Adverse effects of fullerenes on endothelial cells: Fullerenol C60(OH)24 induced tissue factor and ICAM-1 membrane expression and apoptosis in vitro

We studied the effects of a C60 water suspension at 4 μg/mL (nC60) and the water soluble fullerenol C60(OH)24 at final concentrations of 1–100 μg/mL on human umbilical vein endothelial cells (HUVECs) in culture. We found that a 24 hr treatment of HUVECs with C60(OH)24 at 100 μg/mL significantly increased cell surface expression of ICAM-1(CD54) (67 ± 4% CD54+ cells vs. 19 ± 2 % CD54+ cells in control; p < 0.001). In addition, this treatment induced the expression of tissue factor (CD142) on HUVECs (54 ± 20% CD142+ cells vs 4 ± 2% CD142+ cells in control; p = 0.008) and increased exposure of phosphatidylserine (PS) (29 ± 2% PS+ cells vs. 12 ± 5% PS+ cells in control; p < 0.001). Analysis of cell cycle and DNA fragmentation (TUNEL) showed that both nC60 and C60(OH)24 caused G1 arrest of HUVECs and C60(OH)24 induced significant apoptosis (21 ± 2% TUNEL+ cells at 100 μg/mL of C60(OH)24 vs. 4 ± 2% TUNEL+ cells in control; p < 0.001). We also demonstrated that both nC60 and C60(OH)24 induced a rapid concentration dependent elevation of intracellular calcium [Ca2+]i. This could be inhibited by EGTA, suggesting that the source of [Ca2+]i in fullerene stimulated calcium flux is predominantly from the extracellular environment. In conclusion, fullerenol C60(OH)24 had both pro-inflammatory and pro-apoptotic effects on HUVECs, indicating possible adverse effects of fullerenes on the endothelium

A Diagrammatic Approach to Crystalline Color Superconductivity

We present a derivation of the gap equation for the crystalline color superconducting phase of QCD which begins from a one-loop Schwinger-Dyson equation written using a Nambu-Gorkov propagator modified to describe the spatially varying condensate. Some aspects of previous variational calculations become more straightforward when rephrased beginning from a diagrammatic starting point. This derivation also provides a natural base from which to generalize the analysis to include quark masses, nontrivial crystal structures, gluon propagation at asymptotic densities, and nonzero temperature. In this paper, we analyze the effects of nonzero temperature on the crystalline color superconducting phase.Comment: 15 pages. 2 eps figure

The Crystallography of Color Superconductivity

We develop the Ginzburg-Landau approach to comparing different possible crystal structures for the crystalline color superconducting phase of QCD, the QCD incarnation of the Larkin-Ovchinnikov-Fulde-Ferrell phase. In this phase, quarks of different flavor with differing Fermi momenta form Cooper pairs with nonzero total momentum, yielding a condensate that varies in space like a sum of plane waves. We work at zero temperature, as is relevant for compact star physics. The Ginzburg-Landau approach predicts a strong first-order phase transition (as a function of the chemical potential difference between quarks) and for this reason is not under quantitative control. Nevertheless, by organizing the comparison between different possible arrangements of plane waves (i.e. different crystal structures) it provides considerable qualitative insight into what makes a crystal structure favorable. Together, the qualitative insights and the quantitative, but not controlled, calculations make a compelling case that the favored pairing pattern yields a condensate which is a sum of eight plane waves forming a face-centered cubic structure. They also predict that the phase is quite robust, with gaps comparable in magnitude to the BCS gap that would form if the Fermi momenta were degenerate. These predictions may be tested in ultracold gases made of fermionic atoms. In a QCD context, our results lay the foundation for a calculation of vortex pinning in a crystalline color superconductor, and thus for the analysis of pulsar glitches that may originate within the core of a compact star.Comment: 41 pages, 13 figures, 1 tabl

Crystalline Color Superconductivity

In any context in which color superconductivity arises in nature, it is likely to involve pairing between species of quarks with differing chemical potentials. For suitable values of the differences between chemical potentials, Cooper pairs with nonzero total momentum are favored, as was first realized by Larkin, Ovchinnikov, Fulde and Ferrell (LOFF). Condensates of this sort spontaneously break translational and rotational invariance, leading to gaps which vary periodically in a crystalline pattern. Unlike the original LOFF state, these crystalline quark matter condensates include both spin zero and spin one Cooper pairs. We explore the range of parameters for which crystalline color superconductivity arises in the QCD phase diagram. If in some shell within the quark matter core of a neutron star (or within a strange quark star) the quark number densities are such that crystalline color superconductivity arises, rotational vortices may be pinned in this shell, making it a locus for glitch phenomena.Comment: 40 pages, LaTeX with eps figs. v2: New paragraph on Ginzburg-Landau treatment of LOFF phase in section 5. References added. v3: Small changes only. Version to appear in Phys. Rev.

Anticoagulants Influence the Performance of In Vitro Assays Intended for Characterization of Nanotechnology-Based Formulations

The preclinical safety assessment of novel nanotechnology-based drug products frequently relies on in vitro assays, especially during the early stages of product development, due to the limited quantities of nanomaterials available for such studies. The majority of immunological tests require donor blood. To enable such tests one has to prevent the blood from coagulating, which is usually achieved by the addition of an anticoagulant into blood collection tubes. Heparin, ethylene diamine tetraacetic acid (EDTA), and citrate are the most commonly used anticoagulants. Novel anticoagulants such as hirudin are also available but are not broadly used. Despite the notion that certain anticoagulants may influence assay performance, a systematic comparison between traditional and novel anticoagulants in the in vitro assays intended for immunological characterization of nanotechnology-based formulations is currently not available. We compared hirudin-anticoagulated blood with its traditional counterparts in the standardized immunological assay cascade, and found that the type of anticoagulant did not influence the performance of the hemolysis assay. However, hirudin was more optimal for the complement activation and leukocyte proliferation assays, while traditional anticoagulants citrate and heparin were more appropriate for the coagulation and cytokine secretion assays. The results also suggest that traditional immunological controls such as lipopolysaccharide (LPS ) are not reliable for understanding the role of anticoagulant in the assay performance. We observed differences in the test results between hirudin and traditional anticoagulant-prepared blood for nanomaterials at the time when no such effects were seen with traditional controls. It is, therefore, important to recognize the advantages and limitations of each anticoagulant and consider individual nanoparticles on a case-by-case basis

Induction of Cytokines by Nucleic Acid Nanoparticles (NANPs) Depends on the Type of Delivery Carrier

Recent insights into the immunostimulatory properties of nucleic acid nanoparticles (NANPs) have demonstrated that variations in the shape, size, and composition lead to distinct patterns in their immunostimulatory properties. While most of these studies have used a single lipid-based carrier to allow for NANPs’ intracellular delivery, it is now apparent that the platform for delivery, which has historically been a hurdle for therapeutic nucleic acids, is an additional means to tailoring NANP immunorecognition. Here, the use of dendrimers for the delivery of NANPs is compared to the lipid-based platform and the differences in resulting cytokine induction are presented

Hydrodynamic size distribution of fullerene particles in nC and C(OH) preparations

Shown are the volume distributions (each line is the average of at least twelve measurements per sample) of the nC water suspension (), and C(OH) in 10mM Nacl ().<p><b>Copyright information:</b></p><p>Taken from "Adverse effects of fullerenes on endothelial cells: Fullerenol C(OH) induced tissue factor and ICAM-1 membrane expression and apoptosis in vitro"</p><p></p><p>International Journal of Nanomedicine 2008;3(1):59-68.</p><p>Published online Jan 2008</p><p>PMCID:PMC2527653.</p><p>© 2008 Dove Medical Press Limited. All rights reserved</p