Shin methylene blue na magance ƙwayoyin parasite?

Tambayar tana kama da tambaya guda ɗaya. A zahiri kuwa, tambayoyi ne da dama da suka sa kaya iri ɗaya. Ƙwayar malaria da ke cikin jajayen ƙwayoyin jini, tsutsa a cikin hanji, da ƙwayar da ke haddasa cutaneous leishmaniasis kusan ba su da wani abu guda sai kasancewarsu parasite. Maganin da ke cutar da ɗaya ba lallai ya cutar da sauran ba. A riƙe wannan ra'ayi a duk wannan bita: kasancewar wani abu antiparasitic ba halin molecule kaɗai ba ne. Hali ne na molecule tare da takamaiman ƙwayar parasite, a takamaiman matakin rayuwarta, kuma a takamaiman ɓangaren jiki.

Da zarar an raba ƙwayoyin, bayanan methylene blue kan parasites suna rabuwa sarai. Akwai malaria, inda aka yi gwaje-gwaje a kan mutane. Sai kuma duk sauran: gwaje-gwajen petri dish, beraye, maganin fata da haske ke kunna shi, da labaran da suka kai kusan ƙarni guda. Babu wata ka'idar maganin parasite ta gama-gari da za a iya fitarwa daga waɗannan bayanai.

Amsa a taƙaice

Methylene blue ainihin maganin malaria ne na gwaji. Wani bincike na tsari kan nazarin mutane 21 da ya ƙunshi marasa lafiya 1,504 masu malaria ya gano ainihin tasiri kan matakin parasite da ke cikin jini, musamman ma tasiri mai ƙarfi kan matakin gametocyte wanda ke watsa cutar zuwa sauro. A wajen malaria, shaidar da aka wallafa ba ta goyi bayan ɗaukar methylene blue a matsayin maganin antiparasitic mai faɗin aiki ko hanyar tsarkake hanji daga parasites ba. Kusan duk wani sakamakon da ba na malaria ba yana a ƙasan matakan ƙarfi na shaida: yana aiki a dish, wani lokaci yana aiki a bera, amma kusan ba a taɓa gwada shi a mutanen da suka kamu da cuta ba.

Malaria: parasite guda ɗaya da ke da gwaje-gwajen mutane

A 1891, Guttmann da Ehrlich sun bayar da rahoton kula da marasa malaria da methylene blue, wanda za a iya ɗauka a matsayin maganin roba na farko da aka yi amfani da shi kan cutar ɗan Adam. Tarihinsa daga dye zuwa sinadarin jagora na maganin malaria ya kai har zuwa chloroquine, wanda ya gaji ilimin sinadarai da aka fara bincikawa da wannan dye.

Binciken zamani ya dawo da sha'awa gare shi saboda parasites masu juriya sun haifar da buƙata. A culture, methylene blue yana hana chloroquine-sensitive da resistant Plasmodium falciparum a ƙananan nanomolar concentrations, tare da rahoto na synergy da artemisinin derivatives. A matsayin monotherapy a mutane, ya nuna yana aiki a hankali: wani controlled trial a manya masu semi-immune a Burkina Faso ya gano 16 percent early failure rate, kuma marubutan sun yanke cewa bai dace da short-course single drug ba. Haɗaɗɗun magunguna sun yi kyau. A randomized trial a yara 180, methylene blue tare da amodiaquine ya kai 95 percent corrected response a rana ta 28, kuma dukkan rukunan methylene-blue biyu sun rage ɗaukar gametocyte sosai a companion transmission analysis. Daga baya triple-combination trial a yara 221 ya tabbatar da tasirin gametocyte ta microscopy da molecular detection. Sakamako mafi jan hankali ya yi amfani da sauro a matsayin endpoint: a phase 2 trial a Mali, ƙara methylene blue na kwanaki uku ya haifar da median 100 percent reduction a mosquito infectivity zuwa rana ta biyu.

Ana tattauna hanyoyin aiki guda uku da ake zato, kuma bai kamata a haɗa su su zama abu ɗaya ba. Dye ɗin yana hana enzyme glutathione reductase na parasite a test tube (Ki kusa da 6.4 micromolar) kuma yana yin redox-cycling a matsayin substrate da ke cin reducing equivalents (an nuna hakan a human da parasite reductases). Amma parasites da aka cire wa enzyme ɗin ta hanyar genetics suna ci gaba da nuna sensitivity iri ɗaya, don haka wannan ba zai iya zama cikakken bayani ba, kuma tsohuwar shawarar cewa yana katse heme-disposal (wanda aka danganta da nanomolar potency) har yanzu ba a tabbatar da ita a marasa lafiya ba. Taƙaitaccen bayani: akwai ainihin efficacy a mutane, babu manufa guda ɗaya da aka tabbatar, kuma ba shi da matsayi a standard regimen. Bayanai kan regimens da transmission suna cikin bitarmu kan methylene blue don malaria, don haka wannan shafin ba ya maimaita su.

Babesia da Toxoplasma: suna da ƙarfi a culture, amma babu shaidar asibiti

Babesia, ɗan'uwan malaria da ke cikin jajayen ƙwayoyin jini, an kashe shi a dishes a submicromolar concentrations, inda parasites da aka fallasa suka kasa sake girma (Journal of Protozoology Research) kuma wani bincike daga baya ya sanya dye ɗin a matsayin sinadari mafi ƙarfi da aka gwada a kusan 0.2 micromolar (Carvalho da abokan aikinsa, 2020). A beraye, ko da 50 mg/kg ya bayar da raunin inhibition kawai, kuma babu wani binciken babesiosis a mutane.

Toxoplasma ma yana nuna irin wannan tsari. Nazarin culture guda biyu da aka yi da tazarar shekaru da dama sun gano submicromolar suppression na tachyzoites masu yawaita: 0.45 micromolar a macrophages a 1989 da kusan 0.30 micromolar a antimalarial screen a 2018. Babu ɗayansu da ya taɓa latent bradyzoite tissue cyst, wato matakin da ya fi wahala a asibiti, kuma ba a sami wani animal ko human treatment study ba. Adadin tachyzoite a dish ba shaida ba ne game da wata cuta a jikin mutum.

Leishmania da trypanosomes: a kula da haske, a kula da bera

Yawancin rubuce-rubucen Leishmania a zahiri suna magana ne kan photodynamic therapy, ra'ayi dabam da haɗiye dye. Photoactivation ya rage inhibitory concentration kan Leishmania amazonensis daga kusan 100 zuwa 20 micromolar, kuma duk shaidar mutane ita ce marar lafiya guda ɗaya wanda lesions ɗinsa suka samu antimony yayin da ɗaya daga cikinsu kuma ya samu dye da aka kunna da haske. Binciken hamster ya gano topical light-activated treatment ya taimaka yayin da intradermal dye bai taimaka ba (Sbeghen da abokan aikinsa, 2015). Dye na gida tare da red light a fata ba systemic therapy ba ne.

Bayanan trypanosome suna ɗauke da mafi amfani daga cikin sakamakon da bai yi nasara ba a wannan bita: methylene blue ya kashe Trypanosoma brucei in vitro amma ya kasa warkar da beraye masu cuta a 300 mg/kg ta baki ko 200 mg/kg ta allura. Ga Chagas disease, shaidar biochemical ce ta hanyar enzyme trypanothione reductase na parasite (Buchholz da abokan aikinsa, 2008), tare da ƙarin kashewa da haske ya ƙarfafa in vitro (Barbosa da abokan aikinsa, 2020). Blood-bank disinfection na plasma da aka saka parasite a ciki (Gironés da abokan aikinsa, 2006) yana magana ne kan blood products, ba marasa lafiya ba. Masu karatu da suka zo daga batun cututtukan da kaska ke yadawa su lura cewa Lyme disease cutar bacterial ce ba parasitic ba; an tantance shaidarta a bitarmu kan methylene blue don Lyme disease.

Tsutsotsi, flukes, da ikirarin tsarkake hanji

Schistosoma mansoni shi ne mafi ƙarfi daga shaidar da ake da ita kan tsutsotsi, amma har yanzu bai isa ba: dye ya kashe schistosomula a ƙasa da 10 micromolar da manya a 10 zuwa 30 micromolar, amma beraye masu cuta sun nuna kusan 60 percent burden suppression tare da babu cures. Ƙaramin human pilot da ke cikin wannan takarda ya shafi wani drug combination dabam, don haka ba za a iya kiransa human dye trial ba. Kan Strongyloides larvae da manya, inhibitory concentrations kusa da 4 zuwa 6 micromolar sun yi daidai da shigar dye cikin tsutsa, amma berayen da aka ba ta ta baki sun nuna babu meaningful control of infection. Ga scabies da lice, ba a sami wata therapeutic human evidence ba.

Babu wani modern trial, series, ko convincing case report da ya nuna oral methylene blue yana kawar da Giardia, Entamoeba, Strongyloides, ko intestinal helminths a mutane. Abin da ya fi kusa a bayanan da aka index shi ne rahoton 1956 kan gallbladder giardiasis wanda babu accessible dose ko verifiable cure. Takardu biyu na zamani kan Giardia suna da sauƙin a fassara su ba daidai ba: a ɗaya, 1 percent dye shi ne stain da ya bayyana trophozoites, kuma a ɗayan, dilute dye shi ne readout stain bayan standard drugs. Stain da ke sa parasite ya bayyana a ƙarƙashin microscope ba maganin da ke kashe shi a hanji ba ne. Ga Trichomonas, animal study guda ɗaya ma photodynamic ne: vaginal dye tare da haske a beraye masu cuta (Fonseca da abokan aikinsa, 2019), ba oral cleanse ba.

Kwatantawa

Abin da zai iya canza wannan amsa

Gibin shaidar yana da takamaiman matuƙa. Ba a sami wani registered interventional human trial na dye kan wani non-malaria parasite ba har zuwa Satumba 2026, don haka abu na farko da ya ɓace shi ne controlled human study a wajen Plasmodium. Na biyu, dish concentrations da ake ci gaba da amfani da su na kwanaki sun sha kasa a dabbobi saboda fast clearance ko wrong compartments, kamar yadda gazawar trypanosome da Strongyloides a beraye ta nuna. Na uku, bai kamata a ci gaba da ambaton photodynamic results a matsayin systemic evidence ba; dye tare da measured light dose hanya ce ta local disinfection da ke da matsalar delivery ta kanta. Na huɗu, ikirarin hanji yana buƙatar parasitological endpoints, wato tabbatar da kawar da parasite daga stool ko tissue a controlled cohorts, ba kawai hasashen alamomin jiki yayin multi-ingredient cleanse protocols ba.

Bayanan tsaro guda biyu suna iyakance gwajin kai-da-kai. Dye ba ya dace da masu glucose-6-phosphate dehydrogenase deficiency saboda haɗarin hemolysis, kuma pooled analysis na malaria trials guda huɗu a yara ya gano raguwar hemoglobin mafi girma a yara masu cikakken deficiency a antiparasitic doses kusa da 15 mg/kg per day. Haka kuma potent reversible monoamine oxidase A inhibitor ne (mechanism ɗin da ke bayan serotonin toxicity), wanda current labeling ke ɗauke da shi a matsayin boxed warning, kuma blue urine na iya interfere with automated urine testing. Tambayoyi kan dosing, purity, da interactions suna cikin practical guide ɗinmu kan amfani da methylene blue.

Methylene blue ya samu sunansa na antiparasitic bisa ingantacciyar shaida, a kan malaria, cikin randomized trials masu mosquito endpoints. Duk abin da ya wuce wannan yana aro ƙarfin shaida ne daga malaria. Har sai controlled human study ya nuna akasin haka ga takamaiman organism, matsayin da shaida ke ba da damar karewa yana da ƙunci: ainihin transmission-blocking antimalarial da ake ci gaba da bincike, sannan a ko'ina dabam laboratory finding ne da ke jiran hujjar cewa tasirinsa yana ci gaba da kasancewa a cikin living host.