Background And Aims: Determination of the degree of stenosis of atherosclerotic coronary arteries is an important part of postmortem examination of the heart, but, unfortunately, estimation of the degree of luminal narrowing can be imprecise and tends to be approximations. Visual guides can be useful to assess this, but earlier attempts to develop such guides did not employ digital technology. Using this approach, we have developed two computer-generated morphometric guides to estimate the degree of luminal narrowing of atherosclerotic coronary arteries.
View Article and Find Full Text PDFNeurodegeneration and neuroinflammation are key features in a range of chronic central nervous system (CNS) diseases such as Alzheimer's and Parkinson's disease, as well as acute conditions like stroke and traumatic brain injury, for which there remains significant unmet clinical need. It is now well recognized that current cell culture methodologies are limited in their ability to recapitulate the cellular environment that is present in vivo, and there is a growing body of evidence to show that three-dimensional (3D) culture systems represent a more physiologically accurate model than traditional two-dimensional (2D) cultures. Given the complexity of the environment from which cells originate, and their various cell-cell and cell-matrix interactions, it is important to develop models that can be controlled and reproducible for drug discovery.
View Article and Find Full Text PDFSmall molecule isoindoline and tetrahydroisoquinoline derivatives have been identified as selective agonists of human peroxisome proliferator-activated receptor δ (PPARδ. Compound 18 demonstrated efficacy in a biomarker for increased fatty acid oxidation, with upregulation of pyruvate dehydrogenase kinase, isozyme 4 (PDK4) in human primary myotubes.
View Article and Find Full Text PDFInducible nitric oxide synthase (iNOS) is active as a homodimer. A cell-based assay suitable for high-throughput screening (HTS) was generated to identify inhibitors of iNOS dimerization using the InteraX enzyme complementation technology of Applied Biosystems. The cells contain 2 chimeric proteins of complementing deletion mutants of beta-galactosidase, each fused to the oxygenase domain of human iNOS.
View Article and Find Full Text PDFMaintenance of rats on a vitamin A-deficient diet resulting in undetectable levels of plasma retinol and significant reductions in relative testes weight compared to age-matched controls leads to the loss of liver membrane-bound low affinity glucocorticoid binding site (LAGS) activity without any effects on the levels of constitutively expressed CYP3A2 protein. Subsequent daily administration of retinol acetate to vitamin A-deficient rats results in the re-expression of LAGS activity to control levels by 7 days. To determine any role for the LAGS in the modulation of CYP3A2 expression by glucocorticoids, a single dose of dexamethasone 21-phosphate was administered to vitamin A-deficient rats and vitamin A-deficient rats induced to re-express LAGS by daily retinol acetate treatment.
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