Molecular dynamics simulations of mixtures of the ceramide nonhydroxy-sphingosine (NS), cholesterol, and a free fatty acid are performed to gain molecular-level understanding of the structure of the lipids found in the stratum corneum layer of skin. A new coarse-grained force field for cholesterol was developed using the multistate iterative Boltzmann inversion (MS-IBI) method. The coarse-grained cholesterol force field is compatible with previously developed coarse-grained force fields for ceramide NS, free fatty acids, and water and validated against atomistic simulations of these lipids using the CHARMM force field. Self-assembly simulations of multilayer structures using these coarse-grained force fields are performed, revealing that a large fraction of the ceramides adopt extended conformations, which cannot occur in the single bilayer in water structures typically studied using molecular simulation. Cholesterol fluidizes the membrane by promoting packing defects, and an increase in cholesterol content is found to reduce the bilayer thickness due to an increase in interdigitation of the C₂₄ lipid tails, consistent with experimental observations. Using a reverse-mapping procedure, a self-assembled coarse-grained multilayer system is used to construct an equivalent structure with atomistic resolution. Simulations of this atomistic structure are found to closely agree with experimentally derived neutron scattering length density profiles. Significant interlayer hydrogen bonding is observed in the inner layers of the atomistic multilayer structure that are not found in the outer layers in contact with water or in equivalent bilayer structures. This work highlights the importance of simulating multilayer structures, as compared to the more commonly studied bilayer systems, to enable more appropriate comparisons with multilayer experimental membranes. These results also provide validation of the efficacy of the MS-IBI derived coarse-grained force fields and the framework for multiscale simulation.

2014-11-01·Colloids and Surfaces B: Biointerfaces2区 · 工程技术

A study of chitosan hydrogel with embedded mesoporous silica nanoparticles loaded by ibuprofen as a dual stimuli-responsive drug release system for surface coating of titanium implants

2区 · 工程技术

Article

作者: Du, Yumin ; Qin, Caiqin ; Xiao, Ling ; Shi, Xiaowen ; Zhao, Pengkun ; Liu, Hongyu ; Deng, Hongbing

In this study, the complex pH and electro responsive system made of chitosan hydrogel with embedded mesoporous silica nanoparticles (MSNs) was evaluated as a tunable drug release system. As a model drug, ibuprofen (IB) was used; its adsorption in MSNs was evidenced by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and thermogravimetric analysis (TG). In order to prepare the complex drug release system, the loaded particles IB-MSNs were dispersed in chitosan solution and then the complex IB-MSNs/chitosan film of 2mm thickness was deposited as a hydrogel on the titanium electrode. The codeposition of components was performed under a negative biasing of the titanium electrode at -0.75 mA/cm2 current density during 30 min. The IB release from the IB-MSNs/chitosan hydrogel film was studied as dependent on pH of the release media and electrical conditions applied to the titanium plate. When incubating the complex hydrogel film in buffers with different pH, the IB release followed a near zero-order profile, though its kinetics varied. Compared to the spontaneous IB release from the hydrogel in 0.9% NaCl solution (at 0 V), the application of negative biases to the coated titanium plate had profound effluences on the release behavior. The release was retarded when -1.0 V was applied, but a faster kinetics was observed at -5.0 V. These results imply that a rapid, mild and facile electrical process for covering titanium implants by complex IB-MSNs/chitosan hydrogel films can be used for controlled drug delivery applications.

2014-05-01·The American Journal of Surgery3区 · 医学

Influence of nurse navigation on wait times for breast cancer care in a Canadian regional cancer center

3区 · 医学

Article

作者: Baliski, Christopher ; Liberto, Caitlyn M ; Taylor, Marianne ; Ellard, Susan ; McGahan, Colleen E ; Broughton, Sandra ; Lai, Anky ; Bates, Janet

BACKGROUNDThe wait times for breast cancer care in our region do not meet acceptable benchmarks. We implemented the Interior Breast Rapid Access Investigation and Diagnosis (IB-RAPID) nurse navigation program to address this issue.METHODSThe IB-RAPID prospective database was reviewed for patients entering the program between April 1, 2011 and April 30, 2012 (2011/2012 cohort), and was compared with patients from the same area in 2010. The main end point was the time between the 1st diagnostic imaging test and the surgery. Multiple linear regression was performed to investigate factors influencing the wait times.RESULTSThe wait times decreased with the introduction of IB-RAPID (59 vs 48 days; median). Stage of disease, total number of biopsies, and magnetic resonance imaging (MRI) use influenced wait times. MRI significantly delayed surgical intervention in both groups with those not having an MRI having a shorter wait time to surgery (68.5 vs 57.6 days; mean) in 2011/2012.CONCLUSIONThe implementation of nurse navigation for patients with breast cancer appears to be effective at reducing the wait times for surgical treatment.

100 项与 IB-MS 相关的药物交易

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