Tests of renal function in patients with quiescent colitis: effects of drug treatment.

Mesalazine has structural similarities to aspirin and phenacetin and is nephrotoxic when given intravenously in high doses to rats. A number of cases of nephrotoxicity has been reported recently in patients taking oral mesalazine. Sensitive indicators of renal function in a group of patients maintained on long term, delayed release mesalazine and a comparable group on sulphasalazine have been studied. Sixty two patients (32 men, aged 28-82 years) with quiescent colitis were studied. Thirty four had been maintained on delayed release mesalazine 1.6 (0.8-2.4) g/day for 2.9 (0.5-6.9) years and 28 on sulphasalazine 2 (2-3) g/day. Groups were comparable for age, sex, disease duration, and disease extent. Renal function was assessed by: urine microscopy; creatinine clearance; the urinary excretion of two markers of glomerular toxicity, albumin and transferrin; and the urinary excretion for two markers of tubular toxicity, N-acetyl-beta-D-glucosaminidase (NAG) and alpha 1-microglobulin. There were no significant differences in renal function between the two treatment groups. Furthermore, no correlations were found between measures of renal function and either cumulative mesalazine dose or mesalazine treatment duration. In this study, long term maintenance treatment with delayed release mesalazine was no more nephrotoxic than continued treatment with sulphasalazine.     

Disposition of 5-aminosalicylic acid by olsalazine and three mesalazine preparations in patients with ulcerative colitis: comparison of intraluminal colonic concentrations, serum values, and urinary excretion.

To compare the disposition of 5-aminosalicylic acid (5-ASA) and its acetylated metabolite during treatment with olsalazine and mesalazine, 14 patients with inactive ulcerative colitis were randomly assigned to olsalazine (1 g twice daily) and the mesalazines, Asacol (800 + 400 + 800 mg daily), Pentasa (750 + 500 + 750 mg daily), and Salofalk (750 + 500 + 750 mg daily) in a crossover design trial so that all received each drug for seven days. Intraluminal colonic concentrations of 5-ASA were estimated after five days by the method of equilibrium in vivo dialysis of faeces. A predose serum sample and a 24 hour urine collection were obtained on day seven. The 5-ASA and acetyl-5-aminosalicylic acid (Ac-5-ASA) values were determined by high performance liquid chromatography. Olsalazine almost doubled the colonic concentrations (mean 23.7 (SEM) (1.9) mmol/l) of its therapeutically active ingredient (5-ASA) compared with equimolar doses of Pentasa (12.6 (2.2) mmol/l; p less than 0.0003) and Salofalk (15.0 (2.0) mmol/l; p less than 0.003). At the same time, olsalazine treatment was associated with lower serum concentrations and urinary excretions (p less than 0.05) of 5-ASA and Ac-5-ASA compared with the mesalazine preparations. The low systemic load of 5-ASA provided by olsalazine reduces the potential risk of nephrotoxicity during long term treatment.     

Disposition of 5-aminosalicylic acid from 5-aminosalicylic acid-delivering drugs during accelerated intestinal transit in healthy volunteers

In eight healthy volunteers accelerated intestinal transit time was induced with bisacodyl, and urinary and faecal excretion of sulphasalazine, olsalazine, 5-aminosalicylic acid (5-ASA), and acetyl-5-ASA was studied after a single oral dose of 3.3 mmol sulphasalazine, olsalazine, Pentasa, and Salofalk and 2.6 mmol of Asacol. The faecal and urinary excretion of acetyl-5-ASA was lowest after intake of sulphasalazine and olsalazine and highest after intake of Pentasa and Salofalk. The figures for Asacol were intermediate. This indicates insufficient release of 5-ASA from sulphasalazine and olsalazine. When the results of this study are compared with those of a previous study without accelerated transit time, the disposition of 5-ASA from all the 5-ASA-delivering drugs is influenced unfavourably by an accelerated gut transit but most pronounced in the case of sulphasalazine, olsalazine, and Asacol. The impaired release from the azo compounds sulphasalazine and olsalazine is a result of far less complete splitting of the diazo bond.     

Microproteinuria in patients with inflammatory bowel disease： Is it associated with the disease activity or the treatment with 5-aminosalicylic acid？

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 mo). Microalbuminuria (mALB) and urine levels of the renal tubular proteins beta2-microglobulin (beta2mGLB) and beta-N-acetyl-D-glucosamidase (beta-NAG) as well as the creatinine clearance were determined in a 12-h overnight urine collection. Tumor necrosis factor-alpha (TNF-alpha) 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 microproteinuria in UC and CD patients was 12.9% and 6.0% for mALB, 22.7% and 27.7% for beta2mGLB, and 11.3% and 8.4% for beta-NAG, respectively. mALB was not associated with IBD activity. Beta2mGLB and beta-NAG urine levels were correlated to UC activity (UCAI: P<0.01; UCEI: P<0.005). mALB in UC patients and beta-NAG urine levels in CD patients were related to TNF-alpha 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.     

Microproteinuria in patients with inflammatory bowel disease:TS it associated with the disease activity or the treatment with 5-aminosalicylic acid?

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 28.8months (range 1-168 mo). Microalbuminuria (mALB) and urine levels of the renal tubular proteins β2-microglobulin (β2mGLB) and β-N-acetyl-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 totalof 277 measurements (194 in UC patients and 83 in CD patients) were performed. The prevalence of abnormal microproteinuria in UC and CD patients was 12.9% and 6.0% for mALB, 22.7% and 27.7% for β2mGLB, and 11.3% and 8.4% for β-NAG,respectively. mALB was not associated with IBD activity.β2mGLB and β-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-a 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.     

Clinical experience of the tolerance of mesalazine and olsalazine in patients intolerant of sulphasalazine

We assessed the tolerance and safety of two new preparations designed to release 5-aminosalicylic acid in the colon in patients with ulcerative colitis who were intolerant of sulphasalazine. Twenty-eight of 37 patients (76%) given mesalazine and 18 of 21 patients (86%) given olsalazine tolerated the new preparations with no adverse effects. No haematologic or biochemical abnormalities were detected. Adverse reactions to the new preparations were usually but not always similar to those they had previously encountered with sulphasalazine, but a few patients experienced rash and diarrhoea. In some patients intolerant of one of the new preparations, their tolerance of the other was assessed. Three patients intolerant of mesalazine tolerated olsalazine. Similarly, three other patients intolerant of olsalazine tolerated mesalazine. We conclude that not all adverse effects of sulphasalazine are due to the sulphapyridine part of the molecule. Some are due to the released 5-aminosalicylic acid and some to the parent compound. Both drugs are likely to prove useful in the management of patients intolerant of sulphasalazine.     

Disposition of mesalazine from mesalazine-delivering drugs in patients with inflammatory bowel disease, with and without diarrhoea.

The disposition of mesalazine from the azo compounds sulphasalazine and olsalazine (Dipentum) and from the slow-release mesalazine drugs Pentasa, Asacol, and Salofalk was studied in 20 patients with inflammatory bowel disease. Ten of them had diarrhoea, and 10 had normal stools. On the last 2 days of a 7-day maintenance treatment with each of the study drugs urine and faeces were collected for determination of mesalazine, acetyl-mesalazine, and unsplit azo compound. In patients with and without diarrhoea the urinary and the faecal excretion of acetyl-mesalazine was lowest during treatment with olsalazine. The proportion of acetyl-mesalazine in faeces was highest during treatment with Pentasa in both groups. The presence of diarrhoea was associated with a decrease in the proportion of acetyl-mesalazine in faeces during treatment with all drugs, not significant only for Pentasa. The proportion of unsplit azo compound in faeces increased in the case of diarrhoea to almost 50%. It is concluded that in patients with inflammatory bowel disease diarrhoea substantially influences the disposition from all these drugs except Pentasa.     

Kawasaki-like Syndrome after Treatment with Mesalazine

We report a patient who developed a severe hypersensitivity reaction, including rash, lymph node enlargement, fever, hepatitis, and eosinophilia, after sulphasalazine therapy. Five years later, he developed a similar reaction after exposure to mesalazine, the salicylic compound of sulphasalazine. We conclude that patients with known severe systemic reaction to sulphasalazine therapy are also at risk for such a reaction when treated with a 5-ASA preparation.     

Disposition of Mesalazine from Mesalazine-Delivering Drugs in Patients with Inflammatory Bowel Disease,with and without Diarrhoea

Rijk MCM, van Schaik A, van Tongeren JHM. Disposition of mesalazine from mesalazine-delivering drugs in patients with inflammatory bowel disease, with and without diarrhoea. Scand J Gastroenterol 1992;27:863-868.

The disposition of mesalazine from the azo compounds sulphasalazine and olsalazine (Dipentum^®) and from the slow-release mesalazine drugs Pentasa^®, Asacol^®, and Salofalk^® was studied in 20 patients with inflammatory bowel disease. Ten of them had diarrhoea, and 10 had normal stools. On the last 2 days of a 7-day maintenance treatment with each of the study drugs urine and faeces were collected for determination of mesalazine, acetyl-mesalazine, and unsplit azo compound. In patients with and without diarrhoea the urinary and the faecal excretion of acetyl-mesalazine was lowest during treatment with olsalazine. The proportion of acetyl-mesalazine in faeces was highest during treatment with Pentasa in both groups. The presence of diarrhoea was associated with a decrease in the proportion of acetyl-mesalazine in faeces during treatment with all drugs, not significant only for Pentasa. The proportion of unsplit azo compound in faeces increased in the case of diarrhoea to almost 50%. It is concluded that in patients with inflammatory bowel disease diarrhoea substantially influences the disposition from ail these drugs except Pentasa.     

Comparison of delayed release 5 aminosalicylic acid (mesalazine) and sulphasalazine in the treatment of mild to moderate ulcerative colitis relapse.

Oral formulations of 5-aminosalicylic acid (mesalazine) appear less toxic than sulphasalazine. We have therefore compared sulphasalazine, low dose mesalazine and high dose mesalazine in the treatment of mild to moderate relapse of ulcerative colitis. Sixty one patients (32 men, aged 20-78 years) were randomly allocated to sulphasalazine 2 g daily, mesalazine 800 mg daily, or mesalazine 2.4 g daily in a double blind, double dummy, four week trial. Groups were comparable for age, sex, extent of disease, and pretrial sulphasalazine intake. Four patients were unable to complete the study because of treatment failure (two taking sulphasalazine and two high dose mesalazine). A further two patients taking sulphasalazine developed side effects necessitating withdrawal. Within treatment comparisons revealed significant improvement of: sigmoidoscopic grade in the sulphasalazine group; rectal bleeding, sigmoidoscopic and histological grade in the low dose mesalazine group; stool frequency, rectal bleeding and sigmoidoscopic grade in the high dose mesalazine group. Greater improvement in rectal bleeding (p less than 0.05) and sigmoidoscopic appearances (p less than 0.05) occurred in patients taking high dose mesalazine than in those taking sulphasalazine. In two patients taking high dose mesalazine minor rises of plasma creatinine concentrations occurred, suggesting the need to monitor renal function.     

Comparative analysis of the in vitro prosecretory effects of balsalazide, sulfasalazine, olsalazine, and mesalamine in rabbit distal ileum

BACKGROUND: The aminosalicylates remain foundation therapy for mild-to-moderate ulcerative colitis. Pro-drug 5-aminosalicylic acid (5-ASA; mesalamine) formulations have been developed to prevent 5-ASA from the proximal absorption and release of mesalamine, to decrease inflammation, and to improve colonic absorption. Clinically, pro-drugs such as olsalazine have been associated with dose-dependent diarrhea, which was likely secondary to ileal secretion induced by the azo linkages, in 17% of patients. The present study tested the hypothesis that the use of all compounds with azo linkages leads to increased secretion. METHODS: Intestinal tissue was randomly assigned to serve as controls or to receive brush border addition of equimolar concentrations of the compounds, and the change in short-circuit current was measured. RESULTS: Mesalamine did not induce secretion at any dose. Mean equivalent doses (0.1 to 10 mM) of balsalazide (range, 6.3 +/- 1.5 to 16.7 +/- 1.3 microA/cm2), olsalazine (range, 2.0 +/- 1.0 to 7.0 +/- 2.1 microA/cm2), and sulfasalazine (3.2 +/- 1.1 to 6.2 +/- 1.5 microA/cm2) significantly stimulated (P < 0.001) secretion. The values for the effective dose that is half the maximal dose for secretion induced by sulfasalazine, olsalazine, and balsalazide were 0.4, 0.7, and 0.9 mM, respectively. CONCLUSIONS: This study is the first to demonstrate that the use of pro-drugs with azo bonds leads to increased ileal secretion at equimolar concentrations of 5-ASA. Physicians should use caution when providing higher doses of the pro-drug forms of 5-ASA to their patients, as this could lead to increased diarrhea.     

Glomerular and tubular proteinuria as markers of nephropathy in rheumatoid arthritis.

OBJECTIVE: We examined the prevalence of nephropathy in unselected patients with rheumatoid arthritis (RA) by measurement of marker proteins for glomerular and tubular damage in urine. METHODS: A highly sensitive immunoluminometric assay was used to measure albumin, immunoglobulin G and alpha1-microglobulin in 24 h urines of 44 RA patients and a control group of 46 patients with generalized osteoarthritis (OA). RESULTS: Fifty-five per cent of RA patients were found to have proteinuria as a symptom of renal disease. Drug therapy or vasculitis were identified as possible reasons for proteinuria in only 25% of these patients; in most patients (75%), no reason for proteinuria was found. Tubular and mixed proteinuria were more frequent than glomerular proteinuria. Only 15% of the control group exhibited mild proteinuria, which was attributable to nephrotoxic factors. The renal function of RA patients and the control group did not differ significantly. CONCLUSIONS: Proteinuria is a frequent symptom of nephropathy in RA. Screening for renal disease in RA should not only include creatinine measurement and dipstick examination of urine, but also more sensitive methods to detect tubular and glomerular proteinuria as a marker of tubular and early stages of glomerular damage.     

Probiotic Escherichia coli Nissle 1917 (EcN) for successful remission maintenance of ulcerative colitis in children and adolescents: an open-label pilot study

Since about 20 % of patients with ulcerative colitis (UC) are children and adolescents there is a need for therapeutic options custom-tailored to the children's needs. E. coli Nissle 1917 (EcN) as an evidence-based probiotic alternative to mesalazine (5-ASA) in adult UC remission maintenance is a promising agent for such a therapy. The present open-labelled pilot study was undertaken to investigate the clinical benefit of EcN for maintenance therapy in young UC patients. 34 patients with UC in remission aged between 11 and 18 years were allocated either to EcN (2 capsules o. d., n = 24) or 5-ASA (median 1.5 g/d, n = 10) and observed over one year. As a result, the relapse rate was 25 % (6 / 24) in the EcN group and 30 % (3 / 10) in the 5-ASA group. Data on the patients' global health and development were favourable and no serious adverse events were reported. In conclusion, maintenance therapy for UC with the probiotic EcN is effective also in young patients.     

Rapidly reversible albumin and beta 2-microglobulin hyperexcretion in recent severe essential hypertension

Seven young patients with newly diagnosed severe hypertension were studied for one week. The mean age was 34.9 years (range 28-44). The mean initial values +/- s.d. for systolic and diastolic pressures were 223 +/- 27 and 141 +/- 8 mmHg, respectively. Secondary hypertension was excluded by conventional methods and serum creatinine was normal. A pronounced but quite variably elevated albumin excretion 440 +/- 448 micrograms/min (mean +/- s.d.) and a moderately increased beta 2-microglobulin excretion 3.06 +/- 3.29 micrograms/min was noted before treatment. The abnormal albumin excretion with ensuing fall in blood pressure was rapidly and almost completely reversible in all but one patient during conventional treatment and the increased beta 2-microglobulin excretion was totally reversible in all but one patient. Both albumin and beta 2-microglobulin excretion rate were positively correlated to arterial pressures in all patients. Thus glomerular and to some extent tubular protein handling were both affected in untreated patients, but rapidly reversible during initial antihypertensive treatment. The data indicate that the beta 2-microglobulin hyperexcretion is secondary to enhanced filtration of plasma protein saturating the tubular reabsorption capacity, while the hyperexcretion of albumin is mainly due to the increased filtration pressure per se, though other factors may be partly responsible.     

Olsalazine Versus Sulphasalazine for Relapse Prevention in Ulcerative Colitis: A Multicenter Study

Objective : To compare the relapse-preventing effect and the frequency of adverse events of olsalazine and sulphasalazine in sulphasalazine-tolerant patients with ulcerative colitis. Methods : Patients in remission, with at least two episodes of active disease during the last 5 yr, were randomized to 2 g of sulphasalazine or 1 g of olsalazine daily and were followed for 6–18 months. Relapse rates in the two groups were compared using frequency and life-table analysis. Sixty-nine patients with proctitis, 140 with left-sided colitis, and 113 with subtotal or total colitis were evaluated. Results : In the intention-to-treat analysis, the failure rate (relapses plus withdrawals) was 54.7% in the olsalazine and 47.2% in the sulphasalazine group. In the per-protocol analysis excluding withdrawals, 44.7% relapsed in the olsalazine and 39.3% in the sulphasalazine group. Remission curves did not differ significantly, although at all time intervals the frequency of remission was slightly higher in the sulphasalazine group ( p = 0.19 in the intention-to-treat analysis and p = 0.42 in the per-protocol analysis estimated by the log-rank test). Twelve patients (of whom five had diarrhea) in the olsalazine group versus eight patients in the sulphasalazine group discontinued the study because of side effects. Conclusion : The relapse-preventing effect of olsalazine and sulphasalazine in sulphasalazine-tolerant patients did not differ. Furthermore, the tolerability of olsalazine, particularly concerning diarrhea, appears to be better than previously reported.     

Mesalazine induced exacerbation of ulcerative colitis.

5-Aminosalicylic acid (5-ASA) compounds occasionally exacerbate diarrhoea in patients with inflammatory bowel disease. This is thought to be due to a secretory mechanism in most cases. A patient with presumed intolerance to sulphasalazine and 5-ASA preparations who developed endoscopic and histological evidence of disease relapse after a rectal challenge with mesalazine is reported.     

Different therapy for different types of ulcerative colitis in China

AIM: To study the different therapy for different types of ulcerative colitis (UC) in China. METHODS: Among 102 UC patients, 42 chronic relapse type UC patients were randomly divided into olsalazine sodium treatment group (n=21) and SASP group (n=21). Clinical effects and safety were observed in the 2 groups. Forty-two first episode type UC patients were randomly divided into Heartleaf houttuynia herb treatment group (n=21) and SASP group (n=21). Clinical effects were observed in the 2 groups while ultrastructure of colonic mucosa, ICAM-1 and the pressure of distant colon were studied in Heartleaf houttuynia herb group. Eighteen patients (8 males, 10 females) with refractory UC and unresponsive to high-dose prednisolone and sulfasalazine therapy more than one month were treated with Kangshuanling (7200 U/d). Prednisolone was gradually stopped and sulfasalazine was maintained. Stool frequency, rectal bleeding, colonoscopy, general well-being, histology were observed and CD62p, CD63, CD54, Pgp-170 (flow cytometry), TXA2 (RIA), blood platelet aggregation rate and thrombosis length in vitro were assessed. RESULTS: In the 42 chronic relapse type UC patients, the overall clinical effects of olsalazine sodium group (complete remission in 16, improvement in 4, inefficiency in 1) were better than those of SASP group (complete remission in 10, improvement in 4, inefficiency in 7, P<0.05). Symptomatic remission of olsalazine sodium group (complete remission in 15, partial remission in 5, inefficiency in 1) was better than that of SASP group (complete remission in 10, partial remission in 5, inefficiency in 6, P<0.05). The colonoscopic remission of olsalazine sodium group(complete remission in 11, partial remission in 9, inefficiency in 1) was better than that of SASP group (complete remission in 7, partial remission in 8, inefficiency in 6, P<0.05). The histologic remission of olsalazine sodium group (complete remission in 13, partial remission in 7, inefficiency in in 1) was better than that of SASP group (complete remission in 6, partial remission in 10, inefficiency in 5, P<0.05). The side effects of gastrointestinal tract in olsalazine sodium group were less than those of SASP group except for frequency of watery diarrhea. No other side effects were observed in olsalazine sodium group while ALT increase, WBC decrease and skin eruption were observed in SASP group. Two patients relapsed in olsalazine sodium group while 8 cases relapsed in SASP group during the flow-up period (from six months to one year). In the 42 first episode type UC patients, the clinical effect of Heartleaf houttuynia herb group (complete remission in 20, 95.2%; improvement in 1, 4.8%) was better than that of SASP group (complete remission in 15, 72.4%, improvement in 5, 23.8%; inefficiency in 1, 3.8%, P<0.01). The time of stool frequency recovering to normal (5.6+/-3.3 d), and blood stool disappearance (6.7+/-3.8 d) and abdominal pain disappearance (6.1+/-3.5 d) in Heartleaf houttuynia herb group was all shorter than that in SASP group (9.5+/-4.9 d, 11.7+/-6.1 d, 10.6+/-5.3 d, P<0.01). Heartleaf houttuynia herb could inhibit the epithelial cell apoptosis of colonic mucous membrane and the expression of ICAM-1 (45.8+/-5.7% vs 30.7+/-4.1%, P<0.05). Compared with normal persons, the mean promotive speed of contraction wave stepped up (4.6+/-1.6 cm/min vs 3.2+/-1.8 cm/min, P<0.05) and the mean amplitude of the wave decreased (14.2+/-9.3 kPa vs 18.4+/-8.0 kPa, P<0.05) in active UC patients. After treatment with Heartleaf houttuynia herb, these 2 indexes improved significantly (17.3+/-8.3 kPa, 3.7+/-1.7 cm/min, P<0.05). In normal persons, the postprandial pressure of sigmoid (2.9 +/-0.9 kPa) was higher than that of descending colon (2.0+/-0.7 kPa) and splenic flexure (1.7+/-0.6 kPa), while the colonic pressure (1.5+/-0.5 kPa, 1.4+/-0.6 kPa, 1.3+/-0.6 kPa) decreased significantly (P<0.05) in active UC patients. After treatment with Heartleaf houttuynia herb, the colonic pressure (2.6+/-0.8 kPa, 1.8+/-0.6 kPa, 1.6+/-0.5 kPa) recovered to normal. The pain threshold Heartleaf houttuynia herb, the colonic pressure (2.6+/-0.8 kPa, 1.8+/-0.6 kPa, 1.6+/-0.5 kPa) recovered to normal. The pain threshold of distant colon (67.3+/-18.9 mL) in active UC patients decreased significantly compared with that of normal persons (216.2+/-40.8 mL, P<0.05) and recovered to normal after treatment with Heartleaf houttuynia herb(187.4+/-27.2 mL, P<0.05). In the 18 refractory UC patients with platelet activation, after more than 4 wk of combined Kangshuanling and sulfasalazine therapy, 16 patients achieved clinical remission, with a highly significant statistical difference (P<0.01) between pre-and post-treatment mean scores for all disease parameters: stool frequency (8.2/d vs 1.6/d), rectal bleeding (score 2.7 vs 0.3), colonoscopy (score 2.6 vs 1.1), histology (score 12.0 vs 5.0), general well being (score 4.0 vs 0.6) and CD62p (8.0+/-3.1% vs 4.1+/-1.8%), CD63 (6.3+/-2.1% vs 3.2+/-1.6%), TXA2 (548+/-85 ng/L vs 390+/-67 ng/L), platelet aggregation rate (43.2+/-10.7% vs 34.8+/-8.1%), thrombosis length in vitro (2.3+/-0.6 cm vs 1.8+/-0.3 cm), CD54 in blood (26.9+/-6.9% vs 14.4+/-5.1%), CD54 in tissues (51.1+/-6.2% vs 23.1+/-4.1%), Pgp-170 in blood (18.9+/-3.9% vs 10.4+/-2.7%), Pgp-170 in tissues (16.5+/-3.2% vs 10.2+/-2.3%, P<0.01 or 0.05). CONCLUSION: Based on the characteristics of UC cases in China, different therapy should be given to different types of UC with expected satisfactory results.     

Disposition of 5-aminosalicylic acid by 5-aminosalicylic acid-delivering compounds

The disposition of 5-aminosalicylic acid (5-ASA) from 5-ASA-delivering drugs was studied in eight healthy volunteers. Time-related urinary excretion and faecal excretion of 5-ASA and acetyl-5-ASA were measured after a single oral dose of the azo compounds sulphasalazine and olsalazine, of the slow-release compounds Pentasa, Asacol, and Salofalk, and of plain 5-ASA. Plain 5-ASA was rapidly excreted into urine and had a low faecal recovery, indicating fast absorption proximally in the intestine and little availability to the colon. After ingestion of both azo compounds and slow-release compounds, urinary excretion of 5-ASA was markedly delayed and reduced, and faecal excretion was enhanced. At all points of time there was a significant but not very marked difference in urinary excretion of 5-ASA after ingestion of the azo compounds and the slow-release compounds, in favour of the azo compounds. A significantly larger proportion of the ingested 5-ASA, moreover, was excreted in faeces after intake of azo compounds as compared with slow-release compounds.     

Prophylactic effects of olsalazine v sulphasalazine during 12 months maintenance treatment of ulcerative colitis. The Danish Olsalazine Study Group.

In a Danish multicentre trial we compared the relapse preventing effects of olsalazine and sulphasalazine in patients with ulcerative colitis over a 12 month treatment period. Two hundred and twenty seven patients (118 men) with at least two previous attacks of ulcerative colitis were randomly allocated according to a prearranged treatment schedule to olsalazine 500 mg bd or sulphasalazine 1 g bd in a double blind, double dummy fashion. One hundred and ninety seven patients completed the trial. The relapse rate after 12 month in the olsalazine group was 46.9% v 42.4% in the sulphasalazine group with a 95% confidence interval for the difference in proportions of -9% to 18%. Seven per cent of the patients were withdrawn from the trial because of adverse drug reactions and these were equally distributed between the two groups.