Investigation of the Repassivation Process of CoCrMo in Simulated Biological Fluids

A thorough investigation into the repassivation process of CoCrMo in multiple simulated biological environments has been undertaken, looking in detail at both the kinetics and composition of the reformed oxide film. Specific focus of this research was aimed at determining the effect of bovine serum albumin (BSA) on these features. The kinetics of repassivation were obtained by using a variety of electrochemical techniques. The current transients formed were fitted to a second-order decay curve, which accouts for two separate phases: coverage and growth. The reformation of the passive film was fastest in a phosphate buffered saline environment, with the presence of BSA delaying this process because it inhibits the oxygen-reduction reaction as it obstructs the active sites of the alloy when adsorbed onto the surface. The composition of the newly formed film was analyzed with x-ray photoelectron spectroscopy. As expected, the film was primarily composed of chromium (III) oxide with small contributions from cobalt and molybdenum oxides. In the presence of BSA, the quantity of molybdenum within the film was drastically reduced; it was shown to be extracted into the bulk solution via inductively coupled mass spectroscopy. This is observed because BSA is able to complex preferentially to the molybdenum ions when the alloy is exposed, extracting them into solution and altering the composition and integrity of the film

Adverse loading effects on tribocorrosive degradation of 28 mm metal-on-metal hip replacement bearings^*

Following the high clinical failure rates of metal-on-metal total hip replacements much work has been undertaken to investigate their poor performance. So called adverse loading scenarios such as acetabular inclination and microseparation have been attributed to indicators for failure of the implants. The ISO hip simulation standards (ISO 14242:1) still rely on gravimetric and ex situ analysis, considering only the total wear during articulation. Live in situ sensing can provide valuable insight into the degradation mechanisms of metallic interfaces under such scenarios. Clinical 28 mm diameter metal-on-metal components were articulated in a full-ISO hip simulator. The bearings were subjected to increasing angles of acetabular inclination and retroversion over short-term periods of articulation. Corrosive degradation was monitored during sliding by means of an in situ three-electrode cell. Changing acetabular inclination from 30° to 50° resulted in greater cathodic shifts in OCP upon the initiation of sliding; from −50 mV to as much as −150 mV. Under anodic polarisation (0 mV vs. Ag/AgCl) the resultant currents at the initiation of sliding also increased significantly with inclination; from approximately 4–10 µA to over 120 µA. Increased retroversion of 20° also resulted in increased anodic currents of 55–60 µA. Changing the nature of articulation demonstrated increased corrosive material loss compared to a standard ISO 14242 profile. The sole use of gravimetric assessment to determine a wear rate for hip replacement bearings under simulation can therefore neglect important degradation mechanisms, such as tribocorrosive loss in devices with metal sliding interfaces.</p

Highly lubricious SPMK-g-PEEK implant surfaces to facilitate rehydration of articular cartilage

To enable long lasting osteochondral defect repairs which preserve the native function of synovial joint counter-face, it is essential to develop surfaces which are optimised to support healthy cartilage function by providing a hydrated, low friction and compliant sliding interface. PEEK surfaces were modified using a biocompatible 3-sulfopropyl methacrylate potassium salt (SPMK) through UV photo-polymerisation, resulting in a ∼350 nm thick hydrophilic coating rich in hydrophilic anionic sulfonic acid groups. Characterisation was done through Fourier Transformed Infrared Spectroscopy, Focused Ion Beam Scanning Electron Microscopy, and Water Contact Angle measurements. Using a Bruker UMT TriboLab, bovine cartilage sliding tests were conducted with real-time strain and shear force measurements, comparing untreated PEEK, SPMK functionalised PEEK (SPMK-g-PEEK), and Cobalt Chrome Molybdenum alloy. Tribological tests over 2.5 h at physiological loads (0.75 MPa) revealed that SPMK-g-PEEK maintains low friction (μ &lt; 0.024) and minimises equilibrium strain, significantly reducing forces on the cartilage interface. Post-test analysis showed no notable damage to the cartilage interfacing against the SPMK functionalised surfaces. The application of a constitutive biphasic cartilage model to the experimental strain data reveals that SPMK surfaces increase the interfacial permeability of cartilage in sliding, facilitating fluid and strain recovery. Unlike previous demonstrations of sliding-induced tribological rehydration requiring specific hydrodynamic conditions, the SPMK-g-PEEK introduces a novel mode of tribological rehydration operating at low speeds and in a stationary contact area. SPMK-g-PEEK surfaces provide an enhanced cartilage counter-surface, which provides a highly hydrated and lubricious boundary layer along with supporting biphasic lubrication. Soft polymer surface functionalisation of orthopaedic implant surfaces are a promising approach for minimally invasive synovial joint repair with an enhanced bioinspired polyelectrolyte interface for sliding against cartilage. These hydrophilic surface coatings offer an enabling technology for the next generation of focal cartilage repair and hemiarthroplasty implant surfaces.</p

Investigation Into the Repassivation Kinetics of CoCrMo for Applications in a Simulated Biological Environment

The re-passivation kinetics and composition of the passive film of CoCrMo alloys in simulated body fluids have been investigated, with key emphasis being to assess the effect that proteins have on these features. The kinetics were analyzed using potentiostatic polarization, applying a second order exponential decay to the current transients obtained, which consists of two phases: coverage and thickening. Repassivation occurred quickest in a phosphate environment with presence of bovine serum albumin (BSA) hindering the process as it inhibits access of the oxidant. By using X-ray photoelectron spectroscopy (XPS) the composition of the re-passivated layer was studied. As expected, the film is mainly composed of chromium (III) oxide with small amounts of cobalt (II) oxide and molybdenum oxides (IV-VI). When exposed to BSA the percentage of molybdenum in the passive film decreases. This is shown to be due to the protein having a high affinity for the element causing it to be lost to solution when the metal was exposed to corrosion

Fretting–corrosion at the modular tapers interface: Inspection of standard ASTM F1875-98

Interest in the degradation mechanisms at the modular tapers interfaces has been renewed due to increased reported cases of adverse reactions to metal debris and the appearance of wear and corrosion at the modular tapers interfaces at revision. Over the past two decades, a lot of research has been expended to understand the degradation mechanisms, with two primary implant loading procedures and orientations used consistently across the literature. ASTM F1875-98 is often used as a guide to understand and benchmark the tribocorrosion processes occurring within the modular tapers interface. This article presents a comparison of the two methods outlined in ASTM F1875-98 as well as a critique of the standard considering the current paradigm in pre-clinical assessment of modular tapers

Gene set analysis for longitudinal gene expression data

<p>Abstract</p> <p>Background</p> <p>Gene set analysis (GSA) has become a successful tool to interpret gene expression profiles in terms of biological functions, molecular pathways, or genomic locations. GSA performs statistical tests for independent microarray samples at the level of gene sets rather than individual genes. Nowadays, an increasing number of microarray studies are conducted to explore the dynamic changes of gene expression in a variety of species and biological scenarios. In these longitudinal studies, gene expression is repeatedly measured over time such that a GSA needs to take into account the within-gene correlations in addition to possible between-gene correlations.</p> <p>Results</p> <p>We provide a robust nonparametric approach to compare the expressions of longitudinally measured sets of genes under multiple treatments or experimental conditions. The limiting distributions of our statistics are derived when the number of genes goes to infinity while the number of replications can be small. When the number of genes in a gene set is small, we recommend permutation tests based on our nonparametric test statistics to achieve reliable type I error and better power while incorporating unknown correlations between and within-genes. Simulation results demonstrate that the proposed method has a greater power than other methods for various data distributions and heteroscedastic correlation structures. This method was used for an IL-2 stimulation study and significantly altered gene sets were identified.</p> <p>Conclusions</p> <p>The simulation study and the real data application showed that the proposed gene set analysis provides a promising tool for longitudinal microarray analysis. R scripts for simulating longitudinal data and calculating the nonparametric statistics are posted on the North Dakota INBRE website <url>http://ndinbre.org/programs/bioinformatics.php</url>. Raw microarray data is available in Gene Expression Omnibus (National Center for Biotechnology Information) with accession number GSE6085.</p

Malignant melanoma of the conjunctiva: a case report with examination of KIT and PDGFRA

Although many clinicopathological studies of malignant melanoma of the conjunctiva have been reported, there have been no studies of the expression and gene mutations of KIT and PDGFRA in melanoma of the conjunctiva. A 69-year-old Japanese woman consulted our hospital because of black mass (0.7 × 0.7 × 0.6 cm) in the conjunctiva. A biopsy was taken. The biopsy showed malignant epithelioid cells with melanin deposition. Immunohistochemically, the tumor was positive for S100 protein, HMB45, p53, Ki-67 (labeling=30%), KIT and PDGFRA. The tumor was negative for pancytokeratins (AE1/3 and CAM5.2). A genetic analysis using PCR-direct sequencing revealed no mutations of KIT gene (exons 9, 11, 13, and 17) and PDGFRA gene (exons 12 and 18). The pathological diagnosis was conjunctival melanoma. Despite chemotherapy, the patient developed multiple metastases of melanoma, and died of melanoma 7 years after the biopsy. In conclusion, the author reported a case of melanoma of conjunctive expressing KIT and PDGFRA proteins without gene mutations of KIT and PDGFRA

Amplification and PI3KCA Mutation in a Case of Sclerosing Rhabdomyosarcoma

A rare sclerosing variant of rhabdomyosarcoma characterized by prominent hyalinization and pseudovascular pattern has recently been described as a subtype biologically distinct from embryonal, alveolar, and pleomorphic forms. We present cytogenetic and molecular findings as well as experimental studies of an unusual case of sclerosing rhabdomyosarcoma. The primary lesion arose within the plantar subcutaneous tissue of the left foot of an otherwise healthy 23-year-old male who eventually developed pulmonary nodules despite systemic chemotherapy. Two genetic abnormalities identified in surgical and/or autopsy samples of the tumor were introduced into 10T1/2 murine fibroblasts to determine whether these genetic changes cooperatively facilitated transformation and growth. Cytogenetic analysis revealed a complex abnormal hyperdiploid clone, and MDM2 gene amplification was confirmed by fluorescence in situ hybridization. Cancer gene mutation screening using a combination of multiplexed PCR and mass spectroscopy revealed a PIK3CA exon 20 H1047R mutation in the primary tumor, lung metastasis, and liver metastasis. However, this mutation was not cooperative with MDM2 overexpression in experimental assays for transformation or growth. Nevertheless, MDM2 and PIK3CA are genes worthy of further investigation in patients with sclerosing rhabdomyosarcoma and might be considered in the enrollment of these patients into clinical trials of targeted therapeutics

Novel Biomarkers Distinguishing Active Tuberculosis from Latent Infection Identified by Gene Expression Profile of Peripheral Blood Mononuclear Cells

BACKGROUND: Humans infected with Mycobacterium tuberculosis (MTB) can delete the pathogen or otherwise become latent infection or active disease. However, the factors influencing the pathogen clearance and disease progression from latent infection are poorly understood. This study attempted to use a genome-wide transcriptome approach to identify immune factors associated with MTB infection and novel biomarkers that can distinguish active disease from latent infection. METHODOLOGY/PRINCIPAL FINDINGS: Using microarray analysis, we comprehensively determined the transcriptional difference in purified protein derivative (PPD) stimulated peripheral blood mononuclear cells (PBMCs) in 12 individuals divided into three groups: TB patients (TB), latent TB infection individuals (LTBI) and healthy controls (HC) (n = 4 per group). A transcriptional profiling of 506 differentially expressed genes could correctly group study individuals into three clusters. Moreover, 55- and 229-transcript signatures for tuberculosis infection (TB&LTBI) and active disease (TB) were identified, respectively. The validation study by quantitative real-time PCR (qPCR) performed in 83 individuals confirmed the expression patterns of 81% of the microarray identified genes. Decision tree analysis indicated that three genes of CXCL10, ATP10A and TLR6 could differentiate TB from LTBI subjects. Additional validation was performed to assess the diagnostic ability of the three biomarkers within 36 subjects, which yielded a sensitivity of 71% and specificity of 89%. CONCLUSIONS/SIGNIFICANCE: The transcription profiles of PBMCs induced by PPD identified distinctive gene expression patterns associated with different infectious status and provided new insights into human immune responses to MTB. Furthermore, this study indicated that a combination of CXCL10, ATP10A and TLR6 could be used as novel biomarkers for the discrimination of TB from LTBI

Fulminant Staphylococcus lugdunensis septicaemia following a pelvic varicella-zoster virus infection in an immune-deficient patient: a case report

<p>Abstract</p> <p>Introduction</p> <p>The deadly threat of systemic infections with coagulase negative <it>Staphylococcus lugdunensis </it>despite an appropriate antibiotic therapy has only recently been recognized. The predominant infectious focus observed so far is left-sided native heart valve endocarditis, but bone and soft tissue infections, septicaemia and vascular catheter-related bloodstream infections have also been reported. We present a patient with a fatal <it>Staphylococcus lugdunensis </it>septicaemia following zoster bacterial superinfection of the pelvic region.</p> <p>Case presentation</p> <p>A 71-year old male diagnosed with IgG kappa plasmocytoma presented with a conspicuous weight loss, a hypercalcaemic crisis and acute renal failure. After initiation of haemodialysis treatment his condition improved rapidly. However, he developed a varicella-zoster virus infection of the twelfth thoracic dermatome requiring intravenous acyclovir treatment. Four days later the patient presented with a fulminant septicaemia. Despite an early intravenous antibiotic therapy with ciprofloxacin, piperacillin/combactam and vancomycin the patient died within 48 hours, shortly before the infective isolate was identified as <it>Staphylococcus lugdunensis </it>by polymerase chain reaction.</p> <p>Conclusion</p> <p>Despite <it>S. lugdunensis </it>belonging to the family of coagulase-negative staphylococci with an usually low virulence, infections with <it>S. lugdunensis </it>may be associated with an aggressive course and high mortality. This is the first report on a <it>Staphylococcus lugdunensis </it>septicaemia following a zoster bacterial superinfection of the pelvic region.</p