Increased Vulnerability to Stress Following Opiate Exposures: Behavioral and Autonomic Correlates.

The authors used rats to study the impact of a history of opiate exposures on behavioral and autonomic responses to restraint stress. Brief restraint (30 min) provoked tachycardia and a pressor response, anxiety (as indexed by social interaction), grooming, and reduced exploration. The pressor response was reduced at 1 day, but not 7 days, after last opiate exposure; tachycardia was unaffected (Experiment 1). Stress-induced anxiety was potentiated 1 and 7 days after last opiate exposure (Experiment 2), and this potentiation was a function of dose (Experiment 3) and duration (Experiment 4) of opiate exposure. The results show that a history of opiate exposures alters vulnerability to stress and has implications for understanding coping, anxiety, and emotionality in former opiate users. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Informational Turn in Philosophy1

This paper traces the application of information theory to philosophical problems of mind and meaning from the earliest days of the creation of the mathematical theory of communication. The use of information theory to understand purposive behavior, learning, pattern recognition, and more marked the beginning of the naturalization of mind and meaning. From the inception of information theory, Wiener, Turing, and others began trying to show how to make a mind from informational and computational materials. Over the last 50 years, many philosophers saw different aspects of the naturalization of the mind, though few saw at once all of the pieces of the puzzle that we now know. Starting with Norbert Wiener himself, philosophers and information theorists used concepts from information theory to understand cognition. This paper provides a window on the historical sequence of contributions made to the overall project of naturalizing the mind by philosophers from Shannon, Wiener, and MacKay, to Dennett, Sayre, Dretske, Fodor, and Perry, among others. At some time between 1928 and 1948, American engineers and mathematicians began to talk about `Theory of Information' and `Information Theory,' understanding by these terms approximately and vaguely a theory for which Hartley's `amount of information' is a basic concept. I have been unable to find out when and by whom these names were first used. Hartley himself does not use them nor does he employ the term `Theory of Transmission of Information,' from which the two other shorter terms presumably were derived. It seems that Norbert Wiener and Claude Shannon were using them in the Mid-Forties.(Yehoshua Bar-Hillel, 1955)     

Full-body interface pressure testing as a method for performance evaluation of clinical support surfaces

A method for evaluating the performance of clinical support surfaces is required by designers in their efforts to produce better clinical support surfaces that will reduce the incidence of pressure ulcers. In this study, a Pressure Index (P_index) is defined which is derived from an analytical equation used to evaluate the average interface pressure, the peak pressure, the magnitude of the peak pressure, and the number of peak pressures on the entire body. The type of subjects needed to represent a population of users as well as the head of bed elevations necessary to simulate clinical applications were integrated with the P_index to create a single-value mean pressure index which can be used to evaluate any type of surface. To determine the accuracy and repeatability of the mean pressure index, three surfaces (a standard hospital innerspring, a replacement foam mattress, and a low-airloss surface) were tested and evaluated using this method. The low airloss performed the best and the standard innerspring clearly performed the worst (p < 0.0001). The method appeared to accurately and reproducibly predict the relative performance of the three surfaces in reducing pressure.     

Isomeric Carborane Neuromuscular Blocking Agents

We synthesized a family of neuromuscular blocking agents (NMB) based on decamethonium, but containing a carborane cluster in the methylene chain between the two quaternary ammonium groups. The carborane cluster isomers o-NMB, m-NMB, and p-NMB were tested in animals for neuromuscular block and compared with agents used clinically: rocuronium and decamethonium. All three isomers caused reversible muscle weakness in mice as determined by grip strength and inverted screen tests, with a potency rank of p-NMB > rocuronium > decamethonium > m-NMB > o-NMB. The mechanism of action of the compounds was determined by using the in vitro rat phrenic nerve hemi-diaphragm preparation and electrophysiologic measurements in cells. Neostigmine reversed hemi-diaphragm weakness caused by the three isomers and rocuronium, but not succinylcholine. In electrophysiologic recordings of currents through acetylcholine receptor channels, the carborane compounds did not activate channel activity but did inhibit channel activation by acetylcholine. These results demonstrate that the carborane neuromuscular blocking agents are non-depolarizers in contrast to the depolarizing action of the parent compound.     

Rational Optimization of Dihydropyrimidinone-Quinoline Hybrids as Plasmodium falciparum Glutathione Reductase Inhibitors

A series of dihydropyrimidinone-based antimalarial compounds were designed and synthesised based on the previously identified amide-based quinoline hybrids which showed good resistance reversal ability against the resistant strain of Plasmodium falciparum. The aromatic ring on the dihydropyrimidinone of the original hits was exchanged for a methyl group to bring the molecular weights below 500 Da and also determine the effect of the aromatic ring count on the resistance reversal ability of the hybrids. Apart from the previously used amide bond, the hybrid linker was also extended to the triazole linker. Although the triazole linker is synthetically easier to access, the use of an amide linker seems to have an activity advantage. The synthesised compounds in addition to the previously identified hits were subjected to molecular docking particularly targeting the orthosteric site of Plasmodium falciparum glutathione reductase (PfGR) protein. The ligand with the best binding interaction was rationally optimised to increase its suitability as a competitive inhibitor against the cofactor of the PfGR. Two of the optimised ligands showed better binding affinities than the cofactor while one of the two ligands displayed hydrophobically packed correlated hydrogen-bond which is very important in maintaining the ligand stability within the protein. In silico ADME predictions of the synthesised compounds indicate that these compounds possess good pharmacokinetic properties.