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mTavari mkvlevari: Tomas r. zigleri M.D. Tana-mkvlevarebi: henri m. blumbergi M.D.

D vitaminis zegavlena tuberkulozis mikobaqteriis mimarT maspinZlis imunitetsa da mkurnalobis Sedegebze : translaciuri kvlevebisTvis infrastruqturis ganviTareba dietologiasa da infeqciur daavadebebSi saqarTveloSi. mTavari mkvlevari: Tomas r. zigleri M.D.

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mTavari mkvlevari: Tomas r. zigleri M.D. Tana-mkvlevarebi: henri m. blumbergi M.D.

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  1. D vitaminiszegavlenatuberkulozismikobaqteriismimarTmaspinZlisimunitetsa da mkurnalobisSedegebze: translaciurikvlevebisTvisinfrastruqturisganviTarebadietologiasa da infeqciurdaavadebebSisaqarTveloSi.

  2. mTavari mkvlevari: Tomas r. zigleri M.D. Tana-mkvlevarebi:henri m. blumbergi M.D. vin TangpriCa M.D., PhD. reinaldo martoreli PhD. uSa ramakriSnan PhD karlos del rio M.D. aleqsandra iamSikovi M.D ekaterina kurbatova M.D., MPH, PhD naSa talanti, M.D. arCil salayaia M.D., MPH nestan tukvaZe M. D. veriko mircxulava M.D., MPH nino lomTaZe M. D., M.Sc. sponsoris saxeli: emoris jandacvis globaluri instituti

  3. D vitaminiT Terapia da tuberkuloziistoriuli rakursi • nobelis lauriatma ils-finzenma 1900 wlebSi popularizacia gauwia solariumebis gamoyenebas kanis tuberkulozis samkurnalod. • 1947-1998 wlebSi dagrovili masalebi sxvadasxva Sedegebs aCvenebs mziT insolaciisa da D vitaminiT Terapiis efeqturobasTan dakavSirebiT • D vitaminis deficiti zrdis tuberkulozis mimarT winaswarganwyobas • pacientebs aqtiuri tuberkuloziT aqvT Sratis 25(OH)D done ufro dabali vidre maT janmrTel kontrolebs. • D vitaminis deficiti korelaciaSia radiografiuli monacemebiT dadasturebul tuberkulozis rTul formebTan.

  4. kani D vitamini D 25 (OH) D3 1.25 (OH)2 D3

  5. TOLL-LIKEreceptorebis mier D vitaminis gaaqtiurebiT ganpirobebuli antimikrobuli pasuxis CarTva 24, march, 2006DOI: 10.1126/science.1123933Science 311, 1770 (2006); TLR aqtivaciam adamianis makrofagebSi moaxdina D vitaminis receptorebis aqtivacia da vitaminD-1-hidroqsilazas genebiseqspresia, ramac gamoiwviaantimikrobuli cila katelicidinis (LL-37)-is gaaqtiureba da ujredSida Mycobacterium Tuberculosis ganadgureba.

  6. LL-37-is regulacia D vitaminiT, antimikobaqteriuli meqanizmebi

  7. kvlevis dizaini ormagad-brma, randomizirebuli, kontrolirebadi 3 wliani klinikuri kvleva vitamin D –s efeqturobasa da antimikrobul meqanizmebze. filtvis tuberkuloziT daavadebul axlad registrirebul pacientebs (n=110) CautardebaT D vitaminiT Terapia oTxi Tvis manZilze, placebo kontrolis jgufis (n=110) paralelurad. kvlevis monawileebs CautardebaT antituberkulozuri mkurnaloba programul farglebSi DOT meTvalyureobis qveS. radganac tubinfeqcia arsebul kvlevebze dayrdnobiT dakavSirebulia D vitaminis naklebobasTan Seawavlil iqneba 80 arainficirebuli ojaxuri kontaqti piloturi monacemebis Sesagroveblad.

  8. hipoTezebi: 1. D vitaminiT Terapia gamoiwvevs filtvis tuberkuloziT daavadebul pacientebSi antituberkulozuri mkurnalobis gaumjobesebul Sedegebs, aseve gaumjobesdeba am pacinetebis nutriciologiuri statusi placebo kontrolis jgufTan SedarebiT. 2. D vitaminiT Terapia sagrZnoblad gazrdis LL-37-is koncentracias naxvelSi, nerwyvsa da plazmaSi da katelicidin/LL-37-is mRNA da proteinis eqspresias kanSi, D placebos preparatiT mkurnalobasTan SedarebiT. 3. naxvelSi, nerwyvsa da plazmaSi LL-37-is done da kanSi katelicidin/LL-37-is, mRNA-is da proteinis eqspresia filtvis tuberkuloziT daavadebul pacientebSi dadebiT korelaciaSi iqnebaorganizmSi D vitaminis nutriciologiur statustan, rac Sefasdeba plazmaSi 25-hidroqsivitamin D-s koncentraciiT. 4. saqarTveloSi filtvis tuberkuloziT daavadebul pacientebs aqvT D vitaminis naklebobis/deficitis maRali prevalentoba da es problema ufro gamoxatulia maTSi, vidre maT ojaxur kontaqtebSi, romelTac ar daudgindaT aqtiuri tuberkulozi.

  9. kvlevis miznebi da amocanebi amocana 1 : pacientebSi, romelTac daudasturdebaT fitvis tuberkulozis axali SemTxveva, Catardes randomizirebuli ormagad-brma kontrolirebadi kvleva, peroraluri D vitaminisantituberkulozur mkurnalobaSi CarTvis fonze klinikuri da nutriciologiuri statusis SesaZlo gaumjobesebis Sesafaseblad. Mantituberkulozur mkurnalobaSi D vitaminis CarTvis dizaini iTvaliswinebs plazmaSi D vitaminis koncentraciis optimizacias 32ng/ml.-mde

  10. amocana 2 : Sedardes vitaminiT Terapiasa da placebo kontrolze myof pacientebSi sabaziso gamokvlevebSi LL-37-is koncentraciebi naxvelSi, nerwyvsa da plazmaSi da katelicidin /LL-37-is mRNA da proteinis eqspresia kanSi

  11. amocana 3 : LL-37-iskoncentraciebi naxvelSi, nerwyvsa da plazmaSi da katelicidin /LL-37-is mRNA da proteinis eqspresia kanSiseriulad Sedardes plazmis 25 (OH) D vitaminis koncentraciasTan amocana pirvelSi xsenebul monawileebSi amocana 4 : pacinetebSi filtvis tuberkuloziT ganisazRvros sabaziso vitamin D statusi da Sedardes maTi janmrTeli ojaxuri kontaqtebis kohortas

  12. skriningis forma CarTvis kriteriumebi: 1. skriningis momentisaTvis pacienti sul mcire 18 wlisaa 2. pacients aqvs mgb(+) filtvis tuberkulozi 3. pacients utardeba tubsaw. mkurnaloba araumetes erTi kvirisa 4. pacienti tubsawinaaRmdego mkurnalobas Caitarebs TbilisSi Tu pirvel nawilSi yvela kiTxvaze aRiniSneba uaryofiTi pasuxi, individi ar SeiZleba CaerTos kvlevaSi.

  13. gamoricxvis kriteriumebi: 1. pacienti warsulSi namkurnalebia tubsawinaaRmdego medikamentebiT 30 dReze meti xnis manZilze 2. pacienti mimdinare momentSi orsuladaa an meZuZuria 3. pacients warsulSi Catarebuli aqvs organos transplantacia 4. pacients ukanaskneli 5 wlis ganmavlobaSi aReniSneba kibos diagnozi (dasaSvebia kanis kibo - aramelanoma) 5. pacients anamnezSi aReniSneba gulyra 6. pacients aqvs hiperkalcemiis istoria 7. pacients aqvs hiperparaTireoidizmis istoria 8. pacients aqvs sarkoidozis istoria 9. pacients aqvs nefroliTiazis istoria 10. pacienti ukanaskneli 30 dRis ganmavlobaSi iRebda kortikosteroidebs 11. pacienti mimdinare momentSi iRebs citotoqsiur an imunosupresiul wamlebs 12. pacienti saWiroebs dializur Terapias 13. pacients aqvs cirozis istoria 14. pacienti mimdinare momentSi aris patimrobaSi 15. pacients ar surs an ar SeuZlia Seasrulos yvela viziti TbilisSi Tu meore nawilSi romelime kiTxvaze aRiniSneba dadebiTi pasuxi, individi ar SeiZleba CaerTos kvlevaSi

  14. kvlevis algoriTmi

  15. sabaziso informacia : _ kalciumi, D vitamini ( 25(OH)D vitamini ELIZA-s testiT) da PTH _ naxvelSi nerwyvsa da sisxlSi LL-37 is donis gansazRvra (ELIZA-s testiT) _ kanis biofsia LL-37-is mRNA da proteinis eqspresiis gansazRvra ( emoris universitetSi RT- PCR - is gamoyenebiT) _ mikroskopia da kultura. monacemebi nutriciologiur statusze: - sxeulis masis indeqsi (BMI) - sxeulis Semadgenloba bioeleqtrul winaRobaze dayrdnobiT (raTa ganisazRvros sxeulis mWle da cximovani masa da sxeulis siTxis Semcveloba) - samdRiani kvebis kiTxvari, raTa Sefasdes pacientis mier moxmarebuli dRiuri energia, proteinebi, glutamini, vitamini D, vitamini A, seleniumi da cinki.

  16. infrastruqturis ganviTareba Molecular Devices Microplate reader (96-well platereader) Beckman Refrigerated Benchtop Centrifuge Ultracold (-80C) freezer DSL bioelectrical impedance analyzers (BIA machines; n=2) Tanita Digital scales (n=2) Dell labtop computer for web-based data entry of CRFs into database ELISA kits and supplies for LL-37 and 25 OH vitamin D assays in Tbilisi Food models to facilitate food intake record determinations

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