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Clinical features of gastroduodenal injury associated with long-term low-dose aspirin therapy

World Journal of Gastroenterology 2013年第11期19卷 1673-1682页

作者： Junichi Iwamoto Yoshifumi Saito Akira Honda Yasushi Matsuzaki Department of Gastroenterology Tokyo Medical UniversityIbaraki Medical CenterIbaraki 300-0395Japan

Low-dose aspirin(LDA) is clinically used for the prevention of cardiovascular and cerebrovascular events with the advent of an aging society.On the other hand,a very low dose of aspirin(10 mg daily) decreases the gastric mucosal prostaglandin levels and causes significant gastric mucosal damage.The incidence of LDAinduced gastrointestinal mucosal injury and bleeding has increased.It has been noticed that the incidence of LDA-induced gastrointestinal hemorrhage has increased more than that of non-aspirin non-steroidal anti-inflammatory drug(NSAID)-induced lesions.The pathogenesis related to inhibition of cyclooxygenase(COX)-1 includes reduced mucosal flow,reduced mucus and bicarbonate secretion,and impaired platelet aggregation.The pathogenesis related to inhibition of COX-2 involves reduced angiogenesis and increased leukocyte adherence.The pathogenic mechanisms related to direct epithelial damage are acid back diffusion and impaired platelet aggregation.The factors associated with an increased risk of upper gastrointestinal(GI) complications in subjects taking LDA are aspirin dose,history of ulcer or upper GI bleeding,age > 70 years,concomitant use of non-aspirin NSAIDs including COX-2-selective NSAIDs,and Helicobacter pylori(H.pylori) infection.Moreover,no significant differences have been found between ulcer and non-ulcer groups in the frequency and severity of symptoms such as nausea,acid regurgitation,heartburn,and bloating.It has been shown that the ratios of ulcers located in the body,fundus and cardia are significantly higher in bleeding patients than the ratio of gastroduodenal ulcers in patients taking LDA.Proton pump inhibitors reduce the risk of developing gastric and duodenal ulcers.In contrast to NSAIDinduced gastrointestinal ulcers,a well-tolerated histamine H2-receptor antagonist is reportedly effective in prevention of LDA-induced gastrointestinal ulcers.The eradication of H.pylori is equivalent to treatment with omeprazole in preventing recurrent bleeding.Continuous aspirin therapy for patients

关键词： Gastroduodenal ulcer Upper gastrointestinal bleeding Low-dose aspirin Non-steroidal antiinflammatory drugs

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Evaluation of gut dysbiosis using serum and fecal bile acid profiles

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World Journal of Clinical Cases 2022年第34期10卷 12484-12493页

作者： Tadakuni Monma Junichi Iwamoto Hajime Ueda Makoto Tamamushi Fumio Kakizaki Naoki Konishi Shoichiro Yara Teruo Miyazaki Takeshi Hirayama Tadashi Ikegami Akira Honda Department of Gastroenterology and Hepatology Tokyo Medical University Ibaraki Medical CenterInashiki-Gun 300-0395Japan Joint Research Center Tokyo Medical University Ibaraki Medical CenterInashiki-Gun 300-0395Japan

Dysbiosis in the intestinal microflora can affect the gut production of microbial metabolites,and toxic substances can disrupt the barrier function of the intestinal wall,leading to the development of various diseases.Decreased levels of Clostridium subcluster XIVa(XIVa)are associated with the intestinal dysbiosis found in inflammatory bowel disease(IBD)and Clostridium difficile infection(CDI).Since XIVa is a bacterial group responsible for the conversion of primary bile acids(BAs)to secondary BAs,the proportion of intestinal XIVa can be predicted by determining the ratio of deoxycholic acid(DCA)/[DCA+cholic acid(CA)]in feces orserum.For example,serum DCA/(DCA+CA)was significantly lower in IBD patients than in healthy controls,even in the remission period.These results suggest that a low proportion of intestinal XIVa in IBD patients might be a precondition for IBD onset but not a consequence of intestinal inflammation.Another report showed that a reduced serum DCA/(DCA+CA)ratio could predict susceptibility to CDI.Thus,the BA profile,particularly the ratio of secondary to primary BAs,can serve as a surrogate marker of the intestinal dysbiosis caused by decreased XIVa.

关键词： Gut dysbiosis Clostridium subcluster XIVa Bile acids HPLC-MS/MS Inflammatory bowel diseases Clostridium difficile infection

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Small-bowel mucosal injuries in low-dose aspirin users with obscure gastrointestinal bleeding

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World Journal of Gastroenterology 2014年第36期20卷 13133-13138页

作者： Junichi Iwamoto Yuji Mizokami Yoshifumi Saito Koichi Shimokobe Akira Honda Tadashi Ikegami Yasushi Matsuzaki Department of Gastroenterology Tokyo Medical University Ibaraki Medical Center Ibaraki 300-0395 Japan Department of Gastroenterology University of Tsukuba Ibaraki 305-8576 Japan

AIM: To investigate the clinical differences between small intestinal injuries in low-dose aspirin(LDA) users and in non-steroidal anti-inflammatory drug(NSAID) users who were examined by capsule endoscopy(CE) for obscure gastrointestinal bleeding(OGIB). METHODS: A total of 181 patients who underwent CE for OGIB were included in this study. Based on clinical records, laboratory data such as hemoglobin levels, major symptoms, underlying diseases, the types and duration of LDA and NSAID use, and endoscopic characteristics of CE were reviewed.RESULTS: Out of a total of 45 cases of erosive lesions, 27 cases were taking LDA or NSAIDs(7 were on NSAIDs, 9 were on LDA alone, 9 were on LDA and thienopyridine, and 2 were on LDA and warfarin).The prevalence of ulcers or erosion during chronic use of LDA, LDA and the anti-platelet drug thienopyridine (clopidogrel or ticlopidine), and NSAIDs were 64.3%, 80.0%, and 75.0%, respectively. Erosive lesions were observed predominantly in chronic LDA users, while ulcerative lesions were detected mainly in NSAID users. However, concomitant use of thienopyridine such as clopidogrel with LDA increased the proportion of ulcers. The erosive lesions were located in the whole of the small intestine(jejunum and ileum), whereas ulcerative lesions were mainly observed in the ileum(P < 0.05). CONCLUSION: Our CE findings indicate that chronic LDA users and NSAID users show different types and locations of small-bowel mucosal injuries. The concomitant use of anti-platelet drugs with LDA tends to exacerbate the injuries from LDA-type to NSAID-type injuries.

关键词： Non-steroidal anti-inflammatory drugs Lowdose aspi

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Expression of leukotriene B4 receptor 1 defines functionally distinct DCs that control allergic skin inflammation

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Cellular & Molecular Immunology 2021年第6期18卷 1437-1449页

作者： Tomoaki Koga Fumiyuki Sasaki Kazuko Saeki Soken Tsuchiya Toshiaki Okuno Mai Ohba Takako Ichiki Satoshi iwamoto Hirotsugu Uzawa Keiko Kitajima Chikara Meno Eri Nakamura Norihiro Tada Yoshinori Fukui junichi Kikuta Masaru Ishii Yukihiko Sugimoto Mitsuyoshi Nakao Takehiko Yokomizo Department of Biochemistry Juntendo University Graduate School of MedicineTokyo113-8421Japan Department of Medical Cell Biology Institute of Molecular Embryology and GeneticsKumamoto UniversityKumamoto860-0811Japan Department of Cell Signaling Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyo113-8510Japan Department of Pharmaceutical Biochemistry Graduate School of Pharmaceutical SciencesKumamoto UniversityKumamoto862-0973Japan Department of Developmental Biology Graduate School of Medical SciencesKyushu UniversityFukuoka812-8582Japan Laboratory of Genome Research Research Institute for Diseases of Old AgeJuntendo University Graduate School of MedicineTokyo113-8421Japan Division of Immunogenetics Department of Immunobiology and NeuroscienceMedical Institute of BioregulationKyushu UniversityFukuoka812-8582Japan Department of Immunology and Cell Biology Graduate School of Medicine and Frontier BiosciencesOsaka UniversityOsaka565-0871Japan

Leukotriene B4(LTB4)receptor 1(BLT1)is a chemotactic G protein-coupled receptor expressed by leukocytes,such as granulocytes,macrophages,and activated T cells.Although there is growing evidence that BLT1 plays crucial roles in immune responses,its role in dendritic cells remains largely unknown.Here,we identified novel DC subsets defined by the expression of BLT1,namely,BLT1hi and BLT1lo DCs.We also found that BLT1hi and BLT1lo DCs differentially migrated toward LTB4 and CCL21,a lymph node-homing chemoattractant,respectively.By generating LTB4-producing enzyme LTA4H knockout mice and CD11c promoter-driven Cre recombinase-expressing BLT1 conditional knockout(BLT1 cKO)mice,we showed that the migration of BLT1hi DCs exacerbated allergic contact dermatitis.Comprehensive transcriptome analysis revealed that BLT1hi DCs preferentially induced Th1 differentiation by upregulating IL-12p35 expression,whereas BLT1lo DCs accelerated T cell proliferation by producing IL-2.Collectively,the data reveal an unexpected role for BLT1 as a novel DC subset marker and provide novel insights into the role of the LTB4-BLT1 axis in the spatiotemporal regulation of distinct DC subsets.

关键词： LTB4 BLT1 dendritic cells inflammation lipid mediator

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