健脾固肠汤联合美沙拉嗪治疗克罗恩病临床观察

目的 观察健脾固肠汤联合美沙拉嗪治疗克罗恩病的临床疗效.方法 将30例患者随机均分为对照组和治疗组,对照组给予美沙拉嗪,治疗组加用健脾固肠汤;总疗程4周.比较2组治疗前后的ESR、CRP、中医证候疗效、临床疗效、CDAI评分及肠道菌落变化.结果 治疗组中医证候疗效、临床疗效显著高于对照组(P＜0.05),治疗组的肠球菌...     

5-ASA affects cell cycle progression in colorectal cells by reversibly activating a replication checkpoint

BACKGROUND & AIMS: Individuals with inflammatory bowel disease are at risk of developing colorectal cancer (CRC). Epidemiologic, animal, and laboratory studies suggest that 5-amino-salicylic acid (5-ASA) protects from the development of CRC by altering cell cycle progression and by inducing apoptosis. Our previous results indicate that 5-ASA improves replication fidelity in colorectal cells, an effect that is active in reducing mutations. In this study, we hypothesized that 5-ASA restrains cell cycle progression by activating checkpoint pathways in colorectal cell lines, which would prevent tumor development and improve genomic stability. METHODS: CRC cells with different genetic backgrounds such as HT29, HCT116, HCT116(p53-/-), HCT116+chr3, and LoVo were treated with 5-ASA for 2-96 hours. Cell cycle progression, phosphorylation, and DNA binding of cell cycle checkpoint proteins were analyzed. RESULTS: We found that 5-ASA at concentrations between 10 and 40 mmol/L affects cell cycle progression by inducing cells to accumulate in the S phase. This effect was independent of the hMLH1, hMSH2, and p53 status because it was observed to a similar extent in all cell lines under investigation. Moreover, wash-out experiments demonstrated reversibility within 48 hours. Although p53 did not have a causative role, p53 Ser15 was strongly phosphorylated. Proteins involved in the ATM-and-Rad3-related kinase (ATR)-dependent S-phase checkpoint response (Chk1 and Rad17) were also phosphorylated but not ataxia telengectasia mutated kinase. CONCLUSIONS: Our data demonstrate that 5-ASA causes cells to reversibly accumulate in S phase and activate an ATR-dependent checkpoint. The activation of replication checkpoint may slow down DNA replication and improve DNA replication fidelity, which increases the maintenance of genomic stability and counteracts carcinogenesis.     

Modern use of 5-aminosalicylic acid compounds for ulcerative colitis

ABSTRACT

Introduction: For 30 years, 5-aminosalicylic acid (5-ASA) has been the backbone of therapeutic management in patients with ulcerative colitis (UC). In the biologic era, it still remains the treatment of choice in mild-to-moderate UC. Positioning of this therapeutic class in moderate-to-severe UC is less clear.

Areas covered: Several studies demonstrated the ability of 5-ASA to induce endoscopic remission to a similar extent as anti-TNF therapy on the moderate segment of UC. Histologic remission is achieved after induction in up to 45% of patients treated with topical 5-ASA and 30% with oral formulations. Aminosalicylates offer a favorable safety profile compared to that of immunomodulators and biologics. High-dose 5-ASA therapy may be a valuable option for patients with moderately active disease, and physicians should weigh the pros and cons of this strategy in selected patients. Whether aminosalicylates should be continued in combination with thiopurines or biologic therapy remains under debate.

Expert opinion: In the era of biologics, aminosalicylates remain the first-line therapy in patients with mild UC, and have to be considered in case of moderate UC, given their favorable risk-benefit profile. We suggest that 5-ASA should be used in moderate patients without poor prognostic factors, while biologics should be preferred otherwise.     

Changes in the approach to acute diverticulitis

Acute diverticulitis (AD) is one of the most common acute admission diagnoses for general surgery, and its prevalence is increasing, in part due to the ageing population. Currently, most patients who present to a tertiary hospital are admitted for a period of treatment and observation. Simple, safe and cost‐effective strategies for improving our current treatment of this condition will be invaluable in providing the most appropriate management for individual patients and for reducing the health resources expended on hospital admissions and parenteral antibiotics. AD can be categorized as uncomplicated or complicated, these two subtypes have a very different clinical course. The management of uncomplicated AD has become increasingly conservative, with a focus on symptomatic relief and supportive management. Recent research has brought into question the need for extended hospital admission and questioned the current use of antibiotics. Anti‐inflammatory agents that reduce local inflammation in uncomplicated AD may be a useful means of reducing damage caused by inflammation and aiding earlier resolution of the inflammatory response and associated symptoms. Mesalazine is an anti‐inflammatory agent that has been trialled in uncomplicated AD. Mesalazine has been shown to improve time to resolution of endoscopic and histological evidence of inflammation following an episode of AD and also reduce the rate of recurrence. In this literature review, we provide an overview of recent advances in AD classification, pathophysiology and management, and examine the possibility of introducing the use of anti‐inflammatory agents in the management of uncomplicated AD.     

痛泻要方对溃疡性结肠炎模型大鼠血清NPY、VIP表达以及结肠组织病理的影响

目的:探讨痛泻要方对溃疡性结肠炎(ulcerative colitis,UC)模型大鼠血清中神经肽Y(neuropeptide Y,NPY)和血管活性肠肽(vasoactive intestinal peptide,VIP)表达的影响及作用机制。方法:实验动物采用2,4,6-三硝基苯磺酸/乙醇灌肠法+束缚应激+饮食失节方法造模,然后将造模成功的大鼠随机分为模型组,美沙拉嗪组,痛泻要方高剂量组、中剂量组、低剂量组。肉眼观察结肠大体形态损伤并进行评分。采用ELISA法检测大鼠血清中NPY和VIP的表达水平。结果:经肉眼观察发现模型组大鼠结肠组织黏膜层可见炎症和溃疡形成,与空白组比较,差异有统计学意义(P0.05),结合病理、蔗糖水测试实验等证实模型成功。模型组大鼠血清组织中VIP水平低于空白组,NPY水平高于空白组,差异均有统计学意义(P0.05,P0.05);治疗后,痛泻要方组VIP含量较模型组均增加,NPY含量较模型组均降低(P0.05)。结论:痛泻要方对UC模型大鼠脑肠轴的异常有调节作用,其作用机制可能与调节血清中VIP、NPY的含量有关。     

美沙拉嗪并氟哌噻吨美利曲辛对难治性肠易激综合征的治疗效果

目的 观察美沙拉嗪联合氟哌噻吨美利曲辛治疗难治性腹泻型肠易激综合征（I BS）病人的临床效果。方法 选取84例难治性腹泻型IBS病人,随机分为对照组和治疗组各42例。对照组给予美沙拉嗪治疗,治疗组同时给予氟哌噻吨美利曲辛治疗,疗程均为4周。结果 治疗组总有效率为95.2%,显著高于对照组的71.4%,差异有显著性（V2=6.010,P〈0.05）。结论 美沙拉嗪联合氟哌噻吨美利曲辛治疗难治性I BS临床效果显著,可有效缓解症状,宜在临床推广。     

Mesalazine-associated interstitial nephritis

BACKGROUND.: When used for oral treatment of inflammatory bowel disease,Asacol (a coated form of mesalazine = 5-aminosalicylic acid)can cause interstitial nephritis. The spectrum of severity,frequency of occurrence and the best renal function test todetect this complication are not known. The value of immunosuppressionin addition to drug withdrawal is similarly undetermined. METHODS.: Four cases of interstitial nephritis which occurred in associationwith oral Asacol treatment are presented and a further 12 caseswho received similar treatment are reviewed. Clinical trialspublished previously were scrutinized to assess the frequencyof impaired renal function. RESULTS.: The available evidence suggests that renal impairment of anyseverity may occur in up to 1 in 100 patients, but that clinicallysignificant interstitial nephritis occurs in less than 1 in500 patients. This is most reliably detected by an elevatedserum creatinine concentration. If the diagnosis of nephrotoxicityis delayed until 18 months after commencement of medication,restoration of renal function, which is seen on withdrawal ofmedication alone up to 10 months, does not occur and there isno evidence to date to indicate that addition of immunosuppressionconfers any significant advantage at this later stage. CONCLUSIONS.: It is suggested that serum creatinine concentration should bemeasured each month for the first 3 months of treatment, 3-monthlyfor the remainder of the first year and annually thereafter.The use of concurrent immunosuppressive therapy may necessitateextension to the period of intensive monitoring. Any elevationof serum creatinine which cannot be related to a relapse ofinflammatory bowel disease should prompt immediate withdrawalof Asacol and related medications and substitution of alternativetherapy. Neither the lack of urinary abnormalities on routinetesting nor the absence of clinical or laboratory features ofdrug allergy can be relied upon to rule out interstitial nephritisduring oral therapy with these drugs.     

Better quality of therapy with 5-ASA colonic foam in active ulcerative colitis

We evaluated the efficacy, tolerance, and acceptance of a new 5-ASA colonic foam versus 5-ASA liquid enema in the short-term treatment of active ulcerative colitis in a three-week prospective, randomized, investigator-blind study, enrolling 233 patients from 12 outpatient clinics in Italy. In arm 1 of the study, 117 patients with mild attacks received 2 g of 5-ASA as foam or enema at bedtime. In arm 2, 116 patients with moderate attacks were given 4 g of 5-ASA as foam or enema at bedtime. End points were defined as complete relief of symptoms, and endoscopic and histological evidence of remission or improvement. In patients with mild relapse, 34 of 63 (54%) treated with foam were in clinical remission after only 10 days compared with 17 of 51 (31%) treated with enemas (P<0.05). However, there was no statistically significant difference between foam (83%) and enema (74%) after three weeks. In patients with moderate relapse, a higher proportion of patients achieved complete clinical remission in the foam group (63%) compared with enema group (52%) after three weeks (difference 11%, 95% CI –7 to 29). No significant differences were observed in endoscopic and histological evaluation of colonic mucosa between treatment groups in either arm. 5-ASA foam was well tolerated. No unexpected adverse events were reported. Patient evaluation of therapy showed that foam was much better accepted than enema because foam was more comfortable, more practical, easier to retain, and interfered less with daily living. The results of this study suggest that 5-ASA foam may provide prompter remission of symptoms compared to liquid enema and it improves the quality of topical therapy in ulcerative colitis.This paper was presented in part at the Research Forum of the 92nd annual meeting of The American Gastrointestinal Association, New Orleans, May 18–24, 1991.The multicenter group included: M. Campieri, A. Belluzzi, G. Brunetti, P. Gionchetti, M. Miglioli, L. Barbara (Bologna); C. Prantera, A. Andreoli, E. Berto (Roma); P. Paoluzi, M.C. Di Paolo, A.O. Paoluzi (Roma); F. Pallone, F. Luzza (Catanzaro); M. Cottone, L. Oliva (Palermo); G. Bianchi Porro, S. Ardizzone, M. Petrillo (Milano); G. D'Albasio, G. Trallori (Firenze); G.C. Sturniolo, M.C. Montino (Padova); A. Pera, C. Barletti (Torino); R. de Franchis, G. Grandinetti, G.M. Meucci, M. Vecchi (Milano); P. Bianchi, M.C. Campanini, T. Ranzi (Milano); L. Capurso, C. Papi (Roma).Supported by a grant from Bracco and Giuliani (Milan, Italy).     

Baicalin down-regulates the expression of macrophage migration inhibitory factor (MIF) effectively for rats with ulcerative colitis

The purpose of this study was to investigate whether baicalin, a Chinese herbal extract, down-regulates the expression of macrophage migration inhibitory factor (MIF), an inflammatory factor that regulates the function of macrophages (MΦ), in rats with trinitrobenzene sulphonic acid (TNBS)-induced ulcerative colitis (UC). The results showed that baicalin simultaneously down-regulated the expression of MIF, the quantity of MΦs and the amount of MΦ-related cytokines, including macrophage chemotactic factor-1 (MCP-1, CCL2) and macrophage inflammatory protein-3α (MIP-3α, CCL20), in rats with UC. There was no statistical difference between baicailin and mesalazine in down-regulating the expression of MIF. Our study demonstrated that baicalin, an inexpensive but effective monomer, could be a new and alternative pharmaceutical for UC.     

痛泻宁颗粒联合美沙拉秦口服治疗溃疡性结肠炎的疗效观察

目的：观察痛泻宁颗粒联合美沙拉秦颗粒治疗轻度、中度溃疡性结肠炎（U C ）的临床疗效。方法选择380例内镜检查临床确诊的轻度、中度U C患者,将其分为观察组（190例）与对照组（190例）。观察组给予痛泻宁颗粒联合美沙拉秦颗粒口服治疗,对照组予美沙拉秦颗粒口服治疗,疗程均为8周。分别统计两组的总有效率,并测定两组患者治疗前、后血清基质金属蛋白酶‐2（MMP‐2）与基质金属蛋白酶‐9（MMP‐9）水平,免疫组织化学SP法检测肠道标本S100钙结合蛋白A12（S100A12）及晚期糖基化终末产物受体（RAGE）的表达。结果观察组总有效率为94．74％,对照组为89．47％,差异有统计学意义（P＜0．01）;治疗后,两组MMP‐2、MMP‐9表达水平均降低,且观察组低于对照组,差异有统计学意义（P＜0．01）。治疗后,观察组RAGE及S100A12表达水平降低,与对照组比较差异有统计学意义（P＜0．01）。结论痛泻宁颗粒联合美沙拉秦颗粒口服治疗轻度、中度UC较单用美沙拉秦颗粒口服能更好地改善患者的临床症状,具有更好的临床疗效。