Na Cocer Peptides 
hashize iminsi 27
INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBONA AMAKURU N'INTEGO Z'UBUREZI.
Ibicuruzwa byatanzwe kururu rubuga bigenewe gusa mubushakashatsi bwa vitro. Mu bushakashatsi bwa vitro (Ikilatini: * mu kirahure *, bisobanura mu bikoresho by'ibirahure) bikorwa hanze y'umubiri w'umuntu. Ibicuruzwa ntabwo ari imiti, ntabwo byemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), kandi ntigomba gukoreshwa mu gukumira, kuvura, cyangwa gukiza indwara iyo ari yo yose y’ubuvuzi, indwara, cyangwa indwara. Birabujijwe rwose n'amategeko kwinjiza ibyo bicuruzwa mumubiri wabantu cyangwa inyamaswa muburyo ubwo aribwo bwose.
Incamake
Kwandura virusi itera sida no kuvura virusi itera SIDA (ART) -ibiterwa n'amavuta ya metabolisme idasanzwe bitera ibibazo bikomeye ku buzima no ku mibereho y'abarwayi ba virusi itera SIDA. Ibi bidasanzwe bigaragarira muburyo butandukanye, nka lipoatrophy na lipohypertrophy, hamwe no kwirundanya gukabije kwa tipusi adipose tissue (VAT) bigaragara cyane. Ubwiyongere bw'umusoro ku nyongeragaciro ntabwo bugira ingaruka gusa ku isura y'abarwayi gusa ahubwo binafitanye isano rya bugufi n'ingaruka zikomeye ziterwa na metabolike, harimo n'indwara z'umutima n'imitsi, kurwanya insuline, n'indwara y'umwijima idafite inzoga (NAFLD), bikaba bibangamira cyane abarwayi kubaho igihe kirekire ndetse n'ubuzima bwabo.
Tesamoreli, imisemburo ikura ya hormone irekura imisemburo (GHRH), itanga ibyiringiro bishya byo kuvura ibibyibushye bidasanzwe ku barwayi ba virusi itera SIDA. Ihuza cyane cyane na reseptor ya GHRH muri glande y'imbere ya pitoito, itera neza synthesis no kurekura imisemburo ikura ya endogenous (GH). GH igira uruhare runini muguhindura metabolisme yibinure mumubiri wumuntu, guteza imbere lipolysis, kongera okiside ya aside irike, no kugenzura imiterere ya genes zijyanye na metabolisme ya lipide, bityo bikagira ingaruka nziza kuri metabolism. Ubu buryo budasanzwe bwibikorwa butuma Tesamoreli ifasha kunoza imitekerereze ya metabolisme ku barwayi ba virusi itera sida.
Igishushanyo 1 Isesengura. Hakozwe isuzuma rya poroteyine 9 zose za plasma, zihuye na gen zo hejuru ziyobora inzira ya hepatike ya genatike itandukanye na tesamorelin.
Uburyo bwibikorwa bya Tesamoreli kuri Metabolism yibinure muri VIH
Abarwayi
Amabwiriza yo Gukura Hormone-Insuline-Nka Gukura Ibintu Axis
Tesamoreli ihuza reseptor ya GHRH kuri selile ya selile ya pitoito yimbere, ikora inzira yerekana ibimenyetso byerekana inzira nka JAK-STAT yerekana inzira. Ubu buryo bwo gukora buteza imbere gusohora no kurekura imisemburo ikura (GH) na glande y'imbere. Nyuma yo kwinjira mu maraso, igera ku ngingo zigenewe nk'umwijima, itera umwijima guhuza no gusohora insuline imeze nk'ikura-1 (IGF-1). IGF-1 ikora nk'umuhuza w'ingenzi w'ingaruka za metabolike ya GH kandi igira uruhare runini mu guhinduranya amavuta. IGF-1 irashobora gukora inzira yerekana ibimenyetso bya PI3K-AKT, ikabuza adipocyte apoptose, kandi igakomeza imikorere isanzwe ya adipocyte. Itera kandi gufata no okiside ya aside irike na adipocytes, bikagabanya kwirundanya kw'amavuta muri selile. Ku barwayi ba virusi itera sida, imikorere ya hormone yo gukura-insuline imeze nkikintu gikura akenshi iba yangiritse kubera indwara ubwayo n'ingaruka zo kuvura virusi itera SIDA (ART). Tesamoreli irashobora gukora iyi axis kugirango igarure imikorere yayo isanzwe ya metabolism.
Ingaruka zitaziguye kuri metabolism ya adipocyte
Guteza imbere lipolysis: Tesamoreli irashobora kugenzura imvugo nigikorwa cya lipase yangiza imisemburo (HSL) muri adipocytes. HSL ni enzyme yingenzi muri lipolysis, itera hydrolysis ya triglyceride muri glycerol na aside irike, bityo igateza metabolisme ya catabolike yibinure. Muri vitro, kongeramo Tesamoreli kuri adipocytes yumuco byongera ibikorwa bya HSL kandi byongera cyane kurekura aside irike. Tesamoreli irashobora kandi gukora mu buryo butaziguye HSL mu kugenzura cyclic AMP (cAMP) -protein kinase A (PKA) yerekana inzira, bikarushaho guteza imbere lipolysis. Ku barwayi ba virusi itera SIDA, iyi ngaruka itera lipolysis ifasha kugabanya ibinure byinshi, cyane cyane kugabanya ibinure byinjira mu mubiri, bityo bikagabanya ikwirakwizwa ry’amavuta adasanzwe ku barwayi.
Kugenga aside irike: Tesamoreli yongera ibikorwa byimisemburo yingenzi igira uruhare muri okiside ya aside irike muri adipocytes, nka karnitine palmitoyltransferase 1 (CPT1). CPT1 ni enzyme igabanya igipimo cyo kwinjiza aside irike muri mitochondriya ya β-okiside, kandi ibikorwa byayo byongerewe imbaraga bigabanya okiside igabanya aside irike muri mitochondriya, igatanga ingufu za selile. Tesamoreli irashobora kandi kugenzura imvugo yandi misemburo hamwe nabatwara ibintu bigira uruhare muri aside irike β-okiside, nka acetyl-CoA carboxylase 2 (ACC2) hamwe n’abatwara aside irike 1 (FATP1), bikarushaho kunoza imikorere ya metaboliside ya aside irike. Mugutezimbere okiside ya aside irike, Tesamoreli irashobora kugabanya ububiko bwamavuta mungirabuzimafatizo no kunoza imiterere ya lipide metabolism kubarwayi ba sida.
Kugena lipid metabolism bijyanye na gene imvugo
Kugira ingaruka zijyanye na adipogenezi: Tesamoreli irashobora kubuza imvugo ya gen zifitanye isano na adipogenezi, nka peroxisome prolifator-ikora reseptor γ (PPARγ) na CCAAT / poroteyine yongerera imbaraga α (C / EBPα). PPARγ ni ikintu cyingenzi cyo kwandukura adipocyte itandukanya na adipogenez, iteza imbere itandukanyirizo rya fibroblast muri adipocytes ikuze, kandi itera imvugo yuruhererekane rwa gen zifitanye isano na adipogenezesi, nka poroteyine ya fatide ihuza amavuta 4 (FABP4) hamwe na synthase ya aside irike (FAS). C / EBPα nayo igira uruhare runini mugutandukanya adipocyte na adipogenez. Muguhagarika imvugo ya PPARγ na C / EBPα, Tesamoreli igabanya itandukaniro rya adipocyte na adipogenezi, bityo bikagabanya ibinure mu mubiri. Ku barwayi ba virusi itera sida, iyi ngaruka igenga ingirabuzimafatizo ya adipogenezi ifasha gukosora amavuta arenze urugero aterwa na metabolism idasanzwe.
Igishushanyo 2 Isano ryimpinduka muri Plasma VEGFA na CSF1 hamwe nimpinduka mumanota NAS mubitabiriye Tesamoreli.
Kugena ubwikorezi bwa lipide na metabolism genes: Tesamoreli irashobora kugenga imvugo ya genes zijyanye no gutwara lipide na metabolism, nkabagize umuryango wa apolipoprotein (Apo). ApoB ni apolipoproteine yibanze ya lipoprotein nkeya cyane (VLDL) na lipoprotein nkeya (LDL), kandi imvugo yayo ifitanye isano rya bugufi nurwego rwa VLDL na LDL muri plasma. Tesamoreli irashobora kugabanya imvugo ya ApoB, kugabanya synthesis hamwe no gusohora kwa VLDL na LDL, bityo bikagabanya urugero rwa plasma ya lipoproteine ya atherogene. Byongeye kandi, Tesamoreli irashobora kugenzura imvugo ya ApoA-I, apolipoproteine yibanze ya lipoproteine yuzuye (HDL). Kwiyongera kwa ApoA-I imvugo ifasha kuzamura urwego rwa HDL, guteza imbere ubwikorezi bwa cholesterol, no kugabanya ibyago byindwara zifata umutima. Ku barwayi ba virusi itera sida, aho usanga indwara ya lipide metabolism ikunze guherekeza lipide metabolism idasanzwe, ingaruka za Tesamoreli ku mikorere ya transport ya lipide na genes metabolism zirashobora gufasha kunoza imyirondoro y’abarwayi.
Ingaruka zihariye za Tesamoreli kuri Lipid Metabolism ku barwayi ba virusi itera SIDA
Kugabanya Tissue ya Visceral Adipose (TVA)
Tesamoreli igabanya cyane TVA ku barwayi ba virusi itera SIDA. Mu cyiciro cya gatatu cy’amavuriro yerekeye abarwayi ba virusi itera sida, abitabiriye amahugurwa bahawe amahirwe yo kwakira mg 2 za Tesamoreli buri munsi cyangwa umwanya w’ibyumweru 26. Mu itsinda ry’ubuvuzi rya Tesamoreli, abarwayi bagaragaje igabanuka ry’umusoro ku nyongeragaciro, kandi iri gabanuka ryagaragaye ku barwayi bafite imiterere itandukanye (urugero, kuba hari ibinure byo mu ijosi cyangwa kutabaho). Ku babajijwe na Tesamoreli (bisobanurwa nk'abarwayi bafite byibura 8% bagabanijwe ku nyongeragaciro kandi bakurikiza ubuvuzi), TVA yagabanutse cyane hatitawe ku kuba hari amavuta yo mu ijosi no mu mugongo, kandi nta tandukanyirizo rishingiye ku mibare ryakozwe hagati y'ayo matsinda yombi (P = 0.657). Ibi byerekana ko Tesamoreli ifite imbaraga nyinshi mukugabanya TVA ku barwayi ba virusi itera sida, ititaye ku kuba hari amavuta yo mu ijosi. Igabanuka rya TVA ntirishobora gusa kunoza isura y’abarwayi gusa ariko cyane cyane rigabanya ibyago byo guterwa na VAT ziterwa ningaruka ziterwa na metabolike, nk'indwara z'umutima n'imitsi ndetse no kurwanya insuline.
Kunoza ibinure byumwijima metabolism
Kugabanya ibinure byumwijima: Ku barwayi ba virusi itera sida, indwara z’umwijima zidafite inzoga (NAFLD) ni nyinshi kandi zifitanye isano rya hafi na metabolism idasanzwe. Tesamoreli igira ingaruka nziza zo kuvura NAFLD iterwa na virusi itera sida. Mu bushakashatsi butemewe, buhumye-buhumyi, butandukanye, abarwayi banduye virusi itera sida bafite ibice by'amavuta ya hepatike (HFF) ≥5% boherejwe ku bushake mu itsinda rya tesamorelin cyangwa itsinda rya placebo maze bavurwa amezi 12. Ibisubizo byerekanye ko abarwayi bo mu itsinda rya Tesamoreli bagabanutse cyane muri HFF, hamwe ningaruka zingana zingana na -4.1% (95% CI -7.6 kugeza kuri -0.7, P = 0.018) no kugabanuka ugereranije na 37% kuva kuri baseline (95% CI -67 kugeza -7, P = 0.016). Nyuma y'amezi 12 yo kwivuza, 35% by'abarwayi bo mu itsinda rya Tesamoreli bafite urwego rwa HFF munsi ya 5%, ugereranije na 4% gusa mu itsinda rya placebo (P = 0.0069). Ibi byerekana ko Tesamoreli igabanya neza ibinure byumwijima kandi igahindura ibinure byumwijima kubarwayi ba virusi itera sida.
Ingaruka zishobora kubaho ku mateka y’umwijima: Isesengura ry’imiterere y’imiterere y’umwijima ku barwayi ba virusi itera SIDA-NAFLD ryerekanye ko Tesamoreli yagabanije gene igizwe no gutwika, gusana ingirabuzimafatizo, no kugabana ingirabuzimafatizo mu mwijima. Ubundi bushakashatsi bwakozwe na proteomics bwerekanye ko Tesamoreli yatumye igabanuka rikabije rya poroteyine ya plasma y’ikura ry’imitsi ikura ya A (VEGFA), ihindura ibintu bikura β1 (TGFB1), hamwe na macrophage colony-itera ibintu 1 (CSF1), bifitanye isano rya hafi na fibrosis yumwijima no gutwika. Mu barwayi bavuwe na Tesamoreli, igabanuka rya plasma VEGFA na CSF1 ryajyanye no kugabanuka kw'amanota y'ibikorwa bya NAFLD, mu gihe kugabanuka kwa TGFB1 na CSF1 byajyanye no kugabanuka kw'amanota ya fibrosis yo mu rwego rwa gene. Ibi byerekana ko Tesamoreli ashobora kugira ingaruka nziza mumateka yumwijima muguhindura umuriro hamwe ninzira zijyanye na fibrosis mumwijima.
Igishushanyo cya 3 Isano ryimpinduka muri Plasma TGFB1 na CSF1 hamwe nimpinduka mumanota ya Fibrosis ya Gene-Urwego rwa Tesamoreli-Abitabiriye.
Amabwiriza yo gukwirakwiza ibinure umubiri wose hamwe nibigize umubiri
Kugabanya ibinure by'imitsi: Usibye kugabanya umusoro ku nyongeragaciro, Tesamoreli afite n'ingaruka zikomeye zo kugenzura ibinure by'abarwayi ba virusi itera SIDA. Mu bushakashatsi bw’amavuriro, abarwayi bavuwe na Tesamoreli bagaragaje kugabanuka gahoro gahoro ibinure byamavuta, bifasha kunoza imiterere yumubiri no kugabanya ibibazo nko kuva munda biterwa no gukwirakwiza amavuta adasanzwe. Kugabanuka kw'ibinure by'imitsi bifitanye isano no kugabanya umusoro ku nyongeragaciro, hamwe hamwe kuzamura umubiri.
Kunoza umuzenguruko wikibuno: Kuzenguruka mu kibuno nikimenyetso cyingenzi cyo kwegeranya amavuta yo munda. Ubuvuzi bwa Tesamoreli butezimbere cyane kuzenguruka mu kibuno ku barwayi ba virusi itera SIDA. Mu bigeragezo bijyanye n’amavuriro, abajyanama ba Tesamoreli bafite ibinure byo mu ijosi kandi nta mugongo bagaragaje bagabanutse cyane mu kuzenguruka mu kibuno nyuma y’ibyumweru 26 bivurwa. Iterambere ry’umuzenguruko ntirigaragaza gusa ibinure byo mu nda gusa ahubwo bifitanye isano rya bugufi no kugabanya ingaruka ziterwa na metabolike nkindwara zifata umutima.
Ingaruka ku bindi bipimo bigize umubiri: Tesamoreli nayo igira ingaruka ku bindi bipimo bigize umubiri ku barwayi ba virusi itera SIDA. Kurugero, mubushakashatsi bumwe, mugihe indangagaciro zumubiri (BMI) zerekanye ko nta mpinduka zikomeye, ibinure byumubiri byateye imbere. Tesamoreli irashobora guhindura igabanywa ryamavuta yumubiri itagize ingaruka ku buremere rusange, kugabanya ibinure byinshi, kongera ibice byumubiri byumubiri nkimitsi, kandi bikazamura ubwiza bwumubiri wabarwayi.
Ikoreshwa rya Tesamoreli muri Metabolism yibinure kubarwayi ba virusi itera sida
Intego y'abaturage
Abarwayi ba virusi itera SIDA bafite metabolisme idasanzwe: Tesamoreli yerekanwa cyane cyane ku barwayi ba virusi itera SIDA bafite ibinure bidasanzwe, cyane cyane abafite ibinure byinshi byo mu nda (urugero, nk'uko bigaragazwa na scan yo mu nda ya CT cyangwa MRI yerekana ingirabuzimafatizo ya adipose [VAT] irenze urugero rusanzwe). Aba barwayi ubusanzwe bagaragaza umubyibuho ukabije wo munda, kuzenguruka mu rukenyerero, kandi barashobora no kwerekana ubundi buryo bwo kwerekana syndrome de metabolike, nko kurwanya insuline na dyslipidemiya.
Umwanzuro
Nka miti ifatika yo kuvura ibinure bidasanzwe ku barwayi ba virusi itera sida, Tesamoreli igenga metabolisme y’ibinure ikoresheje uburyo bwinshi, igira uruhare runini mu kugabanya umusoro ku nyongeragaciro, kunoza amavuta y’umwijima, kugenzura ikwirakwizwa ry’amavuta mu mubiri, no kunoza imiterere y’umubiri.
Inkomoko
[1] Rahman F, de Chantal M, Mesquita P, n'abandi. 935. Ingaruka za Tesamoreli kubantu banduye virusi itera sida kandi badafite ibinure bya Dorsocervical: Isesengura rya Hoc ryicyiciro cya III Ikigeragezo cya kabiri cya Blind Placebo Igenzura [J]. Fungura Ihuriro Indwara Zandura, 2020,7 (Umugereka_1): S500-S501.DOI: 10.1093 / ofid / ofaa439.1121.
[2] Raporo Yisubiramo Clinical: Tesamoreli (Egrifta) [M]. Ottawa (ON): Ikigo cya Kanada gishinzwe ibiyobyabwenge n'ikoranabuhanga mu buzima, 2016.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=30920787&query_hl=1.
Ibicuruzwa biboneka mubushakashatsi bukoreshwa gusa:
