Ulrike Mueller

Shedding of the amyloid precursor protein-like protein APLP2 by disintegrin-metalloproteinases.

Cleavage of the amyloid precursor protein (APP) within the amyloid‐beta (Aβ) sequence by the α‐secretase prevents the formation of toxic Aβ peptides. It has been shown that the disintegrin‐metalloproteinases ADAM10 and TACE (ADAM17) act as α‐secretases and stimulate the generation of a soluble neuroprotective fragment of APP, APPsα. Here we demonstrate that the related APP‐like protein 2 (APLP2), which has been shown to be essential for development and survival of mice, is also a substrate for both proteinases. Overexpression of either ADAM10 or TACE in HEK293 cells increased the release of neurotrophic soluble APLP2 severalfold. The strongest inhibition of APLP2 shedding in neuroblastoma cells was observed with an ADAM10‐preferring inhibitor. Transgenic mice with neuron‐specific overexpression of ADAM10 showed significantly increased levels of soluble APLP2 and its C‐terminal fragments. To elucidate a possible regulatory mechanism of APLP2 shedding in the neuronal context, we examined retinoic acid‐induced differentiation of neuroblastoma cells. Retinoic acid treatment of two neuroblastoma cell lines upregulated the expression of both APLP2 and ADAM10, thus leading to an increased release of soluble APLP2.

Fretting and Corrosion in Modular Shoulder Arthroplasty: A Retrieval Analysis

Tribocorrosion in taper junctions of retrieved anatomic shoulder arthroplasty implants was evaluated. A comparison of the tribocorrosion between cobalt-chromium and titanium alloy stems was conducted and the observations were correlated with the individuals clinical data. Adverse effects caused by metal debris and subsequent elevated serum metal ion levels are frequently reported in total hip arthroplasty. In total shoulder arthroplasty, to date only a small number of retrieval analyses are available and even fewer address the issue of tribocorrosion at the taper junctions. A total of 36 retrieved hemiarthroplasties and total shoulder arthroplasties were assessed using the modified Goldberg score. The prevalence of fretting and corrosion was confirmed in this cohort. Titanium stems seem to be more susceptible to damage caused by tribocorrosion than cobalt-chromium stems. Furthermore, stemless designs offered less tribocorrosion at the taper junction than stemmed designs. A weak correlation between time to revision and increased levels of tribocorrosion was seen. Whether or not tribocorrosion can lead to adverse clinical reactions and causes failure of shoulder arthroplasties remains to be examined.

Ion release in ceramic bearings for total hip replacement: Results from an in vitro and an in vivo study

IntroductionLiterature on the potential release of trace elements following implantation of Zirconia-platelet toughened alumina (ZPTA) ceramic components is scant. The present study therefore analysed the in vitro and in vivo potential release of ions from ZPTA bearings.Material and MethodsAn in vitro and in vivo study was conducted. The in vitro study compared leaching in bovine serum from two groups: ZPTA ceramic heads and Co-28Cr-6Mo alloy heads, both 28-mm diameter. A third group without implant served as reference group.An in vivo clinical study compared trace elements in the whole blood of patients with 36-mm diameter ZPTA ceramic-on-ceramic articulation after three and 12 months. A cohort of subjects without any prosthesis was used as control group. The release of ions was determined by high resolution-inductively coupled plasma-mass spectrometry.ResultsIn the in vitro experiment, significant differences (p ≤ 0.01) in trace element release for chromium, cobalt and molybdenum were found, with increased levels of ion release in the Co-28Cr-6Mo metal group. The very low detection limit for yttrium allowed detection of a small yttrium release from the ZPTA heads, which was not confirmed by the in vivo study. No significant difference between the groups was found for strontium, aluminium, and zirconium.In the in vivo study, no relevant differences in ion levels between the reference group without any implant and the study group were found at the three and 12-month follow-up.ConclusionThis study supports that ZPTA ceramic articulation components are safe in terms of ion release, and may be an excellent alternative to bearings based on Co-28Cr-6Mo alloys.

Three-dimensional friction measurement during hip simulation

Objectives Wear of total hip replacements has been the focus of many studies. However, frictional effects, such as high loading on intramodular connections or the interface to the bone, as well as friction associated squeaking have recently increased interest about the amount of friction that is generated during daily activities. The aim of this study was thus to establish and validate a three-dimensional friction setup under standardized conditions. Materials and methods A standard hip simulator was modified to allow for high precision measurements of small frictional effects in the hip during three-dimensional hip articulation. The setup was verified by an ideal hydrostatic bearing and validated with a static-load physical pendulum and an extension-flexion rotation with a dynamic load profile. Additionally, a pendulum model was proposed for screening measurement of frictional effects based on the damping behavior of the angular oscillation without the need for any force/moment transducer. Finally, three-dimensional friction measurements have been realized for ceramic-on-polyethylene bearings of three different sizes (28, 36 and 40 mm). Results A precision of less than 0.2 Nm during three-dimensional friction measurements was reported, while increased frictional torque (resultant as well as taper torque) was measured for larger head diameters. These effects have been confirmed by simple pendulum tests and the theoretical model. A comparison with current literature about friction measurements is presented. Conclusions This investigation of friction is able to provide more information about a field that has been dominated by the reduction of wear. It should be considered in future pre-clinical testing protocols given by international organizations of standardization.

Wear Performance of Calcium Carbonate-Containing Knee Spacers

Articulating spacers should be wear-resistant and load-bearing to avoid prolonged immobilization of the patient and to reduce morbidity. However, due to the articulation of both components, a release of cement wear particles is to be expected. The aim of this study was to investigate the wear performance of a new spacer cement that contains calcium carbonate as a radio-opaque substance, in comparison to an established barium sulphate-containing spacer material, and also to characterize the amount, morphology, and size distributions of the released cement particles in detail. Force-controlled simulation was carried out on an AMTI knee simulator. The test parameters were in accordance with the standard ISO 14243-1 with a 50% reduced axial force. Tests were run for 500,000 cycles at a frequency of 1 Hz. For wear analysis, photographic documentation of the wear scars, gravimetric wear measurements and wear particle analysis were performed. The barium sulphate spacer material showed a total articular wear of 375.53 ± 161.22 mg. For the calcium carbonate-containing cement, reduced articular wear of 136.32 ± 37.58 mg was determined. Isolated cement wear particles of the barium sulphate-containing cement had a diameter of 0.429 ± 0.224 μm and were significantly larger compared to the calcium carbonate-containing cement (0.380 ± 0.216 μm, p = 0.02). The calcium carbonate-containing cement showed better wear performance in terms of gravimetric wear and particle release. Thus, calcium carbonate seems to be a promising material as a radio-opaque substrate in cement spacers.

Failure of Polyethylene Inlays in Cementless Total Hip Arthroplasty: A Retrieval Analysis.

A retrieval analysis has been performed on 50 polyethylene inlays of cementless screw ring implants (Mecring, Mecron, Berlin, Germany) to investigate the failure mechanism of this specific open cup hip arthroplasty design that has shown a high clinical failure rate. Design-specific damage modes like rim creep, collar fatigue, and backside wear were assessed. Furthermore, the inlays were measured using a CMM to determine deformation. In 90% backside wear was observed and collar fatigue occurred in 68% of the cases. Rim creep was present in 38% of the polyethylene inlays. In 90% of the cases the cup opening diameter was 32.1 mm or less and 46% had a diameter less than 32 mm. It seems that creep and deformation of the polyethylene leads to a reduced diameter at the cup opening and consequently decreased clearance. To avoid this type of failure, polyethylene inlays should be supported at the back by the cup to reduce the risk of ongoing creep deformation.

Genetic dissection of APP gene family for synaptic function, learning and memory

O1-03-04 GENETIC DISSECTION OFAPP GENE FAMILY FOR SYNAPTIC FUNCTION, LEARNING AND MEMORY Ulrike Mueller, Maja Klevanski, Sascha Weyer, Meike Hick, Andrea Delekate, Dorothee Aydin, Kristin Schaller, Martin Korte, David Wolfer, John Caldwell, Vootele Voikar, Heidelberg University, Heidelberg, Germany; 2 Heidelberg University, Heidelberg, Germany; 3 TU Braunschweig, Braunschweig; University of Colorado, Aurora, Colorado; TU Braunschweig, Braunschweig; Zurich University, Zurich; Zurich University, Zurich.