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Seven- to eight-week-old male C57BL/6 mice were challenged with 2.0 % DSS in drinking water for 5 days and then the colitic mice were arbitrarily allocated into five groups (n = 10 for each group). QDP (0.77, 1.54 and 3.08 g/kg) and sulfasalazine (SASP) (0.20 g/kg) were orally administered for 7 days. The disease activity index was determined by scores of body weight loss, diarrhea and rectal bleeding; histological signs of damage was analyzed by H&E staining; myeloperoxidase activity was measured by colorimetric method, levels of proinflammatory cytokines were determined by ELISA; changes in macrophages in the colon were analyzed by immunohistochemistry (IHC) and flow cytometry. Lipopolysaccharide (LPS)-induced RAW264.7 cells were treated with or without QDP, then the production of TNF-α and IL-6 were measured by ELISA; and protein molecules such as COX-2, iNOS, IкB-α were determined by Western blot.
Mesalamine has demonstrated clinical effectiveness as a therapeutic agent in the treatment of active ulcerative colitis and inactive Crohn's disease. Although its relationship to inflammatory bowel disease has been known for many years, the usefulness of nicotine for the treatment of active ulcerative colitis requires further exploration before it can be recommended as therapeutic agent.
Sulfasalazine (SSZ), which has an arylamine sulfonamide structure, is an anti-inflammatory drug used in the treatment of many rheumatic diseases. Various adverse effects have been reported related to SSZ. In the present study, we aimed to define the frequency of SSZ-related hypersensitivity reaction in patients with rheumatoid arthritis and ankylosing spondylitis.
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The mean age of the patients was 41 years, 74% were male, and the mean disease duration was 7.6 years. The proportion of ASAS20 responders at week 16 was greater among patients treated with etanercept compared with those treated with sulfasalazine (75.9% versus 52.9%; P<0.0001). As early as week 2 of treatment, etanercept was found to be more effective than sulfasalazine (P<0.0001) in ameliorating both the axial symptoms and peripheral manifestations. Serious adverse events rarely occurred, and the rate of serious adverse events did not differ between groups.
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Medline, Excerpta Medica, and Derwent were searched under the terms juvenile, rheumatoid, arthritis, and sulfasalazine.
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Transporter gene knockout rats are practically advantageous over murine models for pharmacokinetic and excretion studies, but their phenotypic characterization is lacking. At present, relevant aspects of pharmacokinetics, metabolism, distribution, and excretion of transporter probes [P-glycoprotein (P-gp): loperamide and paclitaxel; breast cancer resistance protein (Bcrp): sulfasalazine; and multidrug resistance-associated protein 2 (Mrp2): carboxydichlorofluorescein] were studied systematically across SAGE P-gp, Bcrp, and Mrp2 knockout rats. In Mdr1a knockout rats, loperamide and paclitaxel oral bioavailability was 2- and 4-fold increased, respectively, whereas clearance was significantly reduced (40-42%), consistent with the expected 10- to 20-fold reduction in paclitaxel excretion. N-Desmethyl-loperamide pharmacokinetics were not altered in any of the three knockouts after oral loperamide. In rats lacking P-gp, paclitaxel brain partitioning was significantly increased (4-fold). This finding is consistent with observations of loperamide central nervous system opioid pharmacology in Mdr1a knockout rats. Sulfasalazine oral bioavailability was markedly increased 21-fold in Bcrp knockouts and, as expected, was also 2- to 3-fold higher in P-gp and Mrp2 knockout rats. The sulfapyridine metabolite/parent ratio was decreased 10-fold in rats lacking Bcrp after oral, but not intravenous, sulfasalazine administration. Carboxydichlorofluorescein biliary excretion was obliterated in Mrp2 knockout rats, resulting in 25% decreased systemic clearance and 35% increased half-life. In contrast, carboxydichlorofluorescein renal clearance was not impaired in the absence of Mrp2, Bcrp, or P-gp. In conclusion, SAGE Mdr1a, Bcrp, and Mrp2 knockout rats generally demonstrated the expected phenotypes with respect to alterations in pharmacokinetics of relevant probe substrates; therefore, these knockout rats can be used as an alternative to murine models whenever a larger species is practically advantageous or more relevant to the drug discovery/development program.
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In total, during the followup of 10,994 patient-years, 92 malignancies and 341 serious infections were included in the analyses. The aIRR of infections compared to cDMARD users were 1.2 (95% CI 0.63-2.3), 0.84 (95% CI 0.53-1.3), 0.98 (95% CI 0.60-1.6), and 1.1 (95% CI 0.59-1.9) for the patients treated with infliximab (IFX), etanercept, adalimumab, and RTX, respectively. The crude rates of malignancies were highest among the users of cDMARD and RTX, and lowest among patients treated with IFX with no differences in aIRR.
The mean time to diagnosis was 9.4 (0-57) months. The total number of chest pain admissions pre-review was 39 compared with 6 post-review (p < 0.0001). The number of minor investigations was 169 pre-review compared with 17 post-review (p < 0.0001), and major investigations 30 compared with 0 (p < 0.01). All 13 patients treated with corticosteroid injections reported symptomatic improvement, and 10 of the 11 whose symptoms recurred responded to sulfasalazine.
Neu2000 (NEU; 2-hydroxy-5-(2,3,5,6-tetrafluoro-4-trifluoromethyl-benzylamino)-benzoic acid), a recently developed derivative of acetylsalicylic acid and sulfasalazine, potently protects against neuronal cell death following ischemic brain injury by antagonizing NMDA receptor-mediated neuronal toxicity and oxidative stress. However, it has yet to be determined whether NEU can attenuate hypoxia-induced impairment of neuronal electrical activity. In this study, we carried out extracellular recordings of hippocampal slices in order to investigate the effects of NEU on the electrical activity of neurons exposed to a hypoxic insult (oxygen and glucose deprivation). NEU prominently suppressed hypoxia-induced impairment of neuronal activity in a concentration-dependent manner. NEU, at a low dose (1 μM), competently depressed the hypoxia-induced convulsive activity in a manner similar to trolox. Furthermore, high concentrations of NEU (50 μM) markedly abolished all hypoxia-mediated impairment of neuronal activity and accelerated the slow recovery of neuronal activity more efficiently than ifenprodil and APV. These results suggest that NEU attenuates hypoxia-induced impairment of neuronal activity more potently than the antioxidant, trolox, and the NMDA receptor antagonists, ifenprodil and APV. We propose that NEU is a striking pharmacological candidate for neuroprotection against hypoxia because of its defensive action on hypoxia-mediated impairment of electrical neurotransmission as well as its neuroprotective action against neuronal cell death induced by exposure to pathological hypoxic conditions.
persons suffering recently developed, active RA, who cooperated in a randomized study on the effect of patient education. We analyzed the relation between adherence to Sulphasalazine therapy and personal factors, environmental influences, demographic factors, disease-related factors, and barriers to compliance. Moreover, a logistical regression analysis was performed on these factors, considering > or = 80% a high compliance, both with compliance as dependent factor. Only self-efficacy correlated with compliance (r = 0.58; P < 0.001). The logistical regression analysis identified self-efficacy as the only factor determining > or = 80% adherence (P = 0.01). Self-efficacy regarding the use of prescribed medication is related to compliance with this treatment. Further study is needed to determine the test characteristics of self-efficacy as a predictor for compliance with medication.
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Aminosalicylates have been shown to exhibit a wide range of anti-inflammatory and immunomodulatory properties. Since the discovery of sulfasalazine's efficacy in ulcerative colitis and the subsequent development of sulfa-free mesalamine delivery systems, aminosalicylates have evolved to become an integral part of our therapeutic armamentarium and are now first-line therapies for the treatment of mildly to moderately active inflammatory bowel disease and for maintenance of remissions after successful induction therapy. Despite the substantial body of evidence supporting the use of aminosalicylates in ulcerative colitis and Crohn's disease, gaps in our evidence base and controversies surrounding aminosalicylates clinical application have emerged. In this review, issues of dose response and optimization of the treatment regimen in ulcerative colitis, the discrimination between oral mesalamine formulations in left-sided colitis, and their efficacy in active and quiescent Crohn's disease are discussed.
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Two independent reviewers extracted data and assessed methodologic quality using standardized forms.
We here by report a case of a 42 year-old white woman with an eight-year history of watery diarrhea where the rectal biopsies performed in endoscopically normal mucosa led to the diagnosis of collagenous colitis, characterized histologically by a thickening of the colonic subepithelial basement membrane. A brief review of the current etiopathogenic concepts of this entity is done and the importance of performing rectal biopsies in patients with unexplained diarrhea and normal appearing colon mucosa is stressed. A clinical improvement following therapy with Sulfasalazine and Beta-methasone enemas was found in this patient. We discuss the current views on the therapy and the difficulties of assessing responses to drugs in this condition.
After 1 year, 55% of tight-control patients had a DAS28<2.6 versus 30% of usual care patients (OR 3.1, 95% CI 1.8 to 5.2). The median time to first remission was 25 weeks for tight control and more than 52 weeks for usual care (p<0.0001). The DAS28 decreased with -2.5 in tight control and -1.5 in usual care (p<0.0001).
The prognosis of patients suffering from WHO grade 3 and 4 astrocytic glioma remains poor despite surgery, radiation therapy and the use of current chemotherapy regimen. Indeed, the median survival of glioblastoma multiforme (WHO grade 4) patients is at best 14.6 month with only 26.5 percent of the patients still alive after 2 years and the median survival of anaplastic astrocytomas (WHO grade 3) is 19.2 month. Recent evidence suggests that the transcription factor NF-kappaB is constitutively expressed in malignant gliomas and that its inhibition by drugs like Sulfasalazine may block the growth of astrocytic tumors in vitro and in experimental models of malignant gliomas.
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Lymphocytic-plasmacytic colitis was diagnosed in 6 cats. Owners sought veterinary care because of semiformed -to-liquid feces, tenesmus , fresh blood and/or mucus in the feces, or increased frequency of defecation in their cats. Lymphocytic, plasmacytic infiltration in the colonic lamina propria was found on colon biopsies. Clinical signs resolved in all 6 cats after dietary management, utilizing lamb and rice, horsemeat , or a feline prescription diet. Clinical improvement also occurred in 1 cat following sulfasalazine therapy.
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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.
Conflicting reports have appeared concerning the role of Clostridium difficile toxin in chronic inflammatory bowel disease. Therefore, we prospectively evaluated the incidence of C. difficile toxin in 44 children with inflammatory bowel disease of variable clinical severity over a 1-year period. Only 3/128 stool specimens provided by these patients were found to be toxin-positive. These three stool specimens were from three different patients with Crohn's disease of moderate severity who had no recent hospitalization or antibiotic exposure. None received vancomycin therapy and their stools became toxin-negative over 3 weeks with no apparent change in the patients' clinical condition. No patient with severe disease or recent exposure to antibiotics or sulfasalazine was found to have toxin-positive stools. Routine screening for C. difficile toxin in children with inflammatory bowel disease appears unwarranted.
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Low levels of digoxin were noted in a patient receiving digoxin and sulfasalazine (SSA). Discontinuation of SSA resulted in a significant increase in serum digoxin levels. To determine whether or not SSA consistently interfered with the therapeutic effect of digoxin, both drugs were administered to 10 normal subjects in a crossover study. Each received 2 doses of digoxin (0.5 mg, elixir): one dose given alone, and a second dose after 6 days of treatment with SSA. When digoxin was given with SSA, the average area under the serum digoxin curve fell from the control value of 8.79 ng-hr-ml(-1) to 6.66 ng-hr-ml(-1) (p less than 0.05), fell and total urinary excretion decreased from 278 mcg/10 days to 228 mcg/10 days (p less than 0.025). These changes suggest interference with the bioavailability of digoxin by SSA. Studies were conducted to determine whether SSA inhibited digoxin absorption by physically absorbing the glycoside from solution. In vitro tests failed to reveal any significant adsorptive properties for SSA.
A total of 162 patients with ulcerative colitis in remission.
To provide a review of the renal toxicity of disease-modifying antirheumatic drugs (DMARDs) currently used for the treatment of rheumatoid arthritis.
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In the present investigation the clinical effect of treatment with metronidazole or sulfasalazine on patients with Crohn's disease was related to changes in the fetal flora. The clinical effect was evaluated by Crohn's Disease Activity Index (CDAI) and serum(s)-orosomucoid value. Twenty patients were included. All patients were untreated for at least 1 month before entrance to the study. None had any previous history of bowel resection. The results of CDAI, s-orosomucoid values, and the bacterial counts obtained at the start were compared to those at the end of treatment. Only changes of more than 33% of the CDAI or s-orosomucoid and changes of more than 3 log, i.e. 99.9%, of the bacterial counts are considered significant. Seventeen patients had a treatment period of 1-4 months. Their total counts of aerobic and anaerobic bacteria were unchanged. In 6 of 17 patients the Bacteroides counts decreased by more than 99.9%. In 13 of the 17 patients there was a dependence between the Bacteroides counts and s-orosomucoid values (P = 0.05) and in 9 out of 17 patients between the Bacteroides counts and CDAI (P less than 0.05). The use of CDAI and s-orosomucoid as measures for disease activity is discussed, and so are the modes of action of the two drugs in relation to the present results and the etiology and pathogenesis of Crohn's disease.
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To determine whether a regimen of methotrexate, cyclosporin A, and corticosteroids introduced at onset in poor-prognosis rheumatoid arthritis (RA) can produce a significant improvement in outcome compared with standard monotherapy with sulfasalazine (SSZ).
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PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov registry.
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The major treatment strategies for DH are gluten restriction or medical treatment with sulfones. Control of the cutaneous manifestations, but not the gastrointestinal changes, is rapid with dapsone. In addition to control of the cutaneous signs and symptoms of DH, dietary gluten restriction also induces improvement of gastrointestinal morphology and is possibly protective against the development of lymphoma.
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The study group had significant reductions in DAS 28 scores (3.39 versus 4.99 in control group) and significantly more subjects achieved the ACR 20/50/70 criteria at the end of 3 months (100/60/36% versus 84/20/0%) Secondary end-points like tender and swollen joint count, ESR, early morning stiffness, health assessment questionnaire (HAQ) scores and general health status were significantly reduced in the study group. Also, significantly lesser rescue medications were needed in the study group.
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In the period 1963-82 among the patients with aspecific inflammatory bowel disease, the incidence of ulcerative colitis was 3.1 per 100 000 per year, while the frequency of Crohn's disease has doubled during the observation period and now its incidence is 0.58 per 100 000 per year. During the past 20 years, 404 patients with ulcerative colitis were treated. The average follow-up of the patients lasted for 6.6 years. During this period, 40% of the patients could be kept in balance permanently with salicylazosulfapyridine (SASP) monotherapy. A further 34% reacted to SASP plus steroid. The rate of regression was increased by a further 14% when the combination was occasionally completed with a short-term antibiotic or prolonged azathioprine therapy. The inestimable cases and those refractory to treatment made up the other 12% and among them are also the 23 colectomized patients. During the two decades 40 patients with Crohn type ileocolitis were treated. SASP administration by itself was sufficient in only one case among them. In 6 cases steroid, in 4 antibiotics, in 7 azathioprine and in 2 cases metronidazole treatment had to be introduced complementarily. The fact that 21 of the 40 patients had to be subjected to bowel resection in some phase of the disease, shows how impossible it is to evaluate the different therapeutic interventions.
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Medications for rheumatoid arthritis (RA) may affect survival. However, studies often include limited followup and do not account for selection bias in treatment allocation. Using a large longitudinal database, we examined the association between prednisone use and mortality in RA, and whether this risk was modified with concomitant disease-modifying antirheumatic drug (DMARD) use, after controlling for propensity for treatment with prednisone and individual DMARDs.
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.
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During the last decade patients with active rheumatoid arthritis have been offered early and aggressive drug therapy in order to decrease the damaging effect of inflammation on cartilage and bone. Combination of two or more disease-modifying antirheumatic drugs has been used more frequently to achieve better efficacy than with monotherapy without increasing drug side effects.
Management of patients with acquired immunodeficiency syndrome (AIDS) is complicated by a high frequency of adverse drug reactions to trimethoprim-sulfamethoxazole and pentamidine. Because of the lack of suitable alternative antiparasitic drugs, some patients who have experienced previous allergic-type reactions to antimicrobial agents may require readministration with incriminated drugs. We report the outcome of seven drug-allergic patients with AIDS evaluated from 1982 to 85. Readministration of pentamidine was carried out without repeated reactions in three patients, and sulfadiazine and sulfamethoxazole-trimethoprim were readministered after very cautious test dosing in two other patients. A generalized maculopapular rash developed after 10 days of sulfadiazine therapy for Toxoplasma chorioretinitis but has been managed with prednisone, 20 to 30 mg/day for 3 months, and sulfadiazine has been continued. The administration of prednisone, 100 to 200 mg daily for treatment of severe cutaneous vasculitis from azulfidine in another patient, did not result in suprainfection. The complexities and potential legal risk of readministration of drugs in the drug-allergic patient with AIDS are emphasized in that coincidental deaths occurred in two patients 48 and 96 hours after readministration of pentamidine.
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The application of stellate ganglion block effectively improves treatment efficacy in chronic ulcerative colitis, relieves clinical symptoms in patients, and reduces the level of inflammatory factors. Furthermore, this approach also had a positive impact on the disease to a certain extent.
Sulfasalazine is a drug commonly administrated against inflammatory-based disorders. On the other hand, kidney and liver injury are serious adverse events accompanied by sulfasalazine administration. No specific therapeutic option is available against this complication. The current investigation was designed to evaluate the potential protective effects of taurine against sulfasalazine-induced kidney and liver injury in rats.