Chronic pain is a common problem among geriatric nursing home residents and is frequently undetected. Identification of this problem among communicative residents may be markedly improved by direct questioning about this problem at frequent intervals. New methods of assessing pain need to be created to assist in its detection among the non-communicative population.

Background-Aldosterone has been implicated in the effects of angiotensin II in the vasculature. We hypothesized that there is local expression of the mineralocorticoid receptor (MR) in the vasculature and that the use of a selective aldosterone receptor antagonist (SARA) improves endothelial function in early atherosclerosis. Methods and Results-New Zealand rabbits were placed on normal chow or 1% cholesterol diets, randomized to placebo or SARA (eplerenone, 50 mg/kg twice daily), and killed at the end of 6 weeks for various studies. In the hyperlipidemic (HL) chow group, there was a 2.3-fold increase in superoxide (O 2 ⅐Ϫ ) generation. SARA normalized O 2 ⅐Ϫ generation in intact aortas and reduced NADH and NADPH oxidase activity to basal levels (0.31Ϯ0.04 and 0.27Ϯ0.02 in HL versus 0.16Ϯ0.05 and 0.07Ϯ0.02 in HL-SARA, respectively; PϽ0.01 by ANOVA). This was associated with improvements in peak relaxations to the endothelial-dependent agonist acetylcholine (82Ϯ6% in HL-SARA versus 61Ϯ4 in HL; PϽ0.01 by ANOVA; ED 50 6.8ϫ10Ϫ8 mol/L in HL-SARA and 1.2ϫ10 Ϫ7 mol/L in HL; PϭNS) to near-normal levels. Vessels from the HL group demonstrated hyperreactivity to angiotensin II that could not be corrected with SARA. Plasma aldosterone levels by radioimmunoassay demonstrated a 4-to 5-fold increase in response to SARA but no differences with lipid feeding. Real-time reverse transcriptase-polymerase chain reaction studies revealed expression of MR in the aorta of HL rabbits and those of controls. Conclusions-MR antagonism improves endothelial function and reduces O 2⅐Ϫ generation in diet-induced atherosclerosis. Targeting aldosterone by blocking its receptor has potential antiatherosclerotic effects.

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The enantioselective synthesis of endothelin-A antagonist ABT-546 has been accomplished via the discovery and development of a highly selective catalytic asymmetric conjugate addition of ketoesters to nitroolefins. Employing just 4 mol % bis(oxazoline)-Mg(OTf)(2) complex with an amine cocatalyst, we obtained the product nitroketone with 88% selectivity at the aryl-bearing stereocenter and in good yield on scales ranging to 13 mol. The effects of ligand structure, metal salt, and solvent on the reaction are described. Particularly important to the reaction is the water content. While water is necessary during the generation of the catalyst, the water must be then removed to maximize stereoselectivity and reactivity. The reaction has been extended to other dicarbonyl substrates, and a variety of substitution patterns are tolerated on the nitroolefin partner. The reaction has also been employed in the synthesis of the antidepressant rolipram. Investigations relating to the mechanism of the reaction are also described.

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