Enhanced chondrogenesis and Wnt signaling in PTH-treated fractures.

Studies have shown that systemic PTH treatment enhanced the rate of bone repair in rodent models. However, the mechanisms through which PTH affects bone repair have not been elucidated. In these studies we show that PTH primarily enhanced the earliest stages of endochondral bone repair by increasing chondrocyte recruitment and rate of differentiation. In coordination with these cellular events, we observed an increased level of canonical Wnt-signaling in PTH-treated bones at multiple time-points across the time-course of fracture repair, supporting the conclusion that PTH responses are at least in part mediated through Wnt signaling. INTRODUCTION: Since FDA approval of PTH [PTH(1-34); Forteo] as a treatment for osteoporosis, there has been interest in its use in other musculoskeletal conditions. Fracture repair is one area in which PTH may have a significant clinical impact. Multiple animal studies have shown that systemic PTH treatment of healing fractures increased both callus volume and return of mechanical competence in models of fracture healing. Whereas the potential for PTH has been established, the mechanism(s) by which PTH produces these effects remain elusive. MATERIALS AND METHODS: Closed femoral fractures were generated in 8-wk-old male C57Bl/6 mice followed by daily systemic injections of either saline (control) or 30 microg/kg PTH(1-34) for 14 days after fracture. Bones were harvested at days 2, 3, 5, 7, 10, 14, 21, and 28 after fracture and analyzed at the tissue level by radiography and histomorphometry and at the molecular and biochemical levels level by RNase protection assay (RPA), real-time PCR, and Western blot analysis. RESULTS: Quantitative muCT analysis showed that PTH treatment induced a larger callus cross-sectional area, length, and total volume compared with controls. Molecular analysis of the expression of extracellular matrix genes associated with chondrogenesis and osteogenesis showed that PTH treated fractures displayed a 3-fold greater increase in chondrogenesis relative to osteogenesis over the course of the repair process. In addition, chondrocyte hypertrophy occurred earlier in the PTH-treated callus tissues. Analysis of the expression of potential mediators of PTH actions showed that PTH treatment significantly induced the expression of Wnts 4, 5a, 5b, and 10b and increased levels of unphosphorylated, nuclear localized beta-catenin protein, a central feature of canonical Wnt signaling. CONCLUSIONS: These results showed that the PTH-mediated enhancement of fracture repair is primarily associated with an amplification of chondrocyte recruitment and maturation in the early fracture callus. Associated with these cellular effects, we observed an increase in canonical Wnt signaling supporting the conclusion that PTH effects on bone repair are mediated at least in part through the activation of Wnt-signaling pathways.     

A cost-effectiveness comparison of supported employment and rehabilitative day treatment

Recent research suggests that, for some people with severe mental illness, supported employment could improve vocational outcomes for little additional expense. This study describes the costs and client outcomes in one mental health center that converted two rehabilitative day treatment programs to supported employment. Converting from day treatment to supported employment improved vocational outcomes significantly without increasing costs. Although total costs for community treatment were lower in both sites after implementing supported employment, differences appeared to be due to decreasing unit costs over the study period. Results illustrate the importance of testing the effects of cost estimation methods on findings.This study was supported by West Central Services, the New Hampshire Division of Mental Health and Developmental Services, and NIMH grant K02-MH-00839. The authors are grateful to Jesse Turner and Phil Wyzik for facilitating the research.     

Nutrition et fonction immunitaireNutrition and immune function

A deficiency of total energy or of one or more essential nutrients, including vitamins A, B₆, B₁₂, C, and E, folic acid, zinc, iron, copper, selenium, essential amino acids and essential fatty acids, will impair immune function and increase susceptibility of the host to infectious pathogens. This is most likely because these nutrients are involved in the molecular and cellular responses to challenge of the immune system. Providing these nutrients to deficient individuals restores immune function and improves resistance to infection. Thus, appropriate nutrition is required in order for the host to maintain adequate immune defences towards bacteria, viruses, fungi, parasites and tumour celîs. Although the intakes of several nutrients which result in greatest enhancement of immune function appear to be greater than recommended intakes, excess intake of certain nutrients also impairs immune responses. Some nutrients (e.g. glutamine, arginine) may become limiting in critical illness and there is mounting evidence that provision of these will aid patient recovery.