafunika kulunjika, koma analakwitsa pa mmene unkagwirira ntchito. Methylene blue amasonkhanadi mu minofu ya mitsempha ndipo amavulazadi tizilombo ta malungo. Sachita chachiwiricho chifukwa cha choyambacho, ndipo chifukwa cha kemistri chimene anapereka pa zonsezi chinali cholakwika. Chimene anasonyeza mosatsutsika chinali chokhalitsa kuposa kufotokoza kolondola kwa mmene mankhwala amagwirira ntchito: chinthu chingasankhidwe m'malo mongopezeka, ndipo chingasankhidwe potengera umboni wosonkhanitsidwa aliyense asanachipereke kwa wodwala.