Non-IBD and noninfectious colitis.

A wide range of etiologies and pathogenic mechanisms underlie colitis. This Review provides an overview of the pathophysiology, epidemiology, histopathology, and clinical characteristics of noninfectious and non-IBD forms of colitis: microscopic colitis, Behçet's syndrome, diversion colitis, diverticular colitis, eosinophilic colitis, ischemic colitis, and radiation colitis. These more recently characterized and rare forms of colitis occur as either primary conditions or complications of other diseases.

Systematic review: coxibs, non-steroidal anti-inflammatory drugs or no cyclooxygenase inhibitors in gastroenterological high-risk patients?

Selective cyclooxygenase-2 inhibitors have been marketed as alternatives of conventional, non-steroidal anti-inflammatory drugs with the purpose of reducing/eliminating the risk of ulcer complications. Unexpectedly, randomized-controlled trials revealed that long-term use of coxibs, such as rofecoxib, significantly increased the risk of myocardial infarction and stroke, while the use of valdecoxib was associated with potentially life-threatening skin reactions. Subsequently, rofecoxib and valdecoxib were withdrawn from the market.

Expression of inducible nitric oxide synthase and effects of L-arginine on colonic nitric oxide production and fluid transport in patients with "minimal colitis".

Objective: Some patients with idiopathic, chronic diarrhoea have minimal, non-specific colonic inflammation. As nitric oxide (NO) acts as a secretagogue in the colon, we studied the expression of inducible NO synthase (iNOS) in mucosal biopsies and the effects of NOS stimulation on colonic transfer of fluid and output of NO in patients with "minimal colitis".

Material And Methods: Twelve patients with idiopathic, chronic diarrhoea and "minimal colitis" and 6 healthy volunteers were included in the study.

Expression of Toll-like receptor 9 and response to bacterial CpG oligodeoxynucleotides in human intestinal epithelium.

Recognition of repeat CpG motifs, which are common in bacterial, but not in mammalian, DNA, through Toll-like receptor (TLR)9 is an integral part of the innate immune system. As the role of TLR9 in the human gut is unknown, we determined the spectrum of TLR9 expression in normal and inflamed colon and examined how epithelial cells respond to specific TLR9 ligand stimulation. TLR9 expression was measured in human colonic mucosal biopsies, freshly isolated human colonic epithelial cells and HT-29 cells by reverse transcriptase-polymerase chain reaction or Western blotting.

Activation of nuclear factor kappaB in colonic mucosa from patients with collagenous and ulcerative colitis.

Background And Aims: Expression of inducible nitric oxide synthase (iNOS) is greatly upregulated in the colonic mucosa of patients with collagenous and ulcerative colitis. As the transcription factor nuclear factor kappaB (NFkappaB) is a major inducer of iNOS gene expression, we compared activation and transcriptional activity of NFkappaB in colonic mucosal biopsies from these patients.

Patients: Eight patients with collagenous colitis, six with relapsing ulcerative colitis, and eight with uninflamed bowel were studied.

Soluble mediators and the interaction of drugs in IBD.

The chronic idiopathic bowel diseases (IBD) - Crohn's disease and ulcerative colitis - are considered to be the result of an unrestrained inflammatory reaction. Although an explanation for the etiopathogenesis has still not emerged, the explosion of information on the inflammatory process is expected to yield a multitude of drugs targeted at particular elements of the inflammatory process. The final common pathway of immune activation in IBD is the local influx of monocytes, macrophages and polymorphonuclear neutrophils (PMNs).

High glucose impairs superoxide production from isolated blood neutrophils.

Objective: Superoxide (O(2)(-)), a key antimicrobial agent in phagocytes, is produced by the activity of NADPH oxidase. High glucose concentrations may, however, impair the production of O(2)(-) through inhibition of glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the formation of NADPH. This study measured the acute effects of high glucose or the G6PD inhibitor dehydroepiandrosterone (DHEA) on the production of O(2)(-) from isolated human neutrophils.

Superoxide production and expression of NAD(P)H oxidases by transformed and primary human colonic epithelial cells.

Background: Superoxide (O(2)(-)) generation through the activity of reduced nicotinamide dinucleotide (NADH) or reduced nicotinamide dinucleotide phosphate (NADPH) oxidases has been demonstrated in a variety of cell types, but not in human colonic epithelial cells.

Aims: To measure O(2)(-) production and effects of modulators of NAD(P)H oxidase activity and inhibitors of potential O(2)(-) generating enzymes in cultures of human colonic epithelial cells. Expression of the catalytic subunits of NAD(P)H oxidase, Nox1 and gp91(phox) (phox, phagocytic oxidase), and the membrane bound subunit p22(phox) was assessed.

Natalizumab for active Crohn's disease.

Background: In chronic inflammatory conditions such as Crohn's disease, the migration of leukocytes from the circulation into the parenchyma and their activation within inflammatory sites are mediated in part by alpha4 integrins.

Methods: We conducted a double-blind, placebo-controlled trial of the alpha4 integrin-specific humanized monoclonal antibody natalizumab in 248 patients with moderate-to-severe Crohn's disease. Patients were randomly assigned to receive one of four treatments: two infusions of placebo; one infusion of 3 mg of natalizumab per kilogram of body weight, followed by placebo; two infusions of 3 mg of natalizumab per kilogram; or two infusions of 6 mg of natalizumab per kilogram.

Constitutive expression of inducible nitric oxide synthase in the normal human colonic epithelium.

Background: Inducible nitric oxide synthase (iNOS) in the human colon is considered expressed only in inflammatory states such as ulcerative or collagenous colitis. As subtle iNOS labelling was previously observed in some colonic mucosal biopsies from a heterogeneous group of controls with non-inflamed bowel, we studied whether bowel preparation with bisacodyl or polyethylene glycol prior to sigmoidoscopy might induce iNOS expression.

Methods: Ten healthy, non-smoking male subjects were investigated.

Effects of topical ropivacaine on eicosanoids and neurotransmitters in the rectum of patients with distal ulcerative colitis.

Background: Topical administration of lidocaine has been suggested to have beneficial clinical effects in patients with active ulcerative colitis, but the mechanism of action, if any, remains obscure. As local anaesthetics may exert anti-inflammatory actions through their inhibition of nervous reflexes, we have studied the local effects of a single rectal dose of ropivacaine gel on rectal concentrations of eicosanoids and neurotransmittors in patients with relapsing ulcerative colitis.

Methods: In a randomized, double-blind, placebo-controlled study, concentrations of leukotriene B4, thromboxane B2 and prostaglandin E2 in rectal dialysates and concentrations of substance P, neurokinin A, somatostatin, vasoactive intestinal polypeptide and calcitonin gene-related peptide in rectal biopsies from 19 patients with active, distally located, ulcerative colitis were measured before and after rectal administration of a 200-mg dose of ropivacaine- or placebo-gel by use of radioimmunoassays.

Colonic production of nitric oxide gas in ulcerative colitis, collagenous colitis and uninflamed bowel.

Background: Nitric oxide (NO) produced in excess by the inflamed human colon is generally considered a pathway of mucosal damage. In an attempt to quantify colonic mucosal production of NO in various forms of colitis we performed 'steady-state' gas perfusion of whole colon in 11 patients with ulcerative colitis, 10 patients with collagenous colitis and 20 controls with uninflamed mucosa.

Methods: The tip of a Teflon tube was placed in the caecum during colonoscopy.

Review article: the treatment of inflammatory bowel disease with 6-mercaptopurine or azathioprine.

The thioguanine derivative, azathioprine, is a prodrug of 6-mercaptopurine that is further metabolized by various enzymes present in the liver and gut. Azathioprine and 6-mercaptopurine have been used in the treatment of inflammatory bowel disease, i.e.

Expression of nitric oxide synthases and effects of L-arginine and L-NMMA on nitric oxide production and fluid transport in collagenous colitis.

Background And Aims: Luminal nitric oxide (NO) is greatly increased in the colon of patients with collagenous and ulcerative colitis. To define the source and consequence of enhanced NO production we have studied expression of NO synthase (NOS) isoforms and nitrotyrosine in mucosal biopsies from these patients. In addition, effects on colonic fluid transfer caused by manipulating the substrate of NOS were studied in patients with collagenous colitis.

Interleukin 10 (Tenovil) in the prevention of postoperative recurrence of Crohn's disease.

Background And Aims: New lesions of Crohn's disease occur early after ileal or ileocolonic resection and ileocolonic anastomosis. We performed a double blind controlled trial to evaluate the safety and tolerance of recombinant human interleukin 10 (IL-10; Tenovil) in subjects operated on for Crohn's disease. We also assessed the effect of Tenovil in preventing endoscopic recurrence 12 weeks after surgery.

Increased levels of specific leukocyte- and platelet-derived substances during normal anti-tetanus antibody synthesis in patients with inactive Crohn disease.

Background: Crohn disease is considered a consequence of inappropriate upregulation of immune reactions evoked by the intestinal microflora or luminal antigens. Since the intestinal mucosa is continuously exposed to tetanus toxoid we studied the antibody response to tetanus toxoid booster immunization in patients with Crohn disease and the subsequent release of various inflammatory mediators and growth factors in blood.

Methods: Ten patients with inactive disease and no concurrent medication and 12 age-and gender-matched healthy volunteers with anti-tetanus antibody levels less than 0.

Selective inhibitors of COX-2--are they safe for the stomach?

NSAIDs are widely used and beneficial for patients with inflammatory pain. However, NSAIDs cause significant adverse upper gastrointestinal effects, including increased mortality from serious ulcer complications. NSAIDs exert their anti-inflammatory effects by inhibiting the activity of the COX enzyme, which was recently shown to exist in two isoforms, a constitutive COX-1 and an inducible COX-2.

Eradication of Helicobacter pylori compared with long-term acid suppression in duodenal ulcer disease. A randomized trial with 2-year follow-up. The Danish Ulcer Study Group.

Background: Trials evaluating long-term management of duodenal ulcer disease have mainly been focused on recurrence of ulcers, disregarding effects on dyspeptic and reflux symptoms. Profound acid inhibition with a proton pump inhibitor is the gold standard therapy in acid-related diseases. We aimed to compare the symptomatic effects of eradication therapy with those of long-term omeprazole treatment in a design with periods both with and without acid inhibition.

IOIBD questionnaire on the clinical use of azathioprine, 6-mercaptopurine, cyclosporin A and methotrexate in the treatment of inflammatory bowel diseases.

Objective: To obtain information on the clinical experience with azathioprine (AZA), 6-mercaptopurine (6-MP), cyclosporin A (CyA) and methotrexate (MTX) in the treatment of patients with inflammatory bowel disease (IBD) by gastroenterologists and internists in different countries.

Design: A questionnaire designed by the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) was mailed to 300 gastroenterologists, living in North America (n = 76) and Europe (n = 224) (12 countries), to obtain information on clinical experience.

Participants: More than half of the respondents (168/298; 56.

Review article: the potential role of nitric oxide in chronic inflammatory bowel disorders.

The aetiology of the chronic inflammatory bowel diseases-ulcerative colitis and Crohn's disease-as well as 'microscopic colitis'-both collagenous (COC) and lymphocytic colitis (LC)-remains unknown. Autoimmune mechanisms, cytokine polymorphism, commensal bacteria, infectious agents and vascular impairment have all been proposed as playing important roles in the pathogenesis of this spectrum of diseases. A variety of proinflammatory mediators, including tumour necrosis factor alpha, interleukin-1beta, interferon gamma, leukotriene B4 and platelet activating factor, promote the adherence of phagocytes to the venular endothelium and extravasation of these cells into the colonic mucosa.

From basic science to future medical options for treatment of ulcerative colitis.

Both ulcerative colitis (UC) and Crohn's disease are considered the result of an unrestrained inflammatory reaction, but an explanation for the aetiopathogenesis has still not emerged. Until the predisposing and trigger factors have been clearly defined, therapeutic and preventive strategies for these disorders must, therefore, rely on interrupting or inhibiting the immunopathogenic mechanisms involved. Current therapies, such as glucocorticoids and 5-aminosalicylic acid, inhibit raised concentrations of interdependent, soluble mediators of inflammation, which may amplify one another or have parallel effects.

Reappraisal of bicarbonate secretion by the human oesophagus.

Background And Aims: Administration of omeprazole to healthy volunteers was recently reported to increase proximal duodenal mucosal bicarbonate secretion. As human oesophagus also secretes bicarbonate, the hypothesis was tested that omeprazole may stimulate oesophageal bicarbonate secretion and thus contribute to the therapeutic efficacy of the drug in gastro-oesophageal reflux disease.

Subjects And Methods: In nine healthy volunteers, oesophageal "steady state" perfusion of a 10 cm open segment of distal oesophagus was performed twice in random order.

Gastric bicarbonate secretion and release of prostaglandin E2 are increased in duodenal ulcer patients but not in Helicobacter pylori-positive healthy subjects.

Background: Duodenal ulcer (DU) patients have impaired proximal duodenal mucosal bicarbonate secretion at rest and in response to luminal acid with higher acid-stimulated mucosal release of prostaglandin (PG) E2 than healthy subjects. Our purpose was to determine whether this abnormality was present also in the stomach of DU patients.

Methods: Simultaneous determinations of gastric and duodenal bicarbonate secretion and luminal release of PGE2 were performed in 16 healthy volunteers (5 Helicobacter pylori-positive) and 8 inactive DU patients (all H.