Inhibition Of Gastric Acid Secretion Research Articles

A Comprehensive Review of the Benzimidazole Scaffold as a Potential Nucleus for Anti-Ulcer Activity

Abstract: The benzimidazole scaffold is a promising nucleus for developing novel therapeutic agents for ulcer treatment. Its unique chemical structure provides desirable pharmacological properties, such as excellent bioavailability, metabolic stability, and low toxicity, making it an attractive candidate for ulcer treatment. Several benzimidazole derivatives have shown significant anti-ulcer activity in preclinical and clinical studies, acting through multiple pathways, including inhibition of gastric acid secretion, suppression of gastric inflammation, and promotion of mucosal protection. Some benzimidazole derivatives have also demonstrated anti-Helicobacter pylori activity, suggesting their potential for eradicating bacteria associated with ulcer formation. However, challenges such as poor solubility and limited selectivity remain. Various approaches, such as prodrug design and formulation optimization, have been explored to overcome these issues and improve the therapeutic profile of benzimidazole derivatives. Overall, the benzimidazole scaffold holds great promise as a nucleus for developing novel anti-ulcer agents. Further research and optimization efforts are needed to harness its full potential and translate it into effective treatments for ulcers. With continued advancements in medicinal chemistry and drug design, benzimidazole-based compounds may offer new therapeutic options for patients suffering from ulcers and related gastrointestinal disorders. Hence, this review highlights the knowledge about benzimidazole scaffold, the mechanism of ulcer formation, and various benzimidazole derivatives with anti-ulcer activity, which can be further studied in pre-clinical and clinical trials.

Interaction between aqueous extract of Moringa oleifera leaves and rabeprazole in treatment of ethanol induced gastric ulcer in Wistar rats

Background: The effect of concomitant use of herbs and conventional drugs is not widely known because it hasn’t been a common practice especially among the elite and those resident at the urban centers but very common among the rural duelers for co-administered herbs/supplements and conventional drugs. This study was carried out to investigate the interaction between moringa oleifera and rabeprazole in gastric acid secretion. Methods: Twenty (20) adult Wistar albino rats of both sexes weighing 300-450 g were randomly allocated into four (4) groups of five (5) animals per group. Group 1 served as the control and was given normal saline without administration of acid alcohol. Animals in group 2 were given acid alcohol (0.25 ml 0f 36% HCl + 75% ethanol 0.25 ml/100 g body weight). Animals in group 3 were given 50 mg/100 g bw of Moringa oleifera 1 hour before acid alcohol was administered. Group 4 were given: Rabeprazole 20 mg /kg body weight + acid Alcohol (36% HCL 0.25 mls+ 75% Ethanol (0.25 mls). A 30% isoflorane (inhalational anesthesia) by API Manufacturer with FDA, UK, marketed by Macfes medical store, high level Markurdi, Benue State, Nigeria. And 3.5% isoflurane (of the mixture of isoflurane 30%) at 100% oxygen was soaked in a cotton wool and dropped in clean and covered plastic container, and was used to anesthetized the rats, for the purpose of the aqueous extracts administration through a gastric fistula created by a surgical procedure. 10 minutes after aqueous extracts administration, aliquot samples were collected over 4 hours. Gastric acid secretion was measured by titrating the aliquots to a phenolphthalein endpoint. Results: showed that Moringa Olefera significantly delayed the time of onset of action of rabeprazole when co-administered. Moringa alone was a better inhibitor of gastric acid secretion than moringa co-administered with rabeprazole. Conclusion: Moringa delays the time of onset of action of Rabeprazole when co-administered.

The Skeletal Muscle, the Heart, and the Liver Are the Major Organs of the Accumulation of Nitric Oxide Metabolites after Oral Nitrite Treatment.

Nitrite is a nitric oxide (NO) metabolite, which may be bioactivated to generate NO in vivo and supplement endogenous NO formation, especially in cardiovascular and metabolic diseases. However, it is not known whether treatment with oral nitrite results in the accumulation of NO metabolites in different organs. Moreover, treatment with omeprazole, an inhibitor of gastric acid secretion, severely affects the gastric formation of S-nitrosothiols induced with oral nitrite treatment. However, no previous study has examined whether omeprazole affects the nitrite-induced accumulation of NO metabolites in different organs. This study examined in rats the effects of oral sodium nitrite treatment (15 mg/kg via gavage for 1 or 7 days) associated with omeprazole (10 mg/kg or vehicle) on nitrite and nitrate and nitrosylated species (RXNO) concentrations (measured using ozone-based chemiluminescence methods) assessed in the plasma, aorta, heart, liver, brain, and muscle. While our results showed that NO metabolite accumulation in different organs is not uniform, we found that the skeletal muscle, the heart, and the liver accumulate NO metabolites, particularly RXNO. This response was significantly attenuated by omeprazole in the heart and in the skeletal muscle. Together, these findings may indicate that the skeletal muscle, the heart, and the liver are major reservoir sites for NO metabolites after oral nitrite treatment, with major increases in nitrosylated species.

Inhibitors of gastric acid secretion increase oxidative stress and matrix metalloproteinase-2 activity leading to vascular remodeling.

The use of inhibitors of gastric acid secretion (IGAS), especially proton pump inhibitors (PPI), has been associated with increased cardiovascular risk. While the mechanisms involved are not known, there is evidence supporting increased oxidative stress, a major activator of matrix metalloproteinases (MMP), as an important player in such effect. However, there is no study showing whether other IGAS such as histamine H2-receptor blockers (H2RB) cause similar effects. This study aimed at examining whether treatment with the H2RB ranitidine promotes oxidative stress resulting in vascular MMP activation and corresponding functional and structural alterations in the vasculature, as compared with those found with the PPI omeprazole. Male Wistar rats were treated (4 weeks) with vehicle (2% tween 20), omeprazole (10 mg/Kg/day; i.p.) or ranitidine (100 mg/Kg/day; gavage). Then the aorta was collected to perform functional, biochemical, and morphometric analysis. Both ranitidine and omeprazole increased gastric pH and oxidative stress assessed in situ with the fluorescent dye dihydroethidium (DHE) and with lucigenin chemiluminescence assay. Both IGAS augmented vascular activated MMP-2. These findings were associated with aortic remodeling (increased media/lumen ratio and number of cells/μm2). Both IGAS also impaired the endothelium-dependent relaxation induced by acetylcholine (isolated aortic ring preparation). This study provides evidence that the H2RB ranitidine induces vascular dysfunction, redox alterations, and remodeling similar to those found with the PPI omeprazole. These findings strongly suggest that IGAS increase oxidative stress and matrix metalloproteinase-2 activity leading to vascular remodeling, which helps to explain the increased cardiovascular risk associated with the use of those drugs.

The central role of gastrin in gastric cancer.

The prevalence of gastric cancer has markedly declined, but due to the high mortality rates associated with gastric cancer, it is still a serious disease. The preferred classification of gastric cancer is according to Lauren into either the intestinal type, which has a glandular growth pattern, or the diffuse type, which does not have glandular structures. Both types have been classified as adenocarcinomas, with the latter type based on periodic acid-Schiff (PAS) positivity presumed to reflect mucin. However, the presence of mucin in the diffuse type, in contrast to neuroendocrine/enterochromaffin-like (ECL) cell markers, has not been confirmed by immunohistochemistry and in situ hybridization. The ECL cells are probably prone to becoming cancerous because they do not express E-cadherin. Gastric cancer is unique in that a bacterium, Helicobacter pylori, is thought to be its main cause. H. pylori predisposes infected individuals to cancer only after having caused oxyntic atrophy leading to gastric hypoacidity and hypergastrinemia. No single H. pylori factor has been convincingly proved to be carcinogenic. It is probable that gastrin is the pathogenetic factor for gastric cancer due to H. pylori, autoimmune gastritis, and long-term prolonged inhibition of gastric acid secretion. Hypergastrinemia induces ECL cell hyperplasia, which develops into neuroendocrine tumors (NETs) and then into neuroendocrine carcinomas in rodents, a sequence that has also been described in humans. During carcinogenesis, the tumor cells lose specific traits, requiring that sensitive methods be used to recognize their origin. Gastric cancer occurrence may hopefully be prevented by H. pylori eradication at a young age, and by the reduced use of inhibitors of acid secretion and use of a gastrin antagonist in those with previous long-term H. pylori infection and those with autoimmune gastritis.

Proton Pump Inhibitors For HIV+ Patients - A Word Of Caution.

Madam, HIV (human immunodeficiency virus) is on the rise in Pakistan. A Lancet global health modeling study reports that patient registration with the National Aids Control Program (NACP) has risen from 4500 in 2013 to 24331 in 2019 [1]. In HIV+ patients, the gastrointestinal tract is a common site of infection, often leading to anorexia, dysphagia, vomiting, weight loss, and diarrhoea. A study conducted in 2016 showed that 80% of HIV-infected adults had moderate-severe GERD (gastro-oesophageal reflux disorder) symptoms [2]. Physicians often prescribe proton pump inhibitors (PPIs) to treat GERD and stomach or duodenal ulcers. This class of drugs is the most potent inhibitor of gastric acid secretion and is ,unfortunately, prescribed excessively and often inappropriately, regardless of if the patient is HIV+. A recent study shows that 66.2% of patients in a tertiary care hospital in Karachi, Pakistan receive PPIs without proper indication [3]. However, PPIs being prescribed inappropriately pose severe health risks to individuals that are HIV+. A recent study in 2019 raised the valid concern that the use of PPIs in patients already receiving anti-retroviral (ARV) therapy in HIV+ patients could very well be related to an increased risk of acute kidney infection (AKI) [4]. This is not the only research to show the adverse effect of PPI use in HIV patients. A 2017 study shows statistically significant increased innate immune activation due to the translocation of microbial products in HIV+ patients taking PPIs [5]. This can carry serious future implications for these patients post-treatment because higher levels of innate immune activation markers are associated with immunological failure in HIV-treated patients [6]. These statistics raise a very critical question- is it safe for PPIs to be prescribed so freely without any attention to patients being HIV+ or on ARV therapy? It is suggested that existing and future ARV therapies be planned carefully if PPIs are prescribed, and close attention be paid to a patient’s virologic response. In the case of acute hospital admission, where PPIs are prescribed for preventing stress-induced or GI ulcers, medication reconciliation algorithms that acknowledge the interaction between protease inhibitors (PIs) and PPIs should be used [7]. It would be prudent to use PPIs strictly when prescribed and for lesser periods of time.

Famotidine Enhances Rifampicin Activity against Acinetobacter baumannii by Affecting OmpA.

The development of novel antibiotic adjuvants is imminent because of the frequent emergence of resistance in Gram-negative bacteria, which severely restricts the efficiency and longevity of commonly used clinical antibiotics. It is reported that famotidine, a clinical inhibitor of gastric acid secretion, enhances the antibacterial activity of rifamycin antibiotics, especially rifampicin, against Gram-negative bacteria and reverses drug resistance. Studies have shown that famotidine disrupts the cell membrane of Acinetobacter baumannii and inhibits the expression of the outer membrane protein ompA gene, while causing a dissipation of the plasma membrane potential, compensatively upregulating the pH gradient and ultimately increasing the accumulation of reactive oxygen species by leading to increased bacterial mortality. In addition, famotidine also inhibited the efflux pump activity and the biofilm formation of A. baumannii. In the Galleria mellonella and mouse infection models, the combination of famotidine and rifampicin increased the survival rate of infected animals and decreased the bacterial load in mouse organs. In conclusion, famotidine has the potential to be a novel rifampicin adjuvant, providing a new option for the treatment of clinical Gram-negative bacterial infections. IMPORTANCE In this study, famotidine was discovered for the first time to have potential as an antibiotic adjuvant, enhancing the antibacterial activity of rifamycin antibiotics against A. baumannii and overcoming the limitations of drug therapy. With the discovery of novel applications for the guanidine-containing medication famotidine, the viability of screening prospective antibiotic adjuvants from guanidine-based molecules was further explored. In addition, famotidine exerts activity by affecting the OmpA protein of the cell membrane, indicating that this protein might be used as a therapeutic drug target to treat A. baumannii infections.

Current use of proton pump inhibitors and when to limit, stop or not start treatment

Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion that have changed treatment practice for gastric acid-related disorders. The major adequate indications for their use are treatment of gastro-esophageal reflux disease, peptic ulcers, eradication of Helicobacter pylori infection in combination with antibiotics and prophylaxis for patients on non-steroidal anti-inflammatory or antiplatelet drugs. Since their introduction, clinical success has been accompanied by widespread use of PPIs, which has steadily increased over the last decades without concomitant increase in the incidence of acid-related disorders. PPIs are now among the most widely prescribed class of medications worldwide and around 10% of Icelanders are current PPI users. This increase has been linked to PPI prescription without an indication, or continued use for longer duration than recommended. In recent years, concerns have been raised about PPI overuse and the associated increased risk of harm, not only in terms of increased costs but also the potential risk of physical dependence and long-term side effects of PPIs. The article is based on search in PubMed, the authors' own clinical experience and research, and is intended to provide practice advice on the use of PPIs with focus on appropriate prescription and deprescription of PPIs.

Synthesis of Misoprostol, and Intramolecular Isomerization of A-Type Misoprostol into B-Type Misoprostol using 1, 8-Diazabicyclo [5.4.0] undec- 7-ene (DBU).

Misoprostol is a synthetic prostaglandin that is related structurally to naturally occurring prostaglandin (PG), and it has been acknowledged as an effective inhibitor of gastric acid secretion when administered intravenously. In the present study, the novel application of 1,8-Diazabicyclo[5.4.0]undec-7-ene, a cyclic unsaturated amine [DBU] for the conversion of A-type Misoprostol (A-MP) to B-type Misoprostol (B-MP) via intramolecular isomerization. The intramolecular isomerization process was successfully applied for the separation of enantio-pure isomers with no impurities using DBU. The chemical structures of A-MP and B-MP were confirmed using spectral analyses of 1H-NMR, 13C-NMR and Mass spectroscopy.

The Review of Domestic Research on Traditional Korean Medicine for Gastroesophageal Reflux Disease

This study was conducted to examine the current status of traditional korean medicine studies on gastroesophageal reflux disease in Korea, identify deficiencies, and suggest the direction of future medicine research methods to lay the foundation for traditional korean medicine treatment. All domestic papers on the korean traditional treatment of gastroesophageal reflux disease were selected among the literature published until August 2022 in six domestic databases. A total of 52 selected research data were classified into experimental research papers, clinical research papers, and review papers. In experimental papers, to evaluate the effectiveness of treatment, improvement of esophageal mucosal lesions, anti-inflammatory mechanisms, antioxidant mechanisms, esophageal mucosal protection mechanisms, gastric peristalsis control, and gastric acid secretion inhibition mechanisms were used as evaluation measures. In the clinical research paper, the basis for diagnosis of cases was clinical symptoms through medical history listening and diagnosis through visits to hospitals in the past. The average treatment period was 40.7 days, and the duration of treatment was not significantly affected by the duration of the disease. The most widely used Korean medicine treatment intervention was herbal medicine. There were 3 literature review studies, 3 systematic literature review and meta-analysis studies, 1 comparative review study for clinical trial guideline development, all using Chinese papers. This study included all domestic papers on gastroesophageal reflux disease to identify the research trend of the Korean oriental medicine community, and based on this, it is meaningful to confirm areas that need to be supplemented in future research plans.

Discovery of novel benzimidazole derivatives as potent potassium-competitive acid blockers for the treatment of acid-related diseases

H+, K+-ATPase, as the most critical enzyme in gastric acid secretion, has long been an attractive target for the treatment of acid-related diseases. In this study, a series of benzimidazole derivatives were designed and synthesized through conformational restriction and skeleton hopping strategies by using vonoprazan as the lead compound. Among them, compounds A12 (IC50 = 9.32 μM) and A18 (IC50 = 5.83 μM) showed better inhibition at the enzyme level. In addition, gastric acid secretion inhibition was assessed in vivo, and the results showed that A12 and A18 significantly inhibited basal gastric acid secretion, 2-deoxy-d-glucose (2DG) stimulated gastric acid secretion and histamine-stimulated gastric acid secretion. In further in vitro metabolic experiments, A12 and A18 demonstrated excellent stability and low toxicity. Pharmacokinetic studies showed that the p.o. and i.v. half-lives of A18 were 3.21 h and 8.67 ± 1.15 h, respectively. In summary, A18 might be a novel and effective potassium-competitive acid blocker, and this study provides strong support for it use in the treatment of acid-related diseases.

Clinical Characteristics of Peptic Ulcer Disease & its Pharmacological Management in Primary Care

Background: Peptic ulcer diseases (PUD) are common conditions reported in daily clinical practice. Proton pump inhibitors (PPIs) are the most potent pharmacological inhibitors of gastric acid secretion. Aims & objectives: This study aimed to evaluate & understand the clinical presentation and management of PUD with PPIs in general practice. Methods: This prospective study was conducted on 150 diagnosed cases of PUD patients in a single center of private practice in rural areas from February 2022 to August 2022. Patients were enrolled by following inclusion & exclusion criteria with informed written consent. Eight (08) weeks after the completion of treatment by giving PPIs, a repeat endoscopy was done to see the improvement of healing of the ulcer. All data were collated and results were expressed in percentages which are illustrated in different tables & figures. Results: Among 150 endoscopically diagnosed PUD patients major age group was 31-40 years (50%) of both sexes where the male (58.66%) were more predominant. Abdominal pain (82%), heartburn (56.66%), etc were the main clinical symptoms of the patients who were referred for endoscopy. After confirming the diagnosis, PPIs were given to the patients. Esomeprazole (34.66%), lansoprazole (22%), pantoprazole (18.66%), etc were prescribed frequently. After 8 weeks of treatment, repeat endoscopy revealed that the ulcer was completely healed in 65.33% of patients whereas only 6.66% had no improvement. Conclusion: The majority of the patient are almost cured of PUD by receiving various types of PPIs which are very effective drugs for healing peptic ulcer disease. Mediscope 2023;10(1): 22-30

QSAR Study of N-((3-Benzamido-4-oxo-3,4-Dihydroquinazolin 2-yl)methyl)-N-(Substituted) Phenyl Benzamide as Antiulcer Agents

Suppression of gastric acid secretion by use of proton pump inhibitors is an efficient way to control hyperacidity complications. An inhibitory activity of N-((3-Benzamido-4-oxo-3, 4 dihydro quinazolin -2-yl) methyl)-N-(substituted phenyl) benzamides on H+/K+-ATPase was established and reported earlier. Thus, it is significant to develop more promising agents by quantitative structure-activity relationship (QSAR) study of 37 ligands by multi-linear regression method to link the structures of molecules with inhibitory activity on H+/K+-ATPase (pIc50). QSAR model was built using genetic function approximation protocol of the software Discovery Studio Version 2.1 using training set carrying 23 compounds. The remaining 14 compounds were used as a test set. The generated model was showing satisfying statistical qualities, r2=0.84 and predicted correlation coefficient r2pred=0.88. The theoretical approach indicates that an increase in Log D, Shadow_XZ and SC 2, and reduction of Shadow_Z length causes more inhibition of enzyme by molecule.

Effects of vonoprazan and proton pump inhibitors on the efficacy of bevacizumab: a multicentre retrospective study.

Gastric acid secretion inhibitors such as proton pump inhibitors (PPIs) and vonoprazan may change the duration of treatment with bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, for cancer. However, there are no data on this prolongation effect. Here, we aimed to determine whether the use of PPIs or vonoprazan in patients with cancer receiving bevacizumab affected the duration of bevacizumab treatment. This observational study was conducted at two national university hospitals in Japan and involved 222 patients using oral PPIs (N = 190) or vonoprazan (N = 32) at the start of bevacizumab treatment between January 2015 and December 2018. Patients who received only one course of bevacizumab were excluded. The primary endpoint was the duration of bevacizumab treatment. The duration of bevacizumab treatment varied significantly between the PPI and vonoprazan groups. For cancer types other than colorectal cancer (breast, lung, brain, and ovarian cancers), the median duration of treatment was 217days (p < 0.05) and was longer in the vonoprazan group than in the PPI group. However, for colorectal cancer, the median duration of bevacizumab treatment was 147days longer in the PPI group than in the vonoprazan group. Selection of appropriate gastric acid secretion inhibitors may improve the therapeutic efficacy of anti-VEGF drugs, including bevacizumab. Oestrogen is a key regulator of this effect and may be responsible for the varying association between PPI or vonoprazan administration and the difference in bevacizumab treatment duration between colon cancer and other cancer types.

Hepatic invasion of a gastric ulcer confirmed by endoscopy and surgery.

A 66-year-old woman who had been suffering from chronic anorexia for two years was transported to the hospital after being unable to consume food for three days. She had no hematemesis or abdominal pain and had no history of taking nonsteroidal anti-inflammatory drugs. Blood tests showed marked anemia with hemoglobin of 3.3 g/dL, and esophagogastroduodenoscopy revealed a large ulcer lesion in the lesser curvature of the gastric body and a liver-like mass protruding from the ulcer base. Biopsy of the mass showed proliferation of cells showing irregular cord-like structures, suggestive of normal liver tissue or hepatocellular carcinoma. Computed tomography scan showed no obvious free air in the abdomen. Despite conservative treatment, the patient developed hematemesis and progressive anemia, and surgery was performed (total gastrectomy with partial hepatectomy). Surgical specimen showed an ulcer lesion with fibrosis and loss of wall structure in all layers of the stomach, and liver adhesion with fibrosis deep in the ulcer, but no malignant findings. With the advent of powerful gastric acid secretion inhibitors, gastric ulcer invasion into the liver is now very rare, and this case is thus a valuable example showing very clear images.

Prescription of Gastric Acid Secretion Inhibitors before and after the Withdrawal of Ranitidine

Background: In September 2019, ranitidine, the largest share in the gastric acid secretion inhibitor market, was identified as a carcinogen, and sales were banned. The purpose of this study was to investigate how the gastric acid secretion inhibitor market changed after ranitidine withdrawal.Methods: From January 2010 to December 2021, the prescription dose and cost of gastric acid secretion inhibitors were calculated monthly. To investigate the effect of ranitidine withdrawal on the gastric acid secretion inhibitor market, we developed a time-series autoregressive model using data from January 2010 to October 2019. In addition, the P-value was calculated by interrupted time series analysis using the data dating between 2010 and 2021 (interrupted time: October 2019).Results: Since 2010, proton pump inhibitors have increased their market share in terms of prescription volume and drug costs. This trend accelerated since ranitidine was withdrawn from the market in September 2019. In 2021, it was estimated that ranitidine prescriptions would be transferred as follows: famotidine's increased prescription volume was estimated at 323 million (pharmaceutical cost, 53.2 billion won), proton pump inhibitors (PPIs) at 223 million (89.9 billion won), and lafutidine at 137 million (20.5 billion won).Conclusions: The market share expansion of PPIs accelerated due to the withdrawal of ranitidine. The ranitidine prescription was partially transferred to the same H &lt;sub&gt;2&lt;/sub&gt; blockers, such as famotidine and lafutidine, and there was also a significant transfer to PPIs.

Differential effects of proton pump inhibitors and vonoprazan on vascular endothelial growth factor expression in cancer cells.

Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion, used as first-line agents in treating peptic ulcers. However, we have previously reported that PPIs may diminish the therapeutic effect of anti-vascular endothelial growth factor (VEGF) drugs in patients with cancer. In this study, we explored the effects of vonoprazan, a novel gastric acid secretion inhibitor used for the treatment of peptic ulcers, on the secretion of VEGF in cancer cells and attempted to propose it as an alternative PPI for cancer chemotherapy.The effects of PPI and vonoprazan on VEGF expression in cancer cells were compared by real-time reverse transcription-polymerase chain reactionand ELISA. The interaction of vonoprazan and PPIs with transcriptional regulators by docking simulation analysis.In various cancer cell lines, including the human colorectal cancer cell line (LS174T), PPI increased VEGF messengerRNA expression and VEGF protein secretion, while this effect was not observed with vonoprazan. Molecular docking simulation analysis showed that vonoprazan had a lower binding affinity for estrogen receptor alpha (ER-α), one of the transcriptional regulators of VEGF, compared to PPI. Although the PPI-induced increase in VEGF expression was counteracted by pharmacological ER-α inhibition, the effect of vonoprazan on VEGF expression was unchanged.Vonoprazan does not affect VEGF expression in cancer cells, which suggests that vonoprazan might be an alternative to PPIs, with no interference with the therapeutic effects of anti-VEGF cancer chemotherapy.

Can Nizatidine Play a Dual Role of Inhibition of Gastric Acid Secretion and Promotion of Gastric Emptying?

Can Nizatidine Play a Dual Role of Inhibition of Gastric Acid Secretion and Promotion of Gastric Emptying?

Utility of serum interleukin-18 (IL-18) as a tumour marker in gastric cancer

Introduction: Gastric cancer (GC) is the fourth most prevailing cancer globally, attributing to more than 70% of cases in developing countries. Protein cancer biomarkers, such as CEA, CA- 125, AFP and PSA, are clinically helpful diagnostic tools, but they have low sensitivity and specificity for GC. Hence, it is essential to discover better markers for GC diagnosis. Interleukin-18 (IL-18) is the member of Interleukin-1 family. It is hypothesized to be a potent inhibitor of gastric acid secretion, leading to gastric atrophy and causing an increased risk of GC. This study was to evaluate the association between the serum IL-18 in GC. Methodology: We included cases who underwent UGI Scopy and were proven to have GC histopathologically. The patients who presented to the out-patient who underwent UGI scopy and was found to have no growth were selected as controls. Twenty-eight cases and 84 control sample sizes were derived from nMaster V2. Blood samples from patients and controls were collected, and serum IL-18 levels were estimated using a solid-phase sandwich ELISA method. Results: We found that the cut-off value of serum IL-18 was 85.59 pg/ml, had a sensitivity of 63.1% and specificity of 57.1%, with a positive predictive value of 81.5% and a negative predictive value of 34% in diagnosing GC. The study plotted the receiver operating characteristic curve against IL-18 for sensitivity and specificity. Statistically, we found through the Area Under the Curve (AUC) that the rise in serum IL-18 levels was a poor indicator of GC with a p-value of 0.078. Conclusion: Statistically, a cut-off of 85.59pg/ml showed good sensitivity and specificity; however, the probability was insignificant, suggesting that IL-18 may not be of diagnostic importance. Studies with a larger sample size are required to further probe into the usefulness of estimating IL-18 in GC.

ANAPHYLACTIC REACTION TO OMEPRAZOLE AFTER NEGATIVE PANTOPRAZOLE ALLERGY TESTING

<h3>Introduction</h3> Proton pump inhibitors (PPIs) are widely used inhibitors of gastric acid secretion. PPIs are generally well tolerated with very few side effects and hypersensitivity reactions are rarely described. Here we present an adult man who reports anaphylaxis upon treatment with oral omeprazole. <h3>Case Description</h3> A 56-year-old man presented with symptoms of skin rash with pruritus of the skin upon treatment with oral omeprazole in treating Helicobacter pylori on two separate occasions. The reaction occurred after the first dose of the drug. Allergy skin testing (SKT) to pantoprazole was negative, and the patient tolerated the graded oral challenge to Pantoprazole. To treat the H. pylori infection, the patient took Talicia (amoxicillin, rifabutin, and omeprazole) and developed generalized pruritus, itchy tongue, throat, and bilateral hand swelling within 20 minutes of taking this medication. He also experienced chest tightness, shortness of breath, abdominal pain, dizziness, and vomiting. The patient was taken to the emergency department and received IV Benadryl (25 mg), famotidine (20 mg), methylprednisolone (125 mg), and intravenous fluids (1L NS), with an improvement in his symptoms. Upon follow-up for this anaphylactic reaction, allergy SKT and challenge to penicillin were performed which were negative. <h3>Discussion</h3> This case reinforces the importance of performing SKTs and oral drug challenges for each medication within the PPI drug class. The cross-reactivity between different PPIs is not currently well described, and other PPIs should be avoided unless an SKT and oral drug challenge are performed under close observation. Further studies are needed to provide more information on cross-reactivity among PPIs.