Evaluation of RU28318 and RU40555 as selective mineralocorticoid receptor and glucocorticoid receptor antagonists, respectively: receptor measures and functional studies

BACKGROUND: Australia has a high rate of cardiovascular disease mortality and also a significant proportion of migrants. Little is known about the morbidity experience or cardiovascular risk factors among the larger migrant groups, and this is especially true of the Arabic-speaking population. OBJECTIVES: The objectives of the study were to identify the health profile of Arabic-speaking people in Sydney, Australia, to explore the relationship between level of acculturation and health indicators and to identify the morbidity profile of patients presenting to Arabic-speaking general practitioners (GPs). DESIGN: Adult Arabic-speaking patients aged 18-70 years attending 20 Arabic-speaking GPs in Canterbury, Sydney, during the 2-week study period were asked to complete a self-administered questionnaire in Arabic or English while waiting to see the GP. Data on cardiovascular risk factors, level of acculturation and reasons for seeing the GP were collected. RESULTS: Data were collected from 851 patients (62% response rate). Almost three-quarters (73%) of males and 36% of females were considered overweight or obese (body mass index > 25). Of concern, 37% of males and 28% of females were smokers. Females were significantly less likely to have been tested for diabetes (p < .05) or raised blood pressure (p < 0.05) compared with females in NSW. Respondents consumed less bread per day and more fruits than in NSW overall. Respiratory complaints (flu and colds) were the most frequently reported reasons for patient encounters. Except for the youngest age group, males gave more reasons for encounters than females. CONCLUSIONS: Consecutive sampling of ethnic patients attending a GP who speaks their language holds promise as a method of needs assessment with migrant populations. Further, our results suggest that smoking and weight reduction programs are priorities in the Arabic-speaking community. These risk factors are ideal for intervention by GPs speaking the same language.     

Kinetic analysis of the in vitro inhibition, aging, and reactivation of brain acetylcholinesterase from rat and channel catfish by paraoxon and chlorpyrifos-oxon

In rats, the phosphorothionate insecticide parathion exhibits greater toxicity than chlorpyrifos, while in catfish the toxicities are reversed. The in vitro inhibition of brain acetylcholinesterase (AChE) by the active metabolites of the insecticides and the rates at which these inhibitor-enzyme complexes undergo reactivation/ aging were investigated in both species. Rat AChE was more sensitive to inhibition than catfish AChE as demonstrated by greater bimolecular rate constants (ki) in rats than in catfish. In both species, chlorpyrifos-oxon yielded higher ki's than paraoxon. The higher association constant (KA) of chlorpyrifos-oxon than paraoxon in both species and the lack of significant differences in the phosphorylation constants (kp) suggest that association of the inhibitor with AChE is the principal factor in the different potencies between these two inhibitors. In catfish, the ki of chlorpyrifos-oxon was 22-fold greater than that of paraoxon, while in rats it was 9-fold greater, suggesting that target site sensitivity is an important factor in the higher toxicity of chlorpyrifos to catfish but not in the higher toxicity of parathion to rats. No spontaneous reactivation of phosphorylated catfish AChE occurred and there were no differences in the first oder aging constants (ka) between compounds. For phosphorylated rat AChE, there were no differences in the first order reactivation constants (kr) but the ka for chlorpyrifos-oxon was significantly greater than that for paraoxon. This difference suggests that the steric positioning of the diethyl phosphate in the esteratic site is not the same between the two compounds, leading to differences in aging.     

Replication of O6-methylguanine-containing DNA by repair and replicative DNA polymerases

The biological consequences of O6-methylguanine (m6G) in DNA are well recognized. When template m6G is encountered by DNA polymerases, replication is hindered and trans-lesion replication results in the preferential incorporation of dTMP opposite template m6G. Thus, unrepaired m6G in DNA is both cytotoxic and mutagenic. Yet, cell lines tolerant to m6G in DNA have been isolated, which indicates that some cellular DNA polymerases may replicate m6G-containing DNA with reasonable efficiency. Previous reports suggested that mammalian pol beta could not replicate m6G-containing DNA, but we find that pol beta can catalyze trans-lesion replication; however, the lesion must reside in the optimal context for pol beta activity, single- or short nucleotide gapped substrates. Primed single-stranded DNA templates, with or without template m6G, were poor substrates for pol beta as reported in earlier studies. In contrast, trans-lesion replication by bacteriophage T4 DNA polymerase was observed for primed single-stranded DNA templates. Replication of m6G-containing DNA by T4 DNA polymerase required the gp45 accessory protein that clamps the polymerase to the DNA template. The rate-limiting step in replicating m6G-containing DNAs by both DNA polymerases tested was incorporation of dTMP across from the lesion.     

A formal curriculum in breast imaging for radiology residents

RATIONAL AND OBJECTIVES: Training in breast imaging is highly variable among radiology programs. The authors have developed a standardized breast imaging curriculum for radiology residents. METHODS: This curriculum has been implemented within the residency program at the University of North Carolina at Chapel Hill. It includes nine standardized components: 1) the clinical activities of the service; 2) the study of breast imaging teaching file films and contribution of new cases; 3) selected readings; 4) formal discussion with faculty on the readings; 5) review of this material using an interactive computer program; 6) formal conferences; 7) technical and quality control activities; 8) research activities; and 9) an evaluation. The participating residents have been surveyed regarding their opinions of their educational experience. RESULTS AND CONCLUSION: The standardized curriculum has been well received by the participating residents. Conclusions about the educational efficacy of such a curriculum cannot be made until more residents have used it.     

Finally, a central place to evaluate nursing systems

Nurses now have a central place to check standards and evaluate systems. The Nursing Information and Data Set Evaluation Center develops, disseminates and evaluates nursing practice sets used by vendors. This center, established by the American Nurses Association, ensures that interventions and outcomes related to nursing diagnosis are appropriate and accurate.     

Progesterone protects against lipid peroxidation following traumatic brain injury in rats

Large scale use of lysozyme for periplasmic release has been impeded by the cost of the pure enzyme and its subsequent presence as a contaminant in later downstream processing steps. In this paper, we discuss the use of lysozyme for pilot scale recovery of a periplasmic enzyme from E. coli. The effects of concentration of sucrose, lysozyme and cells on periplasmic enzyme release were examined. Lysozyme concentration can be reduced 5-fold from previous reports and a reduction in sucrose concentration from 20 to 15% (w/v) allows an improvement in centrifugal harvesting by reducing viscosity. High levels of release were still achieved using this technique and further improvements in yield were obtained by optimising other components of the releasing mixture. Results show that some release is still achieved in circumstances where no lysozyme use is possible. Results also indicate that a substantial proportion (up to 70%) of lysozyme remains bound to the cellular debris after its action and is removed with this material.     

Mitogenic effect of retinoid X receptor agonists in rat liver

Thirty-nine acrylates and methacrylates that had been used in dental resin materials were evaluated by a cytotoxicity test, and the relationships between their structures and cytotoxicity were studied to predict cytotoxic levels of dental resin materials in order to develop new low-toxic resin materials. All the acrylates evaluated were more toxic than corresponding methacrylates. In both the acrylates and methacrylates, a hydroxyl group seemed to enhance cytotoxicity. Dimethacrylates with 14 or fewer oxyethylene chains showed similar cytotoxicity while dimethacrylates with 23 oxyethylene chains showed lower cytotoxicity. The cytotoxicity ranking of monomers widely used in dental resin materials was bisphenol A bis 2-hydroxypropyl methacrylate (bisGMA) > urethane dimethacrylate (UDMA) > triethyleneglycol dimethacrylate (3G) > 2-hydroxyethyl methacrylate (HEMA) > methyl methacrylate (MMA). In acrylates, methacrylates, and ethylmethacrylates with either substituents, the lipophilicity of substituents affected their cytotoxicity, and an inverse correlation between IC50 and logP was observed. These results will be useful in developing new resin materials with low toxic monomer compositions.