Classical/nonclassical hybrid cannabinoids: southern aliphatic chain-functionalized C-6beta methyl, ethyl, and propyl analogues.

The stereoelectronic requirements for interaction of the southern aliphatic hydroxyl of cannabimimetic pharmacophores with the CB1 and CB2 receptors are explored. The stereoselective syntheses of three series of classical/nonclassical hybrid cannabinoids are described. These compounds were designed to investigate the importance of the southern aliphatic hydroxyl (SAH) pharmacophore for cannabimimetic activity. Variation in the chain length of the SAH moiety in these 6beta-(hydroxyalkyl)dihydrobenzopyran analogues, from 6beta-hydroxymethyl to 6beta-(omega-hydroxyethyl) and 6beta-(omega-hydroxypropyl), and the effects of replacing the hydroxyl functionality by hydride and iodide are reported. Our results indicate that the SAH pharmacophore has less pronounced effects than the C-3 aliphatic chain on cannabinoid activity. Furthermore, it appears that this southern molecular component is capable of interacting with two different subsites on the receptor and that the nature of this interaction is determined by the terminal substituent on the C-6beta alkyl group. One of the subsites can accommodate the relatively polar SAH pharmacophore, while the second subsite interacts with more hydrophobic C-6beta substituents and can accommodate large spherical pharmacophores separated by three methylene carbons from the tricyclic cannabinoid template.

Change in red blood cell relaxation with hydration: application to MR imaging of hemorrhage.

T1 and T2 were measured in unclotted blood samples with 0.24- and 4.7-T spectrometers. The fraction by weight of intracellular water in the red blood cells (RBCs) was varied by either osmotic manipulation or density separation in concentrated (packed RBCs) and dilute (RBCs suspended in buffer or serum) samples. Reducing the cell water content caused a moderate decrease in T1 and a profound decrease in T2 at both 0.24 and 4.7 T. Conversely, increasing the cell water content caused an increase in both T1 and T2. The authors conclude that dehydrated RBCs in an area of hemorrhage would cause a substantial decrease in signal intensity on long TR/TE (T2-weighted) images. Overhydration of RBCs would have the opposite effect.

Optical information for detecting loss in one's own forward speed.

An experiment was conducted to determine whether accuracy and efficiency of detecting loss in one's own forward speed are constant when optical information is invariant over a wide range of environmental variables. Deceleration rate, initial forward velocity, and altitude were varied so as to isolate initial optical flow rate, optical flow deceleration, and optical flow damping invariants specified in observer-relevant metrics. The candidate resulting in the most consistent effect on performance was global damping, which specifies a contrast of flow deceleration with initial flow rate. The finding is a first step toward validating a procedure for identifying functional invariants by assessing the usefulness of mathematically specified optical information for the perception of egomotion. The research represents both a methodological development and empirical support for the broader program of ecological functionalism.