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Edemede na ozi ngwaahịa niile enyere na webụsaịtị a bụ naanị maka mgbasa ozi na ebumnuche mmụta.
Ngwaahịa ndị enyere na webụsaịtị a bụ naanị maka nyocha in vitro. A na-eme nyocha in vitro (Latin: * na iko *, nke pụtara na ihe eji enyo) na mpụga ahụ mmadụ. Ngwaahịa ndị a abụghị ọgwụ, ndị US Food and Drug Administration (FDA) akwadoghị ya, ha agaghịkwa eji ya gbochie, gwọọ, ma ọ bụ gwọọ ọnọdụ ahụike ọ bụla, ọrịa, ma ọ bụ ọrịa. Iwu amachibidoro nke ọma iwebata ngwaahịa ndị a n'ime ahụ mmadụ ma ọ bụ anụmanụ n'ụdị ọ bụla.
Nchịkọta
Ọrịa nje HIV na ọgwụgwọ antiretroviral (ART) na-ebute ọrịa metabolism abụba na-ebute nnukwu nsogbu na ahụike na ndụ nke ndị ọrịa HIV. Ọdịiche ndị a na-egosipụta n'ụdị dị iche iche, dị ka lipoatrophy na lipohypertrophy, yana oke mkpokọta anụ ahụ adipose visceral (VAT) bụ nke a ma ama. Mmụba nke VAT abụghị naanị na-emetụta ọdịdị anụ ahụ nke ndị ọrịa kamakwa ọ na-ejikọta ya na ọtụtụ nsogbu metabolic siri ike, gụnyere ọrịa obi, nguzogide insulin, na ọrịa imeju na-adịghị egbu egbu (NAFLD), na-etinye nnukwu ihe iyi egwu ndụ ogologo oge nke ndị ọrịa na ọnọdụ ahụike.
Tesamoreli, ihe analọgụ nke homonụ na-ewepụta homonụ sịntetik (GHHRH), na-enye olileanya ọhụrụ maka ọgwụgwọ nke abụba metabolism abormalities na ndị ọrịa HIV. Ọ na-ejikọ kpọmkwem na ndị na-anabata GHRH na gland pituitary nke dị n'ihu, na-akpali njikọ na ntọhapụ nke hormone uto endogenous (GH). GH na-arụ ọrụ dị mkpa n'ịhazi metabolism abụba na ahụ mmadụ, na-akwalite lipolysis, na-eme ka oxidation fatty acid dịkwuo elu, na ịhazi okwu mkpụrụ ndụ ihe nketa metụtara metabolism lipid, si otú ahụ na-enwe mmetụta dị mma na metabolism abụba. Usoro omume a pụrụ iche na-enyere Tesamoreli aka inye aka melite nsogbu metabolism abụba na ndị ọrịa HIV.
Ọgụgụ 1 Atụmatụ nyocha. A nwalere ngụkọta nke protein plasma 9, dabara na mkpụrụ ndụ ihe nketa na-eduga n'ime ụzọ mkpụrụ ndụ imeju nke tesamorelin gbanwere.
Usoro nke Omume nke Tesamoreli na Metabolism Fat na HIV
Ndị ọrịa
Iwu nke Hormone Uto-Insulin-dị ka Uto Factor Axis
Tesamoreli na-ejikọta ya na onye na-anabata GHRH na akpụkpọ ahụ cell nke ụbụrụ pituitary nke dị n'ihu, na-eme ka ụzọ mgbaàmà ndị na-anabata ya dị ka ụzọ akara JAK-STAT. Usoro ịgbalite a na-akwalite njikọ na ntọhapụ nke hormone na-eto eto (GH) site na ụbụrụ pituitary anterior. Mgbe ịbanye n'ọbara, rute akụkụ ndị e lekwasịrị anya dị ka imeju, na-akpali imeju iji mepụta ma zoo insulin-dị ka ihe na-eto eto-1 (IGF-1). IGF-1 na-eje ozi dị ka a isi ogbugbo nke GH si metabolic mmetụta na-arụ a dị oké mkpa ọrụ na abụba metabolism. IGF-1 nwere ike ịgbalite ụzọ mgbama PI3K-AKT, gbochie adipocyte apoptosis, ma nọgide na-arụ ọrụ adipocyte nkịtị. Ọ na-akwalite nnabata na oxidation nke fatty acids site adipocytes, na-ebelata mkpokọta abụba n'ime sel. N'ime ndị ọrịa HIV, ọrụ nke hormone na-eto eto-insulin dị ka ihe na-akpata uto na-emekarị ka ọ ghara ịdị irè n'ihi ọrịa ahụ n'onwe ya na mmetụta nke ọgwụgwọ antiretroviral (ART). Tesamoreli nwere ike rụọ ọrụ axis iji weghachi ọrụ nchịkwa metabolism abụba nkịtị ya.
Mmetụta ozugbo na adipocyte metabolism
Ịkwalite lipolysis: Tesamoreli nwere ike ịkwalite okwu na ọrụ nke lipase hormone-sensitive (HSL) na adipocytes. HSL bụ isi enzyme na lipolysis, na-eme ka hydrolysis nke triglycerides banye glycerol na fatty acids, si otú ahụ na-akwalite metabolism nke abụba. Na vitro, ịgbakwụnye Tesamoreli na adipocytes azụlitere na-akwalite ọrụ HSL nke ukwuu ma na-abawanye ntọhapụ acid fatty nke ọma. Tesamoreli nwekwara ike mee ka HSL rụọ ọrụ n'ụzọ na-edoghị anya site na ịhazi ụzọ akara AMP (cAMP) -protein kinase A (PKA), na-akwalitewanye lipolysis. N'ime ndị ọrịa nje HIV, mmetụta a na-akwalite lipolysis na-enyere aka belata mkpokọta abụba gabigara ókè, ọkachasị mbelata abụba visceral, si otú ahụ meziwanye nkesa abụba na-adịghị mma na ndị ọrịa.
Iwu nke oxidation fatty acid: Tesamoreli na-akwalite ọrụ nke enzymes isi na-etinye aka na fatty acid oxidation n'ime adipocytes, dị ka carnitine palmitoyltransferase 1 (CPT1). CPT1 bụ enzyme na-ebelata ọnụego maka ntinye fatty acid n'ime mitochondria maka β-oxidation, yana ọrụ nkwalite ya na-akwalite ndakpọ oxidative nke fatty acids n'ime mitochondria, na-enye ume maka mkpụrụ ndụ. Tesamoreli nwekwara ike imeziwanye okwu nke enzymes ndị ọzọ na ndị na-ebugharị na-etinye aka na fatty acid β-oxidation, dị ka acetyl-CoA carboxylase 2 (ACC2) na fatty acid transporter 1 (FATP1), na-eme ka usoro metabolic oxidation fatty acid dịkwuo elu. Site n'ịkwalite oxidation fatty acid, Tesamoreli nwere ike ibelata nchekwa abụba n'ime sel ma melite nsogbu metabolism lipid na ndị ọrịa HIV.
Iwu nke mkpụrụ ndụ ihe nketa metụtara metabolism lipid
Na-emetụta mkpụrụ ndụ ihe nketa adipogenesis: Tesamoreli nwere ike igbochi okwu nke mkpụrụ ndụ ihe nketa adipogenesis, dị ka peroxisome proliferator-activated receptor γ (PPARγ) na CCAT / enhancer-binding protein α (C / EBPa). PPARγ bụ isi ihe ntụgharị ederede na adipocyte dị iche iche na adipogenesis, na-akwalite ọdịiche nke fibroblasts n'ime adipocytes tozuru okè, ma na-eme ka ngosipụta nke usoro mkpụrụ ndụ ihe nketa metụtara adipogenesis, dị ka protein fatty acid-binding protein 4 (FABP4) na fatty acid synthase (FAS). C/EBPa na-arụkwa ọrụ dị mkpa na adipocyte iche na adipogenesis. Site n'igbochi okwu nke PPARγ na C / EBPa, Tesamoreli na-ebelata ọdịiche adipocyte na adipogenesis, si otú ahụ na-ebelata mkpokọta abụba n'ime ahụ. N'ime ndị ọrịa HIV, mmetụta nchịkwa a na mkpụrụ ndụ ihe nketa metụtara adipogenesis na-enyere aka dozie mmepụta abụba gabigara ókè nke metabolism abụba na-adịghị mma kpatara.
Ọgụgụ 2 Mmekọrịta nke mgbanwe na Plasma VEGFA na CSF1 na Mgbanwe na NAS Score na ndị sonyere Tesamoreli-emeso.
Iwu nke njem lipid na mkpụrụ ndụ ihe nketa: Tesamoreli nwere ike ịhazi okwu nke mkpụrụ ndụ ihe nketa metụtara njem lipid na metabolism, dị ka ndị otu ezinụlọ apolipoprotein (Apo). ApoB bụ apolipoprotein bụ isi nke lipoprotein dị obere (VLDL) na obere njupụta lipoprotein (LDL), yana ọkwa ngosipụta ya jikọtara ya na ọkwa VLDL na LDL na plasma. Tesamoreli nwere ike belata okwu ApoB, belata njikọ na nzuzo nke VLDL na LDL, si otú a na-ebelata ọkwa plasma nke lipoproteins atherogenic. Na mgbakwunye, Tesamoreli nwere ike imeziwanye okwu ApoA-I, bụ isi apolipoprotein nke lipoprotein dị elu (HDL). Mmụba okwu ApoA-I na-enyere aka ibuli ọkwa HDL dị elu, kwalite njem mbugharị cholesterol, ma belata ohere nke ọrịa obi. N'ime ndị ọrịa HIV, ebe nsogbu metabolism lipid na-esokarị mmebi nke metabolism lipid, mmetụta nchịkwa Tesamoreli na njem lipid na mkpụrụ ndụ ihe nketa metabolism nwere ike inye aka melite profaịlụ lipid nke ndị ọrịa.
Mmetụta dị iche iche nke Tesamoreli na Lipid Metabolism na ndị ọrịa HIV
Mbelata Visceral Adipose Tissue (VAT)
Tesamoreli na-ebelata VAT nke ukwuu na ndị ọrịa HIV. N'ime nnwale ụlọ ọgwụ nke Atọ nke metụtara ndị ọrịa HIV, a na-ekenye ndị na-eso ụzọ ka ha nata 2 mg nke Tesamoreli kwa ụbọchị ma ọ bụ placebo maka izu 26. N'ime otu ọgwụgwọ Tesamoreli, ndị ọrịa gosipụtara mbelata dị ukwuu na VAT, a na-ahụkwa mbelata a n'ofe ndị ọrịa nwere njirimara ntọala dị iche iche (dịka ọmụmaatụ, ọnụnọ ma ọ bụ enweghị abụba azụ azụ). Maka ndị na-aza Tesamoreli (akọwapụtara dị ka ndị ọrịa nwere ma ọ dịkarịa ala 8% mbelata na VAT na ndị na-agbaso ọgwụgwọ), VAT belatara nke ukwuu n'agbanyeghị ọnụnọ olu na azụ azụ, ọ nweghịkwa ọdịiche dị ịrịba ama dị n'etiti otu abụọ ahụ (P = 0.657). Nke a na-egosi na Tesamoreli nwere nnukwu arụmọrụ n'ibelata VAT na ndị ọrịa HIV, na-adabereghị na ọnụnọ nke abụba azụ. Mbelata VAT abụghị naanị na-eme ka ọdịdị ahụ nke ndị ọrịa dịkwuo mma mana nke ka mkpa na-ebelata ohere nke nsogbu metabolic metụtara VAT, dị ka ọrịa obi na akwara ozi na nguzogide insulin.
Imezi abụba abụba metabolism
Mbelata ọdịnaya abụba imeju: N'ime ndị ọrịa HIV, ọrịa ọrịa imeju na-adịghị egbu egbu (NAFLD) dị elu yana njikọ chiri anya na metabolism abụba na-adịghị mma. Tesamoreli nwere mmetụta ọgwụgwọ dị mma na NAFLD metụtara HIV. N'ime usoro ọmụmụ, ndị kpuru ìsì abụọ, multicenter, ndị ọrịa bu nje HIV nwere obere abụba imeju (HFF) ≥5% ka e kenyere ndị otu tesamorelin ma ọ bụ ndị otu placebo ma gwọọ ọnwa 12. Nsonaazụ gosiri na ndị ọrịa nọ n'òtù Tesamoreli nwere mbelata dị ukwuu na HFF, na-enwe mmetụta zuru oke nke -4.1% (95% CI -7.6 ruo -0.7, P = 0.018) na nkwụsịtụ nke 37% site na ntọala (95% CI -67 ruo -7, P = 0.016). Mgbe ọnwa 12 gasịrị, 35% nke ndị ọrịa nọ na Tesamoreli nwere ọkwa HFF n'okpuru 5%, ma e jiri ya tụnyere naanị 4% na placebo otu (P = 0.0069). Nke a na-egosi na Tesamoreli na-ebelata abụba imeju nke ọma ma na-emezi abụba imeju na ndị ọrịa HIV.
Mmetụta nwere ike ime na akụkọ ihe mere eme imeju: Nnyocha nke profaịlụ mkpụrụ ndụ imeju na ndị ọrịa HIV-NAFLD gosipụtara na Tesamoreli mebiri usoro mkpụrụ ndụ ihe nketa metụtara mbufụt, nrụzi anụ ahụ, na nkewa sel na imeju. Ọmụmụ ihe ọmụmụ ndị ọzọ gosipụtara na Tesamoreli mere ka mbelata dị ukwuu na protein protein plasma nke vascular endothelial growth factor A (VEGFA), na-agbanwe ihe na-eto eto β1 (TGFB1), na macrophage colony-stimulating factor 1 (CSF1), nke jikọtara ya na fibrosis imeju na mbufụt. N'ime ndị ọrịa a na-emeso Tesamoreli, mbelata plasma VEGFA na CSF1 jikọtara ya na mbelata n'ọtụtụ ọrụ NAFLD, ebe mbelata nke TGFB1 na CSF1 jikọtara ya na mbelata nke ọkwa fibrosis nke mkpụrụ ndụ ihe nketa. Nke a na-egosi na Tesamoreli nwere ike ịkpata mmetụta bara uru na akụkọ ihe mere eme imeju site na ịhazi mbufụt na ụzọ metụtara fibrosis na imeju.
Ọgụgụ 3 Mmekọrịta nke mgbanwe na Plasma TGFB1 na CSF1 na Mgbanwe na Gene-Level Fibrosis Score na ndị sonyere Tesamoreli-emeso.
Iwu nkesa oke abụba na ihe mejupụtara ahụ dum
Mbelata oke abụba: Na mgbakwunye na ibelata VAT, Tesamoreli nwekwara mmetụta nchịkwa dị ukwuu na abụba akpati na ndị ọrịa HIV. N'ime ọmụmụ ụlọ ọgwụ, ndị ọrịa a na-emeso Tesamoreli gosipụtara mbelata nke nta nke nta nke abụba abụba, nke na-enyere aka melite ọdịdị ahụ ma belata okwu ndị dị ka nrịanrịa afọ nke kpatara nkesa abụba na-adịghị mma. Mbelata nke abụba akpati jikọtara ya na mbelata nke VAT, na-emekọ ọnụ na-emeziwanye nhazi ahụ.
Imezi okirikiri úkwù: Ọkpụkpụ úkwù bụ ihe dị mkpa na-egosi mkpokọta abụba afọ. Ọgwụgwọ Tesamoreli na-eme ka ọ dị mma gburugburu úkwù na ndị ọrịa HIV. N'ime ule ụlọ ọgwụ dị mkpa, ma ndị na-aza Tesamoreli nwere ma na-enweghị abụba azụ azụ gosipụtara mbelata dị ukwuu na gburugburu úkwù mgbe izu 26 nke ọgwụgwọ gasịrị. Ọganihu nke okirikiri úkwù ọ bụghị naanị na-egosipụta oke abụba afọ mana ọ na-ejikọkwa ya na mbelata ihe egwu metabolic dị ka ọrịa obi.
Mmetụta dị n'ụdị nhazi ahụ ndị ọzọ: Tesamoreli nwekwara mmetụta nchịkwa na usoro nhazi ahụ ndị ọzọ na ndị ọrịa HIV. Dịka ọmụmaatụ, n'ọmụmụ ihe ụfọdụ, ebe nchịkọta anụ ahụ (BMI) egosighị mgbanwe dị ịrịba ama, mmepụta abụba anụ ahụ ka mma. Tesamoreli nwere ike ịkwalite nkesa abụba anụ ahụ na-emetụtaghị oke ibu, belata mkpokọta abụba gabigara ókè, na-abawanye ihe ndị na-esighi ike nke anụ ahụ dị ka akwara, ma kwalite ogo ahụ ndị ọrịa.
Ngwa nke Tesamoreli na Fat Metabolism na ndị ọrịa HIV
Ndị Ezubere iche
Ndị ọrịa HIV nwere metabolism abụba na-adịghị mma: Tesamoreli bụ isi egosipụtara maka ndị ọrịa HIV nwere abụba na-adịghị mma, ọkachasị ndị nwere oke abụba visceral (dịka ọmụmaatụ, nyocha nke abdominal CT ma ọ bụ MRI nyocha nke na-egosi visceral adipose tissue [VAT] karịa oke nkịtị). Ndị ọrịa a na-egosipụtakarị oke ibu nke afọ, ịba ụba n'úkwù, yana nwekwara ike gosipụta ngosipụta ndị ọzọ nke ọrịa metabolic, dị ka insulin resistance na dyslipidemia.
Mmechi
Dị ka onye na-ahụ maka ọgwụgwọ dị irè maka metabolism abụba na-adịghị mma na ndị ọrịa HIV, Tesamoreli na-achịkwa metabolism abụba site na ọtụtụ usoro, na-arụ ọrụ dị ịrịba ama n'ibelata VAT, meziwanye metabolism abụba imeju, na-achịkwa nkesa abụba anụ ahụ dum, na ịkwalite nhazi ahụ.
Isi mmalite
[1] Rahman F, Chantal M, Mesquita P, et al. 935. Mmetụta nke Tesamoreli na ndị nwere nje HIV nwere na enweghị abụba Dorsocervical: Post Hoc Analysis of Phase III Double Blind Placebo Control Trial[J]. Ọgbakọ mepere emepe ọrịa na-efe efe, 2020,7(Mgbakwunye_1):S500-S501.DOI:10.1093/ofid/ofaa439.1121.
[2] Akụkọ nyocha ụlọ ọgwụ: Tesamoreli (Egrifta)[M]. Ottawa (ON): Agencylọ ọrụ Canada maka ọgwụ na teknụzụ na ahụike, 2016.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=30920787&query_hl=1.
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