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Increased prevalence of methylenetetrahydrofolate reductase C677T variant in patients with inflammatory bowel disease
Abstracts
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21
23 EFFECT OF A SPECIFIC COX-2 INHIDITOR GASTRODUODENAL LESIONS IN PATIENTS FAMILIAL ADENOMATOUS POLYPOSIS
ON WITH
M G.De Polo. YMuigmni, N.MOggiono, A. Partorelli, VRovella, E.&u Torn-, SDu/voi, SRinelii, F, Vecchio, G.Costamagna, MA& UO di Gastroenterologia, ASL Vilerbo; UO di Endoscopia Digestiva Chirurgica; Isfitulo di Anotomia Patologico, Universit& Conolica di Roma. Cyclooxygenase 2 (COX-2)gene expression bes been shown to be upregulatcd in both btlmm cobKstal adelmmas ad edenoearcimmm with rcswct to the ammeenv~ normal nmmse. A significant mdtlctbn in the tmmbef oi &bl&d polyps atIer six mLith of trcatmem with B COX-2 soecific inhibitor hap been recentlv reeorted in ptknts with hmilial Bhemmdow pdyposk (FAP). ~Ex&cdcmic tmudfestetbns of the d&ease incIude multiple gastric fimdic pcdyps and duodenal adenanes. Mmmgement of duodecal end periampullary ademmas remwents one of the major clinical problems in FAF patients after mbnic-surgery. Aim of this s&y WBStoinvestigae the etian of a specific OX-2 inhibitor on upper GI lesions in FAF’ p&eats. MATERL4L AND METHODS. Six FAF patients were recruited for the study. All ptknts had previous colomctel sugery, Five patients lmdenventnndationalmmlvsistlmtsbowed6ml?mbiftmututionsofAFC. Upper 01 endosmpy wasberfomxd and mukipk gmtric aad dwderml biopsies were taken from t&b altered aod eppmently oormal mucosa. PatkIlts were daily treated with 25 a of Rot&xii (MS&D), B spxilic COX-2 inhibitor, for six months. Upper GI e&scogy ti mxdtiile biipsies wes repeated et the end of trial. Samples Were immtmobbtocbcmidly pmasscd to asses3 cell proufcmtbn (Ki-67) apoptosk (TIJNBL), bzl-2 (AK&em) ) and COX-2 (D&o) expression. All embsmpies wax videotaped. A qua&ive a%zssm@ oftbe extent of gestmduodnal lesions was carried out by two expert coaoscx+ts wiii separately gave a videoecdoscopic -score. &doscopisis were UnBabout the seciuences of vidmteees. RESULTS. M oatients showed tic and d& polyps at t&ii end~scopy. In’five of them a dmmtk intprwemetd of duodenal endoscopic eppeama wxs regktercdattheendoftbeshuly. Nos&iiicantchangeswereot%wed in gastric leskms. A me&d induction of apoptosis and an evident reduction of COX-2 expression were sea et the end ofthe treatment. CONCLUSIONS. Rofecoub, a specific COX-2 inbiiir appears to be e very promising therapeutic agent for duodenal lesions in FAP patients afm cobnic surgery.
22
~~~cre~cd prevakncc
of metylcnetetnhydrofolrtc
IWJUCUW
C677T variant in patients with inflammatory bowel disease A.&k* Tuni D **, Simioni P***, Mmtorana G’“, Mariani G** and -9 Cottone Mb. Clinica Medica “R”, Ospedale ‘V.Cervello”, Palermo’; Cattedm di JZmatologia, Universti degli Studi di Palermo**; Semeiotica medica Univesti di FWlova***. Background: Tluomboemboiism is a cause of morbidity in patie& (pts) with inflammatory bowel disease (RID). Hyperhomocyskkmia ban been shown to be a.w~~ieted with risk oftbromboembolism in IBD. An incrwed prevslence of methytenetccrahydmfolate redwtase C677T variant (MTHFR) ha.sbeenreportedinIBD. Aim: To detmmine the imzklence and possible asscciation of MTHFR variant with the developememt of thrombosis in IBD. Patients and methods: Lois study inch&d 17 patients with IBD (10 Crohn’s disease and 7 ulcerative colitis) with history of arkrial(5 ptx) or vemnts (12 pts) thrombosis and other 41 patients with JBD (8 ulcerative wlitis and 33 C&n’s disrate) with no history of tbmmbollis and 98 heal&y ccmtmls.lbepresenceoftheMTHFRvariantwasdetermkedbya polymerase chain reaction method. Subjects were categorised as homozygous for the thermolabile variant (lT), heterozigow for wild type and variant (CT) or hmnozigoos for the wild type (CC). Fischer’s exact twt wasusedforanalysisofdata. BesuIts: A total of 20% (lU58; 3 out of 17 pts with tbmmbc& and 9 out of 41 pts without thrombosis) of IBD were homozygow for the C677T variant wmpared with 11% (10198) of controls @=0.03). Conclusions: In our geographic area, the homozigous MTHF’R variant is more fkquently associated with IBD than with controls but no correlation was found between the presence of the mutation and presence of thmmboembolism.
24
ALDOSTERONEDEPENDENT TUBULAR PHYSIOLOGY
PERTURBATION M
NON-AZOTEMIC
OF HUMAN
RENAL cIRRIIosIs
WITH ASCITES. Sam06 G, l Silvatto S, *Touswz A, * *Mengoti M, *Biavs A, l SmediIe, Bonsrdi L, l Rizzetto M. Gastroentemlogy Unif, Gradenigo Hospital, Torino, Italy.
*Gastroenterology Departmenr and **Division of Internal Medicine, Hospilal, University of Torino, Torino, Italy Apart from the glomendar-tubular balance and the tubologlomendar
MolineIte
feedback, little is known about the mechanisms of intrarenal regulation of electrolyte tubular handling in patients with liver cirrhosis, Aim of this study is to highlight the reciprocal control of sodium metabolism by different tubular segments in patients with liver cirrhosis prior to timctional renal fkihuz development. 2 1 consecutive patients with dinrcti~fiue liva cirrhosis (11 with pma.witic and 10 with non-Bzotemic a&tic disease) were submited to the following tkm&mtiom: a) plasma ti activity (PRA) and aldostaonc (A) ~CVC~S;b) endogcnous dopamineqic activity, measured as incremental aldostenmc and proladin responses after metoclopramide i.v. administration; c) renal clcsrances of sodimq pomssill4 lithium (a measure of 5uid delivery to the distal nephron), idin and pare-aminohippomte; d) nitric oxide systemic plasma levels measured by electron pammagnetic resonsnce spectroscopy as nitrosyl-hemoglobin complexes. Compad with cmnpwsated cirrhotics, patients with ascites showed significantly hi&r A plasma levels (131.4 f 92.7 vs. 70.8 f 32.9 &ml). In the whole group of patients we observed a direct correlation between renal plasma flow (RF-F) and glomenda? 6ltralion rate (GFR) (rO.85, p
propcay is lost hy the ascitic patients perimps by v&e hyperaldosteronism.
A96
of their state of ScconBIy
PROKINETIC SUBJECTS
EFFECT
OF
ALKA-SELTZER
IN
HEALTHY
Q&&&, S Ptgnattelli’, AR Baldassani, S. Manenti, C. Terrani, M Peracchi Catledra dl Gastroenterologia, Dipxtimento di Scienze Mediche, IRCCSOspedale Maggiore di Milano, * Bayer ltalia S.p.A. Background: Alka-Seltzer (AS) combines analgesic and antacid properties. due to its main active components. sodium acetylsalicylate and sodium citrate, and is widely used for self-medication to relieve symptoms such as upset stomach and headache following food overindulgence. However, the effects of AS on gastric emptying rate have never been studied. Aim: To evaluate whether AS influences the gastric emptying of solids, assessed by “C-octanoic acid breath test. Material and methods: Twelve healthy subjects, 6 men and 6 women, aged 19.47 years, mean 30. were studied twice with a 250 kcal test meal consisting of 1 scrambled egg, butter 10 g, white bread 40 g and water 200 ml. The egg yolk was labelled with 100 mg of “C-octanoic acid. At the end of the meal 2 tablets of placebo (I’) or AS, dissolved in a glass of water, were given in double blind, randomized order Breath sameles were taken before the meal and et 15 min intervals for 5 h postprandially, end analyzed by means of isotope selective nondispmwe drared spechometry. Two indexes were calculated, the time’ comsponding to peak “CO2 breath excretion, or lag-far% (TQ), and the b&emptying time (Tml Before the test meals and every 30 min for 5 h postpmndially, the subjects were asked to fill in a questionnaire rating. by a visual analogoe wale. the folkwine meal induced sensations: satiety, fullness. abdominal discomfort, naus~ &d desire to eat. Statistical analysis was performed by non parametric tests. Results: AS significantly shortened both TI, [I 16*5.6 (meat&EM) ys 148+8.9 min; p
~..-, _..
-----
21
23 EFFECT OF A SPECIFIC COX-2 INHIDITOR GASTRODUODENAL LESIONS IN PATIENTS FAMILIAL ADENOMATOUS POLYPOSIS
ON WITH
M G.De Polo. YMuigmni, N.MOggiono, A. Partorelli, VRovella, E.&u Torn-, SDu/voi, SRinelii, F, Vecchio, G.Costamagna, MA& UO di Gastroenterologia, ASL Vilerbo; UO di Endoscopia Digestiva Chirurgica; Isfitulo di Anotomia Patologico, Universit& Conolica di Roma. Cyclooxygenase 2 (COX-2)gene expression bes been shown to be upregulatcd in both btlmm cobKstal adelmmas ad edenoearcimmm with rcswct to the ammeenv~ normal nmmse. A significant mdtlctbn in the tmmbef oi &bl&d polyps atIer six mLith of trcatmem with B COX-2 soecific inhibitor hap been recentlv reeorted in ptknts with hmilial Bhemmdow pdyposk (FAP). ~Ex&cdcmic tmudfestetbns of the d&ease incIude multiple gastric fimdic pcdyps and duodenal adenanes. Mmmgement of duodecal end periampullary ademmas remwents one of the major clinical problems in FAF patients after mbnic-surgery. Aim of this s&y WBStoinvestigae the etian of a specific OX-2 inhibitor on upper GI lesions in FAF’ p&eats. MATERL4L AND METHODS. Six FAF patients were recruited for the study. All ptknts had previous colomctel sugery, Five patients lmdenventnndationalmmlvsistlmtsbowed6ml?mbiftmututionsofAFC. Upper 01 endosmpy wasberfomxd and mukipk gmtric aad dwderml biopsies were taken from t&b altered aod eppmently oormal mucosa. PatkIlts were daily treated with 25 a of Rot&xii (MS&D), B spxilic COX-2 inhibitor, for six months. Upper GI e&scogy ti mxdtiile biipsies wes repeated et the end of trial. Samples Were immtmobbtocbcmidly pmasscd to asses3 cell proufcmtbn (Ki-67) apoptosk (TIJNBL), bzl-2 (AK&em) ) and COX-2 (D&o) expression. All embsmpies wax videotaped. A qua&ive a%zssm@ oftbe extent of gestmduodnal lesions was carried out by two expert coaoscx+ts wiii separately gave a videoecdoscopic -score. &doscopisis were UnBabout the seciuences of vidmteees. RESULTS. M oatients showed tic and d& polyps at t&ii end~scopy. In’five of them a dmmtk intprwemetd of duodenal endoscopic eppeama wxs regktercdattheendoftbeshuly. Nos&iiicantchangeswereot%wed in gastric leskms. A me&d induction of apoptosis and an evident reduction of COX-2 expression were sea et the end ofthe treatment. CONCLUSIONS. Rofecoub, a specific COX-2 inbiiir appears to be e very promising therapeutic agent for duodenal lesions in FAP patients afm cobnic surgery.
22
~~~cre~cd prevakncc
of metylcnetetnhydrofolrtc
IWJUCUW
C677T variant in patients with inflammatory bowel disease A.&k* Tuni D **, Simioni P***, Mmtorana G’“, Mariani G** and -9 Cottone Mb. Clinica Medica “R”, Ospedale ‘V.Cervello”, Palermo’; Cattedm di JZmatologia, Universti degli Studi di Palermo**; Semeiotica medica Univesti di FWlova***. Background: Tluomboemboiism is a cause of morbidity in patie& (pts) with inflammatory bowel disease (RID). Hyperhomocyskkmia ban been shown to be a.w~~ieted with risk oftbromboembolism in IBD. An incrwed prevslence of methytenetccrahydmfolate redwtase C677T variant (MTHFR) ha.sbeenreportedinIBD. Aim: To detmmine the imzklence and possible asscciation of MTHFR variant with the developememt of thrombosis in IBD. Patients and methods: Lois study inch&d 17 patients with IBD (10 Crohn’s disease and 7 ulcerative colitis) with history of arkrial(5 ptx) or vemnts (12 pts) thrombosis and other 41 patients with JBD (8 ulcerative wlitis and 33 C&n’s disrate) with no history of tbmmbollis and 98 heal&y ccmtmls.lbepresenceoftheMTHFRvariantwasdetermkedbya polymerase chain reaction method. Subjects were categorised as homozygous for the thermolabile variant (lT), heterozigow for wild type and variant (CT) or hmnozigoos for the wild type (CC). Fischer’s exact twt wasusedforanalysisofdata. BesuIts: A total of 20% (lU58; 3 out of 17 pts with tbmmbc& and 9 out of 41 pts without thrombosis) of IBD were homozygow for the C677T variant wmpared with 11% (10198) of controls @=0.03). Conclusions: In our geographic area, the homozigous MTHF’R variant is more fkquently associated with IBD than with controls but no correlation was found between the presence of the mutation and presence of thmmboembolism.
24
ALDOSTERONEDEPENDENT TUBULAR PHYSIOLOGY
PERTURBATION M
NON-AZOTEMIC
OF HUMAN
RENAL cIRRIIosIs
WITH ASCITES. Sam06 G, l Silvatto S, *Touswz A, * *Mengoti M, *Biavs A, l SmediIe, Bonsrdi L, l Rizzetto M. Gastroentemlogy Unif, Gradenigo Hospital, Torino, Italy.
*Gastroenterology Departmenr and **Division of Internal Medicine, Hospilal, University of Torino, Torino, Italy Apart from the glomendar-tubular balance and the tubologlomendar
MolineIte
feedback, little is known about the mechanisms of intrarenal regulation of electrolyte tubular handling in patients with liver cirrhosis, Aim of this study is to highlight the reciprocal control of sodium metabolism by different tubular segments in patients with liver cirrhosis prior to timctional renal fkihuz development. 2 1 consecutive patients with dinrcti~fiue liva cirrhosis (11 with pma.witic and 10 with non-Bzotemic a&tic disease) were submited to the following tkm&mtiom: a) plasma ti activity (PRA) and aldostaonc (A) ~CVC~S;b) endogcnous dopamineqic activity, measured as incremental aldostenmc and proladin responses after metoclopramide i.v. administration; c) renal clcsrances of sodimq pomssill4 lithium (a measure of 5uid delivery to the distal nephron), idin and pare-aminohippomte; d) nitric oxide systemic plasma levels measured by electron pammagnetic resonsnce spectroscopy as nitrosyl-hemoglobin complexes. Compad with cmnpwsated cirrhotics, patients with ascites showed significantly hi&r A plasma levels (131.4 f 92.7 vs. 70.8 f 32.9 &ml). In the whole group of patients we observed a direct correlation between renal plasma flow (RF-F) and glomenda? 6ltralion rate (GFR) (rO.85, p
propcay is lost hy the ascitic patients perimps by v&e hyperaldosteronism.
A96
of their state of ScconBIy
PROKINETIC SUBJECTS
EFFECT
OF
ALKA-SELTZER
IN
HEALTHY
Q&&&, S Ptgnattelli’, AR Baldassani, S. Manenti, C. Terrani, M Peracchi Catledra dl Gastroenterologia, Dipxtimento di Scienze Mediche, IRCCSOspedale Maggiore di Milano, * Bayer ltalia S.p.A. Background: Alka-Seltzer (AS) combines analgesic and antacid properties. due to its main active components. sodium acetylsalicylate and sodium citrate, and is widely used for self-medication to relieve symptoms such as upset stomach and headache following food overindulgence. However, the effects of AS on gastric emptying rate have never been studied. Aim: To evaluate whether AS influences the gastric emptying of solids, assessed by “C-octanoic acid breath test. Material and methods: Twelve healthy subjects, 6 men and 6 women, aged 19.47 years, mean 30. were studied twice with a 250 kcal test meal consisting of 1 scrambled egg, butter 10 g, white bread 40 g and water 200 ml. The egg yolk was labelled with 100 mg of “C-octanoic acid. At the end of the meal 2 tablets of placebo (I’) or AS, dissolved in a glass of water, were given in double blind, randomized order Breath sameles were taken before the meal and et 15 min intervals for 5 h postprandially, end analyzed by means of isotope selective nondispmwe drared spechometry. Two indexes were calculated, the time’ comsponding to peak “CO2 breath excretion, or lag-far% (TQ), and the b&emptying time (Tml Before the test meals and every 30 min for 5 h postpmndially, the subjects were asked to fill in a questionnaire rating. by a visual analogoe wale. the folkwine meal induced sensations: satiety, fullness. abdominal discomfort, naus~ &d desire to eat. Statistical analysis was performed by non parametric tests. Results: AS significantly shortened both TI, [I 16*5.6 (meat&EM) ys 148+8.9 min; p
~..-, _..