Impact of chlorpyrifos exposure on lung function in Egyptian adolescent agriculture workers.

Chlorpyrifos (CPF) is a widely used organophosphate insecticide that has been linked to detrimental health effects that range from neurological impacts to respiratory disease. The objective of this study was to assess respiratory symptoms associated with CPF exposure throughout the application season. Urine samples were collected from Egyptian adolescent applicators (n = 206) and non-applicators (n = 72) to assess 3,5,6-trichloro-2-pyridinol (TCPy), a biomarker for CPF exposure, along with spirometry measures to determine lung ventilatory function. Samples were collected over 7 months in 2016. Logistic regression was used to model the odds of reporting wheeze symptoms based on urinary TCPy concentrations while controlling for age and smoking in the household. Ordinal multinomial logistic regression was used to model the percent reference for forced expiratory volume in one second (rFEV1) based on urinary TCPy concentration (µg/g creatinine). Wheezing increased with increasing pesticide exposure (OR = 1.74 (1.32 - 2.31)). There was no statistically significant relationship between rFEV1 and TCPy concentration. Efforts to reduce pesticide exposure should be implemented to prevent the potential onset or exacerbation of any linked respiratory complications in adolescents.

Evaluating how occupational exposure to organophosphates and pyrethroids impacts ADHD severity in Egyptian male adolescents.

BACKGROUND: Attention Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by deficits in attention and hyperactivity/impulsivity that cause impairments to daily living. An area of long-standing concern is understanding links between environmental toxicants, including pesticides, and the development or worsening of ADHD. OBJECTIVES: The present study evaluated associations between occupational pesticide exposure, specifically organophosphate (OP) pesticides, chlorpyrifos (CPF) and the pyrethroids (PYR) alpha-cypermethrin (αCM) and lambda-cyhalothrin (λCH), and symptoms of ADHD in a longitudinal study among Egyptian adolescent males. METHODS: Participants (N = 226, mean age = 17) were Egyptian adolescent males who either applied pesticides or were non-applicators. Urinary trichloro-2-pyridinol (TCPy) was measured as a specific metabolite biomarker of exposure to chlorpyrifos. Urinary 3-phenoxybenzoic acid (3-PBA) was measured as a general metabolite biomarker of exposure to pyrethroids, while urinary cis-3-(2,2- dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA) was measured as a specific biomarker of exposure to αCM and lambda cyhalothric acid (λCH acid) measured as a specific biomarker of exposure to λCH. Ordinal logistic regression models controlling for age were used to determine the likelihood of ADHD development (measured via parent-reported ADHD symptoms) as the level of biomarkers of pesticide exposure increased. RESULTS: Cis-DCCA was the only biomarker associated with higher likelihood ADHD symptoms (> 0.60 vs. 0-0.17 µg/g creatinine; OR = 2.82, 95% CI: 1.29-6.14). All participants reported clinical levels of ADHD symptoms when compared to national norms used in the United States. TCPy, trans-DCCA and λCH acid were not associated with risk of ADHD symptoms after controlling for levels of cis-DCCA. No other metabolites were associated with the number of ADHD symptoms. There were no interaction effects found for exposure to both OPs and Pyrethroids. DISCUSSION: The results suggest that exposure to the pyrethroid αCM is associated with more ADHD symptoms. Methodological and cultural considerations in need of further study are discussed.

Respiratory, hepatic, renal, and hematological disorders among adolescent females environmentally exposed to pesticides, Menoufia governorate, Egypt.

Adolescent females are often environmentally exposed to pesticides by living near agricultural fields, by using pesticides at home, or by having contact with contaminated clothes and pesticide application work tools. This study assessed respiratory, hepatic, renal, and hematological health disorders that might arise due to environmental exposure to pesticides among adolescent females. A cross-sectional study was conducted with 100 adolescent females environmentally exposed to pesticides that had one or more of their family members working as seasonal pesticide applicators and 50 nonexposed (control) adolescent females from Menoufia governorate, Egypt. The studied period of pesticide application season of the cotton crop was from May 1 to September 1, 2017. Participants completed a self-administered questionnaire about pesticide exposure and respiratory, hepatic, renal, and hematological disorders. In addition, serum acetylcholinesterase (AChE), spirometry, complete blood count, and liver and kidney function tests were measured pre and post-pesticide application season. The control adolescent females had a higher AChE activity, a lower prevalence of respiratory symptoms, and higher means of spirometric measurements than the exposed group. During the pre- and postseason, the exposed group presented a prevalence of (6%, 24%) for cough, (4%, 11%) for rhinitis, and (6%, 26%) for dyspnea during the pre and postseason, respectively. In addition, there was a decrease in means of spirometric measurements (FEV1%, FEV1/FVC%, FEF 25-75%, and PEF%) in the postseason compared to preseason among the exposed group. Also, there were significant associations between (AChE) activity and both the prevalence of respiratory manifestations and spirometric measurements among the exposed females. On the other hand, there was a statistically significant increase in red blood corpuscle (RBC) and lymphocyte counts, and a statistically significantly lower mean hemoglobin level among the exposed group (postseason) than each of their pre-season values and the control group (P < 0.05). AChE level, total protein, albumin, and albumin/globulin (A/G) ratio levels were statistically significantly lower, while SGPT, SGOT and globulin, blood urea, and serum creatinine mean levels were statistically significantly higher among the exposed group (postseason) than either of their preseason or the control group (P < 0.05). There was a positive correlation between the AChE level and all studied CBC parameters for the exposed group reaching a statistically significant level with basophils (P < 0.05). Also, there was a negative correlation between the AChE level and each of SGPT, SGOT, ALP, globulin, blood urea, and serum creatinine for the exposed group reaching a statistically significant level with each of SGPT and SGOT (P < 0.05). At the same time, a nonsignificant positive correlation was found between AChE level and each of total protein, albumin, and A/G ratio (P > 0.05). So, environmental exposure to organophosphorus pesticides has a detrimental impact on respiratory, hepatic, renal, and hematological systems of adolescent females living in rural districts at the Menoufia governorate. Educational and training intervention programs on pesticide handling and safety precautions are recommended for protecting both pesticide workers and their family members who might be exposed.

Acute and Cumulative Effects of Repeated Exposure to Chlorpyrifos on the Liver and Kidney Function among Egyptian Adolescents.

BACKGROUND: There is a paucity of research that tracks changes in liver and kidney function among pesticide applicators. The aim of the current study was to investigate the role of repeated seasonal exposure to the organophosphorus pesticide, chlorpyrifos, on serum measures of liver and kidney function. METHODS: Pesticide exposure was assessed by measuring the urinary concentrations of 3,5,6-trichloro-2 pyridinol (TCPy), a specific biomarker for chlorpyrifos. Chlorpyrifos exposure and 8 serum markers of liver and kidney function were measured at 15 timepoints over 3 years prior to, during, and following the end of seasonal pesticide application among adolescent applicators and non-applicators from 4 field stations in Menoufia, Egypt. RESULTS: Urinary TCPy levels showed increases during the application cycles and recovery at the end of each application season. Altered serum markers of liver and kidney function were associated with chlorpyrifos exposure, with some markers recovering 3 months after the end of exposure each year, while other measures demonstrated progressive increase up to 300% the baseline levels at the end of 3 years. CONCLUSION: The study demonstrated that frequent assessment of liver and kidney function is a sound practice to evaluate cellular injury following chronic repeated occupational and environmental exposure to chlorpyrifos.

Evaluation of occupational pesticide exposure on Egyptian male adolescent cognitive and motor functioning.

BACKGROUND: Chronic low-level exposure to organophosphorus pesticides is associated with adverse health effects, including a decline in neurological functioning and long-term impairment. These negative effects may be more detrimental in children and adolescents due to their critical stage in development. Little work has investigated the effects of chronic exposure to pesticides, specifically chlorpyrifos (CPF) during the adolescent period. OBJECTIVES: To examine effects of CPF exposure over a year-long period within a group of male adolescents in Egypt (N = 242, mean age = 17.36), including both pesticide applicators and non-applicators. METHODS: Associations between average CPF exposure (measured via urinary metabolite levels of 3,5,6-trichloro-2-pyridinol [TCPy]) and neurobehavioral functioning were examined in a 1-year longitudinal study. Given previous literature, higher levels of TCPy were expected to be associated with worse neurobehavioral functioning. RESULTS: Using mixed effects linear regression, average TCPy exposure predicted deficits in more complex neurobehavioral tasks (Benton visual retention, digit span reverse, match to sample, serial digit learning, and alternating tapping) with estimates of effects ranging from -0.049 to 0.031. Age (effects ranging from 0.033 to 0.090) and field station (effects ranging from -1.266 to -0.278) were significantly predictive of neurobehavioral functioning over time. An interaction effect was found for field station and TCPy across several neurobehavioral domains. DISCUSSION: Results show that occupational exposure to pesticides may have particularly deleterious effects on complex neurobehavioral domains. Additionally, differences across field stations and the age at which individuals are exposed may be important factors to investigate in future research.

Matrix Metalloproteinase-11 Gene Polymorphisms as a Risk for Hepatocellular Carcinoma Development in Egyptian Patients.

BACKGROUND: Chronic hepatitis C (CHC) virus infection is one of major risk factors of hepatocellular carcinoma (HCC) in Egypt, which is a major cause of cancer mortalityin the world. Matrix metalloproteinase-11 (MMP-11) has an important role in tumor migration and metastasis. Therefore, this study aimed to determine relation between MMP-11 gene polymorphisms and risk of HCC development among Egyptian cirrhotic patients. SUBJECTS AND METHODS: Two hundred and sixty patients were included, 140 of them with HCC on top of CHC and 120 patients with post CHC liver cirrhosis (LC) as well as 140 subjects were enrolled in the study as healthy controls. Two single nucleotide polymorphisms (SNPs) rs738791 and rs738792 for MMP-11 gene were done using real-time PCR. RESULTS: Combination of CT and TT allele of rs738791 genotypes was more significantly frequent in HCC compared to LC patients and controls, however, a higher frequency of T allele was found in HCC patients compared to LC and controls. In spite of lake of significant difference between patient groups regarding the rs738792 genotypes, the CC genotype was considered a risk of developing portal vein thrombosis, and was associated with advanced tumor stage, increased tumor size, higher Cancer of the Liver Italian Program [CLIP] score, more advanced Barcelona stage [D] and with child Pugh class [C]. CONCLUSION: Genetic variations in MMP-11 may be implicated in post HCV-HCC development and might be dependable biomarkers for HCC progression.

Risk perception and behavior in Egyptian adolescent pesticide applicators: an intervention study.

BACKGROUND: Adolescents are engaged in agricultural work, including pesticide application, around the world. Adolescent pesticide applicators are more likely to be exposed to pesticides than their adult counterparts because of their application practice and hygiene habits surrounding pesticide use. There is a need for low-cost interventions to reduce pesticide exposure. We evaluated a theoretically-based educational intervention to change perceptions about the risk of pesticide use and hygiene habits during and after pesticide application for adolescent and young adult pesticide applicators in Egypt. METHODS: Young adult and adolescent male pesticide applicators were given a one-hour educational intervention to inform them about the risk of pesticide use and how to reduce pesticide exposure. The median age of participants was 18 years old. Changes in perceived susceptibility and effectiveness were measured with a survey pre and post-intervention (n = 119) on the same day. The same survey (n = 95) was given 8-months post-intervention to identify sustained effects. Observational checklists of pesticide application practice were also completed during application seasons before and after the intervention. RESULTS: There was an increase in the proportion of individuals who viewed pesticides as being a long-term health risk (74.7% pre-intervention to 97.9% post-intervention, McNemar test p < 0.001). This change remained significant when surveyed at the 8-month follow-up (90.5%, p < 0.001). There was also a sustained improvement regarding participants' views of proper hygiene practice surrounding pesticide application. Applicators were observed wearing goggles, shoes, and masks more frequently post-intervention. CONCLUSION: This theoretically-based intervention is an example of a low-cost solution that can improve adolescents' and young adults' practices regarding pesticide application and personal hygiene practices during and after pesticide application. The intervention can be applied in other countries with similar safety culture surrounding pesticide application.

Occupational pesticide exposure and symptoms of attention deficit hyperactivity disorder in adolescent pesticide applicators in Egypt.

BACKGROUND: Exposure to environmental chemicals, including organophosphorus pesticides, is associated with behavioral disorders such as attention deficit hyperactivity disorder (ADHD). However, the impact of occupational pesticide exposure on ADHD development in adolescents has not been examined. OBJECTIVE: We examined the association between exposure to chlorpyrifos and ADHD symptoms among adolescents in Egypt. METHODS: Adolescent pesticide applicators and non-applicators, 12-21 years old, participated in a 10-month longitudinal study examining health effects from pesticide exposure. Repeated urine and blood samples were collected at various time points during the 10-months to assess biomarkers of chlorpyrifos exposure (urinary trichloro-2-pyridinol or TCPy) and effect (blood acetyl cholinesterase activity and butyryl cholinesterase activity). Parents from a subset of the cohort (N = 64) completed the Short Form of Conners' Parent Rating Scale - Revised. Poisson regressions were used to examine the associations between the number of ADHD symptoms and occupation and biomarkers. RESULTS: Pesticide applicators had significantly more symptoms of ADHD than participants in the non-applicator group. Urinary TCPy levels were associated with increased symptoms, demonstrating a dose-response effect. Applicators with ADHD reported applying pesticides for more hours during the application season and had greater cumulative TCPy levels than participants without ADHD. One fourth of all applicators met the criteria for an ADHD diagnosis (having 6 or more reported symptoms). CONCLUSIONS: This study provides preliminary evidence of an association between occupational exposure to chlorpyrifos and ADHD symptoms among adolescent pesticide applicators in spite of its limited small sample size. There is a critical need to investigate the susceptibility of children and adolescents to repeated occupational and environmental exposures to pesticides because the developing brain may be uniquely sensitive to the neurotoxic effects of these agents.

The Circulating Micro-RNAs (-122, -34a and -99a) as Predictive Biomarkers for Non-Alcoholic Fatty Liver Diseases.

BACKGROUND: It remains essential for patient safety to develop non-invasive diagnostic tools to diagnose non-alcoholic fatty liver rather than invasive techniques. AIM: Our case-control study was to address the value of circulating miRNAs as a potential non-invasive biomarker for the diagnosis of non-alcoholic fatty acid diseases (NAFLD) and monitoring of disease progression. METHODS: Routine clinical assessment, laboratory tests, anthropometric study, and liver biopsy results reported for 210 patients with NAFLD (124 patients of simple steatosis (SS) and 86 of non-alcoholic steatohepatitis (NASH)). Apparently matched for age and gender, healthy participants (n= 90) were enrolled as a control group. Serum samples were tested for micro-RNAs (-122, -34a and -99a) by quantitative-PCR. RESULTS: By histopathology, 124 of the NAFLD group were of SS and 86 patients were of NASH. Compared with the control subjects, both mi-RNA-122 and -34a levels were increased in NAFLD (p< 001) and at a cut-off = 1.261, mi-RNA-122 had 92% sensitivity, 85% specificity to differentiate NAFLD from healthy controls, while mi-RNA-99a were significantly decreased in NAFLD patients with an observed decrease in disease severity, and at a cut-off = 0.46, miRNA-99a had 94% sensitivity and 96% specificity to discriminate SS from NASH. CONCLUSION: The integration of a circulating mi-RNA panel to diagnose NAFLD cases and to discriminate between SS and NASH. Large-scale study is still needed to verify the other mi-RNA profiles and their role in NAFLD pathogenesis and targeting therapy.

Diagnosis of spontaneous bacterial peritonitis in children using leukocyte esterase reagent strips and granulocyte elastase immunoassay.

AIM OF THE STUDY: We aimed to assess the utility and rapidity of granulocyte elastase (GE) latex immunoassay and leukocyte esterase (LE) reagent strips for the diagnosis of spontaneous bacterial peritonitis (SBP) in hepatic children with ascites. MATERIAL AND METHODS: This study included 80 ascitic fluid (AF) samples from 45 patients with chronic liver diseases. They were divided into 2 groups (SBP and non-SBP groups). White blood cells > 500 cell/mm3 or polymorphonuclear leukocytes > 250 cell/mm3 were considered as a positive result for the diagnosis of SBP. The AF obtained at bedside was immediately tested with an LE enzyme reagent strip, and another sample was aliquoted for measurement of serum GE. RESULTS: On doing LE dipstick strips, all the non-SBP group gave no coloration with LE strips while 62% of the SBP group gave coloration. LE strips had accuracy of 86.25% in differentiating SBP and non-SBP at a cut-off value of 1 (color grade 1). The diagnostic performance of GE in differentiating SBP and non-SBP was assessed and showed accuracy of 70% for a cutoff value of 123.5 ng/ml. CONCLUSIONS: Application of LE reagent strips is a bedside, rapid, easy-to-use, and inexpensive method for diagnosis of SBP. It has an accuracy of 86.25% in differentiating SBP and non-SBP, which is higher than more complicated and delayed methods such as GE latex immunoassay, which has an accuracy of 70%.

Longitudinal assessment of occupational determinants of chlorpyrifos exposure in adolescent pesticide workers in Egypt.

Chlorpyrifos (CPF) is an organophosphourus insecticide applied to cotton fields by adolescents employed by the Egyptian Ministry of Agriculture. Urinary 3,5,6-trichloro-2-pyridinol (TCPy) is a biomarker of CPF exposure that has substantial variability among these applicators. In order to identify predictors of CPF exposure, we conducted a longitudinal study of 43 adolescent pesticide applicators in Egypt from April 2010 to January 2011 in Egypt. Urinary TCPy was quantified at 25 time-points, prior to, during, and following application. We used log-linear regression and a best subset selection approach to identify the exposure determinants that were most predictive of cumulative TCPy and participants' highest TCPy values (peak exposure). Applicators had cumulative urinary TCPy levels ranging from 167 to 49,8208µg/g creatinine. Total hours applying CPF (semi-partial r2=0.32), and total hours in the field applying other pesticides (semi-partial r2=0.08) were the strongest predictors of cumulative TCPy. Applicators had peak urinary TCPy levels ranging from 4 to 5715µg/g creatinine. The amount of time applying pesticides prior to blood draw was the strongest predictor of peak TCPy (semi-partial r2=0.30). We also observed evidence that wearing clean clothes to work was associated with lower longitudinal TCPy. Our results suggest there is an opportunity for targeted interventions, particularly related to hygiene or implementation of personal protective equipment usage to reduce CPF exposure among adolescent pesticide workers.

The impact of repeated organophosphorus pesticide exposure on biomarkers and neurobehavioral outcomes among adolescent pesticide applicators.

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.

Evaluation of circulating zonulin as a potential marker in the pathogenesis of nonalcoholic fatty liver disease.

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.

Comparison of neurological health outcomes between two adolescent cohorts exposed to pesticides in Egypt.

Pesticide-exposed adolescents may have a higher risk of neurotoxic effects because of their developing brains and bodies. However, only a limited number of studies have addressed this risk among adolescents. The aim of this study was to compare neurological outcomes from two cohorts of Egyptian adolescents working as pesticide applicators. In 2005 and 2009, two cohorts of male adolescents working as pesticide applicators for the cotton crop were recruited from Menoufia Governorate, Egypt. The same application schedule and pesticides were used at both times, including both organophosphorus, and pyrethroid compounds. Participants in both cohorts completed three neurobehavioral tests, health and exposure questionnaires, and medical and neurological screening examinations. In addition, blood samples were collected to measure butyryl cholinesterase (BChE) activity. Pesticide applicators in both cohorts reported more neurological symptoms and signs than non-applicators, particularly among participants in the 2005 cohort (OR ranged from 1.18 to 15.3). Except for one test (Trail Making B), there were no significant differences between either applicators or non-applicators of both cohorts on the neurobehavioral outcome measures (p > 0.05). The 2005 cohort showed greater inhibition of serum BChE activity than the 2009 cohort (p < 0.05). In addition, participants with depressed BChE activity showed more symptoms and signs than others without BChE depression (p < 0.05). Our study is the first to examine the consistency of health outcomes associated with pesticide exposure across two cohorts tested at different times from the same geographical region in rural Egypt. This similar pattern of findings across the two cohorts provides strong evidence of the health impact of exposure of adolescents to pesticides.

A 10-month prospective study of organophosphorus pesticide exposure and neurobehavioral performance among adolescents in Egypt.

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 (

Chlorpyrifos exposure and respiratory health among adolescent agricultural workers.

Chlorpyrifos (CPF) is a commonly used organophosphate insecticide (OP). In adults, exposure to OPs has been inconsistently associated with reduced lung function. OP exposure and lung function has not been assessed in adolescents. The objective of this study was to assess CPF exposure and lung function among Egyptian adolescents. We conducted a 10-month study of male adolescent pesticide applicators (n = 38) and non-applicators of similar age (n = 24). Urinary 3,5,6-trichloro-2-pyridinol (TPCy), a CPF-specific metabolite, was analyzed in specimens collected throughout the study. Spirometry was performed twice after pesticide application: day 146, when TCPy levels were elevated and day 269, when TCPy levels were near baseline. Applicators had higher levels of TCPy (mean cumulative TCPy day 146 = 33,217.6; standard deviation (SD) = 49,179.3) than non-applicators (mean cumulative TCPy day 146 = 3290.8; SD = 3994.9). Compared with non-applicators, applicators had higher odds of reporting wheeze, odds ratio = 3.41 (95% CI: 0.70; 17.41). Cumulative urinary TCPy was inversely associated with spirometric measurements at day 146, but not at day 269. Although generally non-significant, results were consistent with an inverse association between exposure to CPF and lung function.

Characterizing exposures and neurobehavioral performance in Egyptian adolescent pesticide applicators.

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.

Longitudinal assessment of chlorpyrifos exposure and self-reported neurological symptoms in adolescent pesticide applicators.

OBJECTIVES: Occupational 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. SETTING: The longitudinal study was conducted in two agricultural districts of Menoufia Governorate, Egypt between April 2010 and January 2011. PARTICIPANTS: Male adolescent participants, including CPF applicators (n=57) and non-applicators (n=38), were recruited. PRIMARY AND SECONDARY OUTCOME MEASURES: Self-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. RESULTS: Applicators 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. CONCLUSIONS: These 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.

Longitudinal assessment of chlorpyrifos exposure and effect biomarkers in adolescent Egyptian agricultural workers.

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 five blood samples were collected from participants within this time period. Blood acetylcholinesterase 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 with their respective baseline. The peak TCPy levels during the spray season (95% confidence interval (CI)) for non-applicators and applicators reached 16.8 (9.87-28.5) and 137 (57.4-329) ug/g creatinine, respectively. BChE levels (95% CIs) during the spray were as follows: 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.

Hepcidin levels and iron status in beta-thalassemia major patients with hepatitis C virus infection.

Beta-thalassemia is an inherited anemia in which synthesis of the hemoglobin beta-chain is decreased. Clinical features of beta-thalassemia include variably severe anemia and iron overload due to increased intestinal iron absorption, which may result in damage to vital organs. The hepatic peptide; hepcidin is a key regulator of iron metabolism in mammals. The present study aimed to determine the relationship between hepcidin expression and iron status in beta-thalassemia patients with hepatitis C virus infection. The study included 50 patients diagnosed as beta-thalassemia major (21 of them were HCV infected and 29 were HCV negative), in addition, 20 healthy subjects were enrolled in the study. The hepatic iron and hepcidin mRNA concentration in liver biopsy samples were measured, as well as serum ferritin, serum iron, hemoglobin and levels and serum hepcidin. Result showed remarkable decrease of serum and liver hepcidin mRNA expression in thalassemic patients as compared to controls, and showed a positive correlation with hemoglobin concentration, but negatively correlated with serum ferritin level and hepatic iron index (HII). In HCV infected patients, serum and liver hepcidin mRNA were markedly depressed in HCV positive beta-thalassemia cases, and positively correlated serum albumin and prothrombin concentrations, but inversely correlated with HII and fibrosis score. In HCV positive beta-thalassemia major patients, the hepcidin mRNA level was positively correlated with the synthetic function of the liver (namely serum albumin and prothrombin concentration) and with serum hepcidin level. While, both serum and hepcidin mRNA level was inversely correlated with HII and fibrosis score in these patients. These results suggest a possible role of hepcidin expression in iron overload in beta-thalassemia major, consequent disease progression and development of liver fibrosis.