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OBJECTIVE: Endocannabinoids and neuropeptide Y (NPY) promote energy storage via central and peripheral mechanisms. In the hypothalamus, the two systems were suggested to interact. To investigate such interplay also in non-hypothalamic tissues, we evaluated endocannabinoid levels in obese OE-NPY(DßH) mice, which overexpress NPY in the noradrenergic neurons in the sympathetic nervous system and the brain. METHODS: The levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) were measured in key regulatory tissues, that is, hypothalamus, pancreas, epididymal white adipose tissue (WAT), liver and soleus muscle, over the development of metabolic dysfunctions in OE-NPY(DßH) mice. The effects of a 5-week treatment with the CB1 receptor inverse agonist AM251 on adiposity and glucose metabolism were studied. RESULTS: 2-AG levels were increased in the hypothalamus and epididymal WAT of pre-obese and obese OE-NPY(DßH) mice. Anandamide levels in adipose tissue and pancreas were increased at 4 months concomitantly with higher fat mass and impaired glucose tolerance. CB1 receptor blockage reduced body weight gain and glucose intolerance in OE-NPY(DßH) to the level of vehicle-treated wild-type mice. CONCLUSIONS: Altered endocannabinoid tone may underlie some of the metabolic dysfunctions in OE-NPY(DßH) mice, which can be attenuated with CB1 inverse agonism suggesting interactions between endocannabinoids and NPY also in the periphery. CB1 receptors may offer a target for the pharmacological treatment of the metabolic syndrome with altered NPY levels.
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BACKGROUND AND AIMS: Loss of femoral bone stock in elective revision total hip arthroplasty poses unique and substantial challenges. Structural onlay allografts may provide mechanical stability for the cementless revision prosthesis and increase bone stock. MATERIAL AND METHODS: At least one cortical onlay allograft was used in 40 elective total hip arthroplasty revisions (40 patients) to reconstruct femoral bone defects. The operations were performed between January 1999 and August 2010 in the Turku University Hospital, Finland. The mean follow-up time was 52 months (range: 12-125 months). RESULTS: The allografts were incorporated into the bone tissue in 37 of 40 (92.5%) patients. Cementless revision stems healed in 36 of 40 (90.0%) patients, but these patients were not exactly the same patients whose allografts were successfully incorporated. One or more surgical complications were experienced by 14 of 40 (35.0%) patients during follow-up. In all, 4 of 40 (10.0%) patients (all women) had hip infections during follow-up. Of the 7 patients with rheumatoid arthritis, 4 (57.1%) had at least one complication. CONCLUSIONS: The use of the cortical onlay allografts provides a feasible option for restoring the integrity of the proximal femur in revision total hip arthroplasty, but the complication rate is high, particularly in female patients with rheumatoid arthritis.
