Gastrin Concentrations Research Articles

Soluble and insoluble dietary fiber at different ratios: Hydration characteristics, rheological properties, and ameliorative effects on constipation

The proportion of soluble components in dietary fiber is an important factor affecting its physicochemical properties and physiological functions. The influence mechanisms of insoluble (IDF) and soluble dietary fiber (SDF) at different ratios on constipation were investigated. Results showed that SDF had higher active groups and water swelling capacity than IDF. The viscosity of chyme with SDF alone was the highest in oral and gastric phases. The gastric emptying rate and small intestine propulsion capacity increased significantly, especially when IDF/SDF was 1:1. IDF and a lower proportion of SDF (< 50 %) promoted gut microbiota diversity and short-chain fatty acids production. The contents of 5-hydroxytryptamine, acetylcholinesterase and gastrin reached the maximum value when the IDF ratio was 50 %. In conclusion, IDF could act synergistically with SDF to promote defecation and relieve constipation, and the effect was the best when the ratio of IDF to SDF was 1:1.

Study on the antihypertensive mechanism of acupuncture at "Renying" (ST9) and "Zusanli" (ST36) via gastrin/cholecystokinin B receptors

To observe the effect of acupuncture on serum gastrin content and urinary sodium excretion in spontaneously hypertensive rat (SHR), so as to explore its potential mechanism in the treatment of hypertension. Thirty-two male SHRs were randomly divided into model, hydrochlorothiazide, acupuncture and sham acupuncture groups, with 8 rats in each group, and 8 male Wistar-kyoto rats were taken as the control group. Rats in the hydrochlorothiazide group received gavage of hydrochlorothiazide solution (10 mg·kg-1·d-1), once daily for 4 weeks. Acupuncture was applied to bilateral "Renying" (ST9) and "Zusanli" (ST36) or non-acupoint on both sides for rats in the acupuncture and sham acupuncture groups, with manual stimulation every 10 minutes for a total of 20 minutes, once a day for a total of 4 weeks. The systolic blood pressure of the tail-artery was measured before and 1, 2, 3, and 4 weeks after the intervention. HE staining was used to observe the pathological changes in renal tissue. Serum gastrin contents were detected using enzyme-linked immunosorbent assay (ELISA). Urinary sodium content was measured by atomic absorption spectrometry. The expression levels of cholecystokinin B receptor (CCKBR) and Na+/K+-ATPase proteins in renal tissue were detected by Western blot, and the mRNA expression levels of CCKBR and the α1 subunit of Na+/K+- ATPase (ATP1A1) were detected by fluorescence quantitative PCR. Compared with the control group, the systolic blood pressure of the tail artery in the model group were increased significantly before intervention and at the 1st, 2nd, 3rd and 4th weeks of intervention (P<0.05). Before intervention, the 24 h urine volume of the model, hydrochlorothiazide, acupuncture and sham acupuncture groups were decreased significantly (P<0.05). After intervention, the 24 h urine volume and urinary sodium excretion in the model group were significantly decreased (P<0.05)；the expression levels of CCKBR protein and mRNA in renal tissue were significantly decreased (P<0.05)；the expression levels of Na+/K+-ATPase protein and ATP1A1 mRNA were significantly increased (P<0.05)；the glomerulus was mildly congested with a small amount of lymphocyte infiltration. Compared with the model group, the systolic blood pressure of the tail artery in the hydrochlorothiazide and the acupuncture groups were decreased significantly at the 2nd, 3rd and 4th weeks of intervention (P<0.05)；the 24 h urine volume and urinary sodium excretion in the hydrochlorothiazide and the acupuncture groups were significantly increased (P<0.05)；the serum gastrin content and the expression levels of CCKBR protein and mRNA in renal tissue were significantly increased (P<0.05)；the expression levels of Na+/K+-ATPase protein and ATP1A1 mRNA were significantly decreased (P<0.05)；there were no obvious pathological changes in renal tissue. A small number of lymphocyte focal infiltration around blood vessels was observed in the kidney tissue of the sham acupuncture group. Acupuncture can significantly reduce the tail artery systolic blood pressure of SHR, which may be related to its effect in increasing serum gastrin content and CCKBR expression, inhibiting sodium pump reabsorption, thus promoting urinary sodium excretion.

Evaluation of Two Commercial ELISA Kits for Measuring Equine Serum Gastrin Compared to Radioimmunoassay.

Gastrin is an important hormone involved in gastric acid secretion. Despite its importance, validated methods other than radioimmunoassay (RIA) to assess serum gastrin concentrations in horses are lacking. This study aims to determine the agreement between ELISA and RIA in quantifying equine serum gastrin concentrations. Serum gastrin concentrations were quantified using two ELISA kits and RIA. Samples (196) from 14 horses at different time points were analyzed using one ELISA kit and RIA, selected samples (7) were analyzed using a second ELISA kit, and the correlation between methods was calculated. The level of agreement was analyzed by Bland-Altman analysis and differences between ELISA and RIA were plotted against averages for each sample. The Pearson correlation between gastrin concentrations measured by ELISA and the RIA was 0.27 and -0.32 for ELISA kit 1 and kit 2, respectively. Mean bias (ELISA-RIA) was 198.40 pg/mL (95% CI: -142.95-539.76) and -17.90 pg/mL (95% CI: -89.98-54.19) for ELISA kit 1 and kit 2, respectively. Measurements of horse gastrin by both ELISA methods were highly variable, with an unacceptable correlation to the reference method, RIA. Using non-validated ELISA methods to quantify horse gastrin cannot be recommended.

Vonoprazan as a Long-term Maintenance Treatment for Erosive Esophagitis: VISION, a 5-Year, Randomized, Open-label Study

Background & AimsAcid secretion inhibitors are associated with hypergastrinemia, which can lead to gastric mucosal changes. Potassium-competitive acid blockers, such as vonoprazan, are more potent than proton pump inhibitors, but long-term safety data are lacking. MethodsIn this phase 4, randomized trial, patients with erosive esophagitis (EE) received induction therapy (once-daily vonoprazan 20 mg or lansoprazole 30 mg; ≤8 weeks). Those with healed EE received maintenance therapy (once-daily vonoprazan 10 mg or lansoprazole 15 mg) for 260 weeks (2:1). The primary endpoint was the proportion of patients with malignant epithelial cell alterations, parietal cell hyperplasia, foveolar hyperplasia, enterochromaffin-like (ECL) cell hyperplasia, and G-cell hyperplasia. ResultsOverall, 202/208 patients (vonoprazan n=139; lansoprazole n=69) achieved healed EE and received maintenance therapy. No malignant alterations or gastric neuroendocrine tumors (NETs) were observed; there was one adenoma in each group. At week 260, more patients taking vonoprazan versus lansoprazole had parietal cell hyperplasia (97.1% vs 86.5%) and foveolar hyperplasia (14.7% vs 1.9%); proportions of patients with ECL cell hyperplasia (4.9% vs 7.7%) and G-cell hyperplasia (85.3% vs 76.9%) were similar. Median serum gastrin levels were higher with vonoprazan treatment versus lansoprazole (625 pg/mL vs 200 pg/mL). Incidences of adverse events were comparable for both treatments. ConclusionsThe exploratory VISION study assessed the safety profile of vonoprazan and lansoprazole over 5 years in Japanese patients with healed EE. While gastrin concentration, parietal cell hyperplasia and foveolar hyperplasia were higher in the vonoprazan group, there was no increased risk of malignant epithelial cell alterations and gastric NETs. (ClinicalTrials.gov, NCT02679508.)

Early Enteral Nutrition Does Not Cause Excessive Inflammatory Response in Veno-Arterial Extracorporeal Membrane Oxygenation Patients

Background: To evaluate the safety between early enteral nutrition (EN) and parenteral nutrition (PN) by observing changes in inflammatory cytokines and gastrointestinal hormones in veno-arterial extracorporeal membrane oxygenation (VA ECMO) patients. Methods: This study was a prospective, observational study that enrolled patients receiving VA ECMO treatment from 1 January 2020 to 31 December 2023. Patients were enrolled in an EN group or a PN group according to the inclusion criteria. The concentration of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor α (TNF-α) on the first five days of VA ECMO treatement were tested in both groups. Serum concentrations of Motilin (MOT), Gastrin (GAS), Cholecystokinin (CCK), and Calcitonin gene-related peptide (CGRP) were measured for the EN group. Student t test or Fisher test was used to compare the difference between the two groups. Results: 28 patients were enrolled in this study; 16 in the EN group and 12 in the PN group. The baseline characteristics were comparable between the two groups. The concentration of IL-1β in the EN group was significantly lower than that of the PN group on day 3 and day 4 (day 3: 0.65 ± 0.17 pg/mL vs. 0.93 ± 0.09 pg/mL, p &lt; 0.01, day 4: 0.52 ± 0.16 pg/mL vs. 0.74 ± 0.12 pg/mL, p &lt; 0.01). The concentration of IL-6 and TNF-α in the EN group were also significantly lower than in the PN group on day 3 and day 4. There was no statistical difference in IL-10 serum concentration between the EN group and the PN group from day 1 to day 5. On day 3, the concentration of MOT, GAS and CCK reached the highest level and then gradually decreased. Conclusions: Implementation of early EN in patients receiving VA ECMO does not cause significant elevation of pro-inflammatory cytokines with an excessive inflammatory response.

Oriented immobilization of antibodies through peptide ligands for ultrasensitive detection of gastrin 17 in human serum via lateral flow immunoassay

Gastrin 17 (G-17) is a major biomarker for the diagnosis of gastric cancer. As the serum concentrations of gastrin are low, highly sensitive detection methods are needed. Previous studies have shown that oriented immobilization of detection antibodies can improve the sensitivity of lateral flow immunoassay (LFIA) methods. Herein, the antibody binding capacity of four Fc-specific peptides reported in different studies was evaluated, and two peptides with better binding potency were further modified with cysteine or the peptide GAC at their C-terminus. The peptide FYWHCLDEGAC exhibited the highest antibody binding capacity and was applied to directly immobilize the anti-G-17 antibody on microspheres with carboxyl-functionalized surfaces and europium-based time-resolved fluorescence. An LFIA method was developed to detect G-17 in human serum, and the limit of detection (LOD) of this method for G-17 was 0.08 pmol L-1, which was 10 times less than that of the nonoriented immobilization method. The working range of this method is 0.27 ∼ 600 pmol L-1, with a recovery rate of 85.2 % −106.7 % and a CV value less than 12.4 %. This method is easy to use, and the total detection process takes less than 20 min. The test results for the actual serum samples were consistent with the commercial kit results (R2 > 0.95), demonstrating that the method can be utilized for point-of-care testing of G-17. This approach to orientedly immobilize antibodies on nanomaterials can be used to develop sensitive LFIA methods for various molecules.

Beneficial Effect of Heat-Killed Lactic Acid Bacterium Lactobacillus johnsonii No. 1088 on Temporal Gastroesophageal Reflux-Related Symptoms in Healthy Volunteers: A Randomized, Placebo-Controlled, Double-Blind, Parallel-Group Study.

A randomized, placebo-controlled, double-blind, parallel-group clinical study was conducted to examine the effects of ingesting a heat-killed lactic acid bacterium, Lactobacillus johnsonii No. 1088 (LJ88) on temporal gastroesophageal reflux-related symptoms in healthy volunteers. A total of 120 healthy Japanese volunteers of both sexes, aged between 21 and 63 years, whose Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) total score was 8 or greater, but who were not diagnosed with functional dyspepsia according to the Rome IV classification, were enrolled. They were randomly assigned to either the LJ88 or placebo group and instructed to ingest the test food (1 billion heat-killed LJ88 or placebo) once a day for six weeks. Gastroesophageal reflux-related symptoms were evaluated using FSSG scores as a primary endpoint. The Gastrointestinal Symptoms Rating Scale (GSRS), stomach state questionnaire, and serum gastrin concentration were used as secondary endpoints. In the FSSG evaluation, the heartburn score was significantly improved at 6 weeks in the LJ88 group compared to the placebo group. No severe adverse events related to the test food were observed. In conclusion, daily ingestion of heat-killed LJ88 improved temporal heartburn symptoms in non-diseased individuals.

Evaluation of Gastric pH and Gastrin Concentrations in Horses Subjected to General Inhalation Anesthesia in Dorsal Recumbency.

The prevalence of gastric disorders in high-performance horses, especially gastric ulceration, ranges from 50 to 90%. These pathological conditions have negative impacts on athletic performance and health. This study was designed to evaluate changes in gastric pH during a 24 h period and to compare gastrin concentrations at different time points in horses undergoing general inhalation anesthesia and dorsal recumbency. Twenty-two mixed-breed mares weighing 400 ± 50 kg and aged 8 ± 2 years were used. Of these, eight were fasted for 8 h and submitted to 90 min of general inhalation anesthesia in dorsal recumbency. Gastric juice samples were collected prior to anesthesia (T0), and then at 15 min intervals during anesthesia (T15-T90). After recovery from anesthesia (45 ± 1 min), samples were collected every hour for 24 h (T1 to T24) for gastric juice pH measurement. During this period, mares had free access to Bermuda grass hay and water and were fed a commercial concentrate twice (T4 and T16). In a second group (control), four non-anesthetized mares were submitted to 8 h of fasting followed by nasogastric intubation. Gastric juice samples were then collected at T0, T15, T30, T45, T60, T75, and T90. During this period, mares did not receive food or water. After 45 min, mares had free access to Bermuda grass hay and water, and gastric juice samples were collected every hour for four hours (T1 to T4). In a third group comprising ten non-fasted, non-anesthetized mares with free access to Bermuda grass hay and water, gastric juice samples were collected 30 min after concentrate intake (T0). In anesthetized mares, blood gastrin levels were measured prior to anesthesia (8 h fasting; baseline), during recovery from anesthesia, and 4 months after the anesthetic procedure, 90 min after the morning meal. Mean values of gastric juice pH remained acidic during general anesthesia. Mean pH values were within the physiological range (4.52 ± 1.69) and did not differ significantly between time points (T15-T90; p > 0.05). After recovery from anesthesia, mean gastric pH values increased and remained in the alkaline range throughout the 24 h period of evaluation. Significant differences were observed between T0 (4.88 ± 2.38), T5 (7.08 ± 0.89), T8 (7.43 ± 0.22), T9 (7.28 ± 0.36), T11 (7.26 ± 0.71), T13 (6.74 ± 0.90), and T17 (6.94 ± 1.04) (p < 0.05). The mean gastric juice pH ranged from weakly acidic to neutral or weakly alkaline in all groups, regardless of food and water intake (i.e., in the fasted, non-fasted, and fed states). Mean gastric pH measured in the control group did not differ from values measured during the 24 h post-anesthesia period or in the non-fasted group. Gastrin concentrations increased significantly during the post-anesthetic period compared to baseline (20.15 ± 7.65 pg/mL and 15.15 ± 3.82 pg/mL respectively; p < 0.05). General inhalation anesthesia and dorsal recumbency did not affect gastric juice pH, which remained acidic and within the physiological range. Gastric juice pH was weakly alkaline after recovery from anesthesia and in the fasted and fed states. Serum gastrin levels increased in response to general inhalation anesthesia in dorsal recumbency and were not influenced by fasting. Preventive pharmacological measures are not required in horses submitted to general anesthesia and dorsal recumbency.

Effects of Desmodium caudatum on Gastrointestinal Hormones and Intestinal Flora in Rats with Gastritis.

In order to preliminarily explore the effects of Desmodium caudatum on gastritis and intestinal flora in rats, a chronic gastritis rat model was established using the classic sodium salicylate method. Eighteen SPF rats were divided into three groups: the control group (Group C), the model group (Group M), and the treatment group (Group T). Pathological sections of the gastric wall were taken from rats in each group. Furthermore, the concentrations of gastrin and malondialdehyde in the serum of rats in each group were determined by ELISA. Additionally, the effects of D. caudatum on the intestinal flora of rats with gastritis were explored through a detailed comparison of gut bacterial communities in the three groups, employing Illumina-based 16S rRNA gene sequencing. The results indicated that D. caudatum decoction could reduce the malondialdehyde content and increase the gastrin content. Moreover, D. caudatum decoction was found to enhance the diversity and abundance of intestinal flora, exerting a positive impact on the treatment of gastritis by regulating and restoring the intestinal flora.

The effects of Massa Medicata Fermentata on the digestive function and intestinal flora of mice with functional dyspepsia.

Introduction: The purpose of this study was to identify the chemical components of Massa Medicata Fermentata (MMF) in different fermentation methods, analyze its regulatory effects on gastrointestinal propulsion and intestinal flora in mice with food accumulation, and further explore its mechanism of action in the treatment of dyspepsia. Methods: The chemical compositions of three kinds of MMF were identified using the UPLC-Q- Exactive Orbitrap mass spectrometer. A model of spleen deficiency and food accumulation in mice was established. The gastric emptying rate and intestinal propulsion rate were calculated, serum gastrin concentration and cholinesterase activity were measured, and 16S rRNA microbial detection was performed in different groups of mouse feces. Results: The results showed that a total of 95 chemical components were identified from the three MMF extracts, 62 of which were the same, but there were differences in flavonoids and their glycosides, organic acids, and esters. MMF, PFMMF, and commercial MMF could all significantly improve the gastric emptying rate, intestinal propulsion rate, and GAS concentration in the serum of model mice; PFMMF has a better effect, while there was no significant difference in cholinesterase activity among the groups (p > 0.05). The 16S rRNA sequencing results showed that the MMF and PFMMF could increase the content of beneficial bacteria Bacteroidetes and decrease the pathogenic bacteria Verrucomicrobia in the intestines of model mice, while the commercial MMF could not. Discussion: Studies suggest that MMF has a variety of possible mechanisms for improving food accumulation and treating gastrointestinal dyspepsia, which provides reference value for the quality evaluation and clinical application of MMF.

The mechanism of folic acid on N-methyl-N’-nitro-N-nitrosoguanidine-induced chronic atrophic gastritis through the PI3K/Akt pathway.

Chronic atrophic gastritis (CAG) is a precancerous atrophic gastritis of the stomach, which generates an urge to develop novel therapeu-tic schedules. This study aimed to investigate the effect of experimental folic acid administration on N-methyl-N’-nitro-N-nitrosoguanidine (MNNG)-induced CAG through the PI3K/Akt pathway in rats. The rats were divided into a Model Group, a Folic Acid Group and a Blank Group. Rats in the Model Group were induced by MNNG and given 10 mL/kg/d distilled water by gavage, while rats in the Folic Acid Group were induced by MNNG and given 5 mg/kg/d folic acid suspension by gavage. As a control, rats in the Blank Group were given the same amount of distilled water as MNNG and 10 mL/kg/d distilled water by gavage. The levels of gastrin (GAS) and motilin (MTL) in serum were measured by enzyme-linked immunosorbent assay (ELISA), and the mRNA and protein ex-pressions were detected by quantitative polymerase chain reaction (q-PCR) and Western blot. According to hematoxylin and eosin (H&amp;E) pathological analysis, there were inflammatory factors infiltration and derangement of mucosal epi-thelial cells in the model group, while the gastric tissue injury in the folic acid group was improved. Folic acid could decrease the content of GAS, increase the content of MTL in the serum of the rats, and regulate the expression of PI3K and AKT signal pathways. Folic acid can have a therapeutic effect on CAG by reducing the concentration of GAS in serum and increasing the concentration of MLT in serum. Our study would lay a theoretical foundation for using folic acid to investigate new therapies for CAG in humans.

Long-Term Administration of Omeprazole-Induced Hypergastrinemia and Changed Glucose Homeostasis and Expression of Metabolism-Related Genes.

PPIs, or proton pump inhibitors, are the most widely prescribed drugs. There is a debate regarding the relationship between long-term PPI use and the risk of type 2 diabetes mellitus (T2DM). A potential connection between T2DM and PPIs could be an elevated gastrin concentration. This study is aimed at investigating the long-term effects of PPI omeprazole (OZ) on glucose homeostasis and pancreatic gene expression profile in mice. Healthy adult male BALB/c mice were randomly divided into three equal groups (n = 10 in each one): (1) experimental mice that received OZ 20 mg/kg; (2) control mice that received 30 μl saline per os; (3) intact mice without any interventions. Mice were treated for 30 weeks. Glucose homeostasis was investigated by fasting blood glucose level, oral glucose tolerance test (GTT), insulin tolerance test (ITT), and basal insulin resistance (HOMA-IR). Serum gastrin and insulin concentration were determined by ELISA. Expressions of Sirt1, Pparg, Nfκb1 (p105), Nfe2l2, Cxcl5, Smad3, H2a.z, and H3f3b were measured by RT-PCR. The ROC analysis revealed an increase in fasting blood glucose levels in OZ-treated mice in comparison with control and intact groups during the 30-week experiment. A slight but statistically significant increase in glucose tolerance and insulin sensitivity was observed in OZ-treated mice within 30 weeks of the experiment. The mice treated with OZ exhibited significant increases in serum insulin and gastrin levels, accompanied by a rise in the HOMA-IR level. These animals had a statistically significant increase in Sirt1, Pparg, and Cxcl5 mRNA expression. There were no differences in β-cell numbers between groups. Long-term OZ treatment induced hypergastrin- and hyperinsulinemia and increased expression of Sirt1, Pparg, and Cxcl5 in mouse pancreatic tissues accompanied by specific changes in glucose metabolism. The mechanism of omeprazole-induced Cxcl5 mRNA expression and its association with pancreatic cancer risk should be investigated.

Diagnostic significance of plasma gastrin concentration for the diagnosis of type 1 abomasal ulcer in water buffalo: A preliminary case control study

The type 1 abomasal ulcer (AU1) does not have specific clinical signs, so there is a need to identify some early biochemical markers for its diagnosis in cattle and buffaloes. The plasma gastrin is reported to reflect the gastric mucosa damage but its utility for the diagnosis of AU1 in buffaloes has not been evaluated. The objective of this study was to investigate the test performance of plasma gastrin to distinguish between healthy buffaloes and the buffaloes with AU1. Twenty-three buffaloes with AU1 and six buffaloes without any abomasal ulcer were used. The blood samples were collected from buffaloes, slaughtered in a buffalo specific slaughterhouse for estimation of the plasma gastrin. After slaughter the abomasa were examined for the presence of AU1 and the blood samples were collected for estimation of plasma gastrin. The mean plasma gastrin concentration of the ulcer-positive buffaloes was significantly (P&lt;0.05) higher than the ulcer-negative buffaloes. The receiver operating characteristic curve analysis suggested that the optimal value of plasma gastrin for the diagnosis of AU1 was 106.2 pg/mL. This preliminary work suggests that plasma gastrin could be a valid diagnostic test for the detection of AU1 in the buffaloes. The sensitivity, specificity, positive predictive value and negative predictive value of the plasma gastrin to diagnose AU1 in the buffaloes were 78.3, 100, 100 and 69.9 pg/mL, respectively.

Serum gastrin concentrations in dogs with primary hyperparathyroidism.

Hypercalcemia has been associated with hypergastrinemia in humans. Hypergastrinemia could be responsible for gastrointestinal (GI) signs in dogs with primary hyperparathyroidism (PHPT). (a) Determine whether hypergastrinemia occurs in dogs with PHPT, (b) assess for potential correlations among ionized calcium (iCa), parathyroid hormone (PTH), and serum gastrin concentrations, and (c) determine whether gastrin concentrations decrease after management of PHPT. Phase 1: 151 client-owned dogs at the time of PHPT diagnosis, Phase 2: 24 dogs that underwent treatment for PHPT. Dogs with azotemia, concurrent disease, or those receiving acid suppressants were excluded. Twenty-four treated dogs had baseline and repeat quantification of serum gastrin, PTH, and iCa concentrations 4 weeks after treatment. The effect of treatment on gastrin, iCa, and PTH concentrations was assessed using Wilcoxon signed rank sum tests. Fisher exact testing was used to compare the proportion of dogs with hypergastrinemia in dogs with and without GI signs. Twenty-seven of 151 PHPT dogs (17.9%) had increased pre-treatment serum gastrin concentrations (median, 45.0 ng/L; interquartile range [IQR], 20.0 ng/L). Gastrin concentrations were not correlated with iCa (P = .92) or PTH (P = .60). Treatment of PHPT decreased PTH (P < .001) and iCa concentrations (P < .001), but not gastrin concentrations (P = .15). The proportion of dogs with hypergastrinemia with and without GI signs did not differ (P = 1.00). Mild increases in serum gastrin concentrations may be seen in dogs with PHPT, but this finding is independent of the presence of GI signs.

Elevated Serum Gastrin Is Associated with Melanoma Progression: Putative Role in Increased Migration and Invasion of Melanoma Cells

Micro-environmental factors, including stromal and immune cells, cytokines, and circulating hormones are well recognized to determine cancer progression. Melanoma cell growth was recently shown to be suppressed by cholecystokinin/gastrin (CCK) receptor antagonists, and our preliminary data suggested that melanoma patients with Helicobacter gastritis (which is associated with elevated serum gastrin) might have an increased risk of cancer progression. Therefore, in the present study, we examined how gastrin may act on melanoma cells. In 89 melanoma patients, we found a statistically significant association between circulating gastrin concentrations and melanoma thickness and metastasis, which are known risk factors of melanoma progression and prognosis. Immunocytochemistry using a validated antibody confirmed weak to moderate CCK2R expression in both primary malignant melanoma cells and the melanoma cell lines SK-MEL-2 and G361. Furthermore, among the 219 tumors in the Skin Cutaneous Melanoma TCGA Pan-Cancer dataset showing gastrin receptor (CCKBR) expression, significantly higher CCKBR mRNA levels were linked to stage III–IV than stage I–II melanomas. In both cell lines, gastrin increased intracellular calcium levels and stimulated cell migration and invasion through mechanisms inhibited by a CCK2 receptor antagonist. Proteomic studies identified increased MMP-2 and reduced TIMP-3 levels in response to gastrin that were likely to contribute to the increased migration of both cell lines. However, the effects of gastrin on tumor cell invasion were relatively weak in the presence of the extracellular matrix. Nevertheless, dermal fibroblasts/myofibroblasts, known also to express CCK2R, increased gastrin-induced cancer cell invasion. Our data suggest that in a subset of melanoma patients, an elevated serum gastrin concentration is a risk factor for melanoma tumor progression, and that gastrin may act on both melanoma and adjacent stromal cells through CCK2 receptors to promote mechanisms of tumor migration and invasion.

Pharmacodynamics Research on Danggui-Shaoyao-San through Body Fluid Indexes of Spleen Deficiency-water Dampness Rats using Bio-impedance Technology.

Spleen deficiency-water dampness symptom is closely related to body fluid-mediated organism metabolism and circulation. However, previous clinical evaluation of spleen deficiency-water dampness model was based only on body weight, D-xylose excretion rate, serum gastrin content, etc. Therefore, we established a large sample of normal rats and model rats experiment to verify the scientific nature of bio-impedance measuring body fluid indexes for evaluation of the modeling state. Pharmacodynamics research on Danggui-Shaoyao- San (DSS) was conducted through body fluid index changes of rats using bio-impedance technology. A spleen deficiency-water dampness symptom rat model was established through an inappropriate diet combined with excess fatigue. Experimental rats were divided into a normal control group, a model control group, a positive drug control group (hydrochlorothiazide), a blood-activating group, a water-disinhibiting group, and a DSS group. Total Body Water/Body Weight (TBW%), extracellular fluid/total body water content (ECF%), intracellular fluid/total body water content (ICF%), extracellular fluid/intracellular fluid (ECF/ICF), fat mass/body weight (FM%), fat-free mass/body weight (FFM%), and fat mass/fat-free mass (FM/FFM) of 150 rats were detected by a Bio-Imp Vet Body analyzer. The TBW% of the model control group increased significantly, and the FM/FFM was significantly reduced compared with the normal group (P < 0.05) (P < 0.01), showing symptoms of spleen deficiency and diarrhea; the TBW% of the blood-activating group, and the waterdisinhibiting group decreased significantly, and the FM/FFM increased significantly (P < 0.05) (P < 0.01). The TBW% and FM/FFM in the water-disinhibiting group had returned to nearnormal values compared with the model control group. The blood-activating and waterdisinhibiting split prescriptions in DSS are both effective in treating spleen deficiency-water dampness rats. Comparatively, the fluid-regulating effect of split prescriptions in DSS was even stronger than that of DSS as shown in the present study. These findings suggest that using bio-impedance technology to measure body fluid indexes can pave a road for further exploring the molecular mechanism of the reason why the blood-activating and disinhibit-water split prescriptions in DSS are both effective in treating spleen deficiency-water dampness rats.

Gastric pH and serum gastrin concentration in age-matched healthy dogs and dogs with chronic kidney disease.

Gastric hyperacidity and hypergastrinemia are purported to cause gastric ulceration in dogs with chronic kidney disease (CKD); however, no published studies have evaluated gastric pH with serum gastrin concentrations in dogs with CKD. To compare mean intragastric pH, mean percent pH distribution, and serum gastrin concentrations in dogs with CKD to age-matched, healthy dogs. We hypothesized there would be no difference in mean gastric pH or serum gastrin between groups. Thirteen dogs with CKD; 10 aged-matched healthy dogs. Prospective, case-control study. Serum chemistry, complete blood count, urinalysis, and serum gastrin concentrations were evaluated in all dogs before radiographic-assisted gastric placement of a pH capsule. Forty-eight-hour continuous gastric pH monitoring was performed in all dogs. Serum gastrin concentration, mean pH, and mean percentage time that gastric pH was strongly acidic (pH <1 and pH <2) were compared between groups using a repeated measures mixed-model ANOVA. No significant differences were observed between groups for any pH measurements, including mean ± SD gastric pH (CKD, 2.37 ± 0.87; healthy, 2.39 ± 0.99; P > .05). Serum gastrin concentrations were not significantly different between groups (median [range]: CKD, 10.5 ng/dL [<10-17.1]; healthy, 10.9 ng/dL [<10-15]; P > .05). Our client-owned dogs with CKD did not have lower gastric pH or higher serum gastrin concentrations compared to healthy dogs. Our results suggest that prophylactic gastric acid suppression in dogs with CKD is not warranted unless other clinical indications for use are present.

Gastrin attenuates sepsis-induced myocardial dysfunction by down-regulation of TLR4 expression in macrophages.

Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.

Impact of fatty acid composition on markers of exocrine pancreatic stimulation in dogs.

Chronic pancreatitis in dogs is typically managed with a low-fat diet. Human research suggests that consumption of medium-chain triglycerides (MCT) may lessen pancreatic enzyme release compared to consumption of long-chain fatty acids (LCFA). Twelve healthy adult colony dogs were fed a meal of cod and rice with either 3% metabolizable energy (ME) fat (control), high MCT (25% ME MCT oil, 25% ME butter), high saturated LCFA (50% ME butter), or high unsaturated LCFA (50% ME canola oil) in a 4-period by 4-treatment crossover design. Serum concentrations of canine pancreatic lipase immunoreactivity, gastrin, cholesterol, triglycerides, and serum activities of amylase and DGGR lipase (1,2-o-dilauryl-rac-glycero-3-glutaric acid-(69-methylresorufin) ester lipase) were measured at times 0 (fasted), 30, 120 and 180 minutes post-prandially. Following a 3-or 4-day wash-out period, each dog was assigned a new diet and the process was repeated for all treatments. Data were analyzed as a repeated-measures mixed model ANOVA. Post-hoc pairwise comparisons were run using Tukey-Kramer adjusted p-values. Shapiro-Wilk tests were used to evaluate residual normality. All statistical assumptions were sufficiently met. Statistical significance was defined as P<0.05. Of the markers tested, only serum triglyceride concentrations were affected by treatment, with consumption of high MCT resulting in lower triglycerides than both LCFA groups at times 120 and 180 minutes (P<0.0001). As expected, the high MCT group had higher triglycerides compared to the control group (P<0.0001). The type of dietary fat consumed had little acute impact on most markers of exocrine pancreatic stimulation in healthy dogs.

Establishment of a reference interval for 12-hour fasted serum gastrin concentration in adult dogs.

Adherence to traditional 24-h fasting periods for serum gastrin concentration in dogs can be challenging and may delay the institution of therapies for suspected hypergastrinemia. Peer-reviewed publications regarding serum gastrin reference intervals (RI) are lacking. Hypercalcemia is associated with hypergastrinemia in people; limited data exist in dogs. The objective of the study was to generate a RI for a 12-h fasted serum gastrin concentration in dogs and to investigate whether correlations exist with age, weight, sex, and total calcium concentration. Fifty-five healthy adult dogs (>1 year of age). The screening included: medical history, physical examination, CBC (15 dogs), and serum chemistry (55 dogs). Gastrin was measured via a commercial radioimmunoassay. The RI for 12-h fasted serum gastrin concentration was calculated according to the recommendations of the American Society for Veterinary Clinical Pathology. Additionally, data were evaluated for correlation with selected variables. The RI for serum gastrin following a 12-h fasting period was 15.1-78.9 ng/L with 90% confidence intervals for the lower and upper limits of 14.0-22.9 and 68.3-83.0 ng/L, respectively. A generalized linear model did not detect significant relationships between gastrin and age (P = 0.48), sex (P = 0.30), weight (P = 0.93), or total calcium concentration (P = 0.84). A 12-h fasted serum gastrin concentration RI has been established. Given the limited range of serum calcium concentrations in our healthy study population, additional investigations are needed to determine the effects of hypercalcemia on serum gastrin concentrations in dogs and for any potential clinical consequences thereof.