Deposition of nacystelyn from a dry powder inhaler in healthy volunteers and cystic fibrosis patients

The aim of this study was to compare, using gamma scintigraphy, the lung deposition of a novel mucoactive agent, Nacystelyn (NAL), administered as a dry powder inhaler (DPI) in six healthy volunteers, six adult patients with cystic fibrosis (CF), and six children and adolescents patients with CF. The correlation between in vitro and in vivo results was also tested. It was first demonstrated that the method of labeling of NAL with 99mTc was reliable as tested by three in vitro methods (multistage liquid impinger, multistage cascade impactor, and 2-stage glass impinger). The deposition of unlabeled NAL, labeled NAL, and the radiolabel was similar in all stages of each device. Furthermore, the fine particle fraction (FPF) was the same on all apparatuses. The mean lung deposition obtained in volunteers was 27.5 +/- 13.5%. The results are approximately three times higher than the results obtained previously in healthy volunteers with NAL metered-dose inhalers (MDIs). As expected, the lung deposition observed in patients with CF was lower, e.g., 23.5 +/- 7.0% for adults and 16.5 +/- 5.9% for children and adolescents. A significant correlation was found between lung deposition and both the patient weight (p < 0.02) and height (p < 0.04). Surprisingly, the peripheral:central (P:C) ratio was similar for the three populations, indicating that the presence of mucus in moderately ill patients with CF does not modify the lung distribution of NAL. The FPF measured in vitro was similar to that obtained in volunteers but higher than that found in both patient populations. The DPI formulation of NAL developed will probably improve patient compliance and comfort in future clinical trials and postmarketing use of the drug.     

The longitudinal electrical conductivity of metal-matrix composites at cryogenic temperature in the presence of a longitudinal magnetic field

We solve the Boltzmann equation in the relaxation time approximation with parallel E and B fields parallel to the continuous fibres reinforcing a metal matrix. It is shown that this solution is identical to that described by us elsewhere, except for the addition of the cyclotron frequency. The addition of the cyclotron frequency term shows that the electrons follow helical paths as they drift down the composite. The boundary considered is either the external or the internal surface of a cylinder representing the fibre. To apply this solution to metal-matrix composite materials we assumed that the cylindrical fibres are non-conducting cylinders in a matrix of pure crystalline metal. The electron mean free path is never greater than half the fibre separation distance. In a companion paper we discuss the application of this solution to metal-matrix composites.     

Remarks on the use of Boltzmann's equation for electrical conduction calculations in metal matrix and in situ composites

The Boltzmann equation and its solutions are cental to the development of microscopic models describing the longitudinal and transverse electrical conductivity of metal matrix and in situ composites. Such solutions are needed to describe electron and phonon scattering and transport phenomena in the matrix due to the presence of a second filamentary phase, and to describe electrical conductivity at cryogenic and higher temperatures. In this paper, we derive solutions to the Boltzmann equation in the relaxation time approximation in cylindrical coordinates. It is shown that one solution for the electric field parallel to the fibre direction leads to an expression for composite conductivity at cryogenic and higher temperatures. We also present a solution for the case in which the electric field is normal to the fibre direction.     

Model of transverse electrical conductivity of metal matrix composites above liquid nitrogen temperatures

The present theories of transverse electrical conductivity of metal matrix composites (MMCs) containing nonconducting continuous cylindrical fibres are inadequate to predict experimental measurements. In this paper, we present a model of transverse electrical conductivity that predicts experimental data reasonably well for the case of an MMC material reinforced with nonconducting or poorly conducting continuous fibres. lt is based on the concept that transverse conductivity consists of two contributions: the electrical resistivity of the bulk material modified by periodic variations in the bulk cross-section due to the presence of nonconducting fibres; and a disturbance in electron transport due to nonuniformity in the electric field, caused by the presence of the fibres, that extends some distance away from and all around the fibres. To calculate this nonuniformity, we use the well-known solution of the potential field for a conducting cylinder in a uniform electric field and invert it so that it becomes a problem of nonconducting filaments in a conducting matrix. This gives a value of the transverse electrical resistivity for boron/aluminium (B/Al) containing 60 vol% fibre in nearly exact agreement with experimental data. The theory is compared to a modified capacitance model developed by Keller [1] for dielectric materials. The model discussed in this paper does not predict the trans-verse electrical resistivity of MMCs reinforced with very small-diameter fibres (Gr/Al, Al₂O₃, etc.) where the fibres are randomly distributed in a plane normal to their longitudinal axis. This problem will be discussed in a companion paper.     

A NEW APPARATUS FOR A RAPID SEDIMENTATION ANALYSIS1

A new apparatus for the continuous determination of the cumulative distribution curve of particle size is described. It is based on the known principle of determining the changes in concentration in one definite layer. Instead of drawing off portions of the liquid, the changes are measured by the apparent weight of a suspended body. Two points of the curve are determined independently by measuring the residue in suspension and by an elutriation in the same vessel. A source of errors, the contraction of the crow section in the neighborhood of the suspended body, is eliminated. The apparatus makes it possible to determine reliable distribution curves with any liquid within a few hours and avoids some sources of errors of previous methods.     

A comparative study of a fluidised bed reactor and a gas lift loop reactor for the IBE process: Part I. Reactor design and scale down approach

For the continuous production of isopropanol-butanol mixtures by immobilised Clostridium spp. (the IBE process) two reactor types were studied: a fluidised bed reactor with liquid recycling (FBR) and an external loop gas lift reactor (GLR). A large scale design (50–65 m³) was made for both reactors. A regime analysis, by evaluating the time constants for e.g. mixing and conversion, identified the ruling regime. Via the scale down approach two representative model reactors were developed: a 10 dm³ FBR reactor (H/D=25, D=0.08 m) and a 15 dm³ external loop GLR (H/D = 12.5, D_r=D_d=0.08 m). For both reactors the hydrodynamical behaviour and the total reactor performance were studied and are described in parts II and III of this study.     

Comparison of the in vitro activities of BB-K8 and three other aminoglycosides against 215 strains of Pseudomonas and Enterobacteriaceae with variable sensitivity to kanamycin and gentamicin

215 gram-negative bacilli isolated from clinical materials were tested in vitro against BB-K8 by means of disc diffusion and agar dilution tests; the strains included 40 isolates resistant to gentamicin. Approximately 90% of the strains were inhibited by 3.12 mug/ml or less BB-K8. This antibiotic exhibited a comparable activity, although somewhat inferior, to that of gentamicin, against organisms sensitive to gentamicin. It was considrably more active than gentamicin, and comparable to tobramycin, against the isolates of Klebsiella-Enterobacter-Serratia spp. resistant to gentamicin, but less active than tobramycin against 11 strains of Pseudomonas resistant to gentamicin.     

The elastic and compressive properties of hybrid metal matrix composites/hexagonal prismatic cellular solids

An analysis is presented of the elastic and compressive properties of hybrid metal matrix composite (MMC) materials containing a uniform distribution of hexagonal prismatic cells which form closely spaced arrays separated by thin walls. The cell walls are considered to be reinforced by chopped fibers, whiskers, or particulates, thus forming a MMC. Exact derivations of the moment of inertia, elastic moduli, and compressive strength are presented, and approximations to these expressions are discussed. Results of these analyses are applied to the calculations of elastic moduli, flexural rigidity, and compressive strength of a square beam. Comparisons are made between the cases of unreinforced aluminum and steel cell walls and the cases of graphite chopped fiber reinforced aluminum and tungsten chopped fiber or whisker reinforced steel. The axial modulus and flexural rigidity of this type of structure made from Gr/Al composite are superior to unreinforced steel cellular structures only when the volume fraction of reinforcement exceeds about 30%. The material with reinforced cell walls is distinctly superior to its unreinforced counterpart by a factor of 4·3 at 50 volume percent graphite chopped fiber in aluminum.     

A comparative study of a fluidised bed reactor and a gas lift loop reactor for the ibe process: Part III. Reactor performances and scale Up

Continuous fermentations using Clostridium spp. DSM 2152 immobilised in calcium alginate beads to produce butanol and isopropanol from glucose were carried out in a fluidised bed reactor with liquid recycle (FBR, 10.9 dm³ working volume, 41 % solids) and in a gas lift loop reactor (GLR, 11.4 dm³ working volume, 32% solids). In the FBR in-situ produced non-coalescing gas bubbles had a negligible influence on the fluidisation pattern and the steady state results of the fermentation were in accordance with those predicted by a reactor model. The FBR was operated reliably for 5 weeks without decrease of activity. The GLR behaved as a three phase reactor because of the recycled fermentation gas. The steady state fermentation results were as predicted by the GLR model. Scale up to a 50 m³ FBR and a 65 m³ GLR led to development of a plug flow with recycle model for the FBR and a stirred tank model for the GLR. On the basis of overall reactor performance and ease of integration with a simultaneous product recovery the FBR is preferred to the GLR for application in a large scale butanol/isopropanol process using immobilised Clostridia spp.     

Some theoretical considerations of the surface tension of liquid metals for metal matrix composites

This paper presents a model for calculating the surface tension of pure metals and their alloys. It is based upon the theory of Eyringet al. which uses classical statistical physics to describe the thermodynamic properties of metals in the liquid state. Calculations show the surface tension of pure aluminium to be nearly 9% greater than that measured for pure aluminium having a monolayer of oxide (Al₂O₃), and within about 10% of measured values for Al-xMg and Al−xCu, wherex is the weight percent of the alloying element. In the present calculations 0 ≤x≤8 wt% for magnesium and 0≤x≤30 wt% for copper were used. The values calculated are also in good agreement with results from other models. The model was also used to calculate the temperature coefficient. For pure aluminium the calculated values fall within experimental measurements, and exhibit a slight temperature dependence.