[Three-dimensional finite element analysis responsible to bone cement with customized prosthesis of proximal segmental femur].

OBJECTIVES: To create three-dimensional finite element models for the large defect of proximal femur and the customized prosthesis of proximal segmental defect femur, and to analyze the influence on the stress distribution of femur-cement after the intramedullary implantation of different stem length prostheses. METHODS: Three-dimensional finite element models were established for the large defect of proximal femur and proximal femoral segmental prostheses with different stem-lengths (140 mm, 120 mm, 100 mm, 80 mm and 60 mm). The influence on stress distribution of femur-cement was analyzed for the different stem-length prostheses implanted. RESULTS: The stress on bone cement gradually increased from proximal end to distal end, and reached its highest value near the tip of prostheses. The prostheses with stem lengths of 120 mm, 100 mm, 80 mm and 60 mm could bring the cement mantle stress to the value beyond the fatigue strength of cement. Only when the intramedullary stem-length of prosthesis was 140 mm, the stress on the cement mantle was under the fatigue strength of cement. CONCLUSION: The intramedullary stem of the proximal femoral segmental prosthesis must have enough length to decrease the stress on the cement mantle in order to avoid the prosthesis loosening.

Activation of ERK signaling upon alternative protease nexin-1 internalization mediated by syndecan-1.

Protease nexin-1 (PN-1), an inhibitor of serine proteases, contributes to tissue homeostasis and influences the behavior of some tumor cells. The internalization of PN-1 protease complexes is considered to be mediated by the low-density lipoprotein receptor related protein 1 (LRP1). In this study, both wild-type and LRP1-/- mouse embryonic fibroblasts (MEF) were shown to internalize PN-1. Receptor associated protein (RAP) interfered with PN-1 uptake only in wild-type MEF cells, indicating that another receptor mediates PN-1 uptake in the absence of LRP1. In LRP1-/- MEF cells, inhibitor sensitivity and kinetic values (t(1/2) at 45 min) of PN-1 uptake showed a similarity to syndecan-1-mediated endocytosis. In these cells, PN-1 uptake was increased by overexpression of full-length syndecan-1 and decreased by RNA interference targeting this proteoglycan. Most important, in contrast to PKA activation known to be triggered by LRP1-mediated internalization, our study shows that syndecan-1-mediated internalization of PN-1 stimulated the Ras-ERK signaling pathway.

NGF-Tf Conjugate Prevents Degeneration of Substantia Nigra Neurons in a Mouse Model of Parkinson's Disease.

Nerve growth factor(NGF) was purified from Naja naja atra snake venom and conjugated to transferrin(Tf). This conjugate was intravenously injected into a mouse model of Parkinson's disease (PD). Both immunohistochemical staining and pathological detection showed that the NGF-Tf conjugate could prevent the loss of tyrosine hydroxylase-immunoreactive neurons located in substantia nigra and the cell counts of NGF group were 2 330.0+/-260.3, and those of the MPTP group and the control group were 797.0+/-121.4 and 2 381.0+/-158.0, respectively. In addition, electron microscopic examination revealed significant protection against demyelination and vacuolation in subtantia nigra neurons in contrast to the control group. The i.v. injected NGF-Tf conjugate also reversed the neurodegenerative changes such as karyopyknosis, chromatolysis and intracytoplasmic inclusion in diseased neurons.