Amaranth oil reduces accumulation of 4-hydroxynonenal-histidine adducts in gastric mucosa and improves heart rate variability in duodenal peptic ulcer patients undergoing Helicobacter pylori eradication.

Helicobacter pylori-induced oxidative stress in gastric mucosa (GM) is a milieu for the development of chronic gastritis, duodenal peptic ulcer (DPU), gastric cancer, and a number of extragastric diseases. Because our previous study revealed the accumulation of the protein adducts of lipid peroxidation product 4-hydroxynonenal (HNE) in GM, which persists after eradication of H. pylori, the aim of the study was to test whether Amaranth oil supplementation in addition to standard anti-Helicobacter treatment could prevent such accumulation of HNE in GM in H. pylori-positive DPU patients. Seventy-five patients were randomly split into two groups: group 1 - standard treatment (n = 39) and group 2 - standard treatment with additional supplementation of 1 ml of concentrated oil from amaranth seeds (Amaranthus cruenthus L., n = 36). Clinical analysis, including endoscopy with biopsies from antrum and corpus of the stomach were performed before and after the treatment, as was heart rate variability (HRV) recorded, as parameter of systemic, extragastric pathophysiological alterations in DPU patients. Improvement of clinical, endoscopic and histologic manifestations, and successful ulcer healing were observed in both the groups. Moreover, supplementation of amaranth oil in addition to standard anti-H. pylori treatment significantly reduced accumulation of HNE-histidine adducts in GM and increased HRV in DPU patients (p < .05). Therefore, standard treatments of DPU require additional therapeutic approaches, in accordance with integrative medicine principles, aiming to reduce persistence of oxidative stress, as was successfully done in our study by the use of amaranth oil.

Role of dietary polyphenols in the management of peptic ulcer.

Peptic ulcer disease is a multifactorial and complex disease involving gastric and duodenal ulcers. Despite medical advances, the management of peptic ulcer and its complications remains a challenge, with high morbidity and death rates for the disease. An accumulating body of evidence suggests that, among a broad reach of natural molecules, dietary polyphenols with multiple biological mechanisms of action play a pivotal part in the management of gastric and duodenal ulcers. The current review confirmed that dietary polyphenols possess protective and therapeutic potential in peptic ulcer mediated by: improving cytoprotection, re-epithelialization, neovascularization, and angiogenesis; up-regulating tissue growth factors and prostaglandins; down-regulating anti-angiogenic factors; enhancing endothelial nitric oxide synthase-derived NO; suppressing oxidative mucosal damage; amplifying antioxidant performance, antacid, and anti-secretory activity; increasing endogenous mucosal defensive agents; and blocking Helicobacter pylori colonization associated gastric morphological changes and gastroduodenal inflammation and ulceration. In addition, anti-inflammatory activity due to down-regulation of proinflammatory cytokines and cellular and intercellular adhesion agents, suppressing leukocyte-endothelium interaction, inhibiting nuclear signaling pathways of inflammatory process, and modulating intracellular transduction and transcription pathways have key roles in the anti-ulcer action of dietary polyphenols. In conclusion, administration of a significant amount of dietary polyphenols in the human diet or as part of dietary supplementation along with conventional treatment can result in perfect security and treatment of peptic ulcer. Further well-designed preclinical and clinical tests are recommended in order to recognize higher levels of evidence for the confirmation of bioefficacy and safety of dietary polyphenols in the management of peptic ulcer.

Role of dietary phospholipids and phytosterols in protection against peptic ulceration as shown by experiments on rats.

Geographically the prevalence of duodenal ulceration is related to the staple foods in the diet in regions of developing countries where the diet is stable. It is higher in regions where the diet is based on milled rice, refined wheat or maize, yams, cassava, sweet potato, or green bananas, and is lower in regions where the staple diet is based on unrefined wheat or maize, soya, certain millets or certain pulses. Experiments on rat gastric and duodenal ulcer models showed that it was the lipid fraction in staple foods from low prevalence areas that was protective against both gastric and duodenal ulceration, including ulceration due to non-steroidal anti-inflammatory drugs (NSAIDs). It also promoted ulcer healing. The lipid from the pulse, Dolichos biflorus, horse gram which was highly protective was used to identify the fractions with protective activity in the lipid. The protective activity lay in the phospholipid, sterol and sterol ester fractions. In the phospholipid fraction phosphatidyl choline (lethicin) and phosphatidyl ethanolamine (cephalin) were predominant. In the sterol fraction the sub-fractions showing protective activity contained ß-sitosterol, stigmasterol, and an unidentified isomer of ß-sitosterol. The evidence from animal models shows that certain dietary phospholipids and phytosterols have a protective action against gastroduodenal ulceration, both singly and in combination. This supports the protective role of staple diets in areas of low duodenal ulcer prevalence and may prove to be of importance in the prevention and treatment of duodenal ulceration and management of recurrent ulcers. A combination of phospholipids and phytosterols could also play an important role in protection against ulceration due to NSAIDs.

Geraniol-a flavoring agent with multifunctional effects in protecting the gastric and duodenal mucosa.

Geraniol is an acyclic monoterpene alcohol commonly used as a flavoring agent. The present study was undertaken to investigate antiulcerogenic effects of geraniol and to determine the possible mechanisms involved in this action. In the model of the ethanol-induced ulcer, treatment of rats with geraniol by oral route significantly inhibited gastric lesions by 70 % (7.50 mg/kg) to 99 % (200 mg/kg). Analysis of the gastric tissue of rats treated with geraniol (7.50 mg/kg) revealed that total glutathione content levels (GSH) increased and levels of myeloperoxidase (MPO) decreased in the gastric mucosa. Oral treatment with geraniol significantly decreased the number of ulcerative lesions induced by ischemia/reperfusion injury by 71 % and the duodenal ulcers induced by cysteamine by 68 %. The action of geraniol was mediated by the activation of defensive mucosa-protective factors such as the nitric oxide (NO) pathway, endogenous prostaglandins, increased mucus production, increased sulfhydryl compounds, antioxidant properties and the stimulation of calcitonin gene-related peptide (CGRP) release through the activation of transient receptor potential vanilloid (TRPV). The multifaceted gastroprotective mechanisms of geraniol represent a promising option for the treatment of gastric and duodenal mucosa injury.

No association of coffee consumption with gastric ulcer, duodenal ulcer, reflux esophagitis, and non-erosive reflux disease: a cross-sectional study of 8,013 healthy subjects in Japan.

Probably due to caffeine-induced gastric acid secretion, negative effects of coffee upon various upper-gastrointestinal diseases have been precariously accepted, despite the inadequate epidemiological evidence. Our aim is to evaluate the effect of coffee consumption on four major acid-related diseases: gastric ulcer (GU), duodenal ulcer (DU), reflux esophagitis (RE), and non-erosive reflux disease (NERD) based on the large-scale multivariate analysis. Of the 9,517 healthy adults, GU, DU, and RE were diagnosed by endoscopy, and NERD was diagnosed by the symptoms of heartburn and regurgitation without esophageal erosion. Associations between coffee consumption and the four disorders were evaluated, together with age, gender, body mass index (BMI), Helicobacter pylori (HP) infection status, pepsinogen I/II ratio, smoking, and alcohol. We further performed meta-analysis using the random effects model to redefine the relationship between coffee intake and peptic ulcer disease. The eligible 8,013 study subjects comprised of 5,451 coffee drinkers and 2,562 non-coffee drinkers. By univariate analysis, age, BMI, pepsinogen I/II ratio, smoking, and alcohol showed significant associations with coffee consumption. By multiple logistic regression analysis, positively correlated factors with significance were HP infection, current smoking, BMI, and pepsinogen I/II ratio for GU; HP infection, pepsinogen I/II ratio, and current smoking for DU; HP non-infection, male, BMI, pepsinogen I/II ratio, smoking, age, and alcohol for RE; younger age, smoking, and female for NERD. The meta-analyses could detect any association of coffee consumption with neither GU nor DU. In conclusion, there are no significant relationship between coffee consumption and the four major acid-related upper gastrointestinal disorders.

Effect of methanolic extract of Pongamia pinnata Linn seed on gastro-duodenal ulceration and mucosal offensive and defensive factors in rats.

Pongamia pinnata has been advocated in Ayurveda for the treatment of various inflammatory conditions and dyspepsia. The present work includes initial phytochemical screening and study of ulcer protective and healing effects of methanolic extract of seeds of P. pinnata (PPSM) in rats. Phytochemical tests indicated the presence of flavonoids in PPSM. PPSM when administered orally (po) showed dose-dependent (12.5-50 mg/kg for 5 days) ulcer protective effects against gastric ulcer induced by 2 h cold restraint stress. Optimal effective dose of PPSM (25 mg/kg) showed antiulcerogenic activity against acute gastric ulcers (GU) induced by pylorus ligation and aspirin and duodenal ulcer induced by cysteamine but not against ethanol-induced GU. It healed chronic gastric ulcer induced by acetic acid when given for 5 and 10 days. Further, its effects were studied on various parameters of gastric offensive acid-pepsin secretion, lipid peroxidation (LPO) and nitric oxide (NO) and defensive mucosal factors like mucin secretion and mucosal cell shedding, glycoproteins, proliferation and antioxidants; catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) levels. PPSM tended to decrease acid output and increased mucin secretion and mucosal glycoproteins, while it decreased gastric mucosal cell shedding without any effect on cell proliferation. PPSM significantly reversed the increase in gastric mucosal LPO, NO and SOD levels caused by CRS near to the normal level while it tended to increase CAT and GSH level decreased by CRS and ethanol respectively. Thus, the ulcer protective effects of PPSM may be attributed to the presence of flavonoids and the actions may be due to its effects both on mucosal offensive and defensive factors.

[Long- and short-term results of staged treatment of ulcer patients working in oil production industry].

AIM: To determine clinical and cost-effect efficacy of staged (hospital-day hospital-outpatient clinic) treatment and rehabilitation of patients with ulcer disease (UD). MATERIAL AND METHODS: Of 160 patients with duodenal ulcer 80 patients (controls) received treatment in hospital and 80 patients (the study group) were treated in hospital and day hospital. Efficacy of the treatment was assessed by clinical data, results of device and cost-effect investigations. RESULTS: Clinical and endoscopic remission of duodenal ulcer was achieved for the same time in both the groups. The cost of the treatment of 1 patient was 23,393 and 21,163 rub in the controls and in the study group, respectively. Therefore, treatment in a day hospital reduced cost of the treatment. Later, the remission was consolidated by active follow-up in an outpatient clinic. CONCLUSION: Staged treatment of UD provides good therapeutic and economic effects compared to hospital treatment.

Involvement of nitric oxide in the gastroprotective effects of an aqueous extract of Pfaffia glomerata (Spreng) Pedersen, Amaranthaceae, in rats.

The plants belonging to Pfaffia genus are used in folk medicine to treat gastric disturbances. This study examined the effects of an aqueous extract of Pfaffia glomerata (Spreng) Pedersen (AEP) on the gastrointestinal tract. Wistar rats were pretreated orally (p.o.) with the AEP (125, 250, 500 and 1000 mg.kg(-1)) before induction of ulcers by hypothermic restraint stress (HRS, 3 h restraint stress at 4 degrees C), ethanol (ET, 70%; 0.5 ml/animal; p.o.) or indomethacin (IND, 20 mg.kg(-1); s.c.). Control animals received water (C) or ranitidine (60 mg.kg(-1)) p.o. The AEP protected rats against HRS and ET-induced ulcers, but was not able to protect the gastric mucosa against IND-induced ulcers. When injected into the duodenal lumen, the AEP reduced total acidity and both basal and histamine-stimulated acid secretion in pylorus-ligated rats. In addition, gastric secretion from AEP-treated animals exhibited increased concentrations of nitrite and nitrate. Treatment of animals with L-NAME (120 mg.kg(-1), p.o.) prevented both the reduction of total acidity and the increase in NOx levels promoted by AEP treatment. In conclusion, AEP effectively protected the gastric mucosa and inhibited gastric acid secretion in rats, probably by involving the histaminergic pathway and an enhanced production of nitric oxide in the stomach.

Duodenal ulcer prevalence: research into the nature of possible protective dietary lipids.

The varying geographical prevalence of duodenal ulceration has suggested a relationship to staple diet. Previous experiments on animal peptic ulcer models showed that certain foods, particularly the lipid fraction, are ulceroprotective. This paper reports experiments on animal models further to investigate the nature of the protective substances in the most active lipid, that of horse gram. The free fatty acids and triglycerides, sterols, sterol esters and phospholipids from horse gram were extracted and tested for protective activity on rat peptic ulcer models: the pyloric ligation model which is chronic, involving 14 days pre-feeding, and two acute models using ethanol or cysteamine to induce ulceration. The results showed that sterol esters, but not sterols, were protective in the pyloric ligation model. Sterols were protective in the acute models using ethanol-induced and cysteamine-induced ulceration. Phospholipids were protective in both types of model. The free fatty acids and triglycerides gave no protection using the pyloric ligation model. The presence of sterols, sterol esters and phospholipids in the lipid fraction of foods in staple diets may account for the low prevalence of duodenal ulcer in certain geographical areas, despite a uniformly high prevalence of Helicobacter pylori infection.

Mucosal defense and repair. Role of prostaglandins in the stomach and duodenum.

When considering the diseases of the stomach and duodenum, peptic ulcer disease has been the one of greatest clinical impact. Although there are several components that contribute mechanistically to ulcer disease, it is recognized that gastroduodenal mucosal prostaglandins play a central pathogenic role, especially in ulcers related to the use of NSAIDs. As a result of understanding the mechanisms of NSAID-induced ulceration, the crucial function that gastroduodenal mucosal prostaglandins have in mucosal defense and repair is appreciated. It now is held widely that mucosal prostaglandin deficiency increases susceptibility to ulcer formation and that exogenous administration of supplemental prostaglandins reduces ulcer risk. This article reviews the role that mucosal prostaglandins play in defense of the gastric and duodenal mucosa against injury and ulceration.

Duodenal ulcer prevalence: experimental evidence for the possible role of dietary lipids.

BACKGROUND AND AIMS: Mapping the geographical distribution of duodenal ulcer in relation to staple diets, and experiments on animal peptic ulcer models suggested that the lipid fraction in certain foodstuffs had a protective effect which was most marked in the lipid obtained from Horse gram (Dolichos biflorus). Lipid obtained from stored polished rice or rice bran was ulcerogenic. Further animal experiments were designed to investigate the protective and healing effects of Horse gram lipid (HGL) against peptic ulceration. METHODS: Three effects were investigated in rats: (i) the protective effect of HGL on peptic ulceration produced by using pyloric ligation in combination with South Indian diet or rice bran oil, or by cysteamine, alcohol or aspirin; (ii) the effect of HGL on mast cell degranulation in response to pyloric ligation and rice bran oil; and (iii) the healing effect of HGL on acute gastric ulceration produced by alcohol, on chronic gastric ulceration produced by topical acetic acid or on chronic duodenal ulcer following cysteamine. RESULTS: Horse gram lipid was shown to be protective and to promote ulcer healing in all the models used. Mast cell degranulation was inhibited. CONCLUSION: The experiments confirm the presence of a lipid in certain staple foods that have protective and healing properties in experimental peptic ulcer animal models. The differences in the prevalence of duodenal ulceration between different regions in some developing countries with a high prevalence of Helicobacter pylori infection might be explained by the presence or absence of protective lipids or ulcerogenic factors in the staple diet.

Experimental evaluation of Bocopa monniera on rat gastric ulceration and secretion.

The anti-ulcerogenic effect of fresh juice from the whole plant of Bocapa monniera Wettst. (BMJ) commonly known as Brahmi in Hindi was examined using gastric ulcer models induced by ethanol, aspirin, 2 h cold restraint stress and 4 h pylorus ligation. Bocapa monniera juice (BMJ) at doses of 100 and 300 mg/kg and sucralfate at a dose of 250 mg/kg were given orally, twice daily for 5 days. BMJ 100-300 mg/kg produced significant antiulcer activity in all the experimental gastric ulcer models except in case of ethanol-induced ulcers where 100 mg/kg was not found to decrease it significantly. BMJ (100-300 mg/kg) was found to have little or no effect on the offensive acid-pepsin secretion, while cell shedding (microgram DNA/mg of protein) and mucin secretion in terms of total carbohydrates:protein ration (TC:P), the two important parameters of defensive factors were significantly decreased and increased respectively indicating enhancement of protective mucosal factors. Both BMJ (300 mg/kg) and SF showed tendency to increase the mucosal glycoproteins in terms of TC:P, though individual carbohydrates and total carbohydrates were either increased or showed a tendency to increase. Thus, ulcer protective effect of BMJ may be due to its effect on mucosal defensive factors like enhanced mucin secretion, mucosal glycoprotein and decreased cell shedding rather than on offensive factors such as acid and pepsin.

[Laparoscopic surgery of perforated duodenal ulcer]. / Trattamento laparoscopico dell'ulcera duodenale perforata.

BACKGROUND AND AIM: Endoscopic diagnostic and therapeutic possibilities have been increased by videolaparoscopy. The method enables an immediate reliable diagnosis to be made, associated with possible surgical treatment. METHODS: The authors report their laparoscopic experience relating to the treatment of perforated duodenal ulcer from 1972 to 1995 in 8 patients divided into two groups. Jacob Palmer's laparoscopic operator was used in the first group together with Menghini's needle for the aspiration of peritoneal effusion; the operation was performed under local anesthesia with nitrogen monoxide insufflation using Taylor's technique number I. The second group underwent ulcorrhaphy with omentopexy, again using a laparoscopic route, together with abundant lavage and accurate aspiration of fibrin. RESULTS: The patients in the first group made a prompt recovery in terms of their general conditions following the remission of fever, pain, diminished leukocytes and an early renewal of canalisation; cicatrisation of the ulcer was confirmed by the endoscopic control on day 15. Patients in the second group showed early deambulation approximately 4 hours after surgery; canalisation occurred after about 6 hours and all patients were discharged on day 3. The eradication of Helicobacter pylori led to complete resolution, as was confirmed by subsequent follow-ups. CONCLUSIONS: Laparoscopy was found to be extremely useful both in the immediate diagnosis of acute abdomen following perforated ulcer and in its surgical treatment as a result of the introduction of operating laparoscopes and in particular videolaparoscopes, together with surgical instruments that allow careful abdominal cleansing and ulcorrhaphy. In the authors' opinion, the latter procedure is the most suitable for managing this pathology.

Fermented milk products are associated to ulcer disease. Results from a cross-sectional population study.

BACKGROUND: Prevalence of peptic ulcer disease has been associated to diet. Some dietary factors seem to have bactericidal effect which may modify the risk of peptic ulcer disease. The objective was to analyze associations between dietary habits and peptic ulcers. DESIGN: A cross sectional population study. SUBJECTS: One thousand, one hundred and thirty-five subjects out of 11700 randomly invited men and women, aged 46-67 y, participating in a diet and disease study during 1991-1993. The study population comprised of 764 cases with reported peptic ulcer, 142 with dyspeptic symptoms and 229 randomly selected controls. METHODS: X-ray examinations and endoscopies were reviewed and 332 out of 764 peptic ulcer cases were verified. Mean daily intake of foods and nutrients were assessed with a combined 7d menu book and a quantitative food frequency questionnaire, including dietary supplements. RESULTS: Subjects with verified ulcer had lower intake of fermented milk products and vegetables and higher intake of milk, meat and bread than controls. Intake of total fat, saturated and monounsaturated fatty acids and linolenic acid were higher in the ulcer group. Higher intake of fermented milk products, by quintiles showed a decreased ulcer risk; odds ratio 0.82 (0.71-40.95), adjusted for covariates below. Higher intake of milk, by quintiles, was associated with an increased risk of ulcer; odds ratio 1.17 (1.03-1.32). Smoking, foreign ethnicity and being unmarried or divorced were covariates associated to ulcer. CONCLUSION: This study indicates the multifactorial etiology of peptic ulcer including dietary factors. High intake of fermented milk products was associated with decreased risk for ulcer, whereas increased risk was noted for high milk intake.

One week triple therapy for Helicobacter pylori: does high-dose clarithromycin confer additional benefit?

BACKGROUND: Clarithromycin, a new acid stable macrolide antibiotic with proven efficacy against Helicobacter pylori, has been widely incorporated into eradication regimens but its optimal dosage schedule remains controversial. The standard dose of clarithromycin is 250 mg twice daily. METHODS: In a prospective study designed to evaluate the helicobactericidal efficacy, patient acceptability, and ulcer healing efficacy of a triple therapy regimen incorporating high dose clarithromycin, 100 consecutive patients with H. pylori-positive peptic ulcer received omeprazole 20 mg twice daily in combination with metronidazole 400 mg twice daily and clarithromycin 500 mg twice daily for seven days. H. pylori status was assessed before and at least 4 weeks after therapy by rapid urease test and histology. Adverse events and compliance were assessed by direct questioning. RESULTS: Only two patients failed to attend for repeat endoscopy, leaving 98 evaluable patients. Of these, 94 were H. pylori-negative after therapy, giving an intention-to-treat eradication rate of 94% (95% confidence interval, 89%-99%). The ulcer healing rate was 92% (86%-98%), and ulcer healing was significantly associated with H. pylori eradication (p < 0.01). Adverse events were reported by 33% of patients of which nausea was the commonest (14%). Noncompliance with therapy was significantly associated with H. pylori treatment failure (p < 0.001). CONCLUSIONS: Seven day triple therapy incorporating high dose clarithromycin effectively eradicates H. pylori and heals ulcers, but it is disadvantaged by a relatively high rate of adverse events. In view of these findings and the fact that no direct comparison to date has shown increased efficacy from high dose clarithromycin, we would recommend continued use of low dose clarithromycin when combined with omeprazole and a nitroimidazole.

Protective effect of UL-409, a herbal formulation against physical and chemical factor induced gastric and duodenal ulcers in experimental animals.

UL-409, a herbal formulation, was investigated for its possible ulcero-protective activity in Wistar rats of either sex and male guinea pigs. Oral administration of UL-409 at a dose of 600 mg/kg significantly prevented the occurrence of cold-restraint stress induced ulcerations. It significantly inhibited gastric ulceration induced by alcohol and aspirin, as well as cysteamine and histamine induced duodenal ulcers in rats and guinea pigs, respectively. The volume and acidity of gastric juice in pyloric ligated rats was reduced by UL-409. It also significantly, and dose dependently, promoted gastric mucus secretion in normal as well as in stress, drug and alcohol induced ulceration in animals. On the basis of these observations, we conclude that UL-409 possesses antiulcer activity and that the observed activity may be due to the modulation of defensive factors by improvement in gastric cytoprotection.

[Psychosocial factors in patients with duodenal ulcer]. / Factores psicosociales en la úlcera duodenal.

The authors review the current literature on psychosocial aspects of duodenal ulcer. The initial simple psychosomatic approach, has evolved to a multifactorial schema in which stress and individual vulnerability plays an important role. Psychological features (personality, Type A behaviour, alexithymia, anxiety, depression) and socioenvironmental factors (stress, life events, coping, social support) are analyzed. Newer aspects like the probable stress influence on immunity and infection by Helicobacter pylori are considered.

[Post-radiation duodenal ulceration treated with hyperbaric oxygen]. / Ulcération duodénale post-radique traitée par oxygène hyperbare.

Radiation enteric disorders are rare and difficult to treat. A case of radiation duodenitis treated by hyperbaric oxygen is reported. A sixty-year-old man underwent right nephroureterectomy, chemotherapy (platin and 5 fluorouracil) and radiation therapy (54 Gy) for excretory urinary carcinoma. Six months later, even though he was under omeprazole therapy for reflux oesophagitis, he experienced antroduodenitis, duodenal ulceration, and duodenal telangiectasia. Symptoms and duodenal ulcer disappeared 2 months later with hyperbaric oxygen (10 one hour sessions at 2 ATA). Most likely, hyperbaric oxygen can reduce the consequences of obliterative endarteritis due to irradiation, responsible for ischaemia and fibrosis later on.