Elucidation of Degradation Behavior of Barbiturates in Artificial Gastric Juice: Study on Degradability of Drugs in Stomach (V).

The gastric stability of eight barbiturates (BARs) (barbital, primidone, allobarbital, phenobarbital, cyclobarbital, pentobarbital, secobarbital, and thiobutabarbital (TBB)) was examined in artificial gastric juice using LC/UV detection. Among the eight BARs, only TBB was degraded at higher temperatures. Furthermore, the degradation product of TBB was isolated, structurally analyzed, and finally identified as 5-butan-2-yl-5-ethyl-1,3-diazinane-2,4,6-trione, also known as butabarbital. The study elucidated that butabarbital was formed by substituting the sulfur atom of the carbonyl group at the 2-position of TBB with an oxygen atom under acidic condition.

Interstitial cells of the sip syncytium regulate basal membrane potential in murine gastric corpus.

Smooth muscle cells (SMCs), Interstitial cells of Cajal (ICC) and Platelet-derived growth factor receptor α positive (PDGFRα+) cells form an integrated, electrical syncytium within the gastrointestinal (GI) muscular tissues known as the SIP syncytium. Immunohistochemical analysis of gastric corpus muscles showed that c-KIT+/ANO1+ ICC-IM and PDGFRα+ cells were closely apposed to one another in the same anatomical niches. We used intracellular microelectrode recording from corpus muscle bundles to characterize the roles of intramuscular ICC and PDGFRα+ cells in conditioning membrane potentials of gastric muscles. In muscle bundles, that have a relatively higher input impedance than larger muscle strips or sheets, we recorded an ongoing discharge of stochastic fluctuations in membrane potential, previously called unitary potentials or spontaneous transient depolarizations (STDs) and spontaneous transient hyperpolarizations (STHs). We reasoned that STDs should be blocked by antagonists of ANO1, the signature conductance of ICC. Activation of ANO1 has been shown to generate spontaneous transient inward currents (STICs), which are the basis for STDs. Ani9 reduced membrane noise and caused hyperpolarization, but this agent did not block the fluctuations in membrane potential quantitatively. Apamin, an antagonist of small conductance Ca2+-activated K+ channels (SK3), the signature conductance in PDGFRα+ cells, further reduced membrane noise and caused depolarization. Reversing the order of channel antagonists reversed the sequence of depolarization and hyperpolarization. These experiments show that the ongoing discharge of STDs and STHs by ICC and PDGFRα+ cells, respectively, exerts conditioning effects on membrane potentials in the SIP syncytium that would effectively regulate the excitability of SMCs.

Pseudogenization of NK3 homeobox 2 (Nkx3.2) in monotremes provides insight into unique gastric anatomy and physiology.

The enzymatic breakdown and regulation of food passage through the vertebrate antral stomach and pyloric sphincter (antropyloric region) is a trait conserved over 450 million years. Development of the structures involved is underpinned by a highly conserved signalling pathway involving the hedgehog, bone morphogenetic protein and Wingless/Int-1 (Wnt) protein families. Monotremes are one of the few vertebrate lineages where acid-based digestion has been lost, and this is consistent with the lack of genes for hydrochloric acid secretion and gastric enzymes in the genomes of the platypus (Ornithorhynchus anatinus) and short-beaked echidna (Tachyglossus aculeatus) . Furthermore, these species feature unique gastric phenotypes, both with truncated and aglandular antral stomachs and the platypus with no pylorus. Here, we explore the genetic underpinning of monotreme gastric phenotypes, investigating genes important in antropyloric development using the newest monotreme genomes (mOrnAna1.pri.v4 and mTacAcu1) together with RNA-seq data. We found that the pathway constituents are generally conserved, but surprisingly, NK3 homeobox 2 (Nkx3.2) was pseudogenized in both platypus and echidna. We speculate that the unique sequence evolution of Grem1 and Bmp4 sequences in the echidna lineage may correlate with their pyloric-like restriction and that the convergent loss of gastric acid and stomach size genotypes and phenotypes in teleost and monotreme lineages may be a result of eco-evolutionary dynamics. These findings reflect the effects of gene loss on phenotypic evolution and further elucidate the genetic control of monotreme stomach anatomy and physiology.

Ultrasonography for confirmation of gastric tube placement.

BACKGROUND: Gastric tubes are commonly used for the administration of drugs and tube feeding for people who are unable to swallow. Feeding via a tube misplaced in the trachea can result in severe pneumonia. Therefore, the confirmation of tube placement in the stomach after tube insertion is important. Recent studies have reported that ultrasonography provides good diagnostic accuracy estimates in the confirmation of appropriate tube placement. Hence, ultrasound could provide a promising alternative to X-rays in the confirmation of tube placement, especially in settings where X-ray facilities are unavailable or difficult to access. OBJECTIVES: To assess the diagnostic accuracy of ultrasound alone or in combination with other methods for gastric tube placement confirmation in children and adults. SEARCH METHODS: This systematic review is an update of a previously published Cochrane review. For this update, we searched the Cochrane Library (2021, Issue 6), MEDLINE (to April 2023), Embase (to April 2023), five other databases (to July 2021), and reference lists of articles, and contacted study authors. SELECTION CRITERIA: We included studies that evaluated the diagnostic accuracy of naso- and orogastric tube placement confirmed by ultrasound visualization using X-ray visualization as the reference standard. We included cross-sectional studies and case-control studies. We excluded case series or case reports. We excluded studies if X-ray visualization was not the reference standard or if the tube being placed was a gastrostomy or enteric tube. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the methodological quality and extracted data from each of the included studies. We contacted the authors of the included studies to obtain missing data. There were sparse data for specificity. Therefore, we performed a meta-analysis of only sensitivity using a univariate random-effects logistic regression model to combine data from studies that used the same method and echo window. MAIN RESULTS: We identified 12 new studies in addition to 10 studies included in the earlier version of this review, totalling 1939 participants and 1944 tube insertions. Overall, we judged the risk of bias in the included studies as low or unclear. No study was at low risk of bias or low concern for applicability in every QUADAS-2 domain. There were limited data (152 participants) for misplacement detection (specificity) due to the low incidence of misplacement. The summary sensitivity of ultrasound on neck and abdomen echo windows were 0.96 (95% confidence interval (CI) 0.92 to 0.98; moderate-certainty evidence) for air injection and 0.98 (95% CI 0.83 to 1.00; moderate-certainty evidence) for saline injection. The summary sensitivity of ultrasound on abdomen echo window was 0.96 (95% CI 0.65 to 1.00; very low-certainty evidence) for air injection and 0.97 (95% CI 0.95 to 0.99; moderate-certainty evidence) for procedures without injection. The certainty of evidence for specificity across all methods was very low due to the very small sample size. For settings where X-ray was not readily available and participants underwent gastric tube insertion for drainage (8 studies, 552 participants), sensitivity estimates of ultrasound in combination with other confirmatory tests ranged from 0.86 to 0.98 and specificity estimates of 1.00 with wide CIs. For studies of ultrasound alone (9 studies, 782 participants), sensitivity estimates ranged from 0.77 to 0.98 and specificity estimates were 1.00 with wide CIs or not estimable due to no occurrence of misplacement. AUTHORS' CONCLUSIONS: Of 22 studies that assessed the diagnostic accuracy of gastric tube placement, few studies had a low risk of bias. Based on limited evidence, ultrasound does not have sufficient accuracy as a single test to confirm gastric tube placement. However, in settings where X-ray is not readily available, ultrasound may be useful to detect misplaced gastric tubes. Larger studies are needed to determine the possibility of adverse events when ultrasound is used to confirm tube placement.

Calorie restriction activates a gastric Notch-FOXO1 pathway to expand ghrelin cells.

Calorie restriction increases lifespan. Among the tissue-specific protective effects of calorie restriction, the impact on the gastrointestinal tract remains unclear. We report increased numbers of chromogranin A-positive (+), including orexigenic ghrelin+ cells, in the stomach of calorie-restricted mice. This effect was accompanied by increased Notch target Hes1 and Notch ligand Jag1 and was reversed by blocking Notch with DAPT, a gamma-secretase inhibitor. Primary cultures and genetically modified reporter mice show that increased endocrine cell abundance is due to altered Lgr5+ stem and Neurog3+ endocrine progenitor cell proliferation. Different from the intestine, calorie restriction decreased gastric Lgr5+ stem cells, while increasing a FOXO1/Neurog3+ subpopulation of endocrine progenitors in a Notch-dependent manner. Further, activation of FOXO1 was sufficient to promote endocrine cell differentiation independent of Notch. The Notch inhibitor PF-03084014 or ghrelin receptor antagonist GHRP-6 reversed the phenotypic effects of calorie restriction in mice. Tirzepatide additionally expanded ghrelin+ cells in mice. In summary, calorie restriction promotes Notch-dependent, FOXO1-regulated gastric endocrine cell differentiation.

Estimation of radon concentration in groundwater in the mining zone of Haryana, India, for lungs and stomach annual effective dose.

The groundwater is being used for drinking and irrigation purposes in vast swathes of the Aravalli Mountain range. Since the radioisotope presence in groundwater is affected by the local mining processes, the radiation monitoring in groundwater of mining regions is of paramount importance. In the present work, we have estimated the 222Rn presence in the mining region of Aravalli in the southern part of Haryana. We measured the Radon concentration in 51 water samples from the intended area using the RAD7 alpha detector. The measured radon concentration in some of the water samples collected from the vicinity of the mining zone is higher than that of the United Nations Scientific Committee on the Effects of Atomic Radiation recommended value. Furthermore, we have estimated the annual effective doses for the lungs and stomach contributed by ingestion and inhalation. Though the calculated dose values in collected samples are not in the critical range, further monitoring of background radiation in the Aravalli region is required.

Gastric bezoars secondary to mixed infection with Sarcina ventriculi and G + bacilli: a case report.

Sarcina ventriculi is a bacterium with a specific histological morphology and infection can present with symptoms such as abdominal pain, nausea, vomiting and occasionally fatal complications. Delayed gastric emptying is regarded as the most significant risk factor for infection. Its pathogenicity is currently unknown and treatment options are inconsistent. Here we report a case of gastric bezoars secondary to a mixed infection of Sarcina ventriculi and G + bacilli, which is diagnosed by a pathological biopsy.

Gastric microbiota transplantation as a potential treatment for immune checkpoint inhibitor-associated gastritis.

Immune-related adverse events (irAEs) are complications of the use of immune checkpoint inhibitors (ICIs). ICI-associated gastritis is one of the main irAEs. The gastric microbiota is often related to the occurrence and development of many gastric diseases. Gastric microbiota adjustment may be used to treat gastric disorders in the future. Faecal microbiota transplantation can alter the gut microbiota of patients and has been used for treating ICI-associated colitis. Therefore, we propose gastric microbiota transplantation as a supplementary treatment for patients with ICI-associated gastritis who do not respond well to conventional therapy.

HtrA-Dependent E-Cadherin Shedding Impairs the Epithelial Barrier Function in Primary Gastric Epithelial Cells and Gastric Organoids.

Impaired E-cadherin (Cdh1) functions are closely associated with cellular dedifferentiation, infiltrative tumor growth and metastasis, particularly in gastric cancer. The class-I carcinogen Helicobacter pylori (H. pylori) colonizes gastric epithelial cells and induces Cdh1 shedding, which is primarily mediated by the secreted bacterial protease high temperature requirement A (HtrA). In this study, we used human primary epithelial cell lines derived from gastroids and mucosoids from different healthy donors to investigate HtrA-mediated Cdh1 cleavage and the subsequent impact on bacterial pathogenesis in a non-neoplastic context. We found a severe impairment of Cdh1 functions by HtrA-induced ectodomain cleavage in 2D primary cells and mucosoids. Since mucosoids exhibit an intact apico-basal polarity, we investigated bacterial transmigration across the monolayer, which was partially depolarized by HtrA, as indicated by microscopy, the analyses of the transepithelial electrical resistance (TEER) and colony forming unit (cfu) assays. Finally, we investigated CagA injection and observed efficient CagA translocation and tyrosine phosphorylation in 2D primary cells and, to a lesser extent, similar effects in mucosoids. In summary, HtrA is a crucially important factor promoting the multistep pathogenesis of H. pylori in non-transformed primary gastric epithelial cells and organoid-based epithelial models.

Magnetic-navigable silk fibroin microneedles for oral drug delivery: Ensuring long-lasting helicobacter pylori eradication and rapid hemostasis in the stomach.

The Helicobacter pylori infection in the stomach is the key reason for gastric mucosal bleeding. Eliminating gastric Helicobacter pylori by oral treatment remains difficult due to the presence of the gastric mucosal layer, which acts as a physical barrier to drugs via oral administration. In this study, a magnetic-navigable microneedle drug delivery platform (MNsD) for oral administration, featuring differential dual-mode drug release rate, was designed to fulfil rapid gastric hemostasis and overcome the gastric barriers for long-lasting Helicobacter pylori inhibition in stomach. MNs-D was created by rationally loading the carrier substrate, which was composed of silk fibroin with variable solubility, with antibiotics and hemostats. In vitro experiments showed MNs-D may sustainably eradicate Helicobacter pylori in stimulated gastric juices with long-lasting drug release (79 % in 24 h) and quickly establish hemostasis with instant drug release (92 % within 60 s). Most importantly, in vivo studies demonstrated MNs-D overcame the unsettling gastric mucosal barrier in traditional therapies of oral administration by insertion into the GML under magnetic navigation, resulting in sustained antibiotic release for long-lasting Helicobacter pylori eradiation (99 %). For differential dual-mode medication release against gastric Helicobacter pylori infections, this study may have firstly examined the effects of magnetic navigated microneedles administered orally.

The Helicobacter pylori infection alters the intercellular junctions on the pancreas of gerbils (Meriones unguiculatus).

Helicobacter pylori is a common resident in the stomach of at least half of the world's population and recent evidence suggest its emergence in other organs such as the pancreas. In this organ, the presence of H. pylori DNA has been reported in cats, although the functional implications remain unknown. In this work, we determined distinct features related to the H. pylori manifestation in pancreas in a rodent model, in order to analyse its functional and structural effect. Gerbils inoculated with H. pylori exhibited the presence of this bacterium, as revealed by the expression of some virulence factors, as CagA and OMPs in stomach and pancreas, and confirmed by urease activity, bacterial culture, PCR and immunofluorescence assays. Non-apparent morphological changes were observed in pancreatic tissue of infected animals; however, delocalization of intercellular junction proteins (claudin-1, claudin-4, occludin, ZO-1, E-cadherin, ß-catenin, desmoglein-2 and desmoplakin I/II) and rearrangement of the actin-cytoskeleton were exhibited. This structural damage was consistent with alterations in the distribution of insulin and glucagon, and a systemic inflammation, event demonstrated by elevated IL-8 levels. Overall, these findings indicate that H. pylori can reach the pancreas, possibly affecting its function and contributing to the development of pancreatic diseases.

Gastric slow-wave modulation via power-controlled, irrigated radio-frequency ablation.

BACKGROUND: Recently, radio-frequency ablation has been used to modulate slow-wave activity in the porcine stomach. Gastric ablation is, however, still in its infancy compared to its history in the cardiac field, and electrophysiological studies have been restricted to temperature-controlled, non-irrigated ablation. Power-controlled, irrigated ablation may improve lesion formation at lower catheter-tip temperatures that produce the desired localized conduction block. METHODS AND RESULTS: Power-controlled, irrigated radio-frequency ablation was performed on the gastric serosal surface of female weaner pigs (n = 5) in vivo. Three combinations of power (10-15 W) and irrigation settings (2-5 mL min-1) were investigated. A total of 12 linear lesions were created (n = 4 for each combination). Slow waves were recorded before and after ablation using high-resolution electrical mapping. KEY RESULTS: Irrigation maintained catheter-tip temperature below 50°C. Ablation induced a complete conduction block in 8/12 cases (4/4 for 10 W at 2 mL min-1, 1/4 for 10 W at 5 mL min-1, 3/4 for 15 W at 5 mL min-1). Blocks were characterized by a decrease in signal amplitude at the lesion site, along with changes in slow-wave propagation patterns, where slow waves terminated at and/or rotated around the edge of the lesion. CONCLUSIONS AND INFERENCES: Power-controlled, irrigated ablation can successfully modulate gastric slow-wave activity at a reduced catheter-tip temperature compared to temperature-controlled, non-irrigated ablation. Reducing the irrigation rate is more effective than increasing power for blocking slow-wave activity. These benefits suggest that irrigated ablation is a suitable option for further translation into a clinical intervention for gastric electrophysiology disorders.

Gastric microbiome composition in obese patients and normal weight subjects with functional dyspepsia.

INTRODUCTION: Despite the numerous studies demonstrating gut microbiota dysbiosis in obese subjects, there is no data on the association between obesity and gastric microbiota. The aim of this study was to address this gap in literature by comparing the composition of gastric microbiota in obese patients and a control group which included normal weight volunteers diagnosed with functional dyspepsia (FD). METHODOLOGY: A total of 19 obese patients, and 18 normal weight subjects with FD and normal endoscopy results were included in the study. The gastric tissue samples were collected from participants in both groups by bariatric surgery and endoscopy, respectively, and profiled using 16S ribosomal RNA gene sequencing. RESULTS: There was no significant difference in the α-diversity scores, while distinct gastric microbial compositions were detected in both groups. Significantly lower levels of Bacteroidetes and Fusobacteria, and higher Firmicutes/Bacteroidetes ratio were recorded in the obese patients. A total of 15 bacterial genera exhibited significant difference in gastric abundance with Prevotella_7, Veillonella, Cupriavidus, and Acinetobacter, present in frequencies higher than 3% in at least one subject group. CONCLUSIONS: Our study suggests a significant association between obesity and gastric microbiome composition. Future studies with larger sample size and gastric samples from subjects without any gastrointestinal complications are required to confirm our conclusions.

Stomach as the target organ of Rickettsia heilongjiangensis infection in C57BL/6 mice identified by click chemistry.

Spotted fever group rickettsiae (SFGR) are obligate intracellular bacteria that cause spotted fever. The limitations of gene manipulation pose great challenges to studying the infection mechanisms of Rickettsia. By combining bioorthogonal metabolism and click chemistry, we developed a method to label R. heilongjiangensis via azide moieties and achieved rapid pathogen localization without complex procedures. Moreover, we constructed a C57BL/6 mice infection model by simulating tick bites and discovered that the stomach is the target organ of R. heilongjiangensis infection through in vivo imaging systems, which explained the occurrence of gastrointestinal symptoms following R. heilongjiangensis infection in some cases. This study offers a unique perspective for subsequent investigations into the pathogenic mechanisms of SFGR and identifies a potential target organ for R. heilongjiangensis.

Profiling Luminal pH in Three-Dimensional Gastrointestinal Organoids Using Microelectrodes.

The optimization and detailed characterization of gastrointestinal organoid models require advanced methods for analyzing their luminal environments. This paper presents a highly reproducible method for the precise measurement of pH within the lumina of 3D human gastric organoids via micromanipulator-controlled microelectrodes. The pH microelectrodes are commercially available and consist of beveled glass tips of 25 µm in diameter. For measurements, the pH microelectrode is advanced into the lumen of an organoid (>200 µm) that is suspended in Matrigel, while a reference electrode rests submerged in the surrounding medium in the culture plate. Using such microelectrodes to profile organoids derived from the human gastric body, we demonstrate that luminal pH is relatively consistent within each culture well at ~7.7 ± 0.037 and that continuous measurements can be obtained for a minimum of 15 min. In some larger organoids, the measurements revealed a pH gradient between the epithelial surface and the lumen, suggesting that pH measurements in organoids can be achieved with high spatial resolution. In a previous study, microelectrodes were successfully used to measure luminal oxygen concentrations in organoids, demonstrating the versatility of this method for organoid analyses. In summary, this protocol describes an important tool for the functional characterization of the complex luminal space within 3D organoids.

Double contrast-enhanced ultrasonography improves diagnostic accuracy of T staging compared with multi-detector computed tomography in gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is the most common malignant tumor and ranks third for cancer-related deaths among the worldwide. The disease poses a serious public health problem in China, ranking fifth for incidence and third for mortality. Knowledge of the invasive depth of the tumor is vital to treatment decisions. AIM: To evaluate the diagnostic performance of double contrast-enhanced ultrasonography (DCEUS) for preoperative T staging in patients with GC by comparing with multi-detector computed tomography (MDCT). METHODS: This single prospective study enrolled patients with GC confirmed by preoperative gastroscopy from July 2021 to March 2023. Patients underwent DCEUS, including ultrasonography (US) and intravenous contrast-enhanced ultrasonography (CEUS), and MDCT examinations for the assessment of preoperative T staging. Features of GC were identified on DCEUS and criteria developed to evaluate T staging according to the 8th edition of AJCC cancer staging manual. The diagnostic performance of DCEUS was evaluated by comparing it with that of MDCT and surgical-pathological findings were considered as the gold standard. RESULTS: A total of 229 patients with GC (80 T1, 33 T2, 59 T3 and 57 T4) were included. Overall accuracies were 86.9% for DCEUS and 61.1% for MDCT (P < 0.001). DCEUS was superior to MDCT for T1 (92.5% vs 70.0%, P < 0.001), T2 (72.7% vs 51.5%, P = 0.041), T3 (86.4% vs 45.8%, P < 0.001) and T4 (87.7% vs 70.2%, P = 0.022) staging of GC. CONCLUSION: DCEUS improved the diagnostic accuracy of preoperative T staging in patients with GC compared with MDCT, and constitutes a promising imaging modality for preoperative evaluation of GC to aid individualized treatment decision-making.

The value of oral contrast-enhanced gastric ultrasonography in the diagnosis and staging of benign peptic ulcer.

We evaluate the value of oral contrast-enhanced gastric ultrasonography (OCUS) by comparing it with conventional gastroscopy in diagnosing and staging benign peptic ulcer. From July 2018 to December 2020, 44 patients with gastroscopy-confirmed benign peptic ulcers (a total of 45 ulcers were detected), who also received OCUS, were retrospectively reviewed. Each patient's ultrasound images were compared with gastroscopy and pathology findings. The characteristics of ultrasonic images of different stages of ulcer were analysed. A total of 43 ulcers were detected by OCUS in 44 patients with benign peptic ulcers. There were no false positive results among the OCUS exams, but two ulcers were misdiagnosed. OCUS for benign peptic ulcer staging also shows acceptable clinical practice results. OCUS is useful for detecting and staging benign peptic ulcer, and may be considered an alternative method for conventional gastroscopy. OCUS is especially useful in the follow-up of BPU treatment, but futher study is needed to improve the diagnostic accuracy of benign and malignant ulcers.

Efficacy of robot arm-assisted endoscopic submucosal dissection in live porcine stomach (with video).

Endoscopic submucosal dissection (ESD) is technically challenging and requires a high level of skill. However, there is no effective method of exposing the submucosal plane during dissection. In this study, the efficacy of robot arm-assisted tissue traction for gastric ESD was evaluated using an in vivo porcine model. The stomach of each pig was divided into eight locations. In the conventional ESD (C-ESD) group, one ESD was performed at each location (N = 8). In the robot arm-assisted ESD (R-ESD) group, two ESDs were performed at each location (N = 16). The primary endpoint was the submucosal dissection speed (mm2/s). The robot arm could apply tissue traction in the desired direction and successfully expose the submucosal plane during submucosal dissection in all lesion locations. The submucosal dissection speed was significantly faster in the R-ESD group than in the C-ESD group (p = 0.005). The blind dissection rate was significantly lower in the R-ESD group (P = 0.000). The robotic arm-assisted traction in ESD enabled a significant improvement in submucosal dissection speed, blind dissection rate which suggests the potential for making ESD easier and enhancing procedural efficiency and safety.