Umtapo wocwaningo lwe-methylene blue: izivivinyo kubantu nezifundo zokuhlola

Ukusesha i-methylene blue kuletha izinkulungwane zamaphepha ocwaningo. Ucwaningo esitsheni saselabhorethri, ucwaningo kumagundane, nocwaningo kumavolontiya angamashumi amabili nesithupha kuvela ohlwini olufanayo, kubukeka kunesisindo esilinganayo. Akunakusetshenziswa esikhundleni sokunye, futhi umehluko phakathi kwakho uvame ukunquma impendulo yombuzo obufike nawo.

Leli khasi liyinkomba kunokuba libe yisinqumo. Lihlela umtapo osebenzayo wamaphepha ocwaningo angu-130 nge-methylene blue ngokwezinto ezine ezishintsha lokho iphepha elingakutshela kona: izinga okwenziwa kulo ukuhlola, iqembu elacwaningwa, indlela yokuyinikeza nomthamo, kanye nohlobo lwenhlanganisela eyasetshenziswa. Ithebula lobufakazi elingahlungwa, elakhiwe ngalo mtapo ofanayo, lihambisana nalesi sihloko.

Okukhona ngempela kulo mtapo

Amaphepha angu-130 asukela ku-1928 kuya ku-2026. Ayishumi nesishiyagalolunye angaphambi konyaka ka-2000. Iminyaka yawo-2010 yaletha angu-59, iminyaka yawo-2020 isingeze angu-29 kuze kube manje, kanti iminyaka yawo-2000 yengeza angu-23.

Ukwakheka kweqoqo kubaluleke ngaphezu kobukhulu balo. Amaphepha angamashumi amahlanu ayizifundo ezisebenzisa izilwane eziphelele. Angamashumi amathathu nane acwaninga izicubu, amaseli noma igazi ngaphandle komzimba. Ayisishiyagalombili asebenzisa ama-mitochondria ahlukanisiwe, amahlanu ayizivivinyo ezingeni lama-molecule noma ze-biochemistry, kanti angamashumi amabili nesishiyagalolunye ayizibuyekezo, imibono noma umlando. Amane anikeza abantu i-methylene blue. Zonke lezi zifundo ezine zicwaninga i-methylene blue kumavolontiya anempilo noma kubantu abadala abanempilo.

Lelo nani alisho ukuthi i-methylene blue ayikaze ihlolwe ezigulini; ukwelashwa okugunyaziwe kwe-methemoglobinemia nokwe-encephalopathy ehlobene ne-ifosfamide kusekelwe ekusetshenzisweni ekwelashweni lo mtapo okubandakanya ingxenye yakho kuphela. Lichaza lokho umfundi azokuthola lapha, futhi lishintsha indlela okufanele kufundwe ngayo lonke iqoqo. Inqwaba yocwaningo ngezilwane namaseli iwubufakazi obuhle bendlela yokusebenza. Ayibona ubufakazi balokho okwenzeka kumuntu ogwinya ikhepsuli.

Izifundo ezine kubantu, kuhlanganise nalezo ezaba nemiphumela ephambene neyayilindelwe

Ucwaningo oluqine kakhulu kubantu kulo mtapo luvela eqenjini elilodwa labacwaningi elisebenza ngezithombe zobuchopho.

Isivivinyo esilandela ababambiqhaza kusukela ekuqaleni kuya phambili, esibahlukanisa ngamaqembu ngokungahleliwe, lapho bobabili ababambiqhaza nabacwaningi bengazi ukuthi ubani othola ini, futhi esiqhathaniswa ne-placebo, sabandakanya abantu abangamashumi amabili nesithupha abaneminyaka engu-22 kuya ku-62. Banikezwa umthamo owodwa ophansi we-methylene blue ngomlomo noma i-placebo. Impendulo ebonakala ku-MRI yokusebenza yanda ku-insular cortex ezinhlangothini zombili ngesikhathi somsebenzi wokugxilisa ukunaka isikhathi eside, kanye nase-prefrontal, parietal nase-occipital cortex ngesikhathi somsebenzi wenkumbulo yesikhathi esifushane. Izimpendulo ezifanele ngesikhathi sokubuyisa imininingwane enkumbulweni zanda ngamaphesenti ayisikhombisa, ngenani elibikiwe lamathuba elingu-.01. Lona lelo qembu labe selibonisa esivivinyweni sesibili, esasisebenzisa ukwabiwa okungahleliwe, ukufihlela bobabili ababambiqhaza nabacwaningi kanye nokuqhathanisa ne-placebo, ukuthi umthamo owodwa ophansi ngomlomo wanciphisa ukugeleza kwegazi ebuchosheni kunethiwekhi ehlobene nomsebenzi ngesikhathi somsebenzi ohlanganisa ukubona nokunyakaza. Ngesikhathi esifanayo, waqinisa ukuxhumana ngesikhathi sokuphumula ezifundeni ezixhumanisa ukubona nenkumbulo. Imibiko eshicilelwe iku-PubMed 27351678 naku-PubMed 26961091.

Ucwaningo lwesithathu yilolo ikhasi elifingqayo elingalushiya ngaphandle buthule. Abacwaningi base-King's College London banikeza imithamo emibili ngomthambo, engu-0.5 no-1 mg ngekhilogremu kubantu, nengu-2 no-4 mg ngekhilogremu kumagundane. I-methylene blue yanciphisa ukugeleza kwegazi ebuchosheni bonke kuzo zombili izinhlobo, yanciphisa izinga lokusetshenziswa komoya-mpilo ebuchosheni babantu, futhi yanciphisa izinga lokusetshenziswa kwe-glucose ebuchosheni bamagundane. Ababhali babebikezele okuphambene nalokhu. Incazelo yabo eshicilelwe ithi le mithamo, nakuba ihambisana naleyo esetshenziswa ekwelashweni, ingase ibe engxenyeni eyehlayo yejika le-hormesis elibonisa ukusabela ngokomthamo, nokuthi kumavolontiya anempilo lapho ukusetshenziswa kwamakhemikhali ebuchosheni kujwayelekile khona, mancane amathuba okuthuthuka. Umbiko uku-PubMed 36803299.

Ucwaningo lwesine lubonisa umehluko ocacile phakathi kwezinhlobo. Kumaseli esibindi samagundane nasemagundaneni aphelele, i-methylene blue yandisa ukuguqulwa kwe-ethanol efakwe umaka yaba yi-carbon dioxide ngenqubo ye-oxidation ngamaphesenti angamashumi ayisikhombisa nanhlanu nangamashumi amathathu, ngokulandelana. Kumavolontiya anempilo, anikezwa umthamo osuselwe ohlelweni olusetshenziselwa i-encephalopathy ehlobene ne-ifosfamide, ayishintshanga lutho olungalinganiswa: indlela umzimba omunca, usabalalisa, uguqula futhi ukhiphe ngayo i-ethanol ayithintekanga, futhi akuvelanga ushintsho esilinganisweni se-lactate ne-pyruvate olwalungabonisa ukushintsha kwesimo se-redox kumaseli. Ukuhlola kumagundane nokuhlola kubantu akuvumelani, futhi ukuhlola kubantu akutholanga mphumela. Bheka i-PubMed 11022014.

Ingxenye yezifundo ezinikeza abantu imithamo kulo mtapo ibika imiphumela engayisekeli incazelo edumile. Izivivinyo zenkumbulo nokugxilisa ukunaka kufanele zifundwe ngokuphelele ngenxa yaleso sizathu, kanti ukuthi kungani kunzima ukufihla ukuthi ubani othola ini kulezi zivivinyo kuyinkinga ehlukile ngokwayo.

Elithi "kubantu" lihlanganisa izinto ezimbili ezihlukene

Ngaphandle kwezifundo ezine zokunikeza imithamo, amaphepha ayishumi asebenzisa amasampula avela kubantu ngaphandle komzimba, futhi izifinyezo zivame ukuwahlanganisa esigabeni esifanayo.

Iqembu elilodwa lagcina izicubu zamafutha ezihlobene nenhliziyo nemithambo yegazi, ezazithathwe ezigulini ezingamashumi amabili nanhlanu ngesikhathi sokuhlinzwa kwenhliziyo, endaweni elawulwayo ene-methylene blue engu-0.1 micromolar amahora angamashumi amabili nane. Ukukhiqizwa kwama-enzyme e-monoamine oxidase kwehla, kanjalo nezinkomba zokucindezeleka okubangelwa yi-oxidation (PubMed 39167271). Lobu ubufakazi obuhle bokuthi izicubu zabantu ziyasabela ku-methylene blue. Akubona ubufakazi bokuthi umthamo wenzani kumuntu ophilayo, ngoba kulokho kuhlola kwakungekho lutho olujikeleziswa ngumzimba, oluguqulwa yizinqubo zawo noma olukhishwa kuwo.

Umehluko ofanayo uyasebenza nasesikhumbeni. Ama-fibroblast esikhumba sabantu athathwe kubanikeli abanempilo nasezigulini ezine-progeria asabela kangcono ku-methylene blue kunakwezinye izivimbeli ze-oxidation eziningana, kokubili ekwandeni kwawo nasekubambezelekeni kokuguga kwamaseli. Imodeli yesikhumba somuntu eyakhiwe kabusha enobukhulu obuthathu ayizange ibonise ukucasuka ngisho nasemazingeni aphezulu okugxila kwenhlanganisela (PubMed 28559565). Lobu ngempela ubufakazi obuqinile bomkhiqizo ogcotshwa esikhumbeni, kodwa akukabi yisivivinyo kubantu. Lapho ubufakazi besikhumba buphelela khona kufanele kufundwe kanye nalokhu.

Lapho amaphepha akulo mtapo ephikisana khona

Ukuhlola okubili okwenziwe ngokucophelela akuvumelani ngendlela yokusebenza ephindaphindwe emibhalweni eminingi echaza ucwaningo lwabanye.

Olokuqala lubika ukuthi i-methylene blue isengakwazi ukwenza i-reduction ye-cytochrome c futhi ithuthukise ukuphefumula kuma-mitochondria aphathwe ngezivimbeli ze-complex III, lapho kuhlolwa ama-mitochondria amagundane amakhulu, amagundane amancane nezingulube zaseGuinea (PubMed 33669457). Olwesibili lubika ukuthi i-methylene blue ayikwazi ukudlula ukuvinjwa kwe-complex III yi-antimycin kuma-mitochondria obuchopho bamagundane amancane (PubMed 30734287). Kokubili kushicilelwe, kokubili kusebenzisa izindlela zocwaningo eziqinile, futhi lo mtapo awukuxazululi ukuphikisana kwakho. Noma iyiphi incazelo eyethula le ndlela yokudlula ukuvinjwa njengeseqinisekisiwe isuke ifihle ukuphikisana okusavulekile. Imephu yezinto eziqondiswe yi-methylene blue kubhayoloji yamaseli iyindawo efanele imininingwane yendlela yokusebenza.

Inhlanganisela, nemininingwane amaphepha ayishiyayo

I-methylene blue ayiyona into eyodwa kule mibhalo yocwaningo. Amaphepha abika i-methylene blue, i-methylthioninium chloride, i-methylthioninium esesimweni se-reduction, kanye nezinhlanganisela ezihlobene ne-phenothiazinium njenge-toluidine blue, futhi lezi ezine azinakusetshenziswa esikhundleni sokunye emzimbeni. Izivivinyo zesifo i-Alzheimer's ziyisibonelo esicace kakhulu salokhu, ngoba ingxenye yalolo hlelo yasebenzisa uhlobo olusesimweni se-reduction, olumuncwa ngendlela ehlukile, kunodayi osesimweni se-oxidation.

Cishe awekho kwamaphepha angu-130 asho izinga lekhwalithi yento ayisebenzisile. Izigaba ezichaza izindlela zocwaningo zisho umhlinzeki bese ziphelela lapho. Udayi wokuhlonza izicubu, ikhemikhali yaselabhorethri esetshenziswa ekuhloleni, nesithako esisebenzayo sezinga lekhwalithi lezemithi konke kungabhalwa ngokuthi i-methylene blue ku-oda lokuthenga, kodwa kuhluka ngokuqondile ngokungcola okuhambisana nakho. I-Azure B, izinsimbi ezisindayo nezinsalela zezincibilikisi yikona okuvamile, futhi umfundi ofuna ukuqhathanisa iphepha nomkhiqizo akanakwenza lokho ngaphandle kwesitifiketi sokuhlaziywa. Leso yisizathu esibalulekile kumfundi sokuthi amazinga ekhwalithi abaluleke, ngaphambi kwanoma yimuphi umbuzo wokunambitheka noma womthamo. Abathengisi abaningi abathi bathobela i-monograph ye-USP bahlola izinsimbi ezisindayo kuphela bese bethatha lokho njengayo yonke imibandela. I-Blupreme ihlola yonke imibandela, kuhlanganise nobunikazi, ukuhlolwa kwesilinganiso sesithako, ukungcola kwezinhlanganisela eziphilayo, izinsalela zezincibilikisi, ukungcola kwezakhi zamakhemikhali, insalela ngemva kokushiswa, imikhawulo yamagciwane nezinye izinto ezincane eziphilayo, kanye nama-endotoxin amagciwane, bese ishicilela imiphumela.

Ukusebenzisa ithebula

Ithebula lobufakazi libala wonke amaphepha angu-130 kanye nonyaka wawo, ijenali, uhlobo locwaningo nento eyasetshenziswa ngempela. Uhlobo locwaningo lubhala izinga okwenziwa kulo ukuhlola, okuyisici esishintsha ngokushesha kakhulu njengoba uskrola. Ikholomu yento esetshenzisiwe ikhona ukuze ukwazi ukuhlola ukuhlukaniswa, ngoba amaphepha ahlanganisa amazinga, njengalelo elenza ukuhlola ngaphandle komzimba ngaphambi kokuqinisekisa emzimbeni ophilayo, anikwa izinga eliyinhloko kuphela. Ungahlunga ngohlobo locwaningo, useshe izihloko, amajenali nezinhlobo zezinto eziphilayo, futhi uhlele ngonyaka noma ngesihloko. Ifayela le-CSV ledatha efanayo likufolda efanayo.

Uma usukhethe iphepha, ikhono elinzima kakhulu ukulifunda: ukuhlonza imodeli, into yokuqhathanisa, umphumela olinganiswayo, isikhathi, nokungaqiniseki ababhali abakuvumayo. Indlela yokufunda iphepha elilodwa locwaningo nge-methylene blue ichaza lokho, futhi le nkomba ima ngaphambi kwalokho ngamabomu.

Ukuze ubone lokho ucwaningo kubantu olukusekelayo ngomphumela ngamunye, ukubuka konke kobufakazi kubantu kuyindawo engcono yokuqala. Leli khasi liphendula umbuzo olinganiselwe kakhulu: yiziphi izinhlobo zocwaningo ezikhona, nokuthi zingaki zohlobo ngalunye.