5-aminosalicylic acid preparations in the treatment of inflammatory bowel disease

Multiple new 5-aminosalicylic acid preparations have joined sulphasalazine in our armamentarium of agents for the treatment of inflammatory bowel disease. Rowasa enemas are clearly an advance in our ability to treat distal ulcerative colitis. Oral 5-ASA analogues are equivalent to sulphasalazine in maintaining ulcerative colitis in remission but may have some increased efficacy in high doses for treating mild to moderate active ulcerative colitis. These agents are particularly useful in the sulphasalazine-intolerant individual. Some of the new 5-ASA preparations have been found to be helpful in the treatment of active Crohn’s disease. There is hope that the newer agents having distal small bowel drug release may be beneficial in maintaining Crohn’s disease in remission.     

上消化道疾病患者幽门螺杆菌耐药率的实验室研究

目的：探讨上消化道疾病患者幽门螺杆菌耐药率的检测方法和规律。方法：通过改良幽门螺杆菌分离培养和药物敏感试验研究幽门螺杆菌耐药率的变化规律。结果：胃癌幽门螺杆菌检出率阳性为66.67%,其他胃部疾病的Hp感染阳性率为33.45%～49.96%;Hp对左氧氟沙星的敏感率最高,达到98.35%,对阿莫西林等4种药物的敏感率均在75%以上,而对甲硝唑的耐药率达到96.11%。结论：本实验方法对判断幽门螺杆菌耐药率有较大的敏感率。     

A critical evaluation of the therapeutic benefits and side-effects of aminosalicylate analogues in the treatment of inflammatory bowel disease

Peppercorn MA. A critical evaluation of the therapeutic benefits and side-effects of aminosalicyiate analogues in the treatment of inflammatory bowel disease. Inflammopharmacology. 1993;2:263-276. Sulphasalazine, which consists of sulphapyridine linked to 5-amimosalicylic acid (5-ASA) via an azo bond, is efficacious in the therapy of active and remitted ulcerative colitis and active Crohn’s disease when the colon is involved. Its use is limited by a high incidence of adverse effects. Studies of sulphasalazine’s pharmacology suggested that it may be serving as a vehicle for delivery of its 5-ASA metabolite to distal disease sites. Toxicity studies revealed that most of the side-effects of sulphasalazine could be attributed to its sulpha moiety. These observations led to the development of a new group of agents, the aminosalicylates, based on sulphasalazine’s structure. Topical forms of 5-ASA have proved to be effective in active and remitted distal ulcerative colitis and proctitis. Oral forms of 5-ASA are as effective as sulphasalazine in active ulcerative colitis and in maintaining remission in ulcerative colitis and appear to be useful in active and remitted Crohn’s disease regardless of distribution. Eighty to ninety percent of patients intolerant of or allergic to sulphasalazine will tolerate an aminosalicyiate.     

益生菌治疗炎症性肠病与幽门螺杆菌阳性率的相关性分析

目的评估应用益生菌治疗炎症性肠病(Inflammatory bowel disease,IBD)与幽门螺杆菌(H.pylory,Hp)阳性率的关系。方法益生菌疗法采用双歧杆菌乳杆菌三联活菌片,主要包括双歧杆菌1×10~7CFU/g,保加利亚乳杆菌1×10~6CFU/g和嗜热链球菌1×10~6CFU/g。100例IBD患者分为UC(溃疡性结肠炎,Ulcerative colitis)组和CD(克罗恩病,Crohn's disease)组,每组50例,另有30例健康志愿者为对照组。UC组和CD组每日给予相同剂量三联活菌片(0.5 g/片,4片/次,2次/d),并在3个月内不间断给药。如未出现症状加剧或需要额外治疗,则在用药当日及用药3个月后对临床症状进行评估,并在用药前后同时测定三组Hp阳性率。结果UC组和CD组各有47例参加本研究,共计94例。用药3个月后,UC组Mayo评分显著下降(4.02±2.18vs.7.66±1.83,P<0.01),其中有效40例,无效7例,有效率为85.11%,治疗前后炎症指标(CRP、ESR、Hb、Ab)比较,差异有统计学意义(P<0.05)。CD组Mayo评分显著下降(4.26±1.78 vs.7.38±1.61,P<0.01),其中有效38例,无效9例,有效率为80.85%,治疗前后炎症指标(CRP、ESR、Hb、Ab)比较,差异有统计学意义(P<0.05)。应用益生菌治疗后,UC组和CD组的Hp阳性率均显著升高(80.85%vs.57.45%,57.45%vs.36.17%,P<0.05),但治疗后两组的Hp阳性率均低于对照组(80.85%vs.90%,57.45%vs.90%)。结论对于不同类型的炎症性肠病患者,益生菌可以改善炎症指标并有效缓解临床症状,但幽门螺杆菌阳性率与益生菌疗效呈负相关。     

Possible role of MDR1 two-locus genotypes for young-age onset ulcerative colitis but not Crohn’s disease

Background The role of the single nucleotide polymorphisms (SNPs) on positions 2677G>T/A and 3435C>T of the multi-drug-resistance gene 1 (MDR1) in inflammatory bowel disease (IBD) remains unclear. Aims To further elucidate the potential impact of MDR1 two-locus genotypes on susceptibility to IBD and disease behaviour. Patients and methods Three hundred eighty-eight German IBD patients [244 with Crohn’s disease (CD), 144 with ulcerative colitis (UC)] and 1,005 German healthy controls were genotyped for the two MDR1 SNPs on positions 2677G>T/A and 3435C>T. Genotype–phenotype analysis was performed with respect to disease susceptibility stratified by age at diagnosis as well as disease localisation and behaviour. Results Genotype distribution did not differ between all UC or CD patients and controls. Between UC and CD patients, however, we observed a trend of different distribution of the combined genotypes derived from SNPs 2677 and 3435 (χ² = 15.997, df = 8, p = 0.054). In subgroup analysis, genotype frequencies between UC patients with early onset of disease and controls showed significant difference for combined positions 2677 and 3435 (χ² = 16.054, df = 8, p = 0.034 for age at diagnosis ≥25, lower quartile). Herein the rare genotype 2677GG/3435TT was more frequently observed (odds ratio = 7.0, 95% confidence interval 2.5 – 19.7). In this group severe course of disease behaviour depended on the combined MDR1 SNPs (χ² = 16.101, df = 6, p = 0.017 for age at diagnosis ≥25). No association of MDR1 genotypes with disease subgroups in CD was observed. Conclusions While overall genotype distribution did not differ, combined MDR1 genotypes derived from positions 2677 and 3435 are possibly associated with young age onset of UC and severe course of disease in this patient group.     

New developments in the pharmacotherapy of inflammatory bowel disease

In this article the clinical features and aetiology of inflammatory bowel diseases are described and current pharmacotherapeutic possibilities are explored. Also reviewed are recent developments and future prospects for the pharmacotherapy of inflammatory bowel diseases, including aminosalicylates, corticosteroids, immunosuppressants, lipoxygenase inhibitors, fish oil, sucralfate, bismuth compounds, free radical scavengers, (hydroxy)chloroquine, sodium cromoglycate and methotrexate.     

埃索美拉唑钠三联疗法治疗消化性溃疡合并上消化道出血的临床研究

目的：探讨埃索美拉唑钠三联疗法治疗消化性溃疡合并上消化道出血的临床疗效。方法：将本科收治的90例消化性溃疡合并上消化道出血患者随机分为观察组和对照组,每组45例,观察组采用埃索美拉唑钠、羟氨苄青霉素及克拉霉素三联疗法进行治疗;对照组则采用雷尼替丁、羟氨苄青霉素和克拉霉素进行治疗,疗程为2周,治疗后比较两组的临床疗效。结果：观察组总有效率为97.8%,明显高于对组的77.8%,差异有统计学意义（P〈0.05）;观察组治疗后24、48hpH值升高情况优于对照组,差异有统计学意义（P〈0.05）;观察组幽门螺杆菌（Hp）根除率亦明显高于对照组,差异有统计学意义（P〈0.05）。结论：埃索美拉唑钠治疗消化性溃疡合并上消化道出血疗效显著,能迅速升高胃液pH值,增强抗生素对Hp的根除作用,适合临床上推广应用。     

益生菌对炎症性肠病的治疗作用分析

目的：观察益生菌治疗炎症性肠病的临床效果。方法：选取本院160例炎症性肠病患者,将患者随机分为治疗组和对照组。对对照组患者进行单纯柳氮磺胺吡啶片治疗,对治疗组患者使用柳氮磺胺吡啶片联合益生菌治疗,对比治疗效果。结果：治疗组有效率达到92．5％,出现并发症1例;对照组有效率仅为75．0％,出现并发症4例。治疗组治疗效果明显好于对照组（P〈0．05）,两组差异具有统计学意义。结论：益生菌可以明显提升炎症性肠病治疗效果,改善临床控制有效率,值得临床推广。     

蜂胶在炎症性肠病中相关作用的研究进展

炎症性肠病（inflammatory bowel disease,IBD）包括克罗恩病和溃疡性结肠炎,以慢性复发性肠炎为主要特征。其发病原因目前尚未完全明确,并且缺乏有效的靶向药物,治愈难度很大。蜂胶（propolis）是一种具有多种生物学活性及药理学功效的天然混合物。相关研究表明,富含多酚的蜂胶提取物表现出显著的抗炎...     

Pharmacotherapeutical options in inflammatory bowel disease: an update

Chronic inflamatory bowel disease (IBD) refers to two diseases: Crohn's disease (CD) and ulcerative colitis (UC). The etiology of IBD remains unknown. The understanding of the pathogenesis has expanded greatly over the last decade. The combination of genetic risk factors, abnormalities in the immune system, vascular and neural factors, and random environmental factors may all play an important role.Most treatments currently in use have multiple action. The choice of appropriate medical treatment is determined by the status (inductive or maintenance therapy) and severity of the disease and the potential for toxicity. Despite the variety of medical therapies available for the treatment of IBD, none is ideal. Ongoing research into the wellestablished drugs, as well as novel agents with more precise targets, may contribute to an optimal therapy of IBD in the near future. In this paper the current (5aminosalicylates, glucocorticosteroids, thioguanine derivatives, methotrexate, cyclosporin and infliximab) as well as some of the new (mycophenolate mofetil and thalidomide) therapeutic options are reviewed.     

A new target for the treatment of inflammatory bowel disease: Interleukin-37

Interleukin (IL)-37 belongs to the IL-1 cytokine family. It has anti-inflammatory effects on numerous autoimmune diseases such as asthma, psoriasis, inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), multiple sclerosis (MS) and rheumatoid arthritis (RA). Mechanistically, IL-37 plays an anti-inflammatory role by regulating the expression of inflammatory factors in two ways: binding extracellular receptors IL-18R or transferring into the nucleus with Smad3. IBD is a kind of idiopathic intestinal inflammatory disease with unknown etiology and pathogenesis. Recent researches had proved that IL-37 is negatively involved in the pathogenesis and development of IBD. Among various inflammatory diseases, IL-37 has been shown to regulate inflammatory development by acting on various immune cells such as neutrophils, macrophages (Mϕ), dendritic cells (DCs), T cells and intestinal epithelial cells. This review summarizes the biological role of IL-37, and its immunoregulatory effects on the immune cells, especially anti-inflammatory function in both human and experimental models of IBD.     

调节性T细胞与炎性肠病研究进展

炎性肠病(Inflammatory bowel disease,IBD)为非特异性炎症性肠病,主要包括溃疡性结肠炎(Ul-cerative colitis,UC)和克罗恩病(Crohn’s disease,CD)。其病因和发病机制尚未完全明确。已知肠道粘膜免疫系统异常反应所导致的炎症反应在IBD中发挥着重要作用。笔者对调节性T细胞在肠道免疫系统中的作用与IBD的发病机制相关性的研究进展做一综述,为临床治疗IBD的新药研究提供可能性的途径。     

Pharmacokinetics of intravenous methylprednisolone and oral prednisone in paediatric patients with inflammatory bowel disease during the acute phase and in remission

Objective: The present study was undertaken to evaluate the influence of inflammatory bowel disease on the pharmacokinetics of intravenous methylprednisolone and prednisolone (after oral administration of prednisone). Patients: Twelve children with inflammatory bowel disease, aged 12.3 years were studied during the active phase and in remission. In 6 patients the disease responded to oral prednisone while 6 did not respond. Methods: During the acute phase, intravenous methylprednisolone (2 mg · kg⁻¹) and oral prednisone (2 mg · kg⁻¹) were administered in a random order and blood was sampled over 48 h. Prednisone (2 mg · kg⁻¹) was readministered after remission. The concentrations of methylprednisolone and prednisolone were measured by high-pressure liquid chromatography. Results: During the acute phase, the systemic clearance of methylprednisolone was 0.98 (1 kg⁻¹ · h⁻¹) and the elimination half-life was 1.67 h. The area under the plasma concentration-versus-time curve of prednisolone was 4.00 and 3.20 · mg · h · l⁻¹ respectively during the active disease and remission, while its elimination half-life was 3.51 h during the acute phase and 2.42 h in remission. There were no pharmacokinetic differences between the patients who responded or did not respond to oral treatment. Conclusion: In children with inflammatory bowel disease, the initial response to corticosteroid therapy was not influenced by the pharmacokinetics of prednisolone and methylprednisolone. In addition, the pharmacokinetics of prednisolone was not modified by the inflammatory syndrome. Received: 5 December 1997 / Accepted in revised form: 14 April 1998     

The therapeutic potential of histamine receptor ligands in inflammatory bowel disease

In the intestine of patients suffering from inflammatory bowel disease concentrations of histamine are increased compared to healthy controls. Genetic ablation of histamine production in mice ameliorates the course of experimentally induced colitis. These observations and first pharmacological studies indicate a function of histamine in the pathogenesis of inflammatory bowel disease. However, a closer examination reveals that available data are highly heterogeneous, limiting the rational design of strategies addressing specific histamine receptor subtypes as possible target for pharmacological interaction. However, very recently first clinical data indicate that antagonism at the histamine receptor subtype H₄ provides a beneficial effect in at least the skin. Here, we discuss the available data on histamine effects and histamine receptor subtype functions in inflammatory bowel disease with a special emphasis on the histamine H₄-receptor.     

间充质干细胞在炎症性肠病治疗中的研究进展

现代医学研究表明炎症性肠病的发病机制与患者免疫失调具有密切关系。目前临床对于炎症性肠病治疗主要原则为消除活动性炎症以及改善免疫功能紊乱,比如氨基水杨酸制剂、免疫抑制剂以及糖皮质激素等均是临床治疗常用药物。间充质干细胞为具有自我复制以及多方向分化潜能的成体干细胞,对于组织修复以及免疫调节等均具有良好的治疗效果,目前在心肌梗死以及系统性红斑狼疮等疾病治疗中应用较为广泛。近些年很多专家将间充质干细胞应用于炎症性肠病的治疗中,取得了良好的效果。本文将这些新研究进展进行综述,以期为炎症性肠病的临床治疗提供借鉴。     

Alicaforsen for the treatment of inflammatory bowel disease

Introduction: Intracellular adhesion molecule-1 (ICAM-1), is a transmembrane glycoprotein of the immunoglobulin family, constitutively expressed on vascular endothelial cells and upregulated in inflamed colonic tissue. Alicaforsen, a 20 base ICAM-1 anti-sense oligonucleotide and highly selective ICAM-1 inhibitor, down-regulates ICAM-1 mRNA.

Areas covered: We review mechanism of action, pharmacokinetics, pre-clinical, clinical and safety data of alicaforsen for the treatment of ulcerative colitis (UC), pouchitis and Crohn’s disease (CD).

Expert opinion: After 6 weeks of treatment, topical alicaforsen was significantly more effective than placebo in inducing remission in patients with moderate-severe distal UC, with treatment effects lasting up to 30 weeks. No difference was observed in head-head comparison with mesalamine topical enema, although alicaforsen appeared to have more durable treatment effect. Clinical trials of an intravenous formulation in Crohn’s disease showed no significant treatment effect compared to placebo. An open-label trial in alicaforsen for pouchitis demonstrated encouraging results, now being assessed in a multi-national phase 3 trial. No major safety signals have been observed in UC patients treated with alicaforsen enemas. The potential as a novel therapy for pouchitis has led to orphan designation for this indication by the FDA and European Medicines Agency.     

上消化道大出血患者综合护理效果观察

目的观察上消化道大出血患者综合护理的效果。方法 45例上消化道大出血患者在积极治疗及常规基础护理上给予综合护理措施,观察综合护理的效果。结果治愈38例(84.44%),好转6例(13.33%),死亡1例(2.22%),总有效率为97.78%。结论综合护理干预可提高上消化道大出血患者治疗的成功率。     

Repeat stool testing for Clostridium difficile using enzyme immunoassay in patients with inflammatory bowel disease increases diagnostic yield

Abstract

Background:

The incidence and severity of Clostridium difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is increasing. CDI is diagnosed by toxin enzyme immunoassay (EIA) or real-time polymerase chain reaction (PCR) performed on stool samples. An earlier study evaluating EIA in IBD patients with CDI suggested that more than one stool sample be tested to increase diagnostic yield. We investigated whether repeat stool testing improves diagnostic accuracy for CDI in hospitalized IBD patients compared to hospitalized patients with CDI and no IBD.     

Targeted-mitochondria antioxidants therapeutic implications in inflammatory bowel disease

The role of the mitochondria, particularly its implications in cellular redox and oxidative balance is important for cell survival, and is involved in a variety of human diseases including inflammatory bowel disease (IBD). In this review we address mitochondria physiology and reactive oxygen species as cognate to IBD. Several studies have reported altered mitochondria function in intestinal epithelium in IBD. However, mitochondrion significance in this disease has not been much investigated. Finally, we suggest potential for antioxidants targeted to mitochondria in IBD therapy as a treatment strategy.     

英夫力西治疗炎症性肠病与肠道菌群改变的相关性研究

目的探讨使用英夫力西(IFX)治疗炎症性肠病与肠道菌群改变的关系。方法收集104例炎症性肠病患者,其中溃疡性结肠炎(UC)52例,克罗恩病(CD)52例,使用英夫力西治疗前后测定肠道菌群数量。另取30例健康志愿者新鲜粪便,定量培养进行菌群分析,同时测定三组C反应蛋白、血沉两项数据结果,分析其与肠道细菌组成变化的相关性。结果治疗后,UC组酵母菌(1.09±0.17)、肠球菌(5.01±0.36)和消化球菌(3.99±0.23)的数量显著下降,乳酸杆菌(7.95±0.69)的数量显著上升(P<0.01);CD组酵母菌(1.06±0.19)、肠球菌(4.91±0.37)和消化球菌(3.90±0.19)的数量显著下降,乳酸杆菌(8.07±0.76)的数量显著上升(P<0.01)。治疗后,UC组CRP(10.33±4.64)、ESR(9.10±4.11)水平降低(P<0.01);CD组CRP(7.31±4.68)、ESR(9.27±3.13)水平降低(P<0.01)。结论使用英夫力西治疗炎症性肠病患者后,酵母菌、肠球菌和消化球菌数量显著降低,乳酸杆菌数量显著增加,恢复到正常水平,炎症指标CRP和ESR下降,临床症状得到有效缓解。