CJC 1295 nga erina DAC 5mg

▎ CJC1295 Nga erina Enzimba ya DAC

▎ CJC1295 Ne DAC Okunoonyereza

Kiki ekiva mu kunoonyereza kwa CJC1295 With DAC?

Okukozesa obusimu obufulumya obusimu bw’okukula obw’ekinnansi (GHRH) mu bujjanjabi kuliko ekkomo olw’ebbanga ettono lye likola. Kino kireetedde abanoonyereza okunoonya obusimu obusingawo obukola okumala ebbanga eddene obufulumya obusimu bw’okukula okusobola okulongoosa obulungi bw’obujjanjabi n’okubunguyira. Olw’okuba abantu banoonya obulamu n’obulungi, eddagala ly’abantu ku yintaneeti erya lukale liwadde amaanyi amakubo amampi okutuuka ku kunyweza ebinywa, okukendeeza amasavu, n’olususu olw’obuvubuka. Mu mbeera eno, analogs z’obusimu bw’okukula obukolebwa nga CJC1295 With DAC zisikiriza abantu okufaayo. Okunoonyereza kulaga nti abakozesa forum balaga obukugu n’obumanyirivu mu kugikozesa mu mirimu mingi, era ebigendererwa by’okulonda okukozesa ebintu ng’ebyo mulimu okugejja, okutumbula ebinywa, okuzza obuggya olususu, okulongoosa otulo, n’okuwona ebiwundu, n’ebirala ^[1] . Nga analog y’obusimu obufulumya obusimu bw’okukula ekola okumala ebbanga, okukulaakulanya CJC1295 With DAC kwesigamiziddwa ku kutegeera okw’obwegendereza enkola y’okulungamya obusimu bw’okukula. Wadde ng’abaana abasinga obungi abalina obuzibu bw’obusimu bw’okukula obw’enjawulo (GH) baba n’engeri ennungi ey’okukula ku GHRH, ekitundu ky’obulamu bwa GHRH bumpi nnyo, ekikoma ku bujjanjabi bwayo. Okusobola okukola ku nsonga eno, abanoonyereza bakoze CJC1295 With DAC, analog ya GHRH ekola okumala ebbanga. Okunoonyereza kulaga nti erimu ekibinja kya maleimide ekikola ku C-terminus, ekigisobozesa okusiba mu ngeri ya covalent ku puloteyina za plasma nga serum albumin, bwe kityo ne kyongera ku kitundu ky’obulamu bwayo era n’esobola okusitula okukola obusimu bw’okukula mu bantu okumala ennaku ezisukka mu mukaaga oluvannyuma lw’okugiwa omulundi gumu ^[2].

Enkola ki ey’okukola kwa CJC1295 Ne DAC mu kujjanjaba endwadde ezenjawulo?

Okusitula okufulumya obusimu bw’okukula: 

CJC1295 Nga DAC ddagala erikolebwa mu peptide eriyinza okusitula okukola obusimu bw’okukula (GH) okuva mu nseke y’omubiri ^{[2, 3]} Lirimu ekibinja kya maleimide ekikola ku C-terminus, ekigisobozesa okusiba mu ngeri ya covalent ku puloteyina za plasma nga serum albumin. Okusiba kuno kuwa CJC1295-protein conjugate ekitundu ky’obulamu ekiwanvu ennyo era kigisobozesa okusitula okukola GH mu bantu okumala ennaku ezisukka mu mukaaga oluvannyuma lw’okugiwa omulundi gumu. Okunoonyereza kulaga nti okukuba empiso ya CJC1295 ne DAC wansi w’olususu kiyinza okuvaako okweyongera okuwangaala, okusinziira ku ddoozi mu miwendo gya GH ne insulin-like growth factor I (IGF-I) mu bantu abakulu abalamu ^{[2, 3]} Oluvannyuma lw’okukuba empiso emu eya CJC1295 With DAC, average plasma GH concentration yeeyongera emirundi 2-10 era n’emala ennaku 6 oba okumala ebbanga eddene, era nga average plasma IGF-I concentration yeeyongera emirundi 1.5-3 era yamala ennaku 9-11. Ekitundu ky’obulamu ekibalirirwamu ekya CJC1295 With DAC kiri ennaku 5.8-8.1. Oluvannyuma lw’okuweebwa emirundi mingi, omutindo gwa IGF-I ogwa wakati gwasigala waggulu w’omutindo ogwasooka okumala ennaku 28.

Omulimu mu bbula ly’obusimu bw’okukula: 

Mu bikolwa by’ebisolo ebirina obutaba na busimu bw’okukula (GH), CJC1295 With DAC eraga ebirungi. Ku mbeba ezirina GHRH gene ablation, ebisolo ebifuna dose ya CJC1295 With DAC buli lunaku byalaga obuzito bw’omubiri obwa bulijjo n’obuwanvu bw’omubiri ^[4] Ebibe ebyajjanjabwa buli ssaawa 48 ne 72 byalina obuzito bw’omubiri n’obuwanvu bw’omubiri okusinga ebisolo ebyajjanjabwa placebo. Wadde ng’okuzza enkula mu mbeera eya bulijjo mu bujjuvu tekyatuukibwako, n’okulongoosa okumu kwalagibwa. Mu bibinja byonna eby’obujjanjabi, amasavu agatali malungi n’amasavu agali wansi w’olususu byali bya bulijjo. CJC1295 Ne DAC era yaleeta okweyongera mu total pituitary RNA ne GH mRNA, ekiraga okukula kw’obutoffaali bwa somatotroph, ekivuddemu ekyakakasibwa ebifaananyi by’obusimu obuziyiza endwadde.

CJC1295 Ne DAC etuuka etya empeera esinga okuwangaala mu nsonga z’ensengeka?

Okusiba kwa covalent ne serum albumin: 

CJC-1295 erimu ekibinja kya maleimide ekikola ku C-terminus, ekisobozesa ekintu okusiba mu ngeri ya covalent ku puloteyina za plasma nga serum albumin ^[2] Okuyungibwa kuno kusobozesa CJC-1295 okusigala ng’ekola mu musaayi, era ebbanga lyayo ly’okukola liwanvu nnyo okusinga ery’eddagala lya peptide eritali lya kuyungibwa erifulumizibwa amangu. Oluvannyuma lw’okusibibwa ku serum albumin, CJC-1295 ekola ekizibu ekinywevu ennyo, bwe kityo n’ewangaaza ebbanga lye kikola mu mubiri. Okugeza, ekibinja kya maleimide ekya CJC-1295 bwe kikwatagana mu ngeri ya covalent ku mumiro ogw’eddembe ku serum albumin, ekitundu ky’obulamu bwakyo mu musaayi kyeyongera nnyo. Enkola eno ey’okuyunga ya njawulo mu peptides ezitumbula omulimu era eteekawo omusingi gw’ekikolwa ekiwangaala ekya CJC-1295 ^[5]..

Okulongoosa obutebenkevu: 

Ebiva mu maleimide bisatu byakolebwa nga bakyusa ensonga efulumya obusimu bw’okukula kw’omuntu(hGRF), nga mu bino CJC-1295 ye tetra-substituted form of hGRF (1-29), nga Nε-3-maleimidopropionamide derivative of lysine eyongezeddwa ku C-terminus ^[6] .Ensengekera eno efuula CJC-1295 okweyongera okutebenkera mu vitro ku dipeptidyl peptidase-IV. Mu kwekenneenya okufulumya obusimu bw’okukula kw’obutoffaali bw’envunza obw’omu maaso obukuziddwa, ebiyungo byonna ebisatu ebiyitibwa human serum albumin conjugates byali bikola mu biramu. Ebiva mu maleimide bwe byafukibwa wansi w’olususu byokka mu nvunza ensajja eza bulijjo eza Sprague Dawley, okufulumya obusimu bw’okukula obw’amangu bwazuulibwa mu plasma. Mu byo, CJC-1295 yalaga okweyongera emirundi 4 mu kitundu wansi w’ekikulukusi ky’obusimu bw’okukula bw’ogeraageranya ne hGRF (1-29) mu ssaawa 2. Okugatta ku ekyo, okwekenneenya kwa Western blot ku plasma y’envunza ezafukiddwa CJC-1295 kwalaga nti waliwo ekintu ekikola ku busimu obuziyiza endwadde ekya CJC-1295 mu bbandi ekikwatagana ne serum albumin, ekyalabika nga wayise eddakiika 15 oluvannyuma lw’okukuba empiso era ne kisigala mu ntambula y’omusaayi okumala essaawa ezisukka mu 24. Ebivudde mu kunoonyereza kuno biraga nti CJC-1295 ye hGRF (1-29) analog enywevu era ekola ng’erina ekitundu ky’obulamu bwa plasma ekiwanvuye ^[6]..

Enkola ya CJC-1295 ku buzito bw’omubiri gwonna (TBW; kitegeeza±SE). Ku nkomerero y’ekiseera ky’obujjanjabi ekya wiiki 5, ekibinja kya CJC/24 h kyalaga TBW eya bulijjo ddala. Ebibinja bya CJC/48 h ne CJC/72 h byatuuka ku TBW esingako nnyo bw’ogeraageranya n’ekibinja kya GHRHKO/pbo, wadde nga kyasigala nga kitono okusinga mu kibinja kya HTZ/pbo.

Ensibuko:PubMed ^{[4] .}

Biki ebikozesebwa mu bujjanjabi ebya CJC1295 With DAC?

CJC1295 Ne DAC esobola bulungi okusitula okufulumya obusimu bw’okukula (GH). Okunoonyereza okungi kulaga nti eddagala lino liyinza okwongera ku average plasma GH concentration mu bantu abakulu abalamu mu ngeri eyesigamiziddwa ku ddoozi ^[3] . Okugeza, mu kunoonyereza okwakolebwa ku bantu abalamu, abantu abali wakati w’emyaka 21 ne 61 baalina okweyongera kw’obungi bwa GH mu plasma emirundi 2-10 okumala ennaku 6 oba okusingawo oluvannyuma lw’okufuna empiso ya CJC1295 With DAC wansi w’olususu. Ekikolwa kino eky’okusitula okufulumya obusimu bw’okukula kya makulu nnyo eri abalwadde abalina obutaba na busimu bw’okukula.

Ku baana abalina obuzibu mu busimu bw’okukula, wadde ng’abaana abasinga obungi balina enkula ennungi eri obusimu obufulumya obusimu bw’okukula (GHRH), ekitundu ky’obulamu ekitono ekya GHRH kikoma ku kukozesebwa kwayo mu bujjanjabi. Nga analog ya GHRH ekola ebbanga eddene, CJC1295 With DAC esobola okulonda covalently okusiba ku endogenous albumin, bwe kityo n’eyongera ku kitundu ky’obulamu bwayo n’obudde bw’okukola. Mu kunoonyereza ku mbeba za GHRH gene knockout (GHRHKO), kyazuulibwa nti okuweebwa omulundi gumu buli lunaku CJC1295 With DAC kisobola okukuuma obuzito bw’omubiri obwa bulijjo n’obuwanvu bw’omubiri bw’ebibe, ekiraga nti eddagala lino lirina omugaso oguyinza okukozesebwa mu kujjanjaba obutaba na busimu bw’okukula mu baana ^[4]. .

CJC1295 Nga olina DAC tesobola kukoma ku kusitula kufulumya busimu bwa kukula wabula n’okwongera ku mutindo gwa insulin-like growth factor I. Mu kunoonyereza ku bujjanjabi, oluvannyuma lw’okukuba empiso emu eya CJC1295 Ne DAC, average plasma IGF-I concentration mu bantu abakulu abalamu bweyongera emirundi 1.5-3 mu nnaku 9-11. Era oluvannyuma lw’okuweebwa emirundi mingi, omutindo gwa IGF-I ogwa wakati gusobola okusigala waggulu w’omusingi okumala ennaku 28 ^[4] . IGF-I erina emirimu egy’enjawulo egy’omugaso egy’omubiri mu mubiri gw’omuntu, omuli okutumbula okukula kw’obutoffaali, okwawukana, n’okuwangaala, n’okulungamya enkyukakyuka mu mubiri, n’ebirala N’olwekyo, okwongera ku mutindo gwa IGF-I kiyinza okuba n’akakwate akalungi ku kujjanjaba endwadde ez’enjawulo.

Biki ebiyinza okukozesebwa CJC1295 With DAC mu by’obujjanjabi n’ebikwatagana nabyo?

Obutabeera na busimu bw’okukula: 

CJC1295 Nga olina DAC esobola okusitula obutasalako enseke okufulumya obusimu bw’okukula. Ku balwadde abatafulumya busimu bumala olw’ensonga ez’enjawulo naddala abaana n’abakadde, kisobola bulungi okulongoosa embeera y’okulwawo okukula n’okukula n’okutumbula okukula kw’obuwanvu. Mu kujjanjaba obutaba na busimu bw’okukula, obujjanjabi obw’ekinnansi obw’okukyusa obusimu bw’okukula bufunye ebimu, naye CJC1295 With DAC erina ebirungi eby’enjawulo. Kisobola okwesiba mu ngeri ya covalent ku albumin ey’omunda, bwe kityo ne kyongera ku kitundu ky’obulamu bwakyo n’obudde bw’okukola ^[4] . Okugeza, mu kunoonyereza ku mbeba ezikoona obuzaale bwa GHRH, kyazuulibwa nti okugaba obujjanjabi bwa CJC-1295 buli lunaku kuyinza okukuuma obutonde bw’omubiri ogwa bulijjo n’okukula kw’ebibe bya GHRHKO, omuli obuzito bw’omubiri obwa bulijjo, obuwanvu bw’omubiri, obuzito obugonvu obw’enjawulo, n’amasavu agali wansi w’olususu, era mu kiseera kye kimu era kiyinza okuleeta okweyongera mu RNA yonna ey’omu nseke ne GH mRNA, ekikakasa okukula kw’okukula obutoffaali obufulumya obusimu (Alba M, 2006).

Ku balwadde abakulu abalina obuzibu mu busimu bw’okukula, CJC1295 With DAC tesobola kukoma ku kulongoosa butonde bwa mubiri, okwongera ku binywa, n’okukendeeza amasavu mu mubiri wabula n’okutumbula omutindo gw’obulamu. Obusimu bw’okukula nabwo bukola kinene mu mubiri gw’omuntu omukulu. Yeenyigira mu kulongoosa enkyukakyuka mu mubiri (metabolic regulation) mu puloteyina, amasavu, ne kaboni. Obutabeera na busimu bw’okukula kijja kuleeta obuzibu ng’amasavu mu mubiri okweyongera, ebinywa okukendeeza, n’amagumba okukendeeza. Okukozesa CJC1295 With DAC kiyinza okutereeza obuzibu buno okutuuka ku ddaala eritali limu n’okulongoosa embeera y’omubiri gw’abalwadde.

Okulwanyisa okukaddiwa: 

Emyaka bwe gyeyongera, okufulumya obusimu bw’okukula kw’omuntu kukendeera mpolampola, ekijja okuleetawo enkyukakyuka eziwerako ezikwata ku kukaddiwa. CJC1295 Nga DAC erina omugaso oguyinza okukozesebwa mu kulwanyisa okukaddiwa. Kiyinza okwongera ku kufulumya obusimu bw’okukula okutuuka ku ddaala eritali limu, ekiyamba okulongoosa okukendeera kw’emirimu gy’omubiri egyekuusa ku kukaddiwa. Okugeza, kiyinza okwongera ku bugumu bw’amagumba. Obusimu obukola amagumba busobola okutumbula emirimu gy’amagumba, okwongera ku bunene bw’amagumba, n’okuziyiza okuzimba amagumba; okutumbula amaanyi g’ebinywa. Obusimu bw’okukula busobola okusitula okukola obutoffaali bw’ebinywa, okwongera ku buzito bw’ebinywa n’amaanyi; okulongoosa obugumu bw’olususu n’okumasamasa. Obusimu obukula buyinza okufuula olususu okunywevu era okunyirira nga kitumbula okukola kolagini ^[4]..

Eddagala ly'emizannyo n'okuddaabiriza: 

CJC1295 Nga DAC erina okukozesebwa mu kuddaabiriza obuvune mu mizannyo n’okutumbula omutindo gw’emizannyo. Kiyinza okutumbula okuddaabiriza ebinywa n’okuddamu okukola n’okwanguyiza ebiwundu okuwona. Omuzannyi bw’afuna obuvune, omubiri gwetaaga okuddaabiriza ebitundu ebyonooneddwa amangu ddala nga bwe kisoboka okusobola okuzzaawo obusobozi bw’emizannyo. Obusimu bw’okukula bukola kinene mu nkola eno. Kiyinza okusitula okukula kw’obutoffaali n’okwawukana, okutumbula okukola kwa puloteyina, n’okwanguyiza okuddaabiriza ebinywa n’ebitundu ebirala ^[4] . Mu kiseera kye kimu, CJC1295 With DAC eyinza okwongera ku maanyi g’ebinywa n’okugumiikiriza n’okutumbula obusobozi bw’emizannyo. Obusimu obukula busobola okwongera ku buzito bw’ebinywa n’okulongoosa obusobozi bw’ebinywa okukonziba, bwe kityo ne kyongera amaanyi n’okugumiikiriza kw’abazannyi ^[4]. .

Endwadde ezikwata ku mubiri: 

Ku ndwadde ezimu ezikwata ku nkyukakyuka y’emmere ng’omugejjo n’okuziyiza insulini, CJC1295 With DAC eyinza okukosa enkyukakyuka y’amasoboza n’okusaasaana kw’amasavu n’okulongoosa okuwuliziganya kwa insulini nga etereeza ekisiki ky’ensonga y’okukula eringa obusimu bw’okukula-insulini. Omugejjo bulwadde bwa bulijjo mu nkyukakyuka y’emmere, era okubeerawo kwabwo kwekuusa ku butakwatagana wakati w’amaanyi g’onywa n’okukozesa. Obusimu bw’okukula busobola okutumbula okumenya amasavu n’okwongera okukozesa amaanyi, bwe kityo ne kiyamba okufuga obuzito bw’omubiri. Okuziyiza insulini kitegeeza okukendeera kw’obuwulize bw’omubiri ku insulini, ekivaako ssukaali okweyongera mu musaayi. Obusimu bw’okukula busobola okulongoosa enkola ya insulini n’okukendeeza ku sukaali mu musaayi ^[4]..

Mu kumaliriza, CJC1295 With DAC eraze ebirungi mu bintu ebingi mu kisaawe ky’okulungamya obusimu bw’okukula. Kirina omugaso omukulu si mu kujjanjaba obutaba na busimu bwa kukula kwokka wabula ne mu ddagala ly’emizannyo n’okuddaabiriza n’okunoonyereza ku kulwanyisa okukaddiwa. Enkola yaayo ekola okumala ebbanga eddene ekendeeza ku mirundi gy’egiwa, era obukuumi bwayo obulungi n’okugumiikiriza nabyo biwa obuwagizi obw’amaanyi eri okukozesebwa kwayo mu bujjanjabi. Wadde nga ekyali mu mutendera gw’okunoonyereza mu bintu ebimu ng’okulwanyisa okukaddiwa, ebivaamu ebyalagibwa edda bimala okukakasa ebirungi byayo eby’enjawulo n’essuubi ly’okukozesebwa mu ngeri engazi mu kitundu kya ssaayansi w’obulamu n’ebintu ebikwatagana nabyo.

Ebikwata ku Muwandiisi

Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.

Omuwandiisi wa Scientific Journal

Teichman SL mukugu alina obumanyirivu bungi era alina obuyinza mu by’obusawo n’okukola eddagala. Alina enkolagana ey’oku lusegere n’ebitongole ne kkampuni nnyingi ezimanyiddwa, nga Organizations Concentr Analges Inc, Teichman Drug Dev Consulting, Wroclaw Medical University, BEAT Biotherapeut Corp, Corthera Inc ne kkampuni ezikwatagana nazo Corthera, Chiasma, ARYx Therapeut Inc, n’ebirala Ekirala, era alina akakwate ne Athens Univ Hosp ne Albert Einstein College of Medicine, ekiraga nti alina amaanyi obumanyirivu mu kunoonyereza ku by’obujjanjabi n’enkola y’obujjanjabi. Ebitundu bye eby’ekikugu bikwata ku bintu bingi omuli Cardiovascular System & Cardiology, General & Internal Medicine, Engineering, Endocrinology & Metabolism, ne Pharmacology & Pharmacy, ng’akola eby’ekitalo n’ebintu by’akola naddala mu kukola eddagala n’obujjanjabi bw’ebiramu. Teichman SL ewandiikiddwa mu kiwandiiko ekijuliziddwa mu kiwandiiko ekijuliziddwa [3].

▎ Ebiwandiiko Ebikwatagana

[1] Van Hout MC, Hearne E. Netnography of Female Enkozesa y’ekirungo ky’okukula eky’obutonde CJC-1295: Pulses and Potions[J]. Okukozesa ebiragalalagala & Okukozesa obubi, 2016,51 (1): 73-84.DOI: 10.3109/10826084.2015.1082595.

[2] Timms M, Ganio K, Steel R. Enkola ey’okukakasa okukozesa obubi CJC-1295 mu sampuli za plasma z’embalaasi nga bakozesa LC-MS/MS[J]. Okukebera n'okwekenneenya eddagala, 2019,11 (8): 1248-1257.DOI: 10.1002 / dta.2599.

[3] Teichman S. L., Neale A., Lawrence B., n’abalala. Okusikirizibwa okumala ebbanga eddene kw’obusimu bw’okukula (GH) n’okufulumya ensonga y’okukula I eringa insulini nga CJC-1295, analog ekola ebbanga eddene ey’obusimu obufulumya GH, mu bantu abakulu abalamu[J]. Journal of Clinical Endocrinology & Enkyukakyuka mu mubiri, 2006, 91 (3): 799-805.DOI: 10.1210 / jc.2005-1536.

[4] Alba M, Fintini D, Sagazio A, n’abalala. Omulundi gumu buli lunaku okuweebwa CJC-1295, ekirungo ekimala ebbanga eddene ekifulumya obusimu bw’okukula (GHRH) analog, kifuula okukula okwa bulijjo mu kibe kya GHRH knockout[J]. Ekitabo ky’Amerika eky’eby’omubiri-Endocrinology n’enkyukakyuka y’ebirungo, 2006,291 (6): E1290-E1294.DOI:10.1152/ajpendo.00201.2006.

[5] Timms M, Ganio K, Forbes G, n’abalala. Okukebera enkola ya immuno polymerase chain reaction okuzuula CJC-1295 n’obusimu obulala obufulumya obusimu obukula mu plasma y’embalaasi[J]. Okukebera n'okwekenneenya eddagala, 2019,11 (6): 804-812.DOI: 10.1002 / dta.2554.

[6] Jetté L, Léger R, Thibaudeau K, n’abalala. Ensonga efulumya obusimu bw’omuntu (hGRF) _1-29 -albumin bioconjugates zikola GRF receptor ku anterior pituitary mu nvunza:: Okuzuula CJC-1295 nga GRF analog ewangaala[J]. Endocrinology, 2005, 146 (7): 3052-3058.DOI: 10.1210 / en. 2004-1286.

EBINTU BYONNNA N’AMAWULIRE GW’EBINTU EBIweereddwa KU MUTINDO GUNO BIKOZESEBWA KU KUSASANYA AMAWULIRE N’EBIKOLWA BY’OKUSOMESA BYOKKA.  

Ebintu ebiweereddwa ku mukutu guno bigendereddwamu kunoonyereza mu kisenge (in vitro research) byokka. Okunoonyereza mu kisenge (in vitro research) (Olulattini: *mu ndabirwamu*, ekitegeeza mu bikozesebwa mu ndabirwamu) kukolebwa ebweru w’omubiri gw’omuntu. Ebintu bino si bya ddagala, tebikkiriziddwa kitongole kya Amerika ekivunaanyizibwa ku by’emmere n’eddagala (FDA), era tebirina kukozesebwa kuziyiza, kujjanjaba oba kuwonya mbeera yonna ya bujjanjabi, bulwadde oba bulwadde. Kikugirwa nnyo mu mateeka okuyingiza ebintu bino mu mubiri gw’omuntu oba ebisolo mu ngeri yonna.