Three generations of cyclosporine a formulations: an in vitro comparison

When the microemulsion formulation of the critical dose drug cyclosporine A (CsA) (Sandimmun Optoral) was introduced in the mid-1990s, it became clear that this new formulation improves the oral bioavailability of CsA and has a positive influence on its pharmacokinetic variability. Previous studies with the original CsA formulation (Sandimmun) showed that the size of the emulsion droplets and concomitant food intake has an effect on the absorption of CsA from the small intestine when orally administered. It was suggested that these effects might have an influence on the drugs' pharmacokinetic parameters.In this study, we focused on the two above-mentioned aspects and compared the first and second generations of CsA products (Sandimmun, Sandimmun Optoral) to generic CsA formulations by analyzing the contents of cyclosporine A gel capsules with respect to their emulsion droplet and micelle sizes using photon correlation spectroscopy (PCS). We tried to discern any differences in droplet size between different generations of CsA formulations, primarily the second and third generation, through simple physical tests. Because a high fat content food may influence the absorption of CsA, we also determined the distribution of CsA between hydrophilic and lipophilic phases using high-performance liquid chromatography analysis.It became clear that when compared under simple physical conditions, established cyclosporine formulations and new generic products show significant differences in droplet size and distribution between an aqueous phase and a high fat content food. Whether these differences are of clinical relevance remains to be investigated.     

Sorption of pyrene to dissolved humic substances and related model polymers. 2. Solid-phase microextraction (SPME) and fluorescence quenching technique (FHT) as analytical methods

Sorption coefficients for pyrene on dissolved humic substances and on poly(acrylic acid) esters as well-defined model polymers were determined using solid-phase microextraction (SPME) and the fluorescence quenching technique (FQT). The results of both analytical methods were compared and theoretically evaluated, which led to the conclusion that the sorption coefficients measured by SPME and FQT are inevitably different: SPME measures activity-based and FQT concentration-based sorption coefficients. The environmental relevance of the two types of sorption coefficients is discussed. FQT is inappropriate to measure sorption coefficients for pyrene with the synthetic sorbents. Inspection of the vibrational structure of the fluorescence spectra of those solutions indicates a highly hydrophobic microenvironment of pyrene. This can be explained by an intra- or intermolecular agglomeration of hydrophobic moieties forming a favorable host for hydrophobic solutes.     

Microcosm studies for neutralization of hypolimnic acid mine pit lake water (pH 2.6)

Ten microcosms of 0.088 m3 water volume (0.3 m i.d. and 1.20 m height) were designed for neutralization studies representing hypolimnic ecosystem models for acid mine pit lakes. Sediment and water were collected from an acid lignite mine pit lake (Brandenburg, Germany) and filled into the microcosms. To determine the efficacy of controlled in situ organic carbon amendments as a possible neutralization method, sediment and water were treated with ethanol and Carbokalk with and without wheat straw. The water chemistry was monitored for 1 yr. At start-up and end of the experiments, the sedimentwas characterized. Iron and sulfate were removed with varying intensity from the water phase as a result of microbial iron and sulfate reduction together with a subsequent precipitation of unsoluble sulfide minerals to the sediment. The pH rose, and alkalinity generation and bacterial growth were observed. Neutralization rates were calculated using equivalents of accumulated total reduced inorganic sulfur together with the nonsulfidic reactive ferrous iron in the sediment. In the treated microcosms, the neutralization rates were between 6 and 15 equiv m(-2) a(-1). Carbokalk was most effective in stimulating growth of sulfate-reducing bacteria and probably also served as inoculum. With Carbokalk together with wheat straw, the pH increased from 2.6 to around 6.5 within the whole microcosm. The critical revision of the results indicates that the application of Carbokalk (approximately 3.9 kg m(-2)) together with the application of wheat straw (approximately 9.3 kg m(-2)) is most suitable for further experiments in outdoor enclosures (mesocosms). For that case, the prediction of the water quality for a lake water column after multiple lake turnover events is presented based on batch reaction simulation using the geochemical model PHREEQC.     

Biomass production,water use and photosynthesis of Salix clones grown in a wastewater purification system

An objective of the study was to identify leaf morphophysiological characteristics indicative of high aboveground woody biomass production of Salix clones growing in the vegetation filter of a wastewater purification system. It was hypothesized, that in these extra irrigated stands, the characteristics of photosynthesis are stronger determinants of the production than the characteristics of leaf water relations. The biomass production of the clones was correlated with numerous characteristics of leaf water relations and photosynthesis. Significant correlation was found between the biomass production and the following characteristics of top foliage leaves: daily decrease in water potential, stomatal conductance, stomatal sensitivity to increase in light intensity, and hydraulic conductance (positive); daily minimum and maximum water potentials, instantaneous water use efficiency, and stomatal sensitivity to decrease in leaf water potential (negative); maximum rate of photosynthetic electron transport, chlorophyll content, and the partitioning coefficient for leaf nitrogen into bioenergetics associated with electron transport (positive). In the most productive clones, the vertical gradient (through foliage) of values of almost all the characteristics was the smallest. The biomass correlated more strongly with the characteristics of photosynthesis light stage than with the characteristics of water relations. We conclude that the characteristics of photosynthesis light stage – high maximum rate of photosynthetic electron transport, high chlorophyll content, and also flat vertical gradient (through foliage) in values of the characteristics could be the strongest indicators of high biomass production of Salix clones growing in vegetation filter.     

Reed canary grass yield and fuel quality in Estonian farmers’ fields

Reed canary grass (Phalaris arundinacea) is one of the possible raw materials for bioenergy production in northern Europe. Its cultivation is favoured because its high productivity and local origin. However, problems with the biomass quality for combustion have been reported. Usually delayed harvest in spring is suggested to improve the quality and decrease the moisture content of biomass. On the other hand, the feasibility of spring harvest depends on local climatic conditions and may cause yield losses. In current paper we studied reed canary grass fields in Estonia locating on different soil types and cultivated with various varieties. The influence of several fertilisation schemes on biomass yield was analysed. Our results indicated that production was higher on mineral soils than on the organic soil of abandoned peat extraction sites. Even different types of fertilisation did not increase the production on organic soils to the level comparable to those on mineral soils. Among studied varieties ‘Venture’ had the highest production. The highest yield per area was obtained late in the autumn (12.7 t d.w. per ha and 7.2 t d.w. per ha on mineral and organic soils, respectively). By spring the amount of biomass had decreased in all studied sites. Due to wet soil some of the fields remained unharvested, the others had high yield losses during practical harvesting. The chemical analyses did not reveal significant differences in the composition of biomass between late autumn and spring. Therefore we conclude that late autumn harvest should be preferred in local climatic conditions.     

The advantage of using in-situ methods for studying hydrogen mass transport: Neutron radiography vs. carrier gas hot extraction

Neutron radiography (NR) is compared with the commonly used carrier gas hot extraction (CGHE) technique. We performed isothermal hydrogen effusion experiments at 623 K to study the mass transport kinetics. The investigated material was technical iron. The quantification of the hydrogen mass flow is done for NR by using concentration standards. The temporal hydrogen concentration evolution in the sample coincides well for both methods, i.e. NR and CGHE, and is in good agreement with literature. The advantages of the NR method are the non-destructive nature of measuring and the in-situ determination of hydrogen concentrations with high spatial and temporal resolution. Remaining hydrogen inside the sample can be identified directly by the NR method.     

Hydrogen microscopy – Distribution of hydrogen in buckled niobium hydrogen thin films

Hydrogen absorption in thin metal films clamped to rigid substrates results in mechanical stress that changes the hydrogen's chemical potential by Δμ_H(σ) = −1.124σ kJ/mol_H for σ measured in [GPa]. In this paper we show that local stress relaxation by the detachment of niobium hydrogen thin films from the substrate affects the chemical potential on the local scale: using coincident proton–proton scattering at a proton microprobe, the hydrogen concentration is determined with μm resolution, revealing that hydrogen is not homogenously distributed in the film. The local hydrogen solubility of the film changes with its local stress state, mapping the buckled film fraction. In niobium hydrogen thin films loaded up to nominal concentrations in the two-phase coexistence region, the clamped film fraction remains in the solid solution phase, while the buckles represent the hydride phase. These results are compared to a simple model taking the stress impact on the chemical potential into account.     

Influence of store dimensions and auxiliary volume configuration on the performance of medium-sized solar combisystems

To increase the fractional energy savings achieved with solar thermal combisystems the store volume may be increased. Installation of large stores in single-family houses is, however, often limited by space constraints. In this article the influence of the store dimensions, as well as internal and external auxiliary volume configurations, are investigated for large solar water stores by annual dynamic TRNSYS simulations. The results show that store sizes up to 4 m³ may be used in solar heating systems with 30 m² collector area. It is further shown that well-insulated stores are rather insensitive to the geometry. Stores deviating from the conventional dimensions still yield high fractional energy savings. Furthermore, the simulations show that the performance of an internal auxiliary volume configuration in most cases exceeds that of a solution with an external auxiliary unit. The practical limitations of very thin auxiliary volumes must, however, be further investigated.