Treatment of inflammatory bowel disease (IBD)

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, which includes Crohn's disease (CD) and ulcerative colitis (UC). These diseases have become important health problems. Medical therapy for IBD has advanced dramatically in the last decade with the introduction of targeted biologic therapies, the optimization of older therapies, including rugs such as immunomodulators and 5-aminosalicylic acid (5-ASA), and a better understanding of the mucosal immune system and the genetics involved in the pathogenesis of IBD. The goal of IBD therapy is to induce and maintain remission. The current treatment paradigm involves a step-up approach, moving to aggressive, powerful therapies only when milder therapies with fewer potential side effects fail or when patients declare themselves to have an aggressive disease. This review focuses on the current treatments for inflammatory bowel disease.     

溃结康对三硝基苯磺酸诱导大鼠炎症性肠病的作用研究

目的 观察溃结康经灌肠给药对三硝基苯磺酸(trinitrobenzene sulfonic acid,TNBS)诱导的炎症性肠病动物模型的作用,以明确溃结康对炎症性肠病的治疗作用,为探索药物应用于克罗恩病治疗的可行性。方法 采用TNBS灌肠的方法诱导大鼠溃疡性结肠炎模型,观察溃结康灌肠给药对大鼠疾病活动指数(DAI)评分、血清干扰素-γ(IFN-γ)、白介素-l(IL-1)、白介素-4(IL-4)、白介素-10(IL-10)和肠黏膜中谷氨酰胺(Glutamine,Gln)的含量的影响,并观察药物对大鼠结肠组织损伤评分以及病理学的影响。结果 TNBS诱导的结肠炎模型可引起动物体质量下降,肉眼血便或便潜血阳性,DAI评分增高,血清IFN-γ,IL-1升高,肠黏膜Gln降低,溃结康不同剂量组灌肠给药可改善TNBS引起的DAI评分增高以及降低血清IFN-γ、IL-1水平,升高肠黏膜Gln,缓解结肠炎组织学变化,其中尤以溃结康高剂量组作用更为明显。结论 溃结康灌肠给药对缓解TNBS诱导结肠炎模型有一定治疗作用。     

Unravelling the pathogenesis of inflammatory bowel disease

外泌体是细胞分泌/衍生的囊泡状纳米颗粒,其介导了一种新型的细胞间通讯方式。细胞分泌型mRNA和microRNAs(miRNAs)可随着外泌体在细胞间进行功能转移,并被送入受体细胞作为内源性miRNAs发挥作用,同时调节多个目标基因或信号。外泌体等外囊泡介导的细胞间通讯以及肠道微生物群−宿主细胞通讯参与了炎症性肠病发生、发展相关的状况。本文回顾外泌体在细胞间通讯的方式作用,从细胞间通讯的角度讨论外泌体在炎症性肠病的发病机制、病情进展、治疗诊断中的作用及其临床应用前景。

     

Effect of fruit extract of Fragaria vesca L. on experimentally induced inflammatory bowel disease in albino rats

Aim:

Ulcerative colitis and Crohn’s disease are chronic recurrent inflammatory bowel disease (IBD) of unknown origin. Oxidative stress is believed to be a key factor in the pathogenesis and perpetuation of the mucosal damage in IBD.

Materials and Methods:

Ethanolic extract of Fragaria vesca (EFFV) fruits was prepared by percolation method and subjected to oral toxicity testing using OECD guidelines. Albino rats were pretreated orally for 5 days with 3% gum acacia in control, EFFV 500 mg/kg in test and 5-aminosalisylic acid (5-ASA) 100 mg/kg in standard groups. Colitis was induced by transrectal administration of 4% acetic acid on 5^th day. All the animals were sacrificed with ether overdose 48 hours after colitis induction, and 10 cm colon segment was resected from proximal end. Colon was weighed (for disease activity index) and scored macroscopically and microscopically after histological staining. Biochemical assessments included myeloperoxidase (MPO) and tissue catalase (CAT), glutathione (GSH) and superoxide dismutase (SOD) measurements. Statistical analysis was done using one-way analysis of variance (ANOVA) followed by Dunnett’s “t” test.

Results:

EFFV showed significant (P < 0.05) prevention of increase in colon weight and disease activity index along with decrease in macroscopic and microscopic lesion score as compared to control group. Significant improvement was observed in the levels of MPO, CAT and SOD, except GSH (P < 0.05). However, the effect of EFFV was significantly less than 5-ASA (P < 0.05).

Conclusions:

EFFV at 500 mg/kg showed significant amelioration of experimentally induced IBD, which may be attributed to its antioxidant and anti-inflammatory properties.     

Evaluation of new therapies for inflammatory bowel disease

The pathophysiology of inflammatory bowel disease (IBD) is gradually being unravelled and new therapies are being developed to target the disturbed biological processes. This article outlines the clinical features of IBD, its current therapy and pathogenesis. The difficulties for clinical pharmacologists and gastroenterologists associated with designing, executing and interpreting clinical trials in IBD are then discussed. The final section reviews methods that can used to demonstrate the pharmacological actions of new treatments in patients with IBD. It is emphasized that proof of the therapeutic efficacy of a novel agent with a specific mechanism of action yields not only clinical benefit to patients with IBD, but also indicates the importance of the targeted biochemical pathway in the pathogenesis of the disease.     

Role of probiotics in inflammatory bowel disease and intestinal infections

Bacteria are present throughout the GI tract but their pattern and concentrations vary greatly. Probiotics are living microorganisms that belong to the normal intestinal flora and are important to the health and well-being of the host. The concept of probiotic therapy is still controversial; there are many data from in vitro and animal studies, however, to date the beneficial effects of probiotics in humans have mostly been demonstrated under poorly defined experimental conditions. Several experimental and clinical observations suggest a role for the intestinal microflora in inflammatory bowel disease (IBD) pathogenesis and there is increasing evidence supporting the potential therapeutic role for probiotics in the treatment of IBD. The use of probiotics to treat GI infections has produced contrasting results; their efficacy in the prevention or treatment of infective diarrhoea was evaluated in a large number of studies; however, the most convincing evidence of their benefit concerns rotavirus infection in children. Future research needs to focus on obtaining more precise information on the composition of the enteric microflora and the mechanisms of action of probiotics.     

沙利度胺治疗葡聚糖硫酸钠诱导小鼠炎症性肠病及其机制研究

目的考察沙利度胺对葡聚糖硫酸钠诱导小鼠炎症性肠病的治疗作用,并探讨其可能的作用机制。方法 60只Balb/c小鼠按体质量随机分为对照组、模型组、柳氮磺吡啶(200 mg/kg)组以及沙利度胺30、60、120 mg/kg剂量组,每组10只。试验当天为第1天,试验期间葡聚糖硫酸钠诱导组饮用2.5%葡聚糖硫酸钠饮用水,对照组则饮用纯净水。从试验第5天开始,各给药组开始ig给予相应药物,给药容积10 m L/kg,1次/d,对照组和模型组则给予相应体积的0.5%MC,直至第12天结束试验。试验期间,每天记录各动物体质量变化。试验结束后,测量各动物结肠长度,观察各组结肠组织病理学改变和评分,ELISA法检测结肠组织肿瘤坏死因子-α(TNF-α)含量。结果沙利度胺在120 mg/kg剂量下改善葡聚糖硫酸钠诱导小鼠体质量下降症状,改善小鼠的结肠缩短,降低结肠组织TNF-α含量,减少炎症细胞对结肠组织的浸润。结论沙利度胺对葡聚糖硫酸钠诱导小鼠炎症性肠病呈现较好治疗作用,该作用可能与沙利度胺对TNF-α的调节作用有关。     

Effects of Cream Containing Ficus carica L. Fruit Extract on Skin Parameters: In vivo Evaluation

This study was aimed to investigate the effects of cream containing Ficus carica L. fruit (Fig) extract on various skin parameters such as skin melanin, erythema, moisture content, trans-epidermal water loss and sebum. For this purpose, formulation with 4% concentrated extract of F. carica fruit and base without extract were developed. Base served as a control. Both base and formulation were applied to the cheeks of human volunteers for 8 weeks to investigate the effects on different skin parameters using non-invasive bioengineering instruments. Formulation decreased the skin melanin, trans-epidermal water loss and skin sebum significantly. Formulation increased the skin hydration significantly and insignificant effects on skin erythema. We concluded that a stable topical cream (w/o emulsion) containing F. carica fruit extract have effects on skin melanin, trans-epidermal loss, hydration values and sebum content and possibly could be used against for hyper pigmentation, acne, freckles and wrinkle.     

氨基水杨酸类药物治疗炎症性肠病的应用进展

5-氨基水杨酸及其前体药物是临床治疗炎症性肠病和预防其复发的药物.柳氮磺胺吡啶是应用时间最久的5-氨基水杨酸前体药物,但因其不良反应较大而迫使人们不断寻求安全、有效的新型5-氨基水杨酸制剂.近年来新型5-氨基水杨酸前体药物的研究有了较大进展,本文简要综述其进展情况.     

治疗炎症性肠病的纳米颗粒研究进展

炎症性肠病是一组慢性非特异性肠道炎症性疾病,目前临床上常用的传统非靶向药物可以缓解患者症状,但不能终止黏膜炎症活动、疾病发展,且严重的不良反应限制了这些药物的应用。纳米颗粒由于其独特的大小和物理特性,能够通过黏液层将负载药物传递到肠道细胞,也可以通过内吞作用被巨噬细胞吞噬,从而调节肠道的免疫环境,此外,纳米颗粒还具有改变药物特性的潜力。总结了治疗炎症性肠病的合成纳米颗粒、天然纳米颗粒的研究情况,以期为炎症性肠病的治疗带来新的机遇。     

Management of patients with inflammatory bowel disease and spondyloarthritis

Introduction: More than half of the patients with inflammatory bowel disease (IBD) experience at least one extra-intestinal manifestation (EIM). The most common EIM in patients with IBD is spondyloarthritis (SpA). Microscopic intestinal inflammation is documented in almost 50% of the patients with SpA.

Areas covered: We give an overview of the classification, the epidemiology and the diagnosis of IBD and SpA. The treatment goals, the pharmacologic management options and the available treatment guidelines in IBD patients with SpA are discussed.

Expert commentary: The coexistence of IBD and SpA generates challenges and opportunities for both the gastroenterologist and the rheumatologist. The potential of drugs with a gut-specific mode of action in the treatment of IBD-related arthritis warrants further exploration.     

Antioxidant and antilipid peroxidation potential of supercritical fluid extract and ethanol extract of leaves of vitex negundo linn

Supercritical fluid extract and ethanol extract of Vitex negundo Linn. were subjected to the chromatographic evaluation for identification of their constituents. Free radical scavenging activity of both extracts was studied by subjecting them to DPPH assay. IC(50) values of ethanol and supercritical fluid extract of Vitex negundo indicate that ethanol extract has stronger reducing potential and ability to scavenge free radicals as compared to the supercritical fluid extract. The in vivo effect of extracts on lipid peroxidation was studied using ethanol induced oxidative stress model in rat. Ingestion of extracts for 14 days exhibited significant reduction in plasma MDA level of stressed animals. Ethanol extract exhibited higher in vivo antilipid peroxidation potential as compared to supercritical fluid extract which correlated well with radical scavenging potential of extract.     

Oral colon-specific therapeutic approaches toward treatment of inflammatory bowel disease

Introduction: Inflammatory bowel disease (IBD) is a chronic relapsing idiopathic disease. In clinical terms, most patients require lifelong medication associated with possible unpleasant adverse effects. Oral colon-specific drug delivery systems are designed to deliver therapeutic drugs to the inflamed colon to target pathophysiological manifestations of IBD. The aim is to maintain the drug with proper concentration in the inflamed colon, to enhance drug residence time and to minimize drug absorption by healthy tissues.

Areas covered: This review addresses the main barriers for colon-specific drug delivery from organism, tissue and cell levels, respectively. It also summarizes novel colon-specific therapeutic strategies using microparticles and nanoparticles.

Expert opinion: Oral colon-specific drug delivery represents a possible approach toward efficient treatment of IBD. As the environment of the gastrointestinal tract is harsh and intricate, this approach requires that drug carriers can respond to specific environmental factors of the inflamed colon, permitting stimulus-responsive release of loaded drugs to specific cells or even into specific organelles within cells.     

Hepatoprotective Activity of Ficus carica Leaf Extract on Rifampicin-Induced Hepatic Damage in Rats

Shade dried leaves of Ficus carica were extracted using petroleum ether (60-80°) and tested for antihepatotoxic activity on rats treated with 50 mg/kg of rifampicin orally. The parameters assessed were serum levels of glutamic oxaloacetate transaminase, glutamic pyruvic transaminase, bilirubin and histological changes in liver. Liver weights and pentobarbitione sleeping time as a functional parameter were also monitored. There was significant reversal of biochemical, histological and functional changes induced by rifampicin treatment in rats by petroleum ether extract treatment, indicating promising hepatoprotective activity.     

临床药师参与炎症性肠病多学科会诊的实践

目的:通过介绍临床药师炎症性肠病多学科(IBD-MDT)会诊的药学实践,为临床药师开展IBD-MDT药学服务提供参考。方法:介绍海南省人民医院IBD-MDT会诊的概况和工作流程;结合实践案例,总结分析IBD-MDT会诊的药学服务内容和工作模式。结果:临床药师可通过药物重整、治疗药物监测、药物治疗方案评估与制订、依从性评估及用药教育等方面发挥药学专业优势,参与IBD患者的诊治。结论:通过IBD-MDT会诊,临床药师可与临床形成专业合作、优势互补,提高医疗服务质量,优化慢病管理。     

化学诱导型结肠炎动物模型的研究进展

实验动物模型对于发现抗炎症性肠病的药物及探讨其发病机制具有重要作用。通过文献查阅,综述了目前用于炎症性肠病药理学研究的化学诱导型结肠炎动物模型的研究进展,从制备方法、模型特征、可能的致病机制和用途等方面进行了详细的论述。对于认知和了解炎症性肠病的发病机制及在实验中对IBD实验动物模型的选择提供一定的依据。     

Desensitization of patients with allergic reactions to immunosuppressives in the treatment of inflammatory bowel disease

Crohn's disease and ulcerative colitis are chronic, immune-mediated inflammatory bowel diseases (IBDs) of unknown etiology with high morbidity in patients who are not receiving adequate medical treatment. A variety of medical therapies are currently available, and much progress has been made to alleviate symptoms and restore quality of life. The mainstay of treatment in those with moderate to severe disease consists of medications that alter or suppress the body's immunologic attack on its own gastrointestinal tract. The medications currently in use are highly effective when given in the appropriate clinical context, but side effects are not uncommon and must be treated expeditiously when they occur. One class of immunosuppressive medication, 6-mercaptopurine and its prodrug azathioprine, is effective at inducing remission and improving the lives of patients with IBD. The most common side effects of these drugs are allergic reactions and rarely can they be severe and life threatening. These reactions can sometimes be overcome by desensitizing the immune system to the drug. This review emphasizes allergy to 6-mercaptopurine and azathioprine and the process of desensitization when these allergic reactions occur in order to continue use of this important class of medication in the total treatment of IBD.     

Novel therapies based on enhancement of gut innate immunity in inflammatory bowel disease

Inflammatory bowel disease (IBD), in particular Crohn's disease (CD) and ulcerative colitis (UC), results from several known and unknown genetic and environmental factors, altering the gut innate immunity and the gut adaptive immunity. The first genetic discoveries pointed to dysfunctions of the sensing systems in the intestinal tract towards dangerous as well as innumerable commensal bacteria of the gut lumen, confirming their role as main environmental factors. Recent advances in the pathophysiology of innate immunity are reviewed, concerning chiefly microbial–epithelial interactions, with the role of the mucus barrier (mucins, trefoil factors), the localisation of the microbiota normally absent beneath the mucus layer and present and invasive in IBD, the numerous defensive functions of the epithelial barrier that could be altered in IBD (tight junction proteins, defence receptors: Toll-like receptors, NOD2/CARD15, peroxysome proliferator activated receptor-γ (PPAR- γ), secretion of microcidal β-defensins, release of exosomes, autophagocytosis etc.). In the lamina propria, natural killer cells, macrophages and dendritic cells play an important role in innate immunity, particularly the dendritic cells, potent sensing and antigen- presenting cells, triggering either adaptive immunity with its potentially serious inflammatory consequences or inducing immunotolerance through T regulatory cells. By studying in-depth innate immunity, including the role of mesenteric fat in CD, it may be possible to discover the aetiological primary events of IBD and also to design more therapies based on enhancement of innate immunity. These therapies are reviewed with the impetus of various patented drugs and the still-too-rare randomised clinical trials: agents reinforcing the mucus barrier, the epithelial barrier and the lamina propria cell functions for innate immunity. As recent studies confirmed dysfunctions of granulocytes, particularly neutrophils in IBD, trials aimed at stimulating granulocytes and macrophages were interesting and gave encouraging results. PPAR-γ agonists are also effective in UC patients and may explain one of the modes of actions of sulfasalazine, beside its inhibition of the NF-κB. Many studies underlined the role of some probiotics in enhancement of the intestinal epithelial barrier function, but so far randomised clinical trials were positive only for the prevention and treatment of UC and pouchitis. Genetically modified probiotics delivering trefoil factor or IL-10 are very promising. Finally, treatments based on the enhancement of innate immunity might lower the risks of treatments based on reduction of adaptive immunity (immmunosuppressants and biologicals).