26 research outputs found

    Human Bisphenol a Biomonitoring and Biotransformation Programming in the Developing Fetus.

    Full text link
    The ubiquitous monomer, bisphenol A (BPA), is an endocrine active compound used in the production of polycarbonate plastics and epoxy resin. Environmental biomonitoring and epidemiology studies report continuous exposure in humans that are associated with different adverse health outcomes. The overall goal of this work was to characterize BPA concentrations, toxicokinetic and toxicodynamic profiles that influence tissue-specific BPA biotransformation via xenobiotic metabolizing enzymes (XME), and BPA dependent changes in biotransformation using healthy 1st-2nd trimester clinical specimens obtained from a fetal biobank. First, we reported a wide range of BPA concentrations in N=50 fetal liver specimens (total BPA range: below limit of quantification - 96.8 ng/g). Both concentrations and metabolic profiles varied across age with significant reduction in BPA-specific XME gene expression of UGT2B15, SULT1A1, and STS in fetal versus adult livers. Next, we examined matched fetal liver, kidney, and placenta in N=12 subjects and observed significant tissue-dependent differences in BPA concentrations, XME expression profiles, and global DNA methylation. Fetal livers exhibited higher BPA concentrations compared to matched tissues; however, XME expression profiles suggest an increased likelihood of BPA-glucuronide deconjugation and BPA-sulfate conjugation across the fetal compartments. With organ-specific differences in the epigenome, only placental global methylation measurements were associated with BPA. Finally, we investigated BPA’s role in pathway specific biological outcomes and regulation in fetal liver. In particular, we identified 14 different XME candidate genes that were down regulated with higher BPA concentrations. In summary, results suggest that the 1st-2nd trimester human fetus is exposed to a considerable amount of BPA in utero, especially of the active free BPA form. XME expression profiles reveal an altered capacity for BPA biotransformation in the fetus compared to adults, with distinct metabolic profiles across different tissues. Interestingly, higher BPA concentrations in fetal liver were associated with reduced expression of novel XME candidate genes mediated by epigenetic mechanisms. These findings indicate that environmentally relevant concentrations of BPA, even across a short window of development, result in detectable changes in the host’s toxicological defense system.PhDToxicologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/107192/1/msnahar_1.pd

    Bisphenol A-associated epigenomic changes in prepubescent girls: a cross-sectional study in Gharbiah, Egypt

    Full text link
    Abstract Background There is now compelling evidence that epigenetic modifications link adult disease susceptibility to environmental exposures during specific life stages, including pre-pubertal development. Animal studies indicate that bisphenol A (BPA), the monomer used in epoxy resins and polycarbonate plastics, may impact health through epigenetic mechanisms, and epidemiological data associate BPA levels with metabolic disorders, behavior changes, and reproductive effects. Thus, we conducted an environmental epidemiology study of BPA exposure and CpG methylation in pre-adolescent girls from Gharbiah, Egypt hypothesizing that methylation profiles exhibit exposure-dependent trends. Methods Urinary concentrations of total (free plus conjugated) species of BPA in spot samples were quantified for 60 girls aged 10 to 13. Genome-wide CpG methylation was concurrently measured in bisulfite-converted saliva DNA using the Infinium HumanMethylation27 BeadChip (N‚ÄČ=‚ÄČ46). CpG sites from four candidate genes were validated via quantitative bisulfite pyrosequencing. Results CpG methylation varied widely among girls, and higher urinary BPA concentrations were generally associated with less genomic methylation. Based on pathway analyses, genes exhibiting reduced methylation with increasing urinary BPA were involved in immune function, transport activity, metabolism, and caspase activity. In particular, hypomethylation of CpG targets on chromosome X was associated with higher urinary BPA. Using the Comparative Toxicogenomics Database, we identified a number of candidate genes in our sample that previously have been associated with BPA-related expression change. Conclusions These data indicate that BPA may affect human health through specific epigenomic modification of genes in relevant pathways. Thus, epigenetic epidemiology holds promise for the identification of biomarkers from previous exposures and the development of epigenetic-based diagnostic strategies.http://deepblue.lib.umich.edu/bitstream/2027.42/112909/1/12940_2013_Article_648.pd

    Exposure to phthalates among premenstrual girls from rural and urban Gharbiah, Egypt: A pilot exposure assessment study

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Phthalates have been identified as endocrine active compounds associated with developmental and reproductive toxicity. The exposure to phthalates in premenstrual Egyptian females remains unknown. The objective of this study was to characterize phthalate exposure of a potentially vulnerable population of premenstrual girls from urban and rural Egypt.</p> <p>Materials and methods</p> <p>We collected one spot urine sample from 60 10-13 year old females, 30 from rural Egypt, and 30 from urban Egypt from July to October 2009. Samples were analyzed for 11 phthalate metabolites. Additionally, we collected anthropometrics as well as questionnaire data concerning food storage behaviors, cooking practices, and cosmetic use. Phthalate metabolite concentrations were compared between urban and rural Egyptians as well as to age and gender matched Americans.</p> <p>Results</p> <p>Monoethyl phthalate (MEP), was detected at the highest concentration in urine of Egyptian girls (median: 43.2 ng/mL in rural, 98.8 ng/mL in urban). Concentrations of urinary metabolites of di-(2-ethylhexyl) phthalate and dibutyl phthalate were comparable between Egyptians and age matched US girls. Storage of food in plastic containers was a statistically significant predictor of urinary mono-isobutyl phthalate (MiBP) concentrations when comparing covariate adjusted means.</p> <p>Conclusions</p> <p>Urinary concentrations of phthalate metabolites were similar in Egyptian and US populations, suggesting that phthalate exposure also occurs in developing nations. Dietary intake is likely an important route of exposure to phthalates in both urban and rural populations.</p

    Urinary bisphenol A concentrations in girls from rural and urban Egypt: a pilot study

    Get PDF
    Abstract Background Exposure to endocrine active compounds, including bisphenol A (BPA), remains poorly characterized in developing countries despite the fact that behavioral practices related to westernization have the potential to influence exposure. BPA is a high production volume chemical that has been associated with metabolic dysfunction as well as behavioral and developmental effects in people, including children. In this pilot study, we evaluate BPA exposure and assess likely pathways of exposure among girls from urban and rural Egypt. Methods We measured urinary concentrations of total (free plus conjugated) species of BPA in spot samples in urban (N = 30) and rural (N = 30) Egyptian girls, and compared these concentrations to preexisting data from age-matched American girls (N = 47) from the U.S. National Health and Nutrition Examination Survey (NHANES). We also collected anthropometric and questionnaire data regarding food storage behaviors to assess potential routes of exposure. Results Urban and rural Egyptian girls exhibited similar concentrations of urinary total BPA, with median unadjusted values of 1.00 and 0.60 ng/mL, respectively. Concentrations of urinary BPA in this group of Egyptian girls (median unadjusted: 0.70 ng/mL) were significantly lower compared to age-matched American girls (median unadjusted: 2.60 ng/mL) according to NHANES 2009-2010 data. Reported storage of food in plastic containers was a significant predictor of increasing concentrations of urinary BPA. Conclusions Despite the relatively low urinary BPA concentrations within this Egyptian cohort, the significant association between food storage behaviors and increasing urinary BPA concentration highlights the need to understand food and consumer product patterns that may be closing the gap between urban and rural lifestyles.http://deepblue.lib.umich.edu/bitstream/2027.42/112495/1/12940_2011_Article_523.pd

    Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

    Get PDF
    BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

    Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study