AIM: To study anti-Epstein-Barr virus(EBV) Ig G antibodies in Crohn′s disease in relation to treatment, immune cells, and prior tonsillectomy/appendectomy.METHODS: This study included 36 CD patients and 36 healthy in...AIM: To study anti-Epstein-Barr virus(EBV) Ig G antibodies in Crohn′s disease in relation to treatment, immune cells, and prior tonsillectomy/appendectomy.METHODS: This study included 36 CD patients and 36 healthy individuals(controls), and evaluated different clinical scenarios(new patient, remission and active disease), previous mucosa-associated lymphoid tissue removal(tonsillectomy and appendectomy) and therapeutic regimens(5-aminosalicylic acid, azathioprine, anti-tumor necrosis factor, antibiotics, and corticosteroids). T and B cells subsets in peripheral blood were analyzed by flow cytometry(markers included: CD45, CD4, CD8, CD3, CD19, CD56, CD2, CD3, TCRαβ and TCRγδ) to relate with the levels of anti-EBV Ig G antibodies, determined by enzyme-linked immunosorbent assay.RESULTS: The lowest anti-EBV Ig G levels were observed in the group of patients that were not in a specific treatment(95.4 ± 53.9 U/m L vs 131.5 ± 46.2 U/m L, P = 0.038). The patients that were treated with 5-aminosalicylic acid showed the highest anti-EBV Ig G values(144.3 U/m L vs 102.6 U/m L, P = 0.045). CD19+ cells had the largest decrease in the group of CD patients that received treatment(138.6 vs 223.9; P = 0.022). The analysis of anti-EBV Ig G with respect to the presence or absence of tonsillectomy showed the highest values in the tonsillectomy group of CD patients(169.2 ± 20.7 U/m L vs 106.1 ± 50.3 U/m L, P = 0.002). However, in the group of healthy controls, no differences were seen between those who had been tonsillectomized and subjects who had not been operated on(134.0 ± 52.5 U/m L vs 127.7 ± 48.1 U/m L, P = 0.523).CONCLUSION: High anti-EBV Ig G levels in CD are associated with 5-aminosalicylic acid treatment, tonsillectomy, and decrease of CD19+ cells.展开更多
Despite the advent of biological products, such as anti-tumor necrosis factor-α monoclonal antibodies (infliximab and adalimumab), for treatment of moderate to severe cases of inflammatory bowel disease (I...Despite the advent of biological products, such as anti-tumor necrosis factor-α monoclonal antibodies (infliximab and adalimumab), for treatment of moderate to severe cases of inflammatory bowel disease (IBD), most patients depend upon aminosalicylates as the conventional treatment option. In recent years, the increased knowledge of complex pathophysiological processes underlying IBD has resulted in development of a number of newer pharmaceutical agents like low-molecular-weight heparin, omega-3 fatty acids, probiotics and innovative formulations such as high-dose, once-daily multi-matrix mesalamine, which are designed to minimize the inflammatory process through inhibition of different targets. Optimization of delivery of existing drugs to the colon using the prodrug approach is another attractive alternative that has been utilized and commercialized for 5-aminosalicylic acid (ASA) in the form of sulfasalazine, balsalazide, olsalazine and ipsalazine, but rarely for its positional isomer 4-ASA - a well-established antitubercular drug that is twice as potent as 5-ASA against IBD, and more specifically, ulcerative colitis. The present review focuses on the complete profile of 4-ASA and its advantages over 5-ASA and colon-targeting prodrugs reported so far for the management of IBD. The review also emphasizes the need for reappraisal of this promising but unexplored entity as a potential treatment option for IBD.展开更多
5-aminosalicylic acid（5-ASA） is drug of choice for the treatment of ulcerative colitis（UC）. In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mecha...5-aminosalicylic acid（5-ASA） is drug of choice for the treatment of ulcerative colitis（UC）. In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mechanism of this medication. A flexible tube was inserted into the rat cecum to establish a topical administration model of 2,4,6-trinitrobenzene sulfonic acid（TNBS）-induced UC. A total of 60 rats were divided into sham operation group（receiving an enema of 0.9% saline solution instead of the TNBS solution via the tube）, model group, topical 5-ASA group, oral Etiasa group（a release agent of mesalazine used as positive control） and oral 5-ASA group（n=12 each）. Different treatments were administered 1 day after UC induction. The normal saline（2 mL） was instilled twice a day through the tube in the sham operation group and model group. 5-ASA was given via the tube in the topical 5-ASA group（7.5 g/L, twice per day, 100 mg/kg）, and rats in the oral Etiasa group and oral 5-ASA group intragastrically received Etiasa（7.5 g/L, twice per day, 100 mg/kg） and 5-ASA（7.5 g/L, twice per day, 100 mg/kg）, respectively. The body weight was recorded every day. After 7 days of treatment, blood samples were drawn from the heart to harvest the sera. Colonic tissues were separated and prepared for pathological and related molecular biological examinations. The concentrations of 5-ASA were detected at different time points in the colonic tissues, feces and sera in different groups by using the high pressure liquid chromatography（HPLC）. The results showed that the symptoms of acute UC, including bloody diarrhea and weight loss, were significantly improved in topical 5-ASA-treated rats. The colonic mucosal damage, both macroscopical and histological, was significantly relieved and the myeloperoxidase activity was markedly decreased in rats topically treated with 5-ASA compared with those treated with oral 5-ASA or Etiasa. The mRNA and protein expression of IL-1β, IL-6, and TNF-α was down-regulated in the colonic tissue of rats topically treated with 5-ASA, significantly lower than those from rats treated with oral 5-ASA or Etiasa. The concentrations of 5-ASA in the colonic tissue were significantly higher in the topical 5-ASA group than in the oral 5-ASA and oral Etiasa groups. It was concluded that the topical administration of 5-ASA can effectively increase the concentration of 5-ASA in the colonic tissue, decrease the expression of proinflammatory cytokines, alleviate the colonic pathological damage and improve the symptoms of TNBS-induced acute UC in rats.展开更多
AIM:To compare the mucosal concentrations of 5-aminosalicylic acid(5-ASA)resulting from different pharmaceutical formulations and analyse the influence of inflammation on the mucosal concentrations.METHODS:The study i...AIM:To compare the mucosal concentrations of 5-aminosalicylic acid(5-ASA)resulting from different pharmaceutical formulations and analyse the influence of inflammation on the mucosal concentrations.METHODS:The study included 130 inflammatory bowel disease(IBD)patients receiving 5-ASA as pH-dependent-release formulations(73 patients),time-dependent-release formulations(11 patients),or pro-drugs(18patients).In addition,28 patients were receiving topical treatment(2-4 g/d)with pH-dependent-release formulations.Endoscopic biopsies were obtained from the sigmoid region during the colonoscopy.The 5-ASA concentrations(ng/mg)were measured in tissue homogenatesusing high-pressure liquid chromatography with electrochemical detection.The t test and Mann-Whitney test,when appropriate,were used for statistical analysis.RESULTS:Patients receiving pH-dependent-release formulations showed significantly higher mucosal concentrations of 5-ASA(51.75±5.72 ng/mg)compared with patients receiving pro-drugs(33.35±5.78 ng/mg,P=0.01)or time-dependent-release formulations(38.24±5.53 ng/mg,P=0.04).Patients with endoscopic remission had significantly higher mucosal concentrations of5-ASA than patients with active disease(60.14±7.95ng/mg vs 35.66±5.68 ng/mg,P=0.02).Similar results were obtained when we compared patients with the histological appearance of remission and patients with active histological inflammation(67.53±9.22 ng/mg vs 35.53±5.63 ng/mg,P<0.001).Significantly higher mucosal concentrations of 5-ASA were detected in patients treated with both oral and topical treatments in combination compared with patients who received oral treatment with pH-dependent-release formulations alone(72.33±11.23 ng/mg vs 51.75±5.72 ng/mg,P=0.03).CONCLUSION:IBD patients showed significant variability in mucosal 5-ASA concentrations depending on the type of formulation,and the highest mean concentration was achieved using pH-dependent-release formulations.展开更多
文摘AIM: To study anti-Epstein-Barr virus(EBV) Ig G antibodies in Crohn′s disease in relation to treatment, immune cells, and prior tonsillectomy/appendectomy.METHODS: This study included 36 CD patients and 36 healthy individuals(controls), and evaluated different clinical scenarios(new patient, remission and active disease), previous mucosa-associated lymphoid tissue removal(tonsillectomy and appendectomy) and therapeutic regimens(5-aminosalicylic acid, azathioprine, anti-tumor necrosis factor, antibiotics, and corticosteroids). T and B cells subsets in peripheral blood were analyzed by flow cytometry(markers included: CD45, CD4, CD8, CD3, CD19, CD56, CD2, CD3, TCRαβ and TCRγδ) to relate with the levels of anti-EBV Ig G antibodies, determined by enzyme-linked immunosorbent assay.RESULTS: The lowest anti-EBV Ig G levels were observed in the group of patients that were not in a specific treatment(95.4 ± 53.9 U/m L vs 131.5 ± 46.2 U/m L, P = 0.038). The patients that were treated with 5-aminosalicylic acid showed the highest anti-EBV Ig G values(144.3 U/m L vs 102.6 U/m L, P = 0.045). CD19+ cells had the largest decrease in the group of CD patients that received treatment(138.6 vs 223.9; P = 0.022). The analysis of anti-EBV Ig G with respect to the presence or absence of tonsillectomy showed the highest values in the tonsillectomy group of CD patients(169.2 ± 20.7 U/m L vs 106.1 ± 50.3 U/m L, P = 0.002). However, in the group of healthy controls, no differences were seen between those who had been tonsillectomized and subjects who had not been operated on(134.0 ± 52.5 U/m L vs 127.7 ± 48.1 U/m L, P = 0.523).CONCLUSION: High anti-EBV Ig G levels in CD are associated with 5-aminosalicylic acid treatment, tonsillectomy, and decrease of CD19+ cells.
文摘Despite the advent of biological products, such as anti-tumor necrosis factor-α monoclonal antibodies (infliximab and adalimumab), for treatment of moderate to severe cases of inflammatory bowel disease (IBD), most patients depend upon aminosalicylates as the conventional treatment option. In recent years, the increased knowledge of complex pathophysiological processes underlying IBD has resulted in development of a number of newer pharmaceutical agents like low-molecular-weight heparin, omega-3 fatty acids, probiotics and innovative formulations such as high-dose, once-daily multi-matrix mesalamine, which are designed to minimize the inflammatory process through inhibition of different targets. Optimization of delivery of existing drugs to the colon using the prodrug approach is another attractive alternative that has been utilized and commercialized for 5-aminosalicylic acid (ASA) in the form of sulfasalazine, balsalazide, olsalazine and ipsalazine, but rarely for its positional isomer 4-ASA - a well-established antitubercular drug that is twice as potent as 5-ASA against IBD, and more specifically, ulcerative colitis. The present review focuses on the complete profile of 4-ASA and its advantages over 5-ASA and colon-targeting prodrugs reported so far for the management of IBD. The review also emphasizes the need for reappraisal of this promising but unexplored entity as a potential treatment option for IBD.
基金supported by grants from the National Natural Science Foundation of China(No.81072431)the Innova-tion Foundation of Huazhong University of Science and Tech-nology(No.2010MS027)
文摘5-aminosalicylic acid（5-ASA） is drug of choice for the treatment of ulcerative colitis（UC）. In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mechanism of this medication. A flexible tube was inserted into the rat cecum to establish a topical administration model of 2,4,6-trinitrobenzene sulfonic acid（TNBS）-induced UC. A total of 60 rats were divided into sham operation group（receiving an enema of 0.9% saline solution instead of the TNBS solution via the tube）, model group, topical 5-ASA group, oral Etiasa group（a release agent of mesalazine used as positive control） and oral 5-ASA group（n=12 each）. Different treatments were administered 1 day after UC induction. The normal saline（2 mL） was instilled twice a day through the tube in the sham operation group and model group. 5-ASA was given via the tube in the topical 5-ASA group（7.5 g/L, twice per day, 100 mg/kg）, and rats in the oral Etiasa group and oral 5-ASA group intragastrically received Etiasa（7.5 g/L, twice per day, 100 mg/kg） and 5-ASA（7.5 g/L, twice per day, 100 mg/kg）, respectively. The body weight was recorded every day. After 7 days of treatment, blood samples were drawn from the heart to harvest the sera. Colonic tissues were separated and prepared for pathological and related molecular biological examinations. The concentrations of 5-ASA were detected at different time points in the colonic tissues, feces and sera in different groups by using the high pressure liquid chromatography（HPLC）. The results showed that the symptoms of acute UC, including bloody diarrhea and weight loss, were significantly improved in topical 5-ASA-treated rats. The colonic mucosal damage, both macroscopical and histological, was significantly relieved and the myeloperoxidase activity was markedly decreased in rats topically treated with 5-ASA compared with those treated with oral 5-ASA or Etiasa. The mRNA and protein expression of IL-1β, IL-6, and TNF-α was down-regulated in the colonic tissue of rats topically treated with 5-ASA, significantly lower than those from rats treated with oral 5-ASA or Etiasa. The concentrations of 5-ASA in the colonic tissue were significantly higher in the topical 5-ASA group than in the oral 5-ASA and oral Etiasa groups. It was concluded that the topical administration of 5-ASA can effectively increase the concentration of 5-ASA in the colonic tissue, decrease the expression of proinflammatory cytokines, alleviate the colonic pathological damage and improve the symptoms of TNBS-induced acute UC in rats.
文摘AIM:To compare the mucosal concentrations of 5-aminosalicylic acid(5-ASA)resulting from different pharmaceutical formulations and analyse the influence of inflammation on the mucosal concentrations.METHODS:The study included 130 inflammatory bowel disease(IBD)patients receiving 5-ASA as pH-dependent-release formulations(73 patients),time-dependent-release formulations(11 patients),or pro-drugs(18patients).In addition,28 patients were receiving topical treatment(2-4 g/d)with pH-dependent-release formulations.Endoscopic biopsies were obtained from the sigmoid region during the colonoscopy.The 5-ASA concentrations(ng/mg)were measured in tissue homogenatesusing high-pressure liquid chromatography with electrochemical detection.The t test and Mann-Whitney test,when appropriate,were used for statistical analysis.RESULTS:Patients receiving pH-dependent-release formulations showed significantly higher mucosal concentrations of 5-ASA(51.75±5.72 ng/mg)compared with patients receiving pro-drugs(33.35±5.78 ng/mg,P=0.01)or time-dependent-release formulations(38.24±5.53 ng/mg,P=0.04).Patients with endoscopic remission had significantly higher mucosal concentrations of5-ASA than patients with active disease(60.14±7.95ng/mg vs 35.66±5.68 ng/mg,P=0.02).Similar results were obtained when we compared patients with the histological appearance of remission and patients with active histological inflammation(67.53±9.22 ng/mg vs 35.53±5.63 ng/mg,P<0.001).Significantly higher mucosal concentrations of 5-ASA were detected in patients treated with both oral and topical treatments in combination compared with patients who received oral treatment with pH-dependent-release formulations alone(72.33±11.23 ng/mg vs 51.75±5.72 ng/mg,P=0.03).CONCLUSION:IBD patients showed significant variability in mucosal 5-ASA concentrations depending on the type of formulation,and the highest mean concentration was achieved using pH-dependent-release formulations.
