Abaloparatide miligaramu 3

▎ Abaloparatide (abaloparatide) ka baarakɛcogo

▎ Abaloparatide ɲinini

Abaloparatidi ɲininiw kɛcogo ye mun ye?

Koloci ye kolotugudaw la bana ye min bɛ sɔrɔ fɛn caman fɛ, a bɛ sɔrɔ koloci dɔgɔyali fɛ ani kolotugudaw tiɲɛni ye microarchitectural fɛ. O bɛ na ni kolo karilen caya ye ani ka kari, ni kɔkolo ni kɔkolo kari ye a kɔlɔlɔw ye minnu ka teli ka sɔrɔ. A bɛ nɔba bila banabagatɔw ka ɲɛnamaya kɛcogo la ani ka dɔ fara bololabaara ni saya hakɛ kan. Ni diɲɛ kɔnɔ jamanaden kɔrɔbayara teliya la, koloci bɛ ka caya ka taa a fɛ. A jateminɛna ko musow 42%-56% ani cɛ minnu si tɛmɛna san 50 kan, olu 27%-29% bɛna koloci kɛ, o b’a to a bɛ kɛ foroba kɛnɛyako kɔrɔtɔlen ye. Laadalata furakɛli minnu bɛ kɛ ni koloci ye, i n’a fɔ bisifosifonatiw ni fɛnɲɛnamafagalanw (SERMs), olu bɛ koloci sabati fɔlɔ ni kolotugudaw ka kolotugudaw tali bali ye. Nka, u nafa ka dɔgɔn banabagatɔw la minnu kolo girinya dɔgɔyara kosɛbɛ ani minnu ka kari farati ka bon. Hali ni paratayiroyi ɔrimɔni (PTH) 1-34 yɔrɔ (teriparatide) tun ye anabolic fura fɔlɔ ye min sɔnna Ameriki dumuniko ni furako ɲɛmɔgɔso fɛ (FDA), min bɛ dɔ fara kolo girinya kan kosɛbɛ ani ka kolo karilen farati dɔgɔya, a tali kuntaalajan bɛ danyɔrɔw ta i n’a fɔ kolotuguda jiginni, kalisiyɔmu caya, ani osteosarcoma farati bɛ se ka bonya.

O hukumu kɔnɔ, ka fura kuraw labɛn minnu bɛ farikolojidɛsɛ fangamaw fara ɲɔgɔn kan ka sɔrɔ k’i yɛrɛ tanga o dɛsɛw ma, o nafa ka bon kosɛbɛ. I n’a fɔ parathyroïde hormone-related peptide (PTHrP) analozi, abaloparatide bɛ anabolic baara barikama mara ka sɔrɔ a bɛ dɔ bɔ kolo seginni nɔ na ani ka joli la kalisiyɔmu jiginni dɔgɔya, o b’a to a nafa ka bon koloci la.

Abaloparatidi ka baarakɛcogo ye jumɛnw ye?

Jɛɲɔgɔnya ni Paratayiroyidi ɔrimɔni minɛbaga 1 (PTH1R) ye .

Recepteur Selective Activation : Abaloparatide ye parathyroïde hormone receptor 1 (PTH1R) ka agoniste sugandilen ye. PTH1R bɛ jira kosɛbɛ farikolo yɔrɔw la farikolo yɔrɔw la i n’a fɔ kolo ni sugunɛ, o jɔyɔrɔ ka bon kolotugudaw labɛnni na. Abaloparatide bɛ siri kɛrɛnkɛrɛnnenya la PTH1R la, ka taamasiɲɛw sira caman daminɛ selilɛri kɔnɔ walasa ka kolotugudaw labɛn. Ni a sirilen don, a bɛ adenilati siklazi baara, ka dɔ fara AMP cyclique cyclique intracellular (cAMP) sɔrɔli kan walasa ka selilɛriw ka baara ni u farikolo lamagacogo sɛmɛntiya ^[1,2]..

Danfara minnu bɛ ligandi tɔw ni ɲɔgɔn cɛ: Parathyroïde hormone (PTH) ani parathyroïde hormone-related protein (PTHrP) fana bɛ siri PTH1R la. Hali ni PTH, PTHrP ani Abaloparatide bɛɛ bɛ taamasiɲɛ kɛ PTH1R fɛ, u ka jiginɛ taamasiɲɛw siraw tɛ kelen ye. PTH ni PTHrP bɛ ɲɔgɔndɛmɛ jira PTH1R ka R^G (GTPγS-sensitive) cogoya la. Teriparatide (TPTD, o kɔrɔ ye ko PTH 1–34) ka ɲɔgɔndɛmɛ ka bon R^0 (GTPγS-insensitive) cogoya la siɲɛ naani ka tɛmɛ PTHrP kan, o bɛ na ni cAMP taamasiɲɛ jan ye min bɛ sɔrɔ TPTD fɛ. O ni abaloparatide ta tɛ kelen ye, min bɛ bɔ PTHrP(1–34) la, o dilannen don walasa ka sabatili sabati ani ka se sɔrɔ ko dɔw kan i n’a fɔ anaboliki finɛtiri bɔnɛni ani kalisiyɔmu caya min bɛ tali kɛ TPTD tali la. Ikomi PTHrP-PTH1R complexe ka faranfasi hakɛ ka teliya ka tɛmɛ PTH-PTH1R complexe ta kan, PTHrP ka koloci nɔw bɛ taa ni a tali dɔgɔyali ye ani ka jolidɛsɛ caya ka tɛmɛ TPTD kan. Abaloparatide bɛ o nafa danfaralen in ciyɛn ta ^[1,2,3]..

Kolow ka sukarodunbana ɲɛnabɔli

Kolow bɔli sabatili : Abaloparatide bɛ kolotugudaw baara lawuli, ka dɔ fara kolotugudaw dilanni ni u bilali kan walasa ka kolo dilanni sabati. Kolotugudaw bɛ kolotugudaw yɔrɔw labɛn ani k’u bɔ i n’a fɔ kolajɛni ni kolotugudaw, olu bɛ kɛ minerali ye dɔɔni dɔɔni ka kolotugudaw kura dilan. Kɔlɔsiliw y’a jira ko kalolabɔ kɔfɛ koloci furakɛli la, abaloparatidi bɛ dɔ fara kolotugudaw hakɛ kan kosɛbɛ (BMD) yɔrɔw la minnu bɛ i n’a fɔ kɔkolo bɛɛ, senkɔniw kɔ ani kɔkolo. Ni a bɛ kolotugudaw ni ɲɔgɔn cɛ jamu jirali lawuli, a bɛ farikolojɔlifɛn kolomaw dilanni wuli ka taa a fɛ i n’a fɔ kolotugudaw ni kolajɛ suguya fɔlɔ. O bɛ trabecular thickening ni cortical barika bonya, ka kolo fanga ni a jogo bonya ka sɔrɔ ka dɔ bɔ kari farati la ^[1,2,3]..

Kolow tali balili : Hali ni Abaloparatide bɛ baara kɛ fɔlɔ i n’a fɔ anabolic agent, a bɛ kolotugudaw balicogo dɔw fana jira. A bɛ kolotugudaw ka danfara ni u ka baara kɛcogo sɛmɛntiya — kolotugudaw minnu bɛ kolo seginni ɲɛnabɔ, olu minnu bɛ kolotugudaw ni fɛnɲɛnamafagalanw labɔ ni asidifɛnw ni farikolojɔlifɛnw bɔli ye. Abaloparatide bɛ se ka kolo seginni hakɛ dɔgɔya ni kolotugudaw ɲɛbila selilɛriw danfara dɔgɔyali ye ka kɛ kolotugudaw kɔgɔlenw ye walima ka kolotugudaw kɔgɔlenw ka ɲɛnamaya surunya. O waati kelen na, a bɛ taamasiɲɛw sɛmɛntiya kolotugudaw ni kolotugudaw cɛ, ka balansi fangama mara kolo dilanni ni koloci seginni cɛ. Misali la, a bɛ dɔ bɔ kolotugudaw ka baarakɛcogo la ani ka kolotugudaw lasegin baara la ni a bɛ dɔ bɔ kolotugudaw la minnu bɛ bɔ kolotugudaw la, n’o ye nucléaire facteur κB ligand (RANKL) ka recepteur activateur ye. Abaloparatidi tɛ i n’a fɔ teriparatide, a tɛ dɔ fara RANKL bɔli kan kojugu, o la, a bɛ anabolic window bɔnɛni bali min bɛ kɛ ni resorption tɛmɛna formation kan kɔfɛ ^[1,2,.

Jaa 1 Paratayiroyi ɔrimɔni (PTH)/teriparatidi ni PTH-relilated peptide (PTHrP/abaloparatide activation de parathyroïde hormone type 1 receptor (PTH1R)) ^misali.

A nɔ minnu bɛ sɔrɔ sukarodunbana na (kalan minnu bɛ tali kɛ kolotugudaw la) .

A bɛ kolotugudaw labɛncogo sabati : Kɔlɔsili minnu kɛra kolotugudaw (OA) la, olu y’a jira ko abaloparatide bɛ kolotugudaw lakana. Articules chondrocytes bɛ PTH1R jira, ani Abaloparatide bɛ o recepteur in baara, ka chondrocytes lawuli u ka cartilage matrix yɔrɔw labɛn. Misali la, sɛgɛsɛgɛliw y’a jira ko Abaloparatide bɛ dɔ fara tubrisini (Prg4) jirali kan, o ye farikolojɔli dumuni nafama ye min bɛ kɛ farikolo kɔkanna matirili la kolotugudaw la min nafa ka bon kosɛbɛ kolotugudaw tulu sabatili la ani ka dɔ bɔ ɲɔgɔnkanu na. A bɛ kolajɛ suguya II fana labɛnni sabati, o min ye kolotugudaw matirili yɔrɔ fɔlɔ ye, o min bɛ dɛmɛ ka kolotugudaw jɔcogo n’a baarakɛcogo dafalen sabati. Ni a bɛ dɔ fara nin kolotugudaw matirizi yɔrɔw labɛnni kan, Abaloparatide bɛ dɛmɛ don ka kolotugudaw tiɲɛnenw dilan ani k’u lakana, kolotugudaw taabolo sumaya^ka .

Kɔnɔnatumuw caya ni u tiɲɛni balili : Abaloparatide bɛ se ka kɔndɔrositɛriw ka danfara cayacogo bali. Kolotugudaw bɛ taa ɲɛ tuma min na, kolotugudaw bɛ danfara don u ni ɲɔgɔn cɛ ka caya, o min bɛ sɔrɔ farikolokisɛ hakɛ caya fɛ ani kolotugudaw taamasiɲɛ kɛrɛnkɛrɛnnenw jirali ka caya i n’a fɔ kolajɛ suguya X (Col10). O kɛcogo bɛ na ni kolotugudaw tiɲɛni ye ani kolotugudaw tiɲɛni. Kɔlɔsiliw y’a jira ko Abaloparatide furakɛli bɛ Col10 jirali wulicogo nɔgɔya kolotugudaw la ka sɔrɔ ka dɔ bɔ farikolokisɛ belebelebaw hakɛ la minnu bɛ i n’a fɔ hypertrophique. O b’a jira ko a bɛ se ka kolosinsinnanw ka danfara caya sumaya, ka kɔndɔrositɛriw ka fɛnɲɛnamafagalanw cogoya ɲuman mara, o la, a bɛ kolotugudaw lakana ani ka kolotugudaw taabolo bila ^kɔfɛ.

Abaloparatide kɛcogo ye mun ye?

Koloci furakɛli

Kɔnɔmaya kɔfɛ koloci : Abaloparatide, o ye parathyroïde hormone receptor 1 (PTHR1) ka agoniste sugandilen ye, o ka kan ka kɛ koloci furakɛli la, kɛrɛnkɛrɛnnenya la musow la minnu bɛ kalolabɔ kɔfɛ, farati bɛ minnu na ka kari walima minnu tɛ furakɛli wɛrɛw jaabi. A bɛ dɔ fara kolotugudaw hakɛ kan kosɛbɛ ani ka dɔ bɔ kɔkolo ni kɔkolo tɛ kari kura sɔrɔli la ani ka farati lase musow ma minnu bɛ kalolabɔ kɔfɛ.

Cɛw ka koloci : Chandler H ka sɛgɛsɛgɛli la cɛw koloci kan ni sogo orchidectomisé (ORX wuluw, cɛ koloci modɛli ye), Abaloparatide furakɛli kɛra sababu ye ka dɔ fara kosɛbɛ BMD kan min suman ni dual-energy X-ray absorptiometry (DXA) ani peripheral quantitative computed tomography (pQCT) ye yɔrɔw la farikolo bɛɛ sen bɛ o la, kɔkolo kɔkolo, senkɔni ani senkɔni. A ye trabecular formation, kolo hakɛ ani microarchitecture ɲɛ kosɛbɛ k’a sɔrɔ a ma dɔ fara osteoclast hakɛ kan. O b’a jira ko Abaloparatide bɛ se ka furakɛli nafa sɔrɔ cɛw ka koloci la ^{[6] .}.

Koloci kɔfɛ (PTOA) Furakɛli : Gɛnɛgɛnɛ PTOA bilali kɔfɛ opereli fɛ meniscus destabilisation ménisque (DMM) fɛ dɔgɔkun 16 cɛ C57BL/6 sogow la, don o don, Abaloparatide 40 μg/kg (walima saline i n’a fɔ a kunbɛncogo) pikiri kɛra farikolo jukɔrɔ ka daminɛ dɔgɔkun 2 opereli kɔfɛ fo ka se dɔgɔkun 2 ma opereli kɔfɛ Dɔgɔkun 6 kɔnɔ. Farikoloɲɛnajɛ sɛgɛsɛgɛli kɛra dɔgɔkun 8 kɔnɔ. Jateminɛw y’a jira ko ni i ye a suma ni kulu min furakɛra ni kɔgɔ ye, Abaloparatide furakɛra kulu ye dɔ bɔ DMM fɛ joli-sira-funu bɔnɛni na ani ka senkɔniw sanfɛla kolotugudaw mara. Immunohistochimique sɛgɛsɛgɛli y’a jira ko Abaloparatide furakɛli ye kolajɛ suguya X (Col10) jiginni nɔgɔya kolotugudaw la, ka dɔ fara tubrisini (Prg4) jirali kan kolotugudaw yɔrɔw la minnu tɛ kalisiyɔmu sɔrɔ, ani ka dɔ bɔ farikolokisɛ belebelebaw hakɛ la. min b’a jira ko Abaloparatide bɛ danfara bɔli sumaya ani ka ɲɛgɛnɛsira lakanani nɔ bila sosow ka PTOA la, o bɛ furakɛli fɛɛrɛ kura di PTOA ^ma.

Kɔnɔnatumuw kolo seginni : Ɲɛgɛnɛsiraw bɔli kɔfɛ, o bɛ ɲinw lamagacogo kɔfɛ (OTM) walima ɲinw doncogo bali kosɛbɛ. Tan B ye fositɛri kalisiyɔmu nanobuluw (NF) minnu bɛ se ka tiɲɛ, minnu bɛ se ka tiɲɛ, minnu bɛ baara kɛ fila ye, minnu falen bɛ Abaloparatide (ABL) la, n’u bɛ wele ko ABL@NFs. Nin fɛn in bɛ a jira ko a bɛ kɛ ni porose layered structure ye, a bɛ furaw doncogo ɲuman jira, ani a bɛ biocompatibility ɲumanba jira. ABL bɔra a daminɛ na walasa ka jirisunw ta, o kɔfɛ, Ca⊃2;9 ni PO4⊃3;− bɔli basigilen kɛra ka ɲɛsin in situ interfacial mineralization ma. O ye ɲɛgɛnɛsira kolo min bɛ baara kɛ cogoya ni baarakɛcogo la, o lasegin ka ɲɛ k’a sɔrɔ a ma OTM tiɲɛ ^{[7] .}.

Hypoparathyroïdie réfractaire (HPT): Chamseddin R ye muso dɔ lakali min si bɛ san 39 na, HPT bɛ a la min bɛ wele ko iatrogenic, min ma se ka joli la kalisiyɔmu hakɛ bɛnnen sɔrɔ hali ni witamini D hakɛ caman, kalisiyɔmu faralen ɲɔgɔn kan, ani PTH (rPTH) pikiri minnu bɛ kɛ ɲɔgɔn fɛ. Abaloparatidi tali kɔ farikolo jukɔrɔ Simplicity patch fɛ ni kɔlɔsili ye kosɛbɛ ani ka a tata hakɛ kɛ a yɛrɛ ta ye, a joli la kalisiyɔmu tora a cogo la miligaramu 9/dL kalo 2 kɔfɛ. Kalo 4 kɔnɔ, a ye joli la kalisiyɔmu normal mara ka sɔrɔ a ma kɛ ni kalisiyɔmu dɔgɔyali waatiw ye ka sɔrɔ ka dɔ bɔ dɔɔni dɔɔni kalisiyɔmu da la ni witamini D tali la ^{[3] .}.

Kɔnɔbara basigilen opereli la : Kɔnɔbara ni barajuru seginni opereli la, abaloparatide tun bɛ kɛ ka kɔkolo farali sabati banabagatɔw la minnu ka kɔnɔbara basigilen tɛ u la ani minnu ka kɔnɔbara opereli caman ma ɲɛ. Parikh S ni a ɲɔgɔnnaw. ye banabagatɔ muso dɔ lakali min si bɛ san 66 la, min ye Abaloparatide miligaramu 80 furakɛli daminɛ don o don dɔgɔkun fila opereli kɔfɛ, dɔgɔkun 12 kalan bolodalen kama. Kɔnɔbara basigilen CT scans kalo 3 ni kalo 6 kɔnɔ, a jirala ko kɔnɔbara ni barajuru faralen ɲɔgɔn kan kɛnɛyara ka ɲɛ, ni jɛɲɔgɔnya tɛ taamasiɲɛ si tɛ a la ^{[8] .}.

Kuncɛli

Abaloparatide tali kɛnɛyaso la, o sinsinnen bɛ koloci furakɛli kan. A jiralen don musow ma minnu bɛ kalolabɔ kɔfɛ, koloci bɛ minnu na, minnu ka kari farati ka bon walima minnu tɛ furakɛli wɛrɛw jaabi, o bɛ dɔ fara kolotugudaw hakɛ kan kosɛbɛ (BMD) ani ka kɔkolo ni kɔkolo karibaliya farati dɔgɔya. Cɛw ka koloci la, baganw ka sɛgɛsɛgɛliw y’a jira ko BMD bɛ caya yɔrɔ caman na ani kolotugudaw labɛncogo ɲuman, o b’a jira ko furakɛli nafa bɛ se ka kɛ. Koloci kɔfɛ, a bɛ dɔ bɔ kolotugudaw bɔnɛni na ani ka kolotugudaw ka caya bali walasa ka kolotugudaw lakana. Kolow labɛnni na, ABL@NFs fɛnw minnu doni bɛ nin fura in na, olu bɛ kolo labɛnni sabati, o bɛ fura di kolo dilancogo kɔfɛ ɲinw labɛnni kɔfɛ. Sɛgɛsɛgɛliw fana b’a baara dɛmɛ ka ɲɛsin hypoparathyroïdie refractaire ma ani kɔkolo fusili yiriwali la.

A sɛbɛnbaga ko la

Fɛn minnu kofɔlen dòn san fɛ, olu bɛɛ ɲinini Kɛra, k’u Labɛn ani k’u Lajɛ Cocer Peptides fɛ.

Dɔnniya gafe sɛbɛnbaga

Bin T ye ɲininikɛla ye Pekin Iniwɛrisite ka Simiko ɲɛmɔgɔso la, a ka baara ɲɛsinnen bɛ nanomateriyaliw n’u baarakɛcogo ma biyomedikɛli injiniyɛri la. A ka baara sinsinnen bɛ nano-sɛnɛfɛnw dilanni n’u labɛnni kan furaw dicogo laɲininenw ni farikolo yɔrɔw labɛnni kama. Tan ye sɛbɛn caman sɛbɛn dɔnniya gafeba dɔw kɔnɔ, ka dɛmɛ don ɲɛtaa la nanofurakɛli ni furakɛlicogo kura la. Bin T bɛ sɛbɛn citation (citation) ɲɛfɔli sɛbɛn kɔnɔ [7].

▎ Sɛbɛn minnu bɛ tali kɛ o la

[1] Shirley M. Abaloparatide: Duniya bɛɛ ka sɔnni fɔlɔ. Dɔrɔguko san 2017; 77(12): 1363-1368.DOI: 10.1007/s40265-017-0780-7.. Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew.

[2] Sleeman A, Clements J. N. (2006) Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew. Abaloparatide : Furakɛcogo kura ye koloci furakɛli la. Ameriki ka kɛnɛyako-sɛnɛfɛnw furakɛli gafe 2019; 76: 130-135.Aw ka ɲɛnamaya kɛcogo ɲuman na.

[3] Chamseddin R, Mathew A, Alzohaili O. Abstract #1407986: Abaloparatide tali ni nɔgɔya patɔrɔn ye: Furakɛcogo sugandilen ye hypoparathyroïdie réfractaire la thyroïdectomie kɔfɛ Endocrin baarakɛcogo 2023; 29: S57-S58.DOI: 10.1016/j.eprac.2023.03.131. Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew.

[4] Thompson J. C., Wanderman N., Anderson P. A., Hɔrɔnya B. A., ani mɔgɔw ye baara kɛ ni u ye. Abaloparatide ni kɔkolo: Lakalili seginnkanni. Kɛnɛyaso ka dɛmɛ minnu bɛ kɛ kɔrɔya la san 2020; 15: Ɲɛjirali 1023-1033. DOI:10.2147/CIA.S227611. Ɲɛjirali dɔw bɛ kɛ.

[5] Landgrave S, Ishii T, Maynard R, ani a ɲɔgɔnnaw. 302 Abaloparatide ye fura kura ye koloci kɔfɛ. Kɛnɛyaso ni bamanankan dɔnniya gafe 2022; 6: 53. DOI:10.1017/cts.2022.166.. Ɲɛgɛnɛsiraw ani mɔgɔ dogoyɔrɔw.

[6] Chandler H, Lanske B, Varela A, ani a ɲɔgɔnnaw. Abaloparatide, n’o ye PTHrP analozi kura ye min bɛ kolotugudaw la, o bɛ dɔ fara kolotuguda ni kolotugudaw kolo girinya ni a jɔcogo kan sosow la minnu kɛra orchiectomized ye, a kɛtɔ ka dɔ fara kolo bɔli kan ka sɔrɔ a ma dɔ fara kolo seginni kan. Kolo 2019; 120: 148-155.DOI: 10.1016/j.kolo.2018.10.012.. Ɲɛgɛnɛsiraw ani mɔgɔ dogoyɔrɔw.

[7] Tan B, Wu Y, Wang R, ani a ɲɔgɔnnaw. Nanoflɛri minnu bɛ se ka tiɲɛ ni Abaloparatide ye, olu ɲɛnabɔli yɔrɔ ni waati la, min bɛ kɛ sababu ye ka kolotugudaw lasegin baarakɛcogo la. Nano Sɛbɛnw 2024. Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew.

[8] Parikh S, Lubitz SE, Sharma A. MON-365 Abaloparatide tali kura walasa ka kɔkolo fusili caya banabagatɔ la min bɛ kɔnɔbara basigilen opereli kɛ. Journal de la Société endocrine 2020; 4(Furakɛcogo_1): 365.DOI: 10.1210/jendso/bvaa046.108.

BƐƐRƐ KUNNAFONIW NI FƐRƐW KUNNAFONIW BƐƐ MIN BƐ NI WEBSITE KAN NA, U BƐ KUNNAFONIW FƆLƆ DƆRƆN NI KALANSENW YE.  

Fɛn minnu bɛ di nin siti in kan, olu dabɔra ɲininiw dɔrɔn kama in vitro. Sɛgɛsɛgɛli in vitro (latinkan na: *in glass*, o kɔrɔ ye gilasi minɛnw na) bɛ kɛ hadamaden farikolo kɔkan. Nin fura ninnu tɛ furaw ye, Ameriki dumuniko ni furako ɲɛmɔgɔso (FDA) ma sɔn u ma, wa u man kan ka kɛ ka furakɛli bana, bana walima bana si bali, k’a furakɛ, walima k’a furakɛ. A dagalen don kosɛbɛ sariya fɛ ka nin fɛn ninnu don hadamaden walima bagan farikolo la cogo o cogo.