Elution of gentamicin and vancomycin from polymethylmethacrylate beads and hip spacers in vivo

Background and purpose Late infections after total hip arthroplasty are still a problem. Treatment procedures include resection arthroplasty with implantation of antibiotic-loaded beads or implantation of an antibiotic-impreganted spacer. However, little is known about antibiotic elution from bone cement beyond the first 2–3 postoperative days in humans

Ubiquitination of CXCR7 Controls Receptor Trafficking

The chemokine receptor CXCR7 binds CXCL11 and CXCL12 with high affinity, chemokines that were previously thought to bind exclusively to CXCR4 and CXCR3, respectively. Expression of CXCR7 has been associated with cardiac development as well as with tumor growth and progression. Despite having all the canonical features of G protein-coupled receptors (GPCRs), the signalling pathways following CXCR7 activation remain controversial, since unlike typical chemokine receptors, CXCR7 fails to activate Gαi-proteins. CXCR7 has recently been shown to interact with β-arrestins and such interaction has been suggested to be responsible for G protein-independent signals through ERK-1/2 phosphorylation. Signal transduction by CXCR7 is controlled at the membrane by the process of GPCR trafficking. In the present study we investigated the regulatory processes triggered by CXCR7 activation as well as the molecular interactions that participate in such processes. We show that, CXCR7 internalizes and recycles back to the cell surface after agonist exposure, and that internalization is not only β-arrestin-mediated but also dependent on the Serine/Threonine residues at the C-terminus of the receptor. Furthermore we describe, for the first time, the constitutive ubiquitination of CXCR7. Such ubiquitination is a key modification responsible for the correct trafficking of CXCR7 from and to the plasma membrane. Moreover, we found that CXCR7 is reversibly de-ubiquitinated upon treatment with CXCL12. Finally, we have also identified the Lysine residues at the C-terminus of CXCR7 to be essential for receptor cell surface delivery. Together these data demonstrate the differential regulation of CXCR7 compared to the related CXCR3 and CXCR4 receptors, and highlight the importance of understanding the molecular determinants responsible for this process

Outcome of prosthesis exchange for infected knee arthroplasty: the effect of treatment approach: A systematic review of the literature

Background and purpose Two-stage revision remains the gold standard in the treatment of infected knee arthroplasty. Lately, good long-term results of direct exchange arthroplasty have been reported. The purpose of this literature review is to compare the clinical outcome achieved with one-stage revision and two-stage revision with different types of spacers

A Drosophila Model for EGFR-Ras and PI3K-Dependent Human Glioma

Gliomas, the most common malignant tumors of the nervous system, frequently harbor mutations that activate the epidermal growth factor receptor (EGFR) and phosphatidylinositol-3 kinase (PI3K) signaling pathways. To investigate the genetic basis of this disease, we developed a glioma model in Drosophila. We found that constitutive coactivation of EGFR-Ras and PI3K pathways in Drosophila glia and glial precursors gives rise to neoplastic, invasive glial cells that create transplantable tumor-like growths, mimicking human glioma. Our model represents a robust organotypic and cell-type-specific Drosophila cancer model in which malignant cells are created by mutations in signature genes and pathways thought to be driving forces in a homologous human cancer. Genetic analyses demonstrated that EGFR and PI3K initiate malignant neoplastic transformation via a combinatorial genetic network composed primarily of other pathways commonly mutated or activated in human glioma, including the Tor, Myc, G1 Cyclins-Cdks, and Rb-E2F pathways. This network acts synergistically to coordinately stimulate cell cycle entry and progression, protein translation, and inappropriate cellular growth and migration. In particular, we found that the fly orthologs of CyclinE, Cdc25, and Myc are key rate-limiting genes required for glial neoplasia. Moreover, orthologs of Sin1, Rictor, and Cdk4 are genes required only for abnormal neoplastic glial proliferation but not for glial development. These and other genes within this network may represent important therapeutic targets in human glioma

Diagnosis and Management of Infected Total Knee Arthroplasty§

Infection following total knee arthroplasty can be difficult to diagnose and treat. Diagnosis is multifactorial and relies on the clinical picture, radiographs, bone scans, serologic tests, synovial fluid examination, intra-operative culture and histology. Newer techniques including ultrasonication and molecular diagnostic studies are playing an expanded role. Two-stage exchange arthroplasty with antibiotic cement and 4-6 weeks of intravenous antibiotic treatment remains the most successful intervention for infection eradication. There is no consensus on the optimum type of interval antibiotic cement spacer. There is a limited role for irrigation and debridement, direct one-stage exchange, chronic antibiotic suppression and salvage procedures like arthrodesis and amputation. We examine the literature on each of the diagnostic modalities and treatment options in brief and explain their current significance