Agonistic antibodies to Fas induce a breach in the endothelial lining of the liver and a breakdown in B cell tolerance.

Liver disease can be associated with a breakdown in self-tolerance and the production of autoantibodies such as rheumatoid factors (RF), which bind to IgG. Here we investigated whether primary, non-infectious liver damage was sufficient to induce autoantibody production. We established a model of targeted liver damage induced by weekly sublethal injections of pro-apoptotic anti-Fas (CD95) antibodies. Liver damage, monitored by measurements of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, was minimal 1 week after anti-Fas injection. However, the sublethal Fas stimulation was sufficient to trigger significant haemorrhage in the liver, as assessed by Evans Blue dye leakage into the organ 5 h after anti-Fas antibody injection. We observed an induction of RF in response to the weekly injections of sublethal anti-Fas antibodies but not of isotype control antibodies, indicating a breakdown of self-tolerance induced by Fas engagement. RF induction was unlikely to be due to direct activation of B cells, as splenocytes stimulated with anti-Fas antibodies in vitro did not produce RF. These studies show that sublethal damage to the liver by Fas engagement leads to liver haemorrhage and is sufficient to trigger the breakdown of self-tolerance.

[Bioabsorbable osteofixation devices]. / Les matériels d'ostéosynthèse résorbables.

There is continued interest in the development of new biomaterials. The application of new implantable biomaterials requires intense research and thorough evaluation. Much time and effort has been required to overcome the risks and problems associated with the bioabsorbable devices. For surgical bone fixation, these materials were investigated since the 1960's. Different polymer properties were explored to ensure adequate strength and biocompatibility. High-molecular-weight bioabsorbable polymers were initially used, followed by addition of reinforcement materials. The most recent materials are self-reinforced, small yet strong devices. The newer generations contain bioactive substances such as antibiotics and growth factors. Bioabsorbable materials are constantly changing as we try to adopt the principles of tissue engineering. Surgeons are using new techniques to exploit these polymers and their bioabsorbable properties. It is hoped that this multidisciplinary approach of surgery and research will continue to help the further evolution of biomaterial science.