Serum Gastrin Levels Research Articles

Shuidouchi (Fermented Soybean) Fermented in Different Vessels Attenuates HCl/Ethanol-Induced Gastric Mucosal Injury.

Shuidouchi (Natto) is a fermented soy product showing in vivo gastric injury preventive effects. The treatment effects of Shuidouchi fermented in different vessels on HCl/ethanol-induced gastric mucosal injury mice through their antioxidant effect was determined. Shuidouchi contained isoflavones (daidzein and genistein), and GVFS (glass vessel fermented Shuidouchi) had the highest isoflavone levels among Shuidouchi samples fermented in different vessels. After treatment with GVFS, the gastric mucosal injury was reduced as compared to the control mice. The gastric secretion volume (0.47 mL) and pH of gastric juice (3.1) of GVFS treated gastric mucosal injury mice were close to those of ranitidine-treated mice and normal mice. Shuidouchi could decrease serum motilin (MTL), gastrin (Gas) level and increase somatostatin (SS), vasoactive intestinal peptide (VIP) level, and GVFS showed the strongest effects. GVFS showed lower IL-6, IL-12, TNF-α and IFN-γ cytokine levels than other vessel fermented Shuidouchi samples, and these levels were higher than those of ranitidine-treated mice and normal mice. GVFS also had higher superoxide dismutase (SOD), nitric oxide (NO) and malonaldehyde (MDA) contents in gastric tissues than other Shuidouchi samples. Shuidouchi could raise IκB-α, EGF, EGFR, nNOS, eNOS, Mn-SOD, Gu/Zn-SOD, CAT mRNA expressions and reduce NF-κB, COX-2, iNOS expressions as compared to the control mice. GVFS showed the best treatment effects for gastric mucosal injuries, suggesting that glass vessels could be used for Shuidouchi fermentation in functional food manufacturing.

Efficacy of Gum Chewing on Bowel Movement After Open Colectomy for Left-Sided Colorectal Cancer

Prolonged intestinal paralysis can be a problem after gastrointestinal surgery. Several systematic reviews and meta-analyses have suggested the efficacy of gum chewing for the prevention of postoperative ileus. The purpose of this study was to examine the efficacy of gum chewing for the recovery of bowel function after surgery for left-sided colorectal cancer and to determine the physiological mechanism underlying the effect of gum chewing on bowel function. This was a single-center, placebo-controlled, parallel-group, prospective randomized trial. The study was conducted at a general hospital in Japan. Forty-eight patients with left-sided colorectal cancer were included. The patients were randomly assigned to a gum group (N = 25) and a control group (N = 23). Four patients in the gum group and 1 in the control group were subsequently excluded because of difficulties in continuing the trial, resulting in the analysis of 21 and 22 patients in the respective groups. Patients in the gum group chewed commercial gum 3 times a day for ≥5 minutes each time from postoperative day 1 to the first day of food intake. The time to first flatus and first bowel movement after the operation were recorded, and the colonic transit time was measured. Gut hormones (gastrin, des-acyl ghrelin, motilin, and serotonin) were measured preoperatively, perioperatively, and on postoperative days 1, 3, 5, 7, and 10. Gum chewing did not significantly shorten the time to the first flatus (53 ± 2 vs. 49 ± 26 hours; p = 0.481; gum vs. control group), time to first bowel movement (94 ± 44 vs. 109 ± 34 hours; p = 0.234), or the colonic transit time (88 ± 28 vs. 88 ± 21 hours; p = 0.968). However, gum chewing significantly increased the serum levels of des-acyl ghrelin and gastrin. The main limitation was a greater rate of complications than anticipated, which limited the significance of the findings. Gum chewing changed the serum levels of des-acyl ghrelin and gastrin, but we were unable to demonstrate an effect on the recovery of bowel function.

Ulcer healing and mechanism(s) of action involved in the gastroprotective activity of fractions obtained from Syngonanthus arthrotrichus and Syngonanthus bisulcatus.

BackgroundSyngonanthus arthrotrichus and Syngonanthus bisulcatus, currently known for Comanthera aciphylla (Bong.) L.R.Parra & Giul. and Comanthera bisulcata (Koern.) L.R. Parra & Giul, popularly known in Brazil as “sempre-vivas,” are plants from the family Eriocaulaceae. They are found in the states of Minas Gerais and Bahia. The species are known to be rich in flavonoids to which their gastroprotective activity has been attributed. In this research, experimental protocols were performed to elucidate the associated mechanisms of action.MethodsThe activity was evaluated using induced gastric ulcer models (acetic acid and ethanol-induced gastric lesions in NEM or L-NAME pre-treated mice, and by ischemia/reperfusion). Antioxidant enzymes, serum somatostatin, and gastrin were also evaluated.ResultsIn chronic gastric ulcers, a single daily oral dose of Sa-FRF or Sb-FRF (100 mg/kg body wt.) for 14 consecutive days accelerated ulcer healing to an extent similar to that seen with an equal dose of cimetidine. The pre-treatment of mice with NEM (N-ethylmaleimide) or L-NAME (N-nitro-L-arginine) abolished the protective activity of Sa-FRF, Sa-FDF, Sb-FDF and Sb-FRF or Sa-FRF and Sb-FRF, respectively, which indicates that antioxidant compounds and nitric oxide synthase activity are involved in the gastroprotective. Sa-FRF and Sb-FRF (100 mg/kg p.o) protected the gastric mucosa against ulceration that was induced by ischemia/reperfusion (72 and 76 %, respectively). It also decreased lipid peroxidation and restored total thiols in the gastric wall of mice that had been treated with ethanol. When administered to rats submitted to ethanol-induced gastric lesions, Sa-FRF and Sb-FRF (100 mg/kg, p.o.) increased the somatostatin serum levels, while the gastrin serum levels were proportionally decreased.ConclusionsThe results indicate significant healing effects and gastroprotective activity for the Sa-FRF and Sb-FRF, which probably involves the participation of SH groups, nitric oxide (NO), the antioxidant system, somatostatin, and gastrin. All are integral parts of the gastrointestinal mucosa’s cytoprotective mechanisms against aggressive factors.

An Atypical Endoscopic Presentation of Zollinger-Ellison Syndrome

Zollinger-Ellison syndrome (ZES) is a rare condition characterized by gastrointestinal (GI) ulceration due to a gastrin-secreting tumor and hyper-secretion of gastric acid. Recent studies have shown thickened gastric folds and duodenal ulcers as the two most common endoscopic findings occurring in up to 80.3% and 15.3% of patients. We present a case of ZES with atypical endoscopic findings. A 52 year-old female with type 2 diabetes and hypertension presented with peri-umbilical pain. She described 7 out of 10, dull, aching pain with brown, mucus-like emesis. In the emergency department (ED), she was diagnosed with diverticulitis, prescribed antibiotics, and discharged. Due to severe nausea she did not finish the medications. She returned to the ED in 5 days with worsening pain. A CT abdomen/pelvis with contrast showed a 6.5x4.6x5.5 cm lobular enhancing mass lateral to the 4th part of the duodenum with multiple enlarged lymph nodes and wall thickening of the duodenum, suspicious for malignancy. Gastroenterology was consulted. Push enteroscopy showed severe LA class D esophagitis, and a normal stomach. The proximal duodenum had erosions and small clean based ulcers. Distal to the duodenal bulb, circumferential ulcers were seen with overlying eschar on each duodenal and proximal jejunal fold. There was a high suspicion for ZES given the CT and endoscopic findings. Fasting serum gastrin level was 3804 pg/mL (normal).Figure 1Figure 2Figure 3GI ulcerations are common endoscopic findings in ZES with 91-93% having peptic or duodenal ulcers when diagnosed. ZES is usually characterized by solitary ulcers < 1cm in diameter, with the majority in the 1st part of the duodenum. However, it is not uncommon for ulcers to be located in the distal duodenum or jejunum. Circumferential ulcers of the small bowel are often related to non-steroidal anti-inflammatory medications, or thiazide potassium-chloride use. In this case of Zollinger-Ellison we found multiple, circumferential ulcers extending from the duodenal bulb to the jejunum, which has not been previously reported endoscopically.

Effect of H. pylori infection on gastrin, ghrelin, motilin, and gastroesophageal reflux.

To evaluate the occurrence of gastroesophageal reflux and possible mechanisms in Helicobacter pylori infection. Symptoms of H. pylori-infected children, their total gastroesophageal reflux episodes, acid exposure percentage, gastrin, ghrelin, and motilin levels were evaluated before and after H. pylori eradication. Forty-two H. pylori-infected children were eligible for this study. Acid exposure % and total reflux episodes before and after H. pylori eradication were 10.2%±14.8% vs. 7.71%±5.0% and 94.7%±102.1% vs. 64.6%±55.0%, respectively (p=0.28, p=0.082). There was an insignificant change in the serum gastrin (93.4±153.8 pmol/L vs. 1.28±149.4 pmol/L, p=0.67), ghrelin (7.69±197.5 pg/mL vs. 8.36±299.5 pg/mL, p=0.274), and motilin (75.1±81.2 pg/mL vs. 97.2±80.5 pg/mL, p=0.206) levels after eradication. Gastrin and ghrelin levels were negatively correlated after H. pylori eradication (r=-0.38, p=0.031). There was no association between gastroesophageal reflux episodes and gastrin, ghrelin, and motilin levels (r=0.25 and p=0.11; r= 0.24 and p=0.13; r=-0.23 and p=0.14, respectively). H. pylori infection is neither protective nor harmful in the gastroesophageal reflux. Neither ghrelin nor motilin levels was associated with gastroesophageal reflux. None of gastrin, ghrelin, and motilin levels was affected by H. pylori infection. There is an inverse association between gastrin and ghrelin levels after H. pylori eradication.

Helicobacter pylori, HIV and Gastric Hypochlorhydria in the Malawian Population.

BackgroundHIV and Helicobacter pylori are common chronic infections in sub-Saharan Africa. Both conditions can predispose to gastric hypochlorhydria that may be a risk factor for enteric infections and reduced drug absorption. We have investigated to what extent HIV and H. pylori infections are associated with hypochlorhydria in a Malawian cohort of patients undergoing endoscopy.Methods104 sequential symptomatic adults referred for gastroscopy at Queen Elizabeth Central Hospital, Blantyre, Malawi, had blood taken for rapid HIV testing and fasting serum gastrin analysis. Gastric fluid was aspirated for pH testing, and gastric biopsies were taken.ResultsAfter 9/104 HIV-infected patients who were already established on anti-retroviral therapy were excluded, 17/95 (25.0%) were seropositive for untreated HIV, and 68/95 (71.6%) patients were H. pylori positive by histology. Hypochlorhydria (fasting gastric pH>4.0) was present in 55.8% (53/95) of patients. H. pylori infection was significantly associated with hypochlorhydria (OR 2.91, [1.02-7.75], p=0.046). While single infection with HIV was not significantly independently associated with hypochlorhydria. H. pylori and HIV co-infection was more strongly associated with hypochlorhydria (OR 6.25, [1.33-29.43], p=0.020) than either infection alone, suggesting an additive effect of co-infection. HIV infection was associated with higher serum gastrin levels (91.3pM vs. 53.1pM, p=0.040), while H. pylori infection was not (63.1pM vs. 55.1pM, p=0.610). Irrespective of H. pylori and HIV status, most patients (>90%) exhibited pangastritis. Only three patients had histological evidence of gastric atrophy, of which only one was HIV-infected.Conclusion H. pylori infection was associated with fasting hypochlorhydria, while HIV was not independently associated. HIV and H. pylori co-infection, however, was more strongly associated with hypochlorhydria than H. pylori infection alone. The mechanism of this apparent additive effect between HIV and H. pylori remains unclear, but appears to be related to chronic pangastritis rather than gastric atrophy, and associated with hypergastrinaemia in HIV-infected individuals.

Systematic review: the effects of long-term proton pump inhibitor use on serum gastrin levels and gastric histology.

Proton pump inhibitors (PPIs) have a well-established safety profile. However, concerns have been raised about a potential relationship between PPI-induced hypergastrinaemia and the development of enterochromaffin-like (ECL) cell hyperplasia, neuroendocrine tumours and gastric cancer during long-term therapy. To review the effects of long-term PPI use on serum gastrin levels and gastric histopathology. A systematic literature search was conducted in PubMed on 21 April 2015 to identify studies reporting the effects of long-term (defined as >3 years) PPI use on gastrin levels and gastric histopathology. A total of 16 studies (1920 patients) met the inclusion criteria. During long-term PPI therapy, mean gastrin levels rose to one to three times the upper limit of the normal range (~100 pg/mL), and an increased prevalence of ECL cell hyperplasia was observed (+7.8-52.0%). Helicobacter pylori-positive patients had a significantly increased risk of developing ECL linear/micronodular hyperplasia compared with H. pylori-negative patients [OR: 2.45 (95% CI: 1.47-4.10), P = 0.0006]; however, no evidence of neoplastic changes was found. The risk of corpus atrophy was markedly higher in H. pylori-positive patients than in H. pylori-negative patients [OR: 11.45 (95% CI: 6.25-20.99), P < 0.00001]. Not a single case of gastric adenocarcinoma was found. Long-term PPI therapy induced moderate hypergastrinaemia in most patients and an increased prevalence of ECL cell hyperplasia. H. pylori-positive patients receiving long-term PPI therapy were exposed to a higher risk of corpus atrophy than H. pylori-negative patients. No neuroendocrine tumours or gastric cancers were found.

PWE-189 Helicobacter Pylori, HIV and Gastric Hypochlorhydria in the malawian population

<h3>Introduction</h3> HIV and Helicobacter pylori are common chronic infections in sub-Saharan Africa. Both conditions can predispose to gastric hypochlorhydria that may be a risk factor for enteric infections and reduced drug absorption. We have investigated to what extent HIV and H. pylori infections are associated with hypochlorhydria in a Malawian cohort of patients undergoing endoscopy. <h3>Method</h3> 104 sequential symptomatic adults referred for gastroscopy at Queen Elizabeth Central Hospital, Blantyre, Malawi, had blood taken for rapid HIV testing and fasting serum gastrin analysis. Gastric fluid was aspirated for pH testing, and gastric biopsies were taken. <h3>Results</h3> After 9/104 HIV-infected patients who were already established on antiretroviral therapy were excluded, 17/95 (25.0%) were seropositive for untreated HIV, and 68/95 (71.6%) patients were H. pylori positive by histology. Hypochlorhydria (fasting gastric pH &gt;4.0) was present in 55.8% (53/95) of patients. H. pylori infection was significantly associated with hypochlorhydria (OR 2.91, [1.02–7.75], p = 0.046). While single infection with HIV was not significantly independently associated with hypochlorhydria. H. pylori and HIV co-infection was more strongly associated with hypochlorhydria (OR 6.25, [1.33–29.43], p = 0.020) than either infection alone, suggesting an additive effect of co-infection. HIV infection was associated with higher serum gastrin levels (91.3pM vs. 53.1pM, p = 0.040), while H. pylori infection was not (63.1pM vs. 55.1pM, p = 0.610). Irrespective of H. pylori and HIV status, most patients (&gt;90%) exhibited pangastritis. Only three patients had histological evidence of gastric atrophy, of which only one was HIV-infected. <h3>Conclusion</h3> H. pylori infection was associated with fasting hypochlorhydria, while HIV was not independently associated. HIV and H. pylori co-infection, however, was more strongly associated with hypochlorhydria than H. pylori infection alone. The mechanism of this apparent additive effect between HIV and H. pylori remains unclear, but appears to be related to chronic pangastritis rather than gastric atrophy, and associated with hypergastrinaemia in HIV-infected individuals. <h3>Disclosure of interest</h3> None Declared.

Flavonoid Glycosides of Polygonum capitatum Protect against Inflammation Associated with Helicobacter pylori Infection

The antibacterial and anti-inflammatory activities, and protective effects of extracts (flavonoid glycosides) of Polygonum capitatum were investigated to detect the evidence for the utilization of the herb in the clinical therapy of gastritis caused by H. pylori. A mouse gastritis model was established using H. pylori. According to treating methods, model mice were random assigned into a model group (MG group), a triple antibiotics group (TG group, clarithromycin, omeprazole and amoxicillin), low/middle/high concentrations of flavonoid glycosides groups (LF, MF and HF groups) and low/middle/high concentrations of flavonoid glycosides and amoxicillin groups (LFA, MFA and HFA groups). A group with pathogen-free mice was regarded as a control group (CG group). The eradicate rates of H. pylori were 100%, 93%, 89% in TG, MFA and HF groups. The serum levels of IFN-gamma and gastrin were higher in a MG group than those from all other groups (P < 0.05). The serum levels of IFN-gamma and gastrin were reduced significantly in LF, MF and HF groups (P < 0.05) while little changes were observed in LFA, MFA and HFA groups. In contrast, the serum levels of IL-4 were lower and higher in MG and CG groups compared with other groups (P<0.05). The serum levels of IL-4 were increased significantly in LF, MF and HF groups (P < 0.05) while little changes were found in LFA, MFA and HFA groups. According to pathological scores, flavonoid glycosides therapy showed better protection for gastric injuries than the combination of flavonoid glycoside and amoxicillin (P < 0.05). The results suggested that flavonoid glycoside has repairing functions for gastric injuries. The results suggest that the plant can treat gastritis and protect against gastric injuries. The flavonoid glycosides from Polygonum capitatum should be developed as a potential drug for the therapy of gastritis caused by H. pylori.

Therapeutic effects of Lactobacillus casei Qian treatment in activated carbon-induced constipated mice.

In the present study, the therapeutic effects of Lactobacillus casei Qian (LC-Qian), the key microorganism in Tibetan yak yoghurt, on activated carbon-induced constipation were determined in vivo. ICR mice were treated with LC-Qian for nine days by oral administration. The body weight, defecation status, gastrointestinal transit and defecation time of mice were assessed, and the serum levels of motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) were further evaluated. Bisacodyl was used as the positive control. The time until the first black stool defecation following carbon intake of the normal, control, 100 mg/kg bisacodyl-treated, Lactobacillus bulgaricus (LB)-treated, LC-Qian (L)-and LC-Qian (H)-treated mice was 93, 231, 121, 194, 172 and 157 min, respectively. Following treatment with LC-Qian, the gastrointestinal transit was increased to 52.4% [LC-Qian (L)] and 65.8% [LC-Qian (H)], while that in the group treated with the common lactic acid bacteria of LB was 40.3%. The MTL, Gas, ET, AChE, SP and VIP serum levels were significantly increased and levels of SS were reduced in mice following LC-Qian treatment compared with those in the control mice (P<0.05). Reverse transcription quantitative polymerase chain reaction indicated that LC-Qian raised the c-Kit, GDNF as well as SCF mRNA expression levels and reduced the TRPV1 and NOS expression levels in tissue of the small intestine in mice. These results suggested that lactic acid bacteria prevent constipation in mice, among which LC-Qian was the most effective.

Clinical study of modified Xiaochengqi decoction in the treatment of gastroparesis syndrome

Objective To evaluate the efficacy of modified Xiaochengqi decoction in treatment of gastroparesis syndrome (GS). Methods A total of 81 patients with GS from 2010 July to 2013 July in HuiZhou Municipal Central Hospital were selected and randomly recruited into a control group and a treatment group. The control group was treated with domperidone, 15-30 min before the meal, while the treatment group was additionally treated with modified Xiaochengqi decoction on the basis of the control group. Both groups were treated for 4 weeks. The clinical curative effect, and the symptoms in both groups were observed. The serum motilin and gastrin concentration were measured by radio-immunity, the preprandial and postprandial electrogastrography was performed. Results The total effective rate in the treatment group was significantly higher than that in the control group (72.5% vs. 31.7%; χ2=11.911, P=0.000). The serum levels of motilin (treatment group: 532.8±16.7 ng/L vs. 355.2±14.3 ng/L, t=51.089, P=0.000; control group: 505.1 ± 21.3 ng/L vs. 372.9 ± 18.4 ng/L, t=30.074, P=0.000) and gastrin (treatment group: 69.8 ± 15.3 ng/L vs. 54.3 ± 13.8 ng/L, t=4.758, P=0.000; control group: 62.6 ± 14.2 ng/L vs. 53.4 ± 12.3 ng/L, t=3.136, P=0.002) were significantly reduced, and their decrease in the treatment group were greater than those in the control group (t values were 6.503, 2.196, all P<0.05). After the treatment, the dominant power (preprandial period: 84.5 ± 14.8 μV vs. 72.3 ± 15.0 μV, t=3.684, P＜0.01; postprandial period: 100.5 ± 17.3 μV vs. 89.3 ± 15.9 μV, t=5.713, P=0.000) and dominant frequency (preprandial period: 4.3 ± 0.4 cpm vs. 3.9 ± 0.2 cpm, t=3.035, P=0.000; postprandial period: 4.7 ± 0.5 cpm vs. 4.4 ± 0.5 cpm, t=2.700, P=0.000) were significantly higher, while the percentage of bradygastria (preprandial period: 50.6% ± 16.6% vs. 60.1% ± 16.3%, t=2.599, P=0.000；postprandial period: 36.6% ± 14.8% vs. 57.4% ± 15.3%, t=6.217, P=0.000) was significantly lower in the treatment group compared with the control group at preprandial and postprandial periods. Conclusion Xiaochengqi decoction can obviously promote the gastric motility, and reduce the serum levels of motilin and gastrin in patients with GS. Key words: Gastroparesis; Xiao Cheng Qi Tang; Treatment outcome

Su1128 Evaluating Gastric Cancer Risk by Using Serum Anti-Helicobacter pylori Antibodies and Serum Pepsinogen, Based on the ABC System, As a Mass Screening Tool for Gastric Cancer

Background and Aim: combined panel of serum anti-Helicobacter pylori antibodies and serum pepsinogen (PG) levels (referred to as the system) is effective in evaluating an individual's risk of gastric cancer (GC). In the ABC system, patients who are H. pyloriseronegative and have high PG levels are classified as A; these patients are thought to have a very low risk of developing GC. However, GC cases are occasionally observed in this group, and the most common cause of this discrepancy is the inclusion of subjects with current or past H. pylori infection in Group (the A group). In our study, we aimed to clarify the difference in the clinicopathological features of the A and A groups. Subjects and Methods: total of 1,207 patients who were evaluated for serum anti-H. pylori antibodies and serum PG levels were enrolled in our study. We classified them to according to the ABC system, and 200 patients with gastric biopsy specimens were included in Group for analysis (103 men; mean age, 54.8 years). We used the histological assessments to group patients into the true group (no histological gastritis) and the pseudo group (histologically positive gastritis). Histological gastritis of the antrum and corpus was diagnosed based on atrophy, chronic inflammation, and intestinal metaplasia according to the updated Sydney system. In addition, we evaluated the two groups' serum gastrin levels. Patients with a history of previous H. pylori eradication therapy were excluded. All results are expressed as mean ± standard deviation. Results: Among the Group patients, 19% (38 cases) of patients were pseudo and 81% (162 cases) of patients were true A. Based on the histological evaluation, most pseudo patients had moderate atrophy, mononuclear cells infiltration, and intestinal metaplasia. Based on the endoscopic diagnosis, 15 of 38 patients (39.5%) in the pseudo group had GC, whereas only 1 patient (0.6%) had GC in the true group. The pseudo group had a significantly lower mean PG I/II ratio (5.32 ± 2.05 vs. 6.26 ± 1.85, P < 0.01) and significantly higher gastrin level (175.0 ± 155 pg/ml vs. 120.2 ± 111 pg/ml, P < 0.01) compared to the true group. Conclusions: Our results indicate that the pseudo patients in Group were at risk of developing GC, and a combination of serum markers (pepsinogen and gastrin) and histological assessment was useful for detecting cases of GC within the pseudo group.

Endoscopic and histopathologic gastric changes in chronic users of proton-pump inhibitors.

Proton-pump inhibitors have been used for at least two decades. They are among the most commonly sold drugs in the world. However, some controversy remains about the indications for their use and the consequences of their prolonged use. To evaluate and compare the endoscopic and histopathologic gastric changes in chronic users of proton-pump inhibitors to changes in non-users. A prospective study performed at a tertiary Public Hospital involving 105 patients undergoing upper-gastrointestinal endoscopy. Subjects included 81 proton-pump inhibitor users and 24 non-users (control group). Biopsies of the antral-type mucosa, the antral-fundic transition, and the fundus were evaluated by the Sydney System. The presence of erosion or ulceration, lymphatic follicles, reactive gastropathy, and polypoid or epithelial hyperplasia was also determined. Serum levels of gastrin were measured. We found two polyps, one in each group, both of which were negative for Helicobacter pylori. There were two cases of parietal cell hyperplasia in users of proton-pump inhibitors. Gastrin was elevated in 28 users of proton-pump inhibitors and in four members of the control group. We did not find statistically significant differences in the endoscopic or histopathologic findings between the two groups. Chronic use of proton-pump inhibitors for the duration examined was not associated with significant gastric changes. An interesting finding was that the 4 chronic users of proton-pump inhibitors who had serum gastrin levels above 500 pg/mL also had positive serology for Chagas disease.

Serum gastrin levels in different stages of distal gastric carcinogenesis: is there a role for serum gastrin in tumor growth?

Elevated levels of serum gastrin (SG) have been associated with tumorigenic effects in a number of gastrointestinal cancers. We decided to investigate the relationship between SG and gastric epithelial lesions. A total of 90 patients with gastric epithelial lesions (hyperplastic polyp, 12; adenoma, 41; early gastric cancer, 29; advanced gastric cancer, 8) were enrolled as the case group and 79 patients without epithelial lesions were enrolled as the control group. Serum gastrin levels were significantly different between the case and control groups (p<0.001). A high SG level (>80 pg/mL), intestinal metaplasia, and a pepsinogen I/II ratio <3 were independently associated with an increased risk of epithelial lesions (odds ratio: 14.6, 9.4, and 4.1, respectively, p<0.05). SG levels in case subjects showed a unimodal distribution pattern as the disease progressed. The mean SG level was highest in those with hyperplastic polyps and then decreased significantly to the control level in the gastric cancer group. Higher SG levels in each disease category were not associated with increased tumor size, synchronicity, invasiveness, presence of lymph node metastasis, or a higher cellular proliferation index (p>0.05). An increased SG level was an independent and potent risk factor for gastric epithelial lesions. However, it does not seem to relate with distal gastric tumor growth. Serial decreases in SG levels should be considered a warning sign in index hypergastrinemic patients with no prior Helicobacter pylori eradication.

Multicentric Type 3 Gastric Neuroendocrine Tumors.

A 50-year-old woman with incidentally detected multiple gastric polyps and biopsy-proven neuroendocrine tumor (NET) was referred to our hospital. More than 10 polypoid lesions (less than 15 mm) with normal gastric mucosa were detected from the gastric body to the fundus. The serum level of gastrin was within the normal limits. There was no evidence of atrophic changes on endoscopy and serologic marker as pepsinogen I/II ratio. Computed tomography of the abdomen and pelvis revealed no evidence of metastatic lesions. She refused surgery, and we performed endoscopic polypectomy for almost all the gastric polyps that were greater than 5 mm. Although the histological examination revealed that all the removed polys were diagnosed as NET G1, three of them extended to the lateral or vertical resection margins, while two exhibited lymphovascular invasion. A follow-up upper endoscopy that was performed 6 months after the diagnosis showed multiple remnant gastric polyps that were suggestive of remnant gastric NET.

Preventive Effect of Lactobacillus fermentum Zhao on Activated Carbon-Induced Constipation in Mice.

The aim of this study was to investigate the effects of Lactobacillus fermentum Zhao (LF-Zhao) on activated carbon-induced constipation in ICR mice. ICR mice were administered lactic acid bacteria by gavage for 9 d. Body weight, diet intake, drinking amount, stool status, gastrointestinal transit distance and stool time, in addition to motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) levels in serum were monitored to evaluate the preventive effects of LF-Zhao on constipation. Bisacodyl, a laxative drug, was used as a positive control. Times to the first black stool for normal (untreated), control (no lactic acid bacteria treatment but activated carbon treated), bisacodyl-treated and L. delbrueckii subsp. bulgaricus (LB), LF-Zhao (L) (low concentration of 1×10(8) CFU/mL)- and LF-Zhao (H) (high concentration of 1×10(9) CFU/mL)-treated mice induced by activated carbon were 90, 218, 117, 180, 169 and 156 min, respectively. Following the consumption of LB, LF-Zhao (L) and LF-Zhao (H) or the oral administration of bisacodyl, the gastrointestinal transit distances were reduced by 55.2%, 61.3%, 70.6% and 94.6%, respectively. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with LF-Zhao compared with those in the control mice (p<0.05). These results demonstrated that lactic acid bacteria demonstrate preventive effects on mouse constipation and that LF-Zhao alleviated constipation symptoms better than LB.

Cholelithiasis as a possible manifestation of systemic digestive diseases

To comprehensively study of the function of digestive organs in cholelithiasis (CL). Three hundred and seventeen patients with the early (prestone) stage of CL were examined. The latter was verified by ultrasonography (USG) and biochemical bile tests. The patients underwent pH metry and esophagogastroduodenoscopy, followed by histological examination of gastroduodenal mucosa (GDM) biopsy specimens. Manometry was used to evaluate duodenal function. The serum levels of pepsinogen-1 (PG-1), pepsinogen-2 (PG-2), cholecystokinin (CCK), gastrin, cyclic nucleotides (cAMP and cGMP), α1-antitrypsin, insulin, and C-peptide were analyzed by an enzyme immunoassay. Small intestinal function was examined using a set of diagnostic tests. Gallbladder USG revealed biliary sludge in 273 (86.1%) patients. Biochemical examination of bile established a lower cholatocholesterol coefficient in its cystic as well as hepatic portions, suggesting enhanced bile lithogenicity. Manometry of the duodenum showed its hypertension, hypotension, and normotension in 57.6, 24.8, and 17.6% of the CL patients, respectively. There were significant increases in basal gastric body pH and PG-1 and PG-2 levels as compared to the control group. Morphological examination of GDM biopsy specimens revealed chronic superficial gastritis in 61.8% of the patients, chronic atrophic gastritis in 17.4%, and moderate diffuse duodenitis in 18.3%. In 148 (46.7%) patients with CL, the latter was burdened by pancreatic comorbidity. Stress tests using water-soluble starch, sucrose, and glucose demonstrated impairments in various stages of digestion; substantially decreased levels of CCK, gastrin and cyclic nucleotides were observed in the patients with CL compared to the controls. Most patients with CL were detected to have digestive organ structural and functional disorders. Moreover, CL may be regarded as a possible manifestation of systemic digestive diseases.

Effect of proton pump inhibitors on glycemic control in patients with diabetes.

Gastrin is a linear peptide hormone which is secreted mostly in the stomach pyloric antrum G cells. Although the main role of this hormone is the promotion of the secretion of gastric acid from the stomach parietal cells, gastrin can also behave as a growth factor and stimulate gastric cell proliferation. It is also reported that gastrin promotes β cell neogenesis in the pancreatic ductal complex, modest pancreatic β cell replication, and improvement of glucose tolerance in animal models, in which the remodeling of pancreatic tissues is promoted. These findings suggest the possibility that gastrin has the potential to promote an increase of β cell mass in pancreas, and therefore that gastrin may improve glucose tolerance. Proton pump inhibitors (PPIs) are wildly used clinically for the therapy of gastro-esophageal reflex disease, gastritis due to excess stomach acid, and gastric ulcers. PPIs indirectly elevate serum gastrin levels via a negative feedback effect. Recent evidence has revealed the beneficial effect of PPIs on glycemic control especially in patients with type 2 diabetes mellitus (T2DM), probably via the elevation of the levels of serum gastrin, although the detailed mechanism remains unclear. In addition, the beneficial effects of a combination therapy of gastrin or a PPI with a glucagon-like peptide-1 receptor agonist on glycemic control in animal models have been demonstrated. Although PPIs may be possible candidates for a new approach in the therapy of diabetes, a prospective, long-term, randomized, double-blind, placebo-controlled study is needed to establish the effect of PPIs on glycemic control in a large number of patients with T2DM.

Decrease of serum level of gastrin in healthy Japanese adults by the change of Helicobacter pylori infection.

In Japan, the prevalence of Helicobacter pylori infection is decreasing and the number of patients who receive eradication therapy is increasing. Although the serum level of gastrin is affected by H. pylori infection, the normal level has been unchanged for more than 20 years. The aim of this study was to study whether the present normal range for the serum gastrin level is appropriate for Japanese at present or in the near future. We studied 810 adults (40-80 years old) who participated in a health survey in 2012. We measured H. pylori stool antigen, titer of serum antibody to H. pylori, and serum level of gastrin. The patient's H. pylori status was defined as positive or negative when the results of both stool antigen and serology were concordant. Subjects who were taking proton-pump inhibitor and had a previous history of gastric surgery were excluded. Mean serum level of gastrin was 66.2±49.6 pg/mL in 281 H. pylori-negative subjects and 69.7±42.2 pg/mL in 115 patients who had H. pylori eradicated at least 2 years ago. The level of gastrin was 134.4±145.6 pg/mL in 224 patients with H. pylori infection and the level was significantly higher when compared with those in uninfected subjects and eradicated patients (P<0.01). Because the situation of H. pylori infection has changed remarkably in Japan, a new appropriate normal range of gastrin should be established using current Japanese populations.

A Challenging Cause of Chronic Diarrhea

A Challenging Cause of Chronic Diarrhea