Development Of Gastric Lesions Research Articles

Metabolite Alterations and Interactions with Microbiota in Helicobacter pylori-Associated Gastric Lesions.

Metabolites and their interactions with microbiota may be involved in Helicobacter pylori-associated gastric lesion development. This study aimed to explore metabolite alterations upon H. pylori eradication and possible roles of microbiota-metabolite interactions in progression of precancerous lesions. Targeted metabolomics assays and 16S rRNA gene sequencing were conducted to investigate metabolic and microbial alterations of paired gastric biopsy specimens in 58 subjects with successful and 57 subjects with failed anti-H. pylori treatment. Integrative analyses were performed by combining the metabolomics and microbiome profiles from the same intervention participants. A total of 81 metabolites were significantly altered after successful eradication compared to failed treatment, including acylcarnitines, ceramides, triacylglycerol, cholesterol esters, fatty acid, sphingolipids, glycerophospholipids, and glycosylceramides, with P values of <0.05 for all. The differential metabolites showed significant correlations with microbiota in baseline biopsy specimens, such as negative correlations between Helicobacter and glycerophospholipids, glycosylceramide, and triacylglycerol (P < 0.05 for all), which were altered by eradication. The characteristic negative correlations between glycosylceramides and Fusobacterium, Streptococcus, and Gemella in H. pylori-positive baseline biopsy specimens were further noticed in active gastritis and intestinal metaplasia (P < 0.05 for all). A panel including differential metabolites, genera, and their interactions may help to discriminate high-risk subjects who progressed from mild to advanced precancerous lesions in short-term and long-term follow-up periods with areas under the curve (AUC) of 0.914 and 0.801, respectively. Therefore, our findings provide new insights into the metabolites and microbiota interactions in H. pylori-associated gastric lesion progression. IMPORTANCE In this study, a panel was established including differential metabolites, genera, and their interactions, which may help to discriminate high-risk subjects for progression from mild lesions to advanced precancerous lesions in short-term and long-term follow-up.

Discrimination between Precancerous Gastric Lesions and Gastritis Using a Gastric Cancer Risk Stratification Model.

Seropositivity to certain Helicobacter pylori proteins may affect development of gastric lesions that could become cancerous. Previously, we developed a model of gastric cancer risk including gender, age, HP0305 sero-positivity, HP1564 sero-positivity, UreA antibody titer and serologically defined chronic atrophic gastritis (termed: "Lasso model"). We evaluated the Lasso model's ability to discriminate individuals with precancerous gastric lesions (n=320) from individuals with superficial or mild atrophic gastritis (n=226) in Linqu County, China, a population at high risk for gastric cancer. We also compared its performance to the ABC Method, a gastric cancer risk stratification tool currently used in East Asia. For distinguishing precancerous lesions from those with gastritis, the receiver operating characteristic curve had an area under the curve (AUC) of 73.41% (95% CI: 69.10%, 77.71%) and, at Youden's Index, a sensitivity of 78.44% (59.38%, 82.50%) and specificity of 64.72% (95% CI: 58.85%, 81.42%). Positive predictive value (PPV) was 75.38% (72.78%, 82.51%). Specificity, AUC and PPV were significantly greater (p < 0.05) than those of the ABC Method. When specificity was held constant, the Lasso model had greater sensitivity, PPV and negative predictive value (NPV) than the ABC Method. However, adjusting the ABC Method for age and gender negated the Lasso model's significant improvement in AUC. The Lasso model for gastric cancer risk prediction can classify precancerous lesions with significantly greater AUC than the ABC Method and, at constant specificity, with greater sensitivity, PPV and NPV. However, adding age and gender to the ABC Method, as included in the Lasso model, substantially improved its performance and negated the Lasso model's advantage.

Association of Progranulin Gene Expression from Dyspeptic Patients with Virulent Helicobacter pylori Strains; In Vivo Model.

(1) Background: Gastric cancer, the fourth most common cause of death from tumors in the world, is closely associated with Helicobacter pylori. Timely diagnosis, therefore, is essential to achieve a higher survival rate. In Chile, deaths from gastric cancer are high, mainly due to late diagnosis. Progranulin has reflected the evolution of some cancers, but has been poorly studied in gastric lesions. Aiming to understand the role of progranulin in H. pylori infection and its evolution in development of gastric lesions, we evaluated the genic expression of progranulin in gastric tissue from infected and non-infected patients, comparing it according to the epithelial status and virulence of H. pylori strains. (2) Methods: The genic expression of progranulin by q-PCR was quantified in gastric biopsies from Chilean dyspeptic patients (n = 75) and individuals who were uninfected (n = 75) by H. pylori, after receiving prior informed consent. Bacteria were grown on a medium Columbia agar with equine-blood 7%, antibiotics (Dent 2%, OxoidTM), in a microaerophilic environment, and genetically characterized for the ureC, vacA, cagA, and iceA genes by PCR. The status of the tissue was determined by endoscopic observation. (3) Results: Minor progranulin expression was detected in atrophic tissue, with a sharp drop in the tissue colonized by H. pylori that carried greater virulence, VacAs1m1+CagA+IceA1+. (4) Conclusions: Progranulin shows a differential behavior according to the lesions and virulence of H. pylori, affecting the response of progranulin against gastric inflammation.

Helicobacter pylori infection over bile reflux: No influence on the severity of endoscopic or premalignant gastric lesion development.

Helicobacter (H.) pylori infection and duodenogastric reflux (DGR) are both linked to endoscopic and premalignant gastric lesion development, but it is still unclear whether they are independent or have a causal relationship. This study investigated the histologic gastric changes in patients with primary DGR and H. pylori infection, as well as their endoscopic findings, symptoms, drug consumption, and social behavior in comparison with patients presenting only DGR. The study included 560 patients with primary DGR on endoscopy divided into two groups, according to the presence/absence of H. pylori infection on biopsy (utilizing usual stainings and immunohistochemical methods). There was no significant difference in terms of age and sex, nor in the frequency of diabetes or esophagitis between the studied groups. Epigastric pain was associated with H. pylori-positive biopsies in multivariate logistic regression analysis (P=0.005). Although without statistical significance, severe endoscopic lesions and premalignant gastric lesions were more frequent in the H. pylori group (45.1 vs. 28.4% and 37.4 vs. 32.3%, respectively). In patients with DGR, the final multivariate model revealed a positive association between smoking and immunohistochemically confirmed H. pylori infection (P=0.02, OR=1.88, 95% confidence intervals (CI)=1.10 to 3.21), but a negative effect of proton pump inhibitor consumption (P<0.001, OR=0.50, 95% CI=0.35 to 0.73). In conclusion, in patients with H. pylori infection and DGR, epigastric pain was the main reason for the endoscopic investigation. H. pylori infection over DGR did not influence the severity of endoscopic or premalignant gastric lesion development. Furthermore, smoking is directly related to immunohistochemically assessed active H. pylori infection in patients with bile reflux.

GASTROPROTECTIVE ACTIVITY OF EQUISETUM HYEMALE IN EXPERIMENTAL GASTRIC ULCER RAT MODELS

Equisetum hyemale is traditionally used for dyspepsia and stomach pain. The aim of the present study was to evaluate the gastroprotective activity of the aqueous ethanolic extract of the aerial parts of Equisetum hyemale in gastric ulcer rat models. Gastric ulcer models were induced by ethanol (5 mL/kg bw), acetylsalicylic acid (ASA) (200 mg/kg bw) and pylorus ligation separately. The pH, total acidity, ulcer scoring index and histopathological evaluation were performed. Oral administration of Equisetum hyemale extract (250 and 500 mg/kg bw) significantly reduced the development of gastric lesions in all gastric ulcer models. The pH, total acidity and ulcer scoring index also decreased significantly when compared with the Diseased control group. Histopathological studies are in good agreement with the biochemical findings. Equisetum hyemale might show its gastroprotective activity by decreasing oxidative damage, blockage of H2 receptors activation, increase prostaglandins secretion and formation of mucus layer in different gastric ulcer models. The findings of the present study validate the traditional use of Equisetum hyemale to treat stomach pain, however the determination of phytochemical compounds responsible for gastroprotective activity is required for further confirmation.

Evaluation of a questionnaire to detect the risk of developing ESGD or EGGD in horses

Equine gastric ulcer syndrome (EGUS) affects various categories of horses worldwide. This syndrome is now divided into two different diseases, based on the presence of lesions on either the squamous (Equine Squamous Gastric Disease, ESGD) or the glandular (Equine Glandular Gastric Disease, EGGD) mucosa. Diagnosis is based on the evaluation of the presence of gastric lesions with gastroscopic examination. As a gastroscopy can be considered expensive by clients, therapy is started often on the basis of clinical signs only. The aim of this study was to validate a questionnaire to detect the risk of developing ESGD or EGGD. The owners of 418 horses that were submitted to gastroscopic evaluation were asked to answer a questionnaire on risk factors for ESGD and EGGD. Horses were divided into three groups based on the results of the questionnaire and their risk of developing gastric lesions. In our population the survey was not useful to detect the presence and the severity of the lesions detected during gastroscopic examination, however answers to some of the questions did correlate with the development of gastric lesions. The questionnaire could therefore be a useful tool to evaluate the risk of ESGD or EGGD. Having owners periodically complete the survey could also make them more aware of changes in the conditions of the horses that could lead to gastric lesions. This could then help them seek advice from veterinarians on how to manage this potential risk.

LASSBio-596 protects gastric mucosa against the development of ethanol-induced gastric lesions in mice

LASSBio-596 (2-[4-(1,4-thiazinan-4-ylsulfonyl) phenylcarbamoyl] benzoic acid) is a molecular hybrid of anti-tumor necrosis factor α (TNF-α) and phosphodiesterase 5 inhibitors, and its anti-inflammatory effects have been demonstrated in experimental models of inflammation. The aim of this study was to evaluate the gastroprotective effect of LASSBio-596 in an ethanol-induced acute gastritis model. Before induction of gastric damage, mice were pretreated with LASSBio-596 (20 mg per os (p.o.), Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME; 3 mg/kg, intraperitoneally [i.p.]) or with 1400W (10 mg/kg, i.p.) given alone or in their combinations. Thirty minutes later, gastric damage was induced by intragastric instillation of 50% ethanol (0.5 ml/25 g, by gavage). After 1 h, gastric damage (hemorrhagic or ulcerative lesions) was measured by planimetry. Samples of the stomach were also taken for histopathological assessment and for assays of tissue myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA), and inflammatory cytokines. Ethanol administration induced the development of gastric lesions in mice. LASSBio-596 reduced gastric damage, epithelial cell loss and hemorrhage, and restored the antioxidant defense system by decreasing the levels of MDA and the consumption of GSH in gastric mucosa. LASSBio-596 also decreased gastric TNF-α and interleukin-1β (IL-1β) protein levels, MPO enzymatic activity, and hemoglobin levels. Treatment with the nitric oxide synthase inhibitors L-NAME and 1400W reversed the effects of LASSBio-596 on ethanol-induced gastric lesions. LASSBio-596 did not alter mucus content and pH of gastric secretions. In summary, LASSBio-596 exerts protective effects against ethanol-induced gastric injury. The gastroprotective effects of LASSBio seem to be NO-dependent.

Therapeutic effects of hydro-alcoholic extract of Achillea wilhelmsii C. Koch on indomethacin-induced gastric ulcer in rats: a proteomic and metabolomic approach

BackgroundGastric ulcer is one of the most prevalent diseases worldwide. In Iranian folk medicine, Achillea wilhelmsii (AW) is used as a treatment for gastric ulcer. Previous reports also mentioned Antiulcerogenic properties for this herbal plant. This study investigated the therapeutic effects of Achillea wilhelmsii C. Koch extract on indomethacin-induced gastric lesion in rats, from both proteomic and metabolomic perspectives.MethodsThe rats were divided into 4 groups. Gastric ulceration was induced by a single dose of indomethacin (45 mg/kg) by oral gavage. An amount of 800 mg/kg of AW extract was administered orally. Serum and tissue samples were collected for further investigations. The metabolomic study was performed by 1H-NMR CPMG spectrometry. Proteomic analysis was also executed by using two dimensional gel electrophoresis (2DE) followed by liquid chromatography coupled to tandem mass spectrometry (LC-ESI/MS/MS). Real time PCR was used to confirm some of the genes.ResultsThe macroscopic and microscopic investigations confirmed the effectiveness of the AW extract. There was a panel of metabolites which showed alteration during gastric lesion development. The levels of some of these metabolite reversed nearly to their control values after the administration of AW extract. There were also changes in the levels of some proteins including Alb, Fabp5, Hspb1, Tagln, Lgals7, Csta and Myl9 which were reversed after AW administration.ConclusionsOur findings suggested that Achillea wilhelmsii C. Koch extract could be a potential therapy to be used for indomethacin-induced gastric lesion treatment in the future. However, further investigations are needed to confirm the results.

Melatonin as an armament against non-steroidal anti-inflammatory drug induced gastric injury: An overview

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely prescribed medicines to treat numerous pathophysiological conditions clinically. However, growing evidence indicates the adverse effects of NSAIDs on the different vital organs, among which gastrointestinal (GI) tract seems to be the utmost target in most of the cases. NSAIDs promote over production of harmful reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the gastric mucosa. These toxic species cause microvascular damage, increasing intestinal permeability, leading to the development of gastric lesions including ulcerations. Several strategies have been proposed to reduce the side effects of NSAIDs on the GI tissue, but most of them have failed to achieve this goal. Identification of an appropriate therapeutic strategy is urgently required. It is our opinion that this novel strategy to target GI damage induced by NSAID should include both anti-inflammatory and antioxidant properties. Under such a circumstance melatonin probably is the best choice for this purpose. Melatonin is a broad spectrum antioxidant and anti-inflammatory molecule. Numerous studies have reported the protective role of melatonin against gastric tissue damages caused by NSAIDs in animals or clinically. However, the underlying molecular mechanisms are not fully clarified. Thus, the present review attempts to gather the available information on this topic to provide a clear understanding on the exact scenario of this aspect.

Toll-like receptor 2 and 4 polymorphisms associated with Helicobacter pylori susceptibility and gastric cancer.

Genetic polymorphisms in Toll-like receptors (TLRs) are important influence on gastric lesion development and Helicobacter pylori susceptibility. TLR2 rs3804099 and rs3804100 and TLR4 rs10759932 were determined in a total of 400 patients. The association among genotypes and the risk of gastric lesion development and H. pylori susceptibility were evaluated by the odds ratios (ORs) and 95% confidence intervals (95% CIs) from logistic regression analyses. TLR4 rs10759932, C/C homozygous genotype was associated with an increased risk of premalignant/malignant (OR=2.48, 95% CI=1.96-4.62, p=0.015). The recessive model of TLR4 rs10759932 showed a decreased risk of H. pylori susceptibility (adjusted OR=0.52, 95% CI=0.38-0.82, p=0.046). Meanwhile, the recessive model was associated with an increased risk of non-malignant (OR=3.46, 95% CI=2.25-5.67, p=0.001). In subjects with H. pylori infection, the recessive model was associated with an increased risk of non-malignant (OR=2.28, 95% CI=1.24-3.57, p=0.001) and premalignant/malignant (OR=1.83, 95% CI=1.16-2.84, p=0.027). TLR4 rs10759932, but not TLR2 rs3804099 and rs3804100, was associated with risk of premalignant and/or malignant and H. pylori susceptibility. H. pylori infection seems to contribute to chronic gastritis, and premalignant/malignant supported the development of the premalignant/malignant lesions involved in H. pylori infection that is critical to gastric cancer in Thai patients.

Highly selective CB2 receptor agonist A836339 has gastroprotective effect on experimentally induced gastric ulcers in mice.

Cannabinoid type 2 (CB2) receptors are distributed in central and peripheral tissues, including immunocytes and the gastrointestinal (GI) tract, suggesting that CB2 receptor agonists represent potential therapeutics in GI inflammatory states. In this study, we investigated the effect of highly selective CB2 agonist, A836339, on the development of gastric lesions. We used two models of gastric ulcer (GU) induced by ethanol (EtOH) and diclofenac. To confirm the involvement of CB2 receptors, a selective CB2 antagonist, AM630 was used. Clinical parameters for gastroprotection were assessed based on inhibition of the gastric lesion area. To investigate the anti-inflammatory effect of A836339, the expression of TNF-α and IL-1β was assessed. To establish the mechanism of gastroprotective action, catalase (CAT), superoxide dismutase (SOD) activity and H2O2 and glutathione (GSH) levels were measured. Moreover, expression of CB2 and cyclooxygenase-2 (COX-2) was characterized using immunohistochemistry (IHC). A836339 reduced ulcer index in a dose-dependent manner in both EtOH- and diclofenac-induced GU models. This effect was reversed by the CB2 antagonist AM630. Administration of A836339 reduced TNF-α and IL-1β levels in gastric tissue. Furthermore, A836339 exhibited potent anti-oxidant activity, as demonstrated by reduced H2O2 levels and increased CAT and SOD activities. IHC studies revealed a co-localization of CB2 receptors and COX-2 in the gastric tissue. Activation of CB2 receptors exhibited gastroprotective effect through enhancement of anti-oxidative pathways in the stomach. Activation of CB2 receptors may thus become a novel therapeutic approach in the treatment of GU.

RELATIONSHIP BETWEEN ESOPHAGITIS GRADES AND HELICOBACTER PYLORI.

ABSTRACTBackground: The Helicobacter pylori infection (HP) is related to the development of gastric lesions and lymphoma; however, it is not known if there is a relation with gastroesophageal reflux disease and reflux esophagitis. Aim: To evaluate HP's relationship with esophagitis in patients undergoing upper endoscopy. Methods: Observational, retrospective and cross-sectional study, being evaluated 9576 patients undergoing outpatient endoscopic examination during the period between January and December 2015. Were included patients with any esophageal alteration at the examination; greater than 18; of both genders; independent of the complaint or the reason for the examination, illness or drug use. Were excluded those with active bleeding during the examination and in use of anticoagulants. The variables gender, age, esophagitis and result of the urease test, were studied. For statistical analysis was used the Epi Info software 7.1.5.2. Results: Most of the samples consisted of women and the overall average age was 46.54±16.32 years. The presence of infection was balanced for gender: 1204 (12.56%) women and 952 (13.92%) men. Relating degree of esophagitis HP- and HP+ was observed that the type A was the most common (58.79%, n=1460); 604 (24.32%) had grade B; 334 (13.45%) grade C, and 85 (3.42%) grade D. In the relation between the grade of esophagitis with gender, esophagitis A was predominant in women and present in 929 (63.33%), followed by type B, 282 (46.68%), 136 C (40.71%) and D 30 (35.29%). In men 531 (36.36%) showed type A, 322 (53.31%) B, 198 (59.28%) C, and 55 (64.70%) D. Among the groups 40-50 and over 60 years there was a significant difference in whether have or not have HP+. Conclusion: There is no significant difference between HP infection and the different grades of esophagitis.

Effect of Areca Nut on Helicobacter pylori-Induced Gastric Diseases in Mice.

Areca nut (AN) chewing is a habit in many countries in Central, Southern, and Southeast Asia. It is strongly associated with the occurrence of oral, pharyngeal, and esophageal cancer as well as systemic inflammation. However, the association between AN intake and the development of gastric lesions has not yet been identified. The aim of this study was to investigate the effect of AN on gastric diseases using a mouse model for Helicobacter pylori infection. We studied four groups of mice: those fed a normal diet (ND), those fed a diet containing 2.5% AN (AD), those fed ND and infected with H. pylori PMSS1 strain (ND/HP), and those fed AD and infected with H. pylori PMSS1 strain (AD/HP). Food intake and body weight were monitored weekly during the experiments. At 10 weeks, the mice were sacrificed, and the stomach weight, H. pylori colonization, and gastric inflammation were evaluated. The stomach weight had increased significantly in the ND/HP and AD/HP groups along with increases in H. pylori colonization; however, there was no significant difference between these two groups with respect to stomach weight and colonization. On histological grading, mononuclear cell infiltration was severer in the AD/HP group than in the ND/HP group. These data suggest that chronic gastric inflammation was aggravated by AN treatment in the mice with H. pylori-induced gastric lesions. Furthermore, as previously suggested, this animal model is useful to determine the effect of potential carcinogens on gastric lesions induced by H. pylori infection.

Effects of pelleting diets without or with distillers' dried grains with solubles on growth performance, carcass characteristics, and gastrointestinal weights of growing-finishing barrows and gilts.

Pigs (192 total) were blocked by age and stratified by initial BW (25.75 ± 2.29 kg) into pens (2 barrows and 2 gilts per pen). Within blocks, pens were randomly allotted to treatments in a 2 × 2 factorial arrangement, with 2 diet forms (meal vs. pellet) and 2 distillers' dried grains with solubles (DDGS) inclusion levels (0 vs. 30%). Pigs were weighed at the beginning of the experiment and at the end of each feeding phase (d 35, 70, and 91) and daily feed allotments were recorded. Pigs were slaughtered at the end of the 91-d experiment, and full gastrointestinal (GI) tract and GI tract component weights were recorded immediately following evisceration. Carcass characteristics and meat quality were determined after a 24-h chill. Overall ADG was increased ( < 0.01) 3.2% when pigs were fed pelleted diets rather than meal diets, but there was no effect ( = 0.46) of DDGS inclusion on overall ADG. Overall ADFI of meal-fed pigs fed 30% DDGS was 4.7% greater ( < 0.01) than that of pigs fed 0% DDGS in meal form, but overall ADFI did not differ ( ≥ 0.19) between DDGS inclusion level in pellet-fed pigs (diet form × DDGS inclusion, < 0.01). When fed meal diets, pigs fed 0% DDGS had 2.7% greater ( = 0.02) overall G:F than pigs fed 30% DDGS; however, there was no difference ( = 0.42) in overall G:F between DDGS inclusion levels in pigs fed pelleted diets (diet form × DDGS inclusion, < 0.03). Pigs fed pelleted diets had 2.9% heavier HCW ( = 0.01), 10.4% greater 10th-rib back fat ( = 0.01), and 1.8 percentage units less estimated lean percentage ( = 0.04) than meal-fed pigs. Full GI tracts of pigs fed pelleted diets were 0.33 percentage units less ( = 0.03) of the ending live weight than that of meal-fed pigs due to decreased ( < 0.01) GI tract contents. Inclusion of DDGS increased ( = 0.03) full GI tract weight, large intestine weight ( < 0.01), and GI tract contents ( = 0.02). Severity of parakeratosis of the pars esophagea was greater ( < 0.01) in pellet-fed pigs than in meal-fed pigs, but the magnitude of the difference was likely not great enough to negatively affect drop credit of stomachs. In conclusion, feeding pelleted diets improved growth performance and increased carcass weight and fatness without causing the development of gastric lesions that would reduce the value of the stomach to packers. Furthermore, inclusion of DDGS in diets reduced HCW and dressing percent and increased GI tract and GI tract contents weight but had no effect on gastric lesion development or LM quality.

Occurrence of gastric ulcers in horses exercised on a treadmill

ABSTRACT: The most frequently causes of gastric ulcers in horses are fasting, feeding type and management, as well as administration of certain medications. More recently, exercise has also been identified as an important factor in the development of gastric lesions in athlete horses. The purpose of the present study was to assess whether treadmill exercise predisposes the horses to the occurrence of gastric ulcers. Five Arabian horses underwent a twelve-week training period on a treadmill and a gastroscopic evaluation before and after the training period. All animals showed gastric lesions after the training period. Based on these results, it is concluded that Arabian horses undergoing exercise on a treadmill may develop gastric lesions varying in number and severity.

급성 위염 유발 마우스 동물 모델에서 구기자(枸杞子) 에탄올 추출물의 위점막 손상 보호 효과

Objectives : Gastric lesions affect many people around the world and their development are results of the imbalance between destructive and protective factors in the gastric mucosa. Lycium chinense has been widely used as a traditional Korean medicine, it was recently reported that they have potent anti-inflammatory effects in chronic hepatitis models. Therefore, this study aimed to investigate the anti-inflammatory activity of Lycium chinense extract (LCE) on HCl-Ethanol induced gastric lesion mice. Methods : The ICR mice were divided randomly into five groups of six ani mals each. Group A was normal mice, and group B was treated orally with 0.5 ml 150 mM HCl-60% Ethanol. Mice in group C and D were pre-treatment of LCE (100 mg/kg and 200 mg/kg bodyweight, p.o before HCl/ethanol treatment) and group E was orally administered sucralfate (10 mg/kg). Results : 150mM HCl/60% ethanol-induced gastric mucosal injury mice were ameliorated mucosal damage upon histological evaluation by treatment of LCE. Pre-treatment of LCE attenuated reactive oxidative species (ROS) and produces peroxynitrite (ONOO - ) in stomach tissues. As results of stomach protein analyses, LCE effectively reduce inflammatory-related factors such as cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α ), inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) in gastric lesion mice. In addition, nuclear factor kappa B (NF-κ B) and inhibitor of phosphorylation of nuclear factor kappa B (p-Iκ B) were down-regulated in LCE-administrated gastric lesion mice. Conclusions : Our discovery supports that the therapeutic activity of LCE am eliorate the development of gastric lesion via suppressing the oxidative stress and gastric partial inflammation induced by 150 mM HCl/60% ethanol.

Protective Effects of a Lycium chinense Ethanol Extract through Anti-oxidative Stress on Acute gastric lesion mice

Objectives : Gastric lesions affect many people around the world and their development are results of the imbalance between destructive and protective factors in the gastric mucosa. Lycium chinense has been widely used as a traditional Korean medicine, it was recently reported that they have potent anti-inflammatory effects in chronic hepatitis models. Therefore, this study aimed to investigate the anti-inflammatory activity of Lycium chinense extract (LCE) on HCl-Ethanol induced gastric lesion mice. Methods : The ICR mice were divided randomly into five groups of six ani mals each. Group A was normal mice, and group B was treated orally with 0.5 ml 150 mM HCl-60% Ethanol. Mice in group C and D were pre-treatment of LCE (100 mg/kg and 200 mg/kg bodyweight, p.o before HCl/ethanol treatment) and group E was orally administered sucralfate (10 mg/kg). Results : 150mM HCl/60% ethanol-induced gastric mucosal injury mice were ameliorated mucosal damage upon histological evaluation by treatment of LCE. Pre-treatment of LCE attenuated reactive oxidative species (ROS) and produces peroxynitrite (ONOO - ) in stomach tissues. As results of stomach protein analyses, LCE effectively reduce inflammatory-related factors such as cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α ), inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) in gastric lesion mice. In addition, nuclear factor kappa B (NF-κ B) and inhibitor of phosphorylation of nuclear factor kappa B (p-Iκ B) were down-regulated in LCE-administrated gastric lesion mice. Conclusions : Our discovery supports that the therapeutic activity of LCE am eliorate the development of gastric lesion via suppressing the oxidative stress and gastric partial inflammation induced by 150 mM HCl/60% ethanol.

Effects of conventional and hydrogen sulfide-releasing non-steroidal anti-inflammatory drugs in rats with stress-induced and epinephrine-induced gastric damage

Mechanisms of gastric defence under conditions of combined influence of acute stress and non-steroidal anti-inflammatory drugs (NSAIDs) are still poorly studied. The aim of this study was to explore the effects of different types of NSAIDs (naproxen, celecoxib and ATB-346) in producing experimental gastric lesions (induced by water-restraint stress (WRS) or by epinephrine (EPN) injection) and to determine the role of lipid peroxidation and the nitric oxide (NO) system in the pathogenesis of the damage. Male rats were used (eight per group) in this work. The NSAIDs were all administered at a dose 10 mg kg−1 30 min prior to WRS or EPN injection. Administration of naproxen to the control rats caused development of gastric lesions, whereas administration of a hydrogen sulfide (H2S)-releasing NSAID (ATB-346) or a selective cyclooxygenase-2 inhibitor (celecoxib) did not cause gastric damage. In contrast, lipid peroxidation processes were enhanced in all groups as was the activity of NO synthase (NOS). Pretreatment with naproxen in the WRS model caused an increase in severity of damage and a decrease in NOS activity. ATB-346 displayed beneficial effects, manifested by a decrease in the area of gastric damage, but parameters of lipid peroxidation and the NOS system did not differ substantially from those in the group treated with naproxen. Administration of different NSAIDs under conditions of EPN-induced gastric damage resulted in the decrease in NOS activity and lipid peroxidation. None of the tested NSAIDs exacerbated EPN-induced gastric mucosal injury; indeed, they all reduced the extent of damage.

Influence of Exercise in the Occurrence of Gastric Ulcers in Horses

IntroductionThe most frequently reported causes of gastric ulcers in horses are fasting, type of feed and management, and the administration of some drugs. More recently, physical exercise has also been pointed out as an important factor in the development of gastric lesions in athletic horses. The aim of this study was to evaluate whether treadmill exercise predisposes to the occurrence of gastric ulcers in horses.MethodsFive Arabian horses were exercised on a high‐speed treadmill during twelve weeks. The animals were submitted to gastroscopy before the beginning and the end of the training period. The lesions were classified according to the method proposed by Macallister [1] that assigns scores for number and severity of injuries, with modifications to give a total score for the stomach, considering not only the presence and severity of ulcers, but also other findings as gastritis, hyperkeratosis, desquamation of the mucosa. The results obtained in the two periods were compared using the Wilcoxon test, with significance at P&lt;0.05.ResultsIn the first gastroscopy two animals had very low scores for lesion number and severity and three horses had no injury. In contrast, in the second evaluation, all animals had higher scores. A significant difference was observed between the two periods (before and after training) considering both methods of gastric lesion classification.ConclusionsWe concluded that Arabian horses exercised on a treadmill may develop gastric lesions. The possible influence of these lesions on athletic performance and other parameters should be considered by researchers who study equine exercise physiology.Ethical Animal ResearchThis study was approved by the Ethics Committee on Animal Use (protocol number 1741). Sources of funding: FAPESP 2012/10886‐3. Competing interests: none.

Etodolac, a racemic nonsteroidal anti‐inflammatory drug, exhibits low gastrointestinal toxicity: relation to the effects of the enantiomers (840.13)

Etodolac, a racemic (LR) nonsteroidal anti‐inflammatory drug (NSAID), has higher gastric safety compared to other conventional NSAIDs. However, it remains unknown whether the LR etodolac shows less adverse action in the small intestine. In the present study, we examined the effect of etodolac, both L/R and the enantiomers (S and R) on the gastric and small intestinal mucosa. Methods: Male SD rats were used. Etodolac (5‐50 mg/kg), both LR, S and R, was given p.o. in 18 h‐fasted or non‐fasted rats, and the stomach or the small intestine was examined for lesions 4 or 24 h later, respectively. Results: LR‐etodolac and S‐etodolac dose‐dependently caused lesions in both the stomach and small intestine, yet the effect of the former was much less potent compared to the latter. R‐etodolac did not cause damage even at 50 mg/kg. On the other hand, pretreatment with R‐etodolac dose‐dependently prevented the development of gastric lesions induced by indomethacin. The mucosal PGE2 content in the stomach and small intestine was significantly decreased by both LR‐etodolac and S‐etodolac, but not R‐etodolac. Conclusion: These results suggest that LR‐etodolac has less ulcerogenic properties in the gastrointestinal mucosa and showed that this safety profile of LR‐etodolac may be explained by the mucosal protective action of R‐etodolac.