Healing property of the Piper betel phenol, allylpyrocatechol against indomethacin-induced stomach ulceration and mechanism of action

AIM：To evaluate the protective activity of allylpyrocatechol （APC）, the major antioxidant constituent of Piper betel, against the indomethacin-induced stomach ulceration in the rat model and correlates with its antioxidative and mucin protecting properties.METHODS： Male Sprague-Dawley rats were divided into five groups. Normal control rats （group Ⅰ ） were given the vehicle oral dose of gum acacia in distilled water （1 mL per rat）; ulcerated control and treated rats （groups Ⅱ-V） were given a single dose of indomethacin （30 mg/kg body wt.）; group Ⅱ rats were sacrificed 4 h after indomethacin administration; groups Ⅲ-Ⅴ rats were given the vehicle （1 mL per rat） or APC （2 mg/kg body wt.） or misoprostol （1.43 μg/kg body wt.） once daily by oral intubation for 7 d starting from 4 h after the indomethacin administration. After 7 d, the stomach tissues were excised for histological examination and biochemical analysis. RESULTS： Treatment with APC （2 mg/kg body wt per day） and misoprostol （1.43 μg/kg body wt per day） for 7 d could effectively heal the stomach ulceration as revealed from the ulcer index and histopathological studies. Compared to the zero day ulcerated group, treatment with APC and misoprostol reduced the ulcer index by 93.4% and 85.4% respectively （P 〈 0.05）. Both APC and misoprostol accelerated ulcer healing observed in natural recovery （P 〈 0.05）, their respective healing capacities not being significantly different. The healing capacities of APC and misoprostol could be attributed to their antioxidant activity as well as the ability to enhance the rnucin content of the gastric tissues. Compared to the ulcerated untreated rats, those treated with APC and rnisoprostol showed near normal MDA levels, while the protein levels were 86% and 78% of the normal value respectively （P 〈 0.05）. Likewise, both APC and rnisoprostol increased the SOD, catalase, and rnucin levels significantly （P 〈 0.05）, the effect of APC being better. CONCLUSION： APC can protect indomethacin-induced gastric ulceration due to its antioxidative and mucin protecting properties.

Feed Form Affects Growth and Stomach Ulcers in Yearling Horses

Fourteen yearling standardbred horses were used to test the hypothesis that hay and grain fed as a complete total mixed ration （TMR） cube diet （C） would result in greater average daily gain （ADG）, feed efficiency （gain to feed ratio, G/F） and apparent digestibility in horses on the TMR diet compared to horses fed the same weight and proportion of hay cubes and grain fed separately （diet HG）. Both diets consisted of 75% forage and 25% ground oats. The forage in both the plain hay cubes and the complete cubes was 80% alfalfa and 20% endophyte-free tall rescue. An additional hypothesis that stomach ulceration would not differ between horses fed either of the two diet treatments was also tested by comparing upper gastric endoscopies before and after 70 days of feeding the experimental diets. Horses fed diet C had greater ADG （P 〈 0.046） while G/F between the two treatments was not significantly different （P 〉 0.065） but showed a trend to be higher in the horses consuming diet C. Apparent digestibility of dry matter and crude protein was not different between the diet treatments, and no major gastric ulceration was found in horses consuming either diet treatment. The results of this study found that a complete cubed diet of 75% hay and 25% oats did not cause stomach ulceration while achieving an acceptable growth rate in yearling horses.

Gastrin,somatostatin,G and D cells of gastric ulcer in rats

AIM: To investigate the relationship among gastrin, somatostatin, G and D cells in gastric ulcer and in its healing process in rats. METHODS: Fourty-nine Wistar rats were divided into 7 groups. The gastric ulcer model was induced by acetic acid successfully. The gastrin and the somatostatin in rat plasma, gastric fluid and antral tissue were measured by radioimmunoassay(RIA). G and D cells in antral mucosa were analyzed with polyclonal antibody of gastrin and somatostatin by immunohistochemical method and Quantimet 500 image analysis system. RESULTS: In gastric ulcer, the level of gastrin in plasma, gastric fluid, and antral tissue increased, that of somatostatin declined, and the disorder gradually recovered to the normal level in the healing process. Immunohistochemical technique of G and D cells in antral mucosa demonstrated that the number of G cells increased and that of D cells decreased, both areas of G and D cells declined, the ratio of number and area of G/D increased in gastric ulcer, and the disorder gradually recovered in the healing process. CONCLUSION: In gastric ulcer, the increased gastrin secreted by G cells, the declined somatostatin secreted by D cells, and the disordered G/D cell ratio can lead to gastrointestinal dysfunction.

Association of CagA and VacA presence with ulcer and non-ulcer dyspepsia in a Turkish population

AIM:The mostly known genotypic virulence features,of H.pylori are cytotoxin associated gene A (cagA) and Vacuolating cytotoxin gene A (VacA).We investigated the association of these major virulence factors with ulcer and non-ulcer dyspepsia in our region. METHODS:One hundred and forty two dyspeptic patients were studied (average age 44.8±15.9 years,range 15-87 years,64 males and 78 females).Antral and corpus biopsies were taken for detecting and genotyping of H.pylori.107 patients who were H.pylori positive by histological assessment were divided into three groups according to endoscopic findings:Duodenal ulcer (DU),gastric ulcer (GU) and non-ulcer dyspepsia (NUD).The polymerase chain reaction (PCR) was used to detect CagA and VacA genes of H.pylori using specific primers. RESULTS:H.pyloriwas isolated from 75.4% (107/142) of the patients.Of the 107 patients,66 (61.7%) were cagA- positive and 82 (76.6%) were VacA-positive.CagA gene was positively associated with DU and GU (P<0.01,P<0.02), but not with NUD (P>0.05).Although VacA positivity in ulcer patients was higher than that in NUD group,the difference was not statistically significant (P>0.05). CONCLUSION:There is a significantly positive association between CagA genes and DU and GU.The presence of VacA is not a predictive marker for DU,GU,and NUD in our patients.

Spices, herbal xenobiotics and the stomach: Friends or foes?

Spices and herbal remedies have been used since ancient times to treat a variety of disorders. It has been experimentally demonstrated that spices, herbs, and their extracts possess antimicrobial, anti-inflammatory, antirheumatic, lipid-lowering, hepatoprotective, nephroprotective, antimutagenic and anticancer activities, besides their gastroprotective and anti-ulcer activities. Despite a number of reports on the toxicity of herbs and spices, they are generally accepted as safer alternatives to conventional therapy against gastric ulcers. To this end, it is also believed, that excessive consumption of spices may favor the pathogenesis of gastric and duodenal ulcer and some studies have substantiated this common perception. Based on various in vivo experiments and clinical studies, on the effects of spices and herbs on gastric ulcers, it has indeed been shown that certain spices do possess remarkable anti-ulcer properties mediated by antisecretory, cytoprotective, antioxidant, and anti-Helicobacter pylori effects and mechanisms regulated by nitric oxide, prostaglandins, non-protein sulfhydryl molecules and epidermal growth factor expression. Accordingly, their consumption may attenuate and help prevent peptic ulcer disease. In the present review, the beneficial effects of spices and herbal nutritive components on the gastric mucosa are discussed against the paradigm of their deleterious potential.

Clinical characteristics of peptic ulcer perforation in Korea

AIM To elucidate the epidemiological characteristics and associated risk factors of perforated peptic ulcer(PPU).METHODS We retrospectively reviewed medical records of patients who were diagnosed with benign PPU from 2010 through 2015 at 6 Hallym university-affiliated hospitals.RESULTS A total of 396 patients were identified with postoperative complication rate of 9.1% and mortality rate of 0.8%. Among 174(43.9%) patients who were examined for Helicobacter pylori(H. pylori) infection, 78(44.8%) patients were positive for H. pylori infection, 21(12.1%) were on non-steroidal anti-inflammatory drugs(NSAIDs) therapy, and 80(46%) patients were neither infected of H. pylori nor treated by any kinds of NSAIDs. Multivariate analysis indicated that older age(OR = 1.09, 95%CI: 1.04-1.16) and comorbidity(OR = 4.11, 95%CI: 1.03-16.48) were risk factors for NSAID-associated PPU compared with non-H. pylori, non-NSAID associated PPU and older age(OR = 1.04, 95%CI: 1.02-1.07) and alcohol consumption(OR = 2.08, 95%CI: 1.05-4.13) were risk factors for non-H. pylori, non-NSAID associated PPU compared with solely H. pylori positive PPU.CONCLUSION Elderly patients with comorbidities are associated with NSAIDs-associated PPU. Non-H. pylori, non-NSAID peptic ulcer is important etiology of PPU and alcohol consumption is associated risk factor.

Gastric ulcer penetrating to liver diagnosed by endoscopic biopsy

Liver penetration is a rare but serious complication of peptic ulcer disease.Usually the diagnosis is made by operation or autopsy.Clinical and laboratory data were no specific.A 64-year-old man was admitted with upper gastrointestinal bleeding.Hepatic penetration was diagnosed as the cause of bleeding.Endoscopy showed a large gastric ulcer with a pseudotumoral mass protruding from the ulcer bed.Definitive diagnosis was established by endoscopic biopsies of the ulcer base.

GC/MS-based differential metabolic profiling of human peptic ulcer disease to study Helicobacter pylori-induced metabolic perturbations

Helicobacter pylori infection has been significantly linked to Peptic Ulcer Disease and Gastric Cancer.Metabolomic fingerprinting may offer a principal way of early diagnosis and to understand the molecular mechanism of H.pylori-induced pathogenicity.The rationale of the study is to explore the underlying distinct metabolic mechanisms of H.pylori-induced PUD and to identify potential biomarkers for disease diagnosis and associated risks using Gas chromatography/mass spectrometry.GC/MS-based analytical method was used to compare metabolic profiles of healthy controls(N=20)and peptic ulcer patients(N=45).Acquired metabolomic data were analyzed by constructing a diagnostic model using principal component analysis and a non-parametric two-tailed paired Wilcoxon analysis to identify disease-specific metabolic biomarkers.A total of 75 low-molecular-weight endogenous metabolites were detected during comparative metabolomic analysis of PUD vs.healthy gut tissues,among which 16 metabolites are being proposed to be diagnostic markers of Human PUD.Perturbations related to amino acids,carbohydrates,fatty acids,organic acids,and sterol metabolism were significantly revealed during this differential metabolomic profiling.Results convincingly suggest that metabolic profiles can contribute immensely in early diagnosis of the disease and understanding molecular mechanisms of disease progression for predicting novel drug targets for prophylactic and anaphylactic measures.

Treatment of Peptic Ulcer with Xiao Jianzhong Tang—A Report of 80 Cases

With Xiao Jianzhong Tang (小建中汤), the author has successfully treated 80 cases of peptic ulcer. The therapeutic effects obtained were compared with that of the Western medicine. A report follows.

CLINICOPATHOLOGICAL STUDY ON 3441 CASES OF BENIGN AND MALIGNANT ULCERS——The National Cooperative Group for Pathological Study on the Canceration of Gastric Ulcer

Resected specimens of benign and malignant gastric ulcers from 3441 cases were studied and compared clinically and pathologically. Among them, 421 cases of malignant ulcer were found. The malignant ulcers differed notably from the ulcerated gastric carcinoma and showed many similarities to the benign chronic gastric ulcer (CGU). The most distinct feature of malignant ulcer was lack of cancerous infiltration and muscular residue in the scar tissue of ulcer base. The existence of this type of ulcer clinically and pathomophologically supports the viewpoint that CGU can undergo malignant change. The rate of malignant change of CGU in this study was 3. 48%.

Experimental study on mechanism and protection of stress ulcer produced by explosive noise

AIM To establish an experimental model of stress ulcer produced by explosive noise, and to probe into its mechanism and protection. METHODS The country standard Wistar white rats were randomly divided into control group ( n =8), which were neither stimulated nor protected, and stimulating group (divided into subgroups A, B and C, including 8 rats each which were decapitated to draw blood for test immediately, 12 hours and 24 hours after stimulation) and prevention group (divided into subgroups A, B and C, having 8 rats each, subgroup A was given cimetidine, B anisodamine and C both drugs). Firing noises of submachine guns were used as inflicting factor. The rats were fasted for 24 hours and stimulated by firing noise for 12 hours. The change of ulcer index, gastric mucosal and related serum hormones were observed. RESULTS Stress ulcer was significant in the stimulating group, and its ulcer index (8 6±0 6) was remarkably higher than that in both the control group and prevention group (0 3±0 1, P <0 01). Its serum gastrin (Gas ng/L , 294±163 vs 63±40, P <0 01) and endothelin (ET ng/L , 181±57 vs 135±42, P <0 01) were apparently higher than those in the control group, and its serum nitric oxide (NO) level was conspicuously lower than that in the control group ( ng/L , 0 2±0 1 vs 0 8±0 5, P <0 05), while the serum gastrin level ( ng/L , 556±225) in prevention group was distinctly higher than that in both the control ( P <0 01) and stimulating group ( P <0 05). There were no significant differences in the changes of ET and NO between the control and the stimulating groups. CONCLUSION Stress ulcer model of rats can be successfully established by the stimulation of explosive noise. Gas, ET and NO are related to the formation of stress ulcer, and play an important role in its mechanism. Hepatic function affected by noise is observed in this experiment.

Helicobacter pylori: the primary cause of duodenal ulceration or a secondary infection?

INTRODUCTIONIt is generally accepted that Helicobacter pylori ( H.pylori) infection has a role in duodenal ulceration .Eradicaton of H .pylori accelerates healing compared with placebo in the absence of control of gastric secretion and reduces ulcer recurrence .There is increasing evidence ,however ,that is may not be the primary cause of duodenal ulceration ,but that is may be a secondary factor in a nnmber of cases .This possibility is supported by four sets of observations : 1 Geographical distribution:

Short term effect of Salvia miltiorrhiza in treating rat acetic acid chronic gastric ulcer and long term effect in preventing recurrence

AIM To study the short term effect of Danshen ( Salvia miltiorrhiza ) on acetic acid induced chronic gastric ulcer in rats and its long term effect in preventing recurrence. METHODS Rats with acetic acid induced gastric ulcer were treated with Danshen and cimetidine for 30 days. Traditional gastric mucosal auto radiography and 3H TdR incorporation into gastric mucosa in vitro were employed to study the effects of Danshen in rat acetic acid induced chronic gastric ulcer, including ulcer index (UI), ulcer inhibitory rate (IR) and label rate (LR). RESULTS On the day 5, 30 and 126 of ulcer making, the UI in the Danshen group was obviously lower than that in the cimetidine group and the control group (42 3±3 9, 3 6±1 2, 4 4±2 3; 49 1±3 6, 5 9±1 4, 9 2±1 3; 61 0±3 8, 8 9±2 5, 12 4±2 4, respectively, P <0 01), the IR (%) in the Danshen group was obviously higher than that in the cimetidine group (31, 59, 64 8; 19, 33, 26, respectively), and the LR in the Danshen group was obviously higher than that in the cimetidine group and the control group (10 0±0 5, 16 2±0 8, 15 0±0 6; 9 0±0 5, 13 9±0 6, 10 8±0 7; 6 5±0 7, 10 1±0 5, 8 0±0 7, respectively, P <0 01). There was no obvious difference in UI in the Danshen group on day 30 as compared with that on day 126. CONCLUSION Danshen is effective in promoting ulcer healing and preventing recurrence. The mechanism of action is to strengthen the gastric mucosal barrier and to promote the gastric mucosal cell proliferation along the edge of the ulcer.

Gastroduodenal ulcer treated by pylorus and pyloric vagus-preserving gastrectomy

AIM To evaluate the curative effect of pylorus and pyloric vagus-preserving gastrectomy (PPVPG) on peptic ulcer.METHODS Treating 132 cases of GU and DU with PPVPG, and comparative studies made with 24 cases treated with Billroth Ⅰ (BⅠ) and 20 cases with Billroth Ⅱ (BⅡ); advantages and shortcomings evaluated.RESULTS Not a single death after PPVPG. No recurrence of the disorder in the subsequent follow-up for an average of 6.5 years. Curative effect (visik Ⅰ & Ⅱ) 97.7%. Acidity reduction similar to that found in BⅠ and BⅡ, but 97.7% of the BⅠ and all BⅡ cases having more than second degree intestinal fluid reflux, in contrast to 7.1% in PPVPG cases. Dumping syndrome occurred in the BⅠ and BⅡ cases, none in PPVPG cases. With regard to gastric emptying, food digestion, absorption, body weight and life quality, PPVPG proved to be superior to Billroth procedure.CONCLUSION PPVPG has the advantages of conventional Billroth gastrectomy in reducing acid, removing ulcer focus, and at the same time preserves the pylorus and pyloric vagus for maintaining the normal gastric physiological function. Dumping syndrome, intestinal fluid reflux and other complications of conventional gastrectomy may be avoided.

Influence of interleukin polymorphisms on development of gastric cancer and peptic ulcer

Pro-inflammatory cytokines are produced in the gastric mucosa by inflammatory cells activated by chronic Helicobacter pylori (H. pylori) infection. Polymorphisms of these cytokine genes are associated with individual differences in gastric mucosal cytokine mRNA level, which result in differences in gastric mucosal inflammation, acid inhibition and gastroduodenal disease risk in response to H. pylori infection. Although polymorphisms of interleukin (IL)-1B, IL-1RN and TNF-A have been reported to relate well with gastric cancer and peptic ulcer risk, those of IL-2, IL-4, IL-6 and IL-8 genes are unclear. In combined analyses using data from previous studies, we found that the risk of gastric non-cardia cancer development was significantly associated with IL-4-168 C allele (OR: 0.81, 95% CI: 0.69-1.00) and IL-4-590 T allele carrier status (0.61, 0.53-0.73), and IL-6-174 G/G genotype (2<Abstract>Pro-inflammatory cytokines are produced in the gastric mucosa by inflammatory cells activated by chronic Helicobacter pylori (H. pylori) infection. Polymorphisms of these cytokine genes are associated with individual differences in gastric mucosal cytokine mRNA level, which result in differences in gastric mucosal inflammation, acid inhibition and gastroduodenal disease risk in response to H. pylori infection. Although polymorphisms of interleukin (IL)-1B, IL-1RN and TNF-A have been reported to relate well with gastric cancer and peptic ulcer risk, those of IL-2, IL-4, IL-6 and IL-8 genes are unclear. In combined analyses using data from previous stud- ies, we found that the risk of gastric non-cardia cancer development was significantly associated with IL-4-168 C allele (OR: 0.81, 95% CI: 0.69-1.00) and IL-4-590 T allele carrier status (0.61, 0.53-0.73), and IL-6-174 G/G genotype (2.02, 1.31-3.10). In peptic ulcer development, IL-2-330 G and IL-4-590 T allele carriers had a significantly decreased risk (0.37, 0.27-0.50 and 0.58, 0.34-0.99, respectively). Moreover, IL-2, IL-4, IL-6 and IL-8 gene genotypes prevalence differs among popula- tions. The inflammatory cytokine gene polymorphisms (e.g. IL-4 -590 and IL-6 -572 for gastric cancer, and IL-4-590, IL-6-572 and IL-8-251 for peptic ulcer) have a more potent influence on development of gastroduo- denal diseases in Western than East Asian populations. These cytokine gene polymorphisms, as well as those of IL-1B, IL-1RN and TNF-A, may be used to identify groups at higher risk of gastric cancer and peptic ulcer, and those suitable for their prevention by H. pylori eradication therapy in Western populations..02, 1.31-3.10). In peptic ulcer development, IL-2-330 G and IL-4-590 T allele carriers had a significantly decreased risk (0.37, 0.27-0.50 and 0.58, 0.34-0.99, respectively). Moreover, IL-2, IL-4, IL-6 and IL-8 gene genotypes prevalence differs among populations. The inflammatory cytokine gene polymorphisms (e.g. IL-4 -590 and IL-6 -572 for gastric cancer, and IL-4-590, IL-6-572 and IL-8-251 for peptic ulcer) have a more potent influence on development of gastroduo-denal diseases in Western than East Asian populations. These cytokine gene polymorphisms, as well as those of IL-1B, IL-1RN and TNF-A, may be used to identify groups at higher risk of gastric cancer and peptic ulcer, and those suitable for their prevention by H. pylori eradication therapy in Western populations.

The role of adhesion molecules in gastri c ulcer healing

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Effects of Danshen in prevention and treatment of rat acetic acid gastric ulcer

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Comparison of 5-hydroxytryptophan signaling pathway characteristics in diarrhea-predominant irritable bowel syndrome and ulcerative colitis

AIM: To study differences in the visceral sensitivity of the colonic mucosa between patients with diarrheapredominant irritable bowel syndrome(IBS-D) and those with ulcerative colitis(UC) in remission and to relate these differences with changes in the 5-hydroxytryptophan(5-HT) signaling pathway. METHODS: Gastrointestinal symptoms were used to determine the clinical symptom scores and rectal visceral sensitivity of patients with IBS-D and patients with UC in remission. Blood levels of 5-HT and5-hydroxyindoleacetic acid(5-HIAA) were measured using an HPLC-electrochemical detection system. The levels of 5-HT 3 receptor(3R), 4R, and 7R m RNAs in colonic biopsy samples were detected using reverse transcription-polymerase chain reaction. The protein expression of TPH1 was analyzed by Western blot and immunohistochemistry.RESULTS: Abdominal pain or discomfort, stool frequency, and the scores of these symptoms in combination with gastrointestinal symptoms were higher in the IBS-D and UC groups than in the control groups. However, no significant differences were observed between the IBS-D and UC remission groups. With respect to rectal visceral sensitivity, the UC remission and IBS-D groups showed a decrease in the initial perception threshold, defecating threshold and pain threshold. However, these groups exhibited significantly increased anorectal relaxation pressure. Tests examining the main indicators of the 5-HT signaling pathway showed that the plasma 5-HT levels, 5-HIAA concentrations, TPH1 expression in the colonic mucosa, and 5-HT3 R and 5-HT5 R expression were increased in both the IBS-D and the UC remission groups; no increases were observed with respect to 5-HT7 R expression.CONCLUSION: The IBS-D and UC groups showed similar clinical symptom scores, visceral sensitivity, and levels of serotonin signaling pathway indicators in the plasma and colonic mucosa. However, the pain threshold and 5-HT7 R expression in the colonic mucosa were significantly different between these groups. The results reveal that(1) IBS-D and UC are related to visceral sensitivity pathogenesis and the clinical manifestations of these conditions and(2) the observed differences in visceral hypersensitivity are possibly due to differences in levels of the 5-HT7 receptor, a component of the 5-HT signaling pathway.

Traditional Chinese Medicine Nursing Protocols for Gastric ulcer(peptic ulcer)

Objective Gastric ulcer( peptic ulcer) is one of the most common digestive system diseases. This paper aimed to summarize the common syndromes of gastric ulcer( peptic ulcer),and to discuss related Traditional Chinese Medicine nursing interventions and health guidance.

补益脾胃溃结方对脾胃虚弱型溃疡性结肠炎患者的临床疗效

目的 探讨补益脾胃溃结方对脾胃虚弱型溃疡性结肠炎患者的临床疗效。方法 132例患者随机分为对照组和观察组,每组66例,对照组给予常规治疗,观察组在对照组基础上加用补益脾胃溃结方,疗程4周。检测临床疗效、Mayo评分、SF-36评分、中医证候评分、5-HT、IL-6、TNF-α、IL-4、CD4^(+)/CD8^(+)、LPS、TGF-β1、DAO变化。结果 观察组总有效率高于对照组(P<0.05)。治疗后,2组Mayo评分、中医证候评分、TNF-α、LPS、5-HT、IL-6、CD4^(+)/CD8^(+)、DAO降低(P<0.05),SF-36评分、TGF-β1、IL-4升高(P<0.05),以观察组更明显(P<0.05)。结论 补益脾胃溃结方可减轻脾胃虚弱型溃疡性结肠炎患者炎症反应,调节免疫功能,抑制疼痛介质分泌,促进肠黏膜修复,提高临床疗效。