- Email: [email protected]
Aspirin use – A Prospective Study From Three Danish Centres
M1698
BACKGROUND: Recently, there has been a growing body of evidence suggesting a relationship between H. pylori gastritis and hypoferritinemia or IDA . AIM: To systematically review the role of H. pylori infection in hypoferritinemia and IDA, and to perform a meta-analysis of case-control studies. METHODS: Selection of studies: Case-control studies comparing a) the prevalence of H. pylori infection in patients with and without IDA/hypoferritinemia, and b) the prevalence of IDA/hypoferritinemia in patients with and without H. pylori infection. Search strategy: electronic and manual bibliographical searches. Data synthesis: Meta-analysis combining the Odds Ratios (OR). RESULTS: a) Eight studies compared the prevalence of H. pylori infection in patients with (637 patients) and without (2,305 patients) IDA, showing a higher prevalence of H. pylori infection in anaemic patients (34% vs. 22%; OR=1.6; 95%CI= 1.26-2.03). Only one study compared the prevalence of infection in patients with and without hypoferritinemia (29% vs. 19%; p<0.05). b) Seven studies compared the prevalence of IDA in patients with (3093 patients) and without (1926 patients) H. pylori infection, showing a slightly (and almost statistically significant) higher prevalence of IDA in H. pyloripositive patients (16% vs. 14%; OR=1.4; 95%CI=0.98-2.0). Finally, 5 studies compared the prevalence of hypoferritinemia in patients with (297 patients) and without (129 patients) H. pylori infection, showing a higher prevalence of hypoferritinemia in H. pylori-positive patients (33% vs. 13%; OR=1.7; 95%CI=1.31-2.32). Results were heterogeneous for all comparisons. CONCLUSION: Some epidemiologic studies suggest an association between H. pylori infection and lower iron stores or IDA. However, these data should be interpreted with caution due to marked heterogeneity among studies.
AGA Abstracts
Helicobacter pylori and Iron-Deficiency Anaemia (IDA): A Meta-Analysis of Case-Control Studies Javier P. Gisbert, Olga Pérez Nyssen, Adrian G. McNicholl
* Hp-negative and no use of NSAID/aspirin M1701 Induced Formation of Stress Granules Protects Intestinal Epithelial Cells Against Apoptosis Following Polyamine Depletion Tongtong Zou, Zhengran Jiang, Jaladanki N. Rao, Lan Liu, Lan Xiao, Tingxi Yu, Yu-hong Cui, Douglas J. Turner, Jian-Ying Wang Homeostasis of the mammalian intestinal epithelium is preserved through strict regulation of intestinal epithelial cell (IEC) proliferation and apoptosis. Polyamines play an important role in maintenance of intestinal epithelial integrity and depletion of cellular polyamines promotes the resistance to apoptosis. However, the exact mechanism by which polyamines are involved in the regulation of apoptosis remains unclear. Stress granules (SGs) are microscopically visible ribonucleoprotein granules that cooperatively regulate the translation and decay of mRNAs. Recently, formation of SGs was shown to inhibit apoptosis in COS-7 cells and HeLa cells. The current study determines whether polyamines regulate SG formation, and whether polyamine depletion induces the resistance of IECs to apoptosis by increasing SG formation. Methods: Studies were conducted in IEC-6 cells, derived from normal rat intestinal crypts. Polyamine levels were depleted by inhibiting ODC (key enzyme for polyamine biosynthesis) with DFMO but increased by overexpressing ODC gene. SGs were induced by exposure to sodium arsenite and were examined by immunofluorescence staining using antibodies against the SG signature constituent proteins eIF3b and TIAR. The formation of SGs was inhibited by Sort1 or/and TIA1 silencing. Apoptosis was induced by tumor necrosis factor-α (TNFα) in combination with cycloheximide (CHX). Results: Exposure to sodium arsenite not only induced SG formation in IEC-6 cells but also inhibited TNFα/CHX-induced apoptosis. The percentages of apoptotic cell death after TNFα/CHX treatment were decreased from 51.2% in normal cells to 1.5% in cells that were pretreated with arsenite. Alternatively, disruption of SG formation by silencing Sort1 and TIA1 potentiated TNFα/CHX-induced apoptosis (by ~24%). Depletion of cellular polyamines by DFMO increased basal levels of cytoplasmic eIF3b and TIAR proteins as measured by Western blotting and also enhanced arsenite-induced SG formation (by ~19.1%). Polyamine-deficient cells also exhibited an increase in resistance to TNFα/CHX-induced apoptosis, which was prevented by inhibiting SG formation by Sort1 and TIA1 silencing. In contrast, increased levels of cellular polyamines by ectopic ODC overexpression decreased eIF3b and TIAR proteins, repressed arseniteinduced SG formation, and sensitized IECs to TNF-α/CHX-induced apoptosis. Conclusions: These results indicate that 1) polyamines are implicated in the regulation of SG formation in IECs and 2) polyamine depletion induces the resistance of IECs to apoptosis by increasing the formation of stress granules.
M1699 Inhibitory Effects of Japanese Apricot, (Prunus Mume Siebold ET Zucc.; Ume), on Helicobacter pylori-Related Chronic Gastritis Shotaro Enomoto, Kimihiko Yanaoka, Hirotoshi Utsunomiya, Toru Niwa, Ken-ichi Inada, Hisanobu Deguchi, Kazuki Ueda, Chizu Mukoubayashi, Izumi Inoue, Takao Maekita, Kazuyuki Nakazawa, Mikitaka Iguchi, Hideyuki Tamai, Mitsuhiro Fujishiro, Masashi Oka, Masao Ichinose Background: Since ancient times the Japanese apricot (JA) (“Ume” in Japanese; Prunus mume Siebold et Zucc.) is popular and has been known to possess miscellaneous medical benefits. We investigated the correlation between JA intake and Helicobacter pylori (H. pylori)-related chronic atrophic gastritis (CAG). Methods: A questionnaire on JA intake was administered and serum anti-H. pylori IgG antibodies were measured in 1358 asymptomatic adults. The subjects were divided into a high intake group (≧3 JA daily) and low intake group (<3 JA daily). In addition, histologic and serologic evaluation of H. pylori-related CAG was carried out in non-elderly 68 volunteers by upper GI endoscopy and serum pepsinogen (PG) levels. Results: The H. pylori-negative rate did not differ significantly between the high intake group (968 subjects) and low intake group (390 subjects) (48.5% vs. 48.2%). However, mean antibody titers were lower in the high intake group when compared with the low intake group, but the difference was not statistically significant. We also stratified subjects by age into a non-elderly group (30 to 64 years) and an elderly group (≧65 years), but there was no significant age-related difference in H. pylori-negative rate based on JA intake. However, among H. pylori-positive subjects, although H. pylori antibody titers in the elderly group did not differ significantly based on JA intake; in the non-elderly group, H. pylori antibody titers were significantly lower in the high intake group (P=0.041). On endoscopic tissue biopsy from the non-elderly 68 volunteers, H. pylori bacterial load and mononuclear infiltration, irrespective of gastric site, were significantly less in the high intake group. In the high intake group, neutrophil infiltration in the antrum was significantly less pronounced, and atrophic gastritis was significantly less extensive in the corpus. In the high intake group, serum PGII was significantly lower, and the PGI/II ratio was significantly higher (P<0.001). Conclusion: Our findings strongly suggest that JA intake has a preventive effect on CAG by reducing H. pylori infection and reducing active mucosal inflammation.
M1702 The Transcription Factor SPDEF Inhibits Proliferation of Colon Tumors in Mice Taeko K. Noah, Noah F. Shroyer Background: We recently reported that inducible expression of SPDEF (SAM Pointed domain ETS Transcription Factor, also called PDEF) inhibits proliferation of intestinal epithelial progenitors while promoting goblet cell differentiation. We also found that SPDEF expression is significantly reduced in the majority of human colon cancers. Other studies suggest that SPDEF may be a tumor suppressor in prostate and breast cancers. Here, we hypothesized that SPDEF expression can inhibit proliferation of colon tumor cells In Vivo. Method: Transgenic mice that express SPDEF in an intestine-specific, tetracycline-inducible manner (SPDEF-dox mice) were treated with azoxymethane and dextran sodium sulfate to induce colon tumors. Mice were treated with doxycycline for 6 days prior to sacrifice. Tumor cell proliferation was assessed by BrdU incorporation. Results: Proliferation was significantly reduced in SPDEF-expressing tumors compared to control non-expressing tumors. Conclusions: SPDEF expression is sufficient to inhibit proliferation of colon cancer cells In Vivo. Our results suggest that SPDEF is a functional target for therapeutic intervention in colon cancer.
M1700 Uncomplicated Peptic Ulcer: HP-Status and NSAID/Aspirin use - A Prospective Study From Three Danish Centres Jane M. Hansen, Michael Dall, Axel Malchow-Møller, Søren Jensen Recent studies have suggested that the prevalence of Helicobacter pylori (Hp) infection in patients with peptic ulcer disease has been decreasing in developed countries. Many of these studies have been retrospective, resulting in a risk of unrecognized use of non-steroidal antiinflammatory drugs (NSAID) or aspirin or use of proton pump inhibitors (PPI) or antibiotics before Hp-test which may result in false negative Hp-tests. This prospective study aimed to investigate the prevalence of Hp and NSAID/aspirin use in peptic ulcer patients in Denmark. METHODS: In- or out-patients diagnosed with an uncomplicated peptic ulcer were prospectively registered in a 2 yr period 2007-2008. In a structured interview use of antibiotics and NSAID/aspirin during the previous month and use of PPI during the previous week was registered. Hp-status was assessed by rapid urease test and in addition in some patients with histological examination of gastric biopsies. In case of use of PPI and/or antibiotics a urease breath test was planned at least 2/4 weeks after end of therapy. RESULTS: 131 patients (Males 51 (39%), mean age 65 years) were registered. In patients with PPI/antibiotic use (n=39 (30%)) before Hp-test 30 tested negative. Of these 16 were not re-tested as planned, primarily because of co-morbidity. (see table) CONCLUSION: The prevalence of Hp in patients with peptic ulcer was significantly lower than previously reported, especially for gastric ulcer. However, a high use of PPI and/or antibiotics before HP-test may result in false negative test-results as indicated by the lower Hp-prevalence in this group. The use of NSAID/aspirin was widespread in this population. Results
M1703 Dietary Sphingomyelin Activates Pro-Apoptotic Bid in Intestinal Epithelial Cells Katharina Leucht, Anne Fischbeck, Isabelle Frey-Wagner, Susanne Bentz, Theresa Pesch, Silvia Kellermeier, Michael Fried, Gerhard Rogler, Hans-Ulrich Humpf, Martin Hausmann BACKGROUND Sphingomyelin (SM), a lipoid component of the plasma membrane is prevalent in animal products. Recently we could show that dietary SM induces apoptosis of intestinal epithelial cells (IEC) and aggravates inflammation in DSS-colitis. Metabolism of SM in the bowel generates ceramide which acts as bioactive lipid messenger and increases cathepsin D activity. Cathepsin D conducts activation of pro-apoptotic protein Bid by proteolytic processing to truncated Bid (tBid). tBid translocates to mitochondria and leads to disruption of the organelles. We aimed to investigate whether increased ceramide provides a mechanism to induce the pathway of apoptosis. METHODS Acute colitis was induced to female C57-BL/6J mice by 2 % dextran sulfate sodium (DSS) in drinking water. Mice received
S-401
AGA Abstracts
BACKGROUND: Recently, there has been a growing body of evidence suggesting a relationship between H. pylori gastritis and hypoferritinemia or IDA . AIM: To systematically review the role of H. pylori infection in hypoferritinemia and IDA, and to perform a meta-analysis of case-control studies. METHODS: Selection of studies: Case-control studies comparing a) the prevalence of H. pylori infection in patients with and without IDA/hypoferritinemia, and b) the prevalence of IDA/hypoferritinemia in patients with and without H. pylori infection. Search strategy: electronic and manual bibliographical searches. Data synthesis: Meta-analysis combining the Odds Ratios (OR). RESULTS: a) Eight studies compared the prevalence of H. pylori infection in patients with (637 patients) and without (2,305 patients) IDA, showing a higher prevalence of H. pylori infection in anaemic patients (34% vs. 22%; OR=1.6; 95%CI= 1.26-2.03). Only one study compared the prevalence of infection in patients with and without hypoferritinemia (29% vs. 19%; p<0.05). b) Seven studies compared the prevalence of IDA in patients with (3093 patients) and without (1926 patients) H. pylori infection, showing a slightly (and almost statistically significant) higher prevalence of IDA in H. pyloripositive patients (16% vs. 14%; OR=1.4; 95%CI=0.98-2.0). Finally, 5 studies compared the prevalence of hypoferritinemia in patients with (297 patients) and without (129 patients) H. pylori infection, showing a higher prevalence of hypoferritinemia in H. pylori-positive patients (33% vs. 13%; OR=1.7; 95%CI=1.31-2.32). Results were heterogeneous for all comparisons. CONCLUSION: Some epidemiologic studies suggest an association between H. pylori infection and lower iron stores or IDA. However, these data should be interpreted with caution due to marked heterogeneity among studies.
AGA Abstracts
Helicobacter pylori and Iron-Deficiency Anaemia (IDA): A Meta-Analysis of Case-Control Studies Javier P. Gisbert, Olga Pérez Nyssen, Adrian G. McNicholl
* Hp-negative and no use of NSAID/aspirin M1701 Induced Formation of Stress Granules Protects Intestinal Epithelial Cells Against Apoptosis Following Polyamine Depletion Tongtong Zou, Zhengran Jiang, Jaladanki N. Rao, Lan Liu, Lan Xiao, Tingxi Yu, Yu-hong Cui, Douglas J. Turner, Jian-Ying Wang Homeostasis of the mammalian intestinal epithelium is preserved through strict regulation of intestinal epithelial cell (IEC) proliferation and apoptosis. Polyamines play an important role in maintenance of intestinal epithelial integrity and depletion of cellular polyamines promotes the resistance to apoptosis. However, the exact mechanism by which polyamines are involved in the regulation of apoptosis remains unclear. Stress granules (SGs) are microscopically visible ribonucleoprotein granules that cooperatively regulate the translation and decay of mRNAs. Recently, formation of SGs was shown to inhibit apoptosis in COS-7 cells and HeLa cells. The current study determines whether polyamines regulate SG formation, and whether polyamine depletion induces the resistance of IECs to apoptosis by increasing SG formation. Methods: Studies were conducted in IEC-6 cells, derived from normal rat intestinal crypts. Polyamine levels were depleted by inhibiting ODC (key enzyme for polyamine biosynthesis) with DFMO but increased by overexpressing ODC gene. SGs were induced by exposure to sodium arsenite and were examined by immunofluorescence staining using antibodies against the SG signature constituent proteins eIF3b and TIAR. The formation of SGs was inhibited by Sort1 or/and TIA1 silencing. Apoptosis was induced by tumor necrosis factor-α (TNFα) in combination with cycloheximide (CHX). Results: Exposure to sodium arsenite not only induced SG formation in IEC-6 cells but also inhibited TNFα/CHX-induced apoptosis. The percentages of apoptotic cell death after TNFα/CHX treatment were decreased from 51.2% in normal cells to 1.5% in cells that were pretreated with arsenite. Alternatively, disruption of SG formation by silencing Sort1 and TIA1 potentiated TNFα/CHX-induced apoptosis (by ~24%). Depletion of cellular polyamines by DFMO increased basal levels of cytoplasmic eIF3b and TIAR proteins as measured by Western blotting and also enhanced arsenite-induced SG formation (by ~19.1%). Polyamine-deficient cells also exhibited an increase in resistance to TNFα/CHX-induced apoptosis, which was prevented by inhibiting SG formation by Sort1 and TIA1 silencing. In contrast, increased levels of cellular polyamines by ectopic ODC overexpression decreased eIF3b and TIAR proteins, repressed arseniteinduced SG formation, and sensitized IECs to TNF-α/CHX-induced apoptosis. Conclusions: These results indicate that 1) polyamines are implicated in the regulation of SG formation in IECs and 2) polyamine depletion induces the resistance of IECs to apoptosis by increasing the formation of stress granules.
M1699 Inhibitory Effects of Japanese Apricot, (Prunus Mume Siebold ET Zucc.; Ume), on Helicobacter pylori-Related Chronic Gastritis Shotaro Enomoto, Kimihiko Yanaoka, Hirotoshi Utsunomiya, Toru Niwa, Ken-ichi Inada, Hisanobu Deguchi, Kazuki Ueda, Chizu Mukoubayashi, Izumi Inoue, Takao Maekita, Kazuyuki Nakazawa, Mikitaka Iguchi, Hideyuki Tamai, Mitsuhiro Fujishiro, Masashi Oka, Masao Ichinose Background: Since ancient times the Japanese apricot (JA) (“Ume” in Japanese; Prunus mume Siebold et Zucc.) is popular and has been known to possess miscellaneous medical benefits. We investigated the correlation between JA intake and Helicobacter pylori (H. pylori)-related chronic atrophic gastritis (CAG). Methods: A questionnaire on JA intake was administered and serum anti-H. pylori IgG antibodies were measured in 1358 asymptomatic adults. The subjects were divided into a high intake group (≧3 JA daily) and low intake group (<3 JA daily). In addition, histologic and serologic evaluation of H. pylori-related CAG was carried out in non-elderly 68 volunteers by upper GI endoscopy and serum pepsinogen (PG) levels. Results: The H. pylori-negative rate did not differ significantly between the high intake group (968 subjects) and low intake group (390 subjects) (48.5% vs. 48.2%). However, mean antibody titers were lower in the high intake group when compared with the low intake group, but the difference was not statistically significant. We also stratified subjects by age into a non-elderly group (30 to 64 years) and an elderly group (≧65 years), but there was no significant age-related difference in H. pylori-negative rate based on JA intake. However, among H. pylori-positive subjects, although H. pylori antibody titers in the elderly group did not differ significantly based on JA intake; in the non-elderly group, H. pylori antibody titers were significantly lower in the high intake group (P=0.041). On endoscopic tissue biopsy from the non-elderly 68 volunteers, H. pylori bacterial load and mononuclear infiltration, irrespective of gastric site, were significantly less in the high intake group. In the high intake group, neutrophil infiltration in the antrum was significantly less pronounced, and atrophic gastritis was significantly less extensive in the corpus. In the high intake group, serum PGII was significantly lower, and the PGI/II ratio was significantly higher (P<0.001). Conclusion: Our findings strongly suggest that JA intake has a preventive effect on CAG by reducing H. pylori infection and reducing active mucosal inflammation.
M1702 The Transcription Factor SPDEF Inhibits Proliferation of Colon Tumors in Mice Taeko K. Noah, Noah F. Shroyer Background: We recently reported that inducible expression of SPDEF (SAM Pointed domain ETS Transcription Factor, also called PDEF) inhibits proliferation of intestinal epithelial progenitors while promoting goblet cell differentiation. We also found that SPDEF expression is significantly reduced in the majority of human colon cancers. Other studies suggest that SPDEF may be a tumor suppressor in prostate and breast cancers. Here, we hypothesized that SPDEF expression can inhibit proliferation of colon tumor cells In Vivo. Method: Transgenic mice that express SPDEF in an intestine-specific, tetracycline-inducible manner (SPDEF-dox mice) were treated with azoxymethane and dextran sodium sulfate to induce colon tumors. Mice were treated with doxycycline for 6 days prior to sacrifice. Tumor cell proliferation was assessed by BrdU incorporation. Results: Proliferation was significantly reduced in SPDEF-expressing tumors compared to control non-expressing tumors. Conclusions: SPDEF expression is sufficient to inhibit proliferation of colon cancer cells In Vivo. Our results suggest that SPDEF is a functional target for therapeutic intervention in colon cancer.
M1700 Uncomplicated Peptic Ulcer: HP-Status and NSAID/Aspirin use - A Prospective Study From Three Danish Centres Jane M. Hansen, Michael Dall, Axel Malchow-Møller, Søren Jensen Recent studies have suggested that the prevalence of Helicobacter pylori (Hp) infection in patients with peptic ulcer disease has been decreasing in developed countries. Many of these studies have been retrospective, resulting in a risk of unrecognized use of non-steroidal antiinflammatory drugs (NSAID) or aspirin or use of proton pump inhibitors (PPI) or antibiotics before Hp-test which may result in false negative Hp-tests. This prospective study aimed to investigate the prevalence of Hp and NSAID/aspirin use in peptic ulcer patients in Denmark. METHODS: In- or out-patients diagnosed with an uncomplicated peptic ulcer were prospectively registered in a 2 yr period 2007-2008. In a structured interview use of antibiotics and NSAID/aspirin during the previous month and use of PPI during the previous week was registered. Hp-status was assessed by rapid urease test and in addition in some patients with histological examination of gastric biopsies. In case of use of PPI and/or antibiotics a urease breath test was planned at least 2/4 weeks after end of therapy. RESULTS: 131 patients (Males 51 (39%), mean age 65 years) were registered. In patients with PPI/antibiotic use (n=39 (30%)) before Hp-test 30 tested negative. Of these 16 were not re-tested as planned, primarily because of co-morbidity. (see table) CONCLUSION: The prevalence of Hp in patients with peptic ulcer was significantly lower than previously reported, especially for gastric ulcer. However, a high use of PPI and/or antibiotics before HP-test may result in false negative test-results as indicated by the lower Hp-prevalence in this group. The use of NSAID/aspirin was widespread in this population. Results
M1703 Dietary Sphingomyelin Activates Pro-Apoptotic Bid in Intestinal Epithelial Cells Katharina Leucht, Anne Fischbeck, Isabelle Frey-Wagner, Susanne Bentz, Theresa Pesch, Silvia Kellermeier, Michael Fried, Gerhard Rogler, Hans-Ulrich Humpf, Martin Hausmann BACKGROUND Sphingomyelin (SM), a lipoid component of the plasma membrane is prevalent in animal products. Recently we could show that dietary SM induces apoptosis of intestinal epithelial cells (IEC) and aggravates inflammation in DSS-colitis. Metabolism of SM in the bowel generates ceramide which acts as bioactive lipid messenger and increases cathepsin D activity. Cathepsin D conducts activation of pro-apoptotic protein Bid by proteolytic processing to truncated Bid (tBid). tBid translocates to mitochondria and leads to disruption of the organelles. We aimed to investigate whether increased ceramide provides a mechanism to induce the pathway of apoptosis. METHODS Acute colitis was induced to female C57-BL/6J mice by 2 % dextran sulfate sodium (DSS) in drinking water. Mice received
S-401
AGA Abstracts