Effects of antagonistic peptides binding specifically with first and second extracellular loops of CCR5 on colitis rats induced by TNBS / 中国病理生理杂志

AIM:To study the effects of antagonistic peptides binding specifically with the first and second extracellular loops (ECL1 and ECL2) of C-C chemokine receptor 5 (CCR5) on the colitis rats induced by trinitrobenzenesulfonic acid (TNBS) and the mechanisms.METHODS:The colitis model of SD rats was induced by TNBS (100 mg/kg).The effects of 2 antagonistic peptides at different doses (ECL1:25, 35 and 45 mg/kg;ECL2:15, 25 and 35 mg/kg) on the model rats including the changes of disease activity index (DAI), colon macroscopic damage index (CMDI) and histological grading were observed.The mRNA and protein expression levels of TNF-α and COX-2 in the colonic mucosa were detected by real-time PCR and Western blot, respectively.RESULTS:Compared with model group, the changes of DAI, CMDI and histopathological injury of the rats treated with ECL2 antagonistic peptide HY at an appropriate dose were significantly reduced (P<0.05), and the protein and mRNA expression levels of TNF-α and COX-2 were significantly decreased (P<0.05).However, the effects of ECL1 antagonistic peptide GH on all scores and the expression levels of TNF-α and COX-2 were not obvious.CONCLUSION:ECL2 antagonistic peptide HY relieves TNBS-induced colitis in SD rats via down-regulating the expressions of TNF-α and COX-2 in the colonic mucosa, while the effect of ECL1 antagonist peptide GH was not obvious.

Relationship between Autophagy Abnormalities and Pathogenesis of Inflammatory Bowel Disease / 胃肠病学

Autophagy dysfunction is present in patients with inflammatory bowel disease (IBD), and the single-nucleotide polymorphisms (SNP) of autophagy related genes ATG16L1, NOD2 and IRGM might contribute to an increased susceptibility to IBD.Autophagy might participate in the pathogenesis of IBD through immune response and tolerance, intracellular bacterial infection, abnormalities in immune regulation and Paneth cells, and endoplasmic reticulum stress.This article reviewed the relationship between autophagy abnormalities and pathogenesis of IBD.

Correlation of CCR5 expression with β-arrestin 2 expression in colonic mucosa of patients with inflammatory bowel disease / 中国病理生理杂志

AIM:To analyze the expression of CCR5 and correlation with the expression ofβ-arrestin 2 in the intestinal mucosa of the patients with inflammatory bowel disease ( IBD) , so as to study the role of CCR5 andβ-arrestin 2 in the pathogenesis of IBD.METHODS:Paraffin sections of the colonic mucosa were prepared from 53 patients with active IBD, 26 patients with remissive IBD and 30 healthy people.Immunohistochemical EnVision two-step method was used to test the expression of CCR5 andβ-arrestin 2 in the biopsic intestinal mucosa.RESULTS:The positive rate, strongly posi-tive rate and immunohistochemical score of CCR5 expression in active IBD were significantly higher than those in normal controls or remissive IBD (P<0.05).No correlation of CCR5 expression with clinical severity, lesion distribution, and endoscopic grade in active IBD was observed.The expression ofβ-arrestin 2 was significantly lower in active IBD than that in the remissive IBD and normal controls, and there was a negative correlation ofβ-arrestin 2 expression with CCR5 expres-sion (P<0.05).CONCLUSION:The expression of CCR5 is higher, and expression ofβ-arrestin 2 is lower, and there is a negative correlation of expression of CCR5 with expression ofβ-arrestin 2 in intestinal mucosa of the active IBD.

Panning and identification of antagonistic active peptides specifically bin-ding to the first and second extracellular membrane loops of rat CCR5 by technique of phage display peptide library / 中国病理生理杂志

[ ABSTRACT] AIM: To pan the active peptides which specifically bound to the first and second extracellular membrane loops of rat CC chemokine receptor 5 ( CCR5 ) .METHODS: The technique of phage display peptide library was used and binding ability of the peptides was identified.The amino acid sequences of the first and second extracellular loops of rat CCR5 were searched in the protein database and chemically synthesized corresponding linear peptides were used as targets in the biopanning.After 3 to 4 rounds of screening with Ph.D.TM-7 Phage Display Peptide Library were per-formed, the specific phages were collected and primarily identified by ELISA.RESULTS:The sequences of the peptides displayed on the selected phages were GHWKVWL and HYIDFRW, both of them exhibited positive in phage binding ELISA and the binding to phages and targets were concentration dependent and saturable.CONCLUSION:Two antagonis-tic active peptides specifically binding to CCR5 were successfully obtained by the technique of phage display peptide librar-y, and the binding ability to the first and second extracellular membrane loops of rat CCR5 were proved in vitro.

Clinical evaluation of sulfasalazine in the treatment of patients with mild and moderate ulcerative colitis / 中国临床药理学与治疗学

AIM: To investigate the short-term efficacy and safety of sulfasalazine (SASP) 3 g per day in the treatment of patients with mild and moderate ulcerative colitis (UC). METHODS: 122 patients were treated with SASP ( 1 g, t.i.d.) for 6 weeks. The data of clinical manifestations, colonoscopic and histological involvements were compared before and after the treatment of UC. The short-period efficacy and adverse reactions were evaluated in 110 patients. RESULTS: The therapeutic project was carried out in the 110 out of 122 patients. After 110 patients were treated for 6 weeks, the clinical, colonoscopic and histological remission were 71.8%, 21.8% and 16.4%, respectively. Among the 79 patients with clinical remission, 58.2% and 67.1% of them remained grade 1 in colonoscopic and histological findings, respectively. The curative rates and the effective rates were 63.9% and 82.0%, respectively. Among the 122 patients treated with SASP, 21 of them ( 17.2%) had adverse reactions. Except 4 patients suffered urticaria and leukopenia, no patients quitted the treatment because of obvious adverse reaction. CONCLUSION: SASP ( 3 g per day) can be an effective and safe medicine in treatment of patients with mild and moderate UC, but more than half of the patients in clinical remission still have light inflammation in colonoscopy and histology.

Pathohistologic features and grading of biopsy mucosae and their correlation with disease severity of active ulcerative colitis / 中华消化杂志

Objective To investigate the pathohistologic features and grading of biopsy mucosae and their correlation with disease severity of active ulcerative colitis(UC). Methods A prospective study was conducted in 133 patients with UC who were divided into three groups based on the degree of severity. Pathologic morphometry and grading with HE staining sections were analyzed. Results Pathologic features of active UC: there were neutrophilic leukocytes (100.0%), eosinophils (99.2%), plasmacytes(91.7%) and lymphocytes (75.2%) infiltration among mucosal epithelial cells, and lymphoid follicular formation(72.2%) and small vessels inflammation(63.9%) and focal hemorrhage(68.4%) in lamina propria. There were crypt abscesses(43.6%), glandular abnormalities (44.4%), goblet cell depletion (18.8%), epithelial cell regeneration (36.8%) , atypical hyperplasia (28.6%) and granulation tissue formation (42.9%) in mucosae. With the increase of severity of UC, there was a significant increasing incidence of small vessel inflammation, fiberoid necrosis of vessel wall, glandular abnormality, epithelial cell regeneration, atypical hyperplasia, goblet cell depletion, granulation tissue formation, fiber tissue hyperplasia, and crypt abscess. There was no significant difference of the incidence of lymphocyte hyperplasia, lymphoid follicular formation, eosinophil and plasmacyte infiltration between the groups. Mild UC was mainly characterized by the lesions of Grade Ⅰ and Ⅱ, moderate UC by those of Grade Ⅱ and Ⅲ and severe UC by those of Grade Ⅲ and Ⅳ. There were significant differences of grades among mild, moderate and severe UC. Conclusions There were some pathologic characters in active UC. The partial of markers and histological gradings can reflect the severity and activity of active UC.

Effect of sulfasalazine on biopsy mucosal pathology and histological grading of patients with the mild and moderate active ulcerative colitis / 中华消化杂志

0.05) before and after treatment. The rates of eosinophil infiltration: 98.2% vs. 80.4% in the mild UC (P

Analysis of the clinical, pathological and endoscopic features of patients with ulcerative pancolitis and distal colitis / 中华消化杂志

Objective To investigate the clinical, pathological and endoscopic features of patients with ulcerative pancolitis (PUC) and distal colitis (DUC) and their differentiations. Methods The clinical, pathological and endoscopic data of 52 patients with PUC and 97 patients with DUC were analyzed by case-control study. Results The incidence and the frequency of bloody stool in patients with PUC were both higher than those in DUC (90.38% vs. 71.13%, P

Effect of Clarithromycin on Eradicating Helicobacter Pylori in Pediatric Patients With Peptic Ulcer / 中国药房

0 05) There was significant difference of relieve of abdominal pain in every group before treatment,and in 3 days,1 week after treatment (P0 05) The main adverse drug reactions were nause,vomiting,anorexia and mild diarrhoea,and special taste in a few cases Total incidence of adverse reaction was 28% in group A,4 3% in group B and 25% in group C There were significant differences among three groups(P

Grading of mucosal histological biopsies, clinical appearances and endoscopies in patients with active ulcerative colitis / 中华消化内镜杂志

Objective To investigate the correlations between histological grading of the mucosal biopsies, clinical appearances and endoscopies of patients with active ulcerative colitis ( AUC) , and their roles in the therapeutic outcomes. Methods To analyze the grading in pathological, endoscopic and clinical manifestations of 133 patients, and use the scores to estimate each clinical appearance. A prospective study and Spearman correlation coefficients analysis were taken in this study. Results Among 133 patients, the grading of histological, clinical and endoscopic results in grades Ⅰ ,Ⅱ , Ⅲ , andⅣwere 29,45 ,37 and 22; 85 , 39,9 and 0; 8,30,16 and 79 cases respectively. There were significant positive correlations between histological grading and the following parameters; melena ( r =0. 49, P= 0. 000) , bowel movement ( r =0. 30, P = 0.001) , ESR (r=0. 42, P =0.000) , AI(r=0.56, P=0.000) , clinical grade (r=0.52, P=0.000) endoscopic grade (r = 0. 35 , P =0. 000). And no significant negative correlation with Hb (r = -0. 13, P = 0. 125). In 68 mild and moderate cases after administered SASP for 6 weeks with clinical remission there were 16 and 19 cases with 0 grade in endoscopies and histology respectively, and in the former group 7 cases fall in histological grade I . Conclusion There was no agreement in the clinical, endoscopic and histological grades of the AUC patients. For the evaluation of therapy, the sequence of priority is histological grade, endoscopic grade, and then clinical grade.