Methylene blue ku burwayi bw'ubwonko buterwa na ifosfamide: isesengura ry'ibimenyetso

Ifosfamide ni umuti ukoreshwa cyane mu kuvura kanseri, ukora wongeka amatsinda ya alkyl ku mamolekile. Ukoreshwa kuri sarcoma, lymphoma, kanseri y'inkondo y'umura na kanseri y'ibihaha, n'izindi. Mu barwayi bake, utera ikintu giteye impungenge: nyuma y'amasaha cyangwa iminsi umuti utangiye gutangwa mu mutsi, umurwayi agira urujijo, akabura ituze, agasinzira cyane, rimwe na rimwe akagaragaza ihungabana rikomeye ryo gutekereza cyangwa ntabe agisubiza. Amashusho y'ibizamini akenshi nta kibazo agaragaza. Hanyuma, mu bihe byinshi, ibyo bimenyetso birashira mu minsi mike umuti uhagaritswe. Abaganga bavura kanseri babyita uburwayi bw'ubwonko buterwa na ifosfamide. Kuba budashobora guteganywa ni byo bituma raporo yo mu myaka ya 1990 yavugaga ko irangi ry'ubururu ryabukuyeho ikiganirwaho no muri iki gihe mu byumba by'abarwayi.

Ikibazo iyi nyandiko isubiza kirihariye. Ese methylene blue ivura cyangwa ikumira ubwo burwayi bw'ubwonko, kandi ibimenyetso bibishyigikira birakomeye ku rugero rungana iki? Igisubizo kigufi ni uko inkuru z'abatabawe zitangaje, ariko ibimenyetso bidakomeye, kandi ibyo kuyikoresha mu gukumira byo bikaba bidakomeye kurushaho. Iryo tandukaniro ni ingenzi kuko iki ari icyemezo gifatirwa mu bitaro mu gihe cy'igitutu, si icyemezo cyo gufata inyongera gifatirwa mu rugo.

Uko ubwo burwayi bw'ubwonko bugaragara

Ibimenyetso bikunze gutangira mu gihe ifosfamide irimo gutangwa mu mutsi cyangwa nyuma yaho gato: kutamenya aho uri cyangwa igihe urimo, kubura ituze, kubona cyangwa kumva ibitariho, gusinzira cyane, rimwe na rimwe gufatwa n'ibicuri cyangwa kujya muri koma. EEG akenshi igaragaza ko imikorere y'amashanyarazi y'ubwonko igenda buhoro mu bice byinshi. Ibyago byiyongera iyo hakoreshejwe ingano nini y'umuti, umuti ugatangwa vuba mu mutsi, impyiko zidakora neza, albumin iri hasi, hari uburwayi bw'ubwonko bwabanje, cyangwa hafatwa n'indi miti itera gusinzira. Akenshi ibi bimenyetso birashira mu munsi umwe kugeza kuri itatu hakoreshejwe gusa ubuvuzi bwo gushyigikira umurwayi, nubwo hari abarwara bikomeye cyangwa bikamara igihe kirekire, kandi kongera guhabwa ifosfamide bishobora gutuma byongera kubaho.

Uko ubu burwayi busanzwe bugenda ni byo ugomba kubanza gusobanukirwa mbere yo gusoma raporo iyo ari yo yose yerekeye methylene blue. Umuti watanzwe ku munsi wa kabiri w'urujijo, umurwayi agakira ku munsi wa gatatu, ushobora kuba nta cyo wakoze na busa. Buri cyemezo kivugwa hano kigomba kugereranywa n'uko umurwayi ashobora gukira atawuhawe.

Aho igitekerezo cyo gukoresha methylene blue cyaturutse

Mu 1994, itsinda ry'i Bern ryatangaje ibyabonetse mu nkari z'abarwayi bahabwaga ifosfamide, byasaga n'indwara idakunze kuboneka iterwa n'uruhererekane rwo mu muryango kandi ibangamira ihererekanywa ry'elekitironi muri mitokondiriya. Harimo aside glutaric na sarcosine birenze urugero. Iryo tsinda ryasobanuye kandi uko uburwayi bw'ubwonko bwashize vuba nyuma yo gutanga methylene blue, muri raporo ngufi yo muri Lancet. Isesengura ryakurikiyeho ry'uburyo ikora ryatanze uburyo butatu bukorera hamwe, aho gutanga bumwe gusa.

Ubwa mbere, ifosfamide isenyagurirwa mu mwijima ikabyara chloroethylamine nyinshi, ihura na cysteine bikabyara ikinyabutabire gifite imiterere y'uruziga kirimo soufre, cyitwa thialysine ketimine. Icyo kinyabutabire kibangamira flavoproteins ziri mu ruhererekane rw'imikorere yo guhumeka rwa mitokondiriya, kigahagarika okisidasiyo isanzwe ya NADH. Methylene blue, nk'ikindi kinyabutabire cyakira elekitironi, ishobora gusimbura intambwe yahagaritswe. Icyo gisobanuro cyakuwe ku buryo yari isanzwe ikoreshwa mu bwoko bumwe na bumwe bw'indwara ituma aside glutaric iba nyinshi mu nkari.

Ubwa kabiri, urwo ruhererekane rwa redox rwahagaritswe hamwe na aldehyde nyinshi zituruka ku gutunganywa kwa ifosfamide mu mubiri bigabanya igipimo cya NAD ugereranyije na NADH. Ibyo bibangamira ikurwaho rya aldehyde n'ikorwa rya glucose. Methylene blue yongera gukora okisidasiyo ya NADH ikayihindura NAD, igasubizaho igice cy'ubwo buringanire. Ubwo buryo bwo guhererekanya elekitironi muri redox ni na bwo bushingirwaho mu bindi bikorwa byinshi bivugwa ko ishobora kugira mu ngirabuzimafatizo. Birakwiye gusobanukirwa ukwabyo ihame rusange ry'uko methylene blue ihererekanya elekitironi, ritandukanyijwe n'ubu buryo bwihariye ikoreshwa mu buvuzi.

Ubwa gatatu, methylene blue ibangamira imisemburo ya amine oxidase, iyo itabangamiwe yahindura chloroethylamine ikayigira chloroacetaldehyde. Icyo ni ikinyabutabire gituruka ku itunganywa ry'umuti, kigira ingaruka mbi zitaziguye ku myakura no ku mpyiko, kandi kiboneka kidafashe ku zindi molekile muri plasma y'abarwayi bahabwa ifosfamide. Chloroacetaldehyde nkeya bivuga kwangirika gukurikiraho kuba guke, harimo no kugabanuka kw'ibangamirwa rya okisidasiyo y'aside z'ibinure ryagaragajwe muri mitokondiriya zatandukanyijwe n'ingirabuzimafatizo.

Ubu buryo bwo gukora burumvikana kandi bwasobanuwe mu buryo burambuye bidasanzwe. Kuba bwumvikana ntibivuga ko bwemejwe, ariko bisobanura impamvu abaganga bavura kanseri bahaye agaciro raporo za mbere.

Raporo zo gutabara abarwayi: gukira vuba, ariko nta matsinda yo kugereranya

Raporo ikomeza kuvugwa cyane ni iyo mu 1995 yerekeye umugore w'imyaka 68 wari urwaye kanseri y'inkondo y'umura, wagize urujijo akabura ituze nyuma yo guhabwa ifosfamide ingana na 5 g kuri metero kare mu gihe cy'amasaha 24. CT ye nta kibazo yagaragaje, naho EEG igaragaza ko imikorere y'amashanyarazi y'ubwonko yagendaga buhoro mu bice byinshi. Yahawe 50 mg za methylene blue mu mutsi mu minota itanu, maze bivugwa ko mu minota icumi yari akangutse kandi avuga ibintu byumvikana. Iminota icumi ni igihe kigufi cyane ugereranyije n'uko uburwayi busanzwe bugenda, ari yo mpamvu uyu murwayi umwe yagize uburemere bwinshi mu biganiro.

Amatsinda y'abarwayi yasuzumwe nyuma ntiyagaragaje ibisubizo bitangaje cyane. Mu isesengura risubira ku makuru y'abarwayi 52 bahawe ifosfamide, 12 bagize uburwayi bw'ubwonko bwo ku rwego rwa 2 cyangwa rurushijeho gukomera. Muri bo, umunani bahawe methylene blue ingana na 50 mg mu mutsi inshuro esheshatu ku munsi. Bane bakize burundu mu masaha 24, barimo umwe wari urembye wakize mu isaha imwe hafi, abandi babiri bakira mu masaha 48, naho abandi babiri mu masaha 72. Ariko n'abarwayi bane bose batayahawe bakize mu masaha 48, nk'uko abanditsi ubwabo babitangaje. Itsinda ry'abarwayi 15 b'abana ryagaragaje inyungu zigaragara ku mwana umwe gusa muri batanu bahawe uwo muti. Abarwayi babiri bakuru bavuzwe muri raporo yasohotse mu 2018, bahawe 50 mg buri masaha ane, batangiye koroherwa nyuma y'amasaha 12 kugeza kuri 16 gusa, kandi basubira uko bari basanzwe nyuma y'iminsi ibiri kugeza kuri itatu. Icyo gihe nticyari gitandukanye n'igihe cyo gukira mu buvuzi bwo gushyigikira umurwayi.

Isesengura ry'inyandiko ryakozwe mu 2020 ryabaruye abarwayi 38 bahawe methylene blue bavuzwe muri raporo zasohotse, hafi bitatu bya kane byabo bavugwaho ko bagize ibisubizo byiza. Uwo mubare usa n'uhumuriza kugeza wibutse ko abakira vuba ari bo bakunze kwandikwaho, naho abakira buhoro akenshi ntibandikweho. Kubogama guterwa n'ihitamo ry'ibitangazwa gutuma ikusanyirizo rya raporo z'abarwayi risa n'irigaragaza ibisubizo byiza kurusha uko ibintu bimeze mu by'ukuri.

Imbonerahamwe y'ibimenyetso: tandukanya uburyo ubushakashatsi bwakozwemo

Imbonerahamwe ikurikira ni yo shingiro ry'iri sesengura. Raporo z'umurwayi umwe zishobora gusa gutanga igitekerezo; amatsinda y'abarwayi adafite ayo kugereranya ashobora gusa gusobanura ibyabaye; kandi kuri iki kibazo nta gerageza ryo gupima ubushobozi bwo kuvura rihari ryagabanyije abarwayi mu matsinda hakoreshejwe tombola.

Urwego rw'ibimenyetso	Ubushakashatsi	Uburyo bwakozwe n'abarwayi	Uburyo methylene blue yatanzwe	Ibyabaye
Raporo y'umurwayi	Kupfer n'abandi, Lancet 1994	Umurwayi wa mbere wavuwe n'undi umwe wahawe umuti wo gukumira; ibipimo by'ibinyabutabire byagaragaje imiterere isa n'iy'aside glutaric nyinshi mu nkari	Kuvura: 50 mg IV; gukumira: kunywa umuti	Havuzwe ko uburwayi bwashize vuba; umurwayi wa kabiri ntiyongeye kuburwara igihe yongeye guhabwa ifosfamide
Raporo y'umurwayi	Zulian n'abandi, N Engl J Med 1995	Umugore w'imyaka 68, kanseri y'inkondo y'umura, urujijo nyuma ya ifosfamide 5 g/m2 mu gihe cya 24 h	50 mg IV mu gihe cya 5 min, umuti urimo 1 ku ijana	Yari akangutse kandi avuga ibyumvikana mu gihe cya 10 min
Itsinda ry'abarwayi, isesengura ry'amakuru yabanje rifite abarwayi batavuwe bo kugereranya	Pelgrims n'abandi, Br J Cancer 2000	Abarwayi 52 bahawe ifosfamide; 12 bafite uburwayi bw'ubwonko bwo ku rwego rwa 2 cyangwa rurushijeho gukomera; 8 bavuwe, 4 ntibavurwa	Kuvura: 50 mg IV inshuro esheshatu ku munsi; gukumira: 50 mg inshuro enye ku munsi ku barwayi 3	Abavuwe: 4 muri 8 bakize mu gihe cya 24 h, bose mu gihe cya 72 h. Abatavuwe: bose uko ari 4 bakize mu gihe cya 48 h
Itsinda ry'abarwayi	Turner n'abandi, Clin Oncol 2003	Abarwayi 4 bagize uburwayi butunguranye, 2 nyuma bahabwa umuti wo gukumira	Akenshi 50 mg inyobwa inshuro eshatu ku munsi	Havuzwe koroherwa kugaragara mu gihe cya 24 h; uburwayi bwari bworoheje igihe ifosfamide yongeraga gutangwa hamwe n'umuti wo gukumira
Itsinda ry'abarwayi b'abana	Dufour n'abandi, Arch Pediatr 2006	Abana 15 bagize uburwayi bw'ubwonko	Kuvura: 50 mg IV buri 4 h; gukumira: buri 6 h	Inyungu zemejwe kuri 1 muri 5 bavuwe; 2 muri 2 bahawe umuti wo gukumira ntibongeye kurwara
Ubushakashatsi ku buryo umuti ugenda mu mubiri, nta tsinda ryo kugereranya ubushobozi bwo kuvura	Aeschlimann n'abandi, Drug Metab Dispos 1998	Abarwayi 9 ba kanseri y'ibihaha bahabwaga ifosfamide, mesna, etoposide	50 mg inyobwa inshuro eshatu ku munsi guhera ku mugoroba ubanziriza ubuvuzi bwa kanseri hakoreshejwe imiti	Umuti warihanganirwaga; nta mpinduka zikomeye ku ihindurwa rya ifosfamide mu buryo bukora; havuzwe kurinda imyakura ariko nta tsinda ryo kugereranya
Isesengura ry'amakuru yabanje, ryibanda ku gukumira	Sweiss n'abandi, Drug Safety 2008	Abarwayi 19 bahawe ifosfamide nyinshi; 8 bagize uburwayi bw'ubwonko; 5 bongeye guhabwa ifosfamide hamwe n'umuti wo gukumira	Methylene blue yo gukumira, yatanzwe mu buryo butandukanye	Bose uko ari 5 bongeye guhabwa ifosfamide hamwe n'umuti wo gukumira bongeye kugira uburwayi bw'ubwonko
Igereranya ry'ibyiciro by'ubuvuzi hakoreshejwe amakuru yabanje	Richards n'abandi, J Oncol Pharm Pract 2011	Ibyiciro 166 by'ubuvuzi birimo methylene blue, thiamine cyangwa albumin byo gukumira, bigereranywa n'ibitarimo ibyo	Uburyo butandukanye bwo gukumira	Uburwayi bw'ubwonko mu byiciro 21.1 ku ijana birimo imiti yo gukumira, ugereranyije na 8.4 ku ijana bitayirimo; birashoboka ko itandukaniro ryatewe n'impamvu umurwayi yahiswemo ngo ahabwe umuti
Itsinda ry'abarwayi ryasesenguwe hakoreshejwe amakuru yabanje	Itsinda ry'abana n'abantu bakuru bakiri bato rya MD Anderson, 2025	Abarwayi 24 bafite uburwayi bw'ubwonko; 20 bahawe methylene blue	Akenshi 50 mg IV buri 6 h, umubare wo hagati w'ingano zatanzwe wari 5	19 muri 20 bakize mu gihe cya 24 kugeza kuri 120 h, nta tsinda ritavuwe ryo kugereranya; 3 muri 5 bongeye guhabwa ifosfamide hamwe n'umuti wo gukumira bongeye kurwara

Iyo usomye inkingi y'ibyabaye kuva hejuru ujya hasi, hari ishusho ihoraho: inkuru za mbere zitangaje, zigakurikirwa n'ibisubizo bigenda biza buhoro kandi birushaho kuvanga ibyiza n'ibibi uko umubare w'abarwayi wiyongera n'amagereranya akaboneka. Ibyo ni ibiranga ubuvuzi bufite ingaruka nyakuri nto, niba buzigira.

Ibimenyetso byo gukumira ntibikomeye

Icyemezo cy'uko uyu muti ukumira uburwayi gikwiye gusuzumwa ukwacyo kuko gituma koko imiti yandikirwa abarwayi. Nyuma y'ibyabaye bwa mbere i Bern, aho ifosfamide inyobwa yatanzwe hamwe na 50 mg inshuro eshatu ku munsi kandi ntihagaragare ingaruka mbi ku myakura, ibigo byinshi byagerageje gukoresha methylene blue mu gukumira igihe ifosfamide yongeraga gutangwa. Ibisubizo biratandukanye cyane. Bamwe mu barwayi bongeye guhabwa ifosfamide bagize ibimenyetso byoroheje cyangwa ntibabigira; mu yandi matsinda, buri murwayi wongeye guhabwa ifosfamide hamwe n'umuti wo gukumira yakomeje kugira uburwayi bw'ubwonko. Igereranya rimwe ry'amakuru yabanje ryasanze ubwo burwayi bwinshi kurushaho mu byiciro by'ubuvuzi birimo umuti wo gukumira kurusha ibitarimo uwo muti, hafi nta gushidikanya kubera ko abarwayi bari bafite ibyago byinshi kurusha abandi ari bo batoranywaga kugira ngo bawuhabwe.

Abanditsi b'amabwiriza y'ubuvuzi babibonye. Amabwiriza ahuriweho yerekeye ingaruka mbi ku myakura, yateguwe n'amashyirahamwe y'i Burayi y'abaganga ba kanseri n'abaganga b'indwara z'imyakura, yanzuye ko nta magerageza afite amatsinda yo kugereranya ahari kandi ko, hashingiwe ku bimenyetso biriho ubu, methylene blue idashobora gusabwa mu gukumira cyangwa kuvura. Amakuru agenewe abandika imiti n'amabwiriza y'ibigo bimwe na bimwe byo aroroshya icyo cyemezo, akavuga ko ishobora gutekerezwaho ku burwayi bw'ubwonko buciriritse cyangwa bukomeye. Iyo myanzuro yombi ishingiye ku makuru amwe; itandukanira gusa ku buremere ihabwa inkuru z'abarwayi iyo nta bundi buryo bwiza buhari.

Ibyo umuntu utari inzobere mu kuvura kanseri akwiye kumenya

Ibintu bitatu bifatika ni byo bigena buri cyemezo gifatirwa iruhande rw'uburiri bw'umurwayi. Icya mbere, hano methylene blue ikoreshwa ku buryo butari mu bwo yemerewe ku mugaragaro, igatangwa mu mutsi mu bitaro, akenshi 50 mg buri masaha ane kugeza ku munani kugeza ibimenyetso bishize. Si umuti wo kwivurisha mu rugo, kandi iyi nyandiko si amabwiriza y'ingano y'umuti itangwa.

Icya kabiri, methylene blue ni umuti ubangamira monoamine oxidase A, ufite umuburo ukomeye uri mu gasanduku werekeye sindorome ya serotonin iyo ihujwe n'imiti y'agahinda gakabije ikora kuri serotonin ndetse na opioids zimwe na zimwe. Sindorome ya serotonin yanatangajwe by'umwihariko mu gihe cyo kuvura uburwayi bw'ubwonko buterwa na ifosfamide. Ntigomba kandi gukoreshwa ku bafite ibura rya glucose-6-phosphate dehydrogenase kubera ibyago byo gusenyuka kw'insoro zitukura z'amaraso. Amakuru ku mutekano no ku mikoranire n'indi miti ndetse n'ikibazo cyagutse cyo kumenya niba gukoresha methylene blue ku murwayi runaka bitekanye bigomba kwitabwaho mu gufata icyemezo mbere yo gufungura agacupa ako ari ko kose k'umuti w'ubururu.

Icya gatatu, guhagarika ifosfamide, gutanga amazi ahagije, gukosora ibipimo by'imyunyu ngugu n'indi miti itangwa icyarimwe, no kwemeza ko nta zindi mpamvu zitera urujijo, bikomeza kuba ishingiro. Methylene blue, aho ikoreshwa, yongerwa kuri iryo shingiro, ntirisimbura. Kwiga uko wasoma ubushakashatsi kuri methylene blue birafasha hano: baza niba raporo yari ifite itsinda ryo kugereranya, uko uburwayi bw'ubwonko bwashyizwe mu byiciro by'ubukana, ibindi byahindutse muri icyo gihe, n'uko igihe cyo gukira gitandukana n'igihe gisanzwe kizwi cy'umunsi umwe kugeza kuri itatu.

Umwanzuro w'ingenzi

Gukoresha methylene blue ku burwayi bw'ubwonko buterwa na ifosfamide bishingiye ku buryo bwumvikana bw'imikorere ya mitokondiriya, ku nkuru nke z'abarwayi batabawe bagakira vuba kandi mu buryo butangaje koko, no ku mubare munini kurushaho w'amatsinda y'abarwayi aho abavuwe n'abatavuwe bakira mu bihe bisa. Mu kuyikoresha nk'ubuvuzi bwo gutabara abafite uburwayi bw'ubwonko bukomeye cyangwa bumara igihe kirekire, bamwe mu baganga bavura kanseri babona ko bifite ishingiro kubera kubura ubundi buryo. Mu kuyikoresha buri gihe mu gukumira, ibimenyetso ntibibishyigikira. Umuntu wese uhuye n'iki kibazo, yaba umurwayi, uwita ku murwayi cyangwa umuganga, akwiye kugifata nk'icyemezo cy'inzobere gifatirwa ku murwayi uri mu bitaro, buri murwayi agasuzumwa ku giti cye, kandi agafata inkuru zo gukira vuba nk'igitekerezo kigomba kugeragezwa aho kuzifata nk'ikimenyetso cyemeza.