The mechanism and mitigation of niacin-induced flushing

AimsTo summarise the metabolic responses to niacin that can lead to flushing and to critically evaluate flushing mitigation research.Methods and resultsThis comprehensive review of the mechanism of action of niacin-induced flushing critically evaluates research regarding flushing mitigating formulations and agents. Niacin induces flushing through dermal Langerhans cells where the activation of G protein-coupled receptor 109A (GPR109A) increases arachidonic acid and prostaglandins, such as prostaglandin D(2) (PGD(2)) and prostaglandin E(2) (PGE(2)), subsequently activating prostaglandin D(2) receptor (DP(1)), prostaglandin E(2) receptor (EP(2)) and prostaglandin E receptor 4 (EP(4)) in capillaries and causing cutaneous vasodilatation. Controlling niacin absorption rates, inhibiting prostaglandin production, or blocking DP(1), EP(2) and EP(4) receptors can inhibit flushing. Niacin extended-release (NER) formulations have reduced flushing incidence, duration and severity relative to crystalline immediate-release niacin with similar lipid efficacy. Non-steroidal anti-inflammatory drugs (NSAIDs), notably aspirin given 30 min before NER at bedtime, further reduce flushing. An antagonist to the DP(1) receptor (laropiprant) combined with an ER niacin formulation can reduce flushing; however, significant residual flushing occurs with clinically-relevant dosages.ConclusionsNiacin is an attractive option for treating dyslipidemic patients, and tolerance to niacin-induced flushing develops rapidly. Healthcare professionals should particularly address flushing during niacin dose titration

Atomic X-ray Spectroscopy of Accreting Black Holes

Current astrophysical research suggests that the most persistently luminous objects in the Universe are powered by the flow of matter through accretion disks onto black holes. Accretion disk systems are observed to emit copious radiation across the electromagnetic spectrum, each energy band providing access to rather distinct regimes of physical conditions and geometric scale. X-ray emission probes the innermost regions of the accretion disk, where relativistic effects prevail. While this has been known for decades, it also has been acknowledged that inferring physical conditions in the relativistic regime from the behavior of the X-ray continuum is problematic and not satisfactorily constraining. With the discovery in the 1990s of iron X-ray lines bearing signatures of relativistic distortion came the hope that such emission would more firmly constrain models of disk accretion near black holes, as well as provide observational criteria by which to test general relativity in the strong field limit. Here we provide an introduction to this phenomenon. While the presentation is intended to be primarily tutorial in nature, we aim also to acquaint the reader with trends in current research. To achieve these ends, we present the basic applications of general relativity that pertain to X-ray spectroscopic observations of black hole accretion disk systems, focusing on the Schwarzschild and Kerr solutions to the Einstein field equations. To this we add treatments of the fundamental concepts associated with the theoretical and modeling aspects of accretion disks, as well as relevant topics from observational and theoretical X-ray spectroscopy.Comment: 63 pages, 21 figures, Einstein Centennial Review Article, Canadian Journal of Physics, in pres

Collisional excitation of hydrogen and the determination of the primordial helium abundance from H II regions

This paper investigates the effect of collisional enhancement of the hydrogen lines on the derivation of the helium abundances in low metallicity H II regions. For this, we have constructed a grid of photoionization models relevant for the analysis of giant \hii regions in blue compact galaxies. We show that the effect of collisional excitation on the Halpha/Hbeta ratio can be quite important (up to 8% or more). The impact of this effect on the determination of the helium mass fraction has been tracked on four low-metallicity blue compact galaxies for which Keck spectra are available and which are among the best objects for the quest of the pregalactic helium abundance. We find that taking into account the effects of collisional excitation of hydrogen results in an upward correction of the helium mass fraction Y by up to 5%. However, combining with other systematic effects usually not considered in the determination of the helium abundance in low-metallicity galaxies, the resulting uncertainty should be much less.Comment: 10 pages, 6 Postscript figures, accepted for publication in the Astronomy and Astrophysic

Lipoprotein associated phospholipase A2: role in atherosclerosis and utility as a biomarker for cardiovascular risk

Atherosclerosis and its clinical manifestations are widely prevalent throughout the world. Atherogenesis is highly complex and modulated by numerous genetic and environmental risk factors. A large body of basic scientific and clinical research supports the conclusion that inflammation plays a significant role in atherogenesis along the entire continuum of its progression. Inflammation adversely impacts intravascular lipid handling and metabolism, resulting in the development of macrophage foam cell, fatty streak, and atheromatous plaque formation. Given the enormous human and economic cost of myocardial infarction, ischemic stroke, peripheral arterial disease and amputation, and premature death and disability, considerable effort is being committed to refining our ability to correctly identify patients at heightened risk for atherosclerotic vascular disease and acute cardiovascular events so that they can be treated earlier and more aggressively. Serum markers of inflammation have emerged as an important component of risk factor burden. Lipoprotein-associated phospholipase A2 (Lp-PLA2) potentiates intravascular inflammation and atherosclerosis. A variety of epidemiologic studies support the utility of Lp-PLA2 measurements for estimating and further refining cardiovascular disease risk. Drug therapies to inhibit Lp-PLA2 are in development and show considerable promise, including darapladib, a specific molecular inhibitor of the enzyme. In addition to substantially inhibiting Lp-PLA2 activity, darapladib reduces progression of the necrotic core volume of human coronary artery atheromatous plaque. The growing body of evidence points to an important role and utility for Lp-PLA2 testing in preventive and personalized clinical medicine

Ant-Pollinator Conflict Results in Pollinator Deterrence but no Nectar Trade-Offs

Direct and indirect negative interactions between ant guards and pollinators on ant-plants are expected for two reasons. First, aggressive ants may deter pollinators directly. Second, pollinators benefit from plant investment in reproduction whilst ants benefit from plant investment in indirect defense, and resource allocation trade-offs between these functions could lead to indirect conflict. We explored the potential for ant-pollinator conflict in a Mexican myrmecophile, Turnera velutina, which rewards ants with extrafloral nectar and pollinators with floral nectar. We characterized the daily timing of ant and pollinator activity on the plant and used experiments to test for direct and indirect conflict between these two groups of mutualists. We tested for direct conflict by quantifying pollinator responses to flowers containing dead specimens of aggressive ant species, relative to unoccupied control flowers. We assessed indirect conflict by testing for the existence of a trade-off in sugar allocation between ant and pollinator rewards, evidenced by an increase in floral nectar secretion when extrafloral nectar secretion was prevented. Secretion of floral and extrafloral nectar, activity of ants and pollinators, and pollen deposition all overlapped in daily time and peaked within the first 2 h after flowers opened. We found evidence of direct conflict, in that presence of ants inside the flowers altered pollinator behavior and reduced visit duration, although visit frequency was unchanged. We found no evidence for indirect conflict, with no significant difference in the volume or sugar content of floral nectar between control plants and those in which extrafloral nectar secretion was prevented. The presence of ants in flowers alters pollinator behavior in ways that are likely to affect pollination dynamics, though there is no apparent trade-off between plant investment in nectar rewards for pollinators and ant guards. Further studies are required to quantify the effect of the natural abundance of ants in flowers on pollinator behavior, and any associated impacts on plant reproductive success