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Fluorescent nanodiamonds (FNDs) are nontoxic, infinitely photostable, and emit fluorescence in the near infrared region. Natural killer (NK) cells and monocytes are part of the innate immune system and are crucial to the control of carcinogenesis. FND-mediated stimulation of these cells may serve as a strategy to enhance anti-tumor activity. FNDs were fabricated with a diameter of 70 ± 28 nm. Innate immune cell FND uptake, viability, surface marker expression, and cytokine production were evaluated in vitro . Evaluation of fluorescence emission from the FNDs was conducted in an animal model. In vitro results demonstrated that treatment of immune cells with FNDs resulted in significant dose-dependent FND uptake, no compromise in cell viability, and immune cell activation. FNDs were visualized in an animal model. Hence, FNDs may serve as novel agents with “track and trace” capabilities to stimulate innate immune cell anti-tumor responses, especially as FNDs are amenable to surface-conjugation with immunomodulatory molecules. [ABSTRACT FROM AUTHOR]

Abstract: The distal to proximal degeneration of axons, or “dying back” is a common pattern of neuropathology in many diseases of the PNS and CNS. A long-standing debate has centered on whether this pattern of neurodegeneration is due to an insult to the cell body or to the axon itself, although it is likely that mechanisms are different for specific disease entities. We have addressed this question in a model system of vincristine-induced axonal degeneration. Here, we created a novel experimental apparatus combining a microfluidic divider with a multielectrode array substrate to allow for independent monitoring of injury-induced electrical activity from dorsal root ganglion (DRG) cell bodies and axons while isolating them into their own culture microenvironments. At specified doses, exposure of the cell body to vincristine caused neither morphological neurodegeneration nor persistent hyperexcitablility. In comparison, exposure of the distal axon to the same dose of vincristine first caused a decrease in the excitability of the axon and then axonal degeneration in a dying back pattern. Additionally, exposure of axons to vincristine caused an initial period of hyperexcitability in the cell bodies, suggesting that a signal is transmitted from the distal axon to the soma during the progression of vincristine-induced axonal degeneration. These data support the proposition that vincristine has a direct neurotoxic effect on the axon. [Copyright &y& Elsevier]

Abstract: This paper describes a microfabricated compartmented culture system (μ-CCS) for studying the effects of drugs on cultured neurons. We describe the fabrication of the microsystem and show the ability to culture DRG neurons in the microsystem. Furthermore, we demonstrate the ability to culture neurons with extensions growing into adjoining compartments while maintaining fluid isolation between compartments. The axonal growth pattern was controlled along the surface of the glass microelectrode substrate using a micropatterned collagen film. The ability to isolate fluids to selected compartments while simultaneously allowing intercompartmental growth of the axons enables various studies in which selected segments of neurons or populations of neurons can be selectively exposed to biochemical treatment. The neurotoxin vincristine was used as the test vehicle to demonstrate the functionality of the μ-CCS. Vincristine was applied to the axonal compartment to show that the interaction of drugs with DRG neurons progresses in a way similar to neurons cultured/exposed using conventional techniques. [Copyright &y& Elsevier]

Background Oxidation of encapsulated bioactive compounds is a key challenge that limits shelf-life of bioactive containing products. The objectives of this study were to compare differences between the oxidative barrier properties of biopolymer particle based encapsulation system (zein colloidal particles) and oil-in-water emulsions and evaluate the impact of these differences on oxidative stability of encapsulated bioactives. Methods Both zein colloidal particles and oil-in-water emulsions were stabilized by casein protein. The oxidative barrier properties of the selected encapsulation systems were determined by measuring the permeation rate of peroxyl radicals and oxygen across the interface. Peroxyl radical permeation rates were correlated with stability of a model bioactive, curcumin and oxygen permeation rates were correlated with stability of another model bioactive, retinol. Results Radical permeation rate was significantly higher in oil-in-water emulsions compared to zein colloidal particles, indicating enhanced barrier property of zein colloidal particles against peroxyl radical induced oxidation. Consistent with these results, stability of curcumin encapsulated in zein colloidal particles was significantly higher compared to that in oil-in-water emulsions. Oxygen permeation measurements showed no significant differences in the barrier properties of both encapsulation systems against oxygen permeation. Consistent with these results, the oxidative stability of retinol was similar in both encapsulation systems. Conclusions The results of this study demonstrate the advantages of biopolymer particle based encapsulation system in limiting free radical induced oxidation of encapsulated bioactives and also demonstrate the ineffectiveness of both encapsulation systems in limiting oxygen permeation. [ABSTRACT FROM AUTHOR]

Neuropathologic and genetics studies as well as transgenic animal models have provided strong evidence linking misfolding and aggregation of α-synuclein to the progression of Parkinson disease (PD) and other related disorders. A growing body of evidence implicates various oligomeric forms of α-synuclein as the toxic species responsible for neurodegeneration and neuronal cell death. Although numerous different oligomeric forms of α-synuclein have been identified in vitro, it is not known which forms are involved in PD or how, when, and where different forms contribute to the progression of PD. Reagents that can interact with specific aggregate forms of α-synuclein would be very useful not only as tools to study how different aggregate forms affect cell function, but also as potential diagnostic and therapeutic agents for PD. Here we show that a single chain antibody fragment (syn-10H scFv) isolated from a phage display antibody library binds to a larger, later stage oligomeric form of α-synuclein than a previously reported oligomeric specific scFv isolated in our laboratory. The scFv described here inhibits aggregation of α-synuclein in vitro, blocks extracellular α-synuclein-induced toxicity in both undifferentiated and differentiated human neuroblastoma cell lines (SH-SYSY), and specifically recognizes naturally occurring aggregates in PD but not in healthy human brain tissue. [ABSTRACT FROM AUTHOR]