Chinyorwa
Paul Ehrlich nemethylene blue: kubatsira kwakaita dhayi mukutsvakwa kwemishonga
Chipo chaPaul Ehrlich kumunda wezvokurapa chakanga chisiri mushonga. Chaiva pfungwa yokuti mushonga unofanira kuongororwa sei.
Muna 1878 akaendesa gwaro redhigirii reudhokotera raiva nechikamu chokutanga chainzi "Kunzwisisa Kusvibisa Neruvara Maererano Nemakemikari." Pfungwa yaro yaiva yokuti kusvibisa chidimbu chetishu nedhayi uye kudhayira chidimbu chejira zvinotevera musimboti mumwe chete. Pazvose zviri zviviri, ruvara runonamira nokuda kwokukwezvana kwemakemikari ari mudhayi nechinhu chiri kudhayirwa, kwete nokuti tishu inosveta, ine mafuta, kana kuti ine chimiro chinobata chinhu chinopa ruvara. Ehrlich akanga akura achiona hama yake, nyanzvi yezvirwere Karl Weigert, ichigadzira zvidimbu zvakaiswa ruvara, uye chaimukwezva chakanga chisiri mifananidzo yacho asi chokwadi chokuti dhayi yaisarudza kwaaienda.
Pfungwa iyi inoita seyakareruka. Haina kudaro. Kana dhayi ichinamatira patishu nokuda kwezvikonzero zvemakemikari, nzira inopararira nayo ruvara inoburitsa mashoko pamusoro pemakemikari etishu iyoyo. Siraidhi yakaiswa ruvara haichangori mufananidzo wokutsanangura, asi inova chinhu chinoyera.
Akabva avakira ipapo. Muna 1880 akabatanidza methylene blue neacid fuchsin, akati musanganiswa wacho idhayi isina divi, chinhu chinopa ruvara chisina divi, yaipatsanura marudzi akasiyana emasero machena eropa apo madhayi aishandiswa ari oga panguva iyoyo aisakwanisa. Makore maviri gare gare akaratidza nzira yemethyl violet yokusvibisa mabhakitiriya etibhi, uye Koch akatora nzira yacho akaishandisa mubasa rake.
Dzidziso yakazopa maitiro aya hwaro humwe inyaya yakasiyana, uye nguva yayakatanga inowanzosanganiswa nedzimwe. Dzidziso yaEhrlich yemaketani epadivi, pfungwa yokuti chinhu chinoshanda pasero nokuti makemikari azvo anowirirana, ndeyema1890s, kwete yemakore ake emadhayi. Chakapiwa nebasa rokutanga chaiva chivimbo chakazotungamirira kwairi: kusarudza kunangwa kunobva pamakemikari, saka kunogona kutsvakwa panzvimbo pokungowanikwa netsaona.
Kuyedza kwakashandura dhayi kuva mepu
Muna 1885 Ehrlich akabudisa gwaro rakadzama pamusoro pezvinodiwa nemuviri paokisijeni, rine kamusoro kaitsanangura kuti yaiva ongororo inoshandisa ruvara. Nzira yacho yaiva yokubaya madhayi ane ruvara runoenderana nemamiriro eoxidation, wozofananidza kuti nhengo dzakasiyana dzaiaderedza sei nemakemikari kana kuachengeta asina kuchinja. Dhayi yaishandiswa semudziyo, sokushandiswa kunoitwa thermometer: yaiburitsa mashoko pamusoro pemamiriro ari mukati metishu aisagona kuongororwa zvakananga. Ehrlich pachake akati chinangwa chaiva chokuziva, achibatsirwa nemadhayi akati, simba renhengo mhenyu rokuita reduction yemakemikari.
Mhedzisiro yemethylene blue yakauya muna 1886, mune rimwe gwaro pamusoro pezvinoita dhayi iyi painosangana netishu mhenyu yetsinga, rakaverengerwa sangano rezvokurapa muna Zvita wegore rakanga rapfuura. Methylene blue yakaiswa muropa raitenderera mumuviri wemhuka mhenyu, zvidimbu zvitete zvetishu zvikazobviswa zvichiratidzwa kumhepo kuitira kuti dhayi yakanga yaungana isina ruvara iite oxidation yodzokera kubhuruu, ichiratidza payakanga yaungana. Masero etsinga netambo dzetsinga zvakatora ruvara, uye kusarudza kwazvo kwakanga kwakakwana zvokuti nzira iyi yakava nzira inowanzoshandiswa pakuratidza tishu yetsinga. Mushonga uyu wakanga usisiri chinhu chinopa ruvara chaingoiswa pachidimbu chakafa chiri patafura yebasa. Wakanga wava chiratidzo chaizviparadzira mukati memuviri mhenyu, uye kupararira kwacho kwaigona kuverengwa.
Hunhu hunotsigira kuyedza kwose uku hunofanira kutaurwa zvakajeka, nokuti zvimwe zvose munyaya iyi zvinobva pahuri. Methylene blue inogona kuchinja yodzokera pairi. Chimiro chayo chakaitwa reduction, leucomethylene blue, hachina ruvara, uye painosangana neokisijeni inodzokera kuion ine chaji yakanaka yebhuruu. Dhayi yakanyungudutswa mumvura ine glucose iri muchirongo chakavharwa haina ruvara; vhura chirongo, yobva yava bhuruu. Ehrlich anonzi akaratidza izvi zvakananga nokuisa iron chloride pamwe chete nemhepo pazvidimbu zvakaiswa ruvara, achiona ruvara ruchidzoka. Dhayi inochinja ruvara zvichienderana nemamiriro eredox ezvakaipoteredza mudziyo wokuongorora zvakaipoteredza izvozvo.
Saka paiva nehunhu huviri hwakabatana. Dhayi yaigona kusiyanisa tishu imwe neimwe. Uye ruvara rwedhayi rwaigona kuvhurwa nokudzimwa nokuchinja kwemamiriro eoxidation.
Kana tikatarisa kumashure tichiziva zvakazotevera, hunhu hwechipiri ndiko kutanga kwokurapa nemakemikari. Kana chinhu chichinamatira kune rumwe rudzi rwetishu kwete rumwe, chinhu ichocho chingangosvika kune rumwe rudzi rwechisikwa chipenyu kwete rumwe. Ehrlich akataura mhedziso iyi zvakananga: kana utachiona hwaigona kusvibiswa nedhayi inosarudza kwainoenda, kusvibiswa kwacho kwaigona kuratidza kukuvadzwa kwakanangana noutachiona ihwohwo. Saka dhayi yaigona kushandiswa somushonga, yakanangana nechisikwa chapinda mumuviri panzvimbo pomurwere.
Kuyedza kwokutanga mumurwere kwakanga kusiri kwemarariya. Muna 1890, achishanda nachiremba wepfungwa Arthur Leppmann, Ehrlich akashuma kuti methylene blue yaideredza marwadzo ane chokuita netsinga nereumatism mumhasuru, majoini netambo dzinobatanidza mhasuru nemapfupa. Varume ava vaviri vakakurukura kana mushonga wacho waigona kushanda pazvirwere zvepfungwa, vakasarudza kusauedza. Mumwe chiremba weItaly, Pietro Bodoni wokuGenoa, akaenderera mberi zvakadaro. Musoro wegwaro rake ra1899 unotaura nezvechiito chokudzikamisa mumarudzi akasiyana epsychosis: akatsanangura kudzikama kwevarwere gumi nevana vakanga vakanyanyisa kusagadzikana, akacherechedzawo kuti vamwe vanachiremba vokuGenoa vakanga vatoshandisa dhayi nokuda kwechinangwa ichocho. Kudzikamisa hakusi kushanda pachirwere chacho, uye mutsauko uyu unoramba uchibuda munhoroondo iyi.
Basa remarariya rakauya muna 1891, pamwe chete nenyanzvi yezvirwere Paul Guttmann, pachipatara cheMoabit muBerlin. Methylene blue yakapiwa varwere vaviri, uye mushumo wakabuda muBerliner klinische Wochenschrift ya28 Gunyana 1891. Pachiitiko chokutanga murwere akanwa 0.5 g yedhayi kamwe chete manheru a29 Chikumi; kubatwa nechirwere kwainge kwakatarisirwa hakuna kuuya zvakazara, uye chichemo choga chakanyorwa pashure chaiva kunetseka kudiki kuita weti, iyo yaiva bhuruu. Kubatwa nefivha kwakanyangarika mumazuva okutanga, uye utachiona hwakanga hwapera muropa panosvika zuva rechisere. Pfupiso yevanyori pachavo yaiva yokuti zvavaitarisira zvakanga zvazadziswa zvizere. Zviitiko zviviri zvisina boka rokuenzanisa hazvisi uchapupu hwakakwana. Tsananguro yakazara yemethylene blue nemarariya, inosanganisira kuyedza kwemazuva ano, iri papeji yayo yoga, uye mubvunzo unonakidza pano wakamanikana kupfuura izvozvo: kufunga kwaEhrlich kwakaramba kwakarurama kusvika papi pakasangana mushonga noutachiona.
Pakarurama kufunga kwake nepakwakakundikana
Hazvina zvakawanda zvetsananguro yokushanda zvakaramba zvakamira, kunyanya muchimiro chakataurwa naEhrlich. Tsananguro yakarongeka yokuti ion ine chaji yakanaka, yakati sandara uye ine maringi matatu, inotsvedza ichipinda pakati pemapeya emabhesi eDNA youtachiona, haimiri kana ichitariswa paPlasmodium. Methylene blue inoitwa reduction zviri nyore zvikuru nesero dzvuku reropa rine utachiona zvokuti haitombosviki kuutachiona iri ion yakati sandara ine chaji yakanaka, uye nyaya yokupinda pakati pemabhesi inokodzera madhayi eacridine haikodzeri iyi.
Zvinotsigirwa nouchapupu hazvina kurongeka zvakadaro. Methylene blue inovhiringidza glutathione reductase youtachiona pahuwandu hunogona kusvika mumuviri womurwere. Inodzivisa kushandurwa kwehaem kuva haemozoin, chinhu chinopa ruvara chisinganyanyi kuita mabasa emakemikari chinogadzirwa noutachiona kuti husaiswe chepfu nokugaya kwahwo haemoglobin. Pakuita izvi, inoshanda zvakada kufanana nechloroquine uye zvakanyanya kupfuura quinine. Kutenderera kwayo kweredox kunogadzirawo mhando dzeokisijeni dzinokurumidza kuita mabasa emakemikari musero rinotogadzira mhando idzi. Kuti ndechipi chezviito izvi chiri nzira chaiyo yokushanda, kana kuti zvose zvinobatsira, hazvisati zvagadziriswa.
Pane chimwe chinonetsa, uye chinofanira kutungamirira kuverengwa kwezvinotaurwa munhoroondo pamusoro pechinhu ichi. Methylene blue yaitengeswa panguva iyoyo yakanga isiri chinhu chimwe chete. Masampuli aiva neazure B, imwe kemikari ine ukama nayo yakabviswa boka rimwe remethyl, uye zvinonyungudutswa zvekare zvaiunganidza yakawanda yayo. Azure B idhayi inoshandura ruvara zvichienderana nezvainonamatira, uye inonangana nezvinhu zvakasiyana: inosvibisa DNA ine tambo mbiri kuita bhuruu yakadzika uye RNA kuita girini. Musanganiswa wemadhayi maviri anoenda kunzvimbo dzakasiyana, ari muzvikamu zvisina kunyorwa nomunhu, haugoni kutsigira chirevo chakajeka chezvakaitwa nemethylene blue yaiva mauri.
Dhayi pachayo haina kumbotsiva quinine. Nzira yokutsvakurudza ndiyo yakaita zviri nani. Mudzidzi waEhrlich, Wilhelm Roehl, aishandira boka remakambani emadhayi nemishonga IG Farben, akaramba achisimudzira zvinhu zvakatorwa pamadhayi semishonga yezvirwere zvomunzvimbo dzinopisa, uye akapa mudziyo wakanga usipo: shiri yecanary, yakaiswa marariya yeshiri, senzira yenguva dzose yokusefa makemikari aitarisirwa kushandiswa semishonga. Werner Schulemann akazochinja ketani yepadivi, uye munyu wephenothiazinium wakabva ipapo wakarapa utachiona hwaishandiswa pakuyedza. Wairamba uchishandura varwere kuva bhuruu.
Chakazogara kwenguva refu chakanga chisiri dhayi kana maringi ayo, asi ketani yepadivi. Kuwedzera boka redialkylaminoalkylamino kwakachinja maitiro emorekuru, uye chidimbu ichi chakaramba chiripo mukuchinjwa kwose kwakatevera. Chengeta boka iroro wotsiva ringi rephenothiazinium neacridine, chinobuda iquinacrine. Tsiva nequinoline, chinobuda ichloroquine. Pamaquine, primaquine neamodiaquine, dzose dzichiri muzita remishonga yemarariya, dzine boka iroro. Chinhu chakakundikana somushonga chakapa chidimbu chakabudirira.
Ukama nemishonga yeantipsychotic hunobva paringi, kwete pamushonga wacho. Kujekesa chimiro chemethylene blue ndiko kwakatungamirira Heinrich August Bernthsen kuhwaro hwephenothiazine muna 1883, uye hwaro ihwohwo, hwakawedzerwa mapoka nenzira dzakasiyana, ndihwo hwaishandiswa nenyanzvi dzemakemikari paRhône-Poulenc muma1940s dzichitsvaga maantihistamine. Chimwe chezvinhu izvozvo chakagadzirwa pedyo nokupera kwa1950, chikaedzwa nachiremba wokuvhiya Henri Laborit, uyo akaona kuti chaisiya varwere vakadzikama uye vasina hanya zvikuru nezvaivapoteredza. Kushandiswa kwacho kwekutanga kwepfungwa kwakabudiswa, mumurwere aiva nemania, kwakauya muna Ndira 1952. Mushonga weantipsychotic wokutanga hausi zvikuru mwana womushonga waEhrlich wemarariya, asi ihama yokure yedhayi yaakatanga nayo.
Maitiro matatu anokosha okuchengeta kubva munyaya iyi
- "Mushonga wokutanga wakagadzirwa nemakemikari ukashandiswa pakurapa" inotsanangura boka, uye zvisungo zvechirevo ichi zvakakura kupfuura zvinoratidzwa nemashoko acho. Mashoko aya ava kugara achishandiswa; ongororo inowanzotaurwa yaSchirmer nevamwe muNeurobiology of Aging inoti methylene blue ndiyo mushonga wokutanga chaiwo wakagadzirwa zvizere nemakemikari ukashandiswa pakurapa. Chloral hydrate yakatanga kushandiswa somushonga wokudzikamisa wakagadzirwa nemakemikari muna 1869, makore anopfuura makumi maviri zvisati zvaitika. Gwaro ra1891 pacharo rinopa chikamu chemhinduro, nokuti vanyori varo vanodoma mishonga yokuderedza fivha yakagadzirwa nemakemikari yakanga yatokundikana kurwisa marariya, pakati payo paine quinoline, antipyrine neantifebrin. Mushonga waEhrlich pachake waiva nearsenic wokurapa sifirisi wakauya kunyange gare gare. Chirevo chinogona kutsigirwa ndechokuti nyaya iyi ndeyenzira yakashandiswa, kwete yokuti ndiani akatanga: methylene blue ndechimwe chezvinhu zvokutanga zvakagadzirwa nemakemikari zvakasarudzwa kuti zvishande pachisikwa chipenyu chakanangwa zvichibva padzidziso yemakemikari yokusarudza kunangwa.
- Kupararira kwakanangana nenzvimbo hakurevi kubatsira kwakanangana nenzvimbo iyoyo. Mhedzisiro yaEhrlich ya1886 yaiva yokuti dhayi inoenda kutishu yetsinga. Kunoenda chinhu uye zvachinoita kana chasvika zvinhu zviviri zvakasiyana zvinoda kuyerwa, uye chokutanga chiri nyore zvikuru kuyera. Kubvira ipapo, mukaha iwoyo ndiwo mave muchigara zvizhinji zvinotaurwa pamusoro pemethylene blue nouropi.
- Kuchena chikamu chouchapupu, kwete chokushambadzira. Zvinyorwa zvenhoroondo hazvina kujeka nokuda kwechikonzero ichi chaicho. Misiyano midiki yechimiro inoshandura kunoenda chinhu ichi, ndosaka chitupa chekuongorora chichifanira kusungirirwa kuboka rakati rezvakagadzirwa, panzvimbo pokungopiwa sechirevo chokuti chigadzirwa chinoedzwa. Mutengesi anoti chigadzirwa chinoenderana negwaro remitemo yokuyerwa kwemushonga asi achiedza simbi dzinorema chete anenge achitaura zvinopfuura zvinotsigirwa nomushumo. Blupreme inotora methylene blue kumugadziri wemishonga uye inoedza zvose zvinodiwa negwaro iroro: kuzivikanwa kwechinhu, kuchena, tsvina dzemakemikari ane kabhoni, zvinonyungudutsa zvakasara, tsvina dzezvinhu zvekutanga zvemakemikari, zvasara pashure pokupiswa, miganhu yezvipukanana uye endotoxins dzemabhakitiriya. Mushumo unobudiswa pamwe chete nechigadzirwa, uye peji remethylene blue yegiredhi reUSP rinotsanangura miganhu iyoyo uye nei mhedzisiro yeazure B ichifanira kuva yokutanga kutsvakwa.
Nzira yezvinyorwa zvine mazuva
| Zuva | Zvakaitwa | Pazvakanyorwa |
|---|---|---|
| 1878 | Gwaro redhigirii reudhokotera rinoti kusvibisa nedhayi nokudhayira machira zvinotevera musimboti mumwe chete wokukwezvana kwemakemikari | Ehrlich, gwaro redhigirii, Leipzig, 1878; chikamu charo chokutanga chinonzi "Kunzwisisa Kusvibisa Neruvara Maererano Nemakemikari" |
| 1880 | Methylene blue ine acid fuchsin, "dhayi isina divi", inopatsanura marudzi emasero machena eropa | Krafts, Hempelmann naSkórska-Stania, Parasitol Res 111:1-6, 2012 |
| 1882 | Nzira yemethyl violet yokusvibisa mabhakitiriya etibhi inoratidzwa kuBerlin Medical Society, yozobudiswa gore rinotevera | Ehrlich, Berliner klinische Wochenschrift 20:13, 1883 |
| 1885 | Gwaro rakadzama rokuongorora neruvara rinoshandisa madhayi eredox kuenzanisa simba renhengo rokuita reduction | Ehrlich, Das Sauerstoff-Bedürfniss des Organismus, Berlin, 1885 |
| 1886 | Methylene blue yakabaiwa mumhuka mhenyu inoratidza tishu yetsinga ichisarudza kwainoenda | Ehrlich, "Pamusoro pezvinoita methylene blue patishu mhenyu yetsinga", Deutsche Medizinische Wochenschrift 12(4):49-52, 1886 |
| 1888 | Methylene blue ine eosin inosvibisa utachiona hwemarariya muzvidimbu zvitete zveropa | Chęciński, Centralblatt für Bakteriologie und Parasitenkunde 3(15):457-460, 1888 |
| 1890 | Methylene blue inoshumwa kuti inoderedza marwadzo ane chokuita netsinga nereumatism | Ehrlich naLeppmann, Deutsche Medizinische Wochenschrift 16(23):493-494, 1890 |
| 1891 | Methylene blue inopiwa varwere vaviri vane marariya pachipatara cheMoabit, Berlin | Guttmann naEhrlich, "Pamusoro pekushanda kwemethylene blue pamarariya", Berliner klinische Wochenschrift 28(39):953-956 |
| 1897 | Dzidziso yemaketani epadivi inotsanangurwa muchimiro chayo chakazara, mugwaro pamusoro peseramu yediphtheria | Ehrlich, Klinisches Jahrbuch 6:299-326, 1897 |
| 1899 | Chiito chokudzikamisa chemethylene blue chinoshumwa mumarudzi akasiyana epsychosis | Bodoni, Clinica Medica Italiana 24:217-222, 1899 |
| 1926 | Shiri yecanary ine utachiona inova nzira yenguva dzose yokusefa mishonga yemarariya | Roehl, Deutsche Medizinische Wochenschrift 52, 1926 |
| 1932 | Kutsiviwa kweketani yepadivi kunorapa utachiona hwaishandiswa pakuyedza | Schulemann, Proc R Soc Med 25:897-905, 1932 |
| 1934 | Ringi reacridine rinotsiviwa nerequinoline, zvichigadzira chloroquine | Krafts nevamwe, 2012, vachishandisa zvinyorwa zvakachengetwa neBayer |
| 1950 | Phenothiazine yakawedzerwa mamwe mapoka, yakazonzi chlorpromazine, inogadzirwa paRhône-Poulenc; zvinobudiswa muna 1952 | Charpentier nevamwe, Comptes rendus de l'Académie des Sciences 235:59-60, 1952 |
| 1952 | Kushandiswa kwechlorpromazine kwekutanga pakurapa zvirwere zvepfungwa kunobudiswa | Delay, Deniker naHarl, Annales médico-psychologiques 110:112-117, 1952 |
Kutevedzana kwezviitiko zvakakosha zvine mazuva, kusanganisira makemikari emadhayi akatangira Ehrlich uye magiredhi nezvinodiwa pakuyerwa zvakauya shure kwake, kunotsanangurwa kwakaparadzana munhoroondo yemethylene blue, uye kuzivikanwa kwechinhu chacho kunotsanangurwa muchii chinonzi methylene blue.
Mifananidzo nezvinyorwa zvinotsigira nyaya iyi, zvakadhindwazve muongororo ya2012 yaKrafts, Hempelmann naSkórska-Stania, hazvina uremu hwakaenzana, uye mumwe muenzaniso unoratidza chikonzero chacho. Mufananidzo wegwaro ra1891 ndiwo uchapupu hwokutanga hwekuyedza kwacho; mufananidzo womunhu wa1910 uri parutivi pawo unongoratidza mukurumbira wake panguva iyoyo, kwete chimwe chinhu. Mapeji emubhuku rezvinyorwa raAndersag ra1934 ndiwo uchapupu hwakananga hwokutsiva nequinoline, hwakanyorwa noruoko rwenyanzvi yemakemikari pachayo.
Pfupiso yakatendeseka yokuyedza madhayi kwaEhrlich ndeyokuti akarurama pakusarudza kunangwa uye akarurama pachinhu chakanangwa, asi akakanganisa nzira yokushanda. Methylene blue inoungana zvechokwadi mutishu yetsinga uye inokuvadza zvechokwadi utachiona hwemarariya. Haiiti chechipiri nokuda kwechokutanga, uye chikonzero chemakemikari chaakapa pazvose zviri zviviri chakanga chisina kururama. Zvaakaratidza pasina kupokana zvakagara kwenguva refu kupfuura tsananguro yakarurama yokushanda: chinhu chinogona kusarudzwa panzvimbo pokungowanikwa, uye chichisarudzwa pachishandiswa uchapupu hwakaunganidzwa chisati chapiwa murwere nomunhu upi zvake.