Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new sulfasalazine research articles will be listed here shortly after becoming available to us.
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Modulating effect of ginger extract on rats with ulcerative colitis.
J Ethnopharmacol. 2008 May 15;
El-Abhar HS, Hammad LN, Gawad HS
ETHNOPHARMACOLOGICAL RELEVANCE: Ginger rhizomes are used traditionally for management of different gastrointestinal disturbances. Several studies proved that the rhizome possesses diverse biological activities such as cytotoxic, antioxidant, and anti-inflammatory effects. Recently, interest in ginger for treatment of chronic inflammatory conditions has been renewed. AIM OF THE STUDY: The purpose of the present study is to evaluate the potential role of ginger extract [GE] in modulating the extent and severity of ulcerative colitis (UC), a chronically recurrent inflammatory bowel disease of unknown origin. MATERIALS AND METHODS: Male Wistar rats received 3 different doses of GE, sulfasalazine, or vehicle for 3 consecutive days before induction of UC by intra-rectal acetic acid administration, and continued further for 7 days after the induction. The colonic mucosal injury was assessed by macroscopic scoring, and histological examination. Furthermore, the mucosal content of malondialdehyde (MDA), protein carbonyl (PCO), and reduced glutathione (GSH) with the catalase (CAT) and superoxide dismutase (SOD) activity, were appraised as parameters of the redox state. Acute inflammatory response was determined by measuring myeloperoxidase (MPO), tumor necrosis factor (TNF-alpha), and prostaglandin E(2) (PGE(2)). RESULTS: All parameters were altered in ulcerated rats, and improved in animals receiving GE, an effect that was comparable to that of the standard sulfasalazine, especially at the highest dose level. Colonic mucosal injury parallels with the histological and biochemical evaluations. CONCLUSIONS: Results showed a valuable effect of ginger extract against acetic acid-induced ulcerative colitis possibly by its antioxidant and anti-inflammatory properties.
Ann Dermatol Venereol. 2008 Feb; 135 Suppl 4: S263-8
Claudepierre P, Bagot M
Psoriatic arthritis is a comorbidity frequently associated to psoriasis. A major problem is the absence of diagnostic criteria and the lack of consensus on the classification criteria of this arthritis. The clinical presentation is extremely variable, since axial, peripheric, and enthesopathic lesions can exist alone, successively or in association in a same patient. Peripheric lesions can be mono- or more often oligo- or polyarthritis. Onychopathies and dactylitis are frequently associated to arthritis. The dermatologist must recognize psoriatic arthritis at an early stage, in order to avoid the development of destructive lesions. The treatment includes symptomatic treatments (antalgics, non steroidal anti-inflammatory agents, corticosteroids), long-term treatments (sulfasalazine, methotrexate, azathioprine, ciclosporine, leflunomide), and TNF-alpha-inhibitors. Therapeutic strategies must be adapted to the clinical presentation.
Nat Clin Pract Rheumatol. 2008 May 20;
Ting TV, Lovell DJ
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.
Mesalamine for inflammatory bowel disease: recent reappraisals.
Inflamm Allergy Drug Targets. 2008 Mar; 7(1): 1-5
Actis GC, Pazienza P, Rosina F
Derived from the historical molecule sulfasalazine, mesalamine has remained one of the mainstays for treatment of inflammatory bowel disease in the last 50 years. Recent advancement in both clinical and basic research has led to reappraise the drug under two crucial aspects. Firstly, there has been a re-evaluation of the chemo-protective effect of mesalamine against sporadic colorectal cancer. Evidence that inflammation plays a strong role in tumor induction from one side, and demonstration that mesalamine can touch on specific molecular steps enhancing apoptosis on the other side have re-shaped the indications of mesalamine for ulcerative colitis. Secondly, the role of thiopurines (azathioprine and 6-MP) in the maintenance of remission of ulcerative colitis has been reiterated by the results of several clinical trials. During attempts at clarifying the reasons why certain patients appear to be resistant to thiopurines, it was interestingly found that mesalamine can interfere thiopurine metabolism, causing an increased blood concentration of the specific immunosuppressive metabolites and a sequential enhancement of drug effectiveness. Mesalamine is therefore being studied as a means to overcome the genetically determined resistance to thiopurines. Such sharpened indications have reiterated attention to correct dosing: the results of controlled trials have shown mesalamine to be fully effective at twice the traditional daily dosage (4.8 grams instead of 2.4). The attendant problems of compliance seem to find solution in the availability of multi-matrix system formulations. This mesalamine story reminds us that in the absence of an etiological target capable to guide research to trace one abrogating molecule, (as it has happened for viral hepatitides for example), treatment of inflammatory bowel disease remains anti-inflammatory in nature and thus multifaceted. Besides justified use of cutting-edge technology to find novel molecules, smart re-evaluation of what is already in our hands can sometimes bring about unexpected breakthroughs.
Once-daily MMX mesalamine for the treatment of mild-to-moderate ulcerative colitis.
Ther Clin Risk Manag. 2007 Oct; 3(5): 919-27
Kedia P, Cohen RD
First-line therapies in the treatment of patients with mild-to-moderate ulcerative colitis are sulfasalazine or one of the mesalamine derivatives. Mesalamine is popular given its safety profile and reasonable efficacy in many patients. However, compliance is poor with regimens demanding large number of pills dosed multiple times a day and non-compliance has been correlated with disease relapse. Mesalamine requires direct contact with the inflamed colonic mucosa. To avoid proximal absorption, a variety of delivery systems has been utilized to time the release of active mesalamine to the areas affected by colitis. The most common mesalamine release mechanisms include azo-bond prodrug carriers, pH-dependent dissolution, and moisture-sensitive product dispersion. Novel technology has resulted in the development and FDA-approval of a multi-matrix release (MMX) mesalamine. Pharmacodynamic studies suggest a reliable drug delivery system with homogenous release throughout the entire colon. By incorporating the largest amount of mesalamine (1.2 g) per pill, this new product dramatically decreases the number of pills needed to attain a therapeutic daily dosage, and is the first agent approved at once-daily dosing. These factors are expected to increase patient compliance with prescribed mesalamine dosing, and in turn decrease relapse rates of active ulcerative colitis.
The role of mesalamine in the treatment of ulcerative colitis.
Ther Clin Risk Manag. 2007 Oct; 3(5): 893-903
Karagozian R, Burakoff R
Ulcerative colitis (UC) is a chronic inflammatory condition of unclear etiology affecting the large bowel, most commonly the rectum and extending proximally in a continuous fashion. The overall principle in the pathophysiolgy of ulcerative colitis is the dysregulation of the normal immune system against an antigenic trigger leading to a prolonged mucosal inflammatory response. The diagnosing of UC is made by combining the clinical picture, tissue biopsy with the endoscopic appearance of mucosal ulceration, friable, edematous, erythematous granular appearing mucus. The approach to therapy of UC has been dependent on severity of symptoms with frontline therapy being salicylate based sulfasalazine. Newer formulations of salicylates based drugs with fewer side-effects have been developed. These are free of the sulphur component and are composed of 5-ASA, without the sulfapyridine carrier molecule. Mesalamine is one of these 5-ASA based agents that are currently available and indicated for treatment of UC. In mild/moderate active disease mesalamine has response rates between 40%-70% and remission rates of 15%-20%. Considering that the efficacy of 5-ASA is dose dependent, 4.8 g/day and 2.4 g/day have been shown to be the optimal dosages for mild-moderate distal active disease and for maintenance therapy, respectively. Patients with moderately active ulcerative colitis treated with 4.8 g/d of mesalamine are significantly more likely to achieve overall improvement at week 6 compared to patients treated with 2.4 g/d. In the setting of left-sided distal colitis (proctitis), topical (rectal) formulations have been found to be superior to oral aminosalicylates at inducing remission. Mesalamine has been shown to be safe in short term use with a dose-response efficacy without dose-related toxicity.
Eur J Med Chem. 2008 Apr 8;
Dhaneshwar SS, Chail M, Patil M, Naqvi S, Vadnerkar G
Mutual amide prodrugs of 4-aminosalicylic acid with d-phenylalanine and l-tryptophan were synthesized for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. Stability studies in aqueous buffers (pH 1.2 and 7.4) showed that the synthesized prodrugs were stable in both the buffers over a period of 10h. In rat fecal matter the release of 4-aminosalicylic acid from the prodrugs was in the range of 86-91% over a period of 20h, with half-lives ranging between 343 and 412min following first order kinetics. Targeting potential of the carrier system and the ameliorating effect of the amide conjugates were evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model in rats. The prodrugs were assessed for their probable damaging effects on pancreas and liver with the help of histopathological analysis and for their ulcerogenic potential by Rainsford's cold stress method. They were found to have improved safety profile than sulfasalazine, oral 4- and 5-aminosalicylic acid with similar pharmacological spectrum and advantages of sulfasalazine.
Arthritis Rheum. 2008 May; 58(5): 1310-7
Saunders SA, Capell HA, Stirling A, Vallance R, Kincaid W, McMahon AD, Porter DR
OBJECTIVE: The Tight Control of Rheumatoid Arthritis study previously demonstrated that an intensive step-up disease-modifying antirheumatic drug (DMARD) treatment strategy targeting persistent disease activity was superior to routine care in the management of early rheumatoid arthritis (RA). We undertook this study to test the hypothesis that early parallel triple therapy achieves better outcomes than step-up therapy within an intensive disease management regimen. METHODS: Ninety-six patients with early RA (mean disease duration 11.5 months) were randomized to receive step-up therapy (sulfasalazine [SSZ] monotherapy, then after 3 months, methotrexate [MTX] was added, and when the maximum tolerated dosage of MTX was reached, hydroxychloroquine [HCQ] was added) or parallel triple therapy (SSZ/MTX/HCQ). All patients were assessed monthly for 12 months. If their disease activity score in 28 joints (DAS28) was > or =3.2, the dosage of DMARDs was increased according to protocol, and swollen joints were injected with triamcinolone acetonide (maximum dosage 80 mg per month). A metrologist who was blinded to the treatment allocation performed assessments every 3 months. The primary outcome measure was the mean decrease in the DAS28 score at 12 months. RESULTS: Both groups showed substantial improvements in disease activity and functional outcome. At 12 months, the mean decrease in the DAS28 score was -4.0 (step-up therapy group) versus -3.3 (parallel therapy group) (P = 0.163). No significant differences in the percentages of patients with DAS28 remission (step-up therapy group 45% versus parallel triple therapy group 33%), DAS28 good response (60% versus 41%, respectively), or American College of Rheumatology criteria for 20% improvement (ACR20) (77% versus 76%, respectively), ACR50 (60% versus 51%, respectively), or ACR70 (30% versus 20%, respectively) responses were seen. Radiologic progression was similar in both groups. CONCLUSION: This study confirms that highly effective control of disease activity can be achieved using conventional DMARDs as part of an intensive disease management strategy. Within this setting, step-up therapy is at least as effective as parallel triple therapy.
Arthritis Rheum. 2008 May; 58(5): 1293-8
de Vries-Bouwstra JK, Goekoop-Ruiterman YP, Verpoort KN, Schreuder GM, Ewals JA, Terwiel JP, Ronday HK, Kerstens PJ, Toes RE, de Vries RR, Breedveld FC, Dijkmans BA, Huizinga TW, Allaart CF
OBJECTIVE: To determine the association of HLA-DRB1, rheumatoid factor (RF), and anti-citrullinated protein antibody (ACPA) status with progression of joint damage in early rheumatoid arthritis (RA) treated according to different treatment strategies. METHODS: The present study was conducted using data from the BeSt study (Behandelstrategieën voor Reumatoide Artritis [treatment strategies for rheumatoid arthritis]), a randomized trial comparing 4 targeted (toward achievement of a Disease Activity Score [DAS] of < or =2.4) treatment strategies: sequential monotherapy (group 1), step-up combination therapy (group 2), initial combination therapy with methotrexate, sulfasalazine, and prednisone (group 3), and initial combination therapy with methotrexate and infliximab (group 4), in 508 patients with early RA. Multivariate logistic regression analysis was used to predict progressive disease (increase of Sharp/van der Heijde score over 2 years beyond the smallest detectable change [4.6]) according to the presence or absence of the shared epitope (SE), DERAA, RF, and ACPA, with correction for other baseline characteristics. RESULTS: Progressive disease could not be predicted by presence of the SE: the odds ratio in groups 1, 2, 3, and 4, respectively, was 1.4, 2.6, 1.9, and 3.0. DERAA carriership did not protect against progressive disease (odds ratio 0.4, 1.4, 0.9, and 0.9 in groups 1, 2, 3, and 4, respectively). RF positivity and ACPA positivity predicted progressive disease in group 1 (odds ratio 4.7 [95% confidence interval 1.5-14.5] for RF and 12.6 [95% confidence interval 3.0-51.9] for ACPA), but not in groups 2-4 (for RF, odds ratio [95% confidence interval] 1.5 [0.5-4.9], 1.0 [0.3-3.3], and 1.4 [0.4-4.8] in group 2, group 3, and group 4, respectively; for ACPA, odds ratio [95% confidence interval] 3.4 [0.8-14.2], 1.7 [0.5-5.4], and 1.8 [0.5-6.8] in group 2, group 3, and group 4). CONCLUSION: In patients with early RA treated with the goal of tight control of the DAS, no significant association between HLA-DRB1 status and radiographic progression was found. RF and ACPA were predictive of progressive disease only in patients treated with sequential monotherapy. These observations suggest that effective treatment can prevent radiographic progression, even in patients with risk factors for severe damage.
Clinical images: healing of sacroiliitis with leflunomide and sulfasalazine treatment.
Arthritis Rheum. 2008 May; 58(5): 1527
Li SG