1. D vitaminis zegavlena tuberkulozis mikobaqteriis mimarT maspinZlis imunitetsa da mkurnalobis Sedegebze: translaciuri kvlevebisTvis infrastruqturis ganviTareba dietologiasa da infeqciur daavadebebSi saqarTveloSi.

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 tuberkulozi istoriuli rakursi
nobelis lauriatma ils-finzenma 1900 wlebSi
popularizacia gauwia solariumebis gamoyenebas
kanis tuberkulozis samkurnalod.
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-LIKE receptorebis mier D vitaminis gaaqtiurebiT ganpirobebuli antimikrobuli pasuxis CarTva 24, march, 2006 DOI: /science Science 311, 1770 (2006);
TLR aqtivaciam adamianis makrofagebSi moaxdina D vitaminis receptorebis aqtivacia da vitamin D-1-hidroqsilazas genebis eqspresia, ramac gamoiwvia antimikrobuli 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:
D vitaminiT Terapia gamoiwvevs filtvis tuberkuloziT daavadebul pacientebSi antituberkulozuri mkurnalobis gaumjobesebul Sedegebs, aseve gaumjobesdeba am pacinetebis nutriciologiuri statusi placebo kontrolis jgufTan SedarebiT.
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.
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 iqneba organizmSi 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 vitaminis antituberkulozur 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-is koncentraciebi naxvelSi, nerwyvsa da
plazmaSi da katelicidin /LL-37-is mRNA da proteinis
eqspresia kanSi seriulad 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. monacemebi nutriciologiur statusze:
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