Shigeaki Mizuno

Nihon University, Edo, Tōkyō, Japan

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Publications (19)51.38 Total impact

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    ABSTRACT: BACKGROUND: Prophylactic treatment for esophageal varices has been performed without adequate supporting evidence. We assessed the feasibility of prophylactic and follow-up treatment for high-risk esophageal varices in patients with hepatocellular carcinoma (HCC). METHODS: Patients with HCC were screened prospectively and followed up for esophageal varices and gastroduodenal ulceration. High-risk esophageal varices (huge F3 varices or intermediate F2 varices positive for red color signs) were treated prophylactically. Follow-up endoscopy was performed to assess the impact of prophylaxis and changes in varices at 1 week, 1 month, and 6 months after operation. If high-risk varices were found during follow-up, secondary prophylaxis was performed according to the same criteria. RESULTS: Among 251 patients with HCC, 81 (32.3 %) had esophageal varices on screening endoscopy. Prophylactic endoscopic treatment was required by 13 patients (1 with F3 varices and 12 with F2 varices positive for red color signs). Ten varices worsened, and 4 varices progressed to high-risk varices requiring endoscopic treatment. No F0 or F1 varices at screening endoscopy progressed to high-risk varices, and no bleeding event occurred during 6 months of preplanned follow-up. A preoperative platelet count of less than 10 × 10(4)/μL (odds ratio: 4.21, 95 % confidence interval 3.11-10.6; p < 0.001), the presence of splenomegaly (2.87, 2.16-21.8; p = 0.011), and an indocyanine green retention rate at 15 min of greater than 30 % (2.31, 1.88-24.6; p = 0.026) were independent predictors of worsening varices. CONCLUSIONS: Our protocol for prophylactic and follow-up treatment of high-risk esophageal varices was feasible in patients with HCC.
    Journal of Gastroenterology 06/2013; · 3.79 Impact Factor
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    ABSTRACT: The etiology of Cronkhite-Canada syndrome (CCS) remains unknown and many cases are refractory to treatment. Therefore, new therapies are urgently needed. Furthermore, a number of CCS cases with gastrointestinal carcinoma have been reported. Our patient had rapid onset of CCS and early development of colon carcinoma associated with adenomas. High anterior resection of the sigmoid colon and ileostomy were performed, and her symptoms and endoscopic and histological findings improved. Helicobacter pylori eradication was carried out 2 years later, surgical closure of an ileal fistula the following year. After 4 months, upper gastrointestinal endoscopy and colonoscopy showed that the CCS lesions had completely disappeared, and biopsies confirmed a normal stomach, duodenum, ileum and colon histologically. The patient has maintained remission for 2 years. The clinical course of this case, showing complete regression of CCS lesions following abdominal colectomy and H. pylori eradication, suggests the significance of H. pylori infection in the treatment of CCS.
    Case Reports in Gastroenterology 01/2013; 7(1):140-6.
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    ABSTRACT: To evaluate the influence of Helicobacter pylori and sex difference on peripheral platelet counts, dyspeptic patients without immunohaematologic disorders were evaluated. H. pylori infection was verified with the rapid urease test and serum anti-H. pylori IgG antibody. Platelet counts were analysed with a reference to H. pylori infection and sex difference. Among H. pylori-eradicated patients, changes in platelet counts were separately evaluated. Totally, 655 patients were enrolled: 340 patients were infected with H. pylori and 178 patients received eradication therapy, with a success rate of 88.2% (157/178). Females with H. pylori infection definitely manifested elevated platelet counts (infected vs. uninfected 244 ± 57 vs. 219 ± 54 × 10(9)/l; p < 0.0001). H. pylori eradication reduced peripheral platelets by 8 weeks, 5-6 months, 1, 2 and ≥3 years after eradication in females from 248 ± 54 to 237 ± 49, 237 ± 54, 229 ± 48, 238 ± 61 and 232 ± 50 × 10(9)/l (p = 0.0003, 0.0182, 0.0041, 0.0398 and 0.0289), respectively. In males, the reduction was verified by 8 weeks, 1 year and ≥3 years from 226 ± 52 to 217 ± 47, 214 ± 44 and 200 ± 49 × 10(9)/l (p = 0.0464, 0.0164 and 0.0016), respectively. In conclusion, H. pylori infection upregulates platelet counts mainly in females, and eradication reduced peripheral platelets in both sexes. Females appeared more susceptible to H. pylori infection than males with regard to upregulation of platelet counts.
    Acta Haematologica 07/2011; 126(3):172-5. · 0.89 Impact Factor
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    ABSTRACT: Helicobacter pylori eradication is becoming a first-line therapy against idiopathic thrombocytopenic purpura (ITP) and its long term efficacy has already been reported. In contrast, eradication therapy reduced peripheral platelets in non-ITP patients 8 weeks later. To confirm the long term efficacy of Helicobacter eradication on platelet counts in non-ITP patients, we evaluated changes in peripheral platelet counts in endoscopically diagnosed patients with Helicobacter infection. Endoscopically diagnosed patients with Helicobacter infection received eradication therapy using amoxicillin (1500 mg/day), clarithromycin (400 mg/day) and lansoprazole (60 mg/day). The changes in platelet counts after Helicobacter eradication were serially evaluated for as long as 3 years or more. In total, 294 patients were enrolled: 243 patients successfully received eradication therapy and 51 were unsuccessfully treated. As a whole, peripheral platelet counts significantly decreased after Helicobacter eradication, being reduced by more than 1.0 × 10⁹/l by 5-6 months, 1 year, 2 years and 3 years or more (from 24.2+/-5.6 to 23.1+/-5.0, 23.0+/-5.0, 22.1+/-4.5, 22.4+/-5.6, and 21.6+/-5.3 × 10⁹/l: p = <0.0001, <0.0001, 0.0001, 0.0052, and <0.0001, respectively). Helicobacter pylori eradication finally reduced peripheral platelet counts around 2.0 × 10⁹/l in non-ITP patients. There was a definite difference in platelet regulation by Helicobacter pylori between ITP and non-ITP patients. These bivalent effects, upregulation and downregulation, on the peripheral platelet induced by Helicibacter pylori infection appeared to originate from quite different mechanisms.
    Platelets 01/2010; 21(8):628-31. · 2.24 Impact Factor
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    ABSTRACT: To determine the anti-inflammatory activity of probiotic Bifidobacteria in Bifidobacteria-fermented milk (BFM) which is effective against active ulcerative colitis (UC) and exacerbations of UC, and to explore the immunoregulatory mechanisms. Peripheral blood mononuclear cells (PBMNC) from UC patients or HT-29 cells were co-cultured with heat-killed probiotic bacteria or culture supernatant of Bifidobacterium breve strain Yakult (BbrY) or Bifidobacterium bifidum strain Yakult (BbiY) to estimate the amount of IL-10 or IL-8 secreted. Both strains of probiotic Bifidobacteria contained in the BFM induced IL-10 production in PBMNC from UC patients, though BbrY was more effective than BbiY. Conditioned medium (CM) and DNA of both strains inhibited IL-8 secretion in HT-29 cells stimulated with TNF-alpha, whereas no such effect was observed with heat-killed bacteria. The inhibitory effect of CM derived from BbiY was greater than that of CM derived from BbrY. DNAs of the two strains had a comparable inhibitory activity against the secretion of IL-8. CM of BbiY induced a repression of IL-8 gene expression with a higher expression of IkappaB-zeta mRNA 4 h after culture of HT-29 cells compared to that in the absence of CM. Probiotic Bifidobacterium strains in BFM enhance IL-10 production in PBMNC and inhibit IL-8 secretion in intestinal epithelial cells, suggesting that BFM has anti-inflammatory effects against ulcerative colitis.
    World Journal of Gastroenterology 05/2008; 14(16):2511-6. · 2.55 Impact Factor
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    ABSTRACT: Schönlein-Henoch purpura (SHP) is a systemic condition characterized by purpura associated with leukocytoclastic vasculitis. SHP diagnosis is more difficult in infrequent cases where gastrointestinal (GI) symptoms precede purpura. This report examines 11 cases of SHP at our hospital with specific regard to the incidences and details of GI symptoms. The clinical manifestations and endoscopic findings were investigated for their utility in SHP diagnosis. Among the 11 cases, 3 showed GI symptoms prior to other manifestations. In terms of GI symptoms, abdominal pain was reported in all 11 cases, diarrhea in 4 cases, and bloody stools in 3 cases. Endoscopic findings were seen in the stomach in 7/10 cases, in the small intestine including the duodenum in 10/11 cases, and in the large intestine in 6/10 cases. The frequency of ulcer formation was significantly higher in the small intestine (including the duodenum) than in the stomach. Multiple specific erythematosus lesions were observed in the stomach and large intestine. Familiarity with characteristic endoscopic findings and careful observation of all GI findings are essential for diagnosing SHP in cases in which GI tract symptoms precede cutaneous findings.
    Digestion 02/2008; 77(3-4):236-41. · 1.94 Impact Factor
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    ABSTRACT: Discrepant outcomes of Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura have been reported. Here patients with dyspepsia and no other complications underwent gastroendoscopic examination and evaluation for Helicobacter pylori infection. Helicobacter pylori-infected patients with gastritis and gastric ulcer received eradication therapy: lansoprazole (60 mg/day), clarithromycin (400 mg/day), and amoxicillin (1500 mg/day) for 1 week. Lansoprazole 30 mg/day was administrated additional 7 weeks. Peripheral platelets were counted before treatment, 8 weeks after initiation of therapy, and at follow-up periods. Platelet counts in patients with both gastritis and gastric ulcer were evaluated with reference to the presence of Helicobacter pylori infection. Eighty-seven patients with gastritis and 35 of those with gastric ulcer underwent successful eradication therapy. Peripheral platelet counts in patients with gastritis decreased from 235+/-55 to 228+/-58 (10(3)/microL) (p=0.0337), and those with gastric ulcer decreased from 248+/-60 to 232+/-48 (10(3)/microL) (p=0.020) 8 weeks after initiation of therapy. Non-eradicated patients did not show such a tendency. Helicobacter pylori eradication reduced peripheral platelet counts in patients with gastritis and gastric ulcer. Amelioration of thrombocytopenia by eradicating Helicobacter pylori appears to involve mechanisms specific to idiopathic thrombocytopenic purpura.
    Platelets 03/2007; 18(1):52-5. · 2.24 Impact Factor
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    ABSTRACT: Impaired butyrate metabolism plays a part in ulcerative colitis (UC). To assess the usefulness of measuring butyrate metabolism as an indication of inflammatory activity, we investigated the rate of butyrate metabolism by breath test after administering [1-(13)C]-butyrate rectally to patients with UC. Thirty-eight UC patients (22 active, 16 quiescent) and 15 healthy controls were given [1-(13)C]-butyrate enemas. The (13)CO2 production rate was measured by breath test using an infrared spectrometric analyzer. The quantity of expired (13)CO2 was significantly lower in the active than in the quiescent UC and control groups. Cumulative (13)CO2 production at 240 min showed significant negative correlations with the clinical activity index (r=-0.65, p<0.0001), endoscopic activity index (r=-0.63, p=0.0001) and histology (r=-0.71, p<0.0001) in the active UC group. The (13)CO2 production rate was significantly increased in the quiescent stage as compared with the active stage in six UC patients, in whom clinical remission was achieved, in accordance with improvements in the clinical activity index, the endoscopic activity index, histology and fecal butyrate concentrations. Significant inverse correlations between the cumulative (13)CO2 production rate and these three parameters were seen in these six UC patients assessed in both the active and quiescent stages. Measurement of expired (13)CO2 after rectally administering [1-(13)C]-butyrate in active and quiescent UC appears to be a promising and reliable method for evaluating disease activity and metabolic changes associated with amelioration of inflammation.
    Scandinavian Journal of Gastroenterology 02/2007; 42(2):207-14. · 2.33 Impact Factor
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    ABSTRACT: Background Gastro-oesophageal flap valve (GEFV) grade correlated with endoscopic reflux oesophagitis (RE) prevalence.AimTo investigate relationships among gastro-oesophageal reflux disease (GERD) symptoms, RE and/or non-erosive reflux disease (NERD) and GEFV grades in subjects undergoing endoscopy.Methods We enrolled 1305 subjects from whom endoscopic results and the results of a self-administered questionnaire (QUEST) were available. Subjects were evaluated for GERD symptoms (QUEST score), GEFV grade, RE and gastric mucosal atrophy.ResultsTotal GERD prevalence, including symptomatic GERD (QUEST score ≥ 4) and/or RE, was 27%. RE grade and prevalence increased with GEFV grade. QUEST scores and GEFV grades showed a positive correlation. NERD prevalence was 14% and increased with GEFV grade, but the relationship was weaker than that between RE and GEFV. Comparing RE-negative subjects by GEFV grade, GERD symptoms were noted in 10%, 19%, 36% and 52% with GEFV grades I, II, III and IV, respectively. Neither type of gastric mucosal atrophy correlated with GEFV grade.Conclusions Total GERD, NERD and RE prevalences increased with GEFV grade. Subjects with high GEFV grades often complain of GERD symptoms, even without RE. Our findings suggest that endoscopic GEFV evaluation provides a useful clinical index for diagnosing GERD.
    Alimentary Pharmacology & Therapeutics Symposium Series 01/2007; 24:141-146.
  • Gastrointestinal Endoscopy - GASTROINTEST ENDOSCOP. 01/2007; 65(5).
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    ABSTRACT: Cyclo-oxygenase (COX)-2 overexpression is observed in various neoplasms and COX-2 inhibition has been attempted as prevention and/or therapy in these neoplasms. Carcinoid tumors are thought to arise from neuroendocrine cells and originate mainly in the gastrointestinal tract. Cyclo-oxygenase-2 is reportedly expressed in neuroendocrine cells of normal colorectal mucosa. The role of COX in carcinoids has not previously been investigated. The aim of the present paper was to clarify the expression of COX-1 and -2, and their role in human gastrointestinal carcinoids. Expression of COX-1 and -2 was studied immunohistochemically in 38 gastrointestinal carcinoids. Five bronchopulmonary and seven metastatic carcinoids were also examined, for comparison with gastrointestinal carcinoids. The immunohistochemical score (IHS) was calculated from staining intensity and immunoreactive cell population, and ranked according to four grades (negative to strong). Cyclo-oxygenase-2 was expressed in all gastrointestinal carcinoids (weak, 1; moderate, 13; strong, 24) and bronchopulmonary carcinoids (weak, 1; moderate, 4), as well as their metastases (moderate, 3; strong, 4). The IHS of COX-2 in larger tumors was significantly lower than that in smaller tumors. However, the IHS of COX-2 at the advancing tumor edge was significantly higher than that at the centers of tumors >or=10 mm in size. Faint COX-1 expression was detected in only one duodenal, one rectal and four bronchopulmonary carcinoids. Enhanced COX-2 expression was observed in gastrointestinal as well as bronchopulmonary carcinoids and their metastases, especially at the advancing edges of the tumors. Cyclo-oxygenase-2 may play a role in carcinoid progression.
    Journal of Gastroenterology and Hepatology 08/2006; 21(8):1313-9. · 3.33 Impact Factor
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    ABSTRACT: Intraluminally administered peppermint oil (PO) is reportedly a safe and useful antispasmodic for gastroscopy, colonoscopy and double-contrast barium enema. The aim of this study was to examine the efficacy of oral PO for double-contrast barium meal examination (DCBM) without other antispasmodics. Two hundred and five randomly chosen subjects (PO group) and 215 sex- and age-matched controls were enrolled. All participants underwent DCBM. The PO group was orally administered PO and a barium suspension mixture at the start of DCBM. Radiographs were blindly evaluated for spasm and overlapping with barium-filled duodenal loops (scored 0-3, indicating none to severe). The quality of barium coating of the mucosa and overall diagnostic quality (scored 0-3, indicating not acceptable to excellent) were also evaluated. There was no significant difference in subject acceptance between PO group and controls, and no adverse effects in either group. Scores for spasm at the esophagus, lower stomach and duodenal bulb were significantly lower in the PO than in the control group (P < 0.001). Scores for overlapping at the lower stomach and duodenal bulb were significantly lower in the PO than in the control group (P < 0.05, P < 0.01, respectively). Scores for overall diagnostic quality at the esophagus, lower stomach and duodenal bulb were significantly higher in the PO than in the control group (P < 0.001). Oral PO reduces spasm of the esophagus, lower stomach and duodenal bulb, inhibits barium flow to the distal duodenum, and improves diagnostic quality without other antispasmodics. Oral PO is a safe, easy to use and effective antispasmodic for DCBM.
    Journal of Gastroenterology and Hepatology 08/2006; 21(8):1297-301. · 3.33 Impact Factor
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    ABSTRACT: Background Gastro-oesophageal flap valve (GEFV) grade correlated with endoscopic reflux oesophagitis (RE) prevalence.AimTo investigate relationships among gastro-oesophageal reflux disease (GERD) symptoms, RE and/or non-erosive reflux disease (NERD) and GEFV grades in subjects undergoing endoscopy.Methods We enrolled 1305 subjects from whom endoscopic results and the results of a self-administered questionnaire (QUEST) were available. Subjects were evaluated for GERD symptoms (QUEST score), GEFV grade, RE and gastric mucosal atrophy.ResultsTotal GERD prevalence, including symptomatic GERD (QUEST score ≥ 4) and/or RE, was 27%. RE grade and prevalence increased with GEFV grade. QUEST scores and GEFV grades showed a positive correlation. NERD prevalence was 14% and increased with GEFV grade, but the relationship was weaker than that between RE and GEFV. Comparing RE-negative subjects by GEFV grade, GERD symptoms were noted in 10%, 19%, 36% and 52% with GEFV grades I, II, III and IV, respectively. Neither type of gastric mucosal atrophy correlated with GEFV grade.Conclusions Total GERD, NERD and RE prevalences increased with GEFV grade. Subjects with high GEFV grades often complain of GERD symptoms, even without RE. Our findings suggest that endoscopic GEFV evaluation provides a useful clinical index for diagnosing GERD.
    Alimentary Pharmacology & Therapeutics Symposium Series 06/2006; 2(1):141 - 146.
  • Gastrointestinal Endoscopy - GASTROINTEST ENDOSCOP. 01/2006; 63(5).
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    ABSTRACT: Probiotics are efficacious for treating and maintaining remission of ulcerative colitis. To conduct a randomized placebo-controlled trial of bifidobacteria-fermented milk supplementation as a dietary adjunct in treating active ulcerative colitis. Twenty patients with mild to moderate, active, ulcerative colitis randomly received 100 mL/day of bifidobacteria-fermented milk or placebo for 12 weeks with conventional treatment. Clinical and endoscopic activity indices and histological scores were similar in the two groups before treatment. Although improvements were significant in both groups, the clinical activity index was significantly lower in the bifidobacteria-fermented milk than in the placebo group after treatment. The post-treatment endoscopic activity index and histological score were significantly reduced in the bifidobacteria-fermented milk, but not the placebo group. Increases in faecal butyrate, propionate and short-chain fatty acid concentrations were significant in the bifidobacteria-fermented milk, but not the placebo group. No adverse effects were observed in either group. Supplementation with this bifidobacteria-fermented milk product is safe and more effective than conventional treatment alone, suggesting possible beneficial effects in managing active ulcerative colitis. This is a pilot study and further larger studies are required to confirm the result these preliminary results.
    Alimentary Pharmacology & Therapeutics 12/2004; 20(10):1133-41. · 4.55 Impact Factor
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    ABSTRACT: Research on gastric lesions developing in response to stress is essential to elucidating the pathogenesis of these lesions as well as the interplay with other factors, including Helicobacter pylori infection and non-steroidal anti-inflammatory drug use. Genes expressed individually or in sets, such as heat shock proteins, growth factors, proto-oncogenes and cyclooxygenases, have been investigated in the stomach. However, gene expression in the stomach after stress exposure have not yet been comprehensively examined. We investigated the gastric gene expression profile in response to stress. A high-density oligonucleotide array, representing approximately 850 genes, was used to determine gene expression changes in the stomachs of water immersion-restraint stress (WIRS) rats. Fifty-eight genes including expressed sequence tag (EST) genes were upregulated more than twofold in the 30 min-WIRS rat stomach as compared with the control. Concomitantly, five genes were downregulated. Numbers of up- or downregulated genes decreased rapidly at 1 and 2 h of WIRS. Altered gene expression of heat shock proteins, cell cycle regulators, proto-oncogenes and metabolic enzymes were recognized. Several of these genes, including p38 mitogen-activated protein kinase, did not reportedly show gastric expression changes in response to stress. These results suggest that, in addition to the previously identified stress-induced genes, expression of a number of other genes in the stomach is also involved in stress response.
    Journal of Gastroenterology and Hepatology 12/2004; 19(11):1264-9. · 3.33 Impact Factor
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    ABSTRACT: Whether or not eradicating Helicobacter pylori worsens reflux esophagitis remains controversial. We investigated the relationship between gastroesophageal flap valve grading and endoscopic reflux esophagitis (in patients with peptic ulcer and gastritis) before and after H. pylori eradication in a case controlled study. Whether endoscopic assessment of the gastroesophageal flap valve allows prediction of endoscopic reflux esophagitis development or exacerbation was also assessed. A total of 220 patients with peptic ulcer or chronic gastritis, who received H. pylori eradication therapy, were followed for at least 6 months (range, 6-34 months) for endoscopic changes. Another 88 age- and disease-matched H. pylori-positive controls, without eradication therapy, were also enrolled. Gastroesophageal flap valve grade (I-IV) was assessed using the Hill classification. Endoscopic reflux esophagitis incidence was significantly (p < .01) higher in abnormal gastroesophageal flap valve (grades III and IV) than in normal gastroesophageal flap valve (grades I and II) cases in both H. pylori eradication and control groups. The rate of new endoscopic reflux esophagitis after eradication was significantly (p < .01) higher in the abnormal than in the normal gastroesophageal flap valve group (54.5% vs. 9.1%). By contrast, the endoscopic reflux esophagitis exacerbation rate in patients with endoscopic reflux esophagitis before eradication was low (4.5%) and endoscopic reflux esophagitis improvement was observed in 40.9% of these patients. These results suggest gastroesophageal flap valve grading by endoscopy to be useful for predicting the risk of newly developing endoscopic reflux esophagitis after H. pylori eradication, in addition to predicting the presence of endoscopic reflux esophagitis.
    Helicobacter 03/2004; 9(1):1-8. · 3.51 Impact Factor
  • Gastroenterology 01/2003; 124(4). · 12.82 Impact Factor
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    ABSTRACT: We previously demonstrated the circadian variation of water-immersion restraint stress (WRS)-induced gastric mucosal lesions in rats. To investigate the roles of melatonin and prostaglandin in the gastric mucosa in circadian modulation of WRS. Fasted rats were subjected to 4-h WRS during both the diurnal and nocturnal phases of a light/dark cycle. Mucosal lesions, serum melatonin concentrations, mucosal generation of prostaglandin E2 (PGE2) and mucosal gene expressions of cyclooxygenase (COX)-1 and -2 were evaluated. Lesion area after 4-h stress during the dark phase was significantly smaller than that in light-phase controls. Serum melatonin concentration in control rats during the light phase was significantly increased 4 h after WRS, but PGE2 generation was decreased by 48% as compared to that in intact mucosa before stress. In the dark phase, melatonin concentration after 4-h WRS was significantly depressed as compared with the control level at the corresponding time. PGE2 concentrations after 4-h WRS in the dark phase were not decreased compared with the control level at the corresponding time, although PGE2 level was significantly lower than that in light-phase controls. Expression of COX-1 and COX-2 mRNA was detected after exposure to stress in both the light and dark phases. These results suggest that circadian rhythm has an important role in the formation of stress-induced gastric mucosal lesions in rats. The circadian rhythm of melatonin responses and PGE2 generation may contribute to nocturnal/diurnal rhythmicity of gastric mucosal defences between day and night.
    Alimentary Pharmacology & Therapeutics 05/2002; 16 Suppl 2:29-34. · 4.55 Impact Factor