(Systemic) phototoxicity of drugs and other xenobiotics.

Xenobiotics extensively used in drugs, cosmetics, food and agricultural chemicals can produce adverse biological effects. These toxic effects are separated into classes, e.g. hepatotoxicity, genotoxicity and neurotoxicity. Skin allergy, part of immunotoxicity, is also a subdivision of toxicology. When light is an essential condition for toxicity, the xenobiotic is called phototoxic. Thus it fits into the logic of toxicology that photoallergic compounds are a subdivision of phototoxic compounds. Phototoxicons as a group do not differ from the group of phototherapeutics with regard to their eventual biological effects. The primary photoreactions, secondary molecular processes, biomolecules involved and cellular and tissue damage are similar. The difference between the two groups is in the appreciation of the photobiological effects: adverse vs. desired. The aim of research is to determine the part of the molecular structure which makes a given compound phototoxic. With that knowledge the structure of the phototoxicon can be changed. This can result in a derivative which still has the desired properties of the parent compound, but is no longer phototoxic. This aim can be reached by combining data from both in vitro and in vivo research. The variety and number of phototoxic compounds is large. This, together with the limited research effort devoted to this subject so far, means that for most phototoxic xenobiotics a relationship between structure and in vivo photoreactivity is not available. In this review, emphasis is placed on xenobiotics whose in vitro and in vivo photochemistry have been studied. Furthermore, possible phototoxic effects which do not concern the skin but involve inner organs (systemic effects) are considered. References in this review mostly concern investigations over the last 10 years. For older literature or for additional information, references to other reviews are given. Important groups of phototoxic xenobiotics not dealt with in this article were already sufficiently covered in the reviews referred to.     

Foams and surface rheological properties of β-casein, gliadin and glycinin

Interfacial rheological properties and their suitability for foam production and stability of two vegetable proteins were studied and compared to β-casein. Proteins used ranged from flexible to rigid/globular in the order of β-casein, gliadin and soy glycinin. Experiments were performed at pH 6.7. Network forming properties were characterised by the surface dilational modulus (determined with the ring trough) and the critical falling film length (L_still) at which a stagnant protein film will break. Gliadin had the highest dilational modulus, followed by glycinin and β-casein, whereas glycinin formed the strongest film against fracture in the overflowing cylinder. The rate of decrease in the surface tension was studied at the air–water (Wilhelmy plate method) and the oil–water interface (bursting membrane) and the dynamic surface tension during compression and expansion in the caterpillar. Gliadin had the lowest equilibrium interfacial tensions and β-casein the lowest dynamic surface tension during expansion. Hardly any foam could be formed at a concentration of 0.1 g/l by shaking. At a concentration of 1.4 g/l most foam was formed by β-casein, followed by gliadin and glycinin. It seems that in the first place the rate of adsorption is important for foam formation. For the vegetable proteins, adsorption was slow. This resulted in lower foamability, especially for glycinin.     

U(2, 2) Symmetry as a Common Basis for Quantum Theory and Geometrodynamics

We formulated some criticisms of the Diracequation and its Clifford-algebraic philosophy; inparticular, we show that, within a general-relativisticcontext, they seem to contain hidden action-at-distance concepts. We suggest a new model based on thefour-component Klein-Gordon equation locally invariantunder the U(2,2) gauge group. The usual Dirac equationis then obtained as a certain approximation. The geometrodynamical sector shows reasonablecorrespondence with general relativity.     

Improved high-performance liquid chromatographic method for the determination of ethylmorphine and its metabolites in microsomal incubations and cell culture media.

Ethylmorphine N-demethylation is used as a marker pathway in studies of rat cytochrome P450 3A and 2C11 biotransformations. At present, microsomal activities are generally measured by a colorimetric determination of the formed formaldehyde. In the present study, a high-performance liquid chromatographic method of separating and quantifying both the N-demethylated (norethylmorphine) and the O-de-ethylated (morphine) metabolites is described. Either samples are extracted with ethyl acetate or proteins are precipitated with zinc sulphate-barium hydroxide. Separation is achieved on a CN reversed-phase column, using a mobile phase of phosphate buffer (pH 4.5)-acetonitrile (90:10, v/v). At a flow-rate of 1.5 ml/min, the analysis time is 30 min. The limit of detection (ultraviolet, 210 nm) for ethylmorphine and its metabolites is 0.5 micrograms/ml.     

Relevance of Reflection in Static and Dynamic Light Scattering Experiments

Using a monodisperse PMMA dispersion, it was shown that light reflection at the sample cuvette walls may greatly influence the results of both static (SLS) and dynamic (DLS) light scattering experiments. Considering SLS, this reflection phenomenon mostly causes an overestimation of the scattered intensity at high scattering angles, which may give rise to the emergence of an additional, artificial peak in the lower region of the particle size distribution. On the other hand, the influcence of reflection on DLS measurements was shown to be particularly important in the upper region of the particle size distribution. The experimentally observed phenomena were explained from the basic principles of both particle sizing methods. Finally, it was shown that the disturbing effect of reflection could be avoided by modifying either the hardware or the software of the static and dynamic light scattering technique.