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Arachidonic acid (AA), when cleaved from phospholipids by cytosolic phospholipase A2 alpha (cPLA2a), generates eicosanoids, with pro-hemostatic, pro-inflammatory, vasoactive and gastro-protective functions. We describe a patient (27-year-old man) and his twin-sister with early-onset bleeding diathesis and recurrent gastro-intestinal (GI) ulcers. Platelet aggregation/δ-granules secretion by collagen was impaired, but normal by AA; serum levels of thromboxane (Tx) B2 and 12-hydroxyeicosatetraenoic acid, and urinary levels of 11-dehydro-TxB2 were extremely low. Patients were homozygous for 1723G>C transition in PLA2G4A gene, which changed the codon for Asp575 to His. GI ulcers affected 5/14 heterozygous (< 40 years) and 1/16 wild-type homozygous (> 60 years) family members; none had bleeding diathesis. The proband, his sister and mother also had mildly reduced factor XI levels. Platelet messenger RNA expression did not differ among subjects with different PLA2G4A genotypes. Conversely, platelet cPLA2a was undetectable by Western Blotting in the proband and his sister, and decreased in 1723G>C heterozygous subjects, suggesting that the variant is transcribed, but not translated or translated into an unstable protein. We described a syndromic form of deficiency of cPLA2a , characterised by recurrent GI ulcers and bleeding diathesis, associated with mild inherited deficiency of factor XI. Unlike other reported patients with cPLA2a deficiency, these patients had extremely low levels of platelet TxA2 biosynthesis.

Background/aim: Gastro duodenal ulcer is a common disorder of the gastrointestinal tract. Several Indian medicinal plants have been traditionally and extensively used to prevent different diseases. In the present research studies, Bael fruit (Aegle marmelos (AM), family: Rutaceae) which are also called as Bilva in ancient Sanskrit was used as a herbal drug and its antioxidative role in aspirin- induced gastroduodenal ulceration in albino rat was evaluated using essential biochemical parameters., Patients and Methods: Mucosal thickness (MT), ulcer index (UI), different biochemical parameters, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), and lipid peroxidation (LPO) were measured in all the groups, to study the possible involvement of antioxidants with gastroduodenal protection., Results: A significant decrease in MT, SOD and CAT activities and GSH level and a significant increase in UI, AST, ALT, and ALP activities and LPO level were observed in aspirin treated stomach and duodenum of albino rats., Conclusions: Pretreatment with AM fruit pulp extract for 14 consecutive days showed the reverse effects of aspirin suggesting gastro-duodenal protective and anti- ulcerogenic properties of AM through its antioxidant mechanism.

Background and Aim: Cysteamine is a reducing aminothiol used for inducing duodenal ulcer through mechanisms of oxidative stress related to thiol-derived H(2)O(2) reaction. Cochinchina momordica saponins have been suggested to be protective against various gastric diseases based on their cytoprotective and anti-inflammatory mechanisms. This study was aimed to document the preventive effects of Cochinchina momordica seed extract against cysteamine-induced duodenal ulcer as well as the elucidation of its pharmacological mechanisms., Methods: Cochinchina momordica seed extract (50, 100, 200 mg/kg) was administrated intragastrically before cysteamine administration, after which the incidence of the duodenal ulcer, ulcer size, serum gastrin level, and the ratio of reduced glutathione (GSH)/oxidized glutathione disulfide (GSSG) as well as biochemical and molecular measurements of cytoplasmic phospholipase A(2) (cPLA(2)), cyclooxygenase-2 (COX-2), 5-lipoxygenase and the expression of proinflammatory genes including IL-1β, IL-6, COX-2 were measured in rat model. Additional experiments of electron spin resonance measurement and the changes of glutathione were performed., Results: Cochinchina momordica seed extract effectively prevented cysteamine-induced duodenal ulcer in a dose-dependent manner as reflected with significant decreases in either duodenal ulcerogenesis or perforation accompanied with significantly decreased in serum gastrin in addition to inflammatory mediators including cPLA(2), COX-2, and 5-lipoxygenase. Cochinchina momordica seed extract induced the expression of γ-glutamylcysteine synthetase (γ-GCS)-related glutathione synthesis as well as significantly reduced the expression of cPLA(2). Cochinchina momordica seed extract preserved reduced glutathione through increased expressions of γ-GCS., Conclusion: Cochinchina momordica seed extracts exerted significantly protective effect against cysteamine-induced duodenal ulcer by either cPLA2 inhibition or glutathione preservation., (© 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

The aim of this study was to evaluate the gastroprotective efficacy of andrographolide isolated from Andrographis paniculata in rats induced with duodenal ulcers. Duodenal ulcers were induced by cysteamine administration in rats pretreated with 3 mg kg⁻¹ BW day⁻¹ of andrographolide for 30 days. Ulcer score, myeloperoxidase activity, TBARS level, GSH/GSSG ratio and enzyme antioxidants were measured in the duodenal tissue. Brush border and basolateral membranes were isolated to assay sucrase, maltase, alkaline phosphatase and total ATPases. Ulcer score was significantly minimised in rats pretreated with andrographolide. Elevation in myeloperoxidase and TBARS levels were found to be minimised significantly due to andrographolide treatment. Membrane-bound enzyme activities and the thiol redox status of glutathione were significantly maintained in duodenal mucosa of rats that received andrographolide. This study reveals that the major component of A. paniculata, andrographolide, has potent antiulcer properties that are most likely caused by minimising inflammatory changes, counteracting free radical formation and maintaining the thiol redox status in the duodenum.

Antiulcer activity of Andrographis paniculata was evaluated by cysteamine induced duodenal ulcer model in rats. Male albino Wistar rats were pre-administered with 200 mg/kg body wt. of hydroalcoholic extact of Andrographis paniculata (HAEAP) orally, for 30 days prior to i.p. administration of 420 mg/kg body wt. of cysteamine as a single dose. Rats preadministered with 30 mg/kg body wt. of ranitidine served as standard drug. Ulcer index, thiobarbituric acid reactive substances, mucin, glutathione peroxidase and myeloperoxidase activities, reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, glycoproteins and membrane bound enzyme activities were measured in duodenum of experimental animals. The ulcer score and myeloperoxidase activity were significantly minimized in rats treated with HAEAP. Mucin content was found to be preserved in rats treated with the extract. GSH/GSSG ratio and glutathione peroxidase activities were found to be maintained by the HAEAP. Level of lipid peroxidation products was found to be significantly low in HAEAP treated rats compared to ulcer control rats. The basolateral and brush border membrane bound enzyme activities which were depleted significantly in ulcer control rats were found to be maintained in rats pre-treated with the extract. The ulcer preventing effect was comparable to that of ranitidine treated rats. Level of glycoproteins was also found to be preserved in rats treated with the extract. The normal rats treated with the HAEAP did not show any abnormal alterations in the parameters studied. Histopathological observations also showed the ulcer preventing effect of the HAEAP. It is suggested that the ulcer preventing effect may be due to its mucin preserving and antioxidant nature.

Background: This study investigated if the H. pylori dupA genotype and certain host single nucleotide polymorphisms (SNPs) of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), including MMP-3, MMP-7, MMP-9, TIMP-1 and TIMP-2, might correlate with ulcer risk of H. pylori-infected Taiwanese patients., Results: Of the 549 H. pylori-infected patients enrolled, 470 patients (265 with gastritis, 118 with duodenal ulcer, and 87 with gastric ulcer) received SNPs analysis of MMP-3-1612 6A > 5A, MMP-7-181 A > G, MMP-9exon 6 A > G, TIMP-1372 T > C and TIMP-2-418 G > C by PCR-RFLP. The 181 collected H. pylori isolates were detected for the dupA genotype by PCR. The rates of dupA-positive H. pylori infection were similar among patients with duodenal ulcer (22.8%), gastric ulcer (20.0%), and gastritis (25.5%) (p > 0.05). Males had higher rates of duodenal ulcer and gastric ulcer than females (p < 0.01). Of H. pylori-infected patients, the MMP-3 6A6A genotype were more common in patients with duodenal ulcers than in those with gastritis (87.7% vs. 74.9%, p < 0.05) in females. This genotype had a 2.4-fold (95% CI: 1.02-5.66) increased risk of duodenal ulcer, compared to those with the 5A carrier. Combining the MMP-3/TIMP-1 genotype as 6A6A/CC, the risk of duodenal ulcer increased up to 3.6 fold (p < 0.05) in H. pylori-infected females., Conclusions: The MMP-3 promoter polymorphism, but not the dupA-status, may correlate with susceptibility to duodenal ulcer after H. pylori infection in Taiwanese females.

A comparative kinetic study of the inhibition of urea hydrolysis by 9 substituted 1,5,6,7-tetrahydro-4H-benzimidazol-4-ones (BI I-IX) has been carried out. The inhibition had reversibl competitive character; the inhibition constants K(i), varied from 29 up to 754 microM in dependence of the structure of BI I-IX. Three BI I-III, having the K(i) values from 29 to 82 microM, may be used as the potential therapeutic agents for gastroenterology for treatment of stomach and duodenal ulcers.

Cyclooxygenase-1 (COX-1) has been regarded as a constitutively expressed enzyme that generates prostaglandins for gastrointestinal integrity. We attempted to clarify the association between potentially functional polymorphisms (T-1676C and A-842G/C50T) in the COX-1 gene promoter and gastroduodenal disorders in a Japanese population. The study was performed with 480 stocked DNAs from subjects (gastric ulcers in 93 subjects and duodenal ulcers in 44) with no evidence of gastric malignancy. We employed the PCR-SSCP method to detect gene polymorphisms. The severity of histological chronic gastritis in antral biopsy specimens was classified according to the updated Sydney system. The T-1676C polymorphism was not associated with either gastric mucosal atrophy or infiltration of inflammatory cells into gastric mucosa. In non-NSAID (non-steroidal anti-inflammatory drug) users, male gender and Helicobacter pylori (HP) infection were significantly associated with both gastric and duodenal ulcers, whereas the -1676T allele carrier was significantly associated with only gastric ulcers (OR, 2.86; 95% CI, 1.29-6.34). In NSAID users, the number of -1676T alleles was significantly associated with developing gastroduodenal ulcers (OR, 5.80; 95% CI, 1.59-21.1), whereas male gender and HP infection were not. The -842T/ C50T polymorphism was not detected in any of the 480 Japanese subjects. In conclusion, a carrier of the -1676T allele in the COX-1 gene promoter, as well as HP infection and male gender, seem to be significant risk factors for developing gastric ulcers, and the number of -1676T alleles was also a significant risk factor for the NSAID-induced ulcer, whereas the frequency of the A-842G polymorphism was thought to be very rare in the Japanese population.

Background: Candida sp are frequently isolated from the ascitic fluid of patients with perforated ulcers. The present study was performed to examine whether Candida infection may be involved in the process of ulcer perforation., Methods: Male Wistar rats were divided into a saline group (n = 15) and a Candida group (n = 17). Cysteamine-HCl (Sigma; 31 mg/100 g) was administered thrice on day 1 to both groups of animals. Candida albicans at a density of 10(8) in 0.5 mL of saline was administered 1 h before, and 12 h and 24 h after the first administration of cysteamine in the Candida group., Results: Perforated duodenal ulcers were observed in 94.1% of the rats in the Candida group, but only 26.7% of the rats in the saline group (P < 0.01). The area of the duodenal ulcers in the Candida group was 40.89 +/- 33.07 mm2, whereas that in the saline group was 16.53 +/- 20.4 mm2 (P < 0.05). The mortality rate was significantly higher in the Candida group than in the saline group. In the Candida group, colonization by C. albicans was recognized at the ulcer base, surrounded by marked granulocytic infiltration. The number of eosinophils infiltrating the ulcer base was also significantly greater in the Candida group than in the saline group. Immunohistochemical analysis revealed the expression of secretory aspartyl protease (SAP) in the region of the ulcer showing colonization by C. albicans in the Candida group., Conclusion: Candida albicans aggravates duodenal ulcer perforation in the experimental model of cysteamine-induced duodenal ulcer perforation. The present findings suggest that SAP and host-parasite relationships, including granulocyte-dependent mechanisms, may be involved in the aggravation of ulcer perforation by C. albicans.

The aim of this study was to determine correlation between proteolysis parameters and phenotypes of alpha1-proteinase inhibitor in blood plasma in children with duodenal ulcer. Activation of pepsin- and trypsin like proteinases was accompanied by the decrease in activity of alpha2-macroglobulin and the increase in activity of acid stable inhibitors. The phenotypes M1M3, M1M1, M2M2 of alpha1-proteinase inhibitor were determined. Activation of proteolysis was more pronounced in individuals with subtype M2M2. Activity of alpha1-proteinase inhibitor decreased by 2-fold in M2M2, insignifically differed from the control group in M1M1, and increased by 1,9-fold in M1M3 subtype. Low activity of alpha1-proteinase inhibitor was accompanied by high activity of acid stable inhibitors; this may be regarded as the protective reaction of the body. Determination of alpha1-proteinase inhibitor phenotypes may be a basis for employment of polyvalent proteinase inhibitors for therapy of ulcer.

Backgrounds and Aims: 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., Methods: 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., Results: 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)., Conclusions: 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.

The authors have developed a highly sensitive method of non-invasive diagnostics of Helicobacter pylori, the most frequent human infection. Detection of urease activity is based upon measurement of the degree of the elevation of stable 13C isotope content in exhaled air after administration of C-urea as a test reagent. The method has been scarcely applied in Russia because the test preparation, 13C urea had not been produced domestically until 2002. The method can be easily applied by any healthcare institution; however, it requires special equipment and trained personnel to perform measurement of 13C content in exhaled air samples using mass spectrometers. The article presents the first experience in clinical application of the method.

Aim: To study the role of oxidative stress in mechanism of psychosomatic disorders involvement in pathogenesis of ulcerogenesis., Material and Methods: Psychosomatic disorders (PSD) and oxidative stress (OS) were assessed in 120 students with duodenal ulcer (DU) who had no concomitant pathology. Examination for PSD included interviewing by questionnaires. OS was judged by the level of lipid peroxidation products (malonic dialdehyde and dienic conjugates) and antioxidant activity--by glutathion peroxidase and superoxidedismutase. Melatonin was measured by enzyme immunoassay., Results: A close correlation was discovered between the severity and features of PSD, lowering of melatonin, severity of OS and clinical features of the disease., Conclusion: DU students develop PSD which become leading factors of ulcerogenesis. One of the mechanisms of their participation in ulcerogenesis may be related with lowering of melatonin which is a potent stress regulator and corrector of lipid peroxidation and antioxidant activity.

Purpose: This study was conducted to determine whether relatives of gastric cancer patients (GCF) showed greater gastric cycloxygenase-2 (COX-2) expression or a greater incidence of precancerous lesions after Helicobacter pylori infection and whether H. pylori eradication could reduce COX-2 expression., Experimental Design: Three hundred subjects were enrolled in this study: half were relatives of 50 H. pylori-infected gastric cancer patients, and half were relatives of 50 H. pylori-infected duodenal ulcer (DU) patients (controls). Each relative underwent endoscopy to detect H. pylori infection and related gastric histology. One hundred and twenty GCFs were found to have H. pylori infection. After H. pylori eradication, 90 of the 120 GCFs were followed up with annual endoscopy examinations over the next 2 years. Gastric COX-2 intensity in all of the specimens collected from these patients was immunochemically stained and graded from 0 to 4., Results: H. pylori infection, gastric atrophy, and intestinal metaplasia (IM) were more prevalent in GCFs than in relatives of H. pylori-infected patients with DUs (P < 0.05). H. pylori-infected GCFs also showed a greater COX-2 intensity than H. pylori-infected relatives of patients with DUs (89.1% versus 62.7%, P < 0.001; relative risk: 4.9; 95% confidence interval: approximately 2.34-10.29). Among the H. pylori-infected GCFs, COX-2 intensity correlated with atrophy and IM (P < 0.001). After H. pylori eradication, gastric COX-2 expression disappeared only in those relatives without IM (P < 0.001)., Conclusions: GCFs are more likely to show greater gastric COX-2 expression and a higher incidence of precancerous lesions after H. pylori infection than the relatives of H. pylori-infected patients with only DUs. H. pylori eradication can reverse gastric COX-2 expression in patients without IM but not in patients with IM.

Overproduction of nitric oxide by inducible nitric oxide synthase (iNOS) acts cytotoxically and contributes to inflammation. We explored the roles of iNOS in the pathogenesis of Helicobacter pylori-associated diseases. Using reverse-transcribed PCR, we examined topographical patterns of iNOS mRNA expression in the gastroduodenal mucosa in H. pylori-negative controls and H. pylori-positive patients with duodenal ulcer (DU), gastric ulcer (GU), and ulcer-free gastritis. iNOS expression showed topographical variations among the tested disorders. As compared to controls, DU had a significantly higher expression of iNOS mRNA in the duodenum, GU in the antrum and duodenum, and gastritis in the antrum and corpus. H. pylori eradication yielded a significant reduction of iNOS mRNA in the duodenum of DU and in the antrum of GU. Diverse topographical patterns of H. pylori-induced iNOS expression may contribute to mechanisms by which H. pylori elicits different clinical disorders.

Cyclooxygenase-1 (COX-1) derived eicosanoids promote gastroprotective mucosal defenses and induce platelet aggregation. By sparing COX-1, COX-2 specific inhibitors provide effective anti-inflammatory and analgesic activity while substantially reducing the risk of peptic ulcer disease and GI bleeding compared to dual COX inhibitors (traditional NSAIDs). Clinical studies of the COX-2-selective inhibitors have demonstrated efficacy equivalent to nonselective NSAIDs with significantly lower rates of GI toxicity. The incidence of endoscopic ulcers in some studies with coxibs has approximated placebo. However, as the detection of endoscopic lesions is not always correlated with symptomatic ulcers and ulcer complications, outcome studies of GI safety were performed. The results of large outcome studies have evaluated rofecoxib and celecoxib in over 39,000 patients with osteoarthritis or rheumatoid arthritis. Results of these studies showed that patients taking a supratherapeutic dose of rofecoxib or celecoxib had significantly lower rates of GI-related adverse events than those taking a nonselective NSAID. The GI safety of coxibs for patients using low dose aspirin concomitantly with a coxib appears to be reduced, particularly with regard to ulcer complications. Such data provide support for the COX-2 hypothesis and demonstrate that coxibs provide effective treatment of pain and inflammation with a reduced risk of gastropathy.

Background: Knowledge about the possible role of phospholipase C (PLC) activity of microbial pathogens in the development of disease is increasing. Recently attention has focused on investigating PLC activity elaborated by Helicobacter pylori, but the role of this enzyme in H. pylori pathogenesis is still unknown. The aim of this study was to correlate PLC-activity of H. pylori on the basis of the cagA status with the clinical diagnosis of the patients., Materials and Methods: Helicobacter pylori was isolated from patients with gastritis (G; n = 38), duodenal ulcer (DU; n = 15), gastric ulcer (GU; n = 11) and gastric cancer (GC; n = 12). Polymerase chain reaction primers DZ3/R009 which amplified a 1350-bp fragment were used to detect the cagA gene. PLC activity was determined using p-nitrophenylphosphorylcholine as substrate., Results: Of the strains, 60% were cagA(+) and 40% were cagA(-). All strains showed PLC activity (2.20 +/- 0.91 U mg(-1) protein). PLC activity showed no association with the cagA status: cagA(+) (2.21 +/- 1.03 U mg(-1) protein), cagA(-) (2.18 +/- 0.79 U mg(-1) protein). Patients with GU had the highest PLC activity (2.77 +/- 1.26 U mg(-1) protein) and patients with GC had the lowest activity (1.8 +/- 0.57 U mg(-1) protein)., Conclusions: Although PLC activity was present in all strains tested, it may only have pathological importance in patients with GU. However, the extent of PLC activity was independent of the presence of the cagA gene.

Background: Nitric oxide (NO) is synthesized enzymatically from L-arginine by NO synthase, which is measured by inducible NO synthase (iNOS). Helicobacter pylori (H. pylori) infection produces a state of chronic immunostimulation in the gastric epithelium. Infection with cagA+ H. pylori has greater degree of gastric inflammation and epithelial cell damage. Therefore, we compared the levels of iNOS in patients with H. pylori infection in relation to cagA status and H. pylori-related disease., Materials and Methods: One hundred and seven patients, including 51 patients with gastric cancer, 12 patients with gastric ulcer, 18 patients with duodenal ulcer and 26 patients with chronic gastritis, were enrolled in this study. Biopsies from the antrum and body were obtained for histologic examination, culture and reverse transcriptionase-PCR (RT-PCR) for detection of iNOS gene expression. The presence of H. pylori was confirmed by Giemsa staining or culture and the gene expression of cagA in H. pylori isolates was confirmed by PCR., Results: H. pylori infection was detected in 70.1% (75/107) and cagA was detected in 84.8% (28/33). iNOS expression was detected in 49.5% (53/107) and there was no significant difference in iNOS expression according to H. pylori infection nor the cagA status in the gastroduodenal diseases. However, iNOS expression was more frequently detected in gastric cancer than the other H. pylori-related diseases (64.7% vs. 35.7%, p <.05)., Conclusion: Although NO was thought be involved in the gastric carcinogenesis, the level of NO production was not related to H. pylori infection or cagA status.

Earlier reports suggested that adenosine deaminase activity in the gastric corpus mucosa depends upon either gastric acid secretion or severity of chronic gastritis. Knowing that gastric acid secretion corresponds well with histological status of the gastric mucosa, the aim of this study was to determine the enzyme activity in relation to these two factors evaluated simultaneously. The study was conducted on Helicobacter pylori positive duodenal ulcer patients treated for two weeks with either omeprazole alone or omeprazole in combination with amoxycillin and tinidazole. It was found that these two therapeutic regimens decreased adenosine deaminase activity only in the gastric corpus mucosa and a decline was more deeper in patients on omeprazole monotherapy. Moreover, omeprazole monotherapy inhibited completely basal gastric acid secretion and did not change the severity of chronic gastritis, while omeprazole-based eradication therapy decreased both the gastric acid secretion and severity of chronic gastritis. One month after completion of eradication therapy adenosine deaminase activity returned to the pretreatment values but severity of chronic gastritis decreased further. The results of the present study indicate that adenosine deaminase activity in the gastric corpus mucosa depends primarily upon gastric acid secretion but not upon the severity of Helicobacter pylori associated chronic gastritis.

During investigation of proteolisis of duodenum mucosa in patients of elderly and senile age with duodenal ulcer, complicated by hemorrhage, in terms up 8 for days there was revealed considerable increase of proteolytic activity, especially of high-molecular proteins and collagens, maximum--on the first day of hemorrhage. In all terms the revealed activity of anterior wall of duodenum was higher, than posterior.

Basing upon the histochemical study of SDG and NO-synthase activity in 68 biopsies taken from patients with duodenal ulcer the connection between the clinical specificity and the activity of the disease the SDG activity decreases, while that of NO-synthase increases. At the phase of cicatrization the opposite process is going on. The authors connect the phenomena under investigation with the vasodilatory and protective abilities of the nitrogen oxide.

Background/aim: We examined the prophylactic effect of lafutidine, a novel histamine H(2)-receptor antagonist [(+/-)-2-(furfurylsulfinyl)-N-[4-[4-(piperidinomethyl)-2-pyr idyl]oxy- (Z)-2 butenyl]acetamide], on indomethacin-induced small intestinal ulcers in rats and investigated the relation of this action to capsaicin-sensitive sensory neurons., Methods and Results: Subcutaneously administered indomethacin (10 mg/kg) provoked ulceration in the small intestine, mainly the jejunum and ileum, accompanied by increases in myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities as well as the enterobacterial numbers invading the mucosa. Intestinal ulcerogenic response to indomethacin was prevented by 16,16-dimethyl prostaglandin E(2) (10 microg/kg, p.o.) and capsaicin (10 mg/kg, p.o. ) as well as ampicillin (800 mg/kg, p.o.), but not omeprazole (100 mg/kg, p.o.). Likewise, lafutidine (1-10 mg/kg, p.o.), but not cimetidine (100 mg/kg, p.o.), reduced the occurrence of intestinal ulcers in response to indomethacin in a dose-dependent manner, and a significant effect was observed at 3 mg/kg or greater. The protective action of lafutidine as well as capsaicin was almost totally abolished by chemical ablation of capsaicin-sensitive sensory neurons. Both lafutidine and capsaicin significantly suppressed the increases in MPO and iNOS activities as well as enterobacterial numbers in the mucosa. These agents also significantly enhanced mucus secretion in the small intestine., Conclusion: These results suggest that lafutidine protects the small intestine against ulceration via stimulation of capsaicin-sensitive sensory neurons. This action may be attributable to inhibition of enterobacterial invasion in the intestinal mucosa, probably by increasing the mucus secretion., (Copyright 2000 S. Karger AG, Basel)

The paper covers the results of 32 endoscopic studies. The D. E. Korzhevsky procedure was used to determine the activity of NADP.H diaphorase, a NO-synthase marker, in gastric mucosal biopsy specimens from patients with acute and scarring peptic ulcer. A high activity of NO synthase was found in patients with acute ulcer and its inhibition was ascertained in those with scarring ulcer. The findings lead to the conclusion that NO-dependent mechanisms are involved in the pathogenesis of an ulcerative process.

The authors studied the effect of perftoran (PF) on the morpho-functional parameters of alimentary system organs (ASO) (liver, pancreas, stomach, duodenum, and small intestine) in rats with experimental chronic acetate duodenal ulcer. Inflammatory-infiltrative and dystrophic changes were found in the ASO tissues which led to activation of the enzymes superoxide dismutase and catalase in their homogenates. PF pharmacotherapy reduces the inflammatory-infiltrative changes in the ASO tissues and normalizes the enzyme systems of antioxidant protection.

Aims: To determine the association, if any, between H pylori genotype and the gastric mucosal variations in the levels of gastrin, somatostatin, tryptase, and histamine., Methods: 49 patients affected by duodenal ulcer and 48 by non-ulcer dyspepsia were studied. To identify the H pylori genotype, the presence of the cagA gene and vacA alleles m1, m2, s1, and s2 were analysed by polymerase chain reaction. Gastrin, somatostatin, tryptase, and histamine were measured in antral mucosal biopsies., Results: 57 patients were infected with H pylori (30 with duodenal ulcer and 27 with non-ulcer dyspepsia). Gastrin and tryptase were increased in patients with H pylori infection, although the variations were statistically significant only for gastrin; somatostatin and histamine were not influenced by H pylori infection. In patients with non-ulcer dyspepsia the absence of the cagA gene and the presence of vacA alleles s2 and m2 were associated with higher values of tryptase and to a lesser extent of gastrin. These associations were not found in patients with duodenal ulcer., Conclusions: The cagA negative s2m2 strain of H pylori may be less dangerous for the gastric mucosa than other H pylori strains since it enhances tryptase production by gastric mucosal mast cells; this enzyme is thought to stimulate tissue turnover and favour wound healing.

Aim: To assess activity of superoxide dismutase and catalase in acute ulcer and in the end of its treatment with antisecretory (omeprasole and zaran), anti-Helicobacter (metronidasole) and antioxidant (alpha-tocopherol) drugs in patients with duodenal ulcer., Materials and Methods: 126 patients with duodenal ulcer were divided into 6 groups: group 1 patients had Helicobacter pylori (HP+) and were given omeprasole; group 2 patients had HP and were given omeprasole + metronizarole; group 3 patients were free of HP and received metronidasole + alpha-tocopherol; group 4 HP+ patients received zaran; group 5 HP+ patients got zaran = metronidasole; group 6 free of HP received zaran + alpha-tocopherol. The patients were examined using esophagogastroduodenoscopy, roentgenoscopy of the stomach, tests of the gastric juice., Results: An acute phase of ulcer was accompanied with enhanced activity of superoxide dismutase and low activity of catalase in mucosal biopsies from ulcer lesion and periulcer zone. In remission, antioxidant system resumed normal activity depending on the kind of the combined therapy. The combination omeprasole + metronidasole was more effective in HP eradication than zaran + metronidasole. Effect of alpha-tocopherol was poor., Conclusion: It is suggested that HP stimulates lipid peroxidation and thus maintains inflammation in gastric and duodenal mucosa.

On the basis of investigations designed to study the condition of intragastric proteolysis and membrane digestion in the small intestine in 148 patients it has been found out that peptic ulcer is accompanied by enhancement of digestive processes in the stomach and by decrease thereof in the small intestine. With the development of peptic ulcer complications digestive disorders get aggravated, which fact leads to various manifestations of the enteral syndrome. A conclusion has been reached that study into intragastric proteolysis and membrane digestion can be useful in the objective evaluation of the activity and degree of severity of the ulcerous process as well as in the functional assessment of results of the treatments administered.

Regulation of lipid peroxidation is realized not only by antioxidant enzymes but by natural antioxidants as well. We have lately succeeded, together with the students, in identifying antioxidant properties of quaternary ammonium compounds, which fact makes it possible for the above properties to gain extensive applicability in a setting where there is this variety of disbolism. One of such drug preparations is ethonium. The article contains information about uses of ethonium in the tablet dose form. The tablets are of little toxicity, they stimulate the oxidation-reduction processes and proved to be effective in experimental gastric and duodenal ulcers.

Experiments were performed on male albino rats with acetate duodenal ulcer to detect the changes in the activity of antioxidant protection enzymes--superoxydedismutase and catalase in the tissues of the liver, stomach, duodenum, and small intestine. The pronounced character of the changes depended on the degree of destruction and involvement of the intestinal system organs in the pathological process. Experimental quamatel or omez therapy corrected the detected changes in the antioxidant status of the tissues.

Eradication therapy for Helicobacter pylori (H. pylori) has been established. However, the physiological factors influencing the success of treatment remain unclear. The aim of this study was to analyze these factors and to evaluate the efficacy of sofalcone on H. pylori eradication therapy. Forty-four H. pylori-infected and peptic ulcer patients were enrolled in this study. Twenty-seven patients were treated with lansoprazole (LPZ, 30 mg o.d. for 1-8 weeks) and amoxicillin (AMPC, 500 mg q.i.d, 1-2 weeks), followed by 8 weeks of treatment with famotidine (FAM, 20 mg o.d.). Moreover, sofalcone (SOF, 100 mg t.i.d) was administered to 17 patients throughout the therapeutic period. Endoscopic and serologic evaluations and the urea breath test (UBT) were performed before therapy. At the endoscopic examination, mucosal samples were biopsied and then tissue myeloperoxidase (MPO) content, an index of neutrophil infiltration was measured. Cure of H. pylori infection was determined 8 weeks after the cessation of LPZ. This eradication regimen afforded an overall cure rate of 63.0% (17/27) without SOF and 76.5% (13/17) with SOF. In the control group, treatment success was inversely associated with pre-UBT value (gastric urease activity), whereas this association was not observed in the SOF group. Furthermore, in the patients exhibiting a high preUBT value (>40%), a twofold higher eradication rate was obtained by the administration of SOF. In patients who were successfully eradicated, mucosal MPO level was slightly higher than those of unsuccessful cases, whereas there was no significant association with serum pepsinogen (PG I, PG II) concentration and its ratio (PG I/PG II). These results suggest that a low UBT value is a factor predicting treatment success. SOF administration may improve the eradication rate, especially in the high-UBT subgroup.

Background: The purpose of the present study was to examine the association between interleukin-8 (IL-8) in the gastric body due to Helicobacter pylori infection and histological gastritis, as well as elucidating the effect of acid secretion inhibitors on H. pylori associated body gastritis in duodenal ulcer patients., Methods: Twenty H. pylori-negative patients, 20 H. pylori-positive patients with chronic gastritis without peptic ulceration, and 20 H. pylori-positive duodenal ulcer patients (DU) were studied. Four biopsy samples were taken, each from the greater curvature of the antrum and body of the stomach. Biopsies were histologically investigated by ELISA to determine the density of H. pylori, the degree of neutrophil infiltration and the IL-8 concentration in the mucosa., Results: In the gastric mucosa of H. pylori-negative subjects, no IL-8 and hardly any neutrophil infiltration were observed. In contrast, enhanced IL-8 production and increased neutrophil infiltration were present in those infected with H. pylori. In H. pylori-positive patients, a significant correlation was observed between the IL-8 concentration and the degree of neutrophil infiltration, but no correlation was found in the body mucosa of those with DU. Twelve of 20 DU patients demonstrated hardly any neutrophil infiltration, despite the increased mucosal IL-8 content in the body. The administration of omeprazole in DU patients markedly increased mucosal neutrophil infiltration even though it did not cause any significant change in the H. pylori density and IL-8 concentration in the body. Although the effect of omeprazole was transient, a significant increase in neutrophil infiltration continued in comparison with the status before omeprazole administration in those subsequently undergoing maintenance treatment with H2-blockers., Conclusion: In H. pylori-positive chronic gastritis, IL-8 concentration is enhanced in the mucosa of the body, and is associated with increased neutrophil infiltration. However, in DU patients, despite increases in body IL-8 concentration, neutrophil infiltration is reduced and the gastritis may be localized in the antrum.

Objectives: Cathepsin B and L (cysteine proteases), urokinase- and tissue-type plasminogen activators (serine proteases), and type-1 inhibitor are involved in gastric mucosal injury. We determined tissue protease levels in duodenal ulcer and their relationship to ulcer phase, bleeding tendency, Helicobacter pylori infection, and use of H2-blockers., Methods: Endoscopic biopsies of antral and duodenal mucosa were obtained from 61 patients with active or healed duodenal ulcer and control subjects. Antigen concentrations were measured by ELISA., Results: Significantly higher levels of cathepsins, urokinase-type plasminogen activator, type-1 inhibitor, and significantly lower levels of tissue-type plasminogen activator were found in active ulcers. Bleeders had the highest cathepsins and urokinase-type plasminogen activator levels. Higher levels of urokinase-type plasminogen activator, cathepsin B, and type-1 inhibitor were observed in Helicobacter pylori-positive patients., Conclusions: Our results suggest that impaired fibrinolysis (tissue-type plasminogen activator), intramucosal proteases (cathepsins), tissue remodeling, and angiogenesis (urokinase-type plasminogen activator and type-1 inhibitor) are involved in duodenal ulcer formation and healing.

Objective: To investigate whether duodenal ulcer (DU) is associated with increased free radical generation at the site of ulceration and to attempt, indirectly, to confirm the hypothesis by determining activity of free radical scavengers such as superoxide dismutase (SOD)., Study Design: Prospective study comparing SOD activity in biopsies taken from the ulcer edge, and antrum in DU patients before and after one month of treatment to SOD activity in biopsies from the duodenal bulb and antrum in a control population., Setting: Institute of Gastroenterology of a university hospital., Study Population: Twenty-five patients with DU. The diagnosis was confirmed by endoscopy., Measurements: SOD activity in biopsy specimen, red blood cells (RBC) and serum was measured using the cytochrome c method by spectrophotometry and expressed as U SOD/mg protein. Helicobacter pylori was diagnosed by the rapid urease test (CLO test) from antral biopsies., Results: SOD activity was markedly depleted in the ulcer edge (2.78 +/- 0.9 U SOD/mg protein) as compared to the same patients after one month of treatment (4.59 +/- 2.2 U SOD/mg protein) (P = 0.05) and to biopsies from the duodenal bulb in control population (6.7 +/- 2.4 U.SOD/mg protein) (P = 0.05). SOD activity in the antrum of both groups was similar. There was no difference in SOD activity in RBC and serum of both groups., Conclusion: Products of free radical reactions are implicated in the pathogenesis of DU disease. SOD, which is a key enzyme in gastric mucosal protection, is depleted significantly in the ulcer edge compared with controls and increases after healing. However, it is not clear whether this abnormality in oxygen free radical metabolism reflects, rather than causes, the condition which characterizes DU.

Programmed expression of several matrix metalloproteinases is an important feature of cutaneous wound healing. To study whether this also applies to gastrointestinal ulcer healing, we used in situ hybridization with 35S-labeled probes to localize sites of collagenase, stromelysin-1, and matrilysin expression in 26 samples representing peptic ulcers, Crohn's disease, and ulcerative colitis. In contrast to skin wounds, collagenase mRNA was not detected in the surface epithelium bordering gastrointestinal ulcer areas. However, together with stromelysin-1 mRNA, it was abundantly expressed by the granulation tissue in all types of ulcers. Signal for matrilysin mRNA and protein was detected in the mucosal epithelium bordering the ulcerations but never in the ulcer stroma. The gut basement membrane was disrupted under the matrilysin-producing epithelial cells as assessed by immunostaining for laminin. Tissue inhibitor of metalloproteinases (TIMP-1) mRNA never co-localized with matrilysin-positive mucosal epithelial cells. These data indicate that matrilysin plays a significant role in epithelial remodelling occurring in gastrointestinal ulcerations whereas collagenase and stromelysin-1 are involved in the reparative processes in the ulcer bed.

Objective: To compare the costs of alternative strategies for the treatment of duodenal ulcer., Design: A cost comparison using decision analysis., Methods: A decision model was used to compare the costs per cure of an endoscopically documented duodenal ulcer for three initial treatment strategies: 1) H2-receptor antagonist therapy for 8 weeks, 2) antibiotic therapy for Helicobacter pylori infection plus H2-receptor antagonist therapy, and 3) urease test-based treatment. For symptomatic recurrences, secondary treatment strategies included empiric retreatment with the same or other regimen, and treatment based on repeat endoscopy-guided urease test or biopsy, with an assumption of subsequent cure. The cohort modeled for this analysis consisted of patients at low risk for a malignant ulcer. Probability estimates were derived from published clinical trials, cohort studies, and expert opinion. Side effects from combination therapy with antibiotics and H2-receptor antagonists and resulting costs were included from the perspective of a group practice model health maintenance organization., Results: For all secondary treatment strategies, initial therapy with antibiotics for H. pylori infection plus an H2-receptor antagonist resulted in the lowest average costs per symptomatic cure when the prevalence or likelihood of H. pylori infection exceeded 66% to 76%; the costs ranged from $284 for secondary (re)treatment with empiric antibiotic and H2-receptor antagonist therapy to $398 for endoscopy-guided secondary treatment. Initial treatment with an H2-receptor antagonist resulted in the highest costs, ranging from $372 for secondary treatment with empiric antibiotic and H2-receptor antagonist therapy to $679 for endoscopy-guided secondary treatment. The results were not sensitive to the rates of duodenal ulcer recurrence after either treatment, to the cost of either treatment, or to prevalence of H. pylori., Conclusions: This cost analysis indicates that, regardless of the secondary treatment used for ulcer recurrence, initial therapy with antibiotics for H. pylori infection plus an H2-receptor antagonist provides the lowest costs per symptomatic cure. These cost savings and the lower recurrence rates associated with this treatment favor eradication of H. pylori as part of the initial treatment of duodenal ulcer.

The factors that determine which Helicobacter pylori infected subjects develop duodenal ulcer (DU) are unclear. This study tested the hypothesis that infection density and urease activity are higher in DU than non-DU subjects. Fifty five DU and 55 age and sex matched non-DU subjects were studied. Quantitative methods were used for measuring infection density (viable organism count) and urease activity (Berthelot reaction). DU subjects had a greater antral infection density (geometric mean of colony forming units/mg biopsy protein; 10.5 x 10(5) v 1.3 x 10(5), p < 0.001). They also had higher biopsy urease activity (geometric mean of NH3 nmol/min-1/mg protein-1; 103 v 25, p < 0.001). Urease activity per organism, however, was similar in the two groups showing that high antral urease activity in DU was a reflection of organism density. DU was not present in subjects with an antral infection density less than 10(5) colony forming units/mg protein. A correlation was present between H pylori viable counts and the severity and activity of gastritis. Both severity and activity of gastritis were greater in the antrum of DU compared with non-DU subjects but there was no difference in the body between the two groups. It is concluded that antral H pylori infection density is probably an important determinant of DU development, and that there is a baseline of infection density that is necessary for ulcer formation.

Combined differentiated rehabilitative and staged treatment of 167 patients with peptic ulcer resulted in stable reduction in cellular membrane permeability, subsiding of catabolic processes in cells, steady normalization of enzymic activity of tissue respiration, as well as activation of reparation processes in connective tissue elements and structures located in the connective tissue (capillaries included). The described mode of treatment appeared to be superior to the conventional one, resulting in a substantial improvement in microcirculation in gastric mucosa. Normalization of protein-synthetic processes in the connective tissue makes for enhancing of the gastric mucosa resistance and prevention of the relapse of the disease.

Nitric oxide, the product of nitric oxide synthase in inflammatory cells, may have a role in tissue injury through its oxidative metabolism. Nitric oxide may have a role in the pathogenesis of duodenal ulcer and may be one of the mechanisms responsible for the association between gastric infection with Helicobacter pylori and peptic disease. In this study, calcium independent nitric oxide synthase activity was detected in human gastric mucosa suggesting expression of the inducible isoform. In 17 duodenal ulcer patients gastric antral and fundic nitric oxide synthase activity was found to be two and 1.5-fold respectively higher than its activity in the antrum and fundus of 14 normal subjects (p < 0.05). H pylori was detected in the antrum of 15 of 17 duodenal ulcer patients and only in 7 of 14 of the control subjects. Antral nitric oxide synthase activity in H pylori positive duodenal ulcer patients was twofold higher than in H pylori positive normal subjects (p < 0.05). In duodenal ulcer patients antral and fundic nitric oxide synthase activity resumed normal values after induction of ulcer healing with ranitidine. Eradication of H pylori did not further affect gastric nitric oxide synthase activity. These findings suggest that in duodenal ulcer patients stimulated gastric mucosal nitric oxide synthase activity, though independent of the H pylori state, may contribute to the pathogenesis of the disease.

Background: Despite the close association between gastric Helicobacter pylori infection and duodenal ulcer, little is known about how this organism may promote mucosal damage. A possibility might be that it produces, or induces the host to release, phospholipases that metabolize the protective layer of phospholipids., Methods: Aimed at determination of phospholipase A2 activity and the concentration of choline-containing phospholipids in gastric juice, aspirates were collected during gastroscopy in 38 consecutive referrals with either active (n = 19) or H. pylori-eradicated healed duodenal ulcer (n = 19)., Results: Gastric juice phospholipase A2 activity was 3.1 times higher in active than in healed duodenal ulcers (P = 0.03). Concurrently, the concentration of choline-containing phospholipids in the group with active ulcers was less than half compared with the healed group (P = 0.02)., Conclusion: The results indicate that phospholipase A2 activity and the concentration of choline-containing phospholipids in gastric juice are related to H. pylori status and duodenal ulcer disease.

The synthetic peptides AC-Glu-Phe-Phe (NO2)-Arg-amide (peptide VP) and AC-Ile-Glu-Phe-Phe (NO2)-Arg-amide (peptide VIP) are more readily hydrolyzed by human pepsin in gastric juice of patients of gastritis than those of duodenal ulcer and normal subjects. The kinetic parameters suggest that S3 subsite of the enzyme plays a role in the elevation of enzyme activity in gastric disease.

Liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the principal enzymes responsible for the oxidation of ethanol, are polymorphic at the ADH2, ADH3 and ALDH2 loci in human beings. Our previous studies have shown that, compared with nonalcoholic individuals, Chinese alcoholic patients without liver disease had significantly lower frequencies of the ADH2*2 and ADH3*1 alleles, which encode high maximum velocity beta 2- and gamma 1-ADH subunits, respectively, as well as a lower frequency of the ALDH2*2 allele, which encodes an enzymatically inactive subunit. The data strongly suggest that genetic variation in both ADH and ALDH may influence drinking behavior and the risk of alcoholism developing through acetaldehyde formation. To further investigate the possible role of acetaldehyde in the pathogenesis of alcoholic liver disease, we determined the ADH and ALDH genotype frequencies in patients with alcohol-related cirrhosis (n = 27), viral hepatitis-related cirrhosis (n = 29) and gastric and duodenal ulcer without relevance to alcohol (n = 30). We developed a new restriction fragment length polymorphism method to genotype the mutant and normal ALDH2 alleles by using polymerase chain reaction-directed mutagenesis, which proved to be simpler and faster than the conventional detection methods that use hybridization with allele-specific oligonucleotide probes. We found that the frequencies of the alleles ADH2*2 (57%), ADH3*1 (78%) and ALDH2*2 (9%) in the alcoholic cirrhotic patients were significantly lower than those in the healthy controls and in the patients with cirrhosis from viral hepatitis and with gastric and duodenal ulcer.(ABSTRACT TRUNCATED AT 250 WORDS)