1 pahu (10 Vials)
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▎ He aha ka KPV?
ʻO KPV kahi māhele peptide kūlohelohe me nā hana olaola he nui. He hana maikaʻi loa ia ma ke kahua o ka anti-inflammation. Ma ka hoʻoponoponoʻana i ka pane o ka immune, hoʻohaʻahaʻa ia i ka mumū, he mea nui ia no ka mālamaʻana i nā maʻi e like me ka maʻi maʻi. I kēia manawa, loaʻa i ka KPV nā hopena antibacterial e kūʻē i nā pathogens e like me Staphylococcus aureus a me Candida albicans, e kōkua ana e hōʻemi i nā maʻi. Eia kekahi, hiki iā ia ke hoʻolalelale i ka ho'ōla ʻana i ka ʻeha, hoʻoikaika i ka hoʻoponopono ʻana i ka ʻiʻo, a hoʻomaikaʻi i ke olakino ʻili ma ke kahua o ka cosmetology. Loaʻa iā KPV ka hoʻoheheʻe wai maikaʻi a me ka biocompatibility. ʻAʻole ia e hoʻoulu i kahi pane kūlohelohe, a hiki ke hoʻohaʻahaʻa maoli ʻia e ka hana o nā enzymes i loko o ke kino, e hōʻoia ana i kahi kiʻekiʻe o ka palekana. Hāʻawi kona multifunctionality me nā manaʻo noiʻi ākea ma nā ʻano he nui, me ka lāʻau lapaʻau, cosmetology, a me nā biomaterials.
▎ Hoʻolālā TKPV
Puna: PubChem |
IUPAC Condensed:H-Lys-Pro-Val-OH Hui Molekala: C 16H 30N 4O4 Kaumaha Molekala: 342.43g/mol Helu CAS: 67727-97-3 PubChem CID: 125672 Nā huaʻōlelo like: Msh (11-13);alpha-Msh (11-13);ACTH-(11-13) |
▎ ʻImi KPV
He aha ke kumu noiʻi o KPV?
ʻO KPV kahi tripeptide i loaʻa mai ka α-melanocyte-stimulating hormone (α-MSH). ʻO ka α-MSH he hormone polypeptide me nā hana olaola he nui, e pāʻani ana i kahi kuleana koʻikoʻi i ka hoʻoponopono ʻana i ka pigmentation o ka ʻili, ka hoʻoponopono immune, a me nā mea ʻē aʻe. Ma ke ʻano he ʻāpana o ka α-MSH, ua hoʻokaʻawale ʻia ʻo KPV a ua aʻo hohonu ʻia. ʻOiai ua holomua kekahi ma ka ʻoihana lapaʻau i nā makahiki i hala iho nei, ʻaʻole i ʻoluʻolu nā koho lapaʻau no ka maʻi ʻāʻī o ka ʻōpū (IBD), a ke kiʻekiʻe nei ka helu o ka ʻoki. No laila, ʻo ka loaʻa ʻana o nā ala lapaʻau hou a maikaʻi hoʻi ua lilo i hana koʻikoʻi. Aia ka IBD i ka ulcerative colitis, ka maʻi o Crohn, a me nā mea ʻē aʻe, kahi i hōʻike ʻia e ka ʻāʻī o ka ʻōpū mau a hoʻopilikia nui i ka maikaʻi o ke ola o nā maʻi. ʻO nā ʻano lapaʻau o kēia manawa ka lāʻau lapaʻau a me ka hoʻomaʻamaʻa ʻana, akā loaʻa nā palena ʻelua. I nā makahiki i hala iho nei, ua wehewehe ʻia nā hopena anti-inflammatory o nā peptides melanocortin e like me α-MSH i ka dextran sulfate sodium (DSS) colitis i nā ʻiole. Hāʻawi kēia i kahi hōʻailona no ke aʻo ʻana i ka mana anti-inflammatory o KPV. Loaʻa i ka α-MSH nā hana e like me ka hoʻoponopono immune a me ka hoʻohaʻahaʻa ʻana i ka mumū, a ʻo ka tripeptide KPV i loaʻa mai ia mea i manaʻo ʻia he mau waiwai anti-inflammatory like.
He aha ke ʻano o ka hana a KPV?
Mechanism o ka hana i ka ulcerative colitis
Hoʻomaikaʻi i ke kūpaʻa a me ka maʻalahi o ka hoʻokele rectal:
ʻO KPV (Lys-Pro-Val) he tripeptide i loaʻa mai ka α-MSH (α-melanocyte-stimulating hormone) a he hopena anti-inflammatory e kū'ē i ka colitis. Eia nō naʻe, ʻaʻole paʻa ka hopena KPV i ka wā o ka hoʻokele rectal, e pili ana i kona hopena therapeutic. I loko o ke aʻo ʻana, ua hoʻohui ʻia ka cysteamine-grafted γ-polyglutamic acid (SH-PGA) ma ka hui ʻana i ka cysteamine me ka hui carboxyl o γ-PGA. Me ka hoʻohana ʻole ʻana i kahi mea hoʻopili cross-linking, ua hoʻokumu ʻia kahi 4% polymer content SH-PGA hydrogel ma o ka hoʻopili ponoʻī ʻana o nā pūʻulu sulfhydryl. Ua hōʻike ka KPV/SH-PGA hydrogel i kahi modulus elastic (G') ʻoi aku ka kiʻekiʻe ma mua o ka modulus viscous pili (G'') ma 0.01-10 Hz, e hōʻike ana i ke kūpaʻa mechanical maikaʻi a me ke ʻano hoʻoheheʻe shear, he mea maikaʻi ia no ka hoʻokele rectal. I ka manawa like, ua hoʻonui nui ʻia ke kūpaʻa o KPV i ka SH-PGA hydrogel. ʻO 30% wale nō o KPV i hoʻokuʻu ʻia mai ka KPV/SH-PGA hydrogel i loko o 20 mau minuke, a ukali ʻia e kahi ʻano hoʻokuʻu mau [1].
Hoʻopau i nā hōʻailona colitis:
Ma o nā hoʻokolohua ma nāʻiole me ka ulcerative colitis i hoʻokomoʻia e ka 2,4,6-trinitrobenzene sulfonic acid (TNBS), ua hoʻokūpaʻaʻia ka hopena therapeutic hoʻonui o ka KPV / SH-PGA hydrogel ma ka colitis. Ma hope o ka hoʻohana ʻana o ka KPV/SH-PGA hydrogel, ua hoʻemi nui ʻia nā hōʻailona colitis me ka pohō kaumaha a me nā helu helu hana maʻi. Eia kekahi, ʻo ka mālama ʻana me ka KPV/SH-PGA hydrogel i pale i ka pōkole o ke kolonā i nā ʻiole i hoʻopaʻa ʻia me TNBS a hoʻemi i ka pae o ka colonic myeloperoxidase. Ma hope o ka mālama ʻana me ka KPV/SH-PGA hydrogel, ua hoʻihoʻi ʻia ka morphology o ke kolonā, me ka pale epithelial, nā crypts, a me nā ʻāpana kīʻaha paʻa. I ka manawa like, ua hōʻemi ka KPV / SH-PGA hydrogel i ka hōʻike o nā cytokine pro-inflammatory e like me ka tumor necrosis factor α a me interleukin 6 [1].
Mechanism of action in the mouse model of inflammatory bowel disease
DSS colitis model: I ka DSS colitis model, lapaʻau me KPV i alakaʻi i ka hoʻihoʻi mua a hoʻonui nui i ka hoʻihoʻi ʻana i ke kaumaha. ʻO ka histologically, ua hoʻemi nui ʻia ka infiltration inflammatory i nā ʻiole i mālama ʻia e KPV, i hōʻoia ʻia e ka emi nui o ka hana o ka myeloperoxidase (MPO) i loko o ka ʻiʻo colonic ma hope o ka mālama ʻana KPV [2].
CD45RB (hi) hoʻololi colitis model:
Ke kākoʻo nei i nā ʻike ma luna, ʻo ka mālama ʻana o KPV o ka colitis i hoʻololi ʻia i alakaʻi ʻia i ka hoʻihoʻi ʻana i ka maʻi, ka hoʻihoʻi ʻana i ke kaumaha, a me ka hōʻemi ʻana i nā loli inflammatory mai kahi hiʻohiʻona histological [2].
MC1Re/e kiʻi ʻiole:
I nā ʻiole e hōʻike ana i kahi mea hoʻokipa melanocortin-1 non-functional (MC1Re/e), mālama ʻo KPV i nā holoholona āpau i ka hui lapaʻau mai ka make i ka wā DSS colitis. Hōʻike kēia i ka hopena anti-inflammatory o KPV me he mea lā ua kūʻokoʻa iki ʻia i ka hōʻailona MC1R [2].
Mechanism o ka hana i ka bronchial epithelial cell inflammation
Ke hōʻole nei au i ka hōʻailona NF-κB:
Ma nā pūnaewele epithelial bronchial olaʻole,ʻo ka melanocortin-related peptide KPV a me ka agonist α-MSH o ka epithelium ea (MC3R) i kāohi i ka hōʻailona NF-κB ma ke kāohiʻana i ka laweʻana mai o ka p65RelA a me ka hoʻouluʻana i ka epithelial MC3R. ʻO ke kikoʻī, pili ka hopena o KPV i kāna lawe ʻana i ka nuklea, hiki ke kāohi i ka unuhi nuklea o p65RelA i hōʻailona ʻia me YFP. Ma ka manawa like, aia nā wahi paʻa o KPV a me Imp-α/β ma p65RelA, e pili ana paha i ka pale ʻana i ka importin-α armadillo domain 7 a me 8 [3].
Mechanism o ka hana ma ka chemotherapy-induced oral mucositis
Nā hopena antibacterial, anti-inflammatory, a me ka hoʻoponopono:
Ke hoʻohana nei i ka PLGA-PEG-PLGA (PPP) e pili ana i ka wela e like me ka matrix a me ka epigallocatechin-3-gallate (EGCG) me ka hana antibacterial inherent e like me ka mea hoʻonui adhesion, ua mākaukau maikaʻi ka in-situ mucosal adhesive hydrogel (PPP_E). Ua hoʻoheheʻe ʻia ka tripeptide KPV i ka PPP_2% E precursor solution ma ke ʻano he lāʻau hoʻohālike e hoʻomākaukau ai i ka KPV@PPP_2% E hydrogel. Ua mālama maikaʻi ʻia ka hana anti-inflammatory a me ka hiki ke hāpai i ka neʻe ʻana o ke kelepona o KPV i ka PPP-2% E hydrogel. Eia hou, ua loaʻa i ka KPV@PPP_2% E ka hopena antibacterial ikaika e kū'ē iā Staphylococcus aureus. I ka wā i hoʻohana ʻia ai ka KPV@PPP_2% E hydrogel i ka mucosa gingival o nā ʻiole me ka mucositis waha i hoʻokomo ʻia i ka chemotherapy, hiki iā ia ke hoʻololi koke i hydrogel a pili i ka ʻili o ka ʻeha no 7 mau hola, e hoʻomaikaʻi nui i ka ʻai a me ka hoʻihoʻi ʻana i ke kaumaha o nā ʻiole. Ma ka manawa like, ma ka paipai ʻana i ka ʻōlelo o CK10 a me PCNA, ua hoʻoponopono maikaʻi ka KPV@PPP_E hydrogel i ka morphology kiko o ka gingiva ulcerated. Eia kekahi, ʻo ka KPV@PPP_2% E hydrogel i kāohi nui i nā cytokine inflammatory me IL-1β a me TNF-α, a ma ka manawa like i hoʻoponopono ʻia i ka IL-10 [4].

Puna:PubMed [5]
He aha nā hihia hoʻohana lapaʻau o nā lāʻau KPV?
ʻO ka mālama ʻana i ka ulcerative colitis
Hoʻoponopono ma o ka hydrogel hoʻopili ponoʻī:
I loko o kahi noiʻi, ua hoʻohui ʻia ka cysteamine-grafted γ-polyglutamic acid (SH-PGA) a hana ʻia i hydrogel e hoʻopaʻa i ka tripeptide KPV [1] . Ua hōʻike ka KPV/SH-PGA hydrogel i nā hopena lapaʻau maikaʻi i kahi ʻano ʻiole o ka ulcerative colitis i hoʻokomo ʻia e 2,4,6-trinitrobenzene sulfonic acid (TNBS). Ma hope o ka hoʻoponopono ʻana i ka rectal, ua hoʻemi nui ʻia nā hōʻailona colitis e like me ka pohō kaumaha a me nā helu helu hana maʻi, a hiki ke pale aku i ka pōkole o ke kolonā i nā ʻiole i hoʻopaʻa ʻia me TNBS a hoʻemi i ke kiʻekiʻe o ka colonic myeloperoxidase. I ka manawa like, ua hoʻihoʻi ʻia ka morphology o ke kolonā, me ka epithelial barrier, crypts, a me nā ʻāpana goblet paʻa, ma hope o ka mālama ʻana me ka hydrogel KPV/SH-PGA, a ua hōʻemi pū ka hydrogel i ka hōʻike ʻana o nā cytokine pro-inflammatory e like me ka tumor necrosis factor α a me interleukin 6.
Hoʻoponopono ma o ka hydrogel pūnaewele ʻelua:
ʻO kekahi noiʻi ʻē aʻe i kūkulu i kahi hydrogel pūnaewele ʻelua (PMSP) i hoʻokumu ʻia e ka maleated γ-polyglutamic acid a me ka thiolated γ-polyglutamic acid ma o ka thiol-maleimide cross-linking a me ka oxidation ponoʻī o thiols [5] . Hiki i kēia hydrogel ke hoʻopili pono i ka mucosa inflamed ma mua o ka mucosa olakino, a loaʻa iā ia ka ikaika mechanical a me ka pili ola. ʻO KPV, ma ke ʻano he lāʻau hoʻohālike, hiki ke hopu ʻia e PMSP ma o ka pilina electrostatic, pēlā e mālama ai i kāna hana olaola no ka manawa lōʻihi ma lalo o nā kūlana wela. Ma nāʻiole me ka colitis i hoʻouluʻia e TNBS, ma hope o ka hoʻoponopono ponoʻana o PMSP-KPV, ua hoʻomaikaʻi maikaʻiʻia ka hopena hoʻohaʻahaʻa o KPV ma ka colitis, a ua hoʻihoʻi maikaʻiʻia ka pale epithelial o ke kolonā. Eia kekahi, ua hoʻoponopono ʻo PMSP-KPV i ka flora intestinal a hoʻonui nui i ka nui o nā microorganisms pono i loko o ka ʻōpū.
No ka chemotherapy-induced oral mucositis
Ua hoʻomākaukau ʻia kahi in-situ mucosal adhesive hydrogel (PPP_E) me ka hoʻohana ʻana i ka mahana-sensitive PLGA-PEG-PLGA (PPP) e like me ka matrix a me ka epigallocatechin-3-gallate (EGCG) ma ke ʻano he mea hoʻonui adhesion [4] . Ua hoʻoheheʻe ʻia ka tripeptide KPV i ka PPP_2% E precursor solution ma ke ʻano he lāʻau hoʻohālike e hoʻomākaukau ai i ka KPV@PPP_2% E hydrogel. ʻO kēia hydrogel he anti-inflammatory, antibacterial, a me nā hopena hoʻoponopono i ka mucositis waha i hoʻokomo ʻia i ka chemotherapy. ʻO ke kikoʻī, hiki iā ia ke mālama i ka hana anti-inflammatory o KPV a me ka hiki ke hoʻoikaika i ka neʻe ʻana o ka cell, a he hopena antibacterial ikaika e kū'ē iā Staphylococcus aureus. Ma hope o ka lawelawe ʻana i ka mucosa gingival o nā ʻiole me ka mucositis waha i hoʻokomo ʻia i ka chemotherapy, ua hoʻololi koke ka PPP_2% E precursor solution i hydrogel a pili i ka ʻili o ka ʻeha no 7 mau hola. ʻO ka mālama ʻana me ka KPV@PPP_2% E hydrogel i hoʻomaikaʻi nui i ka ʻai ʻana i ka meaʻai a me ka hoʻihoʻi ʻana o ke kaumaha o nā ʻiole, hoʻoikaika i ka hōʻike ʻana o CK10 a me PCNA, hoʻoponopono maikaʻi i ka morphology kiko o ka gingiva ulcerated, a ma ka manawa like i hoʻopaʻa nui i nā cytokine inflammatory e like me IL-1β a me TNF-α, a hoʻoponopono i ka ʻōlelo o IL-10. He hopena antibacterial kēia hydrogel i nā ʻeha maʻi maʻi gingival i loaʻa i ka methicillin-resistant Staphylococcus aureus (MRSA), a ke kāohi nui nei i ka hoʻokomo ʻana o nā cell inflammatory i loko o ka ʻiʻo submucosal.
Lapaʻau ʻana i ka maʻi ʻeha
Ua hōʻike ʻia kekahi mau haʻawina e lilo paha ʻo KPV i lāʻau lapaʻau hou no ka maʻi inflammatory bowel (IBD) [6] . I loko o nā pūnaewele epithelial intestinal (Caco2-BBE a me HT29-Cl.19A) a me nā pūnaewele T kanaka (Jurkat), ma hope o ka hoʻouluʻana me nā cytokines pro-inflammatory, hiki i ka hoʻohuiʻana o KPV ke kāohi i ka hoʻouluʻana o NF-κB a me MAP kinase inflammatory ala ala a hoʻemi i ka huna o nā cytokines pro-inflammatory. Ua ʻike ʻia ka haʻawina e hana ana ʻo KPV ma o ka hPepT1 i hōʻike ʻia i loko o nā cell epithelial immune a me ka ʻōpū. Eia kekahi, i nā kiʻi kiʻi o ka colitis i hoʻoulu ʻia e ka dextran sulfate sodium (DSS) a me TNBS, hiki i ka hoʻokele waha o KPV ke hōʻemi i ka hōʻike ʻana o nā cytokine pro-inflammatory a me ka hopena o ka colitis.
I ka hopena, ma ke ʻano he mea bioactive me ka mana nui, hōʻike ʻo KPV i nā pono kūʻokoʻa i ka mālama ʻana i nā maʻi like ʻole. Ma ke kahua o ka ma'i inflammatory bowel, inā ma nā ho'okolohua ho'ohālike iole a i 'ole i ka 'imi 'ana i nā 'ano ho'oponopono like 'ole no ka ulcerative colitis, hiki i ka KPV ke ho'emi pono i ka infiltration inflammatory, ho'omaika'i i ka morphology tissue, ho'oponopono i ka cytokine expression, a ho'oikaika i nā hopena anti-inflammatory ko'iko'i ma o nā mīkini e like me ka halihali PepT1. I ka mālama ʻana i ka mucositis waha i hoʻokomo ʻia i ka chemotherapy, ʻo ka hydrogel i loaʻa iā KPV i hoʻomākaukau ʻia me kahi matrix kikoʻī a me ka mea hoʻonui adhesion ʻaʻole hiki ke mālama wale i kāna mau hana anti-inflammatory a me ka neʻe ʻana i ka neʻe ʻana akā loaʻa pū kekahi mana antibacterial ikaika, hoʻomaikaʻi nui i nā hōʻailona pili o nā ʻiole a me ka hoʻoikaika ʻana i ka hoʻoponopono kino. ʻOiai ua kaupalena ʻia nā hihia noiʻi lapaʻau o KPV i kēia manawa, hōʻike piha nā hopena noiʻi i kona waiwai therapeutic. I ka wā e hiki mai ana, inā hiki ke hoʻokō ʻia nā holomua i ka noiʻi hohonu e pili ana i ka hoʻomaikaʻi ʻana i ka lāʻau paʻa a me ka hoʻokō pono ʻana, ka hoʻonui ʻana i nā hōʻailona hōʻailona, a me ka hoʻoikaika ʻana i ka nānā ʻana a me ka hoʻokele ʻana, ua manaʻo ʻia ʻo KPV e lawe mai i nā koho lapaʻau kiʻekiʻe a maikaʻi no nā maʻi hou aʻe a pāʻani i kahi kuleana nui i ka lāʻau lapaʻau.
No ka mea kakau
ʻO nā mea i ʻōlelo ʻia ma luna nei ua noiʻi ʻia, hoʻoponopono ʻia a hōʻuluʻulu ʻia e Cocer Peptides.
Mea kākau moʻolelo ʻepekema
He mea noiʻi ʻo Dalmasso G ma ke kahua o ka lāʻau lapaʻau, me nā kuhikuhi noiʻi e pili ana i ka lāʻau lapaʻau, biochemistry, a me genetics, ma waena o nā wahi ʻē aʻe. Ua hana ʻo ia ma kekahi mau ʻoihana hanohano, ʻo ia hoʻi ʻo Universite Clermont Auvergne (UCA), CHU Clermont Ferrand, INRAE, Institut National de la Sante et de la Recherche Medicale (Inserm), Clermont Univ, Georgia State University, Emory University, Universite Cote d'Azur, a me Universidad Nacional Rio Cuarto. Ua kaulana loa kēia mau kula i kā lākou mau kula, a ʻo ka hui pū ʻana o Dalmasso G me lākou ua kōkua i ka holomua o nā hoʻopaʻi pili. He mea koʻikoʻi paha kāna mau ʻimi noiʻi i ka hoʻomohala ʻana i ka ʻepekema lapaʻau, ʻoi aku ka maikaʻi o ka hoʻomaikaʻi ʻana i nā hopena lapaʻau maʻi a me ka maikaʻi o ke ola o nā maʻi. Ua helu ʻia ʻo Dalmasso G ma ka ʻōlelo kuhikuhi [6].
▎ Nā ʻōlelo pili
[1] Sun J, Xue P, Liu J, et al. ʻO ka Hydrogel i hoʻopaʻa ʻia ma ke keʻa ponoʻī o Cysteamine-Grafted γ-Polyglutamic Acid Stabilized Tripeptide KPV no ka hoʻopau ʻana i ka TNBS-Induced Ulcerative Colitis i nā ʻiole [J]. Acs Biomaterials Science & Engineering, 2021,7(10):4859-4869.DOI:10.1021/acsbiomaterials.1c00792.
[2] Konnengiesser K, Maaser C, Heidemann J, et al. Loaʻa i ka melanocortin tripeptide KPV ka mana anti-inflammatory i nā hiʻohiʻona murine o ka maʻi ʻeha ʻeha [J]. Nā maʻi ʻeha o ka ʻōpū, 2008,14(3):324-331.DOI:10.1002/ibd.20334.
[3] ʻĀina S C. Ka hoʻopaʻa ʻana i nā ʻōnaewele a me nā ʻōnaehana ʻōnaehana i loko o nā pūnaewele epithelial bronchial kanaka e nā peptides pili melanocortin: ʻano hana o ka hana KPV a he kuleana no nā agonists MC3R.[J]. International Journal of Physiology, Pathophysiology and Pharmacology, 2012,4(2):59-73. https://pubmed.ncbi.nlm.nih.gov/22837805/
[4] Shao W, Chen R, Lin G, et al. In situ mucoadhesive hydrogel e hopu ana i ka tripeptide KPV: ka hopena anti-inflammatory, antibacterial a me ka hoʻoponopono ʻana i ka mucositis waha i hoʻokomo ʻia i ka chemotherapy [J]. ʻEpekema Biomaterials, 2021,10(1):227-242.DOI:10.1039/d1bm01466h.
[5] Zhao Y, Xue P, Lin G, et al. Hoʻihoʻi hou ʻia kahi hydrogel pūnaewele pālua KPV i hoʻopaʻa ʻia i ka pā mucosal ʻōpū i loko o kahi colon inflamed [J]. Acta Biomaterialia, 2022,143:233-252.DOI:10.1016/j.actbio.2022.02.039.
[6] Dalmasso G, Charrier-Hisamuddin L, Nguyen HTT, et al. Hoʻemi ʻo PepT1-mediated tripeptide KPV uptake e hōʻemi ana i ka ʻeha ʻōpū [J]. Gastroenterology, 2008,134(1):166-178.DOI:10.1053/j.gastro.2007.10.026.
ʻO nā ʻatikala a me nā ʻike huahana i hāʻawi ʻia ma kēia pūnaewele pūnaewele wale nō no ka hoʻolaha ʻana i ka ʻike a me nā kumu hoʻonaʻauao.
ʻO nā huahana i hāʻawi ʻia ma kēia pūnaewele i manaʻo wale ʻia no ka noiʻi in vitro. Hana ʻia ka noiʻi in vitro (Latin: *i ke aniani*, ʻo ia hoʻi i ka ipu aniani) ma waho o ke kino kanaka. ʻAʻole kēia mau huahana he lāʻau lapaʻau, ʻaʻole i ʻae ʻia e ka US Food and Drug Administration (FDA), a ʻaʻole pono e hoʻohana ʻia no ka pale ʻana, mālama, a hoʻōla paha i kekahi maʻi olakino, maʻi, a i ʻole maʻi. Ua pāpā loa ʻia e ke kānāwai ke hoʻokomo i kēia mau huahana i loko o ke kino kanaka a holoholona paha ma kekahi ʻano.