ajacitidine

vidaja anae brand paerutoe vikrayinche ajacitidine, myelodysplastic syndrome, myeloid leukemia mariyu juvenile myelomonocytic leukemia chikitsaku upayoginche aushadham. idhi cytidine yokka rasayana saaruupyata, idhi dna mariyu rnlo nucleoside. ajacitidine mariyu daani dioxy utpannamaina decitabine (5-ajaa-2′-dioxycytidine anie kooda pilustaaru) modata chekoslovekialo cancerku sambhaavya chemotherapy agentluga samslaeshanha cheyabaddaayi.
baalya myelomonocytic leukemia unna pillalalo atyanta saadhaarana pratikuula praticharyalalo pyrexia, daddurlu, eguva swaasakosha sankramana mariyu raktaheenata unnaayi.
vaidya upayogaalu.
ajacitidine myelodysplastic syndrome chikitsa kosam suuchimchabadutumdi, dheeni kosam dheeniki yuu aamodam pondindi.ess. 2004 mae 19naa phud und drugg administration (fda). ajacitidine nuu sahayaka chikitsato polchina rendu yaadruchchika niyantrita pareekshalalo, ajacitidine sweekarinchadaaniki yaadrucchikamgaa cheyabadina myelodysplastic syndrome unna 16 saatam mandhi rogulu rakta kanaala gananalu mariyu emuka majja padanirmaana shaastram yokka puurti ledhaa pakshika saadhaaraneekarananu kaligi unnaaru, sahayaka samrakshana pondina evarithoonuu poliste, mariyu rakta marpidi avasaramayye rogulalo moodinta rendu vantula mandiki ajacitidine pondina tarvaata vaatini avasaram ledhu.
myeloid leukemia mariyu juvenile myelomonocytic leukemia chikitsa kosam kooda ajacitidine suuchimchabadutumdi. ajacitidine mariyu venetoclax kalayika kooda aaml kosam aamodinchabadindi.
charya yokka yantraangam.
ajacitidine anedi nucleoside cytidine yokka rasayana analog, idhi dna mariyu rnlo untundi. idhi rendu vidhaanaala dwara antineoplastic charyanu kaligi untundani bhaavistunnaaru-takkuva motaadulo, dna methyl transferesnu nirodhinchadam dwara, dna hypomethylationku kaaranamavutundi, mariyu adhika motaadulo, dna mariyu rnlo vileenam cheyadam dwara emuka majjaloni asaadhaarana hematopoietic kanaalaku daani pratyaksha cytotoxicity dwara, phalitamgaa kana maranam. ajacitidine anedi oka ribonucleoside, kabatti idhi dna kante ekkuva sthaayilo rnlo vileenam cheyabadutundi. dheeniki viruddhamgaa, decitabine (5-aza-2 '-dioxycytidine) oka dioxyribonucleosy, kabatti idhi dnalo matrame ponduparachabadutundi. rnalo ajacitidine vileenam polyribosomla vibhajana, lopabhuishta methylation mariyu badilee rna yokka sweekarta paniteeru mariyu proteinla utpattini nirodhinchadaaniki daariteestundi. dnalo daani vileenam dna methyl transferagelatho samayojaneeya bandhaaniki daariteestundi, idhi dna samshlaeshanhanu nirodhistundi mariyu taruvaata cytotoxicityki daariteestundi. idhi human immuno deficiency virus "inn vitro" mariyu human tii-lymphotropic vairasku vyatiraekamgaa prabhaavavantamgaa undani niroopinchabadindi.
methylation nirodham.
ajacitidine vanti azanucleosidelu 5-ajaa-2′-dioxycytidine-trifasphate (akaa, decitabine-trifasphate) gaa jeevakriya cheyabadina taruvaata, vaatini dnalo cherchavacchu mariyu azacetosine cytosineku pratyamnaayamgaa upayoginchavacchu. azacetosine-gwanin dinucleotidelanu dna methyl transferesla dwara uparitalamgaa gurtistaaru, ivi nucleophilic daadi dwara methylation praticharyanu utprerakam chestaayi. idhi cytosine ring yokka carbon-6 anuvu mariyu enjaim madhya samayojaneeya bandhaaniki daariteestundi. bandham saadhaaranamgaa carbon-5 anuvu dwara beata-tolagimpu dwara parishkarinchabadutundi, conny eee taruvaati praticharya ajacetosintho jaragadu endukante daani carbon-5 natrajani dwara bharti cheyabadutundi, enjaimnu samayojaneeyamgaa DNA kii kattubadi vadili daani DNA methyl transferes functionnu addukuntundi. adanamgaa, samayojaneeya protein jodimpu kooda dna yokka kaaryaacharananu raajee chestundi mariyu dna nashtam sankethaalanu prerepistundi, phalitamgaa chikkukunna dna methyl transferrages ksheenataku daariteestundi. paryavasanamga, dna replication samayamlo methylation gurtulu kolpotayi.
vishapuuritam.
ajacitidine raktaheenata (erra rakta kanaala sankhya takkuva), neutropenia (tella rakta kanaala sankhya takkuva), mariyu thrombocytopenia (plateletla sankhya takkuva) laku kaaranamavutundi, mariyu rogulu kaneesam prati motaadu chakraniki mundu vaari puurti rakta gananalanu tarachugaa paryaveekshinchaali. nadir gananalu mariyu hematologic pratispandana aadhaaramgaa motaadunu sardubaatu cheyalsi untundi.
teevramaina kaaleya balaheenata unna rogulalo idhi hepatotoxic kooda kaavacchu, mariyu metastatic vyaadhi kaaranamgaa vistrutamaina kaaleya kanitulu unna rogulu pragatiseela hepatic coma mariyu ajacitidine chikitsa samayamlo maranaanni abhivruddhi chesaaru, mukhyamgaa vaari albumin sthaayilu 30 graa/lii kante takkuvagaa unnappudu. idhi adhunaatana praanaantaka hepatic kanitulu unna rogulalo vyatiraekamainadi.
moothrapindaala vishapuuritam, perigina seeram creatinine nundi moothrapindaala vaiphalyam mariyu maranam varaku, myelodysplastic syndrome kakunda itara paristhitulaku itara chemotherapy agentlatho kalipi intravenous ajacitidintho chikitsa pondina rogulalo nivedinchabadindi. moothrapindaala gottapu aamlam anedi ajacitidine mariyu etoposidetho chikitsa cheyabadina deerghakaalika milogenous leukemia (aamodinchabadani upayogam) unna aiduguru rogulalo abhivruddhi chendindi, mariyu moothrapindaala balaheenata unna rogulaku moothrapindaala vishapuuritatvam vachhe pramaadam ekkuvagaa undavacchu. ajacitidine mariyu daani gvakriyalu pradhanamgaa moothrapindaala dwara visarjinchabadataayi, kabatti deerghakaalika moothrapindaala vyaadhi unna rogulanu itara dushprabhaavaala kosam nisitamgaa paryaveekshinchaali, endukante vaari ajacitidine sthaayilu kramamga peragavacchu.
janthu adhyayanalu mariyu daani charya yokka vidhanam aadhaaramgaa, ajacitidine pindam teevramaina nashtanni kaligistundi. punarutpatti saamarthyam unna laingikamgaa churukaina mahilalu ajacitidine sweekarinche samayamlo mariyu chivari motaadu tarvaata oka vaaram paatu garbhanirodhakatanu upayoginchaali, mariyu punarutpatti saamarthyam unna mahilaa bhaagaswaamulato laingikamgaa churukaina purushulu chikitsa samayamlo mariyu chivari motaadu tarvaata moodu nelala paatu garbhanirodhakatanu upayoginchaali.
elukalalo neuro behavioural asaadhaaranatalapai ajacitidine (5-azakh) kuu oke roeju bahirgatam yokka takshana mariyu deerghakaalika prabhavalanu anchanaa vaeyadaaniki chepattina oka adhyayanamlo, 5-azakh chikitsa dwara dna methylation nirodham neurodenerationku kaaranamavutundani mariyu navjata elukalalo extracellular signal-regulated kines (erk 1/2) activation mariyu activity-regulated cytoskeleton-associated (aark) protein vyakteekarananu balaheenaparustundani mariyu vayojana elukalalo pravartanaa asaadhaaranatalanu prerepistundani kanugonnaru, endukante abhivruddhi samayamlo synaptic circuitla saraina paripakvataku dna methylation-madhyavartitva yantraamgaalu avasaramani anipistundi, mariyu 5-azakh dwara eee prakriyaku antaraayam kaliginchadam asaadhaarana abhignaa paniteeruku daariteeyavachchu.
ajacitidine vikaram, vaantulu, jwaram, atisaaram, daani injection pradaesaalaloo erupu, malabaddhakam, gayalu, petechia, drudhatvam, balaheenata, raktapravaahamlo asadhaaranamgaa takkuva potassium sthaayilu mariyu aneka itara dushprabhaavaalaku kooda kaaranamavutundi, veetilo konni teevramainavi ledhaa praanaantakam kooda kaavacchu.
charitra.
baalya myelomonocytic leukemia unna 18 mandhi pillala rogulalo hematopoietic stem sell transplantationku mundu ajacitidine yokka pharmacokinetics, pharmacodynamics, bhadrata mariyu kaaryaacharananu anchanaa vaeyadaaniki antarjaateeya, bahula kendra, open-label adhyayanam ayina ajaa-jmml-001 (ncta 02447666) loe baalya myelomonocytic leukemia chikitsaku ajacitidine yokka saamarthyaanni anchanaa veyabadindi.
parisoedhana.
dna nundi methyl samuuhaalanu tolaginchadaaniki ajacitidine nuu "inn vitro" gaa upayoginchavacchu. idhi methylationku mundu sambhavinche janyu nissabda vidhaanaala prabhavalanu balaheenaparustundi. konni methylations nissabda sthithilo dnnu bhadraparustaayani nammutaaru, anduvalla demethylation anedi nissabda sankethaala sthirathvaanni taggistundi mariyu saapeksha janyu kriyaaseelatanu andistundi.
ajacitidine elukalalo isocitrate dehydrogenase-1 utparivartana glioma genographtspy kaniti tirogamanaanni prerepistundi.
parisoedhanaloo, vayojana muula kanaala cardiomyocyte bhedaanni prothsahinchadaaniki 5-ajacitidine saadhaaranamgaa upayoginchabadutundi. ayithe, eee aushadham cardiac deferentiation factorga rajipade saamarthyaanni kaligi undani soochinchabadindi, endukante idhi cardiac kanaalanu asthipanjara mayosaitlaku badilee cheyadaanni prothsahistundi.
ajacitidine janthu adhyayanaalalo alaage daani cancer nirodhaka charyalalo antiviral prabhavalanu kooda kaligi undhi, conny clinical upayogam kosam pareekshinchabadaledu.

