Causal Association of Folic Acid Supplementary Therapy and Gastric Ulcer: A Mendelian Randomization Study.

Previous research has suggested a potential link between folic acid supplementary therapy and gastric ulcers. To investigate this relationship further, we conducted a Mendelian randomization (MR) analysis using data from the UK Biobank. Our analysis primarily employed inverse variance-weighted (IVW) methods, including both fixed-effect and random-effect models. To ensure the robustness of our findings, additional methods such as the simple median, the weighted median, and the penalized weighted median were also applied. The MR analysis aimed to explore the causal effect of FA supplementary therapy on gastric ulcers. Seven single nucleotide polymorphisms (SNPs) at genetic loci associated with FA supplementary therapy were identified. Both the random-effect and fixed-effect IVW models indicated that genetically predicted FA supplementary therapy significantly reduced the risk of gastric ulcers (OR, 0.870; 95% CI, 0.826-0.917, p<0.001). This result was consistent across other methods, with similar outcomes observed using the simple median (OR, 0.835; 95% CI, 0.773-0.901, p<0.001), the weighted median (OR, 0.854; 95% CI, 0.794-0.919, p<0.001), and the penalized weighted median (OR, 0.849; 95% CI, 0.789-0.914, p<0.001). Leave-one-out sensitivity analysis confirmed that no individual SNP significantly drove the association between FA supplementary therapy and gastric ulcers. This MR study provides genetic evidence that FA supplementary therapy may decrease the risk of gastric ulcers.

Background factors of idiopathic peptic ulcers and optimal treatment methods: a multicenter retrospective Japanese study.

This study investigated the trends in idiopathic peptic ulcers, examined the characteristics of refractory idiopathic peptic ulcer, and identified the optimal treatment. The characteristics of 309 patients with idiopathic peptic ulcer were examined. We allocated idiopathic peptic ulcers that did not heal after 8 weeks' treatment (6 weeks for duodenal ulcers) to the refractory group and those that healed within this period to the healed group. The typical risk factors for idiopathic peptic ulcer (atherosclerosis-related underlying disease or liver cirrhosis complications) were absent in 46.6% of patients. Absence of gastric mucosal atrophy (refractory group: 51.4%, healed group: 28.4%; p = 0.016), and gastric fundic gland polyps (refractory group: 17.6%, healed group: 5.9%; p = 0.045) were significantly more common in the refractory group compared to the healed group. A history of H. pylori eradication (refractory group: 85.3%, healed group: 66.0%; p = 0.016), previous H. pylori infection (i.e., gastric mucosal atrophy or history of H. pylori eradication) (refractory group: 48.5%, healed group: 80.0%; p = 0.001), and potassium-competitive acid blocker treatment (refractory group: 28.6%, healed group, 64.1%; p = 0.001) were significantly more frequent in the healed group compared to the refractory group. Thus, acid hypersecretion may be a major factor underlying the refractoriness of idiopathic peptic ulcer.

Helicobacter ailurogastricus in Patient with Multiple Refractory Gastric Ulcers, Japan.

We report the isolation of Helicobacter ailurogastricus, a Helicobacter species that infects cats and dogs, from a person with multiple refractory gastric ulcers. In addition to H. suis, which infects pigs, Helicobacter species that infect cats and dogs should be considered as potential gastric pathogens in humans.

Polyaspartic Acid-Stabilized CaCO3-Containing In Situ Hydrogel for Protection and Treatment of Gastric Ulcer.

The lack of effective oral drug delivery systems to treat gastric ulcer is an urgent challenge in clinical practice. Herein, a gastric acid pH-responsive hydrogel of curcumin/sodium alginate/polyaspartic acid@CaCO3 (Cur/SA/PC) was developed for sustained release of Cur, exerting effective protection and treatment of gastric ulcers. The in vitro gelatinization properties and the corresponding gel characteristics of the SA/PC delivery system demonstrated the successful construction of the in situ hydrogel with uniform strength. The cellular uptake illustrated the successful uptake and sustained release of Cur. Besides, Cur effectively inhibited NLRP3-mediated pyroptosis both in vitro and in vivo, exhibited an excellent pro-healing effect by regulating the PI3K/Akt signaling pathway, and alleviated acetic acid-induced chronic gastric injury in rats. Moreover, the relative bioavailability of Cur in the SA/PC hydrogel could effectively increase in the pharmacokinetic study. Importantly, the protective barrier formed by the SA/PC hydrogel could effectively protect against alcohol-induced acute gastric ulcers in rats. Overall, the designed SA/PC oral delivery system is a promising strategy to overcome gastric barriers for oral drug delivery.

Exploring the Effect of Deep-Sea Water on the Therapeutic Potential of the Anti-Inflammatory Response in an Indomethacin-Induced Gastric Ulcer Rat Model.

Gastric ulcers are often exacerbated by factors such as nonsteroidal anti-inflammatory drugs (NSAIDs) and inflammation, and they have a substantial impact on a significant portion of the population. Notably, indomethacin is recognized as a prominent contributor to ulcers. This study investigated this potential method, with normalization to the anti-inflammatory and antiulcer properties of deep-sea water (DSW)-derived mineral water, using an indomethacin-induced gastric ulcer model in rats. The study involved four groups (n = 6 rats/group): normal control group (CON), indomethacin-only group (IND), indomethacin with trace mineral water group (TM), and indomethacin with high magnesium low sodium water group (HMLS). For three weeks, the CON and IND groups consumed tap water, while the TM and HMLS groups had access to mineral water. Gastric ulcers were induced on the final day using indomethacin, for all groups except the CON group. The results demonstrated that HMLS intake significantly improved gastric mucosal damage, preserved mucin stability, and increased gastric thickness, indicating its potential to prevent and alleviate indomethacin-induced gastric ulcers. Furthermore, HMLS consumption led to the upregulation of key genes associated with inflammation and a reduction in inflammatory cytokines. These findings suggest that DSW-derived mineral water, and particularly its high Mg2+ content, may offer promising health benefits including anti-inflammatory and anti-ulcer properties.

Spirulina supplements: an approach moderating aspirin persuaded histological and ultra-structural alterations in albino rats gastric mucosa.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most used drugs. The pathogenesis of aspirin-induced gastric ulceration includes blocking the activities of the cyclooxygenase enzymes (COX-1 and COX-2) leading to reduced mucus and bicarbonate secretion. Spirulina contains many functional bioactive ingredients with antioxidant and anti-inflammatory activities, including phenolic phytochemicals and phycobiliprotein C-phycocyanin. To investigate the possible gastroprotective role of spirulina against aspirin-induced gastric mucosal insults. Forty adult male albino rats were randomly divided into four experimental groups. Group I (Control) and group II (Spirulina control) were given spirulina for 3 days, group III (Ulcer model) were given single dose of acetyl salicylic acid to induce ulcer and group IV (Treatment) were given spirulina for 3 days after induction of ulcer formation. Animals were sacrificed, stomachs were collected and processed for examination of light and scanning electron microscope histopathological examination. Statistical difference mucosal mucin area percentage among groups was determined and data were analyzed. Histological examination of the H&E-stained and combined Alcian-blue-PAS-stained sections of Group III rats illustrated severe destruction of the mucosal architecture and reduction of the mucin surface area while those examined for group IV illustrated minor affection of the gastric mucosa and mucin protective layer. Oxidant antioxidant markers: Nitric oxide (NO) is elevated, Glutathione (GSH) and superoxide dismutase (SOD) are reduced in aspirin treated group. The use of Spirulina restores the normal balance between the oxidant antioxidant system. Spirulina has a great potential in protecting the gastric mucosa against harmful effect of NSAID.

Geraniol accelerates the gastric healing, minimizes ulcers recurrence, and reduces anxiolytic-like behavior in ulcerated rodents by oral or inhaled route.

BACKGROUND: Geraniol (GE) is dietary acyclic monoterpene alcohol found in essential oils from aromatic plants with therapeutic value against gastric ulcers already described. HYPOTHESIS/PURPOSE: To assess whether oral GE accelerates gastric healing or prevents ulcer recurrence, and to evaluate the hypothesis that GE promotes antiulcer effects by the inhaled route and that promotes changes in the behavior of ulcerated rodents. METHODS: Gastric healing effects, underlining mechanisms, and behavioral changes were measured in80% acetic acid-induced gastric ulcer model in rats receiving GE by oral (30 mg/kg) or inhaled route (1 mg/L of air/min); whereas the effects of GE to avoid ulcer recurrence was evaluated in mice submitted to 10% acetic acid plus IL-1ß ulcer. RESULTS: GE administered by both routes accelerates gastric healing, increasing mucin and GSH levels, CAT, and GST activities, and reducing MPO activity. Moreover, oral, and inhaled GE minimized ulcer recurrence reducing gastric TNF and IL-6 levels and preserving mucin levels. Interestingly, the inhalation or oral intake of GE promotes anxiolytic-like effects in ulcerated rats. CONCLUSION: Data altogether suggest that the GE accelerates gastric healing through the strengthening of protective factors of the gastric mucosa, promoting a quality healing that reduces the recurrence of the lesion. Besides, the anxiolytic-like effect of GE may also contribute to its gastric healing action since anxiety is recognized as one of the etiologic agents of ulcers.

First Evidence of Gastroprotection by Schinus molle: Roles of Nitric Oxide, Prostaglandins, and Sulfhydryls Groups in Its Mechanism of Action.

Schinus molle is a plant traditionally used in Mexico to treat gastric disorders. However, no scientific evidence has been reported on its gastroprotective effect. The aim of the current contribution was to conduct a bioassay-guided study on S. molle to evaluate its gastroprotective activity in a model of Wistar rats given ethanol orally to induce gastric lesions. The hexane and dichloromethane extracts from the tested plant showed over 99% gastroprotection at a dose of 100 mg/kg. From the hexane extract, two of the three fractions (F1 and F2) afforded over 99% gastroprotection. The F1 fraction was subjected to column chromatography, which revealed a white solid. Based on the ESI-MS analysis, the two main compounds in this solid were identified. The predominant compound was probably a triterpene. This mixture of compounds furnished about 67% gastroprotection at a dose of 100 mg/kg. Pretreatment with L-NAME, indomethacin, and NEM was carried out to explore the possible involvement of nitric oxide, prostaglandins, and/or sulfhydryl groups, respectively, in the gastroprotective activity of the white solid. We found evidence for the participation of all three factors. No antisecretory activity was detected (tested by pylorus ligation). In conclusion, evidence is herein provided for the first time of the gastroprotective effect of S. molle.

Gastroprotective activity of (E)-ethyl-12-cyclohexyl-4,5-dihydroxydodec-2-enoate, a compound isolated from Heliotropium indicum: role of nitric oxide, prostaglandins, and sulfhydryls in its mechanism of action.

CONTEXT: The gastroprotective effect of Heliotropium indicum L. (Boraginaceae), a plant traditionally used in Mexico to treat gastric ulcers, has been previously reported. However, no active compound was identified. OBJECTIVE: The current contribution aimed to isolate, through a bioassay-guided study, at least one compound from H. indicum with considerable gastroprotective activity, examine its effect on ethanol-induced gastric lesions in mice, and explore possible mechanisms of action. MATERIALS AND METHODS: Three extracts (hexane, dichloromethane, and methanol) were obtained from H. indicum leaves. Their 30 and 100 mg/kg doses were assessed on ethanol-induced gastric lesions in male CD1 mice. Since the dichloromethane extract was the most active, successive chromatographies were carried out leading to the identification of the most active compound. This compound (at 3-100 mg/kg) was compared to carbenoxolone (at 10-100 mg/kg) in biological evaluations in mice. Pre-treatments with indomethacin (10 mg/kg, s.c.), L-NAME (70 mg/kg, i.p.), and NEM (10 mg/kg, s.c.) were performed independently to determine the participation of prostaglandins, nitric oxide, and/or sulfhydryl groups, respectively, in the mechanism of action of the compound. RESULTS: (E)-Ethyl-12-cyclohexyl-4,5-dihydroxydodec-2-enoate, a compound isolated from H. indicum, afforded dose-dependent gastroprotective activity. The maximum effect was observed at 100 mg/kg (90.13 ± 3.08%), with an ED50 of 5.92 ± 2.48 mg/kg. Gastroprotection was not modified by pre-treatment with indomethacin, L-NAME, or NEM. CONCLUSIONS: (E)-Ethyl-12-cyclohexyl-4,5-dihydroxydodec-2-enoate, isolated from H. indicum, was found to produce a substantial gastroprotective effect. Prostaglandins, nitric oxide, and non-protein sulfhydryl groups are not involved in its mechanism of action.

The Gastroprotective Effect of Naringenin against Ethanol-Induced Gastric Ulcers in Mice through Inhibiting Oxidative and Inflammatory Responses.

Naringenin is a major flavanone found in grapes, tangelos, blood oranges, lemons, pummelo, and tangerines. It is known to have anti-inflammatory, antioxidant, anticancer, antimutagenic, antifibrogenic, and antiatherogenic pharmacological properties. This study aims to investigate the anti-inflammatory effects of naringenin in ethanol-induced gastric damage in vivo and ethanol-stimulated KATO III cells in vitro. Our results showed that pretreatment with naringenin significantly protected mice from ethanol-induced hemorrhagic damage, epithelial cell loss, and edema with leucocytes. It reduced gastric ulcers (GU) by suppressing ethanol-induced nuclear factor-κB (NF-κB) activity and decreasing the levels of nitric oxide (NO), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and myeloperoxidase (MPO). In addition, pretreatment with naringenin might inhibit the secretion of TNF-α, IL-6, and IL-8, as well as the proteins cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) via the suppression of NF-κB and mitogen-activated protein kinase (MAPK) signaling in ethanol-stimulated stomach epithelial KATO III cells. Together, the results of this study highlight the gastroprotective effect of naringenin in GU of mice by inhibiting gastric secretion and acidity, reducing inflammation and oxidative stress, suppressing NF-κB activity, and restoring the histological architecture. These findings suggested that naringenin has therapeutic potential in the alleviation of ethanol-induced GU.

Development of raft-forming liquid and chewable tablet formulations incorporating quercetin solid dispersions for treatment of gastric ulcers.

Gastroretentive raft-forming formulations were developed in liquid and chewable tablet dosage forms to achieve prolonged delivery of quercetin in the stomach. The formulations contained a solid dispersion of quercetin and polyvinylpyrrolidone (PVP K 30) at a 1:10 w/w ratio to improve the solubility of the flavonoid. The formulations also contained sodium alginate as a gel forming agent, calcium carbonate as a calcium source and carbon dioxide producer and hydroxypropyl methylcellulose K100M as a drug release retarding polymer. The chewable tablets incorporated mannitol as a diluent. Both liquid and chewable tablet formulations exhibited rapid floating behaviour (lag time < 1 min) and long floating duration (>24 h) in 0.1 N HCl. The optimized liquid formulation showed superior characteristics based on high raft strength (10.4 g) and sustained release of quercetin (93 % over 8 h) whereas the optimized chewable tablet formulation exhibited lower raft strength (7.2 g) and lower drug release (79 % in 8 h). The optimized liquid and chewable tablet formulations were found to induce anti-inflammatory activity in cell culture using RAW 264.7 cells macrophages and enhance the migration of human gastric adenocarcinoma (AGS) epithelial cells in vitro, indicating wound healing potential for treatment of gastric ulcers.

Role of metaplasia during gastric regeneration.

Spasmolytic polypeptide/trefoil factor 2 (TFF2)-expressing metaplasia (SPEM) is a mucous-secreting reparative lineage that emerges at the ulcer margin in response to gastric injury. Under conditions of chronic inflammation with parietal cell loss, SPEM has been found to emerge and evolve into neoplasia. Cluster-of-differentiation gene 44 (CD44) is known to coordinate normal and metaplastic epithelial cell proliferation. In particular, CD44 variant isoform 9 (CD44v9) associates with the cystine-glutamate transporter xCT, stabilizes the protein, and provides defense against reactive oxygen species (ROS). xCT stabilization by CD44v9 leads to defense against ROS by cystine uptake, glutathione (GSH) synthesis, and maintenance of the redox balance within the intracellular environment. Furthermore, p38 signaling is a known downstream ROS target, leading to diminished cell proliferation and migration, two vital processes of gastric epithelial repair. CD44v9 emerges during repair of the gastric epithelium after injury, where it is coexpressed with other markers of SPEM. The regulatory mechanisms for the emergence of CD44v9 and the role of CD44v9 during the process of gastric epithelial regeneration are largely unknown. Inflammation and M2 macrophage infiltration have recently been demonstrated to play key roles in the induction of SPEM after injury. The following review proposes new insights into the functional role of metaplasia in the process of gastric regeneration in response to ulceration. Our insights are extrapolated from documented studies reporting oxyntic atrophy and SPEM development and our current unpublished findings using the acetic acid-induced gastric injury model.

Diagnostic Accuracy of a Noninvasive Test for Detection of Helicobacter pylori and Resistance to Clarithromycin in Stool by the Amplidiag H. pylori+ClariR Real-Time PCR Assay.

The noninvasive detection of Helicobacter pylori and its resistance to clarithromycin could revolutionize the management of H. pylori-infected patients by tailoring eradication treatment without any need for endoscopy when histology is not necessary. Several real-time PCR tests performed on stools have been proposed, but their performances were either poor or they were tested on too few patients to be properly evaluated. We conducted a prospective, multicenter study including 1,200 adult patients who were addressed for gastroduodenal endoscopy with gastric biopsies and who were naive for eradication treatment in order to evaluate the performance of the Amplidiag H. pylori+ClariR assay recently developed by Mobidiag (Espoo, Finland). The results of the Amplidiag H. pylori+ClariR assay performed on DNA from stools (automatic extraction with the EasyMag system [bioMérieux]) were compared with those of culture/Etest and quadruplex real-time PCRs performed on two gastric biopsy samples (from the antrum and corpus) to detect the H. pyloriglmM gene and mutations in the 23S rRNA genes conferring clarithromycin resistance. The sensitivity and specificity of the detection of H. pylori were 96.3% (95% confidence interval [CI], 92 to 98%) and 98.7% (95% CI, 97 to 99%), respectively. The positive and negative predictive values were evaluated to be 92.2% (95% CI, 92 to 98%) and 99.3% (95% CI, 98 to 99%), respectively. In this cohort, 160 patients (14.7%) were found to be infected (positive by culture and/or PCR). The sensitivity and specificity for detecting resistance to clarithromycin were 100% (95% CI, 88 to 100%) and 98.4% (95% CI, 94 to 99%), respectively.

Syntheses, in vitro urease inhibitory activities of urea and thiourea derivatives of tryptamine, their molecular docking and cytotoxic studies.

Urease is an enzyme of amidohydrolase family and is responsible for the different pathological conditions in the human body including peptic ulcers, catheter encrustation, kidney stone formation, hepatic coma, encephalopathy, and many others. Therefore, the search for potent urease inhibitors has attracted major scientific attention in recent years. Urea and thiourea derivatives of tryptamine (1-25) were synthesized via reaction of tryptamine with different substituted phenyl isocyanates/isothiocyanates. The synthetic compounds were evaluated for their urease enzyme inhibitory activity and they exhibited good inhibitory potential against urease enzyme in the range of (IC50 = 11.4 ±â€¯0.4-24.2 ±â€¯1.5 µM) as compared to the standard thiourea (IC50 = 21.2 ±â€¯1.3 µM). Out of twenty-five compounds, fourteen were found to be more active than the standard. Limited structure-activity relationship suggested that the compounds with CH3, and OCH3 substituents at aryl part were the most potent derivatives. Compound 14 (IC50 = 11.4 ±â€¯0.4 µM) with a methyl substituent at ortho position was found to be the most active member of the series. Whereas, among halogen substituted derivatives, para substituted chloro compound 16 (IC50 = 13.7 ±â€¯0.9 µM) showed good urease inhibitory activity. These synthetic derivatives were found to be non-cytotoxic in cellular assay. Kinetic studies revealed that the compounds 11, 12, 14, 17, 21, 22, and 24 showed a non-competitive type of inhibition. In silico study identified the possible bindings interactions of potential inhibitors with the active site of enzyme. These newly identified inhibitors of urease enzyme can serve as leads for further research and development.

Influence of Helicobacter pylori virulence factors CagA and VacA on pathogenesis of gastrointestinal disorders.

Helicobacter Pylori (H. pylori) is a gram-negative bacteria infecting numerous people all over the world. It has been established that H. pylori play an important role in pathogenesis of gastritis, peptic ulcer and gastric cancer. Pathogenic features of this bacterium are mainly attributes to the existence of pathogenic islands (PAI) genes. The most known genes in these islands are cytotoxin-associated gene A (CagA) and vacuolating cytotoxin gene (VacA). Most studies demonstrated various frequency of CagA and VacA in patient with peptic ulcer or gastritis in different countries. This variation in CagA and VacA frequency may be due to the capability of this bacterium to be genetically versatile and can alter the expression of these genes with geographic diversity. Although H. pylori infection is not usually associated with any clinical symptoms, but sometimes leads to inflammation in gastrointestinal system and resulted in peptic ulcer and gastric cancer. In this regard, this review will illustrate the importance of Helicobacter pylori in pathogenesis of gastrointestinal disorders with focusing on CagA and VacA virulence factors.

Evaluation of anti-inflammatory and ulcerogenic potential of zinc-ibuprofen and zinc-naproxen complexes in rats.

Because of numerous indications and high availability, non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed and used medicines in the world. However, long-term therapy with and improper use of NSAIDs may lead to gastrointestinal damage. Therefore, improving the therapeutic index of the existing drugs has become a priority over the past decades. Considerable attention in the field has been concentrated on metal complexes of non-steroidal anti-inflammatory drugs. The aim of this study is to evaluate the effect of complexation with zinc on the anti-inflammatory and ulcerogenic effects of ibuprofen and naproxen after single and triple intragastric administration to rats. The anti-inflammatory effect was assessed in carrageenan-induced inflammatory edema in the hind paw of male albino Wistar rats. The mucosal lesions were inspected and evaluated for gross pathology. Single administration of both the investigated complexes, namely zinc-ibuprofen and zinc-naproxen (20 mg/kg equivalent to ibuprofen and naproxen, respectively) and their parent drugs and physical mixtures with zinc hydroaspartate (ZHA doses: 16.05 and 14.37 mg/kg), caused a significant reduction of the edema after the same time from the carrageenan injection in comparison to the control groups. However, no statistically significant differences between the investigated drugs were observed after their single administration. The mean ulceration score for the mixture of ibuprofen and ZHA was statistically lower than the mean score achieved in rats after treatment with ibuprofen alone. On the other hand, triple intragastric administration of the ZHA-ibuprofen and ZHA-naproxen combination showed substantial enhancement of the anti-inflammatory activity against control groups, as well as against the parent NSAIDs. The most potent anti-inflammatory activity was demonstrated after 2 h from the carrageenan injection in animals receiving ZHA together with naproxen. The edema growth was reduced in these animals by 80.9% as compared to the control group. This result was significantly higher than the results achieved in animals receiving zinc-naproxen (50.2%) or naproxen alone (47.9%). Both NSAID complexes with zinc and mixtures with ZHA alleviated ulcerations caused by parent NSAIDs; however, the mixtures of both ibuprofen and naproxen with ZHA after triple administration were the least damaging. In view of the above results, zinc supplementation during NSAID therapy may have a beneficial effect on ulcer prevention and healing by reducing the effective dose of the parent drug and increasing its potency.

A pilot study comparing the effect of orally administered esomeprazole and omeprazole on gastric fluid pH in horses.

AIMS To compare the efficacy of an enteric coated esomeprazole paste with an enteric coated omeprazole paste to increase gastric pH after oral administration in horses. METHODS Nine adult Standardbred horses were randomly assigned to three groups, each containing three horses, for a study comprising three phases of 10 days, with an 18-day washout period between each phase. In each phase, three horses received either 0.5 mg/kg esomeprazole, 1 mg/kg omeprazole or a placebo, as an oral paste, once daily for 10 days (Days 0-9). Over the course of study all horses received all three treatments. Gastric fluid samples were collected using a gastroscope on Days 1, 3, 5, 8 and 10, with food and water withheld for 16 hours prior to collection of samples. The pH of all samples was measured immediately after collection. RESULTS Mean pH (3.38; SD 1.75) of the gastric fluid samples in the horses that received the placebo was lower than in the horses that received esomeprazole (6.28; SD 1.75) or omeprazole (6.13; SD 1.75) (p<0.001). There was no difference in the mean pH between horses receiving esomeprazole and those receiving omeprazole (p=0.56). CONCLUSIONS AND CLINICAL RELEVANCE Under these study conditions, esomeprazole paste was equally as effective as omeprazole paste in increasing gastric pH in horses. Enteric coated esomeprazole, may be a therapeutic alternative to omeprazole for the prevention of gastric ulcers in horses.

Gastric injury from (90)Y to left hepatic lobe tumors adjacent to the stomach: fact or fiction?

PURPOSE: Radioembolization with (90)Y microspheres is a locoregional radiation therapy for unresectable hepatic neoplasm. Non-target delivery of (90)Y microspheres resulting in gastrointestinal (GI) symptoms is a recognized complication; there is minimal knowledge regarding the radiation effect to the gastric wall from left hepatic lobe (90)Y treatments. Our aim was to study the incidence of GI complications when the target tissue (hepatic parenchyma ± tumor) is in close proximity to the gastric wall. We hypothesized that liver (tumor) to stomach proximity does not correlate with increased toxicity. METHODS: Between November 2011 and September 2013, we studied all patients who underwent left lobe radioembolization with (90)Y glass microspheres. With Institutional Review Board (IRB) approval, we retrospectively reviewed MRI/CT images of these patients, identifying a subset of patients with the left hepatic lobe <1 cm from the gastric wall. Patients were seen in clinic 1 month posttreatment and subsequently at 3-month intervals. Short- and long-term gastric adverse events were tabulated. RESULTS: Ninety-seven patients successfully underwent left hepatic lobe (90)Y microsphere radioembolization in which the average distance from the liver to the stomach wall was 1.0 ± 2.8 mm. The average dose for patients who received radioembolization to the left hepatic lobe was 109 ± 57 Gy. Fifty patients had tumor within 1 cm of the gastric wall. The average dose for patients who received radioembolization to the left hepatic lobe with tumor within 1 cm of the gastric wall was 121 ± 41 Gy. There were no reportable or recordable medical events. Of the patients, 34% reported abdominal pain that was grade 1-2; 65% of the patients reported no abdominal pain. None of the 97 patients developed a clinically evident GI ulcer. CONCLUSION: Patients with left lobe tumors adjacent to or abutting the stomach do not exhibit acute or chronic radiation effects following radioembolization with glass microspheres.

Effects of kramecyne on LPS induced chronic inflammation and gastric ulcers.

Preclinical Research Krameria cytisoides is used for the treatment of inflammation, stomach pain, and gastric ulcers. The active ingredient from this plant is a peroxide, kramecyne (KACY) which has anti-inflammatory effects. The aim of the present study was to evaluate the anti-inflammatory activities of KACY in lipopolysaccharide (LPS)-induced systemic chronic inflammation in mice for 60 days, using dexamethasone (DEX) as the positive control, vehicle (the LPS group) as the negative control and the control group (mice without inflammation). KACY did not affect survival, body weight or relative organ weight in mice but it: decreased nitric oxide (NO) production by 68%; prostaglandin E2 (PGE2 ) by 67%; increased release of anti-inflammatory cytokine IL-10 (2.0-fold), and reduced production of the proinflammatory cytokines, IL-6 (2.0-fold), IL-1ß (2.4-fold), and TNF-α (2.0-fold). Furthermore, the gastroprotective effects of KACY in mice were evaluated in an ethanol-induced gastric ulcer model. The results showed that KACY at 50 and 100 mg/kg exerted gastroprotective effects with similar activity to 50 mg/kg ranitidine. In gastric tissues, KACY decreased the level of malondialdehyde (MDA) but increased the catalase (CAT) activity. KACY have potential for the treatment of chronic inflammatory diseases due its similar activity to that of DEX. It also has gastroprotective effects.

The increased gastroprotective effect of pioglitazone in cholestatic rats: role of nitric oxide and tumour necrosis factor alpha.

The prevalence of gastric ulcers is high in cholestatic patients, but the exact mechanism of this increased frequency remains uncertain. It has been shown that pioglitazone accelerates the healing of pre-existing gastric ulcers. The present study was designed to investigate the effect of pioglitazone, on the gastric mucosal lesions in cholestatic rats. Cholestasis was induced by surgical ligation of common bile duct and sham-operated rats served as control. Different groups of sham and cholestatic animals received solvent or pioglitazone (5, 15, 30 mg/kg) for 7 days. On the day eight rats were killed after oral ethanol administration and the area of gastric lesions was measured. The serums of rats were also collected to determine serum levels of tumour necrosis factor alpha (TNF-α), IL-1ß and bilirubin. The ethanol-induced gastric mucosal damage was significantly more severe in cholestatic rats than sham-operated ones. Pretreatment with pioglitazone dose-dependently attenuated gastric lesions induced by ethanol in both sham and cholestatic rats, but this effect was more prominent in cholestatic ones. The effect of pioglitazone was associated with a significant fall in serum levels of TNF-α in cholestatic rats. L-NAME, a non-selective nitric oxide synthase (NOS) inhibitor, and decreased pioglitazone-induced gastroprotective effect in cholestatic rats, while aminoguanidine, a selective inducible NOS inhibitor, potentiated pioglitazone-induced gastroprotective effect in the cholestatic rats. Chronic treatment with pioglitazone exerts an enhanced gastroprotective effect on the stomach ulcers of cholestatic rats compared to sham rats probably due to constitutive NOS induction and/or inducible NOS inhibition and attenuating release of TNF-α.