Circulating serum xenoestrogens and mammographic breast density

Introduction

Humans are widely exposed to estrogenically active phthalates, parabens, and phenols, raising concerns about potential effects on breast tissue and breast cancer risk. We sought to determine the association of circulating serum levels of these chemicals (reflecting recent exposure) with mammographic breast density (a marker of breast cancer risk).

Methods

We recruited postmenopausal women aged 55 to 70 years from mammography clinics in Madison, Wisconsin (N = 264). Subjects completed a questionnaire and provided a blood sample that was analyzed for mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, butyl paraben, propyl paraben, octylphenol, nonylphenol, and bisphenol A (BPA). Percentage breast density was measured from mammograms by using a computer-assisted thresholding method.

Results

Serum BPA was positively associated with mammographic breast density after adjusting for age, body mass index, and other potentially confounding factors. Mean percentage density was 12.6% (95% confidence interval (CI), 11.4 to 14.0) among the 193 women with nondetectable BPA levels, 13.7% (95% CI, 10.7 to 17.1) among the 35 women with detectable levels below the median (<0.55 ng/ml), and 17.6% (95% CI, 14.1 to 21.5) among the 34 women with detectable levels above the median (>0.55 ng/ml; P_trend = 0.01). Percentage breast density was also elevated (18.2%; 95% CI, 13.4 to 23.7) among the 18 women with serum mono-ethyl phthalate above the median detected level (>3.77 ng/ml) compared with women with nondetectable BPA levels (13.1%; 95% CI, 11.9 to 14.3; P_trend = 0.07). No other chemicals demonstrated associations with percentage breast density.

Conclusions

Postmenopausal women with high serum levels of BPA and mono-ethyl phthalate had elevated breast density. Further investigation of the impact of BPA and mono-ethyl phthalate on breast cancer risk by using repeated serum measurements or other markers of xenoestrogen exposure are needed.     

Childhood obesity: the infancy connection

The prevalence of overweight has risen to 19% in children aged 6 to 11 years and 17% in adolescents aged 12 to 19 years. This paper examines gestational and infancy factors that influence the risk of overweight in childhood. Important factors to eliminate the infancy connection to childhood obesity include the following: (a) maternal lifestyle patterns, (b) infant feeding transitions, and (c) environmental factors. Prevention efforts need to focus on practice, research, and public policy.     

Induction of hepatic cytochrome P450 enzymes: methods,mechanisms, recommendations,and in vitro–in vivo correlations

Induction of drug-clearance pathways (Phase 1 and 2 enzymes and transporters) can have important clinical consequences. Inducers can (1) increase the clearance of other drugs, resulting in a decreased therapeutic effect, (2) increase the activation of pro-drugs, causing an alteration in their efficacy and pharmacokinetics, and (3) increase the bioactivation of drugs that contribute to hepatotoxicity via reactive intermediates. Nuclear receptors are key mediators of drug-induced changes in the expression of drug-clearance pathways. However, species differences in nuclear receptor activation make the prediction of cytochrome P450 (CYP) induction in humans from data derived from animal models problematic. Thus, in vitro human-relevant model systems are increasingly used to evaluate enzyme induction. In this review, the authors’ current understanding of the mechanisms of enzyme induction and the in vitro methods for assessing the induction potential of new drugs will be discussed. Relevant issues and considerations surrounding proper study design and the interpretation of in vitro results will be discussed in light of the current US Food and Drug Administration (FDA) recommendations.     

Neutrophil mean peroxidase: a biologically interesting parameter with a potential for WBC differential quality control

This study has shown the neutrophil mean peroxidase measurement on the Technicon H6000 to be a simple reproducible technique for measuring neutrophil myeloperoxidase. This measurement shows no interference from contaminating eosinophils unlike spectrophotometric methods. The WBC count had little effect on the CV of the neutrophil mean peroxidase within the normal working range of the machine. Variations in the hydrogen peroxide concentration of the peroxidase substrate also had little effect on this measurement. Haemoglobin however had a significant inhibitory effect on the neutrophil mean peroxidase but this was in a predictable manner. The same inhibition of peroxidase also caused a decrease in the eosinophil count. This varied between individuals. The method described represents a suitable assay for the detection of varying degrees of neutrophil myeloperoxidase activity including the acquired and hereditary deficiencies. This parameter is potentially useful for the quality control of the cytochemically derived WBC differential.