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1.  Early adolescent cocaine use as determined by hair analysis in a prenatal cocaine exposure cohort 
Neurotoxicology and teratology  2010;33(1):88-99.
Preclinical and other research suggest that youth with prenatal cocaine exposure (PCE) may be at high risk for cocaine use due to both altered brain development and exposure to unhealthy environments.
Participants are early adolescents who were prospectively enrolled in a longitudinal study of PCE prior to or at birth. Hair samples were collected from the youth at ages 10½ and 12½ (N=263). Samples were analyzed for cocaine and its metabolites using ELISA screening with gas chromatography/mass spectroscopy (GC/MS) confirmation of positive samples. Statistical analyses included comparisons between the hair-positive and hair-negative groups on risk and protective factors chosen a priori as well as hierarchical logistical regression analyses to predict membership in the hair-positive group.
Hair samples were positive for cocaine use for 14% (n=36) of the tested cohort. Exactly half of the hair-positive preteens had a history of PCE. Group comparisons revealed that hair-negative youth had significantly higher IQ scores at age 10½; the hair-positive youth had greater availability of cigarettes, alcohol, and other drugs in the home; caregivers with more alcohol problems and depressive symptoms; less nurturing home environments; and less positive attachment to their primary caregivers and peers. The caregivers of the hair-positive preteens reported that the youth displayed more externalizing and social problems, and the hair-positive youth endorsed more experimentation with cigarettes, alcohol, and/or other drugs. Mental health problems, peer drug use, exposure to violence, and neighborhood characteristics did not differ between the groups. Regression analyses showed that the availability of drugs in the home had the greatest predictive value for hair-positive group membership while higher IQ, more nurturing home environments, and positive attachment to caregivers or peers exerted some protective effect.
The results do not support a direct relationship between PCE and early adolescent experimentation with cocaine. Proximal risk and protective factors—those associated with the home environment and preteens' caregivers—were more closely related to early cocaine use than more distal factors such as neighborhood characteristics. Consistent with theories of adolescent problem behavior, the data demonstrate the complexity of predicting pre-adolescent drug use and identify a number of individual and contextual factors that could serve as important foci for intervention.
PMCID: PMC3675882  PMID: 20647046
Prenatal cocaine exposure; Early adolescents; Hair; Drug testing; Substance abuse
2.  Erythrocyte Membrane Fatty Acid Content in Infants Consuming Formulas Supplemented with Docosahexaenoic Acid (DHA) and Arachidonic Acid (ARA): an Observational Study 
Maternal & child nutrition  2010;6(4):338-346.
In this observational study, we compared erythrocyte membrane fatty acids in infants consuming formula supplemented with docosahexaenoic acid (DHA) and arachidonic acid (ARA) with those consuming other types of milks. In 110 infants who were participants in a cohort study of otherwise healthy children at risk for developing type 1 diabetes, erythrocytes were collected at approximately 9 months of age, and fatty acid content was measured as a percent of total lipids. Parents reported the type of milk the infants consumed in the month of and prior to erythrocyte collection – infant formula supplemented with ARA and DHA (supplemented formula), formula with no ARA and DHA supplements (non-supplemented formula), breast-milk, or non-supplemented formula plus breast-milk. Membrane DHA (4.42 versus 1.79, p < 0.001) and omega-3 fatty acid (5.81 versus 3.43, p < 0.001) levels were higher in infants consuming supplemented versus non-supplemented formula. Omega-6 fatty acids were lower in infants consuming supplemented versus non-supplemented formula (26.32 versus 29.68, p = 0.023); ARA did not differ between groups. Infants given supplemented formula had higher DHA (4.42 versus 2.81, p < 0.001) and omega-3 fatty acids (5.81 versus 4.45, p = 0.008) than infants drinking breast-milk. In infants whose mothers did not receive any dietary advice, use of supplemented formula is associated with higher omega-3 and lower omega-6 fatty acid status.
PMCID: PMC2992442  PMID: 21050388
Arachidonic Acid; Docosahexaenoic Acid; Breastfeeding; Infant Feeding; Infant Formula; Infant Feeding Behavior
3.  Comparison between omega-3 and omega-6 polyunsaturated fatty acid intakes as assessed by a food frequency questionnaire and erythrocyte membrane fatty acid composition in young children 
We conducted a dietary validation study in youth aged 1 to 11 years by comparing dietary intake of omega-3 and omega-6 polyunsaturated fatty acids (PUFA) as assessed by a parent-completed semi-quantitative food frequency questionnaire (FFQ) over time to erythrocyte membrane composition of the same fatty acids.
The study population included youth aged 1 to 11 years who were participants in the Diabetes Autoimmunity Study in the Young (DAISY), a longitudinal study in Denver, Colorado that is following a cohort of youth at risk for developing Type I diabetes. Four hundred four children who had erythrocyte membrane fatty acid data matched to an FFQ corresponding to the same time frame for a total of 917 visits (matches) were included. PUFA intake was expressed as both g/day (adjusted for total energy) and as percent of total fat intake. We used mixed models to test the association and calculate the correlation between the erythrocyte membrane estimates and PUFA intake using all records of data for each youth.
Intakes of total omega-3 fatty acids (β=0.52, p<0.0001, ρ=0.23) and marine PUFAs (β=1.62, p<0.0001, ρ=0.42), as a percent of total fat in the diet, were associated with percent of omega-3 and marine PUFAs in the erythrocyte membrane. Intakes of omega-6 PUFAs (β=0.04, p=0.418, ρ=0.05) and arachidonic acid (β=0.31, p=0.774, ρ=0.01) were not associated.
In these young children, a FFQ using parental report provided estimates of average long-term intakes of marine PUFAs that correlated well with their erythrocyte cell membrane fatty acid status.
PMCID: PMC2896066  PMID: 17440518
4.  Soy Isoflavones Exert Differential Effects on Androgen Responsive Genes in LNCaP Human Prostate Cancer Cells1 
The Journal of nutrition  2007;137(4):964-972.
The high consumption of soy isoflavones in Asian diets has been correlated to a lower incidence of clinically important cases of prostate cancer. This study characterized the effects of a soy-derived isoflavone concentrate (ISF) on growth and gene expression profiles in the LNCaP, an androgen-sensitive human prostate cancer cell line. ISF caused a dose-dependent decrease in viability (P<0.05) and DNA synthesis (P<0.01), as well as an accumulation of cells in G2/M, and G0/G1 phases of the cell cycle compared with controls. Using Affymetrix oligonucleotide DNA microarrays (U133A), we determined that ISF upregulated 80 genes and downregulated 33 genes (P<0.05) involving androgen-regulated genes and pathways controlling cell cycle, metabolism, and intracellular trafficking. Changes in the expression of the genes of interest, identified by microarrays, were validated by Western immunoblot, Northern blot, and luciferase reporter assays. Prostate-specific antigen, homeobox protein NKX3, and cyclin B mRNA were significantly reduced, whereas mRNA was significantly upregulated for p21CIP1, a major cell cycle inhibitory protein, and fatty acid and cholesterol synthesis pathway genes. ISF also significantly increased cyclin-dependent kinase inhibitor p27KIP1 and FOXO3A/FKHRL1, a forkhead transcription factor. A differential pattern of androgen-regulated genes was apparent with genes involved in prostate cancer progression being downregulated by ISF, whereas metabolism genes were upregulated. In summary, we found that ISF inhibits the growth of LNCaP cells through the modulation of cell cycle progression and the differential expression of androgen-regulated genes. Thus, ISF treatment serves to identify new therapeutic targets designed to prevent proliferation of malignant prostate cells.
PMCID: PMC1975677  PMID: 17374662
5.  Dietary exposure of largemouth bass to OCPs changes expression of genes important for reproduction 
Dieldrin and p,p′-DDE are ubiquitous contaminants known to act as endocrine disruptors, causing impaired development and reproduction in fish and wildlife. In order to elucidate the mechanisms by which dieldrin and p,p′-DDE cause endocrine disruption in largemouth bass (Micropterus salmoides), fish were exposed subchronically through the diet to both contaminants. Following 120 days of exposure, p,p′-DDE decreased estradiol in females, but increased 11-ketotestosterone in both sexes. Dieldrin on the other hand, decreased estradiol and 11-ketotestosterone in both sexes. Both pesticides also altered steady state mRNA expression levels of a set of genes chosen to represent three possible mechanisms of endocrine disruption: (1) direct interaction with soluble sex steroid receptors, (2) biosynthesis of endogenous sex hormones, and (3) metabolism of endogenous hormones. p,p′-DDE acted as a weak estrogen, increasing the expression of vitellogenin and estrogen receptor α in the liver. p,p′-DDE also altered the expression of genes involved in the synthesis of endogenous hormones as well as their metabolism. Dieldrin, on the other hand, only altered expression of vitellogenin and not estrogen receptor α . Dieldrin also altered the expression of genes involved in hormone synthesis and metabolism, and it dramatically lowered plasma hormone levels. Both pesticides targeted expression of genes involved in all three modes of action, suggesting that they each have multiple modes of action.
PMCID: PMC1892580  PMID: 16765462
p,p′-DDE; Dieldrin; Largemouth bass; Quantitative real-time PCR; Endocrine disruptors; Organochlorine pesticides

Results 1-5 (5)