Tocotrienols-induced inhibition of platelet thrombus formation and platelet aggregation in stenosed canine coronary arteries

<p>Abstract</p> <p>Background</p> <p>Dietary supplementation with tocotrienols has been shown to decrease the risk of coronary artery disease. Tocotrienols are plant-derived forms of vitamin E, which have potent anti-inflammatory, antioxidant, anticancer, hypocholesterolemic, and neuroprotective properties. Our objective in this study was to determine the extent to which tocotrienols inhibit platelet aggregation and reduce coronary thrombosis, a major risk factor for stroke in humans. The present study was carried out to determine the comparative effects of α-tocopherol, α-tocotrienol, or tocotrienol rich fraction (TRF; a mixture of α- + γ- + δ-tocotrienols) on <it>in vivo platelet thrombosis </it>and <it>ex vivo </it>platelet aggregation (PA) after intravenous injection in anesthetized dogs, by using a mechanically stenosed circumflex coronary artery model (Folts' cyclic flow model).</p> <p>Results</p> <p>Collagen-induced platelet aggregation (PA) in platelet rich plasma (PRP) was decreased markedly after treatment with α-tocotrienol (59%; <b><it>P </it></b>< 0.001) and TRF (92%; <b><it>P </it></b>< 0.001). α-Tocopherol treatment was less effective, producing only a 22% (<b><it>P </it></b>< 0.05) decrease in PA. Adenosine diphosphate-induced (ADP) PA was also decreased after treatment with α-tocotrienol (34%; <b><it>P </it></b>< 0.05) and TRF (42%; <b><it>P </it></b>< 0.025). These results also indicate that intravenously administered tocotrienols were significantly better than tocopherols in inhibiting cyclic flow reductions (CFRs), a measure of the acute platelet-mediated thrombus formation. Tocotrienols (TRF) given intravenously (10 mg/kg), abolished CFRs after a mean of 68 min (range 22 -130 min), and this abolition of CFRs was sustained throughout the monitoring period (50 - 160 min).</p> <p>Next, pharmacokinetic studies were carried out and tocol levels in canine plasma and platelets were measured. As expected, α-Tocopherol treatment increased levels of total tocopherols in post- vs pre-treatment specimens (57 vs 18 μg/mL in plasma, and 42 vs 10 μg/mL in platelets). However, treatment with α-tocopherol resulted in slightly decreased levels of tocotrienols in post- vs pre-treatment samples (1.4 vs 2.9 μg/mL in plasma and 2.3 vs 2.8 μg/mL in platelets). α-Tocotrienol treatment increased levels of both tocopherols and tocotrienols in post- vs pre-treatment samples (tocopherols, 45 vs 10 μg/mL in plasma and 28 vs 5 μg/mL in platelets; tocotrienols, 2.8 vs 0.9 μg/mL in plasma and 1.28 vs 1.02 μg/mL in platelets). Treatment with tocotrienols (TRF) also increased levels of tocopherols and tocotrienols in post- vs pre-treatment samples (tocopherols, 68 vs 20 μg/mL in plasma and 31.4 vs 7.9 μg/mL in platelets; tocotrienols, 8.6 vs 1.7 μg/mL in plasma and 3.8 vs 3.9 μg/mL in platelets).</p> <p>Conclusions</p> <p>The present results indicate that intravenously administered tocotrienols inhibited acute platelet-mediated thrombus formation, and collagen and ADP-induced platelet aggregation. α-Tocotrienols treatment induced increases in α-tocopherol levels of 4-fold and 6-fold in plasma and platelets, respectively. Interestingly, tocotrienols (TRF) treatment induced a less pronounced increase in the levels of tocotrienols in plasma and platelets, suggesting that intravenously administered tocotrienols may be converted to tocopherols. Tocotrienols, given intravenously, could potentially prevent pathological platelet thrombus formation and thus provide a therapeutic benefit in conditions such as stroke and myocardial infarction.</p

Structure and Dynamics of the Sun's Open Magnetic Field

The solar magnetic field is the primary agent that drives solar activity and couples the Sun to the Heliosphere. Although the details of this coupling depend on the quantitative properties of the field, many important aspects of the corona - solar wind connection can be understood by considering only the general topological properties of those regions on the Sun where the field extends from the photosphere out to interplanetary space, the so-called open field regions that are usually observed as coronal holes. From the simple assumptions that underlie the standard quasi-steady corona-wind theoretical models, and that are likely to hold for the Sun, as well, we derive two conjectures on the possible structure and dynamics of coronal holes: (1) Coronal holes are unique in that every unipolar region on the photosphere can contain at most one coronal hole. (2) Coronal holes of nested polarity regions must themselves be nested. Magnetic reconnection plays the central role in enforcing these constraints on the field topology. From these conjectures we derive additional properties for the topology of open field regions, and propose several observational predictions for both the slowly varying and transient corona/solar wind.Comment: 26 pages, 6 figure

Coordinated X-ray optical and radio observations of YZ Canis Minoris

Coordinated X ray, optical, and radio observations of the flare star YZ CMi are reported. Twenty-two minor optical flares and twelve radio events were recorded. No major optical flares, greater than 3 magnitudes, were observed. Although no flare related X ray emission was observed, the measured upper limits in this band enable meaningful comparisons with published flare star models. Three of the five models predicting the relative X ray to optical or radio flare luminosities are in serious disagreement with the observations. For the largest optical flare with coincident X ray coverage, the 3 sigma upper limit on X ray emission in the 0.15 to 0.8 keV band is 8.7 x 10 to the 28th power erg/s, corresponding to a ratio of X ray to B-band luminosity of less than 0.3. Based on the present results, the contribution of the flares UV Ceti flare stars to the galactic component of the diffuse soft X ray background is less than 0.2 percent

On Solving the Coronal Heating Problem

This article assesses the current state of understanding of coronal heating, outlines the key elements of a comprehensive strategy for solving the problem, and warns of obstacles that must be overcome along the way.Comment: Accepted by Solar Physics; Published by Solar Physic

Recurrence quantification analysis as a tool for the characterization of molecular dynamics simulations

A molecular dynamics simulation of a Lennard-Jones fluid, and a trajectory of the B1 immunoglobulin G-binding domain of streptococcal protein G (B1-IgG) simulated in water are analyzed by recurrence quantification, which is noteworthy for its independence from stationarity constraints, as well as its ability to detect transients, and both linear and nonlinear state changes. The results demonstrate the sensitivity of the technique for the discrimination of phase sensitive dynamics. Physical interpretation of the recurrence measures is also discussed.Comment: 7 pages, 8 figures, revtex; revised for review for Phys. Rev. E (clarifications and expansion of discussion)-- addition of the 8 postscript figures previously omitted, but unchanged from version

Heterochromatin: A Rapidly Evolving Species Barrier

Recent work has shown that changes in the sequence composition of heterochromatin, or in the factors that maintain that heterochromatin, may play an important role in speciation

Comprehensive analysis of the chromatin landscape in Drosophila melanogaster.

Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized by nine prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function

The Beneficial Effects of Apical Sodium-Dependent Bile Acid Transporter Inactivation Depend on Dietary Fat Composition

Scope The apical sodium‐dependent bile acid transporter (ASBT, SLC10A2) is important in the enterohepatic cycling of bile acids and thereby in the intestinal absorption of lipids. ASBT inhibition has been shown to improve aspects of the metabolic syndrome, but the underlying mechanisms have remained unclear. Here, the effect of ASBT inhibition on the uptake of specific fatty acids and its consequences for diet‐induced obesity and non‐alcoholic fatty liver disease (NAFLD) are investigated. Methods Intestinal fat absorption is determined in mice receiving an ASBT inhibitor and in Asbt−/− mice. Metabolic disease development is determined in Asbt−/− mice receiving a low‐fat control diet (LFD) or high‐fat diet (HFD) rich in saturated fatty acids (SFAs) or PUFAs. Results Both ASBT inhibition and Asbt gene inactivation reduce total fat absorption, particularly of SFAs. Asbt gene inactivation lowers bodyweight gain, improves insulin sensitivity, and decreases the NAFLD activity score upon feeding a HFD rich in SFAs, but not in PUFAs. Conclusions The beneficial metabolic effects of ASBT inactivation on diet‐induced obesity depend on decreased intestinal absorption of SFAs, and thus on the dietary fatty acid composition. These findings highlight the importance of dietary fatty acid composition in the therapeutic effects of ASBT inhibition

Triggering an eruptive flare by emerging flux in a solar active-region complex

A flare and fast coronal mass ejection originated between solar active regions NOAA 11514 and 11515 on July 1, 2012 in response to flux emergence in front of the leading sunspot of the trailing region 11515. Analyzing the evolution of the photospheric magnetic flux and the coronal structure, we find that the flux emergence triggered the eruption by interaction with overlying flux in a non-standard way. The new flux neither had the opposite orientation nor a location near the polarity inversion line, which are favorable for strong reconnection with the arcade flux under which it emerged. Moreover, its flux content remained significantly smaller than that of the arcade (approximately 40 %). However, a loop system rooted in the trailing active region ran in part under the arcade between the active regions, passing over the site of flux emergence. The reconnection with the emerging flux, leading to a series of jet emissions into the loop system, caused a strong but confined rise of the loop system. This lifted the arcade between the two active regions, weakening its downward tension force and thus destabilizing the considerably sheared flux under the arcade. The complex event was also associated with supporting precursor activity in an enhanced network near the active regions, acting on the large-scale overlying flux, and with two simultaneous confined flares within the active regions.Comment: Accepted for publication in Topical Issue of Solar Physics: Solar and Stellar Flares. 25 pages, 12 figure