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


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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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Mtavari mkvlevari tomas r zigleri m d tana mkvlevarebi henri m blumbergi m d

D vitaminiszegavlenatuberkulozismikobaqteriismimarTmaspinZlisimunitetsa da mkurnalobisSedegebze: translaciurikvlevebisTvisinfrastruqturisganviTarebadietologiasa da infeqciurdaavadebebSisaqarTveloSi.


Mtavari mkvlevari tomas r zigleri m d tana mkvlevarebi henri m blumbergi m d

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


D vitaminit terapia da tuberkulozi istoriuli rakursi

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.


Mtavari mkvlevari tomas r zigleri m d tana mkvlevarebi henri m blumbergi m d

kani

D

vitamini D

25 (OH) D3

1.25 (OH)2 D3


Mtavari mkvlevari tomas r zigleri m d tana mkvlevarebi henri m blumbergi m d

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.


Ll 37 is regulacia d vitaminit antimikobaqteriuli meqanizmebi

LL-37-is regulacia D vitaminiT, antimikobaqteriuli meqanizmebi


Kvlevis dizaini

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.


Hipotezebi

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.


Kvlevis miznebi da amocanebi

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


Amocana 2

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


Amocana 3

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


Skriningis forma

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.


Gamoricxvis kriteriumebi

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


Kvlevis algoritmi

kvlevis algoriTmi


Mtavari mkvlevari tomas r zigleri m d tana mkvlevarebi henri m blumbergi m d

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.


Infrastruqturis ganvitareba

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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