Modelling of the diffusion of carbon dioxide in polyimide matrices by computer simulation

Computer aided molecular modelling is used to visualize the motion of CO2 gas molecules inside a polyimide polymer matrix. The polymers simulated are two 6FDA-bases polyimides, 6FDA-4PDA and 6FDA-44ODA. These polymers have also been synthesized in our laboratory, and thus the simulated properties could directly be compared with “real-world” data. The simulation experiments have been performed using the GROMOS1 package. The polymer boxes were created using the soft-core method, with short (11 segments) chains. This results in highly relaxed and totally amorphous polyimide matrices. The motion of randomly placed CO2 molecules in the boxes during molecular dynamics runs was followed, revealing three types of motion: jumping, continuous- and trapped motion. The calculated diffusivities are unrealistic, but possible shortcomings in our model are given

Fluid-rock interaction during high-grade metamorphism: instructive examples from the Southern Marginal Zone of the Limpopo Complex, South Africa

The Southern Marginal Zone of the Limpopo Complex documents strong evidence that CO2-rich (XCO2=0.7–0.9, XH2O= 0.1–0.3) and brine fluids of greatly reduced water activity interacted with cooling metapelitic granulite during the thrust-controlled emplacement at 2.69–2.62 Ga onto the granite-greenstone terrain of the northern Kaapvaal Craton. Interaction of cooling metapelitic granulite with CO2-rich fluids at T 900°C, P > 7.5 kbar. Interaction of hot melt with metapelitic granulite continued until final emplacement in the middle crust (P = 6 kbar, T = 630°C). Brine fluids also initiated shear zone-hosted metasomatism of quartzo-feldspathic gneisses at T between 600 and 900°C and amphibolite-facies lode-gold mineralization. Available data implicate devolatilization of underthrusted greenstone material as the dominant deep crustal source for infiltrating CO2-rich and brine fluids

Tobramycin Clearance Is Best Described by Renal Function Estimates in Obese and Non-obese Individuals: Results of a Prospective Rich Sampling Pharmacokinetic Study

Item does not contain fulltextPURPOSE: Tobramycin is an aminoglycoside antibiotic of which the 24 h exposure correlates with efficacy. Recently, we found that clearance of the aminoglycoside gentamicin correlates with total body weight (TBW). In this study, we investigate the full pharmacokinetic profile of tobramycin in obese and non-obese individuals with normal renal function. METHODS: Morbidly obese individuals (n = 20) undergoing bariatric surgery and non-obese healthy volunteers (n = 8), with TBW ranging 57-194 kg, received an IV dose of tobramycin with plasma concentrations measured over 24 h (n = 10 per individual). Statistical analysis, modelling and simulations were performed using NONMEM. RESULTS: In a two-compartment model, TBW was the best predictor for central volume of distribution (p < 0.001). For clearance, MDRD (de-indexed for body surface area) was identified as best covariate (p < 0.001), and was superior over TBW ((p < 0.05). Other renal function estimates (24 h urine GFR and de-indexed CKD-EPI) led to similar results as MDRD (all p < 0.001)). CONCLUSIONS: In obese and non-obese individuals with normal renal function, renal function estimates such as MDRD were identified as best predictors for tobramycin clearance, which may imply that other processes are involved in clearance of tobramycin versus gentamicin. To ensure similar exposure across body weights, we propose a MDRD-based dosing nomogram for obese patients

Cost Effectiveness of Treatment With New Agents in Advanced Non-Small-Cell Lung Cancer: A Systematic Review

In past decades, studies focusing on new chemotherapeutic agents for patients with inoperable non-small-cell lung cancer have reported only modest gains in survival. These health gains are achieved at considerable cost, but economic evidence is lacking on superiority of one agent in terms of cost effectiveness. The objective of this systematic review was to assess fully published cost-effectiveness studies comparing the new agents docetaxel, paclitaxel, vinorelbine, gemcitabine and pemetrexed, and the targeted therapies erlotinib and gefitinib with one another.We performed systematic searches in the bibliographic databases PubMed, EMBASE and Health Economic Evaluations (HEED) via the Cochrane Library for fully published studies from the past 10 years. Studies were screened by two independent reviewers according to a priori inclusion criteria. The methodological quality of the included studies was evaluated by two independent reviewers using standardized assessment tools.A total of 222 potential studies were identified; 11 studies and six reviews were included. The methodological quality of the full economic evaluations was fairly good. Transparency in costs and resource use, details on statistical tests and sensitivity analysis were points for improvement. In first-line treatment, gemcitabinecisplatin was cost effective compared with other platinum-based regimens (paclitaxel, docetaxel and vinorelbine). In one study, pemetrexedcisplatin was cost effective compared with gemcitabinecisplatin in patients with non-squamous-cell carcinoma. In second-line treatment, docetaxel was cost effective compared with best supportive care; erlotinib was cost effective compared with placebo; and docetaxel and pemetrexed were dominated by erlotinib.We found indications of superiority in terms of cost effectiveness for gemcitabinecisplatin in a first-line setting, and for erlotinib in a second-line setting. © 2012 Adis Data Information BV. All rights reserved

Role of Curvature-Sensing Proteins in the Uptake of Nanoparticles with Different Mechanical Properties

Nanoparticles of different properties, such as size, charge, and rigidity, are used for drug delivery. Upon interaction with the cell membrane, because of their curvature, nanoparticles can bend the lipid bilayer. Recent results show that cellular proteins capable of sensing membrane curvature are involved in nanoparticle uptake; however, no information is yet available on whether nanoparticle mechanical properties also affect their activity. Here liposomes and liposome-coated silica are used as a model system to compare uptake and cell behavior of two nanoparticles of similar size and charge, but different mechanical properties. High-sensitivity flow cytometry, cryo-TEM, and fluorescence correlation spectroscopy confirm lipid deposition on the silica. Atomic force microscopy is used to quantify the deformation of individual nanoparticles at increasing imaging forces, confirming that the two nanoparticles display distinct mechanical properties. Uptake studies in HeLa and A549 cells indicate that liposome uptake is higher than for the liposome-coated silica. RNA interference studies to silence their expression show that different curvature-sensing proteins are involved in the uptake of both nanoparticles in both cell types. These results confirm that curvature-sensing proteins have a role in nanoparticle uptake, which is not restricted to harder nanoparticles, but includes softer nanomaterials commonly used for nanomedicine applications.</p