Imbali ye-methylene blue: ukusuka kwidayi ukuya kwiyeza nakuphando

I-methylene blue yafikelela kwisigulana ngaphambi kokuba ifike ekhemesti.

Ingxelo ka-1891 kaPaul Guttmann noPaul Ehrlich ngokusetyenziswa kwedayi kwimalariya iqulethe iitshathi ezimbini zobushushu. Eyesibini iqala ngomhla we-13 July ukuya kowesi-5 August, unyango lubhalwe ecaleni komda usuku nosuku. Amanqaku e-18 ne-19 July athi "1 × 0,05 Methylenblau". Kwiintsuku ezilandelayo kudweliswe amathamo amahlanu nesixhenxe omlinganiselo ofanayo, yaye nge-22 July kwakusele kongezwe nomlinganiselo omncinane wequinine kwingxelo. Umgca womkhuhlane, ojikeleza phakathi kwe-37 °C ne-39.5 °C kwisiqingatha sokuqala setshathi, uyazinza emva kokuvela kwedayi uze uhlale phakathi malunga ne-36 °C ne-37.5 °C kwiiveki ezintathu eziseleyo.

Isigulana sasisesinye kwezibini, ezichazwe ephepheni njengomsebenzi wasekhaya nomatiloshe. Ikhompawundi abayifumanayo yayisele iyidayi yorhwebo yamalaphu iminyaka elishumi elinesihlanu, yaye la madoda mabini aphakathi kwabantu bokuqala ekubhalwe ukuba banyangwa ngechiza elenziwe ngokupheleleyo ngokwenziwa elalijoliswe kwinto ephilayo ethile.

Idayi yeza kuqala

Idayi yokuqala eyenziwe ngokwenziwa eyaphumelela kwezorhwebo yenziwa nguWilliam Henry Perkin ngo-1856. UPerkin wayeneminyaka elishumi elinesibhozo, esebenza kwilabhoratri yasekhaya ngexesha leeholide ze-Easter, ezama ukwenza iquinine. Endaweni yoko wafumana intsalela emnyama, wayinyibilikisa, waza wafumana umbala owabambelela kakuhle kakhulu kwisilika. Wafumana ilungelo lobunikazi ngo-August 1856, yaye ekupheleni kuka-1857 wayesele enefektri eyayibonelela indawo yokudaya isilika eLondon.

Ngo-1875 uAdolf von Baeyer wenza idayi ebomvu waza wayibiza ngokuba yi-eosin, evela ku-Eos, igama lesiGrike elithetha ukusa. Ngo-1876 uHeinrich Caro, owayengumlawuli welabhoratri yaseBadische Anilin- und Soda-Fabrik ngelo xesha, waphuhlisa i-methylene blue kunye noBaeyer njenge dayi esekelwe kwi-aniline yomqhaphu. Ubume bayo beekhemikhali abuzange bumiselwe ngokupheleleyo de kwadlula malunga neminyaka elithoba.

Imvelaphi leyo isabonakala nakwindlela le nto ebizwa ngayo. "Methylene blue" ligama lorhwebo elivela kwikhathalogu yeedayi, hayi inkcazelo yekhemikhali. Ikhompawundi ekubhekiselwa kuyo yi-methylthioninium chloride, yaye umahluko phakathi kwegama, ityuwa, kunye nee-hydrate zayo uba ngobalulekileyo nje ukuba umntu alinganise loo mathiriyeli okanye afunde inkcazo yomgangatho.

Ukufakwa kombala kwaba libhulorho

Indlela esuka kumzi-mveliso wedayi ukuya esibhedlele yadlula kwimakroskopu, yaye yaqala ngaphambi kokuba kubekho i-methylene blue. UWilhelm Erb waba ngumntu wokuqala ukusebenzisa idayi eyenziwe ngokwenziwa egazini, esebenzisa i-picric acid ngo-1865, waza wabona ipateni efana nenethi ngaphakathi kwezinye iiseli ezibomvu.

Ithisisi yobugqirha kaPaul Ehrlich ka-1878 yathelekisa ukufakwa kombala kwiisampulu zehistoloji nokudaywa kwamalaphu yaza yaxoxa ukuba zombini ziireakshini zekhemikhali. Esebenza phantsi kukaRobert Koch kwi-tubercle bacillus, wahlela iidayi ze-aniline zaba ziindidi ze-acid nezesiseko waza waqinisekisa ukuba udidi ngalunye lunika umbala kumalungu ahlukeneyo eseli. Ngo-1880 wazixuba zombini: isisombululo esigcweleyo se-methylene blue sagalelwa kwi-acid fuchsin de ulwelo olungaphezulu lwacaca. Isiphumo, awasibiza ngokuba yi-neutralen Farbkörper okanye ibala elingathathi cala, savelisa imibala emithathu endaweni yomnye, satyhila iigranule kwiiseli ze-polymorphonuclear ezazingazange zibonakale ngaphambili, saza senza ukuba kube nokwenzeka ukubala okokuqala iintlobo ezahlukeneyo zee-leukocyte. Ngenxa yokuba ezo granule zazifunxa omabini amacandelo omxube, uEhrlich waqulunqa igama elithi neutrophil kwezo seli zaziziphethe.

Kwiminyaka emibini kamva uKoch wasebenzisa i-methylene blue ukufumana i-tubercle bacillus, yaye ngo-1883 uEhrlich wayiphucula le ndlela. Ngo-1886 wapapasha olunye uhlobo loqwalaselo: watofa idayi kwizilwanyana eziphilayo waza wathelekisa indlela ilungu ngalinye elaliyifunxa ngamandla ngayo, waza wagqiba kwelokuba yayinobudlelwane obuphawulekayo nezicubu zobuchopho kunye nemithambo-luvo. Wathi olu budlelwane bubangelwa ngumjikelo we-oxidation-reduction wedayi, awayewuqaphele kunyaka ongaphambili. Lo mjikelo ukwasisizathu sokuba isisombululo se-methylene blue siphulukane nombala xa ioksijini yaso isetyenzisiwe size siwufumane kwakhona xa kungena umoya. Iimvavanyo ezaqala ukulinganisa iziphumo zalo mjikelo zezesinye ishumi leminyaka elalandelayo, yaye indlela osebenza ngayo ngokwayo sisihloko esahlukileyo kwimbali.

Isifunxi-gazi kunye nenucleus emfusa

UAlphonse Laveran wafumana isifunxi-gazi semalariya ngo-1880 ngokuhlola igazi elitsha elingafakwanga mbala. Ukuze sibonwe rhoqo kwisampulu yegazi eyomisiweyo kwakufuneka ibala, yaye amabala elo xesha ayevelisa kuphela umbala obomvu noluhlaza okwesibhakabhaka.

Ngo-1888 ingcali yezifo yasePoland uCzesław Cheçinski yatshintsha i-acid fuchsin nge-eosin, yaza yavelisa umxube we-methylene blue ne-eosin. Ityala elakhokelela kwindlela yakhe lalilele kwijoni elalisweleke ngenxa yemalariya nge-30 September 1887. Kwiifilimu zegazi uCheçinski wabona iimilo eziluhlaza okwesibhakabhaka ezifana needaisy, ngoku ezaziwa njenge-Plasmodium malariae, kunye neemilo ezinjengerhengqa, ngoku ezaziwa njengeegametocyte ze-Plasmodium falciparum. Esi siphumo saphelisa iinkcazelo ezimbini ezazikhuphisana ngesi sifo ngaxeshanye: ithiyori ye-miasma, kunye nebango likaEdwin Klebs noCorrado Tommasi-Crudeli lokuba imalariya yayibangelwa yibhaktiriya.

Isifunxi-gazi sasibonakala. Inucleus yaso yayingabonakali, nto leyo eyashiya indalo yaso ingacacanga. UErnst Malachowski, ugqirha waseBreslau, wayisombulula loo ngxaki ngempazamo waza emva koko wayenza ngenjongo. Ngo-1889 waqaphela ukufakwa kombala okwahlukileyo kwinucleus ye-plasmodium kwisampulu ethile kodwa akakwazi ukuphinda afumane eso siphumo. Ukwenza i-methylene blue ibe yi-acid ngakumbi akuzange kuncede. Ukuyenza ibe yi-alkaline nge-borax kwavelisa eso siphumo ngalo lonke ixesha. Wayibonisa esidlangalaleni le ndlela nge-15 June 1890 waza wayipapasha kwakuloo nyaka, enendlela ebanzi ngakumbi ngo-August 1891.

UDmitri Romanowsky wapapasha eyakhe inguqulelo ngo-September 1891. Ezona ziphumo zakhe zintle zavela kwibhotile endala, eyayingakhathalelwanga yaye inomngundo, yesisombululo se-methylene blue esasineminyaka engaphezu kweenyanga ezimbini. Inkcazelo kaMalachowski yayiyenziwe ngenjongo yaye, ngamazwi akhe, kulula ukuyiphinda; ekaRomanowsky yaba sisiphelo esingenandlela esasisebenze kube kanye. Nangona kunjalo, igama lesikhumbuzo lanikwa uRomanowsky, yaye impikiswano yokuba ngubani owavelisa umbala omfusa owenza inucleus yabonakala libali elahlukileyo elinamaxwebhu alo.

Umfanekiso: itshathi yesibini yobushushu evela kwingxelo kaGuttmann noEhrlich ka-1891. Icandelo eliphezulu ligubungela i-13 ukuya kwi-24 July, elisezantsi i-25 July ukuya kwi-5 August; amanqaku asemda achaza amathamo anikiweyo, yaye ubushushu buhlala kufutshane nesiqhelo kwiiveki ezintathu zokugqibela zengxelo. Iphinde yaveliswa kwingxelo njengoko iskenelwe uKrafts, Hempelmann noSkórska-Stania, Parasitology Research 111:1–6 (2012), PMID 22411634.

Kwafumaniseka ukuba “ukuvuthwa” yayikukususwa kwamaqela e-methyl

Akukho mntu wayebandakanyekile ngeminyaka yoo-1890 owayesazi ukuba "ukuvuthwa" kwakusenza ntoni kwi-methylene blue. Impendulo yavela kwikhemistri yezoshishino. UHeinrich August Bernthsen wayenze ikhompawundi engumzali i-phenothiazine ngo-1883, waqinisekisa ngo-1885 ukuba i-methylene blue yayiyeyolo sapho, waza kwangelo xesha wabonisa ukuba iimeko ze-alkaline zisusa amaqela e-methyl kwidayi, zivelise iikhompawundi ngoku ezibizwa ngokuba zii-azure.

UBernard Nocht wakhupha icandelo elisebenzayo ngo-1898 nango-1899 yaye wayenokulibiza kuphela ngokuba yi-Rot aus Methylenblau, okubomvu okuvela kwi-methylene blue. UMichaelis walichonga njenge-azure I ngo-1901. UJenner wazisa ukusetyenziswa kwe-methanol engenamanzi njengesinyibilikisi sedayi eqinileyo ngo-1899, nto leyo eyasusa imfuneko yokulungisa iifilimu zegazi ngobushushu; uLeishman noReuter badibanisa zombini ezo nkqubela; uWright wapapasha indlela elula ngo-1902. Igalelo likaGiemsa, nalo lango-1902, yayikukuyeka ukuxhomekeka kwisisombululo esasivuthwa ngendlela engalawulwayo aze endaweni yoko asebenzise imilinganiselo elinganisiweyo yeedayi ezaziwayo. Emva koko wala ukupapasha indlela awayesenza ngayo i-methylene azure ecocekileyo waza wathengisa loo ndlela kwilabhoratri kaDr. Grübler, eyayithengisa imveliso njenge-azure I yaza yabanga ukuba kuphela inguqulelo yayo yayilibala leGiemsa eliyinyani.

Iimfazwe zehlabathi ezimbini zawugqibezela lo msebenzi ngengozi. Xa iidayi zaseJamani zingasafumaneki, uLillie, Roe noWilcox basebenza kwizinto ezazisetyenziswa endaweni yazo eMelika baza bafumanisa ukuba ezona ziphumo zibalaseleyo zokufakwa kombala zazivela kumacandelo amathathu ahlukeneyo: i-methylene blue ecocekileyo, imveliso yayo yokonakala Azure B, kunye ne-eosin. Ezo zinto zintathu zisengawona macandelo aphambili ebala elisetyenziselwa ukuxilonga imalariya namhlanje, phantsi kwegama ngoku elidibanisa uMalachowski, Wright noGiemsa.

Umfanekiso: iimilo zeringi ze-Plasmodium falciparum kwiiseli ezibomvu zomntu, ezifakwe umbala ngendlela yohlobo lukaRomanowsky. Isakhiwo esimfusa ngaphakathi kweringi yi-chromatin eyenziwa yabonakala okokuqala yi-methylene blue kaMalachowski eyayinyangwe nge-borax. Umfanekiso nguErnst Hempelmann, okhutshwe ukuze usetyenziswe luluntu ngaphandle kwemida yelungelo lokushicilela.

Igama elinye, izinto ezininzi

Iminyaka eyahlula loo macandelo yashiya ingxaki eyaphila ixesha elide kunekhemistri ngokwayo. URalph Lillie wahlula ngo-1969 phakathi kwamabala ebhayoloji, "enziwe ngokwemigangatho engqongqo ehambelana nokusetyenziswa kwawo okubuthathaka nokufuna ukuchaneka", kunye namabala angengowebhayoloji okusetyenziswa ekudayeni amalaphu, "afuna imigangatho yokuvelisa engqongqo nengafuni kangako". Zombini iintlobo zemveliso zazithwala igama elifanayo, yaye umahluko phakathi kwazo awuzange ube ngumahluko wobungakanani. Inkcazo yomgangatho ebhalelwe umqhaphu kunye nenkcazo yomgangatho ebhalelwe ireagent yokuxilonga azitshintshiselani, yaye imathiriyeli eyenziwe ngokwenkcazo yamalaphu yayingajoliswanga ekuginyweni.

Azure B ngowona mzekelo ucacileyo. Yindlela ye-methylene blue esuswe iqela elinye le-methyl, inomsebenzi wayo we-pharmacological onokulinganiswa, yaye yayikhona njengecandelo elingalawulwanga kumalungiselelo e-methylene blue ezonyango ngaphezu kwenkulungwane ngaphambi kokuba kubekho nabani na owahlula ezi zinto zimbini. Elinye iqela lafumanisa ukuba izicubu zomntu ezathathwa kuvavanyo lwasemva kokufa emva kokunikezelwa kwe-methylene blue zaziqulethe i-5 ukuya kwi-14 per cent ye-methylene blue engatshintshanga kunye ne-86 ukuya kwi-95 per cent ye-Azure B. Ukuba amalungiselelo athile kufuneka abe ne-Azure B na, nokuba kumda ongakanani, ngumbuzo wenkcazo yomgangatho, yaye uphando nge-Azure B njengongcoliseko kunye nemetabolite luqhubeka ukusuka apho.

Inkcazo yomgangatho ikwayindawo apho kufumaneka khona isiphumo esisebenzayo. Ukuthobela i-USP yindlela yokufikelela kwelona nqanaba liphezulu lobunyulu elinikezelwa yimarike, kuba ngumgangatho wovavanyo opheleleyo opapashiweyo, hayi umlinganiselo omnye. Uquka ukuchongwa, assay, ukungcola kwe-organic kuquka iidayi ze-azure, izinyibilikisi ezishiyekileyo, ukungcola kwezinto eziyimichiza, intsalela emva kokutshiswa, imida yee-microbe, kunye nee-endotoxin zebhaktiriya. Isatifikethi esinika isiphumo sesinyithi esinzima size sisibize ngokuba kukuthobela i-USP sinikezele ngomgca omnye kuphela kolu luhlu.

Blupreme ifumana i-methylene blue yayo kumenzi wamayeza kwaye ipapasha isatifikethi esipheleleyo sohlalutyo, ivavanya yonke inkcazo ye-USP endaweni yezinyithi ezinzima kuphela. Isikhokelo sokufunda isatifikethi sohlalutyo kunye nento eqinisekiswa nengaqinisekiswa ligama le-USP zichaza indlela yokuthelekisa uxwebhu nebango.

Into evunyelwa yimbali, nento engayivumeliyo

Lo mnombo uyinyani, yaye mde kunokuba uninzi lwamaphepha eemveliso lubonisa. I-methylene blue yasetyenziswa kunyango lwemalariya ngo-1891, yaxelwa njenge-sedative kwi-agitated psychosis ngo-1899, yaye ikhonkco layo lecala lidlula kwi-quinacrine, chloroquine, promethazine kunye ne-chlorpromazine. Iphepha likaEhrlich lika-1890 noArthur Leppmann lachaza ukukhululeka kwintlungu ye-neuralgic ne-rheumatic, laza emva koko laqwalasela kodwa lala ukuvavanya idayi kwisifo sengqondo.

Akukho nanye kwezo zinto eqinisekisa ukusetyenziswa kwale mihla. Isiphumo semalariya sango-1891 sasibandakanya izigulana ezimbini kunye netshathi yobushushu. Ukuqhelana ixesha elide nemolekyuli sisizathu sokuyifunda, hayi isiphumo. Imbali yekhompawundi njengechiza kunye novavanyo lwale mihla lwemalariya ziphendula imibuzo eyahlukileyo kuleyo wayeyibuza uEhrlich, yaye iziphumo ekulinganiswa ngazo kufuneka zifundwe ngokwemiqathango yazo.

Kukho inkcukacha enye kwingxelo enxulumene nexesha langoku kunexesha elidlulileyo. Xa abaphandi babesenza iimvavanyo ze-methylene blue zemalariya eBurkina Faso ngeminyaka yoo-2000, bazifumana bekhuphisana ngemathiriyeli yomgangatho wamayeza, baza baxela ukuba ixabiso lemathiriyeli ekrwada lalinyuke malunga nekhulu xa sele inokuqinisekiswa kwe-GMP. Idayi yayinokutshintshwa. Ichiza lalingenakutshintshwa. Umahluko owachazwa nguLillie ngo-1969 ngulowo mnye namhlanje omisela into equlethwe yibhotile.