Increased Folate Intake with No Changes in Serum Homocysteine and Decreased Levels of C-Reactive Protein in Patients with Inflammatory Bowel Diseases

In order to increase dietary folic acid intake and to improve nutritional status regarding folate by controlling homocysteine concentrations, ten patients with inflammatory bowel diseases (Crohn’s disease in the colon and ulcerative colitis) received individualized nutritional guidance and were followed up as outpatients for 2 months. The following procedures were performed at the beginning of the study (T0), after 1 month (T1) and at the end of the study (T2): collection of anthropometric data (weight and height), dietary data (24 h diet recall), and blood under fasting condition for the determination of serum folic acid, homocysteine, C-reactive protein, and vitamin B12. Plasma folic acid deficiency was not detected but hyperhomocysteinemia was present in six individuals and C-reactive protein (CRP) was increased (>0.5 mg/dl) in seven patients. After the patients were instructed there was a significant increase in vitamin B6 intake (about 35%) and in folate intake (49.6%). Mean plasma levels of folic acid, homocysteine, and vitamin B12 did not change, but there was a significant decrease of CRP at T1, 0.36 mg dl⁻¹ on average (P = 0.01), which was maintained at T2. We conclude that the increased folate intake reported by this group of patients was not reflected in improved serum concentrations of folic acid and homocysteine. However, the guidelines for the patients probably induced them to choose a more adequate diet, providing nutrients that help control the inflammatory process.     

Irritable Bowel Syndrome on Inflammatory Bowel Disease in Deep Remission: No Relation with Remission Deepening and Inflammation

Background: The aim of the study was to establish the frequency of irritable bowel syndrome (IBS) in patients with inflammatory bowel disease (IBD) in clinical, endoscopic, and histologic remission and in relation to both the depth of remission and inflammation markers. Methods: Patients with ulcerative colitis (UC) and with Crohn’s disease (CD) in clinical remission for at least 6 months were enrolled in the study. All of the patients underwent colonoscopy, and biopsy specimens were taken to evaluate endoscopic and histopathologic remission. Patients were evaluated according to Rome III criteria for IBS. Fecal calprotectin level and blood samples for C-reactive protein (CRP), sedimentation rate, and fibrinogen levels were studied.Results: IBS frequency was 20.9% in UC cases and 28.9% in CD cases in clinical remission. Rates with and without endoscopic remission in UC (20.5% vs. 22.2%, P = .727) and CD (25% vs. 33.3%, P = .837, respectively) were not different. Similarly, rates with and without histopathologic remission in UC (15.7% vs. 26.6%, P = .723), and CD (21.4% vs. 33.3%, P = .999) were not statistically different. Also, it was not related to inflammation markers.Conclusion: IBS frequency among IBD patients with remission was in a substantial rate; these rates kept up with the process of deep remission and even complete mucosal healing and were irrelevant to inflammation.     

Fatigue Severity and Factors Associated with High Fatigue Levels in Korean Patients with Inflammatory Bowel Disease

Background/Aims

Many patients with inflammatory bowel disease (IBD) often complain of fatigue. To date, only a few studies in Western countries have focused on fatigue related to IBD, and fatigue has never been specifically studied in Asian IBD patients. The aim of the present study was to investigate the fatigue level and fatigue-related factors among Korean IBD patients.

Methods

Patients in remission or with mild to moderate IBD were included. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue and the Brief Fatigue Inventory. Corresponding healthy controls (HCs) also completed both fatigue questionnaires.

Results

Sixty patients with Crohn disease and 68 patients with ulcerative colitis (UC) were eligible for analysis. The comparison group consisted of 92 HCs. Compared with the HCs, both IBD groups were associated with greater levels of fatigue (p<0.001). Factors influencing the fatigue score in UC patients included anemia and a high erythrocyte sedimentation rate (ESR).

Conclusions

Greater levels of fatigue were detected in Korean IBD patients compared with HCs. Anemia and ESR were determinants of fatigue in UC patients. Physicians need to be aware of fatigue as one of the important symptoms of IBD to better understand the impact of fatigue on health-related quality of life.     

Role of the JNK signal transduction pathway in inflammatory bowel disease

The c-Jun NH2-terminal Kinase （JNK） pathway represents one sub-group of the mitogen-activated protein （MAP） kinases which plays an important role in various inflammatory diseases states, including inflammatory bowel disease （IBD）. Significant progress towards understanding the function of the JNK signaling pathway has been achieved during the past few years. Blockade of the JNK pathway with JNK inhibitors in animal models of IBD lead to resolution of intestinal inflammation. Current data suggest specific JNK inhibitors hold promise as novel therapies in IBD.     

大鼠重症急性胰腺炎发病机制中p38丝裂原活化蛋白激酶的作用研究

目的探讨p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38 MAPK)特异性抑制剂SB203580对大鼠重症急性胰腺炎(SAP)的保护作用。方法以胆胰管逆行注射5%牛磺胆酸钠建立SD大鼠SAP模型。将45只SD大鼠随机分为3组,假手术组(SO组,n=15);SAP组(SAP组,n=15);SB203580治疗组(SB组,n=15)。术后3、6、12 h处死大鼠并取血。对胰腺进行病理组织学评分,测定大鼠腹水量。检测血清淀粉酶,ELISA法测定血清IL-6和IL-10水平。并采用免疫组化法观察大鼠胰腺组织p38 MAPK下游靶点P-ATF2表达情况。结果 SO组胰腺组织存在P-ATF2弱表达,SAP组各时间点P-ATF2表达水平明显升高(P<0.01),SB组各时间点表达水平较SAP组下降明显(P<0.01)。SAP组6、12 h时间点IL-6水平,3、6 h时间点IL-10水平,血清淀粉酶,腹水量明显高于SB组(P<0.05)。SAP组各时间点胰腺组织病理学积分显著高于SB组,差异有统计学意义(P<0.05)。结论阻断p38 MAPK信号传导通路可以明显缓解大鼠重症急性胰腺炎的病情。预示此信号传导通路可以为SAP的治疗提供一个有价值的标靶。     

Inflammatory bowel disease in rats： Bacterial and chemical interaction

AIM：To develop a novel model of colitis in rats, using a combination of iodoacetamide and enteropathogenic E. coli（EPEC）, and to elucidate the pathophysiologic processes implicated in the development of ulcerative colitis （UC）.
METHODS： Hale Sprague-Dawley rats （/7 = 158） were inoculated intrarectally on a weekly basis with 4 different combinations： （a） 1% methylcellulose （HC）, （b） 100 μL of 6% iodoacetamide （IA） in 1% HC, （c） 200 p.L containing 4×10^8 colony factor units （CFU） of EPEC, and （d） combined treatment of （IA） followed by bacteria （13） after 2 d. Thirty days post treatment, each of the four groups was divided into two subgroups; the inoculation was stopped for one subgroup and the other subgroup continued with biweekly inoculation until the end of the experiment. Colitis was evaluated by the clinical course of the disease, the macroscopic and microscopic alterations, activity of myeloperoxidase （HPO）, and by TNF-α gene expression. RESULTS： Findings indicative of UC were seen in the combined treatment （IA ＋ B） as well as the IA continued treatment groups： the animals showed slow rate of increase in body weight, diarrhea, bloody stools, high colonic ulcer score, as well as histological alterations characteristic of UC, with an extensive inflammatory reaction. During the course of the experiment, the MPO activity was consistently elevated and the TNF-α gene expression was upregulated compared to the control animals.
CONCLUSION： The experimental ulcerative colitis model used in the present study resembles, to a great extent, the human disease. It is reproducible with characteristics indicative of chronicity.     

Assessing the role of stress signalling via p38 MAP kinase in the premature senescence of Ataxia Telangiectasia and Werner syndrome fibroblasts

The premature ageing Ataxia Telangiectasia (AT) and Werner syndromes (WS) are associated with accelerated cellular ageing. Young WS fibroblasts have an aged appearance and activated p38 MAP kinase, and treatment with the p38 inhibitor SB230580 extends their lifespan to within the normal range. SB203580 also extends the replicative lifespan of normal adult dermal fibroblasts, however, the effect is much reduced when compared to WS cells, suggesting that WS fibroblasts undergo a form of stress-induced premature senescence (SIPS). A small lifespan extension is seen in AT cells, which is not significant compared to normal fibroblasts, and the majority of young AT cells do not have an aged appearance and lack p38 activation, suggesting that the premature ageing does not result from SIPS. The lack of p38 activation is supported by the clinical manifestation, since AT is not associated with inflammatory disease, whereas WS individuals are predisposed to atherosclerosis, type II diabetes and osteoporosis, conditions known to be associated with p38 activation.     

On the Use of Herbal Medicines in Management of Inflammatory Bowel Diseases: A Systematic Review of Animal and Human Studies

Because of potential adverse events and lack of effectiveness of standard therapies, the use of complementary and alternative medicines (CAM), particularly of herbal therapies, for inflammatory bowel disease (IBD) is increasing. Results from the use of herbal therapies for managing IBD are promising, and no serious adverse events have been reported from them. Herbal therapies show their benefit in managing IBD by different mechanisms such as immune system regulation, antioxidant activity, inhibition of leukotriene B4, inhibition of nuclear factor-kappa B (NF-κB), and antiplatelet activity. In this paper, all reported herbal therapies established in animal IBD models or used for managing human IBD are systematically reviewed and their possible mechanisms of action discussed. Conducting clinical trials with high quality and validity (randomized, double blinded, controlled, on a large number of patients) to obtain more conclusive results about the use of herbal therapies in IBD is recommended.     

Increased Expression of Long Pentraxin PTX3 in Inflammatory Bowel Diseases

The aims of this study were to investigate the expression of pentraxin-3 in inflamed gastrointestinal tissue in patients with inflammatory bowel diseases and to elucidate the usefulness of plasma pentraxin-3 level as an inflammation marker in patients with inflammatory bowel diseases. Pentraxin-3 immunoreactivity was found in infiltrating neutrophils and vessels in the inflamed gut. Plasma pentraxin-3 concentration in patients with active inflammatory bowel diseases was significantly higher than that of normal subjects and patients with inactive inflammatory bowel diseases. Significant positive correlations of clinical disease activity with plasma pentraxin-3 concentration and serum CRP concentration were found in patients with inflammatory bowel diseases. Pentraxin-3 is directly produced from the inflamed gut in inflammatory bowel diseases. In conclusion, plasma pentraxin-3 concentration is a useful marker for understanding the disease activity in patients with inflammatory bowel diseases.     

The contribution of long non-coding RNAs in Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBDs) are multifactorial autoimmune diseases with growing prevalence but the interaction between genetic, environmental and immunologic factors in their development is complex and remains obscure. There is great need to understand their pathogenetic mechanisms and evolve diagnostic and therapeutic tools. Long non-coding RNAs (lncRNAs) are RNA molecules longer than 200 nucleotides that are known to interfere in gene regulation but their roles and functions have not yet been fully understood. While they are widely investigated in cancers, little is known about their contribution in other diseases. There is growing evidence that lncRNAs play critical role in regulation of immune system and that they interfere in the pathogenetic mechanisms of autoimmune diseases, like IBDs. Recent studies have identified lncRNAs in the proximity of IBD-associated genes and single nucleotide polymorphisms within IBD-associated lncRNAs as well. Furthermore, blood samples and pinch biopsies were also analyzed and a plethora of lncRNAs are found to be deregulated in Crohn’s disease (CD), Ulcerative colitis (UC) or both. (Especially in UC samples the lncRNAs INFG-AS1 and BC012900 were found to be significantly up-regulated. Similarly, ANRIL, a lncRNA that nest different disease associated SNPs, is significantly down-regulated in inflamed IBD tissue.) This review aims at recording for the first time recent data about lncRNAs found to be deregulated in IBDs and discussing suggestive pathogenetic mechanisms and future use of lncRNAs as biomarkers.     

Association between Inflammatory Bowel Disease and Sarcoidosis: Report of Two Cases and Review of the Literature

Background: Common etiopathogenic factors may explain the association of systemic sarcoidosis with inflammatory bowel disease.

Methods: We report two cases of such an association: one of sarcoidosis that developed 2 years after proctocolectomy for ulcerative colitis and one of sarcoidosis and Crohn's colitis. Factors like increased cellular immunity or circulating immunocomplexes or autoantibodies may have a role. Exogenous agents or familiarity may also be involved.

Conclusions: It is postulated that the association between sarcoidosis and inflammatory bowel disease (both ulcerative colitis and Crohn's disease) does not occur by chance alone and that the two conditions may share some genetic or immunologic alterations. The two diseases, however, follow an independent clinical course.     

硫唑嘌呤治疗炎症性肠病的不良反应分析

目的 了解硫唑嘌呤(AZA)治疗炎症性肠病不良反应的类型、发生率、发生时间及转归.方法 回顾性分析1995年3月～2009年9月北京协和医院接受硫唑嘌呤治疗的85例炎症性肠病患者的病历资料,其中溃疡性结肠炎37例,克罗恩病48例.结果 37例(43.5%)患者出现不良反应共43次,其中48%(20/43)的不良反应发生...     

No Association Between Pseudopolyps and Colorectal Neoplasia in Patients With Inflammatory Bowel Diseases

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血小板参数、C反应蛋白对炎症性肠病患者活动性的评价

目的 探讨血小板参数、C反应蛋白(CRP)对炎症件肠病活动性的评价.方法 分析75例活动性和26例缓解期炎症性肠病患者的血小板参数、CRP的水平及其间的关系,比较临床严重程度对血小板参数及CRP的影响.结果 活动性炎症性肠病患者血小板计数(PLT)和CRP水平明显高丁缓解期患者,平均血小板体积(MPV)明显低于缓解期患者,两组筹异有显著性(P<0.05);重度炎症性肠病患者PUF和CRP水平明显高于中度炎症性肠病患者,MPV明显低于巾度炎症性肠病患者(P<0.05);中度炎症性肠病患者PLT和CRP水平高于轻度患者,MPV水平低于轻度患者(P<0.05).活动性炎症性肠病患者严重程度分别与PLT和CRP之间呈正相关(r=-0.83,P<0.05;r=0.89,P<0.05),与MPV水平呈负相关(r=-0.38,P<0.05).结论 血小板参数和CRP水平能反映活动性炎症性肠病患者的临床严重程度.     

^99mTc-hIgG在炎症性肠病诊断与随访中的临床应用

评价^99mTc-hIgG象法在炎症性肠病定位、疗效随访和预测复发中的临床价值。方法：对54例临床确诊的炎症性肠病病人在正规治疗前、41例经治疗症状得“控制和16例随访过程中症状复发者分别作^99mTc-hIgG核素显象检查。结果：①54例炎症性肠病病人中,50例出现阳性改变,其中2例假阳性,2例因发现新的放射性异常浓集修正丁诊断,4例假阴性,总灵敏度925％,特异性902％,准确率为88.9％;②41例临床缓解病人中,同位素显象出现相应减轻者38例,总符合率92．6％：④16例症状复发者中核素有异常浓集者15例,与临床的符台率为91．6％。结论：在炎症性肠病的诊断方法中,^99mTc-hIgG是一种非创伤性的辅助性方法,具灵敏度高、特异性好的优点,在疗效随访和预测复发方面有良好的实用价值。     

Developing a Neural Network Model for a Non-invasive Prediction of Histologic Activity in Inflammatory Bowel Diseases

Background: Colonoscopy with biopsy is the “gold” standard for evaluating disease activity in inflammatory bowel diseases (IBD). Current research is geared toward finding non-invasive, cost-efficient methods that estimate disease activity. We aimed to develop a neural network (NN) model for the non-invasive prediction of histologic activity in IBD using routinely available clinical-biological parameters.Methods: Standard clinical-biological parameters and histologic activity from 371 ulcerative colitis (UC) and 115 Crohn’s disease (CD) patient records were collected. A training set, a test set, and a validation set were used for building/validating 2 models for each disease. All models had binary output predicting the active/inactive histologic disease status. For both diseases, the first model used both clinical and biological inputs, while the second used only biological data.Results: First UC model obtained an accuracy of 95.59% on the test set and 96.67% on the validation set. The second UC model achieved accuracies of 88.24% and 86.67% on the test and validation sets, respectively. The First CD classifier resulted in 90.48% accuracy on the test set and 91.67% on the validation set. Finally, the second CD classifier obtained an accuracy of 85.71% on the test set and 91.67% on the validation set.Conclusions: An accurate and non-invasive artificial intelligence system to predict histologic disease activity in IBD is designed. Our models achieved similar or better results compared to the documented performance of fecal calprotectin (the best non-invasive IBD biomarker to date). Given these favorable results, we anticipate the future utility in the clinical setting of a non-invasive disease activity prediction.     

Bactericidal Permeability Increasing Protein Gene Polymorphism is Associated with Inflammatory Bowel Diseases in the Turkish Population

Background/Aims:

Inflammatory bowel disease, a chronic inflammatory disease with unknown etiology, affects the small and large bowel at different levels. It is increasingly considered that innate immune system may have a central position in the pathogenesis of the disease. As a part of the innate immune system, bactericidal permeability increasing protein has an important role in the recognition and neutralization of gram-negative bacteria. The aim of our study was to investigate the involvement of bactericidal permeability increasing protein gene polymorphism (bactericidal permeability increasing protein Lys216Glu) in inflammatory bowel disease in a large group of Turkish patients.

Patients and Methods:

The present study included 528 inflammatory bowel disease patients, 224 with Crohn''s disease and 304 with ulcerative colitis, and 339 healthy controls.

Results:

Bactericidal permeability increasing protein Lys216Glu polymorphism was found to be associated with both Crohn''s disease and ulcerative colitis (P = 0.0001). The frequency of the Glu/Glu genotype was significantly lower in patients using steroids and in those with steroid dependence (P = 0.012, OR, 0.80; 95% confidence interval [CI]: 0.68-0.94; P = 0.0286, OR, 0.75; 95% CI: 0.66-0.86, respectively). There was no other association between bactericidal permeability increasing protein gene polymorphism and phenotypes of inflammatory bowel disease.

Conclusions:

Bactericidal permeability increasing protein Lys216Glu polymorphism is associated with both Crohn''s disease and ulcerative colitis. This is the first study reporting the association of bactericidal permeability increasing protein gene polymorphism with steroid use and dependence in Crohn''s disease.