Methylene blue ma daweeyaa dulinnada?

Su’aashu waxay u muuqataa hal su’aal. Dhab ahaantii waa dhowr iyo toban su’aalood oo isku muuqaal ah. Dulin duumo oo ku jira unugyada dhiigga cas, dixiri ku jira mindhicirka, iyo noolaha sababa leishmaniasis-ka maqaarka ku dhaca wax badan iskama wadaagaan marka laga reebo erayga dulin. Dawo waxyeellaysa mid khasab kuma aha inay kuwa kale waxyeellayso. Fikraddan maskaxda ku hay inta dib-u-eegistan oo dhan lagu jiro: antiparasitic ma aha sifo molecule keliya leeyahay. Waa sifo ka dhalata molecule iyo noole gaar ah, marxalad nololeed gaar ah, iyo qayb gaar ah oo jirka ka mid ah.

Marka noolayaasha la kala saaro, xogta methylene blue ee dulinnada si cad ayay laba qaybood ugu kala baxdaa. Waxaa jira duumada, halkaas oo tijaabooyin bini’aadam ay jiraan. Kadibna waxaa jira wax kasta oo kale: saxammo shaybaar, jiir, daaweyn maqaarka ah oo iftiin lagu dhaqaajiyo, iyo sheekooyin boqol sano jira. Midkoodna kama dhalanayo hab-raac guud oo lagu daweeyo dhammaan dulinnada.

Jawaabta kooban

Methylene blue waa dawo tijaabo ah oo dhab ahaan duumada ka hortagta. Dib-u-eegis nidaamsan oo 21 daraasadood oo bini’aadam ah, kana kooban 1,504 bukaan oo duumo qaba ayaa helay firfircooni dhab ah oo ka dhan ah marxaladda dhiigga, gaar ahaan saameyn xooggan oo ka dhan ah marxaladda gametocyte-ka ee caabuqa u gudbisa kaneecada. Duumada ka baxsan, caddaynta la daabacay ma taageerto in methylene blue loo arko antiparasitic baaxad leh ama nadiifiye dulinnada xiidmaha ah. Ku dhowaad dhammaan natiijooyinka aan duumada ahayn waxay yaallaan heerka ugu hooseeya ee jaranjarada caddaynta: wax ku ool ah saxan shaybaar, mararka qaar wax ku ool ah jiir, ku dhowaadna marnaba laguma tijaabin dadka caabuqa qaba.

Duumada: dulinka keliya ee leh tijaabooyin bini’aadam

1891, Guttmann iyo Ehrlich waxay soo sheegeen inay bukaannada duumada ku daaweeyeen methylene blue, taas oo laga yaabo inay ahayd dawadii synthetic-ka ahayd ee ugu horreysay ee loo adeegsado cudur bini’aadam. Taariikhda laga soo bilaabo dheeh ilaa walax hormuud u noqotay dawooyinka duumada waxay gaadhaysaa chloroquine, oo dhaxashay kimistari markii ugu horreysay lagu sahmiyey dheehan.

Shaqada casriga ahi dib ayay u soo noolaysay xiisaha sababtoo ah dulinnada iska-caabbinta yeeshay waxay abuureen baahi. Dhaqanka shaybaarka, methylene blue waxay xannibtaa Plasmodium falciparum chloroquine-u-nugul iyo mid iska-caabbisa labadaba iyadoo la adeegsanayo uruurin nanomolar hoose ah, waxaana la soo sheegay wada-shaqayn ay la leedahay derivatives-ka artemisinin. Marka kaligeed dadka loo siiyey, waxay noqotay mid gaabis ah: tijaabo la xakameeyey oo lagu sameeyey dad waaweyn oo qayb ahaan difaac u lahaa Burkina Faso waxay heshay 16 percent heer fashil hore ah, qoraayaashuna waxay ku qiimeeyeen inaanay ku habboonayn dawo keli ah oo muddo gaaban la isticmaalo. Isku-darradu way ka fiicnaayeen. Tijaabo randomized ah oo lagu sameeyey 180 carruur ah, methylene blue oo lagu daray amodiaquine waxay gaadhay 95 percent jawaab saxan maalinta 28, labada kooxood ee methylene blue-na si weyn ayay u dhimeen qaadista gametocyte-ka sida lagu muujiyey falanqaynta gudbinta ee la socotay. Tijaabo saddex-dawo isku-dar ah oo lagu sameeyey 221 carruur ah ayaa markii dambe xaqiijisay saameynta gametocyte-ka iyadoo la adeegsanayo microscopy iyo ogaansho molecular ah. Natiijada ugu yaabka badan waxay kaneecada u adeegsatay endpoint: tijaabo phase 2 ah oo ka dhacday Mali, ku darista saddex maalmood oo methylene blue ah waxay keentay median 100 percent hoos-u-dhac ku yimid awoodda kaneecadu caabuqa u gudbin karto maalinta labaad.

Saddex hab oo suurtagal ah ayaa laga doodayaa, waana inaan hal hab loo soo koobin. Dheehku wuxuu xannibaa enzyme-ka dulinka ee glutathione reductase gudaha tuubada tijaabada (Ki near 6.4 micromolar) wuxuuna u shaqeeyaa redox-cycle ahaan substrate isticmaala reducing equivalents (lagu muujiyey reductases-ka bini’aadamka iyo dulinka labadaba). Laakiin dulinnada hidde ahaan ka maqan enzyme-kaas waxay sii hayaan isla nuglaanshaha, sidaas darteed tani ma noqon karto sheekada oo dhan, halka fikrad hore oo ahayd faragelinta ka-saarista heme-ka (oo xiriir lala yeeshay awood nanomolar ah) aan weli lagu xaqiijin bukaannada. Soo-koobid sax ah: waxtar dhab ah oo bini’aadam lagu arkay, bartilmaameed keli ah oo la isku raacsan yahay ma jiro, doorna kuma laha hab-raac daaweyn oo caadi ah. Hab-raacyada daaweynta iyo xogta gudbinta waxay ku jiraan dib-u-eegistayada methylene blue ee duumada, bogganna kuma celinayo.

Babesia iyo Toxoplasma: awood badan shaybaarka, laakiin aan ka jirin rugta caafimaadka

Babesia, oo ah qaraabada duumada ee unugyada dhiigga cas, si la filan karo ayaa saxammada shaybaarka loogu dilay uruurin submicromolar ah, iyadoo dulinnadii la soo bandhigay ay ku guuldarraysteen inay dib u koraan (Journal of Protozoology Research) halka baaritaan dambe uu dheehka ku qiimeeyey walaxdii ugu awoodda badnayd ee la tijaabiyey, qiyaastii 0.2 micromolar (Carvalho iyo asxaabtiisa, 2020). Jiirka, xitaa 50 mg/kg wuxuu bixiyey oo keliya xannibaad daciif ah, mana jiro daraasad bini’aadam oo babesiosis ah.

Toxoplasma-na waxay muujisaa qaab la mid ah. Laba daraasadood oo dhaqanka shaybaarka ah oo tobannaan sano kala fog ayaa helay xannibaad submicromolar ah oo ku dhacday tachyzoites-ka tarma: 0.45 micromolar gudaha macrophages 1989 iyo qiyaastii 0.30 micromolar baaritaan dawooyinka duumada ah 2018. Midkoodna ma taaban cyst-ka unugyada ee bradyzoite-ka qarsoon, oo ah marxaladda caafimaad ahaan adag, mana la helin daraasad daaweyn xayawaan ama bini’aadam ah. Tirada tachyzoite ee saxan shaybaar ku jirta caddayn uma aha caabuq qof ku jira.

Leishmania iyo trypanosomes: iftiinka xusuuso, jiirkana xusuuso

Qayb weyn oo suugaanta Leishmania ah dhab ahaantii waxay ku saabsan tahay photodynamic therapy, taas oo ka duwan fikradda ah in dheeh la liqo. Photoactivation-ku wuxuu hoos u dhigay uruurinta xannibaadda ee Leishmania amazonensis qiyaastii 100 ilaa 20 micromolar, dhammaan caddaynta bini’aadamkuna waa hal bukaan oo nabarradiisa lagu daweeyey antimony halka mid ka mid ah nabarrada sidoo kale loo adeegsaday dheeh iftiin lagu dhaqaajiyey. Shaqo hamster ah ayaa heshay in daaweyn dusha ah oo iftiin lagu dhaqaajiyey ay caawisay halka dheeh intradermal ah aanu caawin (Sbeghen iyo asxaabtiisa, 2015). Dheeh maxalli ah oo lagu daray iftiin cas oo maqaarka lagu saaro ma aha daaweyn systemic ah.

Diiwaanka trypanosome-ku wuxuu leeyahay natiijada taban ee ugu faa’iidada badan dib-u-eegistan: methylene blue waxay dishay Trypanosoma brucei in vitro, haddana waxay ku guuldarraysatay inay bogsiiso jiir caabuqsan 300 mg/kg marka afka laga siiyey ama 200 mg/kg marka la duray. Cudurka Chagas, caddayntu waa biochemical, iyadoo loo marayo enzyme-ka dulinka u gaarka ah ee trypanothione reductase (Buchholz iyo asxaabtiisa, 2008), oo ay weheliso dilid iftiinku xoojiyey oo in vitro ah (Barbosa iyo asxaabtiisa, 2020). Jeermis-dilista bangiga dhiigga ee plasma si ula kac ah dulinka loogu daray (Gironés iyo asxaabtiisa, 2006) waxay khusaysaa waxyaabaha dhiigga laga sameeyo, ma aha bukaannada. Akhristayaasha uga imanaya cudurrada shilintu gudbiso waa inay ogaadaan in Lyme disease uu yahay bacterial halkii uu parasitic ka ahaan lahaa; caddayntiisa waxaa lagu qiimeeyey dib-u-eegistayada methylene blue ee Lyme disease.

Gooryaanka, flukes-ka, iyo sheegashada nadiifinta xiidmaha

Schistosoma mansoni waa tusaalaha gooryaanka ee ugu xooggan, haddana weli kuma filna: dheehku wuxuu dilay schistosomula ka hooseeya 10 micromolar iyo kuwa qaangaarka ah 10 ilaa 30 micromolar, laakiin jiir caabuqsan wuxuu muujiyey qiyaastii 60 percent hoos-u-dhac culayska dulinka ah iyadoo aan wax bogsiin ah jirin. Daraasaddaas tijaabadeeda yar ee bini’aadamku waxay ku saabsanayd isku-dar dawooyin kale, sidaas darteed looma sheegan karo inay ahayd tijaabo bini’aadam oo dheeh ah. Ka dhanka ah dirxiga iyo dadka waaweyn ee Strongyloides, uruurinta xannibaadda ee ku dhow 4 ilaa 6 micromolar waxay la socotay sida dheehku ugu dhex gudbay gooryaanka, haddana jiir afka looga siiyey wuxuu muujiyey inaan si macno leh loo xakameyn caabuqa. Scabies iyo lice, wax caddayn daaweyn oo bini’aadam ah lama helin.

Ma jiro tijaabo casri ah, taxane kiis, ama warbixin kiis oo lagu qanci karo oo muujinaysa in methylene blue afka laga qaato ay dadka ka ciribtirto Giardia, Entamoeba, Strongyloides, ama helminths-ka xiidmaha. Qoraalka indexed-ka ah ee ugu dhow waa warbixin 1956 ah oo ku saabsan giardiasis-ka xameetida oo aan lahayn dose la heli karo ama bogsiin la xaqiijin karo. Laba waraaqood oo casri ah oo Giardia ku saabsan si fudud ayaa loo khaldi karaa: midkood, 1 percent dheeh ayaa ahaa stain-ka muujiyey trophozoites-ka, kan kalena, dheeh la khafiifiyey ayaa ahaa stain-ka akhriska kadib dawooyinka caadiga ah. Stain dulin ku midabeeya microscope-ka hoostiisa ma aha dawo ku disha mindhicirka. Trichomonas, daraasadda keliya ee xayawaanku mar kale waa photodynamic: dheeh siilka lagu geliyey oo iftiin lagu daray jiir caabuqsan (Fonseca iyo asxaabtiisa, 2019), ma aha nadiifin afka laga qaato.

Isbarbardhigga

Maxaa beddeli lahaa jawaabtan

Farqiyada caddayntu waa kuwo si gaar ah loo magacaabi karo. Ilaa September 2026, lama helin tijaabo interventional bini’aadam oo diiwaangashan oo dheeh loogu adeegsaday dulin aan duumo ahayn, sidaas darteed waxa ugu horreeya ee maqan waa daraasad bini’aadam oo la xakameeyey oo ka baxsan Plasmodium. Marka labaad, uruurinta saxanka shaybaarka ee maalmo la joogteeyo marar badan ayay xayawaanka ku fashilantay sababtoo ah si degdeg ah ayaa loo saaraa ama qaybta jirka ee saxda ah ma gaadho, sida ay muujinayaan fashilaadaha jiirka ee trypanosome iyo Strongyloides. Marka saddexaad, natiijooyinka photodynamic waa inaan loo sii xigan caddayn systemic ah; dheeh lagu daray qiyaas iftiin oo la cabbiray waa fikrad jeermis-dilis maxalli ah oo leh dhibaato gaarsiin u gaar ah. Marka afraad, sheegashooyinka xiidmaha waxay u baahan yihiin endpoints parasitological ah, taas oo macnaheedu yahay in saxarada ama unugyada laga xaqiijiyo ciribtirka dulinka ee kooxo la xakameeyey, ee aan lagu salayn dareenka calaamadaha inta lagu jiro hab-raacyo nadiifin oo maaddooyin badan leh.

Laba xaqiiqo oo badbaado ayaa xaddidaya tijaabinta qofku iskii u sameeyo. Dheehku waa contraindicated marka uu jiro glucose-6-phosphate dehydrogenase deficiency sababtoo ah khatarta hemolysis, waxaana falanqayn la isu geeyey oo afar tijaabo duumo ah oo carruurta lagu sameeyey ay heshay hoos-u-dhac hemoglobin oo ka weyn carruurta si buuxda u deficient-ka ah marka la isticmaalay qiyaaso antiparasitic ah oo ku dhow 15 mg/kg per day. Waxa kale oo uu yahay potent reversible monoamine oxidase A inhibitor (habka ka dambeeya serotonin toxicity), taas oo labeling-ka hadda jira ku qoran boxed warning ahaan, halka kaadida buluugga ahi ay faragelin karto baaritaanka kaadida ee otomaatiga ah. Su’aalaha ku saabsan dosing, purity, iyo interactions waxay ku jiraan hagahayaga wax-ku-oolka ah ee isticmaalka methylene blue.

Methylene blue waxay si xaq ah ku kasbatay sumcaddeeda antiparasitic-ka iyadoo ka hortimid duumada, tijaabooyin randomized ahna lagu sameeyey iyadoo endpoints-ka kaneecada la cabbirayo. Wax kasta oo intaas dhaafsiisan waa awood laga soo amaahday caddayntaas. Ilaa daraasad bini’aadam oo la xakameeyey ay wax kale ka muujiso noole si gaar ah loo magacaabay, mowqifka caddaynta lagu difaaci karo waa mid kooban: dawo dhab ah oo duumada ka hortagta, isla markaana joojisa gudbinta, oo wali baaritaan ku jirta; meel kasta oo kale-na waa natiijo shaybaar oo weli sugaysa in la caddeeyo inay shaqaynayso marka lala kulmo host nool.