Preventive Effects of Rebamipide on NSAID-Induced Gastric Mucosal Injury and Reduction of Gastric Mucosal Blood Flow in Healthy Volunteers

The precise mechanisms of acute damage and the role of gastric mucosal blood flow in gastric mucosal injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs) remain uncertain. The aim of this study was to evaluate the preventive effect of rebamipide on gastric mucosal injury and reduction of gastric mucosal blood flow (GMBF) after ibuprofen administration. Twenty healthy volunteers were randomized two groups. The rebamipide group took ibuprofen, 1800 mg/day, and rebamipide, 100 mg t.i.d., for 7 days. The placebo group took ibuprofen, 1800 mg/day. The numbers of gastric ulcer subjects were three in the placebo group and zero in the rebamipide group. The mean modified Lanza score after ibuprofen administration was significantly higher in the placebo group than the rebamipide group (2.9±1.7 vs. 1.3±1.0, respectively; P=0.032). The GMBF of the placebo group was significantly decreased at antrum from baseline, from 2.8±0.5 to 2.0±0.5 tissue perfusion units (P=0.005). There was no difference in GMBF change in the rebamipide group. Gastric mucosal injury was correlated with GMBF reduction in antrum (r=−0.677, P=0.001). In conclusion, it is suggested that the decrease in GMBF may have been associated with NSAID-induced gastric mucosal injury, and rebamipide may have prevented NSIAD-induced gastric mucosal injury by maintaining GMBF in healthy subjects.     

Assessing the efficacy of famotidine and rebamipide in the treatment of gastric mucosal lesions in patients receiving long-term NSAID therapy (FORCE—famotidine or rebamipide in comparison by endoscopy)

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori infection are major causes of gastric mucosal lesions. In Japan, histamine-2 receptor antagonists are frequently prescribed, but the literature regarding their efficacy is limited. In this study, we compare the effects of famotidine and rebamipide on NSAID-associated gastric mucosal lesions using upper gastrointestinal endoscopy. Methods This study examined 112 patients taking NSAIDs for either gastric hemorrhage or erosion. Before treat-ment, the patients were assessed by endoscopy. Using blind randomization, patients were divided into two groups: group F (famotidine, 20 mg/day) and group R (rebamipide, 300 mg/day). Efficacy was examined 4 weeks later using endoscopy. Results After treatment, the Lanza score decreased significantly in group F (P < 0.001) but not in group R (P = 0.478). The change in the Lanza score in group F was significantly greater (P = 0.002) than that in group R. Conclusions Famotidine was superior to rebamipide in treating NSAID-associated mucosal lesions.     

Increased circulating platelet-neutrophil, platelet-monocyte complexes, and platelet activation in patients with ulcerative colitis: a comparative study

It is reported that the incidence of thromboembolism is increased in ulcerative colitis (UC), and hypercoagulability persists even when patients are in remission. We evaluated the association of inflammatory response parameters with UC activity, and activation parameters of the platelets, endothelium, and the coagulation system in UC. Eighteen UC patients and 19 healthy subjects were included in the study. The patients' clinical features were recorded down; whole blood counts and acute phase parameters were evaluated. UC patients were divided into two as active (9 patients) and inactive (9 patients) according to combined clinical activity index (CAI) and endoscopic activity index (EAI) scores. In all subjects, platelet CD62P expression, platelet-monocyte complexes (PMC), platelet-neutrophil complexes (PNC), and platelet microparticles (PMP) were determined by flow cytometry. E-selectin, thrombin-antithrombin complex (TAT) levels in plasma, and sCD40L levels in serum were determined by ELISA. In both active and inactive UC patients, platelet CD62P expression, the percentages of PMC, and PNC were significantly higher than those in the control group (P< 0.01). PMP level was higher in the control group than in inactive UC patients (P = 0.001). sCD40L level was significantly higher in active UC group than in the control group (P < 0.01). EAI score correlated significantly with PMP (r = 0.5, P = 0.04) and sCD40L (r = 0.48, P = 0.044); CAI score had a negative correlation (r = -0.68, P = 0.002) with sE-selectin level. In addition to increased CD62P expression and sCD40L, increased formation of PMC and PNC suggests a role for platelet-leukocyte complex formation together with platelet activation in thromboembolic events observed in UC.     

Anti-inflammatory Effects of Rebamipide According to Helicobacter pylori Status in Patients with Chronic Erosive Gastritis: A Randomized Sucralfate-Controlled Multicenter Trial in China—STARS Study

The aim of the study was to investigate the effects of rebamipide on symptom, histology, endogenous prostaglandin, and mucosal oxygen free radicals in chronic erosive gastritis (CEG) patients by using sucralfate as a control. The trial also examined whether Helicobacter pylori infection would affect rebamipide-induced protection. A total of 453 endoscopy-confirmed CEG patients from 11 hospitals in China were enrolled in the study. They randomly received either rebamipide (100 mg t.i.d) or sucralfate (1.0 t.i.d) for 8 weeks with a ratio of 3:1. Per-protocol analysis (n = 415) showed the accumulated symptom score in the rebamipide group dropped from 5.54 ± 0.97 to 0.80 ± 0.47 after 8 weeks (P < 0.001 versus control). The endoscopic inflammation score in rebamipide group also decreased from 2.65 ± 0.09 to 0.60 ± 0.10, which showed better effects than sucralfate. It was shown a significant improvement (P < 0.01) in prostaglandin E2 (PGE₂) contents in rebamipide-treated subjects mucosa (225.4 ± 18.3 pg/g versus 266.7 ± 14.7 pg/g) compared with that in sucralfate group after 8 weeks of treatment. Malondialdehyde (MDA) contents were significantly depressed both in the trial and control group. When Helicobacter pylori infection was considered, no statistically difference was found in the effect of rebamipide on either symptom or inflammation scores. In conclusion, Rebamipide demonstrated a stronger suppressive effect on the mucosal inflammation in chronic erosive gastritis than sucralfate. The gastroprotection induced by rebamipide is not influenced by H. pylori infection, which indicates its usage in the treatment of H. pylori-associated CEG.     

Rebamipide prevents occurrence of gastric lesions following transcatheter arterial embolization in the hepatic artery

BACKGROUND: Transcatheter arterial embolization (TAE) of the hepatic artery is a common treatment method for hepatocellular carcinoma (HCC), but it often induces gastric mucosal injury. We examined whether or not rebamipide administration, beginning 1 week before and ending 2 weeks afterTAE, can prevent worsening of gastric mucosal disorders. METHODS: The subjects were 73 chronic hepatitis C or type C liver cirrhosis patients who concomitantly had HCC and received TAE in our hospital. The patients were randomly allocated to the rebamipide group (oral, 300 mg/day for 3 weeks starting 1 week before TAE) or the non-rebamipide group. Gastric endoscopy was performed 1 week before and 2 weeks afterTAE and the presence of erythema, erosion and/or submucosal haemorrhagic spots was monitored. Based on the findings, gastric mucosal disorder before and after TAE was quantitatively evaluated using the modified Lanza score (MLS). RESULTS: Overall, MLS after TAE increased significantly (P< 0.05). However, in the rebamipide group, MLS did not change. The MLS after TAE increased significantly in patients who had either liver cirrhosis, oesophageal varices or gastropathy (P< 0.01 or < 0.05). In the non-rebamipide group, a significant increase in MLS after TAE was observed in patients who had one of the above-mentioned three diseases (P< 0.01 or < 0.05). CONCLUSIONS: Gastric lesions which were present before TAE were significantly worsened after TAE. Rebamipide administration prevents TAE-induced aggravation of gastric lesions.     

Red Cell Distribution Width for Assessment of Activity of Inflammatory Bowel Disease

Background Impaired iron absorption or increased loss of iron was found to correlate with disease activity and markers of inflammation in inflammatory bowel disease (IBD). Red cell distribution width (RDW) could be a reliable index of anisocytosis with the highest sensitivity to iron deficiency. Aim The importance of RDW in assessment of IBD disease activity is unknown. In this study, we aimed to determine if RDW could be useful in detecting active disease in patients with IBD. Materials and methods A total of 74 patients with ulcerative colitis (UC) and 22 patients with Crohn’s disease (CD) formed the study group with 20 age- and sex-matched healthy volunteers as the control group. CD activity index higher than 150 in patients with CD was considered to indicate active disease. Patients with moderate and severe disease according to the Truelove-Witts scale were accepted as having active UC. In addition to RDW, serum C-reactive protein (CRP) and fibrinogen levels, erythrocyte sedimentation rates (ESR), leukocyte, and platelet counts were measured. Results Fourteen (63.6%) of the patients with CD and 43 (58.1%) of the patients with UC had active disease. RDW, fibrinogen, CRP, ESR, and platelet counts were all significantly elevated in patients having active IBD compared with those without active disease and controls (P < 0.05). The study subjects were further classified into two subgroups: cases with active and inactive UC and those with active and inactive CD. A subgroup analysis indicated that for an RDW cutoff of 14, the sensitivity for detecting active UC was 88% and the specificity was 71% (area under curve [AUC] 0.81, P = 0.0001). RDW was the most sensitive and specific parameter indicating active UC. However, the same was not true for CD since CRP at a cutoff of 0.54 mg/dl showed a sensitivity of 92% and a specificity of 63% (AUC 0.92, P = 0.001), whereas RDW at a cutoff of 14.1 showed 78% sensitivity and 63% specificity to detect active CD. Conclusion Among the laboratory tests investigated, including fibrinogen, CRP, ESR, and platelet counts, receiver operating characteristic (ROC) curve analysis indicated RDW to be the most significant indicator of active UC. For CD, CRP was an important marker of active disease.     

Activated platelets as a possible early marker to predict clinical efficacy of leukocytapheresis in severe ulcerative colitis patients

Background Leukocytapheresis (LCAP) is an effective adjunct for patients with active ulcerative colitis (UC). Because LCAP may have the potential to remove and modulate not only leukocytes but also platelets, we evaluated the correlation between activated platelets and the therapeutic response to LCAP. Methods Fourteen patients with severe UC received weekly LCAP for 5 consecutive weeks. Their average clinical activity index (CAI) and endoscopic index (EI) were 9.6 ± 3.4 and 10.9 ± 1.0, respectively. Their peripheral blood was sampled before and after every LCAP and stained with fluorescent antibodies to the activation-dependent surface antigens of platelets (CD63, CD62-P) prior to flow cytometry. Endoscopic evaluations were performed after the last LCAP. Results Clinical remission (CAI < 4) was induced in 50% of the patients (7/14) after 5 weeks, and there were no significant differences observed in clinical background between the responder group (RG) and the nonresponder group (NG). In the RG, the populations of CD63⁺ (P < 0.03) and CD62-P⁺ (P < 0.05) platelets were significantly decreased after the first LCAP, and their reduction ratio decreased gradually with repeated LCAP. A significant improvement of the EI score, especially mucosal damage, was achieved in RG (P < 0.04) but not in NG. Conclusions These results indicate that the therapeutic responses to LCAP were reflected in modulations of population and/or platelet functions, especially after the first session. The decrease of such activated platelets immediately after the first LCAP may be an early marker for predicting the response in patients with severe UC.     

Inulin-type fructans improve active ulcerative colitis associated with microbiota changes and increased short-chain fatty acids levels

The intestinal microbiota is involved in ulcerative colitis (UC) pathogenesis. Prebiotics are hypothesized to improve health through alterations to gut microbiota composition and/or activity. Our aim was therefore to determine if inulin-type fructans induce clinical benefits in UC, and identify if benefits are linked to compositional and/or functional shifts of the luminal (fecal) and mucosal (biopsy) bacterial communities. Patients (n = 25) with mild/moderately active UC received 7.5 g (n = 12) or 15 g (n = 13) daily oral oligofructose-enriched inulin (Orafti®Synergy1) for 9 weeks. Total Mayo score, endoscopic activity and fecal calprotectin were assessed. Fecal and mucosal bacterial communities were characterized by 16S rRNA tag sequencing, and short chain fatty acids (SCFA) production were measured in fecal samples. Fructans significantly reduced colitis in the high-dose group, with 77% of patients showing a clinical response versus 33% in the low-dose group (P = 0.04). Fructans increased colonic butyrate production in the 15 g/d dose, and fecal butyrate levels were negatively correlated with Mayo score (r = ?0.50; P = 0.036). The high fructan dose led to an increased Bifidobacteriaceae and Lachnospiraceae abundance but these shifts were not correlated with improved disease scores. In summary, this pilot study revealed that 15 g/d dose inulin type fructans in UC produced functional but not compositional shifts of the gut microbiota, suggesting that prebiotic-induced alterations of gut microbiota metabolism are more important than compositional changes for the benefits in UC. The findings warrant future well-powered controlled studies for the use of β-fructans as adjunct therapy in patients with active UC.     

Mucosal proinflammatory cytokine production correlates with endoscopic activity of ulcerative colitis

Proinflammatory cytokines are believed to be involved in the pathogenesis of ulcerative colitis (UC). The aim of this study was to clarify the profiles of proinflammatory cytokine production in patients with UC in terms of disease intractability, endoscopic findings, and host response to lipopolysaccharide (LPS) stimulation. Colonic mucosal tissues were obtained from patients with active UC (n = 15, including 4 patients with intractable disease) and inactive UC (n = 7), non-inflammatory bowel disease (IBD) colitis (n = 11), and controls (n = 20). Organ culture was performed, and the amounts of four cytokines (described below) in the culture media were determined by enzyme-linked immunosorbent assay (ELISA). LPS stimulation enhanced interleukin (IL)-1β, IL-8, and IL-6 production in colonic specimens from all groups, but enhanced tumor necrosis factor (TNF)-α production only in active UC specimens. Levels of IL-6, IL-8, and TNF-α were significantly higher in active UC than in non-IBD colitis, and the production of all three of these cytokines was correlated to the endoscopic grade of inflammation. The production of these cytokines was also significantly higher in patients with intractable disease receiving corticosteroids than in patients with non-intractable disease receiving corticosteroids. These results suggest that enhanced production of mucosal proinflammatory cytokines may be implicated in the pathogenesis of UC. (Received Jan. 30, 1998; accepted Aug. 28, 1998)     

窄带光成像肠镜下黏膜血管形态对溃疡性结肠炎患者肠上皮增殖的预测价值

目的探讨窄带光成像(NBI)肠镜下溃疡性结肠炎(UC)患者不同黏膜血管形态(MVP)分型对UC患者肠上皮增殖的预测价值。方法选择2012年12月1日至2015年1月31日在北京协和医院就诊且接受NBI肠镜检查的42例UC患者,采集所有患者普通白光和NBI模式下119个结直肠病变的图像,并至少取1块病变组织用于病理学分析。根据随机数字表法将所有内镜图像随机分配至1位内镜医师(副主任医师),对肠黏膜组织的MVP分型和梅奥内镜评分(MES)做出判断。采用结肠炎组织学评分标准对肠黏膜炎症程度进行0~4级评分,根据免疫组织化学染色结果分析判断黏膜上皮Ki-67表达分布和表达程度。采用Student-Newman-Keuls(SNK)-q检验和Spearman相关分析进行统计学分析。结果UC患者的NBI肠镜下MVP分为清晰型、模糊型和消失型,根据黏膜表面腺管形态,消失型又分为隐窝开口亚型和绒毛亚型。NBI模式下MVP分型与普通白光模式下MES标准呈正相关(r=0.80,P<0.001)。MVP模糊型、消失型、消失型隐窝开口亚型、消失型绒毛亚型病变的Ki-67染色指数均高于MVP清晰型病变(30.3±12.8、45.9±12.5、45.5±12.1、46.3±13.1比15.6±7.3),差异均有统计学意义(SNK-q检验,均P<0.001);MVP消失型、消失型隐窝开口亚型、消失型绒毛亚型病变的Ki-67染色指数均高于MVP模糊型病变,差异均有统计学意义(SNK-q检验,均P<0.001)。NBI肠镜下不同MVP分型与Ki-67表达分布呈正相关(r=0.49,P<0.001)。组织学炎症程度为2、3、4级的Ki-67染色指数高于1级(28.8±10.9、40.2±11.6、49.5±10.3比17.1±8.4),差异有统计学意义(SNK-q检验,均P<0.001);组织学炎症程度为3、4级的Ki-67染色指数高于2级,组织学炎症程度为4级的Ki-67染色指数高于3级,差异均有统计学意义(SNK-q检验,均P<0.001)。Ki-67表达分布与组织学炎症程度呈正相关(r=0.56,P<0.001)。结论NBI肠镜下MVP分型可间接预测UC患者肠上皮增殖活性,肠上皮增殖活性可能与黏膜炎症程度密切相关。     

窄带光成像肠镜下黏膜血管形态对溃疡性结肠炎患者肠上皮增殖的预测价值

目的探讨窄带光成像(NBI)肠镜下溃疡性结肠炎(UC)患者不同黏膜血管形态(MVP)分型对UC患者肠上皮增殖的预测价值。方法选择2012年12月1日至2015年1月31日在北京协和医院就诊且接受NBI肠镜检查的42例UC患者,采集所有患者普通白光和NBI模式下119个结直肠病变的图像,并至少取1块病变组织用于病理学分析。根据随机数字表法将所有内镜图像随机分配至1位内镜医师(副主任医师),对肠黏膜组织的MVP分型和梅奥内镜评分(MES)做出判断。采用结肠炎组织学评分标准对肠黏膜炎症程度进行0~4级评分,根据免疫组织化学染色结果分析判断黏膜上皮Ki-67表达分布和表达程度。采用Student-Newman-Keuls(SNK)-q检验和Spearman相关分析进行统计学分析。结果UC患者的NBI肠镜下MVP分为清晰型、模糊型和消失型,根据黏膜表面腺管形态,消失型又分为隐窝开口亚型和绒毛亚型。NBI模式下MVP分型与普通白光模式下MES标准呈正相关(r=0.80,P<0.001)。MVP模糊型、消失型、消失型隐窝开口亚型、消失型绒毛亚型病变的Ki-67染色指数均高于MVP清晰型病变(30.3±12.8、45.9±12.5、45.5±12.1、46.3±13.1比15.6±7.3),差异均有统计学意义(SNK-q检验,均P<0.001);MVP消失型、消失型隐窝开口亚型、消失型绒毛亚型病变的Ki-67染色指数均高于MVP模糊型病变,差异均有统计学意义(SNK-q检验,均P<0.001)。NBI肠镜下不同MVP分型与Ki-67表达分布呈正相关(r=0.49,P<0.001)。组织学炎症程度为2、3、4级的Ki-67染色指数高于1级(28.8±10.9、40.2±11.6、49.5±10.3比17.1±8.4),差异有统计学意义(SNK-q检验,均P<0.001);组织学炎症程度为3、4级的Ki-67染色指数高于2级,组织学炎症程度为4级的Ki-67染色指数高于3级,差异均有统计学意义(SNK-q检验,均P<0.001)。Ki-67表达分布与组织学炎症程度呈正相关(r=0.56,P<0.001)。结论NBI肠镜下MVP分型可间接预测UC患者肠上皮增殖活性,肠上皮增殖活性可能与黏膜炎症程度密切相关。     

Epidermal Growth Factor in Gastric Ulcer Healing by Nocloprost,a Stable Prostaglandin E2 Derivative

Background: The gastroprotective and ulcer-healing properties of prostaglandins, especially in gastric ulcers induced by non-steroidal anti-inflammatory drugs, are well established. Ulcer healing is an active process of filling the mucosal defect with migrating and proliferating epithelial cells combined with angiogenesis in granulation tissue at the ulcer bed. Growth factors, especially epidermal growth factor (EGF) and transforming growth factor alpha (TGFa) are crucial in the regulation of the reconstruction of damaged mucosal structures. Methods: In this double-blind, randomized, prospective study 40 patients with gastric ulcer were treated with nocloprost, a stable prostaglandin E₂ derivative, or with ranitidine. All subjects underwent endoscopy before and after 4 and 8 weeks of anti-ulcer therapy. During endoscopy mucosal biopsies were performed for determination of EGF content in gastric mucosa at the ulcer margin and in the intact mucosa. Additionally, EGF output in saliva and its plasma concentrations were determined in all subjects before and during the treatment. Results: The gastric ulcer healing rate after 4 weeks was significantly higher in patients treated with nocloprost than in those treated with ranitidine (63% versus 39%, respectively). At initial examination the EGF content in the gastric mucosa obtained from the ulcer edge was significantly higher than that in the intact mucosa. There was a significant increase in the EGF content in both the ulcer margin and the intact mucosa in subjects treated with nocloprost but not in patients under treatment with ranitidine. Similarly, patients treated with nocloprost had significantly higher EGF output in saliva and higher EGF concentration in plasma throughout the anti-ulcer therapy. Conclusion: Nocloprost is superior to ranitidine in the treatment of chronic gastric ulcers, and these effects could be due, at least in part, to higher expression and mucosal content of EGF in the ulcer area.     

Novel endoscopic activity index is useful for choosing treatment in severe active ulcerative colitis patients

Aim  

Clinical symptoms are the most important factors used by physicians to evaluate the severity and extent of ulcerative colitis (UC). In this context, colonoscopy is also a useful diagnostic tool. We have recently developed an endoscopic activity index (EAI) to assess the severity of UC. Here, we assess the correlations among the EAI, other endoscopic indices, and clinical scores. The usefulness of the EAI for choosing treatment options, such as intravenous corticosteroid or cyclosporine A (CsA), in severe UC patients was also evaluated.     

Efficacy and safety of adalimumab in Japanese patients with moderately to severely active ulcerative colitis

Background

Adalimumab is a fully human, monoclonal antibody against tumor necrosis factor that is approved in Western countries for the treatment of moderately to severely active ulcerative colitis (UC).

Methods

This 52-week, phase 2/3, randomized, double-blind study evaluated adalimumab for induction and maintenance treatment in 273 anti-TNF–naive Japanese patients with UC who were refractory to corticosteroids, immunomodulators, or both. Patients received placebo, adalimumab 80/40 (80 mg at week 0, then 40 mg every other week), or adalimumab 160/80 (160/80 mg at weeks 0/2, then 40 mg every other week) in addition to background UC therapy.

Results

At week 8, remission rates were similar among treatment arms, but more patients treated with adalimumab 160/80 achieved response (placebo, 35 %; 80/40, 43 %; 160/80, 50 %; P = 0.044 for 160/80 vs placebo) and mucosal healing (placebo, 30 %; 80/40, 39 %; 160/80, 44 %; P = 0.045 for 160/80 vs placebo) compared with placebo. At week 52, more patients receiving adalimumab 40 mg every other week achieved response (18 vs 31 %; P = 0.021), remission (7 vs 23 %; P = 0.001), and mucosal healing (16 vs 29 %; P = 0.015) compared with placebo. Week 8 response to adalimumab was associated with greater rates of response (61 %), remission (46 %), and mucosal healing (57 %) at week 52 relative to the overall population. Rates of serious adverse events were similar between treatment arms.

Conclusions

Induction with adalimumab 160/80 mg led to early response and mucosal healing. Maintenance adalimumab had greater rates of long-term response, remission, and mucosal healing compared with placebo. No new safety signals were identified.     

Mucosal Expression of Interleukin-6 and Interleukin-8 Messenger RNA in Ulcerative Colitis and in Crohn's Disease

To elucidate the possible role ofproinflammatory cytokines in inflammatory bowel disease,the expression and localization of interleukin (IL)-6and IL-8 mRNAs were examined in colonic biopsy specimens obtained from 10 patients with activeulcerative colitis (UC), 5 with inactive UC, 6 withCrohn's disease (CD), and 5 normal controls. In situhybridization with digoxigenin-labeled probes andimmunohistochemistry for both cytokines were performed. The IL-6mRNA expression was enhanced in the inflamed mucosa in4 of 6 CD patients, while that of UC patients stayed atbaseline. In contrast, IL-8 mRNA expression was apparently augmented (P = 0.044) in 7 of 10active UC and 3 of 6 CD patients (NS). The cell countpositive for IL-8 mRNA per unit area was definitelyincreased in moderate/severe UC when compared to mild UC (53.1 ± 14.4/mm² vs 9.0± 5.1/mm², P = 0.028) according to thedegree of inflammation. IL-6 mRNA positive cells in CDwere preferentially located in deeper lamina propriathan IL-8 mRNA positive cells in UC. Interestingly, IL-8 mRNA wasexpressed in the mucosal epithelial cells in one UCpatient. The patients treated by corticosteroids tendedto show suppressed expression of each mRNA, except one patient with intractable UC. Our data suggestenhanced expression of mucosal IL-6 mRNA in CD and ofIL-8 mRNA in UC by infiltrating mononuclear cells,indicating the distinct participation of each cytokine in the pathogenesis of UC and CD. Moreover,intestinal epithelial cells in UC occasionally exhibitIL-8 mRNA.     

Effects of sulfasalazine on biopsy mucosal pathologies and histological grading of patients with active ulcerative colitis

AIM: To investigate the mechanisms of sulfasalazine (SASP) in the treatment of ulcerative colitis (UC). METHODS: Changes of pathological signs and histological grading of 106 patients with active UC were observed before and after the treatment with SASP, 1 g, thrice daily for 6 wk. RESULTS: The effect of SASP on the vasculitis in lamina propria was 48.2% and 17.4% in the mild active UC (P<0.001) and 68% and 26.7% in the moderate active UC (P<0.001) before and after treatment. Fibroid necrosis of vessel wall was found in one case of mild UC and two cases of moderate UC before treatment and was not found after treatment. No thrombosis was found in mild UC before and after treatment, while thrombosis was found in one case of moderate UC before treatment. The effect on mucosal glandular abnormality was 30.4% and 13.0% in mild UC (P<0.05), and 42% and 40% in moderate UC (P>0.05) before and after treatment. The rate of eosinophil infiltration was 98.2% and 80.4% in mild UC (P<0.01), and 100% and 91.1% in moderate UC (P<0.05) before and after treatment. The effect on crypt abscess was 21.4% and 4.4% in mild UC (P<0.05), and 48% and 13.3% in moderate UC (P<0.001) before and after treatment. The effect on mucosal pathohistological grading was 2.00+/-0.84 and 0.91+/-0.46 in mild UC (P<0.001), and 2.49+/-0.84 and 1.31+/-0.75 in moderate UC (P<0.001) before and after treatment. CONCLUSION: SASP can improve small vessel lesions and crypt abscesses and reduce neutrophilic and eosinophilic leukocyte infiltration in inflammatory mucosa of UC.