Anaerobic bacterial populations on normal and diseased human biopsy tissue obtained at colonoscopy.

Human epithelium was cultured to characterize differences in microbial populations between regions of normal colon and between polyps, inflammatory bowel disease, and cancer and their respective adjacent normal mucosa. Twenty-one patients (12 polyps, 5 inflammatory bowel disease, 4 cancer) underwent colonoscopy with anaerobic culture of mucosal biopsies from normal and diseased ascending, transverse, descending, and sigmoid colon. No differences for total number of organisms and recovery of species between ascending colon and other normal regions were seen except for sigmoid colon. Significant differences between polyps and adjacent normal tissue were seen for total number of organisms and recovery of genera and species. No significant differences in total number of organisms and recovery of genera were seen between cancer and inflammatory bowel disease and their respective adjacent normal tissue. The recovery of genera from polyps and normal tissue was Bacteroides greater than Fusobacterium greater than Clostridium greater than Eubacterium greater than Peptostreptococcus. These data suggest that (i) the total number of anaerobic organisms and species remained relatively constant, except for lower numbers in normal distal colon which were probably a result of the preparation for colonoscopy; (ii) polyp formation favored increased microbial colonization; and (iii) the increased number of organisms generally reflected those genera and species seen on adjacent normal mucosa.     

TKT maintains intestinal ATP production and inhibits apoptosis-induced colitis

Inflammatory bowel disease (IBD) has a close association with transketolase (TKT) that links glycolysis and the pentose phosphate pathway (PPP). However, how TKT functions in the intestinal epithelium remains to be elucidated. To address this question, we specifically delete TKT in intestinal epithelial cells (IECs). IEC TKT-deficient mice are growth retarded and suffer from spontaneous colitis. TKT ablation brings about striking alterations of the intestine, including extensive mucosal erosion, aberrant tight junctions, impaired barrier function, and increased inflammatory cell infiltration. Mechanistically, TKT deficiency significantly accumulates PPP metabolites and decreases glycolytic metabolites, thereby reducing ATP production, which results in excessive apoptosis and defective intestinal barrier. Therefore, our data demonstrate that TKT serves as an essential guardian of intestinal integrity and barrier function as well as a potential therapeutic target for intestinal disorders.Subject terms: Apoptosis, Mechanisms of disease, Inflammatory bowel disease     

Changes in number of serotonin-containing cells and serotonin levels in the intestinal mucosa of rats with colitis induced by dextran sodium sulfate

The role of serotonin in the pathogenesis of inflammatory bowel disease has not been fully studied. We examined the changes in the serotonin level and the density of serotonin-containing enterochromaffin (EC) and mast cells in the intestinal mucosa of dextran sodium sulfate (DSS)-induced colitis in rats. Rats were treated with 1.5% DSS for 1 month. Serotonin levels were biochemically measured and the density of epithelial EC cells and mucosal mast cells was quantified by serotonin immunohistochemistry. DSS caused malnutrition due to chronic diarrhea. Infiltrated inflammatory cells were microscopically observed in the colonic wall with intact epithelium. The serotonin content in the mucosa/submucosa tissue was increased in the proximal and distal colon in DSS-treated rats, compared to that in control rats. The density of EC cells in the epithelium also increased in the proximal and distal colon in DSS-treated rats. In contrast, the density of mast cells in the lamina propria dramatically increased in the distal, but not in the proximal colon in DSS-treated rats. This discrepancy implies the serotonin released from EC cells and from mast cells may play different roles in the pathogenesis of DSS-induced colitis. Accepted: 30 July 1999     

The Complement Anaphylatoxin C3a Receptor (C3aR) Contributes to the Inflammatory Response in Dextran Sulfate Sodium (DSS)-Induced Colitis in Mice

Inflammatory bowel diseases are a critical public health issue, and as treatment options remain limited, there is a need to unravel the underlying pathomechanisms in order to identify new therapeutic targets. Complement activation was found in patients suffering from inflammatory bowel disease, and the complement anaphylatoxin C5a and its receptor C5aR have been implicated in disease pathogenesis in animal models of bowel inflammation. To further characterize complement-related pathomechanisms in inflammatory bowel disease, we have investigated the role of the anaphylatoxin C3a receptor in acute dextran sulfate sodium-induced colitis in mice. For this, colitis was induced in C3a receptor-deficient BALB/c and C57BL/6 mice, and disease severity was evaluated by clinical and histological examination, and by measuring the mRNA expression or protein levels of inflammatory mediators in the tissue. C3a receptor deficiency was partially protective in BALB/c mice, which had significantly reduced weight loss, clinical and histological scores, colon shortening, and CXCL-1/KC mRNA, myeloperoxidase and interleukin-6 tissue levels compared to the corresponding wild type mice. In C57BL/6 mice the differences between wild type and C3a receptor-deficient animals were much smaller and reached no significance. Our data demonstrate that the contribution of C3a receptor to disease pathogenesis and severity of dextran sulfate sodium-induced colitis in mice depends on the genetic background. Further studies will be required to clarify whether targeting of C3a receptor, possibly in combination with C5a receptor, might be considered as a therapeutic strategy for inflammatory bowel disease.     

Immune sensitization to syngeneic organ-specific intestinal antigens in the Lewis rat

In human chronic inflammatory bowel disease involving mucosal epithelium, sera and lamina propria mononuclear cells are reactive with cell surface components isolated from gut epithelial cells. To define a model system in which the disease-inducing potential of such immune factors could be rigorously evaluated, we sought to immunologically sensitize inbred murine strains to syngeneic colonic epithelial cell-associated components (ECAC-C), to define precise in vivo and in vitro conditions to optimize ECAC-C reactivity, and to initially explore whether such cells could elicit tissue injury in epithelium after adoptive transfer to naive animals. Following footpad immunization, Day 42 lymph node cells but not splenocytes were reactive with syngeneic ECAC-C, as shown by a linear increase in [3H]thymidine incorporation over a wide range of antigen concentration (0.5 to 100 micrograms/ml). A subsequent 48-hr exposure to ECAC-C and/or interleukin 2 resulted in a more restricted responsiveness, proliferation occurring only in the presence of ECAC-C or mitogen and not to a coimmunogen (PPD). Further evidence that lymph node cells from ECAC-C/CFA immunized animals were indeed sensitized to syngeneic ECAC-C included ability of donor animals to mount highly significant earlobe DTH responses to ECAC-C, indicating the presence of antigen-specific T-DTH cells, and the failure of polymyxin B, in doses sufficient to inhibit LPS-induced mitogenesis, to reduce lymph node cell responsiveness to ECAC-C, known to be contaminated with LPS. ECAC-C-specific circulating antibody and T-cytotoxic cells were not detected. Adoptive transfer of Day 42 lymph node cells, sensitized in vivo and conditioned in vitro, was not associated with tissue injury in syngeneic recipients in preliminary experiments. This model system, with antigen-specific cells analogous to those present in diseased mucosa of human chronic inflammatory bowel disease, may be an important means to determine the pathophysiologic significance of anti-epithelial cell immune responses in these disorders.     

Early loss of E-cadherin from cell-cell contacts is involved in the onset of Anoikis in enterocytes

Anoikis, i.e. apoptosis induced by detachment from the extracellular matrix, is thought to be involved in the shedding of enterocytes at the tip of intestinal villi. Mechanisms controlling enterocyte survival are poorly understood. We investigated the role of E-cadherin, a key protein of cell-cell adhesion, in the control of anoikis of normal intestinal epithelial cells, by detaching murine villus epithelial cells from the underlying basement membrane while preserving cell-cell interactions. We show that upon the loss of anchorage, normal enterocytes execute a program of apoptosis within minutes, via a Bcl-2-regulated and caspase-9-dependent pathway. E-cadherin is lost early from cell-cell contacts. This process precedes the execution phase of detachment-induced apoptosis as it is only weakly modulated by Bcl-2 overexpression or caspase inhibition. E-cadherin loss, however, is efficiently prevented by lysosome and proteasome inhibitors. We also found that a blocking anti-E-cadherin antibody increases the rate of anoikis, whereas the activation of E-cadherin using E-cadherin-Fc chimera proteins reduces anoikis. In conclusion, our results stress the striking sensitivity of normal enterocytes to the loss of anchorage and the contribution of E-cadherin to the control of their survival/apoptosis balance. They open new perspectives on the key role of this protein, which is dysregulated in the intestinal epithelium in both inflammatory bowel disease and cancer.     

PG-mediated closure of paracellular pathway and not restitution is the primary determinant of barrier recovery in acutely injured porcine ileum

Small bowel epithelium is at the frontline of intestinal barrier function. Restitution is considered to be the major determinant of epithelial repair, because function recovers in parallel with restitution after acute injury. As such, studies of intact mucosa have largely been replaced by migration assays of cultured epithelia. These latter studies fail to account for the simultaneous roles played by villous contraction and paracellular permeability in recovery of barrier function. NSAIDs result in increased intestinal permeability and disease exacerbation in patients with inflammatory bowel disease (IBD). Thus we examined the reparative attributes of endogenous PGs after injury of ileal mucosa by deoxycholate (6 mM) in Ussing chambers. Recovery of transepithelial electrical resistance (TER) from 20-40 Omega.cm2 was abolished by indomethacin (Indo), whereas restitution of 40-100% of the villous surface was unaffected despite concurrent arrest of villous contraction. In the presence of PG, resident crypt and migrating epithelial cells were tightly apposed. In tissues treated with Indo, crypt epithelial cells had dilated intercellular spaces that were accentuated in the migrating epithelium. TER was fully rescued from the effects of Indo by osmotic-driven collapse of the paracellular space, and PG-mediated recovery was significantly impaired by blockade of Cl- secretion. These studies are the first to clearly distinguish the relative contribution of paracellular resistance vs. restitution to acute recovery of epithelial barrier function. Restitution was ineffective in the absence of PG-mediated paracellular space closure. Failure of PG-mediated repair mechanisms may underlie barrier failure resulting from NSAID use in patients with underlying enteropathy.     

Cell surface-expressed Thomsen-Friedenreich antigen in colon cancer is predominantly carried on high molecular weight splice variants of CD44.

Increased mucosal expression of TF, the Thomsen-Friedenreich oncofetal blood group antigen (galactose beta1-3 N-acetylgalactosamine alpha-) occurs in colon cancer and colitis. This allows binding of TF-specific lectins, such as peanut agglutinin (PNA), which is mitogenic to the colorectal epithelium. To identify the cell surface TF-expressing glycoprotein(s), HT29 and Caco2 colon cancer cells were surface-labeled with Na[(125)I] and subjected to PNA-agarose affinity purification and electrophoresis. Proteins, approximately 110-180 kDa, present in HT29 but not Caco2 were identified by Western blotting as high molecular weight splice variants of CD44 (CD44v). Selective removal of TF antigen by Streptococcus pneumoniae endo-alpha-N-acetylgalactosaminidase substantially reduced PNA binding to CD44v. Immunoprecipitated CD44v from HT29 cell extracts also expressed sialyl-Tn (sialyl 2-6 N-acetylgalactosaminealpha-). Incubation of PNA 15 microg/ml with HT29 cells caused no additional proliferative effect in the presence of anti-CD44v6 mAb. In colon cancer tissue extracts (N = 3) PNA bound to CD44v but not to standard CD44. These data show that CD44v is a major PNA-binding glycoprotein in colon cancer cells. Because CD44 high molecular weight splice variants are present in colon cancer and inflammatory bowel disease tissue but are absent from normal mucosa, these results may also explain the increased PNA reactivity in colon cancer and inflammatory bowel disease. The coexpression of oncofetal carbohydrate antigens TF and sialyl-Tn on CD44 splice variants provides a link between cancer-associated changes in glycosylation and CD44 splicing, both of which correlate with increased metastatic potential.     

A primary dysregulation in the immunoregulatory role of the intestinal mucosal epithelial cell in inflammatory bowel disease pathogenesis? Biology of inflammatory response as tissue pattern entities in Crohn's versus ulcerative colitis

Within a framework of dual involvement of mucosa and submucosa on the one hand, and of the muscularis propria of the bowel wall on the other, it might be valid to consider involvement of the vascular supply as the essential means in itself of not only causing the morphologic lesions in inflammatory bowel disease, but also especially in accounting for persisting patterns of inflammatory response both in ulcerative colitis and in Crohn's disease. Inflammatory bowel disease as a group constitutes a spectrum of biologic and pathobiologic manifestations in terms not only of inflammatory involvement of the bowel wall but also in terms of how the bowel in its turn deals with inflammation as a pathologic lesion in its own right. Parameters of inflammatory bowel activity transcend simple concepts of etiology and pathogenesis as applicable to category disorders such as infections or bowel ischemia. Indeed, the strictly characterized initiation of the inflammatory bowel response as a function of defective regulation of the antigenicity of the luminal contents on the one hand, and on interactions between nitric oxide and free oxygen radicals on the other, might help determine a persistence of tissue damage in inflammatory bowel disease that is either relapsing/remitting or chronic in progression. In a final analysis, perhaps, there might be involved a single central form of pathway induction of dysregulated immune reactivity arising from an early disturbance in activation patterns as induced by the onset of luminal antigenicity at an early or specific-stage, further characterized perhaps by specific forms of intestinal epithelial defects of the bowel mucosa in patients subsequently developing inflammatory bowel disease. Specific genetic markers for disease susceptibility and for therapeutic responsiveness are particularly of interest. The Nucleotide binding oligomerization Domain 2 (NOD2) would recognize microbial lipopolysaccharide or else mark systemic responses to pathogens that are pathogenic to evolving inflammatory bowel disease.     

Mathematical Model of the Roles of T Cells in Inflammatory Bowel Disease

Gut mucosal homeostasis depends on complex interactions among the microbiota, the intestinal epithelium, and the gut associated immune system. A breakdown in some of these interactions may precipitate inflammation. Inflammatory bowel diseases, Crohn’s disease, and ulcerative colitis are chronic inflammatory disorders of the gastrointestinal tract. The initial stages of disease are marked by an abnormally high level of pro-inflammatory helper T cells, Th1. In later stages, Th2 helper cells may dominate while the Th1 response may dampen. The interaction among the T cells includes the regulatory T cells (Treg). The present paper develops a mathematical model by a system of differential equations with terms nonlocal in the space spanned by the concentrations of cytokines that represents the interaction among T cells through a cytokine signaling network. The model demonstrates how the abnormal levels of T cells observed in inflammatory bowel diseases can arise from abnormal regulation of Th1 and Th2 cells by Treg cells.     

Increased migration of IgA lymphocytes to VIP nerve fibers after DSS-induced colitis

Immunoglobulin-positive lymphocytes are present close to vasoactive intestinal polypeptide-positive (VIP(+)) nerve fibers in the lamina propria of the intestinal tract, and have an important role in mucosal defense. The number of immunoglobulin A-positive (IgA(+)) cells close to the epithelial basement membrane and nerve fibers is increased by the administration of lipopolysaccharides, which induce IgA secretion into the intestinal lumen. The relationship between immunoglobulin-positive lymphocytes and the VIP(+) nerve fibers during inflammation, such as in inflammatory bowel disease, however, is not well known. The morphological relationship between immunoglobulin-positive cells and the basement membrane or the VIP(+) nerve fibers in the colon was examined using double immunofluorescent labeling in an inflammatory bowel disease mouse model created by oral administration of dextran sodium sulfate (DSS). DSS administration induced goblet cell loss, crypt loss, intestinal epithelium deformation and infiltration of inflammatory cells in the mucosa. In the colon, the number and percentage of IgA(+) lymphocytes close to the basement membrane and the VIP(+) nerve fibers in the lamina propria increased after DSS administration, in parallel with the pathologic progress in the inflamed tissue. On the other hand, the percentage of immunoglobulin G-positive (IgG(+)) lymphocytes close to the basement membrane and the VIP(+) nerve fibers decreased, although the total number of IgG(+) lymphocytes in the lamina propria increased. We suggest that the immunoglobulin-producing lymphocytes and enteric nerve fibers in the colon normally have a close morphological relationship, and that this relationship is reinforced in a cell-specific manner during inflammation.     

Deficiency of Nuclear Receptor Nur77 Aggravates Mouse Experimental Colitis by Increased NFκB Activity in Macrophages

Nuclear receptor Nur77, also referred to as NR4A1 or TR3, plays an important role in innate and adaptive immunity. Nur77 is crucial in regulating the T helper 1/regulatory T-cell balance, is expressed in macrophages and drives M2 macrophage polarization. In this study we aimed to define the function of Nur77 in inflammatory bowel disease. In wild-type and Nur77^-/- mice, colitis development was studied in dextran sodium sulphate (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced models. To understand the underlying mechanism, Nur77 was overexpressed in macrophages and gut epithelial cells. Nur77 protein is expressed in colon tissues from Crohn’s disease and Ulcerative colitis patients and colons from colitic mice in inflammatory cells and epithelium. In both mouse colitis models inflammation was increased in Nur77^-/- mice. A higher neutrophil influx and enhanced IL-6, MCP-1 and KC production was observed in Nur77-deficient colons after DSS-treatment. TNBS-induced influx of T-cells and inflammatory monocytes into the colon was higher in Nur77^-/- mice, along with increased expression of MCP-1, TNFα and IL-6, and decreased Foxp3 RNA expression, compared to wild-type mice. Overexpression of Nur77 in lipopolysaccharide activated RAW macrophages resulted in up-regulated IL-10 and downregulated TNFα, MIF-1 and MCP-1 mRNA expression through NFκB repression. Nur77 also strongly decreased expression of MCP-1, CXCL1, IL-8, MIP-1α and TNFα in gut epithelial Caco-2 cells. Nur77 overexpression suppresses the inflammatory status of both macrophages and gut epithelial cells and together with the in vivo mouse data this supports that Nur77 has a protective function in experimental colitis. These findings may have implications for development of novel targeted treatment strategies regarding inflammatory bowel disease and other inflammatory diseases.     

Adhesive Escherichia coli in inflammatory bowel disease and infective diarrhoea.

The clinical features of ulcerative colitis and Crohn''s disease are similar to those of infections of the bowel, although their cause is uncertain. Many bacteria that cause intestinal diseases adhere to the gut mucosa, and adhesion of pathogenic Escherichia coli is resistant to D-mannose. The adhesive properties of isolates of E coli were assessed by assay of adhesion to buccal epithelial cells with mannose added. The isolates were obtained from patients with inflammatory bowel diseases (50 with a relapse of ulcerative colitis, nine with ulcerative colitis in remission, 13 with Crohn''s disease, and 11 with infectious diarrhoea not due to E coli) and 22 controls. The median index of adhesion to buccal epithelial cells (the proportion of cells with more than 50 adherent bacteria) for E coli from patients with ulcerative colitis in relapse was significantly higher (43%) than that for controls (5%) and patients with infectious diarrhoea (14%). The index was not significantly different among isolates from patients with ulcerative colitis in relapse, Crohn''s disease (53%), and ulcerative colitis in remission (30%). If an index of adhesion of greater than 25% is taken as indicating an adhesive strain 86% of isolates of E coli from patients with inflammatory bowel disease were adhesive compared with 27% from patients with infective diarrhoea and none from controls. The adhesive properties of the isolates from patients with inflammatory bowel disease were similar to those of pathogenic intestinal E coli, raising the possibility that they may have a role in the pathogenesis of the condition; the smaller proportion of adhesive isolates in patients with infective diarrhoea due to other bacteria suggests that the organism may be of primary importance rather than arising secondarily.     

Ca2+ signaling in identified T-lymphocytes from human intestinal mucosa. Relation to hyporeactivity, proliferation, and inflammatory bowel disease

Ca2+ entry across the plasma membrane is necessary for the activation and proliferation of T-lymphocytes. Human intestinal lamina propria lymphocytes physiologically exhibit minimal proliferation in response to antigen receptor stimulation when compared with peripheral blood T-lymphocytes. This hyporeactivity is partially abolished in inflammatory bowel disease. We hypothesized that differences in Ca2+ signaling could be related to the disease. To test this possibility, we measured Ca2+ signals in identified lymphocytes from human blood and human intestinal mucosa. Ca2+ signals in lamina propria T-lymphocytes from non-inflamed tissue were drastically reduced when compared with Ca2+ signals of blood T-lymphocytes from the same persons. However, Ca2+ signals in T-lymphocytes from inflamed intestinal mucosa were much higher than the ones from non-inflamed mucosa and almost reached levels of Ca2+ signals in peripheral blood T-cells. Furthermore, Ca2+ influx was closely linked to cell proliferation in both peripheral blood T-lymphocytes and lamina propria lymphocytes cells. We conclude that differences in Ca2+ signaling can explain the differences of T-lymphocyte reactivity in blood versus lamina propria and, importantly, also between T-lymphocytes from inflamed and non-inflamed intestinal mucosa. Ca2+ channels in the plasma membrane of T-lymphocytes might thus prove an excellent target to screen for immunosuppressiva to potentially treat the symptoms of inflammatory bowel disease.     

Hypoxia and inflammatory bowel disease

Inflammatory bowel disease (IBD) is a general term to describe inflammatory diseases of the gastrointestinal tract such as Crohn's disease and ulcerative colitis. IBD affects approximately 1 in 200 individuals and exerts a significant health and quality of life burden on patients. Surgical intervention can be curative in ulcerative colitis but there is currently no cure for Crohn's disease. Since this is the case, and the fact that patients are often diagnosed at a young age, IBD exerts a significant financial burden on the health care system, and society as a whole.The underlying pathology of IBD is complex and involves a combination of genetic, environmental and microbial factors. Regardless of the underlying causes of the condition, this disease is universally characterized by disruption to the protective epithelial barrier separating the intestinal lumen above from the mucosal immune system below. Once this barrier becomes compromised a sequence of events ensues, that can occur in repetitive cycles to ensure long-term and serious damage to the gut.The role of hypoxia and hypoxia-dependent signalling pathways are increasingly appreciated to play a role in the physiology and pathophysiology of the intestine. The intestinal epithelium normally exists in a state of physiological hypoxia, with additional tissue hypoxia a feature of active inflammatory disease. Furthermore, recent pre-clinical animal studies have clearly supported the rationale for pharmacologically manipulating the oxygen-sensitive hypoxia-inducible factor (HIF) pathway in models of IBD. Thus, this review will discuss the contribution of hypoxia sensitive pathways in the pathology of IBD. Finally we will discuss the emerging evidence for manipulation of hypoxia-sensitive pathways in the treatment of IBD.     

The congenital chloride diarrhea gene is expressed in seminal vesicle, sweat gland, inflammatory colon epithelium, and in some dysplastic colon cells

Congenital chloride diarrhea (CLD) is an autosomal recessive disorder of intestinal electrolyte transportation caused by mutations in the anion transporter protein encoded by the down-regulated in adenoma (DRA), or CLD, gene. In this study, in situ hybridization and immunohistochemistry were performed to investigate the expression of CLD in extraintestinal normal epithelia and in intestinal inflammatory and neoplastic epithelia. The expression of the closely related anion transporter diastrophic dysplasia sulfate transporter, DTDST, was also examined and compared with that of CLD in colon. The only extraintestinal tissues showing CLD expression were eccrine sweat glands and seminal vesicles. In inflammatory bowel disease and ischemic colitis, expression of CLD mRNA in colon epithelium was similar to histologically normal colon epithelium, but the protein was found deeper in crypts, including proliferative epithelial cells. In intestinal tumors, the expression pattern of CLD was dependent on the differentiation status of the tissue studied: epithelial polyps with no or minor dysplasia showed abundant expression, whereas adenocarcinomas were negative. The DTDST gene was abundantly expressed in the upper crypt epithelium of colonic mucosa.     

炎症性肠病患者肠道菌群分布及其与炎症指标和免疫球蛋白水平的关系

目的 研究炎症性肠病(inflammatory bowel disease,IBD)患者肠道菌群分布特点及其与血清髓过氧化物酶(MPO)、C反应蛋白(CRP)、免疫球蛋白表达的关系。 方法 选择2015年5月至2018年5月在延安市中医医院诊断治疗的65例炎症性肠病患者为观察组,另选取于本院体检的65例无消化系统疾病者作为对照组,分析两组患者肠道菌群分布特点以及血清MPO、CRP和免疫球蛋白表达情况,同时分析其相关性。 结果 观察组患者肠道乳杆菌(t=6.128,P结论 在炎症性肠病的发展中,肠道菌群与血清MPO、CRP水平及免疫球蛋白水平均具有相关性,可作为IBD患者诊断和治疗的依据。     

CT仿真结肠镜与腹部增强CT 在炎症性肠病诊断中的对比分析

目的:对比CT仿真结肠镜(CTC)与腹部增强CT在炎症性肠病诊断中的价值,为临床诊疗提供依据。方法:选取2015年1月到2016年1月我院收治的炎症性肠病患者60例为研究组,另选取非炎症性肠病患者60例为对照组,两组均30例患者接受CTC检查,30例患者接受腹部增强CT检查,对影像图片进行盲法阅读,将炎症性肠病的可信度分为5个等级进行评价,对6项影像学特征进行Logistic回归分析。结果:腹部增强CT对炎症性肠病诊断的准确率、敏感性、特异性分别为68.33%,59.09%,71.39%显著低于CTC的93.33%,95.01%、89.63%,比较差异具有统计学意义(P0.05);Logistic回归分析显示:结肠粘膜呈颗粒状、不光滑;肠壁强化并增厚;结肠袋消失对炎症性肠病具有预测作用;肠壁强化及增厚对炎症性肠病诊断敏感性较高,结肠粘膜呈颗粒状、不光滑联合结肠袋消失诊断炎症性肠病的特异性较高。结论:CTC对炎症性肠病具有较高的检出率,肠壁强化及增厚对炎症性肠病诊断的敏感性较高,结肠粘膜呈颗粒状、不光滑联合结肠袋消失诊断炎症性肠病特异性较高。     

An endogenously anti-inflammatory role for methylation in mucosal inflammation identified through metabolite profiling

Tissues of the mucosa are lined by an epithelium that provides barrier and transport functions. It is now appreciated that inflammatory responses in inflammatory bowel diseases are accompanied by striking shifts in tissue metabolism. In this paper, we examined global metabolic consequences of mucosal inflammation using both in vitro and in vivo models of disease. Initial analysis of the metabolic signature elicited by inflammation in epithelial models and in colonic tissue isolated from murine colitis demonstrated that levels of specific metabolites associated with cellular methylation reactions are significantly altered by model inflammatory systems. Furthermore, expression of enzymes central to all cellular methylation, S-adenosylmethionine synthetase and S-adenosylhomocysteine hydrolase, are increased in response to inflammation. Subsequent studies showed that DNA methylation is substantially increased during inflammation and that epithelial NF-κB activity is significantly inhibited following treatment with a reversible S-adenosylhomocysteine hydrolase inhibitor, DZ2002. Finally, these studies demonstrated that inhibition of cellular methylation in a murine model of colitis results in disease exacerbation while folate supplementation to promote methylation partially ameliorates the severity of murine colitis. Taken together, these results identify a global change in methylation, which during inflammation, translates to an overall protective role in mucosal epithelia.     

The unfolded protein response and its role in intestinal homeostasis and inflammation

The unfolded protein response (UPR) is a signaling pathway from the endoplasmic reticulum (ER) to the nucleus that protects cells from the stress caused by misfolded or unfolded proteins [1, 2]. As such, ER stress is an ongoing challenge for all cells given the central biologic importance of secretion as part of normal physiologic functions. This is especially the case for cells that are highly dependent upon secretory function as part of their major duties. Within mucosal tissues, the intestinal epithelium is especially dependent upon an intact UPR for its normal activities [3]. This review will discuss the UPR and the special role that it provides in the functioning of the intestinal epithelium and, when dysfunctional, its implications for understanding mucosal homeostasis and intestinal inflammation, as occurs in inflammatory bowel disease (IBD).