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‣ Antioxidant activity of 5-aminosalicylic acid against lipid peroxidation in the presence of vitamins C and E

Gonçalves, Elisabete; Almeida, Leonor M.; Dinis, Teresa C. P.
Fonte: Universidade de Coimbra Publicador: Universidade de Coimbra
Tipo: Artigo de Revista Científica Formato: aplication/PDF
Português
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It is now recognized that the antioxidant defences in the colonic mucosa from patients with inflammatory bowel disease (IBD) are particularly low. On account of this we studied the antioxidant capacity of 5-ASA, the first choice therapy in this pathological situation, in combination with the endogenous antioxidants vitamins C (ASC) and E ([alpha]-tocopherol ([alpha]-T)) against lipid peroxidation in phosphatidylcholine (PC) liposomes as a model membrane. The oxidative process was initiated by peroxyl radicals generated at different sites in liposomes by thermal decomposition of azocompounds. 5-ASA interacts additively with ASC in the protection of membranes against peroxyl radicals generated in the aqueous phase, as evaluated by the oxygen consumption or formation of conjugated dienes. HPLC analysis of 5-ASA indicates that this drug is consumed at a constant rate throughout the oxidation reaction, but in the presence of ASC there is a lag phase of its consumption, denoting that ASC affords an efficient protection to 5-ASA. On the other hand, 5-ASA and ASC cooperate, in an additive way, in the protection of [alpha]-T. When the oxidation starts within the membrane, [alpha]-T is the preferential target of peroxyl radicals, but 5-ASA and ASC also interact additively in sparing of [alpha]-T...

‣ Clinical and genetic factors predicting response to therapy in patients with Crohn’s disease

Cravo, Marília; Ferreira, Paula; Sousa, Patrícia; Moura-Santos, Paula; Velho, Sónia; Tavares, Lurdes; Deus, João Ramos; Ministro, Paula; Silva, João Pereira da; Correia, Luís; Velosa, José; Maio, Rui; Brito, Miguel
Fonte: Sage Publicador: Sage
Tipo: Artigo de Revista Científica
Publicado em /03/2014 Português
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Aim - To identify clinical and/or genetic predictors of response to several therapies in Crohn’s disease (CD) patients. Methods - We included 242 patients with CD (133 females) aged (mean ± standard deviation) 39 ± 12 years and a disease duration of 12 ± 8 years. The single-nucleotide polymorphisms (SNPs) studied were ABCB1 C3435T and G2677T/A, IL23R G1142A, C2370A, and G9T, CASP9 C93T, Fas G670A and LgC844T, and ATG16L1 A898G. Genotyping was performed with real-time PCR with Taqman probes. Results - Older patients responded better to 5-aminosalicylic acid (5-ASA) and to azathioprine (OR 1.07, p = 0.003 and OR 1.03, p = 0.01, respectively) while younger ones responded better to biologicals (OR 0.95, p = 0.06). Previous surgery negatively influenced response to 5-ASA compounds (OR 0.25, p = 0.05), but favoured response to azathioprine (OR 2.1, p = 0.04). In respect to genetic predictors, we observed that heterozygotes for ATGL16L1 SNP had a significantly higher chance of responding to corticosteroids (OR 2.51, p = 0.04), while homozygotes for Casp9 C93T SNP had a lower chance of responding both to corticosteroids and to azathioprine (OR 0.23, p = 0.03 and OR 0.08, p = 0.02,). TT carriers of ABCB1 C3435T SNP had a higher chance of responding to azathioprine (OR 2.38...

‣ IL23R polymorphisms influence phenotype and response to therapy in patients with ulcerative colitis.

Cravo, M; Ferreira, P; Sousa, P; Moura-Santos, P; Velho, S; Tavares, L; Deus, JR; Ministro, P; Peixe, P; Correia, L; Velosa, J; Maio, R; Brito, M
Fonte: Lippincott Williams And Wilkins Publicador: Lippincott Williams And Wilkins
Tipo: Artigo de Revista Científica
Publicado em //2014 Português
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38.478196%
OBJECTIVE: We aimed to identify the clinical and genetic [IL23 receptor (IL23R) single nucleotide polymorphisms (SNPs)] predictors of response to therapy in patients with ulcerative colitis. PATIENTS AND METHODS: A total of 174 patients with ulcerative colitis, 99 women and 75 men, were included. The mean age of the patients was 47±15 years and the mean disease duration was 11±9 years. The number of patients classified as responders (R) or nonresponders (NR) to several therapies was as follows: 110 R and 53 NR to mesalazine (5-ASA), 28 R and 20 NR to azathioprine (AZT), 18 R and 7 NR to infliximab. Clinical and demographic variables were recorded. A total of four SNPs were studied: IL23R G1142A, C2370A, G43045A, and G9T. Genotyping was performed by real-time PCR using Taqman probes. RESULTS: Older patients were more prone to respond to 5-ASA (P=0.004), whereas those with pancolitis were less likely to respond to such therapies (P=0.002). Patients with extraintestinal manifestations (EIMs) were less likely to respond to 5-ASA (P=0.001), AZT (P=0.03), and corticosteroids (P=0.06). Carriers of the mutant allele for IL23R SNPs had a significantly higher probability of developing EIMs (P<0.05), a higher probability of being refractory to 5-ASA (P<0.03)...

‣ Effect of polymer coating on faecal recovery of ingested 5-amino salicylic acid in patients with ulcerative colitis.

Mardini, H A; Lindsay, D C; Deighton, C M; Record, C O
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/1987 Português
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It has been suggested that polymer coating might retard jejunal absorption of 5-amino salicylic acid (5-ASA) and thus promote delivery to its colonic site of action. Twenty three patients with active (nine), or quiescent (14) ulcerative colitis were given either uncoated or coated 5-ASA (Asacol) 400 mg qds for one to three weeks, after which they ingested five 1.5 ml dialysis membrane sachets which were recovered from the stool in the next 72 hours. After one week of treatment the concentration of 5-ASA in the faecal dialysate, urine, and fasting plasma in those receiving the coated and uncoated preparations were respectively: 25.4 +/- 5.1 compared with 1.2 +/- 0.4 mmol/l (p less than 0.001); 0.34 +/- 0.21 compared with 0.70 +/- 0.29 mmol/24h (NS) and 11.1 +/- 4.2 compared with 0.07 +/- 0.03 mumol/l (p less than 0.02). Faecal excretion of the drug appeared to be greater in patients with active colitis than in those with quiescent disease. Thus coating with pH dependent methacrylic acid copolymer B is a very effective method of promoting delivery of 5-ASA to the colon, stool dialysate concentrations being 20 fold more than those in controls. Increased trough plasma concentrations in the polymer coating group probably reflect delayed intestinal absorption but no evidence of plasma accumulation after 21 days of therapy was found.

‣ Low dose balsalazide (1.5 g twice daily) and mesalazine (0.5 g three times daily) maintained remission of ulcerative colitis but high dose balsalazide (3.0 g twice daily) was superior in preventing relapses

Kruis, W; Schreiber, S; Theuer, D; Brandes, J; Schutz, E; Howaldt, S; Krakamp, B; Hamling, J; Monnikes, H; Koop, I; Stolte, M; Pallant, D; Ewald, U
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/2001 Português
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BACKGROUND—Balsalazide is a new 5-aminosalicylic acid (5-ASA) containing prodrug. Its efficacy in comparison with standard mesalazine therapy and the optimum dose for maintaining remission of ulcerative colitis are still unclear.
AIMS—To compare the relapse preventing effect and safety profile of two doses of balsalazide and a standard dose of Eudragit coated mesalazine.
METHODS—A total of 133 patients with ulcerative colitis in remission were recruited to participate in a double blind, multicentre, randomised trial: 49 patients received balsalazide 1.5 g twice daily, 40 received balsalazide 3.0 g twice daily, and 44 received mesalazine 0.5 g three times daily. Efficacy assessments were clinical activity index (CAI) and endoscopic score according to Rachmilewitz, and a histological score. In addition, laboratory tests were performed and urinary excretion of 5-ASA and its metabolite N-Ac-5-ASA was analysed. The study lasted for 26 weeks.
RESULTS—Balsalazide 3.0 g twice daily resulted in a significantly higher clinical remission rate (77.5%) than balsalazide 1.5 g twice daily (43.8%) and mesalazine 0.5 g three times daily (56.8%) (p=0.006). The respective times to relapse were 161 days, 131 days (p=0.003), and 144 days (NS). Accordingly...

‣ 5-ASA in ulcerative colitis: Improving treatment compliance

Prantera, Cosimo; Rizzi, Marina
Fonte: The WJG Press and Baishideng Publicador: The WJG Press and Baishideng
Tipo: Artigo de Revista Científica
Português
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5-aminosalicylic acid (5-ASA) compounds are a highly effective treatment for ulcerative colitis (UC). While UC patient compliance in clinical studies is over 90%, only 40% of patients in every day life take their prescribed therapy. Adherence to medication has been emphasized recently by a Cochrane meta-analysis that has suggested that future trials of 5-ASA in UC should look at patient compliance rather than drug efficacy. Better compliance can be obtained by reducing the number of tablets and times of administration. Given that the 5-ASA formulations have different delivery systems that split the active moiety in various regions of the intestine, it is particularly important that an adequate dose of the drug arrives at the inflamed part of the colon. 5-ASA Multi matrix (MMx) is a novel, high strength (1.2 g), oral formulation designed for once-daily dosing. It releases the active moiety throughout the colon. Different studies with this compound have shown that it is as effective as 5-ASA enema in the treatment of mild-to-moderate, left-sided UC, and is comparable to a pH-dependent, delayed release 5-ASA (Asacol®), even if given once daily. Recently, the effectiveness in the acute phase of UC has been confirmed also in maintenance. In conclusion...

‣ 5-ASA Dose-Response: Maximizing Efficacy and Adherence

Katz, Seymour; Lichtenstein, Gary R; Safdi, Michael A
Fonte: Millennium Medical Publishing Publicador: Millennium Medical Publishing
Tipo: Artigo de Revista Científica
Publicado em /02/2010 Português
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Mesalamine (5-aminosalicylic acid; 5-ASA) represents the cornerstone of first-line therapy for mild-to-moderate ulcerative colitis (UC). Current guidelines suggest that the combination of oral and rectal therapies provide optimal symptom resolution and effectively maintain remission in the majority of these patients. Although effective, most oral 5-ASA formulations have a high pill burden and rectal therapies are associated with low adherence. Recent research has examined patterns of compliance, as well as the efficacy of different dose levels of 5-ASA in terms of symptom resolution, the maintenance of remission, and improvements in quality of life. The ASCEND I, II, and III trials found that doses of 4.8 g/day are more effective than 2.4 g/day doses in patients with moderate disease, those with previous steroid use, and those with a history of multiple medications. The benefits of effective long-term 5-ASA therapy include the avoidance of more costly and potentially toxic drugs (such as corticosteroids and biologic therapies), as well as improvements in quality of life, reductions in the need for future colectomy, and a lower risk of developing colorectal cancer.

‣ Recent advances in the management of distal ulcerative colitis

Koutroubakis, Ioannis E
Fonte: Baishideng Publishing Group Co., Limited Publicador: Baishideng Publishing Group Co., Limited
Tipo: Artigo de Revista Científica
Português
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38.476118%
The most frequent localization of ulcerative colitis (UC) is the distal colon. In treating patients with active distal UC, efficacy and targeting of the drug to the distal colon are key priorities. Oral and rectal 5-aminosalicylic acid (5-ASA) preparations represent the first line therapy of mild-to-moderate distal UC for both induction and maintenance treatment. It has been reported that many UC patients are not adherent to therapy and that non-compliant patients had a 5-fold risk of experiencing a relapse. These findings led to the introduction of once-daily oral regimens of 5-ASA as better therapeutic options in clinical practice due to improved adherence. New formulations of mesalazine, including the multi-matrix delivery system, and mesalazine granules, which allow once-daily administration, have been developed. They have been demonstrated to be efficacious in inducing and maintaining remission in mild-to-moderate distal UC in large clinical trials. However, existing data for distal UC are rather insufficient to make a comparison between new and classical 5-ASA formulations. It seems that the new formulations are at least as effective as classical oral 5-ASA formulations. Other treatment options, in the case that 5-ASA therapy is not effective...

‣ Optimizing use of 5-ASA in the treatment of ulcerative colitis: Focus on patient compliance and adherence

Bernick, Steven J; Kane, Sunanda
Fonte: Dove Medical Press Publicador: Dove Medical Press
Tipo: Artigo de Revista Científica
Publicado em 15/06/2010 Português
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Ulcerative colitis is a chronic condition that requires long-term treatment. The first-line therapy remains 5-ASA, which is available in a variety of different formulations and dosing schedules. Multiple studies have demonstrated that adherence rates to prescribed 5-ASA products is below what would have been expected with significant consequences for important outcomes. Worse disease outcomes, higher medical costs, and even potentially higher rates of colorectal cancer have been associated with nonadherence. Nonadherence is multifactorial, fluid in nature over time, and dependent on disease activity level. Interventions to improve adherence rates have to be individualized. With the advent of simpler dosing regimens it was assumed that adherence rates would improve, but this has not necessarily been the case. Despite our current knowledge about nonadherence, it remains difficult to manage in the long term.

‣ Steroids and 5-aminosalicylic acids in moderate ulcerative colitis: addressing the dilemma

Probert, Chris
Fonte: SAGE Publications Publicador: SAGE Publications
Tipo: Artigo de Revista Científica
Publicado em /01/2013 Português
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Steroids have been a mainstay of ulcerative colitis (UC) therapy for many years, based on a thoroughly established efficacy profile for the induction of remission. However, in light of the considerable side effects and negative perceptions they carry, it is important to ensure such treatments are used as effectively as possible. For severe UC, the need for steroids is rarely questioned, and rightly so; it is for moderate UC that the role of steroids should be considered. Both patients and clinicians place a high importance on rapid, effective resolution of symptoms, yet at the same time wish to avoid unnecessary side effects. Through consideration of the available evidence, it becomes clear that both steroids and high-dose 5-aminosalicylic acid (5-ASA) are supported by robust trials demonstrating their efficacy. Indeed, both therapies have been shown to give rise to resolution of symptoms after 2 weeks in many patients. However, a paucity of head-to-head comparisons makes conclusive interpretation challenging. This paper therefore presents a practical approach, which builds on the available evidence and is developed from informed discussions with patients. This approach involves initiating therapy with high-dose 5-ASA, followed by a review of symptom improvements after 2–3 weeks. Steroids can then be introduced...

‣ The 5-aminosalicylic acid antineoplastic effect in the intestine is mediated by PPARγ

Rousseaux, Christel; El-Jamal, Noura; Fumery, Mathurin; Dubuquoy, Caroline; Romano, Olivier; Chatelain, Denis; Langlois, Audrey; Bertin, Benjamin; Buob, David; Colombel, Jean Frederic; Cortot, Antoine; Desreumaux, Pierre; Dubuquoy, Laurent
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Português
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Epidemiological evidences suggested that 5-aminosalicylic acid (5-ASA) therapy may prevent the development of colorectal cancer in inflammatory bowel disease patients. Our aim is to investigate whether peroxisome proliferator-activated receptor-γ (PPARγ) mediates the antineoplastic effects of 5-ASA. HT-29 and Caco-2 cells were treated by 5-ASA, rosiglitazone (PPARγ ligand) or etoposide (anticarcinogenic drug). Epithelial cell growth, proliferation and apoptosis were assessed by cell count, Ki-67 staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, respectively. The antineoplastic effect of 5-ASA was evaluated in a xenograft tumor model in SCID mice and in azoxymethane (AOM)-induced colon carcinogenesis in A/JOlaHsd mice. The role of PPARγ was examined by administration of PPARγ antagonist, GW9662 and in PPAR knockdown cells. Compared with untreated cells, treatment of HT-29 cells by 5-ASA inhibited significantly cell growth and cell proliferation (respectively, 60% and 63%) and induced apoptosis in 75% of cells. These effects were abolished by co-treatment with GW9662 and blunted in PPAR knockdown cells. Contrarily to etoposide, similar inhibitory effects of GW9662 were obtained in HT-29 cells treated with rosiglitazone. In the xenograft model...

‣ Medical Management of Ulcerative Colitis with a Specific Focus on 5-Aminosalicylates

Freeman, Hugh James
Fonte: Libertas Academica Publicador: Libertas Academica
Tipo: Artigo de Revista Científica
Publicado em 18/10/2012 Português
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Medical management of ulcerative colitis has continued to evolve over more than half of a century. Perhaps, the important advance was the development of sulfasalazine, a drug initially used for the treatment of inflammatory joint disease and only later in the treatment of inflammatory bowel disease. Sulfasalazine was a combination designer drug consisting of sulfapyridine, a sulfa-containing antibacterial agent, and 5-amino-salicylate (5-ASA), an anti-inflammatory agent. Its value appeared to be its ability to target a therapeutic concentration of the 5-ASA component of the medication primarily in the colon, largely avoiding proximal small intestinal absorption. With increasing experience, however, it also became evident that many patients treated with sulfasalazine developed intolerance to the drug and, in some rare instances, serious drug-induced hypersensitivity reactions, largely to the sulfapyridine portion. As a result, a number of alternative forms of delivery of 5-ASA were developed consisting of either a similar sulfasalazine-like prodrug formulation requiring luminal destruction of an azo-bond releasing the 5-ASA or a pH-dependent 5-ASA packaging system that permitted release in the distal intestine, particularly in the colon. As a result...

‣ Acute murine colitis reduces colonic 5-aminosalicylic acid metabolism by regulation of N-acetyltransferase-2

Ramírez-Alcántara, Verónica; Montrose, Marshall H.
Fonte: American Physiological Society Publicador: American Physiological Society
Tipo: Artigo de Revista Científica
Português
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Pharmacotherapy based on 5-aminosalicylic acid (5-ASA) is a preferred treatment for ulcerative colitis, but variable patient response to this therapy is observed. Inflammation can affect therapeutic outcomes by regulating the expression and activity of drug-metabolizing enzymes; its effect on 5-ASA metabolism by the colonic arylamine N-acetyltransferase (NAT) enzyme isoforms is not firmly established. We examined if inflammation affects the capacity for colonic 5-ASA metabolism and NAT enzyme expression. 5-ASA metabolism by colonic mucosal homogenates was directly measured with a novel fluorimetric rate assay. 5-ASA metabolism reported by the assay was dependent on Ac-CoA, inhibited by alternative NAT substrates (isoniazid, p-aminobenzoylglutamate), and saturable with Km (5-ASA) = 5.8 μM. A mouse model of acute dextran sulfate sodium (DSS) colitis caused pronounced inflammation in central and distal colon, and modest inflammation of proximal colon, defined by myeloperoxidase activity and histology. DSS colitis reduced capacity for 5-ASA metabolism in central and distal colon segments by 52 and 51%, respectively. Use of selective substrates of NAT isoforms to inhibit 5-ASA metabolism suggested that mNAT2 mediated 5-ASA metabolism in normal and colitis conditions. Western blot and real-time RT-PCR identified that proximal and distal mucosa had a decreased mNAT2 protein-to-mRNA ratio after DSS. In conclusion...

‣ Duration of treatment with 5-aminosalicylic acid compounds

Moshkovska, T; Mayberry, JF
Fonte: Baishideng Publishing Group Co., Limited Publicador: Baishideng Publishing Group Co., Limited
Tipo: Artigo de Revista Científica
Português
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The development of 5-aminosalicylic acid (5-ASA) therapy as a life long treatment for ulcerative colitis is reviewed from its origins in the 1940s to the present day. The drug was designed to treat rheumatoid arthritis, but was found helpful in the management of nine patients with ulcerative colitis. This discovery preceded the emergence of the clinical trial as a tool for assessing a new drug’s efficacy; as a result it lacked scientific rigour and was selective in its presentation of results. Nevertheless it identified the future cornerstone of therapy in ulcerative colitis. In 1962, the first double blind controlled trial of sulphasalazine was conducted on 40 patients. Outcome measures were subjective and included symptoms and an assessment of the rectal mucosa. In 1973, the first two papers on the role of sulphasalazine in maintenance of remission were published. Both used placebo controls and had a stratified design. Outcomes were measured using “an intention to treat” approach. The British study of 64 patients used both subjective and objective criteria to assess outcomes. Patients on placebo had a relapse rate four times patients on active treatment and this founded the basis for a life long approach to therapy with 5-ASA compounds in ulcerative colitis. However...

‣ Drug therapy for ulcerative colitis

Xu, Chang-Tai; Meng, Shu-Yong; Pan, Bo-Rong
Fonte: Baishideng Publishing Group Inc Publicador: Baishideng Publishing Group Inc
Tipo: Artigo de Revista Científica
Português
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Ulcerative colitis (UC) is an inflammatory destructive disease of the large intestine occurred usually in the rectum and lower part of the colon as well as the entire colon. Drug therapy is not the only choice for UC treatment and medical management should be as a comprehensive whole. Azulfidine, Asacol, Pentasa, Dipentum, and Rowasa all contain 5-aminosalicylic acid (5-ASA), which is the topical anti-inflammatory ingredient. Pentasa is more commonly used in treating Crohn’s ileitis because Pentasa capsules release more 5-ASA into the small intestine than Asacol tablets. Pentasa can also be used for treating mild to moderate UC. Rowasa enemas are safe and effective in treating ulcerative proctitis and proctosigmoiditis. The sulfa-free 5-ASA agents (Asacol, Pentasa, Dipentum and Rowasa) have fewer side effects than sulfa-containing Azulfidine. In UC patients with moderate to severe disease and in patients who failed to respond to 5-ASA compounds, systemic (oral) corticosteroids should be used. Systemic corticosteroids (prednisone, prednisolone, cortisone, etc.) are potent and fast-acting drugs for treating UC, Crohn’s ileitis and ileocolitis. Systemic corticosteroids are not effective in maintaining remission in patients with UC. Serious side effects can result from prolonged corticosteroid treatment. To minimize side effects...

‣ The Role of Mesalamine in the Treatment of Ulcerative Colitis

Karagozian, Raffi; Burakoff, Robert
Fonte: Dove Medical Press Publicador: Dove Medical Press
Tipo: Artigo de Revista Científica
Português
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58.392104%
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...

‣ Systematic review: does concurrent therapy with 5-ASA and immunomodulators in inflammatory bowel disease improve outcomes?

Andrews, J.; Travis, S.; Gibson, P.; Gasche, C.
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
Publicado em //2009 Português
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Background: With greater use of immunomodulators in inflammatory bowel disease (IBD), it is uncertain whether concurrent therapy with both 5-aminosalicylic acid [5-ASA, mesalazine (mesalamine)] and an immunomodulator is necessary. Aim: To determine whether concurrent therapy with both 5-ASA and immunomodulator(s) improves outcomes in IBD. Methods: Systematic review with search terms 'azathioprine, 6-mercaptopurine, thiopurine(s), 5 aminosalicylic acid, mesalazine, inflammatory bowel disease, ulcerative colitis, Crohn's disease, immunosuppressant(s), immunomodulator and methotrexate' in November 2007 to identify clinical trials on concurrent 5-ASA and immunomodulator therapy. Results: Two small controlled studies were found. Neither showed a benefit on disease control beyond immunomodulator monotherapy. Potential pharmacological interactions exist between 5-ASA and thiopurines. Whilst circumstantial, epidemiological and laboratory evidence suggests that 5-ASA may assist colorectal cancer (CRC) chemoprevention, it may simply be via anti-inflammatory effects. With changes in practice, ethical issues and the long lead-time needed to demonstrate or disprove an effect, no clinical studies can/will directly answer this. The costs of avoiding one CRC in IBD may be as low as 153 times the annual cost of 5-ASA therapy. Conclusions: It is unclear whether concurrent 5-ASA and immunomodulator therapy improves outcomes of disease control...

‣ Refractory Ulcerative Colitis Treatment

MacDermott, Richard P.; Green, Jesse A.
Fonte: Millennium Medical Publishing Publicador: Millennium Medical Publishing
Tipo: Artigo de Revista Científica
Publicado em /01/2007 Português
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Treatment of refractory ulcerative colitis (UC) is a common clinical challenge. In either acute or chronic refractory UC, the disease may continue to remain active, even though the patient is on appropriate therapy. It is important to reassess and characterize the patient's disease before adding new medications to the current medical regimen. After determining the current extent and severity of the UC—ruling out other causes of bloody diarrhea and determining what complications are present—new treatment approaches can then be started. It is critical to first optimize oral 5-aminosalicylic acid (5-ASA) therapy combined with rectal 5-ASA or corticosteroid suppositories, plus corticosteroid or 5-ASA enemas or foam preparations. Oral or intravenous corticosteroids are appropriate to use if needed, but alternative approaches must be used for long-term maintenance. 6-Mercaptopurine (6-MP) or azathioprine can be very helpful for severe chronic refractory UC. In those patients who do not respond to 5-ASA medications, corticosteroids, and 6-MP or azathioprine, infliximab offers an important approach for induction and maintenance of remission for refractory chronic ulcerative colitis as well as for select cases of refractory acute UC. Cyclosporine use is an alternative medical approach for the refractory acute UC patient. Colectomy with ileal pouch-anal anastomosis remains a valuable option for the refractory chronic or acute UC patient...

‣ Searching for the Delta: 5-Aminosalicylic Acid Therapy for Crohn's Disease

Levesque, Barrett G.; Kane, Sunanda V.
Fonte: Millennium Medical Publishing Publicador: Millennium Medical Publishing
Tipo: Artigo de Revista Científica
Publicado em /05/2011 Português
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Crohn's disease (CD) is a chronic inflammatory condition that often requires lifelong medical therapy for the induction and maintenance of remission. Oral mesalamine (5-aminosalicylic acid [5-ASA]) therapy has several forms, which can be categorized into oral formulations and prodrugs. The ability to demonstrate the efficacy of 5-ASA is limited in most clinical trials by the nonspecific endpoints of the Crohn's Disease Activity Index. Overall, clinical trials have not shown 5-ASA therapy to be superior to placebo for the induction of remission, with the exception of sulfasalazine in colonic CD. 5-ASA therapy has also not been shown to be superior to placebo for maintenance of medically induced remission; however, mesalamine may have a modest effect in surgically induced remission. Further research is needed regarding the optimal monitoring and therapy for patients with mild CD who often achieve remission with placebo in clinical trials.

‣ Addition of Berberine to 5-Aminosalicylic Acid for Treatment of Dextran Sulfate Sodium-Induced Chronic Colitis in C57BL/6 Mice

Li, Yan-hong; Zhang, Man; Xiao, Hai-tao; Fu, Hai-bo; Ho, Alan; Lin, Cheng-yuan; Huang, Yu; Lin, Ge; Bian, Zhao-xiang
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 07/12/2015 Português
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Ulcerative colitis (UC) is a common chronic remitting disease but without satisfactory treatment. Alternative medicine berberine has received massive attention for its potential in UC treatment. Conventional therapies with the addition of berberine are becoming attractive as novel therapies in UC. In the present study, we investigated the preclinical activity of a conventional oral 5-aminosalicylic acid (5-ASA) therapy plus berberine in experimental colitis. A subclinical dose of 5-ASA (200 mg/kg/day) alone or 5-ASA plus berberine (20 mg/kg/day) was orally administered for 30 days to C57BL/6 mice with colitis induced by three cycles of 2% dextran sulfate sodium (DSS). The disease severity, inflammatory responses, drug accumulation and potential toxicity of colitis mice were examined. The results showed that comparing to 5-ASA alone, 5-ASA plus berberine more potently ameliorated DSS-induced disease severity, colon shortening, and colon histological injury. Further, the up-regulation in mRNA level of colonic TNF-α as well as NFκB and JAK2 phosphorylation caused by DSS were more pronouncedly reversed in animals treated with the combination therapy than those treated with 5-ASA alone. Moreover, the addition of berberine to 5-ASA more significantly inhibited lymphocyte TNF-α secretion of DSS mice than 5-ASA alone. In the meanwhile...