chlornafassin

polisithemiya, hodkins rogam ennivayude chikilsaykkaayi 1950-kalil vikasippichedutha naitrajan kaduk aanu 2-nafthylamainil ninnu uruthirinja chlornafassin. ennirunnaalum, chlornaftassin upayogichu chikitsa labhikkuna rogikalil moothrasanchi cancer uyarnna thothil undaakunnath marunninte upayogam nirthalaakkaan kaaranamaayi.
internaashanal ejansi phoor research oonn cancer chlornafaasine oru manushya arbudakaariyaayi pattikappedutthiyittundu.
chlornafassin oru thavitt kharamaayo niramillaatha falakangalaayo kaanapedunnu, 5 emmhgyil 210 digri selshyas thilanilayundu.
charithram.
vaidyashaasthraparamaaya upayogam.
denmark, itali ennivayulppede onniladhikam rajyangalil hodgekins rogathinteyum polisithemiya verayudeyum chikilsaykkaayi chlornafaasine oru cytostatic ejantaayi klinikkal aayi upayogichirunnu. 
upayogam nirtthi.
manushyaril carcinogenesitic mathiyaya thelivukal ullathinaal chlornafaasine oru klinikkal marunnayi nirthalaakki. eee marunnu moothrasanchiyile arbudathinu kaaranamaayi. copenhagenile finsen instittyoottile medical vibhaagathil, danish gaveshakar varshangalayi polycythemia vera baadhicha niravadhi rogikale chlornafaasisinte vyathyastha motham dosukal nalkiyathaayi nireekshichu. 1961ll report cheyyappetta prarambha chikitsa phalangal soochippikkunnathu chlornafassin upayogicha 32 rogikalil 75 sathamaanavum anukoolamaaya phalam anubhavichu ennaanu. vishakalana samayat, ezhu rogikal marikkukayum eee rogikalil oraalude postmorttatthil abadhathil moothrasanchi carcinoma kandethi. finsen instittyoottile medical vibhaagathil ninnulla thudarnnulla padanatthil, chlornafaasine upayogichu chikilsicha polisithemiya vera baadhicha 61 rogikale pinthudarnnu. 61 rogikalil ettu rogikalkku moothrasanchiyude aakramanathmaka carsinoma mattu ettu rogikalkku asaadhaaranamaaya moothrakoshashaasthravum anchu rogikalkku moothrasanchiyude pappillary carcinoma grade II vikasippichathaayum kandethi. ithu 1963ll denmarkile chlornafaasine nirthalaakkunnathilekku nayichu.
pravartthana samvidaanam.
polisithemiya, hodkins rogam ennivaykkulla chikilsayaayi scandinaviayil pradhaanamaayum upayogichirunna oru naitrajan kaduk aanu chlornafassin. yudhavaathakangalude shaareerika prathyaaghaathangalekkurichallu yudhakaala padanangaliloode asaadhaaranamaaya koshavalarchaye raasaparamaayi thadayunnathinulla naitrajan kaduk saadhyatha paryavekshanam cheyyukayum thwarithappeduthukayum cheythu. naitrajan kaduk ennariyappedunna yudhavaathakam, asthimajjayilum prathyekichu hemopoitic systethilum vinashakaramaaya swaadheenam cheluthunnathinaal raktarbudam, hodgekins rogam, pothuve lymphodenopathy ennivayude chikilsaykkulla oru saadhyathayulla marunnaayaan kaanappettath. naitrajan kaduk ennivayude aanti-carcinoma pravartthanam maittosisile avayude pravartthanatthe adisthaanamaakkiyullathaanu, ithu saadhaaranavum asaadhaaranavumaaya vibhajana koshangalude valarchaye thadayunnu. naitrajan kaduk, chlornafasine ennivayude abhikaamyamallaatha paarshwafalangal kaaranam, samanamaaya tumour-inhibitting sheshiyulla naitrajan kaduk shreniyile mattoru amgam vikasippichu. mattu sajeeva naitrajan kaduk pole, chlornafasinum direct acting alkailetting ejantukalil pedunnu. nucleophilic pakarakkaranaayi vaividhyamaarnna jaiva thanmaathrakalude aattathile eaka jody electronukalumaayi oru alkail groupine bandhippichukondu ithu athinte cytotoxic pravartthanam nadathunnu. dnaude eee kovalant parishkkaranatthiloode, dna replication protein synthesis ulppede cancer koshangalile avashya prakriyakalil chlornafaasinu edapedaan kazhiyum. eee marunnu oru bifunctional alkkailettar aayathinal, dnayile rund vyathyastha sthalangalil prathikarichu intra, interstraand cross linkukal roopappeduthaan ithinu kazhiyum. chlornafassin moolamundaakunna dnaude gadanaaparamaaya mattangal dna coode thettayi vaayikkunnathilekkum dna, rna, protein synthesis ennivayude nirodhanathilekkum prograam cheytha koshangalude maranathilekkum nayikkunnu. dna attakuttappanikalkk samayamillaatha athivegam valarunna koshangalil alkailetting ejantukalkku praadhamika swaadheenam cheluthunnathinaal cancer koshangalaan ettavum kooduthal baadhikkappedunnathu.
prathikaranasheshi.
shareerathile chlornafaasisinte prathipravartthanatthinte pradhana vashamaan dna baseukal aalkkailett cheyyaanulla kazhivu. ettavum nucleophilic, axus cheyyaavunna sitaayathinaal gwanine baseukalude n7 aanu alchylation munganana nalkunnathu. dii. enn. ayumaayulla prathikaranatthinte samvidaanam thudarchayaayi rund ezz. enn. 2 prathikaranangaliloode munnott pookunnu, athil chlornafaasinte 2 bhagam (ch2ch2cl) ulppedunnu. aadya prathikaranatthil, naitrajan oru nucleophylayi pravarthichu haalojane sthaanabhramsham varuthunnathiloode oru asyridinium ayoon roopappeduthunnu. asyridinium ionine pinneedu dnayile nucleophilic sittukal akramikkunnu. randaamathe ch2ch2cl side cheyin upayogichu eee rund ghattangalum aavarthikkumbol, intra-allengil interstraand cross-linkukal roopappedaam. 
metabolism.
vaayiloode nalkunnathinum thudarnnulla agiranam cheiyunnathinum sesham, chlornafassin 2-nafthylaamainaayi metabolise cheyyappedunnu, ithu karalile enn-asattail transferase (naatt) 2 vazhi enn-asattailettu cheiyunnu. ithu oru vishaamsham illaathaakkunna prathikaranamaanu, kaaranam ithu prathipravarthanarahitha samyukthangalude roopeekaranathilekku nayikkunnu. pakaramaayi, cytochrome pii 450 suuppar faamiliyile amgamaaya amgamaaya athinte enn-hydroxy mettabolittil parivartthanam cheythekkaam. enn-hydroxy mettabolite karalil kooduthal metabolise cheyyaano moothrasanchiyilekku kondupokaano kazhiyum. karalil, gloottathayon ezz-transferase myoo 1 (jii. ezz. tii. emm 1) vazhi uthejippicha ezz-glutathionilation vidheyamaakaam, athil hydroxy groupine gloottathayon upayogichu maattisthaapikkunnath ulppedunnu. eee prathikaranam enn-hydroxy metabolaittinte vishaamsham illaathaakkunnathilekku nayikkunnu. cosbstrate euridine diphosphate-glucuronic assid (yuu. dii. pii. jii. eiii), ensime yuu. dii. pii-glucuronosil transferase enniva aavasyamulla glucuronic aasidumaayulla samyojanamaanu karalil sambhavikkaavunna mattoru jaiva parivartthanam. neutral piechile enn-glucuronideukalude sthiratha rakthathiloode moothrathilekku visarjjikkunna vrukkakalilekku kondupokaan anuvadikkunnu. moothrathinte neriya acidity avasthayil, glucuronide jalavishleshanam cheyyappedukayum moothrasanchiyile enn-hydroxy metabolaittine mochippikkukayum cheiyunnu. moothraashaya epithelium enn-hydroxy amainine oru arilnitrenium ionilekku kooduthal sajeevamaakkunnu. moothraashayathile moothraashayathile oo-asattileshan vazhiyaan enn-hydroxy mettabolittukale arilnitrinium ionukalilekku sajeevamakkaan kazhiyunna randaamathe samvidaanam. chlornafassen bio transformation uthppannangal moothrathil ninnu neekkam cheyyappedunnu. 
falaprapti.
athinte vyakthamaaya cytostatic prabhavam, vellathil swathanthramaayi layikkal, kudalil ninnu eluppathil agiranam cheyyal enniva kaaranam, hodgekins rogam, polisithemiya vera thudangiya marakamaaya systemic rogangalkk chlornafassen anuyojyamaaya chikilsayaayi thonni. hodgekins rogathinte vipulamaaya ghattangalude lakshanangalaya panii, sareerabhaaram kuraykkal, chorichil, vearp enniva chikilsikkunnathinulla phalapradamaaya marunnaan chlornafassin. 200-400 mg chlornafassin maasangal muthal varshangal vare divasena nalkiyappol eee gunakaramaya phalangal shradheyamaayirunnu. chlornafassen maathram ulkkollunna chemotherapy vazhiyo mattu cytostatic marunnukalumayi samyojippicho hodkins rogam chikilsikkaam. hodgekins rogathinulla cytostatic chikilsayude falaprapti anweshicha oru padanatthil, 23 maasathekku cytostatic marunnukal sweekarichathinu sesham 73 sathamaanam rogikalum poornnamaaya rogamochanathilekku poyathaayi report cheythu. chemotherapy radio theraappiyumaayi samyojippikkaanum kazhiyum. vikiranathe prathirodhikkunna rogikalkku chlornafassin polulla naitrajan kaduk nalkaam. naitrajan kaduk upayogichu chikilsicha hodgekins rogamulla rogikalil tumour pindam athivegam pinnott pooyi. ennirunnaalum, ex-reey theraappiyumaayi thaarathamyappeduthumbol tumours kooduthal vegathil veendum sambhavichu. polisithemiya veraykku chlornafassin phalapradamaaya chikithsayaanenkilum, chlornafaasinte apakadasaadhyatha valare kooduthalaayathinaal badal chikilsakal kooduthal prayojanakaramaanu.
prathikoola phalangal.
thudakkathil, chlornafasinu valia prathikoola phalangalonnum illennu report cheyyappettu, kaaranam udanadi paarshwafalangalonnum kandethiyitla. ennirunnaalum, varshangalkk sesham, hodgekins rogathinaayi chlornafassen upayogichu chikilsikkappedunna rogikalkku chlornafassen chikitsa nirtthi varshangalkk sesham moothraashaya arbudam undennu kandethiyathayi onniladhikam kesukal report cheyyappettu. koodaathe, chlornafassin upayogichu chikilsicha polisithamiya rogikalil 30 sathamaanam perkkum moothrasanchi cancer undaayirunnu. eee kesukalum adhika gaveshanangalum chlornafaasinte eee apakadakaramaaya paarshwafalatthilekku velicham veeshunnu. chlornafassin chikitsa chikilsaykku sesham 3 muthal 10 varsham vare moothrasanchiyile arbudam undaakkumenn nigamanam cheyyappettu. motham 100 gram chlornafassin kuranja alavil labhicha rogikalil maathramaan moothrasanchi kaansarinte vikaasam nireekshikkappettath, athinaal eee vaikia prathikoola phalam dosine aasrayichirikkunnu. alkailetting ejantumaarude saadhaarana prathikoola phalangal maarakathvam, durbalamaaya beejanana, kudal mucosal kedupaadukal, allopesia, anaemiya, paansitopeeniya, amenorrhea ennivayaanu.
vishaamsham.
chlornafassin upayogichu chikilsikkunna pala kesukalilum moothrasanchiyile cancer nireekshikkappettundu. carcinogenic prabhavam metabolittukal moolamaanennu soochippikkappedunnu, athesamayam chemotherapic pravartthanam marunnu moolamaanu. 2-nafthylamine enna adisthaana thanmathrayil naitrajan kaduk group chlornafaasinil adangiyirikkunnu. chloronfaasinte jaiva parivartthanatthil chloroethyl groupinte pilarpp ulppedunnu, ithu 2-nafthylamine roopappedunnathinu kaaranamaakunnu. manushya moothrasanchiyil eee samyukthathinte arbudakaariyaaya prabhavam ellaavarkkum ariyaavunnathaan. karalilum moothrasanchiyilum 2-nafthylamine bio aaktivett cheiyunnathu reactive arilnitrinium ionukal roopappeduthunnathinaayi eluppathil vighadippikkunna uthppannangalude roopeekaranathinu kaaranamaakunnu. proteinukal, dna, rna ennivayile nucleophilic sittukalumaayi sahavarthithvathode bandhippichu aadktukal roopeekarikkunna reactive electrophylukalaanu eee ionukal. chlornafassin derivetteevukalude tumour induction moothrasanchiyil prathyekamaanu, kaaranam moothrathinte acidity anthareekshathiloode maathrame carcinogenic mettabolittukale mochippikkaan kazhiyoo.
mrugangalil swaadheenam.
cornafaasisinte mutagenic efakttukal onniladhikam mruga maathrkakalil padikkappedunnu. manushyarum elikalum thammilulla upapachayam vazhikalile vyathyaasangal kaaranam chlornafaasisinte arbudamundaakkunnathinu padikkaan elikal anuyojyamallaatha mruga maathrkakalaanennu pala padanangalum theliyichittundu. athinaal, chlornafassin upayogichu chikilsikkunna elikalkku saadhaaranayaayi manushyareppole moothrasanchi cancer undaakilla. chainees haamstar shwaasakosha koshangalil chromosomal asaadhaaranathakal, elikalude lymphoma koshangalile mutationukal, elikalude hepattosaittukalile dnaude swaabhaavika "inn vitro" synthesis ennivaykku chlornafassin kaaranamaakumenn theliyikkappettittund. koodaathe, chlornafassin eliyudeyum eliyudeyum asthi majjaile erythrocytukalil chromosomal asaadhaaranathakal undaakkunnu. poost-myotic purusha anukkalil ithu valare mutagenic aayathinal munbu eee marunnin vidheyamaaya elikalkku janithaka apakadamaanu cornafassen ennu report cheyyappettittund. koodaathe, chlornafassen intraperittoniyal kuthivacha elikalkku shwaasakosha tumours vikasichappol chlornafassen subcootanial kuthivacha elikalkku praadeshika saarkomakal vikasichu. elikalil ninnu vyathyasthamayi, chlornafassin polulla moothrasanchi kaarsinojanukale padikkaan naaykkal anuyojyamaanu, kaaranam rund enangaludeyum moothrathinte piechu, moothramozhikkunna aavruthi enniva kaaranam naaykkalile sugandhamulla amainukalude metabolism manushyaril ullathinu samaanamaan. chlornafaasisinte mettabolite 2-naafthailaamaininte carcinogenic efakttukalekkurichulla arivu vipuleekarikkunnathinum mruga pareekshanangal nadathiyittundu. manushyarilethupole, 2-nafthylamine naaykkal, kurangukal, haamstarukal ennivayil moothrasanchi tumours undaakkunnu. moothraashaya arbudam elikalil undakamenkilum moothrathinte piechu, moothramozhikkal aavruthi, punarnirmmaanam enniva kaaranam elikalil valare durbalamaaya arbudakaariyaanu 2-nafthylamine. elikalil, 2-nafthylamine heppattomakal, karal adenomakal, kolaamgiyomakal ennivayude vardhanavinu kaaranamaayi.

