A Yeast Bioassay for Androgenic and Anti-Androgenic Compounds Based on the NH2- and COOH-Terminal Interaction of Androgen Receptor

Androgenic compounds induce an interaction between the NH₂- and COOH-terminal regions (N–C interaction) of androgen receptor (AR). We describe a rapid yeast bioassay for androgenic and anti-androgenic compounds based on androgen-dependent β-catenin-enhanced N–C interaction. The bioassay was also effective at detecting compounds that inhibit the N–C interaction in ways that do not involve binding to the ligand-binding domain.     

The development of chemical‐specific,risk‐based soil cleanup guidelines results in timely and cost‐effective remediation

Millions of dollars of limited state cleanup funds are spent each year in New Hampshire to identify, sample, excavate, and treat thousands of tons of contaminated soil. Cost analyses of numerous sites indicated that soil remediation costs alone reach upwards of $300,000.00 per site. The New Hampshire Department of Environmental Services “Interim Policy for Management of Soils Contaminated from Spills/Releases of Virgin Petroleum Products”; (DES, 1989, 1991) set conservative remediation goals based on total petroleum hydrocarbons in 1989 using the Leaching Potential Analysis method (California Luft Manual, 1989). A current review of available literature and several case histories indicated that chemical‐specific soil cleanup levels may be more appropriate for establishing remedial goals. New chemical‐specific soil cleanup guidelines using a risk‐based approach have been developed. These new guidelines are conservatively based using two principal considerations: (1) an assumed soil exposure scenario that estimated the human health risks associated with potential long‐term exposure to site soils via ingestion, inhalation and dermal contact and (2) the estimated fate and transport of chemicals of concern in the soil unsaturated zone. The first consideration assumed a total cancer risk that did not exceed 1 × 10^‐6. The second consideration employed the use of the SEasonal SOIL Compartment (SESOIL) model which simultaneously models water transport, sediment transport, and pollutant fate (US EPA, 1981). Several state soil standards from Oregon, Wisconsin, Massachusetts, and other states were extensively reviewed in order to develop a level of confidence that use of the SESOIL model was appropriate. A series of “sensitivity”; analyses was also performed in order to evaluate the response of the model to changes in various input parameters unique to New Hampshire's hydrogeologic conditions. Generic soil cleanup guidelines were developed for 24 petroleum‐based volatile and semivolatile chemicals of concern to be applied statewide. Site‐specific soil cleanup guidelines will be allowed if it can be demonstrated that insertion of site‐specific data into the model will not adversely affect groundwater quality. As a result of the above processes, timely and much more cost‐effective remediation will be achieved while still maintaining a high degree of protection of the groundwater quality and human health.     

Feeding response of Aedes aegypti and Anopheles dirus (Diptera: Culicidae) using out‐of‐date human blood in a membrane feeding apparatus

The colonization of Aedes aegypti and Anopheles dirus was performed using out‐of‐date human blood from a blood bank as a nutritional supply dispensed from a common artificial feeder. Preserved human blood was collected and used for feeding on days 5, 15, and 25 after date of expiration and dispensed from a common artificial feeder to rear the mosquitoes. Ae. aegypti had a feeding rate of 78.7, 62, and 18% at the respective intervals while An. dirus had a rate of 80, 56.8, and 7.3% on the same respective days. Direct feeding on live hamsters resulted in a rate of 96 and 90% for Ae. aegypti and An. dirus, respectively. Although egg production rates decreased from the day 5 feeding to the day 25 feeding, all of the developmental stages resulting from An. dirus fed at day 5 and 15 showed insignificant differences when compared with direct feeding on the blood of a hamster.     

N-acetyl-L-cysteine protects SHSY5Y neuroblastoma cells from oxidative stress and cell cytotoxicity: effects on beta-amyloid secretion and tau phosphorylation

Redox changes within neurones are increasingly being implicated as an important causative agent in brain ageing and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD). Cells have developed a number of defensive mechanisms to maintain intracellular redox homeostasis, including the glutathione (GSH) system and antioxidant enzymes. Here we examine the effects of N-acetyl-L-cysteine (NAC) on beta-amyloid (A beta) secretion and tau phosphorylation in SHSY5Y neuroblastoma cells after exposure to oxidative stress inducing/cytotoxic compounds (H(2)O(2), UV light and toxic A beta peptides). A beta and tau protein are hallmark molecules in the pathology of AD while the stress factors are implicated in the aetiology of AD. The results show that H(2)O(2), UV light, A beta 1-42 and toxic A beta 25-35, but not the inactive A beta 35-25, produce a significant induction of oxidative stress and cell cytotoxicity. The effects are reversed when cells are pre-treated with 30 mM NAC. Cells exposed to H(2)O(2), UV light and A beta 25-35, but not A beta 35-25, secrete significantly higher amounts of A beta 1-40 and A beta 1-42 into the culture medium. NAC pre-treatment increased the release of A beta 1-40 compared with controls and potentiated the release of both A beta 1-40 and A beta 1-42 in A beta 25-35-treated cells. Tau phosphorylation was markedly reduced by H(2)O(2) and UV light but increased by A beta 25-35. NAC strongly lowered phospho-tau levels in the presence or absence of stress treatment.