Danshen polysaccharides alleviate AFB1 induced Jejunal injury.

AFB1 is a common foodborne toxin known for its potent carcinogenicity. Danshen polysaccharide (DSP) is an active ingredient of Danshen, which has been demonstrated to possess support intestinal homeostasis and anti-inflammatory activities. We utilized New Zealand White rabbits as an animal model to examine the impact of co-exposure to DSP and AFB1 on the intestines, as well as their underlying mechanisms. The results indicate that DSP elevated the abundance of Oscillospira, Coprococcus, Alistipes, Akkermansia, Bacteroides, Odoribacter, Blautia and Parabacteroides, while decreased the abundance of Sutterella, and Desulfovibrio, correcting AFB1-induced intestinal microbiota dysbiosis and enhancing microbial diversity within the gut. Moreover, DSP reduced the levels of diamine oxidase (DAO), D-Lactate, and malondialdehyde (MDA), while upregulating the expression of total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px), zonula occludens-1 (ZO-1), occludin, claudin-4, mucin-2 (MUC2), and secretory immunoglobulin A (sIgA), thereby alleviating the oxidative stress and intestinal barrier dysfunction induced by AFB1. DSP downregulated jejunal lipopolysaccharide (LPS) levels and the mRNA expression and proteins abundance of toll-like receptor 4 (TLR4), myeloiddifferentiationfactor 88 (MyD88), and nuclear factor kappa-B (NF-κB), thereby inhibiting the jejunal inflammation induced by AFB1. In summary, DSP alleviates AFB1-induced jejunal injury by remodeling the gut microbiota, bolstering antioxidant capabilities within the jejunum, fortifying the intestinal barrier, and suppressing the TLR4-mediated release of pro-inflammatory cytokines.

Small bowel intramural hematoma caused by warfarin: case report and literature review.

BACKGROUND: Intramural hematoma of the small bowel is a rare yet acute gastrointestinal condition typically linked with impaired coagulation function, often posing diagnostic challenges. It is principally encountered in patients undergoing prolonged anticoagulant therapy, specifically warfarin. CASE PRESENTATION: We reported a case of intramural hematoma associated with warfarin use. The patient was admitted to hospital with abdominal pain and had received anticoagulant therapy with warfarin 2.5 mg/day for 4 years. Laboratory examination showed decreased coagulation function, abdominal CT showed obvious thickening and swelling of part of the jejunal wall, and abdominal puncture found no gastroenteric fluid or purulent fluid. We treated the patient with vitamin K and fresh frozen plasma. The patient was discharged after the recovery of coagulation function. Then we undertaook a comprehensive review of relevant case reports to extract shared clinical features and effective therapeutic strategies. CONCLUSION: Our analysis highlights that hematoma in the small intestinal wall caused by warfarin overdose often presents as sudden and intense abdominal pain, laboratory tests suggest reduced coagulation capacity, and imaging often shows thickening of the intestinal wall. Intravenous vitamin K and plasma supplementation are effective non-surgical strategies. Nevertheless, in instances of severe obstruction and unresponsive hemostasis, surgical resection of necrotic intestinal segments may be necessary. In the cases we reported, we avoided surgery by closely monitoring the coagulation function. Therefore, we suggest that identifying and correcting the impaired coagulation status of patient is essential for timely and appropriate treatment.

Melatonin-Activated Receptor Signaling Pathways Mediate Protective Effects on Surfactant-Induced Increase in Jejunal Mucosal Permeability in Rats.

A well-functional intestinal mucosal barrier can be compromised as a result of various diseases, chemotherapy, radiation, and chemical exposures including surfactants. Currently, there are no approved drugs targeting a dysfunctional intestinal barrier, which emphasizes a significant medical need. One candidate drug reported to regulate intestinal mucosal permeability is melatonin. However, it is still unclear if its effect is primarily receptor mediated or antioxidative, and if it is associated with enteric neural pathways. The aim of this rat intestinal perfusion study was to investigate the mechanisms of melatonin and nicotinic acetylcholine receptors on the increase in intestinal mucosal clearance of 51Cr-labeled ethylenediaminetetraacetate induced by 15 min luminal exposure to the anionic surfactant, sodium dodecyl sulfate. Our results show that melatonin abolished the surfactant-induced increase in intestinal permeability and that this effect was inhibited by luzindole, a melatonin receptor antagonist. In addition, mecamylamine, an antagonist of nicotinic acetylcholine receptors, reduced the surfactant-induced increase in mucosal permeability, using a signaling pathway not influenced by melatonin receptor activation. In conclusion, our results support melatonin as a potentially potent candidate for the oral treatment of a compromised intestinal mucosal barrier, and that its protective effect is primarily receptor-mediated.

Spontaneous intramural small bowel hematoma in a patient with acute myeloid leukaemia receiving chemotherapy and nilotinib.

Spontaneous intramural small bowel hematoma (SISBH) is a rare, acute abdominal condition, with increasing incidence in recent years. Excessive anticoagulation with vitamin K antagonists is the most common aetiology. We report the case of a large acute jejunal intramural hematoma in a patient with newly diagnosed acute myeloid leukaemia receiving chemotherapy and nilotinib. The patient presented with abdominal pain, haematochezia, acute anaemia and thrombocytopenia. CT of the abdomen and pelvis revealed SISBH. The patient was managed conservatively with supportive management and cessation of nilotinib therapy. The patient's symptoms improved, with subsequent CT imaging confirming resolution. This case highlights an uncommon cause of gastrointestinal bleed usually diagnosed only after radiological imaging. A correct diagnosis is important as SISBH usually responds to conservative measures, and may obviate the patient from unnecessary invasive investigations.

[Angioneurotic Edema as a Differential Diagnosis of Recurrent Abdominal Pain]. / Angioneurotisches Ödem als Differenzialdiagnose rezidivierender Bauchschmerzen.

History and admission findings A 46-year-old woman was admitted because of recurrent postprandial vomiting including weight loss of 30 kg within the last 5 - 6 months. The physical investigation was indicative of preileus. Investigations CT scan revealed an unclear thickening of the jejunum. Treatment and course Explorative laparotomy was performed because of the considerable degree of suffering and a tendency of worsening. Intraoperatively, the preoperatively observed thickening was confirmed at 3 subsequent segments of the jejunum (3 cm long each) prompting to segmental resection of the jejunum. The postoperative course was uneventful. Histopathology revealed submucous, partially transmural, segmental edema compatible with an angioneurotic edema. Amyloidosis, sprue and malignancy could be excluded. A C1 esterase inhibitor test war normal. A further search for possible causes revealed ACE inhibitor medication for hypertension. Conclusion The differential diagnostic assessment of isolated small intestine diseases must take into account rare systemic disease. The knowledge of the history of medicine can be useful to detect the - not mandatory - connection to angioedema.

Co-exposure to low doses of the food contaminants deoxynivalenol and nivalenol has a synergistic inflammatory effect on intestinal explants.

The global incidence of Fusarium head blight and attendant cereal grains multi-contamination by the trichothecene mycotoxins deoxynivalenol (DON) and nivalenol (NIV) are increasing as a possible result of climate change and inadequate agricultural practices. At the molecular level, these mycotoxins bind to the ribosome, activate the mitogen-activated protein kinase and induce a local and systemic inflammation. DON is of public health concern owing to the narrow margin between exposure and tolerable daily intake. The intestinal inflammatory response to DON, NIV and their mixture was analyzed to determine thresholds for their intestinal pro-inflammatory effects and characterize the type and magnitude of their interaction. Fully differentiated three-dimensional porcine jejunal explants were exposed to increasing doses of DON and NIV alone or in combination; the expression levels of IL-1α, IL-1ß, IL-8, IL-17A and IL-22 were measured by RT-PCR. Doses as low as 0.16 µM DON or 0.73 µM NIV significantly increase the intestinal expression levels of the tested inflammation-related genes. These doses are lower than those previously reported for other intestinal toxicity endpoints. The combined pro-inflammatory activity of DON and NIV was synergistic for all the tested genes with combination index value range of 0.23-0.8. Our results indicate that (1) inflammation is a very sensitive endpoint for the intestinal toxicity of the trichothecenes and (2) co-exposure to DON and NIV has a greater inflammatory effect than induced by mycotoxins alone. This synergy should be taken into account considering the frequent co-occurrence of DON and NIV in the diet.

Jejunitis secondary to Duodopa® probe, a different complication.

Treatment with continuous infusion of intraduodenal (Duodopa®) levodopa / carbidopa is indicated in patients with advanced Parkinson's disease who have not responded to conventional treatment. We present here the case of a patient with this type of probe that debuted jejunitis. A distal phytobezoar was the main causal agent. This rare complication may be favored in cases of intestinal hypomotility. Treatment involves its withdrawal as soon as possible and replacement by a new probe, which results in healing.

Protective Effects of Vitamin E on Methotrexate-Induced Jejunal Mucosal Damage in Rats.

OBJECTIVE: To investigate the possible protective effects of Vitamin E (Vit E) on oxidative stress and jejunal damage in the rat intestinal mucosa after methotrexate (MTX)-induced enterotoxicity. STUDY DESIGN: Rats were divided into 3 groups: control, MTX, and MTX+ Vit E; each group contained 8 animals. The control group was given physiological serum in addition to sunflower oil for 3 days. The second group was given sunflower oil with intragastric tube daily, followed by MTX injection (20 mg/kg intraperitoneally). To the third group, starting 3 days before injection, Vit E was given dissolved in sunflower oil (600 mg/kg orally) in addition to MTX injection. Four days after MTX injection the anesthetized rats were sacrificed, and the tissue samples obtained from their jejunums were investigated for histological and biochemical analysis. RESULTS: Vit E treatment significantly decreased the elevated tissue malondialdehyde levels and increased the reduced glutathione peroxidase and superoxide dismutase activities in comparison to the MTX-treated group. MTX treatment caused severe histopathological injury including mucosal erosions, inflammatory cell infiltration, necrosis, hemorrhage, and villous congestion. Vit E treatment significantly attenuated the severity of intestinal injury caused by MTX via inhibiting induced nitric oxide synthase levels and NF-κB p65 activation. CONCLUSION: Because of its reconstructing and antioxidant effects, Vit E pretreatment may have protective effects in the intestinal tissue of MTX-treated rats.

Protective effects of ß-casofensin, a bioactive peptide from bovine ß-casein, against indomethacin-induced intestinal lesions in rats.

SCOPE: ß-casofensin, also known as peptide ß-CN(94-123), is a milk bioactive peptide that modulates the intestinal barrier through its action on goblet cells. Here, we evaluated whether oral administration of ß-casofensin can prevent indomethacin-induced injury of the jejunum in rats. METHODS AND RESULTS: Rats received ß-casofensin (0.01-100 µM) or tap water by daily gavage (4 µL/g) for eight days, then two subcutaneous injections of indomethacin (10 mg/kg, days 9 and 10) and were euthanized on day 12. In vitro, we investigated the effects of ß-casofensin on the restitution of a wounded monolayer. Preventive administration of ß-casofensin (100 µM) reduced intestinal macroscopic and microscopic damage induced by indomethacin. ß-casofensin also prevented the depletion of goblet cells and increased myeloperoxidase activity, as well as tumor necrosis factor-ɑ (TNF-ɑ) expression and immunostaining of active caspase-3 in the jejunum of rats treated with indomethacin. In wound healing experiments, ß-casofensin promoted epithelial restitution with no effect on cell proliferation. This effect was inhibited by pre-incubation with an anti-CC chemokine receptor 6 (CCR6) neutralizing antibody. CONCLUSIONS: ß-casofensin exerts protective effects in indomethacin-induced enteritis through preservation of goblet cells and improvement in wound healing. ß-casofensin could therefore become vital in nutritional programs for the prevention of intestinal diseases.

Serum-derived bovine immunoglobulin/protein isolate in the alleviation of chemotherapy-induced mucositis.

BACKGROUND: Gastrointestinal (GI) mucositis caused by chemotherapy is associated with diarrhoea and intestinal barrier disruption caused by apoptosis, immune dysfunction and microbiome alterations. Serum-derived bovine immunoglobulin/protein isolate (SBI) has been shown to manage HIV-associated enteropathy and irritable bowel syndrome with diarrhoea (IBS-D). We investigated in a rat model whether SBI was effective in alleviating symptoms of irinotecan-induced GI mucositis. METHODS: Animals were gavaged with 250 or 500 mg/kg of SBI twice daily for 4 days, before intraperitoneal administration of 200 mg/kg irinotecan. Twice daily gavaging of SBI continued for 6 days post-irinotecan. Animals were monitored for bodyweight changes and incidence of diarrhoea and clinical symptoms of stress. Tissues and blood samples were collected at necropsy 6 h, and 2, 4 and 6 days post-irinotecan. H&E-stained colon and jejunum were analysed for histological damage. RESULTS: The overall incidence, severity and duration of diarrhoea, and clinical symptoms of mucositis were decreased in irinotecan-treated animals that had received SBI. Animals receiving 500 mg/kg SBI also tended to lose less bodyweight than animals treated only with irinotecan (P > 0.10). SBI-gavaged animals had less pronounced irinotecan-induced changes in neutrophil (P = 0.04959) and lymphocyte (P = 0.0035) levels, and lower tissue damage scores than those receiving irinotecan alone (P < 0.0001). CONCLUSIONS: Twice daily oral gavage of SBI was well-tolerated and reduced the incidence, severity and duration of irinotecan-induced mucositis. SBI was associated with less pronounced changes in inflammatory cell levels and tissue damage to colon and jejunum. Ongoing experiments aim to investigate the mechanisms of SBI-associated gastrointestinal protection.

Local corticosterone production and angiotensin-I converting enzyme shedding in a mouse model of intestinal inflammation.

AIM: To investigate local corticosterone production and angiotensin-I converting enzyme (ACE) protein expression and their interaction in healthy and inflamed intestine. METHODS: Acute intestinal inflammation was induced to six weeks old male Balb/c mice by administration of either 3% or 5% dextran sodium sulfate (DSS) in drinking water for 7 d (n = 12 in each group). Healthy controls (n = 12) were given tap water. Corticosterone production and ACE protein shedding were measured from ex vivo incubates of the small and large intestine using EIA and ELISA, respectively. Morphological changes of the intestinal wall were assessed in hematoxylin-eosin stained tissue preparations of jejunum and distal colon. Effects of angiotensin II, captopril and metyrapone on corticosterone production was assessed by incubating pieces of small intestine of healthy mice in the presence of 0.1, 1 or 10 µmol/L angiotensin II, 1, 10 or 100 µmol/L captopril or 1, 10 or 100 µmol/L metyrapone solutions and measuring corticosterone released to the incubation buffer after 90 min (n = 5 in each group). RESULTS: Both concentrations of DSS induced inflammation and morphological changes in large intestines but not in small intestines. Changes were observed as distortions of the crypt structure, mucosal erosion, immune cell infiltration to the mucosa and submucosal edema. Ex vivo corticosterone production (2.9 ± 1.0 ng/mL vs 2.0 ± 0.8 ng/mL, P = 0.034) and ACE shedding (269.2 ± 97.1 ng/mL vs 175.7 ± 52.2 ng/mL, P = 0.016) were increased in small intestines in 3% DSS group compared to the controls. In large intestine, corticosterone production was increased compared to the controls in both 3% DSS (229 ± 81 pg/mL vs 158 ± 30 pg/mL, P = 0.017) and 5% DSS groups (366 ± 163 pg/mL vs 158 ± 30 pg/mL, P = 0.002). Large intestine ACE shedding was increased in 5% DSS group (41.5 ± 9.0 ng/mL vs 20.9 ± 5.2 ng/mL, P = 0.034). Angiotensin II treatment augmented corticosterone production in small intestine at concentration of 10 µmol/L (0.97 ± 0.21 ng/mg protein vs 0.40 ± 0.09 ng/mg protein, P = 0.036). CONCLUSION: Intestinal ACE shedding is increased by DSS-induced intestinal inflammation and parallels local corticosterone production. ACE product angiotensin II stimulates corticosterone formation in healthy intestine.