Gastric clot formation and digestion of milk proteins in static in vitro infant gastric digestion models representing different ages.

Gastric digestion conditions change during infancy from newborn towards more adult digestion conditions, which can change gastric digestion kinetics. However, how these changes in gastric digestion conditions during infancy affect milk protein digestion has not been investigated. Therefore, we aimed to investigate milk protein digestion with static in vitro gastric digestion models representing one-, three- and six-month-old infants. With increasing age, gastric clots and soluble proteins were digested more extensively, which may partly be attributed to the looser gastric clot structure. Larger differences with increasing age were found for heated than unheated milk proteins, which might be caused by the presence of denatured whey proteins. Taken together, these findings show that gastric milk protein digestion increases during infancy. These in vitro gastric digestion models could be used to study how milk protein digestion changes with infant age, which may aid in developing infant formulas for different age stages.

Movements of moisture and acid in gastric milk clots during gastric digestion: Spatiotemporal mapping using hyperspectral imaging.

Ruminant milk is known to coagulate into structured clots during gastric digestion. This study investigated the movements of moisture and acid in skim milk clots formed during dynamic gastric digestion and the effects of milk type (regular or calcium-rich) and the presence/absence of pepsin. We conducted hyperspectral imaging analysis and successfully modelled the moisture contents based on the spectral information using partial least squares regression. We generated prediction maps of the spatiotemporal distribution of moisture within the samples at different stages of gastric digestion. Simultaneously to acid uptake, the moisture in the milk clots tended to decrease over the digestion time; this was significantly promoted by pepsin. Moisture mapping by hyperspectral imaging demonstrated that the high and low moisture zones were centralized within the clot and at the surface respectively. A structural compaction process promoted by pepsinolysis and acidification probably contributed to the water expulsion from the clots during digestion.

Immune response modulation in inflammatory bowel diseases by Helicobacter pylori infection.

Many studies point to an association between Helicobacter pylori (H. pylori) infection and inflammatory bowel diseases (IBD). Although controversial, this association indicates that the presence of the bacterium somehow affects the course of IBD. It appears that H. pylori infection influences IBD through changes in the diversity of the gut microbiota, and hence in local chemical characteristics, and alteration in the pattern of gut immune response. The gut immune response appears to be modulated by H. pylori infection towards a less aggressive inflammatory response and the establishment of a targeted response to tissue repair. Therefore, a T helper 2 (Th2)/macrophage M2 response is stimulated, while the Th1/macrophage M1 response is suppressed. The immunomodulation appears to be associated with intrinsic factors of the bacteria, such as virulence factors - such oncogenic protein cytotoxin-associated antigen A, proteins such H. pylori neutrophil-activating protein, but also with microenvironmental changes that favor permanence of H. pylori in the stomach. These changes include the increase of gastric mucosal pH by urease activity, and suppression of the stomach immune response promoted by evasion mechanisms of the bacterium. Furthermore, there is a causal relationship between H. pylori infection and components of the innate immunity such as the NLR family pyrin domain containing 3 inflammasome that directs IBD toward a better prognosis.

Multidisciplinary treatment for acute massive upper gastrointestinal bleeding secondary to post-burn stress in a paediatric patient: a case report.

BACKGROUND: Severe burns can readily induce gastric and duodenal mucosal erosions and superficial ulcers. In severe cases, haemorrhage or perforation of peptic ulcers might occur, threatening the lives of patients. At present, gastrointestinal haemorrhage after burns is treated mainly with drugs and gastrointestinal endoscopy. However, multidisciplinary treatment of gastroscopy combined with vascular embolization is rare. CASE: A boy aged 3 years and 4 months was admitted to the hospital, scalded by boiling water on multiple parts of the body. On the 8th day after the injury, the patient continuously produced a large amount of tarry black stool, and the faecal occult blood test was positive. Haemostatic drug treatment was ineffective, and severe shock and disseminated intravascular coagulation (DIC) occurred. Under the guidance of a multidisciplinary team (MDT), a gastroscopy examination was performed and showed bleeding from a duodenal bulb ulcer. Due to a small intestinal lumen and thin intestinal wall, bleeding could not be controlled by gastroscopy. However, the bleeding point was clarified by gastroscopy and then gastroduodenal artery embolization was performed efficiently. No active gastrointestinal bleeding was observed after the surgery. The patient was followed for 6 months after discharge, and no gastrointestinal haemorrhage recurred. CONCLUSIONS: This is a rare case of acute massive upper gastrointestinal bleeding secondary to post-burn stress in paediatric patients. For paediatric patients who cannot be treated by endoscopy, transcatheter embolization may be safer and more effective for achieving haemostasis. Through the collaboration of the MDT, gastroscopy combined with interventional embolization was performed, which successfully stopped the massive bleeding and saved the child`s life, making it worthy of clinical reference.

Gastric and Duodenal Fistulas in Crohn's Disease, a Surgical Challenge: Report of 5 Cases and a Review of the Literature.

BACKGROUND Fistulas involving the stomach and duodenum in Crohn's disease are rare (occurring in less than 1% of patients). Here, we reviewed registers from 855 patients with Crohn's disease treated in our service from January 2007 to December 2020 and found 4 cases of duodenal fistula and 1 case of gastric fistula. CASE REPORT The fistula origin was in the ileocolic segment in all cases, and all of the patients underwent preoperative optimization with improvement of nutritional status and infection control. They then underwent surgical treatment with resection of the affected segment and duodenal or gastric closure with covering by an omental patch. One case of a duodenal fistula was complicated by duodenal dehiscence. This was treated surgically with duodenojejunostomy. Each of the other patients had an uneventful postoperative course. All patients were successfully cured of their gastroduodenal fistulas, and at the time of this publication, none of them died or had fistula recurrence. CONCLUSIONS Fistulas with the involvement of the stomach and duodenum in patients with Crohn's disease are almost always due to inflammation in the ileum, colon, or previous ileocolic anastomosis. Management of this situation is complex and often requires clinical and surgical assistance; preoperative optimization of the patient's general condition can improve the surgical results. The surgical approach is based on resection of the affected segment and gastric or duodenal closure with covering by an omental patch. Gastrojejunostomy or duodenojejunostomy can be performed in selected patients with larger defects and minor jejunal disease. To prevent recurrence, prophylactic therapy with anti-TNF agents and early endoscopic surveillance are also essential for successful treatment.

The Effect of Residual Gastric Volume on Body Mass Index, Excess Weight Loss Rate and Metabolic Response after Sleeve Gastrectomy.

BACKGROUND/AIM: To investigate the metabolic response and body mass index reduction according to the remaining stomach volume between 6-12 months after the operation in patients who underwent sleeve gastrectomy surgery for obesity and to determine the relationship between the remaining stomach volume and metabolic improvement. Materials and Methods: Patients underwent sleeve gastrectomy in a single center by the same team and with the same standardized method. Residual gastric volumes were calculated from three-dimensional computed tomography images obtained 6-12 months postoperatively. BMI, excess weight loss (EWL), total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), very low density lipoprotein (VLDL), triglyceride, hemoglobin A1c (HbA1c), total protein, albumin values were recorded preoperatively and at the time of residual volume measurement. Results: There were 49 subjects with a mean SD preoperative BMI of 47.26+-6.21 kg/m2 and mean age 37.51+-10.88 years. Mean residual volume was 155.36+-56.71 cc. Residual volume was associated with postoperative mean BMI (28.44+-3.23 kg/m2; p 0.001) and postperative mean EWL%(29.27+-7.66; p=0.001). Residual gastric volume was also negative correlated with postoperative mean HbA1c (p=0.004). HbA1c (p=0.828), LDL (p=0.661), HDL (p=0.848), triglycerides (p=0.641), VLDL (p=0.794), total protein relation (p=0.539) and albumin (p=0.824) were analyzed before and after surgery and were not correlated with residual gastric volume. CONCLUSION: The smaller the residual gastric volume after laparoscopic sleeve gastrectomy, the higher the %EWL and the greater the decrease in HbA1c. This study show that laparoscopic sleeve gastrectomy is an effective surgical procedure in patients with Type 2 diabetes mellitus.

Current Status of Robotic Gastrointestinal Surgery.

Development of surgical support robots began in the 1980s as a navigation and auxiliary device for endoscopic surgery. For remote surgery on the battlefield, a master-slave-type surgical support robot was developed, in which a console surgeon operates the robot at will. The da Vinci surgical system, which currently dominates the global robotic surgery market, received United States Food and Drug Administration and regulatory approval in Japan in 2000 and 2009 respectively. The latest, fourth generation, da Vinci Xi has a good field of view via a three-dimensional monitor, highly operable forceps, a motion scale function, and a tremor-filtered articulated function. Gastroenterological tract robotic surgery is safe and minimally invasive when accessing and operating on the esophagus, stomach, colon, and rectum. The learning curve is said to be short, and robotic surgery will likely be standardized soon. Therefore, robotic surgery training should be systematized for young surgeons so that it can be further standardized and later adapted to a wider range of surgeries. This article reviews current trends and potential developments in robotic surgery.

Space-Flight- and Microgravity-Dependent Alteration of Mast Cell Population and Protease Expression in Digestive Organs of Mongolian Gerbils.

Mast cell (MC)-specific proteases are of particular interest for space biology and medicine due to their biological activity in regulating targets of a specific tissue microenvironment. MC tryptase and chymase obtain the ability to remodel connective tissue through direct and indirect mechanisms. Yet, MC-specific protease expression under space flight conditions has not been adequately investigated. Using immunohistochemical stainings, we analyzed in this study the protease profile of the jejunal, gastric, and hepatic MC populations in three groups of Mongolian gerbils-vivarium control, synchronous experiment, and 12-day orbital flight on the Foton-M3 spacecraft-and in two groups-vivarium control and anti-orthostatic suspension-included in the experiment simulating effects of weightlessness in the ground-based conditions. After a space flight, there was a decreased number of MCs in the studied organs combined with an increased proportion of chymase-positive MCs and MCs with a simultaneous content of tryptase and chymase; the secretion of specific proteases into the extracellular matrix increased. These changes in the expression of proteases were observed both in the mucosal and connective tissue MC subpopulations of the stomach and jejunum. Notably, the relative content of tryptase-positive MCs in the studied organs of the digestive system decreased. Space flight conditions simulated in the synchronous experiment caused no similar significant changes in the protease profile of MC populations. The space flight conditions resulted in an increased chymase expression combined with a decreased total number of protease-positive MCs, apparently due to participating in the processes of extracellular matrix remodeling and regulating the state of the cardiovascular system.

Gastrointestinal organs and organoids-on-a-chip: advances and translation into the clinics.

Microfluidic organs and organoids-on-a-chip models of human gastrointestinal systems have been established to recreate adequate microenvironments to study physiology and pathophysiology. In the effort to find more emulating systems and less costly models for drugs screening or fundamental studies, gastrointestinal system organoids-on-a-chip have arisen as promising pre-clinicalin vitromodel. This progress has been built on the latest developments of several technologies such as bioprinting, microfluidics, and organoid research. In this review, we will focus on healthy and disease models of: human microbiome-on-a-chip and its rising correlation with gastro pathophysiology; stomach-on-a-chip; liver-on-a-chip; pancreas-on-a-chip; inflammation models, small intestine, colon and colorectal cancer organoids-on-a-chip and multi-organoids-on-a-chip. The current developments related to the design, ability to hold one or more 'organs' and its challenges, microfluidic features, cell sources and whether they are used to test drugs are overviewed herein. Importantly, their contribution in terms of drug development and eminent clinical translation in precision medicine field, Food and Drug Administration approved models, and the impact of organoid-on-chip technology in terms of pharmaceutical research and development costs are also discussed by the authors.

Kinetic study on the reaction of sodium nitrite with neurotransmitters secreted in the stomach.

Nitroso-compounds are potentially mutagenic and carcinogenic compounds due to their ability to alkylate DNA bases. One of the most common sources of human exposure to nitroso-compounds is their formation in the acidic environment of the stomach by the reaction between electron-rich molecules present in the lumen and sodium nitrite ingested in the diet. To date, the formation of nitroso-compounds by the reaction of nitrite with food components has been investigated in depth, but little attention has been paid to substances secreted in the stomach, such as dopamine or serotonin, whose reaction products with nitrite have proven mutagenic properties. In this article, we present a kinetic study with UV-visible spectroscopy of the nitrosation reactions of both molecules, as well as of L-tyrosine, the amino-acid precursor of dopamine. We determined the kinetic parameters and reaction mechanisms for the reactions, studying the influence of the reactants concentration, pH, temperature, and ionic strength on the reaction rate. In all cases, the favoured reaction product was a stable nitroso-compound. Serotonin, the molecule whose product was the most mutagenic, underwent two consecutive nitrosation reactions. These findings suggest that additional biological research is needed to understand how this reaction alters the function of these neurotransmitters as well as the potentially toxic effects they may have once nitrosated.

Gastric insufflation and surgical view according to mask ventilation method for laparoscopic cholecystectomy: a randomized controlled study.

BACKGROUND: Proper mask ventilation is important to prevent air inflow into the stomach during induction of general anesthesia, and it is difficult to send airflow only through the trachea without gastric inflation. Changes in gastric insufflation according to mask ventilation during anesthesia induction were compared. METHODS: In this prospective, randomized, single-blind study, 230 patients were analyzed to a facemask-ventilated group (Ventilation group) or no-ventilation group (Apnea group) during anesthesia induction. After loss of consciousness, pressure-controlled ventilation at an inspiratory pressure of 15 cmH2O was performed for two minutes with a two-handed mask-hold technique for Ventilation group. For Apnea group, only the facemask was fitted to the face for one minute with no ventilation. Next, endotracheal intubation was performed. The gastric cross-sectional area (CSA, cm2) was measured using ultrasound before and after induction. After pneumoperitoneum with carbon dioxide, gastric insufflation of the surgical view was graded by the surgeon for each group. RESULTS: Increase of postinduction antral CSA on ultrasound were not significantly different between Ventilation group and Apnea group (0.04 ± 0.3 and 0.02 ± 0.28, p-value = 0.225). Additionally, there were no significant differences between the two groups in surgical grade according to surgeon's judgement. CONCLUSIONS: Pressure-controlled ventilation at an inspiratory pressure of 15 cmH2O for two minutes did not increase gastric antral CSA and insufflation of stomach by laparoscopic view. TRIAL REGISTRATION: http://cris.nih.go.kr (KCT0003620) on 13/3/2019.

Comparison of Gastric Alimetry® body surface gastric mapping versus electrogastrography spectral analysis.

Electrogastrography (EGG) non-invasively evaluates gastric motility but is viewed as lacking clinical utility. Gastric Alimetry® is a new diagnostic test that combines high-resolution body surface gastric mapping (BSGM) with validated symptom profiling, with the goal of overcoming EGG's limitations. This study directly compared EGG and BSGM to define performance differences in spectral analysis. Comparisons between Gastric Alimetry BSGM and EGG were conducted by protocolized retrospective evaluation of 178 subjects [110 controls; 68 nausea and vomiting (NVS) and/or type 1 diabetes (T1D)]. Comparisons followed standard methodologies for each test (pre-processing, post-processing, analysis), with statistical evaluations for group-level differences, symptom correlations, and patient-level classifications. BSGM showed substantially tighter frequency ranges vs EGG in controls. Both tests detected rhythm instability in NVS, but EGG showed opposite frequency effects in T1D. BSGM showed an 8× increase in the number of significant correlations with symptoms. BSGM accuracy for patient-level classification was 0.78 for patients vs controls and 0.96 as compared to blinded consensus panel; EGG accuracy was 0.54 and 0.43. EGG detected group-level differences in patients, but lacked symptom correlations and showed poor accuracy for patient-level classification, explaining EGG's limited clinical utility. BSGM demonstrated substantial performance improvements across all domains.

A type 2 immune circuit in the stomach controls mammalian adaptation to dietary chitin.

Dietary fiber improves metabolic health, but host-encoded mechanisms for digesting fibrous polysaccharides are unclear. In this work, we describe a mammalian adaptation to dietary chitin that is coordinated by gastric innate immune activation and acidic mammalian chitinase (AMCase). Chitin consumption causes gastric distension and cytokine production by stomach tuft cells and group 2 innate lymphoid cells (ILC2s) in mice, which drives the expansion of AMCase-expressing zymogenic chief cells that facilitate chitin digestion. Although chitin influences gut microbial composition, ILC2-mediated tissue adaptation and gastrointestinal responses are preserved in germ-free mice. In the absence of AMCase, sustained chitin intake leads to heightened basal type 2 immunity, reduced adiposity, and resistance to obesity. These data define an endogenous metabolic circuit that enables nutrient extraction from an insoluble dietary constituent by enhancing digestive function.

[Screening and obataining of aptamers for the blood group antigen-binding adhesin (BabA) to block Helicobacter pylori (H.pylori) colonization in the stomach of mice].

Objective To explore the aptamer specific binding blood group antigen-binding adhesin (BabA) of Helicobacter pylori (H.pylori) for blocking of H.pylori adhering host cell. Methods H.pylori strain was cultured and its genome was extracted as templates to amplify the BabA gene by PCR with designed primers. The BabA gene obtained was cloned and constructed into prokaryotic expression plasmid, which was induced by isopropyl beta-D-galactoside (IPTG) and purified as target. The single stranded DNA (ssDNA) aptamers that specifically bind to BabA were screened by SELEX. Enzyme-linked oligonucleotide assay (ELONA) was used to detect and evaluate the characteristics of candidate aptamers. The blocking effect of ssDNA aptamers on H.pylori adhesion was subsequently verified by flow cytometry and colony counting at the cell level in vitro and in mouse model of infection, respectively. Meanwhile, the levels of cytokines, interleukin 6 (IL-6), IL-8, tumor necrosis factor α (TNF-α), IL-10 and IL-4 in the homogenate of mouse gastric mucosa cells were detected by ELISA. Results The genome of H.pylori ATCC 43504 strains was extracted and the recombinant plasmid pET32a-BabA was constructed. After induction and purification, the relative molecular mass (Mr) of the recombinant BabA protein was about 39 000. The amino acid sequence of recombinent protein was consistent with BabA protein by peptide mass fingerprint (PMF). Five candidate aptamers were selected to bind to the above recombinent BabA protein by SELEX. The aptamers A10, A30 and A42 identified the same site, while A3, A16 and the above three aptamers identified different sites respectively. The aptamer significantly blocked the adhesion of H.pylori in vitro. Animal model experiments showed that the aptamers can block the colonization of H.pylori in gastric mucosa by intragastric injection and reduce the inflammatory response. The levels of IL-4, IL-6, IL-8 and TNF-α in gastric mucosal homogenates in the model group with aptamer treatment were lower than that of model group without treatment. Conclusion Aptamers can reduce the colonization of H.pylori in gastric mucosa via binding BabA to block the adhesion between H.pylori and gastric mucosal epithelial cells.

[A women with papules on her stomach]. / Een vrouw met papels op de buik.

A 55-year old woman was seen at the outpatient Dermatology department with orange-red, soft-elastic, asymptomatic papules on her abdomen since five years. A biopsy was positive for Congo-red staining and showed apple-green under bipolarized light. Laboratory work-up showed no systematic amyloidosis. We diagnosed it as primary nodular cutaneous amyloidosis.

Comparison of four digestion protocols on the physical characteristics of gastric digesta from cooked couscous using the Human Gastric Simulator.

In vitro digestion is widely employed in food, nutraceutical and pharmaceutical research, and numerous in vitro gastric digestion protocols have been proposed, with a wide range of experimental conditions. Differences in the simulated gastric fluids (pH, mineral content, enzyme type and enzyme activity) of different digestion protocols may alter the results for the digestion of the same meal. This study aimed to investigate how variations in the gastric secretion rate and composition in four in vitro digestion protocols (Infogest Riddet, Infogest Semi-dynamic, UC Davis and United States Pharmacopeia) impacted the physical properties of the emptied gastric digesta. Cooked couscous was used as a model meal and subjected to simulated gastric digestion using a dynamic gastric model, the Human Gastric Simulator (HGS). The digesta were collected from the outlet of the HGS after 15, 30, 60, 90, 120, 150, or 180 min. The gastric emptying of dry matter, pH, rheological properties, and particle size were evaluated. The digestion protocol significantly influenced the solid content and moisture content of the digesta (p < 0.001), particles per gram of dry matter (p < 0.0001), gastric emptying of dry matter (p < 0.003), shear stress at 0.45 s-1 and consistency coefficient (p < 0.0001). The presence of NaHCO3 in the Infogest Riddet and Infogest Semi-dynamic gastric secretions provided an additional buffering effect and increased the digesta pH during gastric digestion. Similarly, the inclusion of mucin in the UC Davis protocol resulted in a higher flow and viscoelastic properties of the emptied digesta. The highest dilution of gastric content in the United States Pharmacopeia (USP) protocol resulted in larger particles emptied from the HGS and the longest gastric emptying half-time of all digestion protocols. These findings provide new insights into the impact of digestion protocols on the digesta properties, which can be beneficial for the design and standardization of in vitro digestion models.

Solubility of lamotrigine in age-specific biorelevant media that simulated the fasted- and fed-conditions of the gastric and intestinal environments in pediatrics and adults: implications for traditional, re-formulated, modified, and new oral formulations.

BACKGROUND: Lamotrigine is an effective antiseizure medication that can be used in the management of focal and generalized epilepsies in pediatric patients. This study was conducted to quantify and compare the solubility of lamotrigine in age-specific biorelevant media that simulated the fasted and fed conditions of the gastric and intestinal environments in pediatrics and adults. Another aim was to predict how traditional, re-formulated, modified, and new oral formulations would behave in the gastric and intestinal environments across different age groups. METHODS: Solubility studies of lamotrigine were conducted in 16 different age-specific biorelevant media over the pH range and temperature specified by the current biopharmaceutical classification system-based criteria. The age-specific biorelevant media simulated the environments in the stomach and proximal gastrointestinal tract in both fasted and fed conditions of adults and pediatric sub-populations. The solubility of lamotrigine was determined using a pre-validated HPLC-UV method. RESULTS: Lamotrigine showed low solubility in the 16 age-specific biorelevant media as indicated by a dose number of > 1. There were significant age-specific variabilities in the solubility of lamotrigine in the different age-specific biorelevant media. Pediatric/adult solubility ratios of lamotrigine fell outside the 80-125% range in 6 (50.0%) and were borderline in 3 (25.0%) out of the 12 compared media. These ratios indicated that the solubility of lamotrigine showed considerable differences in 9 out of the 12 (75.0%) of the compared media. CONCLUSION: Future studies are still needed to generate more pediatric biopharmaceutical data to help understand the performances of oral dosage forms in pediatric sub-populations.

Organization and morphology of calcitonin gene-related peptide-immunoreactive axons in the whole mouse stomach.

Nociceptive afferent axons innervate the stomach and send signals to the brain and spinal cord. Peripheral nociceptive afferents can be detected with a variety of markers (e.g., substance P [SP] and calcitonin gene-related peptide [CGRP]). We recently examined the topographical organization and morphology of SP-immunoreactive (SP-IR) axons in the whole mouse stomach muscular layer. However, the distribution and morphological structure of CGRP-IR axons remain unclear. We used immunohistochemistry labeling and applied a combination of imaging techniques, including confocal and Zeiss Imager M2 microscopy, Neurolucida 360 tracing, and integration of axon tracing data into a 3D stomach scaffold to characterize CGRP-IR axons and terminals in the whole mouse stomach muscular layers. We found that: (1) CGRP-IR axons formed extensive terminal networks in both ventral and dorsal stomachs. (2) CGRP-IR axons densely innervated the blood vessels. (3) CGRP-IR axons ran in parallel with the longitudinal and circular muscles. Some axons ran at angles through the muscular layers. (4) They also formed varicose terminal contacts with individual myenteric ganglion neurons. (5) CGRP-IR occurred in DiI-labeled gastric-projecting neurons in the dorsal root and vagal nodose ganglia, indicating CGRP-IR axons were visceral afferent axons. (6) CGRP-IR axons did not colocalize with tyrosine hydroxylase or vesicular acetylcholine transporter axons in the stomach, indicating CGRP-IR axons were not visceral efferent axons. (7) CGRP-IR axons were traced and integrated into a 3D stomach scaffold. For the first time, we provided a topographical distribution map of CGRP-IR axon innervation of the whole stomach muscular layers at the cellular/axonal/varicosity scale.