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 synthasederived NO; suppressing oxidative mucosal damage; amplifying antioxidant performance,antacid,and antisecretory 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 downregulation of proinflammatory cytokines and cellular and int e r c e llular adhe s ion age nt s,s uppr e s s ing 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 welldesigned 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.

Proton-pump inhibitors for prevention of upper gastrointestinal bleeding in patients undergoing dialysis

AIM:To investigate the preventive effects of low-dose proton-pump inhibitors(PPIs) for upper gastrointestinal bleeding(UGIB) in end-stage renal disease.METHODS:This was a retrospective cohort study that reviewed 544 patients with end-stage renal disease who started dialysis at our center between 2005 and 2013.We examined the incidence of UGIB in 175 patients treated with low-dose PPIs and 369 patients not treated with PPIs(control group).RESULTS:During the study period, 41 patients developed UGIB, a rate of 14.4/1000 person-years.The mean time between the start of dialysis and UGIB events was 26.3 ± 29.6 mo.Bleeding occurred in only two patients in the PPI group(2.5/1000 person-years) and in 39 patients in the control group(19.2/1000 person-years).Kaplan-Meier analysis of cumulative non-bleeding survival showed that the probability of UGIB was significantly lower in the PPI group than in the control group(log-rank test, P < 0.001).Univariate analysis showed that coronary artery disease, PPI use, anti-coagulation, and anti-platelet therapy were associated with UGIB.After adjustments for the potential factors influencing risk of UGIB, PPI use was shown to be significantly beneficial in reducing UGIB compared to the control group(HR = 13.7, 95%CI:1.8-101.6; P = 0.011).CONCLUSION:The use of low-dose PPIs in patients with end-stage renal disease is associated with a low frequency of UGIB.

Weekend and nighttime effect on the prognosis of peptic ulcer bleeding

AIM:To evaluate whether weekend or nighttime admission affects prognosis of peptic ulcer bleeding despite early endoscopy.METHODS:Retrospective data collection from four referral centers,all of which had a formal out-of-hours emergency endoscopy service,even at weekends.A total of 388 patients with bleeding peptic ulcers who were admitted via the emergency room between January 2007 and December 2009 were enrolled.Analyzed parameters included time from patients' arrival until endoscopy,mortality,rebleeding,need for surgery and length of hospital stay.RESULTS:The weekday and weekend admission groups comprised 326 and 62 patients,respectively.There were no significant differences in baseline characteristics between the two groups,except for younger age in the weekend group.Most patients (97%) had undergone early endoscopy,which resulted in a low mortality rate regardless of point of presentation (1.8% overall vs 1.6% on the weekend).The only outcome that was worse in the weekend group was a higher rate of rebleeding (12% vs 21%,P = 0.030).However,multivariate analysis revealed nighttime admission and a high Rockall score (≥ 6) as significant independent risk factors for rebleeding,rather than weekend admission.CONCLUSION:Early endoscopy for peptic ulcer bleeding can prevent the weekend effect,and nighttime admission was identified as a novel risk factor for rebleeding,namely the nighttime effect.

Detection and evaluation of antibodies against neutrophil-activating protein of Helicobacter pylori in patients with gastric cancer

AIM： To detect and evaluate the antibodies against Helicobacter pylori （H pylori） neutrophil-activating protein （HP-NAP） in patients with gastric cancer and other gastroduodenal diseases.METHODS： Recombinant HP-NAP was prepared from a prokaryotic expression system in Escherichia coll. Serum positivity and level of HP-NAP-specific antibodies in sera from 43 patients with gastric cancer, 28 with chronic gastritis, 28 with peptic ulcer, and 89 healthy controls were measured by rHP-NAP-based ELISA. rHP-NAP-stimulated production of interleukin-8 （IL-8） and growth-related oncogene （GROα） cytokines in the culture supernatant of SGC7901 gastric epithelial cells was also detected.RESULTS： The serum positivity and mean absorbancevalue of HP-NAP-specific antibodies in the gastriccancer group （97.7% and 1.01 ± 0.24） were significantly higher than those in the chronic gastritisgroup （85.7% and 0.89 ± 0.14, P 〈 0.005） and healthy control group （27.7% and 0.65 ± 0.18, P 〈 0.001）. The sensitivity and specificity of ELISA for the detection of HP-NAP-specific antibodies were 95.5% and 91.5%, respectively. HP-NAP could slightly upregulate IL-8 production in gastric epithelial cell lines but had no effect on GROα production.CONCLUSION： Infection with virulent H py/ori strains secreting HP-NAP is associated with severe gastroduodenal diseases, and HP-NAP may play a role in the development of gastric carcinoma, rHP-NAP- based ELISA can be used as a new method to detect H pylori infection. The direct effect of HP-NAP on gastric epithelial cells may be limited, but HP-NAP may contribute to inflammatory response or carcinogenesis by activating neutrophils.

Digestive manifestations of parathyroid disorders

The parathyroid glands are the main regulator of plasma calcium and have a direct influence on the digestive tract.Parathyroid disturbances often result in unknown long-standing symptoms.The main manifestation of hypoparathyroidism is steatorrhea due to a deficit in exocrine pancreas secretion.The association with celiac sprue may contribute to malabsorption.Hyperparathyroidism causes smooth-muscle atony,with upper and lower gastrointestinal symptoms such as nausea,heartburn and constipation.Hyperparathyroidism and peptic ulcer were strongly linked before the advent of proton pump inhibitors.Nowadays,this association remains likely only in the particular context of multiple endocrine neoplasia type 1/Zollinger-Ellison syndrome.In contrast to chronic pancreatitis,acute pancreatitis due to primary hyperparathyroidism is one of the most studied topics.The causative effect of high calcium level is confirmed and the distinction from secondary hyperparathyroidism is mandatory.The digestive manifestations of parathyroid malfunction are often overlooked and serum calcium level must be included in the routine workup for abdominal symptoms.

Relation of atrophic gastritis with Helicobacter pylori-CagA^+ and interleukin-1 gene polymorphisms

AIM： To determine the association of Helicobacter pylori （H pylorl） CagA^＋ infection and pro-inflammatory polymorphisms of the genes interleukin （IL）-IRN and IL-1B with the risk of gastric atrophy and peptic ulcers in a dyspeptic population in Costa Rica, a country with high incidence and mortality of gastric cancer. METHODS： Seven biopsy specimens, a fasting blood sample and a questionnaire concerning nutritional and sociodemographic factors were obtained from 501 consecutive patients who had undergone endoscopy for dyspeptic symptoms. A histopathological diagnosis was made. Pepsinogen concentrations were analyzed by enzyme linked immunosorbent assay （ELISA）. Infection with H pylori CagA^＋ was determined by serology and polymerase chain reaction （PCR）. IL-1B and IL-1RN polymorphisms genotyping was performed by PCRrestriction fragment length polymorphism （PCR-RFIP）and PCR respectively. RESULTS： In this dyspeptic population, 86% were Hpylori positive and of these, 67.8% were positive for CagA. Atrophic antral gastritis （AAG） was associated with CagA^＋ status [odd ratio （OR） = 4.1; P 〈 0.000] and fruit consumption （OR = 0.3; P 〈 0.00）. Atrophic body gastritis （ABG） was associated with pepsinogen PGI/PGII 〈 3.4 （OR = 4.9; P 〈 0.04） and alcohol consumption （OR = 7.3; P 〈 0.02）. Duodenal ulcer was associated with CagA^＋ （OR = 2.9; P 〈 0.04） and smoking （OR = 2.4; P 〈 0.04）. PGI 〈 60 μg/L as well as PGI/PGII 〈 3.4 were associated with CagA^＋. CONCLUSION： In a dyspeptic population in Costa Rica, H pylori CagA^＋ is not associated with ABG, but it is a risk factor for AAG. The pro-inflammatory cytokine poly- morphisms IL-1B ＋ 3945 and IL-1RN are not associated with the atrophic lesions of this dyspeptic population.

Herpes simplex virus type 1 in peptic ulcer disease: An inverse association with Helicobacter pylori

AIM： To assess the frequency of herpes simplex virus type I in upper gastrointestinal tract ulcers and normal mucosa with the modern and better assays and also with a larger number of well characterized patients and controls and its relationship to Helicobacter pylori（H pylori）. METHODS： Biopsy specimens from 90 patients （34 with gastric ulcer of the prepyloric area and 56 with duodenal ulcer） were evaluated. Biopsies from 50 patients with endoscopically healthy mucosa were considered as the control group. The method used to identify herpes simplex virus-1 （HSV-1） was polymerase chain reaction. Hpylori was detected by the CLO-test and by histological method. RESULTS： Herpes simplex virus-1 was detected in 28 of 90 patients with peptic ulcer （31%） Ⅲ of 34 patients with gastric ulcer （32.4%） and 17 of 56 with duodenal ulcer （30.4%）1 exclusively close to the ulcerous lesion. All control group samples were negative for HSV-1. The likelihood of Hpylori negativity among peptic ulcer patients was significantly higher in HSV-1 positive cases than in HSV-1 negative cases （P = 0.009）. Gastric ulcer patients with HSV-1 positivity were strongly associated with an increased possibility of Helicobacter pylori negativity compared to duodenal ulcer patients （P = 0.010）. CONCLUSION： HSV-1 is frequent in upper gastrointestinal tract ulcers but not in normal gastric andduodenal mucosa. There is an inverse association between HSV-1 and Hpylori infection.