Intron 1 retaining cyclooxygenase 1 splice variant is induced by osmotic stress in human intestinal epithelial cells.

The biological roles of intron 1 retaining cyclooxygenase (Cox) 1 splice variants Cox-3 and PCox-1a (Cox-1ir) are not known. In humans, Cox-3 transcription has previously been shown to occur in the brain and in the aorta. However, conclusive evidence regarding the existence of a human Cox-3 protein is lacking. We studied the expression of intron 1 retaining cyclooxygenase 1 splice variants in the human colon cancer cell line Caco-2 and in human colonic tissue samples. In Caco-2 cells, their transcription was induced up to 47-fold by osmotic stress. The corresponding protein, however, could not be detected by Western blotting. In human colonic tissue samples derived from intact and inflamed areas, a low level of Cox-1ir mRNA (1500 +/- 1280 copies per 100 ng total RNA; mean+/-standard deviation; n = 20) was also found. In Caco-2 cells, induction of Cox-1ir under osmotic stress was reversed by addition of the organic osmolyte betaine. Under hypertonic but not under isotonic conditions, splice variant-specific degradation of Cox-1ir mRNA using RNA interference resulted in increased production of fully spliced Cox-1 and Cox-2 mRNA (P = 0.002). In summary, our results indicate that the intron 1 retaining Cox-1 splice variant RNA molecules are expressed by human intestinal epithelial cells in a controlled manner, are most likely not translated and play a regulatory role in the cyclooxygenase mediated epithelial osmoregulation.

The use of a biodegradable mesh plate to augment grafting of an acetabular defect: Laboratory investigation and clinical pilot study.

We used a biodegradable mesh to convert an acetabular defect into a contained defect in six patients at total hip replacement. Their mean age was 61 years (46 to 69). The mean follow-up was 32 months (19 to 50). Before clinical use, the strength retention and hydrolytic in vitro degradation properties of the implants were studied in the laboratory over a two-year period. A successful clinical outcome was determined by the radiological findings and the Harris hip score. All the patients had a satisfactory outcome and no mechanical failures or other complications were observed. No protrusion of any of the impacted grafts was observed beyond the mesh. According to our preliminary laboratory and clinical results the biodegradable mesh is suitable for augmenting uncontained acetabular defects in which the primary stability of the implanted acetabular component is provided by the host bone. In the case of defects of the acetabular floor this new application provides a safe method of preventing graft material from protruding excessively into the pelvis and the mesh seems to tolerate bone-impaction grafting in selected patients with primary and revision total hip replacement.