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1 kits (10 Vials)
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▎ Teriparatid Tsarin
Source: PubChem |
Jeri: SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF Tsarin Halitta: C 181H 291N 55O 51S2 Nauyin Kwayoyin: 4118 g/mol Lambar CAS: 52232-67-4 Saukewa: 16133850 Synonyms: Teriparatida; Teriparatidum; 1-34-PTH na mutum |
▎ Teriparatid Binciken
Menene ma'anar Teriparatid?
Teriparatid analog ne na sake haɗawa da hormone parathyroid (PTH) wanda ya ƙunshi amino acid 34 na farko na hormone parathyroid na ɗan adam. Yana daidaita metabolism na kashi ta hanyar yin kwaikwayon ayyukan physiological na hormone parathyroid endogenous. Teriparatid shine maganin anabolic na roba na farko da aka amince da shi don tsananin osteoporosis. Tsarinsa yana nuna babban homology tare da PTH na endogenous, yana ba da damar kunna mai karɓar PTH don daidaita ayyukan rayuwa na osteoclast.
Menene tsarin aiki don Teriparatid?
Tasiri kan osteoblasts:
Yana haɓaka haɓakar osteoblast: Teriparatid yana haɓaka haɓakar ƙwayoyin osteoblast precursor, ƙara lambobin osteoblast. A cikin nazarin dabba, kulawar teriparatide na tsaka-tsaki yana haɓaka haɓakar ƙwayoyin ƙwayoyin cuta na mesenchymal waɗanda ke iya bambanta cikin osteoblasts a cikin kasusuwa. Wannan ya ba da damar ƙarin sel don bambanta cikin manyan osteoblasts, samar da wadataccen wadataccen salon salula don samuwar kashi. Gwaje-gwajen al'adun sel na in vitro sun nuna cewa rabon sel na precursor na osteoblast a cikin rukunin da aka yi wa Teriparatid ya fi girma fiye da rukunin kulawa, yana nuna cewa Teriparatid kai tsaye yana haɓaka haɓakar ƙwayoyin osteoblast precursor [1,2].
Ingantattun Ayyukan Osteoblast: Teriparatid ba wai kawai yana haɓaka lambobi na osteoblast ba amma yana haɓaka ayyukan su. Yana haɓaka bayanin kwayoyin halittar da ke da alaƙa da haɗin matrix na kashi a cikin osteoblasts, kamar waɗanda ke ɓoye nau'in I collagen da osteocalcin, waɗanda ke nuna haɓakar matakan magana sosai. Nau'in I collagen, babban ɓangaren kwayoyin halitta na matrix na kasusuwa, yana ba da gudummawa ga samuwar tsarin matrix mai ƙarfi ta hanyar haɓaka haɓaka. Osteocalcin yana taka muhimmiyar rawa a cikin ma'adinan kashi ta hanyar haɓaka jigilar calcium ion a cikin matrix, don haka haɓaka haɓakar ƙashi. Ta hanyar waɗannan hanyoyin, osteoblasts suna haɗawa da ɓoye matrix na kasusuwa da inganci, suna sauƙaƙe sabon samuwar kashi [2,3].
Hanawa na osteocyte apoptosis: A ƙarƙashin yanayin yanayin ilimin lissafi na al'ada, osteocytes suna sha apoptosis bayan kammala takamaiman ayyuka na kafa kashi. Teriparatid yana kashe wannan tsarin apoptotic, yana tsawaita tsawon rayuwar osteocyte. Teriparatid yana kunna hanyoyin siginar salula masu dacewa, kamar hanyar PI3K/Akt. Bayan kunnawa, wannan hanyar tana hana maganganun sunadaran da ke da alaƙa da apoptosis, suna ba da damar osteoblasts su ci gaba da ayyukan haɓakar ƙashi da kuma kiyaye ci gaba da kwanciyar hankali na samuwar kashi [1,3].
Tasiri akan Osteoclasts: Tasirin Teriparatid akan osteoclasts yana da rikitarwa. A lokacin dosing na tsaka-tsaki, yana rinjayar osteoclasts ta hanyoyin kai tsaye. Yana haɓaka ɓoyewar osteoblast na osteoprotegerin (OPG), cytokine wanda ke da alaƙa da gasa ga mai kunnawa mai kunnawa na makaman nukiliya κB ligand (RANKL). RANKL shine maɓalli mai daidaitawa na bambancin osteoclast da kunnawa. Lokacin da OPG ya ɗaure zuwa RANKL, RANKL ba zai iya ɗaure ga mai karɓar RANK a saman sel precursor na osteoclast, ta haka yana hana bambance-bambancen osteoclast da maturation da rage haɓakar kashi. A cikin marasa lafiya na osteoporosis, inda resorption kashi ya wuce samuwar da ke haifar da asarar kashi, teriparatide yana rage aikin osteoclast ta wannan tsarin. Wannan yana mayar da ma'auni tsakanin resorption da samuwar, inganta haɓakar kashi [2,3].
Hoto 1 Wuraren aiki don layin farko na jiyya na osteoporosis. Teriparatid, wani yanki na sake hadewa na hormone parathyroid, yana motsa kasusuwa ta hanyar haɓaka aikin osteoblast kuma, zuwa ƙarami, yana hana daukar aikin osteoclast [4].
Daidaita Hannun Sigina masu alaƙa da ƙashi:
Wnt/β-Catenin Siginar Siginar Hanyar: Hanyar siginar Wnt/β-catenin tana taka muhimmiyar rawa a cikin haɓaka ƙashi da kiyaye kasusuwa homeostasis. Teriparatid yana kunna wannan tafarki, yana haɓaka haɓakar intracellular da fassarar makaman nukiliya na β-catenin. Nuclear β-catenin yana ɗaure da abubuwan rubutun da ke da alaƙa, farawa da rubutawa na ƙasusuwan ƙwayoyin halittar da ke da alaƙa da haɓaka furci na ƙayyadaddun bayanan osteoblast Runx2. Runx2 yana ƙara daidaita bambance-bambancen osteoblast da aiki, don haka inganta haɓakar kashi. Kunna wannan hanyar kuma yana hana bambance-bambancen osteoblast zuwa adipocytes, yana tabbatar da bambance-bambancen ɓangarorin ƙasusuwan kasusuwa mesenchymal zuwa layin osteoblast, don haka ƙara yawan kashi [1,3].
Hanyar Siginar Mai karɓa na PTH / PTHrP: Teriparatid, analog na hormone parathyroid (PTH), da farko yana yin tasirinsa ta hanyar ɗaure ga mai karɓar PTH / PTHrP. Bayan ɗaure, Teriparatid yana kunna hanyoyin sigina na ƙasa kamar hanyar cAMP/PKA da hanyar PLC/PKC. Kunna waɗannan hanyoyin yana daidaita aikin osteoblast da osteoclast, inganta haɓakar kashi. Hanyar cAMP/PKA tana haɓaka bayyanar da ƙwayoyin halittar da ke da alaƙa da osteoblast ta hanyar daidaita ayyukan abubuwan rubutu, yayin da hanyar PLC/PKC ke rinjayar sake fasalin cytoskeletal da motsin sel, yana shafar ƙaura da aiki na osteoblast [2,5].
Menene aikace-aikacen Teriparatid?
Maganin Osteoporosis
Osteoporosis bayan menopausal: Teriparatid shine wakili na anabolic na roba na farko da aka amince da shi don magance matan da suka shude tare da kasusuwa mai tsanani. Ta hanyar ƙarfafa samuwar kashi, yana ƙara yawan kashi, don haka yana rage haɗarin karaya. A cikin matan da suka shude, yin amfani da teriparatide na yau da kullum yana ƙara yawan ma'adinai na kasusuwa, yana rage haɗarin ɓarkewar vertebral ta 65% da kuma raunin da ba na vertebral ta 53% idan aka kwatanta da placebo. Wani meta-bincike na mutum-matakin bayanan haƙuri ya nuna raguwar 56% a cikin haɗarin fashewar hip idan aka kwatanta da sarrafawa. Bugu da ƙari kuma, idan aka kwatanta da risedronate, Teriparatid ya rage haɗarin sababbin kasusuwa da kasusuwa na asibiti da 56% da 52%, bi da bi, a cikin mata masu fama da osteoporosis mai tsanani [3,6,7]..
Namiji Kashi: An kuma amince da shi don magance ciwon kashi na namiji. Quattrocchi E et al. ya nuna cewa a cikin marasa lafiya na osteoporosis na maza, Teriparatid (20μg da 40μg injections na yau da kullum) sun haifar da karuwa mai mahimmanci a cikin ƙananan ma'adinai na lumbar kashin baya: 5.9% a cikin ƙungiyar 20μg da 9.0% a cikin ƙungiyar 40μg (duka P <0.001). A wuyan femoral, ƙananan kashi ya karu da 1.5% a cikin ƙungiyar 20μg (P = 0.021) kuma ta 0.9% a cikin ƙungiyar 40μg (P <0.001) [7].
Glucocorticoid-Associated Osteoporosis: Hakanan ana amfani da Teriparatid don bi da osteoporosis na glucocorticoid a cikin maza da mata marasa lafiya tare da karaya, yana taimaka wa waɗannan marasa lafiya ƙara yawan kashi kuma rage asarar kashi da raunin raunin da ke hade da amfani da glucocorticoid [8].
Taimakon Warkar da Karya: Ga marasa lafiya masu rauni, haɓaka haɓakar ƙashi na wucin gadi a wurin karyewar yana da mahimmanci don gyarawa, rawar teriparatide na iya cikawa. An yi nazari a cikin nau'ikan dabbobi da marasa lafiya a matsayin wakili mai yuwuwa don haɓaka waraka. Yayin da ake buƙatar ƙarin bincike, binciken da ake yi yana nuna yuwuwar sa wajen inganta warkar da karaya [3].
Alveolar Bone Regeneration: Abubuwan da ke da alaƙa sun nuna Teriparatid na iya yin amfani da farfadowa na alveolar kashi a cikin yanayi irin su necrosis jawbone, periodontitis na yau da kullum, osseointegration na hakora, da kuma motsin haƙori na orthodontic, inda ya inganta haɓakar ƙashi na alveolar. Koyaya, ana buƙatar ƙarin gwaje-gwajen asibiti na ɗan adam don tabbatar da aikace-aikacen sa da illolinsa a cikin cututtukan kashi daban-daban [9].
Ciki- da Lactation-Related Osteoporosis: A cikin marasa lafiya tare da ciki- da kuma lactation osteoporosis (PLO), jiyya tare da Teriparatid (20μg / rana) tare da alli da bitamin D ya haifar da karuwa mai girma a cikin ƙananan ma'adinai na lumbar a cikin watanni 12 da 24 idan aka kwatanta da calcium da bitamin D kadai. A cikin watanni 12, ma'anar karuwa a cikin ma'adinin ma'adinai na lumbar shine 20.9 ± 11.9% a cikin ƙungiyar teriparatide tare da 6.2 ± 4.8% a cikin ƙungiyar kulawa (P <0.001). A cikin watanni 24, ma'anar karuwar ma'adinin ma'adinai na lumbar kashin baya shine 32.9 ± 13.4% a cikin marasa lafiya 7 da aka bi da su tare da Teriparatid da 12.2 ± 4.2% a cikin marasa lafiya na 6 (P = 0.001). Babu sabon karaya na asibiti da ya faru yayin jiyya [10].
Aikace-aikace na Musamman: An ba da rahoton Teriparatid a cikin nazarin yanayin don takamaiman ƙasusuwan ƙashi, irin su hypoparathyroidism-hade osteodystrophy (ABD) tare da hypercalcemia. Wata mace mai shekaru 51 da ke dogara da dialysis ta sami hypercalcemia post-parathyroidectomy, wanda aka tabbatar ta biopsy na kashi kamar ABD. Bayan watanni 12 na jiyya na Teriparatid, matakan calcium na jini sun daidaita, suna wakiltar shari'ar farko da aka rubuta na Teriparatid magance hypercalcemia mai dangantaka ABD [11].
Kammalawa
Teriparatid yana da tasiri ga osteoporosis mai tsanani tare da haɗarin karaya. An nuna shi ga marasa lafiya tare da tarihin raunin osteoporotic da yawa, ƙananan ƙananan ma'adinai na ƙashi, da iyakanceccen amsa ga jiyya na osteoporosis na al'ada.
Game da Marubuci
Abubuwan da aka ambata a sama duk bincike ne, gyara su kuma Cocer Peptides ne suka haɗa su.
Mawallafin Jaridar Kimiyya
Susan V. Bukata mai bincike ce a Jami'ar Rochester School of Medicine and Dentistry, wacce ta kware a fannin likitancin kasusuwa da cututtukan musculoskeletal. Ta haɗu da wallafe-wallafe da yawa waɗanda ke mai da hankali kan ilmin halitta na kasusuwa, warƙar karaya, da aikace-aikacen asibiti na jami'an anabolic kamar teriparatide a cikin aikin orthopedic. Ayyukanta sun ba da gudummawar fahimtar dabarun warkewa don haɓaka gyaran kashi da sake farfadowa. An jera Susan V. Bukata a cikin ambaton ambaton [1].
