Influence of monochloramine on healing of acute gastric mucosal lesions in rats: Beneficial effects of polaprezinc

A296 AGAABSTRACTS G1212 ARGON PLASMA COAGULATION (APC) FOR ABLATION OF BARRETT'S EPITHELIUM: FIRST CLINICAL RESULTS IN 21 PATIENTS. D. Stiiker, A. D0pieralski, C. Zindel, G. Farin, K.E. Grnnd. Surgical Endoscopy, University Hospital Tuebingen, Germany Background: Barrett's esophagus (BE) is a predisposition for esophageal adenocarcinoma. 10 to 20% of patients with symptoms of gastroesophageal reflux disease develop a BE. The incidence of BE associated adenocarcinoma is increasing rapidly and the risk is 30-50 times higher than in the general population. Argon-Plasma-Coagulation (APC) offers a new method for local treatment of Barrett's epithelium. Patients and Methods: Between 04/1995 and 11/1997 21 consecutive patients with histopathological diagnosis Of BE were treated with APC in combination with PPI medication. An endoscopic investigation has been completed at 1-6, 12 and 18 months after APC treatment. This follow-up had included a re-evaluation protocol with dye techniques (Lugol-spraying -/methylene blue-spraying), standard esophageal biopsies from all four quadrants every two/one centimeters along the whole length of the columnar epithelium (3-6/< 3 cm) and documentation by video and photographs. Results: In a follow-up of 8 months 70% of the patients had an complete restoration of squamous mucosa. The follow-up of 30% of the patients is less than 6 months. There were no major complications (perforation, posttreatment esophageal stricture) and minor complications < 5% (heartburn). Conclusions: This study shows that APC offers an efficient and safe ablation of Barrett's epithelium for restoration of squamous mucosa. This promising therapeutic approach has to be studied and evaluated further in larger series. • G1213 INFLUENCE OF MONOCHLORAMINE ON HEALING OF ACUTE GASTRIC MUCOSAL LESIONS IN RATS: BENEFICIAL EFFECTS OF POLAPREZINC. Y. Sugawa, H. Nishiwaki, S. Kato, T. Yoneta, K. Takeuchi, Department of Pharmacology & Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Kyoto, Japan. An important feature of Helicobacter pylori (Hp) infection in the stomach is infiltration of neutrophils in the gastric mucosa. Since Hp is capable of producing NH3 from urea, it is highly possible that monochloramine (NH2C1) is formed in the inflamed gastric mucosa, where neutrophil and Hp are located in juxtaposition. In the present study, we investigated the effect of NH2CI on the healing of acute gastric damage in rats, and the healing promoting effects of polaprezinc, a novel zinc compound, were assessed. METHODS: Male SD rats (220~240 g) were used. In the first study, the healing of acute gastric lesions induced by PO administration of 1 ml of absolute ethanol or 120 mM NH2C1 was compared. In the second study, the effect of NH2C1 (20 raM, PO) on the healing response of ethanol-induced lesions was examined. In the third study, the healing promoting action of polaprezinc (10-60 mg/kg, PO) was assessed by examining their effects on the healing of NH2Cl-induced lesions and the delayed healing of ethanol-induced lesions caused by NH2C1. In addition, the effects of NH2C1 on various functions such as mucosal DNA synthetic activity, expression of insulin-like growth factor (IGF), mucosal blood flow (GMBF) and luminal acid loss were also examined. RESULTS: Although the severity of gastric lesions induced by NH2CI and ethanol was same on day 0, the healing of NH2Cl-induced lesions took place more Slowly as compared to that of ethanol-induced gastric lesions. The healing of ethanol-induced lesions was significantly delayed by the repeated administration of NH2C1. Administration of NHzCI caused a slight decrease of the mucosal DNA synthetic activity in the stomach and impaired the GMBF response to acid back-diffusion and capsaicin, Polaprezinc ( > 30 mg/kg) significantly accelerated the healing of NH2Cl-induced gastric lesions as well as the impaired healing of ethanol-induced lesions caused by NH2C1. Polaprezinc showed a scavenging action of NH2C1 and also caused an increased expression of IGF mRNA. In addition, polaprezinc prevented the gastric ulcerogenic response to NH2C1. CONCLUSION: These results suggest that NH2C1 impaired the healing of acute gastric mucosal lesions at a low concentration, and this action may be attributable to both the impairment of GMBF caused by dysfunction of capsaicin-sensitive sensory neurons. Polaprezinc not only showed healing promoting action against NH2Cl-induced gastric lesions but ameliorated the impaired healing of ethanol-induced gastric lesions caused by NH2C1 as well, the action being partly mediated by IGF in addition to a scavenging action against NH2CI. This research was funded by Zeria Pharmaceutical Co., Ltd., Tokyo, Japan • G1214 EFFECT OF VITAMIN E ON HELICOBACTER PYLORI-INDUCED GASTRIC MUCOSAL INJURY. N. Sugimoto, N. Yoshida, K. Kassai, H. Ichikawa, T. Yoshikawa. First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan Neutrophils and lipid peroxidation by oxygen-derived free radicals play important roles in the pathogenesis of H. pylori-induced gastric mucosal injury. While vitamin E is a strong antioxidant in various organs. Recently, it has been reported that H. pylori infection model using Mongolian gerbil shows pathophysiological features close to humans. We investigated the effect of vitamin E on gastric mucosal injury induced by H. pylori infection in

GASTROENTEROLOGYVol. 114, No. 4 Mongolian gerbil. [Materials and Methods] 7 weeks old male Mongolian gerbils were divided into 4 groups (normal, vitamin E deficient, control and Vitamin E rich groups). H. pylori (ATCC43504) were inoculated to 3 groups except normal group. Gerbils were fed with the diet containing atocopherol < 0.1 mg/100g diet in vitamin E deficient group, 2mg/100g diet in control group and 50mg/100g diet in vitamin E rich group. 24 weeks after inoculation of H. pylori, gastric mucosal lesions were assessed, and myeloperoxidase (MPO) activity and thiobarbituric acid reactive substances (TBA-RS) in the gastric mucosa were measured as an index of neutrophil accumulation and lipid peroxidation, respectively. [Results] Macroscopic and microscopic findings showed chronic gastritis in all gerbils inoculated with H. pylori. Gastric ulcer was observed only in 2 gerbils in vitamin E deficient group. In vitamin E deficient group, MPO activity was significantly higher than in vitamin E rich group. No significant differences were detected in TBA-RS. [Conclusion] These results suggest that vitamin E has a protective effect on Mongolian gerbil gastric mucosal injury induced by H. pylori infection through inhibiting accumulation of PMN to the gastric mucosa. • G1215 EFFECTS OF CURING HELICOBACTER PYLORI INFECTION ON PRECANCEROUS GASTRIC LESIONS: ONE-YEAR FOLLOW-UP OF A PROSPECTIVE RANDOMIZED STUDY IN CHINA. JY Sune, SR Lin*, JYL Ching, LY Zhou*, KF To, RT Wang*, WK Leung, LX Wang*, EKW Ng, YT Lee, JYW Lau, SCS Chung, W Chao. Chinese University of Hong Kong and Beijing Medical University*. AIM To investigate the effects of H. pylori eradication on histological lesions of the stomach in a high prevalence region for gastric cancer in China. PATIENTS AND METHOD 1024 volunteers were recruited ~n a screening endoscopic study in Yantai county of Shangdong in China. Patients diagnosed to have H. pylori infection were randomized to received either a one-week course of omeprazole, amoxicillin and clarithromycin or placebo. Six weeks after medication, H. pylori status was reassessed by 13C-UBT. One year after UBT, all subjects were invited for repeating endoscopic examination. At both endoscopies, biopsies were taken from antrum (2x) and corpus (2x). Histological assessment was performed according to Updated Sydney Classification by a single blinded pathologist. RESULTS 600 H. pylori infected subjects were randomized, 547 (91%) returned for UBT and 515 (86%) returned for 2nd endoscopy at 1 year. The 2 groups were comparable in pre-treatment activity of gastritis (AG), chronic inflammation (CI), intestinal metaplasia (IM) and atrophy (AT). H. pylori was eradicated in 91% of anti-biotic treated patients returned for UBT. Comparing histological grading before, and one year after medication of the same patient, significant improvement were seen in AG and CI (P < 0.0001) but not in IM or AT even after successful eradication of H. pylori. Fllrnproved I~1 No change I Deteriorated lOO A G..... Cl IM AT

946 6 o

4o

o

+

-

+

-

-4-

H. pylori Status

-

+

-

CONCLUSION. There is no regression of pre-cancerous lesions in the stomach one year after eradication of H. pylori. This research was funded by a grant from the Hong Kong Society of Digestive Endoscopy • G1216 PROSPECTIVE RANDOMIZED COMPARISON OF 1-WEEK RBCTRIPLE THERAPY VERSUS 1-WEEK PPI-TRIPLE THERAPY FOR H. PYLORI-RELATED DUODENAL ULCERS. JY Sung*, WK Leung*, TKW Ling#, MY Yungt, KL Chan*, YT Lee*, SCS Chungt, AFB Cheng #. Depts of Medicine*, Microbiology # and Surgery*, Prince of Wales Hospital, Chinese University of Hong Kong. AIM. To compare the effects of a one-week course of RBC-triple therapy versus PPI-ttiple therapy in curing H. pylori infection and duodenal ulcers (DU). PATIENTS & METHOD. Patients with endoscopic diagnosis of DU and confirmed H. pylori infection (rapid urease test, histology and urea breath test) were randomized to receive either 1. RBC 400 rag, amoxicillin 1 g and clarithromycin 500 mg (RAC) twice daily for one week, or 2. omeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg (OAC) twice daily for one week. No additional ulcer-healing drug was used after the one-week therapies. Endoscopy was repeated at 5 weeks after randomization to monitor ulcer healing and cure of H. pylori infection. Patients with unhealed ulcers at 5 weeks were reendoscoped at 9 weeks. H. pylori eradication was confirmed by