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Chlorpyrifos (CPF) is applied seasonally in Egypt by adolescent agricultural workers and the extent of occupational exposure and the potential for environmental CPF exposure in this population is poorly understood. Adolescent pesticide applicators (n=57; 12–21 years of age) and age matched non-applicators (n=38) from the same villages were followed for 10 months in 2010, spanning pre-application through post-application. Eight urine and 5 blood samples were collected from participants within this time period. Blood acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) (exposure/effect biomarker) and urine 3,5,6-trichloro-2-pyridinol (TCPy) (exposure biomarker) were used to assess occupational CPF exposures in pesticide applicators and environmental exposures in non-applicators. Applicators demonstrated significantly higher TCPy concentration and BChE depression than non-applicators throughout CPF application. This difference persisted for 4–7 weeks after the cessation of agricultural spraying. However, both groups exhibited significantly elevated TCPy and depressed BChE, compared to their respective baseline. The peak TCPy levels during the spray season (95% confidence interval) for non-applicators and applicators reached 16.8 (9.87–28.5) and 137 (57.4–329) ug/g creatinine, respectively. BChE levels (95% confidence intervals) during the spray were 1.47 (1.28–1.68) for non-applicators and 0.47 (0.24–0.94) U/ml for applicators. The longitudinal assessment of CPF biomarkers provided robust measures of exposure and effect throughout CPF application in adolescents and revealed significant exposures in both applicators and non-applicators. Biomarker data in the non-applicators, which mirrored that of the applicators, indicated that non-applicators received environmental CPF exposures. This suggests that similar exposures may occur in other residents of this region during periods of pesticide application.

Chlorpyrifos is an organophosphorus (OP) pesticide widely used around the world for agricultural operations. Although studies have examined exposure in children, there is limited information on adolescents who are occupationally exposed. Furthermore, there is limited research addressing the change in exposure patterns and outcomes across the application season. The goal of the current study was to examine the impact of chlorpyrifos exposure on neurobehavioral performance in adolescents before, during and after the application season. The longitudinal study was conducted in Egypt from April 2010 to January 2011, quantifying exposure and neurobehavioral performance with repeated measures prior to, during, and following the application period. At each test session, participants completed a neurobehavioral test battery and urine was collected for analysis of the chlorpyrifos metabolite 3,5,6-trichloro-2 pyridinol (TCPy) (biomarker of exposure). Cumulative urinary TCPy over the study period was used to classify participants into low (

Children and adolescents may have occupational exposure to pesticides. Although previous studies examining prenatal pesticide exposure have identified neurobehavioral deficits in children, there are limited studies examining the impact of occupational exposure in children. The objectives of this study are to estimate exposures to the organophosphorus pesticide, chlorpyrifos (CPF), by measuring urinary levels of 3,5,6-trichloro-2-pyridinol (TCPy), a specific CPF metabolite, and blood cholinesterase (ChE) activities and to characterize neurobehavioral performance in adolescents working as seasonal pesticide applicators and non-applicator controls. A neurobehavioral test battery, consisting of 14 tests, was used to assess a broad range of functions. Applicators performed worse than controls on the majority of tests. Principal component analysis was used to reduce the number of outcome variables and two components, focused on reasoning-short-term memory and attention-executive functioning, showed significant deficits in applicators compared to non-applicators. Elevated metabolite levels were found in the applicators compared to the non-applicators, confirming CPF exposure in the applicators. Although this study is limited by a small sample size, it provides preliminary evidence of moderate CPF exposures, decreased blood ChE in some applicators and decreased neurobehavioral performance in an adolescent working population.

ObjectivesOccupational exposure of organophosphorus pesticides, such as chlorpyrifos (CPF), in adolescents is of particular concern because of the potential vulnerability of the developing neurological system. The objectives of this study were to examine how neurological symptoms reported over the application season vary across time, whether these effects are reversible postapplication and if there are associations between CPF biomarkers and neurological symptoms in an adolescent study population.SettingThe longitudinal study was conducted in two agricultural districts of Menoufia Governorate, Egypt between April 2010 and January 2011.ParticipantsMale adolescent participants, including CPF applicators (n=57) and non-applicators (n=38), were recruited.Primary and secondary outcome measuresSelf-reported data for 25 neurological symptoms were collected at 32 time points over the 8-month period before, during and after the application season. Additionally, urine and blood samples were collected to measure urine trichloro-2-pyridinol (TCPy), a CPF-specific biomarker and blood cholinesterase activity.ResultsApplicators and non-applicators report the highest numbers of symptoms during the application season, followed by a reduction in symptoms after the application ended. Applicators reported a greater percentage of neurological symptoms, relative to baseline, than non-applicators after accounting for potential covariates. Among the applicators, cumulative TCPy was positively and significantly associated with the average percentage of symptoms (B=4.56, 95% CI 3.29 to 5.84; p<0.001). Significant associations (p=0.03–0.07) between the change in butyrylcholinesterase activity from the preapplication to the postapplication season and several domains of neurological symptoms were also found, even after adjusting for potential covariates.ConclusionsThese observations demonstrate changes in the reporting of symptoms across the application season, showing an increase in symptom reporting during application and recovery following the end of pesticide application. These findings reinforce the growing concern regarding the neurotoxic health effects of CPF in adolescent applicators in developing countries and the need for developing and implementing intervention programmes.

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders ranging from simple hepatic steatosis up to nonalcoholic steatohepatitis (NASH) evolving to cirrhosis and hepatocellular carcinoma (HCC). Liver biopsy is still the gold standard modality for diagnosing and staging NAFLD. The linkage between intestinal microbiota and NAFLD, might suggest a potential role of serum zonulin in NAFLD diagnosis. To appraise the role of circulating zonulin in NAFLD pathogenesis, 56 subjects with proved NAFLD by ultrasonography and liver biopsy, as well as 20 healthy controls were tested. Liver function tests, serum glucose, fasting insulin, C peptide, lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR), IL-6, and circulating zonulin were performed to all subjects. Aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), triglycerides, HDL-c, fasting insulin, C peptide, HOMA-IR, IL-6, and serum zonulin were higher in NAFLD group than in controls (p < 0.05), and in NASH patients than those with simple steatosis (p < 0.05). Zonulin was positively correlated with body mass index (BMI), ALT, triglycerides, fasting insulin, HOMA-IR, liver histopathology, and serum IL-6 (p < 0.05), with inverse correlation to HDL-C (p < 0.05). At cut off 8.3 pc/mL, serum zonulin was found to be of diagnostic value of NASH occurrence with 100% sensitivity and specificity (AUR = 1.000, p-value = <0.001). The increasing zonulin levels in NAFLD patients with steep rise in NASH group denotes a possible role in pathogenesis of NAFLD occurrence and progression. This could open a new avenue of implicating zonulin antagonists as targeted therapies in NAFLD prevention.

Egyptian adolescents are hired as seasonal workers to apply pesticides to the cotton crop and may perform this occupation for several years. However, few studies examined the effects of repeated pesticide exposure on health outcomes The goal of this study was to determine the impact of repeated pesticide exposure on neurobehavioral (NB) performance and biomarkers of exposure (urinary metabolite) and effect (cholinesterase activity). Eighty-four adolescents from two field stations in Menoufia, Egypt, were examined four times: before and during pesticide application season in 2010 and again before and during application season in 2011. At each of the four time points, participants completed a questionnaire, performed an NB test battery, and were assessed for urinary levels of the chlorpyrifos metabolite TCPy (3,5,6-trichloro-2-pyridinol) and blood cholinesterase activity. Following the study cohort over two consecutive pesticide application seasons revealed that TCPy levels significantly increased following exposure, and returned to baseline levels following the end of the application season. Blood butyryl cholinesterase activity exhibited a similar pattern. Although NB outcomes displayed learning and practice effects over time, deficits in performance were significantly associated with increased TCPy levels with reduction in the number of NB measures showing improvement over time. Biomarkers of exposure and effect demonstrated changes associated with pesticide application and recovery after application ended. Deficits in NB performance were correlated with elevated pesticide exposure. Data demonstrated that repeated pesticide exposure may exert a long-term adverse impact on human health.

Background: Systemic lupus erythematosus (SLE) is the most heterogeneous chronic autoimmune disease; it is characterized by the presence of auto reactive B and T cells, responsible for the aberrant production of a broad and heterogeneous group of autoantibodies. Recent studies using various detection methods have demonstrated the elevations of circulating DNA in SLE patients.Aim of the study: The current study aimed to measure cell-free DNA (cf-DNA) in SLE patients as a potential tool to predict disease activity and treatment follow up.Subjects and methods: 52 of SLE patients with age ranging from 10 to 48 years were randomly selected and 25 healthy subjects with age and gender matched with the patients were included as a control group. Thorough clinical examination stressing on the central nervous system, vascular, renal, rash, musculoskeletal, mucocutaneous manifestations, and fever was done for patients. The following investigations were done: Complete blood count (CBC), kidney function tests, Creactive protein (CRP), routine autoantibodies for autoimmune diseases, complements (C3 & C4), anti-nucleosome antibodies and cf-DNA by real time PCR (RT-PCR).Results: The levels of anti-double stranded DNA (anti-dsDNA), anti-nucleosome Ab, and cf-DNA were significantly increased in SLE patients compared to controls. The cf-DNA level was correlated to markers of disease severity namely CRP and anti-nucleosome. A significant reduction in levels of cf-DNA, anti-nucleosome Ab and anti-dsDNA was noticed after therapy. Production and hosting by Elsevier B.V. on behalf of Ain Shams University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article in press as: Hendy OM et al., Circulating cell free DNA as a predictor of systemic lupus erythematosus severity and monitoring of therapy, Egypt J Med Hum Genet (2015), http://dx. Conclusion:Our findings support that the measurement of cf-DNA appears to be a useful marker in addition to laboratory tests used in SLE diagnosis. High correlation with markers of disease severity suggesting its role in disease pathogenesis and decreasing its level after therapy makes it to be a marker of treatment follow-up.Ó 2015 Production and hosting by Elsevier B.V. on behalf of Ain Shams University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).