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samedicino bioteqnologiis institutis 2009 wlissamecniero-kvleviTi muSaobis angariSi

samedicino bioteqnologiis institutis ZiriTadi mizania janmrTelobisproblemebis gadawyveta Teoriuli, eqsperimentuli da klinikuri kvlevebisSedegad axali samkurnalo, profilaqtikuri, sadiagnostiko preparatebisa dateqnologiebis Seqmnisa da maTi praqtikaSi danergvis gziT. arsebulipreparatebis analitikuri, eqsperimentaluri da klinikuri kvleva daSefaseba.

prioritetebi:

sxvadasxva paTologiaTa (autoimunuri, asakTan-dakavSirebuli)diagnozirebisa da monotoringisaTvis biomarkerebis gamovlena daqarTul populaciaSi ZiriTadi risk-faqtorebis Sefaseba

axali samkurnalwamlo formebis Seqmna da arsebulis Sefaseba sakveb produqtebSi arsebuli biologiurad aqtiuri naerTebi da maTi

samedicino mniSvneloba

samedicino bioteqnologiis institutSi 2009 wlis ganmavlobaSi arsebuliprioritetebisa gaTvaliswinebiT ganxorcielda Semdegi samecniero-kvleviTisamuSaoebi:

1. glutamatis gavlena periferiuli sisxlis limfocitebis mier IL-10-issinTezze autoimunuri Tireoiditis dros

mizani: samuSaos mizani iyo Segvswavla periferiuli sisxlis limfocitebismier IL-8 da IL-10–is sekrecia glutamatis sxvadasxva koncentraciebisgavleniT autoimunuri TireoiditiT daavadebul pacientebSi.meTodebi: gamokveluli iyo 15 pacienti (12 qali da 3 mamakaci), saSualo asaki32.5 weli. yvela maTgans hqonda autoimunuri Tireoiditis diagnozi. Yyvelapacients aReniSneboda TSH-is momatebuli da Tireoiduli hormonis dabalidone. pacientebis venuri sisxli ganzavebuli iqna Tanabari moculobisHEPES –buferiT, (pH 7.4; 10 mM HEPES, 0.1% BSA, 5 mM D-glucose, 145 mM NaCl, and5 mM KCl). mononukleuri ujredebi miRebul iqna fikol-verografinisgradientSi centrifugirebiT. ujredebi samjer garecxil iqna glutamatisganTavisufali RPMI 1640–iT, ujredebi (2- 3 x 105 /ml) stimulirebul iqna anti-CD3 antisxeuliT (1 ng/ml, 37°C, 4 h) da inkubirebul iqna 48sT 37 0C-ze RPMI1640–Si, romelic ar Seicavda Srats da damatebuli hqonda glutamatisdabali (0.3 x 10-6 M) da maRali (1 x 10-5 M) koncentracia. inkubirebis Semdegujredebis centrifugireba moxda 800 g, 20wT-is ganmavlobaSi. supernatantSigazomil iqna IL-8 da IL-10–is raodenoba imunofermentuli analiziT.monacemTa damuSaveba xdeboda “ONE -WAY ANOVA” - testiT.Sedegebi: miRebuli monacemebis Tanaxmad, glutamatis maRali koncentraciaaxdens periferiuli sisxlis limfocitebSi IL-10-is sinTezis pozitiurmodulacias. periferiuli sisxlis limfocitebis mier IL-8–is sinTezis

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mniSvnelovani cvlileba ar momxdara glutamatis rogorc maRali, isedabali koncentraciis SemTxvevaSi. Aaseve naCvenebi iqna, rom autoimunuriTireoiditiT daavadebili pacientebis periferiuli sisxlis limfocitebiasinTezireben IL-10-is ufro nakleb raodenobas, vidre janmrTeli individebisperiferiuli sisxlis limfocitebi. ASedegebis analizi: miRebuli monacemebis Tanaxmad, glutamati amcirebs IL-10-is raodenobas, gansakuTrebiT autoimunuri TireoiditiT daavadebilipacientebSi, rac SesaZloa pasuxismgebeli iyos dayovnebul anTebiTreaqciebze. aRniSnuli cvlilebebi SesaZloa dakavSirebuli iyos glutamatisreceptoris mgrZnobelobaze, romlis aqtivobac qveiTdeba autoimunuriTireoiditis dros glutamatis gazrdil raodenobaze sapasuxod.gamoTqmulia mosazreba, rom glutamatis receptorebis mablokirebelisaSualebebi SesaZloa warmatebiTY iqnas gamoyenebuli autoimunuriTireoiditis mkurnalobisas.

2. imunuri sistemis organoebSi ganviTarebuli cvlilebebis amsaxvelibiomarkerebis gamovlena da maTze moqmedi saSualebebis Seswavla asakovanxandazmul populaciaSi

kvlevis mizani iyo janmrTel qarTul xandazmul populaciaSi imunologiurimaxasiaTeblebisa (Th1/Th2 citokinebi) da maTze moqmedi risk faqtorebis(socialuri, cxovrebis wesi, kvebiTi parametrebi da sx.) erTdrouliSefaseba;gamoyenebuli masala da meTodebi:sisxlis nimuSebis aReba. uzmoze idayvis venidan aRebuli iqna 1 sinjara (10ml) periferiuli venuri sisxli EDTA-s Semcvel sterilur sinjarebSi.plazmis gamoyofa – aRebuli sisxlis nawili dacentrifugirda 1500 g-ze15wT-is ganmavlobaSi. gamoiyo plazma, romelic inaxeboda alikvotebadplastmasis sinjarebSi -300C temperaturaze gayinul mdgomareobaSicitokinebis analizis Catarebamde.citokinebis (IFN-gamma, IL-10, TNF-alfa) gazomva ganxorcieldaimunofermentulinakrebebis (Biolegend, San Diego, USA) saSualebiT TandarTuliprotokolis mixedviT. yvela analizi Catarda wyvilebSi da gamoyenebuli iyosaSualo an medianuri maCvenebeli. analizebs Soris variaciis koeficientebiar iyo 8%-ze meti.statistikuri analizi: martivi aRwerilobiTi statitikuri analizi (Statistica8.0, Statsoft, USA) da Seswavlili cvladebis potenciuri kovariantebisSefaseba; cvaldebi, romelTa gnawileba ar iyo normaluri iqnagalogariThmebuli da mxolod amis Semdeg CarTul satatitikurdamusavebaSi. potenciuri kovariantebis gamosavlenad citokinebi da Treg-ebiskanirebuli iyo asakis, sqesis, wonis da sxva faqtorebis mixedviT.Seswavlil prametrebs Soris SesaZlo kavSirebis gamosavlenad Catarebuliiqna mravlobiTi regresiuli analizi.

miRebuli Sedegebi: Cvens mier Sefasebuli iqna agreTve pro- da antianTebiTi

citokinebis done (IL-10, TNF-, INF-). statistikuri damuSavebis Sedegadgamovlinda, rom qarTul populaciaSi Semdegnairad cvalebadobs: il-10 -

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1.33pg/ml-dan 101.98pg/ml-mde, TNF- - 2.2 pg/ml-idan 19.64 pg/ml-mde, INF- -4.71pg/ml-idan 232 pg/ml-mde. citokinebis donis ganawilebis testirebam, aCvena,rom individebi, romelTa il-10-is done aRemateba 18pg/ml-ze arisamovardnili saerTo ganawilebidan. amdenad, aseTi gadaxris mqone individebiamoRebuli iqna Semdgomi kvlevidan.

cxrili. 1 citokinebis koncentracia janmrTel qarTul populaciaSisqesis mixedviT

saSualo+standartuli gadaxra,]minimumi da maqsimumi

mTlianipopulacia

Mkacebi qalebi

TNF 7.83+4.18(2.20-19.64)

8.30+3.76(2.67-19.14)

7.92+4.29(2.20-19.64)

INF- 12.91+20.50(4.71-232.00)

10.49+3.12(6.79-18.01)

13.65+22.97(4.71-232.00)

IL-10 6.84+11.31(1.33-101.98)

5.51+4.47(1.57-17.21)

7.36+12.50(1.33-101.98)

TNF/IL-10Index

1.80+1.08(0.32-7.06)

2.10+1.72(0.43-7.06)

1.73+0.91(0.32-5.29)

rogorc cxrilidan (#1) Cans, citokinebis saSualo koncentracia arvarirebs sqesis da asakis mixedviT, Tumca unda aRiniSnos, rom il-10-ismediana mniSvnelovnad gansxvavdeba axalgazrda da asakovan jgufebSi (p<0.01).kerZod, misi raodenoba xandazmulebSi (3.90+6.33) statistikurad sarwmunodklebulobs axalgazrdebTan SedarebiT (6.80+4.60, sur. 1).

sur. 1 mocirkulire il-10-is medianebi axalgazrda (50 wlamde) daasakovan populaciaSi (60 wlis zemoT) (Mann-Whitney-is U testi, p<0.05).

1 2

Age

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

LNIL

-10

Median 25%-75% Min-Max

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kvlevis Semdgom etapze SevafaseT kavSiri imunologiur parametrebs Soris,kerZod Seswavlil imunokopetentur ujredebsa (Tregs, CD3CD4, CD3CD8) dacitokinebs Soris.miRebuli Sedegebis analizis Sedegad, metad saintereso suraTi gamovlinda.

Sefasebuli pro da antianTebiTi citokinebis (TNF- IL-10, INF-) koncentraciaasakovan populaciaSi mWidro da pirdapir korelaciaSia erTmaneTTan, maSin

roca axalgazrda individebSi mxolod il-10 korelirebs sarwmunod TNF- –Tan (cxr. 2).

cxrili 2. kavSiri Seswavlil citokinebis doneebs Soris axalgazrda(diagonalis qvemoT) da asakovan populaciaSi (diagonalis zemoT).

miRebuli Sedegi, Zalian sayuradReboa, radganac il-10 mniSvnelovaniimunomaregulirebeli citokinia da misi mTavari biologiuri funqciaanTebiTi procesis SezRudva da damTavrebaa. meores mxriv, interferon gamayvela ujreduli programis CarTvis diriJoria da gavlenas axdenstranskripciuli genebze da pro-anTebiTi citokinebis sawinaaRmdego efeqtsavlens. amdenad, Cveni Sedegebi pro- da antianTebiT citokinebs SorisdadebiTi korelacia nawilobriv moulodnelia, Tumca zogierTma mkvlevarmasefsisis dros aRmoaCina pirdapiri kavSiri pro- da antianTebiT citokinebisSoris, romelic adasturebs hipoTezas, romlis mixedviTac sefsisis drosantianTebiTi citokinebis raodenoba anTebiTi procesis ganviTarebisproporciulia. garda amisa, Nishida da sxvebma exlaxans aCvenes, rom il-10isdones dadebiTad korelirebs aseve anTebiT faqtorebTan metabolurisindromis dros.

BMI LNTNF LNINF- LNIL-10 TNF/IL-10Index

BMI -.0178p=.870

.1025p=.350

-.0366p=.739

-.1179p=.285

LNTNF- -.2785p=.160

.5409p=.000

.6166p=.000

.3798p=.000

LNINF- .2160p=.279

.3015p=.112

.6346p=.000

-.1522p=.167

LNIL-10 -.1803p=.399

.6652p=.000

.3659p=.066

-.4255p=.000

TNF/IL-10Index

-.0504p=.815

.0414p=.841

-.0987p=.631

-.5625p=.003

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cxrili 3. korelaciuri kavSiri Seswavlil citokinebsa da ujredebisdoneebsa Soris sqesis mixedviT

dasaxelebakacebi qalebi

TNF- INF- IL-10 TNF- INF- IL-10

CD3CD8 0.328p=.170

0.561p=.012

0.152p=.534

0.274p=.017

0.040p=.733

0.253p=.027

CD3CD4 0.194p=.439

0.493p=.037

0.423p=.080

0.018p=.879

0.070p=.560

-0.078p=.510

T4/T8indeqsi

-0.296p=.232

-0.163p=.516

0.039p=.877

-0.193p=.106

0.083p=.494

-0.164p=.171

CD4CD25 0.395p=.104

0.514p=.029

0.355p=.147

0.381p=.000

0.222p=.036

0.364p=.000

CD4FoxP3 0.439p=.060

-0.168p=.491

0.012p=.960

0.143p=.175

0.003p=.972

0.121p=.250

CD4CD25high -0.269p=.373

0.618p=.024

0.216p=.478

0.260p=.074

0.016p=.913

0.217p=.139

kvlevis saboloo etapze gaavanalizeT citokinebis donesa daujredebis raodenobas Soris arsebuli asociacia mamakacebsa da qalebSi.rogorc cxrilidan (#3) Cans, Treg-ebis raodenoba mamakacebSi interferon-gamas raodenobis pirdapirproporciulia, maSin roca qalebSi is arkorelirebs arcerT Cvens mier Seswavlil citokinTan. aqve unda aRiniSnosis faqtic, rom CD4CD25 ujredebis (gaaqtiurebuli CD4 ujredebi) sixSireqalebsa da asakovan individebSi asocirdeba citokinebis raodenobiszrdasTan (cxr. #4).

cxrili 4. korelaciuri kavSiri Seswavlil citokinebsa da ujredebisraodenobas Soris asakis mixedviT

dasaxelebaaxalgazrdebi (50 wlamde)asakovnebi

(60 wlis zeviT)

TNF- INF- IL-10 TNF- INF- IL-10

CD3CD8 0.101p=.629

0.354p=.083

0.076p=.737

0.200p=.085

0.094p=.428

0.242p=.038

CD3CD4 -.529p=.014

-.075p=.744

.390p=.098

.132p=.269

.212p=.078

0.098p=.417

T4/T8indeqsi

-.803p=.000

-.244p=.285

.259p=.283

-.042p=.723

.109p=.366

-0.092p=.446

CD4CD25 0.308p=.125

0.089p=.665

-0.122p=.577

.432p=.000

0.462p=.000

0.515p=.000

CD4FoxP3 0.067p=.732

0.118p=.547

0.017p=.933

0.176p=.105

-0.005p=.958

0.152p=.167

CD4CD25high 0.439p=.032

.1612p=.452

0.420p=.046

-0.080p=.635

0.059p=.728

0.104p=.537

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miRebuli Sedegebis safuZvelze Cven SegviZlia davaskvnaT, asakovanpopulaciaSi arsebobs mudmivi susti anTebis foni gamowveuli saerTostimuliT, rac ganapirobebs erTdroulad rogorc gaaqtiurebuli Tujredebis, aseve pro da antianTebiTi citokinebis donis matebas. meoresmxriv CD4CD25high ujredebis raodenoba ar icvleba, piriqiT maTi funqciadaTrgunulia, rac kidev ufro metad uwyobs xels anTebiTi fonisSenarCunebas.

amrigad, qarTul xandazmul populaciaSi imunuri sistemaSi ganviTarebuliasakobrivi cvlilebebis gamosavlenad, profilaqtikisa daimunoreabilitaciisaTvis mizanSewonilia:

1. organizmSi imunuri sistemis daberebasTan asocirebuli proanTebiTi fonis

dasadgenad 50 wels gadacilebul pirebSi ganisazRvros TNF-/IL-10 indeqsi;

2. TNF-/IL-10 indeqsis gazrdis (≥4) SemTxvevaSi, asakTan-asocirebulidaavadebebis profilaqtikis mizniT, gamokvleul pirs mieces rekomendacia,kvebis racionSi aucileblad CarTos fenolebiT mdidari produqtebi dagazardos fizikuri aqtivoba, rac proanTebiTi citokinebis donis Semcirebasuzrunvelyofs. indeqsis mkveTri gazrdis SemTxvevaSi aseve mizanSewoniliaanTebissawinaaRmdego mkurnalobis dawyeba (aspirini).

3. imunuri sistemis daberebis Sesafaseblad TNF-/IL-10, CD3CD4/CD3CD8indeqsisa da maregulirebeli CD4Foxp3 ujredebis gansazRvra;

3. imunuri statusis Seswavla damwvrobis daavadebis dros da imuno-reabilitaciis sakiTxebi.

kvlevis ZiriTadi mizani iyo organizmis imunur sistemaze damwvrobisdaavadebis zegavlenisa da am pirobebSi sami samamulo preparatis, kamelinisplaferon lb-s, da fenovinis imunoreabilitaciuri Tvisebebis Seswavla.masala da meTodebi. imunuri statusi Seswavlil iqna 90 pacientSi, romlebicSemovidnen Tbilisis Termuli dazianebaTa da aRdgeniTi plastikuriqirurgiis samedicino-praqtikuli centris stacionarSi, diagnoziT –Termuli travma, damwvrobis daavadeba (asaki 1 wlidan – 72 wlamde);sakontrolo jgufSi Sevida 30 praqtikulad janmrTeli adamiani. gamoyenebuliqna Semdegi parametrebi: B-limfocitebis procenti da sami klasisimunoglobulinebis G, A da M raodenoba T-limfocitebisa da maTisubpopulaciebis (gaaqtiurebeuli, helperebi da supresorebi) procenti,imuno-regulaciis indeqsi, fagocitozis sami maCvenebeli – ricxvi, indeqsi,dasruleba. agreTve Seswavlili iqna interferonis sistema, alfa da gamatipebis saxiT. masalis damuSaveba Catarda specialuri kompiuteruliprogramiT.Sedegebis analizi. warmodgenil naSromSi Sesrulebulia Termuli travmiTada damwvrobis daavadebiT pacientebis imunuri homeostazis analizi. Yyvelaparametri Seswavlilia daavadebis formisa da simZimis gaTvaliswinebiT,dinamikaSi – pacientis stacionarSi Semosvlisas, travmis miRebis me-2-3, me-7-10da me-14-16 dReebSi (damwvrobis daavadebis paTogenezis gadamwyveti etapebi),agreTve Terapiuli midgomisa da mkurnalobis Sedegis gaTvaliswinebiT.

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Termuli travmiT pacientebis gamokvlevis Sedegebma gamoavlinamniSvnelovani cvlilebebi imunur sistemaSi, rac pirdapir korelaciaSi iyodamwvrobis stadiasa da formasTan, agreTve asakTan. yvelaze sarwmuno aRmoC-nda imunitetis T-rgolis depresia, pacientebis stacionarSi Semosvlisastravmis adreul periodSi, e.i. damwvrobis Sokis stadiaze: T-limfocitebisraodenobis daweva 38,8%-mde (kontrolSi – 51,5%); helperuli subpopulacia –20,1%-mde (kontroli – 36,8%); supresorebis momateba 18,6%-mde (14,6%); imuno-regulaciis indeqsis Semcireba 1,08-mde (normaSi – 2,52). aRniSnul dinamikasTan axlda Rrma cvlileba citokinebis “badeSi”, kerZod interferonissistemaSi: alfa-interferonis aqtivoba Semcirda 19,6 erT/ml-mde (norma – 43,4erT), gama interferoni – 11,8 erT/ml-mde (31,8 erT). gvinda davafiqsiroT gama-interferonis sinTezis sruli ararsebobis xSiri faqti, gansakuTrebiT mZimeavadmyofebSi.

endogenuri interferonis daTrgunva iwvevs damaxinjebuli imunuripasuxis formirebas. ase magaliTad, B-limfocitebis daqveiTebam (imunoglobu-linebis meqanikuri danakargis fonze, posttravmatuli plazmis dakargvisSedegad) SeiZleba gamoiwvios humoruli imunitetis meoradi depresia, racfagocito-zis ukmarisobasTan erTad [fagocituri ricxvi – 59,2+4,8%(kontroli 75,5%); indeqsi – 1,8+0,2 (6,3); dasruleba – 48,4+3,6% (72,6%)], xelsuwyobs infeqciur garTulebas.

arsebobs azri, rom imunuri rezistentobis daqveiTeba Termuli travmisadreul periodSi warmoadgens organizmis adaptaciur reaqcias stresulzemoqmedebaze. Semdgom periodSi misi mdgomareoba damokidebulia damwvrobissimZimeze, kontaminirebadi mikrofloris paTogenobaze, dazaralebulisorganizmis konstitucionalur Tvisebebsa da asakze. am faqtorebs Soriswamyvani roli ekuTvnis damwvrobis farTobsa da qsovilebis dazianebissiRrmes. gansakuTrebiT aRvniSvnavT, rom yvelaze seriozuli imunuri Zvrebi(imunuri damblis CaTvliT) Cvens mier dafiqsirda pacientis damwvrobis me-IIIda me-IV stadiaze, kanis dazianebis didi farTobisa da mwvave toqsiemiisumZimesi formis dros. damwvrobis daavadebis am mdgomareobas CvenvaxasiaTebdiT pacientis seriozuli imunodeficitis saxiT.

amJamad, Termuli travmis dros imunitetis sxvadasxva rgolis Seswav-las didi praqtikuli mniSvneloba aqvs, vinaidan gvaZlevs damwvrobiTidaavadebis mimdinareobisa da gamosavlis prognozirebis SesaZleblobas.cnobilia, rom droul da paTogenurad dasabuTebul mkurnalobas homeo-staturi meqanizmebis dazianebis praqtikulad sruli kompensacia SeuZlia.dazaralebulis araracionaluri Terapiis dros, misi imunokompetenturobadidxans rCeba Secvlili, rac zrdis daavadebis torpiduli mimdinareobisSanss da garTulebebis SemTxvevebs (pirobiTad-paTogenuri automikroflorisaqtivobis Sedegad). qirurgiul mkurnalobasTan erTad, Termuli travmiskeTilsaimedo gamosavlisTvis gadamwyveti mniSvneloba eniWeba kompleqsurTerapias, iseTi imunotropuli preparatebis gamoyenebiT, romelTac aqvTimunuri homeosTazis sruli aRdgenis Tvisebebi.

damwvrobis daavadebis dros gamoyenebuli iyo samamulo bad-i fenovini,romelmac gamoavlina arasarwmuno mastimulirebeli zemoqmedeba imunur sis-temaze; agreTve naCvenebia fenovinis mapotencirebeli gavlena plaferonisimunomamodulirebel efeqtze.

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plaferoni-lb (gansakuTrebiT, fenovinTan erTad) aneitralebda damwvrobisdaavadebis imunodepresiul dinamikas da aumjobesebda mkurnalobis xarisxs.rac Seexeba kamelins, preparati aZlierebda damwvrobis daavadebistradiciuli mkurnalobis efeqturobas; imunologiuri poziciebidangamomdinare – kamelini xels uwyobda pacientebis imunoreabilitacias.

naSromis Sedegebi SesaZleblobas gvaZlevs rekomendacia gavuwioTplaferon lb-s, fenovinisa an kamelinis RonisZiebaTa nusxaSi CarTvas,romlebsac iyeneben damwvrobiTi daavadebis mkurnalobaSi, kerZod – imuno-depresiuli zemoqmedebis winaaRmdeg.

4. mcenareul samyaroSi arsebuli (sakveb produqtebSi da sxva)bioaqtiuri naerTebis analizi, gamoyofa, identifikacia da maTibiologiuri aqtivobis Seswavla samedicino gamoyenebis TvalsazrisiT.

miuxedavad imisa, rom saqarTveloSi igive raodenobiT moixmaren Semwvarxorcian sakvebs, rogorc dasavleTis qveynebSi, nawlavis kibos raodenobaTasixSire naklebia. Cven varaudobT, rom es ganpirobebulia swored qarTulsaneleblebSi arsebuli polifenolebis unariT gaaneitralos xorcis mavnezegavlena, rasac Cven „qarTuli paradoqsi“ davarqviT.

mizani: qarTul saneleblebSi arsebuli polifenolebis identificireba,gamoyofa da maTi anqtioqsidanturi Tvisebebis Seswavla.Sedegebi: kvlevis Sedegad dadginda, rom:1) Seswavlil saneleblebs Soris antioqsidanturi aqtivoba yvelaze maRaliaY“yviTel yvavil“-is, rogorc lipofilur aseve hidrofilur fraqciebSi.maRali antioqsidanturi aqtivoba dafiqsirda aseve qondaris, kowaxuris dakvliavis saneleblebSi. lipofilur fraqciebs Soris maRaliantioqsidanturi aqtivoba aqvs aseve wiTel wiwakas. saneleblebishidrofiluri aqtivoba korelirebs polifenolebis raodenobasTan.2) ginkgo bilobas foTlebis sxvadaxva eqstraqtis antioqsidanturiaqtivoba icvleba eqstraqtis saxeobis, flavonoidebisa da saerTofenolebis Semcvelobis zrdis kvalobaze. korelacia aqtivobasa dabiologiurad aqtiur nivTierebaTa Semcvelobas Soris, kargi markeriaginkgo bilobas samkurnalwamlo preparatis damzadebisaTvis. miRebulimonacemebi qmnis garkvul winapirobas axali saxis produqciis ginkobilobas Cais damzadebisaTvis.

3) samomavlo kvlevebisaTvis IL-10-/- da IL-10+/+ Tagvebi Sesyiduli iqna jeqsonislaboratoriidan (Bar Harbor, Maine, USA), romlebic inaxeba da mravldeba CveninstitutSi arsebul vivariumSi.

5. ujredebis (Jurkat-is) erToblivi kultivirebis gziT test-sistemis Seqmnada misi gamoyeneba sxvadasxva naerTebis gavlenis Sesaswavlad.

kvlevis mizani: cxoveluri da mcenareuli fiziologiurad aqtiurinivTierebebis, qarTuli profilaqtikuri da samkurnalo saSualebebisaqtiurobis Sfaseba.

9

amocanebi1. Jurkat ujredebis kulturaze oqsidaciuri da nitrogenuli stresiseqsperimentul modelebze sakvlevi preparatebis apoptozis intensivobazezemoqmedebis Seswavla eqsperimentis dawyebidan 24, 48, da 72 saaTis Semdeg:- oqsidaciuri stresis xarisxis Seswavla (superoqsidradikalebis (O2

-) dalipoperoqsidradikalebis (LOO.) epr signalebis intensivobis mixedviT);- Tavisufali NO-s Semcveloba da mitoqondriuli eleqtronebissatransporto cilebis nitrozilirebis xarisxi (epr meTodiT);- antioqsidanturi fermentebis, katalazas da superoqsiddismutazas aqtivoba.- ujreduli homeostazis cvlilebebis dagrovebuli monacemTa bazisissafuZvelze preparatebis moqmedebis prognozireba.

gamoyenebuli meTodebi:ujreduli kultura: adamianis leikemia transformirebuli momwifebuli Tujredebi (Jurkat ujredebi) (DSMZ-Deutshe Sammulung von Mikroorganismen undZellkulturen (Germania)). Uujredebi mravldebian biologiuri aqtiuri ares RPMI1640 (GIBSO), inaqtivirebuli embrionuli xbos Sratis (Sigma), L-glutaminis(4mM), penicilinis (100 erT/ml) da streptomicinis (100 erT/ml) Semcvelsuspenziaze 370C temperaturaze, 5% CO2 Semcvel areSi. eqsperimentebitardeboda ujredebis koncentraciaze 0,3 – 0,6 x 106 ujredi 1 ml areSi.oqsidaciuri stresis modelireba: oqsidaciuri stresis modelirebis mizniTJurkat ujredebis sainkubacio suspenziaSi emateba 30%-ni wyalbadis zeJangi(H2O2) (Sigma) sxvadasxva doziT 50 μM/l, 20 μM/l; inkubacia mimdinareobs 24saaTis ganmavlobaSi (Kim H., 2004). sakontrolo jgufs Seadgenen intaqturiJurkat ujredebi.sakvlevi preparatebi emateba ujredebis sainkubacio suspenziaSi. inkubacia

mimdinareobs 24 saaTis ganmavlobaSi.ujredebis proliferaciuli aqtivobis Sefasebis (sicocxlisunarianobis)MTT testi. ujredebis suspenzias (2x106 ujredi/ml) sakveb areSi (PRMI-1640+10%xbos embrionuli Srati (Sigma) + 1% penicilin/streptomicini)vainkubirebT (wyalbadis zeJangTan da limfocitTan erTad) 24 saaTisganmavlobaSi 370C –ze 5%-an CO2 atmosferoSi. sainkubacio periodis Semdegsuspenzias vacentrifugirebT 1500 g-ze 5 wuTis ganmavlobaSi, supernatantisgadaqcevis Semdeg ujredebs vamatebT MTT-s (3-(4,5-dimeTilTiazol-2)-2,5-difeniltetrazolium bromidi) (Sigma) xsnars (30 mkl suspenziis 100 mkl-ze)(MTT ixsneba buferSi (140 mM NaCl, 5mM HEPES, pH 7,4) doziT 2,5 mg MTT 300mkl buferze) da vainkubirebT 4 saaTis ganmavlobaSi 370C-ze 5% CO2-ispirobebSi. inkubaciis Semdeg frTxilad viRebT supernatants; naleqsvumatebT gamxsnels 100% dimeTilsulfoqsids (DMSO) 100 mkl-is odenobiT.STanTqma izomeba speqtrofotometrze talRis sigrZeze 570 nm. gamosakvlevisuspenziisaTvis vsazRvravT gazomvis saSualo maCvenebels, vaklebTkontrolis (calke niadagis) saSualo maCvenebels. vangariSobTproliferaciis koeficients formuliT:

K = Acda/Akontroli

10

antioqsidanturi fermentebis aqtivobis gansazRvra:Jurkat ujreduli eqstraqtis miReba: Jurkat ujreduli eqstraqtis miReba

xdeba ujreduli suspenzias 500g-ze dacentrifugirebiT miRebuli ujredulinaleqis homogenizaciiT. naleqs vumatebT orjer meti moculobiT lizisisbufers (1.5mM MgCl2, 10mM KCl, 1mM DTT, leupeptini, aprotinini, 10mM HEPES,pH7,9). ujredebis liziss vawarmoebT№#27 nemsSi aTjer gatarebiT. miRebulhomogenats vacetrifugirebT 20 wuTi 10000g-ze. supernatanti gamoiyenebafermentuli aqtivobis gansazRvrisaTvis

superoqsiddismutazis aqtivobis (sod) gansazRvra. sainkubacio areSeicavs 50 mM kaliumis fosfats, 50 μM nitrotetrazoliumis lurjs (NBT),150 μM NADPH da 50 μM fenazoniumis meTilsulfats (PMS) pH 7.4. reaqciaiwyeba 100μl ujreduli eqstraqtis damatebiT. dakvirveba warmoebsspeqtrofotometrulad 540nm-ze 5 wuTis ganmavlobaSi. aRdgenilinitrotetrazoliumis lurjis koncentraciis cvlileba gadaiTvleba 1 mgcilaze.

gluTationreduqtazas aqtivobis gansazRvra:sainkubacio are Seicavs 67 mM natriumis fosfats, 27 μM daJangul

gluTations, 20 μM NADPH pH 6.6. reaqcia iwyeba 50μl ujreduli eqstraqtisdamatebiT. dakvirveba warmoebs speqtrofotometrulad 340nm-ze 5 wuTisganmavlobaSi. daJanguli NADPH-is koncentraciis cvlileba gadaiTvleba 1mg cilaze.

katalazas aqtivobis gansazRvra:sainkubacio are Seicavs 50 mM kaliumis fosfats, 0.06% wyalbadis zeJangs

pH 6.6. reaqcia iwyeba 100μl ujreduli eqstraqtis damatebiT. dakvirvebawarmoebs speqtrofotometrulad 240nm-ze yovel 10 wamSi 70 wamisganmavlobaSi. daSlili H2O2-is koncentraciis cvlileba gadaiTvleba 1 mgcilaze.

cilis koncentraciis gansazRvra:cilis koncentraciis gansazRvra xdeba louris meTodiT “Sigma”-s kitis

gamoyenebiT.eleqtronuli paramagnituri rezonansi (epr)

ujreduli kulturis epr speqtrebis registracia Catardebaradiospeqtrometrze РЭ-1307, romelic operirebs zemaRal sixSireze 9.77 GHzmodulaciuri sixSiriT 50 kHz Txevadi azotis temperaturaze (-1960C).Jangbadis Tavisufali radikalebis (superoqsidradikalebis) gansazRvrismizniT viyenebT spin-xafangs 5,5 dimeTil-I-pirolin-IV-oqsidi (DMPO) (Sigma).(doziT 50 mM 0,6 x 106 ujredze 0,5 ml areSi) (Sweet M.J. et al 1996).superoqsidradikalebis epr speqtrebs vsazRravT oTaxis temperaturazemikrotalRovan simZlavreze 20 mVt.

Sedegebis analizi: cxrili N1 da diagrama N1-ze mocemulia Jurkat ujredebissicocxlisunarianobis (MTT testi) kvlevis Sedegebi wyalbadis zeJangTan(H2O2) sxvadasxva xangrZlivobis inkubaciis Semdeg.

11

cxrili #1 Jurkat ujredebis sicocxlisunarianobis (MTT testi) kvlevisSedegebi

4sT K 6 sT K 8 sT K 24 sT Kare 0,1 0,1 0,1 0,1

J 0,21 1 0,36 2,4 0,346 2,24 0,338 2,16J+H2O2 (100μl) 0,19 0,8 0,30 0,77 0,239 0,57 0,11 0,04J+H2O2 (50 μl) 0,20 0,9 0,30 0,77 0,306 0,84 0,24 0,6J+H2O2 (25 μl) 0,18 0,7 0,30 0,77 0,27 0,68 0,39 1,2J+H2O2 (10 μl) 0,18 0,7 0,29 0,73 0,26 0,65 0,37 1,13

a b

c ddiagrama 1

intaqturi Jurkat ujredebSi ujredebis inkubaciis xangrZlivobismomatebasTan erTad gamovlenilia STanTqmis intensivobis zrda, racganpirobebulia ujredebis raodenobrivi matebiT bunebrivi proliferaciisSedegd. Jurkat ujredebis wyalbadis zeJangTan (H2O2) inkubaciis pirobebSigamovlenilia STanTqmis intensiurobis STanTqmis intensivobisdozodamokidebuli (100 μl, 50 μl) Semcireba, rac ganpirobebuli unda iyoswylbadis zeJangis citotoqsiuri moqmedebiT (diagram 1 a, b). rogorccxrilSi da diagramebze (diagrama 1 (c,d)) moyvanili monacemebidangamomdinareobs, wyalbadis zeJangis dabali dozebi (25 μlm 11 μl (H2O2) avlenencitotoqsiurobas mxolod mokle drois ganmvlobaSi (8 saaTi). Semdeg ixsnebaam nivTierebis Jurkat ujredebis sicocxlisunarianobaze damaTrgunvelebeli

0

5

10

15

20

25

30

kontrol

H2O2 100

0

5

10

15

20

25

30

kontrol

H2O2 50

0

5

10

15

20

25

30

kontrol

H2O2 25

0

5

10

15

20

25

30

kontrol

H2O2 11

12

efeqti da isini iwyeben gamravlebas, rac Sesabamisad iwvevs StanTqmisintensifikacias.

wyalbadis zeJangis citotoqsiuri moqmedebis Tavisufalradikalurimeqanizmis dadasturebisa da misi moxsnis metad efeqturi antioqsidanturipreparatis moiebis mizniT, Cven SeviswavleT Jurkat ujredebis sicocxlisunarionobis cvlilebebi wyalbadis zeJangTan (H2O2) da sxvadasxvaantioqsidanturi bunebis preparatebTan (C vitamini, E vitamini, C+E vitamini,megaviti, fenovini) erTdrouli inkubaciis pirobebSi (24 saaTis ganmavlobaSi)(cxrili 2). kvlevis Sedegebidan gamomdinareobs, rom C da E vitaminebicalcalke axdenen citotoqsiur zemoqmedebaa intaqtur Jurkat ujredebze,maSin rodesac C da E vitaminebis kompleqsis, megavitisa da fenovinismoqmedeba ar xasiaTdeba citotoqsiurobiT. Jurkat ujredebis wyalbadiszeJangTan (dabali (25 μl) da saSualo dozebTan (50 μl)) da Cvens miergamoyenebul antioqsidantur preparatebTan erTdrouli 24 saaTianiinkubaciis pirobebSi yvela preparati (C vitaminis garda) gamoavlinastatikuri moqmedeba Jurkat ujredebis sicocxlis unarianobaze, rac vlindebaSTanTqmis intensivobis momatebiT. Jurkat ujredebis wyalbadis zeJangis maRaldozasTan (100 μl) 24 saaTiani inkubaciis pirobebSi antioqsidanturipreparatebis citoproteqtoruli aqtivoba sakmaod dabalia.

- cxrilSi 3 mocemulia da diagrama N2-ze mocemulia Jurkat ujredebisantioqsidanturi fermentebis aqtivobis cvlilebebi wyalbadis zeJangTan(H2O2) da antioqsianturi bunebis sxvadasxva preparatebTan 24 saaTianiinkubaciis Semdeg. cxrilSi 3 mocemuli Sedegebidan gamomdinareobs:

- antioqsidanturi fermentebis aqtivobis cvlilebebi damokidebuliaoqsidaciuri stresis intensivobaze;

- C, E vitaminebi, peparatebi fenovini da megaviti xels uwyobenantioqsidantui fermentebis (sod-is da katalazas aqtivobis stimulacias);

- Jurkat ujredebis wyalbadis zeJangis sxvadasxva dozebTan dagamosakvlev antioqsidantur preparatebTan erTdrouli 24 saaTianiinkubaciis pirobebSi icvleboda Seswavlili antioqsidanturi fermebtebisaqtivoba;

cxrili 2 Jurkat ujredebis sicocxlisunarianobis (MTT testi)kvlevisSedegebi

cdispirobebi

I K cdispirobebi

I K cdispirobebi

I K cdispirobebi

I K

are 0,152

J + H

2O2+

(25

μl)

C v 0,150 0

J + H

2O2+

(50

μl)

C v 0,152 0

J + H

2O2+

(100

μl)

C v 0,139 0

Jurkat 0,584 1 E v 0,1580

E v 0,4950,78

E v 0,1240

J+H2O2(25 μl)

0,5200,86

C+E v 0,232 0,15 C+E v 0,332 0,4 C+E v 0,107 0

J+H2O2(50 μl)

0,3420,44 Megavite

0,2140,14

Megavite 0,5520,96

Megavite 0,2060,13

J+H2O2(100 μl)

0,1250 Fenovine

0,2600,25

Fenovine 0,5390,9

Fenovine 0,1600,02

13

cxrili 3. antioqsidanturi fermentebis aqtivoba

sod katalaza GR

Jurkat 46,3±13,4 3,3±0,4 130,5±18,2Jurkat+H2O2 (20 μl) 159,1±46,3* 20,3±15,2* 172,5±34,8*

Jurkat+H2O2 (50 μl) 130,5±47,5* 12,5±3,7* 222,9±63,0*

Jurkat+H2O2 100 μl 95.7 20.1 11Jurkat+H2O2 200 μl 144.87 37.7 3.7

Jurkat+H2O2 500 μl 134.4 28.4 4.7

J+C vit 80.9 87.9 2.53J+E vit 240.4 120.2 13.9

J+C+E vit 127.4 150.4 3.2

J+Megavit 110.6 140.4 3.8

J+fenovin 102.9 66.9 1.9

J+Cvit+ H2O2 (50 μl) 11.7 341.8 10.6

J+Evit+ H2O2 (50 μl) 171.5 133.9 7.4

J+C+Evit+ H2O2 (50 μl) 208.9 104.5 5.8

J+Megvit+ H2O2 (50 μl) 211.6 104 7.6J+Fenovin+ H2O2 (50 μl) 124.3 176.1 6.5

J+Cvit+ + H2O2 (25 μl) 277.7 131.7 26.8J+Evit+ H2O2 (25 μl) 188.7 93.8 6.7

J+C+Evit+ H2O2 (25 μl) 120.2 147.6 4.8

J+Megaviti + H2O2 (25 μl) 175.7 206.3 5.5

J+Fenovini+ H2O2 (25 μl) 150 154.4 5.7

* aRniSnulia statistikurad sarwmuno cvlilebebi sakontrolo donesTan(intaqturi Jurkat ujredebi ) SedarebiT (p<0.001)** aRniSnulia samkurnalo saSualeba "limfomiozoti"-s statistikurad

sarwmuno efeqti (p<0.001)

diagrama 3

0

10

20

30

40

50

60

70

1 2 3 4 5 6

SODkatalazaGR

14

Jurkat ujredebSi antioqsidanturi fermentebis aqtivobis cvlilebebisxvadasxvaa intensivobis oqsidaciuri stresis dros (1 – kontroli, 2 -H2O2 20 μl; 3 - H2O2 4 - 50 μl; 3 - H2O2 100 μl; 5 - H2O2 200 μl; 6 - H2O2 500 μl.

- yvela Seswavlil seriebSi antioqsidanturi preparatebis zemoqmedebiTgamovlenilia wyalbadis zeJangiT inducirebuli superoqsidradikalebisSemcvelobis Semcireba (pr monacemebi, naCvenebi ar aris.daskvna:Seqmnili antioqsidanturi stresi modeli (Jurkat ujredebis kulturaze)warmoadgens Rirebul models sxvadasxva biologiurad aqtiuri naerTebisantioqsidanturi aqtivobis SefasebisaTvis.

6. “ceolituri teqnologiebis gamoyeneba virusologiaSi” - virusebissxvadasxva modelebis kultivirebis pirobebis SerCeva, kerZod rota-virusebze muSaoba;

rotavirusuli infeqcia Zalian farTod gavrcelebulia adamianebSi dacxovelebSi, gansakuTrebiT axalgazrda asakSi. mimdinareobs Zlieri kuWisaSlilobiT, pirRebinebiT, maRali sicxianobiT da Zlieri dehidrataciiT. Tudroulad ar iqna miRebuli swori samkurnalo RonisZiebebi – daavadebaSeiZleba damTavrdes letalurad. gansakuTrebiT maRalia sikvdilianobawiwilebSi, goWebSi da a.S. dReisaTvis ukve arsebobs rotavirusuli vaqcinacxovelebisa da frinvelebisTvis, magram adamianis vaqcina ararissrulyofili.mizani: axali rotavirusuli vaqcinis miReba ceolituri teqnologiisgamoyenebiT da misi danergva klinikur praqtikaSimeTodebi: 1. rotavirusis gamoyofa avadmyofi bavSvis ganavlidan xdebodalaboratoriulad dagenili diagnozis dasmis Semdeg, laboratoria‘testis’ bazaze. virusis suspenziiT saTanado damuSavebis Semdeg(kulturaluri siTxeSi centrifugireba, antibiotikebis damatebiT).vasnebovnebdiT gadasaTes ujredul kultura (Roris embrionis Tirkmlisujredebi), romelSic adamianis rotavirusi kargad mravldeba. ujredulikultura miviReT sazogado jandacvis centris ujreduli kulturebislaboratoriidan) virusis dagrovebisTvis saWiro gaxda ujredebze virusisxuTi pasaJis gakeTeba.2. Semdegi etapi gaxldaT virusis koncentrirebuli suspenziis miReba, racmoxerxda ultracentrifugirebiT. virusi davleqeT, Semdeg resuspendirebagakeTda fosfaturi buferis normalur xsnarSi, romlis moculobadaaxlovebiT 100 naklebi iyo sawyis moculobaze, amrigad moxda virusisgawmenda, paramet-koncentraciac.3. Semdeg etapze moxda bunebrivi ceolitebis damuSaveba (dafqva, gawmenda,gamoSroba, gasterileba).momavali wlisTvis dagegmilia Semdgomi damagvirgvinebeli etapebisCatarebas: 1. miRebuli virusuli suspenziis ceolitebiT damuSavebas; 2.miRebuli vaqcinis Semowmebas jer cxovelebSi, Semdgom klinikaSi.

15

7. qacvidan miRebuli eqstraqtiT gamdidrebuli ceoliTebis efeqti asakTanasocirebuli imunuri pasuxis disregulaciaze

mizani: kvlevis mTavar mizans asakTan asocirebuli imunuri pasuxisdisregulaciasa da daavadebebis ganviTarebaSi qacvidan miRebulieqstraqtiT gamdidrebuli ceoliTebis gavlenis Seswavla warmoadgenda.

kvlevis dasawyisSi Sedgenili kiTxvaris saSualebiT Segrovebuli iqnainformacia 50 individze, romlis safuZvelzec Seiqmna kompiuterizebulibaza. kvleva akmayofilebs helsinkis eTikuri komisiis pirobebs daTiToeuli individis monawileoba nebayoflobiTia, rasac is adasturebskiTxvarze xelis moweriT.

bazis damuSavebis Sedegad moxda 40 xandazmuli janmrTeli pirebisSerCeva Semdgomi kvlevisTvis, romelsac daeniSna qacviT gamdidrebuliceoliTuri dieta (ZSBE) 1 Tvis ganmavlobaSi. dietis dawyebamde dadamTavrebisTanave sakvlev individebSi Seswavlili iqna imunologiurimaCveneblebi (Tregs, CD4, CD3, CD8), aRebuli plazma ki Senaxuli iqna SemdgomigamokvlevisTvis.

martivi aRwerilobiTi statistikuri analizis Sedegad gamovlinda,rom gamokvleul asakovan individebSi CD3CD4 da CD3CD8 ujredebisprocentuli raodenoba meryeobs 36.528+14.853 da 21.776+9.412 farglebSi, racSeesabameba evropul populaciaSi miRebul maCveneblebs. CD4CD25 daCD4Foxp3 ujredebis maCveneblebia 16.233+9.319 da 5.445+6.179 Sesabamisad.

ujredul analizTan erTad Sefasda mocirkulire pro- daantianTebiTi citokinebis done imave individebSi. unda aRiniSnos, rompirvelad iqna gamokvleuli il-17-is done qarTul asakovan individebSi damisi raodenoba meryeobs 1.885+1.891pg/ml-mde.

imisaTvis, rom gagverkvia, moqmedebs Tu ara kvebiTi danamatebi, kerZodqacvis eqstraqtiT gamdidrebuli ceoliTebis miReba imunologiurimaxasiTeblebze Sedarebuli iqna yvela Seswavlili niSnis saSualomaCvenebeli dietis daniSvnamde da mis Semdeg (cxrili #1).

cxrili. @#1 aRwerilobiTi statistika (saSualo+standartuligadaxra; minimumi da maqsimumi) Seswavlili citokinebis raodenobrivianalizi 2 jgufSi (1 – qacviT gamdidrebuli ceoliTuri dietis daniSvnamde;2 - qacviT gamdidrebuli ceoliTis miRebis Semdeg)

saSualo+stand. gadaxra;minimumi da maqsimumi

1 2

IL-6 11.931+6.018(4.313-26.238)

8.008+14.023(3.552-77.340)

IL-17 53.398+127.276(11.938-606.528)

32.139+33.034(2.080-140.642)

IL-10 3.367+1.808(1.762-10.247)

4.462+6.017(1.331-33.887)

TNF-alfa 6.738+3.412(2.537-12.567)

4.226+0.930(3.299-7.791)

INF-gamma 10.084+4.087(6.670-25.056)

8.108+10.885(0.244-42.34)

IL-4 3.162+1.322(1.578-5.674)

2.772+1.988(1.907-12.401)

16

winaswari statistikuri analizis Sedegad gamovlinda, romimunokompetenturi ujredebis raodenoba ar icvleba qacviT gamdidrebuliceoliTis miRebbisas, Tumca aRiniSneba pro- da anti-anTebiTi citokinebiskoncentraciebis cvlilebebi. kerZod kvebiTi danamatis miReba iwvevs il-6,il-4, TNF-alfa da INF-gamma donis statistikurad sarwmuno daqveiTebas, racasakovnebSi susti anTebiTi fonis inhibirebas iwvevs (cxrili 2).

cxrili. #2 Seswavlili cvladebis saSualo maCveneblebis Sedareba 2jgufs (1 - qacviT gamdidrebuli ceoliTuri dietis daniSvnamde; 2 - qacviTgamdidrebuli ceoliTis miRebis Semdeg) Soris (p<0.05 - gansxvavebasarwmuno, NS – gansxvaveba ar aris sarwmuno)

amdenad, miRebuli Sedegebis analizis Sedegad SegviZlia davaskvnaT, romxandazmul individebSi qacviT gamdidrebuli ceoliTuri dieta moqmedebspro da anti-anTebiTi citokinebis raodenobaze da iZleva saSualebas, romkvebiTi danamati rekomendebuli iyos asakovani populaciaSi susti anTebiTifonis mainhibirebel saSualebad.

2010 wels dagegmilia mocvidan miRebuli eqstarqtiT gamdidrebuliceoliTuri dietis gavlenis Seswaval, miRebuli Sedegebis SedarebiTi dasaboloo analizi, kerZod anTropometriul faqtorebisa da kvebiTidanamatebis rolis gavlena imunologiur maCveneblebze

2. gamoqveynebuli samecniero naSromebi:

1. Kvaratskhelia E, Maisuradze E, Dabrundashvili NG, Natsvlishvili N, Zhuravliova E, MikeladzeDG. N-methyl-D-aspartate and sigma-ligands change the production of interleukins 8 and 10 inlymphocytes through modulation of the NMDA glutamate receptor. Neuroimmunomodulation.2009;16(3):201-7.

2. Simonia G., Andronikashvili I. Nozadze P. Normotensive salt sensitivity in the elderely: possiblerole of endothelin-1 and sodium-potassium pump. Eur.Heart.J. 2009, Vol.30, P. 84.

3. Topuria T., Badriashvili N., Ttoputidze M., Chkheidze S. Hepatic damage and cholepathia inpatients with cystic fibrosis and the use of ursobil in complex treatment. J. Experimental andClinical Medicine, 2009, 9, pp.11-15

4. Pantsulaia I, Trofimova S, Kobyliansky E, Livshits G. Relationship between obesity,adipocytokines, and blood pressure: Possible common genetic and environmental factors. Am JHum Biol. 2009 Jan-Feb; 21(1):84-90.

1 2 pIL-6 2.347+0.548 1.622+0.306 0.000

IL-17 3.308+0.832 2.933+0.964 0.166IL-10 1.117+0.425 1.083+0.521 0.806

TNF-alfa 1.752+0.601 1.423+0.185 0.007INF-gamma 2.254+0.320 1.110+1.503 0.001

IL-4 1.070+0.412 0.825+0.184 0.008CD3CD8 26.573+8.072 25.236+9.697 0.681CD3CD4 37.004+9.566 38.653+8.361 0.633

CD4CD25 8.855+9.061 7.648+4.536 0.616C4Foxp3 12.862+14.072 19.692+19.011 0.188

17

5. Ryschich E, Khamidjanov A, Kerkadze V, Büchler MW, Zöller M, Schmidt J. Promotion oftumor cell migration by extracellular matrix proteins in human pancreatic cancer. Pancreas. 2009Oct;38(7):804-10.

6. Abiatari I, Kiladze M, Kerkadze V, Friess H, Kleeff J. Expression of ypel1 in pancreatic cancercell lines and tissues. Georgian Med News. 2009 Oct;(175):60-3.

7. Demetrashvili Z, Kerkadze V, Pipia I, Topchishvili G. [Comparative evaluate of methods ofplacement of polypropylene meshes in alloplastic of incisional hernias.]. Georgian Med News.2009 Oct;(175):7-9.

8. Abiatari I, DeOliveira T, Kerkadze V, Schwager C, Esposito I, Giese NA, Huber P, Bergman F,Abdollahi A, Friess H, Kleeff J. Consensus transcriptome signature of perineural invasion inpancreatic carcinoma. Mol Cancer Ther. 2009 Jun;8(6):1494-504.

9. D. Labartkava. Phagotherapy for patients with infection-induced asthma. J. Experimental andClinical Medicine, 2009, 8, pp. 99-101.

10. suxiaSvili d., eliaZe b., xeCinaSvili s., korsantia b., - cxvirisa dadanamati wiaRebis polopozis endoskopiuri mikroqirurgiuli Carevisa daadgilobrivi steroiduli Terapiis imunologiuri aspeqtebi//eqsperimentuli, klinikuri medicina, 2009, #1(45), 14-19.

11. malaciZe v., b.korsantia, s.kupraZe, l.ZoweniZe, j.mkervaliSvili – pirve-lad ujredul kulturebze bunebrivi ceolitebis (klinoptilolitis)zemoqmedebis Seswavla// iqve, 2009, #2(46), 29-32.

12. Воробьева Е.О., Эмухвари М.Г., Шарашидзе Н.А., Купреишвили С.Б. – Корреляциянекоторых биохимических параметров при атеросклерозе сонных артерий// GeorgianMedical News, 2009, №11, 56-61.

13. Akhvlediani M., Vorobiova E., Balavadze M., Vakhtangadze T., Gachechiladze D. – Theinfluence of one-year treatment with Atorvastatin and Rosuvastatin on intima media thicknessand some biochemical markers// Abstracts of XV Symposium on Atherosclerosis. Boston, USA,2009, p.632.

14. Vorobiova E., Pargalava N., Bockuchava M., Akhvlediani M. – Use of low- molecular Heparinsin pregnance// Abstracts of XXII Conference of International Society of Thrombosis andHaemostasis. Boston, USA, 2009, p.233.

15. axvlediani m., vorobiova e., emuxvari m., gaCeCilaZe d., laiTaZe n. – Tavistvinis discirkulaciebis diagnostika da prognozireba uax-lesilaboratoriuli teqnologiebis gamoyenebiT// rent. da radiologiismacne, 2009, #3-4, 60-65.

16. esaiaSvili m., CxikviSvili i., axvlediani m., SaraSeniZe g. – qlorogenismJavas efeqtebi eqsperimentuli Saqriani diabetis modelze// eqsperiment.klinikuri medicina, 2009, #10 (55), 80-84.

17. Andronikashvili T., Pagava K., Kurashvili T., Eprikashvili L. – Possibility of Application ofNatural Zeolites for Medicinal Purposes// Bulletin of Georgian Academy of Sciences, 2009 (Newseries), v3, #2, 158-167.

18. Pagava K., Samugia I. – Psychological pecularities of children with bronchial asthma// Abstractsof the EAACI Pediatric Allergy and Asthma Meeting. 12-14 November 2009, Venice, Italy / in:Pediatric Allergy and Immunology. – 2009 – Volume 20, Supplement 20, December. – P. 25

19. Oberkanins C., Rauscher B., Korinteli I., M. Korinteli, G. Kriegshäuser, K.Pagava – Thespectrum and frequency of MEFV mutations in newborns from Tbilisi, Georgia// //The Americansociety of Human Genetics, 2009.

20. Pagava K. et al. – Orally taken phages in the urine and feces of pediatric patients// 27th AnnualMeeting of the European Society for Paediatric Infectious Diseases. Brussels, Belgium. June 9-13, 2009. Abstracts – ESPID2009/DVD.

21. Pagava K., Korinteli I., Metskhvarishvili G. – On the Usage of Bacteriophage Therapy in theManagement of Rare Diseases and Rare Forms of Common Diseases in Children and Adolescents//4th Eastern European Conference for Rare Diseases and Orphan Drugs, Plovdiv, 2009, p34.

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22. Pagava K., Korinteli I., Pagava H., Kiseliova T. – Rare diseases management optimization inchildren and adolescents in Georgia (plan of actions)// Ibid, p38.

23. Kiseliova T., Pagava H., Pagava K. – Modelling uncertainty in the connection between socio-economic factors and health & health-related behavior of adolescents in Georgia// FuzzyInformation Processing Society, 2009. NAFIPS 2009. Annual Meeting of the North AmericanPublication Date: 14-17 June 2009

24. faRava y. – Nutrilon Immunofortis - imunitetis gaZliereba bunebrivi gziT//samecniero-praqtikuli konferencia “bavSvTa da mozardTa medicina - II”.Tbilisi, 2009 wlis 16-18 oqtomberi. masalebi. - Tbilisi, 2009, gv. 46-55.

25. korinTeli i., mecxvariSvili g., RonRaZe T., faRava y. – baqterio-fagoTerapiis samecniero safuZvlebi bavSvebsa da mozardebSi// iqve, gv.178-181.

26. faRava y. – antibiotikoTerapia pediatriaSi// iqve, gv. 182-183.27. Pagava K., Korinteli I., Metskhvarishvili G. – On the Usage of Bacteriophage Therapy in the

Management of Rare Diseases and Rare Forms of Common Diseases in Children and Adolescents[reprinti] // iqve, gv. 184-186.

28. Pagava K, Dzuliashvili M. et al. – Some Aspects of the Pharmacokinetics of TherapeuticBacteriophage: Distribution and Elimination of Commercial Eliava pyophage and NeutralizingAntibody Response in Infants and Children [reprinti]// iqve, gv. 185-186.

29. Pagava K, Korinteli I, Pagava I, Kiseliova T. – Rare Diseases Management Optimization in Childrenand Adolescents (Plan of Actions) [reprinti]// iqve, gv. 187-190.

30. Oberkanins C., Rauscher B., Korinteli I., Korinteli M., Kriegshäuser G., Pagava K. – Thespectrum and frequency of MEFV mutations in newborns from Tbilisi, Georgia [reprinti]// iqve,gv. 191.

31. Beridze M, Gogokhia N, Buadze G, Khundadze I, Sanikidze T. Headaches and cerebral bloodflow disturbances in patients with chronic nasal pathology. Georgian Med News. 2009Sep;(174):32-6.

32. Nemsadze K, Sanikidze T, Ratiani L, Gabunia L, Sharashenidze T. Mechanisms of lead-inducedpoisoning. Georgian Med News. 2009 Jul-Aug;(172-173):92-6.

33. Nakashidze IM, Chikovani TI, Tsitsadze NG, Datunashvili IV, Sanikidze TV. [Influence ofantioxidants under polytrauma during traumatic sickness]. Georgian Med News. 2009Jun;(171):72-5.

34. Nakashidze IM, Chikovani TI, Sanikidze TV, Tsintsadze NG. [The condition of oxidation-antioxidation balance of kidney and suprarenal tissue in experimental traumatic shock with whiterats and the influence of Plaferon LB]. Georgian Med News. 2009 Jun;(171):68-72.

35. Ratiani L, Sanikidze T, Sulakvelidze M, Bejitashvili N, Meladze K. Jurkat cell as an appropriatemodel for drug investigation. Georgian Med News. 2009 Mar;(168):117-20.

36. Enukidze MG, Machavariani MG, Intskirveli NA, Bezhitashvili ND, Sanikidze TV. [Cell death inJurkat cells induced by oxygen/nitrogen stress], Georgian Med News. 2009 Feb;(167):109-13.

37. mWedliSvili T., sanikiZe T. da sxv. “samkurnalo saSualeba “solanisantialkoholuri aqtivobis kvleva” saqarTvelos mecn. Akademiis macne,biol. Seria. N 5-6, t. 35, gv. 365-370.

38. Rodov V., Vinokur Y., N. Gogia,I.Chkhikvishvili. Antioxidant Activity of Traditional GeorgianSpices, International Society for Nutraceuticals and Functional Foods ISNFF 2009,SanFrancisco,CA

39. bukia z., gogia n., CxikviSvili i., ginkgo bilobasa (Gingko biloba) da mwvaneCais (Thea Sinensis L.) fenoluri naerTebi da antioqsidanturi aqtivobaeqsperimentaluri da klinikuri medicina, 2009, 7, 9-13.

40. esaiaSvili m., CxikviSvili i., axvlediani m., SaraSeniZe g.. qlorogenismJavas moqmedebis efeqtebi eqsperimentuli Saqriani diabetismodelze.eqsperimentaluri da klinikuri medicina, 2009, #10, 83

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41. Gongadze M., Chkhikvishvili I., Gogia N., Aslamazishvili T., Meladze T., Mesropyan I. RedWine Extract as teratogenic protector. Experimental & Clinical Medicine. #10 (55) 2009; 19-22

42. fanculaia i., sefaSvili a., Ciqovani T. maregulirebeli T ujredebisroli alergiuli daavadebebis paTogenezSi. saqarTvelos respiraciuliJurnali, 2009 t5, #1, 48-52.

43. fanculaia n., qiqoZe n., iobaZe m., rexviaSvili x., jaxutaSvili n.,lasareiSvili b., fanculaia i., Ciqovani T. maregulirebeli T-ujredebisasakTan asocirebuli cvlilebebi janmrTel populaciaSi. eqsperimentulida klinikuri medicina, 2009, 3(47):78-81

44. Pantsulaia N, Kikodze N, Iobadze M, Sepashvili A, Pantsulaia I, Chikovani T. A Plasma Pro- andanti-inflammatory cytokine profiles in apparently healthy aged Georgian population. JExperimental and Clinical Medicine, 2009, 7:(52)13-17

45. I.Pantsulaia, A.Sepashvili, M.Iobadze, I.Chkhikvishvili, N.Kikodze, T.Chikovani The Effect ofCitrus Extract on the Immune-mediared Liver Injury: Involvement of Regulatory T Cells. Intern.J. Immunoreh., 2009, V.11 No 2. p.202

46. I.Pantsulaia, N.Kikodze, M.Iobadze, N.Pantsulaia, Kh.Rekhviashvili, B.Lasareishvili,N.Jakhutashvili, T.Chikovani Aging and Immunoregulatory T Cells in Georgian PopulationIntern. J. Immunoreh., 2009, V.11 No 2. p.203

47. fanculaia n., qiqoZe n., iobaZe m., rexviaSvili x., jaxutaSvili n.,lasareiSvili b., fanculaia i., Ciqovani T. maregulirebeli T-ujredebisasakTan asocirebuli cvlilebebi janmrTel populaciaSi. eqsperimentulida klinikuri medicina, 2009, 3(47):78-81.

48. Simonia G et al. Salt-sensitivity in Normotensive Elderly. Georgian Medical News, 2009, No4(169), pp. 36-39.

3. gamosaqveyneblad gamzadebuli da gamosaqveyneblad gadacemuli samecnieronaSromebi:

Pantsulaia I. Kalichman L., Malkin I., Kobyliansky E. Relationship between Osteoarthritis andRANKL, OPG and Inflammatory Markers. Osteoarhtiris Cartilage (Submitted).

Dabrundashvili N.G. , Kvaratskhelia E.B, Gagua M., Maisuradze E., Chkhikvishvili I ,Zhuravliova E., Mikeladze D. Nobiletin transiently increases the production of nitric oxideand changes the activity of succinate dehydrogenase in human blood lymphocytes. Journalof Food Biochemistry (in press)

Ratiani L., Ratiani T., Sharashenidze G., Janigashvili G., Sanikidze T. Study of potentialantiatherogenic activity of different antioxidants. GMN

4. saavtoro mowmobebze da patentebze miRebuli dadebiTi saeqspertogadawyvetilebebis raodenoba - 0

5. saavtoro mowmobebze da patentebze saeqspertod gamzadebulidokumentaciis paketebis raodenoba - 0

6. samecniero RonisZiebebSi (konferenciebi, simpoziumebi, seminarebi da sxva)monawileoba

1. 13-16, seqtemberi, 2009. berlini, germania, II evropuli kongresiimunologiaSi, citrusis kanis eqstraqtis gavlena RviZlis imunuridazianebis dros: maregulirebeli T ujredebis roli. (N: A-136-0028-00438)(abstraqti, stenduri moxseneba).

2. 2009, 3-7 ivnisi, milani, italia; I saerTaSoriso simpoziumi “axaliproduqtebisa da bioprocesebis kvleva da ganviTareba”. “axali sakvebi

20

danamati mcenareuli eqstraqtebiT gamdidrebuli qarTuli ceoliTebi”momxsenebeli;

3. 28-29 aprili, 2009, praRa, CexeTi, evrokavSiris prezidentis egidiTgamarTuli saerTaSoriso konferencia: “mecnierebi evropaSi sazRvrebsgareT”

4. 25-27 ivnisi, 2009 weli, Tbilisi, saqarTvelo, seminari “ideidan bazramde”inteleqtualuri sakuTrebis dacva”.

5. saerTaSoriso konferencia @”klinikuri da eqsperimentuli medicina”,bakuriani, 2009, 23 Tebervali – 3 marti (saorg. komiteti).

6. saerTaSoriso konferencia @”klinikuri da eqsperimentuli medicina”,qobuleTi, 2009, 18-25 ivlisi (saorg. komiteti).

7. XV simpoziumi aTerosklerozze. bostoni, aSS, 2009.8. XXII Conference of International Society of Thrombosis and Haemostasis. Boston, USA, 2009.9. 27th Annual Meeting of the European Society for Paediatric Infectious Diseases. Brussels,

Belgium. June 9-13, 2009.10. samecniero-praqtikuli konferencia “bavSvTa da mozardTa medicina - II”.

Tbilisi, 2009 wlis 16-18 oqtomberi (organizatori).11. I saerTaSoriso onferencia “janmrTeli qali” Tbilisi 2009, 8-19 ivnisi 2.

saerTaSoriso konferencia “medicina da ekologia” seqtemberi, 2009(siRnaRi)

12. 4th Eastern European Conference for Rare Diseases and Orphan Drugs, Plovdiv, 2009.13. EAACI Pediatric Allergy and Asthma Meeting. 12-14 November 2009, Venice, Italy.14. saerTaSoriso konferencia nutriceftikuli da funqcionaluri sakvebi,

2009 (31 oqtomberi-noemberi 4), san-francisko, kalifornia, aSS,nutircevtikTa da funqcionaluri kvebis saerTaSoriso gaerTianeba

15. fenoluri naerTebis saerTaSoriso konferencia, moskovi, 2009

7. samecniero RonisZiebebze warsadgenad gamzadebuli moxsenebebi raodenoba – 6

1. sanikiZe T. - oqsidaciuri procesebis roli qalis fiziologiuri dapaTofiziologiuri procesebis dros2. sanikiZe T., - plaferon lb-s radioproteqtoruli aqtivoba virTagvebis

sakvercxeebis morfo-funqciur Tvisebebze erTjeradi intensiuriradiaciuli dasxivebis zemoqmedebis dros.3. sanikiZe T., sxv. - oqsidaciuri stresis roli aTerosklerozis

paTogenezSi4. sanikiZe T., sxv. - citrusebis eqstraqti – metaboluri sindromis

koreqciis efeqturi saSualeba5. Enukidze M., Mchedlishvili T., Machavariani M., Mikeladze D., Sanikidze T. - Role of sigma

() receptors in the pathogenesis of preeclampsia6. Pantsulaia et al. - Pro- and anti-inflammatory cytokines profile in patients with different stages

of type I diabetes mellitus – FOCIS, USA, 2010

8. saerTaSoriso da adgilobriv sagranto konkursebisaTvis gadacemuliproeqtebi:

1. Analysis of chloride ion-channel associated macromolecular complexes in genetic disorders –STCU (5048)

2. “Sromis mZime da mavne pirobebSi sicocxlis xarisxis gaumjobesebisimunologiuri aspeqtebi” sesf

3. mutanturi qloris arxis makromolekuluri kompleqsis cvlilebebikisturi fibrozis dros – sesf

21

4. xalxuri medicinis saSualebis “mt”-s prevenciuli efeqturobis Seswavlaniukaslis (frinvelis Wiris) daavadebis dros” (USTC)

5. The mechanisms of development of neurodegenerative processes induced by brain ishemia andchronic stress and thear molecular modulation pathways (USTC)

6. sigma aqtiuri naerTebis farmakologiuri potenciali fsoriazismkurnalobaSi (sesf)

7. Th17/Treg balansisa da citokinebis roli aTerosklerozis paTogenezSi(sesf)

8. potenciuri biomarkerebisa da imunologiuri maCveneblebis rolisakvercxeebis kibos gamovlenaSi (sesf)

9. Na,K-ATPazas endogenuri inhibitorebis rolis SeswavlamarilmgrZnobiarobis ganviTarebasa da arteriuli hipertenziisCamoyalibebaSi (sesf)

9. mopovebuli grantebi (saerTaSoriso, erovnuli da sxv) - 2

1. Possible Interaction of Endogenous Sodium Pump Inhibitors and Genetic Factors in theDevelopment of Salt-sensitive Hypertension (Joint research projects - SCOPES - Swiss nationalscience foundation – 2010-2012).

2. BD Facsarray- Bionalyzer – aparaturis granti 2009 – (ssef)

10. damatebiTi sakiTxebi, romelsac miiCnevT yuradsaRebad.

institutis TanamSromlebis mier sxvadasxva universitetebTan erTadmomzadebulia 2 sadoqtoro programa.

Tbilisis saxelmwifo universitetTan gaformebuli memorandumisa daaparaturis grantis farglebSi 2010wlisTvis institutSi daidgmeba sruliadTanamedrove 2-lazeriani gamdinare citofluorometri.

2009 wels institutis axalgazrda TanamSromeli, biol. mecn. doqtorii.fanculaia aris prezidentis I xarisxis saxelobiTi stipendiis mflobeli.