Indikation für eine immunsuppressive Therapie bei chronisch entzündlichen Darmerkrankungen

Zusammenfassung Der immunsuppressiven Therapie kommt bei chronischen Darmerkrankungen gro?e Bedeutung zu, insbesondere dort, wo die Standardtherapie nicht den gewünschten Erfolg zeigt. Als Therapie der ersten Wahl gelten bei Colitis ulcerosa 5-Aminosalizyls?ure-freisetzende Medikamente, bei Morbus Crohn Kortikosteroide. Innerhalb der Gruppe immunsuppressiver Pr?parate gibt es erhebliche Wirkungsunterschiede. Darüber hinaus ist die Immunsuppression auch mit ernstzunehmenden Nebenwirkungen belastet. über den Stellenwert der Immunsuppression als Erg?nzung, m?gliche oder bei Unvertr?glichkeit notwendige Substitution der Standardtherapien von Colitis ulcerosa und Morbus Crohn wird hier eingehend referiert. Auch die Behandlung dieser Erkrankungen in der Schwangerschaft wird dabei erl?utert.     

Imaging biomarkers of inflammation <Emphasis Type="Italic">in situ</Emphasis> with fun ctionalized quantum dots in the dextran sodium sulfate (DSS) model of mouse colitis

Objective and design: Myeloperoxidase (MPO) and proinflammatory cytokines play an important role in the development of inflammation. These markers are generally measured using tedious ELISA procedures. In this study, a novel technique utilizing antibody conjugated quantum dot nanoparticles was developed to detect Myeloperoxidase, Interleukin-1α (IL-1α) and Tumor Necrosis Factor-α (TNF-α) in vivo in the dextran sodium sulfate (DSS) model of experimental colitis. Materials and methods: Colitis was induced in animals (n = 8 animals/group) by feeding 4% DSS solution ad libitum for seven to eight days. Quantum Dots (QDs) exhibiting fluorescence at various wavelengths were conjugated to MPO, IL-1α and TNF-α polyclonal antibodies and tested in vivo at various stages of colitis. Tissue sections obtained were imaged with confocal microscope. The image intensity obtained from the tissue specimen was correlated with clinical activity measured as Disease Activity Index (DAI). Results: Myeloperoxidase, IL-1α and TNF-α were visualized with quantum dots on various days of disease. The intensity of quantum dots increased with the increase in inflammation. The increase in intensity showed an excellent correlation with the DAI based on the clinical parameters. Conclusion: The study demonstrated that multiple biomarkers can be detected simultaneously and their quantitative expression correlated well with clinical disease severity. This novel technology should facilitate design of a novel optical platform for imaging various biomarkers of inflammation, early detection of acute and chronic disease markers and inflammation-mediated cancer markers. This detection may also facilitate determination of therapeutic success. Received 14 March 2007; returned for revision 8 May 2007; accepted by M. Parnham 27 June 2007     

Long-term treatment with anti-alpha 4 integrin antibodies aggravates colitis in G alpha i2-deficient mice

Targeted deletion of the heterotrimeric G protein, Galphai2, in mice induces lethal colitis closely resembling ulcerative colitis. In chronic colitis, migration of circulating leukocytes into the intestinal mucosa is partially dependent on alpha4 integrins. In previous studies, short-term administration of anti-alpha4 integrin antibodies has been shown to attenuate intestinal inflammation, and here we elucidate the effect of long-term administration of anti-alpha4 integrin antibodies on colitis in Galphai2(-/- )mice. Long-term blockade of alpha4 integrin significantly increased the severity of colitis in Galphai2(-/-) mice. The inflammation was confined to the colon, associated with increased cancer in situ, destruction of crypt architecture, and increased production of IL-1beta, TNF-alpha and IFN-gamma. Blockade of alpha4 integrin reduced the recruitment of activated T cells to the small intestine. In strong contrast, there were significantly higher numbers of activated T cells in the colonic lamina propria and epithelium, most probably due to in situ proliferation. Furthermore, treatment with alpha4 integrin antibodies induced decreased levels of total IgA and IgG in sera, whereas total IgM levels were unchanged. These new findings may have implications in the understanding of the progression of chronic intestinal inflammation.     

Persistent and selective effects of inflammation on smooth muscle cell contractility in rat colitis

Intestinal inflammation affects smooth muscle contractility contributing to altered motility, but changes to the individual smooth muscle cells are not well described. We used video microscopy to study the contractility of circular smooth muscle cells (CSMC) isolated from the rat mid-descending colon throughout the course of TNBS-induced colitis, measuring their shortening response to carbachol (CCh), 5-HT, histamine or high K⁺. In control CSMC, CCh caused a maximal shortening response of 28 (2%), similar to that for 5-HT of 27 (1%), but by day 4 of colitis, these responses were decreased by 35% and 37%, respectively. By day 36, all aspects of cholinergic contraction returned to control levels, while 5-HT-induced contraction remained significantly attenuated. In contrast, the contractile responses to histamine remained similar at all time points. K⁺-induced contraction was impaired only on day 4, and the maximal response remained substantially greater than CCh or 5-HT. Colitis caused a 121% increase in CSMC length by day 2 that persisted through day 36, independent evidence for phenotypic change. We conclude that impaired CSMC contractility at both the receptor and non-receptor levels contribute to altered smooth muscle function during colitis. Persistent changes in contractile response remained detectable after resolution of inflammation, and similar events may occur in post-enteritis syndromes seen in humans.     

70. Ileorectostomie versus ileo-anale Anastomose mit Reservoir bei Colitis ulcerosa und Adenomatosis coli

Zusammenfassung Ca. 2000 Proktomucosektomien sind in den letzten Jahren durchgeführt worden als Alternative zur Proktocolektomie, aber auch zur Ileorectostomie bei AC und CU. Bei minimaler Operationsletalität ist die Rate der Frühkomplikationen (Ileus, Anastomoseninsuffizienz, Anastomosenstenose) nicht unbeträchtlich (> 10%). Die funktionellen Ergebnisse dagegen sind nach einer Phase der Adaptation vorwiegend gut. Die nicht unerheblichen Risiken der Ileorectostomie bei AC (Entartungsrate bis 20%) und bei CU (Entzündungsrezidiv 20–30%, sekundäre Entartung um 5%) haben die Proktomucosektomie an gröeren Zentren zu einem etablierten Verfahren werden lassen.     

武汉市603例炎症性肠病并发症的临床调查

目的:分析武汉市炎症性肠病(IBD)并发症的临床特点,探讨其与病变程度、范围及治疗方式的关系。方法:回顾性收集1990-2005年武汉市5家医院经结肠镜及病理诊断为IBD病例共603例,其中溃疡性结肠炎(UC)521例,克罗恩病(CD)82例,分别观察各种并发症的发生频率及并发症与其他因素的关系。UC与CD间的差异及相关分析用χ2检验。结果:521例UC中,并发症34例(6.5%),82例CD中,并发症40例(48.8%)。重度UC和全结肠炎患者中并发症的发生率显著高于非重度和远端结肠炎患者(分别25.8%比3.9%,12.8%比4.9%,P<0.01)。有并发症的CD患者的手术史发生率显著高于无并发症患者(57.5%比14.3%,P<0.01),但CD病变范围与并发症的发生无相关性(P>0.05)。结论:CD并发症的发生率高于UC。UC的并发症与疾病病变程度和范围有关,而CD与手术方式有关。     

溃疡性结肠炎的中医药治疗进展

文章对近年来中医药治疗溃疡性结肠炎从病因病机、治疗方法,包括分型论治,以基础方加减,成药治疗及治则进行了文献综述,并对存在的问题及发展前景作了阐述。     

温针灸治疗慢性结肠炎疗效观察

目的:寻找提高治疗慢性结肠炎临床疗效的较佳方法。方法:将117例患者随机分为温针组(46例)、针刺组(39例)、药物组(32例)。温针组与针刺组皆取天枢、中脘、关元等穴,分别予温针灸与针刺治疗30min;药物组口服水杨酸柳氮磺胺吡啶片、硫唑嘌呤,均治疗3个疗程后观察疗效。结果:温针组总有效率为93.5%,针刺组为76.9%,药物组为75.0%,温针组疗效优于针刺组与药物组(均P<0.05),针刺组与药物组疗效相当(P>0.05)。结论:温针灸是治疗慢性结肠炎的较佳疗法,且无副作用。     

美沙拉嗪与柳氮磺吡啶治疗溃疡性结肠炎的效果比较

目的：比较美沙拉嗪与柳氮磺吡啶治疗溃疡性结肠炎的效果。方法选取安达市医院2012年8月—2014年8月收治的76例溃疡性结肠炎患者,根据入院顺序分为治疗组与对照组,每组38例。治疗组采用美沙拉嗪治疗,对照组采用柳氮磺吡啶治疗,比较两组的临床效果及不良反应发生情况。结果治疗组的总有效率高于对照组,不良反应发生率低于对照组,差异有统计学意义（ P﹤0.05）。结论美沙拉嗪治疗溃疡性结肠炎的效果优于柳氮磺吡啶,且不良反应少。     

A polyphenol-assisted IL-10 mRNA delivery system for ulcerative colitis

With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.