CHRONIC ULCERATIVE COLITIS—PSYCHOSOMATIC FACTORS

In six cases of idiopathic ulcerative colitis here reported, close correlation with emotional stress was shown. Psychosomatic relationship seemed definite. Experience with 85 patients with ulcerative colitis has led to the suggestion that emotional stress may be causative or a predisposing factor in some, perhaps all, such cases.     

Microdiverticula and submucosal epithelial elements in ulcerative and granulomatous diseases of the ileum and colon

A case of granulomatous ileocolitis which also showed features of ulcerative colitis, and in which lesions were believed to be due to inflammation of previously undescribed structures, microdiverticula, was reported previously. Subsequently, sections of the segments of bowel received from 17 cases of regional enteritis and 16 cases of ulcerative colitis were re-examined for the presence of similar microdiverticula and submucosal epithelial elements. The same structures were present in five cases of regional enteritis and in 14 of ulcerative colitis. A granulomatous type of inflammatory response was found in the bowel and lymph nodes in 14 of the 17 cases of regional enteritis, and in none of the cases labelled ulcerative colitis. In spite of this, difficulty was experienced in placing some cases in one or other diagnostic category. This re-emphasizes the possibility that the two conditions may not be etiologically discrete, and that both may be, in fact, related to the presence of microdiverticula. In addition, it may be that colitis cystica profunda is a result of microdiverticulosis in which the submucosal glandular structures attain unusually large proportions.     

Social prognosis in patients with ulcerative colitis.

One hundred and twenty-two randomly selected patients with ulcerative colitis (28 of whom had undergone colectomy) were interviewed to obtain data on the quality of their family, emotional, social, and professional lives. They were compared with an age- and sex-matched group of patients with acute conditions from the same area. The two groups were similar in marital status, the frequency of severe family or sexual problems, leisure activities, physical and earning capacity, the incidence of mental disorders before the interview, and intake of alcohol and psychopharmacological drugs. A higher proportion of the patients with colitis had had a higher education and belonged to higher socioeconomic groups than the controls, and this difference had been present at the time of diagnosis. These results show that patients with ulcerative colitis seem to adapt themselves well to their condition and suffer few social or professional disabilities.     

不同发病时期溃疡性结肠炎患者肠道菌群差异及对血清TLRs/NFκB和SOCS3 及Cingulin蛋白水平的影响

目的 分析溃疡性结肠炎(UC)患者不同发病时期肠道菌群的差异,同时研究菌群变化及对患者血清TLRs/NFκB、SOCS3、Cingulin蛋白水平的影响。 方法 选取2015年5月至2017年2月在我院确诊的UC患者为研究对象。将活动性溃疡性结肠炎(AUC)患者和缓解性溃疡性结肠炎(RUC)患者按病情不同分为AUC组(48例)和RUC组(42例)。选取同期在我院发现的结肠息肉患者作为对照组(50例)。对3组患者的肠道菌群分布、Cingulin蛋白表达量、肠黏膜中TLRs/NFκB的表达量和外周血中SOCS3及TNFα水平进行对比。 结果 UC患者(AUC组及RUC组)肠道大肠埃希菌数量高于对照组,双歧杆菌数量低于对照组;同时RUC组患者肠道乳杆菌数量低于对照组,差异均有统计学意义(均P结论 TNFα、SOCS3可能参与UC的病程,其在UC患者中存在高表达现象,可导致人体肠道菌群出现紊乱,最终引发人体多部位的炎症应激反应。     

South Asians with ulcerative colitis exhibit altered lectin binding compared with matched European cases

Ulcerative colitis is associated with abnormalities of mucin synthesis and secretion, features that may also be associated with malignant change. It has been shown that South Asians in Britain have a high incidence of ulcerative colitis but a low incidence of colorectal carcinoma compared with their European counterparts. Previous studies have demonstrated changes in colonic mucin sialylation and sulphation in both South Asian and European cases with ulcerative colitis. This was related to disease severity, but changes were also found in quiescent disease. The aim of the present study was to determine glycoconjugate expression in the colon from South Asian cases and to compare results with those from a group of affected Europeans. Glycans were identified in formalin-fixed, paraffin-embedded tissue from 17 South Asian patients with ulcerative colitis and from 11 European patients with a similar degree of colitis, by the application of 10 biotinylated lectins. These were directed against a range of sialyl, fucosyl and 2-deoxy, 2-acetamido-galactosyl sequences, using an avidin--peroxidase revealing system and semiquantitative assessment. The South Asian group showed a reduction in the binding of agglutinins from Sambucus nigra in the apical-membranous region of enterocytes, and a decrease in apical Maackia amurensis agglutinin binding. These results suggest that South Asians with ulcerative colitis show a different distribution of terminal N-acetyl neuraminyl residues, either in their α-2,6 or α-2,3 linkage, compared with their European counterparts. The changes in sialylation observed in European cases compared with normal disease-free control subjects were present in quiescent disease, but were also related to disease activity. Their absence in Asians with ulcerative colitis may imply an inherent, genetically determined variation in this group, which may also play a part in their reduced risk of subsequent malignancy     

葛根芩连汤加蒲公英灌肠治疗溃疡性结肠炎的临床观察

目的:观察中药葛根芩连汤加蒲公英灌肠治疗溃疡性结肠炎的疗效。方法:溃疡性结肠炎患者113例,随机分为治疗组(60例)和对照组(53例),前者用蒲公英葛根芩连汤灌肠,后者用柳氮黄吡啶治疗。结果:治疗组总有效率为90%,对照组总有效率75.5%,差异具有显著性(P<0.01)。结论:中药葛根芩连汤加蒲公英灌肠治疗溃疡性结肠炎疗效好,建议临床推广应用。     

Serum paraoxonase 1 activity and malondialdehyde levels in patients with ulcerative colitis

This study was designed to evaluate the oxidative and antioxidative status in patients with ulcerative colitis by detecting antioxidant enzyme paraoxonase 1 activity together with the level of a well-known marker of oxidative stress, malondialdehyde. Serum paraoxonase 1 activity and malondialdehyde levels were analysed in 30 patients with ulcerative colitis and 30 controls using a spectrophotometric method; correlation analysis was made between these variables. Serum malondialdehyde levels were higher in the ulcerative colitis group (median: 2.5, range: 0.5-9.4 nmol ml(-1)) than among the controls (median:1.1, range: 0.5-2.3 nmol ml(-1); p < 0.001) whereas paraoxonase 1 activities were lower in the ulcerative colitis group (median: 158.4, range: 61.6-264.1 U l(-1)) than in the control group (median: 233.3, range: 114.4-431.0 U l(-1); p < 0.001). There was no correlation between serum malondialdehyde level, paraoxonase 1 activity and disease activity. (1) Increased reactive oxygen metabolites levels in ulcerative colitis may result in a pro-oxidation environment, which in turn could result in decreased antioxidant paraoxonase 1 activity and increased malondialdehyde levels, (2) increased cytokines may be a possible cause of decreased paraoxonase 1 activity and (3) decreased serum paraoxonase 1 activity may be a part of an inflammatory response.     

EW-7197 prevents ulcerative colitis-associated fibrosis and inflammation

EW-7197 is a transforming growth factor-β type I receptor kinase inhibitor with potential anti-inflammatory and antifibrotic properties. Here, we investigate the potential therapeutic effects of EW-7197 in a murine model of ulcerative colitis. EW-7197 attenuated the colitis disease activity index by improving rectal bleeding, body weight, and degree of stool consistency. EW-7197 also reduced colorectal tissue damage and the colon histopathological score by reducing crypt loss, mucosal damage, and tissue inflammation. Moreover, EW-7197 appeared to ameliorate the inflammatory and fibrotic responses by reducing oxidative stress, reducing submucosal edema and inflammatory cell infiltration, downregulating proinflammatory and pro-fibrotic genes, and inhibiting excessive collagen deposition in inflamed and fibrotic ulcerative colitis tissues. These results suggest that EW-7197 has potentially useful therapeutic properties against colitis, with clinically translational potential of inhibiting key pathological responses of inflammation and fibrosis in patients with colitis.     

5-Aminosalicylates Reduce the Risk of Colorectal Neoplasia in Patients with Ulcerative Colitis: An Updated Meta-Analysis

Background

Although the chemopreventive effect of 5-aminosalicylates on patients with ulcerative colitis has been extensively studied, the results remain controversial. This updated review included more recent studies and evaluated the effectiveness of 5-aminosalicylates use on colorectal neoplasia prevention in patients with ulcerative colitis.

Methods

Up to July 2013, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant observational studies (case-control and cohort) about the effect of 5-aminosalicylates on the risk of colorectal neoplasia among patients with ulcerative colitis. The Newcastle-Ottawa Scale was used to assess the quality of studies. Adjusted odds ratios (ORs) were extracted from each study. A random-effects model was used to generate pooled ORs and 95% confidence intervals (95%CI). Publication bias and heterogeneity were assessed.

Results

Seventeen studies containing 1,508 cases of colorectal neoplasia and a total of 20,193 subjects published from 1994 to 2012 were analyzed. 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis (OR 0.63; 95%CI 0.48–0.84). Pooled OR of a higher average daily dose of 5-aminosalicylates (sulfasalazine ≥ 2.0 g/d, mesalamine ≥ 1.2 g/d) was 0.51 [0.35–0.75]. Pooled OR of 5-aminosalicylates use in patients with extensive ulcerative colitis was 1.00 [0.53–1.89].

Conclusion

Our pooled results indicated that 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis, especially in the cases with a higher average daily dose of 5-aminosalicylates use. However, the chemopreventive benefit of 5-aminosalicylates use in patients with extensive ulcerative colitis was limited.     

Oxygen radicals in ulcerative colitis.

This article reviews the pathophysiologic concept that superoxide and hydrogen peroxide, generated by activated leukocytes, together with low-molecular-weight chelate iron derived from fecal sources and from denatured hemoglobin, amplify the inflammatory response and subsequent mucosal damage in patients with active episodes of ulcerative colitis. The putative pathogenic mechanisms reviewed are as follows: (1) Dietary iron is concentrated in fecal material owing to normally limited iron absorption. (2) Mucosal bleeding, characteristic of ulcerative colitis, as well as supplemental oral iron therapy for chronic anemia, further conspire to maintain or elevate mucosal iron concentration in colitis. (3) Fenton chemistry, driven especially by leukocyte-generated superoxide and hydrogen peroxide, leads to formation of hydroxyl radicals. (4) The resultant oxidative stress leads to the extension and propagation of crypt abscesses, either through direct membrane disruption by lipid peroxidation or through generation of secondary toxic oxidants such as chloramines. (5) Chemotactic products of lipid peroxidation, including 4-hydroxynonenal, provide positive feedback to accelerate this inflammatory/oxidative process, leading to acute exacerbations of the disease. (6) Other oxidized products, such as oxidized tryptophan metabolites, created by free radical mechanisms in or near the mucosa, may act as carcinogens or tumor promotors that contribute to the exceedingly high incidence of colon carcinoma in patients suffering from chronic ulcerative colitis. In this way, self-sustaining cycles of oxidant formation may amplify flare-ups of inflammation and mucosal injury in ulcerative colitis. This concept, if proved correct by subsequent research, would provide a rationale for several novel clinical approaches to the management of ulcerative colitis, including use of SOD mimetics, iron chelators, and chain-breaking antioxidants.     

溃疡性结肠炎患者外周血C 反应性蛋白、血清降钙素原及白细胞介素-6 水平及临床意义

目的:分析溃疡性结肠炎(Ulcerative colitis,UC)患者血清降钙素原(Procalcitonin,PCT)、C反应蛋白(C-reactive protein,CRP)及白细胞介素-6(Interleukin-6,IL-6)水平与病情严重程度的关系。方法:选择2013年5月-2015年5月在我院就诊的溃疡性结肠炎患者91例作为研究对象,另选择同期在我院接受健康体检的志愿者69例作为对照组。检测并比较两组研究对象血清降钙素原(PCT)、C反应性蛋白(CRP)及白细胞介素-6(IL-6)的水平,并分析PCT,CRP及IL-6水平与溃疡性结肠炎的相关性。结果:溃疡性结肠炎患者PCT水平为(1.24±0.23)ng/m L,对照组PCT水平为(0.12±0.10)ng/m L,溃疡性结肠炎患者PCT水平显著高于对照组,差异具有统计学意义(P0.05);溃疡性结肠炎患者CRP水平为(105.27±19.93)mg/m L,对照组CRP水平为(7.62±2.97)mg/m L,溃疡性结肠炎患者血清CRP水平显著高于对照组,差异具有统计学意义(P0.05);溃疡性结肠炎患者IL-6水平为(248.15±35.60)ng/m L,对照组IL-6水平为(144.05±20.26)ng/m L,溃疡性结肠炎患者血清IL-6水平显著高于对照组,差异具有统计学意义(P0.05)。溃疡性结肠炎患者血清PCT,IL-6及CRP水平之间均呈正相关关系(r=0.301,0.468,0.413,P0.01)。结论:溃疡性结肠炎患者血清PCT,CRP及IL-6水平均显著高于健康人群,其水平变化与患者病情严重程度有关。因此,我们在临床实践中应予以重视。     

Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis

Background

MUC2 mucin produced by intestinal goblet cells is the major component of the intestinal mucus barrier. The inflammatory bowel disease ulcerative colitis is characterized by depleted goblet cells and a reduced mucus layer, but the aetiology remains obscure. In this study we used random mutagenesis to produce two murine models of inflammatory bowel disease, characterised the basis and nature of the inflammation in these mice, and compared the pathology with human ulcerative colitis.

Methods and Findings

By murine N-ethyl-N-nitrosourea mutagenesis we identified two distinct noncomplementing missense mutations in Muc2 causing an ulcerative colitis-like phenotype. 100% of mice of both strains developed mild spontaneous distal intestinal inflammation by 6 wk (histological colitis scores versus wild-type mice, p < 0.01) and chronic diarrhoea. Monitoring over 300 mice of each strain demonstrated that 25% and 40% of each strain, respectively, developed severe clinical signs of colitis by age 1 y. Mutant mice showed aberrant Muc2 biosynthesis, less stored mucin in goblet cells, a diminished mucus barrier, and increased susceptibility to colitis induced by a luminal toxin. Enhanced local production of IL-1β, TNF-α, and IFN-γ was seen in the distal colon, and intestinal permeability increased 2-fold. The number of leukocytes within mesenteric lymph nodes increased 5-fold and leukocytes cultured in vitro produced more Th1 and Th2 cytokines (IFN-γ, TNF-α, and IL-13). This pathology was accompanied by accumulation of the Muc2 precursor and ultrastructural and biochemical evidence of endoplasmic reticulum (ER) stress in goblet cells, activation of the unfolded protein response, and altered intestinal expression of genes involved in ER stress, inflammation, apoptosis, and wound repair. Expression of mutated Muc2 oligomerisation domains in vitro demonstrated that aberrant Muc2 oligomerisation underlies the ER stress. In human ulcerative colitis we demonstrate similar accumulation of nonglycosylated MUC2 precursor in goblet cells together with ultrastructural and biochemical evidence of ER stress even in noninflamed intestinal tissue. Although our study demonstrates that mucin misfolding and ER stress initiate colitis in mice, it does not ascertain the genetic or environmental drivers of ER stress in human colitis.

Conclusions

Characterisation of the mouse models we created and comparison with human disease suggest that ER stress-related mucin depletion could be a fundamental component of the pathogenesis of human colitis and that clinical studies combining genetics, ER stress-related pathology and relevant environmental epidemiology are warranted.     

凉血止痢汤与锡类散保留灌肠治疗溃疡性结肠炎的疗效对比

目的:观察凉血止痢汤与锡类散保留灌肠治疗溃疡性结肠炎的疗效。方法:选取80例溃疡性结肠炎患者,按随机数字表法分为两组,对照组(39例)给予锡类散治疗,观察组给予凉血止痢汤治疗,观察两组治疗后的疗效,腹痛、腹泻、脓血便消失时间,治疗前后C反应蛋白、白细胞、血红蛋白数目及治疗期间不良反应情况。结果:治疗后,两组治疗有效率比较无明显差别(P0.05),观察组患者腹痛、腹泻、脓血便消失时间均短于对照组(P0.05),两组组白细胞数目、C反应蛋白水平均较治疗前显著下降且观察组上述指标较对照组更低(P0.05)。两组血红蛋白数目均较治疗前显著上升且观察组较对照组更高(P0.05)。两组治疗期间均无肝肾功能异常、胃肠道异常等不良反应发生。结论:凉血止痢汤与锡类散联合对溃疡性结肠炎均具有较好的治疗效果,能更快消退溃疡性结肠炎症状,且安全性高。     

Chemical and histochemical studies of normal and diseased human gastrointestinal tract. I. A comparison between histologically normal colon, colonic tumours, ulcerative colitis and diverticular disease of the colon

Summary Chemical and histochemical methods were used to compare the epithelial glycoproteins from formalin-fixed surgical specimens of normal human large intestine, colonic tumours, ulcerative colitis and diverticular disease. All the epithelial glycoproteins contained fucose, galactose, glucosamine, galactosamine and, in addition, sialic acids both with and withoutO-acyl substituents in the side chain and/or at position C₄. The glycoproteins of the normal ascending and descending colons differed significantly with respect to the percentage of the sialic acids released following digestion of the de-O-acylated glycoprotein withVibrio cholera neuraminidase and to the molar fucose-sialic acid ratio. Statistical analysis of the chemical data showed that (a) compared to normal, the sialic acids of the tumour and ulcerative colitis glycoproteins from the descending colon were significantly less substituted in the side chain and at position C₄; (b) theO-acetyl substitution pattern of the sialic acids of the ulcerative colitis glycoproteins from the ascending colon and the quantitative composition of the carbohydrate prosthetic groups of the ulcerative colitis glycoproteins from both ascending and descending colons differed from normal; (c) it was not always possible to distinguish between the ulcerative colitis and tumour glycoproteins on the basis of theO-acetyl substitution pattern of their sialic acids; and (d), there were minor differences between normal glycoproteins and those from cases of diverticular disease.     

Coincident Salmonella Infections and Ulcerative Colitis: Problems of Recognition and Management

Five cases of coincident salmonellosis and ulcerative colitis are described. In three the diagnostic combination was recognized late. If corticosteroid therapy is given for the colitis once the combination is recognized, then simultaneous systemic antibiotic cover is advisable. One of the five patients died during corticosteroid therapy alone with salmonella septicaemia due to a usually non-invasive organism.     

Inflammatory Bowel Disease Among College Students

Of 52 student patients with chronic inflammatory bowel disease who were observed at Stanford University over a three-year period, 16 had Crohn disease, 17 had ulcerative colitis and 19 had ulcerative proctitis. Patients with ulcerative colitis had relatively few complications. During the study period, only two students from the entire group of 52 were obliged to interrupt college attendance because of bowel disease or complications. Of the patients, 33 were first observed on remission or attained remission during the three-year observation period. Incidence and prevalence rates for Crohn disease and ulcerative colitis were comparable with age-specific rates from other published studies. At Stanford, the high reported frequency of proctitis, which exceeded that of proximal ulcerative colitis, was possibly a reflection of the diagnostic zeal with which patients with rectal bleeding were evaluated at the student health service.     

Smoking and nicotine in inflammatory bowel disease: good or bad for cytokines?

Smoking has either a beneficial or harmful effect on the course and recurrence of ulcerative colitis and Crohn''s disease respectively. Transdermal application of nicotine had similar effects in ulcerative colitis and therefore was considered to be an effective basic drug which could be further developed in the search for new compounds in the treatment of acute exacerbations of corticosteroid resistant ulcerative colitis. In this communication the short-term use of nicotine in ulcerative colitis is reviewed.     

Cancer and Ulcerative Colitis

Ulcerative colitis is a potential precursor of cancer of the colon or rectum. In a series of patients with ulcerative colitis operated on between 1952 and 1968 seven developed carcinoma in the residual rectal stump after total colectomy and ileorectal anastomis. After assessment of the risks of the other available forms of treatment, I believe that ileorectal anastomosis is the best operation in the majority of cases.     

ULCERATIVE COLITIS

In the early stages ulcerative colitis is reversible and a normal bowel can be regained. This is facilitated by the use of cortisone which should be given promptly during the first attack.Surgical operation has an important role in helping to reduce the high initial mortality and in overcoming invalidism in the chronic phase.A clear understanding of the role of emotional tension enables the internist to make an appreciable contribution to the management of the disease.     

Assessment of the influence of the inflammatory process on the activation of blood platelets and morphological parameters in patients with ulcerative colitis (colitis ulcerosa)

Ulcerative colitis (colitis ulcerosa) is a non-specific inflammatory bowel disease of unknown etiology. The symptoms which are observed in the course of ulcerative colitis are: an increase in the number of leukocytes and blood platelets, an increase in the concentration of IL-6 and anemia. Blood platelets are the key element, linking the processes of hemostasis, inflammation and the repair of damaged tissues. Activation of blood platelets is connected with changes in their shape and the occurrence of the reaction of release. P-selectin appears on the surfaces of activated blood platelets and the concentration level of soluble P-selectin increases in the blood plasma. The aim of this study was to define whether the increased number of blood platelets in patients with ulcerative colitis accompanies changes in their activation and morphology. A total of 16 subjects with ulcerative colitis and 32 healthy subjects were studied. Mean platelet count, morphological parameters of platelets and MPC were measured using an ADVIA 120 hematology analyzer. Concentrations of sP-selectin and IL-6 in serum were marked by immunoassay (ELISA). MPC, concentration of sP-selectin and IL-6 were significantly higher in subjects with ulcerative colitis compared to those in the healthy group. There was a decrease of MPV in patients with ulcerative colitis, which is statistically significant. Chronic inflammation in patients with ulcerative colitis causes an increase in the number of blood platelets, a change in their morphology and activation. Decreased MPV value reflects activation and the role blood platelets play in the inflammatory process of the mucous membrane of the colon. A high concentration of sP-selectin, which is a marker of blood platelet activation, demonstrates their part in the inflammatory process. The increase in the concentration of sP-selectin correlated positively with the increase in concentration of IL-6. This is why it may be a useful marker of the activity of colitis ulcerosa.