With the description of more and more complex one-and two-dimensional NMR experiments comes the need to develop methods to make a comprehensive interpretation of the various different experiments that can be carried out on the same sample or series of related samples. We present some examples of modelling one-and two-dimensional solid-state NMR spectra of I = 1 2 spin and quadrupolar nuclei, using laboratory-developed software that is made available to the NMR community.

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Despite total hip replacement (THR) gives generally satisfactory results, the quality of outcome in young patients is markedly decreased compared to the average THR outcome. For this population, pharmacological treatment with bisphosphonate would be beneficial to decrease the peri-implant osteolysis. However, as this population does not necessarily suffer from osteoporosis, a nonsystemic treatment would be preferable. Zoledronate was then grafted to hydroxyapatite (HA) coating of titanium implants. The implants were inserted in rat condyles with various zoledronate concentrations. A positive concentration-dependent effect was observed on the peri-implant bone density and on different histomorphometric parameters. Importantly for the outcome of the implants, the mechanical fixation was increased by the local presence of zoledronate.The obtained results open the way of an easy transformation of currently existing HA-coated implants by grafting bisphosphonate onto the coating in order to increase their service life in the patients. D 2004 Elsevier Inc. All rights reserved.

Abstract:Patients with osteoporosis and joint disabilities represent a constant growing and challenging population to be treated in the musculoskeletal clinical field. Especially in the case of total hip arthroplasty, new solutions should be developed to compensate for the double negative factors, peri-implant osteolysis, and osteoporotic bone loss, affecting the quality of implant outcome. The goal of this study was then to establish a proof of concept for orthopedic implant used as Zoledronate delivery in osteoporotic rats, and in particular, to verify if this approach could increase the initial implant stability. Twenty-five female 6-month-old Wistar rats were ovariectomized 6 weeks before the implantation to induce osteoporosis. The animals were randomly separated in five groups representing the different Zoledronate concentrations in the HA coating: 0, 0.2, 2.1, 8.5, and 16 g/implant. Histomorphometric measures and peri-implant bone volume fraction were assessed and mechanical stability tests were performed. Bone volume fraction and biomechanical results clearly illustrate the positive effect of Zoledronate coated implants in the osteoporotic rats. A remarkable result was to show the existence of a window of Zoledronate content (0.2 to 8.5 g/implant) in which the mechanical fixation of the implant increased. We were able to establish the proof of concept for orthopedic implants used as a drug delivery system in osteoporotic rats. The local bisphosphonate delivery from a calcium phosphate coating allowed increase of the mechanical fixation of an orthopedic implant. This study shows that orthopedic implants containing bisphosphonates could be beneficial for osteoporotic patients in need of a total joint replacement.

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A new approach to oligonucleotide arrays is demonstrated that utilizes zirconium phosphonate-derivatized glass slides. The active slides are prepared by binding Zr(4+) to surfaces terminated with organophosphonate groups previously deposited using either Langmuir-Blodgett or self-assembled monolayer methods. Oligonucleotide probes modified with a terminal phosphate bind strongly to the active zirconium phosphonate monolayer, and arrays for detecting fluorescent targets have been prepared using commercial spotting and scanning instruments. Preferred binding to the surface of the terminal phosphate of the modified probes instead of the internal phosphate diester groups is demonstrated and shown to yield increased fluorescence intensity after hybridization with labeled targets. A significant decrease in background signal is achieved by treating the slides with bovine serum albumin after spotting and before hybridization. A further increase in fluorescence after hybridization is observed when using a poly-guanine spacer between the probe oligomer and the terminal phosphate. Combining these modifications, an intensity ratio of nearly 1000 is achieved when comparing 5'-phosphate-modified 33-mer probes with unmodified probes upon hybridization with fluorescent targets.