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The study aimed to investigate the alleviation of an ethanol-induced gastric ulcer in mice by apolysaccharide (PSP) from purple sweet potato ( Ipomoea batatas (L.) Lam) and explore the mechanism. The anti-ulcer activity was determined by histopathological evaluation, total gastric acidity, pepsin activity, gastric ulcer index and gastric ulcer inhibition rate. The expression levels of inflammatory factors were detected using ELISA. A special protein meter was used to detect the content of immunoglobulin lgM, immunoglobulin lgG, and complements C3 and C4 in the serum of mice. The expression of CD4 + /CD8 + lymphocyte subsets of mice was detected using flow cytometry. Western blot analysis was used to examine the effect of PSP on the PI3K/Akt/Rheb/mTOR pathway. The results showed that PSP could effectively reduce the total gastric acidity, pepsin activity, and the index and inhibition rate of gastric ulcers. At the same time, PSP could significantly increase the levels of immunoglobulins (lgG and lgM) and complements (C3 and C4). It could also increase the activity of peritoneal macrophages in mice and the expression of CD4 + /CD8 + in the spleen. ELISA analysis showed that the contents of TNF-α, IL-1β and IL-6 were significantly decreased and the content of IL-10 was significantly increased in the PSP group. The western blot analysis showed that PSP could upregulate the relative protein expressions of MUC5AC, PI3K, p-Akt, Rheb and mTOR. These results indicate that PSP can activate the PI3K/Akt/Rheb/mTOR signaling pathway to improve the immunity of mice and maintain the balance of the immune system, thereby protecting the gastric mucosa and improving stress gastric ulcers.

Background: The progression to gastric cancer has been linked to chronic infection with Helicobacter pylori (H. pylori). Immune checkpoint inhibitors (programmed cell death -1, PD-1; programmed cell death -ligand 1, PD-L1) have a role in cancer immune escape. The relationship between H. pylori virulence factors with PD-1, PD-L1 T helper 1 (Th1), T helper 17 (Th17), and regulatory T cell (Treg) response genes, has not been thoroughly investigated in the development of gastric cancer. Therefore, we evaluated how H. pylori virulence factors influence the expression levels of immune-related genes in the development of gastric immunopathology., Methods: A total of 92 gastric tissues of normal controls and patients with gastritis, gastric ulcer, and gastric cancer were examined for the expression of immune-checkpoint inhibitor genes (PD-1 PD-L1), Th1 (interferon- γ, IFN-γ), Th17 (interleukin- 17, IL-17, Retinoic-acid-receptor- related orphan nuclear receptor gamma t, RORγ-t), and Treg (Forkhead box P3, FOXP3) response genes with quantitative real-time PCR (qRT-PCR). Furthermore, correlation of H. pylori virulence factors' (cytotoxin-associated gene A, cagA; vacuolating cytotoxin gene A, vacA (s1,s2,m1,m2); blood group antigen-binding adhesin gene A, babA, duodenal ulcer promoting gene A, dupA; the putative neuraminyllactose-binding hemagglutinin homolog, hpaA; neutrophil-activating protein A napA; outer inflammatory protein A, oipA; urease A, ureA; and urease B, ureB) genotypes with a degree of inflammation and density of H. pylori were investigated. Next, the relationship between H. pylori virulence factors and immune-checkpoint inhibitor genes, and T-cell response genes was evaluated. Eventually, a decision tree model was developed to determine the clinical outcome of patients using expression data., Results: The intensity of PD-1 and PD-L1 mRNA expression was increased significantly in gastric tissue of patients with gastric ulcer (PD-1: 2.3 fold, p=0.01; PD-L1: 2.1 fold, p=0.004), and gastric cancer (PD-1: 2 fold, p= 0.04; PD-L1: 1.8 fold, p=0.05) compared with control subjects. Also, PD-1: PD-L1 expression was significantly higher in patients with gastritis, who were infected with a marked density of H. pylori compared with its mildly infected counterparts. Furthermore, a novel negative correlation was found between PD-1 (r= -0.43) and PD-L1 (r= -0.42) with FOXP3 in patients with gastritis. CagA-positive H. pylori strain's negative association with PD-L1 expression (r=-0.34) was detected in patients with gastritis. Interestingly, PD-1 mRNA expression correlated positively with vacA s2/m2, in gastritis (r=0.43) and ulcer (r=0.43) patients. Furthermore, PD-1: PDL1 expression negatively correlated with vacA m1/m2 (r=-0.43 for PD-1; r=-0.38 for PD-L1) in gastritis patients. Moreover, an inverse correlation of PDL1 was present with vacA m1 (r=0.52) and vacA s1/m1 (r=0.46) versus vacA m2 (r=-0.44) and vacA m1 (r=0.52) and vacA s1/m2 (r=-0.14) in ulcer patients, respectively. Also, a correlation of vacA m2 (r=-0.47) and vacA s1/s2 (r= 0.45) with PD-1 was detected in ulcer patients. In addition, a novel negative correlation between FOXP3 mRNA levels and napA was shown in patients with gastritis and ulcer (r=-0.59). Finally, a computer-based model that was developed showed that knowing the expression levels of PD-L1, RORγ-t, and vacA s1/m2 would be useful to detect the clinical outcome of a patient., Conclusion: Our results suggested that PD-1:PD-L1 immune checkpoint inhibitors were increased in gastric pre-cancerous lesions that progress to gastric cancer. Herein, we report the relationship between H. pylori virulence factors and expression of host immune checkpoint inhibitors for diagnostic prediction of gastric malignancies using computer-based models., (Copyright © 2021. Published by Elsevier B.V.)

Peptic ulcer episodes cause damage to the stomach and intestine, with inflammatory cell infiltration and oxidative stress as the main players. In this study, we investigated the potential of anthocyanidin malvidin for preventive and curative peptic ulcer treatment. The anthocyanidin effects were examined in gastric ulcer mouse models induced by ethanol, non-steroidal anti-inflammatory drugs (NSAIDs), ischemia-reperfusion (IR), acetic acid and duodenal ulcer induced by polypharmacy. Expression levels of oxidative and inflammatory genes were measured to investigate the mechanism of anthocyanin activity. At a dose of 5 mg·kg -1 , Malvidin prevented gastric ulcer induction by ethanol, NSAID and repaired the tissue after 6 days of IR. Moreover, the anthocyanidin accelerated the healing of acetic acid-induced ulcer, increased the gene expression of EGF and COX-1, and downregulated MMP-9. Anthocyanin treatment mitigated the effect of polypharmacy on inflammation and oxidative stress observed in the intestine. Additionally, the compound downregulated cytokine expression and TLR4 and upregulated HMOX-1 and IL-10, exhibiting protective activity in the mouse gut. Malvidin thus prevented gastric and duodenal ulcers due to prominent anti-inflammatory and antioxidative effects on the gastrointestinal tract that were related to gene expression modulation and an increase in endogenous defense mechanisms.

The aim of this study was to investigate the immunomodulatory effect and mechanism of the glycopeptides from Paecilomyces sinensis (CPS-II) on ethanol induced ulcers in mice. In this study, histopathological evaluation (H&E staining) and the gastric ulcer score, ulcer index, total acid secretion and gastric pH value were used to determine the anti-ulcer activity. The expression levels of interleukin (IL)-6, interleukin (IL)-10 and tumor necrosis factor-α (TNF-α) were detected by ELISA. The contents of superoxide dismutase (SOD), malondialdehyde (MDA) and epidermal growth factor (PEG2) in serum were measured according to the instructions for the reagents. Western blotting was used to detect the effect of CPS-II on the MEK/ERK pathway. The results showed that CPS-II could inhibit the ulcer score and ulcer index compared with the disease control group. CPS-II could significantly increase gastric pH and decrease gastric acid secretion in mice. The ELISA analysis showed that the expression levels of IL-6 and TNF-α in the CPS-II treatment group were significantly decreased, while the expression levels of IL-10 were significantly increased in the CPS-II treatment group. In the resveratrol treatment group, the content of MDA in serum was decreased, and the level of PEG2 and the activity of SOD in serum were significantly increased, which indicated that CPS-II has immunoregulation and anti-ulcer properties. The CPS-II treatment group could reduce the expression level of miR-9-5p in gastric tissue. pEGFR had been identified as a potential target of miR-9-5p. Western blot analysis showed that CPS-II could up-regulate the relative protein expression of pEGFR/EGFR, pRaf/Raf, pMEK/MEK, pERK/ERK, and ZO-1. The results showed that CPS-II could reduce oxidative stress and inflammatory response by regulating the miR-9-5p-MEK/ERK signaling pathway, thus protecting the gastric mucosa and improving stress gastric ulcers.

Objective: To investigate the efficacy of the extract from Ononis spinosa L. (O. spinosa) on ethanol-induced gastric ulcer in rats., Methods: Phytochemical constituents of the extract from O. spinosa were analyzed using liquid chromatography-mass spectrometry. Rats were classified into 4 equal groups; ulcer control received oral vehicle; positive control was administered with 40 mg/kg esomeprazole (standard drug) and 2 groups received 0.5 and 1 g/kg of O. spinosa extract, respectively. Gastric ulcer was induced by absolute ethanol (5 mL/kg) orally to all groups. Measurement of ulcer index, cyclooxygenase-2 (COX-2) expression and determination of total glutathione level in gastric mucosa were performed., Results: Oral administration of the extract from O. spinosa at doses 0.5 and 1 g/kg lowered the ulcer indices by 80.39% and 98.71% , respectively, compared to 67.89% by esomeprazole (40 mg/kg). Histologically, treatment with the extract decreased necrosis and hemorrhage in mucosa and edema and infiltration by inflammatory cells in submucosa. Using immunohistochemical technique, it was demonstrated that COX-2 expression increased in mucosa of animals treated with the extract as well as by esomeprazole. O. spinosa and esomeprazole increased total glutathione level in the stomach compared to control. Ononin was the major compound of the extract followed by trifolirhizin, myricitrin, gentisic acid, cycloartenol and quercetin., Conclusion: The present study demonstrated that the extract from O. spinosa was able to protect gastric mucosa from ethanol injury by at least 2 mechanisms, namely the induction of COX-2 and decreasing oxidative stress in the stomach.

Rosmarinic acid (RA) is a secondary metabolite present in several plant species that has already demonstrated antioxidant, antiallergic, anticancer, antimicrobial, neuroprotective, and hepatoprotective effects experimentally. Due to the promising pharmacological properties found previously, this study aimed to assess the oral acute toxicity and the gastroprotective effect of RA using animal models. Acute toxicity was assessed according to OECD guide 423. Ethanol, stress, NSAIDs, and pylorus ligature-induced gastric ulcer models were used to investigate antiulcer properties. The related mechanisms of action were also evaluated from ethanol-induced gastric lesions protocol. RA (300 and 2000 mg/kg) showed no changes in behavioral, water and food intake, body and organs weight parameters with LD 50 set around 2500 mg/kg. RA presented gastroprotective activity in all assessed doses (25, 50, 100, and 200 mg/kg) using different animal models. Besides, it was observed that this effect is not related to the modulation of gastric juice parameters (pH, volume, and [H + ]), the participation of nitric oxide, mucus, and prostaglandins. However, increased sulfhydryl groups, GSH and IL-10 levels as well as reduced of proinflammatory cytokine (TNF-α and IL-1β) levels were found for RA-treated groups. RA presents low acute toxicity and gastroprotective activity, preventing ulcer formation via cytoprotective, antioxidant, and anti-inflammatory mechanisms. Graphical abstract.

As a multifactorial cause, gastric ulceration-mediated diarrhea is widely prevalent in the weaned piglets, impairing pig health and economic benefits. With full implementation of antibiotic stewardship programs in China, Bacillus cereus ( B. cereus ) and Aspergillus fumigatus ( A. fumigatus ) were identified frequently in porcine feedstuffs and feeds of the animal industry. Association between feed-borne B. cereus and frequent diarrhea remains unclear. In the present study, we conducted a survey of B. cereus and A. fumigatus from feeds and feedstuffs in pig farms during hot season. Interestingly, B. cereus , B. subtilis , B. licheniformis and B. thuringinesis were isolated and identified from piglets' starter meals to sow feeds, accounting for 56.1%, 23.7%, 13.7% and 6.5%, respectively. Obviously, both B. cereus and B. subtili were dominant contaminants in the survey. In an in vitro study, Deoxynivalenol (DON) contents were determined in a dose-dependent manner post fermentation with B. cereus (405 and DawuC). Subsequently, 36 weaned piglets were randomly assigned to four groups and the piglets simultaneously received the combination of virulent B. cereus (Dawu C) and A. fumigatus while animals were inoculated with B. cereus (Dawu C), A. fumigatus or PBS as the control group. Clinically, piglets developed yellow diarrhea on day 5 and significant reductions of relative body weight were observed in the B. cereus group, and co-infection group. More importantly, IgG titers against Classical swine fever virus (CSFV) and Porcine epidemic diarrhea (PED) were reduced dramatically during 14-day observation in co-infection group, the B. cereus (Dawu C) group or the A. fumigatus group. However, lower Foot and mouth disease (FMD) -specific antibodies were reduced on day 7 compared to those of the control group. Additionally, lower lymphocyte proliferations were found in the B. cereus group and the co-infection group compared to the control group. Postmortem, higher lesions of gastric ulceration were observed in the B. cereus group and the co-infection group from day 7 to day 14 compared with those of the A. fumigatus group and the control group. Compared to the A. fumigatus group, higher DON contents were detected in the stomach inoculated with B. cereus and the co-infection with A. fumigatus . In conclusion, our data support the hypothesis that B. cereus might be associated with severe diarrhea by inducing gastric ulcerations and A. fumigatus might aggravate immune suppression, threating a sustainable swine industry. It is urgently needed to control feed-borne B. cereus contamination.

Background: Estragole is an aromatic organic compound belonging to the class of phenylpropanoids derived from cinnamic aldehydes and present in essential oils of plant species, such asRavensara anisata (madeira), Ocimum basilicum (manjericão/alfavaca) and Croton zehntneri (canelinha). Pharmacological studies report its anti-inflammatory, antioxidant and vasorelaxant activity., Hypothesis/purpose: This study aimed to evaluate the acute non-clinical toxicity, gastroprotective activity and the related mechanisms of action., Methods: Acute toxicity was assessed according to OECD guide 423 in mice. Ethanol, stress, piroxicam and pylorus ligation-induced gastric ulcer models were used to investigate antiulcer properties. The related mechanisms of action were using the ethanol-gastric lesions protocol., Results: In the acute oral toxicity assay, doses of 300 or 2000 mg/kg of estragole administered orally in Swiss mice did not induce any behavioral changes. However, the dose of 2000 mg/kg showed a decrease in water and feed intake. Lethal dose 50 % (LD50) was set to be equal to or greater than 2500 mg/kg, according to OECD. In all evaluated protocols, estragole (31.25, 62.5, 125 and 250 mg/kg) significantly reduced the area of ​​ulcerative lesion when compared to control groups. To investigate the mechanisms involved in the gastroprotective activity, the antisecretory or neutralizing of gastric secretion, cytoprotectant, antioxidant and immunoregulatory effects were evaluated. Results showed that treatment with estragole (250 mg/kg) reduced (p < 0.05) the volume of the gastric juice. Besides, sulfhydryl groups, nitric oxide, mucus and prostaglandins seems to be involved in the gastroprotective property. Treatment also increased (p < 0.001) levels of reduced glutathione (GSH), interleukin-10 (IL-10) and positive cells marked for glutathione peroxidase (GPx) and cyclooxygenase 2 (COX-2). It also reduced (p < 0.001) malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and inducible nitric oxide synthase (iNOS) (p < 0.05) levels., Conclusion: Thus, it is possible to infer that estragole presents gastroprotective activity related to antisecretory, cytoprotective, antioxidant and immunomodulatory mechanisms., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Genipin has been shown to exert anti-inflammatory effects, but its mechanism in protecting the ethanol-induced acute gastric injuries remains largely unclear. The present study aimed to investigate the effects of genipin on ethanol-induced acute gastric injuries in mice. After intragastrical administration of genipin for 7 consecutive days, acute gastric injuries were induced in the mice by ethanol treatment for 1 h. The expression levels of MDA, MPO, SOD, CAT, and NO in gastric tissues, and the levels of IL-6, TNF-α, MTL, SP, VIP and SS in serum samples were measured by ELISA. In addition, Western blotting was used to determine the expression levels of proteins involved in NLRP3 signaling pathway. The findings revealed that oral administration of genipin significantly ameliorated the pathological injury of gastric mucosa induced by ethanol, decreased the oxidative stress induced by ethanol and suppressed the expression levels of in-flammatory cytokines in gastric tissues and serum samples. In addition, it was observed that oral administration of genipin could remarkably inhibit the expression levels of related proteins in the NLRP3 signaling pathway. In conclusion, these results suggest that genipin may exhibit protective roles in ethanol-induced gastric mucosal injuries by activating antioxidant system and attenuating inflammatory reaction., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The gastroprotective effect of Ocimum basilicum L. (Basil) hexane extract (OBHE) in aspirin-induced gastric ulcers in mice and its ameliorative effect on behavioral alterations were determined. Pretreatment with OBHE (100 or 200 mg kg-1) or misoprostol (50 μg kg-1) alleviated the aspirin-induced oxidative stress by significantly decreasing (p < 0.001) gastric ulcer index scores (57, 76 and 79%), gastric TBARS (by 49, 51 and 52%), NO (21, 28 and 29%), H2O2 (24, 42 and 45%), and the serum pro-inflammatory mediator TNF-α (21, 53 and 53%) and IL-6 (29, 30 and 31%), as well as by markedly increasing gastric GSH (41, 61 and 70%), GSH-Px (21, 32 and 34%), GST (33, 63 and 70%), GR (90, 99 and 112%), CAT (167, 211 and 267%) and serum PGE-2 levels (22, 135 and 200%) and IL-4 (64, 81 and 104%), respectively, compared with the aspirin-treated group. Meanwhile, OBHE and misoprostol induced a significant decrease (p < 0.001) in the freezing time (53, 56 and 64%), and the grooming time (by 25, 43 and 44%), respectively, compared to the aspirin treated group. This study provides evidence that OBHE confers anxiolytic, antioxidant and anti-inflammatory prophylactic effects on aspirin-induced gastric ulcers. GC/MS was used for the characterization of OBHE components. Based on the findings of this study, basil may be used as a nutritional supplement or therapeutic drug to protect against aspirin-induced gastric ulcers, a common problem resulting from the use of aspirin.

The roles of gastric acid, mucus, and inflammation on the pro-ulcer-healing effect of thyroid hormone were investigated. Male Wistar rats were randomly divided into four groups: control, thyroidectomised, thyroidectomised with thyroxine treatment (100 μg·kg -1 ·day -1 ), and sham-operated animals treated with thyroxine. Thirty-five days after thyroidectomy, sham surgery, or thyroxine treatment, an ulcer was experimentally induced. Healing was assessed 3, 7, and 10 days post-ulceration by measurement of the ulcer area, gastric mucus and acid secretion, and neutrophil lymphocyte ratio (NLR) as an index of inflammation. By day 10, the ulcer area had decreased in all groups. Recovery was significantly greater (P < 0.05) in thyroxine-treated rats (78.5% ± 1.6% reduction in ulcer area) than in controls (72.3% ± 1.2% reduction) or thyroidectomised rats (63.3% ± 1.9% reduction). Thyroxine-treated animals also had the highest reduction in NLR (65.0% ± 2.5%). Mucus secretion was significantly lower (P < 0.05) in thyroidectomised rats by days 3 and 7. Furthermore, by day 10, the concentration of basal acid decreased by 77.4% ± 2.6% in thyroxine-treated, 65.0% ± 0.0% in control, and 51.5% ± 3.3% in thyroidectomised rats. We conclude that thyroxine accelerates gastric ulcer healing by altering mucus and acid secretion and reducing NLR.

Background Ardisia crispa Thunb A.DC (Myrsinaceae), commonly known as "hen's eyes", has been traditionally used in treating various inflammatory diseases. The present study evaluated anti-arthritic, gastroprotective and antioxidant activities of Ardisia crispa root hexane extract (ACRH) in various animal models. Methods Anti-arthritic activity was evaluated in complete Freund adjuvant (CFA)-induced adjuvant arthritis and gastroprotective effect was studied in the ethanol-induced ulcer model in rats. ACRH was further isolated to yield quinone-rich fraction (QRF) and both were analyzed for their total phenolic content, total flavonoid content and antioxidant activities in various antioxidant assays. Both ACRH and QRF were also analyzed for the quinone composition via gas chromatography analysis. Results ACRH exerted significant reduction of IL-1β and TNF-α at a lower dose range in CFA-induced arthritis, as well as exhibited its cytoprotective effect against ethanol-induced ulcer lesion via involvement of mucosal nonprotein sulfhydryl (NP-SH) groups. ACRH also showed higher phenolic and flavonoid contents, as well as better antioxidant activities than QRF. Conclusions These findings demonstrated the plant as a potential anti-inflammatory agent, with ACRH succeeded in inhibiting both arthritic and ulcerogenic effect, possibly mediated via its antioxidant effect.

Helicobacter pylori is a bacterial pathogen which commonly colonizes the human gastric mucosa from early childhood and persists throughout life. In the vast majority of cases, the infection is asymptomatic. H. pylori is the leading cause of peptic ulcer disease and gastric cancer, however, and these outcomes occur in 10-15% of those infected. Gastric adenocarcinoma is the third most common cause of cancer-associated death, and peptic ulcer disease is a significant cause of morbidity. Disease risk is related to the interplay of numerous bacterial host and environmental factors, many of which influence chronic inflammation and damage to the gastric mucosa. This chapter summarizes what is known about health and disease in H. pylori infection, and highlights the need for additional research in this area.

Research in the treatment of gastric ulcer has involved the investigation of new alternatives, such as anti-depressant drugs. The present study was designed to investigate the gastroprotective effects of fluoxetine against indomethacin and alcohol induced gastric ulcers in rats and the potential mechanisms of that effect. Fluoxetine (20 mg/kg) was administered IP for 14 days. For comparative purposes, other rats were treated with ranitidine (30 mg/kg). Thereafter, after 24 h of fasting, INDO (100 mg/kg) or absolute alcohol (5 ml/kg) was administered to all rats (saline was administered to naïve controls) and rats in each group were sacrificed 5 h (for INDO rats) or 1 h (for alcohol rats) later. Macroscopic examination revealed that both fluoxetine and ranitidine decreased ulcer scores in variable ratios, which was supported by microscopic histopathological examination. Biochemical analysis of fluoxetine- or ranitidine-pre-treated host tissues demonstrated reductions in tumor necrosis factor (TNF)-α and myeloperoxidase (MPO) levels and concomitant increases in gastric pH, nitric oxide (NO) and reduced glutathione (GSH) contents. Fluoxetine, more than ranitidine, also resulted in serotonin and histamine levels nearest to control values. Moreover, immuno-histochemical analysis showed that fluoxetine markedly enhanced expression of cyclo-oxygenases COX-1 and COX-2 in both models; in comparison, ranitidine did not affect COX-1 expression in either ulcer model but caused moderate increases in COX-2 expression in INDO-induced hosts and high expression in alcohol-induced hosts. The results here indicated fluoxetine exhibited better gastroprotective effects than ranitidine and this could be due to anti-secretory, anti-oxidant, anti-inflammatory and anti-histaminic effects of the drug, as well as a stabilization of gastric serotonin levels.

This article reports the case of a 45-year-old male immunocompetent patient who presented with acute epigastric pain and vomiting. Diagnostic tests confirmed a recent cytomegalovirus (CMV) infection as a contributory cause of a florid gastric ulcer. Primary CMV infections affecting the upper gastrointestinal tract are rare in immunocompetent adults. In this case treatment with a proton pump inhibitor and eradication of concomitant Helicobacter pylori colonization led to a full recovery. Anti-CMV treatment was not necessary.

Results of surgical treatment for an acute ulcer gastroduodenal bleeding in 120 patients, ageing 16-75 yrs old, were analyzed. In 20 of them a gastric ulcer was a cause of bleeding, while in 84--a duodenal ulcer, and in 16--a coexistent gastroduodenal ulcer. The bleeding activity was estimated in accordance to J. Forrest classification. In 57 patients (a comparison group) preoperatively and postoperatively a complex of a standard basal conservative therapy without immunocorrection was conducted, and in 63 (the main group)--a systemic cytokinotherapy (SCKTH), using betaleukin, was applied postoperatively additionally in a complex of therapy. A content of CD3+, CD4+, CD8+, CD19+, IgA, IgM, IgG was estimated in dynamics, as well as circulating immune complexes, phagocytic index, phagocytic number. There was established, that a dysbalance depth in the immune status have had depended upon the blood loss severity. The SCKTH application is pathogenetically substantiated, it promotes the immune status normalization, as well as a more favorable course of postoperative period and the results of treatment improvement.

To compare the anti-inflammatory activity of the crude Atractylodes lancea (AL) and AL processed products by stir-baking with bran in rat models of gastric ulcer, and preliminarily explore the anti-ulcer mechanisms of AL, the model of gastric ulcer was imitated by local acetic acid injection into gastric mucosa in rats by surgery according to the modified Okabe method. All rats were randomly divided into the following 10 groups： sham-operation group, model group, omeprazole group, Sanjiu Weitai granule group, crude AL low dose group, crude AL middle dose group, crude AL high dose group, processed AL low dose group, processed AL middle dose group, and processed AL high dose group. Rats were administered via intragastric (ig) two times each day, for 10 consecutive days. Blood was collected from the abdominal aorta, serum was separated, and the ulcer tissues were taken. The levels of inflammatory factors interleukin 6, 8 (IL-6, 8), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) in serum and gastric tissues were determined by enzyme-linked immunosorbent assay (ELISA), and the mRNA expressions of TNF-α and IL-8 in gastric tissues were detected by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). The protein expressions of TNF-α and IL-8 in gastric tissues were detected by immunohistochemistry. Compared with sham-operation group, the levels of TNF-α, IL-8, IL-6, PGE2 as well as the mRNA expressions and protein expressions of TNF-α, IL-8 in gastric tissues were significantly higher in model group. The above levels were reduced in different degrees in all treatment groups. Compared with the crude AL, same dose of processed AL was more effective in decreasing the levels of TNF-α, IL-8, IL-6, PGE2 in serum and gastric tissues and down-regulating the mRNA expressions of TNF-α and IL-8 in gastric tissues, with significant difference in middle dose groups and high dose groups. The results showed that AL had potent anti-inflammatory effects in rat models of gastric ulcer induced by acetic acid, and the processed AL had more obvious effect. The anti-ulcer action of AL could be attributed partly to down-regulating the levels of TNF-α, IL-8, IL-6 and PGE2., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

The Purpose of the Study: To determine the prognostic significance of the expression of molecules of PCNA, Bcl-2, NF-Kb and tachykinins (substance P, neurokinin A) in patients with gastric ulcer (CU) receiving cytotoxic therapy., Materials and Methods: Total surveyed 90 patients divided into 3. equal groups. The first comparison group consisted of patients with chronic atrophic H. pylori-associated gastritis (CAG) (30 pers.). A second control group consisted of patients with gastric ulcer (30 pers.). Third, the study group consisted of 30 people. with CU suffering from hematological malignancies, in a period of complete clinical remission of the disease and receiving supportive polychemotherapy (PCT). Patients underwent endoscopy, morphological and immunohistochemical study of the mucous membrane of the antrum and body of the stomach to detect the expression of molecules of PCNA, Bcl-2, neurokinin A, substance P and factor Nf-Kb., Results: The total level of dyspeptic syndrome on visual scale analogue in patients receiving chemotherapy and GU (GUpct) was significantly higher (p < 0.05) compared with patients with GU. It should be noted that patients with GUpct reducing clinical symptoms is much slower (p < 0.05). At the same time in 13 (43.3%) patients with GUpct determines the duration of ulcer healing, whereas in patients with GU in only 4 (13.3%) patients. Patients with GUpct more frequently (p < 0.05) were verified II and stage Ill chronic gastritis (CG), while Stage I--less (p < 0.05). Patients with GUpct significantly more often (p<0.05) was determined by the II degree of CG and significantly less (p < 0.05)--IV degree. Patients with GUpct determined significantly lower (p < 0.05), the expression performance PCNA, substance P and neurokinin A and higher (p < 0.05)--Bcl-2 and factor Nf-kB., Conclusion: GU in patients receiving chemotherapy, dyspeptic syndrome is characterized by severe, advanced stage of CG on the background of relatively low severity of CG in accordance with the classification of OLGA (2008). Patients with GUpht have a significant level of violation of regeneration changes how is this atrophy, intestinal metaplasia, dysplasia of gastric mucosa association with gross violations of the processes of epithelial cell homeostasis of epithelial cells regulation after molecules PCNA, Bcl-2, NF-kB and tachykinins (substation P, neurokinin A).

Statins are suggested to possess healing properties due to their antioxidant and antiinflammatory effects in animal ulcer models. In contrary, a clinical report indicated the formation of gastric ulcer by the use of atorvastatin. In this study, we aimed to investigate the effects of atorvastatin (0.5, 5 and 50mg/kg, p.o.) after single (acute) and multiple (subchronic, 5 days) applications on indomethacin-induced gastric ulcer in rats. In both acute and subchronic models high dose atorvastatin (50mg/kg), unlike to lower doses (0,5 and 5mg/kg), significantly aggravated ulcer lesions induced by indomethacin (30 mg/kg) although, a direct ulcerogenic influence was lacking. Proulcerogenic effect of atorvastatin are likely to be associated with decreased mucosal defense mechanisms (GSH and PGE2), and increased neutrophil infiltration and proinflammatory factors (TNF-a and iNOS) possibly via independently from mevalonate pathway. Thus, atorvastatin therapy should be monitorized in patients for an increased risk of gastric ulcer particularly when used concomitantly with NSAIDs., (Copyright © 2015. Published by Elsevier Inc.)

The results of surgical treatment of 39 patients, suffering an acute gastroduodenal ulcer hemorrhage, were analyzed. Gastric ulcer disease was diagnosed in 9 patients, duodenal ulcer disease--in 29, combined ulcer--in 1. A light degree blood loss was noted in 13 patients, while a middle degree--in 12, and severe--in 14. In accordance to J. Forrest classification in 6 patients an active bleeding was revealed (FIa, FIb), in 11--nonstable hemostasis (FIIa, FIIb, FIIc), and in 22--FIII. Preoperatively in patients on the third, seventh and fourteenth day the contents of CD3+, CD4+, CD8+, CD19, calculation of a CD4+/CD8+ ratio, the level of immunoglobulins (IgA, IgM, IgG) and circulating immune complexes were determined in peripheral blood. Phagocytic activity of neutrophils was estimated, using determination of phagocytic index and phagocytic number. In an acute gastroduodenal ulcer hemorrhage immunosuppression was noted, and severity of disorders in T- and B-chains of immunity have depended upon a blood loss severity. Conduction of a routine basic conservative therapy in postoperative period did not guarantee elimination of immunosuppression.

The present study investigated the gastroprotective effect of crocin in ethanol-induced gastric injury in rats. Rats were allocated into a normal group, an ulcer group, a crocin-treated group, an ulcer group pretreated with crocin, and an ulcer group pretreated with omeprazole as a reference anti-ulcer drug. Rats were sacrificed 3h after ethanol administration. Prophylactic administration of crocin (50mg/kg/day, i.p.) for 3 consecutive days before the administration of 70% ethanol (10 ml/kg, orally) resulted in significant gastroprotection compared to ethanol-ulcerated rats as manifested by significant reduction in the gastric ulcer index. Crocin pretreatment increased ethanol-lowered levels of gastric juice mucin and mucosal prostaglandin E2 (PGE2) and interleukin-6 (IL-6). Moreover, crocin significantly decreased ethanol-elevated tumor necrosis factor-alpha (TNF-α) level, myeloperoxidase activity and heat shock protein 70 mRNA and protein levels. It also restored ethanol-altered mucosal levels of glutathione, malondialdehyde and superoxide dismutase activity. Furthermore, crocin-pretreatment alleviated ethanol-induced mucosal apoptosis as revealed by significant down-regulation of cytochrome c and caspase-3 mRNA expression, significant decrease in caspase-3 activity and mitigated DNA fragmentation as indicated by significant decrements in comet parameters. The protective efficacy of crocin was further supported by histological assessment. No significant difference was observed between crocin and omeprazole (20mg/kg orally 1h before ethanol administration) regarding their mucin-secretagogue and antioxidant effects, as well as their effects on TNF-α, IL-6 and cytochrome c. On the other hand, omeprazole was superior in enhancing PGE2 level and in alleviating neutrophil infiltration, caspase-3 activation and DNA fragmentation. Conclusively, crocin protects rat gastric mucosa against ethanol-induced injury via anti-inflammatory, anti-oxidative, anti-apoptotic and mucin-secretagogue mechanisms that are probably mediated by enhanced PGE2 release., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Despite the various reports on the pharmacology of Clove bud [Syzygium aromaticum]-derived essential oil and its major component eugenol, systematic information on the bioactivity of clove polyphenols is very limited. Clove buds being one of the richest sources of dietary polyphenols with many traditional medicinal uses, the present contribution attempted to derive their standardized polyphenol-rich extracts as a water soluble free flowing powder (Clovinol) suitable for functional food applications, without the issues of its characteristic pungency and aroma. The extract was characterized by electrospray ionization-time of flight mass spectrometry (ESI-TOF-MS), and investigated for in vivo antioxidant, anti-inflammatory and anti-ulcerogenic activities. Clovinol showed significant antioxidant and anti-inflammatory effects as measured by cellular antioxidant levels, and the ability to inhibit carrageenan-induced paw swelling in mice. Further investigations revealed its significant anti-ulcerogenic activity (>97% inhibition of ethanol-induced stomach ulcers in Wistar rats when orally administered at 100 mg per kg b.w.) and up regulation of in vivo antioxidants such as superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT). Clovinol also reduced the extent of lipid peroxidation among ulcer induced rats, indicating its usefulness in ameliorating oxidative stress and improving gastrointestinal health, especially upon chronic alcohol consumption. The extract was also shown to be safe and suitable for further investigations and development upon acute toxicity studies at 5 g per kg body weight and 28 days of repeated dose toxicity studies at 2.5 g per kg b.w.

Excessive ethanol ingestion causes gastric mucosal damage through the inflammatory and oxidative processes. The present study was aimed to evaluate the protective effect of thalidomide on ethanol-induced gastric mucosal damage in mice. The animals were pretreated with vehicle or thalidomide (30 or 60 mg/kg, orally), and one hour later, the gastric mucosal injury was induced by oral administration of acidified ethanol. The animals were euthanized one hour after ethanol ingestion, and gastric tissues were collected to biochemical analyzes. The gastric mucosal lesions were assessed by macroscopic and histopathological examinations. The results showed that treatment of mice with thalidomide prior to the administration of ethanol dose-dependently reduced the gastric ulcer index. Thalidomide pretreatment significantly reduced the levels of pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6], malondialdehyde (MDA) and myeloperoxidase (MPO) activity. In addition, thalidomide significantly inhibited ethanol-induced nitric oxide (NO) overproduction in gastric tissue. Histological observations showed that ethanol-induced gastric mucosal damage was attenuated by thalidomide pretreatment. It seems that thalidomide as an anti-inflammatory agent may have a protective effect against alcohol-induced mucosal damage by inhibition of neutrophil infiltration and reducing the production of nitric oxide and inflammatory cytokines in gastric tissue., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The work is dedicated to the research of the content of lipids and products of their peroxidation in rats thymocytes in experimental ulceration. It was found significant increase of the content of lipid peroxidation products diene conjugates (DC), malondialdehyde (MDA), schiff base (SB) in experimental models of gastric ulcers (ethanol and stress). It was established that under ethanol gastric the contents of DC increases by 1.8 times, MDA by 2.1 and SB by 1.3 times relative to control values. Under stress model it was observed an increase in the number of DC by 2 times, MDA by 1.9 and SB by 1.3 times relative to control. When ethanol and stress ulcers cholesterol increased by 1.7 and 1.5 times, triacylglycerol by 2 and 2.3 times and fatty acids by 2.2 and 1.9 times, respectively, relative to controls. Phosphatidylethanolamine content decreases by 1.5 and 1.3 times compared to control. Also, the stress model, it was observed reduction of phosphatidylinositol by 1.3 times and increased lizofosfatydylholinu by 1.7 times compared to control. Therefore, our studies indicate quantitative changes of lipid content (neutral- and phospholipids) in rats' thymocytes under experimental (ethanol and stress) ulceration. The reason of this changes may be activation of lipid peroxidation, as shown by the increase of lipid peroxidation products' (DK, MDA, SB) content.

IgG4-related disease is a recently recognized entity linked initially to autoimmune pancreatitis and has been subsequently described in nearly every organ system. Men over the age of 50 represent the most affected demographic group and a comprehensive set of diagnostic criteria has been developed to aid treating clinicians. Though elevated levels of IgG4 in the serum are suggestive of the disease, definitive diagnosis is made on histopathology. Treatment is tailored to the clinical presentation with corticosteroid therapy known to have proven efficacy. Gastric manifestations of the IgG4-related disease primarily come in two varieties, notably chronic ulceration or pseudotumor formation. Autoimmune pancreatitis conveys increased risk for IgG4-related disease of the stomach, which is independent of Helicobacter pylori status. In this case report, we present an acute gastric-pericardial fistula secondary to IgG4-related disease that required urgent operative management. To our knowledge, this is the first report in the medical literature describing this complication of IgG4-related disease.

The paper presents evidence on the important contribution of the peripheral serotonin system in the process of immunomodulation. The main components of the system - serotonin, receptors and serotonin transporter - are described. Possible mechanisms of serotonin regulation of activity of immune cells - lymphocytes, macrophages and dendritic cells - are reviewed.

Helicobacter pylori (H. pylori) is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1) significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB) or chemotaxis (ΔcheY). ΔmotB (10(6)) failed to colonize ulcerated or healthy stomach tissue. ΔcheY (10(6)) colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites, and thereby biases the injured tissue towards sustained gastric damage.

The influence of regulatory peptide type of AFP on the course of experimental ulcers was investigated. It has been shown that activation of apoptosis by AFP enhance local necrotic inflammatory reaction, on the one hand, and enables the development of adhesions with the other.

Background: The present study evaluates the effects of extract of Musa sapientum fruit (MSE) on ulcer index, blood glucose level and gastric mucosal cytokines, TNF-α and IL-1β and growth factor, TGF-α (affected in diabetes and chronic ulcer) in acetic acid (AA)-induced gastric ulcer (GU) in diabetic (DR) rat., Methods: MSE (100 mg/kg, oral), omeprazole (OMZ, 2.0 mg/kg, oral), insulin (INS, 4 U/kg, sc) or pentoxyphylline (PTX, 10 mg/kg, oral) were given once daily for 10 days in 14 days post-streptozotocin (60 mg/kg, intraperitoneal)-induced diabetic rats while, the normal/diabetic rats received CMC for the same period after induction of GU with AA. Ulcer index was calculated based upon the product of length and width (mm2/rat) of ulcers while, TNF-α, IL-1β and TGF-α were estimated in the gastric mucosal homogenate from the intact/ulcer region. Phytochemical screening and HPTLC analysis of MSE was done following standard procedures., Results: An increase in ulcer index, TNF-α and IL-1β were observed in normal (NR)-AA rat compared to NR-normal saline rat, which were further increased in DR-AA rat while, treatments of DR-AA rat with MSE, OMZ, INS and PTX reversed them, more so with MSE and PTX. Significant increase in TGF-α was found in NR-AA rat which did not increase further in DR-AA rat. MSE and PTX tended to increase while, OMZ and INS showed little or no effect on TGF-α in AA-DR rat. Phytochemical screening of MSE showed the presence of saponins, flavonoids, glycosides, steroids and alkaloids and HPTLC analysis indicated the presence of eight active compounds., Conclusion: MSE showed antidiabetic and better ulcer healing effects compared with OMZ (antiulcer) or INS (antidiabetic) in diabetic rat and could be more effective in diabetes with concurrent gastric ulcer.

Eosinophils participate in the immune response against Helicobacter pylori, but little is known about their role in the gastritis associated to the infection. We recently demonstrated that the Hp(2-20) peptide derived from H. pylori accelerates wound healing of gastric mucosa by interacting with N-formyl peptide receptors (FPRs) expressed on gastric epithelial cells. The aim of the present study was to investigate whether eosinophils play a role in the repair of gastric mucosa tissue during H. pylori infection. Immuno-histochemistry and transmission electron microscopy were used to detect eosinophils in gastric mucosal biopsies. Eosinophil re-distribution occurred in the gastric mucosa of H. pylori-infected patients: their density did not change in the deep mucosal layer, whereas it increased in the superficial lamina propria just below the foveolar epithelium; eosinophils entered the epithelium itself as well as the lumen of foveolae located close to the area harboring bacteria, which in turn were also engulfed by eosinophils. The H. pylori-derived peptide Hp(2-20) stimulated eosinophil migration through the engagement of FPR2 and FPR3, and also induced production of VEGF-A and TGF-beta, two key mediators of tissue remodelling. We also demonstrate that Hp(2-20) in vivo induced eosinophil infiltration in rat gastric mucosa after injury brought about by indomethacin. This study suggests that eosinophil infiltrate could modulate the capacity of gastric mucosa to maintain or recover its integrity thereby shedding light on the role of eosinophils in H. pylori infection.

Although Helicobacter pylori (Hp) plays an important role in the pathogenesis of chronic gastritis and gastric ulcer, little is known about the probable mechanisms of these types of gastrointestinal damage. To determine the precise mechanisms involved in ulcer formation, immune responses in patients with gastric ulcer (GUP) caused by Hp infection (Hp(+)) were compared with those of other gastritis patients (GP). The sensitivity and proliferation of peripheral blood mononuclear cells (PBMNCs) obtained from patients were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against exposure with complex Hp crude antigen (HPCA) and mitogen (phytohemagglutinin, PHA). Production of inflammatory cytokines, including interleukin (IL)-1β and IL-8, in serum and supernatants of PBMNCs were then measured by ELISA. It was found that, after stimulation with PHA, both IL-8 and IL-1β concentrations in sera and supernatants as well as proliferation and sensitivity were statistically greater in GUP Hp(+) than GP Hp(-) . Furthermore, HPCA inhibited the proliferation of PBMNCs dose-dependently; however, it stimulated IL-8 and IL-1β production in supernatants of mononuclear cells. Therefore, the up-regulated concentrations of IL-8 and IL-1β may have been caused by increase in the size of mononuclear cell subpopulations or in their cytokine secretory activity, indicating the greatest cell responsiveness in GUP Hp(+) patients. These results suggest that tissue damage and ulcers occur in patients who produce more IL-8 and IL-1β than patients who do not develop ulcers; the former consequently have more activated immune cells at the site of infection. Therefore, both host responses and Hp virulence factors may be involved in the development of gastric ulcers., (© 2013 The Societies and Wiley Publishing Asia Pty Ltd.)

Some phytochemicals demonstrate gastroprotective effects by inhibiting gastric acid secretion or through antioxidant action. One of these antioxidant phytochemicals which have been studied is gallic acid. However, its mechanism in the treatment and prevention of gastric ulcer remains unclear. This study evaluated the anti-ulcerogenic mechanism(s) of gallic acid (GA) and its novel synthetic derivative (GD). Adult male Sprague Dawley rats were orally pretreated with GA and GD and 30min later exposed to acute gastric ulcerogenesis induced by 95% ethanol (5ml/kg). Potential gastric chemoprevention of GA and GD were assessed using qualitative and quantitative evaluation of gastric lesions, gastric juice acidity, mucus production, histolopathology, PAS histochemistry, immunostaining of Hsp70 and Bax, nitric oxide, prostaglandin E2, TNF-α and thiobarbituric acid reactive substances (TBARS) assay. Oral administration of GA and GD (25 and 50mg/kg) inhibited significantly (P<0.05) ethanol-induced gastric lesions. Treatment with the compounds protected rat's stomach and modulated remarkably the levels of PAS-reactive substances, gastric pH, TBARS, immunological and apoptosis marker. The in vivo antioxidant properties, immunomodulator proteins and inhibition of mitochondrial apoptosis may contribute to the gastroprotective activity of gallic acid (GA) and its novel derivative (GD)., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The study included 120 patients with pre-cancer conditions of the stomach and 30 patients with gastric cancer stage II-IV. The ELISA method in the blood serum was used to determine the markers of the infection caused by Herpes simplex virus (HSV) types 1 and 2, Cytomegalovirus (CMV), and Epstein-Barr virus (EBV). The majority of the patients exhibited high titers of markers of Herpesvirus mixed infection. These data allow recommending the determination of IgG antibodies to antigens of herpesviruses in patients with the diseases of the stomach and assigning the appropriate antiviral drugs.

Aim: Study H. pylori strains circulating in St. Petersburg among patients with various gastrointestinal tract pathology as well as study of frequency of infection by H. pylori based on serological markers data among this group of patients., Materials and Methods: By using serological method 162 individuals with various chronic diseases of stomach and duodenum were examined. The presence in blood serum of IgG against H. pylori bacterial antigen and IgG against its toxin--CagA was studied. 129 patients were examined bacteriologically, biopsy samples of stomach mucous membrane were studied. PCR in real time format was used for study of H. pylori strains (49) and biopsy samples (36) of stomach mucous membrane., Results: The analysis performed showed that on the territory of St. Petersburg H. pylori strains containing cagA gene predominate (81.63% of the isolated strains). Genotyping of strains by vacA showed that s1m1 genotype was more frequent (in 57.14% of cases). The fraction of CagA positive strains in patients in St. Petersburg is maximum for stomach cancer (90.8%), whereas for peptic ulcer disease and gastritis it is 64.7% and 72.2%, respectively. In patients with stomach and duodenum pathology the parameters of seropositivity for H. pylori were significantly higher than in individuals without clinical manifestations of H. pylori infection (86.72% against 65.09%; p < 0.05)., Conclusion: The data obtained on increase of fraction of CagA positive strains among H. pylori circulating in St. Petersburg determine the importance of conducting eradication H. pylori.

The local injection of triamcinolone acetonide (TA) is effective in preventing pyloric stenosis and deformity following large endoscopic submucosal dissection (ESD). However, because of its long-acting nature, TA can induce long-term local immunosuppression and subsequent adverse events. We report a case of a cytomegalovirus (CMV) ulcer that formed only at the TA local injection site. A 68-year-old man underwent ESD to treat early gastric cancer that formed over the pylorus. The lesion extended to the duodenum, and an artificial ulcer covered more than two-thirds of the circumference of the pylorus. To prevent pyloric stenosis, TA was locally injected into the ulcer floor. On day 12, a deeper ulcer 10 mm in diameter was discovered in the center of the post-ESD ulcer. Biopsies revealed large cells with intranuclear inclusion bodies, which stained positive for the anti-CMV antibody. Local TA injections are useful, however, CMV ulcer might occur as adverse events.

Unlabelled: The purpose of the study--to determine the serum concentration and the pathogenetic significance of changes of interleukin-18 in patients with chronic atrophic gastritis, peptic ulcer disease and gastric cancer. MATERIAL AND METHODS.:A comprehensive survey of 192 patients with diseases gastroduodenal zone. Diagnostic emphasis was placed on ELISA method as defined in the serum of IL-18, --1beta, interferon-gamma, kantsernogo antigen 19-9, vascular endothelial growth factor, total antibodies to CagA Helicobacter pylori., Results: We examined patients revealed an increase in the concentration of interleukin-18, which correlated with tumor stage, the level of vascular endothelial growth factor, total antibodies to CagA Helicobacter pylori., Conclusion: The data obtained allow to recommend the use of interleukin-18 in serum for diagnostic of atrophic gastritis, peptic ulcer diseases and gastric cancer.

Helicobacter pylori antigen was prepared from an isolate from a patient with a duodenal ulcer. Serum samples were obtained from culture-positive H. pylori infected patients with duodenal ulcers, gastric ulcers and gastritis (n=30). As controls, three kinds of sera without detectable H. pylori IgG antibodies were used: 30 from healthy individuals without history of gastric disorders, 30 from patients who were seen in the endoscopy clinic but were H. pylori culture negative and 30 from people with other diseases. OFF-GEL electrophoresis, SDS-PAGE and Western blots of individual serum samples were used to identify protein bands with good sensitivity and specificity when probed with the above sera and HRP-conjugated anti-human IgG. Four H. pylori protein bands showed good (≥ 70%) sensitivity and high specificity (98-100%) towards anti-Helicobacter IgG antibody in culture- positive patients sera and control sera, respectively. The identities of the antigenic proteins were elucidated by mass spectrometry. The relative molecular weights and the identities of the proteins, based on MALDI TOF/ TOF, were as follows: CagI (25 kDa), urease G accessory protein (25 kDa), UreB (63 kDa) and proline/pyrroline- 5-carboxylate dehydrogenase (118 KDa). These identified proteins, singly and/or in combinations, may be useful for diagnosis of H. pylori infection in patients.

Non steroidal anti-inflammatory drugs (NSAIDs) induce gastric mucosal lesions in part by induction of oxidative stress as well as the activation of inflammatory cells and the production of proinflammatory cytokines. In this study, we examined the protective effect of candesartan (2 and 5 mg/kg) on indomethacin-induced gastric mucosa damage. Pretreatment with candesartan for 10 days reduced significantly the ulcer index induced by indomethacin injection. The preventive index of 2 mg/kg (76.74%) was higher than that of 5 mg/kg (65.11%). Both doses of candesartan were able to reduce significantly the stomach malondialdehyde content compared to indomethacin-treated group. Myeloperoxidase, tumor necrosis factor-α, cytokine-induced neutrophil chemoattractant gastric levels were significantly reduced by 2 mg/kg of candesartan more than 5 mg/kg. The Th1 cytokine interferon γ was also significantly reduced by both doses of candesartan compared to indomethacin injected group. On the other hand, indomethacin significant decreased the anti-inflammatory cytokine IL-10 gastric level. Pretreatment with candesartan (2 and 5 mg/kg) reversed this effect. In conclusion, the present study indicates that pretreatment with candesartan, can protect against the stomach injury induced by indomethacin through its antioxidant and immunomodulatory effects.

Context: Blepharis maderaspatensis L. Roth (BM) (Acanthaceae) and Ammannia baccifera L. (AB) (Lythraceae) are used in folk medicine for various stomach disorders., Objective: The chloroform and ethanol extracts of both plants were evaluated for antioxidant, gastric antisecretory, and gastroprotective properties., Methods: Antioxidant properties of the extracts were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and nitric oxide (NO) scavenging assay. The gastric antisecretory properties of the extracts were assessed, at a dose of 100 and 200 mg/kg, using aspirin-pylorus ligation induced gastric ulcer models and the gastroprotective activity of the extracts was assessed, at a dose of 100 and 200 mg/kg, using HCl-ethanol induced ulcer models in rats., Results and Discussion: Ethanol extract of BM (EBM) possessed good antioxidant property with IC₅₀ values of 37.4 and 44.1 µg/mL in DPPH and NO scavenging assays respectively, where 25-250 µg/mL concentration in DPPH assay and 30-300 µg/mL concentration in NO scavenging assay were used. Ethanol extract of AB (EAB) at a dose of 200 mg/kg reduced the free acidity to 142.66 mEq/L and total acidity to 451.22 mEq/L. It reduced the gastric secretion with increase in pH from 2.2 to 3.15. Possessing good antisecretory activity, it also reduced the ulcer by 92.2% in aspirin and pylorus ligation induced gastric ulcer models. EAB increased the mucus secretion and adherent mucus in the tissues with a 71.43% reduction of ulcerin HCl-ethanol induced ulcer models, at a dose of 200 mg/kg. This activity can be attributed to the various flavonoids like rutin and kaempferol-3-O-β-glucopyranoside, and the phytosterol, β-sitosterol-3-O-β-glucopyranoside, and phenolics present in the extracts., Conclusion: EBM possessed significant antioxidant property while EAB possessed good antisecretory and gastroprotective activity.

Ethnopharmacological Relevance: Aqueous extracts of bark and leaves of C. cordifolia are traditionally used in Mali (West Africa) in the treatment of wounds and gastric ailments like abdominal pain, gastritis and gastric ulcers., Aim of the Study: To evaluate and compare the anti-ulcer and immunological activities, as well as the toxicity of polysaccharide rich water extracts from the bark and leaves of C. cordifolia., Materials and Methods: Gastric ulcers were induced in rats and the inhibition of ulcer formation was calculated based on lesion index. Immunological activities were measured by complement fixation and macrophage activation. Toxicity was tested on brine shrimps. The two extracts were characterised by GC, Yariv-precipitation and quantification of phenolic compounds. An ethnomedical survey on C. cordifolia was carried out in Siby (Mali, West-Africa) to generate more knowledge about the traditional use., Results: Bark and leaf extracts from C. cordifolia significantly inhibited the formation of gastric lesions in rodents in a dose depending manner. CCbark50 showed a high complement fixation activity in vitro. No toxicity was found. The ethnomedical survey showed that C. cordifolia was mainly used for treating pain and wounds., Conclusions: Our results shows that the bark and the leaves comprise a dose dependant anti-ulcer activity in an experimental rat model (no statistical difference between the plant parts). Clinical studies should be performed to evaluate the effect of both bark and leaves of C. cordifolia as a remedy against gastric ulcer in human., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

This study investigates the gastroprotective effects of hecogenin, a steroid saponin isolated from Agave sisalana, on experimental models of gastric ulcer. Male Swiss mice were used in the models of ethanol- and indometacin-induced gastric ulcer. To clarify the hecogenin mechanism of action, the roles of nitric oxide (NO), sulfhydryls (GSH), K⁺(ATP) channels and prostaglandins were also investigated, and measurements of lipid peroxidation (TBARS assay) and nitrite levels in the stomach of hecogenin-treated and untreated animals were performed. Furthermore, the effects of hecogenin on myeloperoxidase (MPO) release from human neutrophils were assessed in vitro. Our results showed that hecogenin (3.1, 7.5, 15, 30, 60 and 90 mg/kg, p.o.) acutely administered, before ethanol or indomethacin, exhibited a potent gastroprotective effect. Although the pretreatments with L-NAME, an iNOS inhibitor, and capsazepine, a TRPV1 receptor agonist, were not able to reverse the hecogenin effect, this was reversed by glibenclamide, a K⁺(ATP) blocker, and indomethacin in the model of ethanol-induced gastric lesions. The hecogenin pretreatment normalized GSH levels and significantly reduced lipid peroxidation and nitrite levels in the stomach, as evaluated by the ethanol-induced gastric lesion model. The drug alone increased COX-2 expression and this effect was further enhanced in the presence of ethanol. It also decreased MPO release and significantly protected the gastric mucosa. In conclusion, we showed that hecogenin presents a significant gastroprotective effect that seems to be mediated by K⁺(ATP) channels opening and the COX-2/PG pathway. In addition, its antioxidant and anti-inflammatory properties may play a role in the gastroprotective drug effect., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Turnera diffusa Willd. ex Schult. has been used for the treatment of several human disorders including peptic ulcer., Objectives of the Study: The current study is an attempt to evaluate the anti-ulcerogenic activities of arbutin, a major constituent of Turnera diffusa on two ulcer models. The possible involvement of lipid peroxidation, nitric oxide, IL-6, IL-10, TNF-α and mucus barrier mechanism has been investigated., Materials and Methods: Effects of arbutin on ulcer index, gastric juice acidity, mucus content and histochemistry, gross and histological gastric lesions, nitric oxide, cytokines levels (IL-6, IL-10 and TNF-α), and thiobarbituric acid reactive substances (TBARS), were evaluated in aspirin or ethanol-induced ulcer in vivo. Acute toxicity of arbutin was also examined in rodent model. MTT assay was used to assess the cytotoxicity of the compound on normal liver cells (WRL-68)., Results: Pre-treatment with arbutin or omeprazole protected the gastric mucosa as seen by reduction in ulcer area and mucosal content, reduced or absence of edema, inflammation and leucocytes infiltration on both models. Arbutin significantly (P<0.05) lowered the elevated TBARS level into gasteric homogenate. Arbutin did not produce significant inhibition of NO. This natural compound has modulated the levels of interleukin-6, interleukin-10 and TNF-α. No in vitro or in vivo toxicities for arbutin were observed., Conclusion: Thus it can be concluded that Turnera diffusa possesses anti-ulcer activity, which could be attributed to lipid peroxidation inhibitory, immuno modulatory and anti-oxidant mechanisms of arbutin but not to the intervention with nitric oxide inflammation pathway., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Alcohol consumption can induce gastric ulcers and zinc deficiency. Zinc complexes were reported to have anti-ulcer activity as it acts as an anti-inflammatory and antioxidant. Zn(II)-curcumin complex and its solid dispersions (SDs) were synthesized and evaluated for its gastroprotective activity and mechanism against ethanol-induced ulcer. The Swiss murine fibroblast cell line (3T3) was used as an alternative in vitro model to evaluate the effects of Zn(II)-curcumin on cell proliferation. Zn(II)-curcumin were administered orally for seven consecutive days prior to induction of ulcers using ethanol. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that solid dispersions (SDs) of Zn(II)-curcumin (2.5-20 μM) enhanced the proliferation of 3T3 cells more significantly than curcumin at the same concentrations (P<0.01). Oral administration of Zn(II)-curcumin (12, 24 and 48 mg/kg) SDs dose-dependently prevented formation of ulcer lesions induced by ethanol. The levels of proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and oxidative stress superoxide dismutase (SOD), glutathione peroxidase (GPX-Px), malonaldehyde (MDA) and H(+)-K(+)-ATPase were in the rats exposed to ethanol in ulceration have been altered. Zn(II)-curcumin prevented formation of ulcer lesions, significantly inhibited TNF-α and IL-6 mRNA expression, increased the activity of SOD and GSH-Px, reduced MDA levels and H(+)-K(+)-ATPase in mucosa of rats compared to controls (P<0.05). These findings suggest that the gastroprotective activity of Zn(II)-curcumin complex might contribute in stimulating cell proliferation and adjusting the proinflammatory cytokine-mediated oxidative damage to the gastric mucosa., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Treatment results of 986 patients with perforative gastroduodenal ulcers were analyzed. The sequence of surgeon's acts was diagnostically effective in 99.5%. 776 (78.7%) of patients presented with duodenal ulcer; 210 (21.3%) had gastric ulcer. Ulcer closure was performed in 934 (94.7%) cases; gastric resection was made in 52 (5.3%) cases. Postoperative lethality rate was 4.3%. Tissue destruction proved to be partly connected with the level of the connective tissue metabolites in blood. The balance of factors of aggression and defense (Helicobacter invasion, level of mucus formation, mucosal leucocytal infiltration, acid level in stomach and level of necrosis factor in blood) was registered in long-term follow-up in dependence of the operation performed. Ulcer perforation recurrence was registered in 18.8% of simple closure cases and in 3.8% of patients after gastric resection.

It has been reported that CagA gene positive Helicobacter pylori (CagA+ H. pylon) induces severe gastric mucosal inflammation. On the other hand, Interleukin (IL)-17 is known to stimulate IL-8 release by the gastric epithelial cells which facilitates chemotaxis of neutrophils through an IL-8-dependent mechanism. The aim of the study is to determine the role of IL-17 and IL-8 in the development of gastritis and gastric ulcer in H. pylori infected patients. Mucosal biopsy samples were obtained from the ulcer site of gastric mucosa of 28 patients with gastric ulcer (GU), 27 with gastritis and 8 controls subjects without gastritis or ulcers. Infection with H. pylori of patients and controls was assessed by a rapid urease test, histological examination and culture. Measurement of the tissue levels of IL-17 and IL-8 were assayed by ELISA. H. pylori cagA gene was assessed by polymerase chain reaction (PCR). Out of the 28 patients with GU, 18 (64.2%) patients were positive for H. pylori infection, while 13 (48.1%) patients with gastritis and none of the controls were positive for H. pylori infection The CagA gene was detected in 12 (66.6%) in H. pylori GU patients, and 7 (53.8%) H. pylori positive gastritis. IL-17 was significantly higher in GU-CagA+ve H. pylori compared to GU-CagA- H. pylori (P <0.05), while IL-8 showed no significant difference between groups. The mean levels of IL-8 in gastritis-CagA+ H. pylori) was significantly higher compared to gastritis--CagA- H. pylori- (P <0.05). IL-17 showed significant association with the number of neutrophils in both GU and gastritis (r = 0.689, P < 0.05 & r = 0.618, P < 0.05). Also, IL-8 showed significant association with the number of neutrophils in both GU and gastritis n (r = 0.468, P < 0.05 & r = 0.727, P < 0.05). It is concluded that the Cag+ve H. pylori is associated with induction of mucosal injury. Also, IL-8 and IL-17 plays a role in the development of GU and gastritis especially in CagA+ H. pylori.