8,320 research outputs found
Extended-release niacin increases anti-apolipoprotein A-I antibodies that block the antioxidant effect of high-density lipoprotein-cholesterol: the EXPLORE clinical trial.
Extended-release niacin (ERN) is the most effective agent for increasing high-density lipoprotein-cholesterol (HDL-C). Having previously identified anti-HDL antibodies, we investigated whether ERN affected the antioxidant capacity of HDL and whether ERN was associated with the production of antibodies against HDL (aHDL) and apolipoprotein A-I (aApoA-I).
METHODS:
Twenty-one patients older than 18 years, with HDL-C ≤40 mg dl-1 (men) or ≤50 mg dl-1 (women) were randomly assigned to receive daily ERN (n = 10) or placebo (n = 11) for two sequential 12-week periods, with 4 weeks of wash-out before cross-over. Primary outcome was change of paraoxonase-1 (PON1) activity and secondary outcomes were changes in aHDL and aApoA-I antibodies. Clinical Trial Unique Identifier: EudraCT 2006-006889-42.
RESULTS:
The effect of ERN on PON1 activity was nonsignificant (coefficient estimate 20.83 U l-1 , 95% confidence interval [CI] -9.88 to 51.53; P = 0.184). ERN was associated with an increase in HDL-C levels (coefficient estimate 5.21 mg dl-1 , 95% CI 1.16 to 9.25; P = 0.012) and its subclasses HDL2 (coefficient estimate 2.46 mg dl-1 , 95% CI 0.57 to 4.34; P = 0.011) and HDL3 (coefficient estimate 2.73 mg dl-1 , 95% CI 0.47 to 4.98; P = 0.018). ERN was significantly associated with the production of aApoA-I antibodies (coefficient estimate 0.25 μg ml-1 , 95% CI 0.09-0.40; P = 0.001). aApoA-I titres at baseline were correlated with decreased PON activity.
CONCLUSIONS:
The rise in HDL-C achieved with ERN was not matched by improved antioxidant capacity, eventually hampered by the emergence of aApoA-I antibodies. These results may explain why Niacin and other lipid lowering agents fail to reduce cardiovascular risk.info:eu-repo/semantics/publishedVersio
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Bortezomib Augments Natural Killer Cell Targeting of Stem-Like Tumor Cells.
Tumor cells harboring stem-like/cancer stem cell (CSC) properties have been identified and isolated from numerous hematological and solid malignancies. These stem-like tumor cells can persist following conventional cytoreductive therapies, such as chemotherapy and radiotherapy, thereby repopulating the tumor and seeding relapse and/or metastasis. We have previously shown that natural killer (NK) cells preferentially target stem-like tumor cells via non- major histocompatibility complex (MHC) restricted mechanisms. Here, we demonstrated that the proteasome inhibitor, bortezomib, augments NK cell targeting of stem cell-like tumor cells against multiple solid human tumor-derived cancer lines and primary tissue samples. Mechanistically, this was mediated by the upregulation of cell surface NK ligands MHC class I chain-related protein A and B (MICA and MICB) on aldehyde dehydrogenases (ALDH)-positive CSCs. The increased expression of MICA and MICB on CSC targets thereby enhanced NK cell mediated killing in vitro and ex vivo from both human primary tumor and patient-derived xenograft samples. In vivo, the combination of bortezomib and allogeneic NK cell adoptive transfer in immunodeficient mice led to increased elimination of CSCs as well as tumor growth delay of orthotopic glioblastoma tumors. Taken together, our data support the combination bortezomib and NK transfer as a strategy for both CSC targeting and potentially improved outcomes in clinical cancer patients
Dynamic communicability predicts infectiousness
Using real, time-dependent social interaction data, we look at correlations between some recently proposed dynamic centrality measures and summaries from large-scale epidemic simulations. The evolving network arises from email exchanges. The centrality measures, which are relatively inexpensive to compute, assign rankings to individual nodes based on their ability to broadcast information over the dynamic topology. We compare these with node rankings based on infectiousness that arise when a full stochastic SI simulation is performed over the dynamic network. More precisely, we look at the proportion of the network that a node is able to infect over a fixed time period, and the length of time that it takes for a node to infect half the network.We find that the dynamic centrality measures are an excellent, and inexpensive, proxy for the full simulation-based measures
Solving the time-dependent Schr\"odinger equation with absorbing boundary conditions and source terms in Mathematica 6.0
In recent decades a lot of research has been done on the numerical solution
of the time-dependent Schr\"odinger equation. On the one hand, some of the
proposed numerical methods do not need any kind of matrix inversion, but source
terms cannot be easily implemented into this schemes; on the other, some
methods involving matrix inversion can implement source terms in a natural way,
but are not easy to implement into some computational software programs widely
used by non-experts in programming (e.g. Mathematica). We present a simple
method to solve the time-dependent Schr\"odinger equation by using a standard
Crank-Nicholson method together with a Cayley's form for the finite-difference
representation of evolution operator. Here, such standard numerical scheme has
been simplified by inverting analytically the matrix of the evolution operator
in position representation. The analytical inversion of the N x N matrix let us
easily and fully implement the numerical method, with or without source terms,
into Mathematica or even into any numerical computing language or computational
software used for scientific computing.Comment: 15 pages, 7 figure
Symmetry-preserving discrete schemes for some heat transfer equations
Lie group analysis of differential equations is a generally recognized
method, which provides invariant solutions, integrability, conservation laws
etc. In this paper we present three characteristic examples of the construction
of invariant difference equations and meshes, where the original continuous
symmetries are preserved in discrete models. Conservation of symmetries in
difference modeling helps to retain qualitative properties of the differential
equations in their difference counterparts.Comment: 21 pages, 4 ps figure
Interactions of asbestos-activated macrophages with an experimental fibrosarcoma
Supernatants from in vivo asbestos-activated macrophages failed to show any cytostatic activity against a syngeneic fibrosarcoma cell line in vitro. UICC chrysotile-induced peritoneal exudate cells also failed to demonstrate any growth inhibitory effect on the same cells in Winn assays of tumor growth. Mixing UICC crocidolite with inoculated tumor cells resulted in a dose-dependent inhibition of tumor growth; this could, however, be explained by a direct cytostatic effect on the tumor cells of high doses of crocidolite, which was observed in vitro
Setting the stage: social-environmental and motivational predictors of optimal training engagement
In this paper, we will firstly explore the central tenets of SDT. Research that has examined the social-environmental and motivation-related correlates of optimal training, performance and health-related engagement through the theoretical lens of SDT will be reviewed. Drawing from SDT-driven work undertaken in educational, sport and dance settings, we will draw conclusions and suggest future directions from a research and applied perspective
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