Citations

Neuromyelitis optica (NMO)-immunoglobulin G (IgG) is a clinically validated serum biomarker that distinguishes relapsing central nervous system (CNS) inflammatory demyelinating disorders related to NMO from multiple sclerosis. This autoantibody targets astrocytic aquaporin-4 (AQP4) water channels. Clinical, radiological, and immunopathological data suggest that NMO-IgG might be pathogenic. Characteristic CNS lesions exhibit selective depletion of AQP4, with and without associated myelin loss; focal vasculocentric deposits of IgG, IgM, and complement; prominent edema; and inflammation. The effect of NMO-IgG on astrocytes has not been studied. In this study, we demonstrate that exposure to NMO patient serum and active complement compromises the membrane integrity of CNS-derived astrocytes. Without complement, astrocytic membranes remain intact, but AQP4 is endocytosed with concomitant loss of Na+-dependent glutamate transport and loss of the excitatory amino acid transporter 2 (EAAT2) . Our data suggest that EAAT2 and AQP4 exist in astrocytic membranes as a macromolecular complex. Transport-competent EAAT2 protein is up-regulated in differentiating astrocyte progenitors and in nonneural cells expressing AQP4 transgenically. Marked reduction of EAAT2 in AQP4-deficient regions of NMO patient spinal cord lesions supports our immunocytochemical and immunoprecipitation data. Thus, binding of NMO-IgG to astrocytic AQP4 initiates several potentially neuropathogenic mechanisms: complement activation, AQP4 and EAAT2 down-regulation, and disruption of glutamate homeostasis.

The number of osteoporotic hip fractures is projected to increase two to three fold in the next 30years. This will lead to increased mortality and nursing home placement with significant costs to our society. Although in clinical trials drug and hormone therapies have shown an important decrease in fracture risk there is a significant role of surgical implantation treatments to further reduce the risk in specific subpopulations. Strength testing was completed on four pairs of osteoporotic, two pairs of osteopenic, and two pairs of normal cadaver femurs. The fracturing was recorded with a video camera at 4000 frames per second. The specially designed test fixture was instrumented with three load cells to measure the femoral forces. Force and moment data were recorded simultaneously and correlated with the frames. The fracture force at the greater trochanter was used to characterize the strength of implanted∕nonimplanted osteoporotic femurs. All femurs began fracturing within about 60ms at a test speed of 100mm∕s. During the first 20ms, the relationship between force and displacement was nonlinear, but linear thereafter until the fracture occurs. The fracture events resolved completely within 10–20ms. The average strength increase of the implanted femurs was 79% compared to the nonimplanted controls. The simultaneous acquisition of fracture images and load data is a powerful tool to understand and characterize numerically the femoral fracture. This methodology allows the researcher to define the best metrics to compare competing reinforcement materials, implant designs and surgical procedures.

Temporomandibular joint disorder afflicts 10 million Americans, many of whom have osteoarthritis of the temporomandibular joint (TMJ). This condition can inflict severe pain and disrupt the lives of sufferers in many ways. Partial or total replacement of the temporomandibular joint is a last resort treatment option. Surgeons at Mayo Clinic believe a new hemijoint implant design coupled with unique surgical technique can improve joint kinematics and reduce pain. They are currently investigating a patent-pending implant design in a series of patient trials. The Division of Engineering at Mayo Clinic has developed a novel process for fabricating TMJ implants for this study. Computed Tomagraphy (CT) images of the surgical site are first converted into a 3D computer model of the mandibular fossa and condyle area. A fused deposition modeling process is used to create a plastic model of the anatomy, and the surgeons use that model to create a wax mold of the implant. The wax mold is laser scanned to create a 3D CAD model that can be machined with a standard four axis milling machine out of implant grade CoCrMo material. Because of the unique shape of the implant, the machining takes place in two phases, with the implant being refixtured between machining phases using a high strength industrial adhesive. Finally, the implant is polished, inspected, passivated and sterilized for surgery. This fabrication process has allowed Mayo Clinic surgeons to quickly and accurately test their unique implant design.