Differences in the metabolism of phospholipids depending on cell population density

Pulse-chase experiments in embryonic mouse fibroblasts at low and high cell population densities using radioactive phosphate and tritiated glycerol as precursors revealed a blocked turnover of phosphatidylinositol and a blocked biosynthesis of phosphatidylethan-olamine in densely packed cells.     

ESR-Untersuchungen an bestrahlten schwefelhaltigen und schwefelfreien Pyridoxinderivaten

Zusammenfassung Sowohl nach UV-Bestrahlung (254 nm) als auch nach Röntgenbestrahlung bei 20 °C ergeben sich für Pyridoxin und einige schwefelhaltige Pyridoxinderivate gleiche Radikalzustände. Wahrscheinlich befindet sich ein unpaares Elektron in der Methylgruppe der Stellung 4 oder 5. Bei den Derivaten, die den Schwefel in Form des Sulfhydryls enthalten, findet eine Radikalwanderung zum Schwefel statt. Dabei wird der Radikalzustand am Schwefel des 4-Mercaptopyridoxins schneller gebildet als im Falle des 5-Mercaptopyridoxins. Die Disulfidbindung des Pyrithioxins ist gegenüber den Sulfhydrylbindungen der Mercaptopyridoxine stabiler. Ist der Schwefel in Form eines Thioäthers vorhanden (4,5-Methylensulfidpvridoxin), so erhält man ein Radikal vom Alkyltyp, ohne daß anschließend eine Radikalwanderung zum Schwefel auftritt. Die ESR-Untersuchungen zeigen darüber hinaus, daß die Bildung und das Zeitverhalten der Radikale nicht nur von ihrer unmittelbaren Umgebung, sondern auch von der ganzen Struktur des Moleküls abhängig sind.Herrn Prof. Dr. KurtSommermeyer zum 60. Geburtstag gewidmet.     

Development of chicken embryos in a pulsed magnetic field

Six independent experiments of common design were performed in laboratories in Canada, Spain, Sweden, and the United States of America. Fertilized eggs of domestic chickens were incubated as controls or in a pulsed magnetic field (PMF); embryos were then examined for developmental anomalies. Identical equipment in each laboratory consisted of two incubators, each containing a Helmholtz coil and electronic devices to develop, control, and monitor the pulsed field and to monitor temperature, relative humidity, and vibrations. A unipolar, pulsed, magnetic field (500-microseconds pulse duration, 100 pulses per s, 1-microT peak density, and 2-microseconds rise and fall time) was applied to experimental eggs during 48 h of incubation. In each laboratory, ten eggs were simultaneously sham exposed in a control incubator (pulse generator not activated) while the PMF was applied to ten eggs in the other incubator. The procedure was repeated ten times in each laboratory, and incubators were alternately used as a control device or as an active source of the PMF. After a 48-h exposure, the eggs were evaluated for fertility. All embryos were then assayed in the blind for development, morphology, and stage of maturity. In five of six laboratories, more exposed embryos exhibited structural anomalies than did controls, although putatively significant differences were observed in only two laboratories (two-tailed Ps of .03 and less than .001), and the significance of the difference in a third laboratory was only marginal (two-tailed P = .08). When the data from all six laboratories are pooled, the difference in incidence of abnormalities in PMF-exposed embryos (approximately 25 percent) and that of controls (approximately 19 percent), although small, is highly significant, as is the interaction between incidence of abnormalities and laboratory site (both Ps less than .001). The factor or factors responsible for the marked variability of inter-laboratory differences are unknown.     

Human HepG2 and Rat Fao Hepatic-Derived Cell Lines Show Different Responses to Ciprofibrate, a Peroxisome Proliferator: Analysis by Flow Cytometry

Peroxisome proliferators, and especially hypolipidemic drugs such as ciprofibrate, are known to be hepatocarcinogens in rodents, but their effect in humans is controversial. In an attempt to investigate the effects of ciprofibrate at a cellular level, the analysis of individual whole cells was performed by flow cytometry on samples from two hepatic-derived cell lines: the rat Fao cell line and the human HepG2 cell line. The increase of light scatter signals in rat Fao cells treated for 3 days with ciprofibrate at 250 μMwas related to modifications of intrinsic cellular parameters, such as size and cytoplasmic granularity. Conversely, no variations appeared in human HepG2-treated cells. Moreover, the study of the cell cycle distribution of asynchronously growing cells showed an increase in the percentage of proliferative cells in Fao-treated cells, but not in HepG2-treated cells. In order to give a simultaneous assessment of changes in cellular parameters and cell metabolism, these flow cytometric experiments were completed with the measurements of the palmitoyl–CoA oxidase activity, used as a marker of peroxisome proliferation. The cellular modifications in the rat Fao cell line were accompanied by a great increase in this enzymatic activity, whereas the human HepG2 cell line, which failed to exhibit changes of cytometric data, presented no, or weak, increase in this oxidase activity. The cellular modifications observed in the rat Fao cell line may be related to the well-known hepatocarcinogenicity of ciprofibrate in rodents, whereas the absence of response of HepG2 cells is in favor of the noncarcinogenicity of this drug in humans. This report validates another methodological approach for the investigation of the safety of peroxisome proliferators in humans.     

Separation of the enantiomers of coumarinic anticoagulant drugs by capillary electrophoresis using maltodextrins as chiral modifiers

The separation and quantitation of coumarinic anticoagulant drug enantiomers were achieved by direct chiral capillary electrophoresis using complex maltooligosaccharide mixtures as stereoselective electrolyte modifiers. Chiral separations were characterized by a high selectivity and efficiency, enabling enantiomeric excess determinations. In addition, preliminary results indicate the applicability of the method for the determination of individual enantiomers in biological samples. So the method can be used to perform stereoselective pharmacokinetic studies. © 1994 Wiley-Liss, Inc.