Development Of Gastric Ulcers Research Articles

Anti-ulcer Activity of Curcumin on Experimental Gastric Ulcer in Rats and Its Effect on Oxidative Stress/Antioxidant, IL-6 and Enzyme Activities

To investigate the possible mechanism by which curcumin protects stomach during the acute chronic phase of gastric ulcer disease. The rats were divided into four groups and fasted for 2 days with free access to water. On the third day, the animals were fasted for a further 24 h with no access to water followed by surgery. Rats received different doses of curcumin (20, 40, and 80 mg/kg) or vehicle by oral gavage. Nineteen hours after ulcer induction, the rats were killed by decapitation. Stomach was opened along the greater curvature and ulcerative lesions were counted. Total juice acidity, neutrophils activity, mitochondrial activity, total antioxidants, paraoxonase (PON 1)/arylesterase and total peroxides were evaluated. DNA fragmentation (%) and pro-inflammatory cytokine IL-6 level were measured. The level of different gastro-cytoprotective effectors including total antioxidants and paraoxonase (PON 1)/arylesterase activities was measured. The anti-ulcer activity of curcumin was displayed by attenuating the different ulcerative effectors including gastric acid hyper-secretion, total peroxides, myeloperoxiase (MPO) activity, IL-6 and apoptotic incidence. Curcumin appears to have a propitious protective effect against gastric ulcer development.

An Unusual Complication of TACE in a Patient with Cirrhosis and Hepatocellular Carcinoma

Purpose: Transarterial Chemoembolization (TACE) has been shown to improve survival in cirrhotic patients with hepatocellular carcinoma (HCC). Patients who are candidates for liver transplantation may benefit from this procedure to keep them listed as an active candidate for extended periods of time. Common complications include a self limiting post-chemoembolization syndrome, but rare complications such as encephalopathy, ascites, GIB have also been described. We present the case of a patient who developed an enterobiliary fistula as a complication of the procedure. To our knowledge, this has not been described before. Case: 67-year-old-man with cryptogenic cirrhosis with HCC who had undergone RFA for two dominant masses in the previous year. On his most recent imaging study his disease had progressed and he underwent TACE of the right lobe of the liver with of cisplatin, mitomycin C and doxorubicin. Results: A day after the procedure, he presented with confusion and was noted to have fever with an elevated white count and new onset ascites. This fluid grew Klebsiella pneumoniae and Candida spp. It was felt that this was most likely secondary bacterial peritonitis. A CT scan showed no evidence of a perforation, however showed hyperdensities inside the gallbladder (GB), thought to represent products of chemoembolization in the lumen of the GB. He was treated with bactrim and fluconazole with good clinical improvement. Six weeks later, the patient was re-admitted with weight loss and loss of appetite and vague abdominal pain. CT scan of abdomen showed persistent haziness surrounding the head of the pancreas, consistent with pancreatitis with adjacent focal fluid collections and pneumobilia. There were no associated inflammatory changes of the GB or adjacent bowel. An upper endoscopy showed a large area of ulceration seen in the post bulbar area with two areas which were thought to represent fistulous communications. An upper GI series was done that revealed a post-bulbar ulcer with an enterobiliary fistula. The patient was placed on total parenteral nutrition (TPN) with resolution of the pain. Subsequently, enteral feeding had been initiated. Conclusion: Our impression is that the TACE caused regurgitation of the embolizing particles into the right or left gastric artery with subsequent, development of possibly ischemic ulcer. Other theories propose that arterial spasm provoked by the manipulation of the catheter and secondary ischemia may have lead to development of gastric and duodenal erosions and ulcers. We think that ischemia caused the duodenal ulcer and the biliary injury in our patient subsequently leading to fistula formation. This is the first time that an enterobiliary fistula has been described as a complication of TACE.

Percutaneous Endoscopic Gastrostomy Tubes: How Safe Are They?

Purpose: To evaluate the indications, complications and survival of patients undergoing percutaneous endoscopic gastrostomy (PEG) tube placement over a one-year period in a large academic community hospital. Methods: Medical records of all patients undergoing PEG placement from August 2006 through September 2007 were reviewed. Data was collected and entered into a PEG registry. Telephone follow up was made after a 1 year period to determine long term outcome. Results: 281 PEGs were performed during the study period. 52.3% were males with a mean age of 71.5 yrs. The indications for PEG placement were as follows: dysphagia 24.5%, organic brain injury 13.1%, dementia 12%, malignancy 16.3%, long term ventilation 8%, CHF/COPD 9.3%, failure to thrive 8.5%, persistent vegetative state 1.4% and other 5%. 52.3% of PEGs were performed by a gastroenterologist, 19% by a surgeon and 28.7% by a combination of surgeon/gastroenterologist. 57 (20.2%) of the cases had reported complications. Complications were as follows: 17 aspirations, 18 peristomal infections, 6 bleeding episodes, 4 cases of gastroparesis, 3 cases of peritonitis, 3 stomal leakage, 3 interval development of gastric ulcers, 7 cases of inadvertent removal, 2 cases of extra-gastric placement, 3 perforations, and 1 case each of bowel obstruction, acute renal failure and necrotizing fasciitis. 87 (31%) and 67 (23.8%) died within 6 and 6-12 months of PEG placement, respectively. 154 (54.8%) patients died within 12 months of PEG placement. 95 (33.4%) survived greater than 12 months. 32 (11.4%) were lost to follow up. Of the 147 procedures performed by a gastroenterologist, 22 cases had 27 reported complications (15%). Of the 81 procedures done by the combination of a gastroenterologist/surgeon, 27 cases had 34 reported complications (33%). Of the 53 procedures done by surgeons alone, 8 cases had 8 reported complications (15%). No patient died as an immediate result of any complication or immediately following PEG placement. Conclusion: The overall complication rate for PEG placement at our institution was 20.2% with the majority of these complications being mild. The fact that 31% of the patients died within 6 months and 23.8% died between 6 and 12 months following PEG placement suggests that PEG tube placement did not alter the course of the underlying disease or improve long-term outcomes. These results bring into question the appropriateness of patient selection and the indications for PEG placement. PEG placement by a combination of gastroenterologist and surgeon had the highest number and percentage of complications. Further analyses should be performed to determined specific risk factors for predicting poor survival following PEG tube placement.

Effect of a feed/fast protocol on pH in the proximal equine stomach

Risk factors for the development of gastric squamous ulcers include various management procedures, such as intermittent feed deprivation that can occur during weight management regimens or stall and dry lot confinement. To investigate the effect of intermittent feed deprivation relative to continuous feed intake on proximal intragastric pH, specifically in the region of the squamous mucosa of the lesser curvature. In 6 horses, pH electrodes were placed just inside of the oesophageal sphincter in the stomach for each of two 72 h protocols (A and B) in a randomised, cross-over design. Protocol A consisted of 12 h fed, 12 h fasted, 24 h fed and 24 h fasted, in sequence. Protocol B consisted of 72 h fed. During the fed periods of each protocol, horses had ad libitum access to coastal Bermuda hay and were fed sweet feed (1 kg, b.i.d.). Horses had ad libitum access to water at all times. Proximal intragastric pH was significantly lower during protocol A, than during protocol B. However, hourly mean pH was significantly different only during the day and evening hours between protocols. During protocol B, mean proximal pH decreased significantly from 03.00 to 09.00 compared to 19.00 to 23.00 h. A moderate positive correlation of hay intake vs. proximal gastric pH could be established. Intermittent feed deprivation decreased proximal gastric pH in horses relative to those horses for which feed was not restricted. However, the effect was only significant when fasting occurred during the day and evening hours, as a nocturnal decrease in pH occurred simultaneously in the fed horses. Episodes of daytime feed deprivation should be avoided if possible, as proximal gastric acid exposure rapidly increases during such events.

Rabeprazole

Rabeprazole (Aciphex, Alfence, Pariet) is a proton pump inhibitor (PPI) used for the treatment of adults with conditions requiring a reduction of gastric acid secretion such as erosive or ulcerative gastro-oesophageal reflux disease (GORD), non-erosive reflux disease (NERD), duodenal and gastric ulcers, and pathological hypersecretory conditions including Zollinger-Ellison syndrome (ZES). It is also used as part of combination therapy for the eradication of Helicobacter pylori, a pathogen frequently implicated in the development of gastric and duodenal ulcers. Rabeprazole has a well established efficacy and safety profile in the treatment of gastric acid-related diseases. Rabeprazole is a useful, well tolerated and cost-effective option for the treatment of GORD, NERD, peptic ulcer and other gastric acid-related diseases (including ZES), and provides an appropriate alternative to other currently available PPIs, with the added benefits of having a consistent efficacy profile and low drug interaction potential due to its predominantly nonenzymatic metabolism.

The Relationship Between <I>Helicobacter pylori</I> Infection and Gastric Adenocarcinoma in Northern Iran

Colonization of the human stomach with Helicobacter pylori induces chronic gastritis and is associated with the development of gastric and duodenal ulcers, gastric carcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Infection with an H. pylori strain containing the cytotoxin-associated (cagA) gene (a marker for a pathogenicity island) may increase the risk of atrophic gastritis and gastric cancer. The exact role of H. pylori in gastric carcinogenesis is still being investigated. Hence, we assessed whether H. pylori infection is associated with the development of gastric adenocarcinoma in northern Iran. Gastric biopsy specimens from 168 patients suffering from gastric adenocarcinoma, gastric ulcer, and non-ulcer dyspepsia were analyzed by means of the polymerase chain reaction. H. pylori was detected in the gastric mucosa of 34 (75.5%) gastric adenocarcinoma, 56 (88.8%) gastric ulcer, and 36 (60%) non-ulcer dyspepsia. In patients with gastric adenocarcinoma, the cagA was less commonly found than those in noncancer patients (4/34 vs. 58/92, p < 0.05). Our work suggests that although H. pylori infection is significantly associated with gastric adenocarcinoma in northern Iran, the cagA is not the dominant virulence in development of gastric adenocarcinoma.

Interleukin‐1 receptor activates Rho kinase to disrupt epithelial tight junctions during Helicobacter pylori infection

The ability of H. pylori (Hp) to modulate tight junction (TJ) permeability may contribute to the development of gastric ulcers and adenocarcinomas. Rho kinase (ROCK) and interleukin (IL)‐1β are known to modulate tight junction (TJ) function. While Hp induces IL‐1β expression, the role of this proinflammatory cytokine and ROCK in Hp‐mediated TJ disruption remains elusive.AIMThis study investigated the role of ROCK and IL‐1β in Hp‐mediated TJ disruption in human gastric epithelial (HGE‐20) cells.RESULTSHGE‐20 monolayers challenged with either Hp or IL‐1β showed an increase in ROCK activity 6 h post infection, which coincided with redistribution and loss of claudin‐4. Inhibition of ROCK prior to bacterial challenge prevented these effects. Hp infection also induced IL‐1 receptor (IL‐1R) phosphorylation. Nevertheless, no increase in IL‐1β could be detected in supernatants of infected monolayers and treatment with co‐culture conditioned media failed to induce IL‐1R phosphorylation. While an IL‐1β neutralizing antibody did not prevent Hp‐induced IL‐1R activation, the use of an IL‐1R blocking antibody prior to infection prevented Hp‐mediated ROCK activation and claudin‐4 loss.CONCLUSIONThese findings suggest that the mechanism by which Hp disrupts gastric epithelial barrier structure involves IL‐1R ‐dependent activation of ROCK, which mediates claudin‐4 disruption. This work was funded by CIHR.

Antiulcer activity of methanolic extract of Momordica charantia L. in rats

Aim of the study Momordica charantia L. (Cucurbitaceae) commonly known as ‘bitter gourd’ is a multi purpose herb cultivated in different parts of the world for its edible fruits. The objective of the present study was to evaluate the effect of standardized methanolic extract of Momordica charantia L. fruits on gastric and duodenal ulcers. Materials and methods The effect was evaluated in acetic acid induced chronic gastric ulcer, pylorus ligation induced gastric ulcer, ethanol induced gastric ulcer, stress induced gastric ulcer, indomethacin induced gastric ulcer and cysteamine induced duodenal ulcer model. The extract was administered orally at two different doses of 100 mg/kg and 500 mg/kg. Results The healing of acetic acid induced gastric ulcer was increased by both doses of the extract. In pylorus-ligated rats, the extract showed significant decrease in ulcer index, total acidity, free acidity and pepsin content and an increase in gastric mucosal content. The extract also reduced the ulcer index in stress induced, ethanol induced and indomethacin induced gastric ulcers and cysteamine induced duodenal ulcer. Conclusion The methanolic extract of Momordica charantia L. fruit increases healing of gastric ulcer and also prevents development of gastric ulcers and duodenal ulcers in rats.

Interleukin-1 and TNF-α polymorphisms and Helicobacter pylori in a Brazilian Amazon population

To study the association between Interleukin-1 (IL-1) and tumor necrosis factor (TNF)-alpha polymorphisms, infection by Helicobacter pylori (H pylori) and the development of gastrointestinal diseases. Genomic DNA was extracted from the peripheral blood of 177 patients with various gastrointestinal diseases and from 100 healthy volunteers. The polymorphisms in IL-1beta and TNF-alpha genes were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) and those from IL-1RN with PCR. The presence of infection due to H pylori and the presence of the CagA toxin were detected by serology. The histopathological parameters in the gastric biopsies of the patients were according to the Sydney classification. A comparison of the frequencies of the different polymorphisms studied among the patients and the control group demonstrated that the allele IL-1RN*2 was more frequent among patients with gastric ulcers and adenocarcinoma. Carriers of the allele IL-RN*2 and those with reactive serology for anti-CagA IgG had a greater risk of developing peptic ulcer and gastric adenocarcinoma, as well as a higher degree of inflammation and neutrophilic activity in the gastric mucosa. Our results indicate a positive association between IL-1RN gene polymorphism and infection by positive H pylori CagA strains and the development of gastric ulcers and adenocarcinoma.

Rho kinase mediates Helicobacter pylori ‐induced tight junctional claudin‐4 disruption in human gastric epithelial cells

Gastric epithelial barrier function is primarily maintained by tight junctions (TJ). Small Rho GTPases and Rho kinase (ROCK) are involved in TJ regulation. The ability of H. pylori (Hp) to subvert normal cellular pathways regulating TJ permeability may contribute to the development of gastric ulcers and adenocarcinomas. The mechanisms involved in Hp‐mediated junctional disruptions remain unclear.AIMThe aim of this study was to assess the role of ROCK in Hp‐induced TJ disruption, using a human gastric epithelial (HGE‐20) cell line.RESULTSImmunostaining/Western blotting and activity assays showed cytosolic translocation of claudin‐4 and a 50% increase in ROCK activity in infected monolayers. ROCK inhibition reduced loss of claudin‐4 from the membrane. Treatment of HGE‐20 with conditioned media failed to induce the Hp‐mediated increase in ROCK activity. Caspase‐3 and Rho GTPases Rac‐1 and RhoA activity was significantly increased post infection, consistent with their involvement in the signaling events leading to ROCK activation and claudin‐4 redistribution.CONCLUSIONThese findings demonstrate that Hp activates ROCK and its upstream effectors caspase‐3 and Rho GTPases. The mechanism by which Hp disrupts gastric epithelial barrier structure involves ROCK‐dependent redistribution of claudin‐4, independently of epithelial or bacterial secreted factors. This work was funded by CIHR.

NSAIDs, coxibs, CINOD and H 2S-releasing NSAIDs: What lies beyond the horizon

Nonsteroidal anti-inflammatory drugs are widely prescribed for treatment of pain and inflammation, despite their association with gastrointestinal complications, including bleeding and perforation. Inhibition of cyclo-oxygenases, is the main mechanism of action of aspirin and nonsteroidal anti-inflammatory drugs. Non-selective nonsteroidal anti-inflammatory drugs inhibit cyclo-oxygenase-1 and cyclo-oxygenase-2. Inhibition of cyclo-oxygenase-1 derived prostanoids in the stomach represent the underlying mechanism involved in development of gastric and duodenal ulcers in patients taking nonsteroidal anti-inflammatory drugs. Selective cyclo-oxygenases-2 inhibitor (coxibs) spare cyclo-oxygenase-1 show enhanced safety profile in the gastrointestinal tract, but increase the risk of heart attack and stroke. Spurred by these findings, two coxibs, rofecoxib and valdecoxib, were withdrawn from the market. In addition to prostanoids, two gaseous mediators, nitric oxide (NO) and hydrogen sulfide (H 2S) exert protective effects in gastric mucosa. The inhibitory effects of NO on nonsteroidal anti-inflammatory drugs-induced leukocyte adherence have been exploited in the development of NO-releasing nonsteroidal anti-inflammatory drugs, also indicated as cyclo-oxygenase-inhibiting NO-donating drugs. Despite its non-selective profile versus cyclo-oxygenase isoenzymes, naprocyclo-oxygenase-inhibiting NO-donating drugs, the prototype of this class of anti-inflammatory agents, reduces systemic blood pressure and might have enhanced cardiovascular safety than coxibs, while causing less gastrointestinal damage than its parent drug, the naproxen. H 2S-releasing nonsteroidal anti-inflammatory drugs derivatives have been recently developed, based on the observed ability of this gaseous mediator to cause vasodilation and to prevent leukocyte adherence. In pre-clinical settings, H 2S-releasing nonsteroidal anti-inflammatory drugs produce less gastric damage as compared to the parent drugs. Cyclo-oxygenases-inhibiting NO-donating drugs and H 2S-releasing nonsteroidal anti-inflammatory drugs represent examples of new anti-inflammatory drugs created through the exploitation of the beneficial effects of endogenous gaseous mediators in the gastrointestinal and cardiovascular systems.

Clinical trial: healing of NSAID‐associated gastric ulcers in patients continuing NSAID therapy – a randomized study comparing ranitidine with esomeprazole

The use of non-steroidal anti-inflammatory drugs (NSAID) is associated with an increased risk of gastric ulcer (GU) development. This multicentre, randomized, double-blind, parallel-group trial compared endoscopic healing rates at 4 and 8 weeks after treatment with oral esomeprazole 40 or 20 mg once daily, or ranitidine 150 mg twice daily, in patients with 1 baseline GU > or = 5 mm but no GUs or duodenal ulcers >25 mm in diameter who received continued cyclooxygenase-2-selective or non-selective NSAID therapies. The primary outcome was the percentage of patients in each treatment group who had no GUs at week 8. Four hundred and forty patients were randomized to treatment. At week 8, GU healing rates (95% CI) with esomeprazole 40 mg, esomeprazole 20 mg and ranitidine were 85.7 (79.8-91.7)%, 84.8 (78.8-90.8)% and 76.3 (69.2-83.3)%, respectively; between-group differences were not statistically significant. Week-4 GU healing rates were 70.7 (62.9-78.4)% and 72.5 (65.0-79.9)% with esomeprazole 40 and 20 mg, respectively, and were significantly higher (P < 0.01 for both doses) than those with ranitidine [55.4 (47.1-63.7)%]. In patients who require continued NSAID therapy, GU healing rates at 8 weeks numerically favoured esomeprazole but were not significantly different from ranitidine.

Helicobacter pylori infection in people who are intellectually and developmentally disabled: A review

The Helicobacter pylori (H. pylori) bacterium has been classified by the World Health Organization as a type 1 carcinogen with associations to the development of peptic and gastric ulcers, gastric carcinoma and primary B-cell lymphoma. Individuals who have intellectual disabilities and developmental disabilities (IDDD) exhibit H. pylori gastric infection at approximately twice the rate of the general population and have recurrences after triple drug treatment at a rate nearly seven times that of the general population. Gastrointestinal malignancy is reported to account for almost 50% of all cancer deaths in this population. Oral-oral and fecal-oral routes are theorized to be the primary modes of transmission for the ingestion of the bacterium. Maladaptive behaviors exhibited by individuals who have IDDD can be considered risk factors for H. pylori infection since H. pylori has been cultivated from vomitus, saliva, and feces. The purpose of this paper is to review information regarding Helicobacter pylori infection in persons with IDDD and highlight the significance of oral infection.

Effects of short-term light to heavy exercise on gastric ulcer development in horses and efficacy of omeprazole paste in preventing gastric ulceration

To determine the effects of 8 days of light to heavy exercise on gastric ulcer development in horses and determine the efficacy of omeprazole paste in preventing gastric ulceration. Randomized, controlled, multicenter clinical trial. 102 horses with normal-appearing gastric mucosa on endoscopic examination that were in light to heavy training. Horses at 4 trial locations were allocated into replicates and sham dosed orally (empty syringe) or treated with a paste formulation of omeprazole (1 mg/kg [0.45 mg/ lb], PO) once daily for 8 days. Training regimens varied among locations and included early training for western performance events; walking, trotting, and cantering in a mechanical exerciser; and race training (2 locations). Prevalences of gastric ulceration at the completion of the 8-day treatment period were compared between groups. At the end of the 8-day treatment period, the proportion of omeprazole-treated horses free from gastric ulceration (88%) was significantly higher than the proportion of sham-dosed horses free from gastric ulceration (27%). Results showed that horses in light to heavy training for as short as 8 days were at risk of developing gastric ulcers and that administration of omeprazole paste decreased the incidence of gastric ulcers.

Effect of peroxisome proliferator‐activated receptor‐α agonist (bezafibrate) on gastric secretion and gastric cytoprotection in rats

The effect of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) on gastric secretion and gastric cytoprotection was evaluated using five different models of gastric ulcers: acetic acid-induced chronic gastric ulcers, pylorus ligation, ethanol-induced, indomethacin-induced and ischemia-reperfusion-induced gastric ulcers. Bezafibrate, a PPAR-alpha agonist was administered at two different doses of 10 and 100 mg/kg body weight intraperitoneanally. Both doses of bezafibrate showed significant antiulcer effect in ethanol-induced, indomethacin-induced and pylorus ligation-induced gastric ulcers. Bezafibrate increased healing of ulcer in acetic acid-induced chronic gastric ulcer model. Both doses were also effective in preventing gastric lesions induced by ischemia-reperfusion. It was concluded that PPAR-alpha activation increases healing of gastric ulcers and also prevents development of gastric ulcers in rats.

Different effects of polymorphisms of tumor necrosis factor‐alpha and interleukin‐1 beta on development of peptic ulcer and gastric cancer

In Western countries, polymorphism of pro-inflammatory cytokine genes is associated with the development of gastric cancer and duodenal ulcer. The aim of this study was to clarify the association of polymorphisms of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha with susceptibility to peptic ulcer diseases and gastric cancer in Japan. The IL-1beta-511/-31 and TNF-alpha-308/-857/-863/-1031 genotypes were determined in Helicobacter pylori-positive patients with gastritis only (n = 164), gastric ulcers (n = 110), duodenal ulcers (n = 94), or gastric cancers (n = 105), and in H. pylori-negative controls (n = 172). Carriage of the alleles TNF-alpha-857 T (odd ratio [OR], 1.826; 95% confidence interval [CI], 1.097-3.039), TNF-alpha-863 A (OR, 1.788; 95% CI, 1.079-2.905) and TNF-alpha-1031 C (OR, 1.912; 95% CI, 1.152-3.171) was associated with increased risk for gastric ulcer development. Carriage of the alleles TNF-alpha-857 T (OR, 1.686; 95% CI, 1.003-2.832), TNF-alpha-863 A (OR, 1.863; 95% CI, 1.118-3.107) and TNF-alpha-1031 C (OR 2.074; 95% CI, 1.244-3.457) was also associated with increased risk of gastric cancer development. There was no relationship between the development of H. pylori-related diseases and polymorphisms of IL-1beta-511/-31 and TNF-alpha-308. The simultaneous carriage of three different high-producer alleles of TNF-alpha-857/-863/-1031 significantly increased the risk of gastric ulcer (OR, 6.57; 95% CI, 2.34-18.40) and gastric cancer (OR, 5.20; 95% CI, 1.83-14.78). Polymorphisms in TNF-alpha rather than IL-1beta are associated with increased risk for gastric ulcers and gastric cancer in Japan. The simultaneous carriage of more than one high-producer allele of TNF-alpha further increased the risks for gastric ulcer and cancer.

Radiation therapy for abdominal lymph node metastasis from hepatocellular carcinoma

We report the results of radiotherapy for abdominal lymph node metastasis from hepatocellular carcinoma (HCC). From 1998 to 2004, 45 cases were treated with radiotherapy (RT), with a dose between 30 and 55 Gy. The radiation response, overall survival, prognostic factors, and complications were evaluated. Thirty-nine cases were able to be evaluated for response: 10 cases showed complete response; 21 cases showed a partial response; and 8 cases showed stable disease. The overall response rate was 79.5%. The response rate was 87.5% for patients receiving >or=40 Gy(10) (biologically effective dose, alpha/beta = 10) and 42.9% for patients receiving <40 Gy(10) (P = 0.02). The median survival time was 10 months for responders and 6 months for nonresponders (P = 0.01). The absence of other concurrent distant metastasis and controllable primary HCC were significant prognostic factors. RT induced gastric or duodenal ulcer development in nine patients. All of these patients had received more than 50 Gy(10), and these complications were not detected among patients receiving <50 Gy(10) (0% vs 37.5%, P < 0.01). RT was an effective treatment modality, and the absence of concurrent distant metastasis and controllable primary tumor were significant prognostic factors. However, considering the high rate of RT-induced morbidity, 40 Gy(10) to 50 Gy(10) might be the optimal RT dose.

Nonsteroidal anti‐inflammatory drugs induce hypermotilinemia and disturbance of interdigestive migrating contractions in instrumented dogs

Nonsteroidal anti-inflammatory drugs (NSAIDs) induce gastric ulcers due to inhibition of prostaglandin production. Prostaglandins have an influence on physiological gastrointestinal motility, but the relationships between NSAID-induced gastric ulcer, gastrointestinal motility and motilin are unknown. Fifteen dogs were allocated randomly to three groups in which either gelatin, meloxicam or indomethacin was administered. Fecal occult blood and gastrointestinal motility were monitored continuously for 6 days. In addition, analyses of the plasma motilin concentration, gastrointestinal endoscopy and gastric emptying, and detection of motilin cells were performed. Gastrointestinal motility was disturbed in the indomethacin group, presenting as disappearance of interdigestive migrating contractions (IMCs) 3 days before gastric ulcers were detected. Delayed gastric emptying and hypermotilinemia were observed significantly more often in the indomethacin group compared with the other groups. Motilin cell-crypt/villi ratio in the indomethacin group significantly decreased in the duodenum and jejunum, compared with the other groups. No significant changes in any tests were observed in the meloxicam group, when compared with the gelatin group. These findings suggest that the disturbance of IMCs caused by hypermotilinemia, with changes in motilin cell distribution, and delayed gastric emptying induced by indomethacin may contribute to the development of gastric ulcers.

Influences of Chymase and Angiotensin I-Converting Enzyme Gene Polymorphisms on Gastric Cancer Risks in Japan

The renin-angiotensin system plays an important role in homeostasis. Angiotensin II, which is generated by chymase and angiotensin I-converting enzyme (ACE), controls blood pressure as well as angiogenesis and cell proliferation. The aim of this study was to clarify the association of the chymase gene (CMA/B) and ACE polymorphisms with susceptibility to gastric cancer and peptic ulcer. We assessed CMA/B A/G and ACE insertion/deletion (I/D) polymorphisms in H. pylori-positive gastric cancers (n = 119), gastric ulcers (n = 127), and duodenal ulcers (n = 105), and controls (n = 294) consisting of H. pylori-positive gastritis alone (n = 162) and H. pylori-negative subjects (n = 132) by PCR methods. In CMA/B polymorphism, the age- and sex-adjusted odds ratios (OR) of A/A and A/G genotypes relative to the G/G genotype for gastric cancer risk were 7.115 (95% confidence interval, 1.818-27.845) and 1.956 (95% confidence interval, 1.137-3.366), respectively. There was an increased risk for gastric ulcer in the A/A genotype (OR, 3.450; 1.086-10.960). However, there was no association between ACE polymorphism and susceptibility to gastric cancer and peptic ulcer. In allele combination analysis of CMA/B and ACE polymorphisms, the A/I allele combinations (CMA/B G/A or A/A and ACE I/I genotype) significantly increased the risk of gastric cancer development (OR, 4.749, 2.050-11.001) compared with the G/I allele combinations (CMA/B G/G and ACE I/I genotype). The CMA/B polymorphism was associated with an increased risk for gastric cancer and gastric ulcer development. The genotyping test of the renin-angiotensin system could be useful for the screening of individuals with higher risks of gastric cancer and gastric ulcer.

Mechanisms involved in the gastro-protective effect of STW 5 (Iberogast®) and its components against ulcers and rebound acidity

The protective effect of a commercial preparation (STW 5, Iberogast), containing the extracts of bitter candy tuft, lemon balm leaf, chamomile flower, caraway fruit, peppermint leaf, liquorice root, Angelica root, milk thistle fruit and greater celandine herb, against the development of gastric ulcers was previously reported in an earlier publication (Khayyal et al., 2001). All extracts produced a dose dependent anti-ulcerogenic effect associated with a reduced acid output, an increased mucin secretion, an increase in prostaglandin E(2) release and a decrease in leukotrienes. The effect on pepsin content was not uniform and did not seem to bear a relationship with the anti-ulcerogenic activity. The best effects were observed with the combined formulation, STW 5. Furthermore, the effect of the latter in protecting against the development of rebound gastric acidity was examined experimentally in rats and compared with the effect of some commercial antacid preparations (Rennie, Talcid and Maaloxan). A model of testing rebound acidity was developed by inducing a marginal increase in gastric acidity through the administration of indomethacin, in such a way that it could be easily neutralized, allowing any eventual secondary increase in acidity to be measured within a few hours of administration. In addition, the serum gastrin level was measured after drug treatment to establish any correlation between it and any rebound acidity. The results obtained demonstrated that STW 5 did not only lower the gastric acidity as effectively as the commercial antacid, but it was more effective in inhibiting the secondary hyperacidity. Moreover, STW 5 was capable of inhibiting the serum gastrin level in rats, an effect which ran parallel to its lowering effect on gastric acid production.