A randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of tegaserod in patients from China with chronic constipation

AIM： To evaluate the efficacy and safety of tegaserod, 6 mg twice daily （b.i.d.）, in men and women with chronic constipation （CC） from China. METHODS： This was a multicenter, double-blind, placebo-controlled study. Following a 2-wk treatmentfree baseline period, patients were randomized to receive either tegaserod （6 mg b.i.d.） or placebo （b.i.d.） for 4 wk. An analysis of covariance with repeated measures was used to determine the overall effect of treatment for the primary efficacy variable; the change from baseline in the number of complete spontaneous bowel movements （CSBMs） during the 4-wk treatment period. Secondary efficacy endpoints included other measures of response in terms of CSBMs, and patients＇ daily and weekly assessment of bowel habits. Safety was also assessed, based on the incidence and severity of adverse events （AEs）. RESULTS： A total of 607 patients were randomized to receive either tegaserod （n = 304） or placebo （n = 303）. Tegaserod treatment resulted in a rapid and significant increase from baseline in the adjusted mean number of CSBMs per week over wk 1-4 compared with placebo （1.39 vs 0.91, P = 0.0002）. A statistically significant difference in favor of tegaserod was also observed for a mean increase ≥ 1 CSBM/wk over wk 1-4 （47.7% vs 35.0%, tegaserod vs placebo, respectively, P = 0.0018） and for the absolute number of≥ 3 CSBMs/wk over wk 1-4 （25.0% vs 14.5%, tegaserod vs placebo, respectively, P = 0.0021）. Improvements in other symptoms of CC were also seen in the tegaserod group, including improved stool form and reduced straining. In addition, more patients in the tegaserod group reported satisfactory relief from their constipation symptoms. The frequency and severity of AEs was comparable between tegaserod and placebo groups, with the exception of a greater incidence of diarrhea in patients receiving tegaserod （3.6%） compared with placebo （1.7%）. CONCLUSION： Tecjaserod treatment improved multiple symptoms of CC and was as     

Ultrastructural changes in hepatocytes after taurine treatment in CCl4 induced liver injury

AIM： To search the organelle based changes in hepatocytes after taurine treatment in experimental liver fibrosis induced by CCl4 administration. METHODS： Thirty rats were divided into two groups. Group 1 （n = 15） was injected with CCl4 plus taurine and Group 2 （n = 15） with CCl4 plus saline for 12 wk. At the end of 12th wk, mitochondria, rough and smooth endoplasmic reticulum, and nuclei of hepatocytes were evaluated using a scoring system. The results were compared with histopathological findings, as well. RESULTS： Taurine treatment reduced fibrosis scores significantly as compared to placebo. Organelle injury scores decreased significantly with taurine treatment. Ultrastructural and histopathological scores in both groups were in strong correlation （r = 0.931 for CCl4 plus taurine and r = 0.899 for CCl4 plus saline group）. CONCLUSION： Organelle based transmission electron microscopy findings can reflect successfully histological results as well as tissue healing in hepatocytes from hepatotoxin-induced liver fibrosis.     

Efficacy and safety of pegylated-interferon α-2a in hemodialysis patients with chronic hepatitis C

AIM： To evaluate the efficacy and safety of pegylated- interferon alpha-2a in hemodialysis patients with chronic hepatitis C. METHODS： Thirty-six hemodialysis patients with chronic hepatitis C were enrolled in a controlled and prospective study. All patients were treatment naive, positive tested for anti-HCV antibodies, and positive tested for serum HCV-RNA. Twenty-two patients received 135 μg peglyated-interferon α-2a weekly for 48 wk （group A）. The remaining patients were left untreated, eleven refused therapy, and three were not candidates for kidney transplantation and were allocated to the control group （group B）. At the end of the treatment biochemical and virological response was evaluated, and 24 wk after completetion of therapy sustained virological response （SVR） was assessed. Side effects were monitored.
RESULTS： Of 22 hemodialysis patients, 12 were male and 10 female, with a mean age of 35.2 ± 12.1 years. Virological end-of-treatment response was observed in 14 patients （82.4%） in group A and in one patient （7.1%） in group B （P = 0.001）. Sustained virological response was observed in 11 patients （64.7%） in group A and in one patient in group B （7.1%）. Biochemical response parameters normalized in 10/14 patients （71.4%） at the end of the treatment. ALT levels in group B were initially high in six patients and normalized in one of them （25%） at the end of the 48 wk. In five patients （22.7%） therapy had to be stopped at mo 4 due to complications of weakness, anemia, and bleeding.
CONCLUSION： SVR could be achieved in 64.7% of patients on hemodialysis with chronic hepatitis C by a treatment with peglyated-interferon α-2a. Group A had a significantly better efficacy compared to the control group B, but the side effects need to be concerned.     

Rifaximin improves survival in cirrhotic patients with refractory ascites: A real-world study

BACKGROUND Rifaximin has been shown to reduce the incidence of hepatic encephalopathy and other complications in patients with cirrhosis.However,few studies have investigated the effect of rifaximin in cirrhotic patients with refractory ascites.AIM To evaluate the effects of rifaximin in the treatment of refractory ascites and to preliminarily explore its possible mechanism.METHODS A total of 75 cirrhotic patients with refractory ascites were enrolled in the study(50 in a rifaximin and 25 in a control group).Patients in the rifaximin group were divided into two subgroups according to the presence of spontaneous bacterial peritonitis and treatment with or without other antibiotics(19 patients treated with rifaximin and 31 patients treated with rifaximin plus intravenous antibiotics).All patients received conventional treatment for refractory ascites,while patients in the rifaximin group received oral rifaximin-α200 mg four times daily for at least 2 wk.The ascites grade,fasting weight,liver and kidney function,and inflammatory factors in the plasma were evaluated before and after treatment.In addition,the gut microbiota was determined by metagenomics sequencing to analyse the changes in the characteristics of the gut microbiota before and after rifaximin treatment.The patients were followed for 6 mo.RESULTS Compared with the control group,the fasting weight of patients significantly decreased and the ascites significantly subsided after treatment with rifaximin(P=0.011 and 0.009,respectively).The 6-mo survival rate of patients in the rifaximin group was significantly higher than that in the control group(P=0.048).The concentration of interferon-inducible protein 10 decreased significantly in the rifaximin group compared with that in the control group(P=0.024).The abundance of Roseburia,Haemophilus,and Prevotella was significantly reduced after rifaximin treatment,while the abundance of Lachnospiraceae_noname,Subdoligranulum,and Dorea decreased and the abundance of Coprobacillus increased after treatment with rifaximin plus intravenous antibiotics.The gene expression of virulence factors was significantly reduced after treatment in both subgroups treated with rifaximin or rifaximin plus intravenous antibiotics.CONCLUSION Rifaximin mitigates ascites and improves survival of cirrhotic patients with refractory ascites.A possible mechanism is that rifaximin regulates the structure and function of intestinal bacteria,thus improving the systemic inflammatory state.     

Effects of n-3 polyunsaturated fatty acids from seal oils on nonalcoholic fatty liver disease associated with hyperlipidemia

AIM： To investigate the efficacy and safety of n-3 polyunsaturated fatty acids （PUFA） from seal oils for patients with nonalcoholic fatty liver disease （NAFLD） associated with hyperlipidemia. METHODS： One hundred and forty-four patients with NAFLD associated with hyperlipidemia were included in the 24-wk, randomized, controlled trial. The patients were randomized into two groups. Group A （n = 72） received recommended diet and 2 g n-3 PUFA from seal oils, three times a day. Group B （n = 72） received recommended diet and 2 g placebo, three times a day. Primary endpoints were fatty liver assessed by symptom scores, liver alanine aminotransferase （ALT） and serum lipid levels after 8, 12, 16, and 24 wk. Hepatic fat infiltration was detected by ultrasonography at weeks 12 and 24 after treatment. RESULTS： A total of 134 patients （66 in group A, 68 in group B） were included in the study except for 10 patients who were excluded from the study. After 24 wk of treatment, no change was observed in body weight, fasting blood glucose （FBG）, renal function and blood cells of these patients. Total symptom scores, ALT and triglyceride （TG） levels decreased more significantly in group A than in group B （P 〈 0.05）. As expected, there was a tendency toward improvement in aspartate aminotransferase （AST）, ~,-glutamyltranspeptidase （GGT）, and total cholesterol （TCHO） and high- density lipoprotein （HDL） cholesterol levels （P 〈 0.05） after administration in the two groups. However, no significant differences were found between the two groups. The values of low-density lipoprotein （LDL） were significantly improved in group A （P 〈 0.05）, but no significant change was found in group B at different time points and after a 24-wk treatment. After treatment, complete fatty liver regression was observed in 19.70% （13/66） of the patients, and an overall reduction was found in 53.03% （35/66） of the patients in group A. In contrast, in group B, only five patients ?     

A randomized controlled trial of imipramine in patients with irritable bowel syndrome

AIM： To study the efficacy of low-dose imipramine in relieving symptoms associated with the irritable bowel syndrome （IBS）. METHODS： A randomized, double-blind trial of 25 mg imipramine vs matched placebo for 12 wk was performed. Doubling the dose was allowed once at week 2 in case of an unsatisfactory early response. Primary efficacy variables were subjective global symptom relief and quality of life （QoL） using SF-36 at week 12. RESULTS： One hundred and seven patients were enrolled by advertisement or referral by general practitioners and 56 （31 imipramine： 25 placebo） completed the 16-wk study. Baseline characteristics were comparable. A high overall dropout rate was noted in the imipramine and placebo arms （47.5% vs 47.9%, P 〉 0.05）, a mean of 25.0 and 37.4 d from enrollment, respectively （P 〈 0.05）. At the end of 12 wk, there was a significant difference in global symptom relief with imipramine over placebo （per-protocol： 80.6% vs 48.0%, P = 0.01） and a trend on intent-to-treat （ITT） analysis （42.4% vs 25.0%, P = 0.06）. This improvement was evident early and persisted to week 16 （P = 0.024 and 0.053 by per-protocol and ITT analyses, respectively）. Mean cumulative and componentspecific SF-36 scores improved in the imipramine group only （per-protocol, P 〈 0.01）. Drug-related adverse events leading to patient dropout were more common in the imipramine group （25.4% vs 12.5%, P 〉 0.05）. CONCLUSION： Imipramine may be effective in the treatment of IBS patients and is associated with improved QoL. Careful patient selection, initiation of a low dose with gradual escalation and monitoring for side effects may result in an improved therapeutic response.     

H pylori eradication：A randomized prospective study of triple therapy with or without ecabet sodium

AIM： To investigate whether adding ecabet sodium to the standard triple therapy for H pylori infection improve eradication rate. METHODS： Two hundred and fifty-seven H pylori-infected patients were randomly assigned to standard triple therapy （group A, n = 129） or triple therapy plus ecabet sodium （group B, n = 128）. Successful eradication was defined as a negative 13C-urea breath test 6-8 wk after completion of treatment. RESULTS： After completion of therapy, 194/257 patients showed negative 13C-urea breath test results. According to intention-to-treat analysis, the infection was eradicated in 93/129 （72.1%） patients in group A and 101/128 （78.9%） in group B （P = 0.204）. Per-protocol analysis showed successful eradication in 93/118 （78.8%） patients from group A and 101/114 （88.6%） from group B （P = 0.044）. There were no significant differences in the side effects experienced by the patients in the two treatment groups. CONCLUSION： Our results suggest that the addition of ecabet sodium improves the efficacy of the standard triple therapy for H pylori.     

Antioxidant therapy for chronic hepatitis C after failure of interferon： Results of phase Ⅱ randomized,double-blind placebo controlled clinical trial

AIM： TO assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus （HCV） infection.
METHODS： One hundred chronic HCV infection patients failed in interferon treatment were enrolled and randomly assigned to receive combined intravenous and oral antioxidants or placebo, or oral treatment alone, Primary end points were liver enzymes, HCV-RNA levels and histology.
RESULTS： Combined oral and intravenous antioxidant therapy was associated with a significant decline in ALT levels in 52% of patients who received antioxidant therapy vs 20% of patients who received placebo （P = 0.05）. Histology activity index （HAI） score at the end of treatment was reduced in 48% of patients who received antioxidant therapy vs 26% of patients who received placebo （P = 0.21）. HCV-RNA levels decreased by l-log or more in 28% of patients who received antioxidant therapy vs 12% who received placebo （P = NS）. In part 11 of the trial, oral administration of antioxidants was not associated with significant alterations in any of the end points.
CONCLUSION： Antioxidant therapy has a mild beneficial effect on the inflammatory response of chronic HCV infection patients who are non-responders to interferon. Combined antiviral and antioxidant therapy may be beneficial for these patients.     

Treatment of functional dyspepsia with sertraline: A double-blind randomized placebo-controlled pilot study

AIM:To evaluate sertraline,a selective serotonin reuptake inhibitor in the treatment of patients with functional dyspepsia.METHODS:Consecutive tertiary hospital patients with a clinical diagnosis of functional dyspepsia(FD) according to the Rome Ⅱ criteria with a Hong Kong dyspepsia index(HKDI) of greater than 16 were recruited.Patients commenced enrolment prior to the inception of the Rome Ⅲ criteria for functional dyspepsia.All patients were ethnic Chinese,had a normal upper endoscopy and were Helicobacter pylori negative prior to enrolment.Study patients were randomized to receive sertraline 50 mg or placebo daily for 8 wk.HKDI symptom scores,quality of life,hospital anxiety and depression(HAD) scale and global symptom relief were evaluated before,during and after treatment.Adverse effects were monitored during and after treatment.RESULTS:A total of 193 patients were randomized in the intention to treat(ITT),and 150 patients were included in the per protocol(PP) analysis.In both the ITT and PP,there was no difference in the primary outcome of global dyspepsia symptoms between the sertraline and placebo groups at week 8.In the ITT analysis,98 and 95 patients were randomized to the sertraline and placebo groups respectively.A total of 43 patients withdrew from the study(22.3%) by week 8,with 23 of the 24 drop-outs in the sertraline group occurring prior to week 4(95.8%).In contrast,in the placebo arm,11 of 19 patients dropped out by week 4(57.9%).Utilizing the last response carried forward to account for the drop-outs,there were no differences between the sertraline and placebo groups at baseline in terms of the HKDI,HKDI 26.08 ± 6.19 vs 26.70 ± 5.89,P = 0.433;and at week 8,HKDI 22.41 ± 6.36 vs 23.25 ± 7.30,P = 0.352 respectively.In the PP analysis,74 and 76 patients were randomized to the sertraline and placebo groups respectively.At baseline,there were no statistically significant differences between the sertraline and placebo groups,HKDI 25.83 ± 6.313 vs 27.19 ± 5.929 respectively,P = 0.233;however by week 8,patients in the sertraline group demonstrated a statistically significant difference in their Hong Kong Dyspepsia Index compared to placebo,HKDI 20.53 ± 6.917 vs 23.34 ± 7.199,P = 0.02,respectively).There was also no statistically significant difference in overall quality of life measures or the HAD scale related to treatment in either the ITT or PP analysis at week 8.CONCLUSION:This pilot study,the first to examine sertraline,a selective serotonin reuptake inhibitor,for the management of FD,did not find that it was superior to placebo.     

Effects of killing Helicobacter pyloriquadruple therapy on peptic ulcer： A randomized double-blind clinical trial

AIM: To study the therapeutic efficacy of a Chinese and Western integrated regimen, killing Helicobacter pylori quadruple therapy on H pylori-associated peptic ulcers (PU). METHODS: With prospective and double-blind controlled method, seventy-five active PU patients with H pylori infection were randomized to receive one of the following three regimens: (1) new triple therapy (group A: lansoprazole 30 mg qd, plus clarithromycin 250 mg bid, plus amoxycillin 500 mg tid, each for 10 d); (2) killing Hp quadruple therapy(group B: the three above drugs plus killing H pylori capsule 6 capsules bid for 4 wk) and (3) placebo(group C: gastropine 3 tablets bid for 4 wk). H pylori eradication and ulcer healing quality were evaluated under an endoscope 4 wk after treatment. The patients were followed up for 5 years. RESULTS: Both the healing rate of PU and H pylori eradication rate in group B were significantly higher than those in group C (100% and 96.4% vs20% and 0%, respectively,P<0.005), but there was no significant difference compared to those in group A (88% and 92%, P>0.05). The healing quality of ulcer in group B was superior to that in groups C and A (P<0.05). The recurrence rate of PU in group B (4%) was lower than that in group A (10%) and group C (100%,P<0.01). CONCLUSION: Killing Helicobacter pylori quadruple therapy can not only promote the eradication of H pylori and healing quality of ulcer but also reduce recurrence rate of ulcer.     

Low dose oral curcumin is not effective in induction of remission in mild to moderate ulcerative colitis: Results from a randomized double blind placebo controlled trial

AIM To evaluate the role of oral curcumin in inducing clinical remission in patients with mild to moderate ulcerative colitis(UC).METHODS A prospective randomized double-blind placebo-controlled trial comparing the remission inducing effect of oral curcumin and mesalamine 2.4 g with placebo and mesalamine 2.4 g in patients of ulcerative colitis with mild to moderate severity was conducted from January 2003 to March 2005. The included patients received 1 capsule thrice a day of placebo or curcumin(150 mg) for 8 wk. Patients were evaluated clinically and endoscopically at 0,4 and 8 wk. The primary outcome was clinical remission at 8 wk and secondary outcomes were clinical response, mucosal healing and treatment failure at 8 wk. The primary analysis was intention to treat worst case scenario(ITT-WCS).RESULTS Of 300 patients with UC, 62 patients(curcumin: 29, placebo: 33) fulfilled the inclusion criteria and were randomized at baseline. Of these, 21 patients did not complete the trial, 41 patients(curcumin: 16, placebo: 25) finally completed 8 wk. There was no significant difference in rates of clinical remission(31.3% vs 27.3%, P = 0.75), clinical response(20.7% vs 36.4%, P = 0.18), mucosal healing(34.5% vs 30.3%, P = 0.72), and treatment failure(25% vs 18.5%, P = 0.59) between curcumin and placebo at 8 wk.CONCLUSION Low dose oral curcumin at a dose of 450 mg/d was ineffective in inducing remission in mild to moderate cases of UC.     

Delayed-release oral mesalamine 4.8 g/day (800 mg tablets) compared to 2.4 g/day (400 mg tablets) for the treatment of mildly to moderately active ulcerative colitis: The ASCEND I trial.

BACKGROUND: Delayed-release oral mesalamine 2.4 g/day to 4.8 g/day has been shown to be effective in treating mildly to moderately active ulcerative colitis (UC), but it is unknown whether an initial dose of 4.8 g/day is more effective than 2.4 g/day in patients with mildly to moderately active UC and in the subgroup with moderate disease. PATIENTS AND METHODS: A six-week, multicentre, randomized, double-blind, controlled trial assessing the safety and clinical efficacy of a new dose (ASCEND I) of medication randomly assigned 301 adults with mildly to moderately active UC to delayed-release oral mesalamine 2.4 g/day (400 mg tablet [n=154]) or 4.8 g/day (800 mg tablet [n=147]). The primary efficacy end point was overall improvement (ie, treatment success), defined as complete remission or response to therapy from baseline to week 6. Primary safety end points were adverse events and laboratory evaluations. Data were also analyzed separately for the prespecified subgroup of patients with moderate UC at baseline. RESULTS: Treatment success was not statistically different between the treatment groups at week 6; 51% of the group (77 of 150) who received delayed-release oral mesalamine 2.4 g/day and 56% of the group (76 of 136) who received 4.8 g/day reached the efficacy end point (P=0.441). Among the moderate disease subgroup, however, the higher initial dose was more effective; 57% of patients (53 of 93) given delayed-release oral mesalamine 2.4 g/day and 72% of patients (55 of 76) given 4.8 g/day achieved treatment success (P=0.0384). Both regimens were well tolerated. CONCLUSIONS: Delayed-release oral mesalamine is an effective and well-tolerated initial therapy in patients with mildly to moderately active UC, and a 4.8 g/day dose may enhance treatment success rates in patients with moderate disease compared with mesalamine 2.4 g/day.     

Effects of oral tacrolimus as a rapid induction therapy in ulcerative colitis

AIM:To determine the efficacy and safety of rapid induction therapy with oral tacrolimus without a meal in steroid-refractory ulcerative colitis(UC)patients.METHODS:This was a prospective,multicenter,observational study.Between May 2010 and August 2012,49 steroid-refractory UC patients(55 flare-ups)were consecutively enrolled.All patients were treated with oral tacrolimus without a meal at an initial dose of 0.1mg/kg per day.The dose was adjusted to maintain trough whole-blood levels of 10-15 ng/m L for the first 2 wk.Induction of remission at 2 and 4 wk after tacrolimus treatment initiation was evaluated using Lichtiger’s clinical activity index(CAI).RESULTS:The mean CAI was 12.6±3.6 at onset.Within the first 7 d,93.5%of patients maintained high trough levels(10-15 ng/m L).The CAI significantly decreased beginning 2 d after treatment initiation.At 2wk,73.1%of patients experienced clinical responses.After tacrolimus initiation,31.4%and 75.6%of patients achieved clinical remission at 2 and 4 wk,respectively.Treatment was well tolerated.CONCLUSION:Rapid induction therapy with oral tacrolimus shortened the time to achievement of appropriate trough levels and demonstrated a high remission rate 28 d after treatment initiation.Rapid induction therapy with oral tacrolimus appears to be a useful therapy for the treatment of refractory UC.     

A randomized trial of nicotine enemas for active ulcerative colitis.

BACKGROUND & AIMS: Ulcerative colitis (UC) is largely a disease of nonsmokers in which transdermal nicotine improves the symptoms but often causes adverse events (AEs). Nicotine enemas cause fewer AEs and were used as supplemental treatment for active UC. METHODS: We treated 104 patients with active UC with either 6-mg nicotine enemas or placebo enemas for 6 weeks in a randomized double-blind study. Patients continued their oral therapy, if any, for UC: 68 patients were taking mesalamine, 15 patients were taking prednisolone, and 12 patients were taking thiopurines during the study. Clinical, sigmoidoscopic, and histologic assessments were made at baseline and at the end of the study and symptoms were recorded daily on a diary card. The primary end point was induction of clinical remission and clinical improvement also was measured by the UC disease activity index. After the study, patients then used nicotine enemas daily for 4 weeks and sigmoidoscopy with a biopsy examination was repeated. AEs and salivary cotinine levels were monitored throughout the study. RESULTS: Clinical remission was achieved in 14 of 52 (27%) patients on active treatment and 14 of 43 (33%) patients on placebo (P = .55). The UC disease activity index improved by 1.45 points in the active group and by 1.65 points for those on placebo (P = .88). Only 1 patient discontinued treatment because of an AE (abdominal pain). In the 47 patients taking mesalamine only, active treatment conferred benefit that was not statistically significant; disease remission occurred in 9 of 25 patients on active therapy and 4 of 21 patients on placebo (P = .20). CONCLUSIONS: Six-milligram nicotine enemas were well tolerated but were not found to be efficacious for active UC.     

Randomized clinical trial of Plantago ovata seeds (dietary fiber) as compared with mesalamine in maintaining remission in ulcerative colitis. Spanish Group for the Study of Crohn's Disease and Ulcerative Colitis (GETECCU)

OBJECTIVE: Butyrate enemas may be effective in the treatment of active distal ulcerative colitis. Because colonic fermentation of Plantago ovata seeds (dietary fiber) yields butyrate, the aim of this study was to assess the efficacy and safety of Plantago ovata seeds as compared with mesalamine in maintaining remission in ulcerative colitis. METHODS: An open label, parallel-group, multicenter, randomized clinical trial was conducted. A total of 105 patients with ulcerative colitis who were in remission were randomized into groups to receive oral treatment with Plantago ovata seeds (10 g b.i.d.), mesalamine (500 mg t.i.d.), and Plantago ovata seeds plus mesalamine at the same doses. The primary efficacy outcome was maintenance of remission for 12 months. RESULTS: Of the 105 patients, 102 were included in the final analysis. After 12 months, treatment failure rate was 40% (14 of 35 patients) in the Plantago ovata seed group, 35% (13 of 37) in the mesalamine group, and 30% (nine of 30) in the Plantago ovata plus mesalamine group. Probability of continued remission was similar (Mantel-Cox test, p = 0.67; intent-to-treat analysis). Therapy effects remained unchanged after adjusting for potential confounding variables with a Cox's proportional hazards survival analysis. Three patients were withdrawn because of the development of adverse events consisting of constipation and/or flatulence (Plantago ovata seed group = 1 and Plantago ovata seed plus mesalamine group = 2). A significant increase in fecal butyrate levels (p = 0.018) was observed after Plantago ovata seed administration. CONCLUSIONS: Plantago ovata seeds (dietary fiber) might be as effective as mesalamine to maintain remission in ulcerative colitis.     

Mesalamine induced symptom exacerbation of ulcerative colitis: Case report and brief discussion

This paper describes a rare case in which the oral administration of mesalamine resulted in the exacerbation of ulcerative colitis (UC) in a patient who was previously responsive to mesalamine and whose colitis had been in remission for eight years. Mesalamine and other 5-aminosalicylic acid compounds are the mainstay of treatment for UC; however up to 8% of patients are unable to take the medications due to intolerance or hypersensitivity reactions. Common drug reactions are fever, nausea, diarrhea and abdominal pain; however, exacerbation of UC has rarely been reported. This study highlights the importance of ruling out mesalamine as the causative agent in cases of UC exacerbations.     

Combined Oral Sodium Butyrate and Mesalazine Treatment Compared to Oral Mesalazine Alone in Ulcerative Colitis

Butyrate represents the main source of energy for colonic epithelial cells; however, its availabilty/utilization is impaired in ulcerative colitis (UC). In the present randomized, double-blind, placebo-controlled pilot study, the safety and efficacy of colonic targeted oral sodium butyrate tablets, coated with a pH-dependent soluble polymer, have been evaluated in ulcerative colitis. Thirty patients with mild to moderate colitis underwent a six-week course of oral sodium butyrate (4 g/day) plus oral mesalazine (2.4 g/day), (Group A) or of oral mesalazine plus placebo (Group B). Clinical, endoscopic, and histologic data were collected at the beginning and the end of the study. Twenty-five patients completed the study (12 in group A, 13 in group B). No untoward side effects were reported. In group A, seven patients underwent remission and four improved; in Group B the numbers were 5 and 5, respectively. After treatment, all clinical parameters had significantly improved in both treatment arms compared to pretreatment findings. The UC disease activity index (UCDAI) score decreased from 7.27 ± 2.02 to 2.58 ± 2.19 (P < 0.05) in the combined treatment group and from 6.07 ± 1.60 to 3.46 ± 1.98 (P < 0.05) in group B. The endoscopic and histologic scores also significantly improved after treatment in both groups (P < 0.05). The difference between the two treatment arms was not significant, but a significantly better improvement vs baseline values (P < 0.05) was observed in the combined treatment group vs the mesalazine group, when considering both the clinical index (9.58 ± 4.19 vs 5.92 ± 3.48) and the UCDAI score (4.67 ± 2.19 vs 2.54 ± 2.18). A more favorable trend, although not significant, was observed for all individual parameters in group A. In conclusion, results of the present pilot study indicate that oral butyrate is safe and well tolerated. These data also suggest that oral butyrate may improve the efficacy of oral mesalazine in active ulcerative colitis and prompt the need of a large scale investigation to confirm the present findings.     

Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: Curcumin is a biologically active phytochemical substance present in turmeric and has pharmacologic actions that might benefit patients with ulcerative colitis (UC). The aim in this trial was to assess the efficacy of curcumin as maintenance therapy in patients with quiescent ulcerative colitis (UC). METHODS: Eighty-nine patients with quiescent UC were recruited for this randomized, double-blind, multicenter trial of curcumin in the prevention of relapse. Forty-five patients received curcumin, 1g after breakfast and 1g after the evening meal, plus sulfasalazine (SZ) or mesalamine, and 44 patients received placebo plus SZ or mesalamine for 6 months. Clinical activity index (CAI) and endoscopic index (EI) were determined at entry, every 2 months (CAI), at the conclusion of 6-month trial, and at the end of 6-month follow-up. RESULTS: Seven patients were protocol violators. Of 43 patients who received curcumin, 2 relapsed during 6 months of therapy (4.65%), whereas 8 of 39 patients (20.51%) in the placebo group relapsed (P=.040). Recurrence rates evaluated on the basis of intention to treat showed significant difference between curcumin and placebo (P=.049). Furthermore, curcumin improved both CAI (P=.038) and EI (P=.0001), thus suppressing the morbidity associated with UC. A 6-month follow-up was done during which patients in both groups were on SZ or mesalamine. Eight additional patients in the curcumin group and 6 patients in the placebo group relapsed. CONCLUSIONS: Curcumin seems to be a promising and safe medication for maintaining remission in patients with quiescent UC. Further studies on curcumin should strengthen our findings.     

Use of infliximab in the prevention and delay of colectomy in severe steroid dependant and refractory ulcerative colitis

AIM： To determine if infliximab can prevent or delay surgery in refractory ulcerative colitis （UC）. METHODS： UC patients who failed to have their disease controlled with conventional therapies and were to undergo colectomy if infliximab failed to induce a clinical improvement were reviewed. Patients were primarily treated with a single 5 mg/kg infliximab dose. The Colitis Activity Index （CAI） was used to determine response and remission. Data of 8 wk response and colectomy rates at 6 mo and 12 mo were collected. RESULTS： Fifteen patients were included, 7 with UC unresponsive or intolerant to Ⅳ hydrocortisone, and 8 with active disease despite oral steroids （all but one with therapeutic dosage and duration of immunomodulation）. All the Ⅳ hydrocortisone-resistant/intolerant patients had been on azathioprine/6-MP 〈 8 wk. At 8 wk, infliximab induced a response in 86.7% （13/15） with 40% in remission （6/15）. Within 6 mo of treatment 26.7% （4/15） had undergone colectomy and surgery was avoided in 46.6% （7/15） at 12 mo. The colectomy rate at 12 mo in those on immunomodulatory therapy 〈 8 wk at time of infliximab was 12.5% （1/8） compared with 100% （7/7） in patients who were on long-term maintenance immunomodulators （P 〈 0.02）. CONCLUSION： Infliximab prevented colectomy due to active disease in immunomodulatory-na？ve, refractory UC patients comparable to the use of Cyclosporine. In patients, however, on effective dosage and duration of immunomodulation at time of infliximab therapy colectomy was not avoided.