Molecular dynamics simulations have been performed for methanol/carbon tetrachloride mixtures over the whole composition range at 323 K and zero pressure. The OPLS ͑optimized potentials for liquid simulation͒ potential energy parameters by Jorgensen were used to model the methanol potential. Both a non-polarizable carbon tetrachloride model taken from McDonald, Bounds, and Klein ͓Mol. Phys. 45, 521 ͑1982͔͒ as well as a polarizable model were used. The latter model was devised by combining the model of McDonald, Bounds, and Klein with the atomic polarizabilities proposed by Applequist, Carl, and Fung ͓J. Am. Chem. Soc. 94, 2952 ͑1972͔͒. We show that the role of the methanol-carbon tetrachloride interactions are very important in discussing the thermodynamic mixing properties. In order to reproduce the asymmetric behavior of the excess enthalpies with respect to composition it is necessary to include the non-additive polarization interaction. The structure and especially hydrogen bonding properties are discussed. Radial distribution functions show a strong tendency of methanol to preserve the local order similar to the one in the pure fluid. The deviations from random mixing are more pronounced at the lower mole fractions. This is explained by a frustration model. At low methanol concentrations the molecules get more freedom to align themselves in energetically favorable ͑hydrogen bonded͒ configurations. Throughout the composition range, the majority of the methanol molecules is found to be engaged in two hydrogen bond, As in the pure fluid, this leads to the pattern of hydrogen bonded winding chains. Upon dilution the degree of cross-linking between the chains diminishes whereas the free monomer fraction rises. Furthermore a significant number of the remaining chains close to form cyclic polymers.
Rationale: Although we and others have recently shown that mast cells play an important role in plaque progressionand destabilization, the nature of the actual trigger for (peri)vascular mast cell activation during atherosclerosis is still unresolved. Objective: In this study, we confirm that perivascular mast cell content correlates with the number of nerve fibers in the adventitia of human coronary atherosclerotic plaque specimen. Because peripheral C-type nerve fibers secrete, among others, substance P, a potent mast cell activator, we set out to study effects of adventitial administration of this neuropeptide on mast cell dependent destabilization of carotid artery plaques in apolipoprotein E-deficient (apoE Key Words: atherosclerosis Ⅲ mast cells Ⅲ neuropeptides Ⅲ substance P Ⅲ hemorrhage A cute coronary syndromes are generally caused by atherosclerotic plaque rupture. 1,2 Mast cells, major players in allergy and asthma, 3 were found to be abundantly present in the intima and adventitia of unstable human atherosclerotic lesions 4,5 and recently, we and others have conclusively demonstrated that (peri)vascular mast cells contribute to atherosclerotic plaque progression and destabilization in mice. 6,7 However, the nature of potential mast cell triggers in atherosclerosis is still unresolved.Adventitial mast cells in human lesions have been reported to colocalize with nerve fibers, 8 fueling the intriguing option of neuronal regulation of mast cell activation. Neuropeptides such as substance P are predominantly released by peripheral C-type sensory neurons 9 and have been demonstrated to be involved in psychological stress-induced disorders 10 and in stress-related cardiovascular events and inflammation. 11 Mast cell activation by neuropeptides proceeds through dedicated receptors, such as neurokinin-1 receptor (NK1R) or by direct activation of G proteins. 12,13 Because tryptase-positive mast cells were seen to colocalize with substance P-positive nerve fibers in skin 14 and in adventitial tissue, 8 this potent mast cell activator may be a likely candidate to mediate perivascular mast cell recruitment and activation in response to stress. In this study, we addressed the role of substance P in mast cell dependent plaque progression and destabilization. MethodsAn expanded Methods section is available in the Online Data Supplement at http://circres.ahajournals.org.Human coronary artery samples were collected, and 10 m sections were prepared. Mast cell presence was established with a Original
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