No abstract

Obsessive‐compulsive disorder (OCD) is a severe anxiety disorder characterized by obsessions and compulsions. The core symptom of OCD is compulsivity, the inability to stop thinking or acting when you want to, despite being aware of the uselessness of the content or the adverse consequences. To initiate a systematic search for genetic mechanisms underlying the pathophysiology of compulsivity, a panel of chromosome substitution (CS) strains, derived from mice that suppress (C57BL/6J strain) or maintain (A/J strain) high levels of repetitive wheel running during 2 hr of daily limited food access, was screened for this compulsive behavior. Following the genetic screen, we found linkage between compulsive wheel running and mouse chromosomes 2, 6, and 7 that show overlap with recently identified human linkage regions for OCD on chromosomes 7p and 15q. In the overlapping (human/mouse) genomic region, the CRH receptor 2 (CRHR2) gene was tested in a human case–control study. An initial exploration in OCD cases versus controls failed to detect an association between four‐candidate CRH2R SNP's within this homologous linkage region and OCD. Genetic fine mapping of compulsivity in mice provides new opportunities to reveal mechanisms underlying this significant psychiatric trait. © 2009 Wiley‐Liss, Inc.

Titanium and its alloys are widely used as implant materials for dental and orthopaedic applications. To improve their wear and corrosion resistance, several surface modifications that give rise to an outer ceramic layer of rutile have been developed. It is expected that after a long period of functional loading, rutile debris will arise from these modified surfaces. We have compared the in vitro biocompatibility of subcytotoxic doses of rutile and titanium particles of phagocytosable size in primary cultures of human osteoblasts. Particles were visualized using a spectral confocal microscope by reflection. Both types of particles aggregated in the culture media and were efficiently internalized by osteoblasts as agglomerates. Treatment of isolated cultures of osteoblasts with rutile particles stimulated the release of IL-6, PGE2, and GM-CSF to a lesser extent than titanium. The influence of macrophages on the particle-induced stimulation of those local factors was analyzed by coculturing TPA-differentiated THP-1 cells with osteoblasts. Under these conditions, levels of IL-6 and PGE2 after treatment of cocultured osteoblasts with rutile particles were lower than after exposure to titanium. These results indicate that rutile debris shows a lower bioreactivity than titanium when tested in cultures of human osteoblasts and support the improved biocompatibility of titanium-based implants modified to create an outer layer of rutile on their surfaces.

ABSTRACT:The purpose of the current study was to evaluate the effects of alumina particles on secretion of several cytokines involved in bone resorption in cocultures of macrophages and osteoblasts. To distinguish the contribution of each individual cell type, we have established a heterologous in vitro system that makes use of mouse J774 cells and primary cultured human osteoblasts. J744 cells decreased the production of TNF-a when they were cocultured with osteoblasts. Treatment of J744 cells with alumina particles increased TNF-a secretion, but the induction was lower when cells were cocultured with osteoblasts. Secretion of IL-6 by J744 cells was very low, and increased in the presence of osteoblasts. Alumina particles were only able to stimulate the release of IL-6 by J744 cells when cells were cocultured with osteoblasts. On the other hand, incubation of osteoblasts with alumina particles enhanced the release of IL-6 and GM-CSF. Coculturing osteoblasts with J744 cells induced them to release IL-6 and GM-CSF, and treatment with alumina further increased the secretion of both mediators by osteoblasts. According to these in vitro results, it seems rather plausible that alumina particles are able to initiate an inflammatory response in vivo. ß

A low proportion of mildly hypertensive patients attended in a primary care setting are microalbuminuric. In this population, UAE is an expression of BP values over 24 h and correlates with several risk factors.