Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD and UC represent a spectrum of chronic IBD that present in protean ways and are accompanied by a variety of systemic sequelae. Sulfasalazine and the newer 5-aminosalicylates are important in the management of mild-to-moderate disease, whereas corticosteroids remain the primary therapy for most patients with moderate-to-severe disease (Tables 2-5). The toxicities associated with long-term steroid therapy, combined with their ineffectiveness as maintenance medications, have led to increased use of immunomodulators, such as azathioprine and 6-MP, for the treatment of steroid-dependent and steroid-resistant IBD. Infliximab is a novel therapeutic adjunct for chronically active and fistulizing CD that will herald a new era of biologic therapy for IBD. Meanwhile, CSA remains an alternative to urgent colectomy in severe UC unresponsive to corticosteroids and also for CD patients with severe disease or refractory fistulas. Finally, continued insights into the etiopathogenic pathways in IBD will provide evolving and innovative approaches until the eventual causes and cures are elucidated. In the meantime, clinicians should remain optimistic regarding current ability to reduce the morbidity and maintain the quality of life for patients suffering with these frustrating diseases.
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PMID:Medical therapy for inflammatory bowel disease. 1037 70

Infliximab, the chimeric monoclonal immunoglobulin (Ig)G1 antibody to tumor necrosis factor (TNF) has changed our therapy of Crohn's disease. Infliximab is indicated in refractory luminal and fistulizing Crohn's disease. In patients with luminal disease, a single intravenous (i.v.) dose of 5 mg/kg is efficacious; in fistulizing disease, an i.v. loading therapy of 5 mg/kg at weeks 0, 2, and 6 is advocated. Because the majority of patients will relapse if not re-treated, a long-term strategy is necessary. The optimal long-term approach is systematic re-treatment with 5 mg/kg every 8 weeks. Episodic therapy on relapse also is possible but is less efficacious and frequently is associated with problems resulting from the formation of antibodies to infliximab (ATI). If treatment is episodic, maintenance therapy with immunosuppression (azathioprine [AZA]/6-mercaptopurine [6-MP] or methotrexate) is mandatory. Trial data suggest that systematic maintenance with 8 weekly doses of infliximab decreases the rate of complications, hospitalizations, and surgeries. These effects probably are achieved thanks to thorough healing of the bowel. Infliximab also is indicated in treating corticosteroid-dependent Crohn's disease and extraintestinal manifestations of Crohn's disease. There are no data yet that support its use as first-line therapy. The data in ulcerative colitis (UC) are conflicting and we should await the results of 2 large controlled trials (ACT1 and ACT2) to position infliximab in the treatment of UC. Other anti-TNF strategies have been less effective than infliximab in the treatment of IBD until now. The results with thalidomide are promising but much more research into small molecules inhibiting TNF and other proinflammatory cytokines is necessary. Safety problems with antibody treatment mainly concern immunogenicity leading to infusion reactions, loss of response, and serum sickness-like delayed infusion reactions. The rate of opportunistic infections is increased mainly in patients treated concomitantly with immunosuppression. Other adverse events associated with anti-TNF strategies are demyelinating disease and worsening of congestive heart failure. Malignancy rates in patients treated with anti-TNF strategies do not seem to be increased.
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PMID:Optimizing anti-TNF treatment in inflammatory bowel disease. 1516 70

Conventional therapy for inflammatory bowel diseases rely on corticosteroids and 5-aminosalicylates combined with immunosuppressive agents for maintenance. These drugs are not always effective and may inflict serious side effects. Other therapies are therefore awaited. Infliximab, a monoclonal antibody against the pro-inflammatory cytokine TNF-alpha has been successfully applied as a treatment for Crohn's disease. The mechanism of action of this drug extends beyond the level of TNF-alpha scavenging and includes induction of apoptosis of effector cells. Numerous anti-TNF antibodies have been developed and are currently evaluated in clinical trials. Other targets for monoclonal antibodies include integrins and cytokines involved in T-cell differentiation and activation. Likewise recombinant proteins that moderate TNF bioactivity and lymphocyte function have been developed. The therapeutic effect of recombinant interleukin-10 seems to be dependent on local delivery of the protein. Antisense therapy targeting lymphocyte migration has also been tested in IBD. Finally, the conventional drug thalidomide and possibly MAP-kinase inhibitors may become novel treatment entities for IBD.
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PMID:New cytokine therapeutics for inflammatory bowel disease. 1558 91

The conventional medical treatment of IBD consists of aminosalicylates, corticosteroids, immunosuppressive drugs (azathioprine, 6-mercaptopurin, methotrexate, cyclosporin) and antibiotics. The only drugs able to modify the disease course are azathioprine, its metabolite 6-mercaptopurin and methotrexate. However, these drugs have a slow onset of action and are associated with important side-effects in some patients, necessitating the discontinuation of the drug. Moreover, up to 60% of patients do not respond to these drugs long-term. Fortunately, the management of IBD has entered a new era in the beginning of the 1990s with the development of new biological therapies, selectively blocking the inflammatory cascade. The novel molecules have arisen from the increasing knowledge about the disease pathogenesis and their production has been precipitated by the techniques of molecular biology. Infliximab, the first available biological for Crohn's disease has certainly revolutionised standard treatment. Because of its profound clinical, endoscopic and histological effects, the standard step up approach in the treatment of IBD has been challenged. A large array of new rationally designed biologicals, with a better safety profile and equally selectively acting is underway, and is likely to change our current practise even more dramatically in the next decade.
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PMID:Management of ulcerative colitis and Crohn's disease. 1564 2

The better understanding of the mechanisms of inflammatory bowel disease has driven our progress into the development of new biological therapies targeting specific molecules. Anti-TNF-alpha biologic compounds have shown great efficacy particularly in Crohn's disease. Infliximab (an IgG1 mouse/human chimeric monoclonal anti-TNF-alpha antibody fragment) is the most efficacious compound in induction and maintenance therapy of active and fistulizing Crohn's disease, being at present the only biological compound approved for therapy, but with the limit of the immunogenicity; CDP-571 (a humanized anti-TNF-alpha antibody) and CDP-870 (a PEGylated anti-TNF-alpha antibody) are less immunogenic, showed some efficacy in induction therapy in Crohn's disease but a rapid loss of response in maintenance therapy. Etanercept and onercept (soluble human recombinant TNF-alpha receptors fusion proteins) seem not to be efficacious in Crohn's disease demonstrating no class-effect for anti-TNF-alpha compounds. In preliminary study, adalimumab (an IgG1 humanized monoclonal anti-TNF-alpha antibody) offers good perspective of efficacy and safety also in infliximab-resistant or allergic patients. Inhibition of lymphocyte trafficking to the gut, through anti-adhesion molecules specific therapies (natalizumab, MLN-02, alicaforsen), has shown promising results: unfortunately, natalizumab, the most effective drug of this class, has recently been suspected to favour serious neurological complications. Other biologic therapies are under evaluation but at present seem to be less promising than infliximab; they consist of antiinflammatory cytokines, inhibitors of proinflammatory cytokines, hormones and growth factors: anti-IL12-antibody, interferon-alpha, interferon-beta, G-CSF, GM-CSF, EGF, growth hormone, anti-interferon-gamma, anti-IL-18, anti-IL-2-receptor and anti-CD3 antibodies. The evaluation of other biological drugs has been suspended for severe side effects as happened for anti-CD40L antibody causing thromboembolism and anti-CD4 antibody causing ly.mphopenia. Other compounds as IL-10 and IL-11 have been proven to be ineffective even if an oral formulation of IL-11 is under evaluation. Among the MAP kinases inhibitors BIRB-796 and RDP58 showed to be ineffective while CNI-1493 is under evaluation. The effort in identifying specific patients features predicting therapy response and the possible combination of different biological therapies represent undoubtedly a very promising perspective. Aim of this article is to review the biological compounds and their efficacy in IBD.
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PMID:Biological therapies for inflammatory bowel disease: research drives clinics. 1684 27

Current treatment of inflammatory bowel disease is rather effective through it is only working in symptomatic fashion. Most recombinant "biologicals" have not been an overwhelming success. Infliximab has shown clinically relevant efficacy and is used in patients not responding to the standards. Alternatives such as modulating the bacterial-epithelial interaction, tightening of the mucosal barrier and maybe even immunostimulation should be studied since most recent finding on etiology and pathophysiology point to a disturbed barrier with consequent abnormal bacterial epithelial interaction as the main problem in the IBD syndrome. We still need to learn much but we should not focus only on immunosuppressive systems.
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PMID:Inflammatory bowel disease: Pandora's box, present and future. 1705 17

The introduction of infliximab into clinical practice is one of the most significant advances in the care of patients who have IBD. Infliximab has become an important part of the medical armamentarium to treat extraintestinal manifestations that often are refractory to other medications and are a significant cause of morbidity in these patients. Two other TNF inhibitors recently have demonstrated efficacy in CD: certolizumab pegol and adalimumab. The Food and Drug Administration has approved adalimumab for use in RA. One predicts that these agents also may have activity in the extraintestinal manifestation for IBD. To determine whether future biologics are effective in the EIM of IBD, one may need to look no further than the vast clinical trial experience in primary chronic inflammatory diseases of the joints and skin: RA and psoriasis. For example, the Food and DRug Administration recently has approved an anti-B-cell therapy, rituximab, and a T-cell costimulation modulator, abatacept, for use in RA. It certainly will be of interest to determine whether these biologic agents demonstrate efficacy in the intestinal and EIM of IBD.
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PMID:Treatment of immune-mediated extraintestinal manifestations of inflammatory bowel disease with infliximab. 1712 19

Infliximab, the monoclonal anti-tumor necrosis factor-alpha (TNF-alpha) antibodies preparation, is efficacious in the treatment of inflammatory bowel diseases. However, the optimal therapeutic approach is still under investigation. Reports on side effects and potential complications of infliximab therapy, as well as of other anti-TNF-alpha blocking agents are accumulating. Hence, the Israeli Gastroenterological Association had initiated a conference in order to discuss the frequent clinical issues that have arisen following the use of infliximab for the treatment of inflammatory bowel diseases. The aim was to report on the published clinical experience and problems regarding several practical aspects of the use of Infliximab, to suggest guidelines that are evidence-based and to discuss them with experienced IBD-oriented gastroenterologists. The subjects that were discussed include: (1) treatment protocols; (2) maintenance therapy in Crohn's disease; (3) prevention of infections and (4) therapeutic potential in ulcerative colitis. These topics reflect everyday issues that gastroenterologists deal with while treating inflammatory bowel disease patients. The manuscript summarizes the literature and evidence that were presented in the conference, the points raised at the discussions as well as guidelines suggested by work groups that were established for each subject. These guidelines may assist and direct the gastroenterologist treating inflammatory bowel disease patients with infliximab.
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PMID:[Infliximab in inflammatory bowel diseases--conference summary and suggested guidelines]. 1718 61

The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) plays a central role in mucosal inflammation and is a key mediator in the inflammatory cascade in both Crohn's disease (CD) and ulcerative colitis (UC). Infliximab, a monoclonal antibody against TNF-alpha has been proved highly effective in the clinical management of both forms of IBD. Aim of this paper is to review the mechanisms of action of infliximab in IBD.
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PMID:Mechanisms of action of infliximab in inflammatory bowel disease: an anti-inflammatory multitasker. 1859 93

IBDs (inflammatory bowel diseases) are lifelong manifestations that significantly impair the quality of life of those who suffer from them. Although many therapies are now available, including immunomodulatory drugs such as Infliximab which have efficacy in IBD, not all patients respond and some patients generate autoantibodies against these drugs. Hence the search for novel treatments is ongoing. HDACs (histone deacetylases) are responsible for condensation of chromatin in the nucleus of cells and inhibition of gene transcription and are often dysregulated during cancer. HDAC inhibitors allow normal gene transcription to be restored and provide attractive therapeutic options, as they have been shown to be anti-inflammatory and anti-proliferative in cancer. Indeed, two HDAC inhibitors have been recently approved for the treatment of cutaneous T-cell lymphoma in the U.S.A. Recent research using animal models has shown that HDAC inhibitors may have a beneficial effect in colitis by boosting levels of Foxp3+ (forkhead box P3+) T-regulatory cells that dampen inflammation. In the present paper, we outline the background to IBD, HDACs and their inhibitors as well as discussing their current use in models of IBD.
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PMID:Histone deacetylase inhibitors and their potential role in inflammatory bowel diseases. 2178 54


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