(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.     

Discovery of a new long-lived isomeric state in 125Ce

A new long-lived isomeric state in the near proton dripline nucleus ¹²⁵Ce has been identified with Schottky mass spectrometry at GSI. The excitation energy E ^* = 103(12)keV and the decay time of 193(1)s have been obtained from a single stored fully ionized ^125m Ce⁵⁸⁺ ion. The data implies an E3 transition and a 1/2⁺ assignment for the spin of the isomer.     

Systematic studies of positron production in heavy-ion collisions near the Coulomb barrier

We present the results obtained from systematic studies of positron creation for a series of heavy-collision systems, with united chargeZ _u =Z ₁ +Z ₂ ranging fromZ _u =164 (Pb + Pb) toZ _u =184 (U+U) at bombarding energies close to the Coulomb barrier, using the Orangeβ-spectrometer at GSI. For each collision system studied, the dominating continuous distributions due to quasiatomic and nuclear positron emission are determined accurately. This is essential in obtaining the characteristics of the still unexplained monoenergetic positron lines which appear in the energy range between 200 keV and 400 keV. Our results are compared with coupled-channels calculations for quasi-atomic positron creation. The latter describe quite well the global features of the measured spectra, but overestimate systematically their absolute values. From the comparison, a common normalization factor of about 0.75 can be established for the calculated spectra. In particular, the dependence onZ _u of the measured emission probabilities was found to follow a power law (∝Z _u ^195±1), in fair agreement with the theoretical prediction.     

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.     

Crossing of shears bands in196Pb

High-spin states in¹⁹⁶Pb have been populated using the reaction¹⁷⁰Er(³⁰Si,4n). The previously observed shears bands in this nucleus have been extended and some of their transitions have been reordered. They now form regular bands with band crossings. One of the bands splits into two pathways at high spin.     

Zeeman transitions in deuterium atoms induced by ultra-relativistic electrons

We present data showing hyperfine transitions in an atomic deuterium beam induced by the (476 MHz) radio-frequency field of a 704 MeV electron beam in a storage ring. A polarized deuterium beam, produced in an atomic beam source, was crossed with a stored electron beam and analyzed with a Breit--Rabi polarimeter. Electron-beam induced transitions were singled out by injecting different combinations of hyperfine states. Transition probabilities as high as 70% were measured at large currents (~ 100 mA). All possible deuterium transitions for a radio-frequency of 476 MHz were observed. In addition, a 1--6 transition resulting from the first harmonic (952 MHz) was observed. The effects of these transitions are of general importance for the polarized internal target technique applied in nuclear and particle physics experiments. The data are reasonably described by numerical estimates. The observed mechanism can be exploited to create nuclear polarized atoms when injecting electron polarized atoms with no net nuclear polarization into a storage cell. However, when nuclear polarized atoms are injected, care should be taken to avoid this mechanism, since it would result in depolarization of the atoms. The studies enabled us to choose the magnetic guide field during our spin-dependent electron--deuteron scattering experiments, such that electron-beam induced depolarizing effects were avoided. This revised version was published online in July 2006 with corrections to the Cover Date.     

The four-loop β-function in quantum chromodynamics

We present the analytical calculation of the four-loop QCD β-function within the minimal subtraction scheme.