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Gastroesophageal reflux disease (GERD) is increasing due to adoption of a western life style and an aging society in recent years. The symptoms of GERD, such as heartburn, regurgitation of gastric contents into the mouth, and chest pain, decrease QOL, and continuous treatment is necessary. Treatment of GERD is mainly drug therapy; however, it is believed that providing guidance in changing life-style and providing information about the disease will permit long-lasting relief of the symptoms.

Previous studies have shown that hypertension causes endothelial dysfunction. To study the influence of exogenous nitric oxide(NO) on endothelial dysfunction produced by hypertension, we administered a non-depressor dose of nipradilol to two-kidney, one-clip renovascular hypertensive rats(2K1C). Sprague-Dawley rats underwent either sham surgery(G-1) or clipping of the left renal artery. From day seven, 2K1C were randomized into 3 groups, placebo treatment(G-2), nipradilol treatment(G-3,) and propranolol treatment(G-4). Urinary NO2- + NO3-(NOx) excretion (UNOx V) was measured 4 weeks after clipping, and then, acetylcholine(Ach), A23187, or sodium nitroprusside(SNP)-induced relaxation were measured in the aorta. Blood pressure was increased in G-2, G-3, and G-4 compared to G-1. UNOx V was lower in G-2, G-3, and G-4 compared to G-1, but UNOx V was higher in G-3 compared to G-2 and G-4. Although Ach or A23187-induced relaxation was significantly decreased in isolated artery from G-2, G-3, and G-4 compared with those from G-1. Ach- or A23187-induced relaxation was improved in G-3. SNP-induced relaxation did not differ among the 4 groups. These results suggest that exogenous NO from nipradilol reduces the endothelial dysfunction caused by hypertension without changing the blood pressure.

I have reviewed the comparison between histamine H2 blocker(H2-RA) and proton pump inhibitor(PPI) on the effects of initial treatment in patients with reflux esophagitis. Pathophysiology of reflux esophagitis has been thought to be gastroesophageal reflux of the gastric acid, due to motor dysfunctions of the esophagus and the stomach. Endoscopic healing rate of reflux esophagitis is significantly higher 84% on PPI treatment than 52% on H2-RA treatment at 8 weeks period. Because suppression of the gastric acid secretion is significantly stronger and longer on PPI than H2-RA, especially this suppression is markedly found in day time and also night time. On the initial treatment of reflux esophagitis, PPI is choice so-called "step down therapy" after healing, H2-RA and/or prokinetic drugs are treated as maintenance therapy.

This study was aimed to clarify the endoscopic findings and the decline of serum IgG titer after successful eradication of H. pylori in long-term (from 2 to 7 years). Forty-six H. pylori-positive peptic ulcer (22 GU and 26 DU) cases were eradicated with antimicrobial therapy. Sixty-nine non-eradicated DU cases who received maintainance therapy with H2-blocker were control group. Biopsy urease test (BUT) and culturing was performed to diagnose the H. pylori infection. Anti-H. pylori IgG titer (EIA) were also measured in some cases, pre and 6, 12, 24 months after the eradication. In 3 cases, H. pylori were recrudescent and only in a case, DU recurred during 5 years after eradication. Meanwhile, in 55% of control cases, DU were recurred during same periods. In 62% of eradicated cases, serum IgG-antibody to H. pylori declined below the cut-off level during 2 years after eradication. It was certified that eradication therapy against H. pylori prevents ulcer recurrence for long time, and re-rise of serum IgG titer to H. pylori might predict a recrudescence of infection.

The contribution of the endogenous nitric oxide (NO) to the distal colonic motility was investigated by inhibiting NO production using NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA). The experiment was carried out in the anaesthetized rat, which was vagotomized and pretreated with guanethidine, phentolamine and propranolol. The colonic motility was evaluated by changes in the increase in intraluminal pressure of the distal colon. L-NMMA infusion (100mg/kg iv) in the presence of atropine (1 mg/kg iv) resulted in a significant increase in arterial blood pressure and intraluminal pressure. The following L-arginine infusion (100mg/kg iv) restored blood pressure and intraluminal pressure to the control level. In contrast, L-NMMA infusion in the absence of atropine resulted in no change in intraluminal pressure with a significant increase in arterial blood pressure. These results indicate that there are NO-dependent and nondependent mechanisms to regulate the distal colonic motility.

To evaluate diagnostic tests of Helicobacter pylori (H. pylori), we compared polymerase chain reaction (PCR) for the specific detection of H. pylori, culture and positivity of serum antibody against the bacteria in 59 patients with gastroduodenal disease. PCR assay was designed to amplify 203bp of DNA fragments. PCR detected 10pg of H. pylori DNA, or 40 CFU of the bacteria. PCR was positive in 82.1% of histological gastritis with neutrophil infiltration. Culture and serum antibody to H. pylori were positive in 65.0%, and 94.1% of those patients. Detection rate by PCR was significantly higher than that by the culture methods in patients with chronic gastritis. These results demonstrate that PCR is a sensitive diagnostic test for H. pylori infection.

Stress ulcer formation is reportedly much less frequent in SHR than in normotensive control rats (Wistar Kyoto Rat: WKY). The purpose of this study was to investigate the mechanism of maintenance of gastric mucosal blood flow (GMBF) during imposed stress in SHR. In stressed-only SHR, GMBF did not significantly change during water immersion and restraint conditions and ulcer index (UI) was significantly lower than that of WKY. Stress conditions led to a fall in blood pressure and a gradual fall in heart rate in WKY and SHR. It was assumed that the changes in blood pressure and heart rate during stress were due to vagal hyperfunction. The catecholamine level in the fundic gland of the gastric tissue was higher in the non-stressed SHR than in the non-stressed WKY. The administration of 6-hydroxydopamine to SHR produced a significant reduction in GMBF during stress conditions and UI was significantly higher in this group than in the stressed-only SHR. In SHR treated with nifedipine, UI was lower than that of the control group and GMBF showed no significant change compared with the stressed-only SHR. However, the administration of verapamil produced a significant reduction in GMBF during stress conditions and increased UI. The norepinephrine and dopamine levels of the groups treated with verapamil were significantly lower than those in the groups treated with nifedipine. These results suggest that local regulation of gastric mucosa mediated by sympathetic hyperfunction in SHR is more important for the maintenance of GMBF during stress conditions than changes in peripheral artery resistance.

One hundred and fourty four patients with non-ulcer dyspepsia (NUD), as defined by the working party of AGA in 1987, (67 men and 77 women, 16-76 years, mean age 42.9 +/- 1.2 years) and 34 asymptomatic controls (25 men and 9 women, 17-75 years, mean age 50.6 +/- 2.4 years) parameters of gastrophysiological function (gastric acid secretion, postprandial gastric emptying-acetaminophen method, serum gastrin levels and cutaneous electrogastrography (EGG)) and the prevalence of Helicobacter pylori (Hp) (histological and urease test of biopsy specimens) were investigated. Based on symptom patterns, there were 68 patients with dysmotility-like dyspepsia, 27 with ulcer-like dyspepsia, 17 with reflux-like dyspepsia, 6 with aerophagia and the 26 with nonspecific or idiopathic dyspepsia. The age distribution of NUD was predominant in the fourth decade, and the sex distribution was not significantly different. In general, hypersecretion of gastric acid and hypergastrinemia were rare in NUD patients. There was no significant difference in gastric acid secretion, basal and food stimulated serum gastrin levels and prevalence of Hp between the two groups. But 51 of 144 NUD patients (41.1%) had delayed gastric emptying (p < 0.05) compared to controls. Indeed gastric emptying was markedly prolonged in patients with dysmotility-like (58.1%) and reflux-like (42.9%) dyspepsia. On EGG, about a half of NUD patients showed evidence of bradygastria or tachygastria, in particular in the postprandial state, which was related to delayed gastric emptying. By chronic administration of cisapride, score of symptoms was significantly decreased and postprandial gastric emptying was significantly accelerated in delayed gastric emptying cases. We conclude that in NUD patients, in particular those with dysmotility-like dyspepsia, tests of postprandial gastric emptying and/or EGG are useful for investigation of gastric motor disorder and therapeutic effects of several prokinetic drugs clinically.

To investigate the effect of 6 weeks administration of proton pump inhibitor (omeprazole) and H2-receptor antagonist (cimetidine) on gastric histamine synthesis and acid secretion, we studied experimentally in the rat stomach. Then gastric mucosal histamine concentration, histidine decarboxylase (HDC) activity and serum gastrin concentration, and HDC positive cell number were examined in time-course. The 6 weeks administration of omeprazole caused more increase of HDC positive cells than cimetidine. After cessation of administration with omeprazole, high plasma gastrin level immediately reduced. However the increase of gastric mucosal HDC activity and histamine concentration were prolonged, compared with cimetidine. These findings suggest to affect differently between omeprazole and cimetidine on gastric acid secretion after cessation of long-term treatment.

Three hundred and one gastric cancer patients have been examined preoperatively to investigate their gastric acid secretions after stimulation by tetragastrin, and serum gastrin stimulation by a test meal, as well as for skin reactions and an evaluation of their serum glycoproteins. The results have indicated that their gastric secretions and serum gastrin response were found to be reduced, according to the advancement of their cancer, and that the gastric acid secretion of patients with signet ring cell carcinoma was higher than that of patients with other histological carcinomas. Gastric acid secretions of patients with an ulcerated type of cancer, that is, type IIc and type III in an early cancer stage and type IIc of an advanced Borrmann V type, was higher than in patients with other types, and there were significant correlationships between gastric secretions and PHA skin test and gastric secretions and the IAP and the sialic acid.

Gastric acid secretions and serum gastrin levels have been examined in 128 patients with early gastric cancer and in 98 gastric ulcer patients. Gastric cancer patients were found to have lower acid secretions than did gastric ulcer patients, and those with elevated types of a differentiated adenocarcinoma had lower acid secretions than did those with depressed types of an undifferentiated adenocarcinoma. Gastric acid secretions in patients with both a gastric ulcer and cancer were found to decrease with aging. However, the serum gastrin levels were found to be decreased in patients with a gastric ulcer and to be increased in patients with a gastric cancer. Incidences of a differentiated adenocarcinoma increased with aging. From these observations, it has been speculated that the carcinogenesis of a differentiated adenocarcinoma may be related to increasing endogenous gastrin levels and decreasing gastric acid secretions. These results suggest that a continuous check of the serum gastrin levels might be a good marker for cancer detection and that gastrin antibodies might be useful for treatment.