Kodi methylene blue imachiza tizilombo?

Funso limeneli limaoneka ngati funso limodzi. Kwenikweni ndi mafunso osiyanasiyana ambiri omwe akuoneka ngati chinthu chimodzi. Tizilombo ta malungo tomwe tili mkati mwa maselo ofiira a magazi, nyongolotsi ya m'matumbo, ndi tizilombo timene timayambitsa cutaneous leishmaniasis sizifanana pafupifupi chilichonse kupatulapo kuti zonse zimatchedwa tizilombo. Mankhwala amene amawononga mtundu umodzi wa tizilombo sakuyenera kugwiranso ntchito pa mitundu ina. Kumbukirani mfundo imeneyi pa kuwunika konseku: mphamvu yolimbana ndi tizilombo si khalidwe la molekyulu yokha. Ndi khalidwe la molekyuluyo pamodzi ndi tizilombo tinaake, pa gawo linaake la moyo wake, komanso pamalo enaake m'thupi.

Mukangolekanitsa mitundu ya tizilombo, umboni wokhudza methylene blue pa tizilombo umaoneka momveka bwino. Pali malungo, komwe kuli mayesero pa anthu. Kenako pali zina zonse: zoyesera m'mbale za labotale, mbewa, chithandizo cha khungu choyatsidwa ndi kuwala, ndi nkhani zakale za zaka zoposa zana. Palibe protocol imodzi yochizira tizilombo tonse yomwe ingachokere pa umboni umenewu.

Yankho lachidule

Methylene blue ndi mankhwala enieni oyesera a malungo. Kuwunika mwadongosolo kwa kafukufuku 21 wa anthu wokhudza odwala malungo 1,504 kunapeza kuti imagwiradi ntchito pa gawo la tizilombo tomwe tili m'magazi, ndipo makamaka ili ndi mphamvu kwambiri pa gawo la gametocyte lomwe limafalitsa matendawa kupita ku udzudzu. Kunja kwa malungo, umboni wofalitsidwa sugwirizana ndi kugwiritsa ntchito methylene blue ngati mankhwala olimbana ndi tizilombo tosiyanasiyana kapena ngati mankhwala oyeretsa tizilombo ta m'matumbo. Pafupifupi zotsatira zonse zosakhudza malungo zili pansi pa mlingo wa mphamvu ya umboni: imagwira ntchito m'mbale ya labotale, nthawi zina imagwira ntchito pa mbewa, ndipo pafupifupi sinayesedwepo kwa anthu omwe ali ndi matendawa.

Malungo: tizilombo tokhatu tomwe tili ndi mayesero pa anthu

Mu 1891, Guttmann ndi Ehrlich ananena za kuchiza odwala malungo ndi methylene blue, zomwe mwina zinali kugwiritsa ntchito koyamba kwa mankhwala opangidwa mwakupanga polimbana ndi matenda a anthu. Mbiri yake kuchokera pa utoto kupita ku mankhwala otsogolera polimbana ndi malungo imafika mpaka ku chloroquine, yomwe idatengera chemistry yomwe inayamba kufufuzidwa pogwiritsa ntchito utoto umenewu.

Kafukufuku wamakono unabwereranso ku mankhwalawa chifukwa tizilombo tosagonja ku mankhwala tinapangitsa kufunikira kwa njira zina. Mu culture, methylene blue imaletsa Plasmodium falciparum yomwe imakhudzidwa ndi chloroquine komanso yomwe imagonjetsedwa nayo pa ma concentration otsika a nanomolar, ndipo zanenedwa kuti imagwira bwino limodzi ndi zotumphukira za artemisinin. Ikagwiritsidwa ntchito yokha kwa anthu, inatsimikizika kuti imagwira ntchito pang'onopang'ono: mayeso oyendetsedwa pa akuluakulu omwe anali ndi chitetezo china ku Burkina Faso anapeza 16 percent ya kulephera koyambirira, ndipo olemba kafukufukuyo anaweruza kuti siyoyenera kugwiritsidwa ntchito yokha ngati mankhwala a nthawi yochepa. Kuphatikiza ndi mankhwala ena kunachita bwino kwambiri. Mu mayeso osankhidwa mwachisawawa pa ana 180, methylene blue pamodzi ndi amodiaquine zinafika pa 95 percent ya kuyankha kokonzedwa pa tsiku la 28, ndipo magulu onse awiri omwe analandira methylene blue anachepetsa kwambiri kunyamula gametocyte mu kafukufuku wotsatira wa kufalikira. Mayeso a kuphatikiza mankhwala atatu pa ana 221 pambuyo pake anatsimikizira mphamvu pa gametocyte pogwiritsa ntchito microscopy ndi kuzindikira kwa molekyulu. Chotsatira chodabwitsa kwambiri chinagwiritsa ntchito udzudzu ngati endpoint: mu phase 2 trial ku Mali, kuwonjezera methylene blue kwa masiku atatu kunabweretsa median 100 percent kuchepa kwa kuthekera kwa udzudzu kutenga matenda pofika tsiku lachiwiri.

Njira zitatu zomwe zingafotokoze momwe zimagwirira ntchito zimakambidwa ndipo siziyenera kuphatikizidwa ngati kuti ndi njira imodzi. Utotowo umaletsa enzyme ya tizilombo ya glutathione reductase mu test tube (Ki pafupi ndi 6.4 micromolar) ndipo umachita redox cycling ngati substrate yomwe imachepetsa reducing equivalents (zasonyezedwa pa reductases za anthu ndi za tizilombo). Koma tizilombo tomwe tasinthidwa mwachibadwa kuti tisakhale ndi enzyme imeneyo timakhalabe ndi sensitivity yomweyo, choncho zimenezi sizingakhale kufotokozera konse, ndipo lingaliro lakale lakuti imasokoneza kuchotsedwa kwa heme (lomwe linagwirizana ndi mphamvu ya nanomolar) silinatsimikizidwebe kwa odwala. Chidule cholondola: pali mphamvu yeniyeni mwa anthu, palibe target imodzi yokhazikika yomwe yavomerezedwa, ndipo palibe malo ake mu standard regimen. Ma regimen ndi deta ya kufalikira zafotokozedwa mu kuwunika kwathu kwa methylene blue pa malungo, zomwe tsambali silibwereza.

Babesia ndi Toxoplasma: zamphamvu mu culture, koma palibe umboni wa kuchipatala

Babesia, wachibale wa malungo amene amakhala m'maselo ofiira a magazi, anaphedwa m'mbale za labotale pa ma concentration a submicromolar, ndipo tizilombo tomwe tinaikidwa pa mankhwalawo sikanathanso kukulanso (Journal of Protozoology Research) ndipo kafukufuku wotsatira unayika utotowo ngati mankhwala amphamvu kwambiri mwa omwe anayesedwa, pafupifupi 0.2 micromolar (Carvalho ndi anzake, 2020). Pa mbewa, ngakhale 50 mg/kg inapereka kuletsa kochepa kokha, ndipo palibe kafukufuku wa babesiosis mwa anthu.

Toxoplasma ili ndi chithunzi chomwecho. Maphunziro awiri a culture omwe anachitika zaka zambiri mosiyana anapeza kuletsa kwa submicromolar kwa tachyzoites zomwe zikuchulukana: 0.45 micromolar mu macrophages mu 1989 ndi pafupifupi 0.30 micromolar mu screening ya mankhwala a malungo mu 2018. Palibe mwa maphunziro amenewa amene anakhudza cyst ya bradyzoite yobisika m'thupi, yomwe ndi gawo lovuta kuchiza kuchipatala, ndipo palibe kafukufuku wa chithandizo pa nyama kapena anthu womwe unapezeka. Chiwerengero cha tachyzoite m'mbale ya labotale si umboni wokhudza matenda aliwonse mwa munthu.

Leishmania ndi trypanosomes: samalani ndi kuwala, samalani ndi mbewa

Zambiri mwa zolemba za Leishmania kwenikweni zikukhudza photodynamic therapy, lingaliro losiyana ndi kumwa utoto. Photoactivation inatsitsa inhibitory concentration motsutsana ndi Leishmania amazonensis kuchokera pafupifupi 100 kufika 20 micromolar, ndipo umboni wonse wa anthu ndi wodwala m'modzi amene zilonda zake zinalandira antimony pamene chimodzi chinawonjezeredwa utoto woyatsidwa ndi kuwala. Kafukufuku wa hamster anapeza kuti chithandizo cha pamalo chomwe chinayatsidwa ndi kuwala chinathandiza pamene utoto woperekedwa intradermally sunathandize (Sbeghen ndi anzake, 2015). Utoto wapamalo kuphatikizidwa ndi kuwala kofiira pakhungu si systemic therapy.

Umboni wa trypanosome uli ndi zotsatira zoipa zothandiza kwambiri mu kuwunikaku: methylene blue inaphedwa Trypanosoma brucei in vitro koma inalephera kuchiza mbewa zomwe zinali ndi matenda pa 300 mg/kg ikaperekedwa pakamwa kapena 200 mg/kg ikabayidwa. Pa matenda a Chagas, umboni wake ndi wa biochemical, kudzera mu enzyme ya tizilombo yokha ya trypanothione reductase (Buchholz ndi anzake, 2008), kuphatikizapo kupha kowonjezeka ndi kuwala in vitro (Barbosa ndi anzake, 2020). Kupha tizilombo mu plasma yomwe yaikidwa tizilombo mwadala ku banki ya magazi (Gironés ndi anzake, 2006) kumakhudza zinthu za magazi, osati odwala. Owerenga omwe afika pano kuchokera ku matenda opatsirana ndi nkhupakupa ayenera kudziwa kuti Lyme disease ndi matenda a bakiteriya osati a tizilombo; umboni wake wawunikidwa mu kuwunika kwathu kwa methylene blue pa Lyme disease.

Nyongolotsi, flukes, ndi zonena za kuyeretsa matumbo

Schistosoma mansoni ndi chitsanzo champhamvu kwambiri pakati pa nyongolotsi koma umboni wake ukusowabe: utotowo unaphedwa schistosomula pansi pa 10 micromolar ndi akuluakulu pa 10 mpaka 30 micromolar, koma mbewa zomwe zinali ndi matenda zinasonyeza kuchepa kwa burden pafupifupi 60 percent ndi palibe zomwe zinachira. Kafukufuku wochepa wa anthu m'pepalalo unakhudza kuphatikiza kwa mankhwala ena, choncho sungatchedwe mayeso a utotowo mwa anthu. Potsutsana ndi mphutsi ndi akuluakulu a Strongyloides, inhibitory concentrations pafupifupi 4 mpaka 6 micromolar zinagwirizana ndi kulowa kwa utotowo m'nyongolotsi, koma mbewa zomwe zinapatsidwa pakamwa zinasonyeza palibe kulamulira kwatanthauzo kwa matendawo. Pa scabies ndi lice, palibe umboni wa chithandizo mwa anthu womwe unapezeka.

Palibe mayeso amakono, mndandanda wa odwala, kapena case report yokhulupirika yomwe imasonyeza kuti methylene blue yomwedwa imathetsa Giardia, Entamoeba, Strongyloides, kapena intestinal helminths mwa anthu. Chinthu chapafupi kwambiri chomwe chili mu index ndi lipoti la 1956 la giardiasis ya gallbladder lomwe lilibe dose yopezeka kapena umboni wotsimikizika wa kuchira. Mapepala awiri amakono a Giardia ndi osavuta kuwamasulira molakwika: mu limodzi, 1 percent ya utoto inali stain yomwe inasonyeza trophozoites, ndipo mu lina, utoto wochepetsedwa unali stain yowerengera zotsatira pambuyo pa mankhwala wamba. Stain yomwe imapaka tizilombo mtundu pansi pa microscope si mankhwala omwe amawapha m'matumbo. Pa Trichomonas, kafukufuku wokhawo wa nyama ndi photodynamic kachiwiri: utoto wa vaginal kuphatikizidwa ndi kuwala pa mbewa zomwe zinali ndi matenda (Fonseca ndi anzake, 2019), osati kuyeretsa komwedwa.

Kuyerekezera

Zomwe zingasinthe yankholi

Mipata ya umboni ndi yeniyeni ndipo ingatchulidwe mwachindunji. Palibe interventional human trial yolembetsedwa ya utotowo pa tizilombo tina kupatulapo malungo yomwe inapezeka mpaka September 2026, choncho chinthu choyamba chomwe chikusowa ndi kafukufuku uliwonse woyendetsedwa pa anthu kunja kwa Plasmodium. Chachiwiri, ma concentration a m'mbale ya labotale omwe amasungidwa kwa masiku alephera mobwerezabwereza pa nyama chifukwa cha kuchotsedwa mwachangu m'thupi kapena kufika m'malo olakwika, monga momwe kulephera pa mbewa kwa trypanosome ndi Strongyloides kukusonyezera. Chachitatu, zotsatira za photodynamic siziyenera kupitiriza kutchulidwa ngati umboni wa systemic; utoto kuphatikizidwa ndi mlingo woyezedwa wa kuwala ndi njira ya local disinfection yomwe ili ndi vuto lake la mmene ingaperekedwere. Chachinayi, zonena za m'matumbo zimafuna parasitological endpoints, kutanthauza kutsimikizira kuchotsedwa kwa tizilombo mu chimbudzi kapena minofu m'magulu oyendetsedwa, osati kungodalira mmene munthu akumvera panthawi ya ma protocol oyeretsa okhala ndi zinthu zambiri.

Mfundo ziwiri za chitetezo zimalepheretsa kuyesera nokha. Utotowo ndi contraindicated kwa anthu omwe ali ndi glucose-6-phosphate dehydrogenase deficiency chifukwa cha chiopsezo cha hemolysis, ndipo pooled analysis ya mayesero anayi a malungo pa ana inapeza kuchepa kwakukulu kwa hemoglobin mwa ana omwe anali ndi deficiency yathunthu pa ma dose olimbana ndi tizilombo pafupifupi 15 mg/kg patsiku. Komanso ndi potent reversible monoamine oxidase A inhibitor (njira yomwe imayambitsa serotonin toxicity), yomwe ili pa labeling yapano ngati boxed warning, ndipo mkodzo wabuluu ukhoza kusokoneza automated urine testing. Mafunso okhudza dosing, purity, ndi interactions ali mu practical guide yathu yogwiritsa ntchito methylene blue.

Methylene blue inapeza mbiri yake yolimbana ndi tizilombo moyenerera, motsutsana ndi malungo, m'mayesero osankhidwa mwachisawawa okhala ndi endpoints za udzudzu. Zina zonse kupitirira pamenepo zikungobwereka mphamvu ya umboni umenewo. Mpaka kafukufuku woyendetsedwa pa anthu asonyeze mosiyana pa tizilombo tina kotchulidwa dzina, malo oyenera kutenga ndi ochepa: ndi mankhwala enieni a malungo omwe amaletsa kufalikira ndipo akufufuzidwabe, ndipo pa zina zonse ndi zotsatira za mu labotale zomwe zikudikirira umboni wakuti zimagwirabe ntchito zikakumana ndi thupi lamoyo.