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At least 19 recordsLinked to original sources

Effect of Ca2+, Mg2+, NaN3, cholinergic agents, and gastrointestinal hormones on the guanylate cyclase from guinea pig gastric mucosa.

Guanylate cyclase in the guinea pig fundic mucosa occurred in two enzymatic forms: a "soluble" form and a particulate form. The mean basal activity of the soluble fraction measured in the presence of 300 micrometer guanosine-5'-triphosphate and 5 mM MnCl2 was 72.6 +/- 5.3 pmoles of cyclic GMP per mg of protein per min. Guanylate cyclase activity was dependent on Mn2+; it was increased by sodium azide (NaN3), CaCl2, cysteine, secretin, and cholecystokinin, but it was not influenced by gastrin, histamine, cholinergic esters, prostaglandins E1 and A1. NaN3 (1 mM) decreased the apparent Km for MnCl2 and potentiated the effects of MgCl2. The activity of the particulate fraction represented about 14% of that of the supernatant fraction. The guanylate cyclase activity of that fraction was not modified by NaN3, gastrin, cholinergic agents, secretin, or cholecystokinin. Cysteine inhibited its activity. These data do not support the hypothesis that cyclic GMP acts as a second messenger for the action of cholinergic agents and gastrin in the guinea pig gastric mucosa.

Animals

Pharmacological properties of n1-piperonyl-n4-3,7,11-trimethyl-2,6,10-dodecatrienyl-piperazine, a new non-anticholinergic gastric antisecretory agent.

The special and general pharmacology of N1-piperonyl-N4-3,7,11-trimethyl-2,6,10-dodecatrienylpiperazine (U-27) is reported. According to the results of the animal experiments the compound turned out to be a well tolerated gastric antisecretory drug devoid of anticholinergic activity. The compound was able to prevent hypersecretion induced by pylorus ligature in rat and guinea pig. Its duration of action was remarkable and no tolerance occurred after a repeated treatment. The compound displayed also an interesting activity on several experimental ulcers.

Animals

Characterization of DPYD pharmacogenetic variation in Mexican patients with gastrointestinal malignancies.

PURPOSE: Fluoropyrimidines are among the most widely used chemotherapeutic agents for gastrointestinal malignancies, but interindividual variability in dihydropyrimidine dehydrogenase (DPD) activity, encoded by DPYD, can lead to severe or lethal toxicities. Most pharmacogenetic data on DPYD originates from European populations, limiting the applicability of current guidelines in admixed groups. METHODS: We evaluated DPYD pharmacogenetic variation and its association with fluoropyrimidine-related adverse events in Mexican patients with gastrointestinal cancers. Adverse events were prospectively assessed using CTCAE v5.0. Genotyping was performed with the Illumina Global Screening Array and analyzed using PLINK and R. RESULTS: A total of 208 patients were enrolled, and 192 samples passed genotyping quality control; 156 patients received fluoropyrimidines. Only three patients (1.5%) carried actionable DPYD variants (rs3918290, rs67376798 and rs75017182), yielding allele frequencies of 0.26%, approximately ten-fold lower than those reported in European cohorts. Genome-wide analyses did not reveal significant genotype-phenotype associations, though suggestive variants in SDK1, ZPBP, and FGF12 were observed. Pharmacodynamic analyses identified frequent variation in TYMS rs2847153 and MTHFR rs1801133, both previously associated with fluoropyrimidine toxicity. Overall, patients exhibited a predominantly Native Mexican ancestry (56.5%), which may explain the markedly low frequency of actionable DPYD alleles commonly found in European populations. CONCLUSIONS: These findings highlight the limited representation of admixed populations in pharmacogenetic research and underscore the need for population-specific data to inform safe and equitable fluoropyrimidine dosing.

Humans

Efficacy and safety of pantoprazole for stress-ulcer prophylaxis in critically ill patients: A systematic review and Meta-analysis of randomized controlled trials.

BACKGROUND: Stress-related mucosal damage (SRMD) is common in critically ill patients, and pharmacologic prophylaxis remains essential. This study evaluated the efficacy and safety of pantoprazole for stress-ulcer prophylaxis in ICU patients. MATERIALS AND METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted per PRISMA-2020 guidelines. PubMed, Scopus, and CENTRAL were searched for studies comparing pantoprazole with placebo in adult and pediatric ICU patients. The primary outcome was clinically important gastrointestinal (GI) bleeding; secondary outcomes included mortality, ventilator-associated pneumonia (VAP), and Clostridioides difficile infection. RESULTS: Seven RCTs (n ≈ 9127; pantoprazole = 4575; placebo = 4552) were included. Pantoprazole significantly reduced clinically important GI bleeding (RR = 0.53; 95% CI 0.29-0.94; p = 0.03) without affecting overall mortality (RR ≈ 0.99 [95% CI 0.92-1.05]; p = 0.68). Infection rates were similar between groups (VAP: RR = 0.99; p = 0.78; C. difficile: RR = 1.11; p = 0.73). Sensitivity analyses confirmed robustness. CONCLUSIONS: Pantoprazole effectively reduces clinically important GI bleeding without increasing infection or overall mortality.

Pantoprazole

Resistome and microbiome-immune interactions in an Eastern European population with high antibiotic use.

The gut microbiome influences host health, affecting gastrointestinal, metabolic, immune, cardiovascular, and neurological functions. A balanced microbiome is associated with favorable health outcomes. However, excessive antibiotic use and dietary habits can disrupt this ecosystem, leading to dysbiosis and affecting body homeostasis. This first comprehensive metagenomic analysis of the gut microbiome in a healthy Romanian cohort, a population underrepresented in microbiome studies and characterized by high antibiotic consumption, addresses a gap in current microbiome research. We report an enrichment of Enterobacteriaceae although overall composition is more comparable to other European than non-European cohorts. Community configurations align with established enterotype patterns, and our analysis provides insight into their relationship with within-phylum diversity. The analysis of antimicrobial resistance provides insight into the prevalence of resistance genes within this reservoir. We specifically report the presence of cfr(E), a Clostridioides difficile gene, and tet(X5), a variant from the ubiquitous tet family, genes not previously reported in healthy European populations. Integration with data from the European Centre for Disease Prevention and Control links the overall prevalence of resistance genes in this reservoir to antibiotic classes with higher community consumption in this population, notably beta-lactams and quinolones, highlighting potential targets for antibiotic stewardship programs. Finally, we investigate the relationship between the microbial profile and the systemic immune responses, inferred from correlations with in vitro cytokine production. Notably, we identify potential immune-priming roles for Collinsella, Flavonifractor, and Bifidobacterium species.IMPORTANCEThis first comprehensive study of the healthy gut microbiome in a Romanian cohort addresses a gap in current microbiome research, dominated by data sets from a limited number of regions. It sets a baseline for the microbiome and resistome composition of this population, and, while definitions of "healthy" microbiomes, or baseline resistomes, remain lacking, such study helps contextualize future studies and support the monitoring of dynamics. The Enterobacteriaceae abundance suggests a microbiome composition potentially influenced by antimicrobial consumption, a relevant pattern in a region with a high burden of nosocomial infections. In addition, the prevalence of antimicrobial resistance genes and the concordance with commonly used antibiotics in the community reinforce the need to address antibiotic use in public health strategies. Although gut microbiome-immunity relationships remain incompletely understood, our findings support a role for microbiome composition in immune-related traits and provide a valuable resource for future studies.

Humans

Pairwise Comparative Safety and Effectiveness of Anti-TNF Blockers, Vedolizumab, and Ustekinumab During Pregnancy: A Systematic Review and Meta-Analysis.

PURPOSE: Biologic therapies, including tumor necrosis factor (TNF) blockers, vedolizumab (VDZ), and ustekinumab (UST), are generally considered safe during pregnancy in patients with inflammatory bowel disease (IBD), though comparative data remain limited. This meta-analysis examines their safety and effectiveness. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL, Cochrane, and Web of Science was conducted through July 2025. Eligible studies reported maternal or neonatal outcomes in pregnant IBD patients treated with biologics. Studies were pooled using a random-effects model to calculate risk ratios (RRs) with 95% confidence intervals. Heterogeneity was assessed using I2. Primary outcomes were preterm birth and disease activity; secondary outcomes included pregnancy and neonatal outcomes. RESULTS: Nine observational studies (n = 6,054) were included. Compared to TNF blockers, VDZ was associated with a higher risk of preterm delivery (RR = 1.35, 95% CI 1.04-1.75, I2 = 0%) and active disease (RR = 1.55, 95% CI 1.01-2.40, I2 = 50%). UST was associated with a higher risk of active disease (RR = 1.30, 95% CI 1.06-1.60, I2 = 0%) and congenital anomalies (RR = 2.08, 95% CI 1.30-3.32, I2 = 0%) compared to TNF blockers. Compared to UST, VDZ was linked to increased risks of preterm birth (RR = 2.60, 95% CI 1.03-6.57, I2 = 0%) and low birth weight (RR = 2.38, 95% CI 1.01-5.60, I2 = 0%). No significant differences were observed for live births, abortions, hospitalizations, or neonatal infections. CONCLUSION: TNF blockers showed a favorable safety and effectiveness profile, VDZ and UST performed broadly similar, and all three biological classes appeared compatible with safe use in pregnancy to maintain effective disease control. Observed differences reflect that VDZ and UST cohorts likely had longer disease duration, prior biologic exposure, and more active disease. The results of this meta-analysis support the continuation of biologic therapy for disease control in pregnant patients with IBD. Treatment decisions should be individualized and tailored to each patient's clinical context.

Female

Calcium ion uptake in isolated pancreas cells induced by secretagogues.

1. Secretagogues of pancreatic enzyme secretion: pancreozymin, carbamylcholine, gastrin I, the octapeptide of pancreozymin, caerulein and the Ca2+ ionophore A 23187 stimulate 45Ca uptake into isolated rat pancreatic cells, whereas adrenaline, isoproterenol, secretin, dibutyrylic cyclic adenosine 3',5'-monophosphate and dibutyrylic cyclic guanosine 3',5'-monophosphate have no effect on 45Ca uptake. 2. A graphical analysis of the Ca2+ uptake curves reveals at least two phases: a fast phase, probably due to binding of Ca2+ to the membrane and a slow phase representing Ca2+ transport into cells. Both phases are stimulated by pancreozymin and carbamylcholine. 3. The 45Ca-exchangeable pool size is increased by both carbamylcholine and pancreozymin, whereas a significant increase of total content of cell calcium was too small to be detected. 4. Atropine blocks the stimulatory effect of carbamylcholine completely but not that of pancreozymin. The Ca2+ antagonist D600 blocks the stimulatory effects of both carbamylcholine and pancreozymin only partially. 5. The data suggest that secretagogues of pancreatic enzyme secretion act by increasing the rate of Ca2+ transfer into the cell most probably through an increase of the cell membrane permeability for Ca2+.

Animals

In vitro lipid metabolism in the rat pancreas. II. Effects of secretagogues on fatty acid metabolism, net lipolysis and ATP levels.

1. The concentration of carbamylcholine, bombesin, pancreozymin, pentagastrin and secretin evoking a similar 4--5-fold maximal increase in amylase secretion from rat pancreatic fragments were 3.10(-6), 10(-7), 10(-8), 3.10(-6), and 3.10(-6) M, respectively. The maximal concentration of vasoactive intestinal peptide tested (3.10(-6) M) increased amylase secretion by 250%. The six secretagogues could be separated into two groups according to their effects on lipid metabolism and ATP levels. 2. When used at their optimal concentrations, carbamylcholine, bombesin, pancreozymin, and pentagastrin lowered pancreatic ATP levels by 18-26% and increased net release of free fatty acids by 68-105%. 3. The effects of 3.10(-6) M carbamylcholine and 10(-8) M pancreozymin on the metabolism of 3H2O, D-[U-14C]glucose and [1-14C]acetate were similar; the incorporation of radioactivity in the fatty acid moiety of glycerolipids decreased by 20--50% whereas the incorporation of 3H from 3H2O and of 14C from [U-14C]glucose increased by 20--35% in the glycerol moiety. In addition, the oxidation of [U-14C]glucose, [1-14C]acetate and [1-14C]palmitate to 14CO2 increased by 15--32% while the esterification of [1-14C]palmitate, [1-14C]-linoleate, and [1-14C]arachidonate was inhibited by 14--23%. The spectrum of fatty acids labeled with [1-14C]acetate indicated an inhibition of the malonic acid pathway whereas the elongation of polyenoic fatty acids was unaltered.

Acetyl Coenzyme A