The cells were then immediately treated with vehicle alone (control), 8mM aspirin (ASA), or 8raM ASA with 10/~M GLP-2.Six, 12, and 24 hours later, wound width was measured using an ocular micrometer.Cell viability was confirmed by trypan blue exclusion.Results: At all timepoints examined, the following observations were made: 1) ASA induced a reduction in cellular migration rates (p<0.Ol vs. control) and 2) GLP-2 restored migration rates to control values in cells treated with ASA (Figure 1).Conclusions: These results suggest a novel role for GLP-2 in regulating cellular migration in the intestinal epithelium.Accelerated restitution may act in concert with the previously described biological actions of GLP-2 to enhance repair and recovery in intestinal disease.

BACKGROUND AND AIMS Constitutive cyclooxygenase (COX) 1 is believed to mediate prostaglandin dependent gastric protection. However, gastric mucosa contains cells capable of expressing inducible COX-2. We therefore investigated COX-1 and COX-2 expression, localisation, and activity in normal and abnormal human gastric mucosa. METHODS COX-1 and COX-2 distribution was investigated by light and electron microscopic immunohistochemistry and by western blot analysis, and their contribution to prostaglandin (PG)E2 synthesis using selective enzyme inhibitors. RESULTS There was strong parietal cell COX-1 and COX-2 immunoreactivity in all sections and isolated cells, with macrophage and myofibroblast reactivity in some sections. Immunostaining was specifically abolished by antigen absorption. Western blot analysis confirmed COX-1 and 2 expression. COX-1 and COX-2 immunostaining was increased inHelicobacter pylori gastritis, particularly the mid glandular zone and lamina propria inflammatory cells. This was associated with increased ex vivo PGE2 synthesis (62.4 (13.5) pg/mg v 36.3 (15.5) pg/mg in uninflamed mucosa; p=0.017) which was significantly inhibited by COX-1 but not COX-2 inhibition. Increased COX-2 immunostaining in macrophages, endothelial cells, and myofibroblasts (with reduced epithelial expression) was seen at the rim of ulcers. CONCLUSION COX-2, as well as COX-1, is expressed by normal human gastric mucosa and is increased at the rim of ulcers. Although both are increased withH pylori, COX-1 contributes more than COX-2 to gastric PGE2 production.

Aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) have a substantial impact upon the gastrointestinal tract with both toxicity and benefit. The major toxicity relates to gastroduodenal ulceration and injury to the small and large intestine. The major benefits relate to evidence that the drugs may prevent, delay or cause regression of progress towards malignancy in the colon, and almost certainly also the stomach. The mechanism of toxicity has been thought to relate to inhibition of the synthesis of prostaglandins, since these are protective to the gastrointestinal mucosa as a result of effects on blood flow and mucus and bicarbonate secretion. It is difficult to attribute any anti-cancer effect to these actions. Promotion of apoptosis, which appears to be independent of prostaglandin synthesis, may better account for both therapeutic benefits and possibly some of the toxicity.

BACKGROUNDThe basement membrane of human colonic mucosa contains numerous discrete pores. We have recently shown that following loss of the surface epithelium, many cells migrate out of the colonic lamina propria via basement membrane pores.AIMSTo characterise cells migrating out via basement membrane pores of the human gastric lamina propria, following loss of the surface epithelium.METHODSFresh human gastric mucosal samples were completely denuded of epithelial cells and placed in culture. Tissue samples were studied by electron microscopy (EM) and cells by EM, FACS analysis, immunohistochemistry, and reverse transcription polymerase chain reaction (RT-PCR).RESULTSEM showed numerous discrete pores (0.65–8.29 μm in diameter) in the subepithelial basement membrane. During culture of mucosal samples denuded of epithelial cells, lymphocytes, macrophages, and myofibroblasts migrated out of the lamina propria via the basement membrane pores. The lymphocytes were predominantly CD45RO+ and CD69+ T cells. Macrophages were shown to express cyclooxygenase (COX) 1 and 2 enzymes. Myofibroblasts were established in culture and, despite prolonged culture and passage, retained their phenotype. They expressed mRNA and protein for COX 1 and 2 enzymes and their release of prostaglandin E2 was inhibited by selective COX 1 and 2 inhibitors.CONCLUSIONSLamina propria cells migrating out of cultured denuded gastric mucosal samples have been characterised phenotypically and functionally. Such cells would be suitable for studies of their interactions with epithelial cells and also with Helicobacter pylori and its products.

The developing popularity of non-steroidal anti-inflammatory drugs (NSAIDs) over the last 100 years has been paralleled by an increase in associated complications, particularly affecting the gastrointestinal (GI) tract [1]. Over this period, there have been several attempts to develop less toxic NSAIDs, most of which have been unsuccessful. Since the discovery that the enzyme cyclooxygenase (COX) exists as two isoforms, the largely constitutive COX-1 and the mainly inducible COX-2, much interest has centred on the development of drugs capable of selectively inhibiting COX-2. Early studies that investigated specific COX-2 inhibitors (with no effect on the COX-1 isoform over the whole range of concentrations achieved in clinical usage) are encouraging, as they demonstrate that these drugs have fewer effects on gastroduodenal mucosa than standard NSAIDs given at equivalent doses. Further clinical experience with these agents outside trial settings and additional studies to assess the role of COX-2 when induced in the GI tract are needed, before such agents can be safely recommended for widespread prescribing.

Whether there is an association between coeliac disease and epilepsy is uncertain. Recently, a syndrome of coeliac disease, occipital lobe epilepsy and cerebral calcification has been described, mostly in Italy. We measured the prevalence of coeliac disease in patients attending a seizure clinic, and investigated whether cerebral calcification occurred in patients with both coeliac disease and epilepsy. Screening for coeliac disease was by IgA endomysial antibody, measured by indirect immunofluorescence using sections of human umbilical cord. Of 177 patients screened, four patients were positive. All had small-bowel histology typical of coeliac disease. The overall frequency of coeliac disease in this mixed patient sample was 1 in 44. In a control group of 488 pregnant patients, two serum samples were positive (1 in 244). Sixteen patients with both coeliac disease and epilepsy, who had previously attended this hospital, were identified. No patient had cerebral calcification on CT scanning. Coeliac disease appears to occur with increased frequency in patients with epilepsy, and a high index of suspicion should be maintained. Cerebral calcification is not a feature of our patients with epilepsy and coeliac disease, and may be an ethnically-or geographically-restricted finding.

The cost of providing medical care is ever-increasing but the resources available are at best static. Major savings can be made by reducing inappropriate investigations. Using serological testing for organisms causing atypical pneumonia as an example, we examined the appropriateness of requests and also physicians' understanding of the test. Of 119 patients tested, only 3 had titres indicative of acute infection. Most patients were tested within 2 days of hospital admission, before receipt of results excluding more likely diagnoses. Forty-five patients had no current or recent respiratory symptoms, in whom infection was highly unlikely. Titres were most often requested by the least experienced members of the clinical team. Of 70 patients with an acute illness in whom a definitive diagnosis, bacteriological or otherwise, was not made, in only 9 was a convalescent specimen sent for follow-up titres. Most requests for serology for organisms causing atypical pneumonia were inappropriate. Furthermore, in the majority of cases the test was incorrectly used.