Search Results (22)

Chronic pancreatitis (CP) precipitates complex malnutrition through synergistic mechanisms: exocrine pancreatic insufficiency–driven maldigestion, duodenal or pancreatobiliary strictures limiting nutrient flow, cholestasis impairing micelle formation, alcohol-related anorexia, pain-induced hypophagia, proteolytic catabolism from type 3c diabetes, and a chronic inflammatory milieu that accelerates sarcopenia and bone demineralisation. Consequent calorie–protein depletion, micronutrient and fat-soluble vitamin deficits, and metabolic derangements markedly amplify morbidity. Pancreatic enzyme replacement therapy (PERT) with targeted micronutrient repletion is foundational; high-protein regimens co-administered with PERT curb muscle loss, and medium-chain triglycerides (MCTs) can augment caloric delivery by bypassing lipase dependence, although their benefit over personalised dietetic counselling is marginal. Optimal dietary fat thresholds and timing of escalation from oral to enteral or parenteral feeding remain unresolved. Comprehensive care also demands alcohol abstinence, effective analgesia and stringent glycaemic control. Serial monitoring—biochemical indices, densitometry, dual-energy X-ray absorptiometry and imaging-based body-composition metrics—permits early detection of high-risk patients and precision tailoring of interventions. Intensified multidisciplinary programmes already improve prognostic endpoints and are unveiling biomarkers of nutritional resilience. A structured, evidence-based strategy integrating PERT, macronutrient engineering, micronutrient repletion and metabolic surveillance is essential to mitigate nutrition-related morbidity, enhance long-term outcomes and optimise quality of life in CP. Full article

Accurate in vitro models of intestinal permeability are essential for predicting oral drug absorption. Standard models like Caco-2 cells have well-known limitations, including lack of segment-specific physiology, but are widely used. Emerging models such as organoid-derived monolayers and microphysiological systems (MPS) offer enhanced physiological relevance but require comparative validation. We performed a head-to-head evaluation of Caco-2 cells, human jejunal (J2) and duodenal (D109) enteroid-derived cells, and EpiIntestinal^TM tissues cultured on either static Transwell and flow-based MPS platforms. We assessed tissue morphology, barrier function (TEER, dextran leakage), and permeability of three model small molecules (caffeine, propranolol, and indomethacin), integrating the data into a physiologically based gut absorption model (PECAT) to predict human oral bioavailability. J2 and D109 cells demonstrated more physiologically relevant morphology and higher TEER than Caco-2 cells, while the EpiIntestinal^TM model exhibited thicker and more uneven tissue structures with lower TEER and higher passive permeability. MPS cultures offered modest improvements in epithelial architecture but introduced greater variability, especially with enteroid-derived cells. Predictions of human fraction absorbed (F_abs) were most accurate when using static Caco-2 data with segment-specific corrections based on enteroid-derived values, highlighting the utility of combining traditional and advanced in vitro gut models to optimize predictive performance for F_abs. While MPS and enteroid-based systems provide physiological advantages, standard static models remain robust and predictive when used with in silico modeling. Our findings support the need for further refinement of enteroid-MPS integration and advocate for standardized benchmarking across gut model systems to improve translational relevance in drug development and regulatory reviews. Full article

Background/Objectives: The objective of this study was to describe the anatomical variants of the pancreaticobiliary junction and how its position or structural change could be associated with hepatic, duodenal, and pancreatic clinical complications. Methods: We searched MEDLINE, Scopus, Web of Science (WOS), Google Scholar, CINAHL, and EMBASE databases from their inception up to September 2024. Results: Two authors independently performed the search, study selection, data extraction, and assessed the methodological quality with an assurance tool for anatomical studies (AQUA). Finally, the pooled prevalence was estimated using a random effects model. A total of 59 studies with a total of 22,752 participants were included in this review. The overall prevalence of the anomalous pancreaticobiliary junction (APBJ) variant was 12% (95% CI = 6% to 18%). The prevalence of cancer associated with variants of APBJ was 29% (95% CI = 23% to 34%). Conclusions: In the present anatomical systematic review and meta-analysis, we found that a longer common channel correlated with a higher prevalence of bile duct or gallbladder malignancy, due to the backward flow of bile which occurs as a result of the position and distance of the bile ducts, as well as pancreatic failing. Hence, APBJs are of great interest for gastroduodenal surgeons. Full article

The objective of this study is to demonstrate the potential of a multicompartmental mathematical model to simulate the activity of the gastrointestinal system after the intake of drugs, with a limited number of parameters. The gastrointestinal system is divided into five compartments, modeled as both continuous systems with discrete events (stomach and duodenum) and systems with delay (jejunum, ileum, and colon). The dissolution of the drug tablet occurs in the stomach and is described through the Noyes–Whitney equation, with pH dependence expressed through the Henderson–Hasselbach relationship. The boluses resulting from duodenal activity enter the jejunum, ileum, and colon compartments, where drug absorption takes place as blood flows countercurrent. The model includes only three parameters with assigned physiological meanings. It was tested and validated using data from in vivo experiments. Specifically, the model was tested with the concentration profiles of nine different drugs and validated using data from two drugs with varying initial concentrations. Overall, the outputs of the model are in good agreement with experimental data, particularly with regard to the time of peak concentration. The primary sources of discrepancy were identified in the concentration decay. The model’s main strength is its relatively low computational cost, making it a potentially excellent tool for in silico assessment and prediction of drug adsorption in the intestine. Full article

Background: The diagnosis of coeliac disease (CD) in adults is based on clinical, serological and histological criteria. The inappropriate performance of intestinal biopsies, non-specificity of mild histological lesions and initiation of a gluten-free diet (GFD) before biopsy may hamper the diagnosis. In these situations, determining the intraepithelial lymphogram of the duodenum by flow cytometry (IEL-FC) can be helpful. Objectives: To describe the clinical scenarios in which the IEL-FC is used and its impact on the diagnosis of CD. Methods: All adult patients with suspected CD at three tertiary centres for whom the duodenal histology and IEL-FC were available were identified. Catassi and Fasano’s diagnostic criteria and changes to a CD diagnosis after the IEL-FCs were collected. Results: A total of 348 patients were included. The following indications for an IEL-FC formed part of the initial study for CD (38%): negative conventional work-up (32%), already on a GFD before duodenal biopsies (29%) and refractoriness to a GFD (2%). The IEL-FC facilitated a definitive diagnosis in 93% of patients with an uncertain diagnosis who had had a conventional work-up for CD or who were on a GFD before histology. Conclusions: The IEL-FC facilitates the confirmation or rejection of a diagnosis of CD in clinical scenarios in which a conventional work-up may be insufficient. Full article

Background: Celiac disease is a gluten-related pathology, highly prevalent and heterogeneous in its clinical presentation, which leads to delays in diagnosis and misdiagnosis. The analysis of duodenal intraepithelial lymphocytes (IELs) by flow cytometry (lymphogram) is emerging as a discriminative tool in the diagnosis of various forms of celiac disease (CD). Aims: The aim of this study was to validate IEL lymphogram performance in the largest adult series to our knowledge, in support of its use as a diagnostic tool and as a biomarker of the dynamic celiac process. Methods: This was a retrospective study including 768 adult patients (217 with active CD, 195 on a gluten-free diet, 15 potential CD patients, and 411 non-celiac controls). The IEL subset cut-off values were established to calculate the diagnostic accuracy of the lymphogram. Results: A complete celiac lymphogram profile (≥14% increase in T cell receptor [TCR]γδ IELs and simultaneous ≤4% decrease in surface-negative CD3 [sCD3⁻] IELs) was strongly associated with active and potential forms in over 80% of the confirmed patients with CD, whereas the remaining patients with CD had partial lymphogram profiles (≥14% increase in TCRγδ or ≤4% decrease in sCD3⁻ IELs), with lower diagnostic certainty. None of these patients had a non-celiac lymphogram. Quantifying the TCRγδ versus sCD3⁻ imbalance as a ratio (≥5) is a discriminative index to discard or suspect CD at diagnosis. Conclusions: We have validated the IEL lymphogram’s diagnostic efficiency (79% sensitivity, 98% specificity), with an LR+ accuracy of 36.2. As expected, the increase in TCRγδ IELs is a reliable marker for celiac enteropathy, while changes in sCD3⁻ IEL levels throughout the dynamic CD process are useful biomarkers of mucosal lesions. Full article

Our study highlighted the immune changes by pro-inflammatory biomarkers in the gut–liver-axis-linked ROS-cell death mechanisms in chronic and acute inflammations when gut cells are exposed to endotoxins in patients with hepatic cirrhosis or steatosis. In duodenal tissue samples, gut immune barrier dysfunction was analyzed by pro-inflammatory biomarker expressions, oxidative stress, and cell death by flow cytometry methods. A significant innate and adaptative immune system reaction was observed as result of persistent endotoxin action in gut cells in chronic inflammation tissue samples recovered from hepatic cirrhosis with the A-B child stage. Instead, in patients with C child stage of HC, the endotoxin tolerance was installed in cells, characterized by T lymphocyte silent activation and increased Th1 cytokines expression. Interesting mechanisms of ROS-cell death were observed in chronic and acute inflammation samples when gut cells were exposed to endotoxins and immune changes in the gut–liver axis. Late apoptosis represents the chronic response to injury induction by the gut immune barrier dysfunction, oxidative stress, and liver-dysregulated barrier. Meanwhile, necrosis represents an acute and severe reply to endotoxin action on gut cells when the immune system reacts to pro-inflammatory Th1 and Th2 cytokines releasing, offering protection against PAMPs/DAMPs by monocytes and T lymphocyte activation. Flow cytometric analysis of pro-inflammatory biomarkers linked to oxidative stress-cell death mechanisms shown in our study recommends laboratory techniques in diagnostic fields. Full article

Background: Systemic inflammation in chronic kidney disease (CKD) is associated (as a cause or effect) with intestinal barrier dysfunction and increased gut permeability, with mechanisms not yet fully understood. This study investigated different parameters of the intestinal barrier in CKD patients, especially tight junction (TJ) proteins and their possible association with systemic endotoxemia and inflammation. Methods: Thirty-three patients with stage I–IV CKD (n = 17) or end-stage kidney disease (ESKD) (n = 16) and 11 healthy controls underwent duodenal biopsy. Samples were examined histologically, the presence of CD3+ T-lymphocytes and the expression of occludin and claudin-1 in the intestinal epithelium was evaluated by means of immunohistochemistry, circulating endotoxin concentrations were determined by means of ELISA and the concentrations of the cytokines IL-1β, IL-6, IL-8, IL-10 and TNF-α in serum were measured using flow cytometry. Results: Patients with stage I–IV CKD or ESKD had significantly higher serum endotoxin, IL-6, IL-8 and IL-10 levels compared to controls. Intestinal occludin and claudin-1 were significantly decreased, and their expression was inversely correlated with systemic endotoxemia. Regarding occludin, a specific expression pattern was observed, with a gradually increasing loss of its expression from the crypt to the tip of the villi. Conclusion: The expression of occludin and claudin-1 in enterocytes is significantly reduced in patients with CKD, contributing to systemic endotoxemia and inflammatory responses in these patients. Full article

Although intestinal microbiota alterations (dysbiosis) have been described in heart failure (HF) patients, the possible mechanisms of intestinal barrier dysfunction leading to endotoxemia and systemic inflammation are not fully understood. In this study, we investigated the expression of the intestinal tight junction (TJ) proteins occludin and claudin-1 in patients with HF with reduced (HFrEF) or preserved ejection fraction (HFpEF) and their possible association with systemic endotoxemia and inflammation. Ten healthy controls and twenty-eight patients with HF (HFrEF (n = 14), HFpEF (n = 14)) underwent duodenal biopsy. Histological parameters were recorded, intraepithelial CD3+ T-cells and the expression of occludin and claudin-1 in enterocytes were examined using immunohistochemistry, circulating endotoxin concentrations were determined using ELISA, and concentrations of cytokines were determined using flow cytometry. Patients with HFrEF or HFpEF had significantly higher serum endotoxin concentrations (p < 0.001), a significantly decreased intestinal occludin and claudin-1 expression (in HfrEF p < 0.01 for occludin, p < 0.05 for claudin-1, in HfpEF p < 0.01 occludin and claudin-1), and significantly increased serum concentrations of IL-6, IL-8, and IL-10 (for IL-6 and IL-10, p < 0.05 for HFrEF and p < 0.001 for HFpEF; and for IL-8, p < 0.05 for both groups) compared to controls. Occludin and claudin-1 expression inversely correlated with systemic endotoxemia (p < 0.05 and p < 0.01, respectively). Heart failure, regardless of the type of ejection fraction, results in a significant decrease in enterocytic occludin and claudin-1 expression, which may represent an important cellular mechanism for the intestinal barrier dysfunction causing systemic endotoxemia and inflammatory response. Full article

This study aimed to evaluate the effects of supplementation with non-protein nitrogen (NPN) or ruminal undegradable protein (RUP) on intake, digestibility, and amino acid (AA) use efficiency of Nellore cattle grazing during the dry season. Eight Nellore steers (12 ± 2 months old) were used in quadruplicate Latin squares (2 × 2). The animals were placed on Urochloa brizantha cv. Xaraés under continuous grazing. The treatments included the following: (1) urea supplementation (NPN) and (2) supplementation of corn gluten meal 60 (CGM, RUP). Animals supplemented with CGM showed higher intakes of dry matter (DM) supplement, total AA, essential AA, and individual AA. The supplementation did not affect the total AA digestibility, total AA flux, and the AA fluxes of microbial origin and RUP from the diet (p > 0.05). The ruminal microorganism origin flux of total AA to the duodenum was 44.5% and 52.7% for animals supplemented with NPN and CGM, respectively. Animals supplemented with CGM showed an increase in blood concentrations of isoleucine (+19.09 μmol/L), cystine (+27.29 μmol/L), and albumin (+0.11 g/dL) (p < 0.05), but this increase was not accompanied by an improvement in N use efficiency of steers (p > 0.05). RUP supplementation via CGM can be an efficient nutritional strategy to enhance the intake and absorption of AA by Nellore cattle grazing low-quality forage during the dry season. Full article

The human gastrointestinal tract (GIT) is home to an abundance of diverse microorganisms, and the balance of this microbiome plays a vital role in maintaining a healthy GIT. The obstruction of the flow of bile into the duodenum, resulting in obstructive jaundice (OJ), has a major impact on the health of the affected individual. This study sought to identify changes in the duodenal microbiota in South African patients with OJ compared to those without this disorder. Mucosal biopsies were taken from the duodenum of nineteen jaundiced patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and nineteen control participants (non-jaundiced patients) undergoing gastroscopy. DNA extracted from the samples was subjected to 16S rRNA amplicon sequencing using the Ion S5 TM sequencing platform. Diversity metrics and statistical correlation analyses with the clinical data were performed to compare duodenal microbial communities in both groups. Differences in the mean distribution of the microbial communities in the jaundiced and non-jaundiced samples were observed; however, this difference did not reach statistical significance. Of note, there was a statistically significant difference between the mean distributions of bacteria comparing jaundiced patients with cholangitis to those without (p = 0.0026). On further subset analysis, a significant difference was observed between patients with benign (Cholelithiasis) and malignant disease, namely, head of pancreas (HOP) mass (p = 0.01). Beta diversity analyses further revealed a significant difference between patients with stone and non-stone related disease when factoring in the Campylobacter-Like Organisms (CLO) test status (p = 0.048). This study demonstrated a shift in the microbiota in jaundiced patients, especially considering some underlying conditions of the upper GI tract. Future studies should aim to verify these findings in a larger cohort. Full article

In this paper, a series of thiacalix[4]arenes were synthesized as potential theranostic molecules for antitumor therapy. We propose an original strategy for the regioselective functionalization of thiacalix[4]arene with a fluorescent label to obtain antiangiogenic agent mimetics. The aggregation properties of the synthesized compounds were determined using the dynamic light scattering. The average hydrodynamic diameter of self-associates formed by the macrocycles in 1,3-alternate conformation is larger (277–323 nm) than that of the similar macrocycle in cone conformation (185–262 nm). The cytotoxic action mechanism of the obtained compounds and their ability to penetrate into of human lung adenocarcinoma and human duodenal adenocarcinoma cells were established using the MTT-test and flow cytometry. thiacalix[4]arenes in 1,3-alternate conformation did not have a strong toxic effect. The toxicity of macrocycles in cone conformations on HuTu-80 and A549 cells (IC₅₀ = 21.83–49.11 µg/mL) is shown. The resulting macrocycles are potential theranostic molecules that combine both the pharmacophore fragment for neoplasmas treatment and the fluorescent fragment for monitoring the delivery and biodistribution of nanomedicines. Full article

Endoscopic bariatric and metabolic therapies are promising for obesity. We developed a novel gastro-duodenal flow restrictor (G-DFR) device for relative weight loss and lowering of glucose level and evaluated its safety and efficacy in a porcine model. The G-DFR comprised self-expandable gastro-duodenal partially covered polytetrafluoroethylene (PTFE) metal stent distally attached to a PTFE skirt. Eleven juvenile pigs were randomized into the evaluation of migration (n = 3), mid-term efficacy (n = 5), and control (n = 3) groups. Five pigs showed G-DFR migration at 2, 4, 7, and 10 weeks after placement in the migration and mid-term efficacy group. Compared to the control group, the mid-term efficacy group showed up to 55.4% relative weight loss in 12 weeks. Compared to the case group, the control group showed higher mean ghrelin hormone level from 6 to 12 weeks. Glucose level was significantly lower in the efficacy group than in the control group after 6 weeks. Serum alanine transferase levels and histological collagen deposition were lower in the liver of the case group than in the control group. Although it did not demonstrate consistent performance with respect to migration, a well-positioned G-DFR in the pyloroduodenal portion may lead to relative weight loss, lowering of glucose levels, and improved hepatic parameters. Full article

We study peristaltic flow in a C-shaped compliant tube representing the first section of the small intestine—the duodenum. A benchtop model comprising of a silicone tube filled with a glycerol-water mixture deformed by a rotating roller was created. Particle image velocimetry (PIV) was used to image flow patterns for deformations approximating conditions in the duodenum (contraction amplitude of 34% and wave speed 13 mm/s). Reversed flow was present underneath the roller with fluid moving opposite to the direction of the peristaltic wave propagation. Deformations of the tube were imaged and used to construct a computational fluid dynamics (CFD) model of flow with moving boundaries. The PIV and CFD vorticity and velocity fields were qualitatively similar. The vorticity field was integrated over the imaging region to compute the total circulation and there was on average a 22% difference in the total circulation between the experimental and numerical results. Higher shear rates were observed with water compared to the higher viscosity fluids. This model is a useful tool to study the effect of digesta properties, anatomical variations, and peristaltic contraction patterns on mixing and transport in the duodenum in health and disease. Full article

The purpose of this study is to investigate the potential effects of 5-hydroxytryptophan (5-HTP) duodenal perfusion on melatonin (MT) synthesis in the gastrointestinal (GI) tract of sheep. 5-hydroxytryptophan is a precursor in the melatonin synthetic pathway. The results showed that this method significantly increased melatonin production in the mucosa of all segments in GI tract including duodenum, jejunum, ileum, cecum and colon. The highest melatonin level was identified in the colon and this indicates that the microbiota located in the colon may also participate in the melatonin production. In addition, portion of the melatonin generated by the GI tract can pass the liver metabolism and enters the circulation via portal vein. The current study provides further evidence to support that GI tract is the major site for melatonin synthesis and the GI melatonin also contributes to the circulatory melatonin level since plasma melatonin concentrations in 5-HTP treated groups were significantly higher than those in the control group. In conclusion, the results show that 10–50 mg of 5-HTP flowing into the duodenum within 6 h effectively improve the production of melatonin in the GI tract and melatonin concentration in sheep blood circulation during the day. Full article