Methylene blue ọ na-agwọ nje parasaiti?

Ajụjụ ahụ na-ada ka otu ajụjụ. N'eziokwu, ọ bụ ọtụtụ ajụjụ dị iche iche yi otu uwe. Nje malaria dị n'ime mkpụrụ ndụ ọbara uhie, ikpuru dị n'eriri afọ, na nje na-akpata leishmaniasis akpụkpọ ahụ enweghị ihe fọrọ nke nta ka ọ bụrụ ihe jikọrọ ha ma e wezụga okwu parasaiti. Ọgwụ na-emerụ otu adịghị mkpa ka ọ merụọ ndị ọzọ. Jidesie echiche ahụ ike n'ime nyocha a niile: ịbụ antiparasitic abụghị naanị njirimara nke molecule. Ọ bụ njirimara nke molecule tinyere otu nje kpọmkwem, n'otu ogbo ndụ kpọmkwem, n'otu akụkụ ahụ kpọmkwem.

Mgbe e kewapụrụ nje ndị ahụ, ndekọ gbasara methylene blue maka parasaiti na-ekewa nke ọma. E nwere malaria, ebe nnwale mmadụ dị. Mgbe ahụ e nwere ihe ndị ọzọ niile: efere ụlọ nyocha, ụmụ oke, ọgwụgwọ akpụkpọ ahụ nke ìhè na-eme ka ọ rụọ ọrụ, na akụkọ ndị karịrị otu narị afọ. Ọ dịghị usoro ọgwụgwọ parasaiti zuru ụwa ọnụ nke a pụrụ isi na nke ọ bụla n'ime ihe ndị a nweta.

Azịza dị mkpirikpi

Methylene blue bụ ezigbo ọgwụ antimalarial nnwale. Nyocha usoro nke ọmụmụ mmadụ 21 gụnyere ndị ọrịa malaria 1,504 chọpụtara na ọ nwere ọrụ n'ezie megide ogbo nje dị n'ọbara, karịchaa mmetụta siri ike megide ogbo gametocyte nke na-ebufe ọrịa gaa n'anwụnta. N'èzí malaria, ihe akaebe e bipụtara anaghị akwado iji methylene blue dịka ọgwụ antiparasitic sara mbara ma ọ bụ dịka ihe nhicha parasaiti nke eriri afọ. Ihe fọrọ nke nta ka ọ bụrụ nchọpụta niile na-abụghị malaria nọ n'ọkwa kachasị ala nke ihe akaebe: ọ na-arụ ọrụ n'efere ụlọ nyocha, mgbe ụfọdụ n'ime òké, ma ihe fọrọ nke nta ka ọ bụrụ na anwaleghị ya n'ime mmadụ nwere ọrịa.

Malaria: naanị parasaiti nwere nnwale mmadụ

Na 1891, Guttmann na Ehrlich kọrọ na ha ji methylene blue gwọọ ndị ọrịa malaria, nke a pụrụ ịsị na ọ bụ ọgwụ sịntetik mbụ e ji megide ọrịa mmadụ. Akụkọ ihe mere eme site na dye ruo na ihe e ji amalite imepụta ọgwụ antimalarial gara n'ihu ruo chloroquine, nke ketara kemistri e bu ụzọ nyochaa site na dye a.

Ọrụ nke oge a laghachiri na ya n'ihi na parasaiti na-eguzogide ọgwụ mepụtara mkpa ọhụrụ. N'ọmụmụ culture, methylene blue na-egbochi Plasmodium falciparum ma nke na-anabata chloroquine ma nke na-eguzogide ya na concentration nanomolar dị ala, yana synergy a kọrọ na artemisinin derivatives. Mgbe ejiri ya naanị ya n'ime mmadụ, ọ gosipụtara na ọ na-arụ ọrụ nwayọ: nnwale a na-achịkwa n'etiti ndị okenye nwere obere mgbochi ọrịa na Burkina Faso chọpụtara 16 percent nke ọdịda n'oge mbụ, ndị dere ọmụmụ ahụ wee kpebie na ọ dabaghị dịka otu ọgwụ a ga-eji n'ime obere oge. Ngwakọta ọgwụ rụpụtara ihe ka mma. N'ime nnwale randomised n'ime ụmụaka 180, methylene blue tinyere amodiaquine ruru 95 percent nzaghachi e doziri na day 28, ma ogwe abụọ nwere methylene blue belatara ibu gametocyte nke ukwuu na nyocha nnyefe so ya. Nnwale ngwakọta ọgwụ atọ n'ime ụmụaka 221 mechara kwado mmetụta gametocyte site na microscopy na nchọpụta molecular. Nsonaazụ kacha pụta ìhè jiri anwụnta dịka endpoint: n'ime nnwale phase 2 na Mali, ịgbakwunye ụbọchị atọ nke methylene blue wetara median 100 percent mbelata n'ike ọrịa ibunye anwụnta ka ọ na-erule day two.

A na-atụle usoro ọrụ atọ nwere ike ịdị, ma ekwesịghị ijikọta ha dịka otu ihe. Dye ahụ na-egbochi enzyme parasaiti glutathione reductase n'ime test tube (Ki nso 6.4 micromolar) ma na-eme redox-cycling dịka substrate nke na-erichapụ reducing equivalents (egosiri nke a n'ofe reductases nke mmadụ na parasaiti). Ma parasaiti e mere ka ha ghara inwe enzyme ahụ site na genetics ka nwere otu sensitivity ahụ, ya mere nke ahụ enweghị ike ịbụ nkọwa niile, ebe echiche ochie banyere igbochi mwepụ heme (nke kwekọrọ na potency nanomolar) ka egosibeghị na ndị ọrịa. Nchịkọta ziri ezi: arụmọrụ n'ime mmadụ dị n'ezie, enweghị otu target a kwadoro nke ọma, enweghịkwa ọrụ n'ime regimen ọkọlọtọ. Usoro ọgwụgwọ na data nnyefe dị na nyocha anyị banyere methylene blue maka malaria, nke ibe a anaghị emegharị.

Babesia na Toxoplasma: siri ike na culture, adịghị na ụlọ ọgwụ

Babesia, nke bụ onye ikwu malaria n'ime mkpụrụ ndụ ọbara uhie, e gburu ya n'efere ụlọ nyocha na concentration submicromolar, ebe parasaiti e kpughere na ọgwụ ahụ enweghị ike itolite ọzọ (Journal of Protozoology Research), ma nyocha ọzọ mechara tinye dye ahụ dịka agent kacha nwee potency n'ime ndị anwalechara na ihe dịka 0.2 micromolar (Carvalho na ndị ọrụ ibe ya, 2020). N'ime ụmụ oke, ọbụna 50 mg/kg nyere naanị obere inhibition, ọ dịghịkwa ọmụmụ babesiosis mmadụ dị.

Toxoplasma na-egosi otu ụdị ihe akaebe ahụ. Ọmụmụ culture abụọ nke ọtụtụ afọ kewara hụrụ suppression submicromolar nke tachyzoites na-amụba: 0.45 micromolar n'ime macrophages na 1989 na ihe dịka 0.30 micromolar n'ime nyocha antimalarial na 2018. Ọ dịghị nke ọ bụla metụrụ cyst tissue bradyzoite zoro ezo, nke bụ ogbo siri ike n'ọrụ ụlọ ọgwụ, ọ dịghịkwa ọmụmụ ọgwụgwọ anụmanụ ma ọ bụ mmadụ achọpụtara. Ọnụọgụ tachyzoite n'efere ụlọ nyocha abụghị ihe akaebe banyere ọrịa ọ bụla n'ime mmadụ.

Leishmania na trypanosomes: leba anya na ìhè, leba anya na òké

Ọtụtụ akwụkwọ gbasara Leishmania bụ n'ezie photodynamic therapy, echiche dị iche na ịṅụ dye. Photoactivation belatara inhibitory concentration megide Leishmania amazonensis site na ihe dịka 100 ruo 20 micromolar, ebe ihe akaebe mmadụ niile bụ otu onye ọrịa nke lesions ya nwetara antimony, ebe otu lesion natakwara dye nke ìhè mere ka ọ rụọ ọrụ. Ọrụ n'ime hamster chọpụtara na topical treatment nke ìhè mere ka ọ rụọ ọrụ nyere aka, ebe intradermal dye enyeghị aka (Sbeghen na ndị ọrụ ibe ya, 2015). Dye mpaghara tinyere ọkụ uhie n'akpụkpọ ahụ abụghị systemic therapy.

Ndekọ trypanosome nwere nsonaazụ ọjọọ kacha baa uru n'ime nyocha a: methylene blue gburu Trypanosoma brucei in vitro mana ọ gwọghị ụmụ oke nwere ọrịa na 300 mg/kg site n'ọnụ ma ọ bụ 200 mg/kg site na injection. Maka Chagas disease, ihe akaebe ahụ bụ biochemical, site na enzyme parasaiti pụrụ iche trypanothione reductase (Buchholz na ndị ọrụ ibe ya, 2008), tinyere igbu nje nke ìhè kwalitere in vitro (Barbosa na ndị ọrụ ibe ya, 2020). Disinfection n'ụlọ akụ ọbara nke plasma e tinyere nje n'ime ya (Gironés na ndị ọrụ ibe ya, 2006) gbasara ngwaahịa ọbara, ọ bụghị ndị ọrịa. Ndị bịara ebe a n'ihi ọrịa sitere n'ata akọrọ kwesịrị ịma na Lyme disease bụ bacterial kama ịbụ parasitic; a nyochara ihe akaebe ya na nyocha anyị banyere methylene blue maka Lyme disease.

Ikpuru, flukes, na nkwupụta banyere nhicha eriri afọ

Schistosoma mansoni bụ ihe atụ ikpuru kacha mma ma ọ ka erughị eru: dye gburu schistosomula n'okpuru 10 micromolar na ndị toro eto na 10 ruo 30 micromolar, mana ụmụ oke nwere ọrịa gosipụtara ihe dịka 60 percent suppression nke parasite burden yana enweghị ọgwụgwọ zuru oke. Obere pilot mmadụ dị n'akwụkwọ ahụ metụtara ngwakọta ọgwụ dị iche, ya mere enweghị ike ịkpọ ya nnwale dye n'ime mmadụ. Megide larvae na ndị toro eto Strongyloides, inhibitory concentrations nso 4 ruo 6 micromolar kwekọrọ na dye penetration n'ime ikpuru, mana ụmụ oke e nyere ya site n'ọnụ gosipụtara enweghị njikwa ọrịa pụtara ìhè. Maka scabies na lice, achọpụtaghị ihe akaebe ọgwụgwọ mmadụ.

Ọ dịghị nnwale nke oge a, usoro ikpe, ma ọ bụ case report doro anya na-egosi na methylene blue a na-aṅụ n'ọnụ na-ekpochapụ Giardia, Entamoeba, Strongyloides, ma ọ bụ intestinal helminths n'ime mmadụ. Ihe indexed kacha nso bụ akụkọ 1956 banyere gallbladder giardiasis nke enweghị dose a pụrụ ịnweta ma ọ bụ cure a pụrụ ikwenye. Akwụkwọ Giardia abụọ nke oge a dị mfe ịghọtahie: n'otu, 1 percent dye bụ stain e ji mee ka trophozoites pụta ìhè, n'aka nke ọzọ, dye diluted bụ readout stain mgbe e jiri ọgwụ ọkọlọtọ. Stain na-agba parasaiti agba n'okpuru microscope abụghị ọgwụ na-egbu ya n'eriri afọ. Maka Trichomonas, naanị ọmụmụ anụmanụ ahụ bụkwa photodynamic: vaginal dye tinyere ìhè n'ime ụmụ oke nwere ọrịa (Fonseca na ndị ọrụ ibe ya, 2019), ọ bụghị oral cleanse.

Ntụnyere

Ihe ga-agbanwe azịza a

Oghere ndị dị na ihe akaebe doro anya nke ukwuu. Ka ọ na-erule September 2026, achọpụtaghị registered interventional human trial nke dye maka parasaiti ọ bụla na-abụghị malaria, ya mere ihe mbụ na-efu bụ controlled human study ọ bụla n'èzí Plasmodium. Nke abụọ, concentrations e debere n'efere ụlọ nyocha ruo ọtụtụ ụbọchị adaala ugboro ugboro n'ime anụmanụ n'ihi clearance ngwa ngwa ma ọ bụ n'ihi na ha eruteghị compartment kwesịrị ekwesị, dịka ọdịda n'ime ụmụ oke maka trypanosome na Strongyloides gosiri. Nke atọ, ekwesịrị ịkwụsị iji nsonaazụ photodynamic dịka systemic evidence; dye tinyere dose ìhè a tụrụ atụ bụ echiche local disinfection nwere nsogbu delivery nke ya. Nke anọ, nkwupụta gbasara eriri afọ chọrọ parasitological endpoints, nke pụtara clearance n'ime stool ma ọ bụ tissue n'ime controlled cohorts, ọ bụghị naanị mmetụta mgbaàmà n'oge multi-ingredient cleanse protocols.

Eziokwu nchekwa abụọ na-amachi nnwale mmadụ na-eme n'onwe ya. A naghị ekwe methylene blue n'ime glucose-6-phosphate dehydrogenase deficiency n'ihi ihe ize ndụ hemolysis, ma pooled analysis nke nnwale malaria anọ n'ime ụmụaka hụrụ mbelata hemoglobin ka ukwuu n'ime ụmụaka nwere deficiency zuru oke na antiparasitic doses nso 15 mg/kg per day. Ọ bụkwa potent reversible monoamine oxidase A inhibitor (usoro ọrụ dị n'azụ serotonin toxicity), nke dị na labeling ugbu a dịka boxed warning, ma mmamịrị na-acha anụnụ anụnụ nwere ike imetụta automated urine testing. Ajụjụ gbasara dosing, purity, na interactions dị na ntuziaka anyị bara uru maka iji methylene blue.

Methylene blue nwetara aha antiparasitic ya n'ụzọ ziri ezi, megide malaria, n'ime randomized trials nwere mosquito endpoints. Ihe niile karịrị nke ahụ na-eji ikike sitere n'ebe ọzọ. Ruo mgbe controlled human study gosiri ihe ọzọ maka organism a kpọrọ aha, ọnọdụ a pụrụ ịgbachitere bụ nke dị warara: ezigbo antimalarial na-egbochi nnyefe nke ka na-eme nchọpụta, ebe n'ebe ndị ọzọ niile ọ bụ nchọpụta ụlọ nyocha na-eche ihe akaebe na ọ ka ga-arụ ọrụ mgbe ọ zutere host dị ndụ.