Dual inhibition of both the epidermal growth factor receptor and erbB2 effectively inhibits the promotion of skin tumors during two-stage carcinogenesis.

The erbB family of receptor tyrosine kinases are known to play important roles in normal epithelial development and epithelial neoplasia. Considerable evidence also suggests that signaling through the epidermal growth factor receptor (EGFR) plays an important role in multistage skin carcinogenesis in mice; however, less is known about the role of erbB2. In this study, to further examine the role of both erbB2 and EGFR in epithelial carcinogenesis, we examined the effect of a dual erbB2/EGFR tyrosine kinase inhibitor, GW2974, given in the diet on skin tumor promotion during two-stage carcinogenesis in wild-type and BK5.erbB2 mice. In BK5.erbB2 mice, erbB2 is overexpressed in the basal layer of epidermis and leads to heightened sensitivity to skin tumor development. GW2974 effectively inhibited skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in wild-type and BK5.erbB2 mice, although a more marked effect was seen in BK5.erbB2 mice. In addition, this inhibitory effect was reversible when GW2974 treatment was withdrawn. GW2974 inhibited 12-O-tetradecanoylphorbol-13-acetate-induced epidermal hyperproliferation, which correlated with reduced activation of both the EGFR and erbB2. These results support the hypothesis that both the EGFR and erbB2 play an important role in the development of skin tumors during two-stage skin carcinogenesis, especially during the tumor promotion stage. Furthermore, the marked sensitivity of BK5.erbB2 mice to the inhibitory effects of GW2974 during tumor promotion suggest greater efficacy for this compound when erbB2 is overexpressed or amplified as an early event in the carcinogenic process.

Gender as a moderator of the relation between PTSD and disgust: a laboratory test employing individualized script-driven imagery.

The present study examines anxiety and disgust responding during exposure to trauma cues as a function of gender and posttraumatic stress disorder (PTSD). Trauma exposed adults without PTSD were compared to adults with PTSD during a script-driven imagery procedure that exposed each participant to individualized traumatic event cues. Anxiety responding during exposure to an individualized traumatic event script was not associated with gender, PTSD, or interaction of gender and PTSD in the present study. However, gender did moderate the relation between disgust responding and PTSD, such that females with PTSD reported more disgust during the script in comparison to females without PTSD and males with and without PTSD. Heart rate during the individualized trauma script was significantly higher among males with PTSD compared to males without PTSD and females with PTSD. Implications of these findings for conceptualizing how gender differences in emotional and physiological responding contribute to development and course of PTSD are discussed.

Iodine supplementation improves cognition in iodine-deficient schoolchildren in Albania: a randomized, controlled, double-blind study.

BACKGROUND: Iodine is required for the production of thyroid hormones, which are necessary for normal brain development and cognition. Although several randomized trials examined the effect of iodine supplementation on cognitive performance in schoolchildren, the results were equivocal. OBJECTIVE: We aimed to ascertain whether providing iodized oil to iodine-deficient children would affect their cognitive and motor performance. DESIGN: In a double-blind intervention trial, 10-12-y-old children (n = 310) in primary schools in rural southeastern Albania were randomly assigned to receive 400 mg I (as oral iodized oil) or placebo. We measured urinary iodine (UI), thyroid-stimulating hormone (TSH), and total thyroxine (TT4) concentrations and thyroid gland volume (by ultrasound). The children were given a battery of 7 cognitive and motor tests, which included measures of information processing, working memory, visual problem solving, visual search, and fine motor skills. Thyroid ultrasound and the biochemical and psychological tests were repeated after 24 wk. RESULTS: At baseline, the children's median UI concentration was 43 microg/L; 87% were goitrous, and nearly one-third had low concentrations of circulating TT4. Treatment with iodine markedly improved iodine and thyroid status: at 24 wk, median UI in the treated group was 172 microg/L, mean TT4 was approximately 40% higher, and the prevalence of hypothyroxinemia was < 1%. In the placebo group after the intervention, these variables did not differ significantly from baseline. Compared with placebo, iodine treatment significantly improved performance on 4 of 7 tests: rapid target marking, symbol search, rapid object naming, and Raven's Coloured Progressive Matrices (P < 0.0001). CONCLUSION: Information processing, fine motor skills, and visual problem solving are improved by iodine repletion in moderately iodine-deficient schoolchildren.