Dehydroepiandrosterone regulation of the hepatic glucocorticoid receptor in the zucker rat. The obesity research program

Dehydroepiandrosterone (DHEA) decreases the activity of hepatic tyrosine aminotransferase (TAT), a glucocorticoid-inducible enzyme, in the obese, hypercorticosteronemic Zucker rat. To investigate the mechanism of this antiglucocorticoid action, the effect of exogenous DHEA on hepatic glucocorticoid receptor (GC) number and affinity was quantitated. Food supplementation with DHEA (0.6% w/w) for 1 or 7 days had no effect on either receptor number or affinity in obese Zucker rats. After 28 days, however, DHEA treatment resulted in a nearly 40% decrease in cytosolic hepatic receptor content (B_max; fmol/mg cytosolic protein) without any change in affinity (K_d) in both lean and obese rats. DHEA treatment for 28 days also resulted in an increased liver size and cytosolic protein content. When the hepatic GC receptor content was normalized based on the change in liver size and protein content, the apparent number of GC binding sites per liver was not affected by DHEA treatment. This observation suggests that DHEA's effect on GC receptor content may not be a specific action and that downregulation of the GC receptor is not the mechanism of DHEA action on GC induced TAT activity. This is supported by the effect of DHEA on obese rat TAT activity in the same experiment where the greatest inhibition occurred after only 1 day of treatment. From these experiments it is concluded that although long-term DHEA treatment may decrease the relative concentration of GC receptors in rat liver, this change is not the mechanism through which DHEA mediates its acute antiglucocorticoid action.     

High-performance liquid chromatographic determination of 1-β- -arabinofuranosyl-E-5-(2-bromovinyl)uracil and its metabolite (E)-5-(2-bromovinyl)uracil in serum

A high-performance liquid chromatographic method was developed to assay 1-β- -arabinofuranosyl-E-5-(2-bromovinyl)uracil and its metabolite (E)-5-(2-bromovinyl)uracil in serum. The chloro analogue of the parent drug is used as internal standard. Human serum samples were assayed to establish the pharmacokinetic parameters. Acetonitrile, used as a protein precipitant, was evaporated to dryness and the residue, containing the analytes and internal reference, was dissolved in mobile phase prior to chromatographic analysis. The minimum quantifiable level was 0.02 μg of each analyte per ml of serum.     

Biosynthesis of modified peptidoglycan precursors by vancomycin-resistant Enterococcus faecium

In the presence of bacitracin, vancomycin-resistant Enterococcus faecium (vanA phenotype) accumulate UDP-N-acetylmuramyl(UDP-Mur-NAc)-tetrapeptide and a UDP-MurNAc-depsipentapeptide containing lactate substituted for the carboxy-terminal-D-alanine residue. In an in vitro peptidoglycan polymerization assay, the modified precursors function and confer resistance to vancomycin.     

Modeling the effects of El Niño, density-dependence, and disturbance on harbor seal (Phoca vitulina) counts in Drakes Estero, California: 1997–2007

Harbor seal ( Phoca vitulina ) haul-out site use may be affected by natural or anthropogenic factors. Here, we use an 11-yr (1997–2007) study of a seal colony located near a mariculture operation in Drakes Estero, California, to test for natural (El Niño-Southern Oscillation (ENSO), density-dependence, long-term trends) and anthropogenic (disturbance or displacement related to oyster production activities) factors that may influence the use of haul-out subsites. Annual mariculture related seal disturbance rates increased significantly with increases in oyster harvest ( r _s= 0.55). Using generalized linear models (GLMs) ranked by best fit and Akaike's Information Criteria, ENSO and oyster production (as a proxy for disturbance/displacement) best explained the patterns of seal use at all three subsites near the mariculture operations, with effects being stronger at the two subsites closest to operations. Conversely, density-dependence and linear trend effects poorly explained the counts at these subsites. We conclude that a combination of ENSO and mariculture activities best explain the patterns of seal haul-out use during the breeding/pupping season at the seal haul-out sites closest to oyster activities.