Influence of blood microcirculation on the acute NSAID-induced gastric injury

A90 AGA ABSTRACTS GASTROENTEROLOGY, Vol. 108, NO. 4 De ec ion o cy oklne ansc ip s in a gas ic mucosa a e exposu e o s ess using he e e se ansc lp ase polyme ase chain eac ion. H. E ns *, P. Kon u ek*, A. Ihlm, T. B zozowski, E.G. Hahn* and S.J. Kon u ek. *Dep . o Med. I, Uni . E langen-Nu embe g, FRG and Ins . o . Physiol., Uni . Sch. Med., K akow, Poland. Cy okines may con ibu e o he pa hogenesis o s ess ulce a ions. They may be di ec ly cy o oxic o ep helial cells, o may change he balance owa ds ulce o ma ion. He e we in es iga e he exp ession o se e al cy okine anscnp s a e a single exposu e o s ess. Ma e ial and Me hods: 25 a s we e exposed o wa e es ain s ess o 3.5h and hen sac i!iced a O, 2, 4, 6 and 12h. The numbe o s ess lesions we e coun ed. Specimens we e ozen in liquid ni ogen and o al RNA was isola ed. cDNA o RT-PCR was syn hesized om RNA by e e se ansc ip ion using oligo(dT)p iming. GAPDH, ~-ac in, IL-la, IL-2, IL-6,1FN-¥, TNF-~ and TGF 51 ansc ip s we e analysed by RT-PCR using speci ic p ime s. Resul s: The a e age numbe o ulce a ions a Oh was 15±3 and hen g adually declined o 4 ± 2 a 12h a e s ess. Con ols o ~-ac in and GAPDH showed equal exp ession o ansc ip s, excep ha GAPDH ansc ip s we e no de ec able 2 h a e s ess induc ion. No IL-2, TNF-c , o IFN-y ansc ip s we e de ec able. IL-6 was ound in he con ol g oup and was also de ec able 4 and 6 h a e exposu e o s ess and dec eased o below no mal le els a 12h. A week signal o IL- la was de ec able a 4 h a e exposu e o s ess. In con as , TGF 31 ansc ip s dec eased a 0 and 2 h a e s ess and i s le els did no di e om hose o con ols a 4, 6, and 1 2 h a e exposu e o s ess. Conclusions: The e is exp ession o a ime-dependen pa e n o cy okine gen ansc ip s a e exposu e o s ess. This signaling o cy okines may e lec he no mal biological esponse o s ess. INFLUENCE OF BLOOD MICROCIRCULATION ON THE ACUTE NSAID-INDUCED GASTRIC INJURY. J. Es eban*. M.A. Rod iguez*, LR. A acama*, C. del Pine*, M.J. Ma in**, V. Mo il a**, C. Ala c6n**, D. Delgado**, J.M. He e las**. *Se icio Cen al de In es igaci6n en Ciencias de la Salud de la Uni e sidad de C idiz. Espaha. **Se ieio de Apa a o Diges i e. Hospi al Vi gen de Maca ena. Uni e sidad de Se ille. Espa ia. Mucosal blood mie oci eula ion has been ela ed wi h NSAID-indnced gas ic inju y. Gas ic mucosal blood mic oci cula ion is con olod by se e al mechanisms including ni ic oxide (NO) and neu opep ide Y (NPY). In o de o cheek he implica ion o bo h mechanisms in he inju ing e ec o he NSAID, we ha e in es iga ed hei e ec on he mucosal le els o NPY and cGMP, as a measu e o NO unc ionalism. Wis a male a s (200-250 g body weig h) ha e been used-The NSAID adminis ed ha e been: pi oxicam 20, 10 and 5 mg/Kg; sodium dielo enac 100, 50, 25, 10, 5 and 2 mg/Kg, ibup 0 en 100 and 50 mg/Kg and ace ylsalicilie acid 500, 300 and 100 mg/Kg. A con ol g oup ea ed wi h saline solu ion has also been used. A e a 24 h s a ed pe iod he d ug has been gi en and 3 h la e he animalswe e anaes he ized (pen oba bi al 20 mg/Kg i.p.), he s omachs we e pe used wi h saline solu ion ia abdominal ao a (15 ml/min), ex ac ed and incised by mino cu a u e, he mucosal gas ic inju y was assessed using a s anda d scale and he mueosa was sc aped and ozen a -70~C un il i is assessed. We ha e de e mined he mucosal~ NPY le els and cGMP concen a ion.The di e ences be ween NSAID"~ea ed g oups and he saline g oup ha e been de e mined using he K uskall-Wallis ANOVA ollowed by Mann-Whi ney U- es when neoessa . The esi l s ob ained show ha all NSAID used (excep ibup o en) induced a signi ica i e and dose- ela ed dec ease o cGMP concen a ion wi hou modi ying he mucosal NPY le els. Fo cGMP he esul s we e: saline (2.88 pmol/mg p o ein) pi oxicam (20 mg/Kg 0.78, 10 mg/Kg 0.68 and 5 mg/Kg 0.63~'pmol/mg p o ein), diclo enae (100 mg/Kg 0.21, 50 mg/Kg 0.52, 25 mg/Kg 0.79 pmol/mg p o ein), ace ylsalicilic acid (500 mg/Kg 0.87, 300 mg/Kg 0.86 pmol/mg p o ein). These esul s a e in ag eemen wi h he hypo hesis ha NSAID-induced gas ic damage can be ela ed wi h a dec ease o NO unc ionalism. TOPICALLY APPLIED NON-STEROIDAL ANTI-INFLAMMATORY DRUGS AND HOSPITALISATION FOR UPPER GI BLEEDING AND PERFORATION: A RECORD-LINKAGE CASE-CONTROL STUDY. JMM E ans, AD McMahon, MM MeGUch is , G Whi e, FE Mu ay, DG McDe i , TM MacDonald. Medicines Moni o ing Uni , Dep o Clinical Pha macology, Ninewells Hospi al, Dundee, Sco land DD19SY. Recen case epo s ha e sugges ed an associa ion be ween uppe GI bleeding and pe o a ion (UGIBP) and opical non-s e oidal an i-in lamma o y d ugs (NSAIDs). A/m To e alua e he ela ionship be ween opical NSAIDs and hospi alisa ion o UGIBP. Me hods A case-con ol s udy was ca ied ou using a pu pose buil eco d-linkage da abase con aining all dispensed p esc ibing da a and all hospi alisa ion da a o he popula ion o Tayside, Sco land. The e we e 1,103 cases o UGIBP be ween Jail 90 and Dec 92 in he s udy popula ion o 319,465 people, esiden since Jan 89. Up o six age and sex-ma ched communi y con ols (n = 6,593) and wo hospi al con ols (n = 2,184) (wi h any diagnosis a he same hospi al wi hin 3 mon hs o he case) we e andomly gene a ed om he s udy popula ion. Exposu e o opical NSAIDs, o al NSAIDs and ulce healing d ugs (UHD) 45 days p io o he index da e and a any ime om Jan 89 was assessed and modelled using condi ional logis ic eg ession. Resul s a e gi en as odds a ios (OR) wi h 95% con idence in e als. Resul s The unadjus ed ORs o he wo exposu e a iables (45 day and E e ) a e shown in he Table. Associa ions we e e,~iden o all h ee classes o d u Topical NSAIDs O al NSAIDs UHD Comm 45 day 2.6 (1.6~ 4.2) 2.8 (2.3, 3.4) 4.6' (3.9, 5.5) con ols E e 1.5 (1.2, 1.9) 1.5 (1.3, 1.8) 4.3 (3.7, 5.0) Hosp 45 day 1.6 (0.9, 2.8) 2.0 (1.6, 2.5) 1.9 (1.6, 2.3) con ols E e 1.0 (0.8, 1.2) 1.0 (0.9, 1.2) 1.8 (1.5, 2.1) Howe e , in a condi ional logis ic eg ession analysis which adjus ed o he con ounding e ec s o all h ee classes o d ug simul aneously, he e we e no associa ions o opical NSAIDs. ORs we e 1.5 (0.8, 2.5) and 1.1 (0.6, 1.9) wi h communi y and hospi al con ols espec i ely. 45 day exposu e o o al NSAIDs was associa ed wi h UGIBP, wi h ORs o 2.6 (2.1, 3.2) and 2.0 (1.6, 2.5). E e exposu e o UHD was also associa ed wi h UGIBP. ORs we e 4.2 (3.6, 4.9) and 1.8 (1.5, 2.1). Conclusion The esul s o o al NSAIDs and UHDs a e consis en wi h o he epidemiological s udies. Topical NSAIDs we e no signi ican ly associa ed wi h hospi alisa ion o UGIBP a e adjus men o con ounding e ec s o o al NSAIDs and UHD. PREVALENCE OF ESOPHAGEAL DISEASE AFTER BARIATRIC SURGERY. S.C. Fab . T.A. Knox, and P.N. Beno i, Dep s. o Gas oen e ology and Su ge y, New England Medical Cen e 0qEMC), Bos on, MA Backg ound: 1.5 million Ame icans ha e clinically se e e obesi y de ined as a body mass index (BMI) o e 40 kg/m2. Su gical op ions o obesi y ha e been used wi h inc easing equency and success. These p ocedu es a e epo ed o educe he isk o esophageal e lux disease. We ha e, howe e , no ed a high p eyalence o esophageal pa hology in pa ien s who ha e had ba ia ic su ge y, who unde wen endoscopy. Me hods: We e ospec i ely e alua ed he p e alence o esophageal disease in 33 pa ien s wi h p io ba ia ic su ge y who unde wen endoscopy a NEMC be ween June 1992 and Augus 1994. We e iewed endoscopic epo s, ope a i e no es, and hospi al and clinic cha s o da a on ype and da e o su ge y, symp oms necessi a ing endosocopy, and endoscopic indings. Resul s: Se en een pa ien s had had a gas ic bypass p ocedu e (p ima ily a Roux-en-Y gas ojejunos omy) and 16 pa ien s a gas ic pa i ioning p ocedu e (gas ogas os omy o gas oplas y). The main indica ions o endoscopy we e abdominal pain, ailu e o lose weigh , and omi ing. The mean age was 42.4 yea s and he mean in e al since su ge y was 5.1 yea s. Six een (48%) pa ien s had esophageal pa hology wi h 11 (33%) cases o esophagi is, 4 (12%) cases o abno mal mo ili y, and 2 (6%) cases o Ba e 's epi helium. The p esen ing complain s o hese pa ien s we e compa able o hose o he en i e g oup. Eigh pa ien s had unde gone a gas ic bypass and 9 pa ien s a gas ic pa i ioning p ocedu e. Eigh pa ien s had non- esophageal pa hology (anas nmo ie s ic u e, mesh ex uding in o he s oma, ma ginal ulce ) ha may ha e con ibu ed o he esophageal disease bu 8 pa ien s had no o he pa hology No pa ien s we e no ed o ha e bo h abno mal esophageal mo ili y and esophagi is. One pa ien had abno mal mo ili y and Ba e 's epi helium. Conclusions: Esophageal pa hology was ound in 16/33 (48%) pa ien s unde going endoscopy. Eigh o he 16 pa ien s had no o he pa hology ha could in luence he esophageal indings. We hypo hesize ha educ ion in gas ic size in luences esophageal unc ion and inc eases he incidence o esophageal disease.