Chinyorwa

Methylene blue inorapa maparasaiti here?

Methylene blue inorapa maparasaiti here?

Mubvunzo uyu unoita sekunge mubvunzo mumwe chete. Asi chaizvoizvo mibvunzo yakawanda yakasiyana yakapfeka nguo imwe chete. Parasaiti yemalaria iri mukati memasero matsvuku eropa, honye iri muura, uye chipenyu chinokonzera cutaneous leishmaniasis zvinenge zvisina chinhu chakafanana kunze kwezita rekuti parasite. Mushonga unokuvadza chimwe chezvazvo hauna chikonzero chekumanikidzwa kukuvadza zvimwe. Chengeta pfungwa iyi mupfungwa muongororo yose iyi: antiparasitic haisi pfuma yemorekuru yoga. Inobva pamorekuru pamwe chete nechipenyu chakati, pachikamu chakati cheupenyu hwacho, uye munzvimbo yakati yemuviri.

Kana ukangoparadzanisa zvipenyu izvi, humbowo hwe-methylene blue pamaparasaiti hunopatsanuka zvakajeka. Kune malaria, uko kune miedzo yakaitwa muvanhu. Zvadaro pane zvimwe zvese: madhishi emurabhoritari, mbeva, kurapwa kweganda kunoshandiswa chiedza, uye nyaya dzemakore anopfuura zana. Hapana protocol yepasi rose yekurapa maparasaiti inogona kubva pane chero chezvinhu izvi.

Mhinduro pfupi

Methylene blue mushonga wekuyedza chaiwo wekurwisa malaria. Ongororo yakarongeka yezvidzidzo 21 zvevanhu zvaisanganisira varwere vemalaria 1,504 yakawana kushanda chaiko pachikamu cheparasaiti chiri muropa uye kunyanya kushanda nesimba pachikamu chegametocyte chinotapurira hutachiona kumosquito. Kunze kwemalaria, humbowo hwakaburitswa hahutsigiri kushandisa methylene blue semushonga weantiparasitic unoshanda pamhando dzakawanda kana sekuchenesa maparasaiti emuura. Zvinenge zvese zvakawanikwa zvisiri zvemalaria zviri pazasi pematanho ehumbowo: zvinoshanda mundiro yemurabhoritari, dzimwe nguva mumbeva, uye zvinenge zvisina kumboyedzwa muvanhu vane hutachiona.

Malaria: parasaiti imwe chete ine miedzo yevanhu

Muna 1891, Guttmann naEhrlich vakashuma kurapa varwere vemalaria ne-methylene blue, zvichida uri iwo mushonga wekutanga wakagadzirwa nesainzi wakashandiswa kurwisa chirwere chevanhu. Nhoroondo kubva padhayi kusvika pakuzova mushonga unotarisirwa wekurwisa malaria inoenderera kusvika kuchloroquine, iyo yakatora makemikari akatanga kuongororwa nedhayi iyi.

Basa remazuva ano rakazoidzorera nekuti maparasaiti akanga ava kuramba mishonga, zvichiita kuti pave nechido chezvimwe zvingashanda. Mukurima masero, methylene blue inodzivisa Plasmodium falciparum inoteerera kana kuramba chloroquine pamaconcentration akaderera e-nanomolar, uye synergy neartemisinin derivatives yakashumwa. Payakashandiswa yoga muvanhu yakaratidza kunonoka: muedzo wakadzorwa muvakuru vane semi-immunity muBurkina Faso wakawana 16 percent yekukundikana kwekutanga, uye vanyori vakati haina kukodzera semushonga mumwe chete wekosi pfupi. Misanganiswa yakaita zviri nani. Mumuedzo wakasarudzwa zvisina rusaruro muvana 180, methylene blue pamwe neamodiaquine yakasvika pa95 percent corrected response pazuva 28, uye mapoka ose maviri ane methylene blue akaderedza zvakanyanya kutakurwa kwegametocyte muongororo yakabatana yekutapuriranwa. Muedzo wemusanganiswa wemishonga mitatu muvana 221 wakazosimbisa kushanda pagametocyte kuburikidza nemicroscopy uye molecular detection. Mhedzisiro yakanyanya kushamisa yakashandisa mosquito sechiyero chemhedzisiro: muphase 2 trial kuMali, kuwedzera mazuva matatu e-methylene blue kwakapa median 100 percent kuderera kwekutapurira mosquito pazuva rechipiri.

Nzira nhatu dzingangotsanangura kushanda kwayo dzinokurukurwa uye hadzifaniri kusanganiswa sekunge chinhu chimwe chete. Dhayi inodzivisa enzyme yeparasaiti glutathione reductase mutest tube (Ki near 6.4 micromolar) uye inoita redox-cycling sesubstrate inopedza reducing equivalents (zvakaratidzwa pama reductase evanhu neparasaiti). Asi maparasaiti akagadzirwa genetically asina enzyme iyoyo anoramba aine sensitivity imwe chete, saka izvi hazvigoni kuva tsananguro yose, uye pfungwa yekare yekuti inokanganisa kubviswa kweheme (yakabatana nenanomolar potency) haisati yaratidzwa muvarwere. Pfupiso yakatendeseka: kune efficacy chaiyo muvanhu, hapana target imwe chete yakasimbiswa, uye haina basa rakajairika muregimen. Regimens nedata rekutapuriranwa zviri muongororo yedu ye-methylene blue pamalaria, izvo peji ino isingadzokorori.

Babesia neToxoplasma: zvine simba muculture, asi hazvina humbowo mukiriniki

Babesia, hama yemalaria inogara mumasero matsvuku eropa, yakaurayiwawo mumadhishi pamaconcentration ari pasi pe-micromolar, uye maparasaiti akanga aiswa pairi akatadza kukurazve (Journal of Protozoology Research) uye ongororo yakazotevera yakaisa dhayi iyi semushonga waive nesimba kupfuura mimwe yakaedzwa, paanenge 0.2 micromolar (Carvalho nevamwe, 2020). Mumbeva, kunyange 50 mg/kg yakangopa kudzivisa kushoma, uye hapana chidzidzo chebabesiosis muvanhu chiripo.

Toxoplasma inoratidza mufananidzo wakafanana. Zvidzidzo zviviri zveculture zvakaparadzana nemakumi emakore zvakawana kudzvinyirirwa kuri pasi pe-micromolar kwetachyzoites dziri kuwanda: 0.45 micromolar mumacrophage muna 1989 uye anenge 0.30 micromolar muantimalarial screen muna 2018. Hapana chazvo chakabata latent bradyzoite tissue cyst, chikamu chinoomesera kurapa mukiriniki, uye hapana chidzidzo chekurapa mumhuka kana muvanhu chakawanikwa. Nhamba yetachyzoite mundiro yemurabhoritari haisi humbowo hwehutachiona huri mumunhu.

Leishmania netrypanosomes: cherechedza chiedza, cherechedza mbeva

Zvinyorwa zvakawanda zveLeishmania chaizvoizvo ndezvephotodynamic therapy, pfungwa yakasiyana nekumedza dhayi. Photoactivation yakaderedza inhibitory concentration yeLeishmania amazonensis kubva paanenge 100 kusvika 20 micromolar, uye humbowo hwose hwevanhu hwuri pamurwere mumwe chete ane maronda akapiwa antimony uku rimwe rawo richiwedzerwa dhayi yakashandiswa nechiedza. Basa rehamster rakawana kuti kurapwa kwepamusoro peganda kwakashandiswa nechiedza kwakabatsira, asi intradermal dye haina kubatsira (Sbeghen nevamwe, 2015). Dhayi yemuno pamwe nechiedza chitsvuku paganda haisi systemic therapy.

Humbowo hwetrypanosome hune mhedzisiro isina kushanda inonyanya kubatsira muongororo iyi: methylene blue yakauraya Trypanosoma brucei in vitro asi yakatadza kurapa mbeva dzine hutachiona pa300 mg/kg nemuromo kana 200 mg/kg nejekiseni. Pachirwere cheChagas humbowo ndehwebiochemistry, kuburikidza neenzyme yakasarudzika yeparasaiti trypanothione reductase (Buchholz nevamwe, 2008), pamwe nekuuraya kunowedzerwa nechiedza in vitro (Barbosa nevamwe, 2020). Kubvisa hutachiona muplasma yakawedzerwa parasite mublood bank (Gironés nevamwe, 2006) kune chekuita nezvigadzirwa zveropa, kwete varwere. Vaverengi vauya pano vachibva kunyaya dzezvirwere zvinotakurwa neticks vanofanira kuziva kuti Lyme disease ibacterial, kwete parasitic; humbowo hwayo hunoongororwa muongororo yedu ye-methylene blue paLyme disease.

Honye, flukes, uye chirevo chekuchenesa ura

Schistosoma mansoni ndiyo ine humbowo hwakanakisisa pakati pehonye asi ichiri kusakwana: dhayi yakauraya schistosomula pasi pe10 micromolar uye dzakura pa10 kusvika 30 micromolar, asi mbeva dzine hutachiona dzakaratidza anenge 60 percent kudzvinyirirwa kweparasite burden asi pasina kurapwa kwakazara. Human pilot diki iri mupepa iroro yaiva yemusanganiswa wemimwe mishonga, saka haigoni kunzi muedzo wedhayi muvanhu. PaStrongyloides larvae nedzakura, inhibitory concentrations dziri pedyo ne4 kusvika 6 micromolar dzakatevedzana nekupinda kwedhayi muhonye, asi mbeva dzakapiwa nemuromo dzakaratidza kusadzorwa kwehutachiona kwakakosha. Pamusoro pescabies nelice, hapana humbowo hwekurapa muvanhu hwakawanikwa.

Hapana muedzo wemazuva ano, series, kana case report inogutsa inoratidza kuti methylene blue inotorwa nemuromo inobvisa Giardia, Entamoeba, Strongyloides, kana intestinal helminths muvanhu. Chinhu chepedyo chakanyorwa mumarekodhi imushumo wa1956 wegallbladder giardiasis usina dose inowanikwa kana kurapwa kunogona kusimbiswa. Mapepa maviri emazuva ano eGiardia ari nyore kududzira zvisiri izvo: mune rimwe, 1 percent dye yaiva stain yairatidza trophozoites, uye mune rimwe, dilute dye yaiva readout stain mushure memishonga yakajairika. Stain inopenda parasaiti pasi pemicroscope haisi mushonga unoiuraya muura. PaTrichomonas, chidzidzo chimwe chete chemhuka zvakare ndechephotodynamic: vaginal dye pamwe nechiedza mumbeva dzine hutachiona (Fonseca nevamwe, 2019), kwete cleanse inotorwa nemuromo.

Kuenzanisa

ChipenyuHumbowo hwakasimba kupfuura hwese hwakawanikwaEfficacy muvanhu?Mhedziso
Plasmodium falciparumMiedzo yakasarudzwa zvisina rusaruro, ongororo yevarwere 1,504, mosquito-infectivity endpointHongu, pamwe nekudzivirira kutapuriranwaAntimalarial chaiyo, basa richiri kuongororwa
BabesiaSubmicromolar culture activity, mhedzisiro isina simba mumbevaKweteHapana hwaro hwekurapa
ToxoplasmaSubmicromolar tachyzoite activity, yakadzokororwa kaviriKweteHapana data yecyst kana yekiriniki
LeishmaniaPhotoactivated local treatment cheteHapana systemic evidencePhotodynamic, kwete systemic
TrypanosomesKuuraya in vitro, kukundikana kwekurapa mumbevaKweteNegative in vivo result
SchistosomaKuuraya in vitro, partial mouse suppressionKweteHapana cure kunyange mumbeva
StrongyloidesLow-micromolar worm activity, kukundikana mumbevaKweteDish activity isina kushanduka kuita kurapwa
Giardia, EntamoebaChinyorwa chekare, kushandiswa sestainKweteHapana humbowo hunotsigira cleanse
Scabies, liceHapana therapeutic yakawanikwaKweteZvinotaurwa hazvina humbowo

Chii chaizochinja mhinduro iyi

Mikaha muhumbowo yakajeka zvekuti inogona kudomwa. Hapana registered interventional human trial yedhayi kune chero parasaiti isiri malaria yakawanikwa kusvika muna September 2026, saka chinhu chekutanga chisipo chero controlled human study kunze kwePlasmodium. Chechipiri, maconcentration emundiro yemurabhoritari anochengetwa kwemazuva akawanda akadzokorora kukundikana mumhuka nekuda kwekukurumidza kubviswa kana kusvika munzvimbo isiri iyo yemuviri, sezvinoratidzwa nekukundikana kwemuedzo wembeva patrypanosome neStrongyloides. Chechitatu, mhedzisiro yephotodynamic haifaniri kuramba ichishandiswa sehumbowo hwesystemic; dhayi pamwe nedose yechiedza yakayerwa ipfungwa yekuuraya utachiona munzvimbo yakatarwa, ine dambudziko rayo rekusvitsa kurapwa. Chechina, zvirevo zvemuura zvinoda parasitological endpoints, kureva kupera kweparasaiti mutsvina kana munyama mumapoka akadzorwa, kwete fungidziro yezviratidzo panguva yemulti-ingredient cleanse protocols.

Zvinhu zviviri zvekuchengeteka zvinodzikamisa kuzviedza wega. Dhayi iyi contraindicated mu glucose-6-phosphate dehydrogenase deficiency nekuda kwengozi yehemolysis, uye pooled analysis yemiedzo mina yemalaria muvana yakawana kuderera kukuru kwehemoglobin muvana vaive fully deficient pamadosi eantiparasitic ari pedyo ne15 mg/kg per day. Uyewo ipotent reversible monoamine oxidase A inhibitor (mechanism iri kumashure kweserotonin toxicity), yakanyorwa palabeling yemazuva ano seboxed warning, uye weti yebhuruu inogona kukanganisa automated urine testing. Mibvunzo yedosing, purity, uye interactions iri mugwaro redu rinoshanda rekushandisa methylene blue.

Methylene blue yakawana mukurumbira wayo seantiparasitic nenzira yakakodzera, pamalaria, mumiedzo yakasarudzwa zvisina rusaruro ine mosquito endpoints. Zvese zvinopfuura ipapo zviri kukwereta simba rehumbowo ihwohwo. Kusvikira controlled human study yaratidza zvakasiyana paparasaiti yakadomwa, chinzvimbo chinotsigirwa nehumbowo chinofanira kuramba chakamanikana: antimalarial chaiyo iri kuongororwa uye inodzivirira kutapuriranwa, uye kune zvimwe zvese chingori chakawanikwa murabhoritari chakamirira humbowo hwekuti chinoshanda kana chasangana nemuviri mupenyu.