Enteric duplication cysts in paediatric population along with literature review / Quistes de duplicación entérica en población pediátrica y revisión de la literatura

The clinical presentation of enteric duplication cysts is dependent on the location of the cyst with symptoms varying from nausea and vomiting to abdominal distension, pain and perforation. Four patients were identified who were diagnosed with enteric duplication cysts within the period from 2019 to 2023. Three of the patients presented with signs of intestinal obstruction-abdominal distension and pain, while one had an antenatally detected abdominal mass. There were three boys and one girl with ages ranging from 4 months to 14 years. Three cases of ileal and one case of caecal duplication cyst were reported. Most of the cases showed ileal/caecal mucosa while one case demonstrated ectopic gastric mucosa. The treatment of these cysts includes surgical excision. Although radiological investigations help in arriving at a provisional diagnosis, the final diagnosis can be confirmed only after histopathological examination. Early treatment prevents complications and results in a good prognosis for the patient. (AU)

La presentación clínica de los quistes de duplicación entérica depende de la ubicación del quiste, y los síntomas varían desde náuseas y vómitos hasta distensión abdominal, dolor y perforación. Se identificaron cuatro pacientes que fueron diagnosticados con quistes de duplicación entérica en el período de 2019 a 2023. Tres de los pacientes presentaron signos de obstrucción intestinal (distensión abdominal y dolor), mientras que uno tenía una masa abdominal detectada prenatalmente. Eran tres niños y una niña con edades comprendidas entre 4 meses y 14 años. Se notificaron tres casos de quiste de duplicación ileal y un caso de quiste de duplicación cecal. La mayoría de los casos mostraron mucosa ileal/cecal, mientras que un caso mostró mucosa gástrica ectópica. El tratamiento de estos quistes incluye la escisión quirúrgica. Aunque las investigaciones radiológicas ayudan a llegar a un diagnóstico provisional, el diagnóstico final solo puede confirmarse después del examen histopatológico. El tratamiento precoz previene complicaciones y redunda en un buen pronóstico para el paciente. (AU)

A Model of Gastric Mucosal pH Regulation: Extending Sensitivity Analysis Using Sobol' Indices to Understand Higher Moments.

Several recent theoretical studies have indicated that a relatively simple secretion control mechanism in the epithelial cells lining the stomach may be responsible for maintaining a neutral (healthy) pH adjacent to the stomach wall, even in the face of enormous electrodiffusive acid transport from the interior of the stomach. Subsequent work used Sobol' Indices (SIs) to quantify the degree to which this secretion mechanism is "self-regulating" i.e. the degree to which the wall pH is held neutral as mathematical parameters vary. However, questions remain regarding the nature of the control that specific parameters exert over the maintenance of a healthy stomach wall pH. Studying the sensitivity of higher moments of the statistical distribution of a model output can provide useful information, for example, how one parameter may skew the distribution towards or away from a physiologically advantageous regime. In this work, we prove a relationship between SIs and the higher moments and show how it can potentially reduce the cost of computing sensitivity of said moments. We define γ -indices to quantify sensitivity of variance, skewness, and kurtosis to the choice of value of a parameter, and we propose an efficient strategy that uses both SIs and γ -indices for a more comprehensive sensitivity analysis. Our analysis uncovers a control parameter which governs the "tightness of control" that the secretion mechanism exerts on wall pH. Finally, we discuss how uncertainty in this parameter can be reduced using expert information about higher moments, and speculate about the physiological advantage conferred by this control mechanism.

Effect of gastric acids on the mechanical properties of conventional and CAD/CAM resin composites - An in-vitro study.

OBJECTIVES: Dental erosion in patients with gastroesophageal reflux disease (GERD) is a current and frequent condition that may compromise the mechanical properties and clinical durability of resin-based composites (RBCs). This study assessed the mechanical properties of conventional and computer-aided design/computer-aided manufacturing (CAD/CAM) RBCs subsequent to simulated gastric acid aging. MATERIALS AND METHOD: Three conventional and three CAD/CAM composites were assessed. They were divided into an experimental group (exposed to simulated gastric acid aging) and a control group (no aging). Both groups were analyzed for Vickers microhardness (VHN), wear and flexural strength over a period of six months. The failure rate probability for each RBC was calculated through the Weibull cumulative distribution function (m). Statistical analysis was conducted using repeated measures ANOVA, 3-way ANOVA, a non-parametric Kruskal-Wallis and U Mann-Whitney tests (α = 0.05). RESULTS: The mechanical properties of all the RBCs dropped significantly after aging (p < 0.05). Lower VHN and flexural strength values, along with greater wear values were evident in the experimental groups, though the effects of the treatment varied between RBCs. The Weibull m of all the RBCs decreased over time. CONCLUSION: Conventional RBCs might show greater reduction in mechanical properties compared to CAD/CAM RBCs when exposed to gastric acid attack. Thus, CAD/CAM composites may represent a suitable choice for the treatment of patients presenting erosive issues.

Rebound Acid Hypersecretion after Withdrawal of Long-Term Proton Pump Inhibitor (PPI) Treatment-Are PPIs Addictive?

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.

Multistimuli responsive microcapsules produced by the prilling/vibration technique for targeted colonic delivery of probiotics.

This study aimed to microencapsulate the probiotic strain Lactiplantibacillus plantarum 4S6R (basonym Lactobacillus plantarum) in both microcapsules and microspheres by prilling/vibration technique. A specific polymeric mixture, selected for its responsiveness to parallel colonic stimuli, was individuated as a carrier of microparticles. Although the microspheres were consistent with some critical quality parameters, they showed a low encapsulation efficiency and were discarded. The microcapsules produced demonstrated high yields (97.52%) and encapsulation efficiencies (90.06%), with dimensional analysis and SEM studies confirming the desired size morphology and structure. The results of thermal stress tests indicate the ability of the microcapsules to protect the probiotic. Stability studies showed a significant advantage of the microcapsules over non-encapsulated probiotics, with greater stability over time. The release study under simulated gastrointestinal conditions demonstrated the ability of the microcapsules to protect the probiotics from gastric acid and bile salts, ensuring their viability. Examination in a simulated faecal medium revealed the ability of the microcapsules to release the bacteria into the colon, enhancing their beneficial impact on gut health. This research suggests that the selected mixture of reactive polymers holds promise for improving the survival and efficacy of probiotics in the gastrointestinal tract, paving the way for the development of advanced probiotic products.

Metabolic regulator ERRγ governs gastric stem cell differentiation into acid-secreting parietal cells.

Parietal cells (PCs) produce gastric acid to kill pathogens and aid digestion. Dysregulated PC census is common in disease, yet how PCs differentiate is unclear. Here, we identify the PC progenitors arising from isthmal stem cells, using mouse models and human gastric cells, and show that they preferentially express cell-metabolism regulator and orphan nuclear receptor Estrogen-related receptor gamma (Esrrg, encoding ERRγ). Esrrg expression facilitated the tracking of stepwise molecular, cellular, and ultrastructural stages of PC differentiation. EsrrgP2ACreERT2 lineage tracing revealed that Esrrg expression commits progenitors to differentiate into mature PCs. scRNA-seq indicated the earliest Esrrg+ PC progenitors preferentially express SMAD4 and SP1 transcriptional targets and the GTPases regulating acid-secretion signal transduction. As progenitors matured, ERRγ-dependent metabolic transcripts predominated. Organoid and mouse studies validated the requirement of ERRγ for PC differentiation. Our work chronicles stem cell differentiation along a single lineage in vivo and suggests ERRγ as a therapeutic target for PC-related disorders.

Sodium citrate buffer improves pazopanib solubility and absorption in gastric acid-suppressed rat model.

Pazopanib exhibits pH-dependent solubility and its absorption depends primarily on the stomach pH. Significant decrease of pazopanib absorption by coadministration with proton pump inhibitors in clinical situation need to be overcome. Thus, the purpose of this study is firstly to investigate the effect of acidic beverages and sodium citrate buffer on the solubility of pazopanib and secondly to examine the effect of sodium citrate buffer on pazopanib absorption in a rat model with esomeprazole-mediated gastric acid suppression. Pazopanib solubility decreased with increasing pH of sodium citrate buffer in vitro. Interestingly, its solubility in some acidic beverages was significantly lower than that in sodium citrate buffer of the same pH. The AUC0-24h of pazopanib administered in tap water to rats treated with esomeprazole (ESP rats) was 66 % lower than that in the control rats treated with saline. However, AUC0-24h was 4.8 times higher in ESP rats that received pazopanib with sodium citrate buffer (pH 2.3) compared to ESP rats that received pazopanib with tap water. Our results indicate that the drug-drug interactions between pazopanib and proton pump inhibitors can be overcome, at least in part, by suspending pazopanib in sodium citrate buffer.

Managing gastrointestinal manifestations in systemic sclerosis, a mechanistic approach.

INTRODUCTION: Systemic sclerosis (SSc) is a connective tissue disease with heterogeneous presentation. Gastrointestinal (GI) complications of SSc are characterized by esophageal reflux, abnormal motility, and microbiome dysbiosis, which impact patient quality of life and mortality. Preventative therapeutics are lacking, with management primarily aimed at symptomatic control. AREAS COVERED: A broad literature review was conducted through electronic databases and references from key articles. We summarize the physiology of gastric acid production and GI motility to provide context for existing therapies, detail the current understanding of SSc-GI disease, and review GI medications studied in SSc. Finally, we explore new therapeutic options. We propose a management strategy that integrates data on drug efficacy with knowledge of disease pathophysiology, aiming to optimize future therapeutic targets. EXPERT OPINION: SSc-GI complications remain a challenge for patients, clinicians, and investigators alike. Management presently focuses on treating symptoms and minimizing mucosal damage. Little evidence exists to suggest immunosuppressive therapy halts progression of GI involvement or reverses damage, leaving many unanswered questions about the optimal clinical approach. Further research focused on identifying patients at risk for GI progression, and the underlying mechanism(s) that drive disease will provide opportunities to prevent long-term damage, and significantly improve patient quality of life.

Potassium-competitive acid blockers: rethinking acid suppression for gastroesophageal reflux disease and Helicobacter pylori.

Gastroesophageal reflux disease (GERD) and Helicobacter pylori (H. pylori) infection are different disease states that are united by the core role of acid suppression in their management. In GERD, proton pump inhibitors (PPIs) have long been standard therapy based on abundant positive clinical trial data supporting their efficacy and safety. In H. pylori, PPIs are also a critical element of therapy in combination with 1 or more antibiotics to achieve and maintain a pH that maximizes the efficacy of therapy. Despite the considerable clinical success and widespread use of PPIs, room remains for agents with differentiated pharmacokinetic and pharmacodynamic profiles. The potassium-competitive acid blockers (PCABs) are mechanistically distinct from PPIs but are acid-stable and do not require activation of the proton pump by coadministration of food. In pharmacodynamic studies, these agents have shown greater durations of acid suppression above the critical threshold of pH 4 (for GERD) and pH 6 (for H. pylori), which have been shown to optimize therapeutic efficacy in these settings. These results have translated in clinical studies to similar and, in some cases, improved outcomes relative to PPIs in these disease states. This review summarizes current knowledge on the physiology of acid secretion, pathophysiology and management of GERD and H. pylori, and key characteristics and clinical trial data for PPIs and PCABs.

[Intracellular Mechanism of Gastric Acid Secretion: What is the True Switch?]

In 1985, I was accepted as postdoc by Professor Forte of UC Berkeley. He discovered H+,K+-ATPase and established the membrane recycling theory as the activation mechanism for acid secretion using whole animals. H+,K+-ATPase is an enzyme that exchanges H+ with K+. In resting state, it locates on the tubulovesicles and the pump does not work because the membrane lacks K+ permeability. Upon stimulation, the tubulovesicles fuse to the apical membrane and acquire K+ permeability, turning the pump on. The main route was known to be protein kinase A (PKA), but its specific targets remained unknown. Right after I joined Forte's lab, I was fortunate enough to reproduce the above mechanism in vitro, and I discovered proteins of molecular weight 120 kDa and 80 kDa that were specifically phosphorylated in stimulated parietal cells. After I returned to Japan, the former was cloned and named as parchorin, which is one of the chloride intracellular channels. Although no progress was made on ezrin, I found out the importance of PIP2 and Arf6 using permeabilized gland models. After I left parietal cell research, the link between ezrin and Arf6 was revealed. PKA phosphorylates S66 of ezrin and also MST4. The former changes the N-terminal structure of ezrin to bind syntaxin3, and the latter phosphorylates ACAP4, an Arf6-GAP, to accelerate binding to ezrin. Subsequently, H+,K+-ATPase, SNAREs, ezrin, and Arf6-GAP are aligned on the apical membrane. However, there are still many unsolved questions and the intracellular mechanism of parietal cells remains an attractive research area.

Gastric acid-responsive deformable sodium alginate/Bletilla striata polysaccharide in situ gel for the protection and treatment of alcohol-induced peptic ulcers.

First-line drugs for peptic ulcer (PU) treatment are typically limited by poor targeting and adverse effects associated with long-term use. Despite recent advancements in novel therapeutic approaches for PU, the development of sustained-release delivery systems tailored to specific pathological characteristics remains challenging. Persistent inflammation, particularly gastric inflammatory microenvironment imbalance, characterizes the PU. In this study, we prepared an in situ gel composed of sodium alginate, deacetylated gellan gum, calcium citrate, and Bletilla striata polysaccharide (BSP) to achieve sustained release of BSP. The BSP in situ gel demonstrated favorable fluidity in vitro and completed self-assembly in vivo in response to the acidic milieu at a pH of 1.5. Furthermore, the shear, extrusion, and deformation properties increased by 26.4 %, 103.7 %, and 46.3 %, respectively, with long-term gastric retention (4 h) and mucosal adaptation. Animal experiments confirmed that the BSP in situ gel could attenuate necrotic injury and inflammatory cell infiltration, maintain mucosal barrier integrity, regulate cytokine imbalance and inflammation-associated hyperapoptosis, thus effectively alleviate the inflammatory microenvironmental imbalance in PU without significant side effects. Overall, our findings demonstrated that the BSP in situ gel is a promising therapeutic strategy for PU and opens avenues for developing self-assembled formulations targeting the pathological features of PUs.

Effect of simulated gastric acid on aesthetical restorative CAD-CAM materials' microhardness and flexural strength.

Background: Gastric acid, which is among erosive substances, gradually rises to the mouth in individuals with reflux and bulimia nervosa disorders, and this causes various effects on dental restorations. Aim: The objective of this study is in vitro investigation of gastric acid's effect on flexural strength and hardness on aesthetic restorative computer-aided design and computer-aided manufacturing (CAD-CAM) materials. Materials and Methods: For this study, four materials have been used, namely Enamic (Vita), Superfect Zir (Aidite) Zirconia, IPS e.max CAD (Ivoclar Vivadent), and Mark II (Vita). From these four different materials, 24 samples with 14 × 4 × 1 dimensions in rectangular prism form are used, which makes a total of 96 samples. One group was separated as the control group, while the rest was allowed to wait at 37°C, 5 ml gastric acid for 96 hours. Hardness value and flexural strengths were measured as pre-exposure and post-exposure to gastric acid. Results: There is a statistically significant difference between the groups in terms of the amount of decrease in the mean hardness after exposure to gastric acid compared to pre-exposure values (p: 0,000; P < 0,05). There was no statistically significant difference between the groups in terms of the amount of decrease in the post-exposure average flexural strength compared to the pre-exposure value (p: 0.063; P > 0.05). There is a statistically significant difference between the groups in terms of the average flexural strength after exposure to the acid. Conclusions: According to the data obtained, it was concluded that exposure to gastric acid affects the hardness and flexural strength properties of dental restorative ceramic materials.

Gastric acid challenge of lithium disilicate-reinforced glass-ceramics and zirconia-reinforced lithium silicate glass-ceramic after polishing and glazing-impact on surface properties.

OBJECTIVES: To investigate the impact of simulated gastric acid on the surface properties of lithium disilicate-reinforced glass-ceramics and zirconia-reinforced lithium silicate glass-ceramic after certain polishing and glazing procedures. MATERIALS AND METHODS: Four different types of square-shaped specimens (10 × 10 × 2 mm3, n = 13) were manufactured: lithium disilicate-reinforced glass-ceramic milled and polished (LDS-P); milled, polished, and glazed (LDS-PG); milled, glazed, and no polishing (LDS-G); and milled and polished zirconia-reinforced lithium silicate glass-ceramic (ZR-LS). Specimens were immersed in hydrochloride acid (HCl 0.06 M, pH 1.2) to simulate gastric acid irritation and stored in the acid for 96 h in 37 °C. Specimen weight, surface gloss, Vickers surface microhardness and surface roughness (Ra, Rq, with optical profilometer), and surface roughness on nanometer level (Sq, Sal, Sq/Sal, Sdr, Sds with atomic force microscope) were measured before and after the acid immersion. RESULTS: ZR-LS specimens lost significantly more weight after acid immersion (p = 0.001), also surface microhardness of ZR-LS was significantly reduced (p = 0.001). LDS-G and LDS-PG showed significantly lower surface roughness (Sa, Sq) values compared to LDS-P before (p ≤ 0.99) and after (p ≤ 0.99) acid immersion and ZR-LS after acid immersion (p ≤ 0.99). CONCLUSIONS: Gastric acid challenge affects the surface properties of lithium disilicate-reinforced glass-ceramic and zirconia-reinforced lithium silicate glass-ceramic. Glazing layer provides lower surface roughness, and the glazed surface tends to smoothen after the gastric acid challenge. CLINICAL RELEVANCE: Surface finish of lithium disilicate-reinforced glass-ceramic and zirconia-reinforced lithium silicate glass-ceramic has a clear impact on material's surface properties. Gastric acidic challenge changes surface properties but glazing seems to function as a protective barrier. Nevertheless, also glazing tends to smoothen after heavy gastric acid challenge. Glazing can be highly recommended to all glass-ceramic restorations but especially in patients with gastroesophageal reflux disease (GERD) and eating disorders like bulimia nervosa.

The effects of gastric acid on pediatric restorative materials: SEM analysis.

In this study, we aimed to demonstrate changes in the surface roughness and microhardness of three different restorative materials routinely used in pediatric dentistry (composite, compomer and resin-modified glass ionomer cement (RMCIS)) in response to continuous daily exposure to gastric acid. Twelve samples of each of type of restorative material were prepared. Eleven of the specimens were included in the gastric acid cycle. The microhardness and surface roughness of ten samples were measured before and after the cycle. Another sample included in the cycle was compared with the sample not included in the cycle by scanning electron microscopy (SEM). There was a significant difference between the groups in terms of roughness scores following gastric acid cycle (p = 0.039). RMCIS material possessed the highest roughness value. A significant difference was identified in terms of microhardness levels before and after the gastric acid cycle (p = 0.001). The most significant change was observed in the compomer material. SEM analysis, performed after the gastric acid cycle, revealed that most cracks were identified in RMCIS material; this was followed by compomer and composite materials, respectively. Our analysis indicates that the restorative materials used frequently in pediatric dental procedures, show increased surface roughness and reduced microhardness when exposed to gastric acid.

Neuroendocrine mechanism of gastric acid secretion: Historical perspectives and recent developments in physiology and pharmacology.

The physiology of gastric acid secretion is one of the earliest subjects in medical literature and has been continuously studied since 1833. Starting with the notion that neural stimulation alone drives acid secretion, progress in understanding the physiology and pathophysiology of this process has led to the development of therapeutic strategies for patients with acid-related diseases. For instance, understanding the physiology of parietal cells led to the developments of histamine 2 receptor blockers, proton pump inhibitors (PPIs), and recently, potassium-competitive acid blockers. Furthermore, understanding the physiology and pathophysiology of gastrin has led to the development of gastrin/CCK2 receptor (CCK2 R) antagonists. The need for refinement of existing drugs in patients have led to second and third generation drugs with better efficacy at blocking acid secretion. Further understanding of the mechanism of acid secretion by gene targeting in mice has enabled us to dissect the unique role for each regulator to leverage and justify the development of new targeted therapeutics for acid-related disorders. Further research on the mechanism of stimulation of gastric acid secretion and the physiological significances of gastric acidity in gut microbiome is needed in the future.

Twenty-four-hour pH metry alone is inferior to additional impedance monitoring in the diagnosis of gastroesophageal reflux disease, particularly in presence of reduced gastric acid secretion.

BACKGROUND: Current gold standard for the diagnosis of gastroesophageal reflux disease (GERD) is 24-hour pH metry though it fails to detect non-acidic reflux. The sensitivity of 24-hour pH metry alone (both catheter-based and Bravo capsule) is questionable, especially if gastric acid secretion is low due to reduced parietal cell mass, Helicobacter pylori-induced gastric atrophy and antisecretory therapy. Accordingly, we analyzed the diagnostic ability of 24-hour pH metry as compared to impedance monitoring in relation to the gastric pH without antisecretory therapy. METHODS: A retrospective analysis of prospectively collected data from 150 patients with suspected GERD undergoing a 24-hour pH impedance study was done. RESULTS: Among 150 patients with symptoms suggestive of GERD, 106 (70.6%) had confirmed GERD diagnosed either by 24-hour pH metry alone (10 [9.4%]), impedance monitoring alone (49 [46.2%]) or both (47 [44.3%]). Abnormal reflux of acidic and non-acidic gastric contents was detected by 24-hour pH metry and 24-hour impedance monitoring in 57/106 (53.7%) and 96/106 (90.5%) of patients, respectively (p < .00001). Patients with GERD diagnosed by 24-hour impedance monitoring had a higher mean gastric pH (2.9 [median 1.3, IQR 5.3]) than those diagnosed by 24-hour pH metry (2.1 [median 1.4, IQR 2.6]) or both (1.6 [median 1.2, IQR 2.1]) (p = 0.001). CONCLUSION: Twenty-four-hour impedance monitoring detects GERD more often than 24-hour pH metry. Patients with higher mean gastric pH leading to non-acidic reflux were more often diagnosed by 24-hour impedance monitoring than 24-hour pH metry. Thus, 24-hour pH metry alone is inferior to additional impedance monitoring in the diagnosis of GERD, particularly in presence of reduced gastric acid secretion.