Small Intestinal Injury Research Articles

ADAR1 prevents small intestinal injury from inflammation in a murine model of sepsis

Adenosine deaminase acting on RNA 1 (ADAR1), a double-stranded RNA-editing enzyme that converts adenosine (A) to inosine (I), has been identified as a modulator of immune responses. However, the role of ADAR1 in small intestinal homeostasis during sepsis remains unclear. In this study, we examined the role of ADAR1 on intestinal inflammation in a murine model of sepsis. We found that ADAR1 was highly expressed in “septic” macrophages and small intestinal tissue of septic mice. Deletion of ADAR1 in “septic” macrophages led to rapid apoptosis. In addition, suppression of ADAR1 in “septic” macrophages significantly enhanced inflammation, while over-expression of ADAR1 significantly suppressed the level of inflammatory cytokines. Furthermore, suppression of ADAR1 in septic mice significantly enhanced inflammation and intestinal damage, while enhanced ADAR1 expression resulted in reduced damage and inflammation. Finally, over-expression of ADAR1 improved survival of septic mice. In conclusion, we have identified a novel ADAR1 protective effect for maintaining intestinal homeostasis. Our findings may provide a new targeted therapy for sepsis treatment.

Mucosal injury of small intestine in patients with advanced gastric cancer who developed chemotherapy induced diarrhea (CID).

28 Background: Fluoropyrimidine is a key drug for patients with advanced or recurrent gastric cancer. It causes diarrhea, a common non-hematological toxicity. The consensus guideline suggests aggressive treatment including intravenous fluids and antibiotics, is necessary for patients with severe diarrhea accompanied by fever and sepsis. However, the frequency of complicating signs and the actual degree of damage of small intestinal mucosa have not been reported. We evaluated complicating signs and mucosal injury in patients with complicated CID. Methods: Between April 2007 and December 2016, 170 patients with advanced or recurrent gastric cancer who underwent S-1 or capecitabine based chemotherapy were retrospectively analyzed. Diarrhea was evaluated with CTCAE v4.0, and complicated CID was defined as CTC grade 3 or 4 diarrhea or grade 1 or 2 diarrhea with following signs: cramping, vomiting, decreased performance status, fever, sepsis, neutropenia, frank bleeding, and dehydration. To evaluate mucosal injury of small intestine, capsule endoscopy was performed in patients with complicated CID. Results: Among 170 patients, 15 patients (8.8%) showed complicated CID during chemotherapy (S-1 based chemotherapy, n = 13/148; capecitabine based chemotherapy, n = 2/22). Among the profile of complicated signs, cramping, fever, and vomiting were frequent, and observed in 11 (73%), 7 (47%), and 5 (33%) patients, respectively. Ten patients received capsule endoscopy after improvement of CID, and 6 (60%) patients had multiple erosions or ulcerations in small intestine. Conclusions: The incidence of complicated CID caused by fluoropyrimidine based chemotherapy was less frequent in patients with advanced or recurrent gastric cancer. However, most patients showed mucosal injury of small intestine in capsule endoscopy. Therefore, these findings strongly support the guideline that recommends aggressive therapeutic approach for patients with complicated CID.

Effect of egualen sodium hydrate on small-intestinal mucosal damage induced by low-dose aspirin: a prospective randomized clinical trial.

Low-dose aspirin, which is widely used to reduce the risk of cardio- and cerebrovascular thrombosis, often induces gastroenteropathy by increasing the permeability of the mucosa. However, therapeutic strategies for patients with low-dose aspirin-induced small intestinal injury have not been determined. We evaluated the preventative effect of egualen sodium hydrate, a gastro-protective agent that suppresses indomethacin-induced small-intestinal damage in rats, against small-intestinal mucosal damage induced by low-dose aspirin in healthy adult male volunteers. Participants were randomly allocated to receive aspirin 100 mg/kg daily (control group, n = 10) or aspirin 100 mg/kg plus egualen sodium 30 mg daily (egualen sodium group, n = 10). Small intestinal mucosal injury was evaluated by capsule endoscopy two weeks after initiation of drug administration. Fecal analyses (occult blood test, immunochemical test, transferrin measurement and calprotectin measurement) were carried out before and after treatment. Egualen sodium significantly suppressed the total number of small intestinal injuries detected by capsule endoscopy and the positive ratio for the fecal occult blood test. Daily use of 30 mg of egualen sodium showed a preventative effect on low-dose aspirin-induced small intestinal injury. Since acid suppression therapy was reported to exacerbate NSAIDs-induced enteropathy via dysbiosis, egualen sodium may be useful for patients treated with low-dose aspirin.

Dual antiplatelet therapy does not affect the incidence of low-dose aspirin-induced small intestinal mucosal injury in patients after percutaneous coronary intervention for coronary stenosis: a multicenter cross-sectional study.

Although low-dose aspirin (LDA) is known to induce small intestinal mucosal injury, the effect of dual antiplatelet therapy (DAPT; LDA + clopidogrel) on small intestinal mucosa in patients after percutaneous coronary intervention (PCI) for coronary stenosis is unknown. Fifty-one patients with a history of PCI and LDA use were enrolled, and 45 eligible patients were analyzed. Patients were grouped based on DAPT (DAPT: n = 10 and non-DAPT: n = 35) and proton pump inhibitor (PPI) use (PPI user: n = 22 and PPI-free patients: n = 23) to compare small intestinal endoscopic findings. The relationship between LDA-use period and small intestinal endoscopic findings was also examined. Multivariate analysis was performed to identify risk factors for LDA-induced mucosal injury using age, sex, DAPT, PPI, gastric mucoprotective drug, and LDA-use period. The rate of small intestinal mucosal injury incidence did not significantly differ between DAPT and non-DAPT patients (50% vs 51.1%, respectively; p = 0.94), or PPI users and PPI-free patients (50% vs 52.2%, respectively; p = 0.88). Additionally, LDA-use period of ≤24 months (n = 15) yielded a significantly higher rate of small intestinal mucosal injury incidence than LDA-use period >24 months (n = 30) (80% vs 36.7%, respectively; p = 0.006). Multivariate analysis revealed that a LDA-use period of ≤24 months was a significant risk factor for small intestinal mucosal injury (odds ratio: 19.5, 95% confidence interval: 2.48–154.00, p = 0.005). Following PCI for coronary stenosis, neither DAPT nor PPI affected LDA-induced small intestinal mucosal injury. Moreover, patients who used LDA within the last 24 months were at a greater risk of small intestinal mucosal injury.

Tanshinone IIA Sodium Sulfonate Attenuates LPS-Induced Intestinal Injury in Mice.

Background Tanshinone IIA sodium sulfonate (TSS) is known to possess anti-inflammatory effects and has exhibited protective effects in various inflammatory conditions; however, its role in lipopolysaccharide- (LPS-) induced intestinal injury is still unknown. Objective The present study is designed to explore the role and possible mechanism of TSS in LPS-induced intestinal injury. Methods Male C57BL/6J mice, challenged with intraperitoneal LPS injection, were treated with or without TSS 0.5 h prior to LPS exposure. At 1, 6, and 12 h after LPS injection, mice were sacrificed, and the small intestine was excised. The intestinal tissue injury was analyzed by HE staining. Inflammatory factors (TNF-α, IL-1β, and IL-6) in the intestinal tissue were examined by ELISA and RT-PCR. In addition, expressions of autophagy markers (microtubule-associated light chain 3 (LC3) and Beclin-1) were detected by western blot and RT-PCR. A number of autophagosomes were also observed under electron microscopy. Results TSS treatment significantly attenuated small intestinal epithelium injury induced by LPS. LPS-induced release of inflammatory mediators, including TNF-α, IL-1β, and IL-6, were markedly inhibited by TSS. Furthermore, TSS treatment could effectively upregulate LPS-induced decrease of autophagy levels, as evidenced by the increased expression of LC3 and Beclin-1, and more autophagosomes. Conclusion The protective effect of TSS on LPS-induced small intestinal injury may be attributed to the inhibition of inflammatory factors and promotion of autophagy levels. The present study may provide novel insight into the molecular mechanisms of TSS on the treatment of intestinal injury.

The Protective Effect of New Compound XH-103 on Radiation-Induced GI Syndrome.

Background Radiation-induced intestinal injury is one of the side effects in patients receiving radiotherapy. The aim of the present study was to investigate the protective effect of XH-103 on radiation-induced small intestinal injury and to explore its mechanism. Methods C57BL/6N mice were irradiated and treated with XH-103. Firstly, the survival rate of mice exposed to 9.0 Gy and 11.0 Gy total body irradiation (TBI) was examined. Subsequently, at 3.5 d after IR, the small intestinal morphological changes were examined by HE. The numbers of crypt cells, the villus height, the expression of Ki67 and Lgr5, and the apoptotic cells in the intestinal crypts were examined by immunohistochemistry. Furthermore, the expression of p53 and Bax was analyzed by WB. Results Compared to the irradiation group, XH-103 improved the mice survival rate, protected the intestinal morphology of mice, decreased the apoptotic rate of intestinal crypt cells, maintained cell regeneration, and promoted crypt proliferation and differentiation. XH-103 also reduced the expression of p53 and Bax in the small intestine compared to the IR group. Conclusion These data demonstrate that XH-103 can prevent radiation-induced intestinal injury, which is beneficial for the protection of radiation injuries.

Activation of intestinal GR-FXR and PPARα-UGT signaling exacerbates ibuprofen-induced enteropathy in mice.

Nonsteroidal anti-inflammatory drugs (NSAIDs)-induced small intestinal injury (enteropathy) occurs in about two-thirds of regular NSAID users. To date, there is no proven-effective treatment for NSAID enteropathy, and its underlying mechanism remains obscure. The present study showed that glucocorticoids are an important determinant of NSAID enteropathy. High dose dexamethasone (DEX, 75mg/kg) markedly exacerbated the acute toxicity of ibuprofen (IBU, 200mg/kg) in the small intestine of mice, which was not due to the pregnane-X-receptor pathway. Instead, glucocorticoid receptor (GR) mediated the effect of DEX (5mg/kg) on both the acute (200mg/kg) and 7-day repeated-dose (50mg/kg) toxicity of IBU in the small intestine. Combined treatment of DEX (5mg/kg) and IBU (50mg/kg) synergistically repressed the intestinal farnesoid X receptor (FXR)-cystathionine-γ-lyase signaling, which was accompanied with an elevation in the biliary excretion of bile acids, especially the FXR antagonist tauro-β-muricholic acid. DEX (5mg/kg) also activated intestinal peroxisome proliferator-activated receptor α (PPARα)-UDP-glucuronosyltransferase (UGT) pathway, which increased the formation and enterohepatic circulation of IBU-acyl glucuronide. Furthermore, DEX (5mg/kg) and IBU (50mg/kg) altered the intestinal microbial composition, characterized with a marked decrease in Actinobacteria. To conclude, the present study for the first time suggests that glucocorticoids play vital roles in control of IBU enteropathy via intestinal GR-FXR and PPARα-UGT signaling.

THE OPTIMAL TROCAR PLACEMENT FOR LAPAROSCOPIC EXCISION OF URACHAL REMNANTS

(Objective) Although laparoscopic excision of urachal remnants has been applied widely, the standard surgical method has yet to be established. The aim of this study, therefore, was to evaluate perioperative outcome and surgical techniques, including the trocar placement at our institution. (Subjects and methods) A total of 20 patients with urachal remnant were treated using laparoscopic surgery between October 2002 and August 2016. 3 trocars were inserted in the peritoneal cavity. Camera trocar was placed at right side of umbilicus and two working trocars were placed at the upper side of umbilicus and right lower quandrant. A 5 mm, 30° angled lens camera was used during operation. (Results) The mean age was 27 years old. There were 16 males and 4 females. The classifications of urachal remnants were urachal sinus (n=18) and urachal diverticulum (n=2). Umbilical excision was performed in 18 case and partial cystectomy were required in 4 cases. 4 trocars were inserted in only one case due to severe adhesion in the peritoneal cavity. Laparoscopic excision was successfully completed in all cases. The mean operative time was 220 minutes and the mean blood loss was minimal. The complications occurred in 5 cases including small intestinal injury (n=2), peritonitis (n=1), wound infection (n=1), intestinal obstruction (n=1) and acute renal failure (n=1) (intestinal obstruction and acute renal failure were occurred in the same case). (Conclusion) Although there are problems such as shortening the operative time and reducing complications, our unique port placement enables good surgical view and easy suturing during partial cystectomy.

Agmatine attenuates intestinal ischemia and reperfusion injury by reducing oxidative stress and inflammatory reaction in rats

AimsOxidative stress and inflammatory response are major factors causing several tissue injuries in intestinal ischemia and reperfusion (I/R). Agmatine has been reported to attenuate I/R injury of various organs. The present study aims to analyze the possible protective effects of agmatine on intestinal I/R injury in rats. Main methodsFour groups were designed: sham control, agmatine-treated control, I/R control, and agmatine-treated I/R groups. IR injury of small intestine was induced by the occlusion of the superior mesenteric artery for half an hour to be followed by a 3-hour-long reperfusion. Agmatine (10mg/kg) was administered intraperitoneally before reperfusion period. After 180min of reperfusion period, the contractile responses to both carbachol and potassium chloride (KCl) were subsequently examined in an isolated-organ bath. Malondialdehyde (MDA), reduced glutathione (GSH), and the activity of myeloperoxidase (MPO) were measured in intestinal tissue. Plasma cytokine levels were determined. The expression of the intestinal inducible nitric oxide synthase (iNOS) was also assessed by immunohistochemistry. Key findingsThe treatment with agmatine appeared to be significantly effective in reducing the MDA content and MPO activity besides restoring the content of GSH. The treatment also attenuated the histological injury. The increases in the I/R induced expressions of iNOS, IFN-γ, and IL-1α were brought back to the sham control levels by the treatment as well. SignificanceOur findings indicate that the agmatine pretreatment may ameliorate reperfusion induced injury in small intestine mainly due to reducing inflammatory response and oxidative stress.

Activation of the mitochondrial apoptotic pathway contributes to methotrexate-induced small intestinal injury in rats.

The efficacy of methotrexate (MTX), a commonly used chemotherapeutic drug, is limited by intestinal injury. As the mechanism of MTX-induced small intestinal injury is not clear, there is no definitive treatment for MTX-induced gastrointestinal injury. The present study investigates the role of mitochondrial apoptotic pathway in MTX-induced small intestinal injury and examines whether aminoguanidine is effective in preventing the damage. Eight Wistar rats were administered 3 consecutive i.p. injections of 7mg/kg body wt. MTX. Some rats were pretreated with 30mg or 50mg/kg body wt. of aminoguanidine (n=6 in each group). Protein expressions of cytochrome c, caspases 3 and 9, and PARP-1 were determined in the small intestines by immunohistochemistry and western blot. Mitochondrial pathway of apoptosis was activated in the small intestines of MTX-treated rats as evidenced by intense immunostaining for cyt c, caspases 9 and 3, and PARP-1 and mitochondrial release of cyt c, activation of caspases, and PARP-1 cleavage by Western blot. Immunofluorescence revealed increased nuclear localization of PARP-1. Aminoguanidine pretreatment ameliorated MTX-induced small intestinal injury in dose-dependent manner and inactivated the mitochondrial apoptotic pathway. Aminoguanidine may possess beneficial intestinal protective effects as an adjuvant co-drug against MTX intestinal toxicity during cancer chemotherapy. As the mechanism of MTX-induced small intestinal injury is not clear, there is no definitive treatment for MTX-induced gastrointestinal injury. The results of the present study show that the mitochondrial pathway of apoptosis plays a role in MTX-induced small intestinal injury as evidenced by cytochrome c release, activation of caspases 9 and 3, PARP-1 cleavage, and DNA fragmentation. Aminoguanidine (AG) pretreatment attenuates the severity of small-intestinal injury induced in rats by MTX treatment. The mechanisms of action of AG involve inhibition of iNOS, and mitochondrial pathway of apoptosis. It is suggested that aminoguanidine may possess beneficial intestinal protective effects as an adjuvant co-drug against MTX intestinal toxicity during cancer chemotherapy.

The protective effects of Resveratrol against radiation-induced intestinal injury

BackgroundIntestinal injury is a potential cause of death after high-dose radiation exposure. The aim of the present study was to investigate the protective effects of resveratrol against radiation-induced small intestine injury.MethodsC57BL/6 N mice were irradiated and treated with resveratrol and/or Ex527 (a potent Sirt1 inhibitor), and subsequent examining intestinal morphological changes, and crypt cell apoptosis. Then, the expression and enzyme activity of SOD2 in the small intestine were examined. Furthermore, Sirt1 and acetylated p53 expression was analysed.ResultsCompared to the vehicle control, treatment with resveratrol improved intestinal morphology, decreased apoptosis of crypt cells, maintained cell regeneration, and ameliorated SOD2 expression and activity. Resveratrol also regulated Sirt1 and acetylated p53 expression perturbed by irradiation in the small intestine. The protective effect of resveratrol against ionizing radiation induced small intestine injury was significantly inhibited by Ex527.ConclusionOur results suggest that resveratrol decreases the effects of radiation on intestinal injury at least partly via activation of Sirt1.

Congestive Preconditioning by Portal Venous Clamping: A Novel Preventive Concept for Small Intestinal Congestive Re-Outflow Injury.

BACKGROUND Congestion of the small intestine, which induces mucosal damage via apoptosis, is a common pathophysiological change in hepato-biliary-pancreatic surgery, including liver transplantation. Small intestinal mucosal damage can trigger postoperative complications via various pathways. Therefore, we investigated the efficacy of intermittent portal venous clamping, which we named congestive preconditioning (CPC), for decreasing congestive re-outflow injury (CRoI) of the small intestine. MATERIAL AND METHODS Small intestinal CRoI was induced in rats by clamping the portal vein (PV) for 30 min, followed by re-outflow. The CPC group underwent 3 episodes of 5 min PV clamping and 5 min re-outflow before CRoI. The Control group underwent CRoI after 30 min simple laparotomy without any preconditioning. Survival and histological changes in the small intestine after CRoI were analyzed. The histological changes were compared CPC group to Control group using a scoring system that expressed histopathological severity. Also, small intestinal apoptosis and expression of apoptosis-related genes were analyzed by immunohistochemistry. RESULTS The survival rate of the CPC group was significantly higher than Control group. Histological scoring of small intestinal damage was significantly lower in the CPC group after 6 h of CRoI. Expression of anti-apoptotic gene, Bcl-xL was significantly increased, but pro-apoptotic gene caspase-3 and apoptotic cells did not differ significantly between the CPC group and Control group. CONCLUSIONS Induction of CPC for small intestinal CRoI was effective, which suggests that an anti-apoptotic pathway is involved in the beneficial mechanism.

Polysaccharides derived from Ganoderma lucidum fungus mycelia ameliorate indomethacin-induced small intestinal injury via induction of GM-CSF from macrophages

Non-steroidal anti-inflammatory drugs often cause ulcers in the human small intestine, but few effective agents exist to treat such injury. Ganoderma lucidum Karst, also known as “Reishi” or “Lingzhi”, is a mushroom. We previously reported that a water-soluble extract from G. lucidum fungus mycelia (MAK) has anti-inflammatory effects in murine colitis induced by trinitrobenzene sulfonic acid, and induction of granulocyte macrophage colony-stimulating factor (GM-CSF) by MAK may provide anti-inflammatory effects. However, its effects on indomethacin-induced small intestinal injuries are unknown. The present study investigated the preventative effects of MAK via immunological function and the polysaccharides from MAK on indomethacin-induced ileitis in mice. Peritoneal macrophages (PMs) were stimulated in vitro with MAK and adoptively transferred to C57BL/6 mice intraperitoneally, which were then given indomethacin. Intestinal inflammation was evaluated after 24h. We performed in vivo antibody blockade to investigate the preventive role of GM-CSF, which derived from PMs stimulated with MAK. We then used PMs stimulated with MAK pre-treated by pectinase in an adoptive transfer assay to determine the preventive role of polysaccharides. Indomethacin-induced small intestinal injury was inhibited by adoptive transfer of PMs stimulated in vitro with MAK. In this transfer model, pre-treatment with anti-GM-CSF antibody but not with control antibody reversed the improvement of small intestinal inflammation by indomethacin. Pectinase pretreatment impaired the anti-inflammatory effect of MAK. PMs stimulated by MAK appear to contribute to the anti-inflammatory response through GM-CSF in small intestinal injury induced by indomethacin. The polysaccharides may be the components that elicit the anti-inflammatory effect.

Role of Sulforaphane in Protection of Gastrointestinal Tract Against H. pylori and NSAID-Induced Oxidative Stress.

Background: Sulforaphane (SFN), a phytochemical found in abundance in broccoli sprouts, potently induces a variety of antioxidant enzymes, and thereby protects cells from injury induced by various kinds of oxidative stresses. It has been suggested that both H. pylori infection and intake of non-steroidal anti-inflammatory drugs (NSAIDs) induce chronic oxidative stress in gastrointestinal (GI) mucosa, thereby causing mucosal injury in the GI tract. Therefore, it would be a reasonable assumption that SFN protects GI mucosa against oxidative injury induced by H. pylori or NSAIDs.Methods: We examined the effects of SFN on H. pylori viability in vitro, levels of gastritis in H.pylori-infected mice in vivo, and in H.pylori-infected human subjects. We also examined the effects of SFN on NSAID-induced small intestinal injury in mice.Results: Our data from the H. pylori infection study clearly demonstrated that SFN inhibited H. pylori viability both in vitro and in vivo, and mitigated H. pylori-induced gastritis in mice and humans. Similar-ly, our study on NSAID-induced small intestinal injury showed that SFN not only mitigated aspirin-induced injury of small intestinal epithelial cells in vitro, but also ameliorated indomethacin-induced small intestinal injury in mice in vivo.Conclusions: These data strongly suggest that SFN contributes to the protection of GI mucosa against oxidative injury induced by H. pylori or NSAIDs.

Autodigestion by migrated trypsin is a major factor in small intestinal ischemia-reperfusion injury

BackgroundThe pathophysiological role of pancreatic digestive hydrolases in intestinal ischemia-reperfusion (I/R) injury is still not clear. Here, we studied whether ischemia-induced injury to the small intestine can be explained by the autodigestion hypothesis. Materials and methodsMesenteric I/R was induced in rats by superior mesenteric artery occlusion (90 min) and reopening (120 min). Thirty minutes before superior mesenteric artery occlusion, aprotinin (14.7 mg/kg), orlistat (5 mg/kg), and their combination or α1-proteinase inhibitor (60 mg/kg) were injected into the lumen of the small intestine. Systemic and vital parameters, intestinal microcirculation, and mucosal barrier function were monitored during the observation phase; markers of small intestinal injury, as well as trypsin-, chymotrypsin-, elastase-, and lipase-like activities in intestinal effluates were assessed at the end. ResultsThe pattern of small intestinal injury correlated inversely with the local alterations in microvascular tissue perfusion and corresponded with the intestinal distribution of trypsin-like activity. Aprotinin almost completely inhibited trypsin-like activity (P < 0.05) and significantly reduced intestinal tissue injury. Combined with orlistat, it also increased the postischemic blood pressure (P < 0.05) but not the intestinal barrier function. Macroscopic as well as the histologic alterations were decreased by α1-proteinase inhibitor, which significantly improved postischemic blood pressure (P < 0.05). ConclusionsThe I/R-induced pattern of small intestinal injury is likely to result from both local differences in tissue ischemia and the digestive activity of migrated pancreatic trypsin. Therefore, administration of aprotinin and orlistat into ischemic small intestines may be a therapeutic option in patients with a poor diagnosis.

Trends in development of gi-safe anti-inflammatory drugs

Despite the introduction of anti-inflammatory drugs that selectively inhibit cyclo-oxygenase-2 (COX-2), and potent inhibitors of gastric acid secretion, the gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) remain a significant clinical problem. Combined use of antisecretory drugs and COX-2 inhibitors is helpful to limit the damage in the proximal gastrointestinal tract (stomach and duodenum), but it increases the risk of injury of small intestine and colon. It was proven that proton pump inhibitors and H2 receptor antagonists significantly worsen NSAID-induced small intestinal damage and microbiota balance. Nowadays, there is no proven effective preventative or curative treatment for NSAID-induced enteropathy. The new strategy of gastrointestinal protection is based on the discovery of endogenous cytoprotective molecules such as hydrogen sulfide (H₂S). H2S is a gaseous mediator that produces strong cytoprotective and antioxidant effect on the gastrointestinal tract. The role of H₂S in promoting mucosal integrity, healing of tissue injury and resolution of inflammation has been well documented. In addition, H₂S stimulates productions of other cytoprotective molecules including prostaglandins, carbon monoxide and nitric oxide. Nowadays, the new generation of H₂S-releasing non-steroidal anti-inflammatory drugs is developed and tested in clinical trials. H₂S-NSAIDs possess enhanced anti-inflammatory activity and high gastrointestinal safety.

Short article: Small intestinal mucosal injury in patients taking chemotherapeutic agents for solid cancers.

Chemotherapy for cancer is a systemic treatment often associated with side effects than can be debilitating and, in some cases, life-threatening. Few data are available on intestinal enterotoxicity. Wireless video capsule endoscopy (VCE) is a noninvasive method of imaging the small intestine. This study presents the results of VCE in patients with solid tumors undergoing antineoplastic regimens with agents, notably for toxicity for the gastrointestinal mucosa (i.e. carboplatin, cyclophosphamide, 5-fluorouracil, methotrexate, and cisplatin). The capsule endoscopy procedure was performed 4-13 days after the end of the antineoplastic course. Each patient received a polyethylene-glycol solution (1000 mg×2 in 2 l of water) for bowel preparation and fasted for 10 h before ingestion of the capsule. Videos were evaluated by one operator, supervised by a second operator, and conclusions were drawn by an expert reader. Twenty (age range: 38-77 years) patients were evaluated. The cecum was reached in 70% before exhaustion of the battery. The video capsule showed small widespread intestinal ulcerations in 25% and erosions in only one patient. The villus architecture appeared normal in all. VCE detected metastases in one patient with a melanoma. Few patients had more than one lesion. All capsules were passed in the stool. Our results suggest that chemotherapy in patients with solid cancers is associated with minimal visual small bowel injury. Factors other than damage of the intestinal mucosa causing loss of epithelium are likely involved in gastrointestinal toxicity and related symptoms.

Su1820 - Loss of Mucous Layer is the key Factor of Acetyl Salicylic Acid- Induced Small Intestinal Mucosal Injury in Rats

Su1820 - Loss of Mucous Layer is the key Factor of Acetyl Salicylic Acid- Induced Small Intestinal Mucosal Injury in Rats

Heat stress induces intestinal injury through lysosome- and mitochondria-dependent pathway in vivo and in vitro.

Damage to the small intestine secondary to heat stroke is a major factor in heat stroke-related morbidity and mortality. However, the underlying mechanisms by which heat stroke causes small intestinal lesions and dysfunction remain unclear. To explore the pathogenesis of small intestinal tissue and epithelial cell injury, the SW480 cell heat stress model and the mice heat stroke model were established to mimic heat stroke. Morphologic changes in intestinal tissue and increased TUNEL-positive index were induced by heat stress in vivo. Heat stress activated the lysosomal-mitochondrial apoptotic pathway in SW480 cells, increasing intracellular reactive oxygen species and causing lysosomal membrane permeabilization with subsequent release of cathepsin B to the cytosol, mitochondrial depolarization, and cytochrome C release to cytosol. An increase in the Bax/Bcl2 ratio, caspase-9 and caspase-3 were observed. N-Acetyl-L-Cysteine was shown to inhibit ROS generation, suppress permeabilization of lysosomal membranes, decrease levels of cathepsin B and cytochrome C in the cytosol, and inhibit Bax/Bcl2 ratio, caspase-9 and caspase-3 activity both in vitro and in vivo. Mitochondrial damage was alleviated when the models were pre-treated with CA-074 Me both in vitro and in vivo, decreasing cathepsin B and cytochrome C levels in the cytosol, Bax/Bcl2 ratio, caspase-9 and caspase-3 activity. In our models, heat stress-induced apoptosis of small intestinal tissue and epithelial cells through accumulation of ROS and activation of the lysosomal–mitochondrial apoptotic pathway involved the release of cathepsin B. These findings may offer potentially pharmaceutical targets and strategies to repair intestinal injury caused by heat stroke.

Traumatic colorectal injuries in children: The National Trauma Database experience

PurposeWe sought to utilize a nationwide database to characterize colorectal injuries in pediatric trauma. MethodsThe National Trauma Database (NTDB) was queried for all patients (age≤14years) with colorectal injuries from 2013 to 2014. We stratified patients by demographics and measured outcomes. We analyzed groups based on mechanism, colon vs rectal injury, as well as colostomy creation. Statistical analysis was conducted using t-test and ANOVA for continuous variables as well as chi-square for continuous variables. ResultsThere were 534 pediatric patients who sustained colorectal trauma. The mean ISS was 15.6±0.6 with an average LOS of 8.5±0.5days. 435 (81.5%) were injured by blunt mechanism while 99 (18.5%) were injured by penetrating mechanism. There were no differences between age, ISS, complications, mortality, LOS, ICU LOS, and ventilator days between blunt and penetrating groups. Significantly more patients in the penetrating group had associated small intestine and hepatic injuries as well as underwent colostomies. Patients with rectal injuries (25.7%) were more likely to undergo colonic diversion (p<0.0001), but also had decreased mortality (p=0.001) and decreased LOS (p=0.01). Patients with colostomies (9.9%) had no differences in age, ISS, GCS, transfusion of blood products, and complications compared to patients who did not receive a colostomy. Despite this, colostomy patients had significantly increased hospital LOS (12.1±1.8 vs 8.2±0.5days, p=0.02) and ICU LOS (9.0±1.7 vs 5.4±0.3days, p=0.02). ConclusionAlthough infrequent, colorectal injuries in children are associated with considerable morbidity regardless of mechanism and may be managed without fecal diversion. Level of evidenceIII. Study typeEpidemiology.