Function Of Release Time Research Articles

8. Controlling the rate of presentation of BMP-2 from a highly structured composite for interbody fusion

<h3>BACKGROUND CONTEXT</h3> Clinical outcomes for patients with intervertebral disc injury or disease could be enhanced by a new generation of regenerative matrices that create tissue environments to control angiogenesis, chondrogenesis and bone formation. Regenerative matrices are a new class of controlled release biomaterials that use surface chemistry, materials architecture, and drug delivery kinetics to create optimised conditions for cell interactions that result in high quality tissue formation. A novel biodegradable polymer matrix that releases bone morphogenetic protein 2 (BMP-2) over a period of one month with a low Cmax and sustained presentation of active protein is investigated in this study. <h3>PURPOSE</h3> BMP-2 release kinetics and protein activity from a new regenerative matrix was quantified to develop an implant with 1-month release of the drug within a macroporous matrix. A rabbit posterolateral (PLF) vertebral fusion model was performed to assess bone formation and fusion outcomes as a function of dose and source of BMP-2 (E coli and CHO cells). <h3>STUDY DESIGN/SETTING</h3> The study was designed to investigate the effect of various biomaterial design factors and manufacturing methods on the rate of release of BMP-2, the activity of BMP-2 and the extent of in vivo bone formation. <h3>PATIENT SAMPLE</h3> This study did not involve patients. <h3>OUTCOME MEASURES</h3> Outcome measures were the mechanical properties of the regenerative matrix, the architecture and porosity of the matrix, BMP-2 release kinetics, BMP-2 activity as a function of release time and bone formation. <h3>METHODS</h3> BMP-2 activity was tested using two in vitro cell-based assays. BMP-2 solutions and regenerative matrix extracts were tested for their ability to induce alkaline phosphatase (ALP) activity in W-20-17 stromal cells using a modified version of the ASTM standard protocol for in vitro biological activity of recombinant human BMP-2 (F2131-02). Cells were exposed to serial dilutions of BMP-2 for 24 h, assayed for ALP activity and EC50s calculated allowing the relative potency to NIBSC WHO BMP-2 standard to be calculated. BMP-2 release was assessed with an in vitro assay of ALP activity in the mouse muscle myoblast cell line C2C12. Formulations were suspended above a C2C12 monolayer in an insert with a porous (8 µm) PET membrane. Following 3-4 days of exposure, the inserts containing LDGraft were transferred to fresh cells for a further 3-4 days. Cells exposed to LDGraft in this manner were assayed for ALP activity (normalised to protein content) once the inserts had been transferred to fresh cells. Fusion rate and new bone formation were compared to INFUSE in a single-level lumbar (L4-L5) posterolateral (PLF) vertebral fusion model in the New Zealand White rabbit based on standard protocols (Boden et al, 1995, ASTM F3207). Pre-formed implants (3 cc) of INFUSE (rhBMP-2 and absorbable collagen sponge) were implanted on decorticated dorsal surfaces of the transverse processes of L4 and L5 adjacent to the laminae. Fusion was assessed by radiograph at 6 weeks and by manual palpation, radiography and microCT at 12 weeks. <h3>RESULTS</h3> BMP-2 activity was retained over one month of release with the addition of protectants in the formulation and precise control of manufacturing processes. The matrix had a porosity of >70% with a high proportion of macropores (>200 micron diameter). Low doses of E. coli-produced BMP-2 induced fusion in the PLF model. <h3>CONCLUSIONS</h3> A one-month releasing BMP-2 formulation is described. This new regenerative matrix had internal architecture designed to host angiogenesis. Manufacturing and design challenges can be overcome to retain high biologic activity throughout the release period. <h3>FDA DEVICE/DRUG STATUS</h3> BMP-2, not approved for this indication.

Changes of Non-Sense Syllabic Word Scores and Preferences as a Function of Release Time on Multi-Channel Hearing Aids

Purpose To determine the effective release time (RT) for listening to Korean sounds when wearing hearing aids, we evaluated Korean non-sense syllabic word recognition scores (NSRS) and the clarity of conversation sounds, the size of noise, and the overall preferences as a function of RT. Methods Twenty adults and elderly people with mild to severe sensorineural hearing loss were participated as subjects. In the quiet and noise environment, NSRS and preferences were evaluated after setting the RT of the multi-channel hearing aids to 70, 200, and 600 ms. Presentation level of non-sense syllabic word was 45 dB HL and signal-to-noise ratio was 6 dB in noise environment. Results NSRS was not different as a function of RT in quiet, but NSRS of 200 ms was higher than 70 ms and 600 ms in noise environment. However, clarity, loudness of noise, and overall preference did not show a difference in RT in a quiet and noisy environment. Conclusion Through this study, it was confirmed that Korean NSRS can be affected by RT. Therefore, in order to develop a hearing aid fitting formula that is effective in recognition of Korean speech sound, it is necessary to consider the RT. Key Words: Hearing aids, Release time, Compression threshold, Compression ratio, Hearing aid fitting formula 중심 단어: 보청기, í•´ì œì‹œê°„, 압축역치, 압축비율, ë³´ì²­ê¸°ì í•©ê³µì‹

Microencapsulation of cells in alginate through an electrohydrodynamic process

The encapsulation of living cells within a semi-permeable matrix is an attractive process for transplanting nonautologous cells by limiting the interaction with the host immune system. The electrohydrodynamic process is a low-cost and high-throughput system to encapsulate cells by means of a static potential. We evaluated the use of this system for cell entrapment by assessing and then manufacturing capsules that had the best dimensions. The effect of different cell densities on the beads was determined to set up the basic parameters of the encapsulation system. The cell viability inside the beads and as a function of release time was observed for their biological response.

UTEX modeling of radioxenon isotopic fractionation resulting from subsurface transport

The underground transport of environmental xenon (UTEX) model is a finite-difference code that was developed at the University of Texas at Austin to simulate the transport of radioxenon from an underground nuclear detonation to the surface. UTEX handles a time dependent source term and includes the effects of radioactive decay to determine isotopic signatures of the various radioxenon species as a function of release time. The model shows that significant perturbations in the isotopic signatures are possible under some geologic conditions. Transport of radioxenon gas in UTEX is driven in large part by atmospheric pumping. A study was undertaken to characterize the dependence of resulting isotopic signatures on the various geologic and physical parameters that define the system model. Additionally, the model was used to roughly simulate isotopic measurements at various depths and position; the potential dependence of isotopic radioxenon fractionation on sampling depth and lateral position between fractures was examined.

Characterisation of prompt and delayed atmospheric radioactivity releases from underground nuclear tests at Nevada as a function of release time

A database with information on about 500 cases of atmospheric radioactivity releases from underground nuclear tests is analysed. The data are statistically evaluated and systematically aggregated in order to characterise prompt uncontrolled as well as delayed operational releases of radioactivity into the atmosphere. The focus is put on the latter. The reported data compare well with theoretically derived xenon activities for reasonable nuclear test scenarios. Conclusions are drawn on the main features of releases that can be expected from underground nuclear tests as a function of release time. These findings are relevant for developing and validating methods to be applied in global monitoring of atmospheric radioactivity with respect to indications of an underground nuclear explosion.

Comparisons of Transport and Dispersion Model Predictions of the Joint Urban 2003 Field Experiment

Abstract For a hazardous material release in a city or densely populated area, effective mitigation requires an understanding of the transport and dispersion of these hazards in the complex urban environment. Improved characterization and understanding of urban transport and dispersion will allow for more robust modeling. The Defense Threat Reduction Agency has developed a Hazard Prediction Assessment Capability (HPAC) that includes features to address hazardous releases within an urban environment. During the summer of 2003, a series of tracer gas releases were carried out in Oklahoma City, Oklahoma, and extensive meteorological and tracer concentration measurements were collected in a field experiment known as Joint Urban 2003 (JU03). This analysis uses the observations of JU03 to evaluate “Urban HPAC.” Twenty sets of simulations, or “predictions,” using four Urban HPAC modes and five meteorological input options, were created and compared using a variety of metrics. Strong consistency was found between the conclusions of this study and those of two previously reported Urban HPAC evaluations. For example, improved predictions were associated with the inclusion of a simple empirically based urban dispersion model within HPAC, whereas improvements associated with the inclusion of a more computationally intensive urban wind module were not found. In this study, two new results are reported. First, there was a substantial difference in the performance of Urban HPAC as a function of release time—day or night—that was not discovered earlier because the previously examined urban field experiments focused on nighttime releases only. Daytime releases tended to be underpredicted and nighttime releases tended to be overpredicted. Second, and with respect to the under- and overpredictions described above, the inclusion of the new “Micro” Stationary Wind Fit and Turbulence (SWIFT) “SPRAY” (MSS) Urban HPAC mode typically led to less underprediction during the day and less overprediction at night than the other Urban HPAC modes. In addition, predictions that included MSS typically resulted in the least scatter between observations and predictions. These improvements warrant further investigation to determine whether this conclusion can be extended to other urban environments.

Spectral Line Shape Variations in Time-Resolved Photoemission from a Solid

Laser assisted photoemission by a subfemtosecond ultraviolet pulse is studied by solving the time-dependent Schrödinger equation for a one-dimensional model crystal. Without the laser field, the shape and the energy location of the spectrum are determined by the energy dependence of the photoemission cross section. In the presence of the laser field, the time growth of the population of the final state is predicted to cause extremely sharp variations of spectral width as a function of release time. This can help enhance time resolution of the measurements. A simple phenomenological model to describe the line shape is proposed.

DSIMS characterization of a drug-containing polymer-coated cardiovascular stent

Dynamic Secondary Ion Mass Spectrometry (DSIMS) was used to study the release behavior of cytochalasin D, an actin polymerase inhibitor effective in the reduction of smooth muscle cell (SMC) proliferation, from a polymer-coated cardiovascular stent. High-performance liquid chromatography (HPLC) was used to determine the percentage of drug released as a function of time and showed the typical behavior of a drug-releasing system that is comprised of a core drug–polymer dispersion surrounded by a drug-free polymeric membrane: an initial burst of the drug followed by a gradual elution over time. DSIMS profiles, as a function of release time, indicated that depletion of the drug initially occurred only in the outer layers of the coating. As release progressed the DSIMS profile showed a gradual decrease of cytochalasin D with increasing depth. This study shows that DSIMS is a powerful tool for the determination of drug distributions in, and the release behavior from, thin polymer layers.