Raltitrexed (Tomudex): an alternative drug for patients with colorectal cancer and 5-fluorouracil associated cardiotoxicity

Two patients with proven 5-fluorouracil (5-FU)-associated cardiotoxicity were treated with the specific thymidylate synthase inhibitor raltitrexed safely, without evidence of cardiotoxicity. Raltitrexed might be an alternative for patients with advanced colorectal cancer and 5-FU-associated cardiotoxicity. 5-FU cardiotoxicity is not due to the antineoplastic mechanisms via thymidilate synthase.     

Structure prediction of subtilisin BPN' mutants using molecular dynamics methods

In this paper we describe the achievements and pitfalls encounteredin doing structure predictions of protein mutants using moleculardynamics simulation techniques in which properties of atomsare slowly changed as a function of time. Basically the methodconsists of a thermodynamic integration (slow growth) calculationused for free energy determination, but aimed at structure prediction;this allows for a fast determination of the mutant structure.We compared the calculated structure of the mutants Met222Ala,Met222Phe and Met222Gln of subtilisin BPN' with the respectiveX-ray structures and found good agreement between predictedand X-ray structure. The conformation of the residue subjectto the mutation is relatively easy to predict and is mainlydetermined by packing criteria. When the side chain has polargroups its exact orientation may pose problems; long-range Coulombinteractions may generate a polarization feedback involvingsystem relaxation times beyond the simulation time. Changesinduced in the environment are harder to predict using thismethod. In particular, rearrangement of the hydration structurewas difficult to predict correctly, probably because of thelong relaxation times. In all conversions made the changes observedin the environment were found to be history-dependent and inparticular the hydrogen bonding patterns provided evidence formetastable substates. In all cases the structure predicted wascompared with available kinetic data and the reduced activitycould be explained in terms of changes in the configurationof the active site.     

Hard coatings on light-metal components under mechanical surface loading

In this work the behaviour of hard coated light-metal components was investigated when they are mechanically loaded. Three lightmetal alloys, Ti-6Al-4V, AlSi7Mg and AlMgSi0.5 and 100Cr6 steel (as a reference material) were coated by two different physical vapour deposition processes: radio frequency magnetron sputtering and electron beam evaporation. The coating materials utilised were CrN and TiN. Standard test methods with different loading conditions were used to evaluate the substrate/coating-combinations: the hardness test (applying a static normal load), the scratch test (applying a combination of a static normal and a static tangential force) and the impact test (applying a dynamic normal load). It was observed that the load support of coated materials depends on the loading conditions. The coated aluminium alloys showed poor load support under all loading test conditions but produced a higher surface hardness than uncoated steel. Coated Ti-6Al-4V showed very good load support properties, similar to coated steel. All coated light-metal substrates demonstrated significant improvement in load support behaviour with an increase in coating thickness. The results of the scratch test, which is commonly used to asses adhesion properties of thin coatings, showed an immediate indenter-breakthrough on the aluminium alloy substrates, but causing no coating delamination. Due to this behaviour, the scratch test is not suitable to evaluate adhesion properties on coated soft light-metals. Yet the impact test allowed assessment of coating delamination on the aluminium alloys, proving its usefulness for adhesion measurement even on soft substrates. The study indicates that substitution of steel with coated lightmetal alloys is a viable proposition for certain applications.     

Spannungsrißbildung und Spannungsrißkorrosion bei Kunststoffen

Environmental stress cracking and stress-corrosion cracking in plastics Plastics are being used to an increasing extent in fields which have hitherto been the reserve of other, usually metallic, materials. Owing to their good processability and chemical resistance, plastics engineering materials are for example employed for vessels, pipes, valves and fittings, blowers, pumps and gear wheels. In these applications they are not only exposed to liquid media but, are also subjected to occasional or continuous mechanical stress. The trouble is that there are media to which plastics in the stress-free state are absolutely immune, but that, when tensile stresses are present, cracking may occur; this phenomenon is called environmental stress cracking. It is therefore necessary for the design engineer both to know whether the medium to be handled causes environmental stress cracking, and to be familiar with the other properties of the material. The following article describes the most important methods of detecting environmental stress cracking and the most important media which cause this form of cracking in common plastics materials.     

Zur biochemischen Bedeutung des Selens bei der Trocknung von Milch

Zusammenfassung Die Ergebnisse von Fink u. Mitarb. über die lebernekrotischen Eigenschaften von Magermilchpulver konnten durch eigene Untersuchungen caber den Selengehalt von Milch, über die geringen Selenverluste bei der Trocknung von Milch (5 %), auf eine neue Basis gestellt werden. Das Verhältnis Schwefel- and Selenatome scheint in den einzelnen Proteinfraktionen konstant zu sein (Mittelwert: 1 : 80 825 ± 1,9 %). Die in der Literatur hervorgehobene antioxydative Wirkung organischer Selenverbindungen und ihre evtl. Bedeutung steht in einem interessanten, wenn auch hypothetischen Einklang mit dem stark erhöhten Selengehalt der Fettkügelchenmembran der Milch und der Erythrocytenmembran des Blutes.[/p]Auszug aus der Dissertation von WOLFGANG WIGAND : Bestimmung and Bedeutung des Selengehaltes der Milch. Technische Hochschule München 1967.