Novel biologic agents that selectively target specific molecules and pathways have been developed recently for the management of inflammatory bowel disease (IBD). Anti-TNF-alpha, an antibody to TNF-alpha is one of the first newly developed drugs to dramatically improve the symptoms of patients with IBD. Therapy with anti-TNF-alpha demonstrates a new paradigm for management of IBD and early treatment with these drugs has demonstrated increased benefit. However, more than one-third of the patients have lost response to the drug. Also, there is the problem of antibody formation. Therefore, enormous efforts to develop novel drugs as an alternatives to anti-TNF-alpha are underway. Anti CD4+ T cell cytokine including IL-12/23 and IL-17 blockers, selective anti-adhesion molecules known as natalizumab, vedolizumab and alicaforsen, T-cell proliferation inhibitors, anti-inflammatory cytokines, immune stimulators, growth factors and mitogen activated protein kinase (MAPK) inhibitors are among the novel therapeutic agents that are currently being investigated for efficacy and safety in the management of IBD. The aim of this paper is to review current knowledge concerning the mechanism of action, the short and long term efficacy, and the safety of these novel biologic therapies, as well as that of anti-TNF-alpha, in IBD.
Antibodies, Monoclonal, Humanized ; Antibody Formation ; Biological Agents ; Biological Therapy ; Cytokines ; Humans ; Inflammatory Bowel Diseases ; Intercellular Signaling Peptides and Proteins ; Interleukin-17 ; Phosphorothioate Oligonucleotides ; Protein Kinases ; T-Lymphocytes ; Tumor Necrosis Factor-alpha ; Natalizumab

Inflammatory bowel disease (IBD) is a chronic progressive idiopathic inflammatory disorder that involves the digestive tract from the mouth to the anus. Over the past decades, many therapeutic strategies have been developed to manage IBD, but therapeutic strategies based only on relief of clinical symptoms have not changed the natural history of this disease entity. This underlines the importance of understanding the natural history of IBD itself. When we look at the natural history of Crohn's disease (CD), it first begins with inflammation of the intestinal mucosa and this inflammatory reaction proceeds to stenosing or penetrating reaction if not adequately controlled. However, it takes a considerable amount of time before mucosal inflammation proceeds to stenosis of the intestinal lumen or penetration into the adjacent bowel. Therefore, it can be expected that if proper care is given during that period, progression of CD to such a complicated disease could be prevented. Even though the concept of mucosal healing was introduced in the early 1990s, no correlation could be observed between healing of mucosal lesions and relief of clinical symptoms. However, the introduction of biologic agents targeting tumor necrosis factor has changed the way to treat IBD that is refractory to standard medications and has allowed us to aim for a new therapeutic goal, 'deep remission'. Further advances in biologic agents have provided highly effective treatments for IBD, making deep remission a realistic goal. Whether IBD patients may benefit by experiencing a 'deep' remission beyond the control of clinical symptoms need to be evaluated in further investigation. Nevertheless, it can be anticipated that attaining deep remission might ultimately have an impact on important outcomes such as the need for surgery and the quality of life.
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Colitis, Ulcerative/drug therapy/metabolism/pathology ; Crohn Disease/drug therapy/metabolism/pathology ; Humans ; Inflammatory Bowel Diseases/drug therapy/metabolism/*pathology ; Intestinal Mucosa/metabolism/pathology ; Mesalamine/therapeutic use ; Tumor Necrosis Factor-alpha/immunology/metabolism

No abstract available.
Capsule Endoscopy* ; Humans

BACKGROUND: Luteolin, a flavone found in various Chinese herbal medicines is known to possess anti-inflammatory properties through its ability to inhibit various proinflammatory signaling pathways including NF-kappa B and p38 MAPK. In this study, we investigated the potential therapeutic effect of luteolin on dextran sodium sulfate (DSS)-induced colitis. MATERILAS AND METHODS: We used a transgenic mouse model expressing the enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-kappa B cis-elements. C57BL/6 NF-kappa BEGFP mice received 2.5% DSS in their drinking water for six days in combination with daily luteolin administration (1mg/kg body weight, 0.1ml vol, intragastric) or vehicle. NF-kappa B activity was assessed macroscopically with a Charge-Coupled Device (CCD) camera and microscopically by confocal analysis. RESULTS: A significant increase in the Disease Activity Index (DAI), histological score (p<0.05), IL-12 p40 secretion in colonic stripe culture (p<0.05) and EGFP expression was observed in luteolin and/or DSS-treated mice compared to water-treated mice. Interestingly, a trend toward a worse colitis (DAI, IL-12p40) was observed in luteolin-treated mice compared to non-treated DSS-exposed mice. In addition, EGFP expression (NF-kappa B activity) strongly increased in the luteolin-treated mice compared to control mice. Confocal microscopy showed that EGFP positive cells were primarily lamina propria immune cells. CONCLUSIONS: These results suggest that luteolin is not a therapeutic alternative for intestinal inflammatory disorders derived for primary defects in barrier function. Thus, therapeutic intervention targeting these signaling pathways should be viewed with caution.
Animals ; Asian Continental Ancestry Group ; Body Weight ; Colitis* ; Colon ; Dextrans* ; Drinking Water ; Humans ; Interleukin-12 ; Luteolin* ; Mice ; Mice, Transgenic* ; Microscopy, Confocal ; Mucous Membrane ; NF-kappa B ; p38 Mitogen-Activated Protein Kinases ; Sodium*

Lower gastrointestinal bleeding (LGIB) is defined as acute or chronic abnormal blood loss distal to the ligament of Treitz. The incidence of LGIB is only one fifth of that of the upper gastrointestinal tract and is estimated to be 21 to 27 cases per 100,000 adults per year. Acute bleeding is arbitrarily defined as bleeding of <3 days' duration resulting in instability of vital signs, anemia, and/or need for blood transfusion. Chronic bleeding is defined as slow blood loss over a period of several days or longer presenting with symptoms of occult fecal blood, intermittent melena, or scant hematochezia. Bleeding means that the amounts of blood in the feces are too small to be seen but detectable by chemical tests. LGIB is usually chronic and stops spontaneously. Bleeding stop (80%), but male gender and older patients suffer from more severe LGIB. The optimal timing of colonoscopic intervention for LGIB remains uncertain. Urgent colonoscopy may serve to decrease hospital stay. However, urgent colonoscopy is difficult to control, and showed no evidence of improving clinical outcomes or lowering costs as compared with routine elective colonoscopy.
Adult ; Anemia ; Blood Transfusion ; Colonoscopy ; Feces ; Gastrointestinal Hemorrhage ; Hemorrhage ; Humans ; Incidence ; Length of Stay ; Ligaments ; Male ; Melena ; Upper Gastrointestinal Tract ; Vital Signs

Understanding of the pathophysiology of inflammatory bowel disease (IBD) is constantly evolving and, recently, a number of biologic agents that selectively target specific molecules or pathways to correct the imbalance of the gut immune system have been developed. Among them, an antibody to tumor necrosis factor (anti-TNF) is the first developed drug which has dramatically improved the management of patients with IBD. However, more than one-third of IBD patients do not respond to medications, and there is the problem of antibody formation. Therefore, enormous efforts have been made into the development of novel anti-cytokines and stem cell injection as an alternative to has been made. However, the efficacy and safety of stem cell treatment are under investigation. Some studies have reported very promising data; however, others have shown conflicting results. In addition, most trials involved a very small number of subjects and did not compare stem cell treatment with anti-TNF. The present paper reviews the function and therapeutic mechanism of stem cells for the treatment of IBD.
Antibody Formation ; Humans ; Immune System ; Inflammatory Bowel Diseases ; Stem Cells ; Tumor Necrosis Factor-alpha

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of unknown etiology that includes two main disease entities-ulcerative colitis and Crohn's disease. Although the pathogenesis of IBD remains unclear, it is widely accepted that genetic, environmental and immunological factors are involved. Animal models of IBD are indispensable for the understanding of the pathogenesis and novel therapeutic applications for IBD. IBD animal models can be divided into several different categories, including models of spontaneous colitis (cotton-top tamarin colitis); inducible forms of colitis (using acetic acid, dextran sulfate sodium and indomethacin); an adoptive transfer model (CD45RB(high) transfer model); genetically engineered models (with IL-10 knockout or TCR-alpha chain knockout mice). However, there is no 'perfect' model for human disease. Investigators must make judicious choices when selecting a model for a particular study. In this review, an overview of the different IBD animal models is provided and the contribution of the models to the current understanding of disease mechanisms is discussed, with the ultimate goal to develop future therapeutic trials.
Acetic Acid ; Adoptive Transfer ; Animals ; Colitis ; Crohn Disease ; Dextran Sulfate ; Disease Models, Animal ; Humans ; Immunologic Factors ; Inflammatory Bowel Diseases ; Interleukin-10 ; Models, Animal ; Research Personnel

No abstract available.
Colon ; Fluorodeoxyglucose F18

No abstract available.

Pseudomonas scleral abscess is characterized by acute onset and rapid progression to scleral perforation, and has a subsequent risk of endophthalmitis. After control of infection with appropriate antibiotics, graft surgery should be performed for reinforcing the defected sclera. We performed a scleral homograft on the eye with large necrotic sclera caused by Pseudomonas aeruginosa infection after pterygium excisIon. And the results were remarkably good.
Abscess* ; Allografts* ; Anti-Bacterial Agents ; Endophthalmitis ; Pseudomonas ; Pseudomonas aeruginosa ; Pterygium* ; Sclera ; Transplants