Ngaba i-methylene blue iyazinyanga izifunxi-gazi?

Umbuzo uvakala ngathi ngumbuzo omnye. Enyanisweni, yimibuzo emininzi eyahlukeneyo enxibe impahla enye. Isifunxi-gazi semalariya esingaphakathi kweeseli ezibomvu zegazi, umbungu osesiswini, kunye nesidalwa esibangela i-cutaneous leishmaniasis phantse akukho nto zabelana ngayo ngaphandle kwegama elithi isifunxi-gazi. Ichiza elenzakalisa esinye alinaxanduva lokwenzakalisa ezinye. Gcina lo mgaqo engqondweni kulo lonke olu phononongo: ukusebenza ngokuchasene nezifunxi-gazi asiyophawu lwemolekyuli yodwa. Luphawu lwemolekyuli kunye nesidalwa esithile, kwinqanaba elithile lobomi, kwindawo ethile yomzimba.

Xa izidalwa zahlulwa, ubungqina nge-methylene blue kwizifunxi-gazi buhluleka ngokucacileyo. Kukho imalariya, apho kukho khona izilingo ebantwini. Emva koko kukho yonke enye into: izitya zelabhoratri, iimpuku, unyango lolusu oluvulwa kukukhanya, kunye neengxelo ezineminyaka elikhulu ubudala. Akukho protocol yokunyanga zonke izifunxi-gazi enokuthathwa nakweyiphi kwezi.

Impendulo emfutshane

I-methylene blue liyeza lokwenene lovavanyo lokulwa nemalariya. Uphononongo olucwangcisiweyo lwezifundo ezingama-21 ebantwini olubandakanya izigulana zemalariya ezili-1,504 lwafumana ukusebenza kokwenene kwinqanaba legazi, ngakumbi iziphumo ezomeleleyo kwinqanaba le-gametocyte elisasaza usulelo kwiingcongconi. Ngaphandle kwemalariya, ubungqina obupapashiweyo abuxhasi ukuphatha i-methylene blue njengeyeza elibanzi lokulwa nezifunxi-gazi okanye njengendlela yokucoca izifunxi-gazi zamathumbu. Phantse zonke iziphumo ezingeyomalariya zikwinqanaba elisezantsi kakhulu lobungqina: ziyasebenza esityeni selabhoratri, ngamanye amaxesha kwimpuku, kodwa phantse azikaze zivavanywe kubantu abosulelekileyo.

Imalariya: isifunxi-gazi esinye esinezilingo ebantwini

Ngo-1891, uGuttmann no-Ehrlich baxela ukunyanga izigulana zemalariya nge-methylene blue, ekusenokwenzeka ukuba yayilichiza lokuqala elenziwe ngokwemichiza elalisetyenziselwa isifo ebantwini. Imbali ukusuka kwidayi ukuya kwikhompawundi ephambili yokulwa nemalariya iya kufikelela kwi-chloroquine, eyazuza kwimichiza eyaqala ukuhlolwa kusetyenziswa le dayi.

Uphando lwangoku lwayibuyisela ngenxa yokuba izifunxi-gazi ezinganyangekiyo ngamachiza zenza kwafuneka ezinye iindlela. Kwinkcubeko yeselabhoratri, i-methylene blue ithintela i-Plasmodium falciparum enovakalelo kwi-chloroquine kunye nenganyangekiyo kuyo kwiikonsentreshini ezisezantsi ze-nanomolar, kwaye kuxelwe ukusebenza ngokudibeneyo nezinye iimveliso ze-artemisinin. Xa isetyenziswa yodwa ebantwini yabonakala isebenza kancinci: isilingo esilawulwayo kubantu abadala abanokhuselo oluthile eBurkina Faso safumana izinga lokungaphumeleli kwangethuba le-16 percent, kwaye ababhali bagqiba ukuba ayifanelekanga njengechiza elinye lekhosi emfutshane. Iindibaniselwano zasebenza ngcono. Kwisilingo esikhethwe ngokungakhethiyo kubantwana abali-180, i-methylene blue kunye ne-amodiaquine yafikelela kwimpendulo elungisiweyo ye-95 percent ngosuku lwe-28, kwaye omabini amaqela e-methylene-blue anciphisa kakhulu ukuthwalwa kwe-gametocyte kuhlalutyo oluhambelana noko lokusasazeka. Isilingo sendibaniselwano yamachiza amathathu kubantwana abali-221 kamva saqinisekisa isiphumo kwi-gametocyte kusetyenziswa imicroscope kunye nokufunyaniswa kwemolekyuli. Esona siphumo sigqamileyo sasebenzisa iingcongconi njengendawo yokulinganisa: kwisilingo sesigaba 2 eMali, ukongeza iintsuku ezintathu ze-methylene blue kwavelisa ukuncipha okuphakathi kwe-100 percent kwisakhono sokosulela iingcongconi ngosuku lwesibini.

Kuxoxwa ngeendlela ezintathu ezinokwenzeka, kwaye akufanele zidityaniswe zibe yinto enye. Idayi ithintela i-enzyme yesifunxi-gazi ebizwa ngokuba yi-glutathione reductase kwityhubhu yovavanyo (Ki malunga ne-6.4 micromolar) kwaye ijikeleza kwi-redox njenge-substrate esebenzisa izinto zokunciphisa (oku kuboniswe kwii-reductase zabantu nezifunxi-gazi). Kodwa izifunxi-gazi eziguqulwe ngokwemfuza ukuze zingabi nayo loo enzyme zigcina uvakalelo olufanayo, ngoko ayinakuba yinkcazelo epheleleyo, kwaye ingcamango endala yokuphazamisa indlela yokulahla i-heme (eyayinxulunyaniswa namandla e-nanomolar) ayikaqinisekiswa kwizigulana. Isishwankathelo esichanekileyo: ukusebenza kokwenene ebantwini, akukho target enye eqinisekisiweyo, kwaye akukho ndawo kwirejimeni esemgangathweni. Iirejimeni kunye nedatha yokusasazeka zichazwe kuphononongo lwethu lwe-methylene blue kwimlariya, kwaye eli phepha aliphindi oko.

Babesia kunye ne-Toxoplasma: zinamandla kwinkcubeko, azikho ekliniki

I-Babesia, esondelelene nemalariya ngokuhlala kwiiseli ezibomvu zegazi, yabulawa ngokwenene kwizitya zelabhoratri kwiikonsentreshini ezingaphantsi kwe-micromolar, kwaye izifunxi-gazi ezazivezwe kuyo azizange ziphinde zikhule (Journal of Protozoology Research) kwaye uhlolo lwamva lwabeka idayi njenge-arhente enamandla kakhulu eyavavanywayo malunga ne-0.2 micromolar (Carvalho kunye noogxa, 2020). Kwiimpuku, nkqu ne-50 mg/kg yanika kuphela ukuthintela okubuthathaka, kwaye akukho sifundo se-babesiosis ebantwini sikhoyo.

I-Toxoplasma ibonisa ipateni efanayo. Izifundo ezimbini zenkcubeko ezahlulwe ngamashumi eminyaka zafumana ukuthintelwa okungaphantsi kwe-micromolar kwee-tachyzoite ezivelisayo: 0.45 micromolar kwi-macrophages ngo-1989 kunye malunga ne-0.30 micromolar kuhlolo lwamachiza okulwa nemalariya ngo-2018. Akukho nanye kwezi eyachaphazela i-bradyzoite tissue cyst efihlakeleyo, eyona nqanaba linzima ngokwekliniki, kwaye akukho sifundo sonyango kwizilwanyana okanye ebantwini safunyanwa. Inani le-tachyzoite esityeni selabhoratri asilobungqina malunga nosulelo emntwini.

Leishmania kunye ne-trypanosomes: qwalasela ukukhanya, qwalasela impuku

Uninzi loncwadi lwe-Leishmania ngokwenene lumalunga ne-photodynamic therapy, ingcamango eyahlukileyo ekuginyeni idayi. I-photoactivation yanciphisa ikonsentreshini ethintelayo ngokuchasene ne-Leishmania amazonensis ukusuka malunga ne-100 ukuya kwi-20 micromolar, kwaye bonke ubungqina obukhoyo ebantwini sisigulana esinye esasifumana i-antimony kwizilonda ngoxa esinye isilonda songezwa idayi evulwa kukukhanya. Uphando kwi-hamster lwafumanisa ukuba unyango lwangaphandle oluvulwa kukukhanya lwalunceda ngoxa idayi efakwe ngaphakathi kwesikhumba ingancedanga (Sbeghen kunye noogxa, 2015). Idayi yendawo kunye nokukhanya okubomvu eluswini ayilonyango lomzimba wonke.

Ubungqina nge-trypanosome bubandakanya esona siphumo singalunganga siluncedo kolu phononongo: i-methylene blue yabulala i-Trypanosoma brucei in vitro kodwa yasilela ukunyanga iimpuku ezosulelekileyo kwi-300 mg/kg ngomlomo okanye kwi-200 mg/kg xa itofwe. Kwisifo se-Chagas ubungqina busekwe kwi-biochemistry, kusetyenziswa i-enzyme ekhethekileyo yesifunxi-gazi ebizwa ngokuba yi-trypanothione reductase (Buchholz kunye noogxa, 2008), kunye nokubulala okwandiswa kukukhanya in vitro (Barbosa kunye noogxa, 2020). Ukubulala iintsholongwane kwi-plasma efakwe isifunxi-gazi kwibhanki yegazi (Gironés kunye noogxa, 2006) kubhekisa kwiimveliso zegazi, hayi kwizigulana. Abafundi abafike apha ngenxa yezifo ezisasazwa ngamakhalane kufuneka baqaphele ukuba isifo se-Lyme sibangelwa ziibhaktiriya, hayi sisifunxi-gazi; ubungqina baso buhlolwe kuphononongo lwethu lwe-methylene blue kwisifo se-Lyme.

Iimbungu, i-flukes, kunye nebango lokucoca amathumbu

I-Schistosoma mansoni yeyona meko ibalaseleyo kwiimbungu kwaye nayo ayifikeli kubungqina obaneleyo: idayi yabulala i-schistosomula ngaphantsi kwe-10 micromolar kunye nabantu abadala kwi-10 ukuya kwi-30 micromolar, kodwa iimpuku ezosulelekileyo zabonisa malunga ne-60 percent yokuncipha komthwalo kungekho kunyanga ngokupheleleyo. Isifundo esincinci sabantu kwelo phepha sasimalunga nendibaniselwano eyahlukileyo yamachiza, ngoko asinakubizwa ngokuba sisilingo sedayi ebantwini. Ngokuchasene nemibungu kunye nabantu abadala be-Strongyloides, iikonsentreshini ezithintelayo malunga ne-4 ukuya kwi-6 micromolar zazihambelana nokungena kwedayi embungwini, kodwa iimpuku ezanikwa idosi ngomlomo zabonisa ukungabikho kolawulo olubalulekileyo losulelo. Kwi-scabies kunye neentwala, akukho bungqina bonyango ebantwini obafunyanwayo.

Akukho silingo sanamhlanje, uthotho lwezigulana, okanye ingxelo yetyala ekholisayo ebonisa ukuba i-methylene blue ethathwa ngomlomo iyayiphelisa i-Giardia, Entamoeba, Strongyloides, okanye ii-helminths zamathumbu ebantwini. Eyona nto ikufutshane efakwe kwizalathiso yingxelo yango-1956 malunga ne-giardiasis ye-gallbladder engenadosi ifikelelekayo okanye ubungqina obunokuqinisekiswa bokunyanga. Amaphepha amabini anamhlanje nge-Giardia kulula ukuwafunda ngendlela engachanekanga: kwelinye, idayi ye-1 percent yayisisichasi sokudaya esibonisa ii-trophozoite, kwaye kwelinye, idayi exutywe kakhulu yayisisichasi sokufunda iziphumo emva kwamachiza aqhelekileyo. Isichasi sokudaya esenza isifunxi-gazi sibonakale phantsi kwe-microscope asilochiza elisibulalayo emathunjini. Kwi-Trichomonas, isifundo esinye kuphela sezilwanyana kwakhona sisebenzisa i-photodynamic: idayi yangasese kunye nokukhanya kwiimpuku ezosulelekileyo (Fonseca kunye noogxa, 2019), hayi ukucoca ngokuyithatha ngomlomo.

Uthelekiso

Yintoni enokutshintsha le mpendulo

Izithuba kubungqina zicace ngokwaneleyo ukuba zingachazwa. Akukho silingo songenelelo ebantwini esibhalisiweyo sedayi ngokuchasene naso nasiphi na isifunxi-gazi esingeyomalariya esafunyanwa ukuya kutsho ngoSeptemba 2026, ngoko into yokuqala engekhoyo nasiphi na isifundo esilawulwayo ebantwini ngaphandle kwe-Plasmodium. Okwesibini, iikonsentreshini ezisezityeni zelabhoratri ezigcinwa iintsuku ziye zasilela ngokuphindaphindiweyo kwizilwanyana ngenxa yokususwa ngokukhawuleza emzimbeni okanye ukufikelela kwiindawo ezingafanelekanga, njengoko ukusilela kwiimpuku nge-trypanosome kunye ne-Strongyloides kubonisa. Okwesithathu, iziphumo ze-photodynamic kufuneka ziyeke ukucatshulwa njengobungqina bonyango lwenkqubo yonke yomzimba; idayi kunye nedosi elinganisiweyo yokukhanya yingcamango yokubulala iintsholongwane kwindawo ethile enengxaki yayo yokuhanjiswa. Okwesine, amabango amathumbu afuna iziphumo ezilinganiswa ngokwe-parasitology, okuthetha ukucocwa kwesitulo okanye kwezicubu kwiikohorti ezilawulwayo, hayi iimvakalelo zeempawu ngexesha leeprotocol zokucoca ezinezithako ezininzi.

Iinyaniso ezimbini zokhuseleko zinciphisa ukuzama okuzenzekelayo. Idayi ayivumelekanga kubantu abanokunqongophala kwe-glucose-6-phosphate dehydrogenase ngenxa yomngcipheko we-hemolysis, kwaye uhlalutyo oludityanisiweyo lwezilingo ezine zemalariya ebantwaneni lwafumana ukuhla okukhulu kwe-hemoglobin kubantwana ababenokunqongophala ngokupheleleyo kwiidosi zokulwa nezifunxi-gazi ezikufutshane ne-15 mg/kg ngosuku. Ikwangu-inhibitor enamandla ebuyiselwa umva ye-monoamine oxidase A (indlela ebangela i-serotonin toxicity), ephawulwe ngoku kwileyibhile njengesilumkiso sebhokisi, kwaye umchamo oluhlaza unokuphazamisa uvavanyo lomchamo oluzenzekelayo. Imibuzo ngedosi, ubunyulu, kunye nokusebenzisana kwamachiza igutyungelwe kwisikhokelo sethu esisebenzayo sokusebenzisa i-methylene blue.

I-methylene blue yazuza igama layo lokulwa nezifunxi-gazi ngokufanelekileyo, ngokuchasene nemalariya, kwizilingo ezikhethwe ngokungakhethiyo ezisebenzisa iziphumo zokosuleleka kweengcongconi. Yonke into engaphaya koko iboleka igunya lobo bungqina. De kube sisifundo esilawulwayo ebantwini esibonisa okwahlukileyo kwisidalwa esichaziweyo, indawo enokuxhaswa bubungqina imxinwa: liyeza lokwenene lokulwa nemalariya elithintela ukusasazeka nelisaphandwayo, kwaye kuyo yonke enye indawo sisiphumo selabhoratri esisalindele ubungqina bokuba siyasebenza na xa sidibana nomzimba ophilayo.