Our understanding of the health risks of farmworkers exposed to pesticides in their work and home environments is rapidly increasing, although studies designed to examine the possible neurobehavioral effects of low-level chronic pesticide exposure are limited. We measured dialkyl phosphate urinary metabolite levels, collected environmental dust samples from a subset of homes, obtained information on work practices, and conducted neurobehavioral tests on a sample of farmworkers in Oregon. Significant correlations between urinary methyl metabolite levels and total methyl organophosphate (azinphos-methyl, phosmet, malathion) house dust levels were observed. We found the neurobehavioral performance of Hispanic immigrant farmworkers to be lower than that observed in a nonagricultural Hispanic immigrant population, and within the sample of agricultural workers there was a positive correlation between urinary organophosphate metabolite levels and poorer performance on some neurobehavioral tests. These findings add to an increasing body of evidence of the association between low levels of pesticide exposure and deficits in neurobehavioral performance.

Growth of the fetal heart involves cardiomyocyte enlargement, division, and maturation. Insulin-like growth factor-1 (IGF-1) is implicated in many aspects of growth and is likely to be important in developmental heart growth. IGF-1 stimulates the IGF-1 receptor (IGF1R) and downstream signaling pathways, including extracellular signal-regulated kinase (ERK) and phosphoinositol-3 kinase (PI3K). We hypothesized that IGF-1 stimulates cardiomyocyte proliferation and enlargement through stimulation of the ERK cascade and stimulates cardiomyocyte differentiation through the PI3K cascade. In vivo administration of Long R3 IGF-1 (LR3 IGF-1) did not stimulate cardiomyocyte hypertrophy but led to a decreased percentage of cells that were binucleated in vivo. In culture, LR3 IGF-1 increased myocyte bromodeoxyuridine (BrdU) uptake by three- to five-fold. The blockade of either ERK or PI3K signaling (by UO-126 or LY-294002, respectively) completely abolished BrdU uptake stimulated by LR3 IGF-1. LR3 IGF-1 did not increase footprint area, but as expected, phenylephrine stimulated an increase in binucleated cardiomyocyte size. We conclude that 1) IGF-1 through IGF1R stimulates cardiomyocyte division in vivo; hyperplastic growth is the most likely explanation of IGF-1 stimulated heart growth in vivo; 2) IGF-1 through IGF1R does not stimulate binucleation in vitro or in vivo; 3) IGF-1 through IGF1R does not stimulate hypertrophy either in vivo or in vitro; and 4) IGF-1 through IGF1R requires both ERK and PI3K signaling for proliferation of near-term fetal sheep cardiomyocytes in vitro.