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BMC Gastroenterology May 2024Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such...
BACKGROUND
Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs.
METHODS
Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers.
RESULTS
Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy.
CONCLUSIONS
Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.
Topics: Animals; Aspirin; Omeprazole; Rats, Sprague-Dawley; Proton Pump Inhibitors; Gastric Mucosa; Gastrins; Male; Rats; Drug Administration Schedule; Humans; Peptic Ulcer; Intestinal Mucosa; Stomach Ulcer
PubMed: 38811868
DOI: 10.1186/s12876-024-03265-0 -
PloS One 2024Functional dyspepsia (FD) refers to a group of clinical symptoms caused by gastric and duodenal dysfunction. Which is a chronic functional disorder of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Functional dyspepsia (FD) refers to a group of clinical symptoms caused by gastric and duodenal dysfunction. Which is a chronic functional disorder of the gastrointestinal tract with no cure. Zhishixiaopi decoction (ZSXP) is a type of Chinese herbal prescription that for treating FD. Although some randomized controlled trials (RCTs) report that ZSXP can significantly improve FD clinical symptoms and/or laboratory results, the trial design varies greatly among studies, making it challenging to draw a conclusion of the efficacy of ZSXP in treating FD.
DESIGN
A systematic review and a meta-analysis.
SETTING
Mianyang Central Hospital.
OBJECTIVE
We conducted a systematic review and a meta-analysis to evaluate the efficacy and safety of ZSXP for treating FD.
METHODS
We developed inclusion and exclusion criteria based on FD diagnosed criteria, interventions to treat FD, and outcomes of these interventions. Search strategies combined disease terms, symptom terms, anatomy terms and intervention terms. Literature search was conducted on eight online databases in English or Chinese, including Medline (via PubMed), Embase (via Ovid), The Cochrane Library, Web of Science, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang Database.
INTERVENTION
The experimental group received oral administration of ZSXP and had a complete treatment process. ZSXP needs to fully contain the key herbal ingredients, regardless of whether the dosage of each herb is consistent with the original prescription. The Control group received monotherapy or combination therapy of other Western medicine and had a complete treatment process.
OUTCOMES
The primary outcomes appraised were Total effective rate (TER), serum levels of Motilin(MOT), Gastrin(GAS) and Somatostatin (SS), Gastric emptying rate (GER) using a Barium meal method (GER(B)) and Gastric half emptying time using an Ultrasonic method (GHET(T1/2)). The Cochrane Bias Risk Tool was used for quality critical appraisal, Review Manager (RevMan) version 5.3 was used for statistical analysis.
RESULTS
A total of 21 medium-quality RCTs were included in the meta-analysis. All 21 included studies were conducted and completed in Mainland China from 1998 to 2020. The treatment duration was between two weeks to two months. The meta-analysis suggests that, compared with the Western medicine treatment group, ZSXP treatment was more effective to improving the TER in FD [Odds ratio, OR = 3.54, 95%CI:(2.49, 5.05), Z = 6.99, P<0.00001] without significant increase in adverse events. However, no statistical significance was found between the groups in serum MOT levels [Standard mean difference, SMD = 1.05, 95%CI:(-0.42, 2.53), Z = 1.04, P = 0.16], serum GAS levels [SMD = -0.16, 95%CI:(-1.20, 0.88), Z = 0.31, P = 0.76], serum SS levels [SMD = -0.04, 95%CI:(-1.97, 1.89), Z = 0.04, P = 0.97], GER(B) [SMD = 1.09, 95%CI:(-0.81, 3.00), Z = 1.12, P = 0.26]or GHET(T1/2) [Mean difference, MD = -2.18, 95%CI:(-5.55, 1.19), Z = 1.27, P = 0.20].
CONCLUSIONS
The meta-analysis suggests that Zhishixiaopi treatment is a relatively effective and safe traditional Chinese medicine prescription and could be used for functional dyspepsia treatment. Considering the limitations of this study, the conclusion needs to be further confirmed by high-quality, multi-center, and large-sample randomized controlled trials.
Topics: Humans; Dyspepsia; Randomized Controlled Trials as Topic; Drugs, Chinese Herbal; Treatment Outcome
PubMed: 38809916
DOI: 10.1371/journal.pone.0301686 -
Pharmaceuticals (Basel, Switzerland) May 2024Gastrin-releasing peptide receptor (GRPR) is overexpressed in various cancers and is a promising target for cancer diagnosis and therapy. However, the high pancreas...
Gastrin-releasing peptide receptor (GRPR) is overexpressed in various cancers and is a promising target for cancer diagnosis and therapy. However, the high pancreas uptake and/or metabolic instability observed for most reported GRPR-targeted radioligands might limit their clinical applications. Our group recently reported a GRPR-targeted antagonist tracer, [Ga]Ga-TacsBOMB2 ([Ga]Ga-DOTA-Pip-D-Phe-Gln-Trp-Ala-Val-Gly-His-LeuψThz-NH), which showed a minimal pancreas uptake in a preclinical mouse model. In this study, we synthesized four derivatives with unnatural amino acid substitutions (Tle-derived Ga-LW01158, NMe-His-derived Ga-LW01160, α-Me-Trp- and Tle-derived Ga-LW01186, and Tle- and N-Me-Gly-derived Ga-LW02002) and evaluated their potential for detecting GRPR-expressing tumors with positron emission tomography (PET). The binding affinities (K(GRPR)) of Ga-LW01158, Ga-LW01160, Ga-LW01186, and Ga-LW02002 were 5.11 ± 0.47, 187 ± 17.8, 6.94 ± 0.95, and 11.0 ± 0.39 nM, respectively. [Ga]Ga-LW01158, [Ga]Ga-LW01186, and [Ga]Ga-LW02002 enabled clear visualization of subcutaneously implanted human prostate cancer PC-3 tumor xenografts in mice in PET images. Ex vivo biodistribution studies showed that [Ga]Ga-LW01158 had the highest tumor uptake (11.2 ± 0.65 %ID/g) and good tumor-to-background uptake ratios at 1 h post-injection. Comparable in vivo stabilities were observed for [Ga]Ga-LW01158, [Ga]Ga-LW01186, and [Ga]Ga-LW02002 (76.5-80.7% remaining intact in mouse plasma at 15 min post-injection). In summary, the Tle substitution, either alone or combined with α-Me-Trp or NMe-Gly substitution, in Ga-TacsBOMB2 generates derivatives that retained good GRPR binding affinity and in vivo stability. With good tumor uptake and tumor-to-background imaging contrast, [Ga]Ga-LW01158 is promising for detecting GRPR-expressing lesions with PET.
PubMed: 38794191
DOI: 10.3390/ph17050621 -
International Journal of Molecular... May 2024Proton pump inhibitors (PPIs) are widely used in the long-term treatment of gastroesophageal reflux disease (GERD) and other upper gastrointestinal disorders, such as... (Review)
Review
Proton pump inhibitors (PPIs) are widely used in the long-term treatment of gastroesophageal reflux disease (GERD) and other upper gastrointestinal disorders, such as the healing of peptic ulcers and/or prophylactic treatment of peptic ulcers. PPIs are also widely used as symptomatic treatment in patients with functional dyspepsia. One of the adverse effects of the long-term use of PPI is rebound acid hypersecretion (RAHS), which can occur after the withdrawal of PPI therapy due to a compensatory increase in gastric acid production. Mechanisms of the RAHS have been well established. Studies have shown that pentagastrin-stimulated acid secretion after the discontinuation of PPIs increased significantly compared to that before treatment. In healthy volunteers treated with PPIs, the latter induced gastrointestinal symptoms in 40-50% of subjects after the discontinuation of PPI therapy but after stopping the placebo. It is important for practicing physicians to be aware and understand the underlying mechanisms and inform patients about potential RAHS before discontinuing PPIs in order to avoid continuing unnecessary PPI therapy. This is important because RAHS may lead patients to reuptake PPIs as symptoms are incorrectly thought to originate from the recurrence of underlying conditions, such as GERD. Mechanisms of RAHS have been well established; however, clinical implications and the risk factors for RAHS are not fully understood. Further research is needed to facilitate appropriate management of RAHS in the future.
Topics: Humans; Proton Pump Inhibitors; Gastroesophageal Reflux; Gastric Acid; Animals
PubMed: 38791497
DOI: 10.3390/ijms25105459 -
In Vivo (Athens, Greece) 2024The long-term use of proton pump inhibitors (PPIs) has been reported to be strongly associated with the development of fundic gland polyps (FGPs). Conversely, a few...
BACKGROUND/AIM
The long-term use of proton pump inhibitors (PPIs) has been reported to be strongly associated with the development of fundic gland polyps (FGPs). Conversely, a few cases of gastric hyperplastic polyps (GHPs) associated with PPI use have been reported. We experienced a case of PPI-associated multiple GHPs with uncontrollable bleeding.
CASE REPORT
A 64 year old man with a history of rheumatoid arthritis presented to the hospital with complaints of vertigo and black stools. Blood tests revealed anemia and hypoproteinemia. Esophagogastroduodenoscopy (EGD) showed blood and black residue accumulated in the stomach. The source of the bleeding was multiple hyperplastic polyps. Bleeding could be stopped even with fasting, and total blood transfusions amounted to 28 units of RBCs were required in 18 days. After the cessation of PPI, EGD showed that the polyps had almost disappeared. Pathological diagnosis of resected polyp was hyperplastic polyp, which was characterized by capillary hyperplasia and edema. Gastrin receptors were over-expressed in the foveolar epithelium and not in the capillaries. Methotrexate (MTX)-induced portal hypertensive gastroenteropathy was revealed during follow-up. We consider that the effect of portal hypertension may have caused the capillary hyperplasia.
CONCLUSION
Although PPI-related polyps are usually fundic gland polyps and do not cause life-threatening adverse events, we experienced PPI-related GHPs in which hemostasis was difficult to control.
Topics: Humans; Male; Proton Pump Inhibitors; Middle Aged; Hyperplasia; Gastrointestinal Hemorrhage; Stomach Neoplasms; Polyps; Endoscopy, Digestive System; Adenomatous Polyps
PubMed: 38688629
DOI: 10.21873/invivo.13592 -
Nutrients Apr 2024A randomized, placebo-controlled, double-blind, parallel-group clinical study was conducted to examine the effects of ingesting a heat-killed lactic acid bacterium, No.... (Randomized Controlled Trial)
Randomized Controlled Trial
Beneficial Effect of Heat-Killed Lactic Acid Bacterium 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, 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.
Topics: Humans; Double-Blind Method; Female; Male; Adult; Gastroesophageal Reflux; Probiotics; Middle Aged; Young Adult; Lactobacillus johnsonii; Healthy Volunteers; Hot Temperature; Heartburn; Gastrins
PubMed: 38674920
DOI: 10.3390/nu16081230 -
Animals : An Open Access Journal From... Apr 2024The use of omeprazole as a preventive treatment for gastrointestinal ulcers in veterinary medicine has been questioned during previous years. The aim of the present...
The use of omeprazole as a preventive treatment for gastrointestinal ulcers in veterinary medicine has been questioned during previous years. The aim of the present study is to assess the long-term effect of omeprazole on cobalamin and serum gastrin levels in healthy dogs. Eighteen healthy dogs were included: 10 in the control group and 8 in the omeprazole group. Three samples were collected: before starting the treatment (T), 30 days after the start of treatment (T), and at 60 days (T). The mean cobalamin value (ng/L) in the control group was 481.4 (±293.70) at T, 481.4 (±170.21) at T, and 513.2 (±174.50) at T. In the omeprazole group, the values were 424.62 (±161.57) at T, 454.5 (±160.96) at T, and 414.87 (±127.90) at T. No statistically significant changes were detected in cobalamin levels between the three-time period in both study groups. These results agree with previous findings in felines but contrast with human medicine studies. The median gastrin values (pg/mL) in the control group were 62.45 [30.17-218.75] at T, 76.06 [30.67-199.87] at T, and 63.02 [35.81-176.06] at T. The median gastrin value in the omeprazole group was 67.59 [55.96-101.60] at T, 191.77 [75.31-1901.77] at T, and 128.16 [43.62-1066.46] at T. Statistically significant differences were detected ( = 0.008), indicating an increase in gastrin levels after initiating treatment with omeprazole. In conclusion, the increased levels of gastrin observed in this population underscore the importance of conducting a comprehensive clinical assessment to identify potential gastrointestinal disorders, particularly in consideration of the usage of omeprazole as a preventive treatment.
PubMed: 38672316
DOI: 10.3390/ani14081168 -
Medicine Apr 2024Qi deficiency in the spleen and stomach is considered to be the fundamental pathogenesis of chronic atrophic gastritis (CAG) in Traditional Chinese medicine. Spleen... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Qi deficiency in the spleen and stomach is considered to be the fundamental pathogenesis of chronic atrophic gastritis (CAG) in Traditional Chinese medicine. Spleen strengthening and Qi replenishment are the basic treatment principles. Sijunzi Decoction serves as the fundamental remedy for spleen notification and Qi replenishment.
METHODS
The Cochrane Library, China National Knowledge Infrastructure China Biology Medicine disc, VIP, Wanfang Database, Web of Science, PubMed, and Embase were retrieved for related randomized controlled trials published from the inception of the databases to June 3, 2023. Literature screening and data extraction were executed by 2 independent investigators. The Cochrane Collaboration tool was leveraged to appraise the quality of included studies. Meta-analysis was implemented utilizing Stata 15.
RESULTS
This analysis incorporated 32 studies with 2780 patients. The analysis results unveiled that compared to Western medicine treatment, modified Sijunzi Decoction significantly enhanced the clinical efficacy (relative risk [RR] = 1.241, 95% confidence interval [95% CI] = 1.199-1.285, P < .0001), lowered symptom scores (standardized mean difference [SMD] = -1.846, 95% CI = -2.160 to -1.532, P < .00001) and gastroscopic pathological scores (SMD = -1.122, 95% CI = -1.492 to -0.752, P < .00001), ameliorated quality of life (SMD = 4.294, 95% CI = 2.982-5.606, P < .00001), increased the Helicobacter pylori eradication rate (RR = 1.297, 95% CI = 1.035-1.625, P < .001), pepsinogen I levels (SMD = 2.615, 95% CI = 2.344-2.886, P < .00001), pepsinogen I/II ratio (SMD = 3.107, 95% CI = 2.811-3.403, P < .00001), and gastrin-17 levels (SMD = 1.004, 95% CI = 0.794-1.215, P < .00001), and reduced the incidence of adverse reactions (RR = 0.361, 95% CI = 0.235-0.556, P < .01) in individuals with CAG, with statistically significant discrepancies.
CONCLUSION
Modified Sijunzi Decoction exhibited superior efficacy to conventional Western medicine in treating CAG. It was shown to improve the Helicobacter pylori eradication rate, reduce symptom scores, enhance quality of life, and improve pepsinogen-related indicators with a high safety profile.
Topics: Humans; Drugs, Chinese Herbal; Gastritis, Atrophic; Randomized Controlled Trials as Topic; Helicobacter pylori; Helicobacter Infections; Treatment Outcome
PubMed: 38669406
DOI: 10.1097/MD.0000000000037648 -
Gut hormone analogues and skeletal health in diabetes and obesity: Evidence from preclinical models.Peptides Jul 2024Diabetes mellitus and obesity are rapidly growing worldwide. Aside from metabolic disturbances, these two disorders also affect bone with a higher prevalence of bone... (Review)
Review
Diabetes mellitus and obesity are rapidly growing worldwide. Aside from metabolic disturbances, these two disorders also affect bone with a higher prevalence of bone fractures. In the last decade, a growing body of evidence suggested that several gut hormones, including ghrelin, gastrin, glucose-dependent insulinotropic polypeptide (GIP), glucagon, and glucagon-like peptide-1 and 2 (GLP-1 and GLP-2, respectively) may affect bone physiology. Several gut hormone analogues have been developed for the treatment of type 2 diabetes and obesity, and could represent a new alternative in the therapeutic arsenal against bone fragility. In the present review, a summary of the physiological roles of these gut hormones and their analogues is presented at the cellular level but also in several preclinical models of bone fragility disorders including type 2 diabetes mellitus, especially on bone mineral density, microarchitecture and bone material properties. The present review also summarizes the impact of GLP-1 receptor agonists approved for the treatment of type 2 diabetes mellitus and the more recent dual or triple analogue on bone physiology and strength.
Topics: Humans; Obesity; Diabetes Mellitus, Type 2; Animals; Gastrointestinal Hormones; Bone Density; Bone and Bones; Glucagon-Like Peptide 1; Gastric Inhibitory Polypeptide
PubMed: 38657908
DOI: 10.1016/j.peptides.2024.171228 -
Frontiers in Microbiology 2024Constipation is a common gastrointestinal disease that seriously affects human physical and mental health. Studies have reported that hemp seeds can improve...
Constipation is a common gastrointestinal disease that seriously affects human physical and mental health. Studies have reported that hemp seeds can improve constipation, however the specific mechanism is still unclear. This study investigates that hemp seed (HS) and its water-ethanol extract (HSE) attenuates loperamide-induced constipation in mice. The research results show that: the fecal water content and small intestinal transit rate of mice in the hemp seed group and hemp seed hydroalcoholic extract group were significantly increased compared with MC group, and the first red feces defecation time was significantly shortened; HS and HSE significantly influence serum levels of Gastrin (Gas), motilin (MTL), substance P (SP), and endothelin (ET), potentially mediating their effects on gastrointestinal motility. HS and HSE can improve colon inflammation in constipated mice with H&E staining. Compared with the model of constipation group, the content of short-chain fatty acids in the HS group and HSE group increased significantly. Gut microbiome studies have shown that the structure and abundance of intestinal flora are altered. HS and HSE changed the abundance of . Together, these results suggest that HS have the potential to stimulate the proliferation of beneficial gut microbes and promote intestinal motility, thereby improving gut health and relieving symptoms of constipation.
PubMed: 38638898
DOI: 10.3389/fmicb.2024.1353015