Glutamine inhibits over-expression of pro-inflammatory genes and down-regulates the nuclear factor kappaB pathway in an experimental model of colitis in the rat

We investigated the effects of glutamine on markers of oxidative stress, nuclear factor kappaB (NF-kappaB) activation, and pro-inflammatory mediators in a rat model of experimental colitis induced by intracolonic administration of 7% acetic acid. Glutamine (25 mg/kg) was given by rectal route 48 and 24h before acetic acid instillation. Glutamine significantly reduced gross damage and histopathological scores, and partially prevented the decrease of anal pressure observed in the animals receiving acetic acid. Increases in the cytosolic concentration of TBARS and hydroperoxide-initiated chemiluminescence were significantly prevented in glutamine-treated animals. Acetic acid instillation induced a marked increase of the NF-kappaB p65 subunit expression in the nucleus and resulted in significant changes in the cytosolic protein level of IkappaB kinases (IKKalpha and IKKbeta) and the non-phosphorylated form of the inhibitor IkappaBalpha. Protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were significantly increased. All these effects were partially prevented by administration of glutamine. It is concluded that the anti-inflammatory activity of glutamine in a rat model of acetic acid-induced colitis may be mediated, at least in part, by inhibition of the expression of certain pro-inflammatory mediators which are regulated by the oxidative stress-sensitive NF-kappaB signalling pathway.     

Clinical and endoscopic outcomes of patients with colonic Crohn's disease treated with 5-aminosalicylates as monotherapy

BackgroundIn spite of the lack of evidence regarding the clinical benefits of oral 5-aminosalicylic acid (5-ASA) compounds in Crohn's disease (CD), these drugs are frequently used in daily clinical practice, particularly for colonic CD. Our aim is to assess the use and clinical outcomes of 5-ASA of those patients with colonic CD treated with 5-ASA as monotherapy.MethodsPatients diagnosed with isolated colonic CD and treated with 5-ASA but never exposed to immunosuppressants or biologicals were identified from the local databases of five referral centres. A retrospective review of clinical and endoscopic outcomes was performed.ResultsOut of 545 patients with isolated colonic CD, 106 (19%) were treated with oral 5-ASA in monotherapy as maintenance therapy. The median follow-up was 144 months (interquartile range [IQR], 48–234). Almost all of the patients (92%) presented an inflammatory pattern and 11% developed perianal disease. Half of the patients had already received 5-ASA at diagnosis, and the median duration of 5-ASA treatment was 107 months (IQR 22.5–187). Endoscopic remission, as defined by the absence of ulcers at the last complete colonoscopy, was observed in 65% of those patients undergoing at least one colonoscopy during follow-up. Male gender and extraintestinal manifestations were associated with a lower likelihood of achieving endoscopic remission. Nine patients required colectomy, but mostly soon after CD diagnosis.Conclusions5-ASA seems to be of benefit in the long-term in one fifth of patients with colonic CD as the only maintenance therapy and should be considered in fragile patients with Crohn's colitis.     

康复新液联合美沙拉嗪对溃疡性结肠炎活动期患者HMGB1、MCP-1、SOCS-3和Beclin1表达的影响

目的探讨康复新液联合美沙拉嗪对溃疡性结肠炎（UC）活动期患者高迁移率族蛋白B1（HMGB1）、单核细胞趋化蛋白-1（MCP-1）、细胞因子信号传导抑制蛋白-3（SOCS-3）和Beclin1表达的影响。 方法选择2019年2月至2021年2月亳州市人民医院UC活动期患者120例,按1∶1比例随机分为对照组和治疗组,各60例。2组患者均给予补液、营养支持、纠正电解质和酸碱平衡紊乱等基础治疗。对照组口服美沙拉嗪肠溶片1 g/次,4 次/d,连续治疗2周。治疗组在美沙拉嗪肠溶片基础上给予康复新液,30 ml加入150 ml 0.9%生理盐水稀释并加温至37℃后灌肠,每次灌肠时间20～30 min,每日2次,连续治疗2周。比较2组治疗效果、主要症状积分、肠道黏膜病变程度（改良Mayo评分和Geboes指数）、HMGB1、MCP-1、SOSC-3、Beclin1水平及炎症性肠病问卷（IBDQ）评分。 结果治疗组UC活动期患者治疗总有效率显著高于对照组（93.33% vs 78.33%,P＜0.05）。治疗前2组症状积分差异无统计学意义（P＞0.05）,治疗后2组各症状积分均显著降低（P＜0.05）,且治疗组显著低于对照组（P＜0.05）。治疗前2组改良Mayo评分和Geboes指数差异无统计学意义（P＞0.05）,治疗后2组指标均降低（P＜0.05）,且治疗组显著低于对照组（P＜0.05）。治疗前2组血清HMGB1、MCP-1、SOSC-3和Beclin1水平、蛋白表达水平差异无统计学意义（P＞0.05）,治疗后2组HMGB1、MCP-1、Beclin1水平均下降,SOSC-3水平均升高,且治疗组各指标水平显著优于对照组（P＜0.05）。治疗前2组IBDQ评分差异无统计学意义（P＞0.05）,治疗后2组评分均升高（P＜0.05）,且治疗组显著高于对照组（P＜0.05）。 结论康复新液联合美沙拉嗪对UC活动期患者治疗效果显著,机制可能与HMGB1、MCP-1、Beclin1的下调及SOSC-3的上调有关。     

A rare and unsuspected complication of Clostridium difficile infection

Objective To report the occurrence of abdominal compartment syndrome (ACS) due to infection with Clostridium difficile. Design Case report. Setting Trauma intensive care unit (TICU) of Hamad General Hospital, a teaching hospital in Doha, Qatar. Patient A 36-year-old man involved in a motor vehicle accident had severe traumatic brain injury and received ceftriaxone. On day 7, he developed severe abdominal distension and diarrhoea followed by paralytic ileus with oliguria, hyperkalaemia, and intra-abdominal hypertension. The patient's stool sample was positive for C. difficile toxin A and B Measurements and results An ACS was diagnosed. The patient was successfully treated in the TICU by stopping the offending antibiotic and starting metronidazole plus neostigmine as a prokinetic agent. The fluid status was guided by pulse-induced continuous cardiac output, and frusemide was added to the treatment. With this aggressive management the abdominal pressure decreased and the renal function improved, with full recovery of renal function by day 21. Unfortunately the patient's Glasgow coma score (GCS) deteriorated, so percutaneous tracheostomy was performed. He was transferred to the neurosurgical ward on day 35. A week later he was shifted to the rehabilitation unit for further management. Conclusions C. difficile colitis can cause intra-abdominal hypertension (IAH) and ACS. Rapid diagnosis, early aggressive supportive care, metronidazole and prokinetics are necessary to lower the morbidity and mortality of C. difficile colitis associated with IAH and ACS. Presented as mini-paper at the 3rd World Congress on Abdominal Compartment Syndrome – WCACS 2007 [Shaikh N, Kettern MA, Elshaffie SS, Louon A, Hanssens Y (2007) Acta Clin Belg (Suppl) 62(1):287 (M9)].     

Basic requirements for the use of terms for reporting adverse drug reactions (II)

This paper is the report of a meeting held in Geneva under the auspices of the Council for International Organizations of Medical Sciences (CIOMS) on 6–7 November 1991. A second group of ADR reporting terms is defined.     

中药肠炎康对溃疡性结肠炎大鼠免疫功能的影响

目的 :探讨溃疡性结肠炎 ( UC)发病过程中的免疫异常机制及中药肠炎康 ( CYK)口服液对本病的治疗机理。方法 :通过免疫方法成功复制 UC大鼠模型 ,应用 CYK口服液及对照药物柳氮磺胺吡啶 ( SASP)分别灌胃治疗 5 0 d,观察并分析治疗前后脾细胞 Con A刺激指数、LPS刺激指数、IL- 2、IFN- r水平及 NKc杀伤活性变化。结果 :模型组大鼠脾细胞 Con A刺激指数、NKc杀伤活性明显下降 ( P<0 .0 1 ) ,IL- 2、IFN- r水平也有下降 ( P<0 .0 5 ) ;而脾细胞 LPS刺激指数明显升高( P<0 .0 5 )。治疗后 ,CYK组大鼠脾细胞 Con A刺激指数、IL- 2、IFN- r水平及 NKc杀伤活性同模型组比较均有明显提高 ;但脾细胞 LPS刺激指数同模型组比较差异无显著性 ( P>0 .0 5 )。SASP组大鼠脾细胞 LPS刺激指数同模型组比较明显下降 ( P<0 .0 5 ) ;其 IL- 2、IFN- r水平及 NKc杀伤活性同模型组比较差异无显著性 ( P>0 .0 5 )。结论 :溃疡性结肠炎大鼠细胞免疫功能减退 ,体液免疫增强。CYK能促进 UC大鼠肠粘膜溃疡修复及炎症消退 ,在恢复其细胞免疫功能方面 ,优于 SASP,但对 UC大鼠体液免疫的抑制作用不及 SASP。     

黏膜耐受治疗对大鼠实验性结肠炎的疗效观察

目的评价口服耐受和经鼻耐受治疗对大鼠实验性结肠炎的疗效,以及分别加用佐剂对其疗效的影响。方法建立三硝基苯磺酸（TNBS）实验性结肠炎大鼠模型。以卵白蛋白（OVA）为诱导抗原,脂多糖为佐剂。将已建立的TNBS结肠炎大鼠模型根据不同的干预方法分为结肠炎组、口服耐受组、经鼻耐受组、口服加佐剂组、经鼻加佐剂组、佐剂对照组和空白对照组。各组大鼠经上述不同治疗后均于灌肠第21天处死,以肠道大体和组织病理学评分为标准评价治疗效果,以脾淋巴细胞增殖实验评价黏膜耐受诱导效果。结果肠道大体评分（平均秩次9．5VS3．5,P〈0．01）和组织病理学评分（平均秩次9．5VS3．5,P〈0．01）显示TNBS诱导的实验性结肠炎模型在无干预情况下可持续至第21天仍有肠道炎症。脾淋巴细胞增殖实验结果显示,在大鼠结肠炎状态下,口服耐受组不能诱导机体对OVA的免疫耐受,而口服加佐剂组（0．11±0．05VS0．30±0．13,P〈0．05）、经鼻耐受组（0．12±0．07,P〈0．05）和经鼻加佐剂组（0．06±0．04VS0．30±0．13,P〈0．05）均可诱导机体免疫耐受,不同途径诱导的免疫耐受效果差异无统计学意义。与结肠炎组大鼠相比,口服加佐剂组（大体评分3．0±1．3VS6．3±0．8,组织学病理评分3．0±1．1VS7．5±1．0,均P〈0．05）,经鼻加佐剂组（大体评分2．0±0．6,组织学病理评分2．7±1．0,均P〈0．05）和佐剂对照组（大体评分4．3±1．0,组织学病理评分4．6±1．6,均P〈0．05）大鼠的肠道评分均显著较低。其中经鼻加佐剂组大鼠的肠道评分下降最显著。结论TNBS实验性结肠炎干扰了口服耐受的诱导,但不影响经鼻耐受的诱导。加用佐剂的口服耐受和加用佐剂的经鼻耐受对实验性结肠炎均有一定治疗作用,单独应用佐剂也有一定疗效,其中加用佐剂的经鼻耐受疗效最好。