Sulfasalazine Group Research Articles

Comparative evaluation of different doses of PPAR-γ agonist alone and in combination with sulfasalazine in experimentally induced inflammatory bowel disease in rats

BackgroundInflammatory bowel disease (IBD) is an idiopathic, chronic inflammatory condition, which affects the gastrointestinal tract and has no curative treatment. The present study aimed to investigate the effect of different doses of pioglitazone alone and in combination with sulfasalazine in TNBS (trinitrobenzenesulfonic acid)-induced inflammatory bowel disease (IBD) in rats. MethodsA total of 36 animals were included in the study. Animals were divided into five groups (n=6): group I – vehicle (ethanol), group II – TNBS + ethanol, group IIIA–TNBS + pioglitazone (15mg/kg), group IIIB – TNBS + pioglitazone (30mg/kg), group IV – TNBS + sulfasalazine (360mg/kg), group V – TNBS + sulfasalazine (360mg/kg) + pioglitazone (least effective dose found in group III). Group III was divided into two subgroups, namely ULA and IIIB, on the basis of different doses of pioglitazone used. After completion of two weeks of treatment, rats were sacrificed under ether anesthesia by cervical dislocation for assessment of intestinal inflammation, histological analysis, myeloperoxidase assay, malondialdehyde assay and TNF-α estimation. ResultsAll the drug-treated groups showed both gross morphological and microscopic score either 1 or 2. None of them showed score of > 2 on both gross and microscopic morphological examination. Both MDA levels and MPO activity were significantly re-duced in the drug-treated groups, with maximum reduction seen in the combination group. TNF-α was reduced in pioglitazone group. It was highly reduced in sulfasalazine group (group V) as compared to TNBS group thereby indicating that pioglitazone is protective in TNBS-induced inflammatory bowel disease. ConclusionThe present study showed reduction in lipid peroxidation, malondialdehyde levels and TNF-α levels in pioglitazone-treated group and hence, there was significant improvement in gross and microscopic features, too. However, combination of pioglitazone and sulfasalazine has shown greater efficacy.

AB0350 Efficacy of non-biological disease-modifying antirheumatic drugs (dmards) in patients (pts) with extra-articular rheumatoid arthritis (exra)

BackgroundThe presence of systemic extra-articular manifestations (EAM) of rheumatoid arthritis (RA) is a sign of higher clinical and laboratory activities associated with the presence and high titers of rheumatoid factor...

The efficacy and safety of Jitongning Capsule (脊痛宁胶囊) in patients with ankylosing spondylitis

To confirm the efficacy and safety of Jitongning Capsule in the treatment of ankylosing spondylitis (AS). A total of 120 AS patients with early-intermediate were randomly and equally assigned to Jitongning Capsule group and sulfasalazine group. Jitongning Capsule was orally taken 4.5 g per day and sulfasalazine was orally taken 2 g daily for 12 months. The primary endpoint was the proportion of patients achieving the Assessment in Ankylosing Spondylitis 20 (ASAS 20), secondary end points included Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), patient's global assessment by VAS rating, spinal pain, general pain and night pain, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-4 (IL-4) in the peripheral blood mononuclear cells (PBMC) of AS patients were measured. A total of 111 patients completed the study. There were 58 patients in Jitongning group and 53 patients in sulfasalazine group. Both drugs showed mild and occasional side effects. After treated by Jitongning Capsule and sulfasalazine, the proportion of ASAS20 responders at 12 month was 72.41% (42/58) and 67.92% (36/53) respectively. Both Jitongning Capsule and sulfasalazine treatment induced significant decrease in the proportion of CD4(+)T cell and CD8(+)T cell expressing TNF-α and IFN-γ at 12-month of treatment compared with baseline values (P<0.05). Jitongning Capsule are effective in a setting close to real-life medical care with a sustained improvement in signs and symptoms of AS, and reduce cytokine levels in PBMC. It showed comparable effects to sulfasalazine.

Association between tongue appearance in Traditional Chinese Medicine and effective response in treatment of rheumatoid arthritis

Explore the associations between the tongue appearances in Traditional Chinese Medicine (TCM) and effective response (ACR20 response based on American College of Rheumatology) in rheumatoid arthritis (RA) patients treated with Chinese medicine (CM) and western biomedical combination therapy (WM). This study used the data from a previous multi-center randomized-controlled clinical trial. Data pertaining to tongue coating and tongue body color were collected. In order to simplify the tongue diagnosis for easily understood by biomedical professionals, only two typical tongue coating (white and yellow) and four typical tongue body colors (purple, pink, pale and red) were identified for this analysis. 170 cases with clear tongue coating and 198 cases with clear tongue body color in TCM treatment (Glucosidorum Tripterygll Totorum tablets and Yishen Juanbi tablets) group, 181 cases with identified tongue coating and 189 cases with identified tongue body color in WM treatment (diclofenec, methotrexate and sulfasalazine) group were included for the analysis. The ACR20 response at 12 weeks and 24 weeks were used as an outcome measure of efficacy. The effective rates in patients with different tongue appearances were analyzed with Chi-square method and the association between the changes of tongue coating/body color and the ACR20 response was analyzed with a repeated measures logistic regression analysis. At 12 weeks, the ACR20 responses in the patients treated with CM and WM therapy were 33.6% and 53.0%, respectively, and at 24 weeks, they were 57.9% and 84.3%, respectively. RA patients with white tongue coating showed higher effective rate than those patients with yellow tongue coating in the treatment with WM intervention (p<0.05), and there was no difference in the patients with CM intervention. Further association analysis showed that TCM would be less effective for the patients with pale tongue body (p=0.0323), and WM would be less effective for the patients with purple or red tongue body (p=0.0291 and 0.0027, respectively). TCM was less effective for the patients with pale tongue body, and WM was be less effective for the patients with purple or red tongue body, or white tongue coating. The results suggest that tongue coating and body color might be used to help identify a subset of RA patients both for CM and WM interventions.

Effects of etanercept versus sulfasalazine in early axial spondyloarthritis on active inflammatory lesions as detected by whole-body MRI (ESTHER): a 48-week randomised controlled trial

PurposeTo evaluate the potential of etanercept versus sulfasalazine to reduce active inflammatory lesions on whole-body MRI in active axial spondyloarthritis with a symptom duration of less than 5 years.MethodsPatients were...

Protective effects of glycyrrhizic acid by rectal treatment on a TNBS-induced rat colitis model

The research compared rectal and oral treatments with glycyrrhizic acid for trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Wistar rats were randomly divided into seven groups: one normal and six with colitis, including TNBS, glycyrrhizic acid (2, 10 and 50 mg/kg, rectally treated and 10 mg/kg, orally treated) and sulfasalazine (positive control, 225 mg/kg rectally treated) groups. Colitis was induced by colonic administration of TNBS in 30% ethanol. There were significant pathological changes in colon in TNBS-treated groups, and rectal glycyrrhizic acid significantly attenuated colitis. Myeloperoxidase, tumour necrosis factor-α and interleukin-1β of colon tissue or serum in the rectal glycyrrhizic acid groups were markedly reduced when compared with the TNBS group, and lower than in the orally treated glycyrrhizic acid group. It was further noted that, in vitro, glycyrrhizic acid (up to 100 µg/ml) inhibited interleukin-6 and elevated interleukin-10 production in lipopolysaccharide-activated macrophages, and significantly inhibited proliferation of spleen lymphocytes, suggesting the immunoregulatory function of glycyrrhizic acid. Rectally administered glycyrrhizic acid has significant protective effects against TNBS-induced colitis in rats, and the rectal route may be a complementary treatment for inflammatory bowel disease.

Efficacy of sulfasalazine in the treatment of generalized lichen planus: randomized double‐blinded clinical trial on 52 patients

Oral sulfasalazine has been reported to be effective in patients with idiopathic cutaneous lichen planus (LP). Our purpose was to evaluate the efficacy of this drug in the treatment of generalized cutaneous lichen planus (GLP). In this study, we evaluated the effectiveness of the anti-inflammatory drug sulfasalazine for the treatment of GLP. A total of 52 patients with GLP presenting at the outpatient clinic were enrolled in this double-blind, randomized, placebo-controlled, prospective study. Of these patients, 44 completed the period of study. The patients were randomly divided into two groups. One group received placebo and the other was given sulfasalazine maximum 2.5 g/day. The patients were evaluated at the third and sixth weeks of treatment for improvement rate and occurrence of complications. After 6 weeks of treatment, the rate of cutaneous lesions improvement was 9.6% (two patients) in the placebo group and 82.6% (19 patients) in the sulfasalazine group. The improvement rate of pruritus was 14.3% in the placebo group and 91.3% in the sulfasalazine group. Side-effects which were mild and tolerable were detected in 30.7% of patients, but three patients left the study because of side effects. Most of the reported side-effects included gastrointestinal upset and headache. Statistically, sulfasalazine was more effective than placebo in reducing cutaneous lesions and improving pruritus after 6 weeks of treatment. According to our study, sulfasalazine is a relatively safe and effective treatment option and may be an alternative therapy for the treatment of generalized lichen planus.

Effect of probiotics on pro-inflammatory cytokines and NF-κB activation in ulcerative colitis

To demonstrate the therapeutic effect of probiotics in patients with ulcerative colitis (UC), and their effect on inflammatory mediators and nuclear factor (NF)-kappaB activation in these patients. Thirty patients with mild to moderate UC were randomly classified into two groups: sulfasalazine group, who received sulfasalazine 2400 mg/d; and probiotic group, who received sulfasalazine 2400 mg/d with probiotic. The patients were investigated before and after 8 wk of treatment with probiotic (Lactobacillus delbruekii and Lactobacillus fermentum). Colonic activity of myeloperoxidase (MPO) was assayed with UV spectrophotometry, the colonic content of interleukin (IL)-6 was determined by enzyme-linked immunosorbent assay (ELISA), fecal calprotectin was determined by ELISA, and expression of NF-kappaB p65 and tumor necrosis factor (TNF)-alpha proteins in colonic tissue was identified by immunohistochemistry and reverse transcription polymerase chain reaction, respectively. At the start of the study, colonic mucosal injury and inflammation were demonstrated in UC patients by hematoxylin and eosin staining, and an increase in colonic MPO activity, fecal calprotectin, and expression of colonic TNF-alpha and NF-kappaB p65 proteins. The use of probiotic for 8 wk significantly ameliorated the inflammation by decreasing the colonic concentration of IL-6, expression of TNF-alpha and NF-kappaB p65, leukocyte recruitment, as demonstrated by a decrease in colonic MPO activity, and the level of fecal calprotectin compared to sulfasalazine group and the control group (P < 0.05). Oral supplementation with probiotics could be helpful in maintaining remission and preventing relapse of UC.

Comparison ofTripterygium wilfordiiHook F Versus Sulfasalazine in the Treatment of Rheumatoid Arthritis

Extracts of the medicinal plant Tripterygium wilfordii Hook F (TwHF) have been used in China for centuries to treat a spectrum of inflammatory diseases. To compare the benefits and side effects of TwHF extract with those of sulfasalazine for the treatment of active rheumatoid arthritis. Randomized, controlled trial. A computer-generated code with random, permuted blocks was used to assign treatment. 2 U.S. academic centers (National Institutes of Health, Bethesda, Maryland, and University of Texas, Dallas, Texas) and 9 rheumatology subspecialty clinics (in Dallas and Austin, Texas; Tampa and Fort Lauderdale, Florida; Arlington, Virginia; Duncanville, Pennsylvania; Wheaton and Greenbelt, Maryland; and Lansing, Michigan). 121 patients with active rheumatoid arthritis and 6 or more painful and swollen joints. TwHF extract, 60 mg 3 times daily, or sulfasalazine, 1 g twice daily. Patients could continue stable doses of oral prednisone or nonsteroidal anti-inflammatory drugs but had to stop taking disease-modifying antirheumatic drugs at least 28 days before randomization. The primary outcome was the rate of achievement of 20% improvement in the American College of Rheumatology criteria (ACR 20) at 24 weeks. Secondary end points were safety; radiographic scores of joint damage; and serum levels of interleukin-6, cholesterol, cortisol, and adrenocorticotropic hormone. Outcome data were available for only 62 patients at 24 weeks. In a mixed-model analysis that imputed data for patients who dropped out, 65.0% (95% CI, 51.6% to 76.9%) of the TwHF group and 32.8% (CI, 21.3% to 46.0%) of the sulfasalazine group met the ACR 20 response criteria (P=0.001). Patients receiving TwHF also had significantly higher response rates for ACR 50 and ACR 70 in mixed-model analyses. Analyses of only completers showed similar significant differences between the treatment groups. Significant improvement was demonstrated in all individual components of the ACR response, including the Health Assessment Questionnaire disability score. Interleukin-6 levels rapidly and significantly decreased in the TwHF group. Although not statistically significant, radiographic progression was lower in the TwHF group. The frequency of adverse events was similar in both groups. Only 62% and 41% of patients continued receiving TwHF extract and sulfasalazine, respectively, during the 24 weeks of the study. Long-term outcome data were not collected on participants who discontinued treatment. In patients who continued treatment for 24 weeks and could also use stable oral prednisone and nonsteroidal anti-inflammatory drugs, attainment of the ACR 20 response criteria was significantly greater with TwHF extract than with sulfasalazine.

Effects of sulfasalazine on lipid peroxidation and histologic liver damage in a rat model of obstructive jaundice and obstructive jaundice with lipopolysaccharide-induced sepsis

Background: Sulfasalazine, an inhibitor of cyclooxygenase, 5-lipoxygenase, and nuclear factor κB (NF-κB), has been found to alleviate oxidative damage, proinflammatory cytokine production, bile-duct proliferation, neutrophil infiltration, and fibrosis. Therefore, it may have a potential effect in attenuating lipid peroxidation and histologic liver damage in patients with biliary obstruction and biliary obstruction with sepsis. Objective: The aim of this study was to investigate the effect of sulfasalazine on lipid peroxidation and histologic liver damage due to obstructive jaundice (OJ) and to OJ with lipopolysaccharide (LPS)-induced sepsis in an experimental model. Methods: Male Wistar rats, weighing 150 to 220 g, were randomized into 6 groups: OJ; OJ + LPS; OJ + sulfasalazine; OJ + sulfasalazine + LPS (sulfasalazine administered before sepsis); OJ + LPS + sulfasalazine (sulfasalazine administered after sepsis); and sham. Liver malondialdehyde (MDA) and myeloperoxidase (MPO) activities were assessed to monitor lipid peroxidation and neutrophil infiltration in liver tissue. Histologic liver damage was evaluated with hematoxylin-eosin stained slides. Liver tissue NF-κB and caspase-3 expression were studied immunohistopathologically to evaluate lipid peroxidation, liver damage, and hepatocyte apoptosis. Results: Forty-eight rats were evenly randomized into 6 groups of 8. MDA ( P = 0.001), MPO ( P = 0.001), NF-κB ( P = 0.003), caspase-3 expression ( P = 0.002), and liver injury scores ( P = 0.002) increased significantly in the OJ group compared with the sham group. Compared with the OJ group, MDA ( P = 0.030) and MPO levels ( P = 0.001), and liver injury scores ( P = 0.033) were decreased significantly in the OJ + sulfasalazine group. In the OJ + sulfasalazine + LPS and OJ + LPS + sulfasalazine groups, MDA ( P = 0.008 and P = 0.023, respectively) and MPO (both, P = 0.001) were significantly decreased; however, liver NF-κB, caspase-3 expression, and liver injury scores were not significantly different compared with the OJ + LPS group. There was no significant difference between the OJ + LPS + sulfasalazine and OJ + sulfasalazine + LPS groups in regard to all end points when comparing the effects of sulfasalazine administered before or after sepsis. Conclusions: Sulfasalazine was associated with decreased neutrophil accumulation and lipid peroxidation in these rats with OJ. Administration of sulfasalazine before or after LPS-induced sepsis was associated with a reduction in lipid peroxidation and neutrophil accumulation; however, it did not attenuate histologic liver damage. There was no difference between the findings when sulfasalazine was administered before or after sepsis in OJ.

Serum homocysteine level in patients with ankylosing spondylitis

In this study serum homocystein (Hcy) level was measured and its relationship with disease activity criteria and treatment protocols was investigated in ankylosing spondylitis (AS) patients. Ninety-two AS patients and 58 healthy individuals were recruited. Erythrocyte sedimentation rate and serum C-reactive protein were determined. Bath AS disease activity index and Bath AS functional index were calculated. Serum Hcy levels >15 micromol/l were considered as hyperhomocysteinemia. The mean serum homocysteine levels were 14.40 and 12.60 micromol/l in patients with AS and the control group, respectively, and the difference between two groups was significant. While there was no significant difference between the sulfasalazine (SSZ) group with 14.25 micromol/l mean Hcy level and the methotrexate (MTX)/SSZ group with 16.05 micromol/l, there was a statistically significant difference between the Hcy levels of these two groups and Hcy level of 12.15 micromol/l of the non-steroidal anti-inflammatory drugs group, and 12.60 micromol/l Hcy level of the control group. Mean serum Hcy level was 13.65 micromol/l in patients with active AS and 14.60 micromol/l in patients with inactive AS, and there was no significant difference between the groups. In our study serum Hcy level was found to be significantly higher in patients with AS than in healthy control subjects. Especially for the AS patients receiving MTX and SSZ treatment without folic acid supplementation, addition of folic acid to their therapy may decrease the risk of cardiovascular disease which in turn decreases the mortality in these patients, but further prospective studies are needed for supporting these results.

Does early sulfasalazine treatment provide long-term benefits to patients with juvenile idiopathic arthritis?

The small, well-designed, observational study by van Rossum et al. raises and addresses questions of great significance for the treatment of children with JIA. The original RCT demonstrated significant benefits of sulfasalazine over placebo that, by today's standards, would be considered only moderate clinical improvement. Despite these initial modest effects, the sulfasalazine group demonstrated improved outcomes compared with the placebo group 9 years later.

Sulfasalazin bei Spondylitis ankylosans: eine prospektive, randomisierte, doppelblinde, placebo-kontrollierte Studie und Vergleich mit anderen kontrollierten Studien

To assess the efficacy and tolerability of sulfasalazine in ankylosing spondylitis including a meta-analysis of comparable trials. In a prospective, randomized, double-blind, placebo-controlled trial 70 patients with established diagnosis of ankylosing spondylitis and a mean disease duration of 16.7 years were investigated in two centers for 26 weeks comparing 3 g/d sulfasalazine to placebo. The main outcome parameters, pain score, fingers-to-floor test, and CRP, did not improve significantly in the sulfasalazine group compared to the placebo group. Altogether sulfasalazine was significantly superior to placebo only concerning the IgA levels. The dropout rate was 47% for the sulfasalazine group and 19% for the placebo group. Due to side effects, 38% and 11%, respectively, stopped treatment. Ten other prospective, double-blind, controlled studies were analyzed. Altogether 959 patients with a mean disease duration of 13.9 years were evaluated. Most parameters did not improve significantly in the sulfasalazine groups compared to the placebo groups. Spinal motility remained nearly unchanged (0.3-3.5% improvement). Pain, morning stiffness, functional index, and global assessment were slightly influenced (1.9-11.7%). Reduction of ESR, CRP, IgA, IgG, and IgM was more distinct (12.6-20.3%). In 4 studies SSZ had greater efficacy in patients with peripheral joint involvement. Sulfasalazine has no clinically relevant benefit in patients with ankylosing spondylitis. The dropout-rate due to adverse effects is high with a daily dose of 3 g. Sulfasalazine may be beneficial in peripheral joint involvement. Only few data exist about patients with a disease duration of less than 10 years.

A double‐blind comparison of balsalazide, 6.75 g, and sulfasalazine, 3 g, as sole therapy in the management of ulcerative colitis

Sulfasalazine is accepted therapy for active ulcerative colitis, but side-effects and intolerance are common. Balsalazide is an azo-bonded pro-drug which also releases 5-aminosalicylic acid into the colon, but uses an inert carrier molecule. To compare the safety and efficacy of sul- fasalazine, 3 g, with balsalazide, 6.75 g, in the initial daily treatment of mild to moderate ulcerative colitis. A randomized, multicentre, double-blind, parallel group study was performed, with a treatment duration of 8 weeks. Patients on previous maintenance treatment were excluded. The trial medication was the sole treatment for the colitis. Efficacy was assessed by patient diaries, symptom assessment, sigmoidoscopic appearance and histology. Fifty patients were recruited: 26 allocated to the balsalazide group and 24 to the sulfasalazine group. More patients withdrew due to adverse events in the sulfasalazine group (nine patients vs. one patient in the balsalazide group, P=0.004). Improvement occurred in both groups, with a tendency to a faster response with balsalazide. Of the patients taking balsalazide, 61% achieved clinical and sigmoidoscopic remission. Balsalazide, 6.75 g, is effective as the sole treatment for patients with mild to moderately active ulcerative colitis, with significantly fewer withdrawals due to side-effects than in a similar group of patients taking sulfasalazine, 3 g.

Sulfasalazine in the prevention of anterior uveitis associated with ankylosing spondylitis

To assess the effects of sulfasalazine in preventing recurrences and reducing the severity of anterior uveitis associated with ankylosing spondylitis and chronic intestinal inflammation. Twenty-two patients with anterior uveitis associated with ankylosing spondylitis were studied. Ten patients were randomised to receive oral sulfasalazine (group 1) and 12 patients randomised to no treatment (group 2); all were followed for 3 years. Blood-aqueous barrier permeability was determined by fluorophotometry and bowel biopsies were taken. A statistically significant difference was observed between the two groups regarding the number of recurrences of uveitis (p = 0.016). The blood-aqueous barrier permeability was significantly higher during acute attacks in group 2 (group 1: 31.3 +/- 26.4 x 10(-4) min-1 vs group 2: 66.2 +/- 28.5 x 10(-4) min-1; p = 0.019) but not during the disease-free period. We observed a higher incidence of chronic intestinal inflammation at the end of the study in group 2 (group 1: 3/8 vs group 2: 7/9, p = 0.153). No relation was observed between blood-aqueous barrier permeability and the number of recurrences. The number of patients with severe persistent posterior synechiae at the end of the study was higher in group 2 (group 1: 4 patients before and 4 patients at the end; group 2: 4 patients before and 8 patients at the end; p = 0.65). Sulfasalazine may be beneficial in preventing recurrences and reducing the severity of anterior uveitis associated with ankylosing spondylitis.

Sulfasalazine for rheumatoid arthritis.

To estimate the short-term efficacy and toxicity of sulfasalazine for the treatment of rheumatoid arthritis (RA). We searched the Cochrane Musculoskeletal Group trials register, and Medline, up to July 1997, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). The search was complemented with bibliography searching of the reference list of the trials retrieved from the electronic search. Key experts in the area were contacted for further published and unpublished articles. All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing sulfasalazine against placebo in patients with RA. Two reviewers determined the studies to be included based on inclusion and exclusion criteria (GW, MSA). Data were independently abstracted by two reviewers (EB, MSA), and checked by a third reviewer (BS) using a pre-developed form for the rheumatoid arthritis sub-group of the Cochrane Musculoskeletal Group. The same two reviewers, using a validated scale (Jadad 1996) assessed the methodological quality of the RCTs and CCTs independently. Rheumatoid arthritis outcome measures were extracted from the publications. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts, pain, and global and functional assessments. Weighted mean differences (WMDs) were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios (OR) for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout and random effects for outcomes showing heterogeneity. Six trials, including 468 patients were included. A statistically significant benefit was observed for sulfasalazine when compared to placebo for tender and swollen joint scores, pain and ESR. The standardized weighted mean difference between treatment and placebo was -0.49 for tender and swollen joint scores, and -0.42 for pain. The difference for ESR was -17.6mm. Withdrawals from adverse reactions were significantly higher in the sulfasalazine group (OR=3.0). Patients receiving placebo were four times more likely to discontinue treatment because of lack of efficacy than patients receiving sulfasalazine. Sulfasalazine appears to have a clinically and statistically significant benefit on the disease activity of patients with RA. Its effects on overall health status and radiological progression are not clear at this time, but would appear to be modest.

Influence of sulfasalazine and olsalamine on colonic epithelial cell folate content in patients with ulcerative colitis

: Inflammatory bowel disease is associated with a reduction in serum and red blood cell folate levels that may contribute to colonic carcinogenesis. Sulfasalazine may exacerbate such deficiencies. Indirect evidence suggests that folate supplements reduce the risk of colonic neoplasia in those using this agent, although a direct effect on colonic epithelial cells has not been shown. The aim of this study was to determine the effect of sulfasalazine and olsalamine on colonic epithelial folate levels. Epithelial cells were isolated from endoscopic colon biopsies obtained from patients with colitis who were using sulfasalazine (7 patients) or olsalamine (11 patients) or from controls (8 patients). The folate content of these isolates were as follows: sulfasalazine, 20.1 ± 2.55 pg/μg DNA; olsalamine, 19.1 ± 1.63 pg/μg DNA and controls 18.7 ± 1.39 pg/μg DNA. Serum folate levels were reduced in the sulfasalazine group (p < 0.04). Neither serum nor red blood cell folate levels correlated with those of colonic epithelial cells. We conclude that sulfasalazine therapy administered orally is not associated with colonic epithelial cell folate deficiency. These data do not support the suggestion that the potential protective effects of folate supplements against colorectal carcinogenesis in patients with ulcerative colitis are due to correction of localized folate deficiency.

Influence of Sulfasalazine and Olsalamine on Colonic Epithelial Cell Folate Content in Patients with Ulcerative Colitis

Inflammatory bowel disease is associated with a reduction in serum and red blood cell folate levels that may contribute to colonic carcinogenesis. Sulfasalazine may exacerbate such deficiencies. Indirect evidence suggests that folate supplements reduce the risk of colonic neoplasia in those using this agent, although a direct effect on colonic epithelial cells has not been shown. The aim of this study was to determine the effect of sulfasalazine and olsalamine on colonic epithelial folate levels. Epithelial cells were isolated from endoscopic colon biopsies obtained from patients with colitis who were using sulfasalazine (7 patients) or olsalamine (11 patients) or from controls (8 patients). The folate content of these isolates were as follows: sulfasalazine, 20.1 ± 2.55 pg/μg DNA; olsalamine, 19.1 ± 1.63 pg/μg DNA and controls 18.7 ± 1.39 pg/μg DNA. Serum folate levels were reduced in the sulfasalazine group (p < 0.04). Neither serum nor red blood cell folate levels correlated with those of colonic epithelial cells. We conclude that sulfasalazine therapy administered orally is not associated with colonic epithelial cell folate deficiency. These data do not support the suggestion that the potential protective effects of folate supplements against colorectal carcinogenesis in patients with ulcerative colitis are due to correction of localized folate deficiency.

Intermittent therapy with high-dose 5-aminosalicylic acid enemas for maintaining remission in ulcerative proctosigmoiditis

Sixty patients who had presented recently with a relapse of mild to moderate ulcerative colitis with rectosigmoid involvement were randomly assigned to treatment with either 5-aminosalicylic acid enemas (N = 29) or oral sulfasalazine (N = 31). All patients were in remission, which was documented by clinical, histologic, and endoscopic criteria. Five-aminosalicylic acid treatment was administered on an intermittent schedule, consisting of 4 gm daily for the first seven days of each month; sulfasalazine was given as continuous therapy (2 gm daily as oral tablets). The study period was 2 years. Overall, 9 relapses occurred in the 5-aminosalicylic acid group and 12 occurred in the sulfasalazine group. The actuarial relapse rate at 12 months was 20 percent in the 5-aminosalicylic acid group and 24 percent in the sulfasalazine group; at 24 months, these rates were 37 and 43 percent, respectively. The actuarial relapse curves of the two groups were very similar. The relapse severity was also similar between the two groups. These results show that the authors proposed schedule of maintenance treatment with high-dose 5-aminosalicylic acid enemas is effective in subjects with rectosigmoiditis. This form of intermittent therapy may therefore be proposed for maintaining remission in patients who are refractory to oral and/or rectal treatment with sulfasalazine and steroids or who are intolerant or allergic to sulfasalazine. Treatment with 5-aminosalicylic acid enemas for seven days each month can also constitute an alternative for patients who favor the intermittent schedule over the classic continuous regimen of oral administrations.

A Comparative Study of Metronidazole and Sulfasalazine for Active Crohn's Disease: The Cooperative Crohn's Disease Study in Sweden

Seventy-eight patients with active Crohn's disease participated in a randomized, double-blind, cross-over trial. The study comprised two 4-mo period. The purpose was to test the efficacy of metronidazole in comparison with that of sulfasalazine. As the main evaluation criteria the Crohn's Disease Activity Index and plasma levels of orosomucoid were chosen. In the first period no difference in efficacy as measured by Crohn's Disease Activity Index was found between the treatment groups. The reduction of the plasma orosomucoid level was significantly more pronounced in the metronidazole group. The hemoglobin concentration increased more in this group than in the sulfasalazine group, possibly due to a toxic effect of sulfasalazine. The erythrocyte sedimentation rate decreased similarly with both drugs. In 15 patients who had active disease throughout the first period, Crohn's Disease Activity Index decreased significantly in the second period for those who switched to metronidazole, but not for those who switched to sulfasalazine. After crossover, no apparent further change in Crohn's Disease Activity Index occurred in either of the treatment groups among patients who had responded favorably in the first period. The plasma concentration of orosomucoid increased significantly among the patients in the sulfasalazine group but not in the metronidazole group. It is therefore concluded that metronidazole is slightly more effective than sulfasalazine in the treatment of crohn's disease. It is worthwhile switching the drug regimen from sulfasalazine, when it fails, to metronidazole, but not from metronidazole to sulfasalazine.