Gastrin Release Research Articles

Linking GERD and the Peptide Bombesin: A New Therapeutic Strategy to Modulate Inflammatory, Oxidative Stress and Clinical Biochemistry Parameters.

Gastroesophageal reflux disease (GERD) represents one of the most prevalent foregut illnesses, affecting a large portion of individuals worldwide. Recent research has shown that inflammatory mediators such as cytokines, chemokines, and enzymes are crucial for causing esophageal mucosa alterations in GERD patients. It seems likely that the expression of various cytokines in the esophageal mucosa also induces oxidative stress by increasing the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). As humoral agents and peptidergic neurotransmitters that may support the enterogastric axis, bombesin and its related bombesin-like peptide, GRP (gastrin releasing peptide), have not been fully investigated. Therefore, considering all these assumptions, this study aimed to evaluate the influence of bombesin in reestablishing biochemical markers linked with inflammation and oxidative/nitrosative stress in GERD pathological settings. C57BL/6 mice were alternatively overfed and fasted for 56 days to induce GERD and then treated with bombesin (0.1, 0.5, and 1 mg/kg intraperitoneally) once daily for 7 days, and omeprazole was used as the positive control. After 7 days of treatment, gastric pain and inflammatory markers were evaluated. Abdominal pain was significantly reduced following bombesin administration, which was also successful in diminishing inflammatory and oxidative/nitrosative stress markers in a manner overlapping with omeprazole. Moreover, bombesin was also able to appreciably modulate gastric pH as a result of the restoration of gastric homeostasis. Overall, these observations indicated that the upregulation of bombesin and interconnected peptides is a promising alternative approach to treat GERD patients.

Effectiveness Analysis of the Combined Detection of CEA, SCC, CYFRA21-1, NSE and ProGRP for Early Diagnosis of Lung Cancer

Objective To explore the diagnostic value and application effect of the combined detection of CEA (carcinoembryonic antigen), SCC (squamous cell carcinoma antigen), CYFRA21-1 (soluble fragment of cytokeratin 19), NSE (neuron specific enolase) and proGRP (gastrin releasing peptide precursor) in early lung cancer. Method 66 patients who admitted to the hospital from April 2019 to February 2024 were selected as the early stage lung cancer group and the other 159 patients were selected as the benign lung group, in which all subjects were tested for NSE, CEA, ProGRP, CYFRA21-1, and SCC levels and were confirmed by histopathological analysis. In ROC analysis, the cut-off point, AUC, accuracy, sensitivity and specificity between single and combined detection indicators are analyzed. Result The size of cut-off point, AUC, accuracy, sensitivity, specificity, positive and negative detection rate and accuracy rate is 0.3072, 0.790, 89.33%, 0.894, 0.893, 89.40% (59/66), 89.31% (142/159) and 89.33% ((142+59)/225) respectively and it is obviously superior to those of single detection method. Meanwhile, indicator of SCC showed the worst performance by single detection. Conclusion The combined detection indicators have high diagnostic value in early diagnosis of lung cancer, and the sensitivity, positive detection rate, AUC value and accuracy have been significantly improved.

Sporadic gastrinoma with refractory benign esophageal stricture: A case report

BACKGROUND Gastrinoma is characterized by an excessive release of gastrin, leading to hypersecretion of gastric acid, subsequently resulting in recurrent peptic ulcers, chronic diarrhea, and even esophageal strictures. This case report aims to improve awareness and facilitate early diagnosis and treatment of gastrinoma by presenting a rare case of gastrinoma with refractory benign esophageal stricture (RBES). Additionally, it highlights the persistent challenges that gastroenterologists encounter in managing RBES. CASE SUMMARY This case demonstrates a patient with gastrinoma who developed RBES and complete esophageal obstruction despite management with maximal acid suppressive therapy, multiple endoscopic bougie dilations and endoscopic incisional therapy (EIT). CONCLUSION It is essential to diagnose gastrinoma as early as possible, as inadequately controlled acid secretion over an extended period increases the risk of developing severe esophageal strictures. In patients with esophageal strictures causing complete luminal obstruction, blind reopening EIT presents challenges and carries a high risk of perforation.

The Impact of Sex on the Response to Proton Pump Inhibitor Treatment.

Proton pump inhibitor (PPI) treatment is responsible for substantial gastrin elevation secondary to reduced intragastric acidity. Due to the increasing global prevalence of PPI users, concerns have been raised about the clinical significance of continuous gastrin elevation and its potential long-term side effects. Hypergastrinemia secondary to PPIs has trophic effects on gastric mucosa, leading to enterochromaffin-like cell hyperplasia and gastric (fundic) polyp formation, and it is believed to provoke acid rebound following PPI withdrawal that induces PPI overutilization. Previous studies have found higher gastrin release following PPI therapy in females compared with males, and sex differences have also been demonstrated in pharmacokinetic parameters and dose requirements for acid reflux. It is conceivable that females might be at increased risk of PPI overuse, because they often receive higher milligram-per-kilogram doses. The prevalence of PPI use is more common among females, and the female sex is a risk factor for adverse drug reactions. This non-systematic review outlines the current knowledge of the impact of biological sex on the response to PPIs. The aim is to highlight the female sex as a potential risk factor that could be a step toward precision medicine and should be considered in future research on the response to PPI treatment.

Radiolabeled iron oxide nanoparticles functionalized with PSMA/BN ligands for dual-targeting of prostate cancer.

Prostate cancer (PCa) is the second most frequent cancer diagnosis in men and the fifth leading cause of death worldwide. Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) receptors are overexpressed in PCa. In this study, we have developed iron oxide nanoparticles (IONs) functionalized with the Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) ligands for dual targeting of Prostate cancer. IONs were developed with a thin silica layer on their surface with MPTES (carrying -SH groups, IONs-SH), and they were coupled either with a pharmacophore targeting PSMA (IONs-PSMA) or with bombesin peptide (IONs-BN), targeting GRP receptors, or with both (IONs-PSMA/BN). The functionalized IONs were characterized for their size, zeta potential, and efficiency of functionalization using dynamic light scattering (DLS) and Fourier-Transform Infrared Spectroscopy (FT-IR). All the aforementioned types of IONs were radiolabeled directly with Technetium-99m (99mTc) and evaluated for their radiolabeling efficiency, stability, and binding ability on two different PCa cell lines (PC3 and LNCaP). The MTT assay demonstrated low toxicity of the IONs against PC3 and LNCaP cells, while the performed wound-healing assay further proved that these nanostructures did not affect cellular growth mechanisms. The observed hemolysis ratio after co-incubation with red blood cells was extremely low. Furthermore, the 99mTc-radiolabeled IONs showed good stability in human serum, DTPA, and histidine, and high specific binding rates in cancer cells, supporting their future utilization as potential diagnostic tools for PCa with Single Photon Emission Computed Tomography (SPECT) imaging.

A semaphorin-plexin-Rasal1 signaling pathway inhibits gastrin expression and protects against peptic ulcers.

Peptic ulcer disease is a frequent clinical problem with potentially serious complications such as bleeding or perforation. A decisive factor in the pathogenesis of peptic ulcers is gastric acid, the secretion of which is controlled by the hormone gastrin released from gastric G cells. However, the molecular mechanisms regulating gastrin plasma concentrations are poorly understood. Here, we identified a semaphorin-plexin signaling pathway that operates in gastric G cells to inhibit gastrin expression on a transcriptional level, thereby limiting food-stimulated gastrin release and gastric acid secretion. Using a systematic siRNA screening approach combined with biochemical, cell biology, and in vivo mouse experiments, we found that the RasGAP protein Rasal1 is a central mediator of plexin signal transduction, which suppresses gastrin expression through inactivation of the small GTPase R-Ras. Moreover, we show that Rasal1 is pathophysiologically relevant for the pathogenesis of peptic ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs), a main risk factor of peptic ulcers in humans. Last, we show that application of recombinant semaphorin 4D alleviates peptic ulcer disease in mice in vivo, demonstrating that this signaling pathway can be harnessed pharmacologically. This study unravels a mode of G cell regulation that is functionally important in gastric homeostasis and disease.

Gastric Neuroendocrine Tumors With Parietal Cell Atrophy in a Long-term Carcinogenicity Study in Rats.

Malignant neuroendocrine tumors were diagnosed in the stomach of two out of sixty female Sprague-Dawley rats treated for 89 weeks with a high dose of a novel, small molecule, cannabinoid-1 antagonist. The tumors were associated with parietal cell atrophy accompanied by foveolar hyperplasia of the glandular stomach mucosa. Parietal cell atrophy/foveolar hyperplasia was considered test article related at the high dose, given the higher incidence and severity relative to untreated controls, although the precise mechanism of the parietal cell atrophy was undetermined. Spontaneous gastric neuroendocrine tumors are very rare in rats, and the current cases were considered secondary to parietal cell atrophy causing reduced gastric acid secretion and subsequent overstimulation of gastrin release through a feedback loop.

Gastrin-17 Levels in Pre-malignancy Gastritis Lesions

Background: Gastritis is an inflammatory process on the lining of the stomach that could be caused by various factors. Untreated inflammatory processes could lead to ulcers. Gastrin hormone is released by gastrin-secreting enteroendocrine cells (G cells) in the stomach, which influence the secretion of gastric acid and helps the proliferation of gastric epithelial cells. Its abnormal secretion in H. pylori infection, with food-stimulated excessive release of gastrin, is the most prominent abnormality. One concern is the relationship of excess gastrin secretion to the incidence of gastric cancer. This study aimed to show the difference in gastrin levels on patients with gastritis, both with and without pre-malignant lesions. Methods: This research was a cross-sectional study with 40 samples that had met the inclusion and exclusion criteria. Endoscopy was performed to assess the gastric mucosa and tissue biopsy was performed afterward. The data was analysed in univariate and bivariate ways. Results: From this study, 20 people were positive for pre-malignant lesions (50%). Mann–Whitney test analysis was used to analyse the data and showed there was a significant difference between gastrin levels on patients with gastritis with and without pre-malignant lesions, with a p value of 0.01. Conclusion: There is a significant difference between gastrin levels in patients with gastritis with and without pre-malignant lesions, which could be the basis for early detection of patients with gastric cancer.

Proton pump inhibitors usage and the risk of cancer

Introduction and purpose of the work:Proton pump inhibitors are used to reduce gastric acidity by irreversibly inhibiting the hydrogen-potassium ATPase present in the parietal cells of the stomach. These drugs are used more and more often, often not in accordance with the recommendations. There are reports suggesting a relationship between chronic PPI use and the occurrence of cancer. The aim of the study is to present information on the relationship between the use of proton pump inhibitors and the risk of developing cancer.State of knowledge:Recent field studies have shown that there is a significant relationship between PPI use and carcinogenesis. One possible mechanism is related to the sustained release of gastrin in large amounts, which in turn stimulates the production of substances with trophic effects on the gastrointestinal mucosa, and cell proliferation over time may lead to cancer formation. The relationship between high gastrin concentration and the formation of gastric neuroendocrine neoplasms, tumors of the liver, pancreas and esophagus has been proven.Summary:Proton pump inhibitors are considered safe drugs. Taking into account the described reports on the increased risk of developing certain cancers, when prescribing PPIs, the risk associated with their use should also be taken into account. However, it seems that the benefits of using these drugs outweigh the risks in most cases.

Blocking GRP/GRP-R signaling decreases expression of androgen receptor splice variants and inhibits tumor growth in castration-resistant prostate cancer

Clinical management of castration-resistant prostate cancer (CRPC) resulting from androgen deprivation therapy (ADT) remains challenging. Many studies indicate that androgen receptor splice variants (ARVs) play a critical role in the development of CRPC, including resistance to the new generation of inhibitors of androgen receptor (AR) action. ARVs are constitutively active and lack the ligand-binding domain (LBD), thereby allowing prostate cancer (PC) to maintain AR activity despite therapies that target the AR (full-length AR; AR-FL). Previously, we have reported that long-term ADT increases the neuroendocrine (NE) hormone – Gastrin Releasing Peptide (GRP) and its receptor (GRP-R) expression in PC cells. Further, we demonstrated that activation of GRP/GRP-R signaling increases ARVs expression by activating NF-κB signaling, thereby promoting cancer progression to CRPC. Most importantly, as a cell surface protein, GRP-R is easily targeted by drugs to block GRP/GRP-R signaling. In this study, we tested if blocking GRP/GRP-R signaling by targeting GRP-R using GRP-R antagonist is sufficient to control CRPC progression. Our studies show that blocking GRP/GRP-R signaling by targeting GRP-R using RC-3095, a selective GRP-R antagonist, efficiently inhibits NF-κB activity and ARVs (AR-V7) expression in CRPC and therapy-induced NEPC (tNEPC) cells. In addition, blocking of GRP/GRP-R signaling by targeting GRP-R can sensitize CRPC cells to anti-androgen treatment (such as MDV3100). Further, preclinical animal studies indicate combination of GRP-R antagonist (targeting ARVs) with anti-androgen (targeting AR-FL) is sufficient to inhibit CRPC and tNEPC tumor growth.

Spinal Cord Injury Causes Reduction of Galanin and Gastrin Releasing Peptide mRNA Expression in the Spinal Ejaculation Generator of Male Rats.

Spinal cord injury (SCI) in men is commonly associated with sexual dysfunction, including anejaculation, and chronic mid-thoracic contusion injury in male rats also impairs ejaculatory reflexes. Ejaculation is controlled by a spinal ejaculation generator consisting of a population of lumbar spinothalamic (LSt) neurons that control ejaculation through release of four neuropeptides including galanin and gastrin releasing peptide (GRP) onto lumbar and sacral autonomic and motor nuclei. It was recently demonstrated that spinal contusion injury in male rats caused reduction of GRP-immunoreactivity, but not galanin-immunoreactivity in LSt cells, indicative of reduced GRP peptide levels, but inconclusive results for galanin. The current study further tests the hypothesis that contusion injury causes a disruption of GRP and galanin mRNA in LSt cells. Male rats received mid-thoracic contusion injury and galanin and GRP mRNA were visualized 8 weeks later in the lumbar spinal cord using fluorescent in situ hybridization. Spinal cord injury significantly reduced GRP and galanin mRNA in LSt cells. Galanin expression was higher in LSt cells compared to GRP. However, expression of the two transcripts were positively correlated in LSt cells in both sham and SCI animals, suggesting that expression for the two neuropeptides may be co-regulated. Immunofluorescent visualization of galanin and GRP peptides demonstrated a significant reduction in GRP-immunoreactivity, but not galanin in LSt cells, confirming the previous observations. In conclusion, SCI reduced GRP and galanin expression in LSt cells with an apparent greater impact on GRP peptide levels. GRP and galanin are both essential for triggering ejaculation and thus such reduction may contribute to ejaculatory dysfunction following SCI in rats.

The Effect of Proton Pump Inhibitors on Insulin-Glucose Homeostasis in Patients With Type 2 Diabetes Mellitus

Introduction: Gastrin release from G cells stimulates cholecystokinin (CCK2) receptors throughout the body, most of which promote gastric acid secretion. However, gastrin also stimulates CCK2 receptors located elsewhere, including the islet of the pancreas. In turn, gastrin increases insulin secretion1. Gastrin also promotes pancreatic β cell neogenesis and replication. Proton pump inhibitors (PPIs) decrease the pH of the stomach and stimulate gastrin secretion, which may indirectly promote insulin secretion and improve hemoglobin A1c (HbA1c). Objective: To understand the effect of PPIs on insulin-glucose homeostasis (c-peptide, HbA1c, and glucose) in patients with type 2 diabetes mellitus (T2DM). Methodology: We retrospectively reviewed the charts of patients with T2DM at least 18 years of age who received care at AnMed Health facilities from Jan. 1, 2018 through Dec. 31, 2018 to compare HbA1c, C‐peptide, and glucose levels in patients with and without active PPI therapy. Slicer-dicer software was used to identify study population with diagnosis of T2DM and labs including both HbA1c and C-peptide. Out of total 215 patients satisfying inclusion criteria, 71 patients were on PPI. Statistical analyses were performed using SPSS version 20.0 (SPSS, Armonk, NY: IBM Corp). All values are presented as means ± SD. A p value of < 0.05 was considered to be significant. Independent T-test and chi-square test were performed to compare parameters in between groups. Results: The PPI and non‐PPI groups had no statistical difference regarding age, sex, race and BMI. There was no significant difference in HbA1c levels between PPI and non‐PPI groups (8.6% ± 2.1 vs 8.3% ± 2.0, respectively; p value = 0.37). However, we found a significant increase in C‐peptide levels (3.1 ng/mL ± 2.4 vs 2.4 ng/mL ± 2.3; p value = 0.037) and decrease in LDL levels (79.6 mg/dL ± 34.0 vs 89.73 mg/dL ± 32.9; p value = 0.046) in the PPI group compared to non-PPI group. In addition, there was a significantly greater prevalence of coronary artery disease in the PPI group (p = 0.01). Conclusion: PPI therapy in patients with T2DM was not associated with improved glycemic control. However, C-peptide levels were significantly higher in patients with T2DM who were on PPI therapy suggesting higher insulin secretion. The lack of difference in HbA1c levels may be a result of aggressive diabetic management by treating clinicians to achieve similar goal HbA1c in both groups. Further research is needed to understand the gastrin pathway as a potential option for improving glycemic control.

Ultra-high-frequency radio-frequency acoustic molecular imaging with saline nanodroplets in living subjects.

Molecular imaging is a crucial technique in clinical diagnostics, but it relies on radioactive tracers or high magnetic fields that are unfavorable for many patients, particularly infants and pregnant women. Ultra-high-frequency-radiofrequency-acoustic (UHF-RF-acoustic) imaging using non-ionizing RF pulses allows deep-tissue imaging with sub-millimeter spatial resolution. However, lack of biocompatible and targetable contrast agents has prevented the successful in vivo application of UHF-RF-acoustic imaging. Here, we report our development of targetable nanodroplets for UHF-RF-acoustic molecular imaging of cancers. We synthesize all-liquid nanodroplets containing hypertonic saline that are stable for at least 2 weeks and can produce high intensity UHF-RF-acoustic signals. Compared with concentration-matched iron-oxide nanoparticles, our nanodroplets produce at least 1600 times higher UHF-RF-acoustic signals at the same imaging depth. We demonstrate in vivo imaging using the targeted nanodroplets in a prostate cancer xenograft mouse model expressing gastrin release protein receptor (GRPR), showing targeting specificity by more than two-fold, compared to untargeted nanodroplets or prostate cancer cells not expressing GRPR.

Perdarahan Gastrointestinal pada Stroke Iskemik Akut: Sebuah Tinjauan Pustaka

Gastrointestinal bleeding in acute ischemic stroke is caused by the process of neuroinflamation in ischemic brain cells. Brain edema that occurs in acute ischemic stroke patients affects the hypothalamus and brainstem. Involvement of the vagal nucleus in the brainstem results in increased stimulation of the vagus and reduced inhibition of the vagus. The neuroinflamation process affects the parasympathetic nervous system causing vagal hyperactivity resulting in an increase in gastrin release which increases gastric acid production. Gastrointestinal bleeding in patients with acute ischemic stroke results in the cessation or delay of antiplatelet or anticoagulant therapy, resulting in a procoagulatory state, making thrombosis easier, thereby increasing the risk of repeated strokes and poor clinical outcomes. Several studies of gastrointestinal bleeding in patients with acute ischemic stroke have a poor prognosis for outcomes. These outcomes include worsening neurological deficits, hospital deaths, and prolonged treatment.

S2162 Hemorrhagic Shock Following a Secretin Stimulating Test

INTRODUCTION: Zollinger-Ellison Syndrome (ZES) is a rare disorder resulting from inappropriate gastrin release, which causes acid hypersecretion and the development of peptic ulcer disease (PUD), severe gastroesophageal reflux, and diarrhea. Diagnosing ZES is challenging in the age of PPIs. Furthermore, discontinuing PPI therapy in patients with suspected ZES can be dangerous and even life-threatening. CASE DESCRIPTION/METHODS: A 44 y.o. male with a history of PUD presented for evaluation for ZES. Due to concern for ZES, a secretin-stimulating test was ordered. One week prior to his test he was instructed to stop his PPI and start Ranitidine 450 mg every 6 hours until 24 hours prior to the test. Immediately following the secretin-stimulating test he presented to the emergency room with nausea, vomiting, and profuse watery diarrhea. A pantoprazole infusion at 8 mg/ hr was started. Overnight he became tachycardic and developed about 400cc of hematemesis. His Hbg dropped from 10.3 g/dL to 7.7 g/dL. He subsequently developed hemorrhagic shock requiring intubation and transfer to the ICU. On EGD, he had a large clot in the second portion of the duodenum. He had hematin in the stomach and over 10 ulcers in the duodenum (Image 1). The pantoprazole infusion was increased to 12 mg/hr with no further recurrence of hemorrhage. The secretin stim test returned, confirming the diagnosis of ZES. This was followed up with an Octreotide scan, which revealed increased radiotracer near the second portion of the duodenum, confirming the location of the gastrinoma (Image 2). DISCUSSION: This case illustrates a rare complication of a patient with suspected ZES undergoing a secretin stimulating test. In patient’s with ZES, a secretin stimulating test causes a paradoxical gastrin response to secretin, likely from secretin receptors on tumor cells (Image 3). Furthermore, PPI withdrawal can cause rebound acid secretion, which can lead to exaggerated acid hypersecretion in patient's with ZES. Our patient had an exaggerated response to secretin leading to acid hypersecretion causing PUD, diarrhea, and hemorrhagic shock. Although complications from a secretin stimulating test are rare, in patients with prior UGIB and high suspicion for ZES, a secretin-stimulating test may need to be performed in a controlled hospitalized setting to minimize complication. This case further illustrates how the diagnosis of ZES has become difficult and whether we need to propose new diagnostic criteria to avoid complications in establishing a diagnosis.Figure 1.: Image 1. Large Clot and Multiple Ulcers (Yellow Arrows) in the Duodenum.Figure 2.: Image 2. Markedly increased radiotracer uptake in a soft tissue nodule medial to the second portion of the duodenum, suggestive of a neuroendocrine tumor (confirmed to be gastrinoma by surgical resection).Figure 3.: Image 3. A. In the antrum, exogenous secretin stimulates gastrin secretion directly and concomitantly inhibits gastrin secretion by stimulating somatostatin (SST) secretion, resulting in little or no gastrin release. B. In patients with ZES, because the gastrinoma does not contain functionally coupled SST cells, the effect of secretin is solely to stimulate gastrin secretion from the tumor.

COMPARISON BETWEEN THE EFFECTS OF THYMOQUINONE OBTAINED FROM THE SEEDS OF NIGELLA SATIVA AND VERAPAMIL ON THE VOLUME AND ACIDITY OF GASTRIC ACID SECRETION

Background and Objectives: The over production of gastric acid results in peptic ulcer. This study was done to compare the effects of thymoquinone and Verapamil on volume and acidity of carbachol induced gastric secretion.&#x0D; Methods: There were 24 rabbits used, weighing 1-1.5 kg. The rabbits were kept on fasting for 48 hours. After fasting, the pylorus of each rabbit was ligated. Thymoquinone 5 mg/kg, Carbachol 600mg/kg and Verapamil 10 mg/kg body weight were administered intraperitoneally. Pylorus ligation method was used for getting gastric contents and titration method was used for finding out acidity.&#x0D; Results: Verapamil has been proved very effective for the treatment of many diseases. The drug verapamil inhibits the release of histamine, acetylcholine and gastrin. Verapamil has also shown effects in reducing the secretion of gastric acid. It was found that Thymoquinone reduced the volume, free and total acidity of gastric secretion, which were statistically highly significant when compared with Carbachol (P=0.000) but when we compared the results of Thymoquinones with that of Verapamil, it was non-significant.&#x0D; Conclusions: It was concluded that Thymoquinone can be used for the treatment of peptic ulcer and all other diseases which are caused by increased gastric acidity like dyspepsia, gastritis and reflux esophagitis.&#x0D; Peer Review History: &#x0D; Received 8 July 2020; Revised 14 August; Accepted 6 September, Available online 16 September 2020&#x0D; UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency.&#x0D; Received file &#x0D; &#x0D; Average Peer review marks at initial stage: 6.0/10&#x0D; Average Peer review marks at publication stage: 8.0/10&#x0D; Reviewer(s) detail:&#x0D; Name: Dr. Hatem Sameir Abbas&#x0D; Affiliation: Al-Azhar University, Egypt&#x0D; E-mail: hsam8406@yahoo.com&#x0D; &#x0D; Name: Prof. Dr. Ali Gamal Ahmed Al-kaf&#x0D; Affiliation: Sana'a university, Yemen&#x0D; E-mail: alialkaf21@gmail.com&#x0D; &#x0D; Name: Dr. Gehan Fawzy Abdel Raoof Kandeel&#x0D; Affiliation: National Research Centre, Egypt&#x0D; E-mail: gehankandeel9@yahoo.com&#x0D; &#x0D; Name: Dr. Mahmut Yıldıztekin&#x0D; Affiliation: Muğla Sıtkı Koçman University, Turkey&#x0D; E-mail: mahmutyildiztekin@mu.edu.tr&#x0D; &#x0D; Comments of reviewer(s): &#x0D; &#x0D; Similar Articles:&#x0D; COMPARISION OF ANTIDYSLIPIEMIC POTENTIAL OF 80 MILLIGRAMS OF FENOFIBRATED WITH 8 GRAMS OF NIGELLA SATIVA SEEDS DAILY &#x0D; GC-MS ANALYSIS OF FIXED OILS OF NIGELLA SATIVA SEEDS &#x0D; WOUND DRESSINGS UPLOADED WITH MYRTLE BERRIES EXTRACT AND NIGELLA SATIVA HONEY

Gastrin release in a mucosal organ culture model exposed to a simulated digest of an equine dietary supplement

Horses are prone to GI diseases including colic, colitis, and gastric ulcers. Equine dietary supplements are commonly used as a means of supporting optimal equine gastrointestinal health. G’s Formula (manufactured by G’s Organic Solutions INC., BC, CAN) is an equine dietary supplement composed of dried cabbage, carrot, oat flour, and hemp meal, formulated to promote optimal GI health in horses. The objective of the current study was to investigate the impact of a simulated gastric digest of GF on gastrin (Gt) release in an in vitro mucosal organ culture model. Porcine stomachs were collected from a local abattoir (Reist and Weber, ON, CAN). A section of mucosa from the pyloric antrum was isolated and the smooth muscle removed. A 4mm punch biopsy was used to divide the mucosa, and 2 biopsies were placed into each well of a 24‐well culture dish. Each well was filled with 1.5 ml of media supplemented with glutamine. Media was changed at 24h, at which time 100 ul of either a simulated gastric digest of GF (GF), a simulated gastric digest blank (BL), or PBS (CO) was added into sample wells. Media and digests were refreshed at 48h, at which time wells were either stimulated with 10−5M carbachol (GF‐s, n=12; BL‐s, n=12; CO‐s, n=11) or sham stimulated with PBS (GF‐n, n=9; BL‐n, n=13; CO‐n, n=10). This process was repeated at 60h, and the experiment was terminated at 72h. Gt release in the media was assessed using a porcine Gt ELISA (MyBioSource INC., SD, USA) and standardized /g tissue. Data was analyzed using a repeated measures ANOVA in SAS 9.4 using PROC GLIMMIX (SAS Institute, NC, USA). There was a difference between the treatments GF and BL (16534±797 vs 14072±723 pg/ml/g, p=0.03) and a trend towards a difference between GF and CO (14581±794 pg/ml/g, p=0.09). At 60h GF‐n was higher than CO‐n (17475±1784 vs 12164±1688 pg/ml/g) and GF‐s was higher than BL‐s (16903±1543 vs 12434±1544 pg/ml/g). GF‐s was higher at 72h compared to 48h (18289±1543 vs 14051±1543, p=0.03). In conclusion, a simulated gastric digest of GF added into an in vitro organ culture of porcine pyloric antrum appears to enhance tissue Gt release.Support or Funding InformationThis project was funded by G’s Organic Solutions INC.J.L. MacNicol was funded by NSERC.

Response and relapse rates after treatment with long-acting somatostatin analogs in multifocal or recurrent type-1 gastric carcinoids: A systematic review and meta-analysis.

Type-1 gastric neuroendocrine tumors represent a recurring disease and long-acting somatostatin analogs can inhibit both gastrin release and endocrine cell proliferation. The efficacy and timing of this treatment are still unclear. We performed a systematic review of the literature to clarify the role of somatostatin analog treatment in type-1 gastric neuroendocrine tumors. A computerized literature search was performed using relevant keywords to identify all the pertinent articles published in the last 15 years. Eight studies were included in this systematic review on somatostatin analogs in type-1 gastric neuroendocrine tumors. A complete response rate ranged from 25-100%. When only the six prospective studies were considered, no significant heterogeneity was observed, and the pooled cumulative complete response rate was 84.5% (confidence interval 73.8-92.8). Three studies evaluated the type-1 gastric neuroendocrine tumor recurrence, with a cumulative relapse rate of 30.2% (confidence interval 13.1-50.6) after 34 months. Somatostatin analogs, namely lanreotide and octreotide, have an excellent response rate, with a good safety profile in selected type-1 gastric neuroendocrine tumors, which cannot be safely managed by endoscopic follow-up or resection due to multiple or frequently recurring disease. After therapy discontinuation, the cumulative relapse rate observed after a median 34-month follow-up was relatively high (30.2%).

Prospective comparison of 68Ga-RM2 PET/CT and 68Ga-PSMA-617 PET/CT for initial staging of prostate cancer.

21 Background: PSMA ( Prostate Specific Membrane Antigen) and GRP-R ( Gastrin Releasing Peptide Receptor) are overexpressed on prostatic cancer cells and can be targeted with a PSMA inhibitor such as 68Ga-PSMA-617 (Liu 2018) or a GRP-R antagonist such as 68Ga-RM2 (Touijer 2019). We aimed to compare 68Ga-PSMA-617 PET/CT and 68Ga-RM2 PET/CT at initial staging of prostate cancer. Methods: We prospectively enrolled 10 treatment-naïve patients with biopsy-confirmed prostate cancer. Fifteen lesions were found (two with Gleason score (GS) 6; seven GS 7(3+4), two GS 7(4+3) and four GS ≥ 8). 68Ga-PSMA-617 PET/CT and 68Ga-RM2 PET/CT were randomly performed before prostatectomy with imaging at 1 and 2 hours after injection (2MBq/kg). Manual (MS) and automatic (AS) segmentation were performed on each PET imaging and then compared to histology (standard-of- truth). Prostatectomy samples were analyzed by an experimented pathologist who identified and staged each lesion according to GS. Each prostatectomy slice available was scanned for comparison between PET and histologic segmentation. Uptake intensity (SUVmax) and signal-to-noise ratio (SNR) relative to non-lesional prostate gland parenchyma were analyzed. Per-lesion analysis was performed on final GS (prostatectomy). Results: Using AS, 68Ga-RM2 PET/CT showed better sensitivity (Se) than 68Ga-PSMA-617 PET/CT: (0.85 vs 0.75) and better specificity (Sp) (0.89 vs 0.60). MS found similar Se (0.94 vs 0.93) but better Sp (0.89 vs 0.80) with 68Ga-RM2 PET/CT. SNR of 68Ga-RM2 PET/CT was high whatever the GS was; while 68Ga-PSMA-617 PET/CT exhibited higher SNR in high GS (p = 0.044). Finally, in low GS, SNR of 68Ga-RM2 PET/CT was significantly higher than 68Ga-PSMA-617 PET/CT (p = 0.004). Conclusions: GRP-R-targeting and PSMA-targeting have been previously compared in patients with biochemically recurrence (Minamimoto 2016) but not at primary staging. Our initial results, in this indication, showed great diagnostic performance of 68Ga-RM2 PET/CT compared to 68Ga-PSMA-617 PET/CT to characterize low Gleason score tumors. 68Ga-PSMA-617 PET/CT is promising for initial staging of high Gleason score tumors. These results need to be confirmed in a larger study.

Helicobacter pylori And Duodenal Ulcer: Systematic Review Of Controversies In Causation.

BackgroundThere are controversies on the causal role of H. pylori in duodenal ulceration. Helicobacter pylori are curved gram-negative microaerophilic bacteria found at the layer of gastric mucous or adherent to the epithelial lining of the stomach. It’s a public health significance bacteria starting from discovery, and the prevalence and severity of the infection varies considerably among populations. H. pylori are a risk for various diseases, while the extent of host response like gastric inflammation and the amount of acid secretion by parietal cells affects the outcome of infection.MethodRelevant literature were searched from databases such as Google Scholar, PubMed, Hinari, Web of Science, Scopus, and Science Direct.ResultThe review evidence supports a strong causal relation between H. pylori infection and duodenal ulcer, as patients are more likely to be infected by virulent strains which later cause duodenal ulceration. Thus, eradication of H. pylori infection decreases the incidence of duodenal ulcers, and prevents its recurrence by reducing both basal gastrin release and acid secretion without affecting parietal cell sensitivity. On the other hand, some studies show that H. pylori infection is not associated with the development of duodenal ulcers and such a lack of association revealed that duodenal ulceration has different pathogenesis.ConclusionDespite controversies observed in the causal role of H. pylori to duodenal ulceration by various studies, Hill criteria of causation proved the presence of a causal relation between H. pylori infection and duodenal ulcers. Other factors are also responsible for the development of duodenal ulcers and such factors are responsible for the differences in the prevalence of the diseases.