Impact of Helicobacter pylori infection on fluid duodenal microbial community structure and microbial metabolic pathways.

BACKGROUND: The bioactivities of commensal duodenal microbiota greatly influence the biofunction of hosts. We investigated the role of Helicobacter pylori infection in extra-gastroduodenal diseases by determining the impact of H. pylori infection on the duodenal microbiota. We sequenced 16 S rRNA genes in samples aspirated from the descending duodenum of 47 (male, 20; female, 27) individuals who were screened for gastric cancer. Samples were analysed using 16 S rRNA gene amplicon sequencing, and the LEFSe and Kyoto Encyclopaedia of Genes and Genomes methods were used to determine whether the duodenal microflora and microbial biofunctions were affected using H. pylori infection. RESULTS: Thirteen and 34 participants tested positive and negative for H. pylori, respectively. We identified 1,404 bacterial operational taxonomic units from 23 phyla and 253 genera. H. pylori infection changed the relative mean abundance of three phyla (Proteobacteria, Actinobacteria, and TM7) and ten genera (Neisseria, Rothia, TM7-3, Leptotrichia, Lachnospiraceae, Megasphaera, F16, Moryella, Filifactor, and Paludibacter). Microbiota features were significantly influenced in H. pylori-positive participants by 12 taxa mostly classified as Gammaproteobacteria. Microbial functional annotation revealed that H. pylori significantly affected 12 microbial metabolic pathways. CONCLUSIONS: H. pylori disrupted normal bacterial communities in the duodenum and changed the biofunctions of commensal microbiota primarily by upregulating specific metabolic pathways. Such upregulation may be involved in the onset of diseases associated with H. pylori infection.

[Efficacy of Antiemetic Therapy with Aprepitant, Palonosetron, and Dexamethasone in Patients Receiving Oxaliplatin-Based Chemotherapy].

Antiemetic therapy with aprepitant, palonosetron, and dexamethasone is recommended for moderately emetogenic chemotherapy in several guidelines to prevent chemotherapy-induced nausea and vomiting. There is a lack of information about the efficacy and safety of antiemetic therapy with aprepitant, palonosetron, and dexamethasone in patients treated with oxaliplatin in Japan. We recruited patients with untreated colorectal cancer who underwent oxaliplatin-based chemotherapy. All patients were treated with aprepitant, palonosetron, and dexamethasone. The complete response and complete protection rates were analyzed. A total of 52 patients were enrolled in this clinical trial. The complete response rate overall, and in the acute and delayed phases was 92.3%, 98.1%, and 92.3%, respectively. The complete protection rate overall and in the acute and delayed phases was 73.1%, 86.5%, and 73.1%, respectively. Grade 3-4 non-hematological toxicity did not occur. Antiemetic therapy with aprepitant, palonosetron, and dexamethasone is effective and safe in patients treated with oxaliplatin.

Alteration of Breath Hydrogen and Methane in Ethanol-Fed Rats.

Chronic alcohol consumption can cause dysbiosis, but it is difficult to determine the effect of alcohol on the structure and activity of gastrointestinal tract microbiota. We therefore designed a noninvasive hydrogen breath test (HBT) to investigate the alteration in the chemical profile of gut microbiota in ethanol-fed rats. Thirteen F344/DuCri rats were fed on a commercial mash food with 16% ethanol solution drinking fluid from 4 weeks of age. HBTs were carried out on six 8-week-old and seven 24-week-old ethanol-fed rats. As controls, HBTs were carried out on sixteen 8-week-old, six 24-week-old, and five 48-week-old male rats. Six 24-week- old male rats were examined twice at 1-week intervals. HBTs were performed after fasting for 24 hr. Rats were orally administrated 4 mL/kg of 65% lactulose solution and housed in an animal chamber. The expired air was collected in a breath-sampling bag at 10-min intervals for 180 min. The hydrogen (H2) and methane (CH4) levels in the breath sample were measured using a breath analyzer and were expressed.as parts- per million (ppm). Elevated H2 and CH4 levels were more frequent in male rats. Maximal values of H2 and CH4 were highest in 8-week- old rats, followed by 48-week-old and 24-week-old rats. No ethanol-fed rat exhaled more than 2 ppm of H2 or CH4 until 180 min after the oral administration of lactulose, unlike the controls. This alteration was more obvious than that of aging or gender differentiation. We conclude that there is a close association between chronic ethanol consumption and H2 and CH4 production. An asymptomatic heavy drinker might have dysbiosis that involves gut microbiota with lower fermentation performance.

Role of infected grandmothers in transmission of Helicobacter pylori to children in a Japanese rural town.

AIM: Although the prevalence of Helicobacter pylori (H. pylori) increases with age and the main period of acquisition is childhood, the route of transmission of H. pylori infection remains unclear. This study aims to evaluate the relationship between prevalence of children and grandparents. METHODS: A total of 838 consecutive children who attended the Urita clinic and whose blood was taken for work up were enrolled in the present study. They were 449 boys and 389 girls, with a mean age of 12.4 years. H. pylori serology of their family members who were living together in one house was picked up to analyse intra-familial clustering of H. pylori infection. The family members of these children consisted of 448 fathers, 597 mothers, 205 grandfathers, 361 grandmothers and 589 siblings. RESULTS: The seropositive rates of mothers, grandmother and siblings in seropositive children were significantly higher than those in seronegative children. H. pylori infection in mothers and grandmothers was a marked risk factor for infection in the index children. Larger family size was not a risk factor for H. pylori infection. In contrast, having an infected father or grandfather was not an independent predictor for children infection. CONCLUSIONS: Our data demonstrate that not only mother-to-child transmission but also grandmother-to-child transmission is an important mechanism for the spread of H. pylori in a three-generation household.

[The chemotherapy of peritoneal malignant mesothelioma].

Peritoneal malignant mesothelioma is a rare disorder with a poor prognosis, and a standard treatment for it has not yet been established. Therefore, treatment of this disorder tends to be selected according to pleura malignant mesothelioma. We analyzed case reports in Japan. The median survival time(MST)with this disease was 12 months and the 1-year survival rate was 47. 3% in the chemotherapy group. It was found through a case-series study that platinum pharmaceutical plus antimetabolite are effective against peritoneal malignant mesothelioma. A gemcitabine(GEM)plus cisplatin(CDDP)regimen had been selected as a conventional treatment, but subsequently, pemetrexed(MTA)was covered by health insurance for pleural malignant mesothelioma in 2007, and the MTA plus CDDP regimen became the standard treatment. However, a phase III trial of GEM plus CDDP regimen and MTA plus CDDP regimen was not performed. There is a need to perform these phase III trials in the future. In our institution, the MTA plus CDDP regimen was the first-line treatment, and the GEM plus CDDP regimen was the second-line treatment against peritoneal malignant mesothelioma. Palonosetron hydrochloride and aprepitant should be used actively in treatment. Also, carboplatin(CBDCA)is effective as an alternative therapy of the CDDP against renal disorder case, but hematotoxicity requires attention.

[Analysis of the correlation with KRAS gene mutation status and the benefit of cetuximab plus irinotecan as third- line chemotherapy for the Treatment of unresectable metastatic colorectal cancer].

Mutation of the KRAS gene in patients with metastatic colorectal cancer(mCRC)has been established as a predictive marker of poor response to anti-EGFR cetuximab. The Japanese Society of Medical Oncology recommends that the KRAS mutation status at codon 12 and codon 13 should be genotyped by direct-sequencing or allele-specific PCR. In this study, we tested the point mutation of codon 12 and 13 in the KRAS gene by Luminex(xMAP)flow cytometry with sequence-specific oligonucleotide probes for 39 out of 64 unresectable mCRC patients enrolled from Sep 2008 to Oct 2009, who were administered cetuximab in combination with irinotecan(CPT-11)as third-line therapy. We retrospectively analyzed the relationship between KRAS mutation status and responses to combination therapy. Mutations in the KRAS gene were detected in 38. 5% of cases(codon12: 73%, codon 13: 27%), and the median follow-up time was 8. 2 months(range, 1. 4-15. 2 months). The response rates for patients with KRAS wild-type and patients with KRAS mutations were 33. 3%(95%CI 14. 5-52. 2%)and 0%(p=0. 015); the disease control rates were 75%(95%CI 57. 7-92. 3%)and 40%(95%CI, 15. 2-64. 8%; p=0. 044); the median TTF was 7 months(95%CI 4. 6-9. 3)and 2. 3 months(95%CI 1. 3-3. 2; p=0. 0007), and the median OS was 12. 9 months(95%CI 6. 7-19. 1)and 10. 8 months(95%CI 5. 0-16. 7; p=0. 15), respectively. Therefore, we concluded that the KRAS mutation in mCRC is a predictive factor for the lack of response to combination therapy with cetuximab plus CPT- 11, as reported in previous clinical studies.

Form of gastric air bubble is associated with gastroesophageal reflux symptoms.

BACKGROUND/AIMS: Gastric bubble is present in approximately 70% of normal chest and abdominal radiograph. Most swallowed air is regurgitated and belching is a physiological phenomenon to expel ingested gas from the stomach and is a common symptom in normal adults. In the present study it was investigated whether gastric bubble detected on abdominal radiograph is associated with GERD symptoms. METHODOLOGY: All of the patients who first attend our hospital were asked to respond the F-scale questionnaire regardless of their chief complaints to diagnose GERD. Plain abdominal films in the erect position were used to measure the size of gastric bubble and to classify the form of gastric bubble into four groups: dome-type; irregular-type; stomach-type; and undetected-type. The quantity of gastric bubble (gastric bubble score) was determined as the pixel value on image collected from hospital's digital database. RESULTS: The gastric bubble score of irregular-type was significant lower than that of dome-type and stomach-type. GERD was most frequently detected in stomach-type group, followed by undetected-type, irregular-type, and dome-type. The mean score of F-scale was significantly higher in stomach-type than in dome-type. CONCLUSIONS: It is concluded that gastric bubble detected on plain abdominal films is an informative marker for evaluating the functional disorder of upper digestive tracts. Physicians have to recognize the importance of plain films of the abdomen in the diagnostic process of GERD.

Is the metabolism of toast alcohol beverages influenced by a meal taken five minutes later?

Alcohol is commonly consumed with, or soon after, a meal that affects gastric emptying and thus, absorption and metabolism of alcohol. The aim of this study is to evaluate the effect of liquid test meal ingested soon after, alcohol ingestion on alcohol metabolism, as is common in the social setting. First, a 100 mL of water containing of 80 mg of 13C-ethanol was administrated orally in 7 healthy subjects, and 200 mL of liquid meal (200 kcal) was administrated 5 min after alcohol ingestion. Breath samples were taken at baseline and at 10-min interval for 150 min. Next, 13C-ethanol breath test was performed without ingestion of liquid meal. Cmax was decreased after ingestion of liquid meal, whereas Tmax was unchanged. The descending gradient of 13CO2 excretion curves after ingestion of liquid meal is parallel to that without liquid meal, while the ascending gradient of 13CO2 excretion curves in the first 10 min had a tendency to be greater after ingestion of liquid meal than without ingestion of liquid meal. A significant delay in breath 13CO2 excretion after ingestion of liquid meal was found and the AUC values were lower after ingestion of liquid meal in each time point, indicating that liquid meal ingested soon after alcohol ingestion may not affect elimination but absorption and/or metabolism of a small amount of alcohol.

13C-glucose breath tests: a non-invasive method for detecting early clinical manifestations of exogenous glucose metabolism in type 2 diabetic patients.

AIMS: 13C-glucose breath tests are reported as an alternative non-invasive method to evaluate glucose metabolism. However, the metabolic results differ based on the site of the carbon atom in the glucose. The aim of this study was to evaluate changes in the metabolism of carbon atoms contained in glucose in patients with diabetes using [1, 2, 3-13C]glucose breath tests. METHODS: Sixteen healthy participants and 20 diabetic patients were enrolled in the study. Three types of breath tests, [1-13C], [2-13C], and [3-13C]glucose breath tests, were performed after an overnight fast. Breath samples were taken at baseline and at 10-min intervals over 150 min, and 13CO2 excretion curves were expressed using non-dispersive infrared isotope spectrometry. RESULTS: 13CO2 levels increased more rapidly, and the peak value of 13CO2 (Cmax) was highest after the administration of [3-13C]glucose followed by [2-13C] and [1-13C]glucose in controls. Delayed 13CO2 excretion and a low area under the curve through 150 min (AUC150) were obtained in diabetic patients. The group with severe diabetes had a significantly lower Cmax and AUC150 in the [1-13C]glucose breath test. CONCLUSIONS: The [1-13C]glucose breath test, which has been used to evaluate glucose metabolism, is suitable for patients with late-stage diabetes, whereas the [2-13C]glucose breath test is ideal in the early stages. Although the [3-13C]glucose breath test is theoretically useful for evaluating the uptake of glucose and the anaerobic glycolysis system, it can be used in practice to distinguish reduced uptake from impaired oxidation of glucose in combination with the other two tests.

Saliva transit from the oral cavity to the esophagus in GERD.

BACKGROUND/AIMS: Normal esophageal acid clearance depends on the neutralization of acid by swallowed saliva, as well as on esophageal peristalsis. This study therefore aimed to investigate the association between saliva production and transport from the oral cavity to the esophagus and developing gastroesophageal reflux disease (GERD) METHODOLOGY: Twenty-eight consecutive patients with GERD symptoms by gastroesophageal reflux self-report questionnaires and 13 healthy volunteers were recruited in the study. After intravenous administration of 99mTc-pertechnetate, anterior sequential imaging was performed every minute for 40 minutes. At 20 minutes after injection of radionuclide, a lemon candy was administered intra-orally to stimulate salivary secretion. Regions of interest (ROI) were selected on the individual oral cavity, the pharynx, and the upper esophagus and time activity curves were drawn for each of these. A time-activity curve in each ROI was subjectively graded, as zero to two-point. The sum of scores in 3 ROIs was considered as a saliva transit total score. RESULTS: The mean transit score of the oral cavity did not differ significantly between GERD patients and healthy volunteers (1.38 vs. 1.61), whereas significantly lower transit scores of pharynx and upper esophagus were found in GERD patients. A 0-point saliva transit score of pharynx and upper esophagus was significantly more frequently detected in GERD patients than in healthy volunteers. CONCLUSIONS: This new modification of saliva scintigraphy is able to evaluate the esophageal motility simply, without a test meal, and to detect impaired saliva transit between pharynx and upper esophagus in GERD patients non-invasively.

Extensive atrophic gastritis linked to increased levels of intraluminal hydrogen gas.

BACKGROUND/AIMS: Gastric acid plays an important part in the prevention of bacterial colonization of the gastrointestinal tract. If these bacteria have an ability of hydrogen (H2) fermentation, intraluminal H2 gas might be detected. We attempted to measure the intraluminal H2 concentrations to determine the bacterial overgrowth in the gastrointestinal tract. METHODOLOGY: Studies were performed in 647 consecutive patients undergoing upper endoscopy. At the time of endoscopic examination, we intubated the stomach and the descending part of the duodenum without inflation by air, and 20 ml of intraluminal gas samples of both sites was collected through the biopsy channel. Intraluminal H2 concentrations were measured by gas chromatography. RESULTS: Over all, intragastric and intraduodenal H2 gas was detected in 566 (87.5%) and 524 (81.0%), respectively. The mean values of intragastric and intraduodenal H2 gas were 8.5 +/- 15.9 and 13.2 +/- 58.0 ppm, respectively. The intraduodenal H2 level was increased with the progression of atrophic gastritis, whereas the intragastric H2 level was the highest in patients without atrophic gastritis. CONCLUSIONS: The intraduodenal hydrogen levels were increased with the progression of atrophic gastritis. It is likely that the influence of hypochlorhydria on bacterial overgrowth in the proximal small intestine is more pronounced, compared to that in the stomach.

Gastroesophageal reflux disease symptoms are more common in general practice in Japan.

AIM: To accurately assess the prevalence of GERD symptoms in general practice. METHODS: 4139 consecutive patients (2025 men and 2114 women with a mean age of 43 years), who first attended the Outpatient Department of General Medicine and Emergency Care at Toho University Omori Hospital, were asked to respond to the F-scale questionnaire regardless of their chief complaints. The questionnaire is a self-report instrument, written in a simple and easy-to-understand language, containing 12 questions. RESULTS: Of 4139 subjects, 1554 patients (37.6%) were identified as GERD according to their F-scale score (> 7). However, there were only 45 consultations (1.1%) for typical GERD symptoms. Although GERD symptoms are common in adults of all ages, the prevalence of GERD was highest in the 20-29 years age group and the age group 70-79 years had the lowest prevalence for both males and females. CONCLUSION: Although there was a high rate indicating GERD in our primary care population, only 1.1% of outpatients attended our hospital with a chief complaint of GERD symptoms. Since about one-third of GERD patients are affected by atypical symptoms, general physicians need to be cautious about extrapolating these results to patients with a chief complaint other than typical GERD symptoms.

Ten-second endoscopic breath test using a 20-mg dose of 13C-urea to detect Helicobacter pylori infection.

BACKGROUND/AIMS: Attempts to improve the 13C-urea breath test (UBT) have focused on decreasing the amount of substrate used and reducing the duration of the test. To render the test less expensive and more convenient, we designed a more rapid and less expensive endoscopic UBT with a low dose of 20 mg and a shortened measurement time. METHODOLOGY: A total of 178 patients who underwent diagnostic upper endoscopy were enrolled. At endoscopy, 150 mL of intragastric gas sample were collected through a biopsy channel. Following inflation with air, 20 mL of water containing 20 mg of 13C-urea were sprayed onto the gastric mucosa using a spraying instrument. After 10 seconds, a gastric gas sample was collected again. The standard UBT was performed after 3-10 days. RESULTS: The delta13CO2 values of intragastric samples in H. pylori-positive patients and H. pylori-negative patients were 76.7 +/- 132.9 per thousand and 1.6 +/- 1.2 per thousand, respectively. With intragastric samples, the maximum sensitivity and specificity of intragastric samples were 83.7% and 100% with cut-off point of 8 per thousand, respectively. CONCLUSIONS: Ten-second endoscopic UBT using a 20-mg dose of 13C-urea is a rapid, inexpensive, and accurate method for the detection of H. pylori infection in clinical practice.

Endoscopic 13C-urea breath test for detection of Helicobacter pylori infection after partial gastrectomy.

BACKGROUND/AIMS: It is difficult to interpret the results of 13C-urea breath test (UBT) in gastrectomy patients because the test urea may pass through the stomach faster. The aim of this study is to evaluate the efficacy of the modified endoscopic UBT for detection of Helicobacter pylori (H. pylori) infection in the residual stomach. METHODOLOGY: An endoscopic UBT was performed in 44 patients who had undergone partial gastrectomy. At endoscopy, 20 mL of water containing 100mg of 13C-urea were sprayed onto the gastric mucosa and an intragastric gas sample was immediately collected through the biopsy channel. Breath samples were collected at 20 min after spraying 13C-urea. RESULTS: The intragastric delta13CO2 value in H. pylori-positive patients was significantly higher than those of 20-minute breath samples. The maximum sensitivity and specificity of intragastric samples were 97% and 100% with cutoff point of 5 per thousand, respectively. The sensitivity and specificity of breath samples at 20 min were 71.4% and 66.7% with cutoff point of 0.6 per thousand, respectively. CONCLUSIONS: An endoscopic UBT was superior to a standard UBT to detect H. pylori infection after partial gastrectomy.

Continuous consumption of fermented milk containing Bifidobacterium bifidum YIT 10347 improves gastrointestinal and psychological symptoms in patients with functional gastrointestinal disorders.

The aim of this study was to investigate whether consumption of probiotic fermented milk containing Bifidobacterium bifidum YIT 10347 improves symptoms in patients with functional gastrointestinal disorders (FGID). Thirty-seven FGID patients (18 male, 19 female) aged 12-80 years (mean ± SD, 52.6 ± 17.5 years) whose condition had not improved despite being seen at several medical institutions consumed 100 mL/day of B. bifidum YIT 10347 fermented milk for 4 weeks. Symptoms were evaluated after the enrollment period (BL: baseline), sample consumption period (CP) and 4 weeks after the CP (FP: follow-up period). Gastrointestinal symptoms were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS) and the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG); psychological symptoms were evaluated using the Profile of Mood States (POMS) short form. Concentrations of salivary stress markers and the oxidative stress marker urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured. GSRS subscale scores for abdominal pain, diarrhea, and constipation significantly improved relative to BL after consumption of the fermented milk, as did FSSG subscale scores for symptoms of acid-related dyspepsia. Some subjective psychological symptoms improved. POMS scores significantly improved, and "Anger-Hostility" subscale scores significantly decreased after the consumption period, while "Vigor" subscale scores marginally increased during the consumption period. The concentrations of urinary 8-OHdG and the stress marker salivary cortisol were significantly lower at CP but returned to baseline levels at FP. Continuous consumption of B. bifidum YIT 10347 fermented milk is expected to improve gastrointestinal symptoms and reduce psychological stress in FGID patients.

How do we apply adjuvant FOLFOX to Japanese patients with curatively resected colorectal cancer?

AIM: In Japan the combination of fluorouracil (5-FU), leucovorin and oxaliplatin (FOLFOX) was approved as adjuvant therapy for stage III or high-risk stage II colon cancer only in September 2009. In this study we evaluated the safety and efficacy of FOLFOX as adjuvant chemotherapy for stage IIIb or IV colorectal cancer (CRC) patients in a Japanese group at a single institute. METHODS: A total of 45 consecutive patients received 12 cycles of adjuvant FOLFOX for stage IIIb (n = 31) or IV (n = 14) CRC. Toxicity and disease-free survival (DFS) were analyzed retrospectively. RESULTS: The median dose intensities of oxaliplatin and 5-FU were 0.7 and 0.74, respectively. Oxaliplatin was discontinued in 10 (22%) patients due to an allergic reaction in five, neurotoxicity in four and gastrointestinal toxicity in one. No severe neurotoxicity occurred. The median duration from completion of treatment until complete recovery from peripheral neuropathy was 582 days (95% CI, 486-678). Two-year DFS for stages IIIb and IV was 56.9% and 56.3%, respectively (log-rank, P = 0.533). Univariate analysis revealed that severe vessel invasion, liver metastasis and higher baseline levels of CA19-9 were associated with shorter DFS in stage IV patients. Multivariate analysis including the selected biomarkers revealed none as a significant prognostic factor. CONCLUSION: Adjuvant FOLFOX was well tolerated in a Japanese cohort of both stage IIIb and IV CRC patients.

Breath Hydrogen Gas Concentration Linked to Intestinal Gas Distribution and Malabsorption in Patients with Small-bowel Pseudo-obstruction.

BACKGROUND: The patient with colonic obstruction may frequently have bacterial overgrowth and increased breath hydrogen (H2) levels because the bacterium can contact with food residues for longer time. We experienced two cases with intestinal obstruction whose breath H2 concentrations were measured continuously. CASE 1: A 70-year-old woman with small bowel obstruction was treated with a gastric tube. When small bowel gas decreased and colonic gas was demonstrated on the plain abdominal radiograph, the breath H2 concentration increased to 6 ppm and reduced again shortly. CASE 2: A 41-year-old man with functional small bowel obstruction after surgical treatment was treated with intravenous administration of erythromycin. Although the plain abdominal radiograph demonstrated a decrease of small-bowel gas, the breath H2 gas kept the low level. After a clear-liquid meal was supplied, fasting breath H2 concentration increased rapidly to 22 ppm and gradually decreased to 9 ppm despite the fact that the intestinal gas was unchanged on X-ray. A rapid increase of breath H2 concentration may reflect the movement of small bowel contents to the colon in patients with small-bowel pseudo-obstruction or malabsorption following diet progression. CONCLUSIONS: Change in breath H2 concentration had a close association with distribution and movement of intestinal gas.

Removal of ovarian hormones affects the ageing process of acetate metabolism.

BACKGROUND: Despite a close association between gastrointestinal motility and sex hormones, it has been unknown whether ovarian hormones affect absorption and metabolism of nutrients. The aim of this study is, therefore, to evaluate metabolism of acetate in rats with age and the influence of ovariectomy on its change. METHODS: Fourteen female rats of the F344 strain were used, and 13C-acetate breath test was performed at 2, 7 and 13 months of age. Seven rats were ovariectomized at three weeks of age (ovariectomy group) and the remaining seven rats were studied as control group. After 24-hr fasting, rats are orally administrated 1ml of water containing sodium (13)C-acetate (100mg/kg) and housed in an animal chamber. The expired air in the chamber is collected in a breath-sampling bag using a aspiration pump. The (13)CO(2) concentration is measured using an infrared spectrometer for 120 min and expressed as delta per mil. RESULTS: The breath (13)CO(2) excretion increased with time and peaked 30 min in control rats. In ovariectomized rats, thee peak time of (13)CO(2) excretion was prolonged to 40 min at 7 and 13 months of age. Cmax was significantly higher at 2 months of age but lower at 4 months of age in ovariectomized rats than in control rats. Those of two groups became equal at 7 months of age. CONCLUSIONS: From the viewpoint of acetate metabolism, removal of ovarian hormones might make rats to be precocious ones and accelerate ageing.

Rebamipide and mosapride enhance pilocarpine-induced salivation.

BACKGROUND: During esophageal acid clearance, salivation plays an important role in defending the esophageal mucosa. Mosapride, an agent used in chronic, long-term therapy of gastro-esophageal reflux disease (GERD) was regarded as mediating its efficacy through prokinetic properties. Rebamipide is also widely used as an anti-gastritis and anti-ulcer agent in GERD patients with chronic gastritis. The aim of this study is to investigate the effects of rebamipide, mosapride, and risperidone on the salivation induced by pilocarpine. MATERIALS AND METHODS: The experiments were conducted on 4-week male SD rats (120-150g). The salivation was induced by intraperitoneally administrated pilocarpine and saliva was collected using preweighted small cotton balls inserted into the animal's mouth every 30 min for 180 min. Thirteen minutes before intraperitoneal administration of pilocarpine, rebamipide, mosapride, and risperidone were administered intraduodenally. Control rats were conducted by intraperitoneal administration of saline and intraduodenal administration of 0.5% methylcellulose solution. RESULTS: The saliva weight at 0-30 min was significantly (p<0.01) increased after administration of pilocarpine, compared to control rats. An additional administration of mosapride and rebamipide increased the saliva weight at 0-30 min. The total volume of saliva for 150 min after administration of pilocarpine was the highest after preadministration of rebamipide, followed by mosapride, and risperidone. CONCLUSIONS: Increase in salivation produced by i.p. pilocarpine was enhanced by preadministration of rebamipide and mosapride.

Influence of chronic ethanol consumption on extra-pancreatic secretory function in rat.

BACKGROUND: The usefulness of the typical direct methods involving duodenal intubation, such as the secretin and secretin-cholecystokinin tests, in the diagnosis of exocrine pancreatic dysfunction is widely accepted. However, these diagnostic tests tend to be avoided because of their technical complexity and the burden on patients. Recently, a simple breath test was developed for assessment of exocrine pancreatic function employing 13C-dipeptide [i.e., benzoyl-L-tyrosyl-[1-13C] alanine (Bz-Tyr-Ala)]. Although alcohol abuse causes pancreatic damage in humans, this has been unclear in rats. AIMS: The aim of the study is to evaluate the effect of ethanol exposure beginning at an early age on extra-pancreatic secretory function in rats. MATERIALS AND METHODS: Twelve female rats of the F344 strain aged 12 months were used. Seven rats were fed on a commercial mash food with 16% ethanol solution (Japanese Sake) as drinking-fluid since at 29 days of age (ethanol group). The remaining five rats were fed on a nutrient-matched isocaloric diet with water as drinking-fluid (control group). After 24-hr fasting, rats are orally administrated 1cc of water containing sodium 13C-dipeptide (5 mg/kg) and housed in an animal chamber. The expired air in the chamber is collected in a breath-sampling bag using a tube and aspiration pump. The 13CO2 concentration is measured using an infrared spectrometer at 10-min interval for 120 min and expressed as delta per mil. RESULTS: The breath 13CO2 level increased and peaked at 20 min in both two groups. In general, 13CO2 excretion peaked rapidly and also decreased sooner in ethanol rats than in control rats. The mean value of the maximal 13CO2 excretion is 34.7 per mil in ethanol rats, greater than in control rats (31.4 per mil), but the difference did not reach the statistically significance. CONCLUSION: Chronic ethanol feeding beginning at an early age does not affect extra-pancreatic secretory function in rats.