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The role of nicotine in IBD: The severity of experimental colitis in mice is dependent on the presence of the α5 neuronal nicotinic acetylcholine receptor subunit (nAChR)
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105 Ths ttak for Dymplwla and Neoplasia In the Awl Pouch - A contrcverelal lame. LeuHuW)n sAmmmwAunlvm McvrrAL hmtnutefef3u~lsdMce Qctebcr(lenEwc Abrtnct: With the lntmducUon of the idealpouch -the Kook pouch and subsequently the fAvlc pouoh . a new syndrome has appeared Pa~+~neius(pouohltis hatsprovedtobeafrequemtkmgte~ compllcatbll.Iti8well i nowrlmatchroIlkmuccsalinflammabo n maydevMplnto~~Seanboth inlfmg~ul~raterrrthre ~%~h~\MththeAof~tlochI pcu&eIsandepllhenaildysplasla with aneuploldlhavfJalsobeen seen. There are eneodotal reporls on adenooaroinoma developing inthewpatienk Methcdr:halongduraUon shoukibeanimpdantfactcfme incidenoe d dyapksia and the muoosal adap&bm m-l=studled in uberaSve cc4itlspdenta who had had their continent ileostoml~for25-3Oyears.45ofthesepatlmt~wem surveyedby flexible videoendcscopy wtth multiple biopsies. Results: VIM,foot@ shorler and broader than normal but often with nomU height. All biopska showed mild or moderate lntlarnmatfan with atrophy and submucosal tlbmsis. The paahorooiststaaedeplth~~alypia~obepresentinlOoltha45 pathlts (22%). Ttue dysplasia was present in only two patients howeverwhiletheatypiawas~thareacWetypeintheother m. Ocndu6lon: The fear for a dyepkiagmcancer -l-of ~tooccurinpstientswitnanilealparchseemstobeIOw. t4ewbbs the flndln~~ underlIne me *kqxxtance of endosoopic follow-upoffheuefmtkntapwUouMythoaewlthapefvicpouch wtweoafoinomamaywelldevelopnotlntheNealrnucosabut from the remnants of pfecanoerow redal muowe left in the muscular rectal alff.
106
Distinctive patterns of inflammatory rcapoosc in microscopic colitis compared with resolving CampyIobacier enteritis D Jenkins, JP Tbomley, ME McAlindon, RC Spiller. University Hospital, Nottingham. UK. Microscopic colitis can have an acute onset suggesting a possible infectious origin. We have recently described persistent lymphocytosis aod increased enteroendocrine cell (EC) numbers in patients following Campylobacter enteritis (CE) and now report a comparison with a group of patients with lymphocytic colitis (LC). Methods: 12 controls undergoing sigmoidoscopy for rectal bleeding or screening for a family cancer history were compared with 11 cases of LC and 19 cases of resolving CE fium our previous study (biopsies at 2 and 12 weeks post infection). Cells were counted on immonocytochemically stained sections from rectal biopsies using antibodies as follows: synaptophysin, serotonin, Peptide YY for ECs, CD8 for i&a-epithelial lymphocytes (IEL, both counted per 100 epithelial cells), mast cell pyptase for mast cells (MC), CD68 for macrophages & CD3 for lamina propria T lymphocytes all expressed as cells
a = P
1070 SEQUENCES AMELIORATE IMMUNOSTIMULA TORY DNA EXPERIMENTALCOLITISINMICEANDRATS. D.F.Kamdi,E.RaqTelAvivMedicalCber,Ismel sod untv. of chl&rnia San Diego, U.S.A. Immuncsdmubtoty DNA scq(ISS) acttvate tImzip illmdty, hducedmoftypc1cytoLinesIukipromote~ldrfferentiatin. ImbaknccofThlm~ytcsisinw~intbepnthogeoesisof clIpmwdcoltttsaIIdTtl2typcrcrponscsafehrvolvatinwlitis. We tested whetkr ISS oligonmleotides (ISS-ODN) ameliorate .rxphcd wlttis. ISS, (Klug/animal) or 0.2 ml dim wae i&cted S.C. to Balw mice 2 lYms bclkrc 2.5% dexlml sdtum surphate(INS) wasad&dtotbcfrdrbkingwater.DiseaseacdvityblbxwasbyscorinSclmngwillbodywt.aIldtheprmcnceofgrossbleedingiuthe std.Onday7,miwwucsac&ed,t&cobnresectedandweighsd. fMitiswa¶aLsobduwdbyintrarcotalrz **- “llof0.1 nll3% lodoacctendde (1A) in 1% mcthybelkbst to rats treated S.C. 2 days befcdld with ISS, (l~animai) 01 0.2 ml saliw. Rats wue .ucd&d3daysattcrI&tkcobnisobtal,lesbnaroamcamnedand muwsdMPofs&itywas-.1sssignificantly-thc sverity of DSS induced colitis T-II 25-32 Dss DGs+ISS 7 ‘-sIgnlrianuy-6un~~o.os)
Dlmosui~ &a-N 5.3f0.4 0.9io.4*
Bodyvt wchnee) -15.3f1.7. -x&0.4*
MPO WEI 4.1fD.3 l.W.4.
ISSalsosi@adlydearaedthesevssityofL4inducedcotitis:Ttlc lesion~inIA+ISSwas6~5-mm2asoompsrcdto57(H74~in ratstnetedwahIAonly.MpoclctivityinIA~rats-6.(H1.8u/Swas six folds high thmt ill IA+1SS -1.lM.l u/g (Two.05). ’ **. “n of ODN cibtively adioraa ma&mux
of rentidon in IBD.
108 THE ROLE OF NICOTINE IN IBD: THB SEVERITY OF EXPERIMENTAL COLITIS IN MICE IS DEPENDENT ON THB PRESENCE OF THE a5 NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR SUBUNIT (nAChR).D. Rachmilewitz, F. Karmeli, M. Kedmi, A. Orr-Um. Genetic Institute and Division ofkkdicinc, Tel Aviv Soumsky Medical Ceotcr, Tel Aviv, Israel. Cigar&e smokiig has diverse eikts on IBD - it is bcnctieial in ulcerative colitis and delctaious in Crdm’s disease. The ingrcdiant and mechanism involved in the relationship khvceo smoking and IBD rcmains to be detincd. In order to stody the possible bwolvcment of the nicdinic recepws in the pathogencais of IL3D we compared the scwIty of experimental colitis in mia dckimt for the a5 ncomnal nAChR subonit to wild type umtml mice. Colitiswasinducedin a5 dclicimt and amtrol miceby the sdditionof 2.5% dextran sodium sulphate (DSS) to the drinking water. Control groups received tap water. Disease aclivily index was determinedby scoring changes in body might and the prcscna of gross bleeding in the stool. On day 7 mice were sacrificed, the colon WBS resected,weighed, seckns were obtained for histology and mumsal MFQ activity and PGEI generation wrc dctcrmined. DSS indoad c&is in the a5 detieient mice (a5 4 ) was sigoificaotly more severe as cxpmsed hy the prnxntage change in body might, and by disease activity and histological szorenthat wre about 1.5 fold higher than in the cootml group (P-zO.05). Mumsal MPO activity and PC& generation wue also significantly higha in DSS treated a.5 4 mice as compared to the reqactive levels in DSS trcatcd control mice. Treatment NONE DSS INDUCED COLITIS Mica (nmnber) Control (5) a5 -I- (8) Control (13) a5 -/-(IS) DiseaseA&i-&y 4.2i0.8 6.3f0.7. Histological score 6.6iO.7 8.9iC.6* Change In Ekdy Wt. (%) -14.lf2.0 -20.7i2.2* 0.2io.05 033.1 MFo Wk?) l.I+xl.2 2.6f0.6. 206f29 173*16 229f24 313f33’ XEs (w40 l - SitifkxntlydiBercot tkwn cootml (p
A31
105 Ths ttak for Dymplwla and Neoplasia In the Awl Pouch - A contrcverelal lame. LeuHuW)n sAmmmwAunlvm McvrrAL hmtnutefef3u~lsdMce Qctebcr(lenEwc Abrtnct: With the lntmducUon of the idealpouch -the Kook pouch and subsequently the fAvlc pouoh . a new syndrome has appeared Pa~+~neius(pouohltis hatsprovedtobeafrequemtkmgte~ compllcatbll.Iti8well i nowrlmatchroIlkmuccsalinflammabo n maydevMplnto~~Seanboth inlfmg~ul~raterrrthre ~%~h~\MththeAof~tlochI pcu&eIsandepllhenaildysplasla with aneuploldlhavfJalsobeen seen. There are eneodotal reporls on adenooaroinoma developing inthewpatienk Methcdr:halongduraUon shoukibeanimpdantfactcfme incidenoe d dyapksia and the muoosal adap&bm m-l=studled in uberaSve cc4itlspdenta who had had their continent ileostoml~for25-3Oyears.45ofthesepatlmt~wem surveyedby flexible videoendcscopy wtth multiple biopsies. Results: VIM,foot@ shorler and broader than normal but often with nomU height. All biopska showed mild or moderate lntlarnmatfan with atrophy and submucosal tlbmsis. The paahorooiststaaedeplth~~alypia~obepresentinlOoltha45 pathlts (22%). Ttue dysplasia was present in only two patients howeverwhiletheatypiawas~thareacWetypeintheother m. Ocndu6lon: The fear for a dyepkiagmcancer -l-of ~tooccurinpstientswitnanilealparchseemstobeIOw. t4ewbbs the flndln~~ underlIne me *kqxxtance of endosoopic follow-upoffheuefmtkntapwUouMythoaewlthapefvicpouch wtweoafoinomamaywelldevelopnotlntheNealrnucosabut from the remnants of pfecanoerow redal muowe left in the muscular rectal alff.
106
Distinctive patterns of inflammatory rcapoosc in microscopic colitis compared with resolving CampyIobacier enteritis D Jenkins, JP Tbomley, ME McAlindon, RC Spiller. University Hospital, Nottingham. UK. Microscopic colitis can have an acute onset suggesting a possible infectious origin. We have recently described persistent lymphocytosis aod increased enteroendocrine cell (EC) numbers in patients following Campylobacter enteritis (CE) and now report a comparison with a group of patients with lymphocytic colitis (LC). Methods: 12 controls undergoing sigmoidoscopy for rectal bleeding or screening for a family cancer history were compared with 11 cases of LC and 19 cases of resolving CE fium our previous study (biopsies at 2 and 12 weeks post infection). Cells were counted on immonocytochemically stained sections from rectal biopsies using antibodies as follows: synaptophysin, serotonin, Peptide YY for ECs, CD8 for i&a-epithelial lymphocytes (IEL, both counted per 100 epithelial cells), mast cell pyptase for mast cells (MC), CD68 for macrophages & CD3 for lamina propria T lymphocytes all expressed as cells
a = P
1070 SEQUENCES AMELIORATE IMMUNOSTIMULA TORY DNA EXPERIMENTALCOLITISINMICEANDRATS. D.F.Kamdi,E.RaqTelAvivMedicalCber,Ismel sod untv. of chl&rnia San Diego, U.S.A. Immuncsdmubtoty DNA scq(ISS) acttvate tImzip illmdty, hducedmoftypc1cytoLinesIukipromote~ldrfferentiatin. ImbaknccofThlm~ytcsisinw~intbepnthogeoesisof clIpmwdcoltttsaIIdTtl2typcrcrponscsafehrvolvatinwlitis. We tested whetkr ISS oligonmleotides (ISS-ODN) ameliorate .rxphcd wlttis. ISS, (Klug/animal) or 0.2 ml dim wae i&cted S.C. to Balw mice 2 lYms bclkrc 2.5% dexlml sdtum surphate(INS) wasad&dtotbcfrdrbkingwater.DiseaseacdvityblbxwasbyscorinSclmngwillbodywt.aIldtheprmcnceofgrossbleedingiuthe std.Onday7,miwwucsac&ed,t&cobnresectedandweighsd. fMitiswa¶aLsobduwdbyintrarcotalrz **- “llof0.1 nll3% lodoacctendde (1A) in 1% mcthybelkbst to rats treated S.C. 2 days befcdld with ISS, (l~animai) 01 0.2 ml saliw. Rats wue .ucd&d3daysattcrI&tkcobnisobtal,lesbnaroamcamnedand muwsdMPofs&itywas-.1sssignificantly-thc sverity of DSS induced colitis T-II 25-32 Dss DGs+ISS 7 ‘-sIgnlrianuy-6un~~o.os)
Dlmosui~ &a-N 5.3f0.4 0.9io.4*
Bodyvt wchnee) -15.3f1.7. -x&0.4*
MPO WEI 4.1fD.3 l.W.4.
ISSalsosi@adlydearaedthesevssityofL4inducedcotitis:Ttlc lesion~inIA+ISSwas6~5-mm2asoompsrcdto57(H74~in ratstnetedwahIAonly.MpoclctivityinIA~rats-6.(H1.8u/Swas six folds high thmt ill IA+1SS -1.lM.l u/g (Two.05). ’ **. “n of ODN cibtively adioraa ma&mux
of rentidon in IBD.
108 THE ROLE OF NICOTINE IN IBD: THB SEVERITY OF EXPERIMENTAL COLITIS IN MICE IS DEPENDENT ON THB PRESENCE OF THE a5 NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR SUBUNIT (nAChR).D. Rachmilewitz, F. Karmeli, M. Kedmi, A. Orr-Um. Genetic Institute and Division ofkkdicinc, Tel Aviv Soumsky Medical Ceotcr, Tel Aviv, Israel. Cigar&e smokiig has diverse eikts on IBD - it is bcnctieial in ulcerative colitis and delctaious in Crdm’s disease. The ingrcdiant and mechanism involved in the relationship khvceo smoking and IBD rcmains to be detincd. In order to stody the possible bwolvcment of the nicdinic recepws in the pathogencais of IL3D we compared the scwIty of experimental colitis in mia dckimt for the a5 ncomnal nAChR subonit to wild type umtml mice. Colitiswasinducedin a5 dclicimt and amtrol miceby the sdditionof 2.5% dextran sodium sulphate (DSS) to the drinking water. Control groups received tap water. Disease aclivily index was determinedby scoring changes in body might and the prcscna of gross bleeding in the stool. On day 7 mice were sacrificed, the colon WBS resected,weighed, seckns were obtained for histology and mumsal MFQ activity and PGEI generation wrc dctcrmined. DSS indoad c&is in the a5 detieient mice (a5 4 ) was sigoificaotly more severe as cxpmsed hy the prnxntage change in body might, and by disease activity and histological szorenthat wre about 1.5 fold higher than in the cootml group (P-zO.05). Mumsal MPO activity and PC& generation wue also significantly higha in DSS treated a.5 4 mice as compared to the reqactive levels in DSS trcatcd control mice. Treatment NONE DSS INDUCED COLITIS Mica (nmnber) Control (5) a5 -I- (8) Control (13) a5 -/-(IS) DiseaseA&i-&y 4.2i0.8 6.3f0.7. Histological score 6.6iO.7 8.9iC.6* Change In Ekdy Wt. (%) -14.lf2.0 -20.7i2.2* 0.2io.05 033.1 MFo Wk?) l.I+xl.2 2.6f0.6. 206f29 173*16 229f24 313f33’ XEs (w40 l - SitifkxntlydiBercot tkwn cootml (p
A31