Ithala lophando lwe-methylene blue: izilingo ebantwini nezifundo zovavanyo

Ukukhangela i-methylene blue kuvelisa amawaka amaphepha ophando. Isifundo esenziwe kwisitya selabhoratri, esenziwe kwiimpuku, nesenziwe kumavolontiya angamashumi amabini anesithandathu zivela kuluhlu olunye, zibonakala zinobunzima obulinganayo njengobungqina. Azinakuthathwa njengezinto ezifanayo, yaye umahluko phakathi kwazo udla ngokuba yeyona nto iphambili ekuphenduleni umbuzo obuzele wona.

Eli phepha lisisalathiso, hayi isigwebo sokugqibela. Lihlela ithala elisetyenziswayo lamaphepha ophando ali-130 nge-methylene blue ngokwezinto ezine ezitshintsha oko iphepha linokukuxelela kona: inqanaba olwenziwa kulo uvavanyo, iqela elifundiweyo, indlela yokunikezelwa nethamo, nemo yekhompawundi esetyenzisiweyo. Itheyibhile yobungqina enokuhluzwa, eyakhiwe ngeli thala linye, ihamba neli nqaku.

Yintoni kanye kanye ekweli thala

Amaphepha ali-130 asusela ku-1928 ukuya ku-2026. Alishumi elinesithoba awangaphambi konyaka ka-2000. Iminyaka yoo-2010 yongeze angama-59, eyoo-2020 yongeze angama-29 ukuza kuthi ga ngoku, yaye eyoo-2000 yongeze angama-23.

Ubume bengqokelela bubaluleke ngaphezu kobukhulu bayo. Amaphepha angamashumi amahlanu zizifundo ezenziwe kwizilwanyana ezipheleleyo. Angamashumi amathathu anesine afunda izicwili, iiseli, okanye igazi ngaphandle komzimba. Asibhozo asebenza ngeemitochondria ezikhutshiweyo, amahlanu ziimvavanyo zeemolekyuli okanye zebhayokhemistri, yaye angamashumi amabini anesithoba ziingxelo zokuphonononga, amagqabaza, okanye imbali. Amane anika abantu i-methylene blue. Ngasinye kwezo zifundo zine sifunda i-methylene blue kumavolontiya asempilweni okanye kubantu abadala abasempilweni.

Elo nani alithethi ukuba i-methylene blue ayizange ivavanywe kwizigulana; unyango oluvunyiweyo lwe-methemoglobinemia nolwe-encephalopathy enxulumene ne-ifosfamide lusekelwe ekusetyenzisweni kwayo kwezonyango, okugutyungelwa ngokuyinxenye kuphela leli thala. Lichaza oko umfundi aza kukufumana apha, yaye litshintsha indlela ekufanele ifundwe ngayo yonke enye ingqokelela. Uphando oluninzi ngezilwanyana neeseli lububungqina obulungileyo bendlela esebenza ngayo. Alubobungqina bento eyenzeka emntwini oginya ikhapsuli.

Izifundo ezine ezenziwe ebantwini, kuquka nezo zavelisa iziphumo ezichaseneyo nezazilindelwe

Olona phando lunamandla ebantwini kweli thala luvela kwiqela elinye lophando elisebenza ngokuthatha imifanekiso yobuchopho.

Isilingo esilandelela abathathi-nxaxheba ukusuka ekuqaleni ukuya phambili, esinokwabiwa ngokungakhethiyo, apho abathathi-nxaxheba nabaphandi bengazi ukuba ngubani ofumana ntoni, nesilawulwa nge-placebo, sabhalisa abantu abangamashumi amabini anesithandathu abaneminyaka engama-22 ukuya kuma-62. Banikwa ithamo elinye eliphantsi le-methylene blue ngomlomo okanye i-placebo. Impendulo ye-MRI esebenzayo yanda kwi-insular cortex kumacala omabini obuchopho ngexesha lomsebenzi wokuqwalasela ngokuqhubekayo, nakwi-prefrontal, parietal, ne-occipital cortex ngexesha lomsebenzi wenkumbulo yexesha elifutshane. Iimpendulo ezichanekileyo ngexesha lokukhumbula zenyuka ngeepesenti ezisixhenxe, ngamathuba achaziweyo angu-.01. Kwaelo qela labonisa kwisifundo sesibini esinokwabiwa ngokungakhethiyo, apho abathathi-nxaxheba nabaphandi bengazi ukuba ngubani ofumana ntoni, nesilawulwa nge-placebo, ukuba ithamo elinye eliphantsi elinikwe ngomlomo lanciphisa ukuhamba kwegazi ebuchotsheni kuthungelwano olunxulumene nomsebenzi ngexesha lomsebenzi odibanisa ukubona nokushukuma. Kwangaxeshanye, laqinisa ukunxibelelana kwamacandelo obuchopho ngexesha lokuphumla kwiindawo ezidibanisa ukuqonda oko kubonwayo nenkumbulo. Iingxelo ezipapashiweyo ziku-PubMed 27351678 naku-PubMed 26961091.

Isifundo sesithathu seso iphepha lesishwankathelo ebelinokuthi lisishiye ngaphandle ngokuthe cwaka. Abaphandi base-King's College London banikezela ngamathamo amabini ngomthambo, i-0.5 ne-1 mg ngekhilogram ebantwini, ne-2 ne-4 mg ngekhilogram kwiimpuku. I-methylene blue yanciphisa ukuhamba kwegazi ebuchotsheni ngokubanzi kuzo zombini ezi ntlobo, yanciphisa isantya sokusetyenziswa kweoksijini yimetabolism yobuchopho ebantwini, yaza yanciphisa isantya sokusetyenziswa kweglucose yimetabolism yobuchopho kwiimpuku. Ababhali babelindele okuchaseneyo. Ingcaciso yabo epapashiweyo kukuba la mathamo, nangona efanelekile ekusetyenzisweni kwezonyango, asenokuba akwindawo eyehlayo yegophe le-hormesis elibonisa unxulumano phakathi kwethamo nempendulo. Bakwachaza ukuba amavolontiya asempilweni anemetabolism yobuchopho eqhelekileyo anika indawo encinane yokuphucuka. Ingxelo iku-PubMed 36803299.

Isifundo sesine sibonisa umahluko ocacileyo phakathi kweentlobo. Kwiiseli zesibindi zeempuku nakwiimpuku ezipheleleyo, i-methylene blue yandisa i-oxidation ye-ethanol enophawu lokuyilandela ibe yi-carbon dioxide nge-75 ekhulwini nange-30 ekhulwini, ngokulandelelana. Kumavolontiya asempilweni, anikwe ithamo elisekelwe kwindlela esetyenziswa kwi-encephalopathy enxulumene ne-ifosfamide, ayizange itshintshe nantoni na enokulinganiswa: indlela umzimba ofunxa, usasaza, uguqula, uze ukhuphe ngayo i-ethanol ayizange ichaphazeleke. Aluzange lubonakale notshintsho kumlinganiselo we-lactate ne-pyruvate olwalunokubonisa utshintsho kwimo ye-redox yeeseli. Uvavanyo lweempuku nolwabantu azivumelani, yaye olwabantu alufumananga siphumo. Jonga PubMed 11022014.

Isiqingatha sezifundo zokunikwa kwamathamo ebantwini kweli thala sichaza iziphumo ezingayixhasiyo ingcaciso exhaphakileyo. Izilingo zenkumbulo nokugxila zifanele ukufundwa ngokupheleleyo ngenxa yoko, yaye isizathu sokuba kube nzima ukufihla ukuba ngubani ofumana ntoni kwezi zilingo yingxaki eyahlukileyo nayo.

"Ebantwini" kubandakanya izinto ezimbini ezahlukeneyo

Ngaphandle kwezifundo ezine zokunikwa kwamathamo, amaphepha alishumi asebenza ngezinto ezithathwe emizimbeni yabantu kodwa ezifundwa ngaphandle komzimba, yaye izishwankathelo zidla ngokuzifaka kudidi olunye.

Elinye iqela lagcina izicwili zamafutha ezinxulumene nentliziyo nemithambo yegazi, ezithathwe kwizigulana ezingamashumi amabini anesihlanu ngexesha lotyando lwentliziyo, phantsi kweemeko ezilawulwayo kunye ne-methylene blue kwi-0.1 micromolar kangangeeyure ezingamashumi amabini anesine. Ukubonakaliswa kwee-enzyme ze-monoamine oxidase kwehla, njengoko kwehla nezalathisi zoxinzelelo lwe-oxidation (PubMed 39167271). Oku bubungqina obulungileyo bokuba izicwili zabantu ziyasabela kwi-methylene blue. Akubobungqina bento eyenziwa lithamo kumntu ophilayo, kuba kolu vavanyo akukho nto yajikeleza emzimbeni, yaguqulwa yimetabolism, okanye yakhutshwa ngumzimba.

Kwa-lo mahluko uyasebenza nakulusu. Ii-fibroblast zolusu lwabantu ezithathwe kubanikeli abasempilweni nakwizigulana ezine-progeria zasabela ngcono kwi-methylene blue kunezinye ii-antioxidant ezininzi, ekwandeni kweeseli nasekulibaziseni ukuguga kwazo. Imodeli yolusu lomntu eyakhiwe ngokutsha enemilinganiselo emithathu ayizange ibonise ukucaphuka, kwanaxa kusetyenziswa ukuxinana okuphezulu (PubMed 28559565). Obo bubungqina obunamandla ngokwenene bokulungiselela into esetyenziswa eluswini, kodwa ayisosilingo esenziwe ebantwini. Apho ubungqina bolusu buphelela khona kufanelekile ukufundwa kunye naso.

Apho amaphepha akweli thala aphikisana khona

Iimvavanyo ezimbini ezenziwe ngononophelo azivumelani ngendlela yokusebenza ephindaphindwe kwimibhalo emininzi echaza uphando lwabanye.

Eyokuqala ichaza ukuba i-methylene blue isenokunika ii-elektroni kwi-cytochrome c ize iphucule ukuphefumla kweeseli kwiimitochondria ezinyangwe ngezithinteli ze-complex III. Oku kwavavanywa kwiimitochondria zeempuku ezinkulu, iimpuku ezincinane, neehagu zaseGuinea (PubMed 33669457). Eyesibini ichaza ukuba i-methylene blue ayidluli kumqobo we-complex III obangelwa yi-antimycin kwiimitochondria zobuchopho beempuku ezincinane (PubMed 30734287). Zombini zipapashiwe, zombini zineendlela zophando ezingqongqo, yaye eli thala aliwusombululi lo mahluko. Nayiphi na ingcaciso ethi indlela yokudlula kulo mqobo sele iqinisekisiwe iyakufihla ukungavumelani okusakhoyo. Imephu yeendawo ekujoliswa kuzo kwibhayoloji yeeseli kulapho iinkcukacha zendlela yokusebenza zifanele khona.

Ikhompawundi, neenkcukacha ezingachazwayo ngamaphepha

I-methylene blue ayiyonto enye kule mibhalo yophando. Amaphepha achaza i-methylene blue, i-methylthioninium chloride, i-methylthioninium ekwimo encitshisiweyo, neekhompawundi ezifana ne-phenothiazinium, ezifana ne-toluidine blue. Ezi zine azinakuthathwa njengezisebenza ngokufanayo emzimbeni. Izilingo zesifo sika-Alzheimer ngowona mzekelo ucacileyo woku, kuba inxalenye yaloo nkqubo yasebenzisa imo encitshisiweyo enendlela eyahlukileyo yokufunxwa endaweni yedayi ekwimo ene-oxidation.

Phantse akukho nalinye kumaphepha ali-130 elichaza ibakala lezinto ezisetyenzisiweyo. Amacandelo eendlela zophando achaza umboneleli aze aphelele apho. Idayi yokwenza izicwili zibonakale xa zihlolwa, ikhemikhali esetyenziswa elabhoratri, nesithako esisebenzayo esikumgangatho wamayeza zonke zinokubhalwa njenge-methylene blue kwi-odolo yokuthenga. Umahluko wazo ukukungcola okuhamba nazo. I-Azure B, iintsimbi ezinzima, nezinyibilikisi ezishiyekileyo zezona zixhaphakileyo, yaye umfundi ofuna ukuthelekisa iphepha nemveliso akanakwenza olo thelekiso ngaphandle kwesatifikethi sohlalutyo. Eso sisizathu esibalulekileyo kumfundi sokuba kutheni amabakala ebalulekile, kwanangaphambi kwawo nawuphi na umbuzo wencasa okanye wethamo. Uninzi lwabathengisi abathi bayahambelana nemonografi ye-USP bavavanya kuphela iintsimbi ezinzima baze bakuthathe oko njengeemfuno ezipheleleyo. I-Blupreme ivavanya zonke iimfuno, kuquka ukuqinisekisa ukuba yinto echaziweyo, ukulinganisa umxholo wayo, ukungcola kweekhompawundi ze-organic, izinyibilikisi ezishiyekileyo, ukungcola kwee-elementi, intsalela emva kokutshiswa, imida yeentsholongwane, nee-endotoxin zebhaktiriya, ize ipapashe iziphumo.

Ukusebenzisa itheyibhile

Itheyibhile yobungqina idwelisa onke amaphepha ali-130 kunye nonyaka wawo, ijenali, uhlobo lwesifundo, nento esetyenziswe ngokwenene. Uhlobo lwesifundo lubonisa inqanaba olwenziwa kulo uvavanyo, nto leyo etshintsha ngokukhawuleza njengoko uskrola. Ikholamu yento esetyenzisiweyo ikhona ukuze ukwazi ukujonga ukuba ukuhlelwa kuchanekile na, kuba amaphepha adibanisa amanqanaba, njengelo liqala ngovavanyo lwe-in vitro phambi kokuqinisekisa nge-in vivo, anikwa kuphela inqanaba eliphambili. Unokuhluza ngokohlobo lwesifundo, ukhangele kwizihloko, kwiijenali, nakwiintlobo zezinto eziphilayo, uze uhlele ngokonyaka okanye ngesihloko. Ifayile ye-CSV yale datha inye ikwifolda enye.

Wakuba ukhethe iphepha, obona buchule bunzima kukulifunda: ukuqonda imodeli, into ekuthelekiswa nayo, isiphumo esilinganisiweyo, ixesha, nokungaqiniseki okuvunywayo ngababhali. Indlela yokufunda iphepha elinye lophando nge-methylene blue ichaza oko, yaye esi salathiso siyema ngabom ngaphambi kokungena kuloo nto.

Ukuze ubone, isiphumo ngesiphumo, oko kuxhaswa luphando ebantwini, isishwankathelo sobungqina ebantwini yindawo engcono yokuqala. Eli phepha liphendula umbuzo omxinwa ngakumbi: zeziphi iintlobo zezifundo ezikhoyo, yaye zingaphi kuhlobo ngalunye.