Study by means of high-performance liquid chromatography of solutes that decrease theophylline/protein binding in the serum of uremic patients.

Substantial changes in protein binding of drugs occur during the progression of renal insufficiency. Protein-bound uremic solutes play a role in the inhibition of drug protein binding. We previously demonstrated that hippuric acid in uremic ultrafiltrate was an inhibitor of the theophylline protein binding. The present study was undertaken to extend the yield of protein-bound uremic solutes by displacing ligands in uremic serum from their binding sites by five deproteinization methods. The inhibitory effect on theophylline protein binding of the deproteinized uremic serum was higher than with ultrafiltrate (p < 0.05). The influence of 30 semi-preparative HPLC fractions from deproteinized uremic serum on the theophylline protein binding was evaluated to identify the responsible compounds and to compare their relative individual impact. The theophylline protein binding was calculated as a percentage (bound versus total). The most important decrease of the protein binding was observed in HPLC fractions 6, 10 to 13, 15 and 28 with protein binding of: 61.5 +/- 10.8, 64.5 +/- 7.6, 60.9 +/- 10.1, 47.5 +/- 3.3, 60.0 +/- 6.7, 60.7 +/- 6.3 and 61.3 +/- 6.9%, respectively versus 69.1 +/- 2.4% for control serum (p < 0.05). The responsible compounds were characterized in the fractions by co-elution: 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), indole-3-acetic acid, indoxyl sulfate, hippuric acid, p-hydroxyhippuric acid and tryptophan. Their concentration was determined by analytical HPLC and a solution containing these compounds at the same concentration as in deproteinized uremic serum was composed. This solution was added to control serum and decreased the theophylline protein binding from 69.0 +/- 4.4% to 61.3 +/- 1.3%, which was less important than in genuine uremic serum (44.4 +/- 3.8%, p < 0.05). Dose-response curves with the characterized compounds revealed that the most important role in binding inhibition could be attributed to hippuric acid and CMPF. Our data suggests that the yield of protein binding inhibiting compounds is more important with deproteinized uremic serum than with uremic ultrafiltrate. The identified uremic compounds are not entirely representative for the decreased protein binding of theophylline, indicating that additional factors than those identified in this study affect the protein binding as well.     

A mathematical model for the dynamics of clustering

The formation of several clusters, arising from attracting forces between nonidentical entities or agents, is a phenomenon observed in diverse fields. Think of people gathered through a mutual interest, swarm behaviour of animals or clustering of oscillators in brain cells.We introduce a dynamic model of mutually attracting agents for which we prove that the long-term behaviour consists of agents organized into several groups or clusters. We have completely characterized the cluster structure (i.e. the number of clusters and their composition) by means of a set of inequalities in the parameters of the model and have identified the intensity of the attraction as a key parameter governing the transition between different cluster structures.The versatility of the model will be illustrated by discussing its relation to the Kuramoto model and by describing how it applies to a system of interconnected water basins.     

On the optimisation of the bed porosity and the particle shape of ordered chromatographic separation media

We report on a theoretical study wherein we considered a large number of ordered two-dimensional porous pillar arrays with different pillar shapes and widely varying external porosity and calculated the flow resistance and the band broadening (under retentive conditions) over the complete range of practical velocities using a commercial computational fluid dynamics software package. It is found that the performance of the small porosity systems is very sensitive to the exact pillar shape, whereas this difference gradually disappears with increasing porosity. The obtained separation impedances are very small in comparison to packed bed and monolithic columns and decrease with increasing porosity. If accounting for the current micromachining limitations, a proper selection of the exact shape and porosity even becomes more critical, and different design rules are obtained depending on whether porous or non-porous pillars are considered.     

Hyperbranched polyselenides as glutathione peroxidase mimics

Novel hyperbranched polyselenides with multi-catalytic sites at the branching units have been synthesized which may provide a new approach towards glutathione peroxidase mimics.     

Involutive invariants of the second kind

Let S be a Krull domain which is divisorially étale of degree two over a Krull domain R. The main purpose of this text is to introduce and study involutive invariants of the second kind of S with respect to R, as well as developing techniques allowing to calculate these in terms of other, classical and involutive, invariants.     

Indirect excitons and double electron-hole layers in a wide single GaAs/AlGaAs quantum well in a strong electric field

The recombination spectra of indirect excitons and double electron-hole layers in a wide single quantum well in an electric field are studied. It is found that electrons and holes in the wide well become spatially separated in a sufficiently strong electric field. This leads to a substantial reorganization of the radiative recombination spectrum and to a significant increase in the carrier lifetime. It is shown that the total charge of the electron-hole system can be changed by varying the photoexcitation frequency and the applied electric field, thus passing from the neutral case of indirect excitons to the case of charged double electron-hole layers. The concentration of excess carriers in the well is measured as a function of the electric field strength. The behavior of the excited states of indirect heavy-hole and light-hole excitions is studied for a neutral excitonic system in a strong electric field. It is shown that the electric-field dependences allow the excited states of indirect excitons with a light hole to be distinguished from the excited states with a heavy hole.     

Dual Responsive Regulation of Host–Guest Complexation in Aqueous Media to Control Partial Release of the Host

The regulation of the concentration of a wide range of small molecules is ubiquitous in biological systems because it enables them to adapt to the continuous changes in the environmental conditions. Herein, we report an aqueous synthetic system that provides an orchestrated, temperature and pH controlled regulation of the complexation between the cyclobis(paraquat-p-phenylene) host ( BBox ) and a 1,5-dialkyloxynaphthalene ( DNP ) guest attached to a well-defined dual responsive copolymer composed of N-isopropylacrylamide as thermoresponsive monomer and acrylic acid as pH-responsive monomer. Controlled, partial release of the BBox , enabling control over its concentration, is based on the tunable partial collapse of the copolymer. This colored supramolecular assembly is one of the first synthetic systems providing control over the concentration of a small molecule, providing great potential as both T and pH chromic materials and as a basis to develop more complex systems with molecular communication.     

Boronic esters as ionophores for potentiometric discrimination of the cis-trans isomeric dicarboxylic acids

Boronic esters incorporated into a poly(vinyl chloride) (PVC)-supported liquid membrane electrodes have displayed an anionic ionophore properties enabling their use in the potentiometric high-throughput screening procedures. These compounds belong to the class of ligands in which the anion recognition process can be explained on the concept of Lewis type acid-base interactions. Membranes containing boronic esters showed fairly good sensitivity for maleate (cis-isomer) in comparison to fumarate anions (trans-isomer). The potentiometric selectivity coefficients of proposed electrodes proved that common anions did not interfered with the maleate anion determination. The influence of structure of the three boronic esters ionophores on generation of potentiometric signal by developed liquid membrane electrodes was shortly discussed.