Understanding the toxicity of chemicals to organisms requires considering the molecular mechanisms involved as well as the relationships between exposure concentration and toxic effects with time. Our current knowledge about such relationships is mainly explained from a toxicodynamic and toxicokinetic perspective. This paper re-introduces an old approach that takes into account the biochemical ...

The toxic actions of scrapie prion protein (PrP(sc)) are poorly understood. We investigated the ability of the toxic PrP(sc) fragment 106-126 to interfere with evoked catecholamine secretion from PC-12 cells. Prion protein fragment 106-126 (PrP106-126) caused a time- and concentration-dependent augmentation of exocytosis due to the emergence of a Ca(2+) influx pathway resistant to Cd(2+) but se...

Understanding the molecular mechanism of the interaction of amphipathic and antimicrobial peptides with membranes is of fundamental interest, especially because of the potential of amphipathic peptides as therapeutics. The most studied amphipathic peptides in this context are certainly melittin, magainin and alamethicin, of which melittin is the only one to exhibit a powerful hemolytic and ther...

The notion of speci®cation frameworks transposes the framework approach from software development to the level of formal modeling and analysis. A speci®cation framework is devoted to a special application domain. It supplies reusable speci®cation modules and guides the construction of speci®cations. Moreover, it provides theorems to be used as building blocks of veri®cations. By means of a suit...

We discuss a patient with cocaine intoxication in whom the initial presentation was that of asystole and ventricular fibrillation. Cocaine has a direct toxic action on the heart and also sensitizes cardiac tissue to the action of catecholamines. Cocaine intoxication should be considered in any patient with unexplained cardiac arrest or ventricular arrhythmias.

Studies of structure-activity relationships and molecular mechanisms of action are fundamental to our understanding of the harmful effects of chemicals on the environment and their more direct effects on human health. It is important to identify factors that determine toxicological effects of foreign chemicals in biological systems and to assess our knowledge about chemical mechanisms of toxici...

The narcosis target lipid model (TLM) was developed to predict the toxicity of chemicals to aquatic organisms that act via narcosis. It is based on the hypothesis that target lipid is the site of toxic action within the organism, that octanol is the appropriate surrogate, and that target lipid has the same physical-chemical properties in all organisms. Here the TLM is extended to available fres...

Determinations have been made of the level of serotonin in various fetal and maternal tissues of goats and rabbits. In the goat, both fetal brain and blood were higher in serotonin content than comparable maternal tissues. Furthermore, in the goat fetal neocortical areas unexpectedly were found to be richer in serotonin than certain subcortical structures. In contrast to the goat, the rabbit wa...

We study the rigidity properties of a class of algebraic Z-actions with entropy rank two. For this class, conditions are found which force an invariant measure to be the Haar measure on an affine subset. This is applied to show isomorphism rigidity for such actions, and to provide examples of non-isomorphic Z-actions with all their Z-sub-actions isomorphic. The proofs use lexicographic half-spa...

Additional experimental work on the subject of eosin hemolysis has been carried out. This indicates that red cells may be protected against the toxic action of eosin in sunlight by the presence of inorganic reducing agents. It is pointed out that a marked parallelism exists between the substances which react with the Folin and Denis reagent and the compounds which afford protection to red cells...