Foods to help if you have Crohns Disease

Cured My Crohns

If you've ever gotten the fateful diagnosis you've got Crohns, you will know the massive upset that it can have on your way of life and how you feel about yourself and your relationship to other people. If you talk to your doctor about natural diets or some other method of curing your Crohns disease they will tell you that there is no way to fix it. However, there is often more to the story than modern medicine will tell you. New Age medicine is not a bunch of nonsense that hokey people subscribe to; New Age medicine fills in the gaps of knowledge that we have with modern medicine and helps us understand what is going on with our bodies. You will learn how to cure Crohns from someone who has cured it himself and has lived for over 10 years completely free of disease!

Cured My Crohns Summary

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Author: Alec Herring
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My Cured My Crohns Review

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All of the information that the author discovered has been compiled into a downloadable pdf so that purchasers of Cured My Crohns can begin putting the methods it teaches to use as soon as possible.

When compared to other e-books and paper publications I have read, I consider this to be the bible for this topic. Get this and you will never regret the decision.

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No More Crohn's Disease

No More Crohn's Disease is a product of Cathy Rubert's personal research and many years of trial and error. This book reveals Cathys powerful 4-step plan against Chron's disease. You will learn about these 4 main natural steps that will immediately get rid of the pain in your lower abdomen. You will learn the single cheap ingredient that will bring your body's digestive system back in balance. This ingredient has the power to eliminate your pain in just days, no matter how bad your condition is. You too can start living a life free from Chrons disease with the help of her book. More here...

No More Crohns Disease Summary

Contents: EBook
Author: Cathy Rubert
Official Website: livecrohnsfree.com
Price: $29.95

Pharmacokinetics in Crohns Disease

Patients with active Crohn's disease were originally randomized to receive placebo or a single infusion of 5, 10 or 20 mg kg infliximab. If they did not show a response by week 4, they received an additional dose of 10 g ml infliximab. Eight weeks later responders were eligible to enter an extension study where they were randomized to either placebo or 10-mg kg infusions of infliximab. Patients were retreated every 8 weeks and evaluated at week 40. In another study in Crohn's disease patients, again dose-dependent serum concentrations were observed in Crohn's disease patients after single infusions of 5,10 or 20 mg kg infliximab. At the recommended 5-mg kg dose, the maximal serum concentration was 118 g ml and the median half-life 9.5 days. In this study at week 12 no antibody levels were detected in the serum after the 5-mg kg infusion (Cornillie et al. 2001).

Inflammatory Bowel Disease Ulcerative Colitis and Crohns Disease

There are two major forms of chronic inflammatory bowel disease (IBD). Ulcerative colitis is an ulcerative disorder of the mucosa of the colon, whereas Crohn's disease is characterized by transmural inflammation, most often in the small intestine. Both produce abdominal pain and diarrhea, which can be bloody. iBd tends to wax and wane, with periods of intense active disease followed by long periods of remission. Although the cause is not clear, IBD appears to be an autoimmune reaction, in which overzealous immune cells attack the tissues of the intestinal wall. for hospital care and intestinal surgery. Food sensitivities may aggravate IBD, and identification and avoidance of offending foods may increase chances of remission.14 During acute exacerbations of Crohn's disease, enteral nutrition with protein hydrolysate diets is effective and reduces need for steroid therapy.15

Biologics in Crohns Disease and Ulcerative Colitis Focus on Tumor Necrosis Factor Antagonists

Elucidation of the cellular and molecular mediators of tissue injury in Crohn's disease (CD) and ulcerative colitis (UC) has expanded the potential management options for these diseases. The discovery of immunologic and inflammatory mediators, in particular, has paved the way for clinical research with biologic agents in this area. Although conventional treatments remain viable options for some patients, those who are intolerant to these agents and those with more serious or refractory disease may require newer biologic therapies.

Clinical Features of Crohns Disease

Crohn's disease is a disease of flares and remissions, although 10-20 of patients have refractory, chronically active, or steroid-dependent disease (Rutgeerts 2002) (Fig. 12.1). It is characterized by chronic transmural inflammation that may affect any part of the gastrointestinal tract. In approximately one-third of patients, CD is confined to the small intestine, whereas 40-50 of patients will have involvement of both the small intestine and the colon. Twenty to 30 of patients have only colonic involvement. When disease is restricted to the colon, it can be difficult to differentiate between CD and UC. This type of disease is referred to as indeterminate colitis and is seen in approximately 5 of patients with CD. Symptoms include abdominal pain and tenderness, chronic and nocturnal diarrhea, rectal bleeding, weight loss, and fever (Hanauer and Present 2003). CD evolves over time from a primarily inflammatory disease into one of two clinical patterns -stricturing (obstructive) or...

Pathogenesis of Crohns Disease

Crohn Disease

Crohn's Disease Crohn's Disease Fig. 12.1. a Anatomic distribution of Crohn's disease. b Comparison ofthe appearance of normal and Crohn's mucosa gross (top) histologic (center) endoscopic (bottom). (Reprinted with permission from Bayless et al. 2006) Fig. 12.2. Treatment algorithm of therapeutic options for Crohn's disease. 5-ASA 5-aminosalicylate, IL interleukin, IV intravenous. (Reprinted with permission from Bayless et al. 2006) Fig. 12.2. Treatment algorithm of therapeutic options for Crohn's disease. 5-ASA 5-aminosalicylate, IL interleukin, IV intravenous. (Reprinted with permission from Bayless et al. 2006) Fig. 12.3. Immunopathogenesis of Crohn's disease. (Reprinted with permission from Bayless et al. 2006) Fig. 12.3. Immunopathogenesis of Crohn's disease. (Reprinted with permission from Bayless et al. 2006)

Biologics for Use in Crohns Disease

Evolving and approved biologics for Crohn's disease and ulcera-tive colitis Table 12.1. Evolving and approved biologics for Crohn's disease and ulcera-tive colitis a Approved for use by the US Food and Drug Administration and the European Agency for the Evaluation of Medical Products for the treatment of Crohn's disease and ulcerative colitis CD Crohn's disease, EGF epidermal growth factor, EGF-R epidermal growth factor receptor, GM-CSF granulocyte-macrophage colony-stimulating factor, GM-CSF-R granulocyte-macrophage colony-stimulating factor receptor, hGH-R human growth hormone receptor, IFN interferon, IL interleukin, TNF tumor necrosis factor, UC ulcerative colitis Table 12.2. Summary of clinical data for each biologic in Crohn's disease Table 12.2. Summary of clinical data for each biologic in Crohn's disease ACCENT A Crohn's Disease Clinical Trial Evaluating Infliximab in a New Long-term Treatment Regimen, CDAI Crohn's Disease Activity Index, CHARM Crohn's Trial of...

Crohns Disease

TNF is recognized as an important cytokine in the pathogenesis of Crohn's disease, and is elevated in the stool, mucosa, and blood of patients with Crohn's disease (Braegger et al. 1992 Murch et al. 1991, 1993 Papadakis et al. 2000). CLASSIC-I (Clinical Assessment of Adalimumab Safety and Efficacy Studied as Induction Therapy in Crohn's Disease), a randomized, double-blind, placebo-controlled, multicenter dose-ranging study, evaluated the efficacy of adalimumab induction therapy in 299 patients with this disease. Patients with moderate to severe Crohn's disease who were nai've to anti-TNF therapy received induction treatment at Weeks 0 and 2 with adalimumab 40 mg 20 mg, 80 mg 40 mg, or 160 mg 80 mg or placebo and were followed for 4 weeks. Statistically significant rates of clinical remission (CDAI 70 or 100 points from baseline, respectively) were achieved by adalimumab-treated patients at Week 4. The optimal induction dosing regimen in this study was 160 mg at Week 0 followed by 80...

Other Mechanisms of Infliximab Activity

Binding and neutralization of soluble TNF-a is probably not the only activity mediated by infliximab. Indeed, in vitro assays have shown that infliximab also binds to membrane-bound TNF- and induces cell death (Scallon et al. 1995). However, clinical observations suggest that infliximab mediated cytotoxicity in vivo is limited. Infliximab infusions are very well tolerated and patients do not experience a cell lysis syndrome (Scallon et al. 1995). Similarly, the number of circulating mononuclear cells does not decrease following infliximab infusions. In contrast, programmed cell death (apoptosis) has been observed in Crohn's patients treated with infliximab within 24 h of a single infusion. In these patients a significant increase in the number of apoptotic T cells was noted in the lamina propria. Interestingly, infliximab dependent apoptosis of T cells appears to be restricted to activated T cells since in an in vitro experiment infliximab only lysed activated, but not resting, Jurkat...

Antibody Formation Against Infliximab

A significantly higher incidence of antibodies to infliximab was detected in Crohn's patients who received episodic treatment, i.e., they received one dose of infliximab at the beginning of the trial, but then only placebo until week 14 or later until the disease worsened. While 30 of patients on this treatment schedule developed HACA, only 8 of patients who received infliximab infusions every 8 weeks developed HACA. In addition, the incidence of HACA was higher in patients who did not receive immunomodulators compared to those who did (18 vs 10 , p 0.02) (Hanauer et al. 2004).

Inflammatory Bowel Disease

Thirty-five patients (17 women and 18 men) with inflammatory bowel disease (IBD) were followed prospectively for 19 months with BMD measurements at the PA lumbar spine and proximal femur with DXA (Hologic QDR-1000) (58). Fourteen patients had Crohn's disease and 21 had ulcerative colitis. They ranged in age from 17 to 60 years with a mean age of 36 years. Crohn's disease patients lost 3.08 4.91 per year in the lumbar spine and 6.91 6.57 per year in the femoral neck. Ulcerative colitis patients without ileoanal anastomosis lost 6.42 7.5 per year in the lumbar spine and 5.59 11.12 per year in the femoral neck. No ulcerative colitis patient with ileoanal anastomosis had a significant bone loss from either site. Patients on steroids had mean bone loss of 6.23 7.04 per year in the spine and 8.97 9.57 per year in the femoral neck. Patients not on steroids had gains of 0.87 0.002 per year in the spine and 0.20 5.78 per year in the femoral neck. In another study of 79 patients with IBD (34...

Selective Adhesion Molecule Inhibitors

In Crohn's disease, an organ-specific autoimmune disease in which the immune system attacks the intestinal mucosa, the therapeutic target of natalizumab is a4 7 integrin, which, like a4pl integrin, is recognized by a4 integrin-specific antibodies. This integrin has multiple functions, including mediating migration of gut-homing T cells via its counter-receptor in the gut, MadCAM. Early in 2005, all dosing of natalizumab was voluntarily suspended by the sponsor after learning of two cases of progressive multifocal leukoencephalopathy (PML) in MS patients receiving natalizumab and IFN-P combination therapy a third case of PML was subsequently discovered in a patient with Crohn's disease receiving natalizumab following extensive therapy with various immunosuppressive medications. One of the two MS patients recovered however, the other two cases proved fatal. Following an exhaustive safety review, the US FDA approved the use of natalizumab in open-label monotherapy clinical trials. The...

Central Role of TNFa in Inflammation

Proteinases and the release of pro-inflammatory cytokines (IL-1, IL-6, IL-8, GM-CSF). TNF-a-conveyed induction of pro-inflammatory cytokines, leukocyte chemotaxis and angiogenesis possibly play a fundamental role in autoimmune diseases of the skin, presumably diseases which are characterized by elevated TNF- serum concentrations, fever and an increase of acute phase proteins. Elevated serum levels of TNF-are detectable in many autoimmune diseases including RA, psoriasis and Crohn's disease.

Protein Energy Malnutrition

The main cause of protein-energy malnutrition in Crohn's disease patients is anorexia, probably resulting from postprandial abdominal pain, diarrhoea, dietary restriction, and the side effects of medications 5,6 . In addition, animal studies have shown that anorexia can result from increased levels of tumour necrosis factor (TNF)-a, interleukin (IL)-1, and other cytokines 7, 8 . These weight-loss-inducing cytokines increase the expression of leptin mRNA in adipose tissue as well as plasma Table 1. Nutritional problems of patients with Crohn's disease. (Data from 9 ) levels of leptin, despite the decrease in food intake that normally suppresses leptin expression 1011 . Thus, leptin may also be involved in anorexia accompanying Crohn's disease. In contrast, Lanfranchi and Geerling showed that energy intake was not decreased, but tended to increase in patients with Crohn's disease in the stage of remission or low activity 13, 14 . These results suggest that the amount of dietary intake...

Calcium and Vitamin D

Osteoporosis is increasingly being recognised as a leading extra-intestinal complication of inflammatory bowel disease. Calcium is absorbed in the proximal small intestine by a vitamin D-depend-ent Ca2+-binding protein, and vitamin D is absorbed in the duodenum and jejunum. Therefore, in Crohn's disease patients with extended inflammation or resection of the small intestine, osteoporosis results from impaired absorption of calcium and vitamin D. However, there are also some conflicting data suggesting that many factors, other than calcium or vitamin D deficiency, contribute to the pathogenesis of osteoporosis in Crohn's disease 23, 24 . These factors include cytokines, such as TNF-a, that disproportionately stimulate osteoclast activity, or corticosteroid usage 25, 26 . Overt vitamin D deficiency disease may occur in Crohn's disease patients and patients often present with bone pain and mild myopathy. Other symptoms at presentation include bone pain and mild myopathy.

Is Hyperalgesia Limited to the Gut in Irritable Bowel Syndrome

The first studies to investigate visceral sensitivity in IBS concluded that enhanced sensitivity in IBS was limited to the gut (43-46). Interestingly, two prior studies have examined cutaneous pain in IBS patients using electrocutaneous stimulation (43,44). In one study, 13 patients with Crohn's disease, 13 control subjects, and 12 patients with IBS had electrodes positioned on the skin of their hands (44). Touch threshold, defined as the current just detectable by the subject, and pain threshold, defined as the current at which the subject first described the stimulus as painful, were significantly higher in both IBS and Crohn's disease, compared to normal subjects. A later study compared somatic transcutaneous electrical nerve stimulation in 17 patients with IBS and 15 healthy controls (43). The perception threshold and threshold for discomfort were both higher in the IBS subjects than controls. A possible limitation common to both studies is that the thresholds for perception and...

Gastrointestinal and Respiratory Epithelium

Stomach and the intestines have a non-stratified epithelium rapidly renewed from the bottom of the intestinal crypts or glands. Like many other simple epithelia, these epithelial cells do not show hyaluronan except for a little in the basolateral surfaces of some cells at the bottom of the crypts (Fig. 3d) (34). However, the enterocytes become positive for hyaluronan and CD44 in the immunological injury caused by Crohn's disease and celiac disease (Kemppainen et al., unpublished data). Introduction of allergens increases hyaluronan in the gut lumen (35). Likewise, transformation of the colon epithelial cells is frequently accompanied by the expression of hyaluronan, while normal colon epithelium is virtually hyaluronan free (Fig. 3g and h) (23). In colon cancer cells, the level of hyaluronan is a strong, unfavorable prognostic indicator of the patient survival (36). The emergence of hyaluronan expression on gastric cancer cells (Fig. 3e) shows a similar negative correlation with the...

The Role Of The Immune System In Promoting Tumor Growth

Although much of the emphasis in tumor immunology has been on the role of the immune system in eradicating tumors, it is clear that the immune system may also contribute to the development of some solid tumors. In fact, chronic inflammation has long been recognized as a risk factor for development of tumors in many different tissues, especially those affected by chronic inflammatory diseases such as Barrett's esophagus, Crohn's disease, pancreatitis, and prostatitis, for example. Some cancers associated with infections are also considered to be an indirect result of the carcinogenic effects of the chronic inflammatory states that are induced by the infectious organisms. These include gastric cancer in the setting of chronic Helicobacter pylori infection and hepatocellular carcinomas associated with chronic hepatitis B and C virus infections. Although the mechanisms by which chronic inflammation can promote tumor development are not well understood, there are several possibilities,...

Experimental Disease Models

The Mdr1a mouse model is one of the few genetic disease models that develop a colitic phenotype in the absence of immune dysfunction. This is in contrast to virtually all other genetically targeted mice, which develop colitis as a result of either impaired immune function, a cytokine imbalance, or colitis that can be induced by reconstituting naive (CD4 + CD45Rbhi) T cells into severe combined immunodeficiency (SCID) mice. Most of the experimental models of IBD in mice have inflammation only in the colon and resemble UC. The one striking exception to this is the SAMP1 Yit mouse and the derivative SAMP1 YitFc strain. These mice spontaneously develop a Crohn's-like transmural ileitis as early as 10 weeks of age, accompanied by prominent muscular hypertrophy, fibrosis, and activation of mesenteric lymph node lymphocytes, which produce high levels of interferon g (IFN-g). Furthermore, a subgroup of SAMP1 YitFc mice ( 5 ) also develops perianal fistulating disease.

Assessing Disease Activity

In CD, the use of the Crohn's disease activity index (CDAI) predominates. This index is constructed from eight domains that are given a relative weighting, and involves the collection of patient data through the use of a diary. Disease severity bands have been constructed within a scale of 0-750. Disease remission has been attributed to a score of less than 150 and clinical improvement defined as a reduction of greater than 70 points (or more recently 100 points), although the clinical significance of such a reduction in patients with severe disease is questionable. Used widely in clinical trials, criticisms still abound on the use of CDAI. These include the near reliance on subjective symptoms, the complexity of the index, and the need for a 1-week patient diary. Studies have also demonstrated substantial interobserver variation in scoring. The poor representation of parameters relating to perianal disease makes improvements in this troublesome presentation difficult to assess using...

Potential Risks of AntiTNFa Therapy

Infliximab is a chimeric (human-murine) IgGlK monoclonal antibody with an approximate molecular weight of 149100 daltons, in the pharmacological class of selective immunosuppressive agents. It is composed of human-constant and murine-vari-able regions and binds specifically to human TNF-a with an association constant of 10-10 M (Fig. 1). Infliximab has a well-documented safety profile throughout clinical development and in post-marketing safety surveillance for the approved indications of Crohn's disease and RA 62-65 . The FDA reported on the risks of histoplasmo-sis 71 , lymphoma 72 , and or listeriosis 73 . The Mayo clinic reviewed the safety of infliximab in 500 Crohn's patients treated with infliximab

Polymorphisms Within Epithelial Receptors

Genetic risk assessment in the setting of allogeneic stem cell transplantation is one of the major goals to optimise future prophylaxis and treatment of patients our group has focused on analysis of single-nucleotide polymorphisms (SNPs) within the intracyto-plasmatic receptor NOD2 CARD15, which recognizes the bacterial cell wall compound muramyl-dipeptide and induces nuclear factor-kB-mediated inflammation. By performing TaqMan PCR of the three major SNPs also identified as risk factors in Crohn's disease in donors and recipients, we were able to demonstrate a major association of NOD2 CARD15 SNPs with the occurrence of severe graft-vs-host disease and resulting treatment-related mortality following human leukocyte antigen-identical sibling transplantation. Although these data need confirmation in further prospective trials, this association may not only be used for risk assessment but also point to a major pathophysiological interaction of dysregulated activation of the innate...

Innate Immunity in the Gastrointestinal Tract

Adiposse Tissue Expansion

Defensins produced by intestinal epithelial cells provide innate immune protection against luminal bacteria, and defects in their production are associated with bacterial invasion and inflammatory bowel disease. Defensins are peptides produced by various cell types in the body that exert lethal toxic effects on microbes by inserting into and causing loss of integrity of their outer phospholipid membranes (see Chapter 4). In the small bowel, the major defensins are the a-defensins, including human defensin 5 (HD5) and HD6, produced constitutively as inactive precursor proteins by Paneth cells located at the base of crypts between microvilli. Active HD5 and HD6 peptides are generated by proteolytic cleavage mediated by trypsin, also produced by Paneth cells. In the colon, P-defensins are produced by absorptive epithelial cells in the intestinal crypts, some constitutively and others in response to IL-1 or invasive bacteria. In addition, neutrophil granules are rich in a-defensins, which...

Diseases Related to Immune Responses in the

Inflammatory bowel disease is a heterogeneous group of disorders characterized by chronic remitting inflammation in the small or large bowel, likely due to poorly regulated responses to commensal bacteria. The two main types of inflammatory bowel disease are Crohn's disease, which can affect the entire thickness of the bowel wall tissue in any part of the gastrointestinal tract but most frequently involves the terminal ileum, and ulcerative colitis, which is restricted to the colonic mucosa. Symptoms include abdominal pain, vomiting, diarrhea, and weight loss. Treatments include various anti-inflammatory drugs, such as sulfasalazine, corticoste-roids, TNF antagonists, and antimetabolites. Although the etiology of Crohn's disease and ulcerative colitis is poorly understood, several types of evidence suggest that these disorders are a result of defects in the regulation of immune responses to commensal organisms in the gut in a genetically susceptible host. A number of immunologic...

Vitamins Minerals and Electrolytes

A wide array of vitamin, mineral, and electrolyte deficiencies frequently occurs in Crohn's disease patients and with variable clinical significance. These deficiencies may result from extensive inflammation, surgical resection of small bowel, or both, and require haematological and biochemical examination. The prevalence of decreased nutrient levels among patients with Crohn's disease is summarised in Table 2. Of particular clinical relevance is the deficiency in iron, vitamin B12, folate, calcium, vitamin D, and zinc. Table 2. Prevalence of nutritional deficiencies among patients with Crohn's disease. (Data from 20 )

Intervention with Adhesion Molecules

In patients with severe immunosuppression, e.g. individuals with AIDS. The most probable explanation of how PML could have occurred in the two patients is that Tysabri potently suppresses the migration of any T cell, not only pathogenic autoreactive cells, but also T cells circulating for detection and elimination of viruses and other pathogens (T-cell surveillance). As a consequence, reactivation of viruses is thought to become insufficiently controlled by T-cell surveillance. Following these events, the marketing authorization holder evaluated most patients having been treated with Tysabri and found no other case of PML, despite a retrospective case of a patient who had died of PML in a clinical trial for Crohn's disease (Van Assche et al. 2005). Based on the observed clinical efficacy and the medical need in the treatment of patients with MS, the Committee for Medicinal Products for Human Use (CHMP, until 2004 CPMP) at the European Medicines Agency EMEA (until 2004 European Agency...

Adverse Reactions in Highly Efficacious Antia4Integrin Therapy with Natalizumab

In striking contrast to previous concepts, which viewed the CNS as an immunoprivileged site completely occluded from the immune system, it is now clear that T lymphocytes regularly patrol the CNS, albeit in small numbers (Wekerle et al. 1986). With the novel concept of persistent immunosurveillance of the brain by immune cells, these autoreactive cells circulating in the peripheral immune system have to be activated, adhere to vascular endothelium, and migrate across the blood-brain barrier (Engelhardt and Ransohoff 2005). In the early 1990s Yednock and Steinman made the remarkable finding that the ligand pair VCAM-1 (vascular cell adhesion molecule-1) VLA-4 (very late adhesion mole-cule-4) was of key importance for egress of inflammatory T-cells into the brain parenchyma (Yednock et al. 1992). Subsequently natalizumab, a humanized mAb directed against the a4 subunit of integrin, was used for MS treatment. a4 Integrin is a member of a large family of cell-surface adhesion molecules...

What is Mycobacterium avium subsp paratuberculosis and how is it controlled

Mycobacterium avium subsp. paratuberculosis (MAP) causes paratuberculosis, or Johne's disease, an inflammatory bowel disease affecting ruminants. This disease is chronic and contagious and eventually results in death of affected animals. In the US, approximately 22 of the dairy herds are affected with Johne's disease. Infected dairy cattle are able to shed MAP in milk. This pathogen has been epidemiologically implicated in association with Crohn's disease in humans. While pasteurisation is thought to provide public health protection from this organism, several studies have revealed the presence of MAP in retail fluid pasteurised milk.

Proinflammatory Cytokines and Their Receptors

Anti-TNF-a therapies are approved for the treatment of RA and Crohn's disease. However, monoclonal antibodies against TNF-a induce SLE, and lead to increased and prolonged exacerbations in MS patients. Further, there is some clinical trial evidence that etanercept, a soluble recombinant TNF receptor Fc protein, designed as a TNF-a inhibitor, may actually lead to the upregulation of TNF-a expression in some MG patients - leading to worsening of the disease. Monoclonal antibodies against IL-12 are currently being tested in clinical trials for MS and Crohn's disease. A monoclonal antibody to the IL-2 receptor daclizumab functions as an IL-2 antagonist. Daclizumab inhibits IL-2-mediated stimulation of lymphocytes, is approved for use in kidney transplant patients, and is being tested in clinical trials as a therapy for RRMS.

Inflammatory Bowel Diseases

The inflammatory bowel diseases (IBD), which include Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders effecting 0.3 of the Western population (Podolsky 2002). CD can affect any part of the gastrointestinal tract, from the oral cavity to the anus, whereas UC is limited to the colon and rectum. The etiology of CD and UC remains unknown, but it probably involves a combination of genetic predisposition, environmental conditions, and abnormalities in immune regulation (Chutkan 2001 Farrell et al. 2001 Podolsky 2002). In particular, the intestinal mucosal immune system

NODlike Receptors

NOD1 and NOD2, members of the CARD domain-containing NOD subfamily of NLRs, are expressed in the cytoplasm of several cell types including mucosal epithelial cells and phagocytes, and they respond to bacterial cell wall peptidoglycans. NOD2 is particularly highly expressed in intestinal Paneth cells, where it stimulates expression of antimicrobial substances called defensins in response to pathogens. NOD1 recognizes substances derived mainly from gram-negative bacteria, whereas NOD2 recognizes a distinct molecule called muramyl dipeptide from both gram-negative and gram-positive organisms. These peptides are released from intracellular or extracellular bacteria in the latter case, their presence in the cytoplasm requires specialized mechanisms of delivery of the peptides into host cells. These mechanisms include type III and type IV secretion systems, which have evolved in pathogenic bacteria as a means of delivering toxins into host cells. When oligomers of NODs recognize their...

Summary

TNF plays a key role in a number of chronic inflammatory and autoimmune disease states, including RA, PsA, psoriasis, AS, and Crohn's disease. The introduction of TNF antagonists has significantly improved the clinical status of many patients with these conditions (Lovell et al. 2000 Breedveld et al. 2005, 2006 Burmester et al. 2004, 2005 Furst et al. 2003 Genovese et al. 2005 Hanauer et al. 2006 Keystone et al. 2004a Lang- Randomized, placebo-controlled trials evaluating the efficacy and safety of adalimumab treatment in a broad spectrum of RA patients have demonstrated substantial improvements in disease symptoms, as well as improvements in QOL and functional status, and arrest of disease progression moreover, adalimumab had a rapid onset of action and sustained efficacy with long-term treatment. In adalimumab OLE studies, patient retention is high, supporting the tolerability data from pivotal trials. Recent evaluations of adalimumab for the treatment of PsA have demonstrated...

Bradykinin Receptors

In 66 of serosal afferents (84), an effect that was mediated via B2 receptors, and responses to probing were potentiated after bradykinin. In this study, another group of bradykinin-responsive LSN afferents were mechanically insensitive. Fewer (11 ) mouse pelvic nerve serosal afferents responded to bradykinin, and no mechanically insensitive pelvic nerve afferents were recruited by bradykinin. This suggests differences in the way each pathway signals bradykinin activation and reveals a chemospecific population of afferents. Interestingly, Bx but not B2 receptor protein is significantly increased in the intestines of both active ulcerative colitis and Crohn's disease patients compared with controls (116), but the relationship of this to symptoms is not known.

Vitamin B12

Since Crohn's disease frequently involves the terminal ileum, where the vitamin B12-intrinsic factor complex is absorbed, serious impairment of the enterohepatic circulation of vitamin B12 is commonly observed in Crohn's disease patients. Moreover, because vitamin B12 stores in the liver must decrease before serum concentrations become low, the incidence of decreased vitamin B12 stores is probably quite high 21 . Megaloblastic anaemia is commonly seen with vitamin B12 deficiency however, the patient seldom manifests symptoms of deficiency, such as paresthaesia, numbness, gait

Others

The precise mechanism involved in the development of Crohn's disease is unknown however, the effects of oxidative stress on the bowels of patients with active Crohn's disease are thought to play a role 29,30 . Unlike normal conditions in the intestine, an imbalance between endogenous anti-oxidant defences and free-radical production is seen in Crohn's disease 31 . Circulating nutritional antioxidants, such as p-carotene, vitamin C, vitamin E, selenium, and zinc, are important factors in the prevention of free-radical-mediated tissue injury however, serum concentrations of these anti-oxi-dants were reported to be low in patients with Crohn's disease 32 , whereas no clinical signs of deficiency were seen.

Nutritional Support

The indications for nutritional support of patients with Crohn's disease are largely based on clinical experience, although the role of enteral diets for inducing remission continues to be debated. Three meta-analyses on enteral nutrition as primary therapy in Crohn's disease have been published 33-35 . These reports similarly demonstrate that clinical remission is more often successfully induced with corticosteroids than enteral diets, although enteral nutrition remains an important therapeutic tool. The precise mechanism by which an enteral diet induces remission in Crohn's disease is not understood, although several mechanisms of action have been proposed, including reduction of immune stimuli in the gut 36 , nutritional improvement 37 , bowel rest, a trophic effect of glutamine 38 , and reduction of intestinal permeability 39 . In any event, more randomised, controlled trial data subjected to meta-analyses are required to confirm the clinical effect of enteral nutrition in the...

Humphrey JF Hodgson

Endoscopic approaches dominate the investigation of the key symptomatology of colorectal disease. Investigations of a history of rectal bleeding, or small volume diarrhoea with blood or pus, demand rapid direct inspection of the colonic mucosa by sigmoidoscopy (an instant outpatient procedure) or colonoscopy (which, of course, requires patient preparation with bowel cleansing). These investigations permit rapid diagnosis of the presence of neoplasia (polyps and cancer) and inflammation (ulcerative colitis, Crohn's disease, diverticulitis or ischaemic colitis). This pragmatic approach reduces the requirement for the use of biomarkers for disease detection. Tumour markers for colorectal cancer are of course available, but, for certainty, endoscopy and biopsy are required. Despite the marked similarity of the inflammatory processes in Crohn's disease and ulcerative colitis, the latter has relied little on serological measurements. As ulcerative colitis virtually always involves the...

Natalizumab

Natalizumab is a humanized IgG4 monoclonal antibody against 4 integrin that inhibits both 4 7- MadCAM-1 and 4 1-vascular cellular adhesion molecule 1 binding. Natalizumab failed to demonstrate efficacy for induction of response or remission in several Crohn's disease controlled trials (Ghosh et al. 2003 Gordon et al. 2001 Sandborn et al. 2005d). In the ENACT-1 (Efficacy of Natalizumab as Active Crohn's Therapy) study, natalizumab was shown to be efficacious for maintenance of response and remission through 36 weeks in those patients who had an initial response (Sandborn et al. 2005d). The ENACT-1 study was the largest phase 3 trial ever conducted in CD. A total of 905 patients received natalizumab (300 mg IV) or placebo at Weeks 0,4, and 8ina4 1 randomization. The primary endpoints of clinical response (CDAI reduction of 70) and clinical remission (CDAI