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Silver nanoparticles (Ag NPs) have unique properties and display an important role in bioactivities such as antimicrobial, antiviral, antifungal, and anticancer. Stable Ag NPs were prepared by reaction of silver nitrate solution with extract of Melissa and characterized by UV-Vis spectroscopy, AFM, SEM, XRD, and Zeta potential. The resulted Ag NPs have a size range between 20 and 35 nm. The current study aims to evaluate the gastroprotective effect of Ag NPs against ethanol-induced gastric ulcers in rats. Thirty rats were randomly divided into five groups. The experimental groups were fed 175 and 350 ppm/p.o of Ag NPs orally. Ag NPs improved the adversative influence of ethanol-induced stomach damage as confirmed by declining ulcer index and raised the percentage of ulcer prevention. Significantly reduced ethanol-induced gastric lesions were evidenced by increased mucus secretion and pH of stomach content, decreased ulcer area, nonappearance of edema, and leucocyte penetration of the subcutaneous layer. In gastric homogenate, Ag NPs displayed a substantial upsurge in superoxide dismutase (SOD), catalase (CAT) activities, and significantly reduced malondialdehyde (MDA) levels., Ag NPs increased the intensity of periodic acid Schiff stained (PAS) and produced over-regulation of HSP-70 and down-regulation of Bax proteins. Ag NPs confirmed gastro-protection which might be attributed to its antioxidant effect, increased mucus secretion, increased SOD, and CAT, reduced MDA level, over-regulation of HSP-70 protein, and down-regulation of Bax protein.

This study investigated the association between antacid administration and lung cancer incidence in a real-world setting. This was a nationwide, retrospective cohort study. The cohort comprised random samples (n = 1,031,392) from the entire South Korean population in 2002. The duration of antacid administration between January 2006 and December 2010 was recorded for each participant. Newly developed lung cancers were counted during the 5-year observation period (January 1, 2006 to December 31, 2010). A total of 437,370 participants aged ≥ 40 years were included, of whom 301,201 (68.9%) had antacid exposure before the diagnosis of lung cancer. A total of 1230 (0.28%) antacid-exposed patients developed lung cancer. Among patients with no antacid exposure or underexposure (n = 136,171), 597 (0.44%) developed lung cancer. In the multivariable analysis, antacid exposure before the diagnosis of lung cancer was independently associated with a reduced incidence of lung cancer (hazard ratio: 0.64; 95% confidence interval: 0.55-0.74; P .001). Antacid use might be independently associated with a decreased risk of lung cancer development in this cohort study.

OBJECTIVES Helicobacter pylori (H. pylori) is the primary cause of gastric cancer and eradication in healthy adults has proven effective in decreasing cancer incidence. H. pylori is acquired largely in early childhood, however, the benefits of eradication in children are controversial. We aimed to determine the effect of H. pylori eradication on clinical and laboratory markers associated with gastric damage in apparently healthy school-aged children. METHODS This was a pilot non-blinded trial including 61 children persistently infected with H. pylori who were randomized to eradication/no treatment and followed for at least 12 months, evaluating clinical and blood markers (Pepsinogen I (PGI) and II (PGII) determined by ELISA) associated with gastric damage. The treatment consisted of a sequential scheme including 7 days of omeprazole + amoxicillin followed by 7 days of omeprazole + clarithromycin + metronidazole; adherence and tolerance were surveyed. Eradication rates were assessed by stool antigen detection or urea breath test 1 month following treatment every 4 months thereafter to detect reinfection. RESULTS Eradication occurred in 30/31 treated children (median age: 8.8, range: 7.9-10.8) and in 0/30 non-treated controls (median age: 8.6, range: 7.9-11) (p

This study reports the synthesis of novel neolignans-celecoxib hybrids and the evaluation of their biological activity. Analogs 8-13 (L13-L18) exhibited anti-inflammatory activity, inhibited glycoprotein expression (P-selectin) related to platelet activation, and were considered non- ulcerogenic in the animal model, even with the administration of 10 times higher than the dose used in reference therapy. In silico drug-likeness showed that the analogs are compliant with Lipinski’s rule of five. A molecular docking study showed that the hybrids 8-13 (L13-L18) fitted similarly with celecoxib in the COX-2 active site. According to this data, it is possible to infer that extra hydrophobic interactions and the hydrogen interactions with the triazole core may improve the selectivity towards the COX-2 active site. Furthermore, the molecular docking study with P-selectin showed the binding affinity of the analogs in the active site, performing important interactions with amino acid residues such as Tyr 48. Whereas the P-selectin is a promising target to the design of new anti-inflammatory drugs with antithrombotic properties, a distinct butterfly-like structure of 1,4-diaryl-1,2,3-triazole neolignan-celecoxib hybrids synthesized in this work may be a safer alternative to the traditional COX-2 inhibitors.

Stomach ulcer is one of the most common gastrointestinal problems in the world.This study aimed to isolate flavonoid compounds from methanol extract of the aerial parts ofChromatographic techniques were used for the identification of the isolated compounds. To explore the effects of the plant extract, it was administrated by oral gavage for one week either before or post-ethanol ulcer induction. Ranitidine was also evaluated as a reference drug. Stomach pH, gastric juice volume, lesions number, glutathione, superoxide dismutase, malondialdehyde, succinate dehydrogenase, lactate dehydrogenase, acid phosphatase, Interleukin-10, intracellular adhesion molecule-1, prostaglandin E2, and total protein levels were estimated in gastric tissue. Stomach histopathological features were also monitored.Six flavonoid compounds were isolated, where five of them were isolated for the first time (vitexin, isovitexin, apigenin 7,4'-dimethyl ether, 5,7,2'-trimethoxyflavone, and scutellarein), while apigenin was previously reported. Treatment with plant extract recorded amelioration in all the biochemical parameters.The methanol extract of plant aerial parts had prophylactic and treatment effects against gastric ulcer in rats, where its treatment effect exceeded its protective role. The extract recorded anti-inflammatory, and antioxidant effects due to the presence of flavonoid compounds.

Qing-Chang-Hua-Shi (QCHS) is a Chinese herbal formula, which is composed of 11 herbs. Studies have also shown that QCHS granules can alleviate colitis in animal models by preventing inflammatory responses and suppressing apoptosis through the MEK/ERK signaling pathway. To determine the efficacy and safety of QCHS granules in patients with moderately active UC. We performed a multicenter, randomized, placebo-controlled, double-blind study of patients with moderately active UC who did not respond to 4 weeks of mesalazine therapy at the maximum dose. Patients were randomly assigned to groups and administered QCHS granules (125 g/day, n = 59) or an identical placebo, which was similar to the QCHS granules in color and taste (125 g/day, n = 60), with continued 5-ASA 4 g/d therapy for 12 weeks. The primary outcome was the rate of clinical response and clinical remission at week 12. The secondary outcomes were health-related quality of life, endoscopic response rate, and mucosal healing rate. Any changes in mucus/bloody stool and diarrhea were recorded. Out of the 119 enrolled patients at 10 different centers in China, 102 patients completed the trial. Clinical remission and clinical response were seen in 31.48% and 92.59% of QCHS-treated patients, and 12.50% and 72.92% of placebo-treated patients, respectively. There was a significant difference between the two treatment groups. More patients receiving QCHS granules vs. placebo achieved remission of mucus/bloody stool (70.37% vs. 47.92%, P = 0.0361). Adverse event rates were similar (QCHS granules 38.33%; placebo 25.42%). In conclusion, QCHS granules were superior to the placebo in introducing clinical remission and mucosal healing, as well as in relieving mucus/blood stool in patients with moderately active and 5-ASA-refractory UC.

This study aimed to investigate the antioxidant and protective effect of E. persicus leaf hydroalcoholic extract (EPE) in preventing gastric ulcers induced by ethanol in rats. Wistar rats weighing 180-220 g were randomly divided into five groups. These groups included negative control (normal) group, positive control (ethanolic) group, comparative control (ranitidine recipient) group, group recipient the dose of 250 mg/kg plant extract, and group recipient the dose of 500 mg/kg plant extract. One hour after gavage of the drug and extract, the gastric ulcer was induced by feeding 1 ml of 96% ethanol to each animal except the rats of the negative control group. After one hour, the rats were killed, and their stomachs were separated. Then, the gastric Ulcer index (UI), pH, oxidative stress parameters, and histopathological changes in the stomach of all groups were measured. Pre-treatment of ethanol-induced rats with the EPE reduced (P 0.05) the ulcer index and gastric juice pH, compared to ethanolic group rats. Furthermore, pre-treatment with EPE at a dose-dependent manner, alleviated the gastric oxidative stress injury in rats through increase the activity of CAT, tissue NO

Black rice is a type of rice in the Oryza sativa L. species. There are numerous reports regarding the pharmacological actions of black rice bran, but scientific evidence on its gastroprotection is limited. This study aimed to evaluate the gastroprotective activities of black rice bran ethanol extract (BRB) from the Thai black rice variety Hom Nil (O. sativa L. indica) as well as its mechanisms of action, acute oral toxicity in rats, and phytochemical screening. Rat models of gastric ulcers induced by acidified ethanol, indomethacin, and restraint water immersion stress were used. After pretreatment with 200, 400, and 800 mg/kg of BRB in test groups, BRB at 800 mg/kg significantly inhibited the formation of gastric ulcers in all gastric ulcer models, and this inhibition seemed to be dose dependent in an indomethacin-induced gastric ulcer model. BRB could not normalize the amount of gastric wall mucus, reduce gastric volume and total acidity, or increase gastric pH. Although BRB could not increase NO levels in gastric tissue, the tissue MDA levels could be normalized with DPPH radical scavenging activity. These results confirm the gastroprotective activities of BRB with a possible mechanism of action via antioxidant activity. The major phytochemical components of BRB comprise carotenoid derivatives with the presence of phenolic compounds. These components may be responsible for the gastroprotective activities of BRB. The 2000 mg/kg dose of oral BRB showed no acute toxicity in rats and confirmed, in part, the safe uses of BRB.

The purpose of this study is to investigate incidence of gastrointestinal symptoms and complications in patients who underwent high-power short-duration (HPSD), posterior left atrial wall isolation during atrial fibrillation ablation and thereafter have received gastrointestinal prophylactic regimen consisting of sucralfate, proton-pump inhibitor and colchicine. Patients were followed and assessed at baseline, up until 6th month following the procedures.Among 115 patients who were included, 5 patients (4.3%) reported gastrointestinal symptoms at follow-up. No complications were diagnosed during the follow-up. In conclusion, the HPSD along with prophylactic regimen has been associated with low incidence of gastrointestinal adverse events.

Ethnomedicinal studies in the Amazon community and in the Northeast region of Brazil highlight the use of Libidibia ferrea fruits for the treatment of gastric problems. However, there are no data in the literature of this pharmacological activity. Thus, the aim of this paper is to provide a scientific basis for the use of the dry extract of L. ferrea pods (DELfp) for the treatment of peptic ulcers. Phytochemical characterization was performed by HPLC/MS. In vitro antioxidant activity was assessed using DPPH, ABTS, phosphomolybdenum, and superoxide radical scavenging activity. The gastroprotective activity, the ability to stimulate mucus production, the antisecretory activity, and the influence of -SH and NO compounds on the antiulcerogenic activity of DELfp were evaluated. The healing activity was determined by the acetic acid-induced chronic ulcer model. Anti-Helicobacter pylori activity was investigated. HPLC/MS results identified the presence of phenolic compounds, gallic acid and ellagic acid, in DELfp. The extract showed antioxidant activity in vitro. In ulcers induced by absolute ethanol and acidified ethanol, the ED50 values of DELfp were 113 and 185.7 mg/kg, respectively. DELfp (100, 200, and 400 mg/kg) inhibited indomethacin-induced lesions by 66.7, 69.6, and 65.8%, respectively. DELfp (200 mg/kg) reduced gastric secretion and H+ concentration in the gastric contents and showed to be independent of nitric oxide (NO) and dependent on sulfhydryl (-SH) compounds in the protection of the gastric mucosa. In the chronic ulcer model, DELfp reduced the area of the gastric lesion. DELfp also showed anti-H. pylori activity. In conclusion, DELfp showed antioxidant, gastroprotective, healing, and antiulcerogenic activities. The mechanism of these actions seems to be mediated by different pathways and involves the reduction of gastric secretion and H+ concentration, dependence on sulfhydryl compounds, and anti-H. pylori activity. All these actions support the medicinal use of this species in the management of peptic ulcers.

Objective This study was conducted to evaluate the difference in acid inhibition function among lansoprazole (LPZ), pantoprazole (PPZ), and their respective stereoisomers following single and multiple intravenous doses in healthy Chinese subjects. Materials and methods The dosage groups were set as follows: 30 mg single and multiple intravenous administrations of LPZ or R-LPZ, 40 mg single and multiple intravenous administrations of PPZ or S-PPZ. Subjects received an intravenous infusion of LPZ, R-LPZ, PPZ, or S-PPZ injection in sterile saline solution (100 mL/h, 60 minutes), respectively. The intragastric pH was sampled every second for 24 hours at baseline and for 24 hours after drug administration. The baseline-adjusted pharmacodynamic (PD) parameters include ΔMean (pH), ΔMedian (pH), ΔTpH≥3 (%), ΔTpH≥4 (%), ΔTpH≥6 (%), and ΔAUECph-tτ1-τ2. The PD parameters were evaluated in different time intervals (0 - 24 hours, 0 - 4 hours and 14 - 24 hours). Results After a single dose, the ΔTpH≥4 (%) of R-LPZ, LPZ, S-PPZ and PPZ was 56.6 ± 19.6, 53.1 ± 23.3, 35.6 ± 24.9 and 26.8 ± 30.2, respectively. The ΔTpH≥6 (%) was 50.7 ± 26.1, 41.4 ± 26.2, 25.4 ± 24.9 and 22.1 ± 27.6, respectively. The ΔAUECph-τ1-τ was 45,564 ± 16,107, 41,798 ± 16,153, 31,914 ± 17,304 and 20,744 ± 21,500, respectively. Statistically significant differences were found with R-LPZ vs. S-PPZ, R-LPZ vs. PPZ, LPZ vs. S-PPZ and LPZ vs. PPZ. The average TpH≥4 of R-LPZ, LPZ, S-PPZ, and PPZ was (47.2 ± 26.1) minutes, (49.6 ± 19.3) minutes, (56.1 ± 23.7) minutes, and (72.1 ± 27.3) minutes, respectively. Statistically significant differences were found with R-LPZ vs. PPZ (p = 0.009) and LPZ vs. PPZ (p = 0.019). After multiple doses, the ΔTpH≥4 (%) of R-LPZ, LPZ, S-PPZ, and PPZ was 71.7 ± 20.2, 63.5 ± 19.4, 59.5 ± 17.8 and 64.0 ± 22.4, respectively. The ΔTpH≥6 (%) was 64.0 ± 22.2, 52.0 ± 19.2, 49.6 ± 20.4 and 50.9 ± 23.8, respectively. The ΔAUECph-τ1-τ was 326,149 ± 94,839, 288,565 ± 93,279, 296,189 ± 83,412 and 300,960 ± 108,057, respectively. No statistically significant differences were found in baseline-adjusted PD parameters during all time periods after multiple doses. Conclusion After a single dose, the mean gastric pH inhibition value of R-LPZ was the highest, followed by LPZ, then S-PPZ and PPZ. R-LPZ and LPZ provided significantly better pH control compared with PPZ and S-PPZ in healthy subjects. The onset time of R-LPZ was the fastest and R-LPZ can provide better acid inhibition during sleeping time. After multiple doses, the mean values in all PD parameters of R-LPZ were the highest, the values of LPZ, S-PPZ, and PPZ were similar. However, no significant difference was found in acid inhibition among these four drugs after multiple doses.

Background Teprenone (geranylgeranylacetone), an anti-ulcer agent, has been reported to inhibit amyloid-β increase, senile plaque formation, and neuronal degeneration, and improve memory in mouse models of Alzheimer's disease (AD). Objective We conducted a randomized, double-blind, placebo-controlled study to ascertain teprenone's therapeutic ability for AD. Methods Patients with mild to moderate AD, with a Mini-Mental State Examination (MMSE) score of 13 to 26, were randomly allocated into two groups depending on the administered drug: donepezil + placebo (placebo group) and donepezil + teprenone (teprenone group). The primary and secondary endpoints included changes in scores of the Japanese version of the AD Assessment Scale-cognitive subscale (ADAS-J cog) and other evaluations, respectively, including MMSE scores, during a 12-month period after the first administration. Results Forty-two and thirty-seven patients were allocated to the teprenone and placebo groups, respectively. ADAS-J cog score changes were not different between groups (placebo, 0.6±0.8; teprenone, 0.4±0.8; p = 0.861). However, MMSE scores significantly improved in the teprenone group (placebo, - 1.2±0.5; teprenone, 0.2±0.5; p = 0.044). Subgroup analysis considering the severity of medial temporal area atrophy revealed that this improvement by teprenone was significant in patients with mild (p = 0.013) but not with severe atrophy (p = 0.611). Adverse events were observed in 17.8 and 10.4% of patients in the placebo and teprenone group, respectively. Conclusion Teprenone may be effective for AD when administered before atrophy progression in the medial temporal areas. Trial registration UMIN ID: UMIN000016843.

Stress ulcer prophylaxis is commonly prescribed in the intensive care unit but can be inappropriately commenced or continued on discharge, exposing patients to potential harm. We aimed to evaluate whether a prescribing guideline, education program and pharmacist oversight would reduce inappropriate continuation of stress ulcer prophylaxis. This was a multicentre pre- (2014) and post- (2016) quality improvement study across five Australian intensive care units. Cost data were estimated using local information about prescribing patterns, and the relationship between long-term use and adverse events. A total of 531 patients were included in the pre- and 393 in the post-implementation periods. The proportion of hospital survivors inappropriately continued on stress ulcer prophylaxis reduced from 78/184 (42.4%) to 11/143 (7.7%) in the post-implementation period (odds ratio = 8.83; 95% confidence interval 4.47–17.45; P

The main goal of this study was to explore the dose-effect relationship of ilaprazole.Ilaprazole is a kind of benzimidazole proton-pump inhibitor, which was confirmed efficacious and safe in treatment of duodenal ulcer (DU). However, the dose-effect relationship of ilaprazole was not clear.This was a double-blind, parallel, randomized study. Patients aged above 18 years with at least one endoscopically confirmed active nonmalignant DU were treated with rabeprazole 10 mg or ilaprazole 10 mg/5 mg for 4 weeks. Healing of ulcer was determined by its resolution from active to scarring stage. Symptoms relief was evaluated using a graded score. Safety and tolerability were evaluated on basis of clinical assessments.A total of 390 patients completed the study finally. Ulcers were successfully healed in 75.38%, 77.86%, and 83.72% of patients after 4-week treatment with rabeprazole 10 mg, ilaprazole 5 mg, and ilaprazole 10 mg, respectively. The 4-week healing rate difference between rabeprazole 10 mg and ilaprazole 5 mg was 2.48% (95% confidence interval: -7.79% to 12.74%) leading to accept the noninferiority hypothesis. Logistic regression model suggested that ilaprazole 10 mg was superior to ilaprazole 5 mg at week 2 (odds ratio, 1.92; 95% confidence interval: 1.02, 3.59; P=0.04). Most patients (80%) became asymptomatic after treatment. At the dosages administered, the 3 drug groups exhibited similar efficacy and a similar safety profile.Ilaprazole 5 mg is not inferior to rabeprazole 10 mg in treating DU, and a dose-effect relationship have been revealed between 5 mg and 10 mg of ilaprazole.

Nowadays, heterocyclic compounds act as a scaffold and are the backbone of medicinal chemistry. Among all of the heterocyclic scaffolds, 1,4-Dihydropyridine (1,4-DHP) is one of the most important heterocyclic rings that possess prominent therapeutic effects in a very versatile manner and plays an important role in synthetic, medicinal, and bioorganic chemistry. The main aim of the study is to review and encompass relevant studies related to 1,4-DHP and excellent therapeutic benefits of its derivatives. An extensive review of Pubmed-Medline, Embase and Lancet’s published articles was done to find all relevant studies on the activity of 1,4-DHP and its derivatives. 1,4-DHP is a potent Voltage-Gated Calcium Channel (VGCC) antagonist derivative which acts as an anti-hypertensive, anti- anginal, anti-tumor, anti-inflammatory, anti-tubercular, anti-cancer, anti-hyperplasia, anti-mutagenic, anti-dyslipidemic, and anti-ulcer agent. From the inferences of the study, it can be concluded that the basic nucleus, 1,4-DHP which is a voltage-gated calcium ion channel blocker, acts as a base for its derivatives that possess different important therapeutic effects. There is a need of further research of this basic nucleus as it is a multifunctional moiety, on which addition of different groups can yield a better drug for its other activities such as anti-convulsant, anti-oxidant, anti-mutagenic, and anti-microbial. This review would be significant for further researches in the development of several kinds of drugs by representing successful matrix for the medicinal agents.

Bioactivity-guided investigation of the methanol extract of Crepis sancta aerial parts, collected off Al-Tafilah, South Jordan, was applied, and in this study, the extract was explored for its phytochemical components and in vivo antiulcer activity. In addition, a docking study involving the purified compounds with the newly crystalized gastric proton pump (PDB # 5YLU) was performed. In-depth phytochemical investigation using the state-of-the-art chromatographic and analytical techniques was implemented resulting in the identification of two eudesmane-type sesquiterpenoids, 3-oxo-γ-costic acid (1) and its methyl ester (2) together with seven different methoxylated flavonols (3-9) as the extract's major components. The in vivo antiulcer study at three different doses (50, 100, and 200 mg/kg) against ethanol-induced gastric ulcer in male albino rats, compared to omeprazole (20 mg/kg) as a standard proton pump inhibitor antiulcer drug, revealed that the tested extract, at the middle and the highest doses, featured comparable or even superior activities relative to omeprazole as deduced from histopathological examination, in particular with regard to reducing inflammatory cell infiltration and ceasing mucosal haemorrhage. The tested extract revealed also a dose-dependent reduction in the volume and titrable acidity of the gastric juice together with a dose-dependent increase in the protective gastric mucin content which may explain the noticeable gastroprotective effect. Molecular modelling study of the isolated compounds showed a binding mode similar to the co-crystallized substrate vonoprazan in 5YLU which strengthens the importance of the tested extract as a potential natural remedy for treating gastric ulcer.

Background/Aims Irsogladine maleate, an enhancer of gastric mucosal protective factors, has demonstrated its efficacy for various gastric mucosal injuries. The aim of this study was to evaluate the efficacy and safety of irsogladine for prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin-induced peptic ulcer and gastritis. Methods In this multicenter, randomized, double-blind, exploratory clinical trial, 100 patients over 50 years of age who needed continuous NSAIDs or aspirin for more than 8 weeks were randomly assigned to either test group (irsogladine maleate 2 mg, twice daily, 39 patients for full analysis) or placebo group (37 patients for full analysis). Primary outcomes were incidence of peptic ulcer and ratio of modified Lanza score (MLS) 2 to 4. Secondary outcome was the number of acute erosions confirmed by endoscopy at 8 weeks. Adverse effects were also compared. Results There were no significant differences in gastric protective effects between test and placebo groups. However, two cases of peptic ulcer in the placebo group but none in the test group were observed. These two cases of peptic ulcer were Helicobacter pylori-negative. In addition, H. pylori-negative group showed significant changes in MLS score (p = 0.0247) and edema score (p = 0.0154) after the treatment compared to those before treatment in the test group. There was no significant difference in adverse events between the two groups. Conclusions The efficacy of irsogladine maleate was found in H. pylori-negative group, suggesting its potential as a protective agent against NSAIDs or aspirin-induced peptic ulcer and gastritis.

This study aimed to investigate the intestinal microbiota in duodenal ulcer (DU) patients, effects of proton pump inhibitors,clarithromycin and amoxicillin, PCA) for Helicobacter pylori (H. pylori) and Bacillus subtilis and Enterococcus faecium (BSEF) on intestinal microbiota. DU patients were randomly assigned to receive either PCA (group TT) or PCA plus BSEF(group TP). The fecal microbiome was conducted using high throughput 16S rDNA gene and internal transcribed spacer sequencings. The diversity and abundance of intestinal bacteria in the DU were significantly lower than health check control (HC) group. In the TT group, the abundance and diversity of both intestinal bacteria and fungi decreased after PCA treatment, compared with those before treatment, whereas in the TP group no obvious changes were observed. In the TT group at all the time points, both the intestinal bacteria and fungi were different from those in the HC group. However, in the TP group, at 10w the bacterial flora abundance was close to that in the HC group. The results indicate that anti- H. pylori treatment induced significant decrease in the diversity of intestinal microbiota, while the combined therapy supplemented with BSEF could protect and restore the intestinal microbiota.

Background Gastric 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. Methods The 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. Results The 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. Conclusions Our 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. Electronic supplementary material The online version of this article (10.1186/s12906-019-2623-4) contains supplementary material, which is available to authorized users.

Clinical signs of syringomyelia and hydrocephalus occur secondary to cerebrospinal fluid (CSF) accumulation within the central nervous system. Omeprazole is recommended to treat these conditions despite little evidence of its capacity to decrease CSF production in the dog. Studies into new treatments are hampered by difficulties in measuring CSF production. The albumin quotient (QAlb), the ratio between CSF and serum albumin concentrations, may reflect CSF production and any decrease in CSF production should be associated with an increase in QAlb. The primary objective of this study was to determine CSF omeprazole concentration after administration of a high intravenous dose of omeprazole and to evaluate its impact on QAlb in the dog. The second aim was to validate QAlb as a surrogate marker of CSF production. Eighteen dogs were included in this prospective crossover placebo-controlled study. Each dog received omeprazole (10 mg/kg), acetazolamide (50 mg/kg) combined with furosemide (1 mg/kg) and saline. Blood and CSF samples were obtained on day 0 and then every 7 days, one hour after drug administration. Omeprazole concentrations (2.0 ± 0.4 μmol/L) reached in CSF after high dose omeprazole were lower than the concentrations previously described as decreasing CSF production in dogs. There was no significant increase in QAlb following administration of acetazolamide/furosemide, prohibiting validation of QAlb as a surrogate marker for CSF production. Several dogs presented transient mild side effects after injection of acetazolamide/furosemide. High dose omeprazole was well tolerated in all dogs.

Background Stress ulcer is a severe complication in critically ill patients and causes a high mortality. The proton pump inhibitor esomeprazole is widely applied in the treatment of stress ulcers because of its powerful acid suppression ability. However, the mechanism of stress ulcer and the precise gastroprotective effect of esomeprazole in stress ulcer remain unclear. Purpose In the present study, the rats with water-immersed and restraint (WIR)-induced stress ulcer were used to further elucidate the anti-ulcerogenic capacity of esomeprazole in stress ulcer in addition to its anti-acid secreting ability. Methods and results The rats were randomly divided into 5 groups: control group (NS), water-immersed and restraint group (WIR), high-dose application of esomeprazole plus stress ulcer-induced group (HE+WIR), low-dose application of esomeprazole plus stress ulcer-induced group (LE+WIR), and high-dose application of esomeprazole without stress ulcer-induced group (HE). Our study showed that the pretreatment of esomeprazole alleviated gastric tissue damage in both macroscopic and histopathological manifestations. Pretreatment of esomeprazole elevated the decline in PEG2 level affected by WIR; and it inhibited the secretion of gastric acid, gastrin and pepsin. Moreover, esomeprazole exerted its antioxidant effects by reducing malondialdehyde levels, enhancing the expressions of antioxidant factors like glutathione and superoxide dismutase (SOD) and reducing the compensatory transcriptional elevation of SOD1 gene. Esomeprazole also reduced the levels of MPO (myeloperoxidase), tumor necrosis factor (TNF)-α and interleukin (IL)-1β according to its anti-inflammatory effects. We further explored the possible mechanism of esomeprazole pretreatment on stress ulcer and demonstrated that esomeprazole attenuated the high phosphorylation levels of nuclear factor kappa B (NF-κB) p65 and p38 MAPK, and decreased the NF-κB p65 nuclear translocation induced by WIR related stress ulcer. Conclusion Our study provides some evidence that the esomeprazole pretreatment exerts gastroprotective effects in WIR-induced stress ulcer through not only its antisecretory effect but also its antioxidant effect by inactivating the p38 MAPK and NF-κB signaling pathways.

Despite the availability of effective antiulcer medications, their suboptimal safety profile ignites the search for alternative/complementary treatments. Drug repositioning is an attractive, efficient, and low-risk strategy. Cilostazol, a clinically used phosphodiesterase 3 inhibitor, has pronounced anti-inflammatory and vasodilatory effects suggesting antiulcer activity. Using ethanol-induced and pyloric ligation–induced gastric ulcer models, we investigated the gastroprotective effect of cilostazol (5 or 10 mg/kg, p.o.) in comparison with the standard antiulcer ranitidine (50 mg/kg, p.o.) in rats. Gastric mucosa was examined macroscopically, histologically, and biochemically for ulcer severity, markers of oxidative stress, proinflammatory cytokines, apoptotic, and cytoprotective mediators. Gastric acidic output, peptic activity, and mucin content were measured in gastric fluids. Pretreatment with cilostazol reduced ulcer number and severity, ameliorated redox status (reduced glutathione and malonaldehyde content), and decreased levels of IL-1β, IL-6, and TNF-훼 in gastric mucosa, in parallel with increases in mucosal defensive factors nitric oxide (NO), prostaglandin E2 (PGE2), and heat-shock protein 70 (HSP70) promoting mucus secretion, tissue perfusion, and regeneration. Histological examination confirmed the beneficial effects of cilostazol in terms of reducing focal necrosis and infiltration of inflammatory cells, as well as increasing mucopolysaccharide content. These beneficial effects are likely secondary to an increase in cAMP and decrease in apoptosis regulator Bcl-2-associated X protein (BAX). Cilostazol, in a dose-dependent effect, exhibited vasodilatory, anti-inflammatory, and antiapoptotic actions in the gastric mucosa resulting in significant antiulcer activity comparable with the standard drug, ranitidine, but devoid of antisecretory activity. Therefore, its use should be dose and ulcer-inducer dependent.

Background Famotidine is sometimes administered as a continuous rate infusion (CRI) to treat gastrointestinal ulceration in critically ill dogs. However, clinical studies have not evaluated the efficacy of a famotidine CRI in dogs. Hypothesis/Objectives To evaluate the efficacy of famotidine at raising intragastric pH when it is administered as a CRI in dogs. We hypothesized that CRI treatment with famotidine would meet clinical goals for raising intragastric pH ≥3 and 4. Animals Nine healthy Beagle dogs. Methods Randomized 2‐way crossover. All dogs received 1.0 mg/kg IV q12h famotidine or CRI famotidine at 1.0 mg/kg IV loading dose and 8.0 mg/kg/d for 3 consecutive days. Beginning on day 0 of treatment, intragastric pH monitoring was used to continuously record intragastric pH. Mean percentage times (MPTs) for which intragastric pH was ≥3 and ≥4 were compared between groups using analysis of variance. Results There was a statistically significant difference (P

BACKGROUND The Simplified Mortality Score for the Intensive Care Unit (SMS-ICU) is a clinical prediction model, which estimates the risk of 90-day mortality in acutely ill adult ICU patients using 7 readily available variables. We aimed to externally validate the SMS-ICU and compare its discrimination with existing prediction models used with 90-day mortality as the outcome. METHODS We externally validated the SMS-ICU using data from 3282 patients included in the Stress Ulcer Prophylaxis in the Intensive Care Unit trial, which randomised acutely ill adult ICU patients with risk factors for gastrointestinal bleeding to prophylactic pantoprazole or placebo in 33 ICUs in Europe. We assessed discrimination, calibration and overall performance of the SMS-ICU and compared discrimination with the commonly used and more complex SAPS II and SOFA scores. RESULTS Mortality at day 90 was 30.7%. The discrimination (area under the receiver operating characteristic curve) for the SMS-ICU was 0.67 (95% CI: 0.65-0.69), as compared with 0.68 (95% CI: 0.66-0.70, P = 0.35) for SAPS II and 0.63 (95% CI: 0.61-0.65, P < 0.001) for the SOFA score. Calibration (intercept and slope) was 0.001 and 0.786, respectively, and Nagelkerke's R2 (overall performance) was 0.06. The proportions of missing data for the SMS-ICU, SAPS II and SOFA scores were 0.2%, 8.5% and 6.8%, respectively. CONCLUSIONS Discrimination for 90-day mortality of the SMS-ICU in this cohort was poor, but similar to SAPS II and better than that of the SOFA score with markedly less missing data.

A 40-year-old man suffered from short bowel syndrome. Since a large amount of intestinal output and watery diarrhea hampered his quality of life, we tried to control the intestinal output by reducing the secretion of gastric acid with lansoprazole. Because the small intestine was only 10 cm in length and effective absorption of oral lansoprazole was doubtful, we monitored his intragastric pH for 24 hours and confirmed that the holding time above pH 3.0 was 14.5 hours (60.4%). He spent his home life eating porridge during the day, and receiving total parenteral nutrition of 1,100 mL/day at night while taking lansoprazole as an oral tablet (30 mg) once a day.

The cytoprotective action of the synthetic resveratrol (Resv) congener, E-3,3′,5,5′-tetrahydroxystilbene (designated as HST-1) against indomethacin (IND)-induced stomach ulceration has been...

Introduction Acid suppression therapy can reduce the development of stress and medication-related mucosal disease when prescribed appropriately. Suboptimal inpatient prescribing of acid suppression therapy therefore may lead to increased development of gastrointestinal hemorrhage in high-risk populations. The aim of this quality improvement study was to improve appropriate acid suppression therapy in patients admitted to ICUs in an academic medical center. Intervention Development, Implementation, and Adaptation An adaptable, multifaceted implementation strategy guided by unit-based root cause analysis was initially developed in a single ICU with a high-risk population. Identifiable targets of intervention, including provider awareness, unstructured rounding protocols, and electronic communication tools, were augmented by the development of an automated alert system. This electronic dashboard risk-stratified patients based on information derived from the electronic medical record (EMR). The dashboard then offered clinical decision support. Use of the dashboard and percentage of appropriate acid suppression therapy prescriptions were tracked over time. Results Appropriate acid suppression therapy prescribing was improved from 72.9% to 86.0% (p Conclusion Automated technology including an EMR-supported electronic dashboard was the foundation of successful intervention. Considering the deleterious effects of both under- and overprescribing of acid suppression therapy, particularly in high-risk patient populations, this type of technology may lead to enhanced patient outcomes.

Made available in DSpace on 2019-10-06T17:03:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-05-10 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Ethnopharmacological relevance: Eugenia punicifolia (Kunth) DC. (Myrtaceae), an Amazonian medicinal plant known as “pedra-ume-caá,” is popularly used as a natural remedy for inflammation, wounds, infections, diabetes, fever, and flu. Its anti-inflammatory, antinociceptive, and gastroprotective effects have already been characterized. We evaluated the gastric healing effect of the hydroalcoholic extract of the leaves of E. punicifolia (HEEP) in male and female Wistar rats against nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol. Materials and methods: The healing effect of HEEP on the gastric mucosa of adult male and female Wistar rats was measured after the chronic application of aggressive factors such as NSAIDs or 80% ethanol. Male, and intact and ovariectomized (OVZ) female rats were treated with HEEP for two days (NSAIDs) or one, two, four, and six days (80% ethanol). The stomachs were analyzed macroscopically for ulcerative lesions (mm 2 ), and the healing process was measured using biochemical analysis with anti-inflammatory and antioxidant parameters. Results: Macroscopic evaluation of the gastric mucosa showed that gastric lesions induced by NSAIDs were significantly healed (66%) and pro-inflammatory interleukin 5 cytokine level was decreased after two-day oral treatment with HEEP compared with those in the negative control group (p < 0.05). However, the gastric lesions induced by NSAIDs did not heal in HEEP-treated female rats (p > 0.05). In addition, four-day treatment with HEEP significantly healed the gastric lesions induced by ethanol in male and female rats (63% and 78%, respectively) compared to those of the negative control group (p < 0.05). However, the OVZ group required six days of HEEP treatment to heal gastric ulcers (67% compared to the control group). HEEP exerts the healing effect against ethanol by significantly reducing neutrophil infiltration into the gastric mucosa by decreasing myeloperoxidase activity in male and OVZ rats after four and six days of treatment, respectively (p < 0.05). Four-day treatment with HEEP also increased the level of a non-enzymatic antioxidant, reduced glutathione in intact females compared to that of the negative control group (p < 0.05). Conclusion: These findings indicated that HEEP was effective in promoting the healing of gastric ulcers induced by NSAIDs or ethanol. The gastric healing effects of this extract could be affected by female sex hormone interference; in future, comprehensive studies should be performed by considering sex differences. Department of Physiology Biosciences Institute UNESP−São Paulo State University Biosciences Institute UNESP−São Paulo State University Department of Biological Science Faculty of Sciences and Languages UNESP−São Paulo State University Department of Physiology Biosciences Institute UNESP−São Paulo State University Biosciences Institute UNESP−São Paulo State University Department of Biological Science Faculty of Sciences and Languages UNESP−São Paulo State University CNPq: 305570/2012-9 CNPq: 306209/2016-0 CAPES: 88882.183585/2018-01 CAPES: 88882.183586/2018-01

The design and synthesis of novel pyrazole based derivatives has been carried out using the ligand based approach like pharmacophore and QSAR modelling of reported pyrazoles from the available literature to investigate the chemical features that are essential for the design of selective and potent COX-2 inhibitors. Both pharmacophore and QSAR models with good statistical parameters were selected for the design of the lead molecule. Also by exploiting the chemical structures of selective and marketed COX-2 inhibitors, celecoxib and SC-558 were used in designing the molecules which are used in the treatment of inflammation and related disorders. The therapeutic action of the Non-Steroidal Anti-inflammatory Agents (NSAIDs) is based primarily on the COX-2 inhibition. With this background we have synthesized some azomethine derivatives of 3-methyl-1-substituted-4-phenyl-6-[{(1E)-phenylmethylene}amino]-1,4-dihydro pyrano[2,3-c]pyrazole-5-carbonitrile 6(a-o) and were characterized by 1HNMR, 13CNMR and Mass spectral techniques. All the synthesized pyrazole derivatives were tested for in vitro membrane stability property in both COX-1 & COX-2 inhibition studies and in vivo anti-inflammatory activity by carrageenan induced rat paw edema model. Among them, compound 6k showed very good activity by in vivo anti-inflammatory activity with 0.8575 mmol/kg as ED50. Similarly compounds 6m, 6o, 6i and 6h exhibited comparable anti-inflammatory activity to standard drugs. Also the active compounds were further screened for ulcerogenic activity and were found be safer with less ulcer index compared to the marketed drugs like aspirin, ibuprofen and celecoxib.

New strategies recently proposed to mitigate injury caused by lithium coin cell batteries lodged in the esophagus include prehospital administration of honey to coat the battery and prevent local hydroxide generation and in-hospital administration of sucralfate suspension (or honey). This study was undertaken to define the safe interval for administering coating agents by identifying the timing of onset of esophageal perforations.A retrospective study of 290 fatal or severe battery ingestions with esophageal lodgment was undertaken to identify cases with esophageal perforations.Esophageal perforations were identified in 189 cases (53 fatal, 136 severe; 95.2% in children ≤4 years). Implicated batteries were predominantly lithium (91.0%) and 92.0% were ≥20 mm diameter. Only 2% of perforations occurred in24 h following ingestion, including 3 severe cases with perforations evident at 11-17 h, 12 h, and 18 h. Another 7.4% of perforations (11 cases) became evident 24 to 47 h post ingestion and 10.1% of perforations (15 cases) became evident 48 to 71 h post ingestion. By 3 days post ingestion, 26.8% of perforations were evident, 36.9% by 4 days, 46.3% by 5 days, and 66.4% by 9 days.Esophageal perforation is unlikely in the 12 h after battery ingestion, therefore the administration of honey or sucralfate carries a low risk of extravasation from the esophagus. This first 12 h includes the period of peak electrolysis activity and battery damage, thus the risk of honey or sucralfate is low while the benefit is likely high.

Acetylsalicylic acid (ASA) is the most highly consumed pharmaceutical product worldwide. Importantly, gastrointestinal ulceration due to ASA is a major complication. Hence, the present work aimed to examine, for the first time, the healing properties of bee venom (BV) in acute gastric ulceration induced by ASA. Forty adult male Sprague-Dawley rats were divided into four groups that received distilled water only, ASA (500 mg/kg BW) twice daily for 3 days, ASA for 3 days followed by BV (2 mg/kg BW) for 7 days, or ASA for 3 days followed by ranitidine hydrochloride (50 mg/kg BW) for 7 days. Haematological analysis, haemostatic evaluation, and inflammatory marker estimation were performed. Rat stomachs were collected for ulcer scoring, gene expression analysis, oxidative stress assays, histopathological and immunohistochemical examinations, and tissue eosinophil scoring. The results revealed that BV markedly decreased the ulcer index, pro-inflammatory cytokine levels, malondialdehyde levels, BAX distribution, caspase-3 expression, and tissue eosinophil levels. Additionally, significant increases in antioxidant enzymes and heat shock protein 70 localization in gastric tissue were evident following BV treatment after ASA exposure. Also, BV has been found to attenuate the haematological, haemostatic, and histopathological alterations induced by ASA. Our findings collectively indicate that the gastroprotective effect of BV against ASA-induced ulceration in rats is mediated by its antioxidant, anti-inflammatory, anti-apoptotic, and anti-secretory properties.

Cochlospermum regium (Bixaceae) is a native shrub of Brazil and its xylopodium (infusion/decoction) is being used for the treatment of gastritis, ulcers, arthritis, intestinal infections, gynaecological infections, skin diseases, among others. The aim of the present study was to evaluate the gastroprotective/antiulcer activity and the mechanism of action of hydroethanolic extract of C. regium xylopodium (HECr), using in vitro and in vivo models. Additionally, phytochemical constituents were identified by high-performance liquid chromatography (HPLC).C. regium xylopodium was macerated with ethanol/water to obtain the HECr. The phytochemical characterisation was carried out by HPLC. The antiulcer efficacy of HECr (25, 100 and 400 mg/kg, p.o.) was evaluated using acute acidified ethanol (HCl/EtOH), piroxicam and water immersion-induced experimental ulcer models. Chronic gastric ulcer healing activity of HECr was evaluated through acetic acid (99.8%) - induced model. Histological analysis and myeloperoxidase (MPO), glutathione (GSH), catalase (CAT) activities were also evaluated in chronic ulcer induced gastric tissues. The plausible mode of action of the HECr was assessed by estimation of gastric wall mucus production and the role of gastric secretion in pylorus ligature. The animals were also pre-treated with various inhibitors which includes indomethacin (10 mg/kg, p.o.) a selective inhibitor of cyclooxygenase, L-NAME (10 mg/kg, i.p.), an inhibitor of nitric oxide synthase, glibenclamide, a ATP-sensitive potassium channels (KThe HPLC analysis data revealed the presence of gallic acid, rutin, myricetin, morin and kaempferol. HECr promoted protective effect against acute ulcers induced by HCl/EtOH with inhibitions of 47.52% (p 0.01) and 62.69% (p 0.001) at 100 and 400 mg/kg, and in piroxicam by 34.11% (p 0.05), 49.14% (p 0.01) and 61.34% (p 0.001), at 25, 100 or 400 mg/kg, respectively, and in water restraint stress by 78.26% inhibition, p 0.001, at the dose of 400 mg/kg when compared to the vehicle control group respectively. In the chronic gastric ulcer model, HECr (25, 100 and 400 mg/kg p.o.) significantly (p 0.001) decreased the injured area by 58.80%, 77.87% and 71.10% respectively. Histological examination indicated that oral treatment of HECr promoted healing of gastric lesions by regenerating gastric mucosa layer with less inflammatory cells. HECr augmented the GSH, CAT activities and reduced MPO level. The pre-treatment with HECr increased the gastric wall mucus production. It also significantly altered the gastric secretion parameters by causing the reduction in the gastric juice volume, elevated the pH level and reduced the total acidity at all doses tested when compared with the vehicle group. HECr at the most active dose (100 mg/kg) reversed completely the reduction of PGs, NO production, closure of KThe HECr presented preventive and curative effects in the experimental gastric ulcer models, besides good anti-Helicobacter pylori activity, which supports the traditional medicinal use of the xylopodium of this plant for gastrointestinal diseases. The underlying mechanisms of this antiulcerogenic/antiulcer action involve, at least, augmentation of mucus production, inhibition of gastric secretion, stimulation of PGs and NO synthesis. And that it involves activation of K

BACKGROUND Previous studies have demonstrated a poor response to healing of gastric glandular lesions with oral omeprazole and other medications. OBJECTIVES To evaluate the efficacy of two novel treatments (misoprostol [M] and combined omeprazole-sucralfate [OS]) in horses for gastric glandular disease. STUDY DESIGN Prospective, clinical study. METHODS Sixty-three sports horses with grade >1/4 glandular disease were identified by gastroscopy. Horses received either 5 μg/kg of misoprostol per os BID 1 h prior to feeding or a combination of 4 mg/kg enteric coated omeprazole per os SID and 12 mg/kg sucralfate per os BID where drugs were given 1 h prior to feeding and sucralfate given 60 min after omeprazole; allocation was dependent upon centre. Gastroscopy was repeated at 28-35 days. Evaluators of the gastroscopy images were blinded to the treatments the horses received and images were reviewed independently. RESULTS The most common presenting sign in both treatment groups was poor performance (Overall - 65.1%; M - 60.5% and OS - 75%). Overall healing (P

Made available in DSpace on 2019-10-06T16:06:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-03-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Ethnopharmacological relevance: Virola elongata is a tree species belonging to the Myristicaceae family, distributed in the North and Midwest regions of Brazil, in the phytogeographic domain of the Amazon. The aqueous infusion or the hydroethanolic macerate of the stem bark of V. elongata are used in Brazilian and Ecuadorian indigenous folk medicine for several ethnopharmacological purposes, principally, in the treatment of stomach pain, indigestions, and gastric ulcers. This study was aimed to investigate the gastroprotective activity of this plant in order to support its popular use with scientific evidence. Materials and methods: The stem bark hydroethanolic extract of the plant (HEVe) was prepared by maceration. Its qualitative and quantitative phytochemical constituents were investigated by classical colorimetric techniques, HPLC, and electrospray ionization-multiple stage fragmentation (ESI-MSn). The gastroprotective and antiulcer activity of HEVe at doses of 100, 300 and 900 mg/kg p.o. were tested using three acute (acidified ethanol, piroxicam, and in-water-restrain stress), and one chronic (acetic acid) animal ulcer models. The probable mode of action of the HEVe was evaluated by analyzing gastric acid secretion, mucus content, nitric oxide effect, and its antioxidant properties (on catalase, myeloperoxidase, and GSH content) in experimental rodents. The direct extract's activity on the growth of Helicobacter pylori was also investigated. Results: Total phenolic content in the HEVe was of 146.20 ± 1.07 mg, being flavonoids about 50% (71.79 ± 0.70 mg) of it. Comparative HPLC fingerprint analysis revealed the presence of known phenolic antiulcer compounds, such as gallic acid, catechin, and rutin. Also, methanol/water fractionation and ESI-MSn analysis of the HEVe reveals the presence of quinic acid, 3,3′,4-trihydroxystilbene, juruenolid D, one catechin dimer, one C-glycosyl flavonoid, one polyketide and two neolignans as the major components of the extract. The HEVe attenuated gastric ulceration in all the different models of acute gastric ulcer, by enhancing gastroprotection through its antioxidant properties in vivo, and reducing also considerably the gastric secretion and total acidity. The HEVe also presented healing properties against the induced chronic ulceration process. On the other hand, the HEVe did not exhibit direct activity against H. pylori. Conclusion: The HEVe exhibited significant gastroprotective/antiulcer effects and contain a relative high proportion of phenolic compounds, especially flavonoids, that could likely account, at least in part, for its pharmacological properties. The results justify its traditional usage and provided scientific evidence for its potential as a new herbal medicine to treat gastric ulcers. Área de Farmacologia Departamento de Ciências Básicas em Saúde Universidade Federal de Mato Grosso (UFMT), Av. Fernando Correa da Costa, no. 2367 Curso de Farmácia Faculdade Noroeste do Mato Grosso Associação Juinense de Ensino Superior (AJES) Laboratório de Pesquisa de Produtos Naturais Faculdade de Medicina Universidade Federal de Tocantins (UFT) Laboratório de Bioprospecção de Produtos Naturais. Instituto de Biociências Universidade Estadual Paulista (UNESP) - Campus do Litoral Paulista Departamento de Química Orgânica Instituto de Química Universidade Estadual Paulista (UNESP) - Campus Araraquara Laboratório de Bioprospecção de Produtos Naturais. Instituto de Biociências Universidade Estadual Paulista (UNESP) - Campus do Litoral Paulista Departamento de Química Orgânica Instituto de Química Universidade Estadual Paulista (UNESP) - Campus Araraquara CNPq: 132286/015-7 CAPES: 23038.000731/2013-56

Background Clausena excavata Burm.f. (Rutaceae) has been used for the treatment of stomach disorders including peptic ulcer. Purpose In this study, we aimed to investigate dentatin isolated from C. excavata Burm.f., for anti-ulcer activity against ethanol ulcer model in rats. Methods Gastric acid output, ulcer index, serum profile, histological evaluation using Hematoxylin and eosin (HE), periodic acid Schiff base stainings and immunohistochemical localization for heat shock proteins 70 (HSP70) were all investigated. Possible involvement of reduced glutathione (GSH), lipid peroxidation, prostaglandin E2 (PGE2), superoxide dismutase (SOD) enzymes, radical scavenging, and anti-Helicobacter pylori activity were investigated. Results Dentatin showed anti-secretory activity against the pylorus ligature model and protected the gastric mucosa from ethanol ulceration, as revealed by the improved macroscopic and histological appearance. Dentatin significantly increased the gastric homogenate content of PGE2 GSH and SOD. Dentatin inhibited the lipid peroxidation as revealed by the reduced gastric content of malondialdehyde (MDA). Moreover, dentatin up-regulated HSP70 expression. However, dentatin showed insignificant anti-H. pylori activity. Conclusion Dentatin possesses gastro-protective activity, which could be attributed to the anti-secretory, mucus production, anti-oxidant, and HSP70 activities.

Oxyresveratrol, an active ingredient of Artocarpus lakoocha, is known to possess anti-inflammatory and immunomodulatory properties. Current study investigates the immunomodulatory effect of oxyresveratrol in mouse model of ethanol-induced ulcer. Anti-ulcer effect was determined using histopathological evaluation (H&E staining) and different tests like, gastric ulcer scoring, ulcer index, total acid secretion, and gastric pH. The mRNA expression levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor-kappaB (NF-ĸB), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and trefoil factor 2 (TFF-2) were evaluated using reverse transcription polymerase chain reaction (RT-PCR). The data showed marked percentage inhibition of erosion, hemorrhage, fibrinoid necrosis, inflammatory infiltrate, and ulcer in low (30 mg/kg b.w.) and high dose (50 mg/kg b.w.) groups of oxyresveratrol. Treatment with oxyresveratrol inhibited ulcer score and ulcer index as compared with disease control group. Oxyresveratrol significantly increased gastric pH (P

Background Famotidine is commonly administered to cats. Prolonged famotidine administration results in decreased efficacy in humans, dogs, and cows, but the long-term effects in cats are unknown. Objectives To compare the effect of 2 oral administration frequencies of famotidine, twice daily (Group 1) and twice daily every second day (Group 2), on intragastric pH and serum gastrin concentrations in cats. We hypothesized a diminished effect on intragastric pH would be observed over time in Group 1 but not Group 2. Animals Sixteen healthy cats. Methods Randomized, 2-factor repeated measures crossover design. Cats received 0.5-1.24 mg/kg (median, 0.87 mg/kg) famotidine twice daily or twice daily every second day for 14 consecutive days. Intragastric pH monitoring was used to record intragastric pH on treatment days 1-3 and 11-13. Mean pH and mean percentage time (MPT) intragastric pH was ≥3 and 4 were compared between and within treatment groups by analysis of variance. Results Significant treatment group by time interactions were observed for mean intragastric pH, MPT intragastric pH ≥3 and 4 (P = .009, P = .02, P = .005, respectively). Interaction post hoc tests identified significant decreases in mean intragastric pH (P = .001), MPT ≥3 (P = .001), and MPT ≥4 (P = .001) on day 13 compared to day 1 in Group 1 but not in Group 2. Conclusions and clinical importance Oral famotidine administration results in a diminished effect on intragastric pH in healthy cats when given twice daily every day.

Objective Gastric endoscopic submucosal dissection (ESD) is currently a standard procedure, and proton pump inhibitors (PPIs) are most commonly used to treat post-ESD ulcers. Vonoprazan, a potassium-competitive acid blocker (P-CAB), reportedly inhibits gastric acid secretions more effectively than PPIs. Combination therapy of a PPI plus rebamipide is effective for treating larger ulcers. Our goal was to evaluate the effects of vonoprazan plus rebamipide compared to esomeprazole plus rebamipide for the treatment of post-ESD ulcers. Methods First, vonoprazan plus rebamipide (V group) or esomeprazole plus rebamipide (E group) was orally administered to subjects for eight weeks. We then evaluated the ulcer healing process at four and eight weeks after the procedure using a gastric ulcer stage system and by measuring the ulcer size. Patients A total of 84 patients who underwent ESD for gastric neoplasms between September 2015 and December 2017 in Tsuchiura Kyodo General Hospital were included in this randomized controlled trial. Results The ulcer scar rates at week 4 in the V group (n=43) and E groups (n=39) were 20.9% and 15.4%, while those at week 8 were 90.7% and 92.3%, respectively. The ulcer reduction rates at week 4 in the V and E groups were 94.6% and 93.8%, and those at week 8 were 99.7% and 99.3%, respectively. The ulcer scar rates and reduction rates were not significantly different between the two groups. Conclusion Combination therapy consisting of vonoprazan plus rebamipide was not superior to that of esomeprazole plus rebamipide for post-ESD ulcer healing (UMIN000019516).

objective In patients continuing antithrombotics, delayed bleeding after gastric endoscopic submucosal dissection (ESD) is a severe complication. Vonoprazan (VPZ) exerts a rapid, potent, and long-lasting antacid effect compared with traditional proton-pump inhibitors (PPIs). This study aimed to compare the incidence of delayed bleeding after gastric ESD between the use of VPZ and PPIs in patients continuing antithrombotics. Methods In this retrospective analysis, we examined 71 patients with 101 lesions treated with traditional PPIs (PPI group) and 59 patients with 90 lesions treated with VPZ (VPZ group). After 2 days (day 0 and 1) of intravenous PPI administration, either an oral PPI or VPZ was administered from postoperative day 2 to 8 weeks after ESD. We assessed the incidence of overall delayed bleeding as well as bleeding that occurred from day 2 until 8 weeks after ESD. Results There was no significant difference in the use of antithrombotic agents between the groups. Overall delayed bleeding occurred 13 times (18%) in 9 patients in the PPI group and 18 times (31%) in 17 patients in the VPZ group (p=0.10). Bleeding from day 2 until 8 weeks after ESD occurred 12 times (17%) in 9 patients in the PPI group and 8 times (14%) in 8 patients in the VPZ group. Conclusion Even with a potent antacid agent, such as VPZ, the incidence of delayed bleeding was high in patients undergoing ESD with continuous antithrombotic agents.

Background Acquired thrombophilia is a potential sequela of malignancy, chronic inflammation, and conditions characterized by severe protein deficiency (for example, nephrotic syndrome, protein-losing enteropathy). As such, venous thrombosis is often a feature, and occasionally a presenting sign, of systemic disease. Ménétrier’s disease is a rare hyperplastic gastropathy that may lead to gastrointestinal protein loss and hypoalbuminemia. To date, reports of venous thrombosis associated with Ménétrier’s disease are exceedingly scarce. Case presentation We report the case of a 40-year-old white man who presented with unprovoked deep venous thrombosis, pulmonary embolism, and renal vein thrombosis. Upon receiving therapeutic anticoagulation, he developed severe gastrointestinal bleeding, and endoscopic evaluation led to a diagnosis of Ménétrier’s disease. A laboratory workup revealed deficiency of protein C, protein S, and antithrombin III, as well as markedly elevated levels of factor VIII. He was determined to have an acquired thrombophilia as a direct result of Ménétrier’s disease. Conclusions This case describes an acquired thrombophilic state in a patient with Ménétrier’s disease and profound hypoalbuminemia. Although this association is rarely described, we discuss the probable mechanisms leading to our patient’s thrombosis. Specifically, we posit that his gastrointestinal protein loss led to a deficiency of several anticoagulant proteins and a compensatory elevation in factor VIII, as occurs in nephrotic syndrome and inflammatory bowel disease. Of note, this patient’s recurrent venous thrombosis was the initial clinical sign of his gastrointestinal pathology.

Context: HemoHIM is a medicinal herbal preparation of Angelica gigas Nakai (Apiaceae), Cnidium officinale Makino (Umbelliferae), and Paeonia japonica Miyabe (Paeoniaceae) developed for immune regulation. HemoHIM has been investigated for its ability to enhance tissue self-renewal and stimulate immune systems. To date, studies on the protective effects of HemoHIM against gastritis and gastric ulcers have not been conducted. Objective: The protective effects of HemoHIM using models of indomethacin and ethanol/hydrochloric acid (EtOH/HCl)-induced gastric mucosal injury were investigated. Materials and methods: Rats were divided into five groups (n = 10): control, indomethacin, or EtOH/HCl groups, HemoHIM 250, 500 mg kg−1, and cimetidine 100 mg kg−1, respectively. Indomethacin (80 mg kg−1) and 60% EtOH/150 mM HCl were administered orally 1 h after the administration of samples and rats were anesthetized 3 h after induction. The lesion area (%), inhibition ratio (%), and total acidity were investigated, and tissues were histopathologically analyzed using hematoxylin and-eosin (H&E) staining. Results: HemoHIM significantly reduced gastric injury in indomethacin-induced model (250 and 500 mg kg−1; 64.30% and 67.75%, p

The chaga medicinal mushroom (Inonotus obliquus) was traditionally used to treat various ailments. To establish the pharmacological properties of I. obliquus, studies were performed to show the antiulcer activity of the ethanolic extract. The ethanolic extract of I. obliquus was prepared. The antiulcer activity of I. obliquus was determined using gastric ulcerated rats (ulceration induced by ethanol). The ethanolic extract of I. obliquus (200 mg/kg) did not cause any sign of toxicity or sensitivity to rats when the extracts were administered by oral feed. Oral administration of ethanolic extract of I. obliquus exhibited antiulcer activity in all models used. The ethanolic extract of I. obliquus showed an effective antiulcer activity, which could be due to the presence of various biologically active compounds. This confirmed the traditional uses of I. obliquus in the treatment of ailments.

Aim: Prophylaxis against stress ulcer in mechanically ventilated patients is one of the causes for ventilator-associated pneumonia (VAP). Our aim was evaluating the effect of intravenous pantoprazole and ranitidine in the incidence of VAP in critically ill patients. Materials and Methods: Patients with at least 48 h of expected mechanical ventilation were allocated randomly to receive either 50 mg ranitidine (R) every 8 h or 40 mg pantoprazole (P) every 12 h intravenously from admission. VAP diagnosis was according to the Clinical Pneumonia Infection Score and positive culture. Results: Eighty-six patients during a 15-month period were analyzed; the study showed a low difference between VAP incidence in the ranitidine and pantoprazole groups. No significant difference was observed in terms of gastrointestinal bleeding, intensive care unit, hospital length of stay, and mortality between the groups. Conclusion: VAP incidence is hardly related to the type of stress ulcer prophylaxis agent with a high rate of VAP and low utilization of VAP prophylaxis bundle.

The dry root of Hedysarum polybotrys Hand.-Mazz., commonly known as "Hong Qi", has a variety of health benefits. The present study was undertaken to explore the anti-gastric ulcer potential effect of Hedysarum polysaccharides (HPS; HPS-50, HPS-80), the principal active fraction of Radix Hedysari (RH). The anti-gastric ulcer effects of HPS were evaluated using an animal model of ulcerative lesions induced by acetic acid. The effects of antioxidant factors, anti-inflammatory cytokines, and mucosal blood flow regulatory factor levels in the gastric tissue homogenate of rats were analyzed for the bioactivities of HPS. The results showed that, compared with the acetic acid-induced ulcerated group, the ulcer inhibition rate of HPS-treated rats was significantly increased. The pathological findings suggested that mucosal regeneration, cell migration, and inflammatory cell infiltration were decreased, and collagen fibers were significantly reduced. Extensive granulation tissue proliferation indicated the healing stage was initiated, suggesting a good prognosis. The oxidative stress status of the gastric ulcer rats was improved, the levels of TNF-α and IL-6 were significantly decreased, and the levels of PGE-2 and NO were increased (P < 0.05). HPS-80-H may be a promising ingredient for incorporation into functional foods or nutritional supplements for the prevention of gastric ulcers.

Aims Memantine is a commonly used drug in treating Alzheimer disease. In the current work, we aimed to evaluate the gastro-protective effect of memantine in indomethacin-induced peptic ulcer in rats. Main methods Peptic ulcer induced by indomethacin and memantine administered either alone or in combination with glibenclamide or nitric oxide synthase (NOS) inhibitor. Ulcer index done and malondialdehyde (MDA), superoxide dismutase (SOD), total nitrites, expression of tumor necrosis factor-α (TNF-α) and expression of nuclear factor kappa B (NF-κB) were measured in gastric mucosa. Key findings Memantine reduced ulcer index, reduced MDA, increased SOD, increased total nitrites and reduced expression of both TNF-α and NF-κB. Glibenclamide and not NOS inhibitor abolished the gastroprotective effect of memantine. Significance Memantine was protective against indomethacin-induced peptic ulcer in rats mostly by affecting potassium channels, antioxidative stress and anti-inflammatory actions.