Phenobarbital use and neurological problems in FMR1 premutation carriers

Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by a CGG expansion in the FMR1 gene located at Xq27.3. Patients with the premutation in FMR1 present specific clinical problems associated with the number of CGG repeats (55–200 CGG repeats). Premutation carriers have elevated FMR1 mRNA expression levels, which have been associated with neurotoxicity potentially causing neurodevelopmental problems or neurological problems associated with aging. However, cognitive impairments or neurological problems may also be related to increased vulnerability of premutation carriers to neurotoxicants, including phenobarbital. Here we present a study of three sisters with the premutation who were exposed differentially to phenobarbital therapy throughout their lives, allowing us to compare the neurological effects of this drug in these patients.     

Long-term epigenetic alterations in a rat model of Gulf War Illness

Gulf War Illness (GWI) is a chronic, multisymptom illness that affects 25% of the 700,000 US veterans deployed to the Persian Gulf during the 1990–1991 Gulf War. Central nervous system impairments are among the most common symptoms reported, including memory dysfunction and depression. After 25 years, the diagnosis remains elusive, useful treatments are lacking, and the cause is poorly understood, although exposures to pyridostigmine bromide (PB) and pesticides are consistently identified to be among the strongest risk factors. Epigenetic changes including altered microRNA (miRNA) expression and DNA methylation play an important role in learning, memory, and emotion regulation and have been implicated in various neurological disorders. In this study, we used an established rat model of GWI to determine whether 1) chronic alterations in miRNA expression and global DNA methylation and DNA hydroxymethylation are mechanisms involved in the pathobiology of GWI, and 2) plasma exosome small RNAs may serve as potential noninvasive biomarkers of this debilitating disease. One year after a 28-day exposure regimen of PB, DEET (N,N-diethyl-3-methylbenzamide), permethrin, and mild stress, expression of 84 mature miRNAs and global 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) content were analyzed in the brains of GWI rats and vehicle controls by PCR array and enzyme-linked immunosorbent assay, respectively. Plasma exosome RNA next-generation sequencing analysis was performed in pooled samples to discover potential noninvasive biomarkers. We found that combined exposure to low doses of GW-related chemicals and mild stress caused epigenetic modifications in the brain that persisted one year after exposure, including increased expression of miR-124-3p and miR-29b-3p in the hippocampus and regional alterations in global 5mC and 5hmC content. GW-relevant exposures also induced the differential expression of two piwi-interacting RNAs (piRNAs) in circulation (piR-007899 and piR-019162). Results from this study implicate a role for epigenetic alterations in GWI. Evaluation of the diagnostic potential of plasma exosome RNAs in veterans with GWI is warranted.     

百草枯致小鼠肺纤维化作用的实验研究

目的探讨百草枯(PQ)对小鼠肺纤维化的作用机制。方法将8周龄健康清洁级雄性C57BL小鼠48只分为百草枯组和对照组(生理盐水),每组24只。百草枯组腹腔注射5mg/ml的百草枯(20mg/kg)连续3d。每天观察并记录各组小鼠的行为学改变。分别于染毒后第1、3、7天处死动物,取肺组织进行普通病理和免疫组化染色,统计肺组织基质金属蛋白酶(MMP-2、MMP-9)阳性细胞数。结果染毒后3d,百草枯组小鼠均出现不同程度的运动障碍、动作迟缓、震颤、竖毛和活动减少。光镜下观察,静脉瘀血、局部出血,中性粒细胞轻度增多,纤维母细胞增多,肺局部纤维组织增生;染毒后7d,出现慢性炎症、出血,局部区域可明显见纤维组织增生,间质增厚。百草枯组小鼠肺组织中MMP-2、MMP-9的表达均强于对照组,差异有统计学意义(P<0.05或P<0.01);且MMP-2、MMP-9的表达随着时间的延长而增强。结论百草枯可引起小鼠肺组织纤维化,MMP-2、MMP-9可能参与了百草枯致肺纤维化的过程。     

Causes and types of health effects during the use of crop protection chemicals: data from a survey of over 6,300 smallholder applicators in 24 different countries

Purpose  The present investigation looks in detail at the causes and types of health incidents reported by 6,300 mainly smallholder agrochemical users in 24 countries during 2005 and 2006. Methods  The investigation is based on a questionnaire survey of knowledge, attitude and practice that concentrated on the sequence of events from purchasing the pesticide to disposal. Information was also collected about health problems experienced while using agrochemicals. The survey targeted mainly smallholder knapsack spray operators who were expected to be at a highest risk of exposure. Results  In the 12 months prior to interview, 1.2% of users reported an agrochemical-related incident that required hospital treatment, 5.8% reported an incident requiring at least trained medical treatment but not hospitalisation and 19.8% reported only a minor sign or symptom. Users who had experienced an incident involving agricultural equipment were 3.38 (95% CI 2.29–4.99) times more likely to experience an agrochemical-related health incident, but confident users who felt that their use of personal protective equipment while spraying was best practice were 0.60 (95% CI 0.44–0.84) times less likely to experience such an incident. Over 80% of product-related incidents were caused by insecticides and the incidence rate per spraying time for incidents linked to insecticides was significantly higher than that for fungicides or herbicides. Headache/dizziness and nausea/vomiting, often smell related, were the most common symptoms reported by users who listed agrochemical products that had caused them health problems (52 and 38% of product mentions, respectively). Conclusions  In most countries, the incidence of serious health effects was low; however, there was a high incidence of minor signs and symptoms in a few countries, especially in Africa. A disproportionate number of incidents occurred during insecticide use relative to the time that they were sprayed. Failure to exercise caution as indicated by whether users had incidents involving agricultural equipment or livestock, and lack of confidence in their practices were the most important predictors of agrochemical-related incidents.     

Arsenic exposure in the wine growing industry in ten French departments

Objectives This study investigated exposure to arsenic, a carcinogenic fungicide used in wine growing.Methods The first phase compared urinary arsenic excretion of controls and workers exposed at the end of application. The second phase measured the increase in urinary arsenic excretion during the first day of use.Results A significant increase in urinary arsenic excretion was observed in arsenic applicators during the first phase. Urinary arsenic concentrations exceeded the American Conference of Governmental Industrial Hygienists (ACGIH) exposure index in one-third of the workers. The second phase showed a significant increase in urinary arsenic excretion by the first day of application. A closed tractor cabin provided a protective effect, but the efficacy of individual protection equipment was not demonstrated.Conclusion This study showed the difficulties of achieving the effective protection of arsenic applicators and has led to the banning of the use of arsenic in French vineyards.     

Residential proximity to agricultural pesticide use and incidence of breast cancer in the California Teachers Study cohort

We examined the association between residential proximity to agricultural pesticide use and breast cancer incidence among members of the California Teachers Study cohort, a large study of professional school employees with extensive information on breast cancer risk factors, followed for cancer incidence since 1995. We identified 1552 invasive breast cancer cases, diagnosed between 1996 and 1999, among 114,835 cohort members. We used California Pesticide Use Reporting data to select pesticides for analysis based on use volume, carcinogenic potential, and exposure potential; a Geographic Information System was used to estimate pesticide applications within a half-mile radius of subjects' residences. We applied Cox proportional hazard models to estimate hazard rate ratios (HR) for selected pesticides, adjusting for age, race, and socioeconomic status. We saw no association between residential proximity to recent agricultural pesticide use and invasive breast cancer incidence. HR estimates for the highest compared to the lowest exposure categories for groups of agents were as follows: probable or likely carcinogens (1.07, 95% confidence interval (CI): 0.86-1.32), possible or suggestive carcinogens (1.06, 95% CI: 0.87-1.29), mammary carcinogens (1.15, 95% CI: 0.90-1.48), and endocrine disruptors (1.03, 95% CI: 0.86-1.25). HR estimates for other groups and individual pesticides did not differ from unity, nor was there a trend for any groupings of or individual pesticides examined. Stratifying by menopausal status or family history of breast cancer did not substantially affect our results. Our analyses suggest that breast cancer incidence is not elevated in areas of recent, high agricultural pesticide use in California.     

氯氰菊酯毒作用研究进展

氯氰菊酯是近年来广泛应用的一类拟除虫菊酯杀虫剂,随着用量和使用时间的增加,对其毒性的研究亦逐渐加深。氯氰菊酯对不同种属的动物和经不同的途径染毒均表现出不同的毒性。该文主要就氯氰菊酯对动物和人的毒作用及其对神经系统、免疫系统、血液系统和淋巴系统的毒作用机制的研究进行综述。     

A descriptive bibliometric study on bioavailability of pesticides in vegetables,food or wine research (1976–2018)

A bibliometric analysis based on the Web of Science© (WOS) database was performed on bioavailability of pesticides in vegetables, food or wine related studies published from inception to 2018. A total of 1202 articles were subjected to examination. The results reveal that yearly production of scientific articles increased steadily. Journal and institution production, and author's keywords frequencies followed the Lotka’s Law. Khan SU and White JC were the most productive authors. The most productive journals were Journal of Agricultural and Food Chemistry (55), and Journal of Ethnopharmacology (48), and the most common WOS subject category was Pharmacology & Pharmacy (419). USA (h-index of 40) produced 21.7 % of all articles, closely followed by China (20.6 %). Chinese Academy of Sciences (34) was the most productive research institutions. Finally, current and future trends in this area should focus on keywords such as pharmacokinetics, curcumin, in-vitro, nanoparticles, oral (bioavailability) and cell.     

胆碱酯酶监测在抢救有机磷农药中毒中的临床意义

目的 探讨胆碱酯酶活性在决定有机磷农药中毒抢救中氯磷定、阿托品的用量,停药时间及对患者预后判断的作用。方法 将口服有机磷农药中毒抢救传统治疗组列为对照组（３２例）,将口服有机磷农药中毒采用胆碱酯酶指导氯磷定、阿托品用量及停药列为观察组（５０例）。结果 观察组阿托品用量和氯磷定用量与对照组阿托品用量和氯磷定用量有显著差异（Ｐ〈０．０１）。观察组治愈５０例,治愈率１００％;对照组治愈２８例,治愈率８７     

Predictors of urinary levels of 2,4-dichlorophenoxyacetic acid, 3,5,6-trichloro-2-pyridinol, 3-phenoxybenzoic acid,and pentachlorophenol in 121 adults in Ohio

Limited data exist on the driving factors that influence the non-occupational exposures of adults to pesticides using urinary biomonitoring. In this work, the objectives were to quantify the urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D), 3,5,6-trichloro-2-pyridinol (TCP), 3-phenoxybenzoic acid (3-PBA), and pentachlorophenol (PCP) in 121 adults over a 48-h monitoring period and to examine the associations between selected sociodemographic and lifestyle factors and urinary levels of each pesticide biomarker. Adults, ages 20–49 years old, were recruited from six counties in Ohio (OH) in 2001. The participants collected 4–6 spot urine samples and completed questionnaires and diaries at home over a 48-h monitoring period. Urine samples were analyzed for 2,4-D, TCP, 3-PBA, and PCP by gas chromatography/mass spectrometry. Multiple regression modeling was used to determine the impact of selected sociodemographic and lifestyle factors on the log-transformed (ln) levels of each pesticide biomarker in adults. The pesticide biomarkers were detected in ≥89% of the urine samples, except for 3-PBA (66%). Median urinary levels of 2,4-D, TCP, 3-PBA, and PCP were 0.7, 3.4, 0.3, and 0.5 ng/mL, respectively. Results showed that 48-h sweet/salty snack consumption, 48-h time spend outside at home, and ln(creatinine) levels were significant predictors (p < 0.05), and race was a marginally significant predictor (p = 0.093) of the adults’ ln(urinary 2,4-D) concentrations. Strong predictors (p < 0.05) of the adults’ ln(urinary TCP) concentrations were urbanicity, employment status, sampling season, and ln(creatinine) levels. For 3-PBA, sampling season, pet ownership and removal of shoes before entering the home were significant predictors (p < 0.05) of the adults’ ln(urinary 3-PBA) levels. Finally for PCP, removal of shoes before entering the home and ln(creatinine) levels were significant predictors (p < 0.05), and pet ownership was a marginally significant predictor (p = 0.056) of the adults’ ln(urinary PCP) concentrations. In conclusion, specific sociodemographic and lifestyle factors were identified that increased the exposures of these adults to several different pesticides in their daily environments.