Zero-order Phase Research Articles

Development of microporous drug-releasing films cast from artificial nanosized latexes of poly(styrene- co-methyl methacrylate) or poly(styrene- co-ethyl methacrylate)

Two sets of copolymers comprising of styrene and either methyl or ethyl methacrylate as comonomer were conveniently synthesized by microemulsion copolymerization. The purified materials were characterized by GPC-MALLS and were shown to form artificial nanolatexes in THF. ATR-FTIR analysis revealed differences in copolymer composition and based on the copolymer properties, a selection of copolymers was chosen to cast drug-loaded, microporous films that exhibit microencapsulation of drug agglomerates. The contact angles of the copolymers suggested potential applications in medical devices to prevent the formation of bacterial biofilms that commonly result in infections. Additionally, the different copolymeric films showed two phases of drug release characterized by a rapid initial drug release followed by a zero-order phase. Depending on the application, one could select the copolymer films that best suited the application i.e. for short-term drug release applications such as urinary catheters or long-term applications such as artificial implants.

Evaluation of in vivo– in vitro release of dexamethasone from PLGA microspheres

Two poly(lactic- co-glycolic acid) (PLGA) microsphere formulations, with different polymer molecular weights were investigated to determine whether an in vitro and in vivo relationship could be established for dexamethasone release. A USP apparatus 4 was used for in vitro testing. The in vivo release kinetics and pharmacodynamic effects of dexamethasone were evaluated using a Sprague Dawley rat model. The in vitro release from both formulations followed the typical triphasic profile of PLGA microspheres (initial burst release, followed by a lag phase and a secondary zero-order phase). The in vivo release profiles differed in that the lag phase was not observed and drug release rates were faster compared to the in vitro studies. It is speculated that the lack of lag phase in vivo may be a result of different PLGA degradation mechanisms in vivo as a consequence of the presence of enzymes as well as other in vivo factors such as interstitial fluid volume, and local pH. This may result in degradation of the PLGA microspheres proceeding from the surface inward in vivo. Whereas, in vitro an “inside out” degradation is thought to occur in some PLGA microsphere systems as a result of the autocatalytic degradation process where build up of acidic oligomeric units can occur within the microspheres. A linear in vitro– in vivo relationship was established after normalization of the time required to reach plateau for the in vitro and in vivo data and the in vitro release data were predictive of the in vivo release. Inflammation was significantly reduced in the tissue surrounding the dexamethasone microspheres compared to the positive control (empty microspheres) and the number of inflammatory cells was similar to that of normal tissue within one to three days.

Automatic phasing of MR images. Part II: Voxel-wise phase estimation

Magnetic resonance images are typically displayed as the absolute value of the discrete Fourier transform of the k-space data. However, absorption-mode images, the real part of the discrete Fourier transform of the data after applying an appropriate phase correction, have significant advantages over absolute-value images. In a companion paper, the problem of estimating the phase parameters needed to produce an absorption-mode image when the phase of the complex image varies linearly as a function of position, a situation common in magnetic resonance images, was addressed. However, some magnetic resonance images have phases that can vary in a complicated, nonlinear, positionally dependent fashion. To produce an absorption-mode image from these data, one must first estimate the positionally dependent phase, and then use that phase estimate to produce an absorption-mode image. This paper addresses both of these problems by first using Bayesian probability theory to estimate the constant or zero-order phase as a function of image position, and then the calculations are illustrated by using them to generate absorption-mode images from data where the phase of the image is a nonlinear function of position.

Automatic phasing of MR images. Part I: Linearly varying phase

In spin-echo and well shimmed gradient-echo images, the phase of the complex image often varies linearly in both the readout and phase-encode directions. Thus, in principle, it is possible to display an image in absorption mode. However, manually determining the two first-order and one zero-order phase parameters needed to display an absorption-mode image is a formidable task. In this paper, the Bayesian calculations needed to automatically determine these parameters are presented, and the calculations are illustrated using spin-echo images.

Spectral phase‐corrected GRAPPA reconstruction of three‐dimensional echo‐planar spectroscopic imaging (3D‐EPSI)

MR spectroscopic (MRS) images from a large volume of brain can be obtained using a 3D echo-planar spectroscopic imaging (3D-EPSI) sequence. However, routine applications of 3D-EPSI are still limited by a long scan time. In this communication, a new approach termed "spectral phase-corrected generalized autocalibrating partially parallel acquisitions" (SPC-GRAPPA) is introduced for the reconstruction of 3D-EPSI data to accelerate data acquisition while preserving the accuracy of quantitation of brain metabolites. In SPC-GRAPPA, voxel-by-voxel spectral phase alignment between metabolite 3D-EPSI from individual coil elements is performed in the frequency domain, utilizing the whole spectrum from interleaved water reference 3D-EPSI for robust estimation of the zero-order phase correction. The performance of SPC-GRAPPA was compared with that of fully encoded 3D-EPSI and conventional GRAPPA. Analysis of whole-brain 3D-EPSI data reconstructed by SPC-GRAPPA demonstrates that SPC-GRAPPA with an acceleration factor of 1.5 yields results very similar to those obtained by fully encoded 3D-EPSI, and is more accurate than conventional GRAPPA.

Zero and first-order phase shift correction for field map estimation with dual-echo GRE using bipolar gradients

A simple phase error correction technique used for field map estimation with a generally available dual-echo gradient-echo (GRE) sequence is presented. Magnetic field inhomogeneity maps estimated using two separate GRE volume acquisitions at different echo times are prone to dynamic motion errors between acquisitions. By using the dual-echo sequence, the data are collected during two back-to-back readout gradients in opposite polarity after a single radio frequency pulse, and interecho motion artifacts and alignment errors in field map estimation can be factored out. Residual phase error from the asymmetric readout pulses is modeled as an affine term in the readout direction. Results from phantom and human data suggest that the first-order phase correction term stays constant over time and, hence, can be applied to different data acquired with the same protocol over time. The zero-order phase correction term may change with time and is estimated empirically for different scans.

Fast Catalytic Hydroxylation of Hydrocarbons with Ruthenium Porphyrins

Ruthenium porphyrin complexes such as carbonylruthenium(II) tetrakispentafluorophenylporphyrin [Ru(II)(TPFPP)(CO)] were found to be efficient catalysts for the hydroxylation of alkanes in the presence of 2,6-dichloropyridine N-oxide as the oxidant under mild, nonacidic conditions. Up to 14 800 turnovers (TO) and rates of 800 TO/min were obtained for the hydroxylation of adamantane. The hydroxylation of cis-decalin afforded cis-9-decalol and cis-decalin-9,10-diol, exclusively, thus, excluding a long-lived radicals mechanism. The kinetics of product evolution in a typical catalytic oxygenation showed an initial induction period followed by a fast, apparently zero-order phase with maximum rates and high efficiencies. Deuterium isotope effects (kH/kD) in the range of 4.2-6.4 were found for the hydroxylation of alkanes. A Hammett treatment of the data for the oxidation of para-substituted toluene derivatives showed a linear correlation with a highly negative rho+ value of -2.0. On the basis of kinetic and spectroscopic evidence, Ru(VI)(TPFPP)(O)2, Ru(II)(TPFPP)(CO), and Ru(IV)(TPFPP)Cl2 observed during catalysis were ruled out as candidates for the active catalyst responsible for the high efficiencies and turnover rates in the oxidation reactions. The fastest rates of adamantane hydroxylation with 2,6-dichloropyridine N-oxide were achieved by the reductive activation of Ru(IV)(TPFPP)Cl2 with a zinc amalgam. This redox activation is consistent with the formation of an active Ru(III) intermediate in situ by a one-electron reduction of the Ru(IV) porphyrin. EPR spectra characteristic of Ru(III) have been observed upon the reduction of Ru(IV)(TPFPP)Cl2 with a zinc amalgam. In the adamantane oxidation mediated with Ru(III)(TPFPP)(OEt), it was found that, during this process, the Ru(III) porphyrin was gradually converted to a dioxoRu(VI) porphyrin. Concomitant with this conversion, the reaction rates decreased. Catalyst activation was also stimulated by autoxidation of the solvent CH2Cl2. On the basis of these data, a mechanism is proposed that incorporates a "fast" cycle involving metastable Ru(III) and oxoRu(V) intermediates and a "slow" oxidation cycle, mediated by oxoRu(IV) and trans-dioxoRu(VI) porphyrin complexes.

In vivo cardiac 1H‐MRS in the mouse

The mouse is the predominant animal model to study the effect of gene manipulations. Imaging techniques to define functional effects on the heart caused by genomic alterations are becoming increasingly routine in mice, yet methods for in vivo investigation of metabolic phenotypes in the mouse heart are lacking. In this work, cardiac 1H-MRS was developed and applied in mouse hearts in vivo using a single-voxel technique (PRESS). In normal C57Bl/6J mice, stability and reproducibility achieved by dedicated cardiac and respiratory gating was demonstrated by measuring amplitude and zero-order phase changes of the unsuppressed water signal. Various cardiac metabolites, such as creatine, taurine, carnitine, or intramyocardial lipids were successfully detected and quantified relative to the total water content in voxels as small as 2 microl, positioned in the interventricular septum. The method was applied to a murine model of guanidinoacetate N-methyltransferase (GAMT) deficiency, which is characterized by substantially decreased myocardial creatine levels. Creatine deficiency was confirmed noninvasively in myocardium of anesthetized GAMT-/- mice. This is the first study to report the application of cardiac 1H-MRS in mice in vivo.

Bragg Gratings Written in All->tex<$rm SiO_2$>/tex<and Ge-Doped Core Fibers With 800-nm Femtosecond Radiation and a Phase Mask

Femtosecond laser pulses at 800 nm and 120 fs were used to fabricate high-quality retroreflecting fiber Bragg gratings in standard Ge-doped telecom fiber (Corning SMF-28) and all-silica-core Fluorine doped cladding single-mode fiber using a deep-etch silica zero-order nulled phase mask. Induced index modulations of 1.9/spl times/10/sup -3/ were achieved with peak power intensities of 2.9/spl times/10/sup 12/ W/cm/sup 2/ without any fiber sensitization such as hydrogen loading. The fiber gratings have annealing characteristics similar to type II damage fiber gratings and demonstrate stable operation at temperatures as high as 950/spl deg/C. The grating devices exhibit low polarization dependence. The primary mechanism of induced index change results from a structural modification to the fiber core.

Cross-sections in Lorenz–Mie theory and quantum scattering: formal analogies

We consider the scattering of a plane wave by a sphere (Lorenz–Mie theory) and the corresponding quantum problem of scattering of an illuminating plane wave beam by a radial potential U( r), and demonstrate that cross-sections in both frameworks are amenable to identical expressions, excepted for zero-order phase shift terms which are specific of the quantum framework.

Fiber bragg gratings made with a phase mask and 800-nm femtosecond radiation.

High-quality retroreflecting fiber Bragg gratings were written in standard Ge-doped telecom fiber (Corning SMF-28) after a few minutes exposure with pulsed 800-nm, 120-fs laser radiation by use of a deep-etch silica zero-order nulled phase mask optimized for 800 nm. Induced index modulations of 1.9 x 10(-3) were achieved with peak power intensities of 1.2 x 10(13) W/cm2 without any fiber sensitization. The fiber gratings are stable and did not erase after 2 weeks at 300 degrees C. The primary mechanism of induced index change results from a structural modification to the fiber core.

Reduction of spectral ghost artifacts in high-resolution echo-planar spectroscopic imaging of water and fat resonances.

Echo-planar spectroscopic imaging (EPSI) can be used for fast spectroscopic imaging of water and fat resonances at high resolution to improve structural and functional imaging. Because of the use of oscillating gradients during the free induction decay (FID), spectra obtained with EPSI are often degraded by Nyquist ghost artifacts arising from the inconsistency between the odd and even echoes. The presence of the spectral ghost lines causes errors in the evaluation of the true spectral lines, and this degrades images derived from high-resolution EPSI data. A technique is described for reducing the spectral ghost artifacts in EPSI of water and fat resonances, using echo shift and zero-order phase corrections. These corrections are applied during the data postprocessing. This technique is demonstrated with EPSI data acquired from human brains and breasts at 1.5 Tesla and from a water phantom at 4.7 Tesla. Experimental results indicate that the present approach significantly reduces the intensities of spectral ghosts. This technique is most useful in conjunction with high-resolution EPSI of water and fat resonances, but is less applicable to EPSI of metabolites due to the complexity of the spectra.

An efficient algorithm for automatic phase correction of NMR spectra based on entropy minimization

A new algorithm for automatic phase correction of NMR spectra based on entropy minimization is proposed. The optimal zero-order and first-order phase corrections for a NMR spectrum are determined by minimizing entropy. The objective function is constructed using a Shannon-type information entropy measure. Entropy is defined as the normalized derivative of the NMR spectral data. The algorithm has been successfully applied to experimental 1 H NMR spectra. The results of automatic phase correction are found to be comparable to, or perhaps better than, manual phase correction. The advantages of this automatic phase correction algorithm include its simple mathematical basis and the straightforward, reproducible, and efficient optimization procedure. The algorithm is implemented in the Matlab program ACME—Automated phase Correction based on Minimization of Entropy.

The effect of gamma-irradiation on drug release from bioerodible microparticles: a quantitative treatment.

The two major objectives of this study were: (i) to monitor the effect of different gamma-irradiation doses (4-33 kGy) on the release kinetics from 5-fluorouracil (5-FU)-loaded poly(D,L-lactide-co-glycolide) (PLGA)-based microparticles, and (ii) to analyze the obtained experimental data with a new mathematical model giving insight into the occurring mass transport phenomena. Drug release was found to depend significantly on the applied gamma-irradiation dose. Interestingly, the obtained release profiles were all biphasic: a rapid initial drug release phase ("burst") was followed by a slower, approximately constant drug release phase. Surprisingly, only the initial rapid drug release was accelerated by gamma-irradiation; the subsequent zero-order phase was almost unaffected. Importantly, the new mathematical model which is based on Fick's second law of diffusion and which considers polymer degradation was applicable to all the investigated systems. In addition, the gamma-irradiation dose could be quantitatively related to the resulting drug release rate. In conclusion, diffusion seems to be the dominating release rate controlling mechanism in all cases, with a significant contribution of the polymer degradation process.

Paclitaxel loaded poly( l-lactic acid) microspheres for the prevention of intraperitoneal carcinomatosis after a surgical repair and tumor cell spill

A controlled release delivery system for paclitaxel was developed using poly( l-lactic acid) to provide local delivery to the peritoneal cavity. Microspheres were made in 1–40 and 30–120 μm size ranges. In an in vitro release study, 30–120 μm microspheres loaded with 10, 20 and 30% paclitaxel exhibited a burst phase of release for 3 days followed by an apparently zero-order phase of release. At all loadings, 20–25% of the original load of paclitaxel was released after 30 days. The effect of microsphere size on retention in the peritoneal cavity was assessed. Control 1–40 μm microspheres were injected intraperitoneally in rats. The rats received either insufflation of the peritoneal cavity using 11 mmHg CO 2 or no further treatment. After sacrifice, microspheres with diameters less than 24 μm were observed in the lymphatic system after being cleared from the peritoneal cavity through fenestrations in the diaphragm. Insufflation of the peritoneal cavity had no effect on the size of microspheres that were cleared. Efficacy studies were carried out using 30–120 μm microspheres that were of sufficient size to be retained in the peritoneal cavity. In a model of a tumor cell spill after a cecotomy repair, 100 mg of 30–120 μm microspheres containing 30% paclitaxel were effective in preventing growth of tumors in the peritoneal cavity at both 2 and 6 weeks post-surgery. No gross or histologically evident tumor growth was observed on any peritoneal surfaces or in the surgical wound site. Rats receiving control microspheres all showed tumor cell implantation and growth after 2 weeks.

Chemical potential quantization and Bose-Einstein condensation

In this paper, first of all, we proved if the ideal Bose gas with a finite volume and number of particles has a non-degenerate single-particle energy level n, the chemical potential μ can take the value μn = n and there is a phase transition temperature Tp,n, where n = 0,1,2 Taking 0 ≤ n Tp,n+1. When the temperature T > Tp,n or T ≤ Tp,n+1, μ # n and the most probable occupation number Nn = 0. In the temperature interval Tp,n ≥ T > Tp,n+1, μ = n and 0 ≤ Nn = N - NjsupNn, where Nj is the most probable occupation number in the degenerate level j. Thus, if the finite ideal Bose gas has some non-degenerate single-particle levels, there exists a characteristic temperature Tp = Tp,0. The chemical potential μ is quantized when T ≤ Tp, and this leads to the creation of a macroscopic quantum state (pure state) or Bose-Einstein condensation phase. Tp = Tp,0 is a first-order phase transition point, Tp,n#0 is a zero-order phase transition point. Next, we obtained a new expression of the most probable distribution of the finite ideal Bose gas. In this expression Nj is directly proportional to gj - 1, where gj and Nj are, respectively, the degeneracy and the most probable occupation number in the degenerate level j. This property agrees with what chemical potential can be quantized if there is a non-degenerate level for the finite ideal Bose gas. Finally, using this expression, we defined a micro-partition function M, obtained the statistical expressions of some thermodynamical quantities.

Characterization of the Product-inhibited Complex in Catalysis by Human Manganese Superoxide Dismutase

The reduction with excess H(2)O(2) of human Mn(III) superoxide dismutase (SOD) and the active-site mutant Y34F Mn(III)SOD was measured by scanning stopped-flow spectrophotometry and revealed the presence of an intermediate in the reduction of the manganese. The visible absorption spectrum of this intermediate closely resembled that of the enzyme in the inhibited, zero-order phase of the catalyzed disproportionation of superoxide. The decay of the visible spectrum of this intermediate was 2-fold faster for the wild-type compared with the mutant Y34F Mn-SOD. This correlates with the enhanced product inhibition of Y34F during the catalysis of O-(2) dismutation. The visible spectrum of the product-inhibited complex resembles that of the azide-Mn-SOD complex, suggesting that the inhibited complex has expanded geometry about the metal to octahedral. This study shows that the inhibited complex responsible for the zero-order phase in the catalysis by Mn-SOD of superoxide dismutation can be reached through both the forward (O-(2)) and reverse (H(2)O(2)) reactions, supporting a mechanism in which the zero-order phase results from product inhibition.

Preoperative Fasting in Children

Preoperative Fasting in Children

Preoperative fasting in children.

Children undergo a preoperative fast in an attempt to minimize the fluid and solid food component of gastric contents. The importance of a preoperative fast was acknowledged early in the evolution of anesthesia as a discipline of medicine. In response to concerns about the aspiration of gastric contents, a prolonged fast presumably came into vogue. With this practice, it was not unusual to have hungry, irritable children who were prone to hypoglycemia after fasts of 8 ‐12 h or even longer. The purpose of this article is to provide the reader with a narrative review of the literature pertaining to preoperative fasting in children. This article is primarily focused on randomized controlled trials (RCTs), but when not available, literature of lesser intensity was used. We present the physiology of gastric emptying with an emphasis on studies focusing on children in the perioperative period. These studies of gastric emptying were, when possible, divided into studies involving solid food and those involving clear fluids. We then present preoperative fasting of children, which was subdivided by age (neonates, infants, toddlers, and adolescents) and by health (elective versus emergent surgery and healthy versus medically compromised patients). In the concluding portions of this review, we present recommendations for the management of perioperative fasting and recommendations with respect to the need for more research, as more questions remain unanswered than those that have been answered. During preparation of this article, we accepted several links. The linkage between gastric fluid volume and aspiration pneumonia for healthy patients has recently been examined by an ASA taskforce, which concluded that the available data were insufficient to confirm or deny a relationship. Although this means that gastric fluid volume is a surrogate end point for aspiration pneumonia, virtually all studies examining preoperative feeding practices have gastric residual volume as their primary end point. For the purpose of this review, we focus on the end point of gastric residual volume, which is the almost exclusive choice of numerous peer-reviewed investigations. Furthermore, in the practice of anesthesia, patients undergoing emergency surgery have increased gastric contents and are at increased risk of aspiration pneumonia. This is an established link, and if we were to refute it, we would deny the need for rapid-sequence induction plus appropriate airway management during general anesthesia for emergency surgery. Although increased gastric contents increase the risk of aspiration pneumonia, there is no known gastric fluid volume that places a particular patient at clinically relevant risk or eliminates all risk.

The reversible enolization and hydration of pyruvate: possible roles of keto, enol, and hydrated pyruvate in lactate dehydrogenase catalysis

The reversible enolization and hydration of pyruvic acid and pyruvate anion were monitored using spectrophotometric methods at several temperatures. Widely varying values for the equilibrium constant for the enolization of pyruvic acid and pyruvate ion appear in the literature. To accurately determine the position of equilibrium for the enolization reaction, we have developed a method that gives consistent results in which purified samples of sodium pyruvate are first "titrated" with triiodide ion to remove any triiodide-scavenging impurities such as those resulting from aldol condensation reactions. After reequilibration to allow the regeneration of enol pyruvate, the addition of small quantities of triiodide result in an initial burst in the decrease of absorbance at 353 nm, followed by the much slower zero-order decrease due to the formation of new enol pyvuvate molecules. The absorbance change during the burst phase of the reaction is proportional to the enol concentration plus that of any triiodide-scavenging impurity which may be present in the original pyruvate solution. Thus, as the quantity of triiodide used in the pretreatment stage of the experiments is increased, these burst absorbance changes, ΔA, decrease until a constant value of ΔA is reached. Accordingly, this final ΔA value is proportional to enol pyruvate (or enol pyruvic acid) in the absence of triiodide-scavenging impurity, allowing the accurate and reproducible determinations of Kenol. The equilibrium constants for both pyruvate and pyruvic acid are relatively temperature insensitive and, typically, Kenol (pyruvate anion) = 2.6 × 10-5 and Kenol (pyruvic acid) = 7.8 × 10-5 at 25.0°C. The zero-order phase of the reaction of triiodide ion may be used to calculate rate constants for enolization. The hydration and dehydration of pyruvic acid were followed directly by following absorbance changes in the peak at 340 nm due to the keto group. The thermodynamic and kinetic results reported in this paper are used to help determine whether the observed "substrate" inhibition of the lactate dehydrogenase catalyzed reduction of pyruvate is actually caused by keto, hydrated, or enol pyruvate.Key words: pyruvate, enolization, hydration, lactate dehydrogenase.