Gastrointestinal Injury Research Articles

Magnolol protects against acute gastrointestinal injury in sepsis by down-regulating regulated on activation, normal T-cell expressed and secreted.

BACKGROUNDSepsis is a major medical challenge. Magnolol is an active constituent of Houpu that improves tissue function and exerts strong anti-endotoxin and anti-inflammatory effects, but the mechanism by which it reduces intestinal inflammation in sepsis is yet unclear.AIMTo assess the protective effect of magnolol on intestinal mucosal epithelial cells in sepsis and elucidate the underlying mechanisms.METHODSEnzyme-linked immunosorbent assay was used to measure tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and regulated on activation, normal T-cell expressed and secreted (RANTES) levels in serum and ileal tissue in animal studies. The histopathological changes of the ileal mucosa in different groups were observed under a microscope. Cell Counting Kit-8 and cell permeability assays were used to determine the concentration of drug-containing serum that did not affect the activity of Caco2 cells but inhibited lipopolysaccharide (LPS)-induced decrease in permeability. Immunofluorescence and Western blot assays were used to detect the levels of RANTES, inhibitor of nuclear factor kappa-B kinase β (IKKβ), phosphorylated IKKβ (p-IKKβ), inhibitor of nuclear factor kappa-B kinase α (IκBα), p65, and p-p65 proteins in different groups in vitro.RESULTSIn rats treated with LPS by intravenous tail injection in the presence or absence of magnolol, magnolol inhibited the expression of proinflammatory cytokines, IL-1β, IL-6, and TNF-α in a dose-dependent manner. In addition, magnolol suppressed the production of RANTES in LPS-stimulated sepsis rats. Moreover, in vitro studies suggested that magnolol inhibited the increase of p65 nucleation, thereby markedly downregulating the production of the phosphorylated form of IKKβ in LPS-treated Caco2 cells. Specifically, magnolol inhibited the translocation of the transcription factor nuclear factor-kappa B (NF-κB) from the cytosol into the nucleus and down-regulated the expression level of the chemokine RANTES in LPS-stimulated Caco2 cells.CONCLUSIONMagnolol down-regulates RANTES levels by inhibiting the LPS/NF-κB signaling pathways, thereby suppressing IL-1β, IL-6, and TNF-α expression to alleviate the mucosal barrier dysfunction in sepsis.

The value of the exertional heat stroke score for the prognosis of patients with exertional heat stroke.

This study aims to evaluate the exertional heat stroke score (EHSS) system for the prognosis of exertional heat stroke (EHS) patients. Forty-two EHS patients who had been treated in our hospital between January 2017 and December 2019 were divided into two groups according to their prognosis, a survival group and a non-survival group. All the patients had received comprehensive EHS treatment after admission, and their EHSS parameters were collected within 24h of admission, including body temperature, hepatorenal function, and coagulation function. A retrospective comparative evaluation was made of the effectiveness of the EHSS, the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) in making an EHS prognosis. Among 42 patients, 28 patients were treated successfully and discharged from the hospital, 5 were given a poor prognosis, and 9 died, amounting to a fatality rate of 21.42%. Univariate analysis showed that within 24h of admission, the differences were statistically significant (p<0.05) in the comparison of the following factors: lactate concentration, platelets, prothrombin time, fibrinogen, troponin, aspartate aminotransferase, total bilirubin, urinary creatinine, acute gastrointestinal injury, temperature, and Glasgow coma score. However, no statistically significant difference in blood pH was observed between the two groups of patients (p=0.117). The EHSS, APACHE II, and SOFA scores of the survival group were significantly lower than those of the non-survival group (p<0.001). The area under the receiver operating characteristic curve of the EHSS, APACHE II and SOFA scores were the area under the curve (AUC) EHSS=0.96 (0.901, 0.990), AUC Apache II = 0.895 (0.802, 0.950), and AUC SOFA = 0.884 (0.837, 0.964), respectively. Thus, the EHSS diagnostic efficacy of the survival group was significantly higher than that of the other two scores. In addition, the sensitivity and specificity of EHSS were higher than those of the APACHE II and SOFA scores. The EHSS has a good diagnostic efficacy for the prognosis of EHS patients and is significantly higher than that of the APACHE II and SOFA scores. This finding provides a theoretical basis for further increasing the rescue success rate of EHS patients and improving their prognostic quality of life.

Acute L-glutamine supplementation does not improve gastrointestinal permeability, injury or microbial translocation in response to exhaustive high intensity exertional-heat stress

ABSTRACT Purpose: Exertional-heat stress adversely distrupts (GI) barrier integrity and, through subsequent microbial translocation (MT), can result in potentially fatal exertional-heat stroke. Acute glutamine (GLN) supplementation is a potential nutritional countermeasure, although the practical value of current supplementation regimens is questionable. Method: Ten males completed two high-intensity exertional-heat stress tests (EHST) involving running in the heat (40°C and 40% relative humidity) at lactate threshold to volitional exhaustion. Participants ingested GLN (0.3 g kg FFM−1) or a non-calorific placebo (PLA) one hour prior to the EHST. Venous blood was drawn pre-, post- and one-hour post-EHST. GI permeability was assessed using a serum dual-sugar absorption test (DSAT) and small intestinal epithelial injury using plasma Intestinal Fatty-Acid Binding Protein (I-FABP). MT was assessed using the Bacteroides/total 16S DNA ratio. Results: Volitional exhaustion occurred after 22:19 ± 2:22 (minutes: seconds) in both conditions, during which whole-body physiological responses and GI symptoms were not different (p > 0.05). GI permeability (serum DSAT) was greater following GLN (0.043 ± 0.020) than PLA (0.034 ± 0.019) (p = 0.02; d = 0.47), but small intestine epithelial injury (I-FABP) increased comparably (p = 0.22; = 0.16) following the EHST in both trials (GLN Δ = 1.25 ± 0.63 ng ml−1; PLA Δ = 0.92 ± 0.44 ng ml−1). GI MT (Bacteroides/total 16S DNA ratio) was unchanged in either condition following the EHST (p = 0.43). Conclusion: Acute low-dose (0.3 g kg−1 fat free mass) GLN supplementation ingested one hour before high-intesity exertional-heat stress worsened GI permeability, but did not influence either small intestinal epithilial injury or microbial translocation. Abbreviations: ANOVA: Analysis of variance; CV: Coefficient of Variation; DSAT: Dual Sugar Absorption Test; EDTA: Ethylenediaminetetraacetic acid; EHST: Exertional Heat Stress Test; ELISA: Enzyme Linked Immunosorbent Assay; FFM: Fat Free Mass; GI: Gastrointestinal; GFR: Glomerular Filtration Rate; GLN: Glutamine; HPLC: High Performance Liquid Chromatography; HR: Heart Rate; I-FABP: Intestinal Fatty-Acid Binding Protein; ISAK: International Society for the Advancement of Anthropometric Kinanthropometry; L/R: Lactulose-to-Rhamnose; LT: Lactate Threshold; MT: Microbial Translocation; mVAS: Modified Visual Analogue Scale; PBS: Phosphate-Buffered Saline; PLA: Placebo; qPCR: Quantitative Polymerase Chain Reaction; RH: Relative Humidity; RPE: Rate of Perceived Exertion; SD: Standard Deviation; SEM: Sensor Electronics Module; Tcore: Core Body Temperature; Tbody: Mean Body Temperature; Tskin: Mean Skin Temperature; TS: Thermal Sensation; V̇O2max: Maximal Oxygen Uptake. Highlights The pathophysiology of exertional-heat stroke is widely hypothesised to be at least in part attributable to a systemic inflammatory response caused by the leak of gastrointestinal microbes into the circulating blood. Acute high-dose (0.9 g kg FFM−1) L-glutamine supplementation is widely promoted as a practical strategy to protect gastrointestinal barrier integrity during exertional-heat stress. However, previously validated doses are often poorly tolerated and cannot be recommended for widespread implementation. This study examined the efficacy of low-dose (0.30 g kg FFM−1; ∼20 grams) acute L-glutamine supplementation on small intestinal injury, permeability, and microbial translocation in response a high-intensity exertional-heat stress test to exhaustion (20–30 min). This type of exercise accounts for the majority of exertional-heat stroke cases in the military. Despite being universally well-tolerated across all participants, acute low-dose L-glutamine supplementation worsened gastrointestinal permeability, without influencing either small intestinal injury or microbial translocation. These findings do not support the application of low-dose L-glutamine supplementation to help prevent exertional-heat stroke.

Profiling of inflammatory cytokines in patients with caustic gastrointestinal tract injury.

Study of inflammatory cytokines in patients with caustic gastrointestinal tract injury is sketchy. This study investigated the cytokine profiling of patients with caustic substance ingestion, and analyzed the differences between patients with severe and mild injury. This prospective, cross-sectional study enrolled 22 patients admitted to Chang Gung Memorial Hospital between March and October 2018. All patients underwent esophagogastroduodenoscopy in 24 hours. Patients were categorized into two subgroups, as mild (<2b, n = 11) or severe (≥2b, n = 11) group. The neutrophil count was higher in severe than mild group (P = 0.032). Patients in mild and severe groups exhibited significantly higher circulating inflammatory cytokines than healthy control, including interleukin (IL)-2, IL-5, IL-8, IL-9, IL-12, IL-13, interferon-gamma inducible protein-10, macrophage inflammatory protein-1 beta, regulated upon activation, normal T cell expressed and presumably secreted and tumor necrosis factor-alpha. Furthermore, the levels of IL-2 and tumor necrosis factor-alpha were significantly higher in patients with severe group than mild group. Although there was no difference in cumulative survival between both groups (P = 0.147), the severe group received more operations (P = 0.035) and suffered more gastrointestinal complications (P = 0.035) than mild group. Caustic substance ingestion produces mucosal damages and leads to excessive neutrophils and inflammatory cytokines in peripheral blood.

Recent advances in medical countermeasure development against acute radiation exposure based on the US FDA animal rule

Recent advances in medical countermeasures (MCMs) has been dependent on the Food and Drug Administration (FDA) animal rule (AR) and the final guidance document provided for industry on product development. The criteria outlined therein establish the path for approval under the AR. The guidance document, along with the funding and requirements from the federal agencies provided the basic considerations for animal model development in assessing radiation effects and efficacy against the potential lethal effects of acute radiation injury and the delayed effects of acute exposure. Animal models, essential for determining MCM efficacy, were developed and validated to assess organ-specific, potentially lethal, radiation effects against the gastrointestinal (GI) and hematopoietic acute radiation syndrome (H-ARS), and radiation-induced delayed effects to lung and associated comorbidities of prolonged immune suppression, GI, kidney and heart injury. Partial-body irradiation models where marginal bone marrow was spared resulted in the ability to evaluate the concomitant evolution of multiple organ injury in the acute and delayed effects in survivors of acute radiation exposure. There are no MCMs for prophylaxis against the major sequelae of the ARS or the delayed effects of acute exposure. Also lacking are MCMs that will mitigate the GI ARS consequent to potentially lethal exposure from a terrorist event or major radiation accident. Additionally, the gap in countermeasures for prophylaxis may extend to mixed neutron/gamma radiation if current modelling predicts prompt exposure from an improvised nuclear device. However, progress in the field of MCM development has been made due to federal and corporate funding, clarification of the critical criteria for efficacy within the FDA AR and the concomitant development and validation of additional animal models. These models provided for a strategic and tactical approach to determine radiation effects and MCM efficacy.

Effect of omeprazole and sucralfate on gastrointestinal injury in a fasting/NSAID model.

Equine gastric ulcer syndrome (EGUS) is a common and significant cause of morbidity in horses, with a range of clinical signs, including inappetence, colic and poor performance. Hospitalised horses are exposed to factors that may induce EGUS, including fasting and nonsteroidal anti-inflammatory drug (NSAID) administration, and may be at risk for development of squamous (ESGD) and glandular gastric disease (EGGD). Prophylactic anti-ulcer medication is often prescribed for these patients, but drug selection is complicated by different aetiology and response to treatment of ESGD and EGGD. To establish the efficacy of sucralfate or omeprazole used prophylactically in horses exposed to a combined feed-fast and NSAID administration EGUS induction protocol. We hypothesised that these drugs would be equally effective for prevention of gastric lesions in the experimental cohort. Randomised crossover experimental design. Horses (n=14) received either omeprazole (1mg/kg PO q24h) or sucralfate (20mg/kg PO q8h) while undergoing the feed-fast/NSAID protocol, allowed an 8-week washout period, and then administered the alternate treatment. Serial gastroscopy, ultrasound and haematology documented treatment effects. ESGD and EGGD score increased over time under both treatments. There was a significant effect of treatment on EGGD scores (P<.001), with post-treatment EGGD scores higher for horses receiving sucralfate (median 3; IQR 2.25,3) than omeprazole (1; 1,1). The effect of treatment on ESGD scores just achieved significance (P=.05), with post-treatment ESGD scores higher for sucralfate (4; 3,4) than omeprazole (2; 2,3). This study was performed in healthy horses, and response to treatment may differ in horses with clinical illness. Additional investigation in a larger population may be required to detect significant differences in other clinical parameters. Omeprazole was superior to sucralfate for mitigating gastric lesion severity in healthy horses exposed to a feed-fast/NSAID model.

Acute gastrointestinal injury in critically ill children: Impact on clinical outcome.

To estimate acute gastrointestinal injury (AGI) in critically ill children and association of its severity with mortality. In a prospective cohort study, critically ill children (1month-18 years) were enrolled. Gastrointestinal symptoms over the first week of admission were classified into AGI grades 1 through 4, using a paediatric adaptation of European Society of Intensive Care Medicine AGI definitions. Performance of AGI grades in predicting 28-day mortality was evaluated. Of 151 children enrolled, 71 (47%, 95% confidence interval (CI): 38.9-55.3%) developed AGI, with AGI grades 1, 2, 3 and 4 in 22.5%, 15.9%, 6.6% and 2%, respectively. The 28-day mortality progressively increased with AGI grade 0 (15%), 1 (35%), 2 (50%), 3 (70%), through 4 (100%), P < 0.001. Association of AGI grades with 28-day mortality was significant even after adjustment for disease severity, age and nutritional status (odds ratio (OR)=2.152, 95% CI: 1.455, 3.184). Among AGI grades, and paediatric logistic organ dysfunction-2 score components, cardiovascular (OR=1.525, 95% CI: 1.142, 2.037) and haematological (OR=1.719, 95% CI: 1.067, 2.772) components of paediatric logistic organ dysfunction-2 score and AGI grades (OR=1.565, 95% CI: 1.001, 2.449) showed significant association with 28-day mortality. Nearly half of the critically ill children developed AGI. AGI grades were independently associated with increased mortality, and mortality progressively increased with AGI grade.

Magnetically Controlled Capsule Endoscopy for Assessment of Antiplatelet Therapy–Induced Gastrointestinal Injury

BackgroundGastrointestinal bleeding is the most frequent major complication of antiplatelet therapy. In patients at low bleeding risk, however, clinically overt gastrointestinal bleeding is relatively uncommon. ObjectivesThe authors sought to assess the effects of different antiplatelet regimens on gastrointestinal mucosal injury by means of a novel magnetically controlled capsule endoscopy system in patients at low bleeding risk. MethodsPatients (n = 505) undergoing percutaneous coronary intervention in whom capsule endoscopy demonstrated no ulcerations or bleeding (although erosions were permitted) after 6 months of dual antiplatelet therapy (DAPT) were randomly assigned to aspirin plus placebo (n = 168), clopidogrel plus placebo (n = 169), or aspirin plus clopidogrel (n = 168) for an additional 6 months. The primary endpoint was the incidence of gastrointestinal mucosal injury (erosions, ulceration, or bleeding) at 6-month or 12-month capsule endoscopy. ResultsGastrointestinal mucosal injury through 12 months was less with single antiplatelet therapy (SAPT) than with DAPT (94.3% vs 99.2%; P = 0.02). Aspirin and clopidogrel monotherapy had similar effects. Among 68 patients without any gastrointestinal injury at randomization (including no erosions), SAPT compared with DAPT caused less gastrointestinal injury (68.1% vs 95.2%; P = 0.006), including fewer new ulcers (8.5% vs 38.1%; P = 0.009). Clinical gastrointestinal bleeding from 6 to 12 months was less with SAPT than with DAPT (0.6% vs 5.4%; P = 0.001). ConclusionsDespite being at low risk of bleeding, nearly all patients receiving antiplatelet therapy developed gastrointestinal injury, although overt bleeding was infrequent. DAPT for 6 months followed by SAPT with aspirin or clopidogrel from 6 to 12 months resulted in less gastrointestinal mucosal injury and clinical bleeding compared with DAPT through 12 months. (OPT-PEACE [Optimal Antiplatelet Therapy for Prevention of Gastrointestinal Injury Evaluated by Ankon Magnetically Controlled Capsule Endoscopy]; NCT03198741)

Evaluation of Fecal Calprotectin, D-Lactic Acid and Bedside Gastrointestinal Ultrasound Image Data for the Prediction of Acute Gastrointestinal Injury in Sepsis Patients.

Objective: To investigate the early warning and prognostic evaluation of fecal calprotectin (FC), D-lactic acid, and bedside gastrointestinal ultrasound (B-GIUS) data for acute gastrointestinal injury (AGI) in sepsis patients.Main Method: Sepsis patients were grouped based on the presence or absence of AGI into AGI and non-AGI groups. Healthy volunteers of the same period were selected as the control group. FC, B-GIUS data, D-lactic acid, etc. were collected on the 1st, 3rd and 7th days of admission. Twenty-eight-day mortality was recorded.Main Results: FC, D-lactic acid levels, gastric antrum cross-sectional area, and small intestine wall thickness were significantly increased in group A and B (P < 0.05); furthermore, inner-to-outer diameter ratio and cross-sectional area of small intestine were lower than those in the control group (P < 0.05). FC, D-lactic acid, gastric antrum cross-sectional area and small intestine wall thickness in AGI group were higher than those in non-AGI group (P < 0.05). Inner-to-outer diameter ratio and cross-sectional area of small intestine in AGI group were smaller than those in non-AGI group (P < 0.05). There was no difference in the thickness, inner-to-outer diameter ratio nor the cross-sectional area ratio of colon between AGI and non-AGI groups (P > 0.05). AUC for D-lactic acid was 0.881, which was higher than FC's (0.74). When the D-lactic acid cutoff value was 22.16 μmol/L, the sensitivity was 77.9% and the specificity was 92% for the prediction of AGI in sepsis. AUC for the cross-sectional area of the gastrointestinal antrum was 0.657, which was higher than the small intestine thickness's (0.629). When the gastric antrum cross-sectional area was larger than 4.20 cm2, the sensitivity was 64% and the specificity was 65.3%.Conclusion: D-Lactic acid and FC were early diagnostic indicators for sepsis with AGI, and D-lactic acid was the superior indicator. The gastric antrum cross-sectional area and the small intestine wall thickness had an early warning effect, and the prediction of the gastric antrum cross-sectional area was superior to that of the latter. Because it is non-invasive and convenient, B-GIUS can help in the diagnosis of sepsis with AGI.

Coronavirus disease 2019 gastrointestinal and liver manifestations in adults: A review.

Coronavirus disease 2019 (COVID‐19) is an important health problem that has a serious adverse impact on the global economy and healthcare systems. The virus is not only involved in the respiratory system, but also causes other systemic effects as well as several gastrointestinal and liver issues. Evidence has shown direct viral invasion into the gastrointestinal tissue and supporting vascular network, causing various manifestations such as diarrhea, nausea, gastrointestinal bleeding, and abnormal liver function tests. The degree of gastrointestinal injury, especially in terms of liver involvement, is correlated with disease severity. There is no specific treatment for gastrointestinal involvement, and the symptoms can be managed with supportive therapy. Moreover, increased liver decompensation and mortality can be found in COVID‐19‐infected patients with coexisting liver disease. As the virus can be identified in gastrointestinal contents, endoscopic procedures during the pandemic should be carefully selected and proper protection strategies should be encouraged to prevent viral transmission.

Review article: drug-induced small bowel injury.

Drug-induced gastrointestinal injury has been increasingly reported, but its exact incidence is not known. The small and large intestines represent the most affected sites of injury, accounting for 20%-40% of all gastrointestinal side effects. To provide an updated literature review detailing medications linked to the development of small bowel injury. We conducted a literature search on PubMed from its inception to May 1, 2021. We included English-language original studies, meta-analyses, systematic reviews, review articles and case reports. Drug-induced enteropathy can range from asymptomatic histological changes resulting in a subtle, self-limited disease to a chronic inflammatory condition mimicking inflammatory bowel disease, or bowel perforation. Endoscopy can demonstrate erythema, mucosal friability, oedema, erosions, ulcers or strictures in severe cases. Histology may include mucosal erosions and ulcerations, focal active enteritis, villous atrophy, epithelial apoptosis or necrotising enteritis. A well-established association has been found with the use of nonsteroidal anti-inflammatory drugs, immunosuppressants, chemotherapeutic agents, antibiotics, immunotherapies, etanercept and olmesartan. Possible associations have been reported with other biologic agents, medications used for glycemic control, antihypertensives, cholinesterase inhibitors, potassium and iron supplements, with conflicting data regarding contraceptives/hormonal therapy and isotretinoin. Physicians should be aware of the manifestations of drug-induced enteropathy as early recognition can lead to prompt discontinuation of the offending therapy and, therefore, a reduced risk of future complications.

Differences of gastrointestinal bleeding after percutaneous coronary intervention with stent implantation among the different dual anti platelet therapies

Abstract Patients who have undergone percutaneous coronary intervention (PCI) must be treated with dual antiplatelet therapy (DAPT) (aspirin and an adenosine diphosphate receptor antagonist (P2Y12)) to prevent thrombotic complications. However, this cornerstone of treatment comes with a higher risk of bleeding, which may have serious adverse outcomes, and affect the prognosis of patients. Gastrointestinal bleeding is one of the most common adverse consequences due to the direct injury that these drugs can cause in the mucosa of the digestive system. Old age, smoking, digestive tract diseases and renal impairment are risk factors for this kind of bleeding. However, the differences between DAPT options on the gastrointestinal injury have not been well studied. The primary objective was to compare the differences of the three different DAPT options in the incidence of gastrointestinal bleeding (defined according to CIE-9) in patients who presented with either acute or chronic coronary syndrome and have had an PCI with stent implantation. The influence of other variables in the incidence of gastrointestinal bleeding (including baseline characteristics of the patients, history of gastrointestinal diseases and other medications) and other complications, such as cardiovascular events and death, were secondary objectives. We conducted a retrospective observational cohort study, and all the patients who have undergone a PCI with stent implantation in two hospitals of our health system between January 2014 and December 2018 were enrolled. Clinical follow-up was the same time the patient was treated with DAPT. The information was extracted anonymously from the Oracle Business Intelligence Enterprise Edition (OBIEE) platform, which can integrate all clinical, analytical, diagnostic and prescription information. A propensity score adjustment was used with the risk covariates to form paired cohorts of each of the antiplatelet therapy groups. A total of 3367 patients were enrolled: 2052 in the clopidogrel group, 806 in the ticagrelor and 509 in the prasugrel group. 208 (6.18%) patients had a gastrointestinal bleeding: 132 (6.43%) in the clopidogrel group, 56 (6.95%) in the ticagrelor group and 20 (3.93%) in the prasugrel group (p=0.064). The baseline characteristics of the patients are listed in Table 1. We conducted a logistic regression to predict a multivariate model, in which, we observed that nine of the baseline characteristics are strongly related with the incidence of gastrointestinal bleeding. Moreover, according to our multivariate model, comparing with clopidogrel, the incidence of gastrointestinal bleeding seemed to be higher in the ticagrelor group (Odds Ratio [OR] 1.293, p=0.154) and lower in the prasugrel group (OR 0.661, p=0.111). There were not found significant differences in the incidence of gastrointestinal bleeding among the three options of DAPT in patients who have undergone a PCI with stent implantation. Funding Acknowledgement Type of funding sources: None. Table 1

Metabolomic Studies for Metabolic Alterations Induced by Non-Steroidal Anti-Inflammatory Drugs: Mini Review.

Non-steroidal anti-inflammatory drugs (NSAIDs) are Food and Drug Administration (FDA) approved antipyretic, anti-inflammatory, and analgesic drugs to mitigate pain, however it is associated with gastrointestinal injury and cardiovascular disease in some individuals. Metabolomics has the potential to understand the interaction of host and the drugs, such as NSAIDs administration. This discipline has been used by many researchers to understand the serious side effects of NSAIDs. We highlighted (1) the potential of metabolomics in understanding the pathogenesis of adverse events due to NSAIDs administration; (2) choice of metabolomics techniques, bio sample handling; (3) review of metabolomics studies in the front of NSAIDs in different biofluids and tissues; (4) pathway analysis of the data presented in the published literature. In our analysis we find tricarboxylic acid cycle (TCA), “glycine serine and threonine metabolism,” “alanine, aspartate, and glutamate metabolism,” and fatty acid metabolism to be altered by the NSAIDs like ibuprofen, indomethacin, naproxen, aspirin, and celecoxib. In conclusion, metabolomics allows the use of biological samples to identify useful pathways involved in disease progression, and subsequently inform a greater understanding of the disease pathogenesis. A further in-depth investigation of the associated pathways mentioned above holds the potential for drug targets for side effects mitigation.

A case of severe upper alimentary tract necrosis by corrosive acid poisoning

Corrosive poisoning is common in South East Asian countries than in the West. It can be accidental or suicidal and can cause gastrointestinal tract injuries. The grade of injuries depends on several factors related to the patient and the substance causing injury. Dilemmas arise at different management levels, whether to resort to a radical surgical approach or consider more conservative approaches. We present a case of suicidal corrosive acid injury in a 23-year-old male with extensive upper gastrointestinal tract injury managed surgically. Ampullojejunostomy may be a feasible option in patients with stomach and duodenal necrosis following corrosive acid poisoning if ampulla is normal. However, its role in the emergency setting may be questionable.

Effect of Huanglian Decoction on the Intestinal Microbiome in Stress Ulcer (SU) Mice.

Background Stress ulcer (SU) is a serious gastrointestinal mucosal lesion under acute stress. Huanglian decoction is a famous traditional Chinese medicine prescription, which has been used to treat digestive system diseases for thousands of years. Many clinical cases have proved that Huanglian decoction has a good effect on SU. Some studies have shown that the intestinal bacteria will be changed accordingly when the gastrointestinal mucosa is damaged. However, there are few published reports on the effect of the intestinal microbiome with SU mice that were treated by Huanglian decoction. In this study, we investigated the effect of the fecal microbiome in mice with SU by the 16S rDNA sequencing technology. Methods Male KM mice were induced by cold-restraint stress except for the normal control group and then treated by Huanglian decoction (Group HD) and Esomeprazole magnesium solution (Group ES) separately for 7 days. 16S rDNA sequencing technology analysis was applied to evaluate the changes of bacterial flora in mice feces. And, histopathological methods and molecular biological detection methods were also performed. Results Huanglian decoction could help to repair the gastric mucosal injury and regulate the relative content of TNF-α and IL-1β. Moreover, Huanglian decoction could increase the relative abundance of intestinal probiotics in the intestine of mice with SU, especially in Verrucomicrobiae and Akkermansia. Conclusions Huanglian decoction might effectively promote the repair of gastrointestinal mucosal injury and regulate the number and species of intestinal bacteria to maintain the stability of gastrointestinal microecology.

Total ginsenosides promote the IEC-6 cell proliferation via affecting the regulatory mechanism mediated by polyamines

Epithelial cell proliferation has been demonstrated to be a critical modality for mucosal repair after gastrointestinal mucosal injury. This research aimed to investigate the effect of total ginsenosides upon the proliferation of intestinal epithelial cells (IEC-6), and elucidate its potential mechanisms through polyamine-regulated pathway including the expression of proliferation-related proteins. Total ginsenosides (PGE3) were extracted from Panax ginseng, a Chinese herbal medicine, whose chromatogram was obtained by high performance liquid chromatographic method with evaporative light scattering detection (HPLC-ELSD). The cell proliferation, cell cycle distribution and the level of c-Myc, RhoA, Cdk2 proteins were detected to determine the effects of PGE3 at 25, 50 and100 mg/l doses on IEC-6. Furthermore, rats model of intestinal mucosal injury were induced by the subcutaneous injection of indomethacin, and the effect of Panax ginseng aqueous extracts (PGE1) on intestinal mucosal injury was observed. PGE3 could promote IEC-6 cell proliferation, reduce the proportion of G0/G1 phase cells and elevate the proportion of G2/M + S phase cells, and revert the proliferation and cell cycle arrest induced by DFMO (DL-a-difluoromethylornithine, an inhibitor of polyamines synthesis). PGE3 exposure enhanced the level of c-Myc, RhoA and Cdk2 proteins, and reversed the inhibition of these proteins expression induced by DFMO. The results of gross and pathological scores showed administration of PGE1 significantly alleviated intestinal mucosal injury of rats. Our findings indicate that total ginsenosides promoted the IEC-6 proliferation presumably via its regulation on cell cycle and the expression of proliferation-related proteins regulated by polyamines, and provided a novel perspective for exploring the repair effect of Panax ginseng upon gastrointestinal mucosal injury.

Extensive mucosal sloughing of the small intestine and colon in a patient with severe COVID‐19

Patients with coronavirus disease 2019 (COVID‐19) primarily cause respiratory symptoms. However, gastrointestinal (GI) symptoms can also occur. The endoscopic characteristics of the GI tract in COVID‐19 patients remain unclear. We herein report a 62‐year‐old male with severe COVID‐19 who needed multidisciplinary treatment, including extracorporeal membrane oxygenation (ECMO). Despite the improvement in his respiratory status, GI bleeding developed. Capsule endoscopy and colonoscopy revealed extensive mucosal sloughing in the lower intestinal tract. Additionally, we performed a comprehensive analysis of the mRNA expression levels of various proinflammatory cytokines in the intestinal mucosal tissues. The results suggested a significant elevation of IL‐6, which could be involved in the pathophysiology of the GI involvement in COVID‐19. Further investigation with more clinical data, including endoscopic findings and molecular analyses, will contribute to a comprehensive understanding of COVID‐19‐associated GI injury.

Investigation of the effects of St. John’s wort (Hypericum perforatum) oil on the methotrexate-induced gastrointestinal mucosa injury and hepatotoxicity in mice

St. John's wort oil is one of the herbal product which used for therapeutic purposes. To investigate the effects of St. John's Wort oil on irritated gastrointestinal mucosa and liver. The study is based on experimental animal trials. 21 healthy swiss albino mice were randomly divided into three groups: control group, group-2, group-3. The methotrexate (20 mg/kg) was given intraperitoneally as a single dose on the 1st day to the group-2 and group-3. St. John's Wort oil (4 ml/kg) was administered by gavages into the stomach daily for 7 days to the group-3. Following the necropsy, the gastrointestinal mucosa samples and the liver tissue samples were collected for histopathological evaluation. No pathology was found in the gastrointestinal mucosa and liver of control group. No pathology was found in the mice of group-3 in histopathological examination of the gastric mucosa. Significant hyperplasia and mononuclear cell infiltrations in lamina propria were observed in the mice of the group-2’s intestinal mucosa. The group-3 mice's intestinal mucosa was similar to control group's intestinal mucosa. In liver histopathology, mononuclear cell infiltrations and locally degenerative changes in the periportal area, vascular congestion and sinusoidal enlargement, thrombotic changes in the vessels, bile duct hyperplasia, megalocytosis in hepatocytes in some areas were observed in the livers of group-2 mice. Only a mild sinusoidal enlargement was noted in group-3's liver. According to the data we obtained in our study, St. John's Wort oil has protective and restorative effects especially on liver and intestinal mucosa if it is used consciously.

Clinical experience with titrating doses of digoxin antibodies in acute digoxin poisoning. (ATOM-6)

Introduction For acute digoxin poisoning, it has been recommended to give bolus doses of 10–20 vials or potentially larger than needed doses calculated from dose ingested or the measured concentration. However, a recent revision of internal Poisons Information Centre guidelines prompted a change of our recommendations, specifically instead of large boluses, to use titrating repeated low doses of digoxin antibodies(Digoxin-Fab) based on bedside assessment of cardiac toxicity. Methods This is a prospective observational study of patients with acute digoxin poisoning identified through two Poisons Information Centres and three toxicology units. Patient demographics, signs and symptoms of digoxin toxicity, doses and response to Digoxin-Fab, free and bound serum digoxin concentrations. Outcomes were recorded and analysed. Results From September 2013 to September 2020, 23 patients with 25 presentations (median age 56 years, females 56%) were recruited. Median dose ingested was 13 mg(IQR: 9.5–25). Median heart rate (HR) was 41 beats/min before treatment. Initial median digoxin and potassium concentrations were 14.5 nmol/L (IQR: 10.9–20) [11.2 µg/L(IQR: 8.4–15.4)] and 5 mmol/L (IQR: 4.5–5.4 mmol/L), respectively. Gastrointestinal symptoms and acute kidney injury were present in 22 patients (88%) and 5 patients (20%), respectively. Four patients received an initial bolus dose of Digoxin-Fab of 5–20 vials. Twenty-one patients received repeated titrated doses (1–2 vials) of Digoxin-Fab and the median total dose was 4 vials (IQR: 2–7.5). Median maximal change in HR post-Digoxin-Fab was 19 beats/min. The median potassium concentration decrease post-Digoxin-Fab was 0.3 mmol/L. Total dose used in the titration group was 25% and 35% of the predicted doses based on the amount of digoxin ingested or measured serum concentration, respectively. Twelve had free digoxin concentrations measured. Free digoxin concentrations dropped to almost zero after any dose of Digoxin-Fab. Ten patients had a rebound of digoxin >2.6 nmol/L (2 µg/L). There were no deaths from acute digoxin toxicity. Conclusions The new practice of using small, titrated doses of Digoxin-Fab led to a considerable reduction in total usage and major savings. The clinical response to titrated doses was safe and acceptable in acute digoxin poisoning.

Plasma Metabolomics in a Nonhuman Primate Model of Abdominal Radiation Exposure.

The acute radiation syndrome is defined in large part by radiation injury in the hematopoietic and gastrointestinal (GI) systems. To identify new pathways involved in radiation-induced GI injury, this study assessed dose- and time-dependent changes in plasma metabolites in a nonhuman primate model of whole abdominal irradiation. Male and female adult Rhesus monkeys were exposed to 6 MV photons to the abdomen at doses ranging between 8 and 14 Gy. At time points from 1 to 60 days after irradiation, plasma samples were collected and subjected to untargeted metabolomics. With the limited sample size of females, different discovery times after irradiation between males and females were observed in metabolomics pattern. Detailed analyses are restricted to only males for the discovery power. Radiation caused an increase in fatty acid oxidation and circulating levels of corticosteroids which may be an indication of physiological stress, and amino acids, indicative of a cellular repair response. The largest changes were observed at days 9 and 10 post-irradiation, with most returning to baseline at day 30. In addition, dysregulated metabolites involved in amino acid pathways, which might indicate changes in the microbiome, were detected. In conclusion, abdominal irradiation in a nonhuman primate model caused a plasma metabolome profile indicative of GI injury. These results point to pathways that may be targeted for intervention or used as early indicators of GI radiation injury. Moreover, our results suggest that effects are sex-specific and that interventions may need to be tailored accordingly.