In Vitro Alveolar Macrophage Viability

A simple, rapid method was developed for the determination of in vitro alveolar macrophage viability after exposure to gases. Air pollutants such as ozone, sulfur dioxide, and oxides of nitrogen killed alveolar macrophages, as determined by the dye exclusion test. Ozone (O₃) was effective at very low concentrations. Other gases such as carbon dioxide (CO₂), carbon monoxide (CO), methane (CH₄), methyl chloride (CH₃Cl), acrolein, acetaldehyde, acetone, isoprene, benzene, and hydrocyanic acid (HCN) had no effect on cell viability.     

Determination of Cholinesterase by an Automated pH Stat Method

Public concern exists about the potential for reproductive damage that may result from exposures to environmental contaminants. Therefore, the authors sought to determine if there was an association between a child's congenital malformation or a child's lowered weight at birth and his or her mother's residence in a census tract where a site of environmental contamination had been documented. Exposure designations were derived from existing sources of information. Except for an elevated risk (odds ratio = 1.5) for infants with malformations of the heart and circulatory system, this investigation did not reveal increased risks for most malformations or for lowered birthweight among babies born to women who lived in these census tracts. Methodologic issues inherent to investigations that rely on existing data sources are discussed.     

Pharmacokinetics,Safety, and Tolerability of GS-9851, a Nucleotide Analog Polymerase Inhibitor for Hepatitis C Virus,following Single Ascending Doses in Healthy Subjects

To investigate the pharmacokinetics, safety, and tolerability of GS-9851 (formerly PSI-7851), a new nucleotide analog inhibitor of hepatitis C virus (HCV), we conducted a double-blind, parallel, placebo-controlled, randomized, single-ascending-dose study. Healthy subjects received oral doses of 25 to 800 mg GS-9851. Peak concentrations of GS-9851 in plasma were achieved more rapidly than those of the metabolites GS-566500 (formerly PSI-352707) and GS-331007 (formerly PSI-6206), with time to maximum concentration of drug in plasma (t_max) values of 1.0 to 1.8 h, 1.5 to 3.0 h, and 3.0 to 6.0 h, respectively. The majority of systemic drug exposure was from the nucleoside GS-331007, with maximum concentration of drug in plasma (C_max) and area under the concentration-time curve to the last measurable concentration (AUC_0–t) values at least 7- and 41-fold higher, respectively, than those obtained for GS-9851 after adjusting for differences in molecular weight. The terminal elimination half-life (t_1/2) of GS-331007 increased with the dose, achieving a t_1/2 of 25.7 h at 800 mg GS-9851. Dose proportionality was not observed for GS-331007. The majority of drug recovered in urine was in the form of GS-331007, with the percentage of this metabolite in urine samples ranging from 57% to 27% with increasing dose. GS-9851 was generally well tolerated, with no maximum tolerated dose identified. In conclusion, GS-9851 and its metabolites demonstrated a favorable pharmacokinetic profile consistent with once-daily dosing, and therefore, further clinical studies evaluating GS-9851 in HCV-infected patients are warranted.     

Assessing Strengths in Residential Treatment: Looking at the Whole Child

This article outlines the importance of assessing both within-child and environmental strengths for children and adolescents admitted to residential treatment facilities (RTFs). Discussed are the theoretical underpinnings behind strength-based assessment, as well as a number of organizations and initiatives that aim at raising the bar for children's care, creating a holistic viewpoint. Assessments such as the BASC-2, ASEBA, and Vineland-II are well-established measures that have moved to meet these demands, and measures like the BERS-2, RSCA, and DESSA have an overt strengths orientation. The CASA and the DCASC are omnibus strengths measures that can be utilized to fill the “intake gap.”