NSAID-induced Ulcers Research Articles

Pharmaceuticals agents for preventing NSAID-induced gastric ulcers: a patent review

ABSTRACT Introduction Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of drugs widely used due to their pharmacological potential, demonstrating anti-inflammatory, analgesic, or antipyretic activity. However, prolonged use of these medications can lead to the development of gastric ulcers in patients. This review aimed to find patents for drugs with an anti-inflammatory and gastroprotective character to treat NSAID-induced gastric ulcers. Areas covered For the treatment of NSAID-induced gastric ulcers, formulations with different action mechanisms were found, including donors of nitric oxide, heterocyclic compounds, and natural products. Expert Opinion Many of the structures found have already been used in clinic settings and others, and according to the results found, they are promising for the treatment of gastric ulcers.

Peptic Ulcer Disease: An Overview of Aetiology, Pathophysiology, Clinical Presentation, Diagnosis and Treatment Options

Introduction: Peptic ulcer disease (PUD) is endemic in all parts of the world. It is estimated that as high as 5-10% of the world’s population is affected by PUD. Disruption in the gastric protective factors within the gastrointestinal lumen is responsible for the development of PUD. Aggravating factors that promote formation of peptic ulcers include gastric acids, decreased bicarbonate and general decrease in mucosal defences. Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (H. pylori) infection are the two major aetiologic factors contributing to damages to the mucosal defence. The major clinical symptom of PUD is epigastric pain. Others includes bloating, heartburn, nausea or vomiting. Testing for H. pylori is important in treatment of PUD. The major complications of H pylori-associated and NSAID-induced ulcers include upper gastrointestinal bleeding, perforation, penetration, gastric outlet obstruction and gastric adenocarcinoma. Purpose: The purpose of this review is to present a general overview of the aetiology, pathophysiology, clinical presentation, diagnosis and treatment options for peptic ulcer disease (PUD). Conclusion: PUD remains a global health challenge requiring that all patients should be treated. Conventional treatments include gastric acid suppressing agents such as proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists as well as mucosal protective agents. Eradication of H. Pylori is critical in pharmacotherapy of H. pylori associate PUD. New approaches to treatments may include the use of antioxidants containing medicinal plants.

Prevention of Non-steroidal Anti-inflammatory Drug-induced Peptic Ulcers.

Nonsteroidal anti-inflammatory drugs (NSAID) are some of the most commonly prescribed medications in clinical practice. The long-term use of NSAIDs is one of the main causes of peptic ulcers and the increased risk of upper gastrointestinal tract complications, such as perforation and bleeding. Thus, the prevention of NSAID-induced peptic ulcers is an important clinical issue. Previous studies have evaluated various strategies for preventing ulcers in patients requiring prolonged NSAID use. The Korean clinical practice guidelines have been published recently based on the evidence of the currently available data. This review describes the strategies for the prevention of peptic ulcers due to NSAID. An assessment of the risk factors for peptic ulcers from NSAID is recommended to identify patients who should be considered for primary prophylaxis. The risk of NSAID-induced peptic ulcers can be reduced by the concomitant use of proton pump inhibitors (PPI), misoprostol, and histamine-2 receptor antagonists. Selective cyclooxygenase-2 inhibitors can be used with caution due to concerns regarding cardiovascular toxicity. Attempts should be made to use the lowest dose and shortest duration of the NSAID.

Protective Effects of Quercetin and Melatonin on Indomethacin Induced Gastric Ulcers in Rats.

Medications to prevent the development of NSAID-induced gastric ulcers have a large range of unpleasant side effects. Recent efforts have been focused on determining safer alternative nontoxic and natural forms of anti-ulcer treatments. Twenty-four male rats were divided into 4 groups: 1: control group that received no treatment; 2: the ndomethacin-treated group that received 20 mg/kg of indomethacin for 2 days to induce the development of gastric ulcers; 3: quercetin-treated group that in addition to the indomethacin treatment, received 50 mg/kg of quercetin 6 hours after and then daily for 14 days and; 4: the melatonin-treated group which received 20 mg/kg of melatonin 6 hours after each indomethacin treatment and then daily for 14 days. All drugs were administered orally. The following parameters were assessed in each group: mean ulcer index of gastric tissue, gastric acid volume and pH, oxidative stress markers: malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH), inflammatory markers: PGE-2, TNF-α, and IL-10, nitric oxide (NO) levels and the relative gene expression of BAX, BCL-2 and COX-2 by real time PCR. Our findings revealed that the indomethacin-treated group had a significantly increased (p< 0.05) ulcer index, gastric acid volume, and elevated levels of stress, inflammatory, and apoptotic markers compared to controls. In the groups that received quercetin or melatonin, these factors were all significantly decreased (p< 0.05). Between quercetin and melatonin, there was no significant difference in their gastroprotective effect. Both quercetin and melatonin had protective antioxidant, anti-inflammatory and antiapoptotic activity against indomethacin-induced gastric ulcers.

Galectin-3 as a Therapeutic Target for NSAID-Induced Intestinal Ulcers.

Non-steroidal anti-inflammatory drugs (NSAIDs) induce ulcers in the gastrointestinal tract, including the stomach and small intestine. NSAID-induced gastric ulcers can be prevented by taking acid-neutralizing/inhibitory drugs and cytoprotective agents. In contrast, there are no medicines to control NSAID-induced small intestinal ulcers, which are accompanied by a mucosal invasion of bacteria and subsequent activation of immune cells. Galectin-3 (Gal3), an endogenous lectin, has anti-microbial and pro-inflammatory functions. In the small intestine, since Gal3 is highly expressed in epithelial cells constitutively and macrophages inducibly, the Gal3 level can affect microbiota composition and macrophage activation. We hypothesized that the modulation of Gal3 expression could be beneficial in NSAID-induced intestinal ulcers. Using Gal3 knockout (Gal3KO) mice, we determined whether Gal3 could be a therapeutic target in NSAID-induced intestinal ulcers. Following the administration of indomethacin, an NSAID, we found that small intestinal ulcers were less severe in Gal3KO mice than in wild-type (WT) mice. We also found that the composition of intestinal microbiota was different between WT and Gal3KO mice and that bactericidal antibiotic polymyxin B treatment significantly suppressed NSAID-induced ulcers. Furthermore, clodronate, a macrophage modulator, attenuated NSAID-induced ulcers. Therefore, Gal3 could be an exacerbating factor in NSAID-induced intestinal ulcers by affecting the intestinal microbiota population and macrophage activity. Inhibition of Gal3 may be a therapeutic strategy in NSAID-induced intestinal ulcers.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT03832946.

Pumpkin Oil-Based Nanostructured Lipid Carrier System for Antiulcer Effect in NSAID-Induced Gastric Ulcer Model in Rats.

BackgroundPeptic ulcer disease, a painful lesion of the gastric mucosa, is considered one of the most common gastrointestinal disorders. This study aims to investigate the formulation of pumpkin seed oil (PSO)-based nanostructured lipid carriers (NLCs) to utilize PSO as the liquid lipid component of NLCs and to achieve oil dispersion in the nano-range in the stomach.MethodsBox–Behnken design was utilized to deduce the optimum formula with minimum particle size. The optimized PSO-NLCs formula was investigated for gastric ulcer protective effects in Wistar rats by evaluating ulcer index and determination of gastric mucosa oxidative stress parameters.ResultsPSO was successfully incorporated as the liquid lipid (LL) component of NLCs. The prepared optimum PSO-NLCs formula showed a size of 64.3 nm. Pretreatment of animals using the optimized PSO-NLCs formula showed significantly (p< 0.001) lower ulcer index compared to indomethacin alone group and significantly (p<0.05) less mucosal lesions compared to the raw oil.ConclusionThese results indicated great potential for future application of optimized PSO-NLCs formula for antiulcer effect in non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulcer.

Malabaricone C Attenuates Nonsteroidal Anti-Inflammatory Drug-Induced Gastric Ulceration by Decreasing Oxidative/Nitrative Stress and Inflammation and Promoting Angiogenic Autohealing.

Aims: Nonsteroidal anti-inflammatory drugs (NSAIDs), among the most commonly used drugs worldwide, are associated with gastrointestinal (GI) complications that severely limit the clinical utility of this essential class of pain medications. Here, we mechanistically dissect the protective impact of a natural product, malabaricone C (Mal C), on NSAID-induced gastropathy. Results: Mal C dose dependently diminished erosion of the stomach lining and inflammation in mice treated with NSAIDs with the protective impact translating to improvement in survival. By decreasing oxidative and nitrative stress, Mal C treatment prevented NSAID-induced mitochondrial dysfunction and cell death; nuclear factor κ-light-chain enhancer of activated B cell induction, release of proinflammatory cytokines and neutrophil infiltration; and disruptions in the vascular endothelial growth factor/endostatin balance that contributes to mucosal autohealing. Importantly, Mal C failed to impact the therapeutic anti-inflammatory properties of multiple NSAIDs in a model of acute inflammation. In all assays tested, Mal C proved as or more efficacious than the current first-line therapy for NSAID-dependent GI complications, the proton pump inhibitor omeprazole. Innovation: Given that omeprazole-mediated prophylaxis is, itself, associated with a shift in NSAID-driven GI complications from the upper GI to the lower GI system, there is a clear and present need for novel therapeutics aimed at ameliorating NSAID-induced gastropathy. Mal C provided significant protection against NSAID-induced gastric ulcerations impacting multiple critical signaling cascades contributing to inflammation, cell loss, extracellular matrix degradation, and angiogenic autohealing. Conclusion: Thus, Mal C represents a viable lead compound for the development of novel gastroprotective agents.

Study of the Inhibitory Effects of Enteral Nutrition Formula on Indomethacin-Induced Gastric Lesions in Mice.

We investigated the effects of enteral nutrition formula on non-steroidal anti-inflammatory drug (NSAID)-induced gastric lesions in mice. Male ICR mice aged 7–9 weeks old were fasted, then orally given either purified water, Mermed® One, or 2-fold diluted Terumeal® 2.0α as enteral nutrition (25 or 50 mL/kg each). Indomethacin (IND) was orally administered at 20 mg/kg after 30 min, and the stomach was removed 6 h later and fixed in formalin. The number and area of lesions in the stomachs of the mice given enteral nutrition showed a significant, dose-dependent decrease compared to the purified water-treated group, and no significant difference was seen between the two enteral nutrition-treated groups. Comparable time courses of plasma IND concentrations suggest that enteral nutrition does not inhibit gastrointestinal absorption of IND. Our findings indicate that administering enteral nutrition could inhibit the onset of NSAID-induced gastric ulcers.

Secreting healing factors

Regenerative Medicine One of the main complications associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is the development of gastric ulcers. Proton-pump inhibitors are used to alleviate this condition; however, they are also associated with serious adverse events. Xia et al. developed a porcine model of NSAID-induced gastric ulcers and showed that intragastric administration of adipose tissue–derived mesenchymal stem cells rapidly promoted healing and reduced gastric inflammation. The therapeutic effect was mediated by activation of signaling pathways in ulcer tissue induced by stem cell–secreted factors. Mesenchymal stem cells or their secretome could be useful in treating NSAID-induced gastric ulcers. Sci. Transl. Med. 11 , eaat7455 (2019).

2032 Push Enteroscopy in the Diagnosis of a Gastrointestinal Bleed Caused by Diffuse Large B-Cell Lymphoma

INTRODUCTION: Only 5-10% of gastrointestinal bleeding is from the small intestine, and in these cases, video capsule endoscopy (VCE) is considered as a first line procedure for small bowel investigation. The most common causes of small intestinal bleeding in patients older than 40 years include angioectasias and NSAID-induced ulcers. In younger patients, its is more common to see bleeding events as a result of Crohn disease, Meckel diverticula, Dieulafoy lesions, and tumors. Celiac disease can cause bleeding in both age groups. Our case reports on an uncommon presentation of a rare gastrointestinal malignancy, and the utility of push enteroscopy in the diagnosis thereof. CASE DESCRIPTION/METHODS: A 77-year-old female with a past medical history of gastric carcinoid, iron deficiency anemia, and history of pulmonary embolism now on rivaroxaban had presented after a syncopal episode. Upon review of systems, the patient did report dark stools, which she attributed to her iron pills. On presentation, the patient was found to have severe iron deficiency anemia and heme-positive stools. EGD and colonoscopy were performed, which did not reveal an active source of bleeding. She was taken off of rivaroxaban and her hemoglobin subsequently stabilized and she had no further episodes of melena. She was discharged with instructions to follow up for an outpatient VCE. Ten days later, before the scheduled VCE, the patient returned to the hospital with another episode of melena, and was again found to have a substantial decline in her hemoglobin. The patient then underwent push enteroscopy, which revealed multiple actively bleeding, cratered ulcers ranging in size from 10 mm to 20 mm in the distal duodenum and proximal jejunum which were endoscopically ablated. Biopsy of these ulcers was positive for non-germinal center derived diffuse large B-cell lymphoma. The patient was subsequently transferred to a tertiary care center for further staging and possible treatment. DISCUSSION: This case demonstrates the utility of push enteroscopy for both diagnosis and treatment in clinically significant, obscure, occult gastrointestinal bleeds. In this patient in particular, it also enabled the early diagnosis of a rare and morbid malignancy for which survival without treatment is measured in months. While small bowel tumors are among the most common causes of obscure GI bleed in young patient, this is a rare finding in the elderly. As this case demonstrates though, the possibility of malignancy should not be overlooked.

1884 Migration of Embolization Coil in a Crohn’s Patient With NSAID-Induced Peptic Ulcer Disease

INTRODUCTION: Peptic ulcer-related bleeding has a high mortality rate if not controlled. If endoscopic interventions fail, interventional radiology or surgical intervention is often considered. We report a case of rare complication of Transcatheter Arterial Embolization (TAE) for bleeding duodenal ulcer in a patient with Crohn’s Disease. CASE DESCRIPTION/METHODS: A 69-year-old female with a previous medical history of Crohn's colitis (on prednisone taper for active Crohn’s disease/pending initiation of biologic therapy) presented to the emergency department for generalized weakness, nausea, non-bloody, non-bilious emesis and melena. No prior history of gastrointestinal bleeding, antiplatelet or anticoagulation use was reported. Medications includes: Prednisone 20mg and Naproxen 400mg (BID or TID). Hemoglobin was 6.0 (11.0-16.2 g/dL), BUN 46 (8-26mg/dL), Cr 1.54 (0.44 – 1.00 mg/dL). Upper GI bleed was suspected with the initiation of Pantoprazole 80mg IV, 3 units of pRBC and Intravenous fluids. Endoscopy performed post-resuscitation revealed LA Grade D esophagitis, large non-bleeding duodenal bulb ulcer with extension into the sweep. No endoscopic therapy was performed. Twenty hours later, the patient became hemodynamically unstable requiring massive transfusion. As ulcer was not amenable to endoscopic therapy, Interventional radiology was consulted who TAE with the placement of two coils in the gastroduodenal artery (GDA). The patient tolerated the procedure well without any recurrence of bleeding. A follow-up endoscopy four weeks later, showed improvement in ulceration with only a 3-4 mm area of non-bleeding, healing ulcer with a coil protruding from ulcer site. The coil was left in place without any manipulation to the area. The patient was advised to discontinue NSAIDs and continue Pantoprazole 40 mg BID. In the interim, the patient was started on Vedolizumab (Entyvio) with improvement in CRP and abdominal pain. DISCUSSION: Embolization of GDA is safe and effective in patients with high surgical risk. Complications such as duodenal ischemia, hepatic artery embolization, duodenal stenosis do exist. Migration/Erosion of coil into lumen can occur, especially in a patient with active Crohn’s disease. Ulceration surrounding the coil can occur with a consequence of bleeding, which would require surgical intervention if endoscopic hemostasis is unable to be achieved.

Etiology of isolated terminal ileal ulcers in symptomatic patients

Introduction: Isolated terminal ileal ulcers (ITIUs) are being frequently encountered by the clinicians with the increasing numbers of ileal intubation during colonoscopies. This study was aimed at finding the etiologies of these ulcers in symptomatic patients and their association with various clinical features.&#x0D; Methods: This was a hospital based prospective, observational, descriptive study performed on all consecutive patients who underwent ileocolonoscopy for various gastrointestinal symptoms between 1 July 2018 and 30 June 2019. Clinical, endoscopic and histopathological findings were analyzed to determine the etiology of ITIUs in symptomatic patients. Statistical analysis was done by SPSS 20.&#x0D; Results: Among 60 (7.67%) of 782 symptomatic patients who had ITIUs on ileocolonoscopy, specific etiologies were established in 28 (46.67%) of them. Intestinal TB was the most common specific diagnosis, which was seen in 18 (30%) patients. Chronic abdominal pain with or without chronic diarrhea was the most common indication for ileocolonoscopy.&#x0D; Conclusions: Specific etiologies like tuberculosis, Crohn’s disease, NSAID-induced ulcer and intestinal spirochetosis were seen in 28 (46.67%) of patients with isolated terminal ileal ulcers. The most common clinical features were chronic abdominal pain (65%) and abdominal pain with diarrhea (16.7%). No clinical presentation was significantly associated with any specific etiology, thus emphasizing the need for routine ileal intubation and tissue sampling for histopathological examination in all symptomatic patients undergoing colonoscopy.

Recurrent lymphoma as a cause of obscure massive small bowel bleeding

Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy that accounts for the largest proportion of non-Hodgkin lymphoma. Recurrent lymphoma is unusual to present as obscure massive small bowel bleeding, especially after long-standing remission. This case describes a 72-year-old man with a history of DLBCL presenting with gastrointestinal hemorrhage. Common causes of small bowel bleeding include underlying Crohn’s disease, arteriovenous malformations, Dieulafoy’s lesion, or NSAID-induced ulcers, and malignant neoplasms. Because massive small bowel bleeding is extremely rare, it is crucial to evaluate with a systematic approach using both radiographic and endoscopic imaging to determine the source of bleeding.

Selective serotonin reuptake inhibitor fluvoxamine ameliorates stress- and NSAID-induced peptic ulcer possibly by involving Hsp70.

Background Selective serotonin reuptake inhibitors (SSRIs) have recently become potential candidates for a new therapeutic approach to ulcer and gastric bleeding. Heat shock protein 70 (Hsp70) plays an important role in cellular resistance to nonsteroidal anti-inflammatory drugs (NSAIDs). However, there is lack of evidence that fluvoxamine recruits Hsp70 to affect stress-induced gastric ulcer. Therefore, we investigated the effect of fluvoxamine on NSAID- and stress-induced gastric ulcer and the possible involvement of Hsp70. Methods ICR mice were used in the study. Stress induction was made by the water-immersion-plus-restraint method. NSAID-induced gastric ulcer was produced by oral administration of indomethacin. Fluvoxamine was given orally 30 min before stress induction and indomethacin treatment. Results Stress and indomethacin treatment significantly increased the ulcer index and intraluminal bleeding score. Stress and indomethacin treatment also significantly increased the expression of Hsp70. Fluvoxamine significantly decreased the ulcer index and intraluminal bleeding in both ulcer models. Moreover, fluvoxamine further increased the expression of Hsp70 in the gastric tissue of stress- and indomethacin-treated mice. Conclusions Our results indicate that fluvoxamine may have a protective effect against stress- as well as NSAID-induced gastric ulcer. In addition, the present study suggests the possible involvement of Hsp70 in the amelioration of gastric ulcer by fluvoxamine.

EXPRESSIONS OF BASIC FIBROBLAST GROWTH FACTOR IN THE PEPTIC ULCER HEALING DUE THE NONSTEROIDAL ANTI-INFLAMMATORY DRUGS

Background: Basic Fibroblast Growth Factor (bFGF) or FGF2 is the most active angiogenic peptide and plays important role in the pathogenesis of ulcers healing. High levels of bFGF have been describe in healing ulcer in gastrointestinal (GI) or systemic disease. However, its role in phase of peptic ulcer especially at NSAIDs user remains limited data in human. This study was to know the expressions of bFGF in the process of NSAID-induced peptic ulcer healing. Method: Peptic ulcer biopsies were processed for immunohistochemical staining characterization from 46 patients with a history of NSAIDs consumption and upper GI bleeding. Expression of bFGF was quantified as semiquantitative scoring of positive stain as a whole (from 0-+3). Phase evaluation of healing peptic ulcer (Active=A), Healing=H, Cicatrix=C) by Sakita and Fukotomi endoscopy classification. Results: Twenty-seven (58,7%) subject were male patient, mean age 61 ± 8 years and most frequently consumed NSAIDs are meloxicam (12/26,1%). Majority of the subject was in active (A) phase of peptic ulcer healing (27/58,7%). Expression of bFGF was significantly higher in patients with A phase (2.4±0,5) compared with H and C Phase (1.2±0.4; 0.4±0.5 respectively; p

Misoprostol for NSAID-induced small bowel erosions and ulcers

Misoprostol for NSAID-induced small bowel erosions and ulcers

An Uncommon Cause of a Refractory Gastric Ulcer

A 29-year-old female with a history of bipolar disorder presented to the emergency department (ED) with worsening epigastric pain. Two years ago, esophagogastroduodenoscopy (EGD) showed a 1.5-cm benign-appearing superficial ulcer in the pylorus. She was presumed to have an NSAID-induced peptic ulcer and was treated with proton pump inhibitor therapy. She had multiple hospitalizations for abdominal pain and several subsequent EGDs showing refractory gastric ulcer.

Characteristics of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)-Induced Small Bowel Injury Identified by Single-Balloon Endoscopy or Capsule Endoscopy.

BackgroundThe special features of nonsteroidal anti-inflammatory drugs (NSAIDs) enteropathy were partially clarified by single-balloon endoscopy(SBE).We aimed to investigate the characteristics of NSAIDs injuries that were differ from other ulcer diseases and efficacy of SBE compared with capsule endoscopy(CE).Material/Methods1,644 symptomatic patients (221 patients taking NSAIDs) hospitalized between January 2006 and March 2016 were recruited and underwent SBE and/or CE.ResultsNSAIDs damages were identified in 110 patients (49.77%). The special features of NSAIDs lesions included: variform, superficial, multiple and irregular arrangement; <1 cm in diameter (67.27%); the location in jejunum and ileum was similar; ileocecal valve was rarely influenced (20.91%). The specificity and positive predictive value of SBE for diagnosing NSAIDs breaks were higher than CE (95.74% vs. 80.00%; 95.45% vs. 81.63%, p<0.05). There were no differences in the detection rate and the diagnostic accuracy rate of small bowel diseases between SBE and CE in the NSAIDs group (69.4% vs. 66.3% and 83.58% vs. 80.65%, p>0.05 respectively). The consistency in diagnosing NSAIDs breaks for the 2 methods was 82.61%. More tiny lesions at the distal ileum were detected by SBE. Four patients misdiagnosed by CE got accurate diagnose through biopsy by SBE. Three patients with active bleeding caused by NSAIDs-induced ulcers underwent hemostasis successfully by SBE.ConclusionsNSAIDs injuries might be distinguished from other diseases by endoscopic features and biopsy through SBE, which appeared to be an effective method for diagnosis and treatment.

Symptomatic isolated terminal ileal ulcers: etiology and clinical significance.

Background With an increasing number of ileal intubations, isolated terminal ileal ulcers (ITIU) are frequently found during colonoscopies. The present study aimed at studying the etiology and clinical significance of these ulcers in patients having gastrointestinal symptoms. Methods This was a prospective observational study performed on consecutive patients who underwent ileocolonoscopy for various gastrointestinal symptoms between 1 January 2014 and 31 December 2014. Clinical, endoscopic, and histological findings of patients with ITIUs were assessed to determine the etiology and they were treated accordingly. Symptom resolution was assessed within 3 – 6 months of initial diagnosis, and colonoscopy was repeated for consenting patients. Results Among 74 (4.9 %) of 1497 patients who had ITIUs on ileocolonoscopy, 41 (55.4 %) had specific etiologies on initial testing. After 3 – 6 months follow-up, definitive diagnosis was ascertained in 44 (59.5 %) patients [Crohn’s disease (CD): 19 (25.7 %), NSAID-induced ulcers: 11 (14.9 %), intestinal tuberculosis (ITB): 9 (12.2 %), and eosinophilic enteritis: 5 (6.8 %)], and 30 patients (40.5 %) had nonspecific ulcers. After treatment, symptomatic and endoscopic resolution were noted in 55/60 patients (91.7 %) and 28/36 patients (77.8 %), respectively. Of 5/60 patients who remained symptomatic, three were initially diagnosed with nonspecific ulcers and two with CD, and they were finally diagnosed with CD and ITB respectively, and treated accordingly. Conclusions In patients with gastrointestinal symptoms, more than half of the ITIUs have specific etiologies, and timely diagnosis and appropriate treatment can prevent serious complications. Nonspecific ulcers can be managed with symptomatic treatment, but need close monitoring and re-evaluation in the case of persistence of symptoms.

ANTI-ULCEROGENIC EFFICACY AND MECHANISMS OF EDIBLE AND NATURAL INGREDIENTS IN NSAID-INDUCED ANIMAL MODELS.

Background:Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of the most commonly used medicines and proven to be effective for certain disorders. Some people use NSAIDs on daily basis for preventive purpose. But a variety of severe side effects can be induced by NSAIDs. Studies have shown that edible natural ingredients exhibit preventive benefit of gastric ulcer. This paper reviews the efficacy and safety of edible natural ingredients in preventing the development of gastric ulcer induced by NSAIDs in animal models.Methods:A systematic literature search was conducted on PubMed, using the terms “herbal medicines” and “gastric ulcer”, “herbal medicines” and “peptic ulcer”, “food” and “peptic ulcer”, “food” and “gastric ulcer”, “natural ingredient” and “peptic ulcer”, “natural ingredient” and “gastric ulcer”, “alternative medicine” and “peptic ulcer”, “alternative medicine” and “gastric ulcer”, “complementary medicine” and “peptic ulcer”, “complementary medicine” and “gastric ulcer” in papers published in English between January 1, 1960 and January 31, 2016, resulting in a total of 6146 articles containing these terms. After exclusion of studies not related prevention, not in NSAID model or using non-edible natural ingredients, 54 articles were included in this review.Results:Numerous studies have demonstrated that edible natural ingredients exhibit antiulcerogenic benefit in NSAID-induced animal models. The mechanisms by which edible, ingredient-induced anti-ulcerogenic effects include stimulation of mucous cell proliferation, antioxidation, inhibition of gastric acid secretion, as well as inhibition of H (+), K (+)- ATPase activities. Utilization of edible, natural ingredients could be a safe, valuable alternative to prevent the development of NSAID-induced gastric ulcer, particularly for the subjects who are long-term users of NSAIDs.