Synthesis and Reduction Kinetics of Sterically Shielded Pyrrolidine Nitroxides

A series of sterically shielded pyrrolidine nitroxides were synthesized and their reduction by ascorbate (vitamin C) indicate that nitroxide 3 – a tetraethyl derivative of 3-carboxy-PROXYL – is reduced at the slowest rate among known nitroxides, i.e., at a 60-fold slower rate than that for 3- carboxy-PROXYL

Experimental Fracture Model versus Osteotomy Model in Metacarpal Bone Plate Fixation

Introduction. Osteotomy or fracture models can be used to evaluate mechanical properties of fixation techniques of the hand skeleton in vitro. Although many studies make use of osteotomy models, fracture models simulate the clinical situation more realistically. This study investigates monocortical and bicortical plate fixation on metacarpal bones considering both aforementioned models to decide which method is best suited to test fixation techniques. Methods. Porcine metacarpal bones (n = 40) were randomized into 4 groups. In groups I and II bones were fractured with a modified 3-point bending test. The intact bones represented a further control group to which the other groups after fixation were compared. In groups III and IV a standard osteotomy was carried out. Bones were fixated with plates monocortically (group I, III) and bicortically (group II, IV) and tested for failure. Results. Bones fractured at a mean maximum load of 482.8 N ± 104.8 N with a relative standard deviation (RSD) of 21.7%, mean stiffness was 122.3 ± 35 N/mm. In the fracture model, there was a significant difference (P = 0.01) for maximum load of monocortically and bicortically fixed bones in contrast to the osteotomy model (P = 0.9). Discussion. In the fracture model, because one can use the same bone for both measurements in the intact state and the bone-plate construct states, the impact of inter-individual differences is reduced. In contrast to the osteotomy model there are differences between monocortical and bicortical fixations in the fracture model. Thus simulation of the in vivo situation is better and seems to be suitable for the evaluation of mechanical properties of fixation techniques on metacarpals

Cooperative effects in differentiation and proliferation between PDGF-BB and matrix derived synthetic peptides in human osteoblasts

Background: Enhancing osteogenic capabilities of bone matrix for the treatment of fractures and segmental defects using growth factors is an active area of research. Recently, synthetic peptides like AC- 100, TP508 or p-15 corresponding to biologically active sequences of matrix proteins have been proven to stimulate bone formation. The platelet-derived growth factor (PDGF) BB has been identified as an important paracrine factor in early bone healing. We hypothesized that the combined use of PDGF-BB with synthetic peptides could result in an increase in proliferation and calcification of osteoblast-like cells. Methods: Osteoblast-like cell cultures were treated with PDGF and synthetic peptides, singly and as combinations, and compared to non-treated control cell cultures. The cultures were evaluated at days 2, 5, and 10 in terms of cell proliferation, calcification and gene expression of alkaline phosphate, collagen I and osteocalcin. Results: Experimental findings revealed that the addition of PDGF, p-15 and TP508 and combinations of PDGF/AC-100, PDGF/p-15 and PDGF/TP508 resulted in an increase in proliferating osteoblasts, especially in the first 5 days of cultivation. Proliferation did not significantly differ between single factors and factor combinations (p > 0.05). The onset of calcification in osteoblasts occurred earlier and was more distinct compared to the corresponding control or PDGF stimulation alone. Significant difference was found for the combined use of PDGF/p-15 and PDGF/AC-100 (p < 0.05). Conclusions: Our findings indicate that PDGF exhibits cooperative effects with synthetic peptides in differentiation and proliferation. These cooperative effects cause a significant early calcification of osteoblast-like cells (p < 0.05). We suggest the combination of synthetic peptides and PDGF as a potential clinical approach for accelerating bone healing or coating osteosynthesis materials.

Redox-responsive branched-bottlebrush polymers for \u3ci\u3ein vivo\u3c/i\u3e MRI and fluorescence imaging

Stimuli-responsive multimodality imaging agents have broad potential in medical diagnostics. Herein, we report the development of a new class of branched-bottlebrush polymer dual-modality organic radical contrast agents—ORCAFluors—for combined magnetic resonance and near-infrared fluorescence imaging in vivo. These nitroxide radical-based nanostructures have longitudinal and transverse relaxation times that are on par with commonly used heavy-metal-based magnetic resonance imaging (MRI) contrast agents. Furthermore, these materials display a unique compensatory redox response: fluorescence is partially quenched by surrounding nitroxides in the native state; exposure to ascorbate or ascorbate/glutathione leads to nitroxide reduction and a concomitant 2- to 3.5-fold increase in fluorescence emission. This behaviour enables correlation of MRI contrast, fluorescence intensity and spin concentration with tissues known to possess high concentrations of ascorbate in mice. Our in vitro and in vivo results, along with our modular synthetic approach, make ORCAFluors a promising new platform for multimodality molecular imaging

The preliminary design of a scaled Composite UHBR Fan for a wind tunnel test campaign

AbstractThe ambition of the CA3ViAR project is to design an open test case fan that experiences instability mechanisms, which are representative for ultra-high bypass ratio (UHBR) fans of civil aircrafts, and to perform a comprehensive experimental investigation to measure aerodynamic, aeroelastic and aeroacoustic performance in a wide range of operational conditions. Experimental tests will be performed in the Propulsion-Test-Facility (PTF) of the Institute of Jet Propulsion and Turbomachinery (IFAS) of Technische Universität Braunschweig, Germany. The final objective of the project is to provide an open test case for the entire research community, with geometries, numerical and experimental results to establish a new reference for composite UHBR fan design. This will support the development of new methods and tools for the development of safer, lighter and more efficient composite fans for greener UHBR engines. In this work the preliminary design of the low transonic fan (LTF) to be used as test article, whose main requirement is to be operated in a safe and controlled way in conditions of aerodynamic and/or aeroelastic instability during wind tunnel operations, is presented. More in particular, consolidated aerodynamic design, strategy adopted to drive the structural design, flutter analysis taking into account acoustic reflection at the intake, dynamic and stress analyses, as well as aeroacoustic measurement optimization are presented and discussed. The preliminary mechanical design of composite blades and the rotor hub, together with the rotor instrumentation and related studies to embed sensors in the composite blades, are also part of this article, and complemented by manufacturing trials and demonstration tests give the full picture of all the project activities up to the preliminary design review

Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors

Metal-free magnetic resonance imaging (MRI) agents could overcome the established toxicity associated with metal-based agents in some patient populations and enable new modes of functional MRI in vivo. Herein, we report nitroxidefunctionalized brush-arm star polymer organic radical contrast agents (BASP-ORCAs) that overcome the low contrast and poor in vivo stability associated with nitroxide-based MRI contrast agents. As a consequence of their unique nanoarchitectures, BASP-ORCAs possess per-nitroxide transverse relaxivities up to ∼44-fold greater than common nitroxides, exceptional stability in highly reducing environments, and low toxicity. These features combine to provide for accumulation of a sufficient concentration of BASP-ORCA in murine subcutaneous tumors up to 20 h following systemic administration such that MRI contrast on par with metal-based agents is observed. BASP-ORCAs are, to our knowledge, the first nitroxide MRI contrast agents capable of tumor imaging over long time periods using clinical high-field 1H MRI techniques. Includes Supplementary materia

Adjacent thoracic lymph node metastases originating from two separate primary cancers: case report

Reported is an unusual case of adjacent thoracic lymph nodes demonstrating metastases from two different primary malignancies. A 51 year-old woman with a previous history of bilateral breast cancer underwent a radical gastro-oesophagectomy for adenocarcinoma of the lower third of the oesophagus. The resection specimen demonstrated breast and oesophageal metastases in adjacent thoracic lymph nodes. Mechanisms for this phenomenon, including the known local immune suppression on lymphoid cells by oesophageal carcinoma cells, are discussed

Electrospun PLLA Nanofiber Scaffolds and Their Use in Combination with BMP-2 for Reconstruction of Bone Defects

Introduction Adequate migration and differentiation of mesenchymal stem cells is essential for regeneration of large bone defects. To achieve this, modern graft materials are becoming increasingly important. Among them, electrospun nanofiber scaffolds are a promising approach, because of their high physical porosity and potential to mimic the extracellular matrix (ECM). Materials and Methods The objective of the present study was to examine the impact of electrospun PLLA nanofiber scaffolds on bone formation in vivo, using a critical size rat calvarial defect model. In addition we analyzed whether direct incorporation of bone morphogenetic protein 2 (BMP-2) into nanofibers could enhance the osteoinductivity of the scaffolds. Two critical size calvarial defects (5 mm) were created in the parietal bones of adult male Sprague-Dawley rats. Defects were either (1) left unfilled, or treated with (2) bovine spongiosa, (3) PLLA scaffolds alone or (4) PLLA/BMP-2 scaffolds. Cranial CT-scans were taken at fixed intervals in vivo. Specimens obtained after euthanasia were processed for histology, histomorphometry and immunostaining (Osteocalcin, BMP-2 and Smad5). Results PLLA scaffolds were well colonized with cells after implantation, but only showed marginal ossification. PLLA/BMP-2 scaffolds showed much better bone regeneration and several ossification foci were observed throughout the defect. PLLA/BMP-2 scaffolds also stimulated significantly faster bone regeneration during the first eight weeks compared to bovine spongiosa. However, no significant differences between these two scaffolds could be observed after twelve weeks. Expression of osteogenic marker proteins in PLLA/BMP-2 scaffolds continuously increased throughout the observation period. After twelve weeks osteocalcin, BMP-2 and Smad5 were all significantly higher in the PLLA/BMP-2 group than in all other groups. Conclusion Electrospun PLLA nanofibers facilitate colonization of bone defects, while their use in combination with BMP-2 also increases bone regeneration in vivo and thus combines osteoconductivity of the scaffold with the ability to maintain an adequate osteogenic stimulus