Pharmaceutical companies that produce gastrointestinal(GI)medications often utilize phthalates for their ability to localize medication release.Commonly prescribed GI medications that may utilize phthalates are 5-Amin...Pharmaceutical companies that produce gastrointestinal(GI)medications often utilize phthalates for their ability to localize medication release.Commonly prescribed GI medications that may utilize phthalates are 5-Aminosalicylates,proton pump inhibitors,and pancreatic enzymes.Our understanding of the cumulative health effects of phthalates from medications remains unclear,and there is increasing evidence that phthalates are not harmless.Experimental studies in animals have shown that phthalates,specifically dibutyl phthalate and Di-(2-ethyl-hexyl)phthalate,have the potential to alter and/or inhibit reproductive biology and in utero development.Despite the lack of definitive human data,many cohort and cross-sectional studies demonstrate concerning associations between phthalates and poor health status,specifically developmental problems.Longitudinal studies and studies with larger sample sizes are required to determine whether phthalates actually cause negative health consequences.It is also important that physicians regularly review and discuss with patients the medicinal ingredients in their medications and supplements,specifically in pregnant woman with inflammatory bowel disease.展开更多
AIM To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates(5ASA) with corticosteroids(CS) versus corticosteroids alone for patients with active ulcerative colitis(...AIM To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates(5ASA) with corticosteroids(CS) versus corticosteroids alone for patients with active ulcerative colitis(UC). METHODS A cross-sectional questionnaire exploring physicians' attitude toward 5ASA + CS combination therapy vs CS alone was developed and validated. The questionnaire was distributed to gastroenterology experts in twelve countries in five continents. Respondents' agreement with stated treatment choices were assessed by standardized Likert scale. Background professional characteristics of respondents were analyzed for correlation with responses. RESULTS Six hundred and sixty-four questionnaires were distributed and 349 received(52.6% response rate). Of 340 eligible respondents, 221(65%) would continue 5ASA in a patient hospitalized for intravenous CS treatment due to a moderate-severe UC flare, while 108(32%) would stop the 5ASA(P < 0.001), and 11(3%) are undecided. Similarly, 62% would continue 5ASA in an out-patient starting oral CS. However, only 140/340(41%) would proactively start 5ASA in a hospitalized patient not receiving 5ASA before admission. Most(94%) physicians consider the safety profile of 5ASA as very good. Only 52% consider them inexpensive, 35% perceive them to be expensive and 12% are undecided. On multi-variable analysis, less years of practice and perception of a plausible additive mechanistic effect of 5ASA + CS were positively associated with the decision to continue 5ASA with CS. CONCLUSION Despite the absence of data supporting its benefit, most gastroenterologists endorse combination of 5ASA + CS for patients with active moderate-to-severe UC. Randomized controlled trials are needed to assess if 5ASA confer any benefit for these patients.展开更多
AIM： To investigate whether microproteinuria in patients with inflammatory bowel disease （IBD） is associated with the disease activity or the treatment with 5-aminosalicylic acid （5-ASA）. METHODS： We prospective...AIM： To investigate whether microproteinuria in patients with inflammatory bowel disease （IBD） is associated with the disease activity or the treatment with 5-aminosalicylic acid （5-ASA）. METHODS： We prospectively studied microproteinuria in 86 consecutive patients with IBD, 61 with ulcerative colitis （UC） and 25 with Crohn＇s disease （CD）, before as well as 2 and 6 months after their inclusion in the study. Forty-six patients received 5-ASA for a period of 28.8 months （range 1-168 too）. Microalbuminuria （mALB） and urine levels of the renal tubular proteins β2-microglobulin （β2mGLB） and β-N-acetyI-D-glucosamidase （β-NAG） as well as the creatinine clearance were determined in a 12-h overnight urine collection. Tumor necrosis factor-α （TNF-α） serum levels were also measured. RESULTS： A total of 277 measurements （194 in UC patients and 83 in CD patients） were performed. The prevalence of abnormal microoproteinuria in UC and CD patients was 12.9% and 6.0% for mALB, 22.7% and 27.7% for B2mGLB, and 11.3% and 8.4% for β-NAG, respectively, mALB was not associated with IBD activity. β2mGLB and B-NAG urine levels were correlated to UC activity （UCAI： P〈0.01; UCEI： P〈0.005）. mALB in UC patients and β-NAG urine levels in CD patients were related to TNF-α serum levels. An association was noticed between microproteinuria and smoking habit. Treatment with 5-ASA was not correlated to the severity of microproteinuria or to the changes of creatinine clearance.CONCLUSION： Microproteinuria is mainly associated with UC and its activity but not affected by 5-ASA.展开更多
INTRODUCTIONThe 1990’s have brought a significant promise and the hopefor a better and brighter future in the new millennium forpatients with inflammatory bowel disease(IBD).A betterunderstanding of the pathophysiolo...INTRODUCTIONThe 1990’s have brought a significant promise and the hopefor a better and brighter future in the new millennium forpatients with inflammatory bowel disease(IBD).A betterunderstanding of the pathophysiology of IBD symptoms hasled to newer treatment modalities and streamlining oftherapy for specific subsets of patients.展开更多
AIM： To observe if the total amount of platelet P-selectin （tP-selectin） in patients with inflammatory bowel disease （IBD） was related to disease entity or activity, 5-aminosalicylic acid （5-ASA） medication or ...AIM： To observe if the total amount of platelet P-selectin （tP-selectin） in patients with inflammatory bowel disease （IBD） was related to disease entity or activity, 5-aminosalicylic acid （5-ASA） medication or gender. METHODS： tP-selectin was measured by immunoassay in seventeen IBD patients and twelve healthy controls. RESULTS： Compared to controls, there was no difference of tP-selectin in patients related to disease entity or activity and 5-ASA medication. When the groups were split according to gender the male patient group showed higher levels of tP-selectin compared to male controls （153 ng/mL vs 94 ng/mL, P〈 0.05）. CONCLUSION： Increased tP-selectin levels may alter the inflammatory response and susceptibility to thromboembolic disease. As previously shown with soluble P-selectin, tP-selectin shows gender dependent differences important to consider in future studies.展开更多
Inflammatory bowel disease (IBD) is classically subdivided into ulcerative colitis (UC) and Crohn's disease (CD). Patients with IBD have increased risk for colorectal cancer. Because the pathogenesis of colorectal...Inflammatory bowel disease (IBD) is classically subdivided into ulcerative colitis (UC) and Crohn's disease (CD). Patients with IBD have increased risk for colorectal cancer. Because the pathogenesis of colorectal carcinoma has not been entirely defined yet and there is no ideal treatment for colon cancer, cancer prevention has become increasingly important in patients with IBD. The two adopted methods to prevent the development of colon cancer in clinical practice include the prophylactic colectomy and colonoscopic surveillance.But patients and physicians seldom accept colectomy as a routine preventive method and most patients do not undergo appropriate colonoscopic surveillance. Chemoprevention refers to the use of natural or synthetic chemical agents to reverse, suppress, or to delay the process of carcinogenesis.Chemoprevention is a particularly useful method in the management of patients at high risk for the development of specific cancers based on inborn genetic susceptibility, the presence of cancer-associated disease, or other known risk factors. Prevention of colorectal cancer by administration of chemopreventive agents is one of the most promising options for IBD patients who are at increased risks of the disease. The chemopreventive efficacy of nonsteroidal antiinflammatory drugs (NSAIDs) against intestinal tumors has been well established. But with reports that NSAIDs aggravated the symptoms of colitis, their sustained use for the purpose of cancer chemoprevention has been relatively contraindicated in IBD patients. Another hopeful candidate chemoprevention drug for IBD patients is 5-aminosalicylic acid (5-ASA), which is well tolerated by most patients and has limited systemic adverse effects, and no gastrointestinal toxicity. 5-ASA lacks the well-known side effects of longterm NSAIDs use. Retrospective correlative studies have suggested that the long-term use of 5-ASA in IBD patients may significantly reduce the risk of development of colorectal cancer. According to the literature, this agent might w展开更多
Severe reactions to mesalamine products are rarely seen in pediatric patients. We report a case of a 12-year-old boy who had a severe cardiac reaction to a mesalamine product Asacol. Past medical history is significan...Severe reactions to mesalamine products are rarely seen in pediatric patients. We report a case of a 12-year-old boy who had a severe cardiac reaction to a mesalamine product Asacol. Past medical history is significant for ulcerative colitis (UC) diagnosed at 9 years of age. Colo- noscopy one week prior to admission revealed pancoli- tis. He was treated with Asacol 800 mg three times per day and prednisone 20 mg/d. He was subsequently ad- mitted to the hospital for an exacerbation of his UC and started on intravenous solumedrol. He had improvement of his abdominal pain and diarrhea. The patient com- plained of new onset of chest pain upon initiating Asacol therapy. Electrocardiogram (ECG) revealed non-specific ST-T wave changes with T-wave inversion in the lateral leads. Echocardiogram (ECHO) revealed low-normal to mildly depressed left ventricular systolic function. The left main coronary artery and left anterior descending artery were mildly prominent measuring 5 mm and 4.7 mm, respectively. His chest pain completely resolved within 24-36 h of discontinuing Asacol. A repeat echo- cardiogram performed two days later revealed normal left ventricular function with normal coronary arteries (< 3.5 mm). Onset of chest pain after Asacol and im- mediate improvement of chest pain, as well as improve- ment of echocardiogram and ECG findings after discon- tinuing Asacol suggests that our patient suffered from a rare drug-hypersensitivity reaction to Asacol.展开更多
BACKGROUND Congestive ischemic colitis is a rare subtype of ischemic colitis with an unknown pathophysiology.Excluding conservative management,such as fasting,no established treatment exists;therefore,surgical interve...BACKGROUND Congestive ischemic colitis is a rare subtype of ischemic colitis with an unknown pathophysiology.Excluding conservative management,such as fasting,no established treatment exists;therefore,surgical intervention should be considered in some cases if symptoms worsen.Current literature suggests that anti-inflam-matory agents may effectively treat congestive ischemic colitis.CASE SUMMARY We present the case of a 68-year-old female patient who underwent laparoscopic left hemicolectomy for transverse colon cancer 3 years ago.Postoperatively,follow-up included an annual colonoscopy and abdominal computed tomography(CT)at a local clinic.However,progressive erythema and edema of the sigmoid colon were observed 1 year postoperatively.Upon admission to our hospital,she complained of abdominal pain and diarrhea.Abdominal CT showed thickening of the sigmoid colon walls,and colonoscopy revealed erythema,edema,and multiple ulcers with exudate in the sigmoid colon.CT angiography showed engorgement of the sigmoid vasa recta without any vascular abnormalities.The diagnosis was congestive ischemic colitis,and we treated the patient with anti-inflammatory agents.After 2 mo of glucocorticoid therapy(20 mg once daily)and 7 mo of 5-aminosalicylate therapy(1 g twice daily),the ulcers completely healed.She has not experienced any recurrence for 2 years.CONCLUSION Anti-inflammatory therapy,specifically glucocorticoids and 5-aminosalicylate,has demonstrated promising efficacy and introduces potential novel treatment options for congestive ischemic colitis.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
Inflammatory bowel diseases(IBD)are chronic diseases with a relapsing-remitting disease course necessitating lifelong treatment.However,non-adherence has been reported in over 40%of patients,especially those in remiss...Inflammatory bowel diseases(IBD)are chronic diseases with a relapsing-remitting disease course necessitating lifelong treatment.However,non-adherence has been reported in over 40%of patients,especially those in remission taking maintenance therapies for IBD. The economical impact of non-adherence to medical therapy including absenteeism,hospitalization risk, and the health care costs in chronic conditions,is enormous.The causes of medication non-adherence are complex,where the patient-doctor relationship, treatment regimen,and other disease-related factors play key roles.Moreover,subjective assessment might underestimate adherence.Poor adherence may result in more frequent relapses,a disabling disease course, in ulcerative colitis,and an increased risk for colorectal cancer.Improving medication adherence in patients is an important challenge for physicians.Understanding the different patient types,the reasons given by patients for non-adherence,simpler and more convenient dosage regimens,dynamic communication within the health care team,a self-management package incorporating enhanced patient education and physician-patient interaction,and identifying the predictors of nonadherence will help devise suitable plans to optimize patient adherence.This editorial summarizes the available literature on frequency,predictors,clinical consequences,and strategies for improving medical adherence in patients with 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-展开更多
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
AIM:To assess patients' understanding for the reasons for taking 5-aminosalicylic acid or ursodeoxycholic acid as chemoprophylaxis against colorectal carcinoma associated with in? ammatory bowel disease (IBD). MET...AIM:To assess patients' understanding for the reasons for taking 5-aminosalicylic acid or ursodeoxycholic acid as chemoprophylaxis against colorectal carcinoma associated with in? ammatory bowel disease (IBD). METHODS: A questionnaire-based study using a 5 point opinion scale was performed. One hundred and ninety-two patients with colitis only and 74 patients with primary sclerosing cholangitis and IBD were invited to take part. RESULTS: Overall response rate was 58%. Sixtyfour percent of patients claimed full concordance with chemoprophylaxis for maintenance of remission. Eightyfour percent of patients considered daily concordance during remission to be very important. Seventy-five percent stated they understood the reasons for taking the drugs. However, only 50% of the patients were aware of any link of their condition to bowel cancer. Seventy-nine percent of patients felt their concordance and understanding would be improved if they were informed of the chemoprophylactic potential of the medication.展开更多
5-aminosalicylic acid(5-ASA)compounds are a highly effective treatment for ulcerative colitis(UC).While UC patient compliance in clinical studies is over 90%, only 40%of patients in every day life take their prescribe...5-aminosalicylic acid(5-ASA)compounds are a highly effective treatment for ulcerative colitis(UC).While UC patient compliance in clinical studies is over 90%, only 40%of patients in every day life take their prescribed therapy.Adherence to medication has been emphasized recently by a Cochrane meta-analysis that has suggested that future trials of 5-ASA in UC should look at patient compliance rather than drug efficacy. Better compliance can be obtained by reducing the number of tablets and times of administration.Given that the 5-ASA formulations have different delivery systems that split the active moiety in various regions of the intestine,it is particularly important that an adequate dose of the drug arrives at the inflamed part of the colon.5-ASA Multi matrix(MMx)is a novel,high strength(1.2 g),oral formulation designed for oncedaily dosing.It releases the active moiety throughout the colon.Different studies with this compound have shown that it is as effective as 5-ASA enema in the treatment of mild-to-moderate,left-sided UC,and is comparable to a pH-dependent,delayed release 5-ASA (Asacol ),even if given once daily.Recently,the effectiveness in the acute phase of UC has been confirmed also in maintenance.In conclusion,at present,5-ASA MMx seems theoretically the best agent for maintaining patient compliance,and consequently,treatment effectiveness.展开更多
5-aminosalicylate(5-ASA)agents remain the mainstay treatment in ulcerative colitis(UC).A number of oral 5-ASA agents are commercially available,including azobond pro-drugs,as well as delayed-and controlledrelease form...5-aminosalicylate(5-ASA)agents remain the mainstay treatment in ulcerative colitis(UC).A number of oral 5-ASA agents are commercially available,including azobond pro-drugs,as well as delayed-and controlledrelease forms of mesalazine.However,poor adherence due to frequent daily dosing and a large number of tablets has been shown to be an important barrier to successful management of patients with UC.Recently, new,once-daily formulations of mesalazine,including the unique multi-matrix delivery system and mesalazine granules,were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC,with a good safety profile comparable to that of other oral mesalazine formulations.In addition,they offer the advantage of a low pill burden and might contribute to increased long-term compliance and treatment success in clinical practice.This editorial summarizes the available literature on the short-and medium-term efficacy and safety of the new once-daily mesalazine formulations.展开更多
Adverse reactions to mesalamine,a treatment used to induce and maintain remission in inflammatory bowel diseases,particularly ulcerative colitis,have been described in the literature as case reports.This case illustra...Adverse reactions to mesalamine,a treatment used to induce and maintain remission in inflammatory bowel diseases,particularly ulcerative colitis,have been described in the literature as case reports.This case illustrates an unusual adverse reaction.Our patient developed an isolated fever of unexplained etiology,which was found to be related to mesalamine treatment.A 22-year-old patient diagnosed with ulcerative colitis developed a fever with rigors and anorexia 10 d after starting oral mesalamine while his colitis was clinically resolving.Testing revealed no infection.A mesalamineinduced fever was considered,and treatment was stopped,which led to spontaneous resolution of the fever.The diagnosis was confirmed by reintroducing the mesalamine.One year later,this side effect was noticed again in the same patient after he was administered topical mesalamine.This reaction to mesalamine seems to be idiosyncratic,and the mechanism that induces fever remains unclear.Fever encountered in the course of a mesalamine treatment in ulcerative colitis must be considered a mesalamine-induced fever when it cannot be explained by the disease activity,an associated extraintestinal manifestation,or an infectious etiology.展开更多
New once daily mesalamine formulations may improve adherence to medication usage.Response to Asacol and other forms of 5-aminosalicyclic acid(5-ASA)is better correlated with tissue concentrations and best predicted by...New once daily mesalamine formulations may improve adherence to medication usage.Response to Asacol and other forms of 5-aminosalicyclic acid(5-ASA)is better correlated with tissue concentrations and best predicted by concentrations of the drug within the lumen of the colon.Our group used computer simulation to predict colonic 5-ASA levels after Asacol administration.In our study,the model simulated Asacol distribution in the healthy colon,and during quiescent and active ulcerative colitis.An Asacol dosage of 800 mg,threetimes a day,was compared to 2400 mg given once a day.Under ideal conditions,the predicted maximum drug in the total colon and individual colonic segments over 100 d differed by less than 3%between single and multiple doses.Despite changes in motility and defection rates,the predicted maximum and average 5-ASA concentrations in the total colon and individual colonic segments differed by less than 10%between dosing regimens.Asymmetric distribution of 5-ASA in the colon was influenced by frequency of bowel movements and colonic transit rate.In active colitis,sigmoid 5-ASA concentration becomes negligible.Our model supports once daily administration of Asacol as standard treatment for ulcerative colitis.展开更多
AIM: To investigate the effects of 5-aminosalicylic acid (5-ASA) in combination with nimesulide on the proliferation of HT-29 colon carcinoma cells and its potential mechanisms. METHODS: Inhibitory effects of drugs (5...AIM: To investigate the effects of 5-aminosalicylic acid (5-ASA) in combination with nimesulide on the proliferation of HT-29 colon carcinoma cells and its potential mechanisms. METHODS: Inhibitory effects of drugs (5-ASA,nimesulide and their combination) on HT-29 colon carcinoma cells were investigated by thiazolyl blue tetrazolium bromide (MTT) assay. Cellular apoptosis and proliferation were detected by TUNEL assay and immunocytochemical staining,respectively. RESULTS: Pretreatment with 5-ASA or nimesulide at the concentration of 10-1000 μmol/L inhibited proliferation of HT-29 colon carcinoma cells in a dose-dependent manner in vitro (t = 5.122,P < 0.05; t = 3.086,P < 0.05,respectively). The inhibition rate of HT-29 colon carcinoma cell proliferation was also increased when pretreated with 5-ASA (100 μmol/L) or nimesulide (100 μmol/L) for 12-96 h,which showed an obvious time-effect relationship (t = 6.149,P < 0.05; t = 4.159,P < 0.05,respectively). At the concentration of 10-500 μmol/L,the apoptotic rate of HT-29 colon carcinoma cells significantly increased (t = 18.156,P < 0.001; t = 19.983,P < 0.001,respectively),while expression of proliferating cell nuclear antigen (PCNA) was remarkably decreased (t = 6.828,P < 0.05; t = 14.024,P < 0.05,respectively). 5-ASA in combination with nimesulide suppressed the proliferation of HT-29 colon carcinoma cells more than either of these agents in a dose-dependent and time-dependent manner (t = 5.448,P < 0.05; t = 4.428,P < 0.05,respectively). CONCLUSION: 5-ASA and nimesulide may inhibit the proliferation of HT-29 colon carcinoma cells and coadministration of these agents may have additional chemopreventive potential.展开更多
Inflammatory bowel diseases(IBD), including Crohn's disease(CD) and ulcerative colitis, are chronic relapsing and remitting diseases of the bowel, with an unknown etiology and appear to involve interaction between...Inflammatory bowel diseases(IBD), including Crohn's disease(CD) and ulcerative colitis, are chronic relapsing and remitting diseases of the bowel, with an unknown etiology and appear to involve interaction between genetic susceptibility, environmental factors and the immune system. Although our knowledge and understanding of the pathogenesis and causes of IBD have improved significantly, the incidence in the pediatric population is still rising. In the last decade more drugs and treatment option have become available including 5-aminosalicylate,antibiotics, corticosteroids, immunomodulators and biological agents. Before the use of anti-tumor necrosis factor(TNF)-α became available to patients with IBD, the risk for surgery within five years of diagnosis was very high, however, with anti-TNF-α treatment the risk of surgery has decreased significantly. In the pediatric population a remission in disease can be achieved by exclusive enteral nutrition. Exclusive enteral nutrition also has an important role in the improvement of nutritional status and maintained growth. In this review we summarize the current therapeutic treatments in CD. The progress in the treatment options and the development of new drugs has led to optimized tactics for achieving the primary clinical goals of therapy- induction and maintenance of remission while improving the patient's growth and overall well-being.展开更多
文摘Pharmaceutical companies that produce gastrointestinal(GI)medications often utilize phthalates for their ability to localize medication release.Commonly prescribed GI medications that may utilize phthalates are 5-Aminosalicylates,proton pump inhibitors,and pancreatic enzymes.Our understanding of the cumulative health effects of phthalates from medications remains unclear,and there is increasing evidence that phthalates are not harmless.Experimental studies in animals have shown that phthalates,specifically dibutyl phthalate and Di-(2-ethyl-hexyl)phthalate,have the potential to alter and/or inhibit reproductive biology and in utero development.Despite the lack of definitive human data,many cohort and cross-sectional studies demonstrate concerning associations between phthalates and poor health status,specifically developmental problems.Longitudinal studies and studies with larger sample sizes are required to determine whether phthalates actually cause negative health consequences.It is also important that physicians regularly review and discuss with patients the medicinal ingredients in their medications and supplements,specifically in pregnant woman with inflammatory bowel disease.
文摘AIM To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates(5ASA) with corticosteroids(CS) versus corticosteroids alone for patients with active ulcerative colitis(UC). METHODS A cross-sectional questionnaire exploring physicians' attitude toward 5ASA + CS combination therapy vs CS alone was developed and validated. The questionnaire was distributed to gastroenterology experts in twelve countries in five continents. Respondents' agreement with stated treatment choices were assessed by standardized Likert scale. Background professional characteristics of respondents were analyzed for correlation with responses. RESULTS Six hundred and sixty-four questionnaires were distributed and 349 received(52.6% response rate). Of 340 eligible respondents, 221(65%) would continue 5ASA in a patient hospitalized for intravenous CS treatment due to a moderate-severe UC flare, while 108(32%) would stop the 5ASA(P < 0.001), and 11(3%) are undecided. Similarly, 62% would continue 5ASA in an out-patient starting oral CS. However, only 140/340(41%) would proactively start 5ASA in a hospitalized patient not receiving 5ASA before admission. Most(94%) physicians consider the safety profile of 5ASA as very good. Only 52% consider them inexpensive, 35% perceive them to be expensive and 12% are undecided. On multi-variable analysis, less years of practice and perception of a plausible additive mechanistic effect of 5ASA + CS were positively associated with the decision to continue 5ASA with CS. CONCLUSION Despite the absence of data supporting its benefit, most gastroenterologists endorse combination of 5ASA + CS for patients with active moderate-to-severe UC. Randomized controlled trials are needed to assess if 5ASA confer any benefit for these patients.
文摘AIM： To investigate whether microproteinuria in patients with inflammatory bowel disease （IBD） is associated with the disease activity or the treatment with 5-aminosalicylic acid （5-ASA）. METHODS： We prospectively studied microproteinuria in 86 consecutive patients with IBD, 61 with ulcerative colitis （UC） and 25 with Crohn＇s disease （CD）, before as well as 2 and 6 months after their inclusion in the study. Forty-six patients received 5-ASA for a period of 28.8 months （range 1-168 too）. Microalbuminuria （mALB） and urine levels of the renal tubular proteins β2-microglobulin （β2mGLB） and β-N-acetyI-D-glucosamidase （β-NAG） as well as the creatinine clearance were determined in a 12-h overnight urine collection. Tumor necrosis factor-α （TNF-α） serum levels were also measured. RESULTS： A total of 277 measurements （194 in UC patients and 83 in CD patients） were performed. The prevalence of abnormal microoproteinuria in UC and CD patients was 12.9% and 6.0% for mALB, 22.7% and 27.7% for B2mGLB, and 11.3% and 8.4% for β-NAG, respectively, mALB was not associated with IBD activity. β2mGLB and B-NAG urine levels were correlated to UC activity （UCAI： P〈0.01; UCEI： P〈0.005）. mALB in UC patients and β-NAG urine levels in CD patients were related to TNF-α serum levels. An association was noticed between microproteinuria and smoking habit. Treatment with 5-ASA was not correlated to the severity of microproteinuria or to the changes of creatinine clearance.CONCLUSION： Microproteinuria is mainly associated with UC and its activity but not affected by 5-ASA.
文摘INTRODUCTIONThe 1990’s have brought a significant promise and the hopefor a better and brighter future in the new millennium forpatients with inflammatory bowel disease(IBD).A betterunderstanding of the pathophysiology of IBD symptoms hasled to newer treatment modalities and streamlining oftherapy for specific subsets of patients.
基金Supported by grants from the County Council of■stergtland,Sweden(No.2000/080 and 2001/039)
文摘AIM： To observe if the total amount of platelet P-selectin （tP-selectin） in patients with inflammatory bowel disease （IBD） was related to disease entity or activity, 5-aminosalicylic acid （5-ASA） medication or gender. METHODS： tP-selectin was measured by immunoassay in seventeen IBD patients and twelve healthy controls. RESULTS： Compared to controls, there was no difference of tP-selectin in patients related to disease entity or activity and 5-ASA medication. When the groups were split according to gender the male patient group showed higher levels of tP-selectin compared to male controls （153 ng/mL vs 94 ng/mL, P〈 0.05）. CONCLUSION： Increased tP-selectin levels may alter the inflammatory response and susceptibility to thromboembolic disease. As previously shown with soluble P-selectin, tP-selectin shows gender dependent differences important to consider in future studies.
文摘Inflammatory bowel disease (IBD) is classically subdivided into ulcerative colitis (UC) and Crohn's disease (CD). Patients with IBD have increased risk for colorectal cancer. Because the pathogenesis of colorectal carcinoma has not been entirely defined yet and there is no ideal treatment for colon cancer, cancer prevention has become increasingly important in patients with IBD. The two adopted methods to prevent the development of colon cancer in clinical practice include the prophylactic colectomy and colonoscopic surveillance.But patients and physicians seldom accept colectomy as a routine preventive method and most patients do not undergo appropriate colonoscopic surveillance. Chemoprevention refers to the use of natural or synthetic chemical agents to reverse, suppress, or to delay the process of carcinogenesis.Chemoprevention is a particularly useful method in the management of patients at high risk for the development of specific cancers based on inborn genetic susceptibility, the presence of cancer-associated disease, or other known risk factors. Prevention of colorectal cancer by administration of chemopreventive agents is one of the most promising options for IBD patients who are at increased risks of the disease. The chemopreventive efficacy of nonsteroidal antiinflammatory drugs (NSAIDs) against intestinal tumors has been well established. But with reports that NSAIDs aggravated the symptoms of colitis, their sustained use for the purpose of cancer chemoprevention has been relatively contraindicated in IBD patients. Another hopeful candidate chemoprevention drug for IBD patients is 5-aminosalicylic acid (5-ASA), which is well tolerated by most patients and has limited systemic adverse effects, and no gastrointestinal toxicity. 5-ASA lacks the well-known side effects of longterm NSAIDs use. Retrospective correlative studies have suggested that the long-term use of 5-ASA in IBD patients may significantly reduce the risk of development of colorectal cancer. According to the literature, this agent might w
文摘Severe reactions to mesalamine products are rarely seen in pediatric patients. We report a case of a 12-year-old boy who had a severe cardiac reaction to a mesalamine product Asacol. Past medical history is significant for ulcerative colitis (UC) diagnosed at 9 years of age. Colo- noscopy one week prior to admission revealed pancoli- tis. He was treated with Asacol 800 mg three times per day and prednisone 20 mg/d. He was subsequently ad- mitted to the hospital for an exacerbation of his UC and started on intravenous solumedrol. He had improvement of his abdominal pain and diarrhea. The patient com- plained of new onset of chest pain upon initiating Asacol therapy. Electrocardiogram (ECG) revealed non-specific ST-T wave changes with T-wave inversion in the lateral leads. Echocardiogram (ECHO) revealed low-normal to mildly depressed left ventricular systolic function. The left main coronary artery and left anterior descending artery were mildly prominent measuring 5 mm and 4.7 mm, respectively. His chest pain completely resolved within 24-36 h of discontinuing Asacol. A repeat echo- cardiogram performed two days later revealed normal left ventricular function with normal coronary arteries (< 3.5 mm). Onset of chest pain after Asacol and im- mediate improvement of chest pain, as well as improve- ment of echocardiogram and ECG findings after discon- tinuing Asacol suggests that our patient suffered from a rare drug-hypersensitivity reaction to Asacol.
文摘BACKGROUND Congestive ischemic colitis is a rare subtype of ischemic colitis with an unknown pathophysiology.Excluding conservative management,such as fasting,no established treatment exists;therefore,surgical intervention should be considered in some cases if symptoms worsen.Current literature suggests that anti-inflam-matory agents may effectively treat congestive ischemic colitis.CASE SUMMARY We present the case of a 68-year-old female patient who underwent laparoscopic left hemicolectomy for transverse colon cancer 3 years ago.Postoperatively,follow-up included an annual colonoscopy and abdominal computed tomography(CT)at a local clinic.However,progressive erythema and edema of the sigmoid colon were observed 1 year postoperatively.Upon admission to our hospital,she complained of abdominal pain and diarrhea.Abdominal CT showed thickening of the sigmoid colon walls,and colonoscopy revealed erythema,edema,and multiple ulcers with exudate in the sigmoid colon.CT angiography showed engorgement of the sigmoid vasa recta without any vascular abnormalities.The diagnosis was congestive ischemic colitis,and we treated the patient with anti-inflammatory agents.After 2 mo of glucocorticoid therapy(20 mg once daily)and 7 mo of 5-aminosalicylate therapy(1 g twice daily),the ulcers completely healed.She has not experienced any recurrence for 2 years.CONCLUSION Anti-inflammatory therapy,specifically glucocorticoids and 5-aminosalicylate,has demonstrated promising efficacy and introduces potential novel treatment options for congestive ischemic colitis.
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.
文摘Inflammatory bowel diseases(IBD)are chronic diseases with a relapsing-remitting disease course necessitating lifelong treatment.However,non-adherence has been reported in over 40%of patients,especially those in remission taking maintenance therapies for IBD. The economical impact of non-adherence to medical therapy including absenteeism,hospitalization risk, and the health care costs in chronic conditions,is enormous.The causes of medication non-adherence are complex,where the patient-doctor relationship, treatment regimen,and other disease-related factors play key roles.Moreover,subjective assessment might underestimate adherence.Poor adherence may result in more frequent relapses,a disabling disease course, in ulcerative colitis,and an increased risk for colorectal cancer.Improving medication adherence in patients is an important challenge for physicians.Understanding the different patient types,the reasons given by patients for non-adherence,simpler and more convenient dosage regimens,dynamic communication within the health care team,a self-management package incorporating enhanced patient education and physician-patient interaction,and identifying the predictors of nonadherence will help devise suitable plans to optimize patient adherence.This editorial summarizes the available literature on frequency,predictors,clinical consequences,and strategies for improving medical adherence in patients with 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-
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AIM:To assess patients' understanding for the reasons for taking 5-aminosalicylic acid or ursodeoxycholic acid as chemoprophylaxis against colorectal carcinoma associated with in? ammatory bowel disease (IBD). METHODS: A questionnaire-based study using a 5 point opinion scale was performed. One hundred and ninety-two patients with colitis only and 74 patients with primary sclerosing cholangitis and IBD were invited to take part. RESULTS: Overall response rate was 58%. Sixtyfour percent of patients claimed full concordance with chemoprophylaxis for maintenance of remission. Eightyfour percent of patients considered daily concordance during remission to be very important. Seventy-five percent stated they understood the reasons for taking the drugs. However, only 50% of the patients were aware of any link of their condition to bowel cancer. Seventy-nine percent of patients felt their concordance and understanding would be improved if they were informed of the chemoprophylactic potential of the medication.
文摘5-aminosalicylic acid(5-ASA)compounds are a highly effective treatment for ulcerative colitis(UC).While UC patient compliance in clinical studies is over 90%, only 40%of patients in every day life take their prescribed therapy.Adherence to medication has been emphasized recently by a Cochrane meta-analysis that has suggested that future trials of 5-ASA in UC should look at patient compliance rather than drug efficacy. Better compliance can be obtained by reducing the number of tablets and times of administration.Given that the 5-ASA formulations have different delivery systems that split the active moiety in various regions of the intestine,it is particularly important that an adequate dose of the drug arrives at the inflamed part of the colon.5-ASA Multi matrix(MMx)is a novel,high strength(1.2 g),oral formulation designed for oncedaily dosing.It releases the active moiety throughout the colon.Different studies with this compound have shown that it is as effective as 5-ASA enema in the treatment of mild-to-moderate,left-sided UC,and is comparable to a pH-dependent,delayed release 5-ASA (Asacol ),even if given once daily.Recently,the effectiveness in the acute phase of UC has been confirmed also in maintenance.In conclusion,at present,5-ASA MMx seems theoretically the best agent for maintaining patient compliance,and consequently,treatment effectiveness.
文摘5-aminosalicylate(5-ASA)agents remain the mainstay treatment in ulcerative colitis(UC).A number of oral 5-ASA agents are commercially available,including azobond pro-drugs,as well as delayed-and controlledrelease forms of mesalazine.However,poor adherence due to frequent daily dosing and a large number of tablets has been shown to be an important barrier to successful management of patients with UC.Recently, new,once-daily formulations of mesalazine,including the unique multi-matrix delivery system and mesalazine granules,were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC,with a good safety profile comparable to that of other oral mesalazine formulations.In addition,they offer the advantage of a low pill burden and might contribute to increased long-term compliance and treatment success in clinical practice.This editorial summarizes the available literature on the short-and medium-term efficacy and safety of the new once-daily mesalazine formulations.
文摘Adverse reactions to mesalamine,a treatment used to induce and maintain remission in inflammatory bowel diseases,particularly ulcerative colitis,have been described in the literature as case reports.This case illustrates an unusual adverse reaction.Our patient developed an isolated fever of unexplained etiology,which was found to be related to mesalamine treatment.A 22-year-old patient diagnosed with ulcerative colitis developed a fever with rigors and anorexia 10 d after starting oral mesalamine while his colitis was clinically resolving.Testing revealed no infection.A mesalamineinduced fever was considered,and treatment was stopped,which led to spontaneous resolution of the fever.The diagnosis was confirmed by reintroducing the mesalamine.One year later,this side effect was noticed again in the same patient after he was administered topical mesalamine.This reaction to mesalamine seems to be idiosyncratic,and the mechanism that induces fever remains unclear.Fever encountered in the course of a mesalamine treatment in ulcerative colitis must be considered a mesalamine-induced fever when it cannot be explained by the disease activity,an associated extraintestinal manifestation,or an infectious etiology.
文摘New once daily mesalamine formulations may improve adherence to medication usage.Response to Asacol and other forms of 5-aminosalicyclic acid(5-ASA)is better correlated with tissue concentrations and best predicted by concentrations of the drug within the lumen of the colon.Our group used computer simulation to predict colonic 5-ASA levels after Asacol administration.In our study,the model simulated Asacol distribution in the healthy colon,and during quiescent and active ulcerative colitis.An Asacol dosage of 800 mg,threetimes a day,was compared to 2400 mg given once a day.Under ideal conditions,the predicted maximum drug in the total colon and individual colonic segments over 100 d differed by less than 3%between single and multiple doses.Despite changes in motility and defection rates,the predicted maximum and average 5-ASA concentrations in the total colon and individual colonic segments differed by less than 10%between dosing regimens.Asymmetric distribution of 5-ASA in the colon was influenced by frequency of bowel movements and colonic transit rate.In active colitis,sigmoid 5-ASA concentration becomes negligible.Our model supports once daily administration of Asacol as standard treatment for ulcerative colitis.
基金Supported by The Key Laboratory of Digestive Diseases of Anhui Province and colleagues from Department of Gastroenterology, The First Affiliated Hospital, Anhui Medical University, China
文摘AIM: To investigate the effects of 5-aminosalicylic acid (5-ASA) in combination with nimesulide on the proliferation of HT-29 colon carcinoma cells and its potential mechanisms. METHODS: Inhibitory effects of drugs (5-ASA,nimesulide and their combination) on HT-29 colon carcinoma cells were investigated by thiazolyl blue tetrazolium bromide (MTT) assay. Cellular apoptosis and proliferation were detected by TUNEL assay and immunocytochemical staining,respectively. RESULTS: Pretreatment with 5-ASA or nimesulide at the concentration of 10-1000 μmol/L inhibited proliferation of HT-29 colon carcinoma cells in a dose-dependent manner in vitro (t = 5.122,P < 0.05; t = 3.086,P < 0.05,respectively). The inhibition rate of HT-29 colon carcinoma cell proliferation was also increased when pretreated with 5-ASA (100 μmol/L) or nimesulide (100 μmol/L) for 12-96 h,which showed an obvious time-effect relationship (t = 6.149,P < 0.05; t = 4.159,P < 0.05,respectively). At the concentration of 10-500 μmol/L,the apoptotic rate of HT-29 colon carcinoma cells significantly increased (t = 18.156,P < 0.001; t = 19.983,P < 0.001,respectively),while expression of proliferating cell nuclear antigen (PCNA) was remarkably decreased (t = 6.828,P < 0.05; t = 14.024,P < 0.05,respectively). 5-ASA in combination with nimesulide suppressed the proliferation of HT-29 colon carcinoma cells more than either of these agents in a dose-dependent and time-dependent manner (t = 5.448,P < 0.05; t = 4.428,P < 0.05,respectively). CONCLUSION: 5-ASA and nimesulide may inhibit the proliferation of HT-29 colon carcinoma cells and coadministration of these agents may have additional chemopreventive potential.
文摘Inflammatory bowel diseases(IBD), including Crohn's disease(CD) and ulcerative colitis, are chronic relapsing and remitting diseases of the bowel, with an unknown etiology and appear to involve interaction between genetic susceptibility, environmental factors and the immune system. Although our knowledge and understanding of the pathogenesis and causes of IBD have improved significantly, the incidence in the pediatric population is still rising. In the last decade more drugs and treatment option have become available including 5-aminosalicylate,antibiotics, corticosteroids, immunomodulators and biological agents. Before the use of anti-tumor necrosis factor(TNF)-α became available to patients with IBD, the risk for surgery within five years of diagnosis was very high, however, with anti-TNF-α treatment the risk of surgery has decreased significantly. In the pediatric population a remission in disease can be achieved by exclusive enteral nutrition. Exclusive enteral nutrition also has an important role in the improvement of nutritional status and maintained growth. In this review we summarize the current therapeutic treatments in CD. The progress in the treatment options and the development of new drugs has led to optimized tactics for achieving the primary clinical goals of therapy- induction and maintenance of remission while improving the patient's growth and overall well-being.
