ACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes

Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesterol esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. Minor changes in subsequent structure were found to have a significant effect in optimization of the biological activity of this series of compounds.     

Oxygenation in the rabbit myocardium: assessment with susceptibility-dependent MR imaging

PURPOSE: To determine the feasibility of using hemoglobin (Hb) desaturation as an indicator of myocardial oxygenation. MATERIALS AND METHODS: High-resolution gradient-echo nuclear magnetic resonance (MR) images of isolated, blood-perfused rabbit hearts were obtained at various blood oxygenation levels. The hearts were perfused at 37 degrees C with a Langendorff apparatus modified for nuclear MR imaging. The perfusate contained bovine red blood cells in a cardioplegic solution that eliminated motion artifacts and minimized arteriovenous oxygenation differences. Hb saturation was varied (7%-100%) randomly. Perfusion pressure was continuously monitored, and blood samples were obtained. RESULTS: There was a substantial correlation between image signal intensity in the myocardium and Hb saturation in the blood, believed to be due to susceptibility effects of the paramagnetic species deoxyhemoglobin. CONCLUSION: Direct and noninvasive determination of regional Hb saturation with susceptibility-dependent MR imaging may provide information regarding regional myocardial O2 content.     

Modeling phosphorus in the upper Etowah River basin: identifying sources under uncertainty.

The Uniform Covering by Probabilistic Rejection (UCPR) algorithm was used, in conjunction with the Soil and Water Assessment Tool (SWAT) model, to identify P loads from point source and nonpoint source polluters in the upper Etowah River basin (UERB) in Georgia. The key findings of the research are as follows. The mean absolute error was preferred over the root mean square error as a search criterion for the UCPR algorithm when water quality observations are scarce. The undocumented P load from point sources in the UERB was consistently estimated as about 43 kg/d by the proposed method; but the method was not able to identify the broiler litter application rate to the poultry/beef operation pastures. Point sources (both documented and undocumented), poultry/beef operation pastures, and forests are the three major contributors of P. During 1992-1996, on average they accounted for 36.4, 31.7, and 17.2% of P load from the UERB, respectively.     

Differentiating anxiety and depression in older adults with generalized anxiety disorder.

To examine affect and cognition in differentiating anxiety and depression, 83 older participants with generalized anxiety disorder completed the Cognitive Checklist (CCL) and the Positive and Negative Affect Schedule (PANAS). A 3-factor solution was found for the PANAS: positive affect (PA), anxiety and anger (Negative Affect 1 [NA-1]), and guilt and shame (Negative Affect 2 [NA-2]). A 2-factor structure was noted for the CCL. Correlations with anxiety and depression measures suggested that the CCL Depression (CCL-D) subscale showed stronger correlations with depression, whereas the CCL Anxiety subscale did not uniquely correlate with anxiety. The NA-1 subscale correlated positively with measures of depression and anxiety, whereas the PA subscale showed negative correlations. Hierarchical regression suggested that the CCL-D subscale was a significant predictor of self-reported depression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cell cycle. The NIMA kinase joins forces with Cdc2

The NIMA and Cdc2 protein kinases cooperate to regulate mitosis in Aspergillus nidulans. NIMA-related pathways have now begun to emerge in higher eukaryotes.