Bisphosphonates (tshuaj): piav qhia, cov lus qhia, tshuaj xyuas. Bisphosphonates hauv kev kho mob osteoporosis

Cov txheej txheem:

Bisphosphonates (tshuaj): piav qhia, cov lus qhia, tshuaj xyuas. Bisphosphonates hauv kev kho mob osteoporosis
Bisphosphonates (tshuaj): piav qhia, cov lus qhia, tshuaj xyuas. Bisphosphonates hauv kev kho mob osteoporosis

Video: Bisphosphonates (tshuaj): piav qhia, cov lus qhia, tshuaj xyuas. Bisphosphonates hauv kev kho mob osteoporosis

Video: Bisphosphonates (tshuaj): piav qhia, cov lus qhia, tshuaj xyuas. Bisphosphonates hauv kev kho mob osteoporosis
Video: Saib Mis paub Poj niam (hluas nkauj) tus yam ntxwv lub siab 2024, Lub Xya hli ntuj
Anonim

Thaum tus neeg cov pob txha ua nkig thiab nkig, thiab qhov no tshwm sim nrog qee cov kab mob pob txha, lub neej zoo yuav txo qis. Kev puas tsuaj ntau zaus, mob hauv pob qij txha, txha nraub qaum thiab ceg ceg pib nrog ib tus neeg nyob txhua qhov chaw, vim qhov uas koj tuaj yeem tso tseg tsis muaj kev xyiv fab thiab poob rau hauv kev poob siab tag.

Tab sis hmoov zoo rau peb, muaj kev npaj tshwj xeeb hauv lub ntiaj teb niaj hnub no uas tuaj yeem txhim kho cov pob txha zoo. Nws yog hais txog lawv uas yuav tau tham hauv peb tsab xov xwm. Cov tshuaj no hu ua "bisphosphonates" - tshuaj, tshuaj xyuas uas tuaj yeem muab kev cia siab rau kev rov qab los rau ntau tus neeg xav tau kev pab. Ntseeg kuv, muaj ntau! Peb yuav qhia koj txog keeb kwm ntawm kev tsim cov nyiaj no, vim li cas lawv thiaj li zoo, lawv cov txiaj ntsig zoo li cas, peb yuav tshaj tawm cov npe ntawm bisphosphonates, uas yog cov nyiam tshaj plaws thiab siv tau zoo.

tshuaj bisphosphonate
tshuaj bisphosphonate

Cov lus yuav muaj txiaj ntsig rau txhua tus. Tom qab tag nrho, txawm tias niaj hnub no txhua yam nyob rau hauv kev txiav txim nrog kev noj qab haus huv ntawm koj thiab koj cov neeg koj hlub, ces, hmoov tsis, qhov no tsis txhais hais tias nws yuav ib txwm ua li ntawd. Xyoo dhau mus, nrog lawvqhov sib ntxiv ntawm cov kab mob ua ntau dua. Yog li cov ntaub ntawv hais txog cov tshuaj niaj hnub no yuav tsis yog superfluous. Tab sis txaus qhia! Cia peb mus rau qhov kev kawm loj dua ntawm lub ncauj lus ntawm peb tsab xov xwm.

Bisphosphonates rau pob txha noj qab haus huv

Ib pawg ntawm cov tshuaj siv hluavtaws uas muaj peev xwm los thaiv kev ua haujlwm ntawm osteoclasts (cov cell uas rhuav tshem cov pob txha) hauv lub cev thiab kho cov pob txha pob txha hu ua bisphosphonates.

Cov tshuaj tam sim no yog siv los pab cov neeg mob pob txha thiab lwm yam kab mob uas ua rau cov pob txha nkig. Cov cuab yeej tseem ceeb tshaj plaws ntawm bisphosphonates yog tias lawv tuaj yeem siv rau hauv cov kab mob oncological yam ntxwv los ntawm kev tsim cov qog hauv cov pob txha. Hauv cov xwm txheej no, cov tshuaj uas peb tsab xov xwm hais txog tiv thaiv kev kis tus kabmob metastases thiab txo qhov mob ntawm cov neeg mob.

Mechanism ntawm kev ua ntawm bisphosphonates hauv kev kho mob pob txha

Koj tau kawm los ntawm tshooj dhau los uas bisphosphonates yog cov tshuaj uas txhawb cov pob txha noj qab haus huv. Nws yog lub sij hawm los tham hauv kev nthuav dav ntxiv txog cov txheej txheem ntawm lawv qhov kev ua. Cov hlwb ntawm peb lub cev muaj lub peev xwm zoo tshaj plaws los kho dua tshiab thiab hloov kho ib ntus. Cov pob txha tsis muaj kev zam. Qhov sib npaug ntawm lawv cov qauv yog khaws cia tas li, ntawm ib sab, los ntawm osteoblast hlwb, uas yog lub luag haujlwm rau kev tsim cov ntaub so ntswg tshiab, thiab ntawm qhov tod tes, los ntawm osteoclasts, uas yog lub luag haujlwm rau kev puas tsuaj. BFs tau txais txiaj ntsig nrog lub zog los tiv thaiv kev ua haujlwm ntawm osteoclasts thiabtxawm ua rau lub tshuab ntawm lawv tus kheej puas tsuaj. Kev kho mob pob txha nrog bisphosphonates yog ua raws li cov cuab yeej zoo kawg no.

Nws yuav tsum tau hais tias txog niaj hnub no, cov kws tshawb fawb tseem tsis tau nkag siab tag nrho cov txheej txheem ntawm kev thaiv cov pob txha puas tsuaj nrog kev pab ntawm bisphosphonates. Nws paub tseeb tias cov tshuaj no tuaj yeem khi rau thaj chaw hydroxyapatite ntawm cov pob txha, vim tias lawv tuaj yeem hloov kho nws txoj kev khoov thiab tib lub sijhawm txo cov concentration ntawm hydroxyproline thiab phosphatase hauv cov ntshav.

bisphosphonates rau osteoporosis
bisphosphonates rau osteoporosis

Qee lub sij hawm BF npaj tuaj yeem raug sau rau hauv kev kho mob ntawm cov kab mob xws li hernia lossis protrusion ntawm intervertebral discs, xws li tshuaj tua kab mob. Thiab cov ntaub ntawv ntxiv me ntsis: bisphosphonates rau cov pob txha pob txha tau siv rau lub sijhawm ntev, tab sis rau cov kab mob oncological lawv tau pib siv tsis ntev los no. Nrog kev pab los ntawm kev tshawb fawb, nws tau pom tias thaum nkag mus rau hauv lub cev, qhov twg muaj cov txheej txheem qog nqaij hlav, bisphosphonates tsis tso cai rau cov qog nqaij hlav fuse nrog cov pob txha matrix thiab yog li thaiv kev tsim ntawm metastases. Qhov no yuav tau tham ntau ntxiv hauv tshooj cais.

keeb kwm me ntsis

Nws hloov tawm tias bisphosphonates tau tshawb pom los ntawm cov kws tshawb fawb ntev dhau los, rov qab rau xyoo 19th. Thawj zaug, kev sib txuas ntawm thawj BPs tau ua nyob rau hauv lub teb chaws Yelemees. Nws yog qhov xav tsis thoob tias thaum xub thawj cov tshuaj no tsuas yog siv rau hauv ntau qhov chaw lag luam (hauv kev tsim cov pob zeb hauv av chiv, ntaub, roj refining, thiab lwm yam) thiab tsis muaj dab tsi ua rau cov tshuaj.

Kev kho mob - kho pob txhacov ntaub so ntswg - bisphosphonates tau pib siv tsuas yog nyob rau hauv nruab nrab ntawm lub xyoo pua nees nkaum, thaum lawv cov cuab yeej zoo kawg nkaus tau pom los cuam tshuam cov txheej txheem ntawm ob qho tib si calcification thiab decalcification. Bisphosphonates rau osteoporosis tau dav siv txij thaum ntawd los thoob ntiaj teb.

Kev faib tawm ntawm bisphosphonates

Hnub no, kws tshuaj tau tsim lub cim thib peb ntawm biosphosphonates. Tab sis qhov no tsis tau txhais hais tias cov kws kho mob tau tso tseg tag nrho kev siv cov tshuaj thib ib thiab thib ob, uas tau tsim ntau dhau los. Tsis muaj txhais tau tias! Niaj hnub no, muaj ntau yam tshuaj raws li bisphosphonates. Tag nrho cov tshuaj no tau muab faib ua ob pawg: cov tshuaj tsis muaj nitrogen thiab cov tshuaj muaj nitrogen. Lawv qhov kev ua ntawm osteoclast hlwb muaj ib qho kev sib txawv. Hauv qab no peb yuav saib ob pawg hauv kev nthuav dav ntxiv.

Nitrogen-muaj bisphosphonates

Cov no yog kev npaj ntawm pawg bisphosphonate uas muaj cov khoom xyaw hauv qab no:

  • Ibandronate acid. Cov tshuaj no tau raug tsim los tsis ntev los no, yog li nws yog cov tshuaj thib peb. Nws yog siv tau zoo tshaj plaws hauv kev kho mob thiab tiv thaiv kev mob pob txha hauv cov poj niam uas tau nkag mus rau lub sijhawm nyuaj ntawm kev mob ntshav qab zib. Cov txiv neej tsis pom zoo kom noj cov tshuaj no. Ibandronate acid kuj tseem siv rau cov calcium ntau ntau hauv cov ntshav (hypercalcemia).
  • Zolendronic acid. Kuj tseem nyob rau tiam thib peb ntawm bisphosphonates. Muaj peev xwm xaiv tau rau cov pob txha pob txha. Vim li no, nws yog siv tau zoo rau kev kho mob osteoporosis. xaiv uazoledronic acid ntawm cov pob txha qauv yog raws li nws cov affinity siab rau cov pob txha lattice, uas muab zoo heev inhibition ntawm osteoclasts. Lwm cov cuab yeej tseem ceeb ntawm cov tshuaj no yog cov nyhuv antitumor. Raws li zoledronic acid, nrov bisphosphonates "Zometa", "Zolendronate" yog tsim.
  • Alendronate Sodium yog ib tiam thib ob bisphosphonate. Nws yog ib qho uas tsis yog-hormonal corrector ntawm cov pob txha cov nqaij mos metabolism, tsim cov pob txha raug. Qhia rau kev siv pob txha pob txha ntawm cov poj niam thiab txiv neej.
  • Sodium ibandronate ("Bonviva", "Bondronat", "Boniva" - bisphosphonates, kev npaj ua los ntawm nws lub hauv paus) - tiam thib peb ntawm cov tshuaj. Tshem tawm cov haujlwm ntawm osteoclasts, tsis cuam tshuam rau lawv tus lej. Nws tsis muaj kev phom sij rau kev tsim cov pob txha pob txha, thaum txo lawv txoj kev puas tsuaj. Zoo rau cov poj niam postmenopausal raws li prophylactic tiv thaiv pob txha fractures.
bisphosphonates tshuaj npe
bisphosphonates tshuaj npe

Kev npaj uas tsis muaj nitrogen

Thiab tam sim no peb yuav tham txog dab tsi nitrogen-free bisphosphonates. Cov tshuaj koj tab tom yuav nyeem yog thawj tiam bisphosphonates:

  • "Clodronate". Tiv thaiv ob qho tib si osteolysis thiab kev loj hlob ntawm hypercalcemia. Tsim cov ntawv cog lus nyuaj nrog cov pob txha cov ntaub so ntswg hydroxyapatite, hloov cov siv lead ua lattice thiab nquag tawm tsam kev sib cais ntawm calcium molecules.thiab phosphates. Nrog cov pob txha metastases, nws inhibits lawv txoj kev loj hlob thiab thaiv kev yug me nyuam tshiab.
  • "Sodium etidronate". Txhawb txoj kev kho cov pob txha hauv cov poj niam uas kuaj mob osteoporosis. Kuj tseem siv tau rau Paget tus kab mob, hypercalcemia, thiab lwm yam.
  • "Tiludronate sodium". Mineralizes thiab ntxiv dag zog rau cov pob txha cov ntaub so ntswg, accumulating molecular compounds ntawm phosphates thiab calcium nyob rau hauv nws, inhibits kev puas tsuaj ntawm pob txha. Nws raug sau tseg rau cov neeg mob kuaj mob osteodystrophy deformans lossis Paget tus kab mob, nws tuaj yeem muab tshuaj tsis yog tshuaj hormones.

Bisphosphonates - cov tshuaj uas peb tau luam tawm - yog muag los ntawm kev tshuaj xyuas nkaus xwb, vim lawv yog cov tshuaj muaj zog. Kev siv lawv ntawm koj tus kheej txiav txim siab tuaj yeem ua rau muaj kev phom sij rau kev noj qab haus huv! Nco ntsoov tias BF tsis yog cov vitamins lossis calcium ntxiv. Cov tshuaj no nquag cuam tshuam cov txheej txheem tshwm sim hauv lub cev, thiab yog tias siv tsis raug, lawv tuaj yeem tsim kev puas tsuaj es tsis txhob pab.

Admission rules

Bisphosphonates cov tshuaj yog qhov nyuaj rau zom los ntawm txoj hnyuv, lawv qhov nqus tau nyuaj. Yog li, cov lus qhia tau hais kom haus cov tshuaj no tshwj xeeb rau ntawm lub plab khoob, txog 30 feeb ua ntej noj mov - txoj cai no pab kom nqus tau cov tshuaj nquag. Cov neeg mob yuav tsum paub tias cov tshuaj pab pawg no tuaj yeem ua rau mob thiab yaig nyob rau ntau qhov chaw ntawm txoj hnyuv. Txhawm rau zam qhov teeb meem no, tom qab noj cov tshuaj, koj yuav tsum sim tsis txhob uapw thiab nyob twj ywm. Cov koob tshuaj yog xaiv los ntawm tus kws kho mob.

Kev kho mob bisphosphonate
Kev kho mob bisphosphonate

Feem ntau, thaum muab tshuaj bisphosphonates, tus kws kho mob kuj tau sau ntawv rau tus neeg mob kom noj cov calcium ntau ntau. Yog li, kev txais tos ib txhij ntawm ob qho tib si raug cais tawm. Cov tshuaj calcium yuav tsum tsis txhob noj tom qab noj bisphosphonate kom txog thaum ob teev dhau los, thiab tsis ua ntej. Lwm qhov kev pom zoo tseem ceeb: BF yuav tsum tsis txhob ntxuav nrog tshuaj yej, mis nyuj, kua txiv los yog kas fes, tab sis nrog dej dawb (loj ntau).

Kev siv bisphosphonates hauv kev mob qog noj ntshav

Cia tham ntxiv txog kev kho mob bisphosphonates ntawm cov kab mob nrog rau kev loj hlob ntawm cov qog ntawm ntau yam xwm txheej. Qhov tshwm sim ntawm cov pob txha metastases mus sib koom tes nrog kev sib cuam tshuam ntawm cov qog hlwb thiab cov ntaub so ntswg metabolically active pob txha. Nyob rau hauv lem, lub dynamic kev loj hlob ntawm metastases yog nrog los ntawm adhesion ntawm qog hlwb rau cov pob txha lug, nrog rau kev ntxeem tau, proliferation, thiab neoangiogenesis. Ntau qhov kev tshawb fawb preclinical tau tso cai rau cov kws tshawb fawb xav tias BP inhibit txhua theem ntawm cov kab mob pathogenesis.

bisphosphonates rau cov pob txha metastases
bisphosphonates rau cov pob txha metastases

Ntau qhov kev tshawb fawb tau soj ntsuam cov txiaj ntsig ntawm bisphosphonate Clodronate ntawm kev txhim kho pob txha metastases hauv cov poj niam kuaj mob qog noj ntshav. Cov txiaj ntsig tau zoo tau txais: cov tshuaj tau pab txo qhov zaus ntawm kev tsim thiab kev loj hlob ntawm cov metastases tshiab hauv cov pob txha ntawm cov neeg mob. Tam sim nokev tshawb fawb nyob rau hauv cov kev taw qhia no yog nquag mus txuas ntxiv. Bisphosphonates tuaj yeem pab nrog pob txha metastases.

Cov qog nqaij hlav mob feem ntau nrog hypercalcemia (tso calcium los ntawm cov pob txha). Nrog rau kev swb ntawm cov pob txha metastases, kev poob sai ntawm calcium tshwm sim vim nws kev puas tsuaj los ntawm osteoclasts. Tsis tas li ntawd, hypercalcemia hauv qog noj ntshav tuaj yeem tshwm sim vim qhov cuam tshuam ntawm peptide ntawm cov qog. Kev ua kom ntxiv ntawm osteoclasts tshwm sim, uas ua rau hypercalcemia. Cov txheej txheem no nyuaj ntxiv thiab nrawm los ntawm kev txo lub raum ua haujlwm.

Cov txheej txheem no tau pom nyob rau hauv cov qog nqaij hlav xws li squamous cell carcinoma, ntau yam myeloma, mob qog noj ntshav mis, mob raum cell carcinoma thiab qee hom lymphomas. Rau kev mob qog noj ntshav vim hypercalcemia, cov tshuaj txhaj tshuaj bisphosphonates yog cov tshuaj zoo tshaj plaws. Cov tshuaj Bisphosphonate xws li Zoledronic acid thiab Pamidronate tau ua pov thawj lawv tus kheej zoo hauv cov xwm txheej no.

Kev soj ntsuam qhia tau hais tias ob peb hnub tom qab pib txhaj tshuaj ntawm cov tshuaj no rau cov neeg mob, qhov concentration ntawm calcium nyob rau hauv cov ntshav normalizes, thiab cov nyhuv txuas ntxiv mus ntev (los ntawm ib mus rau ob lub lis piam).

Daim ntawv teev cov kab mob uas bisphosphonates tau siv tau zoo

  • Osteoporosis.
  • Myeloma.
  • Kev mob hauv pob txha.
  • Paget's disease (deforming osteodystrophy).
  • YPrimary hyperparathyroidism.
  • hlav thiab pob txha metastases, tshwj xeeb tshaj yog cov cuam tshuam nrog hypercalcemia.
Zometa bisphosphonates
Zometa bisphosphonates

Side effects

Hmoov tsis zoo, kev kho mob nrog bisphosphonates tuaj yeem ua txhua yam tab sis tsis muaj mob. Tshwj xeeb tshaj yog thaum nws los txog rau intravenous tswj ntawm cov tshuaj no. Lawv tuaj yeem ua rau muaj qhov tsis zoo hauv qab no:

  • Nrog kev tswj hwm txoj hlab ntshav - hypocalcemia.
  • Muaj peev xwm cuam tshuam rau lub raum, ua rau qaug cawv.
  • Qee zaum noj amine-muaj bisphosphonates provokes kev loj hlob ntawm osteonecrosis ntawm lub puab tsaig.
  • Pab txhawb kev loj hlob ntawm cov kab mob hauv txoj hlab pas thiab plab.
  • Yuav ua rau cem quav lossis raws plab, thiab qee zaus, nqos nyuaj.
  • Nyob zoo malaise, qaug zog, xeev siab.
  • mob leeg.
  • teeb meem tsis pom kev.
  • Raws ntawm lub cev.

Yog, bisphosphonates tuaj yeem ua rau tag nrho cov teeb meem no. Cov tshuaj uas koj lub npe tau ntsib hauv peb tsab xov xwm tsis tuaj yeem sau rau koj tus kheej ntawm koj tus kheej, yog li tsis txhob ua yuam kev ua rau lub cev tsis zoo. Peb txhob txwm tshaj tawm qhov no hauv cov ntawv nyeem ob peb zaug! Kev txiav txim siab los ntawm cov kev txheeb xyuas uas tuaj yeem nyeem ntawm ntau lub rooj sab laj, tib neeg nquag qhia cov ntaub ntawv hais txog qee yam BFs rau ib leeg thiab txaus siab qhia lawv rau lwm tus. Qhov no yog me ntsis tsis ncaj ncees lawm. Nws yog ib qho tsim nyog yuav tau noj cov tshuaj muaj zog no tsuas yog raws li kev pom zoo ntawm tus kws kho mob uas tuaj koom thiab nyob rau hauv nws kev saib xyuas ib txwm.

Bisphosphonates - tshuaj xyuas ntawm cov kws kho mob thiab cov neeg mob

Koj puas paub tias txhua xyoo, lub Kaum Hlis 20,Puas yog txhua lub tebchaws ua kev zoo siab Hnub Ntiaj Teb Osteoporosis? Tus kab mob no tau dhau los ua kis mob tiag tiag hauv xyoo tas los no. Txawm hais tias qee tus kws tshaj lij ntseeg tias qhov cuam tshuam ntawm qhov teeb meem ntawm cov pob txha pob txha yog me ntsis exaggerated, vim hais tias tus kab mob no tsis yog tuag rau nws tus kheej. Txawm li cas los xij, feem pua ntawm cov neeg laus uas tuag tom qab pob txha pob txha, uas feem ntau tshwm sim nrog kev mob pob txha, yog siab heev. Yog li ntawd, coob tus neeg muaj kev cia siab tshwj xeeb rau bisphosphonates. Cov lus teb los ntawm cov neeg mob uas tau txais kev cia siab rau kev rov qab los ua tsaug rau cov tshuaj no yog ua tsaug rau cov kws kho mob thiab cov kws tshuaj niaj hnub, uas muaj peev xwm muab kev pabcuam raws sijhawm.

bisphosphonates tshuaj xyuas
bisphosphonates tshuaj xyuas

Dr. med. Svetlana Rodionova, PhD, xib fwb thiab lub taub hau ntawm Lub Chaw Tshawb Fawb thiab Kho Mob Osteoporosis, ntseeg hais tias qhov xwm txheej nrog osteoporosis hauv Russia yog qhov nyuaj heev. Ib tug kws kho mob paub zoo hais tias tam sim no, thaum noj zaub mov ntawm cov neeg feem coob tsis txaus (tsis muaj calcium), cov cwj pwm phem xws li haus luam yeeb, siv yeeb tshuaj thiab haus cawv muaj ntau, thiab kev ua si ntawm lub cev tau nce mus txog xoom, ntau cov tub ntxhais hluas, feem ntau yog poj niam. yog doomed los ua mob osteoporosis nyob rau hauv ntau mature xyoo. Yog li xav tau cov tshuaj zoo los pab kho tus kab mob no zoo heev.

Raws li cov tshuaj nquag nquag ntawm bisphosphonates los ntawm cov kws kho mob, tus xibfwb qhia qhov kev xav tias qhov no tsis yog ib txwm muaj tseeb. Bisphosphonates - tshuajmuaj txiaj ntsig zoo, tab sis ua ntej yuav muab tshuaj rau tus neeg mob, tus kws kho mob yuav tsum coj mus rau hauv tus account yam xws li cov pob txha metabolism thiab calcium homeostasis. Nrog kev xav thiab kev kho tsis tau nrog bisphosphonates, cov teeb meem loj tuaj yeem tshwm sim: atrial fibrillation, osteonecrosis ntawm lub puab tsaig, subtrochanteric fractures ntawm femur.

Raws li tus kws kho mob uas muaj kev hwm, bisphosphonates tsis yog universal panacea, lawv yuav tsum tau ua kom ceev faj. Lub caij no, Txoj Haujlwm Kev Noj Qab Haus Huv tab tom tshaj tawm hauv TV cov ntxaij vab tshaus, qhov twg Elena Malysheva yaum cov neeg tuaj saib nrog lub ntsej muag luag ntxhi tias tsis muaj dab tsi yooj yim dua li kev kho pob txha pob txha nrog bisphosphonates thib peb. Tsis txhob ntseeg qhov kev tshaj tawm qhia ntau dhau. Rau qee tus neeg, noj BF yog nruj me ntsis contraindicated. Piv txwv li, cov neeg mob raum mob hnyav.

Tam sim no rau cov lus qhia txog yuav ua li cas bisphosphonates ua haujlwm rau cov pob txha metastases. Cov kev xav ntawm cov kws kho mob tsis muaj tseeb: cov tshuaj no muaj peev xwm tiv thaiv kev loj hlob ntawm cov qog nqaij hlav hauv cov pob txha, uas, tau kawg, pab cov neeg mob kov yeej ib qho mob hnyav tshaj plaws uas muaj nyob hauv ntiaj teb.

Zoo kawg

Tam sim no koj paub tias nws yog dab tsi - bisphosphonates. Cov lus qhia rau lawv siv tau teev tseg ntawm no, nrog rau cov npe tshuaj, tsis yog muab los ntawm peb raws li cov lus pom zoo thiab yog rau cov ntaub ntawv xov xwm nkaus xwb - thov ua tib zoo saib xyuas qhov no! Yog tias muaj teeb meem kev noj qab haus huv hnyav, koj tsis tas yuav kho tus kheej, qhov zoo tshaj plaws yog mus ntsib kws kho mob sai,kom nws muab tshuaj rau koj. Peb thov kom sawv daws noj qab nyob zoo thiab muaj kev zoo siab!

Pom zoo: