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‣ Decreased oxidative stress in patients with ulcerative colitis supplemented with fish oil omega-3 fatty acids

Barbosa, D. S.; Cecchini, R.; El Kadri, M. Z.; Rodriguez, MAM; Burini, R. C.; Dichi, I
Fonte: Elsevier B.V. Publicador: Elsevier B.V.
Tipo: Artigo de Revista Científica Formato: 837-842
Português
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OBJECTIVE: the potential pathogenicity of free radicals may have a pivotal role in ulcerative colitis. Fish oil omega-3 fatty acids exert anti-inflammatory effects on patients with ulcerative colitis (UC), but the precise mechanism of the action of fish oil on oxidative stress is still controversial. The aim of the present work was to verify the blood oxidative stress in patients with UC and determine whether the association of sulfasalazine to fish oil omega-3 fatty acids is more effective than isolated use of sulfasalazine to reduce the oxidative stress.METHODS:, Nine patients (seven female and two male; me. an age = 40 +/- 11 y) with mild or moderate active UC were studied in a randomized crossover design. In addition to their usual medication (2 g/d of sulfasalazine), they received fish oil omega-3 fatty acids (4.5 g/d) or placebo for 2-mo treatment periods that were separated by 2 mo, when they only received sulfasalazine. Nine healthy individuals served as control subjects to study the oxidative stress status. Disease activity was assessed by laboratory indicators (C-reactive protein, alpha(1)-acid glycoprotein, alpha(1)-antitrypsin, erythrocyte sedimentation rate, albumin, hemoglobin, and platelet count), sigmoidoscopy, and histology scores. Analysis of oxidative stress was assessed by plasma chemiluminescence and erythrocyte lipid peroxidation...

‣ Comparison of omega-3 fatty acids and sulfasalazine in ulcerative colitis

Dichi, I; Frenhane, P.; Dichi, J. B.; Correa, C. R.; Angeleli, AYO; Bicudo, M. H.; Rodrigues, MAM; Victoria, C. R.; Burini, R. C.
Fonte: Elsevier B.V. Publicador: Elsevier B.V.
Tipo: Artigo de Revista Científica Formato: 87-90
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Fish oil omega-3 fatty acids exert antiinflammatory effects on patients with ulcerative colitis. However, a comparative study in patients with mild to moderate ulcerative colitis receiving only sulfasalazine or omega-3 fatty acids has not been performed. We sought to detect changes in the inflammatory disease activity with the use of either fish oil omega-3 fatty acids or sulfasalazine in patients with ulcerative colitis. Ten patients (five male, five female; mean age = 48 +/- 12 y) with mild to moderate active ulcerative colitis were investigated in a randomized cross-over design. They received either sulfasalazine (2 g/d) or omega-3 fatty acids (5.4 g/d) for 2 mo. Disease activity was assessed by clinical and laboratory indicators, sigmoidoscopy, histology, and whole-body protein turnover (with N-15-glycine). Treatment with w-3 fatty acids resulted in greater disease activity as detected by a significant increase in platelet count, erythrocyte sedimentation rate, C-reactive protein, and total fecal nitrogen excretion. No major changes in protein synthesis and breakdown were observed during either treatment. In conclusion, treatment with sulfasalazine is superior to treatment with omega-3 fatty acids in patients with mild to moderate active ulcerative colitis. Nutrition 2000;16:87-901 (C) Elsevier B.V. 2000.

‣ Dietary Polydextrose Prevents Inflammatory Bowel Disease in Trinitrobenzenesulfonic Acid Model of Rat Colitis

Witaicenis, Aline; Fruet, Andrea C.; Salem, Leticia; Di Stasi, Luiz C.
Fonte: Mary Ann Liebert, Inc. Publicador: Mary Ann Liebert, Inc.
Tipo: Artigo de Revista Científica Formato: 1391-1396
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Inflammatory bowel disease (IBD) is a multifactorial intestinal disorder that involves interactions among the immune system, genetic susceptibility, and environmental factors, especially the bacterial flora. Polydextrose, a polysaccharide constituted by 90% nondigestible and nonabsorbable soluble fibers, has several physiological effects consistent with those of dietary fibers, including proliferation of colon microflora. Because sulfasalazine presents serious side effects through long-term use at high doses, the aim of the present study was to evaluate the preventative effect of polydextrose on trinitrobenzenesulfonic acid-induced intestinal inflammation and its effects on the intestinal anti-inflammatory activity of sulfasalazine. Results indicated that polydextrose and its association with sulfasalazine present an anti-inflammatory effect that reduces myeloperoxidase activity, counteracts glutathione content, and promotes reductions in lesion extension and colonic weight/length ratio.

‣ The effect of 677C>T and 1298A>C MTHFR polymorphisms on sulfasalazine treatment outcome in rheumatoid arthritis

Pawlik,A.; Kurzawski,M.; Gawronska-Szklarz,B.; Gornik,W.; Dziedziejko,V.; Safranow,K.; Juzyszyn,Z.; Drozdzik,M.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/07/2009 Português
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Despite the availability of several new agents for the treatment of rheumatoid arthritis (RA), sulfasalazine remains the mainstay because of both cost and experience with its use. Methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism and several polymorphisms have been described in the MTHFR gene. Of these, the 677C>T and 1298A>C polymorphisms have been associated with altered enzyme activity. To examine the association between 677C>T and 1298A>C MTHFR polymorphisms and sulfasalazine efficacy for the treatment of RA, a total of 117 RA patients treated with sulfasalazine (1 g daily; duration of treatment 17 ± 5 months) were analyzed. The 677C>T and 1298 A>C polymorphisms were detected using a PCR-RFLP method. RA was diagnosed according to the criteria of the American College of Rheumatology (ACR). The remission of RA symptoms was evaluated according to the ACR 20% response criteria. Allele and genotype frequencies were compared by the two-sided Fisher exact test. The frequency of remission was 47.2% and 44.6% in carriers of 677T and 1298C alleles, compared to 40.7% and 42.0% in carriers of 677C and 1298A alleles, respectively. These differences were statistically non-significant. When the multivariate analysis was additionally adjusted for patients’ age...

‣ Sulfasalazine-induced DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms)

Aquino,Renata Telles Rudge de; Vergueiro,Carmen Silvia Vieitas; Magliari,Maria Elisa Ruffolo; Freitas,Thais Helena Proença de
Fonte: Associação Paulista de Medicina - APM Publicador: Associação Paulista de Medicina - APM
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/07/2008 Português
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CONTEXT: DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms) is a type of drug reaction commonly mistaken for a viral infection. It must be recognized promptly due to its high morbidity and 10% mortality rate. Few cases of DRESS syndrome induced by sulfasalazine have been reported in the literature. CASE REPORT: The case of a 47-year-old white Brazilian woman who developed DRESS syndrome eight weeks after starting a course of sulfasalazine for treatment of seronegative arthritis is reported. She presented a skin rash, fever, hepatitis, lymphadenopathy, eosinophilia and atypical lymphocytes. The causative drug was discontinued immediately, but she only improved after treatment with prednisone.

‣ Inhibition of Folate Enzymes by Sulfasalazine

Selhub, Jacob; Dhar, G. Jeelani; Rosenberg, Irwin H.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1978 Português
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Sulfasalazine (salicylazosulfapyridine), an agent widely used for the treatment of ileitis and colitis, is also a competitive inhibitor of intestinal folate transport (1, 2). The mechanism of action of sulfasalazine remains uncertain. To further explore the mechanism of sulfasalazine action, the interaction of the drug with the folate recognition site was tested with three enzymes: dihydrofolate reductase, methylenetetrahydrofolate reductase, and serine transhydroxymethylase, each catalyzing a reaction involving a different folate derivative. Each of these enzymes was inhibited by sulfasalazine in the same concentration range as that previously observed to inhibit intestinal folate transport; the kinetic data are consistent with a competitive mode of inhibition. Specificity of inhibition was demonstrated by the finding that the reduction of the pteridine ring of pteroylheptaglutamic acid by dihydrofolate reductase was subject to inhibition, whereas the hydrolysis of the γ-glutamyl peptide side chain by chicken pancreas conjugase was not affected. These results are interpreted to indicate that sulfasalazine interferes with a folate recognition site which is common to these enzymes and to the intestinal transport system. Sulfasalazine...

‣ Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B.

Wahl, C; Liptay, S; Adler, G; Schmid, R M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/03/1998 Português
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Transcription factors of the NF-kappaB/Rel family are critical for inducible expression of multiple genes involved in inflammatory responses. Sulfasalazine and its salicylate moiety 5-aminosalicylic acid are among the most effective agents for treating inflammatory bowel disease and rheumatoid arthritis. However, the mode of action of these drugs remains unclear. Here we provide evidence that the transcription factor NF-kappaB is a target of sulfasalazine-mediated immunosuppression. Treatment of SW620 colon cells with sulfasalazine inhibited TNFalpha-, LPS-, or phorbol ester- induced NF-kappaB activation. NF-kappaB-dependent transcription was inhibited by sulfasalazine at micro- to millimolar concentrations. In contrast, 5-aminosalicylic acid or sulfapyridine did not block NF-kappaB activation at all doses tested. TNFalpha-induced nuclear translocation of NF-kappaB was prevented by sulfasalazine through inhibition of IkappaBalpha degradation. When blocking proteasome-mediated degradation of IkappaBalpha, we could demonstrate that sulfasalazine interfered with IkappaBalpha phosphorylation, suggesting a direct effect on an IkappaBalpha kinase or on an upstream signal. Inhibition of NF-kappaB activation seems to be specific since other DNA-binding activities such as AP1 were not affected. These results demonstrate that sulfasalazine is a potent and specific inhibitor of NF-kappaB activation...

‣ Sulfasalazine-induced colitis complicating idiopathic ulcerative colitis.

Ring, F A; Hershfield, N B; Machin, G A; Scott, R B
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/07/1984 Português
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A diagnosis of idiopathic ulcerative colitis was made in a previously healthy 9-year-old boy. Symptoms persisted despite therapy with sulfasalazine, 50 mg/kg daily, but they eventually responded to treatment with parenteral nutrition and prednisone, 40 mg daily. Metronidazole was also given to eradicate persistent Dientamoeba fragilis from the stools. The symptoms resolved over 3 weeks, and the daily dose of prednisone was tapered. On two subsequent occasions a challenge with sulfasalazine caused an immediate recurrence of loose, blood-streaked stools and of nonspecific histologic features of ulcerative colitis, which resolved when the sulfasalazine was discontinued.

‣ Inhibition of nuclear factor kappa B and induction of apoptosis in T-lymphocytes by sulfasalazine

Liptay, Susanne; Bachem, Max; Häcker, Georg; Adler, Guido; Debatin, Klaus M; Schmid, Roland M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/1999 Português
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Chronic inflammatory diseases have been shown to be associated with NF-κB activation and impaired apoptosis of immune cells. The aim of the present study was to investigate if sulfasalazine and its colonic metabolites 5-aminosalicylic acid (5ASA) and sulfapyridine affect NF-κB/Rel activation and viability of T-lymphocytes.Sulfasalazine inhibits NF-κB/Rel activation in the murine T-lymphocyte cell line RBL5 using electrophoretic mobility shift assays. In transfection assays sulfasalazine treatment for 4 h inhibits κB-dependent transcription with an IC50 value of ∼0.625 mM.Higher doses or prolonged treatment result in cell death of T-lymphocytes in a dose- and time-dependent manner. Cell death is caused by apoptosis as judged by DNA fragmentation, annexin V and Apo 2.7 staining. Induction of apoptosis is a fast event with 50% apoptotic cells after a 4 h incubation with 2.5 mM sulfasalazine. The ED50 value for apoptosis induction after 24 h treatment was ∼0.625 mM.In contrast, 5ASA and sulfapyridine neither inhibit NF-κB/Rel activation nor induce apoptosis in T-lymphocytes at doses up to 5.0 mM.These results demonstrate that sulfasalazine, but not 5ASA or sulfapyridine, strongly inhibits NF-κB activation and potently induces apoptosis in T-lymphocytes. Inhibition of NF-κB/Rel activation and subsequent clearance of activated T-lymphocytes by apoptosis might thus explain the beneficial effects of sulfasalazine in the treatment of chronic inflammatory disorders.

‣ Molecular mechanisms of sulfasalazine-induced T-cell apoptosis

Liptay, Susanne; Fulda, Simone; Schanbacher, Marta; Bourteele, Soizic; Ferri, Karine F; Kroemer, Guido; Adler, Guido; Debatin, Klaus M; Schmid, Roland M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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Impaired apoptosis of T-lymphocytes is involved in the development of chronic inflammatory disorders. Previously we have shown that the anti-inflammatory drug sulfasalazine induces apoptosis in a murine T-lymphocyte cell line. The aims of the present study were to expand these observations to human systems and to analyse the molecular basis for sulfasalazine-induced apoptosis.Sulfasalazine induces apoptosis both in Jurkat cells, a human T-leukaemia cell line (ED50 value ∼1.0 mM), and in primary human peripheral blood T-lymphocytes (ED50 value ∼0.5 mM). In contrast SW620 colon carcinoma cells or primary human synoviocytes are not affected at these concentrations suggesting a cell type-specific sensitivity to sulfasalazine.Sulfasalazine triggers the mitochondrial accumulation of Bax and induces a collapse of the mitochondrial transmembrane potential (ΔΨm).Sulfasalazine causes cytochrome c release from mitochondria and subsequent activation of caspase-3 and downstream substrates. However, the pan-caspase inhibitor Z-VAD.fmk fails to inhibit sulfasalazine-induced apoptosis.Sulfasalazine stimulates mitochondrio-nuclear translocation of the novel apoptogenic factor apoptosis-inducing factor (AIF) and triggers large-scale DNA fragmentation...

‣ Treatment of active rheumatoid arthritis with leflunomide: two year follow up of a double blind, placebo controlled trial versus sulfasalazine

Scott, D; Smolen, J; Kalden, J; van de Putte, L B A; Larsen, A; Kvien, T; Schattenkirchner, M; Nash, P; Oed, C; Loew-Friedrich, I
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/2001 Português
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OBJECTIVE—Recent studies have demonstrated the short term efficacy of leflunomide. This study evaluates the efficacy and safety of leflunomide and sulfasalazine in rheumatoid arthritis over a two year follow up period.
METHODS—358 patients with rheumatoid arthritis in a double blind trial were randomly allocated to receive either leflunomide 20 mg/day, placebo, or sulfasalazine 2 g/day. Those completing six months of treatment (n=230) were given the option to continue in 12 (n=168) and 24 (n=146) month double blinded extensions; the placebo group switched to sulfasalazine. This report compares efficacy and safety of leflunomide with sulfasalazine in the 6, 12, and 24 month patient cohorts.
RESULTS—The efficacy seen at six months was maintained at 12 and 24 months. Twenty four month cohorts on leflunomide showed significant improvement compared with sulfasalazine in doctor (−1.46 v −1.11, p=0.03) and patient (−1.61 v −1.04, p<0.001) global assessments, ACR20% response (82% v 60%, p<0.01), and functional ability (Δmean HAQ −0.65 v −0.36, p=0.0149; ΔHAQ disability index −0.89 v −0.60, p=0.059). Improvement in other variables was comparable for the two drugs, including slowing of disease progression. Improved HAQ scores in 6...

‣ Sulfasalazine prevents T-helper 1 immune response by suppressing interleukin-12 production in macrophages

Kang, B Y; Chung, S W; Im, S-Y; Choe, Y K; Kim, T S
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /09/1999 Português
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Interleukin-12 (IL-12) plays a pivotal role in the development of T-helper 1 (Th1) immune response, which may be involved in the pathogenesis of chronic inflammatory autoimmune disorders. In this study we investigated the effects of sulfasalazine, a drug for treating inflammatory bowel disease and rheumatoid arthritis, on the production of IL-12 from mouse macrophages stimulated with lipopolysaccharide (LPS). Sulfasalazine potently inhibited the production of IL-12 in a dose-dependent manner, in part through the down-regulation of nuclear factor κB (NFκB) activation in IL-12 p40 gene. Activation of macrophages by LPS resulted in markedly enhanced binding activities to the κB site, which significantly decreased upon addition of sulfasalazine as demonstrated by an electrophoretic gel shift assay. Importantly, macrophages pretreated with sulfasalazine either in vitro or in vivo reduced their ability to induce interferon-γ (IFN-γ) and increased the ability to induce IL-4 in antigen-primed CD4+ T cells. From these results, sulfasalazine may induce the Th2 cytokine profile in CD4+ T cells by suppressing IL-12 production in macrophages, and sulfasalazine-induced inhibition of IL-12 production in macrophages may explain some of the known biological effects of sulfasalazine.

‣ Immune Modulation with Sulfasalazine Attenuates Immunopathogenesis but Enhances Macrophage-Mediated Fungal Clearance during Pneumocystis Pneumonia

Wang, Jing; Gigliotti, Francis; Bhagwat, Samir P.; George, Thaddeus C.; Wright, Terry W.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Although T cells are critical for host defense against respiratory fungal infections, they also contribute to the immunopathogenesis of Pneumocystis pneumonia (PcP). However, the precise downstream effector mechanisms by which T cells mediate these diverse processes are undefined. In the current study the effects of immune modulation with sulfasalazine were evaluated in a mouse model of PcP-related Immune Reconstitution Inflammatory Syndrome (PcP-IRIS). Recovery of T cell-mediated immunity in Pneumocystis-infected immunodeficient mice restored host defense, but also initiated the marked pulmonary inflammation and severe pulmonary function deficits characteristic of IRIS. Sulfasalazine produced a profound attenuation of IRIS, with the unexpected consequence of accelerated fungal clearance. To determine whether macrophage phagocytosis is an effector mechanism of T cell-mediated Pneumocystis clearance and whether sulfasalazine enhances clearance by altering alveolar macrophage phagocytic activity, a novel multispectral imaging flow cytometer-based method was developed to quantify the phagocytosis of Pneumocystis in vivo. Following immune reconstitution, alveolar macrophages from PcP-IRIS mice exhibited a dramatic increase in their ability to actively phagocytose Pneumocystis. Increased phagocytosis correlated temporally with fungal clearance...

‣ Sulfasalazine and Mesalamine Modulate Beryllium-Specific Lymphocyte Proliferation and Inflammatory Cytokine Production

Dobis, Dave R.; Sawyer, Richard T.; Gillespie, May M.; Newman, Lee S.; Maier, Lisa A.; Day, Brian J.
Fonte: American Thoracic Society Publicador: American Thoracic Society
Tipo: Artigo de Revista Científica
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Occupational exposure to beryllium (Be) results in Be sensitization (BeS) that can progress to pulmonary granulomatous inflammation associated with chronic Be disease (CBD). Be-specific lymphocytes are present in the blood of patients with BeS and in the blood and lungs of patients with CBD. Sulfasalazine and its active metabolite, mesalamine, are clinically used to ameliorate chronic inflammation associated with inflammatory bowel disease. We tested whether sulfasalazine or mesalamine could decrease Be-stimulated peripheral blood mononuclear cell (PBMC) proliferation in subjects with CBD and BeS and Be-induced cytokine production in CBD bronchoalveolar lavage (BAL) cells. CBD (n = 25), BeS (n = 12) and healthy normal control (n = 6) subjects were enrolled and ex vivo proliferation and cytokine production were assessed in the presence of Be and sulfasalazine or mesalamine. Be-stimulated PBMC proliferation was inhibited by treatment with either sulfasalazine or mesalamine. Be-stimulated CBD BAL cell IFN-γ and TNF-α cytokine production was decreased by treatment with sulfasalazine or mesalamine. Our data suggest that both sulfasalazine and mesalamine interfere with Be-stimulated PBMC proliferation in CBD and BeS and dampens Be-stimulated CBD BAL cell proinflammatory cytokine production. These studies demonstrate that sulfasalazine and mesalamine can disrupt inflammatory pathways critical to the pathogenesis of chronic granulomatous inflammation in CBD...

‣ Effect of Sulfasalazine on Inflammation and Endothelial Function in Patients with Established Coronary Artery Disease

Tabit, Corey E; Holbrook, Monica; Shenouda, Sherene M; Dohadwala, Mustali M; Widlansky, Michael E.; Frame, Alissa A; Kim, Brian H; Duess, Mai-Ann; Kluge, Matthew A; Levit, Aaron; Keaney, John F.; Vita, Joseph A; Hamburg, Naomi M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/2012 Português
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Inflammation is critical for atherosclerosis development and may be a target for risk-reduction therapy. In experimental studies, activation of the inflammatory regulator, nuclear factor κB (NFκB), contributes to endothelial activation and reduced nitric oxide production. We treated patients with coronary artery disease with sulfasalazine, an inhibitor of NFκB, and placebo in a randomized, double-blind, crossover design. Brachial artery flow-mediated dilation (FMD) and digital vascular function were measured at baseline and after each 6 week treatment period. Of the 53 patients enrolled in the crossover study, 32 (age 60±10, 22% female) completed all the visits, with a high-rate of study withdrawal due to gastrointestinal side-effects. In a subset of 10 participants, we compared the effects of four days of sulfasalazine treatment (n=5) to no treatment (n=5) on NFkB-regulated gene expression in peripheral blood mononuclear cells. Tumor necrosis factor α-stimulated expression of CD69 and NFκB subunit p50 was significantly blunted after 4 days of sulfasalazine treatment but not after no treatment. However, FMD and digital vasodilator response did not significantly change from baseline with long-term sulfasalazine treatment. Short-term sulfasalazine inhibited NFκB activity; however long-term treatment was poorly tolerated and did not improve endothelial function. Our findings suggest that sulfasalazine therapy is not the optimal anti-inflammatory treatment for reversing endothelial dysfunction in cardiovascular disease. Further studies are warranted to investigate the potential for NFκB inhibition to reduce cardiovascular risk.

‣ Breast cancer resistance protein (ABCG2) and drug disposition: intestinal expression, polymorphisms and sulfasalazine as an in vivo probe

Urquhart, Bradley L.; Ware, Joseph A.; Tirona, Rommel G.; Ho, Richard H.; Leake, Brenda F.; Schwarz, Ute I.; Zaher, Hani; Palandra, Joe; Gregor, Jamie C.; Dresser, George K.; Kim, Richard B.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/2008 Português
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Breast cancer resistance protein (BCRP) is an efflux transporter expressed in tissues that act as barriers to drug entry. Given that single nucleotide polymorphisms (SNPs) in the ABCG2 gene encoding BCRP are common, the possibility exists that these genetic variants may be a determinant of interindividual variability in drug response. The objective of this study is to confirm the human BCRP-mediated transport of sulfasalazine in vitro, evaluate interindividual variation in BCRP expression in human intestine and to determine the role of ABCG2 SNPs to drug disposition in healthy patients using sulfasalazine as a novel in vivo probe. To evaluate these objectives, pinch biopsies were obtained from 18 patients undergoing esophagogastro–duodenoscopy or colonoscopy for determination of BCRP expression in relation to genotype. Wild-type and variant BCRP were expressed in a heterologous expression system to evaluate the effect of SNPs on cell-surface trafficking. A total of 17 healthy individuals participated in a clinical investigation to determine the effect of BCRP SNPs on sulfasalazine pharmacokinetics. In vitro, the cell surface protein expression of the common BCRP 421 C>A variant was reduced in comparison with the wild-type control. Intestinal biopsy samples revealed that BCRP protein and mRNA expression did not significantly differ between patients with 34GG/421CC versus patients with 34GG/421CA genotypes. Remarkably...

‣ Sulfasalazine Attenuates Staphylococcal Enterotoxin B-Induced Immune Responses

Krakauer, Teresa
Fonte: MDPI Publicador: MDPI
Tipo: Artigo de Revista Científica
Publicado em 13/02/2015 Português
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Staphylococcal enterotoxin B (SEB) and related exotoxins are important virulence factors produced by Staphylococcus aureus as they cause human diseases such as food poisoning and toxic shock. These toxins bind directly to cells of the immune system resulting in hyperactivation of both T lymphocytes and monocytes/macrophages. The excessive release of proinflammatory cytokines from these cells mediates the toxic effects of SEB. This study examined the inhibitory activities of an anti-inflammatory drug, sulfasalazine, on SEB-stimulated human peripheral blood mononuclear cells (PBMC). Sulfasalazine dose-dependently inhibited tumor necrosis factor α, interleukin 1 (IL-1) β, IL-2, IL-6, interferon γ (IFNγ), and various chemotactic cytokines from SEB-stimulated human PBMC. Sulfasalazine also potently blocked SEB-induced T cell proliferation and NFκB activation. These results suggest that sulfasalazine might be useful in mitigating the toxic effects of SEB by blocking SEB-induced host inflammatory cascade and signaling pathways.

‣ Common polymorphisms in the folate pathway predict efficacy of combination regimens containing methotrexate and sulfasalazine in early rheumatoid arthritis

James, H.; Gillis, D.; Hissaria, P.; Lester, S.; Somogyi, A.; Cleland, L.; Proudman, S.
Fonte: J Rheumatol Publ Co Publicador: J Rheumatol Publ Co
Tipo: Artigo de Revista Científica
Publicado em //2008 Português
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OBJECTIVE: To study genetic polymorphisms in the folate pathway, a site of action of methotrexate (MTX) and sulfasalazine (SSZ), as predictors of efficacy of combination disease modifying antirheumatic drug (DMARD) regimens containing MTX and SSZ in early rheumatoid arthritis (RA). METHODS: Ninety-eight Caucasian patients with early RA received MTX with SSZ, hydroxychloroquine, and folate according to a standardized protocol. Efficacy was evaluated using the Disease Activity Score (DAS28) and European League Against Rheumatism response criteria at 12 months. Nine polymorphisms in 7 genes of the folate pathway were studied. RESULTS: Response to therapy was associated with SLC19A1, MTR, and TYMS polymorphisms. Two favorable allele combinations associated with responder status at 12 months were identified: the MTR 2756A allele in combination with either the SLC19A1 80A allele or the TYMS 3R-del6 haplotype (multivariate analysis, p = 0.0002, p = 0.009 respectively). Seventy of the 72 patients with these allele combinations responded compared to 12/24 patients without [odds ratio (OR) 35.0, 95% confidence interval (CI) 6.9-176, p < 0.0001]. An association with remission (DAS28 < 2.6) was also observed (OR 3.4, 95% CI 1.1-10.0, p = 0.04). When analyzed over 3 years...

‣ Sulfasalazine inhibits the growth of primary brain tumors independent of nuclear factor-κB

Chung, W. Joon; Sontheimer, Harald
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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Nuclear factor-κB (NF-κB) is a pleiotropic transcription factor that generally enhances cellular resistance to apoptotic cell death. It has been shown to be constitutively active in some cancers and is being pursued as potential anticancer target. Sulfasalazine which is used clinically to treat Crohn's disease has emerged as a potential inhibitor of NF-κB and has shown promising results in two pre-clinical studies to target primary brain tumors, gliomas. Once digested, sulfasalazine is cleaved into sulfapyridine and 5-aminosalicylic acid (5-ASA; mesalamine) by colonic bacteria, and the latter, too, is reported to suppress NF-κB activity. We now show that glioma cells obtained from patient biopsies or glioma cell lines do not show significant constitutive NF-κB activation, unless exposed to inflammatory cytokines. This does not change when gliomas are implanted into the cerebrum of severe combined immundeficient mice. Nevertheless, sulfasalazine but not its cleaved form 5-ASA caused a dose-dependent inhibition of glioma growth. This effect was entirely attributable to the inhibition of cystine uptake via the system xc− cystine–glutamate transporter. It could be mimicked by S-4-carboxy-phenylglycine (S-4-CPG) a more specific system xc− inhibitor...

‣ Development, characterization and evaluation of the dissolution profile of sulfasalazine suspensions

Costa, Mayre Aparecida Borges da; Villa, Ana Lucia Vazquez; Barros, Rita de Cássia da Silva Ascenção; Ricci-Júnior, Eduardo; Santos, Elisabete Pereira dos
Fonte: Universidade de São Paulo. Faculdade de Ciências Farmacêuticas Publicador: Universidade de São Paulo. Faculdade de Ciências Farmacêuticas
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; ; ; ; ; ; Formato: application/pdf
Publicado em 01/06/2015 Português
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This paper reports the development, characterization and;in vitro;dissolution behavior of sulfasalazine suspensions for treatment of chronic intestinal inflammatory diseases. Three formulations were developed, from powdered sulfasalazine obtained from different suppliers. The sulfasalazine was characterized regarding concentration, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), particle size distribution, polydispersion and solubility. The suspensions were developed and characterized regarding pH, viscosity, density, particle size, sedimentation volume, concentration and dissolution. The pH values were slightly acidic. The method of preparing the suspensions reduced the particle sizes and made the size distribution more homogeneous. The dissolution studies showed that the sulfasalazine suspensions had low solubility in acidic media, but dissolve quickly, reaching levels of 85%, in neutral media or media containing 0.5% of surfactants such as polysorbate 80. Besides this, the sulfasalazine suspensions were classified as having immediate dissolution because they reached dissolution levels near 100% in 20 minutes.; ;O trabalho reporta o desenvolvimento, caracterização e estudo ;in vitro; de dissolução de suspensões de sulfassalazina para uso em doenças inflamatórias crônicas intestinais. Desenvolveram-se três formulações baseadas em fornecedores diferentes de pó de sulfassalazina. A sulfassalazina foi caracterizada quanto a Teor...