艾迪莎与柳氮磺胺吡啶治疗溃疡性结肠炎90例疗效比较

目的比较艾迪莎与柳氮磺胺吡啶治疗溃疡性结肠炎的疗效。方法将符合诊断标准的溃疡性结肠炎患者180例按数字随机表法分为治疗组和对照组,每组90例。所有患者均给予柔软、易消化、富含营养、富含维生素的饮食,同时按病情不同分别给予输血、补充铁剂等对症治疗。对照组同时口服柳氮磺胺吡啶片1.0g,4次/d。治疗组同时用艾迪莎,1.0/次;4次/d。2组均以20d为1个疗程。2组均在治疗2个疗程后观察疗效。结果痊愈率、总有效率治疗组分别为55.56%、93.33%,对照组分别为38.89%、78.89%。2组相比较有显著性差异(P<0.05)。治疗组患者腹痛、腹泻、脓血便及里急后重等症状改善情况均较对照组患者明显(P<0.01)。不良反应发生率治疗组为3.33%,对照组为14.44%。2组相比有率计学意义(P<0.01)。结论艾迪莎与柳氮磺胺吡啶相比,艾迪莎治疗溃疡性结肠炎具疗效显著,可迅速改善症状、体征,减少了不良反应的发生,降低医疗成本的特点。     

柳氮磺胺吡啶的合成工艺改进

以4-氨基-N-(2-吡啶基)苯磺酰胺为起始原料,经过重氮化、偶合反应合成柳氮磺胺吡啶,通过控制偶合反应的p H,减少了副反应,同时考察了反应温度、反应时间、析晶溶剂、析晶温度等因素对收率和纯度的影响,确定了最佳工艺条件,收率85%,纯度98.9%,其结构经1H NMR和MS表征。     

慢性溃疡性结肠炎临床治疗分析

目的 探讨柳氮磺吡啶与逍遥丸联合治疗慢性溃疡性结肠炎的临床疗效。方法 选择2008年至2010年间在我院治疗的慢性溃疡性结肠炎病人,将他们随机分为治疗组与对照组,对照组给予西药常规治疗;治疗组除常规治疗外,还给予逍遥丸治疗。随访1年。结果 治疗组和对照组的总有效率为93.8%、53.6%,经χ2检验,2组总有效率和半年复发率均存在显著性差异(P<0.01)。结论 柳氮磺吡啶与逍遥丸联合治疗慢性溃疡性结肠炎可以快速控制病情、改善临床症状,提高总有效率减少复发。     

康体多联合锡类散治疗溃疡性结肠炎48例

目的观察康体多锡类散治疗溃疡性结肠炎的临床疗效。方法将溃疡性结肠炎患者随机分成观察组和对照组,观察组48例,应用锡类散口服,康体多保留灌肠,对照组47例,应用柳氮磺胺嘧啶和醋酸泼尼松口服。疗程均为4周。结果观察组总有效率为81.25%,对照组总有效率为76.60%,2组比较,无显著差异性。结论康体多联合锡类散治疗溃疡性结肠炎疗效好,副作用少,值得推广。     

硫普罗宁与炎症性肠病

目的就硫普罗宁与柳氮磺胺吡啶(SASP)对溃疡性结肠病的治疗效果进行评估。方法将在我院就诊的溃疡性结肠炎患者40例随机分成2组。硫普罗宁与柳氮磺胺吡啶(SASP)组;单纯(SASP)组各20例,前者口服硫普罗宁0.2g/d,tid,同时口服SASP1g/d,tid,4周为1个疗程;后者口服SASP1g/d4次,4周为1个疗程。结果比较2组治疗,结果加服硫普罗宁组有效17例,3例症状改善不明显;单纯(SASP)组9例有效,11例症状不明显。结论SASP与硫普罗宁治疗溃疡性结肠炎效果明显。     

一种柳氮磺吡啶杂质Ⅰ磺酸乙酯杂质的制备方法

本文主要研究一种柳氮磺吡啶杂质Ⅰ磺酸乙酯杂质的制备方法.此杂质为柳氮磺吡啶杂质Ⅰ结构上的磺酸基团和生产工艺中用到的乙醇缩合成的磺酸乙酯,化学名为5-((4-(磺酸乙酯)苯基)偶氮)-2-羟基苯甲酸,此杂质具有遗传毒性和致癌性杂质的警示结构,但目前的PubChem的CCRIS等相关数据库并没有此杂质的毒理研究数据,因此合...     

柳氮磺吡啶与维生素K3联合应用对神经胶质瘤C6细胞增殖的影响

目的观察柳氮磺吡啶(SAS)与维生素K3(VK3)联合应用对神经胶质瘤C6细胞增殖的影响,并探讨二者的作用机制。方法取对数生长期的大鼠神经胶质瘤C6细胞,分别加入不同浓度的SAS、VK3,MTT法检测各组细胞增殖水平,RT-PCR及Western blot法分别检测细胞IKBα基因mRNA的转录水平及P65蛋白的表达水平;TUNEL法检测细胞凋亡。结果SAS单独作用于C6细胞,呈剂量依赖性地抑制细胞增殖;SAS与VK3联合作用,抑制细胞增殖效果更明显。SAS与VK3联合作用4、8、12h,C6细胞IKBα基因mRNA的转录水平逐渐下降,4h时,C6细胞P65蛋白的表达水平增加,而8、12h时降低。SAS与VK3联合作用,TUNEL阳性细胞率明显高于空白对照组及SAS、VK3单独作用组。结论SAS与VK3联合应用,可通过影响NF-κB/IKBα基因的表达,抑制C6细胞增殖,二者联合应用可减少单独药物用量,减轻对正常细胞的毒性作用。     

腐殖酸钠保留灌肠治疗溃疡性结肠炎40例临床观察

观察单纯腐殖酸钠保留灌肠治疗轻中度溃疡性结肠炎的临床疗效。观察组40例,2%的腐殖酸钠液100mL保留灌肠;对照组40例,柳氮磺吡啶片SASP1.0,3次/天口服,2组对照比较治疗效果。试验结果表明,观察组有效率为90%,对照组有效率为72.5%,2组治疗效果经统计学处理有明显差异,达P<0.05显著水平。因此,可以看出,观察组疗效明     

黄腐植酸钠治疗溃疡性结肠炎疗效及对免疫功能影响

本文就我院16年来,经纤维结肠镜(下称纤结镜)并病理报告诊断的溃疡性结肠炎Uicove Colitis(下称UC)68例。使用黄腐植酸钠Fumid Acide(下称FA)及对照治疗8周疗效:FA组46例,有效率91.3％,对照组22例,有效率45.5％。两组一年期满随访到FA组34例,复发3例占8.8％和对照组20例,复发15例占75％。同步检测免疫指标结果:FA组血清IgG、M总补体CH_(50)与对照组比较无显著差异。但FA组IgA、C_3和血色素各总量的增加与淋巴细胞转化率的改善优于对照组。作者认为FA对UC疗效较满意对人体免疫功能有调节作用。本文对FA作用机理与免疫功能影响进行讨论。     

溃疡性结肠炎50例内镜分析及治疗

目的观察溃疡性结肠炎内镜下表现及临床治疗疗效。方法对我院消化科2009年1月至2010年3月住院的有长期反复下腹部不适伴腹痛、腹泻等消化道症状的160例患者行结肠镜、病理活检,根据病理及内镜诊断结果进行综合治疗。结果 160例患者经内镜检查确诊为溃疡性结肠炎的患者为67例,加病理活检确诊为溃疡性结肠炎的患者共50例,占总患者的31.25%,经内镜诊断确诊率为78.13%。50例溃疡性结肠炎患者内镜下表现主要有肠粘膜弥漫性充血水肿或伴糜烂溃疡,经治疗后患者临床症状随访3个月无复发。结论应用结肠镜检查消化道异常患者并行活检取病理是目前最可靠的确诊方法,对良性溃疡患者镜下综合治疗,治愈率高,值得临床广泛推广。     

Microbiota-Immune Interactions in Ulcerative Colitis and Colitis Associated Cancer and Emerging Microbiota-Based Therapies

Ulcerative colitis (UC) is a chronic autoimmune disorder affecting the colonic mucosa. UC is a subtype of inflammatory bowel disease along with Crohn’s disease and presents with varying extraintestinal manifestations. No single etiology for UC has been found, but a combination of genetic and environmental factors is suspected. Research has focused on the role of intestinal dysbiosis in the pathogenesis of UC, including the effects of dysbiosis on the integrity of the colonic mucosal barrier, priming and regulation of the host immune system, chronic inflammation, and progression to tumorigenesis. Characterization of key microbial taxa and their implications in the pathogenesis of UC and colitis-associated cancer (CAC) may present opportunities for modulating intestinal inflammation through microbial-targeted therapies. In this review, we discuss the microbiota-immune crosstalk in UC and CAC, as well as the evolution of microbiota-based therapies.     

Protective Effect of Ethyl Rosmarinate against Ulcerative Colitis in Mice Based on Untargeted Metabolomics

Aiming at assessing the therapeutic effect of ethyl rosmarinate (ER) on ulcerative colitis (UC), the following activities were performed in vitro and in vivo in the present study. Firstly, a lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model was established to determine the level of inflammatory factors. Then, a UC mice model induced by dextran sodium sulfate (DSS) was established to further investigate the effects of ER on symptoms, inflammatory factors and colon histopathology. Finally, serum and colon metabolomics studies were performed to identify the biomarkers and metabolisms closely related to the protective effect of ER on UC. The results showed that after ER intervention, the levels of inflammatory factors (NO, TNF-α, IL-1β and IL-6) and key enzyme (MPO) in cell supernatant, serum or colon were significantly decreased, and the disease activity index and colon tissue damage in mice were also effectively improved or restored. In addition, 28 biomarkers and 6 metabolisms were found to be re-regulated by ER in the UC model mice. Therefore, it could be concluded that ER could effectively ameliorate the progression of UC and could be used as a new natural agent for the treatment of UC.     

Epigenetic DNA Methylation of EBI3 Modulates Human Interleukin-35 Formation via NFkB Signaling: A Promising Therapeutic Option in Ulcerative Colitis

Ulcerative colitis (UC), a severe chronic disease with unclear etiology that is associated with increased risk for colorectal cancer, is accompanied by dysregulation of cytokines. Epstein–Barr virus-induced gene 3 (EBI3) encodes a subunit in the unique heterodimeric IL-12 cytokine family of either pro- or anti-inflammatory function. After having recently demonstrated that upregulation of EBI3 by histone acetylation alleviates disease symptoms in a dextran sulfate sodium (DSS)-treated mouse model of chronic colitis, we now aimed to examine a possible further epigenetic regulation of EBI3 by DNA methylation under inflammatory conditions. Treatment with the DNA methyltransferase inhibitor (DNMTi) decitabine (DAC) and TNFα led to synergistic upregulation of EBI3 in human colon epithelial cells (HCEC). Use of different signaling pathway inhibitors indicated NFκB signaling was necessary and proportional to the synergistic EBI3 induction. MALDI-TOF/MS and HPLC-ESI-MS/MS analysis of DAC/TNFα-treated HCEC identified IL-12p35 as the most probable binding partner to form a functional protein. EBI3/IL-12p35 heterodimers (IL-35) induce their own gene upregulation, something that was indeed observed in HCEC cultured with media from previously DAC/TNFα-treated HCEC. These results suggest that under inflammatory and demethylating conditions the upregulation of EBI3 results in the formation of anti-inflammatory IL-35, which might be considered as a therapeutic target in colitis.     

Impaired Butyrate Induced Regulation of T Cell Surface Expression of CTLA-4 in Patients with Ulcerative Colitis

Patients with ulcerative colitis (UC) have reduced intestinal levels of short-chain fatty acids (SCFAs), including butyrate, which are important regulators of host–microbiota crosstalk. The aim was therefore to determine effects of butyrate on blood and intestinal T cells from patients with active UC. T cells from UC patients and healthy subjects were polyclonally stimulated together with SCFAs and proliferation, activation, cytokine secretion, and surface expression of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) were analyzed. Butyrate induced comparable, dose dependent inhibition of activation and proliferation in blood T cells and activation in intestinal T cells from UC patients and healthy subjects. However, surface expression of the inhibitory molecule CTLA-4 on stimulated blood and intestinal T cells was impaired in UC patients and was not restored following butyrate treatment. Furthermore, unlike intestinal T cells from healthy subjects, butyrate was unable to downregulate secretion of interferon gamma (IFNγ), interleukin (IL)-4, IL-17A, and IL-10 in UC patients. Although seemingly normal inhibitory effects on T cell activation and proliferation, butyrate has an impaired ability to reduce cytokine secretion and induce surface expression of CTLA-4 in T cells from UC patients with active disease. Overall, these observations indicate a dysfunction in butyrate induced immune regulation linked to CTLA-4 signaling in T cells from UC patients during a flare.     

Pequi Oil,a MUFA/Carotenoid-Rich Oil,Exhibited Protective Effects against DSS-Induced Ulcerative Colitis in Mice

Inflammatory bowel diseases (IBD) affect the gastrointestinal tract, and the imbalance of intestinal immune homeostasis can trigger them. Pequi oil (PO), a monounsaturated (MUFA) and carotenoid-rich food with nutraceutical potential, could help reshape the intestinal immune response, ameliorating IBD outcomes. This study investigates the effects of a 28 days intake of PO on elements of the intestinal immune response of mice with DSS-induced ulcerative colitis (disease activity index, colonic damage, inflammatory cells and markers). PO reduces body weight, colonic crypt and goblet cell losses and ameliorates diarrhea. In the colon, it increases γδT cells and secretory-IgA and decreases CD8+T cells. In lymphoid organs, it reduces CD8+T cells. Moreover, it also reduces the IL-17 and CRP in plasma. PO oil promotes a less cytotoxic response that may protect mice from immunological injuries caused by an IBD in the intestinal mucosa, improving the disease prognosis. Practical applications: This study demonstrates that the intake of pequi oil contributes to the regulation of immune response and improves clinical and histological signs of DSS-induced ulcerative colitis in mice. Its effects in cytotoxic cell reduction and other inflammatory markers and stimulation of regulatory cells, and preservation of mucus-producing cells, provide news insights about the importance of the regular intake of this food to better prognosis of ulcerative colitis acute episodes. In addition, these findings encourage further studies with foods with a protective potential for the intestinal mucosa.     

High Acetate Concentration Protects Intestinal Barrier and Exerts Anti-Inflammatory Effects in Organoid-Derived Epithelial Monolayer Cultures from Patients with Ulcerative Colitis

Short-chain fatty acids as well as their bacterial producers are of increasing interest in inflammatory bowel diseases. Although less studied compared to butyrate, acetate might also be of interest as it may be less toxic to epithelial cells, stimulate butyrate-producing bacteria by cross-feeding, and have anti-inflammatory and barrier-protective properties. Moreover, one of the causative factors of the probiotic potency of Saccharomyces cerevisae var. boulardii is thought to be its high acetate production. Therefore, the objective was to preclinically assess the effects of high acetate concentrations on inflammation and barrier integrity in organoid-based monolayer cultures from ulcerative colitis patients. Confluent organoid-derived colonic epithelial monolayers (n = 10) were exposed to basolateral inflammatory stimulation or control medium. After 24 h, high acetate or control medium was administered apically for an additional 48 h. Changes in TEER were measured after 48 h. Expression levels of barrier genes and inflammatory markers were determined by qPCR. Pro-inflammatory proteins in the supernatant were quantified using the MSD platform. Increased epithelial resistance was observed with high acetate administration in both inflamed and non-inflamed conditions, together with decreased expression levels of IL8 and TNFα and CLDN1. Upon high acetate administration to inflamed monolayers, upregulation of HIF1α, MUC2, and MKI67, and a decrease of the majority of pro-inflammatory cytokines was observed. In our patient-derived human epithelial cell culture model, a protective effect of high acetate administration on epithelial resistance, barrier gene expression, and inflammatory protein production was observed. These findings open up new possibilities for acetate-mediated management of barrier defects and inflammation in IBD.     

Inverse and Concordant Mucosal Pathway Gene Expressions in Inflamed and Non-Inflamed Ulcerative Colitis Patients: Potential Relevance to Aetiology and Pathogenesis

Ulcerative colitis (UC) arises from a complex interplay between host and environmental factors, but with a largely unsolved pathophysiology. The pathophysiology was outlined by RNA-sequencing of mucosal biopsies from non-inflamed and inflamed colon of UC patients (14 and 17, respectively), and from 27 patients without intestinal inflammation. Genes differentially expressed (DE), or present in enriched gene sets, were investigated using statistical text analysis of functional protein information. Compared with controls, inflamed and non-inflamed UC mucosa displayed 9360 and 52 DE genes, respectively. Seventy-three non-pseudogenes were DE relative to both gender and inflammation. Mitochondrial processes were downregulated in inflamed and upregulated in non-inflamed UC mucosa, whereas angiogenesis and endoplasmic reticulum (ER) stress were upregulated in both tissue states. Immune responses were upregulated in inflamed mucosa, whereas the non-inflamed UC mucosa presented both up- and downregulated gene sets. DE and enriched genes overlapped with genes present in inflammatory bowel disease genome-wide associated loci (p = 1.43 × 10⁻¹⁸), especially regarding immune responses, respiratory chain, angiogenesis, ER stress, and steroid hormone metabolism. Apart from confirming established pathophysiological mechanisms of immune cells, our study provides evidence for involvement of less described pathways (e.g., respiratory chain, ER stress, fatty-acid oxidation, steroid hormone metabolism and angiogenesis).     

Triggers for the Nrf2/ARE Signaling Pathway and Its Nutritional Regulation: Potential Therapeutic Applications of Ulcerative Colitis

Ulcerative colitis (UC), which affects millions of people worldwide, is characterized by extensive colonic injury involving mucosal and submucosal layers of the colon. Nuclear factor E2-related factor 2 (Nrf2) plays a critical role in cellular protection against oxidant-induced stress. Antioxidant response element (ARE) is the binding site recognized by Nrf2 and leads to the expression of phase II detoxifying enzymes and antioxidant proteins. The Nrf2/ARE system is a key factor for preventing and resolving tissue injury and inflammation in disease conditions such as UC. Researchers have proposed that both Keap1-dependent and Keap1-independent cascades contribute positive effects on activation of the Nrf2/ARE pathway. In this review, we summarize the present knowledge on mechanisms controlling the activation process. We will further review nutritional compounds that can modulate activation of the Nrf2/ARE pathway and may be used as potential therapeutic application of UC. These comprehensive data will help us to better understand the Nrf2/ARE signaling pathway and promote its effective application in response to common diseases induced by oxidative stress and inflammation.