M. Onomura

Adrenomedullin promotes epithelial restitution of rat and human gastric mucosa in vitro

We have investigated the effect of adrenomedullin (AM) on restitution of mucosal integrity following damage in rat and human gastric mucosa, measuring the potential difference (PD) on a mucosal strip mounted on an Ussing chamber. Mucosal damage was induced by 0.5, 1.0, and 2.0 M NaCl solution, and it caused an immediate and significant decrease in PD. In the rat AM group, PD recovered significantly more than in control group at 120 min after exposure to 0.5 M (p < 0.01) and 1.0 M (p < 0.05) NaCl solution. In the human AM group, PD completely recovered at 120 min after exposure to 0.5 M (p < 0.05) NaCl solution. In rat mucosa damaged by 0.5 M NaCl solution, the effect was inhibited by human (h)-CGRP(8-37) and there was no significant difference between the h-CGRP(8-37) group and control group. On immunohistochemical examination of rat gastric mucosa, AM was detected within the chief cell. AM probably promotes epithelial restitution primarily through the CGRP receptor, but it does not ameliorate more severe damage of gastric mucosa in vitro.

Effect of adrenomedullin on ion transport and muscle contraction in rat distal colon

We have investigated the effects of adrenomedullin (AM) on mucosal ion transport using the Ussing method and smooth muscle contraction using the Magnus method in rat. Our results indicate that AM increases Isc (short-circuit current) for Cl- secretion (100 nM:170.0 +/- 41.2%, 1 microM:193.8 +/- 45.5%, 100% Isc:28.2 +/- 3.1 microA/cm2) with an initial small decrease of Isc, inhibiting Na+ absorption. Tetrodotoxin (TTX) inhibits the Isc response elicited by AM (86%). In addition, AM relaxes potassium-induced contraction (10 nM:11.1 +/- 8.51%, 100 nM:33.4 +/- 12.7%, 100% contraction: 1.8 +/- 0.22 g), and TTX inhibits the response elicited by AM (90%). We conclude that AM modulates water and ion transport as well as bowel movement, mainly through the colonic nervous system.

Effects of okadaic acid on rat colon

Effects of okadaic acid (OA) on mucosal damagewere examined in rat colon. OA was sprinkled on ratcolon mucosa under observation with anelectronic-endoscopic system, and OA was also applied tothe in vivo microscopic field. The OA-induced changesin transepithelialconductance (Gt) weremeasured by the Ussing voltage clamp technique. Byendoscopic observation, the luminal sprinkling of OA (60nmol/kg) evoked transient microthrombi in the submucosalvenule, which was followed by mucosal edema.Histological study after endoscopic observation showedsubmucosal fluid retention, suggesting an increase of vascular permeability. The microthrombi werealso detected by in vivo microscopy. Byelectrophysiological study after endoscopic observationwith and without OA addition, the basal Gtvalues were 54 ± 6.2 and 36.2 ± 4.2 mS/cm2,respectively (P < 0.01). Furthermore in control rats,the serosal addition of OA evoked an increase inGt in a concentration-dependent mannerwithout increasing lactate dehydrogenase release. 2,4,6-Triaminopyrimidinium inhibitedOA-induced Gt change by 60%. These resultsindicate that OA evokes an increase in paracellularpermeability of epithelium. We conclude that thedeveloped microthrombi are the first key event of OA-induced mucosaldamage, followed by an increase in permeability in thesubmucosal venule and in the paracellular pathway of theepithelium.

Effect of argatroban on trinitrobenzene sulfonic acid-induced colitis.

Background : Recent studies have suggested that heparin is effective for treatment of inflammatory bowel disease (IBD) and its various effects (in addition to the anticoagulant effect). We evaluated the effects of argatroban as an antithrombin drug on trinitrobenzene sulfonic acid (TNB)‐induced colitis, an established model of IBD.

7084 Endoscopic aspiration mucosectomy using a bipolar snare for gastric neoplasms.

PURPOSE: Although tissue damage is minimized using the bipolar snare, it is not widely used for endoscopic mucosal resection of the stomach because of slippage. The purpose of this study is to determine whether a bipolar snare can be used effectively for endoscopic mucosal resection of the stomach if aspiration is added to avoid slippage of the snare. METHODS: Patients with gastric adenoma or early gastric intestinal type adenocarcinoma were enrolled. Depressed lesions which were ulcerated or greater than 10 mm in diameter and elevated lesions greater than 20 mm in diameter were excluded. The utility of endoscopic aspiration mucosectomy using a bipolar snare (EAM-B) was examined retrospectively and compared with respect to specimen size, rate of complete resection, and occurrence of complication with endoscopic mucosal resection with a capfitted panendoscope using a monopolar snare (EMRC-M). RESULTS: EAM-B was performed in five lesions of five patients and EMRC-M was performed in five lesions of four patients. The resected specimen size was 20.0 ± 0.9 mm after EAM-B and 16.2 ± 4.5 mm after EMRC-M. There was no significant difference in the resected specimen size (P=0.0611) after EAM-B and EMRC-M. Complete resection was achieved in all cases. There were no complications. CONCLUSIONS: A bipolar snare can be used effectively for endoscopic mucosal resection of the stomach if aspiration is added to avoid slippage of the snare.

7085 Preventive clipping following bipolar snare removal of pedunculated colonic polyps.

PURPOSE : Bipolar snares minimize tissue damage, but are not used generally for colonic polypectomy in Japan, probably because increased risk of bleeding reflecting insufficient coagulation is suspected. Since clipping has been reported to be useful in preventing bleeding after monopolar snare polypectomy, we sought to determine whether clipping can prevent bleeding in removal of pedunculated polyps using the bipolar snare. METHODS: We studied patients whose colonic lesions were pedunculated polyps=5 mm in diameter and endoscopically appeared confined to the mucosal layer.We performed bipolar snare polypectomy and added preventive clipping to clamp the stump immediately after polypectomy even when no bleeding was encountered.We assessed retrospectively the histologic diagnosis of the resected specimen, the completeness of polypectomy, and the occurrence of bleeding and perforation. RESULTS : Between April 1997 and March 1999, we evaluated 11 lesions in 10 patients. 11 pedunculated polyps (diameter of head, 10.0 ± 4.1 mm) were resected completely. Histologically, 10 lesions were purely adenoma while 1 contained focal admocarcinoma that arose in the adenoma but was confined to the mucosa. Technical success with clipping was achieved in all cases. No postpolypectomy bleeding, perforation, or complications from dipping occurred. CONCLUSIONS :We found clipping to be effective in preventing bleeding after bipolar snare removal of pedunculated colonic polyps. A bipolar snare which has the advantage of shallow tissue damage can be employed safely by using preventive clipping.

Adrenomedullin inhibits gastric acid secretion and motility in rat

Aim of the study; Adrenomedullin(AM) is a novel hypotensive peptide discovered by Kitamura et al in 1993. It was reported that AM exists in the digestive tract, but nothing is known about the physiological effects of AM in the stomach. We evaluate the effect of intravenous injection of AM on the gastric acid secretion and motility in rat. Methods; Male Wistar rats weighing 200 to 250 g were fastened for 24 h but allowed free access to water up to the beginning of the experiment. 1) Gastric acid secretion: Under urethane anesthesia (1.7g/kg;IP), the physiological saline (pH 7.0 -+ 0.14) was infused through the polyethylene catheter via oral, the gastric secretion was collected continuously through the gastric eannula implanted in the pylorus (lml/min), the gastric acid output and the pepsin activity were measured for every 5min. The gastric acid secretion was stimulated by the infusion of pentagastrin (PG:16~tg/kg/h) for the duration of the experiment and rat-AM was injected through the femoral vein after the stable value of the gastric acid output. 2) Gastric motility: Under urethane anesthesia, the intra-gastric pressure (IGP) and motility were measured by the rubber balloon implanted through an incision in the forestomach and rat-AM was injected through the femoral vein after the stable value of the IGP. CGRP(8-37) was preadministrated, vagotomy and adrenectomy were performed to evaluate the mechanism of this action in the stomach, respectively. Result ; 1) AM did not effect basal gastric secretion (0.9 + 0.04laM/5min). AM inhibited the pentagasrin-stimulated gastric acid secretion significantly, but pepsin activity was not changed. These effects were dose-dependent and not prevented by CGRP(8-37), vagotomy and adrenectomy. 2)AM decreased the basal IGP and gastric motility, significantly. These effects were dose-dependent but not suppressed by CGRP(8-37), vagotomy, adrenectomy.