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Basic Clin Pharmacol Toxicol. 2008 Jul; 103(1): 9-16
Prakash O, Medhi B, Saikia UN, Pandhi P
The present study was carried out to evaluate the effect of different doses of thalidomide in experimentally induced inflammatory bowel disease in rats. Adult Wistar rats of either sex were used (n = 36). Colitis was induced by a single intra-colonic application of 20 mg 2,4,6-trinitrobenzene sulfonic acid (TNBS) dissolved in 35% ethanol into the descending colon. Rats were divided into six groups (n = 6). Animals were treated with vehicle (ethanol), TNBS dissolved in 35% ethanol, thalidomide (with different doses of 50, 100 and 150 mg/kg body weight), and sulfasalazine (360 mg/kg body weight) for 14 days. After completion of 14 days of treatment, animals were killed and the following parameters were assessed: morphological score, histological score and biochemical parameters (myeloperoxidase, malondialdehyde and tumour necrosis factor-alpha). Results showed thalidomide with different doses provided protection against TNBS-induced colonic damage. There was significant protection with thalidomide 150 mg/kg body weight compared to controls (P < 0.001). All the biochemical parameters were highly reduced in the entire thalidomide-treated group compared to controls particularly with thalidomide 150 mg/kg body weight (P < 0.001). Treatment with thalidomide restored malondialdehyde as well as reduction of myeloperoxidase and tumour necrosis factor-alpha towards normal levels. Morphological and histological score were significantly reduced in all the treated groups with significant effect found with 150 mg/kg (P < 0.001). Our results indicate efficacy of thalidomide in TNBS induce experimental colitis model in rats but present findings requires further investigation to establish the real safety and efficacy in human beings.
Automated Measurement of Joint Space Width in Small Joints of Patients with Rheumatoid Arthritis.
J Rheumatol. 2008 Jun 15;
Lukas C, Sharp JT, Angwin J, Boers M, Duryea J, Hall JR, Kauffman JA, Landewé R, Langs G, Bernelot Moens HJ, Peloschek P, van der Heijde D
OBJECTIVE: Comparison of performances of 5 (semi)automated methods in measuring joint space width (JSW) in rheumatoid arthritis. METHODS: Change in JSW was determined by 5 measurement methods on 4 radiographs per patient from 107 patients included in the COBRA trial (comparing sulfasalazine alone or in combination with methotrexate and corticosteroids). For each method the number of patients with sufficient available results was assessed (efficiency). An independent repeated measurement was carried out on a random sample of 30 patients' baseline and 1-year radiographs, to evaluate within-method reliability of change scores. Discriminatory ability (DA) of the measurement methods (between the 2 treatment arms) was compared with the DA of the Sharp-van der Heijde score (SHS) and its 2 components (erosion and JSW scores). RESULTS: The overall success rate varied widely between methods. Applying the chosen threshold of a minimum of 50% available joints with a change score per patient resulted in a success rate > 92% in 4/5 methods. Repeatability of measurements was good for most methods (intraclass correlation coefficient >/= 0.80 in 4/5 methods). Almost all measurement methods in 3 followup periods (12/14) showed a lower mean loss of JSW in patients from the intensive treatment group, although this was rarely statistically significant, confirming the known difference in structural damage. JSW as measured by the (semi)automated systems often showed higher DA than the JSW score of the SHS, but was lower than the total SHS and erosion scores. CONCLUSION: Although efficiency of the methods should be improved further, results already show good reliability and encouraging DA of most methods. Optimal information may be obtained with a combination of scoring of erosions and (semi)automated measurement of JSW.
PLoS ONE. 2008; 3(7): e2537
Juste RA, Elguezabal N, Garrido JM, Pavon A, Geijo MV, Sevilla I, Cabriada JL, Tejada A, García-Campos F, Casado R, Ochotorena I, Izeta A, Greenstein RJ
BACKGROUND: Mycobacteria, such as M. leprae and M. tuberculosis infect billions of humans. However, because of appropriate immune responses and antibiotic therapy, overt mycobacterial diseases occur far less frequently. M. avium subspecies paratuberculosis (MAP) causes Johne's disease in ruminants, an affliction evocative of inflammatory bowel disease (IBD). Several agents used to treat IBD (5-ASA, methotrexate, azathioprine and its metabolite 6-MP) have recently been shown to be antiMAP antibiotics. We herein evaluate the prevalence of MAP DNA in healthy individuals and compare them with IBD patients on antiMAP antibiotics. METHODS: We studied 100 healthy individuals (90 blood donors) and 246 patients with IBD. IS900 MAP DNA was identified using a nested primer PCR in the buffy coat of blood. Positive signal was confirmed as MAP by DNA sequence analysis. PCR positive results frequencies were compared according to medications used. Significance was accepted at p
Ter Arkh. 2008; 80(5): 25-30
AIM: To compare efficacy and tolerability of combined therapy with methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ) with MTX-monotherapy in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: RA patients (n = 60) who had not been treated with the above drugs were randomized (1:1) to receive either the triple drug combination or MTX alone in a 2-year open study. SSZ was given in a dose of 2.0 g/day, HCQ--200 mg/day. A MTX dose was gradually increased from 7.5 mg/week to 17.5 mg/week in an attempt to achieve remission in all the patients. Basic criterion of the treatment efficacy was achievement of a significant clinical effect (> 50% response according to the American College of Rheumatology--ACR criteria) in stability of the positive effect beginning from the ninth month of the study up to its end with no evidence of serious drug toxicity. RESULTS: 13 of 18 patients treated with the triple therapy (72.2%) and 6 of 20 patients treated with MTX alone (30.0%; p = 0.013) achieved an ACR > 50% response by the end of 18 months of therapy. 11 of 18 patients (61.1%) from the combined therapy group and 5 of 20 patients (25%; p = 0.024) from MTX monotherapy group maintained ACR > 50% response from month 9 to 18 of the study without any evidence of major drug toxicity. Two patients (11.1%) in the combined therapy group and 4 patients (20%) in the MTX group discontinued the treatment because of drug toxicity. CONCLUSION: In patients with RA the triple combination therapy with MTX, SSZ and HCQ given during 1.5 year is more effective than MTX alone. The triple combination of MTX, SSZ and HCQ is well tolerated.
J Korean Med Sci. 2008 Jun; 23(3): 521-5
Lee JH, Park HK, Heo J, Kim TO, Kim GH, Kang DH, Song GA, Cho M, Kim DS, Kim HW, Lee CH
Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome reflects a serious hypersensitivity reaction to drugs, characterized by skin rash, fever, lymph node enlargement, and internal organ involvement. So far, numerous drugs such as sulfonamides, phenobarbital, sulfasalazine, carbamazepine, and phenytoin have been reported to cause the DRESS syndrome. We report a case in a 29-yr-old female patient who had been on celecoxib and anti-tuberculosis drugs for one month to treat knee joint pain and pulmonary tuberculosis. Our patient's clinical manifestations included fever, lymphadenopathy, rash, hypereosinophilia, and visceral involvement (hepatitis and pneumonitis). During the corticosteroid administration for DRESS syndrome, swallowing difficulty with profound muscle weakness had developed. Our patient was diagnosed as DRESS syndrome with eosinophilic polymyositis by a histopathologic study. After complete resolution of all symptoms, patch tests were positive for both celecoxib and ethambutol. Although further investigations might be needed to confirm the causality, celecoxib and ethambutol can be added to the list of drugs as having the possibility of DRESS syndrome.
Carcinogenesis. 2008 Jun 25;
Calvisi DF, Pinna F, Ladu S, Pellegrino R, Muroni MR, Simile MM, Frau M, Tomasi ML, De Miglio MR, Seddaiu MA, Daino L, Sanna V, Feo F, Pascale RM
Mounting evidence underlines the role of inducible nitric oxide synthase (iNOS) in hepatocellular carcinoma (HCC) development, but its functional interactions with pathways involved in HCC progression remain uninvestigated. Here, we analyzed in preneoplastic and neoplastic livers from F344 and BN rats, possessing different genetic predisposition to HCC, in TGF-alpha and c-Myc-TGF-alpha transgenic mice, characterized by different susceptibility to HCC, and in human HCC: (a) iNos function and interactions with nuclear factor kB (NF-kB) and Ha-RAS/ERK during hepatocarcinogenesis; (b) influence of genetic predisposition to liver cancer on these pathways, and role of these cascades in determining a susceptible or resistant phenotype; (c) iNOS prognostic value in human HCC. We found progressive iNos induction in rat and mouse liver lesions, always at higher levels in the most aggressive models represented by HCC of rats genetically susceptible to hepatocarcinogenesis and c-Myc-TGF-alpha transgenic mice. iNOS, IKK/NF-kB, and RAS/ERK upregulation was significantly higher in HCC with poorer prognosis (as defined by patients' survival length) and positively correlated with tumor proliferation, genomic instability and microvascularization, and negatively with apoptosis. Suppression of iNOS signaling by Aminoguanidine led to decreased HCC growth and NF-kB and RAS/ERK expression, and increased apoptosis both in vivo and in vitro. Conversely, block of NF-kB signaling by Sulfasalazine or siRNA, or ERK signaling by UO126 caused iNOS downregulation in HCC cell lines. These findings indicate that iNOS crosstalk with NF-kB and Ha-RAS/ERK cascades influences HCC growth and prognosis, suggesting that key component of iNOS signaling could represent important therapeutic targets for human HCC.
Metastatic Crohn's disease: a review.
J Eur Acad Dermatol Venereol. 2008 Jun 19;
Palamaras I, El-Jabbour J, Pietropaolo N, Thomson P, Mann S, Robles W, Stevens H
Metastatic Crohn's disease (MCD) indicates the presence of non-caseating granuloma of the skin at sites separated from the gastrointestinal tract by normal tissue and is the least common dermatologic manifestation of CD. In adults, MCD usually appears after the initial diagnosis of CD in 70% of cases, whereas in children, it appears at the same time as CD in almost half of the cases. The most frequent skin lesions in adults are nodules, plaques with or without ulceration on the extremities and ulcers on the genitals. In children, genital swelling with or without erythema is the most frequent presentation of MCD. Simultaneous presence of perianal CD affects more females (60%) and particularly children. Associated gastrointestinal symptoms are present in one third of the cases in adults and in half of the cases in children. Treatment is often unsatisfactory. Randomised controlled trials are lacking. Various chemotherapeutic agents have been used such as oral metronidazole, topical and/or oral steroids, azathioprine, cyclosporine, sulfasalazine, tetracyclines, topical or systemic tacrolimus, infliximab alone or with methotrexate, and surgical treatment with oral zinc sulphate. MCD represents another 'great imitator'. This reviews the most relevant characteristics of this disease, in order to increase awareness and to avoid delay in diagnosis and improve management of the whole CD complex.
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 Jul; 4(7): 344-5
Ting TV, Lovell DJ