Browsing by keyword "Pesticides"
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Association between chlorinated pesticides in the serum of prepubertal Russian boys and longitudinal biomarkers of metabolic functionOrganochlorine pesticides (OCPs) have been linked to adult metabolic disorders; however, few studies have examined these associations in childhood. We prospectively evaluated the associations of baseline serum OCPs (hexachlorobenzene, beta-hexachlorocyclohexane, and p,p'-dichlorodiphenyldichloroethylene) in Russian boys with subsequent repeated measurements of serum glucose, insulin, lipids, leptin, and calculated homeostatic model assessment of insulin resistance (IR). During 2003-2005, we enrolled 499 boys aged 8-9 years in a prospective cohort; 318 had baseline serum OCPs and serum biomarkers measured at ages 10-13 years. Multivariable generalized estimating equation and mediation regression models were used to examine associations and direct and indirect (via body mass index (BMI) (weight (kg)/height (m)(2))) effects of prepubertal OCP tertiles and quintiles with biomarkers. In multivariable models, higher p,p'-dichlorodiphenyldichloroethylene (quintile 5 vs. quintile 1) was associated with lower leptin, with relative mean decreases of 61.8% (95% confidence interval: 48.4%, 71.7%) in models unadjusted for BMI and 22.2% (95% confidence interval: 7.1%, 34.9%) in models adjusted for BMI; the direct effect of p,p'-dichlorodiphenyldichloroethylene on leptin accounted for 27% of the total effect. IR prevalence was 6.6% at ages 12-13 years. Higher hexachlorobenzene (tertile 3 vs. tertile 1) was associated with higher odds of IR in models adjusted for BMI (odds ratio = 4.37, 95% confidence interval: 1.44, 13.28). These results suggest that childhood OCPs may be associated with IR and lower leptin.
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Farm residence and reproductive health among boys in rural South AfricaBACKGROUND: Few studies have investigated reproductive health effects of contemporary agricultural pesticides in boys. OBJECTIVES: To determine the association between pesticide exposure and reproductive health of boys. METHODS: We conducted a cross-sectional study in rural South Africa of boys living on and off farms. The study included a questionnaire (demographics, general and reproductive health, phyto-estrogen intake, residential history, pesticide exposures, exposures during pregnancy); and a physical examination that included sexual maturity development ratings; testicular volume; height, weight, body mass index; and sex hormone concentrations. RESULTS: Among the 269 boys recruited into the study, 177 (65.8%) were categorized as farm (high pesticide exposures) and 98 (34.2%) as non-farm residents (lower pesticide exposures). Median ages of the two groups were 11.3 vs 12.0 years, respectively (p
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Genetic modification of the association between peripubertal dioxin exposure and pubertal onset in a cohort of Russian boysBACKGROUND: Exposure to dioxins has been associated with delayed pubertal onset in both epidemiologic and animal studies. Whether genetic polymorphisms may modify this association is currently unknown. Identifying such genes could provide insight into mechanistic pathways. This is one of the first studies to assess genetic susceptibility to dioxins. OBJECTIVES: We evaluated whether common polymorphisms in genes affecting either molecular responses to dioxin exposure or pubertal onset influence the association between peripubertal serum dioxin concentration and male pubertal onset. METHODS: In this prospective cohort of Russian adolescent boys (n = 392), we assessed gene-environment interactions for 337 tagging single-nucleotide polymorphisms (SNPs) from 46 candidate genes and two intergenic regions. Dioxins were measured in the boys' serum at age 8-9 years. Pubertal onset was based on testicular volume and on genitalia staging. Statistical approaches for controlling for multiple testing were used, both with and without prescreening for marginal genetic associations. RESULTS: After accounting for multiple testing, two tag SNPs in the glucocorticoid receptor (GR/NR3C1) gene and one in the estrogen receptor-alpha (ESR1) gene were significant (q < 0.2) modifiers of the association between peripubertal serum dioxin concentration and male pubertal onset defined by genitalia staging, although not by testicular volume. The results were sensitive to whether multiple comparison adjustment was applied to all gene-environment tests or only to those with marginal genetic associations. CONCLUSIONS: Common genetic polymorphisms in the glucocorticoid receptor and estrogen receptor-alpha genes may modify the association between peripubertal serum dioxin concentration and pubertal onset. Further studies are warranted to confirm these findings.
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Pathophysiology of Respiratory Failure Following Acute Organophosphate Poisoning : A DissertationOrganophosphate (OP) poisoning is a health issue worldwide with over 200,000 deaths per year. Although not a problem in most developed countries, in some third world countries, one third of a hospital’s population could be patients with OP exposure. Even with the most aggressive therapy, 10-40% of patients admitted to an intensive care unit will die. Research into the best practice for treating OP poisoning is lacking, due somewhat to a lack of detailed understanding of the physiology of OP poisoning. Our research uses animal models of acute OP poisoning to explore the mechanism of OP-induced respiratory failure. Our research shows that animals poisoned with dichlorvos demonstrated a uniformly fatal central apnea that, if prevented, was followed immediately by a variable pulmonary dysfunction. Potential mechanisms for dichlorvos-induced central apnea can be divided into direct effects on the central respiratory oscillator (CRO) and feedback inhibition of the CRO. Two afferent pathways that can induce apnea include vagal feedback pathways and feed-forward pathways from the cerebral hemispheres. In our studies we found that vagal feedback and feed forward inhibition from the cerebral hemispheres were not required for OP-induced central apnea. The pre-Botzinger complex in the brainstem is thought to be the kernel of the CRO, but exposure of the pre-Botzinger complex to dichlorvos was not sufficient for apnea. Although OP induced central apnea was uniformly fatal, partial recovery of the CRO occurred post apnea with mechanical ventilation. Central apnea was ubiquitous in our rat poisoning model, but pulmonary dysfunction was extremely variable, with a range of pulmonary effects from fulminate pulmonary failure with prominent pulmonary secretions to no pulmonary dysfunction at all. Vagal efferent activity is involved in neural control of pulmonary tissue but the vagus was not involved in OP-induced pulmonary dysfunction. Anti-muscarinic medications are the mainstay of clinical therapy and are commonly dosed by their effects on pulmonary secretions. Our studies found that atropine (the most common therapeutic agent for OP poisoning) resulted in a ventilation-perfusion mismatch secondary to effects on the pulmonary vasculature.
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Prepubertal organochlorine pesticide concentrations and age of pubertal onset among Russian boysBACKGROUND: In animal studies, organochlorine pesticide (OCP) exposure alters pubertal development; however, epidemiological data are limited and inconsistent. OBJECTIVE: To evaluate the associations of serum OCP concentrations [hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE)] with male pubertal onset. METHODS: In Chapaevsk, Russia, a town environmentally contaminated with OCPs, 350 8-9 year old boys with measured OCPs were enrolled during 2003-2005 and were followed annually for eight years. We evaluated three measures of pubertal onset: testicular volume (TV) > 3 mL in either testis, or stage 2 or greater for genitalia (G2+), or pubic hair (P2+). We used multivariable interval-censored models to evaluate associations of OCPs (quartiles) with physician-assessed pubertal onset. RESULTS: In adjusted models, boys with higher HCB concentrations had later mean ages of TV > 3 mL and P2+ (but not G2+). Mean age at attaining TV > 3 mL was delayed 3.6 (95% CI: -2.6, 9.7), 7.9 (95% CI: 1.7, 14.0), and 4.7 months (95% CI: -1.4, 10.9) for HCB Q2, Q3, and Q4, respectively, compared to Q1 (trend p: 0.06). Boys with higher HCB concentrations reached P2+ 0.1 months earlier (95% CI: -5.8, 5.6) for Q2, 4.7 months later (95% CI: -1.0, 10.3) for Q3 and 4.6 months later (95% CI: -1.1, 10.3) for Q4 compared to Q1 (trend p: 0.04). There were no associations of serum beta-HCH and p,p'-DDE concentrations with age of pubertal onset. CONCLUSION: Higher prepubertal serum HCB concentrations were associated with later age of gonadarche and pubarche.
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Serum concentrations of organochlorine pesticides and growth among Russian boysBACKGROUND: Limited human data suggest an association of organochlorine pesticides (OCPs) with adverse effects on children's growth. OBJECTIVE: We evaluated the associations of OCPs with longitudinally assessed growth among peripubertal boys from a Russian cohort with high environmental OCP levels. METHODS: A cohort of 499 boys enrolled in the Russian Children's Study between 2003 and 2005 at 8-9 years of age were followed prospectively for 4 years. At study entry, 350 boys had serum OCPs measured. Physical examinations were conducted at entry and annually. The longitudinal associations of serum OCPs with annual measurements of body mass index (BMI), height, and height velocity were examined by multivariate mixed-effects regression models for repeated measures, controlling for potential confounders. RESULTS: Among the 350 boys with OCP measurements, median serum hexachlorobenzene (HCB), beta-hexachlorocyclohexane (betaHCH), and p,p -dichlorodiphenyldichloroethylene (p,p -DDE) concentrations were 159 ng/g lipid, 168 ng/g lipid, and 287 ng/g lipid, respectively. Age-adjusted BMI and height z-scores generally fell within the normal range per World Health Organization standards at entry and during follow-up. However, in adjusted models, boys with higher serum HCB, betaHCH, and p,p -DDE had significantly lower mean [95% confidence interval (CI)] BMI z-scores, by -0.84 (-1.23, -0.46), -1.32 (-1.70, -0.95), and -1.37 (-1.75, -0.98), respectively, for the highest versus lowest quintile. In addition, the highest quintile of p,p -DDE was associated with a significantly lower mean (95% CI) height z-score, by -0.69 (-1.00, -0.39) than that of the lowest quintile. CONCLUSIONS: Serum OCP concentrations measured at 8-9 years of age were associated with reduced growth, particularly reduced BMI, during the peripubertal period, which may affect attainment of optimal adult body mass and height.
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Serum Concentrations of Organochlorine Pesticides and Growth among Russian BoysBackground: Limited human data suggest an association of organochlorine pesticides (OCPs) with adverse effects on children's growth.Objective: We evaluated the associations of OCPs with longitudinally assessed growth among peripubertal boys from a Russian cohort with high environmental OCP levels. Methods: A cohort of 499 boys enrolled in the Russian Children's Study between 2003 and 2005 at 8-9 years of age were followed prospectively for 4 years. At study entry, 350 boys had serum OCPs measured. Physical examinations were conducted at entry and annually. The longitudinal associations of serum OCPs with annual measurements of body mass index (BMI), height, and height velocity were examined by multivariate mixed-effects regression models for repeated measures, controlling for potential confounders. Results: Among the 350 boys with OCP measurements, median serum hexachlorobenzene (HCB), β-hexachlorocyclohexane (βHCH), and p,p´-dichlorodiphenyldichloroethylene (p,p´-DDE) concentrations were 159 ng/g lipid, 168 ng/g lipid, and 287 ng/g lipid, respectively. Age-adjusted BMI and height z-scores generally fell within the normal range per World Health Organization standards at entry and during follow-up. However, in adjusted models, boys with higher serum HCB, βHCH, and p,p´-DDE had significantly lower mean [95% confidence interval (CI)] BMI z-scores, by -0.84 (-1.23, -0.46), -1.32 (-1.70, -0.95), and -1.37 (-1.75, -0.98), respectively, for the highest versus lowest quintile. In addition, the highest quintile of p,p´-DDE was associated with a significantly lower mean (95% CI) height z-score, by -0.69 (-1.00, -0.39) than that of the lowest quintile. Conclusions: Serum OCP concentrations measured at 8-9 years of age were associated with reduced growth, particularly reduced BMI, during the peripubertal period, which may affect attainment of optimal adult body mass and height.
