Survival of DA neurons is independent of CREM upregulation in absence of CREB.

cAMP response element binding protein (CREB) and the related factors CREM (cAMP response element modulator) and ATF1 (activation transcription factor 1) are bZIP-domain-containing transcription factors activated through cAMP and other signaling pathways. The disruption of CREB function in developing and mature neurons affects their development and survival when associated with loss of CREM. Since dopaminergic (DA) neurons are affected in several neurological diseases, we generated CREB conditional mutants in DA neurons by using a newly generated transgenic Cre line targeting the dopaminergic system (DATCre). Here we report the generation and analysis of mutant mice lacking CREB in DA neurons (CREB(DATCre) mutants). During adulthood, lack of CREB leads to a partial loss of DA neurons. Since CREM is upregulated in absence of CREB, we have introduced this mutation in a CREM-/- genetic background to assess a compensatory role of CREM. Additional inactivation of CREM does not lead to a more severe phenotype.

Comparative in vitro wear testing of PEEK and UHMWPE capped metacarpophalangeal prostheses.

Six metacarpophalangeal prostheses were each wear tested to five million cycles. Each prosthesis consisted of a metacarpal component with an approximately hemispherical shell on a titanium body, articulating against a titanium phalangeal component. Four prostheses had a shell made from ultra-high molecular weight polyethylene (UHMWPE) and two had a shell made from polyether ether ketone (PEEK). The tests were undertaken using a finger wear simulator. Despite pre-soaking and the use of control components, lubricant uptake by the metacarpal components was significant. Gravimetrically, the UHMWPE test components showed a greater weight gain than the UHMWPE control components. Therefore there was no apparent wear of any of the UHMWPE test metacarpal components. The original concentric machining marks of the UHMWPE components could still be seen after five million cycles of testing. For the metacarpal components with PEEK shells, gravimetric wear could be measured. Gravimetrically, all of the titanium phalangeal components showed little or no wear. Light scratches in the direction of sliding appeared on the articulating faces of all metacarpal and phalangeal test components, indicating slight abrasive wear.

Tribology considerations for hip joint articulations in relation to the "new orthopaedic patient".

The purpose of this review is to examine alternative bearings used in total hip arthroplasty (THA) and discuss the specific tribologic needs of the "New Orthopaedic Patient". As orthopaedic patients today are younger and more active, there is a clear need for hip joint implants and articulations minimising the amount of wear and guarantying better stability. Recent modern developments in tribology with highly cross-linked polyethylenes and hard-on-hard bearings allow the safe and effective use of larger diameter articulations in THA.

Transient elastohydrodynamic lubrication analysis of metal-on-metal hip implant under simulated walking conditions.

The transient elastohydrodynamic lubrication (EHL) analysis was performed in this study for a typical metal-on-metal bearing employing a polyethylene backing underneath a metallic cup inlay under dynamic operating conditions of load and speed representative of normal walking. A ball-in-socket configuration was adopted to represent the articulation between the femoral head and the acetabular cup. The governing Reynolds and elasticity equations were solved simultaneously by using both finite difference and finite element methods. The predicted transient film thickness from the present study was compared with the estimation based on the quasi-static analysis. It was found that the polyethylene backing employed in the typical metal-on-metal hip bearing, combined with dynamic squeeze-film action, significantly improved the transient lubricant film thickness under cyclic walking and consequently a fluid film lubrication regime was possible for smooth bearing surfaces with an average roughness less than 0.005 microm.

Effect of wear of bearing surfaces on elastohydrodynamic lubrication of metal-on-metal hip implants.

The effect of geometry change of the bearing surfaces owing to wear on the elastohydrodynamic lubrication (EHL) of metal-on-metal (MOM) hip bearings has been investigated theoretically in the present study. A particular MOM Metasul bearing (Zimmer GmbH) was considered, and was tested in a hip simulator using diluted bovine serum. The geometry of the worn bearing surface was measured using a coordinate measuring machine (CMM) and was modelled theoretically on the assumption of spherical geometries determined from the maximum linear wear depth and the angle of the worn region. Both the CMM measurement and the theoretical calculation were directly incorporated into the elastohydrodynamic lubrication analysis. It was found that the geometry of the original machined bearing surfaces, particularly of the femoral head with its out-of-roundness, could lead to a large reduction in the predicted lubricant film thickness and an increase in pressure. However, these non-spherical deviations can be expected to be smoothed out quickly during the initial running-in period. For a given worn bearing surface, the predicted lubricant film thickness and pressure distribution, based on CMM measurement, were found to be in good overall agreement with those obtained with the theoretical model based on the maximum linear wear depth and the angle of the worn region. The gradual increase in linear wear during the running-in period resulted in an improvement in the conformity and consequently an increase in the predicted lubricant film thickness and a decrease in the pressure. For the Metasul bearing tested in an AMTI hip simulator, a maximum total linear wear depth of approximately 13 microm was measured after 1 million cycles and remained unchanged up to 5 million cycles. This resulted in a threefold increase in the predicted average lubricant film thickness. Consequently, it was possible for the Metasul bearing to achieve a fluid film lubrication regime during this period, and this was consistent with the minimal wear observed between 1 and 5 million cycles. However, under adverse in vivo conditions associated with start-up and stopping and depleted lubrication, wear of the bearing surfaces can still occur. An increase in the wear depth beyond a certain limit was shown to lead to the constriction of the lubricant film around the edge of the contact conjunction and consequently to a decrease in the lubricant film thickness. Continuous cycles of a running-in wear period followed by a steady state wear period may be inevitable in MOM hip implants. This highlights the importance of minimizing the wear in these devices during the initial running-in period, particularly from design and manufacturing points of view.

Steady-state elastohydrodynamic lubrication analysis of a metal-on-metal hip implant employing a metallic cup with an ultra-high molecular weight polyethylene backing.

The elastohydrodynamic lubrication (EHL) analysis was carried out in this study for a 28 mm diameter metal-on-metal hip prosthesis employing a metallic cup with an ultra-high molecular weight polyethylene (UHMWPE) backing under a simple steady state rotation representing the flexion/extension during walking. Both Reynolds and elasticity equations were coupled and solved numerically by the finite difference method. The elastic deformation was determined by means of the fast Fourier transform (FFT) technique using the displacement coefficients obtained from the finite element method. Excellent agreement of the predicted elastic deformation was obtained between the FFT technique and the conventional direct summation method. The number of grid points used in the lubrication analysis was found to be important in predicting accurate film thicknesses, particularly at low viscosities representative of physiological lubricants. The effect of the clearance between the femoral head and the acetabular cup on the predicted lubricant film thickness was shown to be significant, while the effect of load was found to be negligible. Overall, the UHMWPE backing was found not only to reduce the contact pressure as identified in a previous study by the authors (Liu et al., 2003) but also significantly to increase the lubricant film thickness for the 28 mm diameter metal-on-metal hip implant, as compared with a metallic mono-block cup.

[Tribologic investigation of a metacarpophalangeal prosthesis]. / Tribologische Untersuchungen einer metakarpophalangealen Prothese.

It is the goal of this paper to introduce modern tribological investigations into the development of a new finger prosthesis, with the particular aim of optimising the material component.A new, unconstrained metacarpophalangeal prosthesis restoring the anatomy of the joint has been developed in two versions (UHMWPE-metal and PEEK-metal). In order to determine the version having better wear behaviour, these two versions were tested on a Joyce finger simulator. As the UHMWPE-metal version showed a lower amount of wear in vitro, this version was chosen to conduct a clinical study. This investigation showed the importance of conducting an in vitro wear test before any clinical studies. Such tests allow the optimisation of the wear behaviour of the tested metacarpophalangeal prosthesis and therefore permit a minimisation of the possible risks to the patients.

Contact mechanics of metal-on-metal hip implants employing a metallic cup with a UHMWPE backing.

The contact mechanics in metal-on-metal hip implants employing a cobalt chromium acetabular cup with an ultra-high molecular weight polyethylene (UHMWPE) backing were analysed in the present study using the finite element method. A general modelling methodology was developed to examine the effects of the interfacial boundary conditions between the UHMWPE backing and a titanium shell for cementless fixation, the coefficient of friction and the loading angle on the predicted contact pressure distribution at the articulating surfaces. It was found that the contact mechanics at the bearing surfaces were significantly affected by the UHMWPE backing. Consequently, a relatively constant pressure distribution was predicted within the contact conjunction, and the maximum contact pressure occurred towards the edge of the contact. On the other hand, the interfacial boundary condition between the UHMWPE backing and the titanium shell, the coefficient of friction and the loading angle were found to have a negligible effect on the contact mechanics at the bearing surfaces. Overall, the magnitude of the contact pressure was significantly reduced, compared with a similar cup without the UHMWPE backing. The importance of the UHMWPE backing on the tribological performance of metal-on-metal hip implants is discussed.

In vivo tribological performance of 231 metal-on-metal hip articulations.

231 cobalt-chromium metal-on-metal (METASUL design) retrieved articulations (297 retrieved components) were examined for their in vivo wear behaviour. A running-in period of about one year is observed where the in vivo wear rate for the whole articulation is approximately 35 m/year. After this running-in period, the measured in vivo wear rate of the whole articulation decreases to about 5 m/year. The metal-on-metal articulation can be considered as a very low wear articulation system. The combination of the specially designed components is mandatory to assure this low wear behaviour. In case of a mismatched bearing (stainless steel head - cobalt-chromium inlay), large amount of wear was measured. (Hip International 2002; 2: 73-6).

In vitro comparison of the two hard-hard articulations for total hip replacements.

Polyethylene particle disease is one of the major causes of late aseptic loosening of total hip replacement. Two hard-hard articulations (alumina-on-alumina and metal-on-metal) have been developed in Europe as an alternative to the ultra-high molecular weight polyethylene (UHMWPE) articulations. Even though these hard-hard articulations are on the market and numerous reports have been published about them, only a very limited number of studies allowing a direct in vitro comparison of the two articulations have been published so far. This paper compares in vitro these two types of articulation (alumina-on-alumina and metal-on-metal), which have been tested with a hip simulator for their tribological behaviour using exactly the same experimental methodology. This comparison shows that these two types of hard-hard articulation have very similar abrasive wear behaviour with four main features: 1. A running-in wear period (1 x 10(6) cycles) gives a cumulative wear of about 20 microns with head diameters of 28 mm. 2. After the running-in wear, there is a stabilization of the linear wear behaviour with a low linear wear rate/10(6) cycles for both types of articulation. 3. The volumetric wear rate of both articulations (< 2.0 mm3/year for head diameters of 28 mm) is significantly lower than that observed for metal-on-polyethylene or ceramic-on-polyethylene articulations having the same head diameter. 4. Abrasive wear is readily apparent (indicating a mixed lubrication regime) with both types of articulation. The extremely low wear performance of these articulations is confirmed and they constitute a low-wear alternative to the UHMWPE articulations currently used.

Analysis of 118 second-generation metal-on-metal retrieved hip implants.

Osteolysis is due to particulate wear debris and is responsible for the long-term failure of total hip replacements. It has stimulated the development of alternative joint surfaces such as metal-on-metal or ceramic-on-ceramic implants. Since 1988 the second-generation metal-on-metal implant Metasul has been used in over 60 000 hips. Analysis of 118 retrieved specimens of the head or cup showed rates of wear of approximately 25 microm for the whole articulation per year in the first year, decreasing to about 5 microm per year after the third. Metal surfaces have a 'self-polishing' capacity. Scratches are worn out by further joint movement. Volumetric wear was decreased some 60-fold compared with that of metal-on-polyethylene implants, suggesting that second-generation metal-on-metal prostheses may considerably reduce osteolysis.

Metal-on-metal articulation for artificial hip joints: laboratory study and clinical results.

As wear is inevitable with artificial joint replacement, it has to be minimized to avoid possible aseptic loosening following osteolysis due to particle-initiated foreign body reaction. Co-Cr-Mo-C alloys have a long history with only minimum wear when articulating with themselves. This investigation shows that the choice of the alloy has an effect on the wear rate of this articulation couple. Tribological studies in a screening device, a pendulum apparatus and a hip joint simulator showed a marked influence of the environment as well as the diameter of the implants with metal-on-metal articulation. A wear-resistant combination with low friction characteristics has been developed by using a wrought Co-Cr-Mo-C alloy and reducing the implant diameter to 28 mm. Clinical wear rates are comparable with laboratory data and demonstrate the potential of the metal-on-metal articulation to solve the problem of wear-induced osteolysis of hip joint endoprostheses.