Methylene blue mu myitozo no kugarura imbaraga: ibyapimwe koko

Muri Werurwe 2022, umukinnyi wo ku rwego rwo hejuru wiruka marato yashyize ku mbuga ubutumwa bwamamaza yishyuriwe, ashyigikira ikinini cya methylene blue kiyengera mu kanwa. Yavuze ko “gishobora gufasha kongera ubushobozi bwo kwibanda ku kintu, kwihanganira imyitozo no gusinzira”, kandi ko yagikoreshaga mbere y'imyitozo ikomeye. Muri icyo cyumweru, abaganga bavuzwe mu binyamakuru byo ku rwego rw'igihugu basobanuye uwo muco wari ukwirakwira nk'abantu bafite abayoboke benshi ku mbuga nkoranyambaga banywera umuti wo gusukura ibigega by'amafi. Nta ruhande muri izo ebyiri rusubiza ikibazo nyacyo uwiruka aba afite.

Ese hari uwigeze guha abantu methylene blue akapima intera bagezeho, umuvuduko bagenderagaho, cyangwa uko bagaruye imbaraga? Ishakisha ryakozwe ku bw'iyi nyandiko ntiryabonye ubushakashatsi na bumwe bugenzurwa ku bantu bwapimye ubushobozi mu myitozo cyangwa kugarura imbaraga. Gukurikirana inyandiko zagiye zitangwaho ibimenyetso biganisha ku moko atatu y'inyamaswa, uburyo butandukanye bwo gutegura ibipimwa muri laboratwari, n'ikinyabutabire kimwe kitari methylene blue na gato.

Kwihanganira imyitozo, kugarura imbaraga, n'uburyo ikinyabutabire gikora ni ibintu bitandukanye

Igipimo gishobora guhinduka mu cyerekezo gitandukanye n'ubushobozi mu myitozo, cyangwa kigahinduka ubushobozi bwo butahindutse na gato. Ibyo si akantu ka tekiniki gusa: ni byo byagaragaye neza mu bushakashatsi kuri methylene blue n'imyitozo buvugwa cyane kurusha ubundi.

Ubushakashatsi ku mbwa bwakoresheje irindi rangi

Inyandiko ikunze gutangwaho ibimenyetso kuri methylene blue n'imyitozo ni ubushakashatsi bwa Imai na bagenzi be bwo mu 1986 ku mbwa zari maso ziruka ku mashini yo kwirukiraho. Bwapimye niba ukwiyongera kw'amaraso umutima wohereza mu gihe cy'imyitozo guterwa n'imiterere y'ihinduranyamakuru rya elegitoroni mu ngirangingo, hakoreshejwe icyo igice gisobanura uburyo ubushakashatsi bwakozwe cyita “4 mg/kg za new methylene blue 3,7-bis(ethylamino)-2,8-dimethylphenazothonium chloride, Eastman Kodak Company”. New methylene blue ni irindi rangi ryo mu muryango wa thiazine, rifite amatsinda abiri ya ethylamino aho methylene blue ifite amatsinda abiri ya dimethylamino, kandi rizwi cyane nk'irangi rikoreshwa mu gusiga reticulocytes. Igisubizo cyabonetse hakoreshejwe iryo rangi si igisubizo cyabonetse hakoreshejwe methylene blue.

Ubwo bushakashatsi buracyafite agaciro, kuko ari bwo bwerekana neza cyane ko igipimo n'imikorere y'umubiri bishobora guhinduka ukwabyo. Imbwa zirutse mu byiciro bibiri by'iminota 20, ku muvuduko wa 2.5 hanyuma wa 5.0 mph, ahazamuka ku gipimo cya 6 ku ijana. Imyitozo yikubye kabiri ingano y'amaraso umutima wohereza, kandi yongereye ogisijeni ikoreshwa n'umubiri wose inshuro eshatu kugeza kuri enye mu matsinda yombi. Mu itsinda ryahawe umuti w'amazi arimo umunyu, igipimo cya lactate ugereranyije na pyruvate mu maraso yo mu mitsi ivana amaraso mu mutima cyavuye kuri 6.0 kigera kuri 9.97. Mu itsinda ryahawe irangi, nticyazamutse.

Nta gipimo na kimwe cy'imikorere cyahindutse. Umuvuduko w'umutima, umuvuduko w'amaraso mu mitsi iyavana mu mutima, ubushobozi bw'icyumba cy'ibumoso cyo hasi cy'umutima bwo kwikanya, na catecholamines zo mu gice cy'amazi cy'amaraso byose byazamutse kimwe mu matsinda yombi. Kandi isano hagati y'ingano y'amaraso umutima wohereza na ogisijeni ikoreshwa n'umubiri wose ntiyagaragaje itandukaniro mu mibare y'ibarurishamibare. Abanditsi bashoje bavuga ko impinduka muri icyo gipimo “atari zo zitera kwiyongera kw'imikorere y'itembera ry'amaraso kuba mu myitozo yoroheje kugeza ku iringaniye.”

Icyo gipimo ntigifite uburemere bw'ikimenyetso umuntu yakwibwira. Cyaragabanutse kuko pyruvate yazamutse, iva kuri 0.14 igera kuri 0.38 mmol kuri litiro, mu gihe lactate na yo yazamutse, iva kuri 1.05 igera kuri 2.85 mmol kuri litiro. Mu mbwa zahawe irangi ziruhutse, ogisijeni yakoreshwaga yazamutse ho gato, pH y'amaraso yo mu mitsi ivana amaraso mu mutima irazamuka, na diyokiside ya karuboni iragabanuka. Abanditsi bita izo mpinduka “izisa” n'iziterwa na 2,4-dinitrophenol, ikinyabutabire gitandukanya guhumeka kwa mitokondiriya no gukora ATP. Umuvuduko wari wagenwe n'amabwiriza y'igerageza, bityo nta mbwa yigeze yirukishwa kugeza inaniwe burundu.

Ubushakashatsi ku mbeba nini zoga, n'ingano y'ikinyabutabire zahawe

Igisubizo gikomeye kurusha ibindi ku bushobozi bw'inyamaswa mu myitozo kiva mu igerageza rya Peng na bagenzi be ryo mu 2025 ryasohotse muri Frontiers in Behavioral Neuroscience. Imbeba nini zogaga amajoro icumi akurikirana, zifite imitwaro ingana na 3 ku ijana by'ibiro byazo iboshye ku mirizo yazo, nibura amasaha abiri buri joro, kugeza zigeze ku rwego rwo kunanirwa burundu rwagenwaga n'amanota. Nyuma ya buri cyiciro, itsinda rimwe ryahabwaga methylene blue mu mazuru, irindi rigahabwa umuti w'amazi arimo umunyu muri ubwo buryo. Imbeba zahawe methylene blue zogaga igihe kirekire mbere yo kuzuza ibipimo byo kunanirwa burundu, zikagendagenda cyane ahantu hafunguye ku munsi ukurikira, zikagaragaza imyitwarire isa n'iy'ihungabana rito. Zanagize igabanuka rito ry'uturemangingo tw'imyakura, iyangirika rito rya myelin, n'icikagurikamo rito rya mitokondiriya muri hippocampus na striatum.

Ingano zahawe ikunze kutavugwa iyo ubwo bushakashatsi busubirwamo. Umuti ufite igipimo cya 1 ku ijana uba urimo 10 mg/mL; microlitres icumi zashyizwe muri buri zuru, bityo igiteranyo cyari hafi microlitres 20, cyangwa 0.2 mg kuri buri mbeba muri buri cyiciro. Gutanga ikinyabutabire mu mazuru bihitwamo kugira ngo kigere mu bwonko kinyuze mu nzira z'imyakura y'impumuro n'iya trigeminal. Abanditsi bavuga ko ubushakashatsi bwabo “butapimye impinduka ziterwa na ogisidasiyo, kubyimbirwa, cyangwa urugero rw'imisemburo mu bwonko no mu gice cy'amazi cy'amaraso.” Intambwe ikurikira basaba ni ukwiga “ingaruka zose zo gufata MB nk'inyongera mbere y'imyitozo.”

Ibyo ni byo uwiruka yakwifuza ko bipimwa. Muri aya mabwiriza y'igerageza, ikinyabutabire cyatanzwe nyuma y'imyitozo kugira ngo kigabanye kwangirika. Kuba imbeba zinaniwe cyane zaroze igihe kirekire ku munsi ukurikira ni igisubizo kijyanye no kugarura imbaraga, si igisubizo ku muntu usanzwe atoza umubiri ufata ikinyabutabire mbere y'imyitozo.

Aho ijambo “kwihanganira imyitozo” ryaturutse

Ubushakashatsi ku mbeba nto bukunze gusobanurwa nk'ubwo bwagaragaje kongera ubushobozi bwo kwihanganira imyitozo ni ubushakashatsi bwa Gureev na bagenzi be bwo mu 2016 bwasohotse muri Neuroscience Research. Imbeba nto zanyoye amazi arimo methylene blue ku gipimo cya 15 mg/kg ku munsi mu minsi 60. Icyiswe “ubushobozi bw'umubiri bwo kwihanganira imyitozo” ni igerageza ryo kwihambira ku mugozi cyangwa ku tubari dutambitse, ritanga amanota ahuriza hamwe imbaraga zo gufata, guhuza ingendo z'umubiri, no kudahungabana. Imbeba zigeze mu myaka yo hagati zitahawe ikinyabutabire zagize amanota 1.17; izagihawe zagize 2.23, hafi y'urwego rw'imbeba zikuze. Imbeba zikuze ntizagaragaje iterambere muri kimwe muri ibyo.

Ogisijeni yakoreshwaga ziruhutse yiyongereye hafi 15 ku ijana. Ikorwa rya perogiside ya hidurojeni muri mitokondiriya zo mu bwonko ryavuye kuri 94.9 rigera kuri 176.7 pmol ku munota kuri miligarama ya poroteyine. ADN ya mitokondiriya yiyongereye inshuro 2.3. Ibyo ni ukwiyongera kw'isimburana rya mitokondiriya mu nyamaswa zisaza, hamwe n'ubutumwa bwo mu turemangingo bushingiye kuri ogisidasiyo bubitera. Si ikimenyetso cy'uko umukinnyi ufite ubuzima bwiza yakwihuta kurushaho.

Amagerageza ku turemangingo, n'aho agarukira

Louters na bagenzi be batangaje mu 2005 ko methylene blue ituma gutwara glucose binyuze muri GLUT1 mu turemangingo twa fibroblast L929 byiyongera kugeza kuri 800 ku ijana ku gipimo cya micromolar 50. Ubushakashatsi bwakurikiyeho mu 2008 bwagaragaje ko methyl-beta-cyclodextrin yifatanya na methylene blue ubwayo, ikabuza iyo ngaruka. Icyo ni igisubizo ku bwoko bw'uturemangingo buhingwa muri laboratwari; nticyigeze kigaragazwa mu mitsi ihuza amagufwa.

N'uburyo ikora ubwabwo buracyagibwaho impaka

Mu bushakashatsi bwa Tretter na bagenzi be bwo mu 2014 kuri mitokondiriya zatandukanijwe n'ubwonko bw'imbeba zo mu bwoko bwa guinea pig, methylene blue ku gipimo cya nanomolar 100 kugeza kuri micromolar 1 yongereye ogisijeni ikoreshwa mu gihe cyo kuruhuka, igarura itandukaniro ry'amashanyarazi ku gihu n'ikorwa rya ATP igihe urusobe I cyangwa urusobe III rwari rwahagaritswe, kandi yongera ikorwa rya perogiside ya hidurojeni. Icy'ingenzi ni uko “guhumeka gushishikarizwa na ADP kutahinduwe na MB kuri na kimwe mu binyabutabire byifashishwaga” byapimwe. Guhumeka kwinshi gushoboka gufatanye n'ikorwa rya ATP, ari na ko ibyemezo ku myitozo bishingiraho, ntikwiyongereye.

Mu bushakashatsi bwa Gureev na bagenzi be bwakurikiyeho mu 2019, laboratwari imwe n'iyabonye igisubizo ku mbeba nto yasanze methylene blue “idashobora kugarura itandukaniro ry'amashanyarazi ku gihu no guhumeka byahagaritswe na antimycin” muri mitokondiriya zo mu bwonko bw'imbeba nto. Yashoje ivuga ko ahakira elegitoroni ari ahitwa Qo mu rusobe III, aho kuba ahandi haza nyuma muri urwo ruhererekane. Igitekerezo cyoroshye cy'uko irangi ritwara elegitoroni rikazambutsa ahahagaritswe mu ruhererekane rw'imikorere yo guhumeka ntigikora mu buryo bwose ibipimwa biba byateguwe.

Nta na kimwe muri ibi gihamya ko nta ngaruka yaba ku bantu. Ariko bivuze ko impamvu ishingiye gusa ku buryo ikinyabutabire gikora, aho imikorere y'ubutabire bwa mitokondiriya ishoboka ifatwa nk'igisubizo cyamaze kuboneka, ifite ibibazo no muri ubwo buryo bwo gukora ubwabwo.

Ibibazo bibiri mu gutegura igerageza ku bantu byakenera gukemurwa

Biragoye guhisha methylene blue mu igerageza. Ihindura inkari ubururu buvanze n'icyatsi, kandi abantu barabibona. Igerageza ryo mu 2017 aho abitabiriye basimburanaga ku buryo bwo kuvurwa indwara y'ihindagurika rikabije ry'amarangamutima ryabivuze mu buryo bweruye: “Twahisemo ubu buryo kuko methylene blue ihindura ibara ry'inkari, bityo ntitwashoboraga gukoresha umuti w'igerageza udafite ikinyabutabire gikora usanzwe ukoreshwa.” Iryo gerageza ryagereranyije ingano nto n'ingano nini, aho kugereranya n'ikinini kidafite ikinyabutabire gikora.

Iki kibazo kirakomeye cyane mu bushakashatsi ku myitozo kurusha hafi ahandi hose, kuko uko umuntu yumva uburemere bw'imyitozo n'ubushobozi bwo kurangiza intera mu gihe gito bigirwaho ingaruka zikomeye n'ibyo aba yiteze. Igerageza ridashobora guhisha abaryitabiriye ibyo bahawe riba ryapimye ibyo bemera ku rugero rungana n'uko ryapimye umuti.

Hari igisubizo cyanditswe. Igerageza ryo mu 2016 ryakoresheje amashusho y'ubwonko, rigabanya abantu bakuru 26 bafite ubuzima bwiza mu matsinda hakoreshejwe tombola ryatanze 280 mg za methylene blue yujuje urugero rwa USP, hafi 4 mg/kg, cyangwa umuti w'igerageza udafite ikinyabutabire gikora urimo irangi ry'ibiribwa FD&C blue no. 2. Byashyizwe mu bikoresho by'imiti bisa kandi bitabonerana, maze abitabiriye basabwa kunyara mbere yo gufata ibyo bahawe, ariko ntibongere kunyara, “kugira ngo ibara iryo ari ryo ryose ry'inkari ritabangamira ihishwa ry'ibyo bahawe.”

Ikibazo cya kabiri ni ingano itangwa n'inzira itangwamo. Igice cya methylene blue ifatwa mu kanwa gisohokera mu nkari, kandi ingano igera mu bwonko iyo ifashwe mu kanwa ni hafi kimwe cya kabiri cy'igera mu bwonko iyo itanzwe mu mutsi, nk'uko itsinda rya Gureev ribivuga ritanga ubushakashatsi bwa Peter na bagenzi be ku buryo umuti ugenda mu mubiri nk'ikimenyetso. Kuyitanga mu mazuru y'imbeba ntibihwanye no kuyitanga mu kinini, kandi ingano zahawe abantu mu bushakashatsi bwasohotse ziri hagati ya 0.5 na 4 mg/kg. Igerageza ry'amashusho y'ubwonko ryo mu 2016 ryavuze ko hejuru ya 10 mg/kg habonetse ingaruka zinyuranye.

Ubushakashatsi ku bantu bupima ibindi

Amagerageza abiri agenzurwa ku bantu agaragara mu nkuru zisubiramo iyi ngingo, kandi nta na rimwe ryapimye imyitozo. Mu igerageza ry'amashusho y'ubwonko ryo mu 2016, igihe cyo kwitabira igisaba kuba maso nticyagaragaje imikoranire ifatika hagati y'umuti n'igihe. Ku bahawe umuti w'igerageza udafite ikinyabutabire gikora, cyari milisegonda 230 hanyuma 220; ku bahawe methylene blue, cyari milisegonda 230 hanyuma 230, P = .43. Mu bushakashatsi bwo mu 2023 ku bagore umunani bafite ubuzima bwiza bahawe ikinyabutabire mu mutsi, amaraso atembera mu bwonko n'umuvuduko ubwokoresherezamo ogisijeni byombi byaragabanutse aho kwiyongera. Inyandiko iyobora ku bimenyetso byerekeye imbaraga n'umunaniro isobanura ubwo bushakashatsi bwombi.

Niba uhisemo kuyigerageza nubwo bimeze bityo

Kwigeragerezaho ntibizemeza ko ikora, ariko ushobora kwandika amakuru yabyo neza bihagije kugira ngo wirinde kwishuka. Andika igicuruzwa n'icyiciro cyacyo cyakozwe, inzira wagifatiyemo, igihe wagifatiye mbere y'imyitozo, imyitozo nyayo wakoze n'intera cyangwa umutwaro, uburemere bw'imyitozo wumvise ku gipimo gifite imibare, ibitotsi, kafeyine n'imiti yose wafashe, n'ububabare bwo ku munsi ukurikira hamwe n'ubushobozi nyuma y'amasaha 48 mu bwoko bumwe bw'imyitozo. Hanyuma usubiremo iyo myitozo utagikoresheje.

Umuntu umwe ukurikirana ikintu kimwe ntashobora gutandukanya ingaruka z'umuti n'urwego rw'imbaraga z'umubiri, ubushake, ikirere, n'ihindagurika risanzwe ryo mu myitozo. Igice gishingiye ku byo umuntu yiyumvamo ni cyo gishobora kumuyobya cyane kurusha ibindi.

Methylene blue ifite kandi ibyago bidafite aho bihuriye n'ubushobozi mu myitozo. Ibuza imikorere ya monoamine oxidase A, bikayishyira mu miti igomba kwitabwaho hamwe n'imiti yandikirwa kuvura agahinda gakabije n'indi miti ikora kuri serotonine. Ntigomba kandi gukoreshwa ku bafite ibura rya G6PD kubera ibyago byo kugira amaraso make biturutse ku isenyuka ry'uturemangingo dutukura tw'amaraso. Inyandiko iyobora ku mutekano isobanura ibyo byombi, naho inyandiko iyobora ku mikoranire y'imiti igashyira ibibazo byerekeye imiti mu byiciro byayo. Niba witabira amarushanwa agengwa n'amategeko abuza gukoresha ibinyabutabire byongera ubushobozi, reba ayo mategeko aho kwishingikiriza ku byo umucuruzi avuga.

Ubwiza bw'ikinyabutabire ni ikintu gihinduka muri buri bushakashatsi bwavuzwe haruguru

Buri ngano yavuzwe hano yari ingano yapimwe y'ikinyabutabire cyasobanuwe neza. Icupa rivuye ku mucuruzi utagenzuwe si cyo kimwe. Kuzuza ibisabwa n'inyandiko ya USP igena ibiranga icyo kinyabutabire ni urugero umuguzi ashobora kugenzura. Ikinyabutabire kitabyujuje gishobora kuba ari icyagenewe gusiga imyenda, kikaba gishobora kuba kirimo imyanda y'ibinyabutabire birimo karuboni nka Azure B, ibisigazwa by'ibishongesha, n'ibyuma biremereye ku ngano ibisabwa ku binyabutabire byo gukora imiti bigenzura. Icyo izina USP ryemeza n'icyo ritemeza gisobanura urwego rw'ubwiza, naho uburyo bwo gupima imyanda irimo bugasobanura ibyo laboratwari ishakisha.

Abacuruzi benshi bavuga ko igicuruzwa cyabo cyapimwe n'urundi ruhande bigenga bapima ibyuma biremereye gusa, hanyuma bakerekana iryo tsinda rimwe ry'ibizamini nk'aho ryuzuza ibisabwa byose. Blupreme ipima ibisabwa byose bya USP: umwirondoro w'ikinyabutabire, ubuziranenge, imyanda y'ibinyabutabire birimo karuboni, ibisigazwa by'ibishongesha, imyanda y'ibintu shingiro by'ubutabire, ibisigazwa nyuma yo gutwikwa, ingano ntarengwa z'udukoko, n'uburozi bwa bagiteri bwa endotoxins. Buri cyiciro cyakozwe cyoherezwa gifite icyemezo cy'isesengura, kandi kugisoma neza bisaba guhuza nomero y'icyiciro cyakozwe na laboratwari n'icupa ufite.

Umwanzuro

Nta bushakashatsi bugenzurwa ku bantu bwigeze bupima methylene blue ku bushobozi bwo kwihanganira imyitozo, umuvuduko, imbaraga, cyangwa kugarura imbaraga. Ubushakashatsi ku mbwa butangwaho ikimenyetso cy'ingaruka kuri lactate bwakoresheje irindi rangi kandi ntibwabonye itandukaniro mu bushobozi mu myitozo. Ubushakashatsi ku mbeba nini zoga bwatanze 0.2 mg mu mazuru nyuma y'imyitozo. Ubushakashatsi ku mbeba nto bwatumye hakoreshwa ijambo “kwihanganira imyitozo” bwakoresheje igerageza ry'imbaraga zo gufata no guhuza ingendo z'umubiri mu nyamaswa zisaza, kandi uburyo ikinyabutabire gikora buracyagibwaho impaka mu nyandiko z'ubushakashatsi kuri mitokondiriya.

Hasigara rero uburyo bwo gukora bushoboka, ibisubizo by'ubushakashatsi buto butandukanye ku nyamaswa, ikibazo kimwe cyo gutegura ubushakashatsi gifite igisubizo cyanditswe, kandi nta makuru ku bushobozi bw'abantu mu myitozo. Isuzuma ry'ibimenyetso by'inyungu ku bantu rishyira ibyemezo ku myitozo iruhande rw'izindi nyandiko z'ubushakashatsi ku bantu, naho ububiko bw'ubushakashatsi bugashyira ku rutonde ubushakashatsi buri cyemezo gishingiraho.

Niba witoza kugira ngo ugere ku kintu runaka, ikintu gifite ibimenyetso bikomeye kurusha ibindi bigishyigikira ni imyitozo ubwayo.