Total colonic ischemia

The involvement of the entire colon in an ischemic process is unusual because of the dual source of blood supply to the large bowel. Three cases of total ischemic colitis are presented. A precipitating cause to account for the distribution of ischemia was identified in each patient.     

Effects of iron manipulation on trace elements level in a model of colitis in rats

AIM: Trace elements (TE) metabolism is altered in inflammatory bowel diseases. TE (zinc and copper) are constituents of antioxidant enzymes. Iron is involved in the pathogenesis of chronic inflammation. The aim was to evaluate zinc and copper status and the effects of iron manipulation in experimental colitis. METHODS: Twenty-four male Sprague-Dawley rats were divided into four groups: standard diet, iron-deprived diet, iron-supplemented diet, and sham-treated controls. Macroscopic damage was scored. DNA adducts were measured in the colon. Liver and colonic concentration of TE were measured. RESULTS: Macroscopic damage was reduced in iron-deprived groups and increased in iron-supplemented rats. Damage to the DNA was reduced in iron-deprived groups and increased in iron-supplemented groups. Liver and colonic iron concentrations were reduced in iron-deprived and increased in iron-supplemented rats. Liver zinc concentration was reduced after supplementation whereas colonic levels were similar in controls and treated rats. Liver copper concentration was reduced in all the colitic groups except in the iron-supplemented group whereas colonic concentration was increased in iron-deprived rats. CONCLUSION: Iron deprivation diminishes the severity of DNBS colitis while supplementation worsens colitis. Zinc and copper status are modified by iron manipulation.     

趋化因子CCL20及其受体CCR6在实验性结肠炎小鼠中的表达及其意义

背景：溃疡性结肠炎（UC）的病因和发病机制尚不完全明确，趋化因子异常可能在其发生、发展中起重要作用。目的：研究趋化因子CCL20及其受体CCR6在葡聚糖硫酸钠（DSS）诱导的实验性结肠炎小鼠结肠黏膜中的表达以及CCL20与CCR6的相关性，探讨两者在结肠炎发病机制中的作用。方法：30只雌性BALB／c小鼠分为对照组和模型组。模型组小鼠自由饮用5％DSS溶液7d，建立实验性结肠炎模型；对照组小鼠自由饮用蒸馏水7d。第8d处死小鼠，观察疾病活动指数（DAI）、结肠组织学评分。以逆转录聚合酶链反应（RT．PCR）检测小鼠结肠黏膜CCL20、CCR6mRNA表达，以免疫组化和蛋白质印迹法检测结肠黏膜CCL20、CCR6蛋白表达，并分析CCL20与CCR6的相关性。结果：模型组DAI和结肠组织学评分均显著高于对照组（P〈0．01）；CCL20、CCR6mRNA和蛋白表达显著高于对照组（P〈0．01），且与结肠炎症程度呈正相关。CCL20mRNA表达与CCR6mRNA表达有明显相关性（r＝0．763．P=0．000071）。结论：CCL20和CCR6表达参与了结肠炎的发生和发展，两者相互作用可能在结肠炎局部结肠组织破坏和病理变化中起重要作用，有望成为UC的潜在治疗靶点。     

Bursting pressure in anastomotic healing in experimentally induced colitis in rats

BACKGROUND: Experimental studies on healing of colonic anastomosis have been thoroughly investigated. However, clinical parameters of the healing process of anastomosis in the inflamed colon has not yet been reported. METHODS: In the present study, healing of anastomosis in trinitrobenzene-sulfonic acid-induced colitis in rats was assessed by measuring the bursting pressure and bursting wall tension. RESULTS: On postoperative day 4, bursting pressure and bursting wall tension were significantly lower (P<0.001) in rats with colitis with or without anastomosis and normal colon with anastomosis, compared with normal colon without anastomosis. On postoperative day 7, bursting pressure and bursting wall tension of normal colon with anastomosis approached that of normal colon without anastomosis. However, bursting pressure and bursting wall tension of rats with colitis with or without anastomosis remained significantly lower (P<0.001) than the latter. Furthermore, unlike rats without colitis in which perforation occurred mostly at the anastomotic line, the bursting site in colitic rats was predominantly away from the anastomotic line. CONCLUSIONS: These results suggest that in surgery for inflammatory bowel disease, it is the adjoining inflamed bowel wall that is vulnerable to be perforated in response to increasing intraluminal pressure rather than the anastomosis that is braced by the sutures.     

Astilbin promotes the induction of regulatory NK1.1− CD4+ NKG2D+ T cells through the PI3K,STAT3, and MAPK signaling pathways

Astilbin is a potential agent for autoimmune and inflammatory diseases and has a protective effect in mice with DSS-induced colitis. NK1.1⁻ CD4⁺ NKG2D⁺ T cells are a subpopulation of regulatory T cells that produce TGF-β1 and IL-10. Whether astilbin directly promotes the induction of NK1.1⁻ CD4⁺ NKG2D⁺ T cells and whether these astilbin-stimulated T cells exert an immune-regulatory role remain unclear. Here, we show that astilbin efficiently induces the production of NK1.1⁻ CD4⁺ NKG2D⁺ T cells with high expressions of TGF-β1, IL-10, CCR6, and CCR9 in a dose-dependent manner ex vivo. These regulatory T cells also substantially inhibit the activities of CD8⁺ T cells and macrophages. Intraperitoneal injection of astilbin ameliorates the severity of colitis with an increase in the frequency of NK1.1⁻ CD4⁺ NKG2D⁺ T cells in the colon tissue of DSS-treated mice. Moreover, adoptive transfer of NK1.1⁻ CD4⁺ NKG2D⁺ T cells induced by astilbin remarkably protects against the onset of DSS-induced colitis. Finally, the PI3K, STAT3, and MAPK signaling pathways are involved in the induction of NK1.1⁻ CD4⁺ NKG2D⁺ T cells by astilbin. Taken together, our study elucidates a new immune-regulatory mechanism of astilbin by inducing the regulatory NK1.1⁻ CD4⁺ NKG2D⁺ T cells and indicates a potential clinical use of astilbin for patients with inflammatory bowel diseases.     

二甲双胍与美沙拉嗪在小鼠结肠炎中的疗效比较

目的 探讨二甲双胍与美沙拉嗪在治疗小鼠结肠炎中的疗效差异性。方法 选取6 ~ 8周龄的C57BL/6雄性小鼠32只,随机分为Control组、硫酸葡聚糖（DSS）组、DSS+美沙拉嗪组、DSS+二甲双胍组,每组8只。Control组小鼠自由饮用高压灭菌双蒸水,并每日予0.2 ml 磷酸盐缓冲液（PBS）灌胃。采用3%DSS诱导C57BL/6雄性小鼠结肠炎模型。DSS组小鼠自由饮用3%DSS溶液,每日予0.2 ml PBS灌胃,DSS+美沙拉嗪组、DSS+二甲双胍组自由饮用3%DSS溶液,予100 mg/（kg·d） 的美沙拉嗪或100 mg/（kg·d） 二甲双胍灌胃。评估各组小鼠体质量变化、结肠长度、疾病活动指数、组织病理学改变及肠道炎症因子表达情况。结果 与DSS组相比,DSS+二甲双胍与DSS+美沙拉嗪组均可降低小鼠结肠炎所致的体质量丢失、疾病活动度评分、组织病理学评分及肠道炎症因子表达水平（P均< 0.05）,但DSS+二甲双胍组与DSS+美沙拉嗪组上述指标比较差异均无统计学意义（P均> 0.05）。结论 二甲双胍可以减轻DSS诱导的小鼠结肠炎,其疗效不亚于美沙拉嗪。     

Proton pump inhibitor use and risk for recurrent Clostridioides difficile infection: a systematic review and meta-analysis

ObjectivesProton pump inhibitor (PPI) therapy is a potentially modifiable risk factor for recurrent Clostridioides difficile infection (CDI). Citing an absence of clinical trials, many guidelines do not provide recommendations for addressing PPI management. Our aim was to perform an updated systematic review and meta-analysis evaluating the association between PPI use and recurrent CDI addressing prior methodological limitations.MethodsData sources were MEDLINE and EMBASE. Eligible studies were cohort and case–control studies; there were no restrictions on study setting or duration of follow-up. Participants were adults with prior CDI who did or did not receive PPI therapy and were assessed for recurrent CDI. Summary (unadjusted) odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model. Prespecified subgroup analyses were performed to explore heterogeneity including study design, study quality, duration of follow-up, adjustment for confounders, and outcome definition.ResultsSixteen studies were included in the meta-analysis, comprising 57 477 patients with CDI, of whom 6870 (12%) received PPIs. The rate of recurrent CDI was 24% in patients treated with PPIs versus 18% in those who were not. A meta-analysis that pooled unadjusted odds ratios demonstrated higher odds of recurrent CDI in patients who received PPIs (OR 1.69, 95%CI 1.46–1.96) versus those who did not. There was moderate heterogeneity between studies (I² 56%); however, a sensitivity analysis restricted to studies with 56 days of follow-up substantially reduced the heterogeneity (OR 1.59, 95%CI 1.36–1.85; I² 12%). An analysis restricted to multivariate studies that combined adjusted ORs also demonstrated higher odds of recurrent CDI in patients who received PPIs (OR 1.49, 95%CI 1.12–2.00). No publication bias was identified.ConclusionsWe found significantly higher odds of recurrent CDI among users of PPIs that persisted across multiple sensitivity analyses. These results support stronger recommendations for PPI stewardship at CDI diagnosis.