Calcific Enthesopathy of the Superior Extensor Retinaculum - An Unusual Cause of Medial Ankle Pain.

Aim of the study: Ankle pain can present a clinical dilemma to the foot and ankle surgeons, with a multitude of entities to which the symptoms could potentially be attributed. Enthesopathy around the ankle joint could be due to overuse, injury, inflammation or infection. Calcific ligamentous enthesopathy around the ankle is a well-recognised condition with a spectrum of causes. Case description: To our knowledge, a clinically symptomatic presentation of calcific enthesopathy specifically affecting the entheses of the superior extensor retinaculum has not been described in the literature. We report the first case of symptomatic calcific enthesopathy of the superior extensor retinaculum in a healthy young female, and highlight the role of radiological interventions in its diagnosis. The condition was managed successfully by ultrasound-guided barbotage. Conclusions: Calcific enthesopathy of the attachment of the superior extensor retinaculum is a rare condition that should be considered in the differential diagnosis of patients with medial ankle pain.

Parallel synthesis of poly(amino ether)-templated plasmonic nanoparticles for transgene delivery.

Plasmonic nanoparticles have been increasingly investigated for numerous applications in medicine, sensing, and catalysis. In particular, gold nanoparticles have been investigated for separations, sensing, drug/nucleic acid delivery, and bioimaging. In addition, silver nanoparticles demonstrate antibacterial activity, resulting in potential application in treatments against microbial infections, burns, diabetic skin ulcers, and medical devices. Here, we describe the facile, parallel synthesis of both gold and silver nanoparticles using a small set of poly(amino ethers), or PAEs, derived from linear polyamines, under ambient conditions and in absence of additional reagents. The kinetics of nanoparticle formation were dependent on PAE concentration and chemical composition. In addition, yields were significantly greater in case of PAEs when compared to 25 kDa poly(ethylene imine), which was used as a standard catonic polymer. Ultraviolet radiation enhanced the kinetics and the yield of both gold and silver nanoparticles, likely by means of a coreduction effect. PAE-templated gold nanoparticles demonstrated the ability to deliver plasmid DNA, resulting in transgene expression, in 22Rv1 human prostate cancer and MB49 murine bladder cancer cell lines. Taken together, our results indicate that chemically diverse poly(amino ethers) can be employed for rapidly templating the formation of metal nanoparticles under ambient conditions. The simplicity of synthesis and chemical diversity make PAE-templated nanoparticles useful tools for several applications in biotechnology, including nucleic acid delivery.

Discovery of antibiotics-derived polymers for gene delivery using combinatorial synthesis and cheminformatics modeling.

We describe the combinatorial synthesis and cheminformatics modeling of aminoglycoside antibiotics-derived polymers for transgene delivery and expression. Fifty-six polymers were synthesized by polymerizing aminoglycosides with diglycidyl ether cross-linkers. Parallel screening resulted in identification of several lead polymers that resulted in high transgene expression levels in cells. The role of polymer physicochemical properties in determining efficacy of transgene expression was investigated using Quantitative Structure-Activity Relationship (QSAR) cheminformatics models based on Support Vector Regression (SVR) and 'building block' polymer structures. The QSAR model exhibited high predictive ability, and investigation of descriptors in the model, using molecular visualization and correlation plots, indicated that physicochemical attributes related to both, aminoglycosides and diglycidyl ethers facilitated transgene expression. This work synergistically combines combinatorial synthesis and parallel screening with cheminformatics-based QSAR models for discovery and physicochemical elucidation of effective antibiotics-derived polymers for transgene delivery in medicine and biotechnology.

Poly(aminoether)-gold nanorod assemblies for shRNA plasmid-induced gene silencing.

Gold nanorods (GNRs) have emerged as promising nanomaterials for biosensing, imaging, photothermal hyperthermia treatments, and therapeutic delivery for several diseases. We generated poly(aminoether)-GNR nanoassemblies using a layer-by-layer deposition approach based on the 1,4C-1,4Bis polymer from a library recently synthesized in our laboratory. Subtoxic concentrations of 1,4C-1,4Bis-GNR nanoassemblies were employed to deliver expression vectors that express shRNA ("shRNA plasmid") against firefly luciferase gene to knock down expression of the protein constitutively expressed in prostate cancer cells. The role of hydrodynamic size and zeta potential in determining nanoassembly mediated luciferase silencing was investigated. Finally, the theranostic potential of 1,4C-1,4Bis-GNR nanoassemblies was demonstrated using live cell two-photon induced luminescence bioimaging. Our results indicate that poly(aminoether)-GNR nanoassemblies are a promising theranostic platform for delivery of therapeutic payloads capable of simultaneous gene silencing and bioimaging.

Delivery of plasmid DNA to mammalian cells using polymer-gold nanorod assemblies.

Functionalized and surface-modified gold nanorods (GNRs) have emerged as promising vehicles for the delivery of several therapeutic agents. Ease of functionalization, increased stability, biocompatibility, and size-dependent plasmonic properties make gold nanorods attractive in sensing, imaging, and delivery to different cellular types. Here, we demonstrate the use of polyelectrolyte-coated GNRs (PE-GNRs) for delivering plasmid DNA to mammalian cells for transgene expression.

A prospective series of patients with chronic Achilles tendinopathy treated with autologous-conditioned plasma injections combined with exercise and therapeutic ultrasonography.

Chronic Achilles tendinopathy is a difficult problem to manage, because it can result in significant patient morbidity. We conducted a prospective case series involving 26 patients (2 bilateral cases) with painful and ultrasound-confirmed Achilles tendinopathy for a minimum duration of 6 months. Our objective was to assess whether this condition can be effectively treated with a treatment protocol combining an intratendinous autologous-conditioned plasma injection followed by a standardized rehabilitation protocol. The rehabilitation protocol consisted of full weightbearing in a pneumatic cast boot for 6 weeks, therapeutic ultrasound treatment, and an eccentric exercise program. Our results showed statistically significant improvements in terms of pain (p < .0001), other symptoms (p = .0003), activities of daily living (p = .0002), sports activities (p = .0001), and quality of life (p = .0002). We believe that the use of autologous-conditioned plasma can provide a potential treatment solution for chronic Achilles tendinopathy.

Generation of a focused poly(amino ether) library: polymer-mediated transgene delivery and gold-nanorod based theranostic systems.

A focused library of twenty-one cationic poly(amino ethers) was synthesized following ring-opening polymerization of two diglycidyl ethers by different oligoamines. The polymers were screened in parallel for plasmid DNA (pDNA) delivery, and transgene expression efficacies of individual polymers were compared to those of 25 kDa polyethylenimine (PEI), a current standard for polymer-mediated transgene delivery. Seven lead polymers that demonstrated higher transgene expression than PEI in pancreatic and prostate cancer cells lines were identified from the screen. All seven lead polymers showed highest transgene expression at a polymer:pDNA weight ratio of 5:1 in the MIA PaCa-2 pancreatic cancer cell line. Among the conditions studied, transgene expression efficacy correlated with minimal polymer cytotoxicity but not polyplex sizes. In addition, this study indicated that methylene spacing between amine centers in the monomers, amine content, and molecular weight of the polymers are all significant factors and should be considered when designing polymers for transgene delivery. A lead effective polymer was employed for coating gold nanorods, leading to theranostic nanoassemblies that possess combined transgene delivery and optical imaging capabilities, leading to potential theranostic systems.

Transgene delivery using poly(amino ether)-gold nanorod assemblies.

Gold nanorods (GNRs) have emerged as promising nanomaterials for biosensing, imaging, photothermal treatment, and therapeutic delivery for several diseases, including cancer. We have generated poly(amino ether)-functionalized gold nanorods (PAE-GNRs) using a layer-by-layer deposition approach; polymers from a poly(amino ether) library recently synthesized in our laboratory were employed to generate the PAE-GNR assemblies. PAE-GNR assemblies demonstrate long-term colloidal stability as well as the capacity to bind plasmid DNA by means of electrostatic interactions. Sub-toxic concentrations of PAE-GNRs were employed to deliver plasmid DNA to prostate cancer cells in vitro. PAE-GNRs generated using 1,4C-1,4Bis, a cationic polymer from our laboratory demonstrated significantly higher transgene expression and exhibited lower cytotoxicities when compared to similar assemblies generated using 25 kDa poly(ethylene imine) (PEI25k-GNRs), a current standard for polymer-mediated gene delivery. The roles of polyelectrolyte chemistry and zeta-potential in determining transgene expression efficacies of PAE-GNR assemblies were investigated. Our results indicate that stable and effective PAE-GNR assemblies are a promising engineered platform for transgene delivery. PAE-GNRs also have the potential to be used simultaneously for photothermal ablation, photothermally enhanced drug and gene delivery, and biological imaging, thus making them a powerful theranostic platform.

Discovery of cationic polymers for non-viral gene delivery using combinatorial approaches.

Gene therapy is an attractive treatment option for diseases of genetic origin, including several cancers and cardiovascular diseases. While viruses are effective vectors for delivering exogenous genes to cells, concerns related to insertional mutagenesis, immunogenicity, lack of tropism, decay and high production costs necessitate the discovery of non-viral methods. Significant efforts have been focused on cationic polymers as non-viral alternatives for gene delivery. Recent studies have employed combinatorial syntheses and parallel screening methods for enhancing the efficacy of gene delivery, biocompatibility of the delivery vehicle, and overcoming cellular level barriers as they relate to polymer-mediated transgene uptake, transport, transcription, and expression. This review summarizes and discusses recent advances in combinatorial syntheses and parallel screening of cationic polymer libraries for the discovery of efficient and safe gene delivery systems.

Moje first metatarsophalangeal replacement--a case series with functional outcomes using the AOFAS-HMI score.

We report the functional results of a case series of Moje first metatarsophalangeal total joint replacements carried out between February 2001 and November 2006. All patients who underwent Moje arthroplasty under the care of a single surgeon were included; outcome scores and complications were recorded annually. A total of 32 joints in 29 consecutive patients were followed for a mean duration of 34 (range 6 to 74) months, and the mean patient age at the time of operation was 56 (range 38 to 79) years. Hallux rigidus was the primary diagnosis in 28 (87.5%) of the cases. The mean American Orthopaedic Foot & Ankle Society Hallux-Metatarsophalangeal-Interphalangeal score at final follow-up was 74/100 (range 9 to 100), with 13 (40.63%) joints rated good to excellent. Two (6.25%) joints were revised to arthrodesis at a mean of 52 (range 41 to 63) months following the arthroplasty procedure, and the overall prevalence of postoperative complications was 6 (18.75%). Based on these results, we concluded that first MTPJ total joint replacement with the Moje device remains promising, but still has room for improvement before the results match those obtained with larger joint (knee, hip) arthroplasty.

The accuracy of magnetic resonance imaging in diagnosing chronic posterior cruciate ligament injury.

Magnetic resonance imaging (MRI) is widely believed to be highly accurate in diagnosing injuries of the posterior cruciate ligament (PCL). The aim of this study was to determine the accuracy of MRI in diagnosing chronic PCL injury. MRI was performed on 10 knees with a clinical and arthroscopic diagnosis of a PCL injury sustained at least 6 months previously. Seven experienced musculoskeletal radiologists subsequently reviewed the scans. Their accuracy in diagnosing a PCL injury was 57% (40-80%). Thus, although MRI may be reliable in diagnosing acute PCL injury, MRI is not so reliable in evaluating chronic injuries. We postulate that, in the case of a chronic PCL injury, healing in continuity may occur, producing an intact but lax ligament. As demonstrated by our study, MRI may then be less accurate. This should be borne in mind when assessing the MRI scans of a suspected chronic PCL injury.