71 research outputs found

    Preparation of Active Proteins, Vaccines and Pharmaceuticals as Fine Powders using Supercritical or Near-Critical Fluids

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    Supercritical or near-critical fluid processes for generating microparticles have enjoyed considerable attention in the past decade or so, with good success for substances soluble in supercritical fluids or organic solvents. In this review, we survey their application to the production of protein particles. A recently developed process known as CO2-assisted nebulization with a Bubble Dryer® (CAN-BD) has been demonstrated to have broad applicability to small-molecule as well as macromolecule substances (including therapeutic proteins). The principles of CAN-BD are discussed as well as the stabilization, micronization and drying of a wide variety of materials. More detailed case studies are presented for three proteins, two of which are of therapeutic interest: anti-CD4 antibody (rheumatoid arthritis), α1-antitrypsin (cystic fibrosis and emphysema), and trypsinogen (a model enzyme). Dry powders were formed in which stability and activity are maintained and which are fine enough to be inhaled and reach the deep lung. Enhancement of apparent activity after CAN-BD processing was also observed in some formulation and processing conditions

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    Use of backscattered Doppler signal intensity in estimation of volume flow ratios

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    Increased heart rate can cause underestimation of regurgitant jet size by Doppler color flow mapping

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    AbstractObjectives. This study addressed the hypothesis that at a constant peak flow rate, an increasing heart rate could decrease the maximal apparent jet size by Doppler color flow mapping.Background. Recent studies have attempted to predict the severity of regurgitation from maximal jet area by Doppler color flow mapping, which correlates with flow rate for free jets at constant driving pressure and steady flow. In patients, however, maximal jet area exists for only a limited time per beat and the likelihood of visualizing it by Doppler color flow mapping depends on its duration relative to the color frame sampling rate. Increased heart rate could potentially diminish apparent jet size, particularly at slow frame rates that may not permit visualization of the maximal jet area in all beats.Methods. This interaction was examined in pulsatile flow, holding orifice size and peak flow rate constant and varying pump pulse rate (70 to 180 beats/min) and frame rate (three rates) for jets of low and high momentum. Maximal jet area was measured in 10 consecutive beats at each pulse rate and frame rate and averaged.Results. For the low momentum jet, the 10-beat average of peak jet area decreased progressively with increasing poise rate. As pulse rate increased from 70 to 180 beats/min, maximal jet area decreased 23% at the fastest frame rate and 42% at the slowest frame rate, with prominent beat to beat variability. Jet area decreased 13% to 20% at pulse rates as low as 90 beats/min. In contrast, for the high momentum jet, maximal jet area decreased by ≤9% from low to high pulse rate at any frame rate.Conclusions. Increased heart rate can cause underestimation of apparent jet size by Doppler color flow mapping for a given peak flow rate, particularly for jets with low momentum and delayed penetration into the receiving chamber. This observation may be relevant to acute severe regurgitation with increased heart rate in which such underestimation has been reported, as well as to right-sided lesions and children with rapid heart rates. It will also affect new techniques proposed to quantify regurgitation on the basis of velocities derived from Doppler color flow images. In practice, this effect can be reduced by increasing frame rate and selecting maximal apparent jet size at rapid heart rates and should be considered in relating jet size to the severity of regurgitation
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