Nkhani
Chithandizo cha photodynamic cha methylene blue: mmene chithandizochi chimafufuzidwira
Chithandizo cha photodynamic chogwiritsa ntchito methylene blue chimamveka ngati chili ndi njira ziwiri. Kupaka utoto wabuluu, kenako kuunikira ndi kuwala kofiira. Kumvetsa zinthu motere n'kolakwika, ndipo ndi kumene kusamvetsetsana kwakukulu kokhudza chithandizochi kumachokera. Njira imene imafufuzidwa ili ndi zinthu zitatu zimene ziyenera kupezeka pamalo amodzi pa nthawi yomweyo: photosensitizer, chinthu chimene chimayamba kugwira ntchito chikayamwa kuwala, ili mumpangidwe wake woyamwa kuwala; ma photon a utali woyenera wa mafunde pa mlingo woyezedwa; ndi mamolekyu a oxygen kuti alandire mphamvu yosamutsidwayo. Chotsani chimodzi mwa zinthu zimenezi ndipo palibe njira imene zotsatira zonenedwazo zingachitikire.
Nkhaniyi imafotokoza mmene ofufuza amafotokozera dongosolo la zinthu zitatu limeneli, zinthu zimene amawongolera, ndi chifukwa chake nambala yofalitsidwa ya utali wa mafunde ndi mphamvu singasinthidwe kukhala njira yogwiritsa ntchito kunyumba. Zotsatira zokhudza khansa zili mu kuwunika kwapadera kwa kafukufuku wa methylene blue ndi khansa, ndipo ntchito zake za mano zasonkhanitsidwa mu kafukufuku wa photodynamic wa mkamwa ndi mano. Zonsezi sizinabwerezedwe pano.
Utotowo ndi photosensitizer, osati chinthu chongopatsa mtundu
Methylene blue imayamwa kwambiri kuwala kofiira, ndipo kuyamwa kwakukulu kwa monomer kumakhala pafupi ndi 664 mpaka 666 nm, komanso imakhala ndi mphamvu yaikulu kwambiri yoyamwa kuwala pa mol. Gawo limeneli la kuyamwa kuwala ndi chifukwa chake maphunziro a chithandizo cha photodynamic chogwiritsa ntchito methylene blue amagwiritsa ntchito magwero a kuwala kofiira, nthawi zambiri pafupifupi 630 mpaka 680 nm. Nyali ya kuwala komwe kuli kunja kwa gawoli ingaoneke yowala koma ikupereka mphamvu yochepa kwambiri imene ingadzutse utotowo. Mfundo za utali wa mafunde zimene zimatsogolera kusankha kumeneku zafotokozedwa mu mmene methylene blue imayamwira kuwala kofiira.
Kuyamwa kuwala ndi sitepe yoyamba yokha. Utoto wolandira mphamvuyo umasinthira ku mkhalidwe wa triplet womwe umakhalitsa nthawi yaitali, ndipo kuchokera pamenepo pali njira ziwiri za kusintha kwa mankhwala chifukwa cha kuwala. Mu kusintha kwa Type I, utoto wolandira mphamvuyo umasinthana ma electron kapena ma atomu a hydrogen ndi zinthu zapafupi zomwe ukuchita nazo, ndipo umatulutsa ma radical, kuphatikizapo kusintha komwe pambuyo pake kumakhudza superoxide. Mu kusintha kwa Type II, utoto wa mkhalidwe wa triplet umasamutsa mphamvu mwachindunji ku oxygen ya mkhalidwe wake woyambirira ndipo umatulutsa singlet oxygen. Pamene oxygen ilipo, methylene blue imagwira ntchito makamaka ngati chinthu chothandiza kupanga singlet oxygen, ndipo quantum yield yake m'madzi yanenedwa kukhala pafupi ndi 0.5, pamene kuchuluka kwa ntchito ya Type I kumakwera kapena kutsika malinga ndi zinthu za pamalopo. Kuwunika kwa 1993 kwa kusintha kwa methylene blue chifukwa cha kuwala ikamachita ndi zinthu za m'zamoyo kumafotokoza njira zonse ziwiri ndipo kumasonyeza chifukwa chake kuchuluka kwa iliyonse sikungadziwike kuchokera pa chizindikiro cha utoto.
Kuwunika komweko kumatchula nucleic acid imene imakhudzidwa kwambiri. Guanine ili ndi oxidation potential yotsika kwambiri mwa ma base a DNA, choncho singlet oxygen imachita nayo oxidation mosavuta kuposa enawo, n'kupanga zinthu monga 8-oxo-deoxyguanosine. Kulowa kwa utoto pakati pa ma base a DNA sikofunikira kuti kuwonongeka kumeneku kuchitike. Koma kuwunikaku kumachenjezanso kuti DNA siyenera kuonedwa ngati ndiyo nkhani yonse. Methylene blue imachititsa oxidation ya mapuloteni, ma lipid, ndi ma membrane, ndipo chinthu chimene kuwonongeka kwake kumabweretsa imfa pa kuyesa kulikonse chimadalira malo amene utotowo umasonkhana. Choncho, kuchuluka kwa utoto mumadzi amene chinthucho chaviikidwa sikupereka chithunzi chabwino cha mlingo pa chinthu chimene chikukhudzidwa. Owerenga amene akuyerekeza kusintha kwa mankhwala koyendetsedwa ndi kuwalaku ndi ntchito za redox za utoto pamene palibe kuwala ayenera kuzisiyanitsa, monga zafotokozedwa m'nkhani ya mmene methylene blue imagwirira ntchito m'maselo.
Chinthu choyambira popanga mankhwala, osati mankhwala okonzedwa bwino kwambiri
Gwero lachiwiri lofunika ndi kuwunika kwa 2005 kwa kupangidwa kwa ma photosensitizer a phenothiazinium, komwe kumaona methylene blue ngati kapangidwe koyambira komwe kali ndi zofooka zodziwika, osati ngati photosensitizer yomalizidwa bwino. Kusintha pang'ono kwa kapangidwe kake kumasintha kuthekera kwake kusakanikirana ndi mafuta, kulowa m'maselo, malo amene imasonkhana mkati mwa maselo, kutulutsa singlet oxygen, poizoni wake pamene palibe kuwala, ndi kukana kwake reduction. Mwachitsanzo, kuwonjezera magulu a methyl ku chromophore kumakulitsa kuthekera kwake kusakanikirana ndi mafuta ndi kupanga singlet oxygen, ndipo kumachedwetsa reduction yake kukhala mtundu wa leuco wosagwira ntchito. Zinthu zofanana nazo zomwe zinawonjezeredwa methyl zinasonyeza kuwononga kwakukulu chifukwa cha kuwala pa pafupifupi 7.2 J per square cm mu kafukufuku woyambirira. Komabe, kusakanikirana kwambiri ndi mafuta sikutanthauza kuti ndi bwino nthawi zonse, chifukwa kusasakanikirana kwambiri ndi madzi kumachepetsa kusungunuka, kumalimbikitsa kusonkhana kwa mamolekyu, ndipo kungasokoneze kapangidwe kamene kusintha kwa mankhwala chifukwa cha kuwala kumafunikira.
Mfundo ya leuco iyenera kutsindika chifukwa siyioneka. Methylene blue yomwe yachita oxidation imakhala yabuluu ndipo imayamwa kuwala kofiira. Leuco-methylene blue yomwe yachita reduction imakhala pafupifupi yopanda mtundu ndipo siiyamwa bwino kuwala m'gawo lomwelo. Choncho, utoto umene wachita reduction mkati mwa maselo kapena m'minyewa yopanda oxygen yokwanira umachoka kwakanthawi m'gulu la utoto umene ungagwire ntchito ndi kuwala, mpaka utachitanso oxidation. Mkhalidwe wa redox wa minyewa umasintha kuchuluka kwa photosensitizer yogwira ntchito, ngakhale kuchuluka komwe kwaperekedwa sikunasinthe. Mbiri ya kapangidwe ka mankhwalawa, kuphatikizapo ntchito zoyambirira zachipatala ndi za m'malo ofufuzira za gulu la utotoli, yafotokozedwa mu mbiri ya methylene blue m'zachipatala.
Tebulo la maphunziro: zimene zimasiyanasiyana ndi tanthauzo lake
Tebulo ili pansipa lapangidwa koyambirira kuti liyerekezere zinthu za m'nkhaniyi. Mzere uliwonse ukuimira chinthu chimodzi cha chithandizo chimene maphunziro ayenera kufotokoza. Werengani mzere wonse kuti muone chifukwa chake kusintha chinthu chimodzi kumasintha tanthauzo la zina zonse.
| Chinthu chosinthika | Zimene maphunziro amafotokoza | Chifukwa chake chimasintha zotsatira |
|---|---|---|
| Kapangidwe ka photosensitizer | Utoto wopanda chonyamulira m'madzi, madzi amchere, kapena madzi owongolera pH; ethanol ndi Cremophor monga zosakanizira mu kafukufuku wa nyama; ma liposome, tinthu ta polymer, kapena zonyamulira za cyclodextrin mu kafukufuku woyesera | Zosakanizira ndi zonyamulira zimasintha kulowa kwa utoto, malo amene umasonkhana, ndi kudutsa zotchinga monga kapangidwe ka biofilm kapena minyewa ya chotupa |
| Kuchuluka koperekedwa | Maphunziro a anthu okhudza kulimbana ndi tizilombo amafotokoza pafupifupi 0.0003 mpaka 0.06 M, ndi mipata ya 1 mpaka 5 minute pakati pa kupereka mankhwala ndi kuunikira; kafukufuku wa zotupa m'nyama uli ndi zitsanzo pafupi ndi 500 micrograms per mL zoperekedwa mkati mwa chotupa | Kuchuluka kwambiri m'madzi onse kungawonjezere kupanga ma dimer pafupi ndi 590 nm ndi kuchepetsa kusintha kopindulitsa kwa monomer chifukwa cha kuwala, choncho kuchulukitsa utoto kawiri sikutanthauza kuchulukitsa zotsatira kawiri |
| Mpata pakati pa kupereka mankhwala ndi kuunikira | Mphindi pa njira zopaka pamwamba zolimbana ndi tizilombo; nthawi yaitali ndiponso yodalira chosakanizira m'mayesero a zotupa | Mpatayo umatsimikizira malo amene utoto uli pamene kuwala kufika, ndipo zimenezi zimatsimikizira chinthu chachikulu cha m'zamoyo chimene chimakhudzidwa |
| Utali wa mafunde | Nthawi zambiri pafupifupi 630 mpaka 680 nm | Uyenera kugwirizana ndi gawo limene monomer imayamwa kuwala; madzi okhala ndi ma dimer ambiri amasintha kuyamwa kwa kuwala komwe kumagwira ntchito |
| Mphamvu ya kuwala pa gawo la malo pa nthawi | Malipoti a anthu okhudza kulimbana ndi tizilombo amakhala pafupifupi 50 mpaka 750 mW per square cm; maphunziro a zilonda m'nyama nthawi zambiri amakhala pa 100 mW per square cm kapena pansi pake | Mphamvu yaikulu ya kuwala ingathe kugwiritsa ntchito oxygen ya pamalopo mofulumira kuposa mmene magazi amaibwezeretsera, zomwe zimachepetsa kugwira ntchito ngakhale mphamvu yonse ya kuwala yotchulidwa ili yofanana |
| Mphamvu yonse ya kuwala pa gawo la malo (fluence) | Malipoti a anthu okhudza kulimbana ndi tizilombo amakhala pafupifupi 6 mpaka 18 J per square cm pa nthawi ya 8 seconds mpaka 10 minutes; maphunziro a zilonda m'nyama amakhala pafupifupi 12 mpaka 360 J per square cm | Mphamvu yonse yokha, popanda mphamvu pa nthawi, nthawi yeniyeni, ndi kapangidwe ka malo, si mlingo wofotokozedwa mokwanira |
| Kupezeka kwa oxygen | Sikuwongoleredwa mwachindunji kawirikawiri; kumaganiziridwa kuchokera ku mtundu wa minyewa, liwiro lopereka mphamvu ya kuwala, ndi kugawa kuunikira m'magawo | Kusintha kwa Type II kumagwiritsa ntchito oxygen, choncho makonzedwe ofanana a kuwala angapereke zotsatira zosiyana pa zinthu zofikiridwa bwino ndi magazi ndi pa zimene zili ndi oxygen yochepa |
| Chinthu cholunjikidwa ndi malo oyesera | Mayesero a matenda a pakhungu ndi m'zilonda, mayesero a biofilm ya mkamwa, maselo a carcinoma ndi melanoma okulitsidwa m'malo ofufuzira, zotupa za mbewa, malipoti akale a zotupa za pakhungu | Kapangidwe ka malo, kuya, mmene kuwala kumayendera, ndi kuwonongeka kovomerezeka kwa minyewa ya wolandira chithandizo zimasiyana kwambiri moti manambala a ntchito zolimbana ndi tizilombo sangatengedwe n'kugwiritsidwa ntchito mofanana mu kafukufuku wa zotupa |
Milingo ili pamwambayi ndi imene yaoneka m'maphunziro, osati njira yolimbikitsidwa yotsatira. Kusiyana kumeneko ndi cholinga cha tebulo. Kusiyanasiyana kwakukulu kwa milingo ya kuwala yofotokozedwa ndi umboni wokha wakuti palibe mlingo wa kuwala wa methylene blue umene ungatengedwe n'kugwiritsidwa ntchito kulikonse. Mfundo zina za m'malo ofufuzira zokhudza biofilm ndi kuwala zili mu methylene blue polimbana ndi ma biofilm, ndipo mfundo zambiri za khungu ndi chithandizo cha kuwala zili m'nkhani ya kukhudzidwa kwa khungu ndi kuwala ndi mfundo zoyambirira za mlingo wa kuwala.
Chifukwa chake manambala ofanana a mphamvu angapereke zotsatira zosiyana m'zamoyo
Kusamvetsetsana kwa mitundu inayi kumabwerezabwereza pamene zinthu zofalitsidwa m'maphunziro zikutchulidwa popanda kufotokoza mmene zinagwiritsidwira ntchito.
Choyamba, fluence si mlingo wonse wa chithandizo. Kuunikira kawiri ndi utali wa mafunde wofanana komanso J per square cm yofanana kumasiyana ngati kwina kwaperekedwa mofulumira ndipo kwina pang'onopang'ono. Izi zili choncho chifukwa kuchepa kwa oxygen, kukonza kuwonongeka pamene kuunikira kukuchitika, ndi kutayika kwa mphamvu ya utoto chifukwa cha kuwala zonse zimadalira liwiro ndi nthawi. Kufotokoza mphamvu popanda mphamvu ya kuwala pa nthawi ndi nthawi ya kuunikira kumasiya kuyesako kosafotokozedwa mokwanira.
Chachiwiri, mmene kuwala kumayendera m'minyewa kumasintha tanthauzo la makonzedwe a nyali. Kuyamwa kuwala, kufalikira kwake, mawonekedwe a pamwamba, ndi kubalalika kwake kubwerera kumbuyo zimatanthauza kuti fluence ya mkati mwa minyewa ingasiyane kwambiri ndi mtengo woyezedwa pa potulukira kuwala pa nyali. M'mikhalidwe ina, kusiyana kumeneku kungayandikire kuwirikiza kawiri, malinga ndi mabuku a zachipatala okhudza kuyeza milingo. Nambala yotengedwa m'pepala la kafukufuku imafotokoza kapangidwe ka malo a kafukufukuyo, osati kapangidwe kalikonse.
Chachitatu, malo amene utoto umasonkhana amatsimikizira chinthu chimene umakhudza. Utoto wokhala ndi chaji yabwino ungagawikire m'ma membrane, mitochondria, lysosome, zotchingira mabakiteriya, kapena kapangidwe ka kunja kwa maselo, malinga ndi kapangidwe ka mankhwala, chaji, kuthekera kwake kusakanikirana ndi mafuta, mpata wa nthawi, ndi minyewa. Kuwunika kwa 1993 kwa kusintha kwa mankhwala chifukwa cha kuwala kumalemba kuwonongeka kwa nucleic acid, mapuloteni, ma lipid, ma membrane, ziwalo zazing'ono za m'maselo, mavairasi, mabakiteriya, maselo a nyama zoyamwitsa, ndi machitidwe a zotupa. Ichi ndicho chifukwa chake utoto womwewo ukaphatikizidwa ndi kuwala ungaphe mwa njira zosiyanasiyana m'mayesero osiyanasiyana.
Chachinayi, oxygen ndi chinthu chimene chimatha chikagwiritsidwa ntchito. Kupereka mphamvu ya kuwala mofulumira kwambiri kungapitirire liwiro limene oxygen imabwerera kudzera mu kufalikira kwake ndi kayendedwe ka magazi, n'kuyambitsa kusowa kwa oxygen kwakanthawi pakati pa kuunikira. Izi zikachitika, kuwonjezera kuwala kumawonjezera zotsatira za Type II pang'ono kapena sikuwonjezera chilichonse. Kugawa kuunikira m'magawo ndi kuchepetsa mphamvu ya kuwala pa nthawi zikufufuzidwa mwa zina ngati njira zothana ndi malire amenewa. Ichi ndichifukwa chakenso malire otetezeka ndi kupezeka kwa oxygen m'minyewa ziyenera kukhala m'miyezo ya chitetezo ndi kuyang'anira kwachipatala, osati m'buku la malangizo a nyali.
Njira yotsogoleredwa ndi katswiri wa zachipatala, osati malangizo ochitira kunyumba
Chithandizo chimene chikufufuzidwa chimaperekedwa pamalo amene kuzindikira matenda, kuyeza milingo, ndi kuyang'anira zimapezeka limodzi. Munthu ayenera kutsimikizira kuti vuto la minyewa ndi chiyani ndiponso lafika pakuya kotani; kusankha kapangidwe ka mankhwala ndi mpata pakati pa mankhwala ndi kuunikira wogwirizana ndi chinthu cholunjikidwa; kuyeza ndi kukonza gwero la kuwala pa malo odziwika bwino okhala ndi kapangidwe kodziwika bwino; ndi kuyang'anira khungu, maso, ululu, ndi mmene minyewa ya pamalopo ikuyankhira. Kuwunika kwa kupangidwa kwa phenothiazinium komwe kuli maziko a nkhaniyi kumaika ntchito yonseyi ngati kukonza ubale pakati pa kapangidwe ndi ntchito yake m'mikhalidwe yowongoleredwa, osati kungophatikiza utoto ndi kuwala kofiira kulikonse.
Kuyesera kutsanzira kunyumba kumalephera pa zinthu zonse zimene ziyenera kuwongoleredwa nthawi imodzi. Nyali zogulitsidwa kwa anthu wamba sizifotokoza kawirikawiri mphamvu ya kuwala yoyezedwa ndi kutsimikizidwa pa utali uliwonse wa mafunde komanso pa mtunda wa chithandizo. Kuchuluka kwa utoto woperekedwa sikunena chilichonse za gawo lake limene lili ngati monomer kapena malo amene wasonkhana mkati mwa maselo. Kupezeka kwa oxygen m'minyewa sikudziwika ndipo kumasintha panthawi ya kuunikira. Palibe mlingo uliwonse mwa imene yatchulidwa umene umavomereza njira yochitira kunyumba, ndipo nkhaniyi mwadala sipereka malangizo ogwiritsidwa ntchito kuchita zimenezo. Owerenga amene akuwunika kudalirika kwa umboni ayenera kugwiritsa ntchito mmene mungawerengere kafukufuku wa methylene blue asanapange mfundo kuchokera ku pepala limodzi lililonse. Owerenga amene akufuna kudziwa njira za kuwala kokha popanda photosensitizer ayenera kuyamba ndi chithandizo cha kuwala kofiira popanda photosensitizer.
Zimene nkhaniyi sikutsimikizira
Sikutsimikizira kuti chithandizo cha photodynamic cha methylene blue chimachiritsa vuto lililonse la pakhungu, chimathetsa matenda aliwonse oyambitsidwa ndi tizilombo, kapena chimachiza chotupa chilichonse. Ndemanga zofotokoza njira za ntchito zotchulidwa pano zinayeza kusintha kwa mankhwala chifukwa cha kuwala ndi kuyerekeza kapangidwe ka utoto; sizinapereke kuchuluka kwa mankhwala kapena fluence yogwiritsidwa ntchito kuchipatala. Milingo yotchulidwa pamwambayi imachokera ku malipoti osiyanasiyana a anthu ndi mayesero a nyama okhala ndi zinthu zolunjikidwa, kuya, kapangidwe ka mankhwala, ndi zotsatira zoyezedwa zosiyanasiyana, ndipo siyingaphatikizidwe kukhala malangizo pogwiritsa ntchito avareji. Umboni wokhudza zotupa mwapadera, kuphatikizapo malire a malipoti oyambirira a zachipatala pa basal cell carcinoma, Kaposi sarcoma, ndi melanoma, ukuwunikidwa padera m'gulu la kafukufuku wa khansa. Mafunso okhudza chiyero ndi komwe mungapeze zinthu za mulingo wa m'malo ofufuzira ndi nkhani zosiyana ndi chithandizo, ndipo afotokozedwa mu mmene mungasankhire chinthu cha methylene blue.