The Selective 5-HT1A Agonist SR57746A Protects Intestinal Epithelial Cells and Enteric Glia Cells and Promotes Mucosal Recovery in Experimental Colitis.

Background: Neurotrophic growth factors can stabilize the intestinal barrier by preventing the apoptosis of enteric glial cells (EGCs) and enterocytes. We reasoned that a selective 5-HT1A receptor agonist may have neuroprotective properties in the gut and that topical application of SR57746A might be an effective treatment strategy in inflammatory bowel disease (IBD).

Methods: The therapeutic potential of 5-HT1A receptor agonist SR57746A in IBD was evaluated in vitro (nontransformed NCM460 colonic epithelial cells, SW480 colorectal carcinoma cells) and in vivo (murine dextran sulfate sodium [DSS] colitis and CD4-T-cell transfer colitis).

First multicenter study of modified release phosphatidylcholine "LT-02" in ulcerative colitis: a randomized, placebo-controlled trial in mesalazine-refractory courses.

Objectives: Phosphatidylcholine is a key component of the mucosal barrier. Treatment with modified release phosphatidylcholine aims to improve the impaired barrier function. The primary objective is to evaluate the efficacy of LT-02, a newly designed modified release phosphatidylcholine formula, in a multicenter setting.

Age-of-onset-dependent influence of NOD2 gene variants on disease behaviour and treatment in Crohn's disease.

Background: Influence of genetic variants in the NOD2 gene may play a more important role in disease activity, behaviour and treatment of pediatric- than adult-onset Crohn's disease (CD).

Methods: 85 pediatric- and 117 adult-onset CD patients were tested for the three main NOD2 CD-associated variants (p.R702W, p.

Brain derived neurotrophic factor inhibits apoptosis in enteric glia during gut inflammation.

Background: Enteric glia cells (EGCs) are essential for the integrity of the bowel. A loss of EGCs leads to a severe inflammation of the intestines. As a diminished EGC network is postulated in Crohn's disease (CD), we aimed to investigate if EGCs could be a target of apoptosis during inflammation in CD, which can be influenced by Brain derived neurotrophic factor (BDNF).

GDNF protects enteric glia from apoptosis: evidence for an autocrine loop.

Background: Enteric glia cells (EGC) play an important role in the maintenance of intestinal mucosa integrity. During the course of acute Crohn's disease (CD), mucosal EGC progressively undergo apoptosis, though the mechanisms are largely unknown. We investigated the role of Glial-derived neurotrophic factor (GDNF) in the regulation of EGC apoptosis.

NOD2 polymorphism predicts response to treatment in Crohn's disease--first steps to a personalized therapy.

Background And Aims: Great efforts have been made to predict disease behavior over time and the response to treatment in Crohn's disease (CD). Such understanding could personalize therapy. Early introduction of more aggressive therapies to patients at high risk and no introduction of predictable refractory treatments could become possible.

The role of enteric glia in gut inflammation.

A neuro-glia interaction is part of gut inflammation and essential for the integrity of the bowel. A loss of enteric glia cells (EGCs) led to a fatal haemorrhagic jejuno-ileitis and death in a few days. Although a diminished EGC network is postulated in inflammatory bowel disease and enteric glia pathology is described in Chagas' disease the role of EGCs in the onset of these disease complexes is not definitely clear.

Intravenous ibandronate or sodium-fluoride--a 3.5 years study on bone density and fractures in Crohn's disease patients with osteoporosis.

Background And Aim: Osteoporosis commonly afflicts Crohn's disease (CD) patients. Management remains unclear, with limited results for intravenous (i.v.

Bones and Crohn's: no benefit of adding sodium fluoride or ibandronate to calcium and vitamin D.

Aim: To compare the effect of calcium and cholecalciferol alone and along with additional sodium fluoride or ibandronate on bone mineral density (BMD) and fractures in patients with Crohn's disease (CD).

Methods: Patients (n =148) with reduced BMD (T-score < -1) were randomized to receive cholecalciferol (1000 IU) and calcium citrate (800 mg) daily alone(group A, n = 32) or along with additional sodium fluoride (25 mg bid) (group B, n = 62) or additional ibandronate (1 mg iv/3-monthly) (group C, n = 54). Dual energy X-ray absorptiometry of the lumbar spine (L1-L4) and proximal right femur and X-rays of the spine were performed at baseline and after 1.

Distribution of enteric glia and GDNF during gut inflammation.

Background: The enteric glia network may be involved in the pathogenesis of inflammatory bowel disease (IBD). Enteric glia cells (EGCs) are the major source of glial-derived neurotrophic factor (GDNF), which regulates apoptosis of enterocytes. The aim of the study was to determine the distribution of EGCs and GDNF during gut inflammation and to elucidate a possible diminished enteric glia network in IBD.

The endothelin axis influences enteric glia cell functions.

Background: The biologic effects of endothelin-1 (ET-1) are not limited to its vasoconstricting activity. A new and highly interesting role of the endothelin axis is its involvement in immune functions. As ET-1 is highly increased during gut inflammation, the aim of this study was to see if the endothelin axis influences enteric glia cell (EGC) functions, and through them, the immune response, during gut inflammation.

Optimal timing of oral refeeding in mild acute pancreatitis: results of an open randomized multicenter trial.

Objectives: The aim of this study was to compare 2 protocols regarding the initiation of oral nutrition in patients with mild acute pancreatitis.

Methods: We randomized 143 patients to the Lipase directed (LIP) (n = 74) and the self selected PAT (n = 69) group. In the (PAT) group, the patients restarted eating through self-selection.

Glutamate receptor subunit expression in primary enteric glia cultures.

Excitotoxicity, which is mediated via glutamate receptors, is also a phenomenon of the enteric nervous system. Whether enteric glial cells (EGCs), which resemble astrocytes of the central nervous system, express glutamate receptors and hence are involved in gut excitotoxicity is not yet known. To investigate glutamate receptor subunit expression in EGCs, primary EGC cultures of the myenteric plexus were analyzed by real-time PCR and Western blotting.

Proinflammatory cytokines induce neurotrophic factor expression in enteric glia: a key to the regulation of epithelial apoptosis in Crohn's disease.

Objectives: Imbalanced apoptosis of enterocytes is likely to be 1 of the mechanisms underlying Crohn's disease (CD). Apoptosis of enterocytes is regulated by glial-derived neurotrophic factor (GDNF), which is increased in CD. The cellular source of GDNF during gut inflammation is unclear.

Glial-derived neurotrophic factor regulates apoptosis in colonic epithelial cells.

Background & Aims: Ablation of the enteric glia leads to a fulminant hemorrhagic jejunoileitis. We hypothesized that glial-derived neurotrophic factor (GDNF) may be involved in mucosal protection of the gut. Therefore, we examined the regulation of GDNF and its receptor (GFR-alpha1) in colonic inflammation and its effects on colonic epithelial cell apoptosis.

Enteric nervous plasticity and development: dependence on neurotrophic factors.

The enteric nervous system in the mammalian gut is histologically and to some extent functionally similar to the central nervous system. Thus, structural and functional similarities between these systems are evident. As shown for the central nervous system, differentiation of neural crest-derived precursor cells of the enteric nervous system also depends essentially on different neurotrophic factors.

Role of neurotrophins in inflammation of the gut.

Until now neurotrophins like nerve growth factor (NGF), brain-derived neurotrophic factor (BDNA), neurotrophin (NT)-3 and neurotrophic factors like glial-derived neurotrophic factor (GDNF) have been almost exclusively investigated concerning their role in differentiation, growth and survival of specific neurons in the peripheral and central nervous system. However, in the last decade several non-neuronal functions of neurotrophins and neurotrophic factors have been characterized. In the gastrointestinal tract, neurotrophins and neurotrophic factors regulate neuropeptide expression, interact with immunoregulatory cells and epithelial cells and regulate motility during inflammation.

Submucosal hypoganglionosis causing chronic idiopathic intestinal pseudo-obstruction.

A 39-year-old woman presented with recurrent symptoms suggestive of intestinal obstruction. She was put on total parenteral nutrition (TPN) and consequently developed sepsis and endocarditis. TPN was stopped and a venting enterostomy was performed.