Tatsuro Tanaka

Receptor subtype specific activation of the rat gastric vagal afferent fibers to serotonin

Systemic administration (i.v.) of serotonin (5-HT) evoked a transient vagal afferent nerve discharge, bradycardia, and hypotension in the rat. The half-effective dose of 5-HT for nerve discharge was 13 micro g/kg. The time- and dose-dependent kinetics of the nerve discharge rate were similar to the change of heart rate. The afferent neuronal discharge was mimicked by a selective 5-HT3 receptor agonist, 1-phenylbiguanide hydrochloride (PBA), and inhibited by a selective 5-HT3 antagonist, granisetron. The 5-HT(3/4) agonist, cisapride partially activated the vagus nerve, but the 5-HT4 agonist, RS6733 had no effect on the vagal afferent activity. Intra-gastric perfusion of lidocaine, moreover, abolished the 5-HT-induced vagal activation. These results indicate that the 5-HT transmission signal in the gastric mucosa inputs to the brain stem via 5-HT3 receptor-mediated vagal nerve afferent.

Significance of anaerobic preincubation of Helicobacter pylori for measuring metronidazole susceptibility by the Etest.

The Etest is widely used for measuring the susceptibility of Helicobacter pylori to metronidazole. By using 55 H. pylori isolates from 55 patients and a standard H. pylori strain, NCTC11637, we compared metronidazole susceptibility results obtained from the Etest with or without anaerobic preincubation to those obtained from the agar dilution method. Mueller Hinton agar plates supplemented with 5% horse blood were used for both methods. For the Etest, plates were incubated for 72 hr at 35 C under microaerophilic conditions after 0‐, 4‐ or 24‐hr periods of anaerobic preincubation. For the agar dilution method, the plates were incubated at the same microaerophilic conditions as those for the Etest. Without anaerobic preincubation for the Etest, 39 of the 56 (70%) H. pylori isolates were categorized as resistant to metronidazole (minimal inhibitory concentration >8 mg/liter), whereas only one of the 56 (1.8%) isolates was resistant according to the agar dilution method. The resistant and susceptible agreement rate was 32%. Four‐hour anaerobic preincubation did not alter the readings of the Etest significantly. However, when the Etest was performed with 24‐hr anaerobic preincubation, the number of isolates categorized as resistant was reduced to six (11%), improving the agreement rate to 91%. For measuring the metronidazole susceptibility of H. pylori by the Etest, 24‐hr anaerobic preincubation is necessary to agree with the results obtained by the agar dilution test.

Early gastric cancer successfully treated by endoscopic submucosal resection 1 year after laparoscopic sleeve gastrectomy with duodenal-jejunal bypass: De novo early gastric ca. after LSG-DJB

This case involved a 64‐year‐old female patient with a BMI of 35.3 kg/m2 and poorly controlled type 2 diabetes mellitus. Preoperative upper gastrointestinal endoscopy revealed chronic, atrophic gastritis. Helicobacter pylori antibody was negative. The patient underwent laparoscopic sleeve gastrectomy with duodenal‐jejunal bypass as a metabolic surgery to treat obesity and type 2 diabetes mellitus. At 1 year postoperatively, routine endoscopy detected a flat elevated lesion at the distal gastric sleeve, near the posterior wall of the antrum; biopsy revealed adenocarcinoma. Endoscopic submucosal resection was performed without complication. This case shows the advantage of laparoscopic sleeve gastrectomy with duodenal‐jejunal bypass in screening the excluded stomach as compared to laparoscopic Roux‐en‐Y gastric bypass. Therefore, laparoscopic sleeve gastrectomy with duodenal‐jejunal bypass can be a viable alternative to laparoscopic Roux‐en‐Y gastric bypass for regions where gastric cancer is endemic.

S2091 Dietary Free Glutamate Augments Portal Increase of Free Amino Acids After Intragastric Protein Load in Rats

Background: Dietary free glutamate promotes gastric emptying of protein-rich diet in healthy humans (Biol Pharm Bull.10:1841-3, 2008). However it is not known whether it could affect the process of digestion and/or absorption of dietary protein as a result of faster gastric emptying. Aim: In this study we examined the effects of glutamate on amino acids (AAs) increase both in portal and peripheral blood and on gastric emptying rate after intragastric protein-rich meal load in rats. Methods: Male SD rats (20 weeks) were fitted with portal vein cannula under nembutal anesthesia. Ten days later, blood samples were taken from a lateral tail vein and the portal vein of awake rats at 0, 5, 15, 30, 60, 90 and 120 min after protein-rich liquid diet load (10 ml/kg p.o., energy density: 1.0 kcal/ml) containing 12.5% casein-calcium and 12.5% dextrin. Plasma AAs were analyzed by AA analyzer (L-8800, Hitachi-high tech, Japan). Monosodium L-glutamate (0.5% w/v, normal habitual concentration for human) was used as an active ingredient and equimolar NaCl (0.18% w/v) was used as a control. To measure gastric emptying rate, 13CO2 excretion was measured by an open-circuit metabolic gas analysis system equipped with a mass spectrometer (Model RL600, ArcoSystem, Japan) after p.o. load of the same meal labeled by 13C-sodium acetate (100 mg/kg). Results: Intragastric load of the diet rapidly increased plasma glucose and all 20 AAs both in portal as well as peripheral vein with their peaks at 15 or 30 min. Free glutamate enrichment augmented the increase in portal plasma AUC (during 2hr) of AAs, but not in portal glucose. Significant augmentation was observed in both essential and nonessential AAs (mg/dl.hr, ** P<0.01, * P<0.05); alanine** (8.0±1.8 vs 4.3±1.2), leucine** (4.1±1.0 vs 2.4±0.5), glutamate**(1.9±0.7 vs 0.7±0.5), lysine*(7.5±2.4 vs 4.7±1.7), serine*(2.8±0.8 vs 1.8±0.7), arginine*(2.5±0.6 vs 1.8±0.4), lsoleucine*(2.2±0.2 vs 1.5±0.2), phenylalanine*(1.7±0.5 vs 1.0±0.3), histidine* (1.5±0.4 vs 1.0±0.4), methionine*(1.3±0.4 vs 0.8±0.3) . On the other hand, free glutamate enrichment did not change significantly either peripheral plasma AUC of glucose and AAs or gastric emptying rate of the meal (T 1/2, 1.07±0.03 vs 1.03±0.06 hr, P=0.10). Conclusions: Free glutamate significantly enhanced the portal increase in 10 out of 20 natural AAs composing proteins without affecting portal glucose increase or gastric emptying rate after the meal in rats, indicating that it facilitates the process of protein digestion and/or absorption rather than gastric motility. Differences of its effect on gastric emptying rate between species and its sites of action remain to be elucidated.

Mucosal Regeneration of Gastric Ulcer Confirmed by Electronic Endoscopy

We studied the detailed surface structure and changes in the regenerated mucosa during the course of healing of recurrent gastric ulcers treated with lansoprazole or famotidine, using a magnifying electronic endoscope (videoendoscope) and a dye contrast method. The detailed patterns of regenerated mucosa were classified into five types: membranous, spindle-shaped, palisade-shaped, cobblestone-shaped, and almost normal structure. Initially, the membranous regenerated mucosa appears at the ulcer margin and grows into the spindle- and palisade-shaped regenerated mucosa. These latter types of mucosa change gradually into the cobblestone-shaped type, which finally develops into an almost normal structure. Lansoprazole appeared to bring about more rapid growth and changes of the regenerated mucosa than famotidine, although the difference was not statistically significant. We suggest that it is useful, in the assessment of gastric ulcer therapy, to observe the detailed patterns of the regenerated mucosa during the healing process using a magnifying electronic endoscope