Lanthanide-based ß-Tricalcium Phosphate Upconversion Nanoparticles as an Effective Theranostic Nonviral Vectors for Image-Guided Gene Therapy.

Lanthanide-based beta-tricalcium phosphate (ß-TCP) upconversion nanoparticles are exploited as a non-viral vector for imaging guided-gene therapy by virtue of their unique optical properties and multi-modality imaging ability, high transfection efficiency, high biocompatibility, dispersibility, simplicity of synthesis and surface modification. Ytterbium and thulium-doped ß-TCP nanoparticles (ßTCPYbTm) are synthesized via co-precipitation method, coated with polyethylenimine (PEI) and functionalized with a nuclear-targeting peptide (TAT). Further, in vitro studies revealed that the nanotheranostic carriers are able to transfect cells with the plasmid eGFP at a high efficiency, with approximately 60% of total cells producing the fluorescent green protein. The optimized protocol developed comprises the most efficient ßTCPYbTm/PEI configuration, the amount and the order of assembly of ßTCPYbTm:PEI, TAT, plasmid DNA and the culturing conditions. With having excellent dispersibility and high chemical affinity toward nucleic acid, calcium ions released from ßTCPYbTm:PEI nanoparticles can participate in delivering nucleic acids and other therapeutic molecules, overcoming the nuclear barriers and improving the transfection efficacy. Equally important, the feasibility of the upconversion multifunctional nanovector to serve as an effective contrast agent for imaging modality, capable of converting low-energy light to higher-energy photons via a multi-photons mechanism, endowing greater unique luminescent properties, was successfully demonstrated.

Nanoparticles as contrast agents for the diagnosis of Alzheimer's disease: a systematic review.

Nanoparticle (NP)-based magnetic contrast agents have opened the potential for MRI to be used for early diagnosis of Alzheimer's disease (AD). This article aims to review the current progress of research in this field. A comprehensive literature search was performed based on PubMed, Medline, EMBASE, PsychINFO and Scopus databases using the following terms: 'Alzheimer's disease' AND 'nanoparticles' AND 'Magnetic Resonance Imaging.' 33 studies were included that described the development and utility of various NPs for AD imaging, including their coating, functionalization, MRI relaxivity, toxicity and bioavailability. NPs show immense promise for neuroimaging, due to superior relaxivity and biocompatibility compared with currently available imaging agents. Consistent reporting is imperative for further progress in this field.

Solution Synthesis, Surface Passivation, Optical Properties, Biomedical Applications, and Cytotoxicity of Silicon and Germanium Nanocrystals.

Silicon and germanium nanocrystals (NCs) are attractive materials owing to their unique size and surface-dependent optical properties. The optical properties of silicon and germanium NCs make them highly suitable for a range of applications, including bioimaging, light-emitting diodes, and solar cells. In this review, the solution synthesis, surface passivation, optical properties, biomedical applications, and cytotoxicity of silicon and germanium NCs are compared and contrasted. Over the last 10 years, synthetic protocols have improved considerably, with size control readily achieved. Investigations have begun into a range of silicon and germanium nanostructures, including doped, alloy, and metal-semiconductor hybrid NCs, which represent the next generation of silicon and germanium nanomaterials. Silicon and germanium NCs are actively researched for a wide array of biomedical applications, including, long-term in vivo cellular imaging, fluorescent nanocarriers for drug delivery, and as contrast agents for magnetic resonance imaging (MRI). Cytotoxicity studies have shown the low toxicity of Si NCs, while demonstrating that Ge NCs are less toxic than CdSe NCs at similar concentrations, giving these materials a strong future in nanomedicine applications.

Clinical improvement after extracranial venoplasty in multiple sclerosis.

PURPOSE: This study proposed to prospectively evaluate safety and clinical changes in outpatient endovascular treatment in patients with multiple sclerosis (MS) and chronic cerebrospinal venous insufficiency (CCSVI). MATERIALS AND METHODS: Two hundred fifty-nine patients with MS were followed with the Multiple Sclerosis Impact Scale (MSIS-29) before and for 1 and 6 months after treatment of extracranial internal jugular vein and azygos vein stenoses and occlusions using venous angioplasty, as well as stent placement in 2.5% of patients. Before treatment, the patients were tested with magnetic resonance (MR) venography and flow quantification. RESULTS: We found statistically significant improvements in the MSIS-29 scores (P < .01) at both 1 and 6 months. At 1 and 6 months, 67.9% and 53.6% were improved on the physical scale, respectively, and 53.0% and 44.4% were improved on the psychological scale, respectively. Women showed greater improvement than did men on the physical scale at 6 months (P = .01). Patients with primary progressive MS (PPMS) showed less improvement than did those with relapsing-remitting MS (RRMS) on the psychological scale at 1 month, and venoplasty treatment of more vein sites versus fewer vein sites showed greater improvement on the physical scale at both 1 and 6 months. Fifteen patients (6.3%) reported recurrent symptoms after clinical improvement and were treated again. There was one serious adverse event, a deep venous thrombosis at the catheter insertion site, which resolved with treatment. CONCLUSIONS: Endovascular treatment of CCSVI in patients with MS appears to be a safe procedure resulting in significant clinical improvement.

Multi-analyte sensing: a chemometrics approach to understanding the merits of electrode arrays versus single electrodes.

A peptide-modified electrode array with a different peptide on each electrode is compared with a single electrode modified with many peptides for the voltammetric measurement of concentrations of Cu(2+), Cd(2+) and Pb(2+) in solution. The single gold electrode was modified simultaneously with peptides Gly-Gly-His, glutathione and angiotensin I each coupled to thioctic acid, and thioctic acid itself, and the calibration of mixtures of ions was compared with previously published data from an array of four sensors each with an individual modification. Calibration at the multi-peptide single-electrode sensor was by two-way partial least squares (voltammetric current measured with variables 'sample' x 'potential') and for the electrode array by three-way NPLS1 ('sample' x 'potential' x 'electrode'). The advantage of designing experiments to yield multi-way data is demonstrated and discussed.

Long-term patency and clinical outcome of the Viabahn stent-graft for femoropopliteal artery obstructions.

PURPOSE: To assess the long-term patency of the Viabahn stent-graft after placement for the treatment of occlusive disease of the femoropopliteal artery (FPA). MATERIALS AND METHODS: Viabahn stent-grafts were placed into 87 limbs in 76 patients for the treatment of atherosclerotic occlusive disease of the FPA. Mean lesion length was 14.2 cm (range, 2.8-40 cm), with 80 of 87 lesions (92%) at least 7 cm in length. Patients were followed by duplex ultrasound (US), resting ankle brachial index (ABI) measurement, and clinical status at 6 months, 1 year, and yearly thereafter for a maximum of 8.5 years. A systolic velocity ratio greater than 2.0 on duplex US anywhere in the FPA was defined as a loss of primary vessel patency. RESULTS: Primary, primary assisted, and secondary vessel patency rates were 76%, 87%, and 93%, respectively, at 1 year and 55%, 67%, and 79%, respectively, at 4 years. Mean resting ABI improved from 0.70 before the procedure to 0.90 as of the most recent follow-up (P<.001). Mean Rutherford-Becker classification improved from 3.4 before the procedure to 0.68 as of the most recent follow-up (P<.001). Eighty-eight percent of limbs showed a maintained improvement in clinical status. Primary patency was independent of lesion length and type but dependent on device diameter (P=.001). The primary vessel patency rate in devices of at least 7 mm (n=21) was 82% at 4 years. No stent fractures were observed despite the use of multiple overlapping stent-grafts in 36.8% of limbs (n=32). CONCLUSIONS: This study demonstrates durable vessel patency to 4 years for long Transatlantic Inter-Society Consensus class C and D lesions treated with the Viabahn stent-graft. Results were independent of lesion length and type but dependent on device diameter. This study helps confirm the durability and clinical utility of this device in the treatment of FPA occlusive disease.

Endograft use in the femoral and popliteal arteries.

The results of infra-inguinal intervention for atherosclerotic occlusive disease have not changed dramatically in the last 15 years despite the advent of many different designs of uncovered stents. "Plain old balloon angioplasty" remains the treatment of choice for short lesions (<3 cm) with good morphologic characteristics. Stents have improved suboptimal angioplasty results somewhat, but results in longer lesions >5 cm have remained poor in most series. Although there are no endografts currently approved for arterial use by the FDA, expanded polytetraflouroethylene (ePTFE) covered endoprostheses are available and their use in the femoropopliteal arteries can dramatically improve the results of endovascular treatment for longer lesions and allow one to treat vascular ruptures and aneurysms. In this article, we will review the published results for the use of endografts in the femoropopliteal arteries and describe what we believe to be the current indications for their use.

Long-term results of ePTFE stent-graft versus angioplasty in the femoropopliteal artery: single center experience from a prospective, randomized trial.

PURPOSE: To describe a single-center experience as part of a U.S. multicenter prospective randomized trial of PTA versus percutaneous transluminal angioplasty (PTA)- and ePTFE (expanded polytetrafluoroethylene)-covered endoprosthesis placement for the treatment of superficial femoral artery (SFA) and proximal popliteal artery stenoses and occlusions. MATERIALS AND METHODS: Twenty-eight patients with claudication or ischemia were treated by PTA alone (n = 13) or PTA and endoprosthesis placement (n = 15). Baseline characteristics, including exercise ankle/brachial index (ABI), number of patent runoff vessels, Rutherford-Becker ischemia score, and lesion length, were equivalent. Follow-up included postprocedure, objective, noninvasive vascular evaluation and a clinical status scale for a minimum of 24 months. RESULTS: Technical success was achieved in 15 of 15 patients (100%) in the endoprosthesis group and 12 of 13 patients (92%) in the PTA group. Complications in the endoprosthesis group included clinically significant embolization (n = 1, successfully treated by thrombolysis) and transient thigh pain that required medication in three patients (20%). Clinical improvement was achieved initially in all patients with a significant increase in exercise ABI in both groups (mean increase from baseline was 0.51 with 95% CI: 0.37-0.64 in endoprosthesis patients and 0.39 with 95% CI: 0.31-0.47 in PTA patients; P =.13). At 6-month follow-up with duplex US, 93% of patients (14 of 15) treated with the Hemobahn endoprosthesis (W.L. Gore & Associates, Flagstaff, AZ) remained primarily patent versus 42% of patients (five of 12) treated with PTA alone. At 2 years follow-up, primary patency remained 87% (13 of 15 patients) in the endoprosthesis group versus only 25% (three of 12 patients) in the PTA group (P =.002). Exercise ABI was >0.15 higher than baseline in 93% of patients (14 of 15) treated with endoprosthesis placement versus 54% of patients (seven of 13) treated by PTA alone. Clinical success was maintained in 87% of patients (13 of 15) in the endoprosthesis group versus 46% of patients (six of 13) in the PTA group. CONCLUSION: This single-center experience with placement of the Hemobahn endoprosthesis (W.L. Gore & Associates) in the SFA demonstrated a statistically significant improvement in both patency and clinical outcome compared with PTA alone.