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1kits (10Vials) .
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▎ Sermorelin ƒe Dɔwɔɖoɖo
Dzɔtsoƒe: PubChem |
Nusiwo woɖo ɖe wo nɔewo yome: YADAXFXNSYRKVLGQLSARKLLQDXMSR Molekyulãwo ƒe Mɔfiame: C 149H 246N 44O 42S Molekyulã ƒe Kpekpeme: 3357.9 g/mol CAS ƒe xexlẽdzesi: 86168-78-7 PubChem ƒe CID: 16129620 Nya siwo sɔ kple wo nɔewo: Sermorelin (INN);CHEBI: 9118 |
▎ Sermorelin Ŋuti Numekuku
Nukae nye Sermorelin?
Sermorelin nye tsitsi ƒe lãmetsiŋusẽ si ɖea asi le nu ŋu (GHRF) ƒe kpeɖeŋutɔ si wowɔ. Eƒe dɔ vevitɔe nye be wòabla ɖe tsitsi ƒe lãmetsiŋusẽ si ɖea asi le lãmetsiŋusẽ ŋu (GHRH) xɔlawo ŋu le ŋgɔgbe lãkusi me, ana lãmenugbagbeviwo me dzesimɔwo (abe cAMP/PKA mɔ ene) nawɔ dɔ, aʋã lãmenugbagbeviwo ƒe tsitsi ƒe lãmetsi (GH) ƒe wɔwɔme kple eƒe dodo, eye wòato esia me ado ɖeviwo ƒe tsitsi kple tsitsi ɖe ŋgɔ. Wozãnɛ koŋ tsɔ daa tsitsi ƒe lãmetsiŋusẽ gbãtɔ ƒe anyimanɔmanɔ (tsitsi ƒe nutete le ɖeviwo me si tsoa pituitary ƒe dɔmawɔmawɔ nyuie gbɔ). To GH ƒe dodo gbugbɔgaɖoanyi me la, ate ŋu ana ame ƒe kɔkɔme ƒe tsitsi kple lãmenugbagbeviwo ƒe dɔwɔwɔ nanyo ɖe edzi. To vovo na amegbetɔ ƒe tsitsi ƒe lãmetsi si wogbugbɔ ƒo ƒu, si kpena ɖe GH si tso gota ŋu tẽ la, Sermorelin ɖoa ŋu ɖe lãkusia ŋutɔ ƒe ʋuʋu ƒe ŋutete ŋu eye wòsɔ na dɔnɔ siwo ƒe lãkusi ƒe dɔwɔwɔ sɔ gake GHRH mesɔ gbɔ o.
Nukae nye numekuku si wowɔ le Sermorelin ŋu?
Numekuku si wowɔ tso Sermorelin ŋu la tso akpa vevi si tsitsimeŋusẽ wɔna le amegbetɔ ƒe tsitsi kple tsitsi me gbɔ. Tsitsi ƒe lãmetsi gbãtɔ ƒe anyimanɔmanɔ ate ŋu ana ɖeviwo natsi tsitsi nu eye wòakpɔ ŋusẽ ɖe woƒe kɔkɔme mamlɛtɔ dzi. Eyata atikewɔwɔmɔnu nyuiwo didi nye nya vevi aɖe le atikewɔwɔ ŋuti numekuku me ɣesiaɣi. Togbɔ be wozãa amegbetɔ ƒe tsitsimeŋusẽ si wogbugbɔ ƒo ƒu ƒe geɖe eye wòna ɖevi siwo ƒe tsitsime lãmetsiŋusẽ mele o ƒe kɔkɔme mamlɛtɔ dzi ɖe edzi ŋutɔ hã la, esi atikewɔwɔ ŋuti numekukuwo le goglom ɖe edzi ta la, amewo le atikewɔmɔnu geɖe wu kple atikewɔwɔmɔnu nyuitɔwo hã dim. Le nɔnɔme sia me la, Sermorelin, abe amegbetɔ ƒe tsitsime lãmetsiŋusẽ si wowɔ ene, do. Esi wòʋã tsitsimeŋusẽ ƒe dodo me la, ena mɔkpɔkpɔ yeye va li na tsitsimeŋusẽ ƒe anyimanɔmanɔ dada eye wòdo ɖeviwo ƒe tsitsi kple tsitsi ɖe ŋgɔ.
Dɔwɔwɔ ƒe Mɔnu
Nuka koŋue nye Semorelin ƒe mɔnu le tsitsi ƒe lãmetsi gbãtɔ ƒe anyimanɔmanɔ dada me?
Nusi dzi Semorelin ƒe nuwɔnaa nɔ te ɖo
Abe nusi ɖea tsitsi ƒe lãmetsiwo ɖa ene la, Sermorelin koŋ wɔa eƒe ŋusẽkpɔɖeamedziwo to eƒe kadodo kple lãmenugbagbevi tɔxɛ aɖewo me. Esrɔ̃a tsitsi ƒe lãmetsi si ɖea asi le dzɔdzɔme nu ƒe dɔwɔwɔ le amegbetɔ ƒe ŋutilã me eye wòʋãa ŋgɔgbe lãkusi be wòaɖe tsitsi ƒe lãmetsi. Dɔwɔwɔ ƒe mɔnu sia sɔ kple tsitsiŋusẽ ƒe lãmetsi bubuwo, abe tsitsimeŋusẽ si ɖea peptidewo (GHRPs) ene, tɔ.
Tsitsi ƒe lãmetsiŋusẽ ƒe dodo
Akpa si hypothalamic-pituitary axis wɔna le ɖoɖowɔwɔ me:
Sermorelin nye amegbetɔ ƒe tsitsime lãmetsiŋusẽ si wowɔ. Le nɔnɔme siwo sɔ me la, hypothalamic-pituitary axis ye kpɔa tsitsiŋusẽ ƒe dodo le amegbetɔ ƒe ŋutilã me dzi vevie. Hypothalamus ɖea lãmetsi si ɖea tsitsi ƒe lãmetsiŋusẽ (GHRH) ɖa, si ʋãa ŋgɔgbe lãkusi be wòawɔ tsitsi ƒe lãmetsi (GH) ahaɖee ɖa. Sermorelin srɔ̃a GHRH ƒe dɔwɔwɔ, blana ɖe lãmenugbagbevi tɔxɛ siwo le hypothalamus me ŋu, eye wòdoa pituitary gland ɖe ŋgɔ be wòaɖe tsitsi ƒe lãmetsiŋusẽ ɖe go.
Dzesimɔa ƒe dɔwɔwɔ :
Ne Sermorelin bla ɖe nusi xɔa nyatakakaa ŋu vɔ la, enaa lãmenugbagbeviwo me dzesimɔa wɔa dɔ. Esia ate ŋu abia be enzyme ƒe dɔwɔwɔ ɖe wo nɔewo yome kple amedɔdɔ ƒe ɖoɖo evelia, si ana tsitsi ƒe lãmetsi ƒe wɔwɔme kple eƒe dodo nadzi ɖe edzi mlɔeba. Le kpɔɖeŋu me, ate ŋu ana adenylate cyclase nawɔ dɔ, ana cAMP ƒe agbɔsɔsɔ si le lãmenugbagbeviwo me nadzi ɖe edzi, eye emegbe wòana protein kinase A nawɔ dɔ, si ana tsitsiŋusẽ ƒe domenyiŋusẽfianu ƒe nuŋɔŋlɔ kple egɔmeɖeɖe nado ŋgɔ.
Ŋusẽ si wòkpɔna ɖe tsitsi ƒe lãmetsiŋusẽ ƒe anyimanɔmanɔ dzi
Tsitsi kple ŋgɔyiyi dodo ɖe ŋgɔ:
Zi geɖe la, ɖevi siwo ƒe tsitsime lãmetsiŋusẽ gbãtɔ mesɔ gbɔ o la ɖea tsitsi blewu eye woƒe kɔkɔme nɔa kpuie. Sermorelin xea fe ɖe tsitsimeŋusẽ ƒe anyimanɔmanɔ le ŋutilãa me to tsitsimeŋusẽ ƒe dodo me. Tsitsi ƒe lãmetsi ate ŋu awɔ dɔ ɖe ƒuwo, lãmekawo, kple lãmenugbagbevi bubuwo dzi tẽ, ado lãmenugbagbeviwo ƒe dzidziɖedzi kple vovototodedeameme ɖe ŋgɔ, eye wòato esia me ado tsitsi kple tsitsi ɖe ŋgɔ. Tsitsi ƒe lãmetsi ate ŋu aʋã ŋutinuwo abe aklã ene hã be woawɔ tsitsinu si le abe insulin ene (IGF-1), eye IGF-1 gawɔa ŋusẽ si doa tsitsi ɖe ŋgɔ.
Lãmetsiŋusẽ ƒe dɔwɔwɔ nyuie wu:
Menye ɖeko tsitsi ƒe lãmetsiŋusẽ ƒe anyimanɔmanɔ kpɔa ŋusẽ ɖe tsitsi kple tsitsi dzi ko o, ke ate ŋu ahe lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe kuxiwo hã vɛ. Semorelin zazã ate ŋu ana lãmenugbagbeviwo ƒe dɔwɔwɔ nanyo ɖe edzi, abe protein ƒe wɔwɔme dzi ɖeɖe kpɔtɔ, ami ƒe gbagbã dodo ɖe ŋgɔ, kple sukli zazã nyuie wu ene. Tɔtrɔ siawo siwo vaa lãmenugbagbeviwo me kpena ɖe ŋutilãa ƒe ŋutilã ƒe dɔwɔwɔ nyuie ŋu eye wònaa dɔnɔwo ƒe agbenɔnɔ nyona ɖe edzi.
Kɔkɔme-SDS ƒe tɔtrɔ le ɖevi siwo ŋu kadodoŋusẽdɔlélewo le siwo wotsɔ dɔlékuiwutikewo da dɔe me.
Dzɔtsoƒe:PubMed [1] .
Nukae nye Semorelin ƒe dɔwɔwɔ?
Tsitsi ƒe lãmetsiŋusẽ ƒe anyimanɔmanɔ ƒe atikewɔwɔ:
Tsitsi ƒe lãmetsi gbãtɔ ƒe anyimanɔmanɔ ate ŋu ahe ɖeviwo ƒe tsitsi kple tsitsi ɖe megbe eye wòakpɔ ŋusẽ ɖe woƒe kɔkɔme mamlɛtɔ dzi. Wozãa amegbetɔ ƒe tsitsimeŋusẽ si wogbugbɔ ƒo ƒu le atikewɔnyawo me ƒe geɖe eye wòna ɖevi siwo ƒe tsitsimeŋusẽ mele o ƒe kɔkɔme mamlɛtɔ dzi ɖe edzi ŋutɔ. Esi wònye be Semorelin nye nusi ɖea tsitsime lãmetsiwo ɖa ta la, ewɔa akpa vevi aɖe hã le tsitsime lãmetsiŋusẽ ƒe anyimanɔmanɔ dada me.
Sermorelin doa ɖeviwo ƒe tsitsi kple tsitsi ɖe ŋgɔ to alesi wòʋãa lãkusi si woyɔna be pituitary gland be wòaɖe tsitsi ƒe lãmetsiŋusẽ ɖa. Ate ŋu asrɔ̃ alesi ŋutilãa ƒe dzɔdzɔmeŋusẽ si nye tsitsimeŋusẽ dona, ana tsitsimeŋusẽ ƒe agbɔsɔsɔ nadzi ɖe edzi, eye wòato esia me ado ƒuwo ƒe tsitsi kple ŋutilã ƒe tsitsi ɖe ŋgɔ. Ne wotsɔ Semorelin sɔ kple amegbetɔ ƒe tsitsimeŋusẽ si wogbugbɔ ƒo ƒu la, viɖe tɔxɛ aɖewo le eŋu. Le kpɔɖeŋu me, ate ŋu anye be woate ŋu alɔ̃ ɖe edzi nyuie wu eye wòanɔ dedie wu, si aɖe nugbegblẽ aɖewo siwo ate ŋu ado tso eme dzi akpɔtɔ.
Nukae nye Sermorelin ƒe atikewɔwɔ ƒe ŋusẽkpɔɖeamedzi ɖe ɖevi siwo ŋu dɔléle siwo nɔa anyi didi alo domenyiŋusẽfianu ƒe dɔléle vovovowo le dzi?
Ðevi siwo ŋu dɔléle siwo nɔa anyi didi le
Ðevi siwo ŋu kadodoŋusẽdɔléle siwo nɔa anyi didi le:
Le ɖevi siwo ŋu lãmekawo ƒe dɔléle siwo nɔa anyi didi (CTD) le, abe ɖeviwo ƒe ƒunukpeƒetetedɔ kple ɖeviwo ƒe ƒunukpeƒetetedɔ (JIA) ene, le lãmekawo ƒe dɔdzẽ tẽ kple glucocorticoid zazã ta la, tsitsi ƒe agbɔsɔsɔ dzi ɖeɖe kpɔtɔ dzɔna zi geɖe. Dɔdamɔnu siwo li fifia koŋ zãa dɔlékuiwutikewo abe tumor necrosis factor-α blockers (etanercept, adalimumab, golimumab) kple interleukin-6 receptor blockers (tocilizumab), siwo ate ŋu ana ɖeviwo ƒe tsitsi nawɔ kabakaba vivivi ahawɔe wòasɔ to mɔxexe ɖe dɔdzẽ nu kple glucocorticoids ƒe agbɔsɔsɔme si wozãna gbesiagbe dzi ɖeɖe kpɔtɔ me. Gake fifia la, womewɔ numekuku aɖeke tso Sermorelin zazã kple eƒe atikewɔwɔ ŋu le ɖevi mawo tɔgbe ŋu o [1]..
Ðevi siwo ŋu aklãdɔ si nɔa anyi didi le:
Aklãdɔ si nɔa anyi didi bɔ ɖe ɖevi ŋutsuwo me wu, ebɔ ɖe kɔƒenutowo me wu dugãwo me, eye vovototo aɖeke medze ƒã le ƒexɔxɔ alo ɣeyiɣiwo me o. Le ɖevi siwo mexɔ ƒe 3 haɖe o siwo ŋu dɔléle siwo gbɔ wòtso dome la, yaƒoƒo kple aklã ƒe tsitsi ƒe dɔmawɔmawɔ nyuie si wodzina la bɔ, gake dɔlélenutsiŋutete ƒe dɔmawɔmawɔ nyuie ƒe dɔléle gbãtɔwo ya bɔ ɖe ɖevi siwo xɔ ƒe 3 kple edzivɔ me. Dɔlékuiwo ƒe dɔlékuiwo, vevietɔ dɔlékui siwo nye Gram-negative dɔlékuiwo, ye nye nusiwo koŋ gbɔ wòtsona le ƒexɔxɔ ƒe hatsotsowo katã me [2] ..
Nuka koŋue nye Semorelin ƒe mɔnu le ɖeviwo ƒe tsitsi ƒe nutete si tso tsitsi ƒe lãmetsi gbãtɔ ƒe anyimanɔmanɔ gbɔ la dada me?
Tsitsi ƒe lãmetsiŋusẽ ƒe dodo:
Sermorelin nye amegbetɔ ƒe tsitsime lãmetsiŋusẽ si wowɔ. Tsitsi ƒe lãmetsiŋusẽ ƒe nusiwo ɖea asi le ame ŋu ateŋu abla ɖe tsitsi ƒe lãmetsi ƒe asiɖeɖe le nu ŋu ƒe xɔlawo ŋu le ŋgɔgbe lãkusi me, si aʋã lãkusi ƒe lãmenugbagbeviwo be woawɔ tsitsi ƒe lãmetsi eye woaɖe asi le eŋu[3]. To mɔ sia dzi la, Semorelin ate ŋu ana tsitsi ƒe lãmetsi si le ŋutilãa me nadzi ɖe edzi, si ana ɖeviwo natsi.
Le nɔnɔme siwo sɔ me la, nu vovovowoe kpɔa tsitsi ƒe lãmetsi ƒe dodo dzi, siwo dometɔ aɖewoe nye tsitsi ƒe lãmetsi si ɖea lãme na ame (GHRH), somatostatin, ahɔhɔ̃mekawo, kple bubuawo Abe tsitsi ƒe lãmetsi si dona le gota ene la, Semorelin ate ŋu asrɔ̃ GHRH ƒe dɔwɔwɔ eye wòado tsitsi ƒe lãmetsi ƒe dodo ɖe ŋgɔ.
Ŋusẽkpɔkpɔ ɖe tsitsi ƒe lãmetsi si le abe insulin ene ƒe tsitsi ƒe akpa si le abe insulin ene dzi:
Ne tsitsiŋusẽ ƒe dodo dzi ɖe edzi vɔ la, ewɔa dɔ ɖe lãmekawo abe aklã ene dzi eye wòdoa ŋusẽ insulin-like growth factor (IGF) ƒe wɔwɔme kple eƒe dodo. IGF nye tsitsi ƒe ɖoɖo vevi aɖe si ate ŋu ado lãmenugbagbeviwo ƒe dzidziɖedzi, vovototodedeameme, kple protein ƒe wɔwɔ ɖe ŋgɔ, si wɔa akpa vevi aɖe le ɖeviwo ƒe tsitsi kple tsitsi me[3].
Sermorelin doa IGF ƒe wɔwɔme kple eƒe dodo ɖe ŋgɔ le mɔ si mele tẽ o nu to tsitsime lãmetsiŋusẽ ƒe dodo ɖe ŋgɔ me, si wɔnɛ be ŋusẽ si doa tsitsi ɖe ŋgɔ la gadzi ɖe edzi. IGF ate ŋu abla ɖe IGF xɔla siwo le lãmenugbagbevi siwo woɖo taɖodzinu na dzi, ana dzesimɔ siwo le anyime nawɔ dɔ, eye wòado lãmenugbagbeviwo ƒe tsitsi kple woƒe lãmenugbagbeviwo ƒe dɔwɔwɔ ɖe ŋgɔ.
Ŋusẽ si wòkpɔna ɖe ƒu ƒe tsitsi dzi:
Tsitsi ƒe lãmetsi kple IGF kpɔa ŋusẽ vevi aɖe ɖe ƒu ƒe tsitsi dzi. Woate ŋu ado ƒumeŋuɖuiwo ƒe dzidziɖedzi kple vovototodedeameme ɖe ŋgɔ, si ana ƒu ƒe didime kple ƒu ƒe kpekpeme nadzi ɖe edzi[3]. Semorelin daa tsitsi ƒe nutete le ɖeviwo me si tso tsitsime lãmetsi gbãtɔ ƒe anyimanɔmanɔ gbɔ to tsitsime lãmetsi kple IGF ƒe agbɔsɔsɔ dzi ɖeɖe kpɔtɔ me, si doa ƒu ƒe tsitsi kple tsitsi ɖe ŋgɔ.
Tsɔ kpe ɖe eŋu la, tsitsi ƒe lãmetsi ate ŋu aɖɔ tomenu abe calcium kple phosphorus ene ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ hã ɖo, si ana ƒuwo ƒe wɔwɔme kple dɔwɔwɔ nyuie nanɔ anyi. Semorelin ate ŋu ado ƒu ƒe tsitsi ɖe ŋgɔ to ŋusẽkpɔkpɔ ɖe lãmenugbagbeviwo ƒe dɔwɔwɔ siawo dzi me.
Ŋusẽ si wòkpɔna ɖe lãmekawo kple ami ƒe asitɔtrɔ le lãmenugbagbeviwo ŋu dzi:
Menye ɖeko tsitsi ƒe lãmetsi kple IGF kpɔa ŋusẽ ɖe ƒu ƒe tsitsi dzi ko o, ke wokpɔa ŋusẽ ɖe lãmekawo kple ami ƒe asitɔtrɔ hã dzi. Tsitsi ƒe lãmetsi ate ŋu ado protein ƒe wɔwɔme ɖe ŋgɔ, ana lãmekawo nadzi ɖe edzi, eye le ɣeyiɣi ma ke me la, ami ƒe ƒoƒo ɖe lãme na ame dzi akpɔtɔ[3]. Semorelin zazã ate ŋu ana ɖeviwo ƒe lãmekawo kple ami ƒe asitɔtrɔ nanyo ɖe edzi to tsitsime lãmetsiŋusẽ ƒe agbɔsɔsɔ dzi ɖeɖe kpɔtɔ me, si ana ŋutilã ƒe tsitsi kple tsitsi nado.
Tsɔ kpe ɖe eŋu la, tsitsi ƒe lãmetsi ate ŋu aɖɔ ŋusẽ ƒe asitɔtrɔ hã ɖo, ana basal metabolic rate nadzi ɖe edzi, eye wòana ŋusẽzazã nadzi ɖe edzi. Esia kpena ɖe ɖeviwo ƒe kpekpeme kple woƒe ŋutilã ƒe wɔwɔme si sɔ ŋu eye wòdoa tsitsi nyuie ɖe ŋgɔ.
Nukae nye Sermorelin zazã siwo do ƒome kplii?
Wozãnɛ tsɔ daa ɖeviwo ƒe tsitsi ƒe mɔxexeɖedɔléle nu:
Abe tsitsime lãmetsiŋusẽ ƒe asiɖeɖe le nu ŋu ƒe kpeɖeŋutɔ si wowɔ ene la, Semorelin doa tsitsi ƒe lãmetsi si le lãme na ame ƒe dodo ɖe ŋgɔ le mɔ si mele tẽ o nu to GHRH xɔla siwo le ŋgɔgbe lãkusi me ƒe dɔwɔwɔ me, si wɔnɛ be ɖevi siwo ƒe tsitsime lãmetsi gbãtɔ mesɔ gbɔ o ƒe kɔkɔme ƒe tsitsi kple woƒe lãmenugbagbeviwo ƒe dɔwɔwɔ nyona ɖe edzi ŋutɔ. Eƒe vevienyenye le atikewɔwɔ ƒe tiatia si me ŋutilã ƒe dɔwɔwɔ dzi kpɔkpɔ ƒe mɔnu le nana dɔnɔ siwo ƒe dɔlékuiwo ƒe dɔwɔwɔ nyuie gake GHRH mesɔ gbɔ o, si aƒo asa na afɔku siwo le dɔlékuiwutikewo ƒe dɔwɔwɔ alo lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe kuxi siwo ate ŋu ahe to gotagome tsitsimeŋusẽ ɖɔliɖɔli ƒe atikewɔwɔ me. Viɖe siwo le semorelin ŋue nye be eɖoa ŋu ɖe eya ŋutɔ ƒe nusiwo dona le lãme na ame ŋu, eɖea lãmetsiŋusẽ ƒe ŋusẽkpɔɖeamedzi dzi kpɔtɔna, eye wòte ɖe ŋutilã ƒe ɖoɖowɔwɔ ƒe mɔnu ŋu wu.
Le Agbalẽŋlɔla La Ŋu
Nusiwo míeyɔ ɖe etame la katã nye esiwo ŋu Cocer Peptides [4] wɔ numekuku le, trɔ asi le wo ŋu eye woƒo wo nu ƒu..
Dzɔdzɔmeŋutinunya ƒe Agbalẽŋlɔla
Simon TJ nye numekula si do ƒome kple habɔbɔ xɔŋkɔ geɖe. Esiawo dometɔ aɖewoe nye Zoetis Vet Med Regulatory Affairs, Akili Interact Labs, California Yunivɛsiti Davis, Univ Calif, Dept Psychiat & Behav Sci, UC Davis MIND Inst, California Dukɔa ƒe Yunivɛsiti Sacramento, MIND Inst, UCDHS, Ðeviwo ƒe Kɔdzi si le Philadelphia, NIH Dukɔa ƒe Atike Vɔ̃ɖiwo Zazã Ŋuti Nusrɔ̃ƒe (NIDA), Emory Yunivɛsiti, Georgia Mɔ̃ɖaŋununya Dɔwɔƒe, kple Merck & Company. Habɔbɔ vovovo mawo ƒe kadodowo te gbe ɖe eƒe sukudede kple numekuku ƒe nuteƒekpɔkpɔ gbadzaa dzi.
Eƒe numekuku ƒe didiwo keke ta le nusɔsrɔ̃ vovovowo abe Neurosciences & Neurology, Psychiatry, Psychology, Genetics & Heredity, kple Gastroenterology & Hepatology ene me. Eƒe dɔwɔwɔ le go siawo me ɖe eƒe sidzedze deto kple akpa vevi siwo wòwɔ le atikewɔwɔ ŋuti dzɔdzɔmeŋutinunya dodo ɖe ŋgɔ kple lãmesẽnyawo gbɔ kpɔkpɔ ƒe ɖoɖowo dodo ɖe ŋgɔ me fia. Woŋlɔ Simon TJ ŋkɔ ɖe nyayɔyɔ ƒe nyatakaka me [4].
