Mmene methylene blue imagwirira ntchito: kusamutsidwa kwa ma electron, ndi kumene ma electron amapita

Botolo lotsekedwa bwino lomwe lili pa benchi ndi njira yachidule komanso yolondola yofotokozera mmene methylene blue imagwirira ntchito. Madzi, glucose, sodium hydroxide pang'ono, ndi utoto wokwanira kupangitsa madziwo kukhala abuluu kwambiri moti sangasokonezeke ndi mtundu wina. Dikirani mphindi zochepa ndipo mtundu wabuluu umatha mpaka botololo kuwoneka ngati lili ndi madzi okha. Ligwedezeni, ndipo mtunduwo umabwereranso nthawi yomweyo. Kenako umatheranso, ndipo izi zipitirirabe bola ngati pali glucose yomwe ingapereke ma electron ndi oxygen yomwe ingawalandire.

Palibe chimene chasintha pa utotowo kupatulapo kuchuluka kwa ma electron omwe wanyamula. Ukakhala oxidised, ndi wabuluu. Ukakhala reduced, suli wabuluu. Pafupifupi zonse zina zomwe zalembedwa m'mabuku a chithandizo ndi kafukufuku wokhudza molekyuluyi zimachokera pa sitepe imodzi imeneyi yomwe ingabwezeretsedwe, chifukwa molekyulu yomwe ingalandire ma electron kuchokera kwa mnzake n’kuwapereka kwa wina ndi njira yolumikizira, ndipo njira imeneyo payokha sichichita chilichonse. Zimene imachita zimadalira kwathunthu zimene zili kumapeto kulikonse kwa njirayo.

Mitundu iwiri, ndi chifukwa chake awiriwa ali ofunika

Mtundu wa oxidised ndi dongosolo la mphete lathyathyathya lokhala ndi positive charge. Kapangidwe kathyathyathya kokhala ndi charge kameneka n’kamene kamapangitsa kuti izisonkhana pafupi ndi nucleic acids, kumangirira ku zinthu za sialylated pa ma membrane a maselo, komanso kuyamwa kwambiri kuwala kowoneka pakati pa pafupifupi 600 ndi 700 nanometres, gawo la spectrum limene diso la munthu limawona ngati buluu.

Mtundu wa reduced ndi wosiyana. Ulibe charge, umasungunuka m'mafuta m'malo mwa madzi, ndipo ulibe mtundu. Ionisation yake ndi yotsika kwambiri pa pH ya mkati mwa thupi, pafupifupi ma peresenti ochepa. Choncho molekyulu ya reduced imadutsa mosavuta pa membrane ya selo kudzera mu diffusion, ndipo ikalowa mkati, kumene chilengedwe chimakhala oxidising kwambiri, imatha kukhala re-oxidised ndipo motero kutsekerezedwa mkati. Dongosolo la mphete la oxidised ndi lathyathyathya; la reduced limatha kupindika. Zotsatira za kapangidwe kameneka, komanso kusintha kwa mtundu komweko, ndi mbali ya nkhani ya mitundu iwiriyi, ndipo zafotokozedwa mwatsatanetsatane mu kuyerekezera kwa methylene blue ndi leucomethylene blue.

Kulandira ma electron

Utoto wa oxidised umatha kulandira ma electron kuchokera kwa opereka osiyanasiyana. Glucose yomwe ili m'botolo la chitsanzocho ndi imodzi mwa iwo. Mkati mwa selo, reduced pyridine nucleotides ndi zigawo za mitochondrial electron transport chain ndi ena. Methylene blue ikakhala reduced mu tissue yomwe ili ndi oxygen, cycle yomwe imayambitsa imagwiritsa ntchito reducing agent ndi oxygen zonse, ndipo imapanga reactive oxygen species, makamaka hydrogen peroxide. Utotowo umatuluka mu cycleyo osasintha, wokonzeka kuyambiranso.

Mfundo yomalizayi imafotokoza kusagwirizana komwe popanda kufotokozeraku kungawoneke ngati kulemba mosasamala. M'mabuku, methylene blue imafotokozedwa ngati pro-oxidant komanso antioxidant, ndipo mafotokozedwe onsewa ali ndi maziko. Imatha kuchepetsa kupanga kwa superoxide pochita ngati artificial electron acceptor, kutembenuza kayendedwe ka ma electron kuti kasapite ku malo a ma enzyme kumene oxygen ikanakhala ikusandulika kukhala superoxide radicals. M'ma culture a maselo a chiwindi yasonyezedwa kuti imayambitsa phase-2 antioxidant defence enzymes, kuphatikizapo thioredoxin reductase 1 ndi NADPH quinone oxidoreductase. Mbali iti mwa ziwirizi yomwe imaoneka imadalira mbali iti ya njira yolumikizirayo yomwe ikusowa ma electron panthawiyo. Funso ngati "kodi methylene blue ndi antioxidant" silinapangidwe bwino mpaka mutanena dongosolo limene mukunena, concentration yake, komanso zinthu zina zomwe zilipo.

Kupereka ma electron edasi

Utoto ukangokhala ndi electron yowonjezera, zinthu zitatu zosiyana kwambiri zingachitike, ndipo nthawi zambiri zimafotokozedwa pansi pa mutu umodzi. Siziyenera kutero.

Ukhoza kupereka electron ku metal centre. Chitsanzo chomveka kwambiri ndi haemoglobin yomwe yasinthidwa kuchokera ku ferrous kupita ku ferric state chifukwa cha oxidation. Ikakhala motero, siinganyamule oxygen. M'maselo ofiira a magazi, enzyme imachititsa utotowo kukhala reduced, kenako utoto wa reduced umapereka ma electron ku oxidised haem iron popanda enzyme, kubwezeretsa haemoglobin yogwira ntchito ndi kubwezera utotowo ku mtundu wake wa oxidised. Utotowo sugwiritsidwa ntchito mpaka kutha pa izi; umangozungulira mu cycle. Kugwiritsa ntchito kwa chipatala komwe kumadalira reaction imeneyi ndi nkhani ya chisamaliro cha kuchipatala, ndipo kufotokoza kwa methylene blue mu methemoglobinemia kumafotokoza mmene imagwiritsidwira ntchito ndi chifukwa chake imayang'aniridwa mosamala kwambiri.

Cholemba chofunika pa zomwe zawerengedwa: ma review awiri omwe nkhaniyi yatengera satchula reducing cofactor yomweyo pa sitepe ya enzyme, imodzi imati NADH ndipo ina NADPH. Kusagwirizanaku kulipo ndipo sikunathetsedwe m'magwero omwe alipo pano, choncho kufotokoza kotetezeka ndi kufotokoza ntchito ya gawo lililonse m'malo mosankha dzina limodzi la cofactor.

Ukhoza kupereka mphamvu, kapena electron, ku oxygen, ngati pali kuwala. Njirayi imapezeka pokhapokha pali kuwala. Utoto womwe walandira mphamvu umafika pa triplet state, ndipo kuchokera pamenepo njira ziwiri zingatheke. Yoyamba, utoto womwe walandira mphamvu umachita mwachindunji ndi molekyulu yapafupi, kutenga hydrogen kapena kusamutsa electron, zomwe zimapanga radicals; kuchita motere ndi madzi kumapanga hydroxyl radicals. Yachiwiri, mphamvu yomwe yatengedwa imaperekedwa ku oxygen yokha, kupanga singlet oxygen, mtundu wokhala ndi electrophilic reactivity kwambiri womwe umasowa mkati mwa microseconds ndipo nthawi zambiri umavomerezedwa ngati njira yaikulu yomwe methylene blue yowunikidwa imawonongera maselo a microbial. Reactions ndi ma lipid ndi ma peptide a cell envelope, komanso guanine bases mu DNA, ndi zina mwa zotsatira zomwe zalembedwa.

Zotsatira zake pa ntchito yeniyeni n’zakuti kuunikira kumasintha manambala ndi ma orders of magnitude. Mu data yomwe Wainwright ndi Crossley anasonkhanitsa, methylene blue motsutsana ndi Pseudomonas aeruginosa ili ndi minimum bactericidal concentration ya pafupifupi 500 micromolar mumdima, ndi pafupifupi 25 micromolar pansi pa light dose ya 12 joules per square centimetre. Motsutsana ndi strain imodzi ya Staphylococcus aureus, ma value a mumdima ndi a pakuunika onse ndi 5 micromolar. Mwa kuyankhula kwina, ngati molekyuluyi ingawerengedwe ngati antimicrobial kapena ayi si katundu wa molekyuluyo yokha; ndi katundu wa molekyuluyo pamodzi ndi kuwala.

Ikhoza kugwira ntchito mwachindunji pa enzyme site, popanda njira yolumikizira. Methylene blue imachititsa oxidation ya ferrous iron yomwe yamangiriridwa ku nitric oxide synthase, zomwe zimalepheretsa enzyme kugwira ntchito. Imaletsa soluble guanylate cyclase, ndipo pakati pa 1 ndi 10 micromolar ndi concentration yomwe imagwiritsidwa ntchito nthawi zonse mu labotale pa cholinga chimenecho. Imaletsa monoamine oxidase type A ndi IC50 pakati pa 27 ndi 180 nanomolar, yomwe ndi mechanism yomwe imayambitsa interaction yodziwika bwino ndi serotonin reuptake inhibitors komanso chifukwa chake drug interactions za methylene blue ndi gulu lake lokha.

Njira zitatuzi ndi zosiyana pa chemistry. Kuziphatikiza zonse n’kuzinena ngati claim imodzi yakuti methylene blue imagwira ntchito kudzera mu redox cycling ndiye chifukwa chachikulu chomwe zolemba zambiri zokhudza iyo zimawoneka nthawi imodzi ngati zotsimikiza koma zosamveka bwino.

Kusiyana kanayi komwe kumatsimikizira ngati mawu okhudza mechanism ali ndi tanthauzo

Mtundu uti. Utoto wa reduced sungangosinthanitsidwa ndi wa oxidised ngati kuti ndi chinthu chomwecho. Acetylcholinesterase inhibition imasonyeza msampha wake: mu in vitro incubation yayitali, methylene blue imasinthidwa pang'onopang'ono kukhala mtundu wake wopanda mtundu, ndipo inhibition imachepa, chifukwa molekyulu ya reduced siletsa enzyme imeneyo. Assay yomwe yayendetsedwa nthawi yokwanira kusintha mtundu wa molekyuluyo idzawonetsa effect yofooka ndipo ingapangitse kufotokoza kolakwika.

Concentration iti. Laboratory range ya soluble guanylate cyclase inhibition ndi 1 mpaka 10 micromolar. Kuthetsa glutamate-mediated transmission mu rat hippocampal slices kunafuna 5 mpaka 50 micromolar. Toxic effects mu cell culture zalembedwa pamwamba pa 100 micromolar. Izi si experiment yomweyo, ndipo mechanism yomwe yatsimikiziridwa pa 50 micromolar siitanthauza kuti imapezekanso mwachindunji kwa wodwala amene plasma concentration yake ndi kachigawo chabe ka imeneyo.

Njira iti. Absolute oral bioavailability ndi pafupifupi 72 per cent, ndipo terminal plasma half-life ndi 5 mpaka 7 hours. Kuperekedwa pakamwa kumapanga concentrations zapamwamba m'matumbo ndi chiwindi; intravenous administration imapanga concentrations zapamwamba mu ubongo. Njira yoperekera imatsimikizira tissue yomwe imakumana ndi ma electron.

Model iti, komanso ngati magetsi anali kuyaka. Zambiri mwa mechanistic literature ndi kafukufuku wa cell culture ndi makoswe, ndipo zotsatira za in vitro pa molekyuluyi zimadalira light exposure, membrane potential ndi redox state ya maselo, chifukwa kuwala kwa microscope kokha n’kokwanira kuyambitsa photosensitisation yake. Pakati pa 65 ndi 85 per cent ya dose yomwe yaperekedwa imasinthidwa kukhala mtundu wopanda mtundu m'maselo ofiira a magazi ndi peripheral tissue. Variable iliyonse mwa zimenezi imakhala pakati pa mechanism yomveka bwino mu dish ndi claim yokhudza munthu.

Chifukwa chake funso la purity ndi funso la chemistry

Kuunikira kumachititsa demethylation ya methylene blue. Product yoyamba ndi Azure B, kenako Azure A, kenako thionin, ndipo light intensity yapamwamba imapanga breakdown yambiri kuposa yotsika. Choncho molekyulu yomwe phindu lake limachokera pa kuthekera kolandira ndi kupereka ma electron ndi molekyulu yomwe degradation products zake zomwe zingayembekezeredwe ndi achibale apafupi pa chemistry ndipo zimakhalabe mu solution yomweyo. Zomwe zili m'chidebecho si nkhani ya maonekedwe chabe.

Ichi ndi chifukwa chake kutsatira specification ya USP ndi mayeso ofunika kwa wogula. Product yomwe siyikwaniritsa specification imeneyo ndi utoto, ndipo utoto umatha kukhala ndi impurities, kuphatikizapo Azure B, heavy metals ndi residual solvents, zomwe munthu amene akumwa sakufuna. Msampha wina ndi wogulitsa amene amayesa heavy metals zokha n’kupereka zotsatirazo ngati kuti ndi full compliance. Blupreme yagwirizana ndi pharmaceutical manufacturer wa methylene blue ndipo imayesa specification yonse: identity, purity, organic impurities, residual solvents, elemental impurities, residue on ignition, microbial limits ndi bacterial endotoxins. Chikalata cha kuyezetsa mu labotale cha batch iliyonse chimasindikizidwa, ndipo kusankha supplier makamaka kumangokhala nkhani yotsimikizira ngati chikalatacho chilipo komanso zomwe chimaphimba.

Reversible couple imodzi. Njira zingapo zotulukamo. Njira yomwe yagwiritsidwa ntchito ndiyo imatsimikizira zomwe claim inganene.