维得利珠单抗治疗炎症性肠病的研究进展

炎症性肠病是一种慢性非特异性肠道炎症性疾病,探索一种疗效佳、副作用少的药物是临床治疗炎症性肠病的重点研究内容.维得利珠单抗是一种通过阻断肠道选择性淋巴细胞转运发挥治疗效果的特异性针对α4β7整合素的人源化单克隆抗体.文章系统总结维得利珠单抗治疗炎症性肠病的作用机制、临床疗效及安全性评价,为炎症性肠病的临床治疗提供参考.     

炎症性肠病传统治疗的常用药物

炎症性肠病（inflammatory bowel disease,IBD）是慢性非特异性炎症,包括溃疡性结肠炎（ulcerative colitiS,UC）和克罗恩病（Crohn sdisease,CD）,其发病机制可能由感染、遗传、免疫等因素作用于易感人群,使肠道免疫反应紊乱导致肠组织炎症病变与结构破坏所致。炎症性肠病的传统药物包括氨基水杨酸制剂、糖皮质激素以及免疫抑制剂,其基本药理作用是抑制或调节过度的炎症反应,是治疗IBD的基础用药,现将这3类药物逐一介绍。     

临床药师对1例溃疡性结肠炎合并慢性乙肝患者的SOAP模式药学监护

摘要：炎症性肠病是一种慢性非特异性肠道炎症性疾病,包括溃疡性结肠炎和克罗恩病。肝炎病毒感染是炎症性肠病患者中常见的病毒感染之一。炎症性肠病合并乙肝病毒感染的患者由于接受免疫抑制药或生物制剂治疗可能会导致乙肝病毒复制活跃、肝功异常,甚至肝衰竭的风险。临床药师结合溃疡性结肠炎及慢性乙肝的治疗原则和诊疗方案,运用SOAP工作模式参与1例溃疡性结肠炎合并慢性乙肝患者的治疗药物调整,并对药物疗效及不良反应等实施全程药学监护,及时发现药物治疗问题,向医师提出合理建议保证患者用药安全性和有效性。     

核受体作为炎症性肠疾病治疗靶点的研究进展

炎症性肠疾病是一种慢性肠道炎症疾病,其发病机制尚不明确,目前多认为与炎症和肠黏膜损伤有关。核受体是一种重要的转录调节因子,包括孕烷X受体(pregnane X receptor,PXR)、法尼酯X受体(farnesoid X receptor,FXR)和组成型雄甾烷受体(constitutive androstane receptor,CAR)等。近年深入研究发现,核受体可以通过抑制炎症信号通路、调节肠道紧密连接蛋白及代谢酶的表达减轻肠道炎症,并维持肠黏膜屏障功能,在炎症性肠疾病肠道保护方面发挥重要作用。因此,本文综述核受体PXR、FXR和CAR对炎症性肠疾病肠道的保护作用机制,为以核受体为靶点的炎症性肠疾病药物治疗提供新思路。     

艾克曼菌与炎症性肠病的研究进展

肠道微生物的生态失调是引起胃肠道疾病的主要原因之一.艾克曼菌是一种肠道细菌,在平衡肠道细菌、维持肠道黏膜生态、缓解肠道黏膜炎症、调节人体糖和脂类的代谢,提高癌症免疫治疗方面有效果.炎症性肠病是累及回肠、直肠、结肠的一种特发性肠道炎症性疾病,常见治疗药物有氨基水杨酸盐、糖皮质激素、免疫抑制剂和生物制剂等,但临床疗效欠佳,患者需长期服药,且症状易有反复.本文综述艾克曼菌与炎症性肠病的研究进展.     

黄芩苷治疗炎症性肠病的作用机制研究进展

炎症性肠病是一种以慢性、复杂性、免疫介导为特点的炎症性疾病,结肠黏膜免疫系统在其发生发展过程中起到了重要作用。黄芩苷是从传统中药黄芩中提取分离出的一种黄酮衍生物,具有显著的药理活性,包括抗炎、调节免疫、抗氧化等。黄芩苷通过影响免疫细胞调节肠道炎症反应、调节免疫活性因子影响肠道免疫、调控信号通路调节肠道免疫、多靶点多角度影响肠道屏障等多种环节、多条通路、多个靶点共同作用来实现治疗炎症性肠病。综述了黄芩苷治疗炎症性肠病的作用机制,以期为进一步开展相关研究提供参考。     

炎症性肠病的认识与治疗进展

炎症性肠病（Inflammatoryboweldisease,IBD）是一组不明原因的慢性肠道炎症性疾病,包括溃疡性结肠炎（Ulcerativecolitis,UC）和克罗恩病（Crohn’sdisease,CD）.前者又称非特异性溃疡性结肠炎,是一种原因不明的直肠和结肠的炎症,病变主要限于大肠黏膜与黏膜下层。后者为一种慢性肉芽肿性炎症,病变可累及胃肠道各部位,而以末段回肠及临近结肠为主,多呈节段性、非对称性分布。炎症性肠病的发病机制尚未阐明,目前认为是基因上易感人群对肠道共生微生物产生的过度的先天或后天免疫反应所导致的。近几年,随着深人的基础研究和临床验证,炎症性肠病的诊断与治疗又有了新的进展。     

纳米颗粒在医学领域的应用现状和毒性问题

纳米颗粒的发展为生物医学领域带来革新性突破,其凭借独有的特性在靶向治疗、分子影像、早期诊断及药物转运等方面发挥重要作用.纳米颗粒的毒性作用是限制其临床应用推广的主要原因之一.本文综述纳米颗粒在生物医学中的应用现状和毒性问题.     

免疫抑制剂治疗炎症性肠病的研究进展

炎症性肠病在临床较为常见,具有慢性、复发性高等特点,可进一步导致肠道黏膜损伤、出血、穿孔等病症,严重影响患者生活质量。临床认为,炎症性肠病的发生发展与肠道微生态、肠道上皮屏障、免疫功能三者互相作用有关。在治疗方面,硫唑嘌呤、甲氨蝶呤以及环孢素A等免疫抑制剂是目前临床上常用的治疗炎症性肠病的药物,但长期用药可能导致不良反应,影响治疗效果及用药安全性。本文针对炎症性肠病的发病机制及免疫抑制剂治疗效果进行综述,以期为临床规范用药提供参考。     

英夫利西单抗治疗克罗恩病的护理

炎症性肠病是一种病因尚不明确的慢性非特异性肠道炎症性疾病,包括溃疡性结肠炎和克罗恩病,病程长,患者心理压力大,易复发,严重影响患者的生活质量。注射用英夫利西单抗（Infliximab,商品名为类克）,为单克隆抗体,2008年我国炎症性肠病诊治共识意见中推荐用于激素和免疫抑制剂治疗无效的重度克罗恩病[1]。有国内学者进行了英夫利西单抗治疗     

9例腹部术后早期炎性肠梗阻的诊断与治疗

目的：总结9例腹部术后早期炎性肠梗阻（early postoperative inflammatory small bowel obstructon,EPISBO）患者的临床特点及诊治情况,为该病的正确处置奠定理论基础。方法：对本院2009年2月～2011年3月发生的9例腹部术后致早期炎性肠梗阻的患者临床资料、治疗方法进行回顾性分析。结果：1例患者疑肠坏死立即实施手术并行粘连松解小肠排列术,余8例患者均行保守治疗获得成功。结论：腹部术后早期炎性肠梗阻治疗以保守治疗为首选,有效的胃肠减压、肠外营养和促进肠管炎症水肿消退药物的运用是治疗本病的关键。     

Inhibition of intestinal macrophage chemotaxis to leukotriene B4 by sulphasalazine, olsalazine, and 5-aminosalicylic acid

Purified intestinal macrophages obtained at resections for colonic neoplasms were investigated for chemotaxis to leukotriene B4 (LTB4) by the Millipore filter assay and leading front technique. Possible inhibition by drugs effective in the treatment of chronic inflammatory bowel disease (sulphasalazine, olsalazine, its active moiety 5-aminosalicylic acid (5-ASA), and the 5-ASA metabolite N-acetylated-5-ASA (ac-5-ASA)) was tested at therapeutic colonic concentrations of 0.01-10 mM. Leukotriene B4 at a dose of 10 nM was equipotent with casein (5 g litre-1) as regards chemoattraction of macrophages. Sulphasalazine, olsalazine and 5-ASA were potent inhibitors of macrophages chemotaxis to LTB4 with IC50 values of 0.43, 0.39 and 0.24 mM, respectively. These concentrations are below the lowest concentration of 5-ASA (2 mM) in the colonic lumen during conventional sulphasalazine treatment of patients with chronic inflammatory bowel disease. The inhibition of macrophage chemotaxis by these drugs may be important for this limitation of the local inflammatory process in chronic inflammatory bowel disease, and may in part explain the beneficial effect of systemic and local treatment with sulphasalazine. Leukotriene B4 appears to be an important inflammatory mediator for the activation of macrophages in colonic inflammation.     

Review article: a critical approach to new forms of treatment of Crohn's disease and ulcerative colitis

Most patients with inflammatory bowel disease can be managed with conventional immunosuppressive therapy. The choice of agents to prevent relapses of inflammatory bowel disease must be based on efficacy, toxicity and cost. Studies in animal models of inflammatory bowel disease indicate that chronic intestinal inflammation results from enhanced immune responses to bacteria that are present normally in the lumen. Loss of tolerance, an abnormal function or defective healing of the mucosal barrier may all give raise to chronic intestinal inflammation. This hypothesis is the basis of new therapies aimed at either decreasing the levels of luminal bacterial antigens and/or selectively blocking detrimental mucosal immune responses. Anti-TNF is an example of this novel approach that is very effective in Crohn's disease. The use of biological therapy is costly, however, and the long-term complications are not yet known. The recent increase of tuberculosis in patients treated with anti-TNF indicates that careful monitoring is necessary. It is clear that the new forms of treatment may play an important role in tailoring the appropriate drug to a specific group of patients. However, for the time being, fine-tuning in the use of conventional immunosuppression is necessary. New knowledge in the pharmacogenetics of these compounds allows improvements to be made in their use. It is to be hoped that a critical approach in the use of current and future drugs, taking into account the advances in the aetiopathogenesis of inflammatory bowel disease, will contribute to the quality of life of patients with inflammatory bowel disease.     

A critical approach to new forms of treatment of Crohn's disease and ulcerative colitis

Most patients with inflammatory bowel disease can be managed with conventional immunosuppressive therapy. The choice of agents to prevent relapses of inflammatory bowel disease must be based on efficacy, toxicity and cost. Studies in animal models of inflammatory bowel disease indicate that chronic intestinal inflammation results from enhanced immune responses to bacteria that are present normally in the lumen. Loss of tolerance, an abnormal function or defective healing of the mucosal barrier may all give raise to chronic intestinal inflammation. This hypothesis is the basis of new therapies aimed at either decreasing the levels of luminal bacterial antigens and/or selectively blocking detrimental mucosal immune responses. Anti-TNF is an example of this novel approach that is very effective in Crohn's disease. The use of biological therapy is costly, however, and the long-term complications are not yet known. The recent increase of tuberculosis in patients treated with anti-TNF indicates that careful monitoring is necessary. It is clear that the new forms of treatment may play an important role in tailoring the appropriate drug to a specific group of patients. However, for the time being, fine-tuning in the use of conventional immunosuppression is necessary. New knowledge in the pharmacogenetics of these compounds allows improvements to be made in their use. It is to be hoped that a critical approach in the use of current and future drugs, taking into account the advances in the aetiopathogenesis of inflammatory bowel disease, will contribute to the quality of life of patients with inflammatory bowel disease.     

The mode of action of the aminosalicylates in inflammatory bowel disease

Sulphasalazine and other 5-aminosalicylic acid (5-ASA)-containing drugs are used in the treatment of acute inflammatory bowel disease and in the maintenance of clinical remission. Despite their use for over 50 years, the mechanism of action of this class of drugs remains uncertain, although a number of possibilities are discussed in this review. It seems likely that the aminosalicylates are important free radical scavengers, can reduce leukotriene production and can inhibit the cellular release of interleukin-1, all of which are likely to be important in reducing the acute inflammatory response in inflammatory bowel disease, The effects of these drugs on prostaglandin production are more contentious, but it appears that 10^-5 to 10^-4 M concentrations stimulate production of prostaglandins which may be cytoprotective, while higher doses of these drugs inhibit prostaglandin production. The aminosalicylates may maintain remission in inflammatory bowel disease by preventing leucocyte recruitment into the bowel wall. The drugs inhibit the chemotactic response to leukotriene B₄, reduce the synthesis of platelet activating factor and also inhibit leucocyte adhesion molecule upregulation.     

Nonsteroidal anti-inflammatory drugs and inflammatory bowel disease: current perspectives.

Mechanisms underlying the gastric toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) have been extensively investigated, whereas those leading to intestinal damage are not completely understood. Several hypotheses have been put forward on the pathophysiology of intestinal damage by NSAIDs: enhanced intestinal permeability, inhibition of cyclooxygenase (COX), enterohepatic recirculation, and formation of adducts. The effects of COX-2 selective inhibitors, which appear to have better gastric tolerability when compared to nonselective NSAIDs, on normal and inflamed intestinal mucosa (as in Crohn's disease or ulcerative colitis) are still largely unexplored. If COX-2 inhibition plays a key role in suppressing the inflammatory process, recent evidence suggests that COX-2 products are involved in maintaining the integrity of intestinal mucosa, in the healing of gastrointestinal ulcers and in the modulation of inflammatory bowel disease (IBD). Animal models of intestinal inflammation have so far yielded conflicting results on the effects of COX-2 selective inhibitors on the intestinal mucosa. It is now clear that NSAIDs do not act through cyclooxygenase inhibition, but also have different targets such as nuclear factor-kappaB and/or peroxisome proliferator-activated receptors gamma. The peculiar pharmacological profile of each compound may help to explain the different impact of each NSAID on the inflammatory process and on IBD. Notably, the salicylic acid derivative 5-ASA is widely used in the treatment of IBD and is believed to act through nuclear factor-kappaB inhibition. Although the use of COX-2 selective inhibitors remains contraindicated in patients with IBD, studying their effects on intestinal mucosa may offer new insights into their subcellulars mechanisms of action and open new avenues for the development of novel therapies for IBD.     

Application of chitosan/alginate nanoparticle in oral drug delivery systems: prospects and challenges

Oral drug delivery systems (ODDSs) have various advantages of simple operation and few side effects. ODDSs are highly desirable for colon-targeted therapy (e.g. ulcerative colitis and colorectal cancer), as they improve therapeutic efficiency and reduce systemic toxicity. Chitosan/alginate nanoparticles (CANPs) show strong electrostatic interaction between the carboxyl group of alginates and the amino group of chitosan which leads to shrinkage and gel formation at low pH, thereby protecting the drugs from the gastrointestinal tract (GIT) and aggressive gastric environment. Meanwhile, CANPs as biocompatible polymer, show intestinal mucosal adhesion, which could extend the retention time of drugs on inflammatory sites. Recently, CANPs have attracted increasing interest as colon-targeted oral drug delivery system for intestinal diseases. The purpose of this review is to summarize the application and treatment of CANPs in intestinal diseases and insulin delivery. And then provide a future perspective of the potential and development direction of CANPs as colon-targeted ODDSs.     

Bone and joint diseases in inflammatory bowel disease

The intestinal and articular systems are closely linked in inflammatory bowel disease. Clinical and immunological studies support an important aetio-pathogenetic link between intestinal and articular inflammation. There is increasing evidence for a negative link between bone mass density and intestinal inflammation. This paper will focus on the prevalence, aetio-pathogenesis and treatment of arthritis (peripheral, sacroiliitis and spondylitis) and osteoporosis in inflammatory bowel disease.